title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Participants | SECONDARY | We performed a monocenter, single-blind randomized, placebo-controlled trial comparing cognitive training to concurrent anodal tDCS (target intervention) with cognitive training to concurrent sham tDCS (control intervention), registered at ClinicalTrial.gov (Identifier NCT03838211). The primary outcome (performance in ... | PMC10238397 | |
Cognitive training with concurrent tDCS | Cognitive training consisted of a letter updating task | PMC10238397 | ||
MRI data acquisition | MR images were acquired at the Baltic Imaging Center (Center for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald) on a 3-T Siemens verio scanner (SIEMENS MAGNETOM Verio syngo MR B17) using a 32-channel head coil. Resting-state fMRI scans were acquired using an echo-planar-imaging sequence (3 × 3... | PMC10238397 | ||
MRI data analyses | PMC10238397 | |||
Structural T1-weighted images and DTI analysis | T1 and DTI data were processed by Freesurfer version 6 (Regional volumes were extracted for the ROI corresponding to the stimulation target (i.e., left middle frontal gyri from the Desikan-Killiani atlasDTI data preprocessing included eddy current and head motion correction using an automated affine registration algori... | PMC10238397 | ||
Statistical analyses | To assess the statistical significance of differences in microstructural MRI markers between stimulation conditions, R | PMC10238397 | ||
Reporting summary | Further information on research design is available in the | PMC10238397 | ||
Supplementary information |
Supplementary InformationPeer Review FileReporting Summary | PMC10238397 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41467-023-38910-x. | PMC10238397 | ||
Acknowledgements | Research reported in this publication was supported by the Bundesministerium für Bildung und Forschung, Grant/Award Number: 01GQ1424A (AF); the Deutsche Forschungsgemeinschaft, Grant/Award Numbers: 327654276 - SFB1315 (A.F.) and INST 292/155-1 FUGG. The funders had no role in the design and conduct of the study; collec... | PMC10238397 | ||
Author contributions | D.A. and A.F. conceived the study and designed the experiments; F.T. performed the experiments and collected the MR data; D.A. supervised data collection; D.A., F.T., and A.E.F. processed the MR data; D.A. and A.E.F. analyzed the data and prepared the figures; D.A. prepared the brain images. D.A. and U.G. performed sta... | PMC10238397 | ||
Peer review | PMC10238397 | |||
Funding | Open Access funding enabled and organized by Projekt DEAL. | PMC10238397 | ||
Data availability | The processed data of this study are available upon request from the corresponding author. The raw data are not publicly available due to potential identifying information that could compromise participant privacy. Source data are provided with the paper, where the relevant data from each figure or table is represented... | PMC10238397 | ||
Code availability | All analyses were performed using the available toolboxes: R version 4.1.2 ( | PMC10238397 | ||
Competing interests | The authors declare no competing interests. | PMC10238397 | ||
References | PMC10238397 | |||
Objective | PT/LBW, LBW, stunting | SPM-H and PO are joint first authors.Data on long-term outcomes of preterm (PT) and low birth weight (LBW) infants in countries with high rates of neonatal mortality and childhood stunting are limited, especially from community settings. The current study sought to explore growth and neurodevelopmental outcomes of PT/L... | PMC10476111 | |
Design | Cross-sectional study. | PMC10476111 | ||
Setting | Migori County, Kenya. | PMC10476111 | ||
Participants | PT/LBW | Three hundred and eighty-two PT/LBW infants (50.2% of those identified as eligible) from a cluster randomised control trial evaluating a package of facility-based intrapartum quality of care interventions for newborn survival consented for follow-up. | PMC10476111 | |
Outcome measures | REGRESSION | Caregiver interviews and infant health, growth and neurodevelopmental assessments were completed at 6, 12 or 18 months±2 weeks. Data included sociodemographic information, medical history, growth measurements and neurodevelopmental assessment using the Ten Questions Questionnaire, Malawi Developmental Assessment Tool a... | PMC10476111 | |
Results | Neurodevelopmental delays | MALNOURISHED, CEREBRAL PALSY | The final sample included 362 PT/LBW infants, of which 56.6% were moderate to late PT infants and 64.4% were LBW. Fewer than 2% of parents identified their child as currently malnourished, but direct measurement revealed higher proportions of stunting and underweight than in national demographic and health survey repor... | PMC10476111 |
Conclusions | Malnutrition, PT/LBW, neurodevelopmental delays | MALNUTRITION | Malnutrition and neurodevelopmental delays are common among PT/LBW infants in this setting. Close monitoring and access to early intervention programmes are needed to help these vulnerable infants thrive. | PMC10476111 |
STRENGTHS AND LIMITATIONS OF THIS STUDY | LBW, disability, neurodevelopmental delays | This study used directly administered, standardised neurodevelopmental assessment tools to enhance evaluation at the community-level.The sample included largely moderate to late preterm (PT) infants, with predominately normal or low birth weight (LBW), as opposed to very or extremely PT/LBW infants and, therefore, may ... | PMC10476111 | |
Introduction | deaths, PT/LBW, LBW | COMPLICATIONS | Complications associated with preterm (PT) birth and low birth weight (LBW) contribute to 25%–50% of all neonatal deaths and 12% of under-5 mortality worldwide.Data from community-based PT/LBW samples in areas without NICUs are extremely limited, meaning outcomes of the majority of PT/LBW infants born in low- or middle... | PMC10476111 |
Materials and methods | PMC10476111 | |||
Design | MAY | This cross-sectional study was conducted between October 2018 and May 2019 among a subset of mothers and babies previously enrolled in PTBi-K, a cluster randomised control trial (cRCT) of a package of interventions to improve quality of care during labour and the immediate postnatal period and evaluate the intervention... | PMC10476111 | |
Setting | The current study was conducted in Migori County, Kenya. The county is mostly rural, has poor access to healthcare and has higher infant and under-5 mortality than national statistics (50 vs 39 per 1000 live births, and 82 vs 52 per 1000 live births, respectively). | PMC10476111 | ||
Study participants and sampling strategy | LBW | RECRUITMENT | Participants in the parent cRCT were identified from maternity registers. Eligible participants were LBW (<2500 g at birth) or PT (gestational age <37 weeks with birth weight <3000 g) infants delivered at one of 17 facilities across the county. A list of potentially eligible infants, alive at 28 days and approaching 6,... | PMC10476111 |
Procedures | illnesses and simple games, malnutrition | HEARING IMPAIRMENT, RECRUITMENT, BLIND, MALNUTRITION | Caregivers of eligible infants were contacted via phone, and a standard participation invitation script was used to explain the study. Appointments were scheduled at a study facility nearest the family’s home. All consent forms and questionnaires were translated and back translated from English to Kiswahili and Dholuo.... | PMC10476111 |
Patient and public involvement | neurodevelopmental delays | For the larger parent study in which participants were involved, national and community advisory boards provided input on intervention priorities. Health facility providers, managers and local authorities were involved in implementation activities and influenced the focus and content of those activities based on their ... | PMC10476111 | |
Statistical analysis | anaemia, scabies, convulsions, congenital cataract, abscess, skin infection, Overweight WLZ>2, thrush, malnutrition, dermatitis | ANAEMIA, SCABIES, OBESE, ABSCESS, SKIN INFECTION, OTITIS MEDIA, THRUSH, MALNUTRITION, REGRESSION, DERMATITIS | Analyses involved the use of descriptive statistics, as well as univariate regression models. Descriptive statistics involved the use of frequencies and proportions for categorical variables, and mean, median, range, IQR and SD for continuous variables. Sociodemographic and clinical factors associated with neurodevelop... | PMC10476111 |
Results | death | Of 761 eligible infants, 564 (74.1%) of caregivers were located. A total of 28 infants (3.7% of eligible) had died after 28 days of life and prior to study contact. While the specific causes of death for these infants are not known, a larger verbal and social autopsy study of the full parent study sample was conducted.... | PMC10476111 | |
Characteristics at delivery and immediate postnatal period | Most babies were female (60.2%) and moderate to late PT (56.6%, >32 weeks’ gestation; median gestational age and range=36.3 weeks (22.0–41.7)). Of infants born PT, 66.1% were late PT (34 to <37 weeks), 17.6% were moderate PT (32 to <34 weeks), 13.9% were very PT (28 to <32) and only 2.5% were extremely PT (22 to <28). ... | PMC10476111 | ||
Growth and health | malaria, febrile illness | MALARIA, RESPIRATORY TRACT INFECTIONS, FEBRILE ILLNESS | Anthropometric measurement and caregiver-reported health findings are in Univariate analyses for malnutrition***P value <0.001.**P value <0.01.*P value <0.05.PF: no variability due to low numbers causes the model to perfectly predict failure or success.HINE, Hammersmith Infant Neurological Examination; MDAT, Malawi Dev... | PMC10476111 |
Neurodevelopment | Neurodevelopmental | Delays on one or more of the standardised neurodevelopmental assessment tools were identified in 8.6% of infants (Neurodevelopmental outcomes*A fail score on the total MDAT can occur with a fail in any one or more subscales, thus this number does not represent the sum of children failing on the domain scores.†Neurodeve... | PMC10476111 | |
Discussion | illness, malaria, PT/LBW, motor disability, acute illness, cerebral palsy, malnutrition, disability | MALARIA, RECRUITMENT, FEBRILE ILLNESS, NEONATAL ENCEPHALOPATHY, CEREBRAL PALSY, MALNUTRITION | This study describes growth and neurodevelopmental outcomes for a rural community sample of PT/LBW survivors. Infants were similar in gestational age to other community-based samples from countries with NMR>5 and constituted a relatively low-risk sample of PT/LBW infants compared with high-resource contexts or LMIC set... | PMC10476111 |
Conclusion | wasting, disability | WASTING | The current study adds to very limited community-based literature on PT/LBW infants born in countries with high NMR and suggests higher than background rates of wasting and underweight, high rates of parental concern for development, and a clinically impactful number of children with neurodevelopmental delay or risk fo... | PMC10476111 |
Supplementary Material | PMC10476111 | |||
Reviewer comments | PMC10476111 | |||
Data availability statement | Data are available upon reasonable request. | PMC10476111 | ||
Ethics statements | PMC10476111 | |||
Patient consent for publication | Not applicable. | PMC10476111 | ||
Ethics approval | This study involves human participants and was approved by University of California San Francisco Institutional Review Board (IRB #: 18-25555) and Scientific and Ethics Review Unit (SERU) of the Kenya Medical Research Institute (KEMRI) #KEMRI/SERU/CCR/0104/3668. Written authorisation was obtained from the Migori County... | PMC10476111 | ||
References | PMC10476111 | |||
Background | Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infant’s neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal me... | PMC10413600 | ||
Method | depression, PTSD, perinatal post-traumatic stress disorder | This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. | PMC10413600 | |
Results | depression, NICU stress, PTSD | 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received ... | PMC10413600 | |
Conclusion | depression, PTSD | Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms. | PMC10413600 | |
Keywords | PMC10413600 | |||
Introduction | critically ill, pain | CRITICALLY ILL | Parents provide essential caregiving support for preterm infants admitted to neonatal intensive care units (NICU) to promote infant growth and development, including breastfeeding, skin-to-skin contact, developmentally supportive care, positive sensory stimulation, pain management and massage [Family-Integrated Care (F... | PMC10413600 |
Methods | SECONDARY | This analysis of pre-defined secondary aims was part of a larger quasi-experimental, time-lagged non-randomized intervention trial of the mFICare intervention compared with FCC (NCT03418870; 01/02/2018) [ | PMC10413600 | |
Participants | congenital anomaly | Parents/primary caregivers of infants born ≤ 33 weeks gestation were invited to participate. Participants were excluded if: (1) the parent was not English literate, < 18 years of age, or had no smart phone or tablet access; or (2) the infant had a life-threatening congenital anomaly or was receiving palliative care. Pa... | PMC10413600 | |
Intervention | RECRUITMENT | Parents of current and former NICU patients and NICU healthcare professionals were extensively involved in the design of the trial and the adaptation of the FICare intervention to the local settings. Parents also co-designed and pilot-tested a mobile app for parents. Details of the FCC and mFICare interventions are pro... | PMC10413600 | |
Measures | depression, Depression, PTSD | The primary outcomes for this analysis were maternal symptoms of perinatal PTSD and depression measured at least three months after the infant’s NICU discharge. The Perinatal PTSD Questionnaire (PPQ) [Maternal depression was assessed by self-report using the Edinburgh Postnatal Depression Scale (EPDS) [We examined four... | PMC10413600 | |
Statistical analysis | REGRESSION | Analyses were performed using R v4.1 [We tested for associations between PPQ and EPDS scores (log-transformed) and intervention group using a linear regression model. We first tested for main effects of the intervention. We adjusted for additional covariates using a hybrid approach, forcing in site, and then using a ba... | PMC10413600 | |
Results | PMC10413600 | |||
Sample characteristics | Stress Disorder, Depression, PTSD | Of the 237 mothers enrolled in the study between April, 2017 and June, 2020, 178 (75%; 89 FCC, 89 mFICare) completed PPQ and EPDS measures a mean of 4.2 (SD 1.9) months after their infant’s NICU discharge and were included in this analysis (Fig. Maternal characteristics are summarized in Table
Participant flow diagram... | PMC10413600 | |
Measures of maternal mental health by intervention group | Measures of maternal mental health for each intervention group are shown in Table | PMC10413600 | ||
Main intervention effects and moderators | Stress Disorder, depression, Depression, PTSD | INTERACTION | As shown in Table Of the four potential moderators evaluated, there was no evidence that the intervention was differentially associated with the infant’s gestational age, infant age when mFICare was started, or whether the infant was discharged on a feeding and/or respiratory device (tested with an interaction effect, ... | PMC10413600 |
Per protocol analyses | β=-1.09, PTSD, Stress Disorder, depression, Depression | INTERACTION | Per protocol analyses were conducted to determine whether specific intervention components were differentially associated with maternal mental symptoms based on the mother’s level of NICU-related stress (i.e., an interaction effect with NICU-related stress). For mothers who experienced high levels of NICU-related stres... | PMC10413600 |
Discussion | PTSD | RECRUITMENT | Worldwide, approximately 25% of NICU parents report clinically significant PTSD symptoms [Previous studies have tended to focus on specific parent-focused therapies, for example trauma-focused therapy for PTSD [
It is now widely recognized that comprehensive perinatal care must include preventative parental mental heal... | PMC10413600 |
Acknowledgements | PRETERM BIRTH |
The authors are grateful for the support of the research team from each site, all the staff and parents who participated in the research and for the valuable partnership of the UCSF California Preterm Birth Initiative Parent Clinician Advisory Board. | PMC10413600 | |
Authors’ contributions |
LF conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. RK coordinated data acquisition, conducted data curation and provided project administration and critically reviewed the manuscript for important intellectual content. CD, PJ, RB contributed to conceptual... | PMC10413600 | ||
Funding | PRETERM BIRTH | University of California, San Francisco, California Preterm Birth Initiative, funded by Marc and Lynne Benioff. | PMC10413600 | |
Data Availability | Deidentified data will be shared upon reasonable request directed to Linda S. Franck (linda.franck@ucsf.edu) from qualified investigators beginning 6 months and ending 5 years after publication. | PMC10413600 | ||
Declarations | PMC10413600 | |||
Ethics approval and consent to participate |
All study procedures were performed in accordance with the Declaration of Helsinki and were approved by the Institutional Review Boards at the University of California, San Francisco (16-19542) and participating hospitals. Written informed consent was obtained from all parents/legal guardians for their participation a... | PMC10413600 | ||
Consent for publication | N/A. | PMC10413600 | ||
Competing interests | The authors declare no competing interests. | PMC10413600 | ||
References | PMC10413600 | |||
Results | PMC10471167 | |||
RBCs release a cardioprotective factor during hypoxia. | hypoxia, ischemia | HYPOXIA, ISCHEMIA | First, we investigated whether RBCs exposed to hypoxia release a cardioprotective mediator by administration of RBC supernatant to an isolated heart subjected to global IR. To this end, the supernatant collected from mouse RBCs exposed to normoxia or hypoxia was given to mouse hearts at the onset of ischemia. The super... | PMC10471167 |
The cardioprotective effect of hypoxia is mediated by RBC sGC and export of cGMP. | hypoxia, IR injury | HYPOXIC, HYPOXIA | Having determined that a cardioprotective factor was released from RBCs during hypoxia, we next sought to determine the nature of this compound. The focus was directed toward sGC-cGMP as this pathway has been shown to be present in RBCs. To determine the involvement of sGC, we exposed RBCs collected from mice lacking t... | PMC10471167 |
Dietary nitrate augments RBC-induced hypoxic cardioprotection. | Inorganic nitrate can be reduced to nitrite and deoxygenated hemoglobin can further reduce nitrite to NO (To identify the mechanism by which nitrate induces protection via RBCs, we again focused on the sGC-cGMP pathway. In these experiments, control RBCs collected from mice given normal drinking water (vehicle) or nitr... | PMC10471167 | ||
Cardiac protection of RBCs is PKG-dependent. | hypoxia | HYPOXIA | After having established the signaling pathway in RBCs under hypoxia and following nitrate administration, we investigated the downstream signaling in the heart focusing on protein PKG, the major target of cGMP. In these experiments we used 2 distinct inhibitors of PKG. In a first set of experiments, the inhibitor of c... | PMC10471167 |
Pharmacological sGC stimulation in RBCs also induces cardioprotection and cGMP release. | hypoxia | HYPOXIA | To verify that pharmacological activation of RBC sGC produce effects similar to those of hypoxia, RBCs from WT and sGC-KO mice were preincubated with the sGC stimulator BAY 41-2272 in combination with the NO donor DEA/NO and the PDE5 inhibitor sildenafil before administration to the isolated heart. Preincubation of RBC... | PMC10471167 |
RBCs from nitrate-treated humans induce cardioprotection. | To translate the beneficial effect of nitrate administration in mice to the clinical situation, RBCs were collected from 3 groups of subjects randomized to a 5-week dietary intervention: 2 groups with high nitrate in the form of a potassium nitrate pill or nitrate-rich vegetables and 1 group receiving a low dietary int... | PMC10471167 | ||
Discussion | cardiac IR injury, hypoxia, hypertension, IR injury | ACUTE MYOCARDIAL INFARCTION, MYOCARDIAL INFARCTION, HYPOXIA, HYPOXIC, VASODILATATION, EVENTS, HYPERTENSION | Here, we show that RBCs under hypoxic conditions induce cardioprotection through a mechanism that is dependent on sGC in the RBC and associated with export of cGMP that, via a paracrine effect, is involved as a mediator of the cardioprotection through activation of PKG in the heart. This cardioprotective effect is boos... | PMC10471167 |
Methods | PMC10471167 | |||
Animals. | Wistar rats were purchased from Charles River and used for experiments at 12 to 14 weeks of age. C57Bl/6J mice were purchased from Janvier and used for experiments at 8 to 15 weeks of age. Mice lacking the α1-subunit of sGC — and thus α1β1-sGC (α1-GC KO mice) — were generated and genotyped as described previously ( | PMC10471167 | ||
Heart isolation and perfusion. | Isolated hearts from rats (for human RBCs) or mice (for mouse RBCs) were perfused in a Langendorff system as described previously in detail ( | PMC10471167 | ||
RBC isolation. | Heparinized blood from mice and humans was centrifuged at 1,000 | PMC10471167 | ||
Supernatant of RBCs. | hypoxia | HYPOXIA | The RBCs suspension was exposed to hypoxia (1% O | PMC10471167 |
Nitrate treatment in mice. | C57Bl/6J mice at age of 8 weeks were housed under standard environmental conditions (room temperature at 22 | PMC10471167 | ||
Experimental protocol. | ischemia | ISCHEMIA | After the start of perfusion, all hearts were allowed to stabilize for at least 30 minutes and baseline LVDP was registered. The duration of global ischemia, induced by clamping the inflow tubing, was 40 minutes for mouse hearts and 25 minutes for rat hearts (Additional experiments were performed using pharmacological ... | PMC10471167 |
Clinical study protocol. | hypertension | HYPERTENSION | Patients were recruited as a substudy of a double-blinded clinical trial investigating the effect of dietary nitrate on blood pressure in patients with mild hypertension (clinicaltrials.gov NCT02916615). The clinical trial was described in detail previously ( | PMC10471167 |
Determination of heart infarct size. | Necrotic | NECROTIC | At the end of reperfusion, hearts were frozen at –20°C and sectioned into 1 mm–thick slices from the apex to the base, stained with triphenyltetrazolium chloride for 15 minutes, and fixed in 1% formaldehyde for 18 hours. Necrotic negatively stained myocardium was measured using Adobe Photoshop Elements 2019 Edition by ... | PMC10471167 |
Expression of cardiac vasodilator specific phosphoprotein. | ischemia | HYPOXIC, ISCHEMIA | In separate experiments, isolated and perfused mouse hearts were subjected to 5 minutes of ischemia following 30 minutes of stabilization. The supernatant from hypoxic or normoxic mouse RBCs was given to the isolated heart at the start of ischemia. After 1 minute reperfusion, the hearts were harvested using liquid nitr... | PMC10471167 |
Cyclic GMP detection in supernatant of RBCs. | hypoxia | HYPOXIA | Mouse RBC suspension (hematocrit about 70%) was exposed to hypoxia (1% O | PMC10471167 |
Statistics. | infarct | INFARCT | LVDP during reperfusion is expressed as a percentage of the preischemic values. The differences in functional cardiac parameters were analyzed by 2-way ANOVA followed by Tukey’s multiple comparison test. Differences in infarct size were analyzed using 1-way ANOVA followed by Tukey’s multiple comparison test or Kruskal-... | PMC10471167 |
Study approval. | All animal experiment protocols were approved by the Ethical Committee of Stockholm and conform to the Guide for the Care and Use of Laboratory Animals published by the United States National Institute of Health (NIH publication No. 85-23, revised 1996). All procedures involving humans were conducted according to the D... | PMC10471167 | ||
Author contributions | JP | JY, EW, JOL, and JP conceived and designed the study. JY and TJ performed and collected research data. JY and JP analyzed research data and performed statistical analysis. MLS, EW, JOL, and JP recruited patients and collected samples. JY, JOL, and JP wrote the manuscript. XZ, TJ, AC, YT, AM, JT, EM, SBC, ZZ, MMCK, TA, ... | PMC10471167 | |
Supplementary Material | PMC10471167 | |||
Supplemental data | PMC10471167 | |||
09/01/2023 | Electronic publication | PMC10471167 | ||
09/06/2023 | Term clarification on page 7 | PMC10471167 | ||
RBCs release a cardioprotective factor during hypoxia. | ( | PMC10471167 | ||
Hypoxia-induced release of cardioprotective cGMP from RBCs. | ( | PMC10471167 |
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