The CLoCk study: A retrospective exploration of loneliness in children and young people during the COVID-19 pandemic, in England

by Kelsey McOwat, Snehal M. Pinto Pereira, Manjula D. Nugawela, Shamez N. Ladhani, Fiona Newlands, Terence Stephenson, Ruth Simmons, Malcolm G. Semple, Terry Segal, Marta Buszewicz, Isobel Heyman, Trudie Chalder, Tamsin Ford, Emma Dalrymple, Consortium , Roz Shafran

Background

During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness.

Methods and findings

Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness “Often/Always” and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28–3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3–4 siblings and lived in more deprived areas.

Conclusions

We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time.

A cohort study on the biochemical and haematological parameters of Italian blood donors as possible risk factors of COVID-19 infection and severe disease in the pre- and post-Omicron period

by Chiara Marraccini, Lucia Merolle, Davide Schiroli, Agnese Razzoli, Gaia Gavioli, Barbara Iotti, Roberto Baricchi, Marta Ottone, Pamela Mancuso, Paolo Giorgi Rossi

To investigate the association between biochemical and blood parameters collected before the pandemic in a large cohort of Italian blood donors with the risk of infection and severe disease. We also focused on the differences between the pre- and post-Omicron spread in Italy (i.e., pre- and post-January 01, 2022) on the observed associations. We conducted an observational cohort study on 13750 blood donors was conducted using data archived up to 5 years before the pandemic. A t-test or chi-squared test was used to compare differences between groups. Hazard ratios with 95% confidence intervals for SARS-CoV-2 infection and severe disease were estimated using Cox proportional hazards models. Subgroup analyses stratified by sex, age and epidemic phase of first infection (pre- and post-Omicron spread) were examined. We confirmed a protective effect of groups B and O, while groups A and AB had a higher likelihood of infection and severe disease. However, these associations were only significant in the pre-Omicron period. We found an opposite behavior after Omicron spread, with the O phenotype having a higher probability of infection. When stratified by variant, A antigen appeared to protect against Omicron infection, whereas it was associated with an increased risk of infection by earlier variants. We were able to stratify for the SARS CoV-2 dominant variant, which revealed a causal association between blood group and probability of infection, as evidenced by the strong effect modification observed between the pre- and post-Omicron spread. The mechanism by which group A acts on the probability of infection should consider this strong effect modification.

The effectiveness of nursing interventions in adherence to self‐care for preventing venous ulcer recurrence: A systematic literature review

Abstract

Venous ulcers affect up to 3% of the global population, with a high impact on economies and quality of life. This is exacerbated by its recurrence rates, which reach 70% at 12 months after healing. The perpetuation of these cycles of healing and recurrence is not interrupted or even attenuated by the self-care activities recommended and directed toward their prevention. In this context, we sought to identify the effectiveness of interventions that promote adherence to self-care to prevent venous ulcer recurrence. In August 2022, we conducted a literature search via EBSCO in the following databases: CINAHL Complete, MEDLINE Complete, Cochrane Database of Systematic Reviews, Scopus, and Web of Science. The inclusion criteria were researched in the form of randomised controlled trials or systematic literature reviews, and 99 studies were identified. During the different times of selection, four studies met the defined inclusion criteria and were included. As the main conclusions, the emphasis goes to the importance of the use of compression and the greater effectiveness of higher compression classes for the prevention of recurrence. Different educational methodologies seem to be important to increase knowledge about prevention, specifically regarding the aetiology of recurrence and the implementation of prevention measures.

Glutamate delta-1 receptor regulates oligodendrocyte progenitor cell differentiation and myelination in normal and demyelinating conditions

by Sukanya G. Gakare, Jay M. Bhatt, Kishore Kumar S. Narasimhan, Shashank M. Dravid

In this study, we investigated the role of glutamate delta 1 receptor (GluD1) in oligodendrocyte progenitor cell (OPC)-mediated myelination during basal (development) and pathophysiological (cuprizone-induced demyelination) conditions. Initially, we sought to determine the expression pattern of GluD1 in OPCs and found a significant colocalization of GluD1 puncta with neuron-glial antigen 2 (NG2, OPC marker) in the motor cortex and dorsal striatum. Importantly, we found that the ablation of GluD1 led to an increase in the number of myelin-associated glycoprotein (MAG+) cells in the corpus callosum and motor cortex at P40 without affecting the number of NG2+ OPCs, suggesting that GluD1 loss selectively facilitates OPC differentiation rather than proliferation. Further, deletion of GluD1 enhanced myelination in the corpus callosum and motor cortex, as indicated by increased myelin basic protein (MBP) staining at P40, suggesting that GluD1 may play an essential role in the developmental regulation of myelination during the critical window period. In contrast, in cuprizone-induced demyelination, we observed reduced MBP staining in the corpus callosum of GluD1 KO mice. Furthermore, cuprizone-fed GluD1 KO mice showed more robust motor deficits. Collectively, our results demonstrate that GluD1 plays a critical role in OPC regulation and myelination in normal and demyelinating conditions.

Determinants of academic achievement among higher education student found in low resource setting, A systematic review

by Chalachew Kassaw, Valeriia Demareva

Background

Academic success is a measure of students’ ability to attain their educational objectives, often assessed through regular evaluations or examinations. To establish effective policies and programs that align with academic accomplishments, conducting comprehensive data analysis is pivotal. Hence, this systematic review aimed to synthesize the factors impeding the academic achievements of Ethiopian students in higher education.

Methods

A comprehensive review was conducted on studies involving Ethiopian university students from 2013 to 2022. The review encompassed 24 papers that were gathered from different databases like PubMed, Google Scholar, African Journals Online, Scopus, and Web of Science.

Results

The findings of this research revealed that inadequate classroom environments, experiencing dysmenorrhea, and engaging in excessive social media usage were all linked to a decline in academic performance. Conversely, adopting healthy sleep habits, achieving high scores in entrance exams, and avoiding recent substance abuse were all factors positively influencing academic success. In addition, there was a positive correlation between academic excellence and being a health science college student and age range of 20 to 24 years old.

Conclusion

To enhance academic performance, it is crucial to address the negative factors identified, such as inadequate classroom environments, dysmenorrhea, and excessive social media usage, while promoting positive factors like healthy sleep habits, high scores in exams, and avoiding substance abuse. Additionally, being a health science college student and belonging to the age range of 20 to 24 were found to be associated with academic excellence.

Dietary replacement of soybean meal with black soldier fly larvae meal in juvenile <i>Labeo rohita</i> and <i>Catla catla</i>: Effects on growth, nutritional quality, oxidative stress biomarkers and disease resistance

by Shafaq Fatima, Ayesha Afzal, Hamna Rashid, Saba Iqbal, Rosheen Zafar, Komal Khalid, Ayman Rauf, Maryam Majeed, Aqsa Malik, Chris G. Carter

This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0

Intravenous acetaminophen for postoperative pain in the neonatal intensive care unit: A protocol for a pilot randomized controlled trial (IVA POP)

by Victoria Anne Archer, Samira Samiee-Zafarghandy, Forough Farrokyhar, Daniel Briatico, Luis H. Braga, J. Mark Walton

Background

In neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g.

Objective

The proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery.

Methods and design

This protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant’s gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well.

Conclusion

This external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment.

Trial registration

ClinicalTrials.gov NCT05678244, Registered December 6, 2022.

Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial

Introduction

Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.

Methods and analysis

This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg^-1 min^-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.

Ethics and dissemination

The trial protocol was approved by the local Institutional Review Board (#20–30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.

Trial registration number

ClinicalTrials.govNCT04901169

Incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first seven days in Northwest Ethiopia Comprehensive Specialized Hospitals, 2023: A retrospective follow-up study

Introduction

Respiratory distress syndrome is a catastrophic respiratory problem among low birth weight neonates. It increases the suffering of neonates and the economic expenditure of the countries. Notably, it is a major public health issue in low-income and middle-income countries such as Ethiopia. Despite this, studies regarding respiratory distress syndrome among low birth weight neonates were limited in Ethiopia.

Objective

To assess the incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first 7 days in Northwest Ethiopia Comprehensive Specialized Hospitals.

Method

Multicentred institution-based retrospective follow-up study was conducted from 19 September 2021 to 1 January 2023, among 423 low birthweight neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.6. and analysed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Weibull regression was carried out to identify predictors of respiratory distress syndrome. Statistical significance was declared at a p≤0.05.

Result

The incidence rate of respiratory distress syndrome was found to be 10.78 (95% CI 9.35 to 12.42) per 100 neonate days. Fifth minute Appearance, Pulse, Grimace, Activity, Respiration (APGAR score)

Conclusion

The incidence of respiratory distress syndrome was higher than other studies conducted on other groups of neonates. Multiple pregnancy, fifth minute APGAR score, caesarean section, prematurity, extremely low birth weight and very low birth weight were predictors of respiratory distress syndrome. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention for these predictors.

Protocol for a cluster randomised trial of a goal-oriented care approach for multimorbidity patients supported by a digital platform

Introduction

Health information systems represent an opportunity to improve the care provided to people with multimorbidity. There is a pressing need to assess their impact on clinical outcomes to validate this intervention. Our study will determine whether using a digital platform (Multimorbidity Management Health Information System, METHIS) to manage multimorbidity improves health-related quality of life (HR-QoL).

Methods and analysis

A superiority, cluster randomised trial will be conducted at primary healthcare practices (1:1 allocation ratio). All public practices in the Lisbon and Tagus Valley (LVT) Region, Portugal, not involved in a previous pilot trial, will be eligible. At the participant level, eligible patients will be people with complex multimorbidity, aged 50 years or older, with access to an internet connection and a communication technology device. Participants who cannot sign/read/write and who do not have access to an email account will not be included in the study. The intervention combines a training programme and a customised information system (METHIS). Both are designed to help clinicians adopt a goal-oriented care model approach and to encourage patients and carers to play a more active role in autonomous healthcare. The primary outcome is HR-QoL, measured at 12 months with the physical component scale of the 12-item Short Form questionnaire (SF-12). Secondary outcomes will also be measured at 12 months and include mental health (mental component Scale SF-12, Hospital Anxiety and Depression Scale). We will also assess serious adverse events during the trial, including hospitalisation and emergency services. Finally, at 18 months, we will ask the general practitioners for any potentially missed diagnoses.

Ethics and dissemination

The Research and Ethics Committee (LVT Region) approved the trial protocol. Clinicians and patients will sign an informed consent. A data management officer will handle all data, and the publication of several scientific papers and presentations at relevant conferences/workshops is envisaged.

Trial registration number

NCT05593835.

Traditional management of female infertility in Africa: a scoping review protocol

Introduction

Infertility adversely affects the sexual reproductive health and overall quality of life of people. Recent estimates show that about one in six people (both men and women) experience infertility in their lifetime. This scoping review will, therefore, map the existing evidence on traditional management of female infertility in Africa including the effectiveness of the traditional healthcare systems, to inform policy and practice.

Methods

The scoping review will be guided by the Arksey and O’Malley framework in conjunction with the Joanna Briggs Institute updated methodological guidance for scoping reviews. A search strategy will be developed, which will target the following databases: PubMed, Scopus, Embase, CINAHL, Google Scholar and Africa-Wide Information including grey literature. The screening of titles, abstracts and full text will be done by two independent reviewers. Data will be extracted, analysed numerically and thematically. The reporting of the scoping review will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist.

Ethics and dissemination

This scoping review will not require ethical approval as this is secondary analysis of peer-reviewed articles. The findings of the review will be disseminated on various platforms including conferences, meetings to key stakeholders and in a peer-reviewed journal for wider sharing.

Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach

by Katayi Mwila-Kazimbaya, Samuel Bosomprah, Obvious Nchimunya Chilyabanyama, Caroline Cleopatra Chisenga, Mwelwa Chibuye, Natasha Makabilo Laban, Michelo Simuyandi, Bert Huffer Jr, Miren Iturriza-Gomara, Robert K. M. Choy, Roma Chilengi

Background

Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach.

Methods

Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers.

Results

Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only.

Conclusion

MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.

Two mouse models of Alzheimer’s disease accumulate amyloid at different rates and have distinct Aβ oligomer profiles unaltered by ablation of cellular prion protein

by Silvia A. Purro, Michael Farmer, Elizabeth Noble, Claire J. Sarell, Megan Powell, Daniel Yip, Lauren Giggins, Leila Zakka, David X. Thomas, Mark Farrow, Andrew J. Nicoll, Dominic Walsh, John Collinge

Oligomers formed from monomers of the amyloid β-protein (Aβ) are thought to be central to the pathogenesis of Alzheimer’s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrP^C) is now an established receptor for Aβ oligomers. However, studies of the Aβ-PrP^C interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrP^C ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrP^C, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aβ oligomers, which did not interact with PrP^C when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aβ assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aβ oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aβ toxicity mediated by PrP^C.

Associations of production characteristics with the on-farm presence of <i>Fasciola hepatica</i> in dairy cows vary across production levels and indicate differences between breeds

by Andreas W. Oehm, Yury Zablotski, Martina Hoedemaker, Amely Campe, Christina Strube, Daniela Jordan, Andrea Springer, Markus Klawitter, Gabriela Knubben-Schweizer

Fasciola hepatica is one of the economically most important endoparasites in cattle production. The aim of the present work was to evaluate the relevance of production level on the associations of on-farm presence of F. hepatica with farm-level milk yield, milk fat, and milk protein in Holstein cows, a specialised dairy breed, and in Simmental cows, a dual purpose breed. Furthermore, we investigated whether differential associations were present depending on breed. Data from 560 dairy farms across Germany housing 93,672 cows were analysed. The presence of F. hepatica antibodies was determined via ELISA on bulk tank milk samples. Quantile regression was applied to model the median difference in milk yield, milk fat, and milk protein depending on the interaction of breed and fluke occurrence. Whereas a reduction in milk yield (-1,206 kg, p F. hepatica positive German Holstein farms, only milk fat (-33.8 kg, p = 0.01) and milk protein (-22.6 kg, p = 0.03) were affected on F. hepatica positive German Simmental farms. Subsequently, production traits were modelled within each of the two breeds for low, medium, and high producing farms in the presence of F. hepatica antibodies and of confounders. On Holstein farms, the presence of F. hepatica seropositivity was associated with lower production, while on German Simmental farms such an association was less evident. This work demonstrates that production level is relevant when assessing the associations between the exposure to F. hepatica with production characteristics. Moreover, both models indicate a breed dependence. This could point towards a differential F. hepatica resilience of specialised dairy breeds in comparison with dual purpose breeds.

Experience and impact of gender-based violence in Honiara, Solomon Islands: a cross-sectional study recording violence over a 12-month period

Objective

This study aims to collect data on the experience and impact of gender-based violence experienced by women attending health clinics in Honiara, Solomon Islands.

Method

Any woman over the age of 18 who attended a local health clinic in Honiara, Solomon Islands during the time of recruitment (ten consecutive weekdays in May 2015) was eligible to participate in an interviewer administered, in-person survey, gathering data on gender-based violence over the past 12 months.

Results

A total of 100 women were recruited into this study. Of these women, 47% of women reported experiencing physical or sexual violence in the past 12 months. The most common perpetrators were the woman’s husband or boyfriend. There are low rates of reporting, particularly through formal avenues such as to police or village leaders. Alcohol was involved in more than half the cases of reported violence.

Conclusion

Women in this study report high rates of gender-based violence. To our knowledge, this is the only study examining women’s personal experience of gender-based violence in the Solomon Islands, with self-reported data on the frequency and nature of the violence, and the impact on women, including physical and mental, utilisation of healthcare services, police and legal involvement. Efforts to reduce gender-based violence should aim to reduce intimate partner violence, increase reporting and address wider social attitudes towards gender equality.

Individual, family, and environmental determinants of vision-related quality of life of children and young people with visual impairment

by Ana Šemrov, Valerija Tadić, Mario Cortina-Borja, Jugnoo Sangeeta Rahi, on behalf of The Resilience and Childhood Visual Impairment Study Group

Childhood visual impairment can have a significant impact on an individual’s development. To improve clinical care and develop appropriate psychosocial interventions of these patients, it is necessary to understand the contributing and modifiable factors that both identify individuals in greater need and could be targeted in interventions. Here we investigate the broader individual, family, and environmental factors associated with vision-related quality of life (VQoL) of children and young people with visual impairment (CYP-VI). Data for this cross-sectional study were collected from September 2014 to May 2017 to develop and validate two vision-specific patient-reported outcome measures (PROMs) for CYP-VI. Patients were recruited from 22 hospitals in the United Kingdom and were aged 7–18 years with visual impairment as per WHO criteria. Participants self-completed the two PROMs, VQoL and Functional Vision Questionnaires. Clinical characteristics were extracted from medical records. Their carers provided information on family sociodemographic backgrounds. Associations between the VQoL scores and other factors were examined using Spearman’s correlation, Kruskal-Wallis, Wilcoxon rank-sum tests, and quantile regression models. The sample consisted of 152 CYP-VI (67 females). Better VQoL was significantly associated with better functional vision overall (r_Spearman = –0.52), parent-reported absence of additional chronic conditions (d_Cohen = 0.46), attending mainstream (versus other) school (d_Cohen = 0.44), higher socio-economic status (r_Spearman = 0.17) and higher parental education level (r_Spearman = 0.20). No other investigated factors were significantly associated with VQoL. The final quantile regression model included functional vision scores and the presence of additional health condition. Variation in self-reported VQoL in CYP-VI can be partly accounted for by factors relating to the clinical status of the affected child and, more importantly, by non-health-related factors. This needs to be considered in clinical practice when assessing vision-specific outcomes and providing support to CYP-VI, as well as in the development of future interventions.

Study of heavy metal resistance genes in <i>Escherichia coli</i> isolates from a marine ecosystem with a history of environmental pollution (arsenic, cadmium, copper, and mercury)

by Ashley S. Tseng, Marilyn C. Roberts, Scott J. Weissman, Peter M. Rabinowitz

We analyzed whole genome sequences of 308 Escherichia coli isolates from a marine ecosystem to determine the prevalence and relationships of heavy metal resistance genes (HMRGs) and antibiotic resistance genes (ARGs), as well as the presence of plasmid sequences. We screened all genomes for presence of 18 functional HMRGs conferring resistance to arsenic, cadmium, copper, or cadmium/mercury. In subset analyses, we examined geographic variations of HMRG carriage patterns in 224 isolates from water sources, and sought genetic linkages between HMRGs and ARGs in 25 genomes of isolates resistant to antibiotics. We found high carriage rates of HMRGs in all genomes, with 100% carrying at least one copy of 11 out of 18 HMRGs. A total of 173 (56%) of the isolates carried both HMRGs and plasmid sequences. In the 25 genomes of antibiotic-resistant isolates, 80% (n = 20) carried HMRGs, ARGs, and plasmid sequences, while 40% (n = 10) had linked HMRGs and ARGs on their assembled genomes. We found no evidence of geographic variation in HMRG frequency, nor any association between locational proximity to Superfund sites and co-carriage of HMRGs and ARGs. Our study findings indicate that HMRGs are common among E. coli in marine ecosystems, suggesting widespread heavy metal presence in water sources of a region with history of environmental pollution. Further research is needed to determine the role HMRGs play in driving antimicrobial resistance in human pathogens through genetic linkage and the value their detection in environmental bacterial genomes may offer as an indicator of environmental heavy metal pollution.

In silico exploration of <i>Serratia</i> sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin

by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn’s disease on biological therapy with TNFα inhibitors–A single center study

by Martin Wasserbauer, Sarka Mala, Katerina Stechova, Stepan Hlava, Pavlina Cernikova, Jan Stovicek, Jiri Drabek, Jan Broz, Dita Pichlerova, Barbora Kucerova, Petra Liskova, Jan Kral, Lucia Bartuskova, Radan Keil

Objective

Crohn’s disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy.

Material and methods

A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy.

Results

Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn’s Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test).

Conclusions

This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

Effects of 36 hours of sleep deprivation on military-related tasks: Can ammonium inhalants maintain performance?

by Jan Maleček, Dan Omcirk, Kateřina Skálová, Jan Pádecký, Martin Tino Janikov, Michael Obrtel, Michal Jonáš, David Kolář, Vladimír Michalička, Karel Sýkora, Michal Vágner, Lubomír Přívětivý, Tomáš Větrovský, Zdeňka Bendová, Vít Třebický, James J. Tufano

Introduction

A lack of sleep can pose a risk during military operations due to the associated decreases in physical and cognitive performance. However, fast-acting ergogenic aids, such as ammonia inhalants (AI), may temporarily mitigate those adverse effects of total sleep deprivation (TSD). Therefore, the present study aimed to investigate the acute effect of AI on cognitive and physical performance throughout 36 hours of TSD in military personnel.

Methods

Eighteen male military cadets (24.1 ± 3.0 y; 79.3 ± 8.3 kg) performed 5 identical testing sessions during 36 hours of TSD (after 0 [0], 12 [–12], 24 [–24], and 36 [–36] hours of TSD), and after 8 [+8] hours of recovery sleep. During each testing session, the following assessments were conducted: Epworth sleepiness scale (ESS), simple reaction time (SRT), shooting accuracy (SA), rifle disassembling and reassembling (DAS), and countermovement jump height (JH). Heart rate (HR) was continuously monitored during the SA task, and a rating of perceived exertion (RPE) was obtained during the JH task. At each time point, tests were performed twice, either with AI or without AI as control (CON), in a counterbalanced order.

Results

There was faster SRT (1.6%; p 0.05). Independent of AI, the SRT was slower (3.2–9.3%; p Conclusion

Although there were detrimental effects of TSD, the usage of AI did not reduce those adverse effects. However, regardless of TSD, AI did result in a short-term increase in HR, improved SRT without affecting the number of errors, and improved JH while concurrently decreasing the RPE. No changes, yet, were observed in SA and DAS. These results suggest that AI could potentially be useful in some military scenarios, regardless of sleep deprivation.