bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between psychological wellbeing, depression, general anxiety, perceived social support, tooth brushing frequency and oral ulcers among adults resident in Nigeria during the first wave of the COVID-19 pandemic
Authors: Folayan Morenike Oluwatoyin , Ibigbami Olanrewaju Ibikunle , Oloniniyi Ibidunni Olapeju , Oginni Olakunle , Aloba Olutayo
Published: October 2021

Introduction

The aims of this study were to determine the associations between psychological wellbeing, and the frequency of tooth brushing and presence of oral ulcers during the COVID-19 pandemic; and to identify the mediating roles of psychological distress (general anxiety and depression) and perceived social support in the paths of observed associations.

Methods

This cross-sectional study recruited 996 adults in Nigeria between June and August 2020. Data collected through an online survey included outcome variables (decreased frequency of tooth brushing and presence of oral ulcers), explanatory variable (psychological wellbeing), mediators (general anxiety symptoms, depression symptoms and perceived social support) and confounders (age, sex at birth, educational and employment status). Multivariate logistic regression was used to determine the risk indicators for the outcome variables. A path analysis was conducted to identify the indirect effect of mediators on the association between the outcome and explanatory variables.

Results

Of the 966 respondents, 96 (9.9%) reported decreased tooth-brushing frequency and 129 (13.4%) had oral ulcers during the pandemic. The odds of decreased tooth-brushing during the pandemic decreased as the psychological wellbeing increased (AOR: 0.87; 95% CI: 0.83–0.91; p < 0.001) and as generalized anxiety symptoms increased (AOR: 0.92; 95% CI: 0.86–0.98; p = 0.009). The odds of having an oral ulcer was higher as the generalized anxiety symptoms increased (AOR: 1.15; 95% CI: 01.08–1.21; p < 0.001). Only generalized anxiety (indirect effect: 0.02; 95% CI: 0.01–0.04; P = 0.014) significantly mediated the relationship between wellbeing and tooth-brushing accounting for approximately 12% of the total effect of wellbeing on decreased toothbrushing. Generalized anxiety (indirect effect 0.05; 95% CI: − 0.07–0.03; P < 0.001) also significantly mediated the relationship between wellbeing and presence of oral ulcer accounting for 70% of the total effect of wellbeing on presence of oral ulcer. Depressive symptoms and perceived social support did not significantly mediate the associations between psychological wellbeing, decreased frequency of tooth brushing and the presence of oral ulcers.

Conclusion

Patients who come into the dental clinic with poor oral hygiene or oral ulcers during the COVID-19 pandemic may benefit from screening for generalized anxiety and psychological wellbeing to identify those who will benefit from interventions for mental health challenges.
The impact of data from remote measurement technology on the clinical practice of healthcare professionals in depression, epilepsy and multiple sclerosis: survey
Authors: Andrews J. A. , Craven M. P. , Lang A. R. , Guo B. , Morriss R. , Hollis C. ,   The RADAR-CNS Consortium
Published: October 2021

Background

A variety of smartphone apps and wearables are available both to help patients monitor their health and to support health care professionals (HCPs) in providing clinical care. As part of the RADAR-CNS consortium, we have conducted research into the application of wearables and smartphone apps in the care of people with multiple sclerosis, epilepsy, or depression.

Methods

We conducted a large online survey study to explore the experiences of HCPs working with patients who have one or more of these conditions. The survey covered smartphone apps and wearables used by clinicians and their patients, and how data from these technologies impacted on the respondents' clinical practice. The survey was conducted between February 2019 and March 2020 via a web-based platform. Detailed statistical analysis was performed on the answers.

Results

Of 1009 survey responses from HCPs, 1006 were included in the analysis after data cleaning. Smartphone apps are used by more than half of responding HCPs and more than three quarters report that their patients use smartphone apps or wearable devices for health-related purposes. HCPs widely believe the data that patients collect using these devices impacts their clinical practice. Subgroup analyses show that views on the impact of this data on different aspects of clinical work varies according to whether respondents use apps themselves, and, to a lesser extent, according to their clinical setting and job role.

Conclusions

Use of smartphone apps is widespread among HCPs participating in this large European survey and caring for people with epilepsy, multiple sclerosis and depression. The majority of respondents indicate that they treat patients who use wearables and other devices for health-related purposes and that data from these devices has an impact on clinical practice.
Quality of care is what we make of it: a qualitative study of managers’ perspectives on quality of care in high-performing nursing homes
Authors: Asante Brigitte Lalude , Zúñiga Franziska , Favez Lauriane
Published: October 2021

Background

Leadership has a vital role regarding quality of care in nursing homes. However, few studies have explored upper-level managers’ views on how to assure that residents receive high quality of care. Therefore, this study’s aim was to examine how managers of top-quality nursing homes define, develop and maintain high-quality of care.

Method

We used interpretive description, an inductive, qualitative approach. Our research included 13 semi-structured interviews with 19 managers. We analyzed their input using reflexive thematic analysis, which is an iterative approach.

Results

Quality development and maintenance are cyclic processes. Managers in high-performing nursing homes lead with high commitment towards a person-centred quality of care, creating appropriate working conditions and continuously co-creating a vision and the realization of quality of care together with employees.

Conclusions

This study confirms that, in high-performing nursing homes, a person-centered approach—one where both residents and employees are at the center—is essential for quality development and maintenance. The most effective managers exemplify “person centeredness”: they lead by example and promote quality-focused working conditions. Such strategies motivate employees to provide person-centered care. As this means focusing on residents’ needs, it results in high care quality.
Prevalence and associated risk factors of asymptomatic malaria and anaemia among school-aged children in Dara Mallo and Uba Debretsehay districts: results from baseline cluster randomized trial
Authors: Zerdo Zerihun , Bastiaens Hilde , Anthierens Sibyl , Massebo Fekadu , Masne Matewos , Biresaw Gelila , Shewangizaw Misgun , Tunje Abayneh , Chisha Yilma , Yohannes Tsegaye , Van Geertruyden Jean-Pierre
Published: October 2021

Background

Despite the growing evidence that malaria and anaemia are two interlinked health problems of school-aged children (SAC) in developing countries, there is scarce information about malaria among SAC in Ethiopia. Moreover, anaemia-related studies were more concentrated in easily accessible areas. This study aimed to assess the prevalence of malaria and anaemia and corresponding risk factors among SAC in Dara Mallo and Uba Debretshay districts, in hard to reach areas, so as to inform appropriate integrated interventions for both diseases.

Methods

This study was part of baseline data collected for a cluster-randomized trial registered in Pan African Clinical Trials Registry (PACTR202001837195738). Data were collected from 2167 SAC and their households through face-to-face interview; malaria was diagnosed by using rapid diagnostic test (RDT); haemoglobin concentration was determined using hemoCue hb 301 and adjusted for altitude to determine anaemic status; helminth infections were determined by using kato-katz, and anthropometric measurements were made to determine nutritional status of children. Generalized mixed effects logistic regression model was used to assess the association between predictor variables and malaria and anaemia using school as a random variable.

Results

The overall prevalence of malaria was 1.62% (95% CI 1.15–2.27%) (35/2167). Of the 35 children positive for malaria, 20 (57.14%), 3 (8.57%) and 12 (34.29%) were due to Plasmodium falciparum, Plasmodium vivax and mixed infections of P. falciparum and P. vivax, respectively. Malaria was significantly lower among children from literate household head (Adjusted OR  =  0.38; 95% CI 0.15–0.95) and residence house located at an altitude range above 1100 masl (AOR  =  0.40; 95% CI 0.17–0.94). The prevalence of anaemia was 22.00% (95% CI 20.3–23.8%) (477/2167) and was significantly reduced by eating legumes, nuts or seed group of food in their 24-h dietary diversity recall (AOR  =  0.64; 95% CI 0.41–0.99).

Conclusions

The prevalence of malaria was low and unevenly distributed per school while the overall prevalence of anaemia was moderate. It is important to implement integrated interventions targeting both malaria and anaemia, with special emphasis given to children from illiterate households and living at an altitude below 1100 masl. The micronutrient content of locally grown legumes should be further investigated to recommend specific interventions to overcome anaemia.
Laser-assisted selection of immotile spermatozoa has no effect on obstetric and neonatal outcomes of TESA-ICSI pregnancies
Authors: Chen Huanhua , Wang Caizhu , Zhou Hong , Shu Jinhui , Gan Xianyou , Xu Kongrong , Wu Zhulian , Deng Xihe , Huang Guiting , Lin Ruoyun
Published: October 2021

Background

Azoospermic patients have benefited from both epididymal and testicular spermatozoa intracytoplasmic sperm injection (ICSI) treatment and lasers have been used to identify viable, immotile spermatozoa before the procedure. There are limited studies on the safety of laser-assisted selection of immotile spermatozoa. The aim of this study was to investigate the impact of laser-assisted selection of immotile spermatozoa on the obstetric and neonatal outcomes after ICSI.

Methods

A retrospective comparative study was conducted on outcomes of ICSI cycles with testicular spermatozoa from June 2014 to June 2018. Of 132 cycles, 33 were allocated to the test group and oocytes were injected with immotile spermatozoa selected by laser, 99 cycles were allocated as control group.

Results

Compared with the control group, no significant differences were found in the pregnancy, implantation, miscarriage and live birth rates in the test group in either fresh or frozen transfer cycles. The cumulative live birth rate in the test group was 69.70%, which was slightly higher than in the control group (60.61%), but this was not statistically different. There were no differences in the average gestational age, premature birth rate, neonatal birth weight, and the malformation rate between the test and control groups (P > 0.05). In addition, the obstetric outcome between the two groups were not different (P > 0.05).

Conclusions

No negative effect on perinatal and neonatal outcomes was seen by using laser-assisted selection of immotile spermatozoa for TESA-ICSI. This study endorses the use of laser-assisted selection of viable spermatozoa for ICSI cycles.
Downregulation of the FBXO43 gene inhibits tumor growth in human breast cancer by limiting its interaction with PCNA
Authors: Ma Rulan , Zhu Kun , Yuan Dawei , Gong Meijun , Li Yijun , Li Kang , Meng Lei
Published: October 2021

Background

The function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC.

Methods

FBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43.

Results

FBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells.

Conclusion

Downregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.
Neuroimmune multi-hit perspective of coronaviral infection
Authors: Hayley Shawn , Sun Hongyu
Published: October 2021

It is well accepted that environmental stressors experienced over a one’s life, from microbial infections to chemical toxicants to even psychological stressors, ultimately shape central nervous system (CNS) functioning but can also contribute to its eventual breakdown. The severity, timing and type of such environmental “hits”, woven together with genetic factors, likely determine what CNS outcomes become apparent. This focused review assesses the current COVID-19 pandemic through the lens of a multi-hit framework and disuses how the SARS-COV-2 virus (causative agent) might impact the brain and potentially interact with other environmental insults. What the long-term consequences of SAR2 COV-2 upon neuronal processes is yet unclear, but emerging evidence is suggesting the possibility of microglial or other inflammatory factors as potentially contributing to neurodegenerative illnesses. Finally, it is critical to consider the impact of the virus in the context of the substantial psychosocial stress that has been associated with the global pandemic. Indeed, the loneliness, fear to the future and loss of social support alone has exerted a massive impact upon individuals, especially the vulnerable very young and the elderly. The substantial upswing in depression, anxiety and eating disorders is evidence of this and in the years to come, this might be matched by a similar spike in dementia, as well as motor and cognitive neurodegenerative diseases.
Mixed-species groups in bats: non-random roost associations and roost selection in neotropical understory bats
Authors: Kelm Detlev H. , Toelch Ulf , Jones Mirkka M.
Published: October 2021

Background

Mixed-species groups in animals have been shown to confer antipredator, foraging and other benefits to their members that may provide selective advantages. In most cases, however, it is unclear whether functional benefits are a principal driver of heterospecific groups, or whether groups simply result from simultaneous exploitation of common resources. Mixed-species groups that form independently of environmental conditions may, however, evidence direct benefits of species associations. Bats are among the most gregarious mammals, with sometimes thousands of individuals of various species roosting communally. Despite numerous potential functional benefits of such mixed-species roosting groups, interspecific attraction has never been shown. To explore alternative explanations for mixed-species roosting, we studied roost selection in a speciose neotropical understory bat community in lowland rainforest in Costa Rica. Long term roost data were recorded over 10 years in a total of 133 roosts comprising both natural roosts and structurally uniform artificial roosts. We modelled bat roost occupancy and abundance in each roost type and in forest and pasture habitats to quantify the effects of roost- and environmental variability.

Results

We found that bat species presence in natural roosts is predictable from habitat and structural roost parameters, but that the presence and abundance of other bat species further modifies roost choice. One third of the 12 study species were found to actively associate with selected other bat species in roosts (e.g. Glossophaga commissarisi with Carollia sowelli). Other species did not engage in communal roosting, which in some cases indicates a role for negative interspecific interactions, such as roost competition.

Conclusions

Mixed-species roosting may provide thermoregulatory benefits, reduce intraspecific competition and promote interspecific information transfer, and hence some heterospecific associations may be selected for in bats. Overall, our study contributes to an improved understanding of the array of factors that shape diverse tropical bat communities and drive the dynamics of heterospecific grouping in mammals more generally.
A new Hendra virus genotype found in Australian flying foxes
Authors: Wang Jianning , Anderson Danielle E. , Halpin Kim , Hong Xiao , Chen Honglei , Walker Som , Valdeter Stacey , van der Heide Brenda , Neave Matthew J. , Bingham John , O’Brien Dwane , Eagles Debbie , Wang Lin-Fa , Williams David T.
Published: October 2021

Background

Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Flying foxes are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequent surveillance of Australian flying foxes for this novel virus over a nine year period using qRT-PCR testing of tissues from flying foxes submitted primarily for Australian bat lyssavirus diagnosis. Genome sequencing and characterisation of the novel HeV variant was also undertaken.

Methods

Spleen and kidney samples harvested from flying fox carcasses were initially screened with two real-time qRT-PCR assays specific for the prototype HeV. Two additional qRT-PCR assays were developed specific for the HeV variant first detected in samples from a flying fox in 2013. Next-generation sequencing and virus isolation was attempted from selected samples to further characterise the new virus.

Results

Since 2013, 98 flying foxes were tested and 11 were positive for the new HeV variant. No samples were positive for the original HeV. Ten of the positive samples were from grey-headed flying foxes (GHFF, Pteropus poliocephalus), however this species was over-represented in the opportunistic sampling (83% of bats tested were GHFF). The positive GHFF samples were collected from Victoria and South Australia and one positive Little red flying fox (LRFF, Pteropus scapulatus) was collected from Western Australia. Immunohistochemistry confirmed the presence of henipavirus antigen, associated with an inflammatory lesion in cardiac blood vessels of one GHFF. Positive samples were sequenced and the complete genome was obtained from three samples. When compared to published HeV genomes, there was 84% sequence identity at the nucleotide level. Based on phylogenetic analyses, the newly detected HeV belongs to the HeV species but occupies a distinct lineage. We have therefore designated this virus HeV genotype 2 (HeV-g2). Attempts to isolate virus from PCR positive samples have not been successful.

Conclusions

A novel HeV genotype (HeV-g2) has been identified in two flying fox species submitted from three states in Australia, indicating that the level of genetic diversity for HeV is broader than first recognised. Given its high genetic relatedness to HeV, HeV-g2 is a zoonotic pathogen.
Firearm violence: a neglected “Global Health” issue
Authors: Werbick Meghan , Bari Imran , Paichadze Nino , Hyder Adnan A.
Published: October 2021

Populations around the world are facing an increasing burden of firearm violence on mortality and disability. While firearm violence affects every country globally, the burden is significantly higher in many low- and middle-income countries. However, despite overwhelming statistics, there is a lack of research, reporting, and prioritization of firearm violence as a global public health issue, and when attention is given it is focused on high-income countries. This paper discusses the impact of firearm violence, the factors which shape such violence, and how it fits into global public health frameworks in order to illustrate how firearm violence is a global health issue which warrants evidence-based advocacy around the world.
Long-term effects of cemented and cementless fixations of total knee arthroplasty: a meta-analysis and systematic review of randomized controlled trials
Authors: Chen Cheng , Shi Yanyan , Wu Zhanpo , Gao Zengxin , Chen Youmin , Guo Changzheng , Bao Xianguo
Published: October 2021

Background

To determine the long-term effects (a minimum follow-up time 8.8 years) of cemented and cementless fixations used for total knee arthroplasty (TKA).

Methods

PubMed, EMBASE, Ovid, Cochrane Library, CINAHL, China National Knowledge Infrastructure and China Wangfang database were interrogated for appropriate randomized controlled trials (RCTs) through July 2020. Data were extracted and assessed for accuracy by 2 of the authors acting independently. Any controversial discrepancies were resolved after discussion with a third author.

Result

Eight RCTs were included with low to moderate bias risks. The cemented fixation of TKA was comparable to cementless fixation in terms of implant survival (relative risk, 1.016; 95% CI 0.978 to 1.056;P = 0.417), Knee Society (KS) knee score (standardized mean difference (SMD), − 0.107; 95% CI − 0.259 to 0.045;P = 0.168), KS function score (SMD − 0.065; 95% CI − 0.238 to 0.109;P = 0.463), KS pain score (SMD − 0.300; 95% CI − 0.641 to 0.042;P = 0.085), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (SMD − 0.117; 95% CI − 0.307 to 0.073;P = 0.227), HSS score (SMD − 0.027; 95% CI − 0.270 to 0.217;P = 0.829), range of motion (SMD 0.061; 95% CI − 0.205 to 0.327;P = 0.652) at ≥ 8.8 years of follow-up. In terms of radiographic outcomes at ≥ 8.8 years of follow-up, the incidence of a radiolucent line in the cementless group was lower than for the cemented group (SMD 3.828; 95% CI 2.228 to 6.576;P < 0.001). However, the maximum total point motion (MTPM) of the cementless group was greater than for the cemented group (SMD − 0.739; 95% CI − 1.474 to − 0.005;P = 0.048).

Conclusions

Long-term follow-up verified that cementless and cemented fixation have similar prosthesis survival rates, clinical scores and mobility. However, radiography suggested that each technique had an advantage with regard to the radiolucent line and MTPM.
Bovine xenograft pericardial patch use for definitive single stage repair of a large esophageal defect: a case report
Authors: Shennib Hani , Baribault Michelle , Heuser Richard
Published: October 2021

Background

Large esophageal perforations are challenging and often treated with exclusion or resection. This case demonstrates the feasibility of definitive surgical repair of a large esophageal perforation using large bovine pericardial patch.

Case

A patient with missed Boerhaave Syndrome underwent transesophageal echocardiography causing worsening perforation and sepsis. At thoracotomy and faced with a large esophageal defect, a large Bovine pericardial patch was used for repair with omentopexy. The patient recovered promptly and at 8 months was asymptomatic with satisfactory studies.

Conclusion

Xenograft pericardium is available and widely used for vascular reconstructions. It’s use for primary repair of large esophageal perforations should be considered.
Quality of life: modified triple-branched stent graft implantation versus frozen elephant trunk technique
Authors: Luo Zeng-Rong , Tang Mi-Rong , Li Jia-Hui , Chen Liang-Wan , Yan Liang-Liang
Published: October 2021

Objective

To compare the effects of modified triple-branched stent implantation and frozen elephant trunk technique on the quality of life (QoL) of acute Stanford Type A aortic dissection (AAAD) patients at different follow-up times.

Methods

Data from 175 AAAD survivors was collected which were divided into two groups according to different surgical techniques: (group A): modified triple-branched stent graft implantation; (group B): frozen elephant trunk. The SF-36 were used to assess the QoL at discharge (AD), the third postoperative month (POM3), and the twelfth postoperative month (POM12).

Results

(1) The total scores at each time of both groups showed lower than the normal level; Group A scored higher than group B at some time points in terms of some items (role physical, role emotion and mental health; all P = 0.000), and some items at POM3 or POM12 scored higher than at discharge (role physical, social function; both P = 0.000). (2) There were less patients with heavy self-perceived burden in group A than group B at discharge (P = 0.032) and patients with heavy self-perceived burden decreased over time. (3) Young postoperative AAD patients (P = 0.002) in group B (P = 0.005) with heavy self-perceived burden (P = 0.000), acute renal failure (P = 0.008), long LOS (P = 0.026) and blood loss (> 1000 mL/24 h) (P = 0.039) seemed to get a worse QoL.

Conclusion

The impact on QoL of the modified triple-branched stent graft implantation technique seemed to be better than those of frozen elephant trunk surgery in role physical, role emotion and mental health.
Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma
Authors: Liang Lei , Li Chao , Wang Ming-Da , Wang Hong , Zhou Ya-Hao , Zeng Yong-Yi , Zhang Wan-Guang , Chen Ting-Hao , Wang Nan-Ya , Li Jie , Zhang Yao-Ming , Wang Yu , Gu Wei-Min , Xing Hao , Diao Yong-Kang , Lau Wan Yee , Zhang Cheng-Wu , Pawlik Timothy M. , Shen Feng , Huang Dong-Sheng , Yang Tian
Published: October 2021

Background and aims

Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC.

Methods

From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE.

Results

A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE.

Conclusions

Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.
Lethal variants in humans: lessons learned from a large molecular autopsy cohort
Authors: Shamseldin Hanan E. , AlAbdi Lama , Maddirevula Sateesh , Alsaif Hessa S. , Alzahrani Fatema , Ewida Nour , Hashem Mais , Abdulwahab Firdous , Abuyousef Omar , Kuwahara Hiroyuki , Gao Xin ,   Molecular Autopsy Consortium, Aldhalaan Hesham , Alfaifi Abdullah , Alhashem Amal , Alhasan Khalid , Alnemer Maha , Alsahan Nada , Alyamani Suad , Alzaidan Hamad , Brownyn Kerr , Condie Angela , Faqeih Eissa , Khan Rubina , Kurdi Wesam , Muthaffar Osama , Nabil Amira , Newman William , Al-Qattan Mohammad M. , Rahbeeni Zuhair , Sunbul Rawda , Temsah Mohamad-Hani , Tulbah Maha , Zain Mohammed , Alkuraya Fowzan S.
Published: October 2021

Background

Molecular autopsy refers to DNA-based identification of the cause of death. Despite recent attempts to broaden its scope, the term remains typically reserved to sudden unexplained death in young adults. In this study, we aim to showcase the utility of molecular autopsy in defining lethal variants in humans.

Methods

We describe our experience with a cohort of 481 cases in whom the cause of premature death was investigated using DNA from the index or relatives (molecular autopsy by proxy). Molecular autopsy tool was typically exome sequencing although some were investigated using targeted approaches in the earlier stages of the study; these include positional mapping, targeted gene sequencing, chromosomal microarray, and gene panels.

Results

The study includes 449 cases from consanguineous families and 141 lacked family history (simplex). The age range was embryos to 18 years. A likely causal variant (pathogenic/likely pathogenic) was identified in 63.8% (307/481), a much higher yield compared to the general diagnostic yield (43%) from the same population. The predominance of recessive lethal alleles allowed us to implement molecular autopsy by proxy in 55 couples, and the yield was similarly high (63.6%). We also note the occurrence of biallelic lethal forms of typically non-lethal dominant disorders, sometimes representing a novel bona fide biallelic recessive disease trait. Forty-six disease genes with no OMIM phenotype were identified in the course of this study. The presented data support the candidacy of two other previously reported novel disease genes (FAAH2 and MSN). The focus on lethal phenotypes revealed many examples of interesting phenotypic expansion as well as remarkable variability in clinical presentation. Furthermore, important insights into population genetics and variant interpretation are highlighted based on the results.

Conclusions

Molecular autopsy, broadly defined, proved to be a helpful clinical approach that provides unique insights into lethal variants and the clinical annotation of the human genome.
Exploring sensory phenotypes in autism spectrum disorder
Authors: Scheerer Nichole E. , Curcin Kristina , Stojanoski Bobby , Anagnostou Evdokia , Nicolson Rob , Kelley Elizabeth , Georgiades Stelios , Liu Xudong , Stevenson Ryan A.
Published: October 2021

Background

Atypical reactions to the sensory environment are often reported in autistic individuals, with a high degree of variability across the sensory modalities. These sensory differences have been shown to promote challenging behaviours and distress in autistic individuals and are predictive of other functions including motor, social, and cognitive abilities. Preliminary research suggests that specific sensory differences may cluster together within individuals creating discrete sensory phenotypes. However, the manner in which these sensory differences cluster, and whether the resulting phenotypes are associated with specific cognitive and social challenges is unclear.

Methods

Short sensory profile data from 599 autistic children and adults between the ages of 1 and 21 years were subjected to a K-means cluster analysis. Analysis of variances compared age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder across the resultant clusters.

Results

A five-cluster model was found to minimize error variance and produce five sensory phenotypes: (1) sensory adaptive, (2) generalized sensory differences, (3) taste and smell sensitivity, (4) under-responsive and sensation seeking, and (5) movement difficulties with low energy. Age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder were found to differ significantly across the five phenotypes.

Limitations

The results were based on parent-report measures of sensory processing, adaptive behaviour, traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder, which may limit the generalizability of the findings. Further, not all measures are standardized, or psychometrically validated with an autism population. Autistic individuals with an intellectual disability were underrepresented in this sample. Further, as these data were obtained from established records from a large provincial database, not all measures were completed for all individuals.

Conclusions

These findings suggest that sensory difficulties in autistic individuals can be clustered into sensory phenotypes, and that these phenotypes are associated with behavioural differences. Given the large degree of heterogeneity in sensory difficulties seen in the autistic population, these sensory phenotypes represent an effective way to parse that heterogeneity and create phenotypes that may aid in the development of effective treatments and interventions for sensory difficulties.
CM from intact hAM: an easily obtained product with relevant implications for translation in regenerative medicine
Authors: Silini Antonietta Rosa , Papait Andrea , Cargnoni Anna , Vertua Elsa , Romele Pietro , Bonassi Signoroni Patrizia , Magatti Marta , De Munari Silvia , Masserdotti Alice , Pasotti Anna , Rota Nodari Sara , Pagani Giorgio , Bignardi Mario , Parolini Ornella
Published: October 2021

Background

It is now well established that factors (free or in extracellular vesicles) secreted by mesenchymal stromal cells (MSC) are important mediators of MSC regenerative actions. Herein we produced the secretome (conditioned medium, CM) from MSC isolated from the amniotic membrane (hAMSC) and CM from the intact amniotic membrane (hAM, no manipulation or enzymatic digestion) in order to potentially identify an effective, easy and less expensive secretome to produce for potential applications in regenerative medicine. Given that immunomodulation is a key mechanism of action through which hAMSC contributes to tissue regeneration, we used a comprehensive panel of in vitro immunomodulatory tests to compare the CMs.

Methods

Amniotic membranes were either cut into fragments or used for hAMSC isolation. CMs from hAMSC at passages 0 and 2 were collected after a standard 5-day culture while CM from hAM was collected after a 2- and 5-day culture. Immunomodulation was assessed in terms of PBMC and T-cell proliferation, T-cell subset polarization, T-regulatory cell induction, cell cytotoxicity and monocyte differentiation toward antigen-presenting cells. Furthermore, we performed a comparison between CM obtained from single donors and pooled CM. We also assessed the impact of lyophilization on the immunomodulatory properties of CM.

Results

We demonstrate that CM from hAM has comparable immunomodulatory properties to CM from hAMSC at passages 0 and 2. Furthermore, we demonstrate that pooled CMs have similar effects when compared to CM from single donors used separately. Finally, we demonstrate that lyophilization does not alter the in vitro immunomodulatory properties of CM from hAM and hAMSC.

Conclusions

The results presented herein support the possibility to produce secretome from intact hAM and open the prospect to highly improve the scalability of the GMP production process while reducing the costs and time related to the process of cell isolation and expansion. Moreover, the possibility of having a lyophilized secretome that maintains its original properties would allow for a ready-to-use product with easier handling, shipping and storage. The use of a lyophilized product will also facilitate clinicians by permitting customized reconstitution volumes and methods according to the most suitable formula required by the clinical application.
Alteration of neuroinflammation detected by 18F-GE180 PET imaging in place-conditioned rats with morphine withdrawal
Authors: Li Junpeng , Shao Da , Jiang Donglang , Huang Qi , Guan Yihui , Lai Bin , Zhao Jun , Hua Fengchun , Xie Fang
Published: October 2021

Background

Accumulating evidence indicates that neuroinflammation (NI) significantly contributes to drug addiction, but the conversion of NI after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of NI during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180.

Methods

Twelve male adult Sprague–Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A 18F-GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t test using SPM8.

Results

Both the DW group and the CPA group spent less time in the conditioning cage during the post-test phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. − 159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group.

Conclusion

In morphine-dependent rats, Neuroinflammation (NI) became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this NI induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.
Impact of interprofessional service-learning on the effectiveness of knowledge transfer of antimicrobial resistance to Hong Kong elders: a quasi-experiment
Authors: Lo Anna C. Y. , Li Joyce T. S. , Chau Janita P. C. , Wong Samuel Y. S. , Hui David S. C. , Lee Vivian W. Y.
Published: October 2021

Background

Community perception on antimicrobials plays a role in driving the development of antimicrobial resistance (AMR). The aim of the study was to evaluate the impact of interprofessional service-learning on the effectiveness of AMR knowledge transfer in Hong Kong elders aged 65 or above and students from university and secondary schools.

Methods

A quasi-experimental pretest–posttest controlled study was carried out from July 2018 to March 2019 for elderly subjects and a pre- and post-test were conducted in students from May to August 2018. Elderly subjects were recruited from the university-based community outreach program. The community outreach team consisted of both university and secondary school students. Students were provided with training of geriatric care and AMR before they reached out to the community. The one-to-one intervention with the aid of video and verbal explanation to educate the elderly about the definition, causes, and consequences of AMR, and preventive measures against AMR was provided. Questionnaires on knowledge of antibiotics and AMR were used as tools to reflect on the effectiveness for both students and elderly subjects. The questionnaire was completed twice, before and 1 week after the intervention. Chi-square test, t tests and regression analysis were used to analyze the data.

Results

A total of 93 Chinese elders, 61 of them in the intervention group and 32 in the control group participated in the study. The score obtained by the intervention group increased from 40.1 to 83.3% (p < 0.001) following intervention, while that of control group increased from 33.0 to 44.0% (p < 0.001). The increase attained in the intervention group was significantly greater than that of the control group (p < 0.001). A total of 95 secondary students and 88 university students have completed the pre-post questionnaires with 42.21% and 13% increment in AMR knowledge after the training (p < 0.001).

Conclusion

The significant change in knowledge level showed effective AMR knowledge transfer to both elders and students. The study could be used as a reference when allocating resources to implement effective interprofessional service-learning for better community health education in elderly populations.

Trial registration: This study was approved by the Chinese University of Hong Kong Survey and Behavioural Research Ethics Committee in December 2018 (Ref no. SBRE-18-214).
Economic impact of a care bundle to prevent surgical site infection after craniotomy: a cost-analysis study
Authors: Jiménez-Martínez Emilio , Cuervo Guillermo , Carratalà Jordi , Hornero Ana , Ciercoles Pilar , Gabarrós Andreu , Cabellos Carmen , Pelegrin Ivan , Domínguez-Luzón Maria Angeles , Càmara Jordi , Moreno-Fuentes Ramon , Adamuz Jordi , Pujol Miquel
Published: October 2021

Background

Surgical site infections after craniotomy (SSI-CRAN) significantly impact patient outcomes and healthcare costs by increasing length of stay and readmission and reoperation rates. However, to our knowledge, no study has yet analysed the economic impact of a surgical care bundle for preventing SSI-CRAN. The aim is to analyse the hospital cost saving after implementation of a care bundle for the prevention of SSI-CRAN.

Methods

A retrospective cost-analysis was performed, considering two periods: pre-care bundle (2013–2015) and care bundle (2016–2017). A bottom-up approach was used to calculate the costs associated with infection in patients who developed a SSI-CRAN in comparison to those who did not, in both periods and on a patient-by-patient basis. The derived cost of SSI-CRAN was calculated considering: (1) cost of the antibiotic treatment, (2) cost of length of stay in the neurosurgery ward within the 1-year follow up period, (3) cost of the re-intervention, and (4) cost of the implant for cranial reconstruction, when necessary.

Results

A total of 595 patients were included in the pre-care bundle period and 422 in the care bundle period. Mean cost of a craniotomy procedure was approximately €8000, rising to €24,000 in the case of SSI-CRAN. Mean yearly hospital costs fell by €502,857 in the care bundle period (€714,886 vs. €212,029). Extra costs between periods were mainly due to increased length of hospital stay (€573,555.3 vs. €183,958.9; difference: €389,596.4), followed by the cost of implant for cranial reconstruction (€69,803.4 vs. €9,936; difference: €59,867.4). Overall, implementation of the care bundle saved the hospital €500,844.3/year.

Conclusion

The implementation of a care bundle for SSI-CRAN had a significant economic impact. Hospitals should consider the deployment of this multimodal preventive strategy to reduce their SSI-CRAN rates, and also their costs.
Dementia in military and veteran populations: a review of risk factors—traumatic brain injury, post-traumatic stress disorder, deployment, and sleep
Authors: Raza Zara , Hussain Syeda F. , Ftouni Suzanne , Spitz Gershon , Caplin Nick , Foster Russell G. , Gomes Renata S. M.
Published: October 2021

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia. Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have a higher prevalence in this group in comparison to the civilian population. By delving into the individual relationships between TBI and dementia, and PTSD and dementia, we are able to better explore dementia in the military and veteran populations. While there are some inconsistencies in results, the TBI-dementia association has become more widely accepted. Moderate-to-severe TBI has been found to increase the risk of being diagnosed with Alzheimer’s disease. A correlation between PTSD and dementia has been established, however, whether or not it is a causal relationship remains unclear. Factors such as blast, combat and chemical exposure may occur during a deployment, along with TBI and/or PTSD diagnosis, and can impact the risk of dementia. However, there is a lack of literature exploring the direct effects of deployment on dementia risk. Sleep problems have been observed to occur in those following TBI, PTSD and deployment. Poor sleep has been associated with possible dementia risk. Although limited studies have focused on the link between sleep and dementia in military and veteran populations, sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors. This review aims to inform of various risk factors to the cognitive health of military members and veterans: TBI, PTSD, deployment, and sleep.
Sacubitril/valsartan is well tolerated in patients with longstanding heart failure and history of cancer and improves ventricular function: real-world data
Authors: Frey Maria Klara , Arfsten Henrike , Pavo Noemi , Han Emilie , Kastl Stefan , Hülsmann Martin , Gyöngyösi Mariann , Bergler-Klein Jutta
Published: October 2021

Background

Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in patients with reduced ejection fraction (HFrEF) when compared to enalapril. Data about sacubitril/valsartan in patients with a history of cancer are scarce, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer.

Methods

We identified 225 patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan. Out of these, 9.3% (n = 21) had a history of histologically confirmed cancer. Oncologic surgery was performed in 16 (76.2%) patients, 11 (52.4%) patients received previous antineoplastic therapy and 9 patients (42.9%) radiation.

Results

Sacubitril/valsartan was withdrawn in 3 of 21 patients (14.3%) because of dizziness (n = 2) or pruritus (n = 1). After a median follow-up of 12 months (range 1–34 months), NYHA functional class improved significantly from NYHA 3 to NYHA 2 (mean -0.6, p = 0.006) and left ventricular ejection fraction as assessed by echocardiography increased significantly from 26.8 ± 5.4% to 39.2 ± 10% (mean + 12%, CI 95% [8.4–16.4], p = 0.0004). NT-proBNP was significantly reduced (baseline median 2774 pg/ml, range 1441 – 12,982 vs follow-up 1266 pg/ml, range 199–6324, p = 0.009). There was no significant change in creatinine levels (1.18 ± 0.4 vs 1.22 ± 0.4 mg/dl; mean + 0.005 mg/dl, CI 95% [-0.21- 0.12], p = 0.566).

Conclusions

In our pilot study we show that sacubitril/valsartan is generally well tolerated in patients with HFrEF and history of cancer. Importantly, even patients with long-standing cardiotoxicity induced heart failure can be treated and up-titrated with sacubitril/valsartan to usual target dosages, leading to improvement in LV function and biomarkers. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.