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INTRODUCTION | rash, pain, Herpes zoster, HZ, PHN | POSTHERPETIC NEURALGIA, PHN, VIRUS INFECTION, DISEASE, HERPES ZOSTER, NEUROINFLAMMATORY RESPONSE, PATHOGENESIS, COMPLICATIONS | Herpes zoster (HZ) is a comment disease with distinctive clinical conditions, it is caused after varicella‐zoster virus infection. According to epidemiological investigation, one in four people might suffer from HZ during their lifetime, and for individuals aged over 50, the incidence for HZ increased to almost 50% (Da... | PMC10097047 |
METHODS | PIAN | This open‐label pilot study was undertaken in the Pian Center of Shanghai Changhai Hospital, China, from February 1, 2020 to January 30, 2022. The protocol is in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. This trial was prospectively registered at Chictr.o... | PMC10097047 | |
Study design | PHN, herpetic neuralgia, rash, pain | PHN, HERPETIC NEURALGIA, SYNDROME | This is a prospective, single‐arm, and single‐center pilot study to investigate autologous fat grafting to the thoracic paravertebral space for elders with herpetic neuralgia in the rash phase, the main object of this trail is to investigate the feasibility and safety of this treatment in preventing PHN. Participants w... | PMC10097047 |
Interventions | allodynia, Pain, hyperalgesia | All included patients were treated with autologous fat grafting to the thoracic paravertebral space with hyperalgesia and allodynia in related region. All procedures were performed by a skilled plastic surgeon. Before harvest, the region was injected by a tumescent solution (0.5% lidocaine + 0.0005% adrenaline). The fa... | PMC10097047 | |
Electoral pain threshold assessment | pain | In this trial, we assessed the pain threshold based on patients’ response to a gradual increased electrical stimulus (0.1 mA, pulse width 0.3 ms, impulse frequency 50 Hz) using a pain vision detection device (PS‐2100, Nipro Corporation, Osaka, Japan). During each assessment, a 1‐inch square electrode was placed either ... | PMC10097047 | |
Data collection and outcomes | neuropathic pain, skin eruption, pain, PHN, herpetic pain, herpetic neuralgia | PHN, HERPETIC NEURALGIA, SKIN ERUPTION | Baseline data collected included demographic information; pain level (as perceived by the patient using visual analog scale, VAS, a 10‐cm unmarked line, with anchors: 0 = no pain and 10 cm = worst pain imaginable); current medications; smoking status; and pain threshold of the patient's affected dermal area as well as ... | PMC10097047 |
Sample size and statistical methods | This is a hypothesis‐generating feasibility study; the collected data and information are supposed to identify the safety and treatment responses, and to calculate a preliminary sample size for a randomized controlled trial. We chose to include a total of eight patients in this trial. Data were analyzed using the SPSS ... | PMC10097047 | ||
RESULTS | PHN, pain, rash, abdominal pain | HERPES ZOSTER, PHN, EVENTS | Eight patients accept the intervention and complete all follow‐ups. All of them are female, with a mean age of 63.7 years (range from 50 to 76 years), while seven of them have a high school degree. All patients are suffered from chest, back or abdominal pain due to emerging herpes zoster, the mean duration for pain is ... | PMC10097047 |
DISCUSSION | neuropathic pain, mood disorders, rash, pain, PHN | ADVERSE EVENTS, PHN, PATHOGENESIS, SYNDROME | In this trial, we identify that autologous fat grafting to the paravertebral space of the algogenic segment is a potentially valid method to prevent PHN. Among the eight patients accepted fat grafting, most of them have experienced immediate pain relief after the intervention, while eight of them have a lasting allogen... | PMC10097047 |
CONCLUSION | PHN | ADVERSE EVENTS, PHN | In this prospective, single‐armed trial, we first report the feasibility and the safety of autologous fat transplantation to the paravertebral space in preventing PHN. More advantages of this technique including rich in fat content, easy to obtain, cost‐benefit as well as less adverse events makes it a promising treatm... | PMC10097047 |
AUTHOR CONTRIBUTIONS | XJ Li designed the trial and conducted the experiments, R Tao conducted the experiments, XY meng analyzed the data and wrote the manuscript, H Wang revised the manuscript, HD Bi conceived the study and conducted the experiments, YC Xiong conceived the study. All authors read and approved the final version. | PMC10097047 | ||
CONFLICT OF INTEREST STATEMENT | The authors declare that they have no competing interests. | PMC10097047 | ||
PEER REVIEW | The peer review history for this article is available at | PMC10097047 | ||
DATA AVAILABILITY STATEMENT | Data are available from the corresponding author with reasonable requesting. | PMC10097047 | ||
REFERENCES | PMC10097047 | |||
ABSTRACT | infusion-site, pain | RHD, SECONDARY, RHEUMATIC HEART DISEASE | The authors declare no conflict of interest.Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is... | PMC10720493 |
KEYWORDS | PMC10720493 | |||
INTRODUCTION | skin infections, throat, infections, ARF | ARF, AUTOIMMUNE RESPONSE, INFECTIONS, SKIN INFECTION, SECONDARY, ACUTE RHEUMATIC FEVER | Acute rheumatic fever (ARF) results from an abnormal autoimmune response to inadequately treated throat or skin infections with Group A Streptococcus (There is no specific treatment for ARF. However, the mainstay of current therapy, benzathine penicillin G (BPG), which is a long-acting formulation, is directed at preve... | PMC10720493 |
RESULTS | PMC10720493 | |||
Participants | Seventy-seven adults were screened for eligibility, and 24 eligible participants were recruited; four were females. The median (range) screening age and body mass index (BMI) were 26.9 (18.0–54.1) years and 25.1 (21.9–34.0) kg/mConsort diagram for trial participants. | PMC10720493 | ||
Study infusion | pain | Three participants did not receive the planned dose of BPG. The first two participants in cohort 1 received 3.1 MIU because ~1 mL infusate failed to progress through the flow control extension tubing, while one participant in cohort 3 received 8.2 MIU as the infusion after a period of cessation due to pain. All other p... | PMC10720493 | |
Pain scores | NRS, pain | Reported numerical rating scale (NRS) pain scores ranged from 0 to 8 with the greatest intensity recorded during the infusion, but the median (range) pain scores were 2.5 (0–6), 3 (0–8), and 2.5 (0–6) for cohorts 1, 2, and 3, respectively. Moderate pain (NRS 4–7) was not experienced beyond 2 days, and no pain was repor... | PMC10720493 | |
Modified Skindex-16 scores | Normalized overall Skindex-17 scores ranged from 0 to 61 with the highest scores reported in the first 2 days after infusion. Scores decreased thereafter with only four participants reporting scores beyond Day 14. The highest normalized domain (symptoms) score was 75 reported by a cohort 2 participant on Day 2. The nor... | PMC10720493 | ||
Adverse events | swelling, erythema, pain, infusion-site, tenderness/pain | ADVERSE EVENTS, ERYTHEMA, HYPERPIGMENTATION | There were 101 adverse events reported during the study with no serious adverse events (Table S5). All participants experienced some infusion-site reaction including erythema, swelling, tenderness/pain, and pigmentation ranging in duration from less than 1 day (pain) to 217 days (hyperpigmentation). There were two off-... | PMC10720493 |
Pharmacokinetic modeling | From the 24 individuals, there were 400 samples included in the PK analysis. The fraction of samples below the limit of quantification (LOQ) (BLQ) was low (11%), those measured between the LOQ and limit of detection (LOD), Visual inspection of the population data demonstrated a change in the terminal phase occurring af... | PMC10720493 | ||
DISCUSSION | hyperpigmentation, Hyperpigmentation, erythema, pain, PD, bruising, infusion-site, NRS | HYPERPIGMENTATION, HYPERPIGMENTATION, ERYTHEMA, RHD, HYPERMELANOSIS | Subcutaneous infusion of high-dose BPG (SCIP) is tolerable and safe. Despite all participants experiencing some degree of infusion-site reaction, they all resolved spontaneously with no serious adverse outcomes. While pain is a subjective experience, the maximum reported pain at injection was severe (NRS 8), requiring ... | PMC10720493 |
MATERIALS AND METHODS | PMC10720493 | |||
Study design | SECONDARY | We conducted a phase 1 open-label study using three cohorts with increasing doses of BPG, with the primary objective of assessing the safety and tolerability of SCIP. The secondary objectives were to characterize the PK, including the time above the current accepted pharmacological surrogate for protection against | PMC10720493 | |
Participants | Twenty-four healthy participants were recruited into the study from eligible adults aged 18–65 years, without significant co-morbidities. Full eligibility/exclusion criteria are provided (Table S6). To explore the effect of body composition, 12 participants with an ideal BMI (20–24.9 kg/m | PMC10720493 | ||
Study intervention | ADVERSE EVENTS, RECRUITMENT, SKIN NECROSIS | Participants received a single SC infusion of 3.6 (2,700 mg, 9 mL), 7.2 (5,400 mg, 13.8 mL), or 10.8 MIU (8,100 mg, 20.7 mL) of BPG (Bicillin L-A, Pfizer, Sydney, Australia) delivered under ultrasound guidance. To achieve sustained plasma penicillin concentrations of 73% and 99% for a 3-month period above target concen... | PMC10720493 | |
Study infusion | Prior to infusion, participants underwent an ultrasound examination (Acuson S3000 and Acuson 18L6 probe, Siemens Medical Solutions, Malvern, USA) to assess SC fat using a validated protocol (The prescribed BPG dose was transferred to a 30 mL syringe (JMS Co. Ltd, Hiroshima, Japan) and delivered into a single injection ... | PMC10720493 | ||
Pharmacokinetic samples | Pharmacokinetic samples consisted of serial dried blood spots and venous samples. DBSs were collected 2, 6, 12, 24, 48, and 72 hours pre-dose and 5, 7, 14, 21, 28, 42, 56, 70, 84, 98, and 112 days post-dose, and two venous blood samples were collected at 12 hours and 14 days post-dose. Three to five drops of mixed capi... | PMC10720493 | ||
Safety monitoring | NRS, pain | Safety and tolerability were assessed using the numerical rating scale for pain (The NRS with scores from 0 to 10 was used for its ease of application and validity in assessing acute and change in pain over time, with 0 and 10 representing “no pain” and “worst pain imaginable,” respectively. The minimally clinically im... | PMC10720493 | |
Population pharmacokinetic analysis | LogThe principal structure of the pharmacokinetic modeling was based on our previous published population of PK models (Inter-individual variability as well as correlations between IIV terms was then evaluated for each parameter. The IIV was exponentially modeled for all parameters. Given the wide range of participant ... | PMC10720493 | ||
Simulations | Once a final population pharmacokinetic model was established, simulations were performed based on weight and BMI data from the CDC for 20-year-olds (Penicillin concentrations were determined every 6 hours for all simulations. Four-weekly doses of 1.2 MIU of BPG given IM at steady state ( | PMC10720493 | ||
ACKNOWLEDGMENTS | INFECTIOUS DISEASES, STREP | We gratefully acknowledge the assistance of Elizabeth Eadie-Mirams, Renae Barr, Christine Everest, Rebecca Trowman, Jana Ilievski, David Pham, and Evelyn Carapetis in the planning, administration, and conduct of the study. We also acknowledge Lara Hatchuel, Nicola Norton, and the Linear Clinical Research team for their... | PMC10720493 | |
SUPPLEMENTAL MATERIAL | The following material is available online at | PMC10720493 | ||
aac.00962-23-s0001.docx | Supplemental material.Click here for additional data file.ASM does not own the copyrights to Supplemental Material that may be linked to, or accessed through, an article. The authors have granted ASM a non-exclusive, world-wide license to publish the Supplemental Material files. Please contact the corresponding author ... | PMC10720493 | ||
REFERENCES | PMC10720493 | |||
1. Introduction | HS.Hidradenitis suppurativa, TNF-α, psoriasis | DISEASE, PATHOPHYSIOLOGY, PSORIASIS, SKIN CONDITION, ABSCESSES, HIDRADENITIS SUPPURATIVA, SCARRING, PATHOLOGY, PATHOGENESIS | Janus kinase (JAK)/signal transducer and activator of transcription signaling (STAT) has been implicated in the pathophysiology of hidradenitis suppurativa (HS). This study evaluated treatment-related transcriptomic and proteomic changes in patients with moderate-to-severe HS treated with the investigational oral JAK1-... | PMC10139090 |
2. Results | PMC10139090 | |||
2.1. Transcriptomics | Lesional skin punch biopsies from 12 sample pairs taken from the edge of an active HS lesion [In the pathway enrichment analysis, a number of inflammatory pathways were found to be enriched in the Week 8 DEGs from the 30 mg povorcitinib QD group (We previously reported on a 128-gene signature of HS [Treatment-related c... | PMC10139090 | ||
2.2. Proteomics | Based on paired comparisons and the significance cutoff, a total of 33 differentially expressed proteins (DEPs) of interest were selected (6 upregulated and 27 downregulated proteins), representing the union of statistically significant upregulated and downregulated proteins for each treatment at Weeks 4 and 8 (FDR < 0... | PMC10139090 | ||
3. Discussion | Hidradenitis suppurativa, tissue damage | HIDRADENITIS SUPPURATIVA, DISEASE, SCARRING | Hidradenitis suppurativa is a chronic, painful disease that can lead to permanent tissue damage and scarring, and it has a significant negative impact on quality of life [Treatment with povorcitinib QD over 8 weeks was associated with a dose-dependent modulation of several proteins of interest, some of which have been ... | PMC10139090 |
4. Materials and Methods | PMC10139090 | |||
4.1. Study Design and Patients | Clinical samples were collected from two phase 2 studies of patients with moderate-to-severe HS [Serum was collected from all participants at baseline and Weeks 4 and 8 for proteomic analysis. Availability of skin biopsy samples for transcriptomic analysis was limited to 12 sample pairs (15 mg povorcitinib once daily [... | PMC10139090 | ||
4.2. Transcriptomic Analyses | RNA sequencing was conducted on frozen samples at the Beijing Genomics Institute using the Illumina HiSeq 4000 system (Illumina, Inc., San Diego, CA, USA), and sequences were aligned by using the Human Genome B38 library (National Center for Biotechnology Information) and the Gencode.V29 gene model (Gencode Project, EM... | PMC10139090 | ||
4.3. Proteomic Analyses | BLOOD | Blood samples were obtained at baseline, Week 4, and Week 8 from multiple dose groups (15 mg povorcitinib QD, | PMC10139090 | |
4.4. Statistical Analyses | For transcriptomic analyses, a paired | PMC10139090 | ||
5. Conclusions | DISEASE, PATHOLOGY | In conclusion, based on findings observed in skin biopsies and blood of patients with moderate-to-severe HS, 8 weeks of treatment with the JAK1 inhibitor povorcitinib was associated with the reversal of a previously identified HS transcriptomic signature, as well as dose-dependent changes in a number of circulating pro... | PMC10139090 | |
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10139090 | ||
Author Contributions | Conceptualization: H.L., L.L.S. and S.H.S.; Data curation: H.L., L.L.S. and S.H.S.; Formal analysis: H.L., L.L.S. and S.H.S.; Resources: H.L., L.L.S. and S.H.S.; Software: H.L.; Visualization: H.L., L.L.S. and S.H.S.; Writing—reviewing & editing: H.L., L.L.S. and S.H.S. All authors have read and agreed to the published... | PMC10139090 | ||
Institutional Review Board Statement | Ethikkommission der Universität zu Lübeck, Ethik-Kommission der Medizinischen | The clinical studies were conducted in accordance with the Declaration of Helsinki and approved by the institutional review board (IRB) or institutional ethics committee (IEC) at each participating site (United States and Canada central IRB/IEC: Advarra; United States local IRBs/IECs: Penn State College of Medicine IRB... | PMC10139090 | |
Informed Consent Statement | All patients provided written informed consent. | PMC10139090 | ||
Data Availability Statement | Access to individual patient-level data is not available for this study. Information on Incyte’s clinical trial data sharing policy and instructions for submitting clinical trial data requests are available at: | PMC10139090 | ||
Conflicts of Interest | H.L., L.L.S. and S.H.S. are employees and shareholders of Incyte Research Institute/Incyte Corporation. Incyte was involved in the design of the study; the collection, analysis, and interpretation of data; and in writing the manuscript. | PMC10139090 | ||
Methods | MINOR | We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor ( | PMC10645316 | |
Results | muscle mass | Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (m... | PMC10645316 | |
Conclusion | These data suggest that polymorphic variation in the | PMC10645316 | ||
Data Availability | The data are provided in the attached Excel file. | PMC10645316 | ||
Introduction | muscle mass, sarcopenia, Sarcopenia, sarcopenic | SARCOPENIA, ATROPHIC, SARCOPENIA | The maintenance of a healthy muscle mass is important in giving individuals the strength to perform the tasks of daily living. Muscle protein is continually turned over such that muscle mass is maintained by balancing the rates of protein synthesis and degradation within relatively tight windows [Sarcopenia, is defined... | PMC10645316 |
Materials and methods | PMC10645316 | |||
Participants and physiological analysis | sarcopenia | SARCOPENIA | Participants aged 70 years and over with sarcopenia, according to the EWGSOP definition (2010) [ | PMC10645316 |
DNA analysis | Whole blood samples were taken at the first study visit and frozen. DNA was extracted from the first 110 whole blood samples received using the QIAamp DNA blood mini kit according to the manufacturer’s instructions. This set of samples were the first batches received from the various trial sites by the laboratory, and ... | PMC10645316 | ||
Statistical analysis | All of the data used in this analysis is available in Whether the alleles were in Hardy-Weinberg equilibrium was determined by Chi squared test using allele frequencies published for the European Caucasian population (rs10783486, MAF = 0.26 and rs2854464, MAF = 0.26) [The threshold for statistical significance (alpha) ... | PMC10645316 | ||
GTEX data | NINDS | The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the GTEx analyses described in this manuscript were obtained from: the GTEx Portal ( | PMC10645316 | |
Results | The demographics of participants included in this analysis are given in | PMC10645316 | ||
Baseline demographics of the study population. | CONTRACTION | BMI: body mass index, cv: coefficient of variation, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD ... | PMC10645316 | |
rs10783486 | muscle mass | Given population differences in body composition and strength between males and females, the sexes were analysed separately. There were no associations of genotype with strength, total body muscle mass (quantified by bioimpedance) or limb muscle mass (quantified by DXA) in either sex ( | PMC10645316 | |
Associations of rs10783846 with height and limb fat mass in individuals in the LACE study. | MINOR | Height and limb fat were compared in males and females possessing the minor allele for rs10783846 with those homozygous for the major allele. Median height (A, p = 0.023), arm fat mass (B, p = 0.008) and leg fat mass (C, p = 0.046) were higher in males with the minor allele than their counterparts homozygous for the ma... | PMC10645316 | |
Effect of the minor allele of rs10783846 on body composition and strength in females and males at baseline. | CONTRACTION | BMI: body mass index, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD and for data that did not show... | PMC10645316 | |
Association of height with limb fat mass in individuals in the LACE study. | Height was compared with limb fat mass in males and females from the LACE study. In males there was a weak association of leg fat mass with height (r = 0.31, p = 0.025) but not in females. Arm fat mass was not associated with height in males or females. | PMC10645316 | ||
Association of height with limb muscle mass in individuals in the LACE study. | muscle mass | Height was compared with limb muscle mass in males and females from the LACE study. In both males (r = 0.57 p<0.001) and females (r = 0.61, p<0.001) there was a strong association of leg muscle mass with height. Arm muscle mass was also associated with height in both males (r = 0.51, p<0.001) and females (r = 0.52, p<0... | PMC10645316 | |
Arm and leg fat mass in LACE males adjusted for height. | Limb fat mass was log | PMC10645316 | ||
rs2854464 | muscle mass or limb muscle mass | Analysis of the rs2854464 allele showed a similar pattern to that described for rs10783486 both with no associations with total muscle mass or limb muscle mass ( | PMC10645316 | |
Associations of rs2854464 with height and limb fat mass in males and females in the LACE study. | MINOR | Height and limb fat were compared in males and females possessing the minor allele for rs2854464 with those homozygous for the major allele. Median height (A, p = 0.023), arm fat mass (B, p = 0.008) and leg fat mass (C, p = 0.046) were higher in males with the minor allele than their counterparts homozygous for the maj... | PMC10645316 | |
Effect of the minor allele of rs2854464 on body composition and strength in females and males at baseline. | CONTRACTION | BMI: body mass index, SARC-F: Strength, assistance with walking, rising from a chair, climbing stairs, and falls questionnaire score, SPPB: Short Physical Performance Battery score: QMVC: Quadriceps Maximal Voluntary contraction. For normally distributed data values are given as mean ± SD and for data that did not show... | PMC10645316 | |
Expression of different alleles in skeletal muscle | MINOR | Previous data have suggested that the rs2854464 polymorphism is located in a miR-24 binding site and that the major A allele has greater affinity for miR-24 leading to a reduction in ACVR1B mRNA. If this hypothesis was correct, it might be expected that there would be differential expression of the two ACVR1B alleles w... | PMC10645316 | |
Discussion | PROLIFERATION, GIANT, MINOR | These data show that males in the LACE cohort with at least one minor allele for either rs10783486 or rs2854464 were taller than those homozygous for the major allele and had more arm fat but we did not see any associations of these alleles with body composition in females. Previous studies have shown that polymorphism... | PMC10645316 | |
Limitations of the study | muscle mass, sarcopenia, appendicular muscle mass | RECRUITMENT, SARCOPENIA | This analysis is limited by the size of the study populations and by the lack of a control group of individuals of similar age who did not have sarcopenia. Both these limitations arise from the samples coming from the LACE clinical trial. Firstly, the trial was placebo-controlled trial within the sarcopenia population,... | PMC10645316 |
Conclusions | muscle mass, obesity, sarcopenic, sarcopenia, sarcopenic obesity | OBESITY, OBESE, SARCOPENIA | Our data suggest that polymorphisms in the activin I B receptor locus are associated with height and limb fat mass rather than muscle mass and strength in older men with sarcopenia. These findings are potentially of clinical significance; interventions that target the activin/myostatin pathway could potentially exert b... | PMC10645316 |
Supporting information | PMC10645316 | |||
All data used. | (XLSX)Click here for additional data file. | PMC10645316 | ||
SPSS statistics output from ANCOV analysis. | (XLSX)Click here for additional data file. | PMC10645316 | ||
Genotype frequencies in sarcopenia. | (DOCX)Click here for additional data file. | PMC10645316 | ||
Associations of rs10783846 with limb muscle mass in individuals in the LACE study. | MINOR | Arm and leg muscle masses were compared in males and females possessing the minor allele for rs10783846 with those homozygous for the major allele. Median arm muscle mass and leg muscle mass did not differ based on possession of the minor allele of rs10783846 in either gender.(TIF)Click here for additional data file. | PMC10645316 | |
Associations of rs2854464 with limb muscle mass in individuals in the LACE study. | MINOR | Arm and leg muscle masses were compared in males and females possessing the minor allele for rs2854464 with those homozygous for the major allele. Median arm muscle mass and leg muscle mass did not differ based on possession of the minor allele of rs2854464in either gender.(TIF)Click here for additional data file. | PMC10645316 | |
Association of polymorphisms in the ACVR1B locus with height and arm fat in the UK biobank study. | The UK biobank data set ((TIF)Click here for additional data file. | PMC10645316 | ||
eQTL analysis of rs2854464 and rs10783846 in skeletal muscle. | MINOR | The GTEx data set was analysed to determine whether either polymorphism showed differential expression. In skeletal muscle both minor alleles of rs2854464 and rs10783846 were more highly expressed than the major alleles. The data are shown in violin plot form taken from the GTEx portal.(TIF)Click here for additional da... | PMC10645316 | |
Tissue eQTL analysis of rs2854464. | The GTEx data set was analysed for eQTL associations with rs2854464. The strongest effects of the polymorphism on expression were observed in the lung and in skeletal muscle.(TIF)Click here for additional data file. | PMC10645316 | ||
STROBE statement—Checklist of items that should be included in reports of observational studies. | (DOCX)Click here for additional data file.(DOCX)Click here for additional data file.AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Healt... | PMC10645316 | ||
References | PMC10645316 | |||
Subject terms | knee osteoarthritis, human abuse, KOA | CHRONIC PAIN, KNEE OSTEOARTHRITIS | The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delt... | PMC10516978 |
Introduction | chronic pain, pain | ADVERSE EVENTS, ADVERSE EFFECTS, CHRONIC PAIN, DRUG EFFECT | The potential synergistic effects of combining cannabinoids and opioids for analgesia have drawn significant attention following preclinical evidence that cannabinoids and opioid combinations have additive nociceptive benefit with limited adverse effects [Evidence for the cannabinoid-opioid synergistic effects in human... | PMC10516978 |
Materials and methods | PMC10516978 | |||
Participants | KOA | Individuals with KOA were recruited between 11/2017 and 12/2020 using locally posted and online flyers and print/radio advertisements. A CONSORT flow diagram is depicted in Fig. | PMC10516978 | |
Study consort diagram. | A/E | ADVERSE EVENT | A/E adverse event. | PMC10516978 |
Study design and procedure | This Phase II study used a randomized, double-blind, placebo-controlled, within-subject study design. Potential participants completed a phone and in-person screening, during which they provided a urine sample that was tested for recent drug exposure and pregnancy (for premenopausal females) and were excluded if they r... | PMC10516978 | ||
Experimental study sessions | Eligible participants completed four experimental study sessions scheduled ≥7 days apart. All sessions started around 0800. Participants were asked to refrain from over-the-counter medications on session days and maintain steady doses of prescribed and non-contraindicated medications throughout participation. After pro... | PMC10516978 | ||
Measures | PMC10516978 |
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