bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty, sarcopenia, cachexia and malnutrition as comorbid conditions and their associations with mortality: a prospective study from UK Biobank
Authors: Petermann-Rocha Fanny , Pell Jill P , Celis-Morales Carlos , Ho Frederick K
Published: November 2020

Background

Frailty, sarcopenia, cachexia and malnutrition are clinical conditions that share similar diagnostic criteria. This study aimed to investigate the clustering and mortality risk among these clinical conditions in middle- and older-aged adults.

Methods

111 983 participants from UK Biobank were included. Sarcopenia was defined according to the EWGSOP 2019 while frailty using a modified version of the Fried criteria. Cachexia was defined using the Evans et al. classification and malnutrition using the Global Leadership Initiative on Malnutrition. The exposure variable was categorized as: no conditions; frailty only (one condition); frailty with sarcopenia (two conditions); frailty with ≥2 other conditions (three or four conditions). Its association with all-cause mortality was investigated using Cox-proportional hazard analysis.

Results

Frailty had the highest prevalence (45%) and was present in 92.1% of people with malnutrition and everyone with sarcopenia or cachexia. Compared with people with no conditions, those with frailty only and frailty with sarcopenia had higher risk of all-cause mortality. Individuals with frailty plus ≥2 other conditions had even higher risk (HR: 4.96 [95% CI: 2.73 to 9.01]).

Conclusions

The four clinical conditions investigated overlapped considerably, being frailty the most common. The risk of all-cause mortality increased with the increasing number of conditions in addition to frailty.
Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease
Authors: Xu Antao , Ye Yan , Fu Qiong , Lian Xinyue , Chen Sheng , Guo Qiang , Lu Liang-jing , Dai Min , Lv Xia , Bao Chunde
Published: November 2020

Objective

Anti-Ro52 antibody often co-occurs with anti-Jo1 antibody in antisynthetase syndrome and their co-occurrence correlates with a more aggressive clinical phenotype and poorer prognosis. The strong association of anti-Ro52 antibody with anti-melanoma differentiation-associated protein-5 (anti-MDA5) antibody has been indicated in juvenile myositis. The aim of this study was to assess the clinical significance of anti-Ro52 antibody in a cohort of adult patients with anti-MDA5-positive clinically amyopathic dermatomyositis with interstitial lung disease (CADM-ILD).

Methods

We assessed a cohort of 83 consecutive patients with anti-MDA5-positive CADM-ILD. Anti-MDA5 antibodies and anti-Ro52 antibodies were detected in immunoblotting and semi-quantitatively analysed by densitometry. Clinical features and the 24 month survival were compared between anti-MDA5-positive patients with and without anti-Ro52 antibodies.

Results

Anti-Ro52 antibodies were found in 74.7% of anti-MDA5-positive CADM-ILD patients and were associated with an increased frequency of rapidly progressive interstitial lung disease (RP-ILD; 54.8% vs 23.8%; P = 0.014) and cutaneous ulcerations (27.4% vs 4.8%; P = 0.033). The cumulative 24 month survival rate tended to be lower in patients with anti-Ro52 antibodies than patients without (59.9% vs 85.7%; P = 0.051). The combination of anti-Ro52 antibody status and anti-MDA5 antibody levels further stratified patients’ survival rates, showing that the survival rate of patients who were dual positive for anti-MDA5 antibody and anti-Ro52 antibody was significantly lower than patients with mild positive anti-MDA5 antibody alone (59.9% vs 100%; P = 0.019).

Conclusion

Anti-Ro52 antibody is highly prevalent in anti-MDA5-positive CADM-ILD patients and their coexistence correlates with a subgroup of patients with more aggressive phenotypes. The combination of anti-MDA5 antibody levels and anti-Ro52 antibody status could help to predict patients’ prognosis and guide risk-based therapy.
ESTIMATING RADIATION DOSE TO MAJOR ORGANS IN DENTAL X-RAY EXAMINATIONS: A PHANTOM STUDY
Authors: Li Yong , Huang Bingsheng , Cao Jun , Fang Tianqi , Liu Guoqing , Li Xuguang , Wu Jiabao
Published: November 2020

The radiation doses absorbed by major organs of males and females were studied from three types of dental X-ray devices. The absorbed doses from cone-beam computed tomography (CBCT), panoramic and intraoral X-ray machines were in the range of 0.23–1314.85 μGy, and were observed to be high in organs and tissues located in or adjacent to the irradiated area, there were discrepancies in organ doses between male and female. Thyroid, salivary gland, eye lens and brain were the organs that received higher absorbed doses. The organ absorbed doses were considerably lower than the diagnostic reference level for dental radiography in China. The calculated effective radiation doses for males and females were 56.63, 8.15, 2.56 μSv and 55.18, 8.99, 2.39 μSv, respectively, when using CBCT, the panoramic X-ray machine and intraoral X-ray machine. The effective radiation dose caused by CBCT was much higher than those of panoramic and intraoral X-ray machines.
The impact of frailty in older women undergoing pelvic floor reconstructive surgery
Authors: Shaw Jonathan S. , Erekson Elisabeth , Richter Holly E.
Published: November 2020

Importance and Objective:

Women ≥ 65 years old commonly undergo pelvic surgery but are often not screened for coexisting frailty, the presence of which increases the risk of postoperative complications. In the absence of a current consensus, the objective of this review is to discuss the incorporation of a frailty assessment into the work-up of women undergoing pelvic floor reconstructive surgery.

Methods:

This is a review of the literature, focusing on measurements of frailty including the Edmonton Frail Scale, FRAIL scale, Groningen Frailty Indicator, frailty phenotype, Tilburg Frailty Indicator, a 70-item frailty index, Mini-Cog score, Charlson comorbidity index, timed up and go test, and life-space assessment. Their use in the perioperative management of older women undergoing pelvic floor reconstructive surgery will be discussed.

Discussion and Conclusion:

Understanding the concept of frailty and how it may affect surgical decisions and outcomes is essential. The timed up and go test, life space assessment and Mini-Cog assessment at a minimum should be considered preoperatively in patients over the age of 65 years old planning pelvic floor or elective surgery.

Video Summary:

http://links.lww.com/MENO/A676.
ASSOCIATION OF PIGMENTED PARAVENOUS RETINOCHOROIDAL ATROPHY WITH A PATHOGENIC VARIANT IN THE HK1 GENE
Authors: Shah Saumya M. , Schimmenti Lisa A. , Chiang John , Iezzi Raymond
Published: November 2020

Purpose:

To report a case of pigmented paravenous retinochoroidal atrophy in a patient that was found to have an autosomal dominant pathogenic variant of the hexokinase 1 (HK1) gene.

Methods:

A case report.

Results:

A 41-year-old White woman with a distant family history of retinitis pigmentosa presented with a 5-year history of bilateral blurry and decreased vision that led to eventual loss of ability to drive. Color funduscopic photographs revealed retinochoroidal atrophy, hyper-reflective spots within the retina, and a paravenous distribution of pigment bilaterally. Given the patient's familial ocular history and workup, she was diagnosed with inherited retinal degeneration with phenotype suggestive of pigmented paravenous retinochoroidal atrophy. Genetic testing revealed a single rare variant, c.2551 G>A in the HK1 gene.

Discussion:

This case describes a pathogenic variant in HK1, a gene that has been associated with RP, but has not been previously reported in association with the pigmented paravenous retinochoroidal atrophy phenotype. This expands the phenotypes associated with HK1 pathogenic variant, p.Glu851Lys, and the genetic association of pigmented paravenous retinochoroidal atrophy to include HK1. Although pigmented paravenous retinochoroidal atrophy has been previously reported to be associated with CRB1 gene, no previous relationship to the HK1 gene has been described.
CLINICAL VARIANTS OF PRESUMED ACUTE FOVEALITIS
Authors: Moraes Remo Turchetti , Vianna Raul N. G. , Cunha de Souza Eduardo , Moraes Lucas Silveira
Published: November 2020

Purpose:

To describe four eyes of three patients with presumed acute fovealitis to expand the clinical variants of this recently described disorder.

Method:

The patients underwent a comprehensive ophthalmic examination, including multimodal imaging and electrophysiological tests.

Results:

Three female patients aged from 18 to 24 years presented sudden central visual disturbances in one or both eyes. The visual acuity ranged from 20/25 to 20/70 in the affected eyes. All of them showed a subtle yellowish lesion in the foveola. Fundus autofluorescence and fluorescein angiography were unremarkable. Optical coherence tomography disclosed focal disarrangement of the outer retinal layers restricted to the fovea and hyperreflective lesions above the external limiting membrane. Multifocal electroretinography responses were attenuated. The electrooculogram response was normal. All patients recovered normal visual acuity and the outer retinal layers.

Conclusion:

Attenuated multifocal electroretinography foveal response and normal electrooculogram are newly described clinical findings in patients with acute fovealitis.
US Department of Defense Warfighter Brain Health Initiative: Maximizing performance on and off the battlefield
Authors: Lee Katherine M. , Khatri Trisha L. , Fudge Elizabeth R.
Published: November 2020

The US Department of Defense (DoD) recognizes the importance of warfighter brain health with the establishment of the Warfighter Brain Health Initiative and Strategy. For a warfighter, also known as a service member, to perform at their highest level, cognitive and physical capabilities must be optimized. This initiative addresses brain health, brain exposures, to include blast overpressure exposures from weapons and munitions, traumatic brain injury (TBI), and long-term or late effects of TBI. The DoD's pursuit of maximal strength hinges on the speed of decisions (neurocognitive) and detection of brain injury when it occurs. The strategy creates a framework for deliberate, prioritized, and rapid development of end-to-end solutions for warfighter brain health. Through this strategy, DoD is addressing the needs of our service members, their families, line leaders/commanders, and their communities at large. The implications of this initiative and strategy are noteworthy for practitioners because the DoD Warfighter Brain Health construct lends itself to nurse practitioner engagement in clinical practice, patient education, policy development, and emerging research.
Multifocal Renal Cell Carcinomas With Somatic IDH2 Mutation: Report of a Previously Undescribed Neoplasm
Authors: Merino Maria J. , Ricketts Christopher J. , Moreno Vanessa , Yang Ye , Fan Teresa W.M. , Lane Andrew N. , Meltzer Paul S. , Vocke Cathy D. , Crooks Daniel R. , Linehan William M.
Published: November 2020

Renal cell carcinoma (RCC) is a heterogenous disease composed of several different cancer types characterized by distinct histologies and genetic alterations, including mutation of the Krebs cycle enzyme genes for fumarate hydratase and succinate dehydrogenase (SDH). This report describes a patient with multifocal renal tumors that presented with a novel, biphasic histologic morphology with one component consisting of small cells growing in a diffuse pattern occasionally forming glandular and cystic structures, reminiscent of type 1 papillary RCC, and the other component having larger cells with abundant eosinophilic and clear cytoplasm and appearing in a solid pattern of growth. Genetic analysis of multiple tumors showed that all had a somatic mutation of the IDH2 gene that created the known pathogenic, gain-of-function p.R172M alteration that results in abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Analysis of multiple tumors demonstrated highly elevated levels of 2-HG and a CpG island methylator phenotype that is characteristic of 2-HG-related inhibition of the Ten-eleven translocation (TET) family of DNA demethylases. In combination with fumarate hydratase–deficient and succinate dehydrogenase–deficient RCCs that have increased levels of the fumarate and succinate oncometabolites, respectively, the mutation of isocitrate dehydrogenase 2 represents the third Krebs cycle enzyme alteration to be associated with oncometabolite-induced RCC tumorigenesis. This study associates the discovery of a new histologic presentation of RCC with the first report of an IDH2 gain-of-function mutation in RCC.
Outcomes of fertility investigations in a cohort of adults with perinatally acquired HIV-1 infection: a UK cross-sectional observational study
Authors: Pasvol Thomas J. , Teh Jhia , Balfoussia Danai , Hall Rebecca , Petersen Claire , Khan Maryam , Ayres Sara , Jayasena Channa N. , Foster Caroline , Fidler Sarah
Published: November 2020

There are no published studies of fertility measurements in people living with perinatally acquired HIV (PaHIV). We performed fertility investigations in 25 adults with PaHIV. Seven (78%) men had sperm morphology normal forms (%) below the fifth centile for the general population with four (44%) having no normal forms. Mean (SD) serum anti-Müllerian hormone level was 19.4 (9.5) pmol/l; lower than expected for this age group. A larger study is needed to verify our findings.
Nasoalveolar Molding: Assessing the Burden of Care
Authors: Wlodarczyk Jordan R. , Wolfswinkel Erik M. , Fahradyan Artur , Rhee Claire , Liu Alice , Gibreel Waleed , Magee William , Urata Mark M. , Hammoudeh Jeffrey A.
Published: November 2020

Over the last 3 years a shift at our institution has taken place in which patients who would have been offered nasoalveolar molding (NAM) as an adjunct to cleft lip repair (repair after 3 months) have instead undergone early cleft lip repair (ECLR) (2–5 weeks of life) without NAM. This study sought to examine the financial and social impact of the transition away from NAM to ECLR. The efficacy of NAM is limited by patient compliance to a rigorous treatment schedule requiring weekly visits for appliance adjustments. Nasoalveolar molding patients required an average of 11 dental visits, accounting for $2132 in indirect lost income per family. Average direct charges for NAM totaled $12,290 for the hospital, physician, and appliance costs. Over the entire study period, the cumulative direct cost of NAM separate from the surgical repair of the lip was $970,910. Following the introduction of ECLR as an alternative to NAM with standard lip repair, NAM usage decreased by 48% and unilateral cleft lip patients undergoing NAM decreased by 86%. Those diverted from NAM to ECLR resulted in a decreased healthcare cost burden of $368,700 ($111,727 per year). In addition to the time burden, the financial burden of NAM is significant. Early cleft lip repair without NAM is more cost effective. Nasoalveolar molding has significantly decreased utilization since the implementation of ECLR. We believe that ECLR, with increased experience, long-term data, and increased awareness, has the potential to decrease the burden of health care costs in the United States.
Home Language Environment of Children With Orofacial Clefts as a Target for Intervention
Authors: Gallagher Emily R. , Wallace Erin , Thach Jenny , Kinter Sara , Collett Brent R.
Published: November 2020

Objective:

To evaluate the home language environment (HLE) in children with orofacial clefts as a potential modifiable target for language and literacy intervention.

Design:

Feasibility study examining longitudinal trends in HLE and responses to parent-focused literacy intervention.

Setting:

Tertiary care children's hospital.

Participants:

HLE data were collected for 38 children with orofacial clefts between ages 7 and 23 months. Twenty-seven participants received parent-focused literacy intervention.

Interventions:

Reach Out and Read, a literacy intervention, was introduced during a clinic visit. To assess response, participants were randomized to age at intervention (9, 18, or 24 months).

Main Outcome Measures:

Primary outcome measures included measurements from recordings in the home language environment of adult word count, child vocalizations, and conversational turns.

Results:

Baseline (preintervention) results showed lower adult word count and conversational turns for caregivers and children with cleft lip and palate, as well as for those from lower socioeconomic groups. After the literacy intervention was introduced, this cohort showed increasing measures of child and caregiver vocalizations, particularly when introduced at 18 months.

Conclusions:

Although these results are preliminary, findings suggest that HLE characteristics vary as a function of children's cleft type as well as family socioeconomic status. Further, our caregiver-focused literacy intervention was feasible and resulted in short-term improvements in HLE. This is the first study to document HLE as a target for intervention in children with oral clefts. These findings support further research on HLE and caregiver-focused intervention to improve language/literacy outcomes for children with oral clefts.
Malignant Melanoma Arising From a Giant Congenital Melanocytic Nevus in a 3-Year Old: Review of Diagnosis and Management
Authors: Kugar Meredith , Akhavan Arya , Ndem Idorenyin , Ollila David , Googe Paul , Blatt Julie , Wood Jeyhan
Published: November 2020

Introduction:

Giant congenital nevi (GCN), defined as abnormal collections of melanocytes with a diameter greater than 20 cm, occur in 1 in 20,000 births. The lifetime risk of malignant transformation in GCN is reported between 5% and 20% and most commonly occurs in the first 3 to 5 years of life. This article reviews the risk factors of malignant transformation and highlights the diagnostic challenges of malignant melanoma in the pediatric population utilizing a clinical report of a patient with GCN.

Case Description:

A male patient with giant congenital nevus of the scalp with over 20 satellite nevi was evaluated at the authors’ institution at 1 week of life. Beginning at 9 months of age, he underwent serial excision of GCN and satellite lesions. Initial pathology showed compound congenital melanocytic nevus. Subsequent pathology on serial excisions demonstrated compound nevus with clonal expansion of pigmented epithelioid melanocytoma (PEM). He then underwent complete excision of GCN. Pathology demonstrated malignant melanoma that was confirmed by consensus review with outside institutions. The patient was diagnosed with stage III metastatic melanoma after further imaging. He was treated with cervical nodal dissection and interferon alpha-2b. At the time of last visit, the patient had no evidence of melanoma.

Discussion:

This case highlights the difficulties of clinical and pathologic diagnosis of malignant melanoma in the setting of GCN. Pathology can vary between biopsy sites and initial biopsies can suggest nonmalignant melanocytic lesions, as demonstrated in this patient's case. Correct histologic evaluation often requires input from a relatively few centers that treat a larger volume of childhood melanoma. Analysis of gene expression profiles aids in accurate diagnosis of PEM, proliferative nodule or melanoma. It is important to differentiate PEM, a low-grade, indolent melanoma, from malignant melanoma as the treatment differs significantly. Review of pathology by expert dermatopathologists from multiple institutions is vital for diagnostic accuracy, and patients with malignant transformation of GCN are best served by multidisciplinary teams.
Mandibular Fractures Epidemiology and Treatment Plans in the Center of Italy: A Retrospective Study
Authors: Gualtieri Matteo , Pisapia Francesco , Fadda Maria Teresa , Priore Paolo , Valentini Valentino
Published: November 2020

The epidemiology of maxillofacial fractures is variable in different geographic regions. Economic and social conditions, laws and types of behavior can be considered the most important factors influencing these differences.

Mandibular fractures were first cited in 1650 BC in an Egyptian papyrus. Today, these fractures are one of the most prevalent facial skeletal injuries.

A 4-year retrospective study was performed and the trauma – related data were collected from medical and radiological archives. The analysis comprised patients admitted for mandibular fracture at Sapienza University of Rome – Policlinico Umberto I between January 1, 2016 and December 31, 2019. The data include age, sex, etiology, anatomical sites of the fractures, eventual maxillofacial associated fractures and treatment.

We collected 172 patients, 138 males (80.2%) and 34 females (19.8%) with 270 mandibular fractures. The average age was 35.4 years. The youngest and oldest patients were aged 6 and 90 years, respectively. The age group 20 to 29 years was the most represented with 52 patients (30.2% of the total sample). Assaults were the most common etiology (n = 53, 30.8%), followed by falls (n = 45, 26.2%). The condyle was the most involved region (n = 86, 32%), followed by parasymphysis region (n = 72, 26.6%) and angle (n = 62, 23%).

154 patients (89.5%) reported only mandibular fractures. Eighteen patients (10.5%) had other associated maxillofacial fractures; the most frequently encountered maxillofacial fractures associated with mandibular fractures were the zygomatic complex fractures (n = 9, 5.2%). Open reduction and internal fixation was the most preferred surgical treatment (n = 115, 66.9%).

This study showed that mandibular fractures predominate in 20 to 29 years group and in the male sex. Assaults are the most frequent cause. The prevalent fracturing site is condylar process. Orbital – maxillary – zygomatic complex fractures were the most common associated maxillofacial fractures and open reduction and internal fixation was the preferred surgical strategy.

The results of this analysis agree to other studies and provide important clinical information that will help in study of these injuries.
Cerebrospinal fluid circulating tumour DNA as a liquid biopsy for central nervous system malignancies
Authors: Escudero Laura , Martínez-Ricarte Francisco , Seoane Joan
Published: November 2020

Purpose of review

The molecular characterization of central nervous system (CNS) malignancies is crucial for obtaining the correct diagnosis and prognosis, and to guide the optimal therapeutic approach. However, obtaining surgical specimens can be challenging because of the anatomical location of the tumour and may limit the correct characterization of these malignancies. Recently, it has been shown that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) can be used as a liquid biopsy to characterize and monitor CNS malignancies and here we review its implications and advances.

Recent findings

In the last 5 years, several groups including ours have shown that ctDNA is highly present in the CSF, in larger amounts than in plasma, and that ctDNA can be sequenced to provide information about the diagnosis and prognosis of brain malignancies. Furthermore, the analysis of CSF ctDNA has allowed the selection of optimal therapeutic approaches monitoring response to treatment and tracking tumour evolution, providing crucial information about the molecular changes during tumour progression.

Here, we review the recent discoveries and data relative to CSF ctDNA and discuss how CSF ctDNA can be used as a liquid biopsy to facilitate and complement the clinical management of patients with CNS malignancies.
Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco
Authors: Clarity Cassidy , Trowbridge Jessica , Gerona Roy , Ona Katherine , McMaster Michael , Bessonneau Vincent , Rudel Ruthann , Buren Heather , Morello-Frosch Rachel
Published: November 2020

Background

Environmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential marker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.

Methods

We measured serum levels of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters and office workers who participated in the 2014-15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.

Results

Regression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (β(95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis(2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (−0.14(−0.28, −0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and levels of exposure between the two groups and/or potential unmeasured confounding.

Conclusion

Our findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.
Alzheimer’s and Parkinson’s diseases predict different COVID-19 outcomes, a UK Biobank study
Authors: Yu Yizhou , Travaglio Marco , Popovic Rebeka , Leal Nuno Santos , Martins L. Miguel
Published: November 2020

In December 2019, a coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began infecting humans causing a novel disease, coronavirus disease 19 (COVID-19). This was first described in the Wuhan province of the People’s Republic of China. SARS-CoV-2 spread throughout the world causing a global pandemic. To date, thousands of cases of COVID-19 were reported in the United Kingdom, and over 45,000 patients have died. Some progress has been achieved in managing this disease, but the biological determinants of health, besides age, that affect COVID-19 infectivity and mortality are under scrutiny. Recent studies show that several medical conditions, including diabetes and hypertension, increase the risk of COVID-19 infection and death. The increased vulnerability of the elderly and those with comorbidities, together with the prevalence of neurodegenerative diseases with advanced age, led us to investigate the links between neurodegeneration and COVID-19. We analysed the primary health records of 13,338 UK individuals tested for COVID-19 between March and July 2020. We show that a pre-existing diagnosis of Alzheimer’s disease predicts the highest risk of COVID-19 infection and mortality among the elderly. In contrast, Parkinson’s disease patients were found to be at increased risk of infection but not mortality from COVID-19. We conclude that there are disease-specific differences in COVID-19 susceptibility among patients affected by neurodegenerative disorders.
COVID-19 Wastewater Epidemiology: A Model to Estimate Infected Populations
Authors: McMahan Christopher Steven , Self Stella , Rennert Lior , Kalbaugh Corey , Kriebel David , Graves Duane , Deaver Jessica A. , Popat Sudeep , Karanfil Tanju , Freedman David L.
Published: November 2020

BACKGROUND

Wastewater-based epidemiology (WBE) provides an opportunity for near real-time, cost-effective monitoring of community level transmission of SARS-CoV-2, the virus that causes COVID-19. Detection of SARS-CoV-2 RNA in wastewater can identify the presence of COVID-19 in the community, but methods are lacking for estimating the numbers of infected individuals based on wastewater RNA concentrations.

METHODS

Composite wastewater samples were collected from three sewersheds and tested for SARS-CoV-2 RNA. A Susceptible-Exposed-Infectious-Removed (SEIR) model based on mass rate of SARS-CoV-2 RNA in the wastewater was developed to predict the number of infected individuals. Predictions were compared to confirmed cases identified by the South Carolina Department of Health and Environmental Control for the same time period and geographic area.

RESULTS

Model predictions for the relationship between mass rate of virus release to the sewersheds and numbers of infected individuals were validated based on estimated prevalence from individual testing. A simplified equation to estimate the number of infected individuals fell within the 95% confidence limits of the model. The unreported rate for COVID-19 estimated by the model was approximately 12 times that of confirmed cases. This aligned well with an independent estimate for the state of South Carolina.

CONCLUSIONS

The SEIR model provides a robust method to estimate the total number of infected individuals in a sewershed based on the mass rate of RNA copies released per day. This overcomes some of the limitations associated with individual testing campaigns and thereby provides an additional tool that can be used to better inform policy decisions.
Xingnaojing injection can regulate dysbacteriosis and increase the concentration of short chain fatty acids in the feces after stroke in mice
Authors: Lin Jingfeng , Liu Ganlu , Han Zhenyun , Gao Qiang , Wang Zhenyi , Chang Ze , Gao Ying , Ma Dayong
Published: November 2020

Background

Xingnaojing injection (XNJ) is extracted from the Chinese ancient prescription “An-Gong-Niu-Huang Pill”, is widely used for stroke in China. We mainly observe the effect of XNJ (Xingnaojing) injection on the gut microbiota in stroke model mice.

Methods

Forty-two 7-to 8-week-old male C57 mice weighing 22-24 g were chosen for the experiment. There were 6 mice in each group; the 7 groups were the normal group (NG), the MCAO group (CG), the MCAO+XNJ group (EG), the sham surgery group (SG), the sham germ-free normal group (SGFNG), the sham germ-free+MCAO group (SGFCG), and the sham germ-free+MCAO+XNJ group (SGFEG). Two days before modeling, we abdominally administered Xingnaojing (6 mg/kg) the SGFEG and EG groups. The processing time of sustained XNJ was 5 days. Three days after modeling, 1 ~ 2 mouse feces were collected, and after a MiSeq PE library was constructed, an Illumina MiSeq PE 300 platform was used for high-throughput sequencing. After cleaning the sequencing data, the microbiome and microbiomeseq packages were used for analysis using R software (version 3.6.2).

Results

Alpha diversity analysis revealed that the diversity was not different between the CG and EG. The Simpson index was different between the SGFCG and SGFEG. XNJ increased the levels ofSutterellaceaeand decreased the level ofDeferribacteresandMorganella. LEfSe analysis showed that SGFCG mice were also enriched withMorganella. XNJ increased the concentrations of the SCFAs PA (propionate), VA (valerate), IBA (isobutyrate), and IVA (isovalerate) in the feces of the SGFEG group. BA (butyrate) had greater positive correlation with gut bacteria than other acids in the SGFCG, and XNJ changed this trend. KEGG analysis showed that peptidoglycan biosynthesis was most different between the CG and EG.

Conclusion

Ischemic stroke (IS) causes dysbiosis of some specific bacteria in the gut microbiota in MCAO mice. Xingnaojing ameliorated this condition by increasing the levels ofSutterellaceaeand decreasing the level ofDeferribacteresandMorganella. These results are in accordance with other research on Chinese medicines for IS that affect the gut microbiota. Enrichment analysis of SCFAs revealed that XNJ improved the levels of SCFAs through an energy metabolism-related pathway.
Single-cell dissection of schizophrenia reveals neurodevelopmental-synaptic axis and transcriptional resilience
Authors: Ruzicka W. Brad , Mohammadi Shahin , Davila-Velderrain Jose , Subburaju Sivan , Tso Daniel Reed , Hourihan Makayla , Kellis Manolis
Published: November 2020

Schizophrenia is a devastating mental disorder with a high societal burden, complex pathophysiology, and diverse genetic and environmental risk factors. Its complexity, polygenicity, and small-effect-size and cell-type-specific contributors have hindered mechanistic elucidation and the search for new therapeutics. Here, we present the first single-cell dissection of schizophrenia, across 500,000+ cells from 48 postmortem human prefrontal cortex samples, including 24 schizophrenia cases and 24 controls. We annotate 20 cell types/states, providing a high-resolution atlas of schizophrenia-altered genes and pathways in each. We find neurons are the most affected cell type, with deep-layer cortico-cortical projection neurons and parvalbumin-expressing inhibitory neurons showing significant transcriptional changes converging on genetically-implicated regions. We discover a novel excitatory-neuron cell-state indicative of transcriptional resilience and enriched in schizophrenia subjects with less-perturbed transcriptional signatures. We identify key trans-acting factors as candidate drivers of observed transcriptional perturbations, including MEF2C, TCF4, SOX5, and SATB2, and map their binding patterns in postmortem human neurons. These factors regulate distinct gene sets underlying fetal neurodevelopment and adult synaptic function, bridging two leading models of schizophrenia pathogenesis. Our results provide the most detailed map to date for mechanistic understanding and therapeutic development in neuropsychiatric disorders.
Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry
Authors: Kirkup Christian , Pawlowski Colin , Puranik Arjun , Conrad Ian , O’Horo John C. , Gomaa Dina , Banner-Goodspeed Valerie M. , Mosier Jarrod M , Zabolotskikh Igor Borisovich , Daugherty Steven K. , Bernstein Michael A. , Zaren Howard A. , Bansal Vikas , Pickering Brian , Badley Andrew D. , Kashyap Rahul , Venkatakrishnan AJ , Soundararajan Venky
Published: November 2020

COVID-19 patients are at an increased risk of thrombosis and various anticoagulants are being used in patient management without an established standard-of-care. Here, we analyze hospitalized and ICU patient outcomes from the Viral Infection and Respiratory illness Universal Study (VIRUS) registry. We find that severe COVID patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (311 deceased patients out of 760 total patients = 41%) compared to patients administered enoxaparin but not unfractionated heparin (214 deceased patients out of 1,432 total patients = 15%), presenting a risk ratio of 2.74 (95% C.I.: [2.35, 3.18]; p-value: 1.4e-41). This difference persists even after balancing on a number of covariates including: demographics, comorbidities, admission diagnoses, and method of oxygenation, with an amplified mortality rate of 39% (215 of 555) for unfractionated heparin vs. 23% (119 of 522) for enoxaparin, presenting a risk ratio of 1.70 (95% C.I.: [1.40, 2.05]; p-value: 2.5e-7). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to those administered enoxaparin, including acute kidney injury (227 of 642 [35%] vs. 156 of 608 [26%] respectively, adjusted p-value 0.0019), acute cardiac injury (40 of 642 [6.2%] vs. 15 of 608 [2.5%] respectively, adjusted p-value 0.01), septic shock (118 of 642 [18%] vs. 73 of 608 [12%] respectively, adjusted p-value 0.01), and anemia (81 of 642 [13%] vs. 46 of 608 [7.6%] respectively, adjusted p-value 0.02). Furthermore, a higher percentage of Black/African American COVID patients (375 of 1,203 [31%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (595 of 2,488 [24%]), for a risk ratio of 1.3 (95% C.I.: [1.17, 1.45], adjusted p-value: 1.6e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (272 of 959 [28%] for Black/African American vs. 213 of 959 [22%] for White/Caucasian, adjusted p-value: 0.01, relative risk: 1.28, 95% C.I.: [1.09, 1.49]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research in order to elucidate potential socioeconomic, racial, or other disparities underlying the use of anticoagulants to treat severe COVID patients.
Human cardiac stromal cells exposed to SARS-CoV-2 evolve into hyper-inflammatory/pro-fibrotic phenotype and produce infective viral particles depending on the levels of ACE2 receptor expression
Authors: Amendola Alessandra , Garoffolo Gloria , Songia Paola , Ferrari Silvia , Bernava Giacomo , Canzano Paola , Myasoedova Veronika , Colavita Francesca , Castilletti Concetta , Sberna Giuseppe , Capobianchi Maria Rosaria , Agrifoglio Marco , Colombo Gualtiero I. , Poggio Paolo , Pesce Maurizio
Published: November 2020

Patients with severe respiratory syndrome caused by SARS-CoV-2 undergo cardiac complications due to hyper-inflammatory conditions. Although the presence of the virus has been detected in the myocardium of infected patients, and infection of cardiac cells may involve ACE2 receptor, the underlying molecular/cellular mechanisms are still uncharacterized. We analyzed expression of ACE2 receptor in primary human cardiac stromal cells using proteomic and transcriptomic methods before exposing them to SARS-CoV-2 in vitro. Using conventional and high sensitivity PCR methods, we measured virus production in the cellular supernatants and monitored the intracellular viral bioprocessing. We performed high-resolution imaging to show the sites of intracellular viral production. We finally used Q-RT-PCR assays to detect genes linked to innate immunity and fibrotic pathways coherently regulated in cells exposed to virus. Our findings indicate that human cardiac stromal cells have a susceptibility to SARS-CoV-2 infection and produce variable viral yields depending on the extent of cellular ACE2 receptor expression. Interestingly, these cells also evolved toward hyper-inflammatory/pro-fibrotic phenotypes independently of ACE2 levels, suggesting a dual cardiac damage mechanism that could account for the elevated numbers of cardiac complications in severe COVID-19 cases.
Testosterone and socioeconomic position: Mendelian Randomization in 306,248 men and women participants of UK Biobank
Authors: Harrison Sean , Davies Neil M , Howe Laura D , Hughes Amanda
Published: November 2020

Men with more advantaged socioeconomic position (SEP) and better health have been observed to have higher levels of testosterone. It is unclear whether these associations arise because testosterone has a causal impact on SEP and health. In 306,248 participants of UK Biobank, we performed sex- stratified genome-wide association analysis to identify genetic variants associated with testosterone. Using the identified variants, we performed Mendelian randomization analysis of the influence of testosterone on socioeconomic position, including income, employment status, area-level deprivation, and educational qualifications; on health, including self-rated health and BMI, and on risk-taking behaviour. We found little evidence that testosterone affected socioeconomic position, health, or risk-taking. Our results therefore suggest it is unlikely that testosterone meaningfully affects these outcomes in men or women. Differences between Mendelian randomization and multivariable-adjusted estimates suggest previously reported associations with socioeconomic position and health may be due to residual confounding or reverse causation.
Interventions targeting nonsymptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case-study
Authors: Lovell-Read Francesca A. , Funk Sebastian , Obolski Uri , Donnelly Christl A. , Thompson Robin N.
Published: November 2020

During infectious disease epidemics, an important question is whether cases travelling to new locations will trigger local outbreaks. The risk of this occurring depends on the transmissibility of the pathogen, the susceptibility of the host population and, crucially, the effectiveness of surveillance in detecting cases and preventing onward spread. For many pathogens, transmission from presymptomatic and/or asymptomatic (together referred to as nonsymptomatic) infectious hosts can occur, making effective surveillance challenging. Here, using SARS-CoV-2 as a case-study, we show how the risk of local outbreaks can be assessed when nonsymptomatic transmission can occur. We construct a branching process model that includes nonsymptomatic transmission, and explore the effects of interventions targeting nonsymptomatic or symptomatic hosts when surveillance resources are limited. We consider whether the greatest reductions in local outbreak risks are achieved by increasing surveillance and control targeting nonsymptomatic or symptomatic cases, or a combination of both. We find that seeking to increase surveillance of symptomatic hosts alone is typically not the optimal strategy for reducing outbreak risks. Adopting a strategy that combines an enhancement of surveillance of symptomatic cases with efforts to find and isolate nonsymptomatic infected hosts leads to the largest reduction in the probability that imported cases will initiate a local outbreak.
Associations Between Major Psychiatric Disorder Polygenic Risk Scores and Blood-Based Markers in UK Biobank
Authors: Sewell Michael D.E. , Shen Xueyi , Jiménez-Sánchez Lorena , Edmondson-Stait Amelia J. , Green Claire , Adams Mark J. , McIntosh Andrew M. , Lyall Donald M. , Whalley Heather C. , Lawrie Stephen M.
Published: November 2020

Background

Major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors and abnormalities in blood-based measures of inflammation and blood-brain barrier (BBB) permeability. The relationships between such genetic architectures and blood-based markers are however unclear. We investigated relationships between polygenic risk scores for these disorders and peripheral biomarkers in the UK Biobank cohort.

Methods

We calculated polygenic risk scores (PRS) for samples of n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) individuals from the UK Biobank cohort. We examined associations between each disorder PRS and 62 blood markers, using two generalized linear regression models: ‘minimally adjusted’ controlling for variables including age and sex, and ‘fully adjusted’ including additional lifestyle covariates such as alcohol and smoking status.

Results

12/62, 13/62 and 9/62 peripheral markers were significantly associated with MDD, SCZ and BD PRS respectively for both models. Most associations were disorder PRS-specific, including several immune-related markers for MDD and SCZ. We also identified several BBB-permeable marker associations, including vitamin D for all three disorder PRS, IGF-1 and triglycerides for MDD PRS, testosterone for SCZ PRS, and HDL cholesterol for BD PRS.

Conclusions

This study suggests that MDD, SCZ and BD have shared and distinct peripheral markers associated with disorder-specific genetic risk. The results implicate BBB permeability disruptions in all three disorders and inflammatory dysfunction in MDD and SCZ, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.
Primary school staff perspectives of school closures due to COVID-19, experiences of schools reopening and recommendations for the future: a qualitative survey in Wales
Authors: Marchant Emily , Todd Charlotte , James Michaela , Crick Tom , Dwyer Russell , Brophy Sinead
Published: November 2020

School closures due to the COVID-19 global pandemic are likely to have a range of negative consequences spanning the domains of child development, education and health, in addition to the widening of inequalities and inequities. Research is required to improve understanding of the impact of school closures on the education, health and wellbeing of pupils and school staff, the challenges posed during reopening and importantly to identify how countries can return to in-school education and to inform policy. This qualitative study aimed to reflect on the perspectives and experiences of primary school staff (pupils aged 3-11) in Wales regarding school closures and the initial reopening of schools and to identify recommendations for the future. A total of 208 school staff completed a national online survey through the HAPPEN primary school network, consisting of questions about school closures (March to June 2020), the phased reopening of schools (June to July 2020) and a return to full-time education. Thematic analysis of survey responses highlighted that primary school staff perceive that gaps in learning, health and wellbeing have increased and inequalities have widened during school closures. Findings from this study identified five recommendations; (i) prioritise the health and wellbeing of pupils and staff; (ii) focus on enabling parental engagement and support; (iii) improve digital competence amongst pupils, teachers and parents; (iv) consider opportunities for smaller class sizes and additional staffing; and (v) improve the mechanism of communication between schools and families, and between government and schools.