title
stringlengths
0
1.13k
abstract
stringlengths
1
15.7k
PMID
int64
22
36.5M
Post-exposure targeting of specific epitopes on ricin toxin abrogates toxin-induced hypoglycemia, hepatic injury, and lethality in a mouse model.
Effects in the liver of fatal intoxication with the binary toxin ricin are unclear. We report a robust neutrophil influx into the liver of C57BL/6 mice after lethal parenteral ricin challenge, occurring in peri-portal and centro-lobular hepatic areas within 2 h, followed by the abrupt disappearance of hepatic macrophages/Kupffer cells. Chemokine profiles determined by microarray, ribonuclease protection assays, northern blotting, and enzyme-linked immunosorbent assays showed rapid (2 h) upregulation and persistence of those for neutrophils (CXCL1/KC, CXCL2/MIP-2) and monocytes (CCL2/MCP-1). Red blood cell pooling (8-12 h), loss of hepatocyte glycogen (8-48 h) associated with progressive hypoglycemia, fibrin deposition (24-48 h), and death (72-96 h) followed. Monoclonal antibody to ricin A chain, administered intravenously, blunted hypoglycemia, and abrogated death. This outcome was observed when anti-ricin antibody was given before toxin exposure as well as when administered approximately 10 h after toxin exposure. Targeting antibody to specific amino-acid sequences on the ricin A chain (HAEL and QXXWXXA) was critical to the therapeutic effect. Re-emergence of liver macrophages/Kupffer cells and replenishment of glycogen in previously depleted hepatocytes preceded full recovery of the host. These data identify critical events for liver injury and healing in ricin intoxication, as well as a new means and specific targets for post-exposure therapeutic intervention.
18,779,782
DNA-based patents: an empirical analysis.
The perception of rising litigation rates is driving the push for patent reform.
18,779,808
Behavioral immunization: immunity to self-antigens contributes to psychological stress resilience.
The psychobiological mechanisms that contribute to the development of stress resilience are not fully elucidated. One potential approach for enhancing resilience is the exposure to mild challenges. According to this approach, a mildly stressful episode may immunize the individual, thereby strengthening resistance to subsequent stressors. This phenomenon is often viewed as a form of behavioral immunization. Although, the term 'behavioral immunization' was borrowed from the field of immunology, the involvement of the adaptive immune system in stress resilience was never investigated. However, based on accumulated new data, we suggest that the immunological memory does have a significant role in developing coping responses to stress. Although, immune deficiency results in an impaired ability to cope with stress, boosting immunological memory can increase stress resilience. Therefore, we propose that defense against mental challenge, similarly to defense against intruders, involves an immunological mechanism, which establishes stress resilience to a later challenge. Here, we review the involvement of the adaptive immune system in coping mechanisms in response to psychological stress, and discuss the connection between cognitive memory and immunological memory in establishing ability to efficiently cope with stressful episodes.
18,779,818
Association of maternal dopamine transporter genotype with negative parenting: evidence for gene x environment interaction with child disruptive behavior.
Although maternal parenting is central to child development, little is known about the interplay between molecular genetic and environmental factors that influence parenting. We tested the association of the 40-bp variable number tandem repeat polymorphism of the dopamine transporter (DAT1; SLC6A3) gene with three dimensions of observed maternal parenting behavior (positive parenting, negative parenting and total maternal commands). A significant nonadditive association was found between maternal DAT1 genotype and both negative parenting and total commands during a structured mother-child interaction task, even after controlling demographic factors, maternal psychopathology and disruptive child behavior during the task. Furthermore, the association between maternal DAT1 genotype and negative parenting was significantly stronger among mothers whose children were highly disruptive during the mother-child interaction task, suggesting a gene-environment interaction.
18,779,819
Thalidomide plus dexamethasone as primary therapy for newly diagnosed patients with multiple myeloma.
Thalidomide with dexamethasone (thal-dex) is an active therapy for patients with relapsed or refractory multiple myeloma (MM). In this Practice Point, we discuss the findings of a trial by Rajkumar et al. that aimed to compare the response rate, time to progression and progression-free survival among previously untreated patients with MM who received either thal-dex or placebo plus dexamethasone. The thal-dex regimen was associated with a significantly higher response rate at the expense of more-frequent adverse effects, in particular deep-vein thrombosis, which occurred in almost 20% of patients. Median time to progression was three times longer with thal-dex than with placebo plus dexamethasone, but was shorter, however, than the time to progression observed in studies in which thalidomide or bortezomib was added to melphalan and prednisone. Nevertheless, thal-dex is a convenient oral and relatively inexpensive non-myelosuppressive regimen, which can be used in patients with previously untreated MM.
18,779,849
Elevated systemic antibodies towards commensal gut microbiota in autoinflammatory condition.
Familial Mediterranean fever (FMF) is an autoinflammatory condition, which is characterized by acute, self-limiting episodes of fever and serositis and chronic subclinical inflammation in remission. Here we investigated the consequence of this condition on the level of systemic antibodies directed towards common intestinal bacteria. The level of systemic antibodies towards the antigens of Bacteroides, Parabacteroides, Escherichia, Enteroccocus and Lactobaccilus was measured by ELISA in FMF patients at various stages of the disease and in healthy controls. The difference between remission and attack was not significant. IgG antibodies against the antigens of Bacteroides, Parabacteroides, Escherichia and Enteroccocus were significantly increased in FMF compared to control while IgA levels were not significantly affected. Western blot analyses demonstrated the IgG reactivity against multiple antigens of commensal bacteria in FMF. Serological expression cloning was performed to identify these antigens. No single dominant antigen was identified; the response was generalized and directed against a variety of proteins from Bacteroides, Parabacteroides, Escherichia, and other gut commensals. This autoinflammatory syndrome is characterized by the increased systemic reactivity against commensal gut microbiota. This is probably the consequence of hypersensitivity of the inflammasome in FMF that triggers the inflammation and contributes to the excessive translocation of bacteria and bacterial antigens through the gut barrier.
18,779,861
Change in long-spacing collagen in Descemet's membrane of diabetic Goto-Kakizaki rats and its suppression by antidiabetic agents.
We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet's membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long-spacing collagen fibrils were observed in Descemet's membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age-dependent increase in the density of the long-spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long-spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly suppressed the formation of the long-spacing collagen in the diabetic rats. Long-spacing collagen would thus be a useful indicator for studying diabetic changes in the cornea and the effect of antidiabetic agents.
18,779,868
Pathogenicity of Chinese H5N1 highly pathogenic avian influenza viruses in pigeons.
It has long been thought that pigeons are resistant against H5 highly pathogenic avian influenza (HPAI) viruses. Recently, however, highly pathogenic H5N1 avian influenza viruses have demonstrated distinct biological properties that may be capable of causing disease in pigeons. To examine the susceptibility of domestic pigeons to recent H5N1 viruses, we inoculated pigeons using H5N1 viruses isolated in China from 2002 to 2004. Within 21 days following inoculation, all pigeons had survived and fully recovered from temporary clinical signs. However, seroconversion assays demonstrated that several viruses did in fact establish infection in pigeons and caused a certain amount of viral shedding in the oropharynx and cloaca. There was not, however, a definitive relationship between viral shedding and viral origin. Viruses were also inconsistently isolated from various organs of pigeons in infected groups. Pathological examination revealed that the infection had started as respiratory inflammation and caused the most severe lesions in the brain in later stages. These results indicate that pigeons are susceptible to the more recent Asian H5N1 HPAI and could be a source of infection to other animals, including humans.
18,779,923
Sequential anaerobic-aerobic degradation of munitions waste.
A sequential anaerobic-aerobic biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was studied. The results demonstrated that: (i) a complete degradation of RDX was achieved within 20 days using a consortium of bacteria from a wastewater activated sludge, (ii) RDX degradation did not occur under aerobic conditions alone, (iii) RDX-degrading bacterial strain that was isolated from the activated sludge completely degraded RDX within 2 days, and (iv) RDX- induced protein expressions were observed in the RDX-degrading bacterial strain. Based on fatty acid composition and a confirmation with a 16S rRNA analysis, the RDX-degrading bacterial strain was identified as a Bacillus pumilus-GC subgroup B.
18,779,925
Seasonal trends and tissue distribution of organochlorine pollutants in wild and farmed gilthead sea bream (Sparus aurata) from the Western Mediterranean Sea and their relationship with environmental and biological factors.
Seasonal trends and tissue distribution of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in gilthead sea bream (Sparus aurata) samples from the Western Mediterranean were investigated. Hexane extracts of white and red muscle, liver, and gills from wild and cultured specimens were purified by normal-phase high-performance liquid chromatography, and selected OCPs and PCBs were determined by gas chromatography coupled to mass spectrometry as indicators of contamination. The limits of detection for the analytical methodology allowed was 0.25 ng/g. Data obtained showed the presence of DDTs and PCBs in the different tissues, with the highest concentration of pollutants being in tissues of higher lipid content. Concentrations of organochlorine compounds in sea bream tissues strongly correlated with seasonal changes and the biological cycle of the species. In general, cultured fish had lower concentrations of contaminants and smaller season variability than wild fish. Trace levels of contaminants were found in fish muscle throughout the year, but always below the guidelines recommended for human consumption.
18,779,940
Uterotrophic assay, Hershberger assay, and subacute oral toxicity study of 3-amino-1,2,4-triazole based on the Organization for Economic Co-operation and Development draft protocols.
We performed a uterotrophic assay, the Hershberger assay, and the 28-day repeated-dose toxicity study (enhanced OECD test guideline no. 407) of 3-amino-1,2,4-triazole based on the OECD draft protocols. In the uterotrophic assay, female SD rats were subcutaneously injected with the chemical at doses of 0, 100, 300, and 1,000 mg/kg on each of 3 days from postnatal day 20 to day 22, and no changes were observed. In the Hershberger assay, the test chemical was orally administered at doses of 0, 40, 200, and 1,000 mg/kg/day to castrated male Wistar rats for 10 consecutive days beginning on postnatal day 56, and no androgen agonistic and antagonistic changes were observed. Alternatively, when the test chemical was orally administered at doses 0, 5, 25, and 125 mg/kg/day for at least 28 days in the subacute oral toxicity study, thyroid follicular epithelial cell hypertrophy with increased thyroid weights was detected in the male and female rats in 25 and/or 125 mg/kg groups, and hypertrophy of the anterior pituitary cells with increased pituitary weights in male and female rats was also observed in the 125 mg/kg group. Furthermore, serum T3 and T4 values decreased and serum TSH values increased in male and female rats in the 125 mg/kg group. Therefore, 3-amino-1,2,4-triazole was concluded to have anti-thyroid acting as endocrine-mediated effects, but no estrogenic or androgenic effects. In addition, decreased body weight, and abnormal biochemical parameters attributed to thyroid, liver or kidney dysfunction were observed in male and female rats in the 25 and/or 125 mg/kg groups.
18,779,953
Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide.
Patients with primary (AL) amyloidosis and heart failure have a very poor prognosis and cannot tolerate aggressive therapy, such as autologous stem cell transplantation and high-dose dexamethasone-based regimens. We prospectively treated 22 patients with advanced cardiac amyloidosis combining oral melphalan, thalidomide, and reduced intensity dexamethasone (MTD). Six patients died due to cardiac amyloidosis before completing cycle 3. Early death was associated with reduced ejection fraction. Eight patients achieved a hematological response and four achieved a durable improvement of cardiac dysfunction. Treatment with MTD is feasible in patients with advanced cardiac AL amyloidosis and effective in subjects with preserved systolic function.
18,779,964
[Sudden visual loss in a 7-year old patient].
A 7-year-old boy presented to us with a sudden bilateral decrease in visual acuity. At the age of 4 months bilateral congenital glaucoma had been diagnosed and trabeculotomy performed. Eye pressure and fundus were monitored regularly. Both magnetic resonance imaging and computed tomography revealed a giant supraclinoid aneurysm originating in the right internal carotid artery. After comprehensive examinations endovascular balloon occlusion of the internal carotid artery was performed in conjunction with extracranial-intracranial bypass to augment the insufficient circulation.
18,779,968
Linkage of 35S and 5S rRNA genes in Artemisia (family Asteraceae): first evidence from angiosperms.
Typically in plants, the 5S and 35S ribosomal DNA (rDNA) encoding two major ribosomal RNA species occur at separate loci. However, in some algae, bryophytes and ferns, they are at the same locus (linked arranged). Southern blot hybridisation, polymerase chain reactions (PCR), fluorescent in situ hybridisation, cloning and sequencing were used to reveal 5S and 35S rDNA genomic organisation in Artemisia. We observed thousands of rDNA units at two-three loci containing 5S rDNA in an inverted orientation within the inter-genic spacer (IGS) of 35S rDNA. The sequenced clones of 26-18S IGS from Artemisia absinthium appeared to contain a conserved 5S gene insertion proximal to the 26S gene terminus (5S rDNA-1) and a second less conserved 5S insertion (5S rDNA-2) further downstream. Whilst the 5S rDNA-1 showed all the structural features of a functional gene, the 5S-rDNA-2 had a deletion in the internal promoter and probably represents a pseudogene. The linked arrangement probably evolved before the divergence of Artemisia from the rest of Asteraceae (>10 Myrs). This arrangement may have involved retrotransposons and once formed spread via mechanisms of concerted evolution. Heterogeneity in unit structure may reflect ongoing homogenisation of variant unit types without fixation for any particular variant.
18,779,974
Development of Thanatophilus micans (Fabricius 1794) (Coleoptera: Silphidae) at constant temperatures.
Thanatophilus micans is capable of finding corpses at least as quickly as most fly species and, as the most widespread species of the Silphidae in Africa, offers a useful model for estimating post-mortem interval. Larvae were reared at ten constant temperatures from 15 degrees C to 35 degrees C and their length measured at 4, 8, or 12-h intervals depending on their instar. Length generally increased with increased rearing temperature, but decreased at extremely high temperatures. Note was made of the age at which individuals progressed past developmental milestones. Development took longer at lower temperatures. These results are presented as a combined isomegalen and isomorphen diagram. Developmental constants were generated for each milestone using major axis regression. Developmental threshold values did not differ significantly between milestones. Development took longer than in blow flies, but was faster than in Dermestidae. The three models presented here, therefore, cover an important time frame in estimating minimum PMI once fly larvae have matured to the point of leaving a corpse, and, therefore, provide a tool that was not previously available to forensic entomologists.
18,779,975
Monitoring demyelination and remyelination by magnetization transfer imaging in the mouse brain at 9.4 T.
The aim of this study was to assess quantitatively structural changes in myelin content occurring during demyelination and remyelination by magnetization transfer imaging (MTI). In a reversible model of demyelination with no axonal loss, mice intoxicated by cuprizone were studied by MTI in vivo at 9.4 T. MRI data were compared to histopathological examinations. Data revealed that the magnetization transfer ratio (MTR) decreased significantly during demyelination and increased during remyelination with strong correlation to the myelin content (r=0.79, P=0.01). This study demonstrated that MTR is a sensitive and reproducible quantitative marker to assess myelin loss and repair. This may lead to in vivo monitoring of therapeutic strategies promoting remyelination.
18,779,984
Correlation of echocardiographic markers and therapy in persistent pulmonary hypertension of the newborn.
Persistent pulmonary hypertension of the newborn (PPHN) causes morbidity and mortality in neonates. High-frequency ventilation (HFV), inhaled nitric oxide (iNO), and extracorporeal membrane oxygenation (ECMO) are used when conventional treatment fails. This study aimed to identify echocardiographic predictors of progression to these therapies before clinical deterioration. Echocardiographic parameters were compared for survival and need for ECMO, HFV, iNO, and prolonged mechanical ventilation (MV, >or=10 days). Of 63 neonates, 95% survived, with 14% requiring ECMO, 52% requiring HFV, 67% requiring iNO, and 35% requiring MV. The following echocardiographic indices reflecting left ventricular output were decreased in sicker infants: (1) A decreased ascending aortic velocity time integral indicated an increased likelihood of ECMO (p=0.02), iNO (p=0.01), or MV (p=0.05), (2) Shorter transverse aortic arch antegrade ejection time indicated HFV (p<0.01), iNO (p<0.01), and MV (p=0.03), (3) Absent or retrograde transverse aortic diastolic flow correlated with HFV (p=0.01, iNO (p=0.01), and MV (p<0.01). These sicker patients were more likely to have smaller left ventricular end-diastolic areas (p<0.03 for all) and right-to-left atrial shunting (ECMO, HFV, and MV). There were no differences in survival. Decreased left ventricular size and output correlates with the need for advanced therapies in infants with PPHN. Early identification may allow more effective management and placement of neonates at risk.
18,779,989
Tuberculous pyomyositis of forearm muscles.
Tuberculous pyomyositis is a rare entity reported in literature. The presented case reports the occurrence of such a lesion in forearm muscles, without any bony involvement. The ambiguity in its diagnosis led to inadequate management by the primary care physician. Clinical suspicion, positive tuberculin test, culture of acid-fast bacilli, 'effective drainage', and timely anti-tubercular chemotherapy ultimately resulted in a good clinical recovery. This case has been presented to increase the awareness about the existence of such an entity in clinical practice, thereby influencing its workup and the possible modes of management.
18,780,002
Surgical treatment of thumb carpometacarpal joint arthritis: a single institution experience from 1995-2005.
There are numerous techniques for the surgical management of thumb carpometacarpal (CMC) joint arthritis. The four senior authors of this study employ three such techniques: trapeziectomy with hematoma distraction arthroplasty, hemitrapeziectomy with osteochondral allograft, and ligament reconstruction tendon interposition (LRTI). This study examines the three commonly utilized procedures at a single institution. This study examines the 10-year experience from 1995-2005 with a minimum 3-month follow-up. Disabilities of the arm, shoulder, and hand (DASH) scores, pre-and postoperative pinch strength, and operative time were examined. After approval from the institutional review board of our institution was obtained, all patients treated surgically by three of the senior authors were contacted via mail and phone. Each patient was asked to complete and return a DASH questionnaire. Of the 115 patients treated during that period, 60 participated in this study. Each patient's final postoperative pinch measurement was obtained from occupational therapy and clinic records. This pinch strength was compared to the preoperative pinch and contralateral pinch strength. Lastly, the total operative time for each procedure was obtained from the operative record. The only significant finding in this study was a shorter mean operative time with the trapeziectomy group (76.90 min) and osteochondral allograft group (90.45 min) when compared to the LRTI group (139.00 min; p = 0.001 and p = 0.001, respectively). We found no significant difference between groups in terms of DASH score and pinch strength. There was no difference between the techniques in terms of postoperative pinch strength and patient satisfaction measured by DASH scores. The operative times for trapeziectomy and hematoma interposition as well as the osteochondral allograft were significantly shorter than that of the LRTI. This presents further evidence that potentially, "less is more" in the treatment of thumb CMC arthritis. We used a retrospective study design to evaluate potential differences between the three surgical techniques described above, therapeutic, levels III-IV.
18,780,018
Absent flexor pollicis longus: case report with review of literature.
An asymptomatic absence of flexor pollicis longus without association with any other anomaly or hypoplasia of the thenar muscles in a 28-year-old patient is reported due to its rarity. The inability to flex the interphalangeal joint of the thumb and the absent flexor crease of the thumb led us to identify the absent tendon, and the tendon could not be palpated in the flexor crease of the thumb. Routine X-rays, ultrasound scans, and a computed tomography with soft tissue enhancement was used to confirm and document the condition. The patient was not referred for a magnetic resonance imaging, facilities for which are not available in the center where the author is working, as he was not keen in surgical interference.
18,780,020
Flucloxacillin reduces stiffness following flexor tendon repair.
To determine the benefit of antibiotic prophylaxis on postoperative mobility in flexor tendon repairs, case notes of 72 flexor tendon injuries in twenty four patients were analyzed retrospectively (2001-2003). Only patients with non-contaminated injuries from sharp instruments in flexor zone 2 were included in the study; 57% were male, average age was 31 years, and 24% were smokers. The majority of injuries were caused by metal blades (45%). Most tendons were repaired with modified Kessler technique (69%). Twenty-five percent received intravenous flucloxacillin or co-amoxiclav perioperatively. Reduced total active motion (TAM, found in 25% of patients more than 7 weeks after surgical repair) significantly complicated patients without perioperative intravenous flucloxacillin cover. The use of intravenous perioperative flucloxacillin is a plausible adjunct in surgery to prevent postoperatively reduced mobility.
18,780,024
Compression of the deep palmar branch of the ulnar nerve by a ganglion : a case report.
A ganglion originating from the pisotriquetral joint is the most common cause of distal ulnar nerve compression. Midpalmar ganglions causing ulnar nerve compression are rare. This case describes a ganglion arising from the third carpometacarpal joint causing compression of the deep motor branch of the ulnar nerve.
18,780,033
Current status of outcomes research in carpal tunnel surgery.
More than 3,000 publications on carpal tunnel syndrome (CTS) have been presented in the literature. Although surgery for treating CTS is commonly performed, the outcomes of these surgical procedures are still relatively unclear. This paper will summarize relevant publications on the surgical treatment of CTS to critically examine outcomes data based on the best available evidence.
18,780,037
Treatment of distal radius fractures with percutaneous pinning and pin-in-plaster.
This article describes a modified technique that combines percutaneous pinning and casting. A prospective study was conducted on 54 patients with distal radius fracture who were treated with percutaneous Kirschner wire (K-wire) fixation and pin-in-plaster technique. The surgical indications of this technique included displaced extra-articular fracture, intra-articular fracture without significant comminution, and articular step-off less than 2 mm. The average radial height was 10.96 mm, and the volar tilt was 3.97 degrees on immediate postoperative radiographs. Upon removal of pin-in-plaster and percutaneous K-wires, the average radial height was 9.92 mm, and the volar tilt was 3.93 degrees . Bony union was achieved in all patients; the satisfaction rate was 90.7%. Pin-in-plaster technique is effective for maintaining reduction during bone healing. The procedure provides the ability to achieve anatomic reduction and then maintains this reduction through an adequate method of immobilization.
18,780,104
Cryopreservation of composite tissue transplants.
Composite tissue allotransplantation holds great promise for upper extremity reconstruction but is limited by donor part availability. Cryopreservation may increase the availability of donor parts and even reduce antigenicity. The purpose of the study was to evaluate the viability of cryopreserved composite tissues and to demonstrate the feasibility of microvascular isotransplantation of cryopreserved composite flaps. Twenty epigastric flaps were harvested from Lewis rats. Ten flaps were analyzed fresh. Ten flaps were perfused with dimethyl sulfoxide (DMSO)/trehelose cryoprotectant agent (CPA), frozen by controlled cooling to -140 degrees C, and stored for 2 weeks. Flaps were evaluated by factor VIII endothelial staining and MTT tetrazolium salt assay. For the in vivo phase, 30 flaps were harvested. Ten were transplanted fresh to isogenetic recipient animals, ten were perfused with CPA and transplanted, and ten were cryopreserved for 2 weeks, thawed, and transplanted. All cryopreserved samples displayed intact vascular endothelia on factor VIII staining. On MTT analysis, the epithelial viability index for the cryopreserved samples was not significantly different from fresh controls (p = 0.12). All freshly transplanted flaps (10/10) were viable at 60 days. Nine of ten flaps in the perfused/transplanted group were viable at 60 days. Survival of cryopreserved/transplanted flaps ranged from 5 to 60 days. The skin and vascular endothelial components of composite tissue flaps appear to retain their viability after cryopreservation. The in vivo studies demonstrate that the long-term survival of cryopreserved composite tissue transplants is feasible and support an indirect injury, rather than direct injury from freezing or cryoprotectant agents, as the mechanism of flap loss.
18,780,115
The safety of percutaneous trigger finger release.
This study attempted to determine the safety of percutaneous release of trigger fingers, with particular attention given to border digits and the thumb. We performed percutaneous release of the A1 pulley in six fresh frozen cadaveric hands utilizing established surface landmarks. After freezing all specimens, we performed cross-sections at the A1 pulley, avoiding dissection of soft tissues, which could alter the natural position of the digital nerves. There was no difference in the distance from the needle tract to the neurovascular bundle when comparing between digits, and the closest distance was 2.7 mm. There was no significant difference between the needle tract and the radial and ulnar digital nerves. Based on our findings, percutaneous trigger finger release can safely be performed on all digits, including the thumb, small fingers, and index fingers.
18,780,120
Posttraumatic stress and complicated grief in family members of patients in the intensive care unit.
Family members of patients in intensive care units (ICUs) are at risk for mental health morbidity both during and after a patient's ICU stay. To determine prevalences of and factors associated with anxiety, depression, posttraumatic stress and complicated grief in family members of ICU patients. Prospective, longitudinal cohort study. Fifty family members of patients in ICUs at a large university hospital participated. We used the Control Preferences Scale to determine participants' role preferences for surrogate decision-making. We used the Hospital Anxiety and Depression Scale, Impact of Event Scale, and Inventory of Complicated Grief to measure anxiety and depression (at enrollment, 1 month, 6 months), posttraumatic stress (6 months), and complicated grief (6 months). We interviewed all 50 participants at enrollment, 39 (78%) at 1 month, and 34 (68%) at 6 months. At the three time points, anxiety was present in 42% (95% CI, 29-56%), 21% (95% CI, 10-35%), and 15% (95% CI, 6-29%) of participants. Depression was present in 16% (95% CI, 8-28%), 8% (95% CI, 2-19%), and 6% (95% CI, 1-18%). At 6 months, 35% (95% CI, 21-52%) of participants had posttraumatic stress. Of the 38% who were bereaved, 46% (95% CI, 22-71%) had complicated grief. Posttraumatic stress was not more common in bereaved than nonbereaved participants, and neither posttraumatic stress nor complicated grief was associated with decision-making role preference or with anxiety or depression during the patient's ICU stay. Symptoms of anxiety and depression diminished over time, but both bereaved and nonbereaved participants had high rates of posttraumatic stress and complicated grief. Family members should be assessed for posttraumatic stress and complicated grief.
18,780,129
Bariatric surgery improves atherogenic LDL profile by triglyceride reduction.
Small dense low-density lipoprotein (LDL) are atherogenic particles frequently observed in obese patients. Fatty acids modulate LDL. Objective of this study was to determine the relations between plasma phospholipid fatty acid composition and the presence of small dense LDL particles in morbidly obese patients treated with laparoscopic gastric banding (LAGB). Small dense LDL, plasma lipids, lipoproteins, apoproteins, and phospholipid fatty acid composition (a marker of dietary fatty acid intake) were quantified before and 12 months after surgery in four men and 11 women who were morbidly obese and (BMI > 40 kg/m(2)) eligible for surgery, consecutively treated with LAGB at the Department of Medical and Surgical Sciences of the University of Padova. BMI was 48.3 +/- 4.8 kg/m(2) before and 36.1 +/- 5.5 kg/m(2) after LAGB. Plasma triglycerides and apoprotein E levels significantly decreased, while HDL cholesterol significantly increased after LAGB. A reduction of small dense LDL with an increase of LDL relative flotation (0.34 +/- 0.04 before vs 0.38 +/- 0.03 after LAGB, p < 0.001) was also observed. These modifications were neither related to weight reduction nor to changes in phospholipid fatty acid composition, but they were associated to triglyceride reduction, which explained 76.7% of the LDL relative flotation variation. Weight loss obtained by LAGB in morbidly obese subjects was accompanied by triglyceride reduction, high-density lipoprotein increase, and an improvement of the atherogenic LDL profile. Triglyceride reduction, but not the extent of weight loss or dietary fatty acid modifications, is the determinant of modifications of LDL physical properties in these patients.
18,780,133
Role of protein flexibility in the design of Bcl-X(L) targeting agents: insight from molecular dynamics.
Detailed understanding of protein-ligand interactions is crucial to the design of more effective drugs. This is particularly true when targets are protein interfaces which have flexible, shallow binding sites that exhibit substantial structural rearrangement upon ligand binding. In this study, we use molecular dynamics simulations and free energy calculations to explore the role of ligand-induced conformational changes in modulating the activity of three generations of Bcl-X(L) inhibitors. We show that the improvement in the binding affinity of each successive ligand design is directly related to a unique and measurable reduction in local flexibility of specific regions of the binding groove, accompanied by the corresponding changes in the secondary structure of the protein. Dynamic analysis of ligand-protein interactions reveals that the latter evolve with each new design consistent with the observed increase in protein stability, and correlate well with the measured binding affinities. Moreover, our free energy calculations predict binding affinities which are in qualitative agreement with experiment, and indicate that hydrogen bonding to Asn100 could play a prominent role in stabilizing the bound conformations of latter generation ligands, which has not been recognized previously. Overall our results suggest that molecular dynamics simulations provide important information on the dynamics of ligand-protein interactions that can be useful in guiding the design of small-molecule inhibitors of protein interfaces.
18,780,145
Structural and functional aspects of the MSP (PsbO) and study of its differences in thermophilic versus mesophilic organisms.
The Manganese Stabilizing Protein (MSP) of Photosystem II (PSII) is a so-called extrinsic subunit, which reversibly associates with the other membrane-bound PSII subunits. The MSP is essential for maximum rates of O(2) production under physiological conditions as stabilizes the catalytic [Mn(4)Ca] cluster, which is the site of water oxidation. The function of the MSP subunit in the PSII complex has been extensively studied in higher plants, and the structure of non-PSII associated MSP has been studied by low-resolution biophysical techniques. Recently, crystal structures of PSII from the thermophilic cyanobacterium Thermosynechococcus elongatus have resolved the MSP subunit in its PSII-associated state. However, neither any crystal structure is available yet for MSP from mesophilic organisms, higher plants or algae nor has the non-PSII associated form of MSP been crystallized. This article reviews the current understanding of the structure, dynamics, and function of MSP, with a particular focus on properties of the MSP from T. elongatus that may be attributable to the thermophilic ecology of this organism rather than being general features of MSP.
18,780,158
The multisite violence prevention project: impact of a universal school-based violence prevention program on social-cognitive outcomes.
This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence. The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites (N = 5,581) were randomized to four conditions: (a) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers; (b) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence; (c) a combined intervention condition; and (d) a no-intervention control condition. Short-term and long-term (i.e., 2-year post-intervention) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students' pre-intervention level of risk. High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression, and increases in self-efficacy, beliefs and attitudes supporting nonviolent behavior. Effects on low-risk students were in the opposite direction. The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth. These findings have important research and policy implications for efforts to develop effective violence prevention programs.
18,780,181
Effects of Ramadan upon fluid and food intake, fatigue, and physical, mental, and social activities: a comparison between the UK and Libya.
Two studies were performed during Ramadan, one in the UK (N=31) and the other in Libya (N=33). The aims were to assess some changes to lifestyle that are produced by fasting as well as effects due to culture. Subjects were studied on eight separate occasions: four control days (two before and two after Ramadan) and four days during the four weeks of Ramadan itself. A questionnaire was answered that asked about naps and fluid and food intake. The questions elicited if an individual had slept, drank, or eaten, plus the reasons for doing or not doing so. Also, subjects were asked to describe their physical, mental, and social activities, their fatigue, and their perceived abilities to perform physical or mental work. The questionnaire was answered five times per day: at sunrise, at 10:00 h, at 14:00 h, at sunset, and on retiring to sleep at night. Urine samples were collected at sunset and measured for osmolality. Differences between control and Ramadan days, as well as between subjects studied in UK and Libya, were assessed by analysis of variance. Correlations between fatigue and physical, mental, and social activities were also assessed, as were differences in urine osmolality. Fasting during Ramadan resulted in fewer activities and increased fatigue and frequency of napping during daytime. Changes in fluid and food intake indicated some degree of preparation for fasting before sunrise and a marked "recuperation" from fasting after sunset. The reasons given for napping in the daytime, for drinking or not drinking, and for eating or not eating, changed during Ramadan compared with control days; as a result, links between fatigue and activities, and fatigue and fluid and food intake, were all altered during Ramadan, particularly after sunset. Subjects become dehydrated during the daytime, but this was not reduced when females who were menstruating drank during this time. Several differences between the two studies were found. There was a greater frequency of napping during the daytime in the Libya study, and evidence for the conservation of energy during the daytime and reduced physical, mental, and social activities. Subjects' preparations for fasting and recovering from it--their fluid and food intakes and associated reasons for these--also differed. Possible explanations of these differences are discussed.
18,780,199
Day-night variations of serum interleukin-6 in patients with severe obstructive sleep apnea syndrome before and after continuous positive airway pressure (CPAP).
Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin-6 (IL-6) is one of the important proinflammatory cytokines. We examined the levels of serum IL-6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL-6 levels were significantly reduced after CPAP therapy by 46% (6.2+/-1.0 vs. 3.3+/-0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL-6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL-6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL-6 in severe OSAS patients.
18,780,208
Lead removal and toxicity reduction from industrial wastewater through biological sulfate reduction process.
The practicability of lead removal from sulfate-rich wastewater through biological sulfate reduction process with hydrogen as electron donor was investigated. Sulfide, which was converted from sulfate by a sulfate-reducing bacteria (SRB) in a gas-lift reactor, was used to remove lead as lead sulfide precipitate. Furthermore, the toxicity of wastewater in terms of whole effluent toxicity (WET) before and after treatment was analyzed by using Microtox analyzer. The experiment was divided into three stages as follows: Stage I, startup and operation of sulfidogenic process fed with synthetic wastewater in a gas-lift reactor; Stage II, operation of sulfidogenic process fed with real wastewater in the same reactor and analysis of toxicity; and Stage III, separation of lead from wastewater. In stage I, the volumetric sulfate-sulfur loading rate was gradually increased from 1.0 g/L.d until no improvement of sulfide-sulfur production efficiency was evident at 2.58 g/L.d and maximum sulfide-sulfur concentration was set to 340 mg/L. In stage II, the results showed that the laboratory scale reactor could treat a real wastewater without inhibition or any remarkable problem. The produced sulfide-sulfur, 200 mg/L, was a little less in comparison with that of the previous stage. It could be due to the higher concentration of total dissolved solid (TDS). However, the sulfate concentration was still reduced by approximately 30%. The WET test by Microtox showed that toxicity was reduced more than 13 times. In stage III, the effluent from the reactor containing sulfide-sulfur of about 200 mg/L and lead-containing solution of 20 mg/L were fed with sulfide to lead ratio 3 moles: 1 mole into the precipitation chamber in which the optimum pH for lead sulfide precipitation of 8.0 was maintained. It was found that lead removal of 99% was attained.
18,780,220
Soil-skin adherence from carpet: use of a mechanical chamber to control contact parameters.
A computer-controlled mechanical chamber was used to control the contact between carpet samples laden with soil, and human cadaver skin and cotton sheet samples for the measurement of mass soil transfer. Mass soil transfers were converted to adherence factors (mg/cm2) for use in models that estimate dermal exposure to contaminants found in soil media. The contact parameters of pressure (10 to 50 kPa) and time (10 to 50 sec) were varied for 369 experiments of mass soil transfer, where two soil types (play sand and lawn soil) and two soil sizes (< 139.7 microm and > or = 139.7 < 381) were used. Chamber probes were used to record temperature and humidity. Log transformation of the sand/soil transfers was performed to normalize the distribution. Estimated adjusted means for experimental conditions were exponentiated in order to express them in the original units. Mean soil mass transfer to cadaver skin (0.74 mg/cm2) was higher than to cotton sheets (0.21 mg/cm2). Higher pressure (p < 0.0001), and larger particle size (p < 0.0001) were also all associated with larger amounts of soil transfer. The original model was simplified into two by adherence material type (i.e., cadaver skin and cotton sheets) in order to investigate the differential effects of pressure, time, soil size, and soil type on transfer. This research can be used to improve estimates of dermal exposure to contaminants found in home carpets.
18,780,223
Virus-host interaction in the simian immunodeficiency virus-infected brain.
With the increased survival of human immunodeficiency virus (HIV)-infected individuals resulting from therapy, disorders in other target organs of the virus, such as the brain, are becoming more prevalent. Here the author reviews his laboratory's work on the simian immunodeficiency virus (SIV)/nonhuman model of acquired immunodeficiency syndrome (AIDS), which has revealed unique characteristics of both the virus that infects the brain, and the innate and adaptive immune response within the central nervous system (CNS) to infection. Similar to findings in humans, neurocognitive/neurobehavioral disorders during the chronic phase of infection can be detected in monkeys, and recent findings reveal potential mechanisms of CNS damage due to the virus-host interaction.
18,780,229
Behavioral and neurophysiological hallmarks of simian immunodeficiency virus infection in macaque monkeys.
Macaque monkeys infected with various neurovirulent forms of simian immunodeficiency virus (SIV) represent highly effective models, not only of systemic acquired immunodeficiency virus (AIDS), but also neuroAIDS. Behavioral studies with this model have clearly established that SIV-infected monkeys show both cognitive and motor impairments resembling those that have been reported in human immunodeficiency virus (HIV)-infected humans. This paper combines data from a number of behavioral studies in SIV-infected macaque monkeys to obtain an overall estimate of the frequency of impairments in various motor and cognitive domains. The results were then compared to similar data from studies of HIV-infected humans. Whereas cognitive functions are most commonly impaired in HIV-infected humans, motor function is the domain most commonly impaired in SIV-infected monkeys. Electrophysiological studies in SIV-infected macaques have revealed deficits in motor-, somatosensory-, visual-, and auditory-evoked potentials that also resemble abnormalities in human HIV infection. Abnormalities in motor-evoked potentials were among the most common evoked potential deficits observed. Although differences in behavioral profiles of human HIV disease and SIV disease in monkeys exist, the results, nevertheless, provide strong validation for the use of macaque models for translational studies of the virology, immunology, pathophysiology, and treatment of neuroAIDS.
18,780,231
Characteristics of fatty acids and essential oil from sweet fennel (Foeniculum vulgare Mill. var. dulce) and bitter fennel fruits (F. vulgare Mill. var. vulgare) growing in Turkey.
Oil content in sweet and bitter fennels was obtained 12.22% and 14.41%, respectively. The C(18:1 c6), C(18:2), C(18:1 c9) and C(16:0) acids corresponding to approximately 97% of total oil was recorded as principal fatty acids. The ratios of essential oil from sweet and bitter fennels were found similar (average 3.00%). trans-Anethole, estragole and fenchone were found to be the main constituents in both fennels. The compound with the highest value in the two oil samples was trans-anethole as 95.25% (sweet) and 75.13% (bitter). While estragole was found in bitter fennel oil in a remarkable amount (15.51%), sweet fennel oil contained small amounts of estragole (2.87%). Fenchone was found <1% in sweet and approximately 5% in bitter fennel. p-Anisaldehyde in bitter fennel essential oil, and alpha-pinene and gamma-terpinene in sweet fennel essential oil were not recorded, and these compounds were found very low or <1%.
18,780,240
Micropropagation and production of Camptothecin from in vitro plants of Ophiorrhiza rugosa var. decumbens.
Camptothecin and its derivatives are used as anticancer alkaloids. At present, they are obtained by the extraction from the Chinese tree Camptotheca acuminata and the indigenous tree Nothapodytes foetida. Identification of alternate species of plants like Ophiorrhiza species and development of tissue culture methods may be a suitable alternative for large-scale micropropagation as well as for the production of camptothecin. Plantlets were successfully regenerated from shoot cultures of Ophiorrhiza rugosa initiated from axillary meristems on medium containing benzyladenine (BA) (4.0 mg L(-1)) + alpha-naphthalene acetic acid (NAA) (0.05 mg L(-1)). Rooting was initiated in half concentration of Murashige and Skoog's (MS) basal medium devoid of growth hormones. Tissue culture derived plants of O. rugosa were similar to the normal plants in their morphological characteristics and chemical constitution. Ten O. rugosa plants that were obtained through micropropagation showed when analysed a higher alkaloid content compared to the normal plant. Chemical analysis of the different organs of the tissue culture plant of O. rugosa established in soil indicated 0.002% dry weight of camptothecin in the roots, 0.011% dry weight in the stems, 0.090% dry weight in the leaves and 0.015% in the floral parts.
18,780,241
Chemical composition of essential oil and headspace-solid microextracts from fruits of Myrica gale L. and antifungal activity.
The essential oil and the volatile compounds of Myrica gale fruits were analysed by gas chromatography (GC) and GC-mass spectrometry (GC-MS). The volatile compounds were detected using two different fibres for headspace-solid phase microextraction (HS-SPME), Carboxen/PDMS and PDMS. Sixty two compounds were identified, which represented more than 90% of the total extracts. Major components of fruit essential oil are alpha-pinene (22.6%), 1,8-cineole (18.9%) and germacrone (14.2%), whereas they are germacrone (25.1%), alpha-pinene (12.2%), limonene (8.1%) and alpha-phellandrene (8.0%) for the leaf essential oil. Major volatile fruit compounds detected in HS-SPME were alpha-pinene, 1,8-cineole, p-cymene and eth-cadinene. As M. gale fruits are traditionally used in brewery for flavouring beer or as a spice in soups or stews, the antifungal properties of these essential oils were investigated on a panel of foodborne fungi, namely Aspergillus flavus, Cladosporium cladosporioides and Penicillium expansum. A complete antifungal activity was observed at 1000 ppm against C. cladosporioides. Both essential oil and entire fruits could thus be used as an additive in food or cosmetic preparations for their flavour, odour and their conservative properties.
18,780,242
Isolation of antibacterial diterpenoids from Cryptomeria japonica bark.
The aims of the present study were to determine the antibacterial activity of bark extract of Cryptomeria japonica D. Don and to isolate potential antibacterial constituents. The results showed that the ethanolic extract of C. japonica bark possessed a good antibacterial activity. Nine compounds including seven diterpenoids (ferruginol (I), isopimaric acid (II), iguestol (III), isopimarol (IV), phyllocladan-16alpha-ol (V), sandaracopimarinol (VI) and sugiol (VII)) and two steroids (beta-sitosterol (VIII) and beta-sitostenone (IX)) were isolated from active subfractions; beta-sitostenone was isolated for the first time from this plant. Among these compounds, ferruginol possessed the strongest antibacterial activity and had MIC values ranging from 6.3 to 12.5 microg mL(-1) against all bacteria tested. Isopimaric acid was also an antibacterial natural product. Cryptomeria japonica bark extract and its diterpenoids, ferruginol and isopimaric acid, have the ability to inhibit the bacterial growth and can be used as the source for natural bactericides.
18,780,250
Maternal demographic and socioeconomic characteristics of live-born infants with isolated ocular congenital abnormalities.
To evaluate maternal age and birth order, in addition socioeconomic status and finally occupational background of mothers who delivered babies with different isolated ocular congenital abnormalities. The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002 was used and the evaluation of maternal variables was based on both medical records and maternal information. Mean maternal age and birth order was lower in the mothers of cases with isolated an/microphthalmia. The mean birth order was also lower in the mothers with isolated congenital cataract compared with the control groups. The mothers of cases with isolated coloboma had the usual mean maternal age with a very high proportion of second birth order. The proportion of unmarried women, low maternal socio-economic status and unemployment was larger in the groups of isolated an/microphthalmia and isolated primary congenital glaucoma and these mothers frequently worked in the agriculture. Cases with different isolated ocular congenital abnormalities showed different maternal characteristics as the reference controls, therefore it is necessary to evaluate each isolated ocular congenital abnormality separately and maternal characteristics can be considered as potential confounders in the analyses of ocular congenital abnormalities.
18,780,259
[Poor premorbid adjustment linked to deterioration in theory of mind skills: a study in stabilised schizophrenic patients].
Previous studies suggest that there is a deficit in theory of mind (ToM) in stabilised schizophrenic patients. More specifically, it has been claimed that poor premorbid adjustment covaries with the abnormalities in ToM skills detected in such patients. It has also been suggested that this deficit could be a trait marker for schizophrenic disorders. The aim of this study was to examine the performance in mentalistic skills in 36 stabilised schizophrenic patients in comparison to a standard control group. We also sought to examine the relation between ToM skills and premorbid adjustment in our target sample. Premorbid adjustment was evaluated using the modified Cannon-Spoor premorbid adjustment scale, and ToM measurements were obtained by means of first- and second-order verbal experimental tasks. Schizophrenic patients presented statistically significant poorer performances in first- and second-order ToM tasks, although no differences were observed between these patients and the control sample as regards overall cognitive acuity. Poor premorbid adjustment in areas of social functioning in the patients was also associated with statistically significant poorer performance in both ToM tasks. Deficient premorbid adjustment in schizophrenia may be linked to a ToM deficit that can be assessed with simple tasks.
18,780,269
Architectonic subdivisions of neocortex in the gray squirrel (Sciurus carolinensis).
Squirrels are highly visual mammals with an expanded cortical visual system and a number of well-differentiated architectonic fields. To describe and delimit cortical fields, subdivisions of cortex were reconstructed from serial brain sections cut in the coronal, sagittal, or horizontal planes. Architectonic characteristics of cortical areas were visualized after brain sections were processed with immunohistochemical and histochemical procedures for revealing parvalbumin, calbindin, neurofilament protein, vesicle glutamate transporter 2, limbic-associated membrane protein, synaptic zinc, cytochrome oxidase, myelin or Nissl substance. In general, these different procedures revealed similar boundaries between areas, suggesting that functionally relevant borders were being detected. The results allowed a more precise demarcation of previously identified areas as well as the identification of areas that had not been previously described. Primary sensory cortical areas were characterized by sparse zinc staining of layer 4, as thalamocortical terminations lack zinc, as well as by layer 4 terminations rich in parvalbumin and vesicle glutamate transporter 2. Primary areas also expressed higher levels of cytochrome oxidase and myelin. Primary motor cortex was associated with large SMI-32 labeled pyramidal cells in layers 3 and 5. Our proposed organization of cortex in gray squirrels includes both similarities and differences to the proposed of cortex in other rodents such as mice and rats. The presence of a number of well-differentiated cortical areas in squirrels may serve as a guide to the identification of homologous fields in other rodents, as well as a useful guide in further studies of cortical organization and function.
18,780,299
Parallels between the development of therapeutic drugs and cancer health disparity programs: implications for Disparities Reduction.
There are analogies between the development of therapeutic drugs for cancer and the development of interventions for reducing cancer health disparities. In both cases, it can take between 12 and 15 years for the benefits to become apparent. The initial preclinical phase of drug development is analogous to the development of community partnerships and helping the community learn about cancer. The preclinical phase of in vitro and in vivo testing is analogous to identifying the disparities in the community. Then clinical testing begins with phase 1, toxicity, and dose-establishing studies. Analogously, community-based participatory research is used to develop disparities-reducing interventions (DRIs) within the community. The phase 2 clinical studies to determine whether the drug has activity are analogous to the DRI being implemented in the community to determine whether it can cause behavioral changes that will reduce cancer health disparities. If a drug passes phase 1 and 2 studies, phase 3 clinical trials are initiated. These are controlled studies to examine the efficacy of the drug. The similar activity for disparities research is to determine whether the DRI is better than the current standard/usual practice in controlled trials. If the drug is beneficial, the final phase is the dissemination and adoption of the drug. Analogously in disparities, if the DRI is beneficial, it is disseminated and is culturally adapted to other racial/ethnic groups and finally adopted as standard practice. The process of creating an effective DRI can be envisioned to have 4 stages, which can be used to aid in measuring the progress being made in reducing cancer health disparities.
18,780,311
Receipt of guideline-recommended follow-up in older colorectal cancer survivors : a population-based analysis.
After curative resection for colorectal cancer, routine follow-up with office visits, carcinoembryonic antigen (CEA), and colonoscopy is recommended. The actual adherence to these guidelines as well as the potential overuse of testing in routine practice has not been well studied. The authors identified 9426 eligible patients aged > or = 66 years in a linked tumor registry-claims database who were diagnosed with adenocarcinoma of the colon or rectum from 2000 to 2001. Patients were observed to 3 years after diagnosis. Receipt of > or = 2 office visits per year, > or = 2 CEA tests per year (years 1 and 2), and > or = 1 colonoscopy within 3 years constituted guideline fulfillment. Guidelines for office visits, colonoscopy, and CEA testing were met in 92.3%, 73.6%, and 46.7% of patients, respectively. In addition, receipt of 2 nonrecommended procedures, abdominal/pelvic computed tomography scans and positron emission tomography scans, was documented in 47.7% and 6.8%, respectively. Overall, 60.2% received testing below recommended levels, 17.1% at recommended frequency, and 22.7% above guideline recommendations. In a multivariate analysis, factors associated with meeting guidelines included younger age group, white race, regional stage cancers, and poorly differentiated tumors. Considerable geographic variation in meeting guidelines was also observed. Many older colorectal cancer survivors in this population-based cohort underwent testing below a minimum frequency specified by clinical practice guidelines, especially with regard to CEA. Further studies should ascertain the reasons for poor compliance and the effect on patient outcome.
18,780,338
Synthesis and characterization of semi-interpenetrating polymer networks based on polyurethane and N-isopropylacrylamide for wound dressing.
Thermosensitive semi-interpenetrating polymer networks (semi-IPNs) composed of crosslinked poly(N-isopropylacrylamide) (PNiPAAm) and linear segmented polyurethane urea (SPUU) were synthesized via thermal initiated free radical polymerization. Synthesized semi-IPNs of various compositions were characterized by Fourier transform infrared spectroscopy, water equilibrium swelling at different temperatures, drug lading, drug release, cell adhesion, and detachment. The semi-IPN films of all the compositions were transparent in dry state and negative thermosensitivity in their swelling ratio, that is, lower swelling levels with increasing temperature. The drug release study revealed that the rate of drug release is fast in case of pure SPUU compared to PNiPAAm and semi-IPN film. Drug release depended mainly on solubility of the drugs and physical networks between SPUU and PNiPAAm. Finally NIH3T3 cells were seeded on the semi-IPN films and found that cells were securely attached and proliferated to confluence. Upon cooling, cells were detached from the semi-IPN films. Therefore, the semi-IPN films may be good candidate materials for wound dressing applications.
18,780,359
Chiral HPLC separation and absolute configuration of novel S-DABO derivatives.
Chiral 2-(sec-butylthio)-6-[1-(2,6-dichlorophenyl)propyl]-5-methylpyrimidin-4(3H)-one (compound 1) was synthesized to serve as a model compound for structural elucidation of novel S-DABO (dihydroalkoxybenzyloxopyrimidine) derivatives endowed with potential HIV-1 reverse transcriptase inhibitory activity. Stereochemical characterization of four stereoisomers of 1 was achieved by an experimental approach based on the following steps: (a) direct HPLC enantio- and diastereoseparation at semipreparative scale; (b) determination of elution order of stereomeric mixture by using chiroptical detection (polarimeter or circular dichroism (CD)); (c) X-ray crystallography of two diastereoisomers isolated at semipreparative scale. The CD analysis of 1 and its two analogues (compounds 2 and 3), both having a single stereogenic center located in two different alkyl side chains of the dihydropyrimidinone structure, was carried out. The results of this study indicated a correlation between the absolute configuration at C-1 of alkyl side chain of the dihydropyrimidinone structure and the sign of the CD band at around 245 nm.
18,780,368
Breast filariasis: real-time sonographic imaging of the filarial dance.
A 50-year-old woman presented with a palpable tender nodule in the upper quadrant of the breast that was clinically thought to be a fibroadenoma, with mammographic findings of a well-defined lobulated density. Sonographic examination revealed a "filarial dance sign" within the cystic lesion, which is diagnostic of lymphatic breast filariasis. In endemic areas, sonographic examination is recommended to search for this pathognomonic real-time diagnostic feature and, if present, to initiate treatment without delay.
18,780,376
DNA with branched internal side chains: synthesis of 5-tripropargylamine-dU and conjugation by an azide-alkyne double click reaction.
5-Tripropargylamine-2'-deoxyuridine (1 a) containing two terminal triple bonds was synthesized by a Pd-assisted Sonogashira cross-coupling reaction and was subsequently converted into the corresponding phosphoramidite building block (9) and employed in solid-phase oligonucleotide synthesis. T(m) experiments demonstrate that the presence of covalently attached branched tripropargylamine residues has a positive effect on the base pair stability. The two terminal C[triple chemical bond]C bonds of modified DNA were functionalized by means of Cu(I)-mediated 1,3-dipolar cycloaddition reactions (click chemistry) with azides such as 3-azido-7-hydroxycoumarin or 3'-azido-3'-deoxythymidine (AZT) both in solution and on solid support. In particular, with the nonfluorescent 3-azido-7-hydroxycoumarin a strongly fluorescent oligonucleotide bis-dye conjugate was generated. For comparison, the N(3)-propargylated 2'-deoxyuridine 2 was prepared from 2'-deoxyuridine and propargyl bromide and incorporated into DNA. The two terminal triple bonds of 1 a allow the simultaneous post-modification of DNA by two reporter molecules and can be applied to almost any azido derivatives (oligonucleotides, proteins, polysaccharides etc.) including those forming dendrimeric side chains.
18,780,386
Reactivity of the 4-amino-5H-1,2-oxathiole-2,2-dioxide heterocyclic system: a combined experimental and theoretical study.
The reactivity of the 4-amino-5H-1,2-oxathiole-2,2-dioxide (or beta-amino-gamma-sultone) heterocyclic system has scarcely been studied. Here we describe the reactivity of this system towards electrophiles and amines on readily available model substrates differently substituted at the C-5 position. A variety of C-electrophiles, carbonyl electrophiles (such as acyl chlorides, isocyanates, or aldehydes) and halogen or nitrogen electrophiles have been explored. Both the C-3 and 4-amino positions of the beta-amino-gamma-sultone system are able to undergo electrophilic reactions, and the reaction products depend on the electrophile used and on the reaction conditions. On the other hand, nucleophilic attack of amines occurs at the C-4 position of the beta-amino-gamma-sultone system only in spiranic substrates bearing alicyclic substituents at the C-5 position. A comparative computational study between spiranic and non-spiranic substrates suggests that conformational changes, undergone on intermediate compounds, account for the observed reactivity differences. Moreover, these conformational changes seem to bring about an increase of electron density on the N-4 and C-3 atoms of the enaminic system, and a possible enhancement in the reactivity of spiranic substrates towards electrophiles in the presence of amines. Experimental data consistent with this predicted enhanced reactivity is also presented.
18,780,390
In situ proteomics with imaging mass spectrometry and principal component analysis in the Scrapper-knockout mouse brain.
Imaging MS is emerging as a useful tool for proteomic analysis. We utilized this technique to analyze gene knockout (KO) mice in addition to traditional 2-DE analysis. The Scrapper-knockout (SCR-KO) mouse brain showed two types of neurodegenerative pathologies, the spongiform neurodegeneration and shrinkage of neuronal cells. 2-DE analysis of the whole brain lysates of SCR-KO mice indicated slight changes in annexin A6, Rap1 GTPase, and glyoxalase domain containing four spots while most of the main components did not show significant changes. By imaging MS analysis based on principal component analysis (PCA), we could find numerous alterations in the KO mouse brain. Furthermore, we could also know the information on the position of altered substances all together. PCA provides information about which molecules in tissue microdomains have altered and is helpful in analyzing large dataset of imaging MS, while exact identification of each molecule from peaks in MALDI imaging MS may require additional analyses such as MS/MS. Direct imaging with PCA is a powerful tool to perform in situ proteomics and will lead to novel findings. Our study shows that imaging MS yields information complementary to conventional 2-DE analysis.
18,780,397
Healthcare in the cross hairs. California patient-dumping investigation unwinds into billing probe, fueling enforcers' national fraud-fighting efforts.
Fraud enforcers say the FBI's raid of three Southern California hospitals last week offered new evidence that aggressive measures are needed to battle abuse. Los Angeles City Attorney Rocky Delgadillo, left, sees the case as emblematic. "Our healthcare system in America is broken--it's never been more clear to me that is the case," he said. "There's so much pressure ... to make profits".
18,780,442
[Three-dimensional finite element analyses of bone surface stress of two kinds of conjunction implant].
To establish a three-dimension finite element model of mandible with two kinds of dental implant and to study the stress of implant-bone interface. Measuring the data of the components of the dental implant and using spiral CT image reconstruction technique to scan the cross section of the mandible. Three-dimension finite element analysis software Unigraphics and MSC. Marc/Mentat were used to build the conjunction model and bone model of two implant systems. Loading 200 N axially and 100 N 30 degrees obliquely on the models respectively, the stress distribution patterns of the bone interface of two implant systems were analyzed. The stress distribution on the bone interface of two implant systems was similar. The peak stress of oblique loading was higher than that of axial loading. The peak stress district of the bone was concentrated on the stricture of the implant cervix, which was more obviously displayed on the Replace Select implant. The peak stresses on the bone interface of Replace Select implant were higher than that of Replace implant in all loadings. To Replace Select especially, oblique force should be avoided in clinical practice in case of the bone absorption.
18,780,511
History of dyspepsia in Scotland. Admissions to the Edinburgh Royal Infirmary 1729-1830, doctoral theses 1726-1823, and contemporary British publications.
The aim of the study was to assess whether the rise in the occurrence of dyspepsia in Scotland during the eighteenth century was a true epidemiologic phenomenon or just an increase in medical awareness. Admissions for dyspepsia to the Edinburgh Royal Infirmary from 1729 until 1830 were analysed by consecutive five-year time periods. The titles of MD theses on dyspepsia from 1726 to 1823 were extracted from the Edinburgh University index. Monographs and articles on dyspepsia from Britain during the same time period were sought in the Catalogues of the US Surgeon-General's Library. During the eighteenth century, the annual number of dyspepsia patients admitted to the Edinburgh Royal Infirmary showed an extraordinary increase from none in 1730 to 900 per million population in 1760. About 4000 MD theses were presented to the Edinburgh University between 1726 and 1823. There were none on dyspepsia or gastritis between 1726 and 1749, after when it gradually started to rise. British publications on dyspepsia similarly appeared only in the 1790s and then rapidly increased. We suggest that the rise in MD theses and publications on dyspepsia were responses to a real increase in dyspepsia during the mid eighteenth century.
18,780,526
Short-term effectiveness of a prefabricated occlusal appliance in patients with myofascial pain.
To compare the short-term effectiveness of a stabilization appliance with a prefabricated occlusal appliance in myofascial pain patients in a randomized controlled trial. Sixty-five patients at 2 centers were assigned to a stabilization appliance group (S group, n = 33) or a prefabricated appliance (Relax) group (R group, n = 32). The patients had been suffering from temporomandibular disorder (TMD) pain for 3 months to 40 years. The patients were examined for symptoms and signs of temporomandibular disorders according to the Research Diagnostic Criteria for TMD and treated by a general practitioner. Treatment outcomes regarding pain, registered on a visual analog scale, and overall ratings of pain, registered on a verbal scale, were evaluated at 6- and 10-week follow-up appointments, and the data from the groups were compared statistically. The main treatment outcome in the 2 groups was a positive improvement of overall symptoms without any statistically significant differences between groups at either 6 or 10 weeks. At the 6-week follow-up, 72% of all patients reported a 30% reduction of the worst pain, and 55% of the patients reported a 50% reduction of the worst pain, whereas at the 10-week follow-up, the percentages were 69% and 61%, respectively. According to the verbal scale, 85% of all patients reported themselves to be "better," "much better," or "symptom-free" at the 6-week follow-up, and 83% reported this at the 10-week follow-up. The effectiveness of the prefabricated occlusal appliance seemed to be the same as that of the stabilization appliance. The prefabricated appliance can therefore be recommended as a short-term therapy in adult patients with myofascial pain.
18,780,534
The jaw functional limitation scale: development, reliability, and validity of 8-item and 20-item versions.
To develop the Jaw Functional Limitation Scale (JFLS), comprising 3 constructs and a global scale, based on a preliminary instrument, and to investigate content validity of the overall functional limitation construct, reliability, and generalizability. A temporomandibular disorders (TMD) patient group, compared to other diagnostic groups, was hypothesized to report further limitation in each of the 3 new proposed constructs. One hundred thirty-two consecutive patients from 5 diagnostic groups (TMD, primary Sjogren syndrome, burning mouth syndrome, skeletal malocclusion, and healthy controls) participated in a known-groups validity design. Fifty-two jaw functional limitation items were identified by an expert panel for content validity. Rasch methodology was used for item reduction and assessment of model fit. The instrument was retested 1 to 2 weeks later. Three constructs (mastication, vertical jaw mobility, and emotional and verbal expression) comprising a total of 20 items were identified along with a global scale (the JFLS-20), and each exhibited excellent psychometric properties with respect to modeled variance, item fit, reliability, and internal consistency. The psychometric properties of each construct remained satisfactory when analyzed separately among the 5 diagnostic groups. Temporal stability was satisfactory. A shorter 8-item form (JFLS-8) also proved useful for assessing global functional jaw limitation. The JFLS-20 is an organ-specific instrument comprising 3 constructs for assessing functional status of the masticatory system; the 3 scales exhibit properties that are ideal for both research and patient evaluation in patient groups with a range of functional limitations of the jaw. The JFLS-8 emerged as a short form for measuring global functional limitation of the jaw.
18,780,535
[Ethnic origin and alveolar bone loss in Israeli adults].
The aim of this study was to evaluate the association of alveolar bone loss and ethnic origin among Israeli adults. The study population consisted of 815 male military personnel, aged 25 to 60 years (average 38.1 +/- 7.0 yr), who arrived at a military dental clinic for routine dental examination during 2004-5. The distance between CEJ and alveolar bone crest was measure on pair of standardized posterior bitewing radiographs. Associations between the periodontal score and place of birth, the father ethnic origin and the mother ethnic origin were evaluated using the chi2-test. The individual's place of birth had no influence on the radiographic alveolar bone loss. Father of Yemenite-, North-African- or Mediterranean-origin, and mother of Yemenite-, North-African- or Asian-origin have associated to the occurrence and severity of alveolar bone loss, whereas sons to father or mother from Israeli or European descent were found to have less bone loss (p < 0.001). Ethnic origin has an influence on the alveolar bone loss in Israeli adults. However, more research is needed on the role of the potentially confounders in the association between origin and periodontal health.
18,780,541
3D-VAS--initial results from computerized visualization of dynamic occlusion.
Visualization of the dynamic occlusion is one of the central tasks in both clinical dentistry and dental engineering. Many aspects of dynamic occlusion, such as the interocclusal function in the posterior region, cannot be seen directly clinically and at best can be recorded with contact paper. Therefore, analyses of the dynamic occlusion using mounted models in the articulator are unavoidable in many cases for reproduction of dynamic occlusion. However, the reproduction of dynamic occlusion in the mechanical articulator has clear restrictions inherent to the process, but also caused by biological variability. Virtual articulators can expediently supplement mechanical articulators, since with them it is possible to display in relation to time unusual and extraordinary perspectives, such as sectional images and flowing, sliding contact points. One of the latest developments in the field of virtual articulation is the 3D virtual articulation system module of the Zebris company, D-Isny. By means of a specially developed coupling tray, 3D-scanned rows of teeth can be matched with computerized motion recordings of mandibular function. The software displays the movements of the 3D-scanned rows of teeth not only with jaw motion but also with chewing motion--therefore movements under chewing pressure--in real time and facilitates special analytical methods transcending mechanical occlusion analysis in conventional articulators: This includes displays of the strength of the contact points and surfaces, the occurrence of the contact points in relation to time, sectional images of the dentition, analyses of the interocclusal gap in the occlusal region, etc. This software and its possibilities are described and explained by reference to individual cases.
18,780,558
[Urgent states in hematology: acute promyelocytic leukemia--principles of diagnosis].
A review of diagnosis of acute promyelocytic leukemia (APL) is presented. There are still many patients with progressive disease with leukocytosis at presentation. These are at greater risk of early death due to bleeding (often intracranial), or, less frequently, due to thrombotic complications. In Czechia, we have, in some instances, noted an unacceptably long time from the first symptoms to diagnosis and to administration of the highly specific differentiation therapy with tretinoin (ATRA) along with anthracycline chemotherapy. This combination is highly efficient--cures are seen in some 70% of patients. Therefore, we present a diagnostic minimum for each and every internist, and even better for every general practician, to get acquainted with. All cases of pancytopenia and consumption coagulopathy should be suspected of APL and referred to a specialized hematologist without any delay. In the following more detailed review of diagnostic measures, much attention is given to APL morphology, which is the first clue leading to diagnosis. The finding of the typical hypergranular FAB M3 morphology and of cells with bundles of Auer rods ("faggot cells"), along with the HLA-DR, CD33+ immunophenotype, is highly (but not absolutely) specific for APL. In cases of the micro-/hypo-granular variant FAB M3v Form, and whenever APL cannot be ruled out with certainty, a test to prove the presence of the PML/RARalpha fusion gene is indicated, using either RT-PCR or, eventually, immunological demonstration of the specific distribution of the PML protein in the cell nucleus. Given that morphology of APL cases, as defined according to WHO criteria (95% of which carry the PML/RARalpha fusion gene), admits extremely divergent morphological pictures ofthe variant forms, we recommend these investigations to be performed in every case of de novo acute myeloid leukemia. A review of the less frequent morphological, as well as genetic variants is given, and the principles of immunophenotypic, cytogenetic and molecular diagnostics are also reviewed.
18,780,572
[Leukemogenesis and therapy of acute promyelocytic leukemia: from the worse to the most favorable subtype of acute myeloid leukemia].
The evolution of therapy of acute promyelocytic leukemia (APL) from 1964 to present is reviewed. The paper is focused on the main findings and key studies which formed current and almost standard therapeutic approach to APL. The first important development was the use of anthracyclines for the initial therapy of APL in 1967. Starting 1972, heparin was introduced into a treatment of coagulopathy and the intensity of substitutional transfusion therapy was remarkably enhanced. The main breakthrough was the initiation of differentiation therapy using all-trans retinoic acid (ATRA). The first clinical study which brought information about the effect of ATRA in APL started in China in 1986. A number of the most important subsequent studies focused on pathogenesis and therapy of APL are analyzed and reviewed. The additional considerable finding was the discovery of arsenic trioxide (ATO) therapeutic efficacy in APL and ATO is now in particular used for a therapy of relapsed APL. The publication gives also a recent insight into a leukemogenesis of APL and development of a resistance to ATRA. At the conclusion, the authors emphasize the need of early diagnosis as a one of the main conditions for successful treatment of APL.
18,780,571
Gender role across development in adults with 46,XY disorders of sex development including perineoscrotal hypospadias and small phallus raised male or female.
Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.
18,780,596
[Role of retroperitoneal laparoscopic nephroureterectomy in the current treatment of upper urinary tract urothelial carcinoma].
Nowadays, the standard treatment for upper tract transitional cell carcinoma is open nephroureterectomy, by double lumbar and iliac approach, with peri-meat bladder cuff excision. Since the first laparoscopic nephroureterectomy was performed, several surgical teams were interested by this approach for the treatment of the upper tract transitional cell carcinoma. To plead for retro-peritoneoscopic nephroureterectomy and to assess the surgical indications. Were analyzed the results of the recent published series on nephroureterectomy for upper urinary tract transitional cell carcinoma. Were included studies on conventional, laparoscopic and retro-peritoneoscopic nephroureterectomy, with at least 10 cases, published after 2000. The advantages of retro-peritoneoscopic nephroureterectomy are: minimum blood loss, reduced analgesic intake, a shorter hospital stay and a faster return to previous activities, lower rate of intra- or postoperative complications compared with trans-peritoneal laparoscopy or conventional surgery. With a proper case selection the oncologic safety of the retro-peritoneoscopy is equivalent with open surgery. On short term, retro-peritoneoscopic approach shows similar oncological outcome with other techniques. Retroperitoneal laparoscopic nephroureterectomy is a viable alternative to conventional or trans-peritoneoscopic procedure, with clear cut benefits for the patient. Retro-peritoneoscopy is associated with a low morbidity.
18,780,617
[Development of infectious pseudo-particle harboring three subtypes hepatitis C virus glycoproteins and their application in neutralization assays].
In this study, three expression vectors encoding unmodified glycoproteins E1 and E2 from H77 (1a), Hebei (1b) and JFH1 (2a) strains were constructed to form pVRC-H77-E1E2, pVRC-HeBei-E1E2 and pVRC-JFH1-E1E2 expressing constructs. The protein expression was confirmed by immunofluorescene assay(IFA) and Western blot. The Lentiviral vector has the ability to package the cellular membrane into pseudo-particles. The plasmid expressing HCV E1-E2 glycoproteins in native form was co-transfected into 293FT cells with a lentiviral packaging plasmid (pHR'CMV delta R8.2)and a self-inactivated (SIN) transfer plasmid (pCS-CG) containing a reporter EGFP gene to produce infectious HCV pseudo-particles(pp). Flow cytometry assays showed that the HCVpp could infect Huh7 and Huh7-CD81, and the infectivity in Huh7-CD81 was about 2-3 times higher than that in Huh7 cells. Meanwhile, HCVpp could neither infect non-liver cells, for example, the 293 cells, nor HepG2 cell . Titration of HCVpp by p24 ELISA assay or infection assay showed that this HCVpp may contain 5-25 ng/mL p24 or 10(4)-10(5) TU (transducing unit)/ ml. An in vitro HCV neutralizing assays based on HCVpp (1a, 1b, 2a) were then established using AP33, a monoclone antibody with cross-neutralizing ability to different HCV strains. The neutralizing ability of the antibodies from HCV infected patients was further studied with this HCVpp system. In summary, three kinds of HCVpp (1a, 1b, 2a subtype) were successfully developed; In vitro HCV neutralizing assays based on HCVpp and SIN lentiviral system were established. This system paves a way for characterization of early steps of HCV infection (host tropisms, receptor binding, membrane fusion, et al. ) or screening anti-HCV drugs (such as inhibitor to virus entry). This system can be further applied to assess the human immune responses in HCV patients or evaluate HCV vaccine candidates.
18,780,632
[Development and comparison of real-time and conventional RT-PCR assay for detection of human coronavirus NL63 and HKU1].
We designed specific primers and fluorescence-labeled probes to develop real-time and conventional RT-PCR assays for detection of human coronavirus NL63 or HKU1. Subsequently, experiments were undertaken to assess diagnostic criteria such as specificity, sensitivity and reproducibility. The detection limit of the real-time RT-PCR assays was 10 RNA copies per reaction mixture. No cross-reactivity was observed between RNA samples derived from designed HCoV and other HCoV or human metapneumovirus. A total of 158 nasopharyngeal swab specimens collected from adult patients with acute respiratory tract infection in Beijing were screened for the presence of human coronavirus NL63 and HKU1 by using real-time RT-PCR and conventional RT-PCR method. The fluorescence quantitative RT-PCR method detected six specimens positive for human coronavirus NL63, five specimens positive for human coronavirus HKU1; and conventional RT-PCR method detected three HCoV-NL63 positive and three HCoV-HKU1 positive, respectively. The convention RT-PCR products of positive samples were obtained and sequence analysis confirmed the reliability of the above methods. In summary, the real-time RT-PCR assay for HCoV- NL63 or HKU1 was more sensitive than conventional RT-PCR and with less time (less than 4 hours) for completion. It may be suitable for molecular epidemiological surveillance and clinical diagnosis for human coronavirus NL63 and HKU1.
18,780,635
Comparison of lipid lowering effect of sibutramine in patients treated or not treated with statins--3 month follow-up.
Older sibutramine studies showed beneficial effects on lipid profile compared to placebo. However, nowadays many obese patients are treated with lipid lowering drugs before the start of sibutramine therapy and their effects in these patients have not been investigated. Therefore we started a long-term follow up of patients on sibutramine with or without previous and continuing statins. Here we present results of the first 3 months follow up of 11 patients on sibutramine 10 mg +statin group, and that of 13 patients on sibutramine 10 mg alone. Sibutramine led to the weight loss from 101.6 to 96.9 kg and in BMI from 36.35 to 34.66 kg/m2. Lipid profile changed thus: total cholesterol 4.97...5.01mmol/l (p = 0.7), LDL cholesterol 2.83...2.82 mmol/l mmol/l (p = 0.9), HDL cholesterol 1.13...1.27 mmol/l (p = 0.003), triglycerides 1.98...1.91 mmol/l (p = 0.01). Comparison between the 2 groups did not show any significant differences in lipid levels, patients react to sibutramine in the same way regardless to the concomitant statin therapy. We can therefore preliminarily conclude that sibutramine therapy has significant positive effect on the lipid profile even in patients who were started on statins prior to initiation of sibutramine treatment.
18,780,645
The values of estimated glomerular filtration rate calculated with creatinine and cystatin C based equations in healthy adults.
The glomerular filtration rate (GFR) is widely accepted as the best overall index of kidney function. GFR can be measured as the clearance of exogenous or endogenous filtration markers or clinically estimated from serum concentrations of creatinine or cystatin C. Recently, it has been recommended that an estimated GFR (eGFR) should be reported in addition to the value of filtration markers. In this study, we determined the values of eGFR, based on creatinine and cystatin C equations, in 125 healthy volunteers aged 20-75 years. Creatinine was measured by a kinetic alkaline picrate method on an ARCHITECT ci8200 analyzer (Abbott Diagnostics, Wiesbaden, Germany). Cystatin C was determined by a latex particle-enhanced immunonephelometric assay (BNII, Dade Behring, Marburg, Germany). The eGFR values were calculated for creatinine using the Modification of Diet in Renal Disease (MDRD) study equation and Rule's quadratic equation and for cystatin C according to the equation published by Hoek et al. The reference intervals for eGFRs with MDRD, Rule's quadratic and Hoek's equations were calculated nonparametrically and were determined to be 63.5-124.6 mL/min/1.73 m2, 78.3-139.2 mL/min/1.73 m2 and 72.2-115.6 mL/min/1.73 m2, respectively. According to the US National Kidney Foundation, chronic kidney disease (CKD) can be defined as a GFR < 60 mL/min/1.73 m2. Our results showed that healthy adults had eGFR values > 63.5 mL/min/1.73 m2. However, it is important to note that these normal values overlap with values in stages 1 and 2 of CKD, thus an eGFR greater than 60 mL/min/1.73 m2 does not exclude kidney disease.
18,780,660
Ionized calcium: whole blood, plasma or serum?
To determine an optimal specimen type to be used for measurements of ionized calcium (iCa) so that it applies properly to the reference interval. Also to determine the validity of the pH correction that is applied to iCa measurements. A reference interval study of normal volunteers was performed using four sample types namely balanced heparin (BH) whole blood, lithium heparin (LH) whole blood, plasma and serum. The sample was treated in an anaerobic fashion and analyzed at 0 and 40 minutes after venipuncture. The effect of pH correction as well as analysis time after collection was also studied. The mean iCa was the highest in BH-treated whole blood when measured immediately. However, it was slightly lower at 40 min after collection (p < 0.001). In contrast, there did not appear to be a significant difference in results when LH-treated whole blood was analyzed at 0 or 40 min. The reference interval for serum was similar to that of whole blood. The reference interval for plasma was dramatically lower than whole blood and plasma. The reference intervals for pH adjusted ionized calcium (iCa-adj) were dramatically lower than those from all specimens without adjustment. The reason for this was that the reference interval for pH in this study had a strong alkaline bias on one instrument and a strong acidic bias on the other. The sample of choice for ionized calcium analysis appears to be whole blood with either BH or LH. For the LH specimen, there is no significant change over 40 min whereas there is significant change for the BH specimens (-0.030 mmol/L, p < 0.0001). iCa-adj should not be used unless (i) very strict attention is paid to standardization of both the calcium and the pH and (ii) there is a very good reason to believe that the patients' pH is normal at 7.4.
18,780,665
Adjusting to personal and organisational change: views and experiences of female nurses aged 40-60 years.
The Australian nursing workforce is ageing and there is a well-documented shortage of nurses. This global phenomenon means that retaining nurses in the workforce is gaining in importance as older nurses retire and leave nursing. The existing literature reveals deficiencies in knowledge about older nurses as they adapt to ageing often within stressful work environments. The aim of this narrative-based study, informed by feminist principles, was to explore the views and experiences of female registered nurses aged 40-60 years, in acute hospital and community health care settings. In-depth semi-structured interviews of approximately 1 h duration were gathered during late 2004. The transcribed narratives were subjected to thematic analysis. Two major themes were identified. The first theme: "Feeling uncared for" contained three sub-themes--Unsupportive work relationships: "We should be helping each other"; Workplace bullying: "It hurts me and I feel really bad"; and, Stress and burnout: "It's just like being in a pressure cooker all the time". The second major theme identified was "Adapting to ageing: my nursing career". Findings of this research suggest some unmet support needs for older nurses in the workforce which could discourage them from remaining in nursing. The findings highlight a need for further research into the support needs of older nurses.
18,780,674
How to choose a mentor.
Mentors will play important roles in the careers of most successful scientists. Mentors are trusted advisors that give constructive criticism and provide information in many areas of a scientific life. Mentors will likely change throughout your career as your position changes and thus the areas of advice needed changes. Despite the fact that you gain new mentors, the relationships with the old mentors likely will continue and often grow into strong friendships. The American Physiological Society is a member of MentorNet, which is an award-winning, free, one-on-one electronic mentoring program for graduate students, postdoctoral fellows, and early career scientists who are APS members. Mentees and mentors are matched based on their responses to several questionnaires regarding research interests, mentoring needs, time needed, etc. Once assigned, mentors and mentees are allowed to approve their matches, and once done, contact information is given to each pair. A new mentor can be assigned every eight months. These electronic mentoring relationships are especially helpful if you are not comfortable discussing certain things with your thesis or postdoctoral advisor. APS encourages all members to participate either as a mentee or mentor in this valuable program. To comment on this article, go to http://www.the-aps.org/careers/ careers 1/mentor/mentoring.htm.
18,780,679
In vivo analysis of key elements within the renin regulatory region.
Renin is responsible for initiating the enzymatic cascade that results in the production of angiotensin II, the major effector molecule of the renin-angiotensin system (RAS). Extensive information on the regulatory region of the renin gene has been derived by transient transfection studies in vitro, particularly using the As4.1 cell line. To verify key factors within the regulatory region of renin in vivo, homologous recombination was used to introduce a green fluorescent protein (GFP) cassette into exon one of the renin gene contained within a 240 kb bacterial artificial chromosome (BAC) to create a construct that has GFP expression controlled by the renin regulatory region (RenGFP BAC). Within the regulatory region of the RenGFP BAC construct we independently deleted the enhancer, as well as mutated the HOX-PBX site within the proximal promoter element. Transgenic lines were generated for each of these BAC constructs and GFP expression was analyzed throughout a spectrum of tissues positive for renin expression including the kidney, adrenal gland, gonadal artery, and submandibular gland. The results described within this manuscript support the interpretation that the renin enhancer is critical for regulating baseline expression where as the Hox/Pbx site is important for the tissue specificity of renin expression.
18,780,761
Study of hypothalamic leptin receptor expression in low-birth-weight piglets and effects of leptin supplementation on neonatal growth and development.
Low birth weight resulting from intrauterine growth retardation (IUGR) is a risk factor for further development of metabolic diseases. The pig appears to reproduce nearly all of the phenotypic pathological consequences of human IUGR and is likely to be more relevant than rodents in studies of neonatal development. In the present work, we characterized the model of low-birth-weight piglets with particular attention to the hypothalamic leptin-sensitive system, and we tested whether postnatal leptin supplementation can reverse the precocious signs of adverse metabolic programming. Our results demonstrated that 1) IUGR piglets present altered postnatal growth and increased adiposity; 2) IUGR piglets exhibit abnormal hypothalamic distribution of leptin receptors that may be linked to further disturbance in food-intake behavior; and 3) postnatal leptin administration can partially reverse the IUGR phenotype by correcting growth rate, body composition, and development of several organs involved in metabolic regulation. We conclude that IUGR may be characterized by altered leptin receptor distribution within the hypothalamic structures involved in metabolic regulation and that leptin supplementation can partially reverse the IUGR phenotype. These results open interesting therapeutic perspectives in physiopathology for the correction of defects observed in IUGR.
18,780,769
Contractile C2C12 myotube model for studying exercise-inducible responses in skeletal muscle.
Adequate exercise leads to a vast variety of physiological changes in skeletal muscle as well as other tissues/organs and is also responsible for maintaining healthy muscle displaying enhanced insulin-responsive glucose uptake via GLUT4 translocation. We generated highly developed contractile C(2)C(12) myotubes by manipulating intracellular Ca(2+) transients with electric pulse stimulation (EPS) that is endowed with properties similar to those of in vivo skeletal muscle in terms of 1) excitation-induced contractile activity as a result of de novo sarcomere formation, 2) activation of both the AMP kinase and stress-activated MAP kinase cascades, and 3) improved insulin responsiveness as assessed by GLUT4 recycling. Tbc1d1, a Rab-GAP implicated in exercise-induced GLUT4 translocation in skeletal muscle, also appeared to be phosphorylated on Ser(231) after EPS-induced contraction. In addition, a switch in myosin heavy-chain (MHC) expression from "fast type" to "slow type" was observed in the C(2)C(12) myotubes endowed with EPS-induced repetitive contractility. Taking advantage of these highly developed contractile C(2)C(12) myotubes, we identified myotube-derived factors responsive to EPS-evoked contraction, including the CXC chemokines CXCL1/KC and CXCL5/LIX, as well as IL-6, previously reported to be upregulated in contracting muscles in vivo. Importantly, animal treadmill experiments revealed that exercise significantly increased systemic levels of CXCL1/KC, perhaps derived from contracting muscle. Taken together, these results confirm that we have established a specialized muscle cell culture model allowing contraction-inducible cellular responses to be explored. Utilizing this model, we identified contraction-inducible myokines potentially linked to the metabolic alterations, immune responses, and angiogenesis induced by exercise.
18,780,777
Creatine supplementation does not affect clinical health markers in football players.
To study the effects of 8-week creatine monohydrate (CrM) supplementation on blood and urinary clinical health markers in football players. 14 football players were randomly assigned in a double-blinded fashion to Cre (n = 7) or Pla (n = 7) group. The Cre group ingested 15 g/day of CrM for 7 days and 3 g/day for the remaining 49 days, whereas the Pla group ingested maltodextrin following the same protocol. Football-specific training was performed during the study. Total body mass was determined and blood and urine samples were analysed for metabolic, hepatic, renal and muscular function markers, before and after supplementation. A gain of total body mass was observed after CrM intake, but not with placebo. Blood and urinary markers remained within normal reference values. There were no significant changes in renal and hepatic markers after CrM intake. However, total creatine kinase (CK) activity significantly increased, and uric acid level tended to decrease after CrM use. Likewise, serum glucose decreased in the Cre group following supplementation. No significant differences in urine parameters were found in either group after supplementation. 8 weeks of CrM supplementation had no negative effects on blood and urinary clinical health markers in football players. Properties of CrM may, however, be associated with an increase in CK activity, improving the efficiency for ATP resynthesis, a phenomenon indirectly confirmed by the decreasing tendency in uric acid concentration. Furthermore, CrM seems to slightly influence glucoregulation in trained subjects.
18,780,799
Compatibility and aerosol characteristics of formoterol fumarate mixed with other nebulizing solutions.
Patients with chronic obstructive pulmonary disease (COPD) are often given admixtures of nebulizable drugs to minimize the time of administration in treatment regimens. To evaluate the physicochemical compatibility and aerodynamic characteristics of formoterol fumarate 20 microg/2 mL when mixed or sequentially nebulized with budesonide inhalation suspension 0.5 mg/2 mL, ipratropium bromide 0.5 mg/2.5 mL, cromolyn sodium 20 mg/2 mL, or acetylcysteine 10% (100 mg/mL). The admixtures were prepared in triplicate and analyzed for physicochemical compatibility at 0, 15, 30, and 60 minutes after mixing at room temperature. Physical compatibility was determined by visual examination and measurements of pH, osmolality, and turbidity. Chemical stability was evaluated using compendial or in-house-validated high-performance liquid chromatography (HPLC) assay methods. The aerodynamic characteristics of the admixtures or sequentially nebulized drugs were determined from aerosols generated from a Pari LC Plus nebulizer, using an 8-stage cascade impactor followed by HPLC analysis of the deposited drug. The admixtures remained clear, colorless solutions with no precipitation, except for cloudiness observed in the formoterol/budesonide combination due to budesonide suspension. The pH, osmolality, and turbidity for all admixtures were within the initial values (< or = 3%), and there were no significant changes (< or = 2%) in potency of the active components throughout the 1-hour study period. Due to increased drug volume or reconcentration in the nebulizer cup, the respirable fraction/delivered dose increased significantly (p < 0.05) for the mixed or sequentially nebulized drug. However, the fine particle fraction (FPF), mass median aerodynamic diameter, and geometric standard deviation generally remained unchanged for all admixtures, with the exception of FPF for the formoterol/budesonide combination. Our results indicate that admixtures of formoterol with budesonide, ipratropium, cromolyn, or acetylcysteine are physically and chemically compatible. However, admixing or sequential nebulization significantly increased the amount of drug delivered compared with single drug nebulization. The clinical implications of the in vitro data in patients with COPD have not been determined.
18,780,805
Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.
Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. In diabetic rats, chronic administration of macitentan decreased blood pressure and proteinuria and prevented end-organ damage (renal vascular hypertrophy and structural injury). In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation.
18,780,830
Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer.
Intraperitoneal chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous intraperitoneal therapy used the paclitaxel/Cremophor EL (polyethoxylated castor oil) formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for intraperitoneal treatment (referred to as tumor-penetrating microparticles or TPM). Evaluation of TPM was performed using intraperitoneal metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming, whereas the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor EL: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of intraperitoneal therapy.
18,780,831
CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy.
CD20 is expressed in approximately one- half of pediatric acute lymphoblastic leukemia (ALL) cases with B-cell precursor (BCP) origin. We observed that it is occasionally up-regulated during treatment. To understand the impact of this on the potential effectiveness of anti-CD20 immunotherapy, we studied 237 CD10(+) pediatric BCP-ALL patients with Berlin-Frankfurt-Munster (BFM)-type therapy. We analyzed CD20 expression changes from diagnosis to end-induction, focusing on sample pairs with more than or equal to 0.1% residual leukemic blasts, and assessed complement-induced cytotoxicity by CD20-targeting with rituximab in vitro. CD20-positivity significantly increased from 45% in initial samples to 81% at end-induction (day 15, 71%). The levels of expression also increased; 52% of cases at end-induction had at least 90% CD20(pos) leukemic cells, as opposed to 5% at diagnosis (day 15, 20%). CD20 up-regulation was frequent in high-risk patients, patients with high minimal residual disease at end-induction, and patients who suffered later from relapse, but not in TEL/AML1 cases. Notably, up-regulation occurred in viable cells sustaining chemotherapy. In vitro, CD20 up-regulation significantly enhanced rituximab cytotoxicity and could be elicited on prednisolone incubation. In conclusion, CD20 up-regulation is frequently induced in BCP-ALL during induction, and this translates into an acquired state of higher sensitivity to rituximab. This study was registered at http://www.clinicaltrials.gov as #NCT00430118.
18,780,832
US residency training before and after the 1997 Balanced Budget Act.
Graduate medical education (GME) determines the size and characteristics of the future workforce. The 1997 Balanced Budget Act (BBA) limited Medicare funding for additional trainees in GME. There has been concern that because Medicare is the primary source of GME funding, the BBA would discourage growth in GME. To examine the number of residents in training before and after the BBA, as well as more recent changes in GME by specialty, sex, and type and location of education. Descriptive study using the American Medical Association/Association of American Medical Colleges National GME Census on physicians in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs to examine changes in the number and characteristics of residents before and after the BBA. Differences in the number of physicians in ACGME-accredited training programs overall, by specialty, and by location and type of education. The number of residents and fellows changed little between academic year (AY) 1997 (n = 98,143) and AY 2002 (n = 98,258) but increased to 106,012 in AY 2007, a net increase of 7869 (8.0%) over the decade. The annual number of new entrants into GME increased by 7.6%, primarily because of increasing international medical graduates (IMGs). United States medical school graduates (MDs) comprised 44.0% of the overall growth from 2002 to 2007, followed by IMGs (39.2%) and osteopathic school graduates (18.8%). United States MD growth largely resulted from selection of specialties with longer training periods. From 2002 to 2007, US MDs training in primary care specialties decreased by 2641, while IMGs increased by 3286. However, increasing subspecialization rates led to fewer physicians entering generalist careers. After the 1997 BBA, there appears to have been a temporary halt in the growth of physicians training in ACGME programs; however, the number increased from 2002 to 2007.
18,780,846
The frequency of regulatory CD3+CD8+CD28- CD25+ T lymphocytes in human peripheral blood increases with age.
Aging is commonly associated with immune deficiency and dysregulation. The aging of the immune system involves a progressive reduction in naïve T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. We have investigated frequency, phenotype, and function of CD3+CD8+CD28(-)CD25+ T cells in healthy volunteers over a wide age range. We demonstrate that the frequency of CD3+CD8+CD28(-)CD25+ T cells in healthy volunteers increases with age. Peripheral CD3+CD8+CD28(-)CD25+ T cells share phenotypic and functional features with CD3+CD4+CD25+ regulatory T cells (Tregs): In particular, they strongly express CTLA-4 and forkhead box P3. We observed that in vitro, functional titration assays of CD3+CD8+CD28(-)CD25+ T cells show equivalent regulatory function in young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. Finally, CD3+CD8+CD28(-)CD25+ T cells seem to specifically express the CD122 receptor. Altogether, these observations demonstrate an increase in peripheral blood CD8+ Tregs associated with aging.
18,780,874
Swing phase resistance enhances flexor muscle activity during treadmill locomotion in incomplete spinal cord injury.
This study investigated whether loading the legs during the swing phase of walking enhances flexor muscle activity in ambulatory patients with incomplete spinal cord injury (SCI). Nine patients had surface electromyography (EMG) and joint kinematics recorded from the lower extremities during treadmill walking. Swing phase loading of the legs was achieved by weights (1-3 kg) attached to each lower extremity or by a velocity-dependent resistance applied by the Lokomat robotic gait orthosis. When patients walked with the weights, there was a consistent increase in the activity of the knee flexors and sometimes of hip or ankle flexor activity during swing. Similarly, when the robot applied the velocity-dependent resistance during walking, swing phase flexor EMG activity tended to be greater. Enhanced knee flexion was observed in all patients after the weights or the robot-generated resistance was removed. Flexor muscle activity during swing can be enhanced through additional proprioceptive input in patients with incomplete SCI with brief aftereffects. Further testing of this strategy is necessary to determine if it can improve the gait of ambulatory patients.
18,780,879
Motor imagery to enhance recovery after subcortical stroke: who might benefit, daily dose, and potential effects.
Motor imagery may enhance motor recovery after stroke. To estimate the proportion of patients able to perform motor imagery, the feasibility of delivery of motor imagery training (MIT), and the effects of MIT on motor recovery in an exploratory study. An immediate pretreatment and posttreatment single-group design was used to study 10 patients after subcortical stroke with neuromuscular weakness in the upper limb. MIT that included upper limb activities reflecting everyday tasks was provided for 10 consecutive working days. Measures included assessment of chaotic motor imagery, patient report of tolerability of MIT, Motricity Index (MI), Nine Hole Peg Test (9HPT), and quality of movement (MAL-QOM). MIT dose was changed in response to patient feedback. Graphed motor function scores were inspected visually for clinically important changes. Four of the 10 patients were unable to perform motor imagery. Patient opinion was positive about the content and shaped daily dose of MIT given in two 20-minute periods separated by a 10-minute rest. Clinically important changes in motor scores were found. Four patients increased MI score (range 8-16), 3 patients increased 9HPT score (range 0.02-0.04 pegs/second), and 4 patients increased MAL-QOM score (range 0.63-1.29). MIT was received positively by patients, but 40% were unable to perform imagery and interindividual variations were found on motor function.
18,780,881
Accounting for health spending in developing countries.
Data on health system financing and spending, together with information on the disease prevalence and cost-effectiveness of interventions, constitute essential input into health policy. It is particularly critical in developing countries, where resources are scarce and the marginal dollar has a major impact. Yet regular monitoring of health spending tends to be absent from those countries, and the results of international efforts to stimulate estimation activities have been mixed. This paper offers a history of health spending measurement, describes alternative sources of data, and recommends improving international collaboration and advocacy with the private sector for the way forward.
18,780,927
Aligning Forces for Quality: a program to improve health and health care in communities across the United States.
The Robert Wood Johnson Foundation's Aligning Forces for Quality program features partnerships with leaders in targeted communities. The program is working to achieve dramatic, sustainable improvements in quality across the continuum of care by 2015. These improvements will affect patients of all races and ethnicities.
18,780,937
The effects of cured dentin bonding agents on secretion of pro-inflammatory cytokines, IL-1beta and TNF-alpha, by human monocytes.
Dentin Bonding Agents (DBA) have been used as root-end filling materials. Present study evaluated the effects of polymerized DBA on secretion of pro-inflammatory cytokines by normal human monocytes. In this study, monocytes were directly isolated from human peripheral blood, and exposed to cured Scotch Bond 1 (single bond) and Prime and Bond for 36 and 72 hours. Secretion of IL-1beta and TNF-alpha in the presence of lipopolysaccaharide was evaluated in supernatants of monocyte culture.DBAs significantly caused reduction of cytokine production by human monocytes after 36 and 72 hours. Prime and bond exposure caused more prominent decrease in TNF-alpha production after 72 hours. We conclude that DBA in polymerized form can alter normal function of human monocytes.
18,780,953
Adaptive fractionation therapy: II. Biological effective dose.
Radiation therapy is fractionized to differentiate the cell killing between the tumor and organ at risk (OAR). Conventionally, fractionation is done by dividing the total dose into equal fraction sizes. However, as the relative positions (configurations) between OAR and the tumor vary from fractions to fractions, intuitively, we want to use a larger fraction size when OAR and the tumor are far apart and a smaller fraction size when OAR and the tumor are close to each other. Adaptive fractionation accounts for variations of configurations between OAR and the tumor. In part I of this series, the adaptation minimizes the OAR (physical) dose and maintains the total tumor (physical) dose. In this work, instead, the adaptation is based on the biological effective dose (BED). Unlike the linear programming approach in part I, we build a fraction size lookup table using mathematical induction. The lookup table essentially describes the fraction size as a function of the remaining tumor BED, the OAR/tumor dose ratio and the remaining number of fractions. The lookup table is calculated by maximizing the expected survival of OAR and preserving the tumor cell kill. Immediately before the treatment of each fraction, the OAR-tumor configuration and thus the dose ratio can be obtained from the daily setup image, and then the fraction size can be determined by the lookup table. Extensive simulations demonstrate the effectiveness of our method compared with the conventional fractionation method.
18,780,956
High-speed evaluation of track-structure Monte Carlo electron transport simulations.
There are many instances where Monte Carlo simulation using the track-structure method for electron transport is necessary for the accurate analytical computation and estimation of dose and other tally data. Because of the large electron interaction cross-sections and highly anisotropic scattering behavior, the track-structure method requires an enormous amount of computation time. For microdosimetry, radiation biology and other applications involving small site and tally sizes, low electron energies or high-Z/low-Z material interfaces where the track-structure method is preferred, a computational device called a field-programmable gate array (FPGA) is capable of executing track-structure Monte Carlo electron-transport simulations as fast as or faster than a standard computer can complete an identical simulation using the condensed history (CH) technique. In this paper, data from FPGA-based track-structure electron-transport computations are presented for five test cases, from simple slab-style geometries to radiation biology applications involving electrons incident on endosteal bone surface cells. For the most complex test case presented, an FPGA is capable of evaluating track-structure electron-transport problems more than 500 times faster than a standard computer can perform the same track-structure simulation and with comparable accuracy.
18,780,958
Management of synchronized network activity by highly active neurons.
Increasing evidence supports the idea that spontaneous brain activity may have an important functional role. Cultured neuronal networks provide a suitable model system to search for the mechanisms by which neuronal spontaneous activity is maintained and regulated. This activity is marked by synchronized bursting events (SBEs)--short time windows (hundreds of milliseconds) of rapid neuronal firing separated by long quiescent periods (seconds). However, there exists a special subset of rapidly firing neurons whose activity also persists between SBEs. It has been proposed that these highly active (HA) neurons play an important role in the management (i.e. establishment, maintenance and regulation) of the synchronized network activity. Here, we studied the dynamical properties and the functional role of HA neurons in homogeneous and engineered networks, during early network development, upon recovery from chemical inhibition and in response to electrical stimulations. We found that their sequences of inter-spike intervals (ISI) exhibit long time correlations and a unimodal distribution. During the network's development and under intense inhibition, the observed activity follows a transition period during which mostly HA neurons are active. Studying networks with engineered geometry, we found that HA neurons are precursors (the first to fire) of the spontaneous SBEs and are more responsive to electrical stimulations.
18,780,962
Effects of sildenafil on nigrostriatal dopamine neurons in a murine model of Parkinson's disease.
The objective of this study was to determine if the phosphodiesterase 5 (PDE-5) inhibitor, sildenafil, could be used as a neuroprotective agent in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease. The underlying hypothesis of these studies is that blockade of PDE-5 catabolism of cGMP will attenuate the loss of nigrostriatal dopamine (NSDA) neurons following chronic neurotoxin exposure. Chronic MPTP-treated mice were administered sildenafil using three different regimens. Animals were: 1) treated with sildenafil and then exposed to chronic MPTP; 2) treated concurrently with sildenafil and MPTP; and 3) first exposed to MPTP and subsequently treated with sildenafil. End points of neurotoxicity included dopamine (DA) and tyrosine hydroxylase (TH) concentrations in NSDA axon terminals in the striatum, and stereological cell counts of TH immunoreactive neurons in the substantia nigra. Results reveal that sildenafil did not prevent neurotoxicity produced by chronic MPTP exposure regardless of the treatment paradigms employed. On the other hand, sildenafil did not produce any deleterious effect on NSDA neuron function nor did it potentiate the neurotoxic effects of MPTP. These results suggest that sildenafil would not accelerate DA cell loss when used as a treatment for erectile dysfunction in men diagnosed with Parkinson's disease.
18,780,970
Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein.
We investigated how synaptic plasticity is related to the neurodegeneration process in the human dorsolateral prefrontal cortex. Pre- and postsynaptic proteins of Brodmann's area 9 from patients with Alzheimer's disease (AD) and age-matched controls were quantified by immunohistochemical methods and Western blots. The main finding was a significant increase in the expression of postsynaptic density protein PSD-95 in AD brains, revealed on both sections and immunoblots, while the expression of spinophilin, associated to spines, remained quantitatively unchanged despite qualitative changes with age and disease. Presynaptic protein alpha-synuclein indicated an increased immunohistochemical level, while synaptophysin remained unchanged. MAP2, a somatodendritic microtubule protein, as well as AD markers such as amyloid-beta protein and phosphorylated protein tau showed an increased expression on immunosections in AD. Altogether these changes suggest neuritic and synaptic reorganization in the process of AD. In particular, the significant increase in PSD-95 expression suggests a change in NMDA receptors trafficking and may represent a novel marker of functional significance for the disease.
18,780,974
A comparison of selected isokinetic trunk strength parameters of elite male judo competitors and cyclists.
Each sporting activity appears to require some distinctive motor functions. The purpose of this study was to establish referential isokinetic strength parameters in competitive judo athletes because no previous studies have examined trunk strength of judo athletes isokinetically and to test the hypothesis that the isokinetic strength parameters of competitive judo athletes, who are specifically trained with respect to trunk strength, are significantly different from those in another well-trained population (racing cyclists), who train very differently. Twenty-eight male top judo athletes and 34 top racing cyclists, all without back trouble, were tested by means of the Cybex Trunk Extension Flexion (TEF) unit and the Torso Rotation (TR) unit. This was done at four different speeds-30, 60, 90 and 120 degrees /set. The results of MANOVA showed that the judo athletes have statistically higher performance than cyclists (p < 0.05) on all of the isokinetic variables (ie., peak torque, best work repetition, and average power corrected for body weight) in trunk extension, flexion, left rotation, and right rotation. The ratios of flexion to extension and left rotation to right rotation were not significantly different between the cyclists and the judo athletes. The authors concluded that for clinical purposes, the ratios of flexion to extension and left rotation to right rotation may be of more importance than separate values as such. Research in this area is of utmost importance to provide a needed shift in emphasis from injury treatment to injury prevention. J Orthop Sports Phys Ther 1992;16(2):92-96.
18,780,991
Current concepts in the treatment of anterior cruciate ligament disruption.
Treatment of anterior cruciate ligament injuries has changed considerably in recent years. The purpose of this paper is to discuss the past and present treatment for anterior cruciate ligament (ACL) disruptions in athletic individuals. In addition, this paper will discuss current trends in rehabilitation, such as immediate motion, weight bearing, and close kinetic chain exercises, and provide the scientific rationale for these rehabilitation principles. The treatment of individuals who have suffered an ACL disruption has changed dramatically over the years. The treatment of ACL ruptures has made a full circle. The first reconstructive procedure described used a patellar tendon graft. Then primary ACL repairs were advocated. With the limited success of that procedure, the nonoperative treatment was popularized, with reconstruction performed only after the conservative program failed. With this treatment plan, clinicians noted early degenerative joint changes and an increase in meniscus tears in the ACL deficient knee. Thus, reconstructive surgery using a patellar tendon graft was again advocated. Today, the current trend in the treatment of ACL tears is an arthroscopically assisted procedure to reconstruct the ACL using a bone-tendon-bone graft, such as a patellar tendon. The surgery employs accurate graft placement, tensioning, and fixation, which allows the therapist the opportunity to utilize immediate motion and weight bearing, in addition to strengthening exercises. This paper attempts to explain the rehabilitation process following ACL reconstruction using current scientific and clinical research. The program is based on the anatomy, biomechanics, and healing process of the knee, joint, and ACL. The clinical implications of this paper are numerous. First, we believe the information will assist clinicians in developing their own programs. Second, the data will assist the reader in understanding the sequential healing process. Finally, this paper documents that immediate aggressive rehabilitation is not deleterious to the ACL graft, and early therapy improves the functional outcome. J Orthop Sports Phys Ther 1992;15(6):279-293.
18,781,001
The Editor's Role in the Science and Art of Physical Therapy.
James A. Gould, MS, PT, delivered the Paris Distinguished Service Award Lecture at the Combined Sections meeting in San Francisco in February. Gould is the second recipient of the Orthopaedic Section's Paris Award, which was named for its first recipient and the founder of the Orthopaedic Section, Stanley Paris, PhD, PT. In 1968, Gould graduated from Central Michigan University with a BS degree in biology. He earned a BS degree in physical therapy from the University of Kentucky in 1971 and a master's degree in education from the University of Kentucky in 1974. Gould was then appointed a faculty member of the University of Wisconsin-La Crosse, where he is now an associate professor. In 1979, Gould founded The Journal of Orthopaedic and Sports Physical Therapy and served as editor until 1990. He is currently treasurer of the Private Practice Section, editor of PT Today, and co-owner of OPTions, a clinical practice in La Crosse, WI. J Orthop Sports Phys Ther 1992;15(6):323-325.
18,781,005
Ion exchange and protonation equilibria of an amphoteric ion-exchange resin in the presence of simple salt.
The influence of simple salts on the ion exchange and protonation equilibria of an amphoteric ion-exchange resin, which has strong base and weak acid moieties in a single functional group fixed onto the styrene-DVB matrix, has been investigated. Concentrations of ionic species in the amphoteric ion-exchange resin in equilibrium with various sodium salt solutions were estimated by (23)Na NMR spectroscopy. For the NaClO(4) system, the ratio of sodium ion concentration in the resin phase to that in the equilibrium solution was greater than 1 and increased with a decrease in the salt concentration. In contrast to an ordinary cation-exchange resin, the ion exchange behavior of Mg(2+) and Ca(2+) on the amphoteric ion-exchange resin showed a marked dependence on the kinds of salts: the distribution coefficients for the NaCl system were independent of the salt concentration, while the log D vs. log[Na(+)] plots for the NaClO(4) system showed linear relationships with slopes being neither -2 nor 0. Apparent protonation constants of the carboxylate in the functional group of the resin in equilibrium with NaClO(4) solutions were greater than those with NaCl solutions. The ion exchange and protonation properties of the amphoteric ion-exchange resin were elucidated on the basis of the information about the salt concentrations in the resin phase estimated by the NMR method.
18,781,023
Determination of psoralen in human plasma using excitation-emission matrix fluorescence coupled to second-order calibration.
A new algorithm, an alternating normalization-weighted error (ANWE) method, and the parallel factor analysis (PARAFAC) have been used to directly determine psoralen (PSO) in human plasma. The two methods fully exploit the second-order advantage of the applied three-way fluorescence data. Interestingly, the calibration samples need only the components of interest, and the prediction samples allow containing not only the components of interest, but also unknown interferents. Consequently, the determination of PSO in plasma becomes no longer troublesome or time-consuming. The results are satisfying. Furthermore, compared with PARAFAC, the newly introduced ANWE method can obtain more satisfactory results.
18,781,031
Folic acid prevents congenital malformations in the offspring of diabetic mice.
It is well known that maternal diabetes causes various congenital malformations. Although there are many reports that folic acid (FA) administration in pregnancy reduces the risk of birth defects including neural tube defects (NTDs), a precise analysis on the preventive effect of FA against diabetic embryopathy has not been done yet. In this study, we analyzed the preventive effects of FA on congenital malformations including NTDs, cardiovascular, and skeletal malformations using a diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were examined for congenital malformations. FA did not affect plasma glucose levels. In the DM control group, the incidence of NTDs, cardiovascular, and skeletal malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of embryos from DM control group on day 9.5, and the apoptosis was decreased by FA treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly lowered in DM control group compared with those in non-DM group, and FA treatment did not show a significant effect. These results indicate that FA is effective for the prevention of various diabetic embryopathy including NTDs, cardiovascular, and skeletal malformations, and suggested that this effect is independent from homocysteine metabolism and possibly mediated by decreasing the abnormal apoptosis during organogenesis.
18,781,038
Rat gastric banding model for bariatric surgery.
Adjustable gastric banding is a surgical approach to weight reduction. In this study we created a gastric banding model in rats to better understand the mechanism of body weight loss. Male Sprague-Dawley rats weighing 260 to 280 g were subjected to gastric banding (band group) (n=8) or to a sham operation (control group) (n=8). Body weights were monitored for 14 days, and daily food and water intake and nitrogen balance were monitored for 7 days. Two rats in the band group died of malnutrition due to gastric stomal stenosis and obstruction caused by the gastric banding. Body weight gain during the 14 days after the operation was less in the band group than in the control group (p<0.01). Food intake during the 7 days after the operation was significantly less in the band group than in the control group (p<0.01), and water intake during the 7 days after the operation was significantly less in the band group than in the control group (p<0.01). Cumulative nitrogen balance was significantly less in the band group than in the control group (p<0.01). Gastric banding decreased the body weight gain of rats by decreasing the amount of food intake because of the creation of a small gastric pouch.
18,781,041
The excellent water-solubility of N-[3-(dimethyl-amino)propyl] docosanamide chloride : the most eco-friendly cationic hair conditioning agent.
A new hair-conditioning agent, N-[3-(dimethylamino)propyl]docosanamide (APA-22) hydrochloric acid salt (APA-22 HCl), has excellent solubility in water with a solubility limit over 10-times larger than that of other APA hydrochloric salts with shorter alkyl chain lengths. The physicochemical characteristics of APA-22 HCl were studied at 25 degrees C by using equilibrium surface tension (gamma), solubilization of an oil-soluble dye, steady-state fluorescence, and chloride ion selective electrode techniques. The APA-22 HCl salt is considered to form an aggregate at a concentration, C(1), which is about twice the concentration of the solubility limit of APAs with shorter alkyl chains. At a higher concentration, C(2), the aggregates of APA-22 HCl start forming another kind of aggregate, which is able to solubilize oil-soluble materials. That is, C(1) is considered to represent the critical aggregation concentration (cac) and C(2) a morphology transition. In the concentration region between C(1) and C(2) the solutions are seemingly transparent whereas at above C(2) they appear bluish or translucent. Since the Krafft point of APA-22 HCl is 55 degrees C, all the solutions, including the aggregates, are thought to exist in metastable states. Notably, however, these metastable solutions do not change significantly over a few months. The excellent solubility of APA-22 HCl in water is considered to be a result of this unique stepwise aggregation with increasing concentration.
18,781,052
Effect of starch and sucrose on dental biofilm formation and on root dentine demineralization.
The cariogenicity of starch alone or in combination with sucrose is controversial and the effect on dentine demineralization and on the dental biofilm formed has not been explored under controlled conditions. A crossover, single-blind study was conducted in four steps of 14 days each, during which 11 volunteers wore palatal appliance containing 10 slabs of root dentine to which the following treatments were applied extraorally: 2% starch gel-like solution (starch group); 10% sucrose solution (sucrose group); a solution containing 2% starch and 10% sucrose (starch + sucrose group), or 2% starch solution followed by 10% sucrose solution (starch --> sucrose group). On the 14th day of each phase the biofilms were collected for biochemical and microbiological analyses, and dentine demineralization was assessed by hardness. A higher demineralization was found in dentine exposed to sucrose and starch sucrose combinations than to starch alone (p < 0.01), but the sucrose-containing groups did not differ significantly from each other (p > 0.05). The concentrations of soluble and insoluble extracellular polysaccharides (EPS), and the proportion of insoluble EPS, were lower in the biofilm formed in presence of starch (p < 0.01) than in those formed in the presence of sucrose or sucrose/starch combinations; however, no significant difference was observed among the groups containing sucrose (p > 0.05). RNA was successfully isolated and purified from in situ biofilms and only biofilms formed in response to sucrose and starch/sucrose combinations showed detectable levels of gtfB and gtfC mRNA. The findings suggest that the combination of starch with sucrose may not be more cariogenic to dentine than sucrose alone.
18,781,066
Calcium pre-rinse greatly increases overnight salivary fluoride after a 228 ppm fluoride rinse.
Large increases in salivary fluoride were reported 1 h after a calcium pre-rinse/NaF rinse. This study examined the persistence of these increases. 12 subjects rinsed in the evening with water, with a 228 microg/g (ppm) F rinse or with 150 mmol/l calcium lactate followed by a 228 microg/g F rinse. In a second experiment these same patients rinsed with a 912 microg/g F rinse. Saliva samples were obtained the morning after rinsing, centrifuged and the supernatants analyzed. The Ca pre-rinse/228 microg/g F rinse induced an increase in overnight salivary F over the 912 microg/g F rinse (approximately 2.5 times) and a statistically significant increase over the 228 mug/g F rinse (approximately 5.5 times). The results suggest that a Ca pretreatment may increase the cariostatic effect of topical F agents.
18,781,069