bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted ablation of afferent renal nerves by periaxonal capsaicin abolishes the reno‐renal reflex
Authors: Banek Christopher , Osborn John
Published: June 2021

Recent clinical findings report targeted renal sympathetic denervation (RDNx) as a novel therapy to treat cardiovascular diseases. However, the contribution of ablation of afferent vs. efferent nerves in mediating responses to RDNx is unclear. Foss and colleagues have reported a novel method for afferent‐specific RDNx by periaxonal application of capsaicin (CAP), which may have an anti‐hypertensive effect. However, functional confirmation of CAP remains untested. To this end, we aimed to test the ability of CAP to block the reno‐renal reflex. Male Sprague Dawley rats (275‐300g) underwent unilateral (left) CAP (n=4) or sham (n=5) procedure. Acute experimentation was performed 3‐5 days post‐operation. Under 2% isoflurane, the left femoral artery and vein were cannulated for arterial pressure (AP) measurement and saline infusion (150mM; 50ul/min), respectively. Each renal pelvis was cannulated to control pelvic pressure and collect urine. After a 90‐minute stabilization, urine flow from the right kidney was measured while the left pelvic pressure was maintained at 0 and 20mmHg for one hour. Data was averaged over each time interval and analyzed by two‐way ANOVA with a Bonferroni post‐hoc test. Data presented as change from baseline (mean+SEM). In sham rats, a 20mmHg increase in pelvic pressure increased contralateral urine flow (Δ1.8±0.5µl/min;p<.05) and Na+ excretion (Δ0.40±0.16µmol/min; p<.01). CAP abolished both responses (p<.01; p<.001). CAP had no effect on basal levels of AP, urine output or Na+ excretion. Collectively, these data provide a functional confirmation of targeted afferent renal nerve ablation by CAP treatment. Further study is underway to further elucidate the role of renal afferent nerves in cardiovascular health and disease. NIH R01 HL116476
Reduction Of Adiposity Improves Preeclampsia (PE) Symptoms In BPH/5 Mice
Authors: Lob Heinrich , Sones Jennifer , Song Jiunn , Davisson Robin
Published: June 2021

Preeclampsia (PE) is a hypertensive proteinuric disorder of pregnancy that can result in fetal demise and growth restriction. Although it is a major cause of fetal and maternal morbidity/mortality, the underlying mechanisms remain unclear. Increased adiposity is a risk factor for PE. However, longitudinal studies to investigate the contribution of adiposity to PE are difficult to perform in humans. We utilized the BPH/5 mouse, a spontaneous model of PE, to test the hypothesis that calorie restriction (cr) before and during gestation would improve adverse pregnancy outcomes in this model. Food intake was measured in non‐pregnant (NP) BPH/5 and C57 controls. We found that NP BPH/5 are hyperphagic (3.42 ± 0.1 g; C57: 2.91 ± 0.1 g, n=7, P<0.05). Matching food availability for BPH/5 to the amount consumed by C57 significantly reduced NP and late‐gestational (e18.5) gonadal white adipose tissue in BPH/5 (NP: adlib: 0.46 ± 0.06 g, cr : 0.30 ± 0.03 g, n=9‐15, P<0.05; e18.5: adlib: 0.90 ± 0.19 g, cr : 0.33 ± 0.08 g, n=4, P<0.05). This strategy also prevented proteinuria at e18.5 as well as improved fetal outcomes, including litter size (BPH/5 ad‐lib: 4.0 ± 0.6; cr: 6.7 ± 0.3, n=3, P<0.05) and pup weight (BPH/5 ad‐lib: 1.5 ± 0.08 g; cr: 1.9 ± 0.04 g, n=6‐9, P<0.05). These data show that reducing food intake before pregnancy has beneficial effects on maternal and fetal outcomes in this model of PE. These data point towards adiposity playing an important role in the pathogenesis of PE.

12SDG9160019, HL084207, HL63887
Fibroma of the external nose
Authors: Batyrov T.W. , Sagyndyk H.L. , Kozhakov B.B.
Published: June 2021

Defects of the external nose of any origin difficult tolerated as it causes disfigurement of the face. That is why any cosmetic defects of the nose are severe traumatic factor, regardless of gender and age of the patient.

Introduction

The use of pedicled flap helped to avoid the negative aspects of the classical “Italian” rhinoplasty, such as prolonged immobilization, and the ability to multi‐stage stem necrosis in the transfer process due to lack of blood supply to the axis, which brought great inconvenience to the patient.

Results

Patient S., 33goda, turned 5 years first appearance of Education of the left wing and nose. Diagnosis: Fibroma tip and the left wing of the nose (histological diagnosis is the same). We removed under local anesthesia education within the healthy tissue to cartilage, a defect oval 32,0 x 28,0mm. Is cut skin and fat flap pedicled from the left nasolabial fold, which moved to the defect and sutured in layers. On the 12 day cut off pedicle and made the correction.

Discussion

It should be emphasized availability of flaps, a cut from the skin of the forehead which is not always justified, and the only method of rhinoplasty. Its use is most effective when combined rhinoplasty. However, this method also many stages are not perceived by patients due to the fact that leaves rough, sometimes deforming noticeable scars on her forehead. Multi‐stage operation is uncomfortable for patients.

Conclusions

To date, we have used with great success Acute dermal fat flap of nasolabial folds. This method allows simultaneously closed a defect, perform simple technical and patient in a short time back into everyday life. This method we used in 37 cases, with good long‐term results.
Elevated oxidative stress in type 2 diabetic OLETF rat liver
Authors: Tsuzuki Takamasa , Nakamoto Hideko , Kobayashi Hiroyuki , Goto Sataro , Ichinoseki‐Sekine Noriko , Naito Hisashi
Published: June 2021

Purpose

To investigate the oxidative stress level at the initial stage of diabetes in Otsuka Long‐Evans Tokushima Fatty (OLETF) rat liver.

Methods

Male OLETF rats, which are used as an animal model of type 2 diabetes, and their counterparts (Long‐Evans Tokushima Otsuka [LETO] rats) were studied (n = 4, respectively). Liver samples were collected from 25‐week‐old rats under anesthesia following an overnight fast. Reduced and oxidized glutathione (GSH and GSSG, respectively) and thiobarbituric acid reatctive substance (TBARS) concentrations were measured. Glutathione reductase (GR) and glutathione peroxidase (GPx) mRNA levels were analyzed by RT‐PCR. Protein carbonylation was analyzed in cytosolic and mitochondrial fractions by Western blotting.

Results

There were no differences in GSH concentration and GR mRNA level between the animals. In contrast, the TBARS and GSSG concentrations and GPx mRNA expression level were significantly higher in the OLETF rats (+82.9%, +31.1% and +100.4%, respectively) than in LETO rats (p < 0.05). The protein carbonylation level in the mitochondrial fraction was significantly higher in OLETF rats (+19.6%) than in LETO rats (p < 0.05), whereas no difference in the protein carbonylation level in the cytosolic fraction were observed between the animals.

Conclusion

Our data suggest that oxidative stress increases in the OLETF rat liver at the initial stage of type 2 diabetes.
Inhibitory Effect of Musa paradisiaca on Enzymes Linked to Diabetes and Hypertension
Authors: Shodehinde Sidiqat , Nwanna Esther , Adeyemo Adenike
Published: June 2021

The purpose of this study was to determine whether unripe plantain products has hypoglycemic properties by comparing its potency with commercial drug (arcabose) on key enzymes linked to diabetes (α‐amylase and α‐glucosidase) and hypertension [(Angiotensin‐I Converting Enzyme) (ACE)]

Diabetes was induced by combined feeding of the adult male Wistar rats with High fat diet (Lard) plus intraperitoneal injection of streptozotocin (25 mg/kg body weight). After sacrifice, the pancreas was examined for α‐amylase, α‐glucosidase angiotensin‐1 converting enzyme. The plasma obtained was also studied by testing for GST, GSH and Malonadialdehyde (MDA) activities. The diabetic rats showed elevated (P<0.05) levels of α‐amylase, α‐glucosidase and ACE and MDA (end product of lipid peroxidation). However, the effect of treatment of unripe plantain products supplement diets on diabetic rats (after 30 days) was significantly (P<0.05) reversing the above mentioned parameters toward normalcy.

These results imply that there is more to unripe plantain than mere consumption. It also brings about a new dimension to the management of diabetes and its attendant complications.
The Endothelial Receptor Tyrosine Kinase Tie2 is Essential for Vascular Integrity Dependent/Independent of Inflammation
Authors: Ghosh Chandra , David Sascha , Milam Katelyn , Mukherjee Aditi , Santel Ansgar , Lu Shulin , Yano Kiichiro , Dumont Daniel , Parikh Samir
Published: June 2021

Endothelial Receptor Tyrosine Kinase Tie2, and its two principal ligands Angiopoietin1&2 (Angpt‐1&2), play an important role in heath and diseases. Its agonistic ligand Angpt‐1 mainly expressed in perivascular cells whereas Angpt‐2, stored in Weible –Palade‐Bodies, compete with Angpt‐1 and function as partial agonist/antagonist. However, the consequence of the loss of Tie2 and potential contribution to vascular dysfunction in health and disease has not been investigated so far.

In the present study we found mice with one copy of Tie2 gene a) are more vulnerable to death in murine sepsis models, endotoxemia (83% vs. 42%, P < 0.05) and Cecal Ligation and Perforation (CLP) (76% vs. 32%, P < 0.05); b) has enhanced vascular leak as measured by Evans's blue extravasation assay. Similarly,siRNA mediated knock‐down of Tie2 results in enhanced vascular leak in lungs with perturbed downstream signaling of Tie2. In vitro by using shRNA ‐lentiparticles we found Angpt‐1 induced prevention of Lipo‐polysaccharide (LPS) ‐mediated vascular barrier dysunction in Tie2 dependent fashion. Above all, the effect of reduced Tie2 expression in‐vivo and in‐vitro is independent of changes to the inflammatory milieu.

In conclusion, our study demonstrates a novel inflammation independent role for Tie2 mediating endothelial vascular function in sepsis. Further studies are underway to investigate the upstream and downstream regulators of Tie2 and reveal the diagnostic and therapeutic implication of this important pathway.
Role of standardized reporting and novel imaging markers in chronic pancreatitis
Authors: Tirkes Temel , Dasyam Anil K. , Shah Zarine K. , Fogel Evan L.
Published: June 2021

Purpose of review

This article reviews recent efforts about standardized imaging features and reporting of chronic pancreatitis and recently published or ongoing imaging studies, which aim to establish novel imaging biomarkers for detection of parenchymal changes seen in chronic pancreatitis.

Recent findings

New novel MRI techniques are being developed to increase the diagnostic yield of chronic pancreatitis specifically in the early stage. T1 relaxation time, T1 signal intensity ratio and extracellular volume fraction offer potential advantages over conventional cross-sectional imaging, including simplicity of analysis and more objective interpretation of observations allowing population-based comparisons. In addition, standardized definitions and reporting guidelines for chronic pancreatitis based on available evidence and expert consensus have been proposed. These new imaging biomarkers and reporting guidelines are being validated for prognostic/therapeutic assessment of adult patients participating in longitudinal studies of The Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer.

New imaging biomarkers derived from novel MRI sequences promise a new chapter for diagnosis and severity assessment of chronic pancreatitis; a cross-sectional imaging-based diagnostic criteria for chronic pancreatitis combining ductal and parenchymal findings. Standardized imaging findings and reporting guidelines of chronic pancreatitis would enhance longitudinal assessment of disease severity in clinical trials and improve communication between radiologists and pancreatologists in clinical practice.
Dietitians' Change in Practice
Authors: Sheffer-Hilel Galia , Drach-Zahavy Anat , Goldblatt Hadass , Endevelt Ronit
Published: June 2021

Dietetics has recently begun implementing the nutrition-focused physical examination, based on a physical examination of oral health. This qualitative study, interviewing 18 dietitians, examined how dietitians experience and cope with this change. Inductive thematic analysis revealed that dietitians experienced the change as either a threat or a challenge, as well as stemming from within or outside the profession. Dietitians' preferred coping strategies that derive from their personal experiences. Managers are recommended to develop coaching programs for dietitians to help them perceive the change as a challenge, focus on the opportunity for mastery, and gain skills to lead the interdisciplinary team.
Serum Vitamin D Levels and the Risk of Pneumonia in Children
Authors: Tang Jinghai , Lu Qinghua , Li Yuhong , Huang Lei
Published: June 2021

This systematic review and meta-analysis aimed to evaluate the association between serum vitamin D concentrations and the risk of pneumonia in children. Human studies reporting serum vitamin D levels in children with pneumonia and healthy controls were collected from different databases. The standardized mean difference and 95% confidence interval were calculated to evaluate the relationship between risk incidence of pneumonia and serum vitamin D levels. The results of analysis showed that serum vitamin D levels in children with pneumonia were significantly lower than those in healthy control children.
Clinical Leadership in Dietetics
Authors: Patten Emily Vaterlaus , Sauer Kevin , Osborne Sharee Leany , Rose Kara
Published: June 2021

Clinical leadership has been addressed in many health care professions; yet, there is little research in dietetics. This qualitative study explored registered dietitian nutritionists' (RDNs'; n = 561) perspectives on what clinical leadership is in dietetics practice and what barriers exist to practicing it. Two thematic analyses were explored. RDNs described dietetics clinical leadership as including strong technical skills, interpersonal interactions, and specific personal attributes. RDNs described barriers to practicing clinical leadership that included the work environment, limited resources, and individual circumstances/attributes. Managers may consider these perspectives as they work with clinical RDNs, and educators can incorporate these findings into the dietetics curriculum.
Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa
Authors: Salaam-Dreyer Zubeida , Streicher Elizabeth M. , Sirgel Frederick A. , Menardo Fabrizio , Borrell Sonia , Reinhard Miriam , Doetsch Anna , Cudahy Patrick G.T. , Mohr-Holland Erika , Daniels Johnny , Dippenaar Anzaan , Nicol Mark P. , Gagneux Sebastien , Warren Robin M. , Cox Helen
Published: June 2021

Rifampicin mono-resistant TB (RMR-TB) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting. Patient-level clinical data and stored RR-TB isolates from 2008-2017 with available whole genome sequencing (WGS) data were used to describe risk factors associated with RMR-TB and to compare rifampicin-resistance (RR) conferring mutations between RMR-TB and MDR-TB. A subset of isolates with particular RR-conferring mutations were subjected to semi-quantitative rifampicin phenotypic drug susceptibility testing. Among 2,041 routinely diagnosed RR-TB patients, 463 (22.7%) had RMR-TB. HIV-positive individuals (adjusted Odds Ratio 1.4, 95% CI 1.1-1.9) and diagnosis between 2013-2017 versus 2008-2012 (aOR 1.3, 1.1-1.7) were associated with RMR-TB. Among 1,119 (54.8%) patients with available WGS data showing RR-TB, significant differences in the distribution of rpoB RR-conferring mutations between RMR-TB and MDR-TB isolates were observed. Mutations associated with high-level RR were more commonly found among MDR-TB isolates (811/889, 90.2% versus 162/230, 70.4% among RMR-TB, p<0.01). In particular, the rpoB L430P mutation, conferring low-level RR, was identified in 32/230 (13.9%) RMR-TB versus 10/889 (1.1%) in MDR-TB (p<0.01). Among 10 isolates with an rpoB L430P mutation, 7 were phenotypically susceptible using the critical concentration of 0.5 µg/ml (range 0.125-1 µg/ml). The majority (215/230, 93.5%) of RMR-TB isolates showed susceptibility to all other TB drugs, highlighting the potential benefits of WGS for simplified treatment. These data suggest that the evolution of RMR-TB differs from MDR-TB with a potential contribution from HIV infection.
Widespread Contamination of SARS-CoV-2 on Highly Touched Surfaces in Brazil During the Second Wave of the COVID-19 Pandemic
Authors: da Silva Severino Jefferson Ribeiro , do Nascimento Jéssica Catarine Frutuoso , dos Santos Reis Wendell Palôma Maria , da Silva Caroline Targino Alves , da Silva Poliana Gomes , Germano Mendes Renata Pessôa , Mendonça Allyson Andrade , Rodrigues Santos Bárbara Nazly , de Magalhães Jurandy Júnior Ferraz , Kohl Alain , Pena Lindomar
Published: June 2021

Although SARS-CoV-2 surface contamination has been investigated in temperate climates, few studies have been conducted in the tropics. Here, we investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil. A total of 400 surface samples were collected in February 2021 in the City of Recife, Northeastern Brazil. A total of 97 samples (24.2%) tested positive for SARS-CoV-2 by RT-qPCR using the CDC-USA protocol. All the collection sites, except one (18/19, 94.7%) had at least one environmental surface sample contaminated. SARS-CoV-2 positivity was higher in public transport terminals (47/97, 48.4%), followed by health care units (26/97, 26.8%), public parks (14/97, 14.4%), public markets (4/97, 4.1%), and beach areas (4/97, 4.1%). Toilets, ATMs, handrails, playground, and outdoor gym were identified as fomites with the highest rates of viral contamination. Regarding the type of material, SARS-CoV-2 RNA was found more commonly on metal (45/97, 46.3%), followed by plastic (18/97, 18.5%), wood (12/97, 12.3%), rock (10/97, 10.3%), concrete (8/97, 8.2%), and glass (2/97, 2.0%). Taken together, our data indicated extensive SARS-CoV-2 contamination in public surfaces and identified critical control points that need to be targeted to break SARS-CoV-2 transmission chains.

Synopsis

We investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil and identified critical points to establish effective control measures aimed at breaking transmission.

Abstract Figure
Recovery from Covid-19 critical illness: a secondary analysis of the ISARIC4C CCP-UK cohort study and the RECOVER trial
Authors: Pauley Ellen , Drake Thomas M , Griffith David M , Lone Nazir I , Harrison Ewen M , Baillie J Kenneth , Scott Janet T , Walsh Timothy S , Semple Malcolm G , Docherty Annemarie B
Published: June 2021

Background

We aimed to compare the prevalence and severity of fatigue in survivors of Covid-19 versus non-Covid-19 critical illness, and to explore potential associations between baseline characteristics and worse recovery.

Methods

We conducted a secondary analysis of two prospectively collected datasets. The population included was 92 patients who received invasive mechanical ventilation (IMV) with Covid-19, and 240 patients who received IMV with non-Covid-19 illness before the pandemic. Follow-up data was collected post-hospital discharge using self-reported questionnaires. The main outcome measures were self-reported fatigue severity and the prevalence of severe fatigue (severity >7/10) 3 and 12-months post-hospital discharge.

Results

Covid-19 IMV-patients were significantly younger with less prior comorbidity, and more males, than pre-pandemic IMV-patients. At 3-months, the prevalence (38.9% [7/18] vs. 27.1% [51/188]) and severity (median 5.5/10 vs. 5.0/10) of fatigue was similar between the Covid-19 and pre-pandemic populations respectively. At 6-months, the prevalence (10.3% [3/29] vs. 32.5% [54/166]) and severity (median 2.0/10 vs. 5.7/10) of fatigue was less in the Covid-19 cohort. In the Covid-19 population, women under 50 experienced more severe fatigue, breathlessness, and worse overall health state compared to other Covid-19 IMV-patients. There were no significant sex differences in long-term outcomes in the pre-pandemic population. In the total sample of IMV-patients included (i.e. all Covid-19 and pre-pandemic patients), having Covid-19 was significantly associated with less severe fatigue (severity <7/10) after adjusting for age, sex, and prior comorbidity (adjusted OR 0.35 (95%CI 0.15-0.76, p=0.01).

Conclusion

Fatigue may be less severe after Covid-19 than after other critical illness.
Tocilizumab in COVID-19 – A Bayesian reanalysis of RECOVERY
Authors: Albuquerque Arthur M. , Tramujas Lucas , Sewanan Lorenzo R. , Brophy James M.
Published: June 2021

Background

Randomised Evaluation of COVID-19 Therapy (RECOVERY) demonstrated that tocilizumab reduces mortality in hospitalized COVID-19 patients. However, substantial uncertainty remains whether tocilizumab’s effect is similar across clinically relevant subgroups. Whether this uncertainty can be resolved with Bayesian methods is unknown.

Design, Setting, Participants, and Interventions

RECOVERY was a controlled, open-label, platform UK trial that randomized (1:1) 4116 adults with oxygen saturation <92% on room air or receiving oxygen therapy with C-reactive protein ≥75 mg/L to either usual care or tocilizumab plus usual care.

Main outcome measures

Mortality and hospital discharge within 28 days.

Methods

Using Bayesian methods, we combined RECOVERY with evidence-based priors in-corporating previous COVID-19 tocilizumab RCTs. The probability of tocilizumab’s benefit for respiratory support and corticosteroid subgroups and sensitivity analyses were performed with different prior distributions and baseline risks.

Results

For all-cause mortality, the posterior probabilities of decreased deaths with tocilizumab were >99% and 19% in patients using and not using corticosteroids, respectively. In patients on simple oxygen only, non-invasive ventilation and invasive mechanical ventilation, the probabilities of decreased mortality were 96%, >99% and 77%, respectively. The probabilities for a clinically significant mortality reduction, as assessed by an absolute risk difference > 3% (number needed to treat ≤ 33), were 77%, 96%, 56%, respectively. Sensitivity analyses highlighted the uncertainty and lack of conclusive evidence for tocilizumab’s effect in patients on invasive mechanical ventilation and those without concurrent corticosteroids. Posterior probabilities of benefit for hospital discharge outcome were high and consistent across most subgroups.

Conclusions

In this Bayesian reanalysis, COVID-19 hospitalized patients exposed to corticosteroids or on non-invasive ventilation have a high probability of a clinically meaningful mortality benefit from tocilizumab. Tocilizumab also likely improves discharge from hospital in most subgroups. Future research should further address if patients on invasive mechanical ventilation can also benefit from tocilizumab.
App-based COVID-19 syndromic surveillance and prediction of hospital admissions: The COVID Symptom Study Sweden
Authors: Kennedy Beatrice , Fitipaldi Hugo , Hammar Ulf , Maziarz Marlena , Tsereteli Neli , Oskolkov Nikolay , Varotsis Georgios , Franks Camilla A , Nguyen Diem , Spiliopoulos Lampros , Adami Hans-Olov , Björk Jonas , Engblom Stefan , Fall Katja , Grimby-Ekman Anna , Litton Jan-Eric , Martinell Mats , Oudin Anna , Sjöström Torbjörn , Timpka Toomas , Sudre Carole H , Graham Mark S , du Cadet Julien Lavigne , Chan Andrew T. , Davies Richard , Ganesh Sajaysurya , May Anna , Ourselin Sébastien , Pujol Joan Capdevila , Selvachandran Somesh , Wolf Jonathan , Spector Tim D , Steves Claire J , Gomez Maria F , Franks Paul W , Fall Tove
Published: June 2021

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Data from 19,161 self-reported PCR tests were used to create a symptom-based model to estimate the individual probability of symptomatic COVID-19, with an AUC of 0.78 (95% CI 0.74–0.83) in an external dataset. These individual probabilities were used to estimate daily regional COVID-19 prevalence, which were in turn used together with current hospital data to predict next week COVID-19 hospital admissions. We found that this hospital prediction model demonstrated a lower median absolute percentage error (MdAPE: 25.9%) across the five most populated regions in Sweden during the first pandemic wave than a model based on case notifications (MdAPE: 30.3%). During the second wave, the error rates were similar. When applying the same model to an English dataset, not including local COVID-19 test data, we observed MdAPEs of 22.3% and 19.0%, respectively, highlighting the transferability of the prediction model.
“It’s hard to keep a distance when you’re with someone you really care about” — a qualitative study of adolescents’ pandemic-related health literacy and how Covid-19 affects their lives
Authors: Riiser Kirsti , Richardsen Kåre Rønn , Haraldstad Kristin , Helseth Sølvi , Torbjørnsen Astrid
Published: June 2021

Purpose

The aim of this study was to explore how adolescents accessed, understood, appraised, and applied information on pandemic preventive measures, how their lives were impacted by long-lasting regulations and how they described their quality of life.

Methods

A qualitative design with focus group interviews was used to elaborate on the quantitative survey results obtained and analyzed in a previous survey study from the first phase of the Covid-19 pandemic. Five focus groups with seventeen adolescents were conducted digitally during the second pandemic phase in November and December 2020. The interview data were analyzed with directed content analysis.

Results

The adolescents reported using traditional media and official websites as sources for Covid-19 information. They engaged in preventive behavior, and washing hands and keeping a distance from strangers had become a habit. However, not being physically close to friends felt strange and unpleasant. The measure most frequently discussed was limiting social contact, which was a constant struggle. No one disputed the authorities’ guidelines and rules, but the social restrictions caused boredom and despair, particularly due to interrupted schooling and missed opportunities to engage in life events, and freely socialize with friends.

Conclusion

The adolescents gave an overall impression of being health literate, which corresponds well with the results from our previous survey study. Their descriptions of how they translated protective measures into their everyday lives demonstrate that they took responsibility and accepted personal costs for the collective good. However, life with social restrictions decreased their quality of life.
Use of the Internet and digital devices among people with severe mental ill health during the COVID-19 pandemic restrictions
Authors: Spanakis Panagiotis , Heron Paul , Walker Lauren , Crosland Susanne , Wadman Ruth , Newbronner Elizabeth , Johnston Gordon , Gilbody Simon , Peckham Emily
Published: June 2021

Background

Restrictions due to the COVID-19 pandemic have led to everyday reliance on digitalisation of life, including access to health care services. People with severe mental ill health (SMI – e.g., bipolar or psychosis spectrum disorders) are at greater risk for digital exclusion and it is unknown to what extent they are able to adapt to online service delivery. This cross-sectional survey study explored use of the Internet and digital devices during the pandemic restrictions and its association with physical and mental health changes.

Methods

367 adults with an SMI diagnosis completed a survey (online or offline) and provided information on access to Internet connection and devices, internet skills, online activities, and barriers to using the Internet. They also self-reported changes in mental and physical health.

Results

During the pandemic restrictions 61.6% were limited or non-users of the Internet. The majority had access to the Internet and digital devices but around half reported knowledge deficits. Most common activities were accessing information and entertainment (88.9%), staying in touch with friends and families (84.8%), and purchasing goods (other than food) (84.3%). Most common barriers were finding the Internet ‘not interesting’ (28.3%) or ‘too difficult’ (27.9%), as well as ‘security concerns’ (22.1% to 24.3%). Using the Internet ‘a lot’ (vs ‘just a bit or not at all’) during the pandemic was associated with younger age (Adj ORs = 4.76 – 6.39, Ps < .001), having a diagnosis of bipolar disorder (compared to psychosis; Adj OR = 3.88, P < .001), or reporting a decline in mental health (compared to no decline; Adj OR = 1.92, P = .01).

Conclusion

Most people with SMI were limited or non-users of the Internet during the pandemic, which seems to be mainly attributable to lack of interest and skills, rather than lack of devices or connectivity. Older adults with psychosis should be the focus of interventions to support digital engagement in people with SMI.
EXAMINING THE DOUBLE BURDEN OF MALNUTRITION FOR PRESCHOOL CHILDREN AND WOMEN OF REPRODUCTIVE AGE IN LOW- AND MIDDLE-INCOME COUNTRIES: A SCOPING REVIEW PROTOCOL
Authors: Were Jason Mulimba , Stranges Saverio , Sharma Ishor , Vargas-González Juan-Camilo , Campbell M. Karen
Published: June 2021

Introduction

The majority of the populations in Low-and Middle-Income Countries (LMICs) are encountering the double burden of malnutrition (DBM): the coexistence of both undernutrition and overnutrition sequalae. With DBM being a new phenomenon in research, little is known about its etiology, operational definitions and risk factors influencing its manifestation. The proposed scoping review is aimed at mapping literature with regards to the DBM phenomenon among preschool children and women of reproductive age in LMICs who are among the most high-risk groups to encounter DBM.

Methods

A comprehensive literature search will be conducted in the following electronic databases: MEDLINE, EMBASE, Scopus, CINAHL, LILACS and ProQuest Dissertations & Thesis Global. Additionally, searches in other government and institutional sources (World Health Organization website and university repositories) and forward and backward citation tracking of seminal articles will also be done. Two reviewers will independently conduct title and abstract screening and full text screening. Similarly, data extraction and coding will independently be done by two reviewers. Information extracted from included literature will be analysed qualitatively using thematic analysis approach and reported as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines.

Ethics and Dissemination

Ethical approval is not required for this study because the review is based on literature from publicly available sources. The dissemination of our findings will be done through presentations in relevant conferences and publication in a peer-reviewed journal.

Strengths and limitations

To the best of our knowledge, this is the first scoping review that focuses on exploring the etiology of the double burden of malnutrition among preschool children and women of reproductive age in Low-and Middle-Income Countries.

This review will encompass comprehensive literature search and will utilize a renowned thematic analysis framework to synthesis the findings of the study.

The findings of this review will be important in not only mapping the current literature with regards to the double burden of malnutrition phenomenon for risk populations but also guiding secondary data analysis for our subsequent studies.

The anticipated dearth of causation literature and longitudinal studies in this area of research may limit our findings, specifically in understanding the etiology of double burden of malnutrition.
Lipid droplets protect human β cells from lipotoxic-induced stress and cell identity changes
Authors: Tong Xin , Stein Roland
Published: June 2021

Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD structural protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties. Glucose stimulated insulin secretion was blunted in PLIN2KD cells and improved in PLIN2OE cells. An unbiased transcriptomic analysis revealed that limiting LD formation induced effectors of endoplasmic reticulum (ER) stress that compromised the expression of critical β cell function and identity genes. These changes were aggravated by exogenous treatment with FFAs toxic to islet β cells, and essentially reversed by PLIN2OE or using the ER stress inhibitor, tauroursodeoxycholic acid. These results strongly suggest that LDs are essential for adult human islet β cell activity by preserving FFA homeostasis.
A Parsimonious Description of Global Functional Brain Organization in Three Spatiotemporal Patterns
Authors: Bolt Taylor , Nomi Jason S. , Bzdok Danilo , Salas Jorge A. , Chang Catie , Yeo B.T. Thomas , Uddin Lucina Q. , Keilholz Shella D.
Published: June 2021

Resting-state functional MRI has yielded seemingly disparate insights into large-scale organization of the human brain. The brain’s large-scale organization can be divided into two broad categories - zero-lag representations of functional connectivity structure and time-lag representations of traveling wave or propagation structure. Here we sought to unify observed phenomena across these two categories in the form of three low-frequency spatiotemporal patterns composed of a mixture of standing and traveling wave dynamics. We showed that a range of empirical phenomena, including functional connectivity gradients, the task-positive/task-negative anti-correlation pattern, the global signal, time-lag propagation patterns, the quasiperiodic pattern, and the functional connectome network structure are manifestations of these three spatiotemporal patterns. These patterns account for much of the global spatial structure that underlies functional connectivity analyses, and unifies phenomena in resting-state functional MRI previously thought distinct.
Single molecule studies reveal branched pathways for activator-dependent assembly of RNA polymerase II pre-initiation complexes
Authors: Baek Inwha , Friedman Larry J. , Gelles Jeff , Buratowski Stephen
Published: June 2021

RNA polymerase II (Pol II) transcription reconstituted from purified factors suggests pre-initiation complexes (PICs) can assemble by sequential incorporation of factors at the TATA box. However, these basal transcription reactions are generally independent of activators and co-activators. To study PIC assembly under more realistic conditions, we used single-molecule microscopy to visualize factor dynamics during activator-dependent reactions in nuclear extracts. Surprisingly, Pol II, TFIIF, and TFIIE can pre-assemble on enhancer-bound activators before loading into PICs, and multiple Pol II complexes can bind simultaneously to create a localized cluster. Unlike TFIIF and TFIIE, TFIIH binding is singular and dependent on the basal promoter. Activator-tethered factors exhibit dwell times on the order of seconds. In contrast, PICs can persist on the order of minutes in the absence of nucleotide triphosphates, although TFIIE remains unexpectedly dynamic even after TFIIH incorporation. Our kinetic measurements lead to a new branched model for activator-dependent PIC assembly.

HIGHLIGHTS

Single molecule microscopy reveals unexpected dynamics of RNA Pol II and GTFs

Multiple Pol IIs cluster on UAS/enhancer-bound activators before binding the core promoter

Pol II, TFIIF, and TFIIE, but not TFIIH, can pre-assemble at the UAS/enhancer

Activators increase the rates of Pol II and GTF association with DNA

eTOC Blurb

Single-molecule microscopy experiments by Baek et al. show that RNA polymerase II and basal transcription factors TFIIF and TFIIE preassemble on UAS/enhancer-bound activators, poised for loading into initiation complexes with TFIIH at the core promoter. Transcription activators kinetically enhance factor recruitment, creating a localized cluster of polymerases at the UAS/enhancer.
The novel Rab5 effector FERRY links early endosomes with the translation machinery
Authors: Schuhmacher J. S. , tom Dieck S. , Christoforidis S. , Landerer C. , Davila Gallesio J. , Hersemann L. , Seifert S. , Schäfer R. , Giner A. , Toth-Petroczy A. , Kalaidzidis Y. , Bohnsack K. E. , Bohnsack M. T. , Schuman E. M. , Zerial M.
Published: June 2021

Localized translation is vital to polarized cells and requires precise and robust distribution of different mRNAs and ribosomes across the cell. However, the underlying molecular mechanisms are poorly understood and important players are lacking. Here we show that the novel Rab5 effectorFive-subunitEndosomalRab5 andRNA/ribosome intermediarY, FERRY complex recruits mRNAs and ribosomes to early endosomes, through direct mRNA interaction. FERRY displays preferential binding to certain groups of transcripts, including mRNAs encoding mitochondrial proteins. Deletion of FERRY subunits reduces the endosomal localization of transcripts in cells and has a significant impact on mRNA and protein levels. Clinical studies show that genetic disruption of FERRY causes severe brain damage. We found that, in neurons, FERRY co-localizes with mRNA on early endosomes and mRNA loaded FERRY-positive endosomes are in close proximity of mitochondria. FERRY thus transforms endosomes into mRNA carriers and plays a key role in regulating mRNA distribution and transport.
A Machine Learning-Enabled Pipeline for Large-Scale Virtual Drug Screening
Authors: Gupta Aayush , Zhou Huan-Xiang
Published: June 2021

Virtual screening is receiving renewed attention in drug discovery, but progress is hampered by challenges on two fronts: handling the ever increasing sizes of libraries of drug-like compounds, and separating true positives from false positives. Here we developed a machine learning-enabled pipeline for large-scale virtual screening that promises breakthroughs on both fronts. By clustering compounds according to molecular properties and limited docking against a drug target, the full library was trimmed by 10-fold; the remaining compounds were then screened individually by docking; and finally a dense neural network was trained to classify the hits into true and false positives. As illustration, we screened for inhibitors against RPN11, the deubiquitinase subunit of the proteasome and a drug target for breast cancer.

TOC Graphic
Systematic evaluation of genome-wide metabolic landscapes in lactic acid bacteria reveals diet-induced and strain-specific probiotic idiosyncrasies
Authors: Koduru Lokanand , Lakshmanan Meiyappan , Lim Pei-Yu , Ho Pooi-Leng , Banu Mazlina , Park Doo-Sang , Ow Dave Siak-Wei , Lee Dong-Yup
Published: June 2021

Lactic acid bacteria (LAB) naturally occur in animal and plant niches and are well-known to elicit several health benefits in humans. Yet, how they adapt their functional metabolic landscapes to diverse nutrient environments and synthesize relevant bioactive compounds remain unexplored across genera, species and strains. Hence, presented herein is a systematic framework for comprehensively characterizing the genome-wide metabolisms of six representative LAB by combining multi-omics data within silicomodeling. We analyse the differences in their growth and cellular fitness, biosynthetic capability of health-relevant compounds, i.e., postbiotics, and probable interactions with 15 common gut microbiota under 11 virtual dietary regimes, and show such attributes are diet- and species-specific. Particularly, some LAB exhibit a desirable balance between synthesis of beneficial postbiotic compounds, positive interactions with beneficial gut commensals, and the ability to colonize and persist in gut environment. We also observe that “high fat-low carb” diets likely lead to detrimental outcomes in most LAB. Our results clearly highlight that probiotics are not “one size fits all” commodities and need to be formulated in a personalised manner for their use as dietary supplements and live biotherapeutics. Overall, the proposed framework will systematize the probiotic administration and could also widen the strain repertoire.
Ectopic expression of KRASG12D and p53R167H in porcine mammary epithelial cells results in transformation and tumorigenesis
Authors: Remmers Neeley , Carlson Mark A.
Published: June 2021

We describe our initial studies in the development of an orthotopic, genetically-defined, large animal model of breast cancer, using immunocompetent pigs. Primary mammary epithelial cells were isolated from the porcine gland. Primary mammary cells were immortalized with hTERT, and then transformed cell lines were generated from these immortalized cells with oncogenic KRAS and dominant negative p53. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion. Three transformed cell lines were selected based on in vitro performance, and were able to grow tumors when injected subcutaneously in nude mice, with undifferentiated morphology. Tumorigenic porcine mammary cell lines were generated in this report.
Toolkit for Oscillatory Real-time Tracking and Estimation (TORTE)
Authors: Schatza Mark J , Blackwood Ethan B , Nagrale Sumedh S , Widge Alik S
Published: June 2021

Background

Closing the loop between brain activity and behavior is one of the most active areas of development in neuroscience. There is particular interest in developing closed-loop control of neural oscillations. Many studies report correlations between oscillations and functional processes. Oscillation-informed closed-loop experiments might determine whether these relationships are causal and would provide important mechanistic insights which may lead to new therapeutic tools. These closed-loop perturbations require accurate estimates of oscillatory phase and amplitude, which are challenging to compute in real time.

New Method

We developed an easy to implement, fast and accurate Toolkit for Oscillatory Real-time Tracking and Estimation (TORTE). TORTE operates with the open-source Open Ephys GUI (OEGUI) system, making it immediately compatible with a wide range of acquisition systems and experimental preparations.

Results

TORTE efficiently extracts oscillatory phase and amplitude from a target signal and includes a variety of options to trigger closed-loop perturbations. Implementing these tools into existing experiments is easy and adds minimal latency to existing protocols.

Comparison with Existing Methods

Most labs use in-house lab-specific approaches, limiting replication and extension of their experiments by other groups. Accuracy of the extracted analytic signal and accuracy of oscillation-informed perturbations with TORTE match presented results by these groups. However, TORTE provides access to these tools in a flexible, easy to use toolkit without requiring proprietary software.

Conclusion

We hope that that the availability of a high-quality, open-source, and broadly applicable toolkit will increase the number of labs able to perform oscillatory closed-loop experiments, and will improve the replicability of protocols and data across labs.

Highlights

TORTE provides a toolkit to investigate closed loop oscillation-informed experiments.

The toolkit is versatile and open-source promoting replicability across scientists.

The analytic signal algorithm within TORTE preforms equally to existing algorithms.
Comparative plastomics of Amaryllidaceae: Inverted repeat expansion and the degradation of the ndh genes in Strumaria truncata Jacq
Authors: Könyves Kálmán , Bilsborrow Jordan , Christodoulou Maria D. , Culham Alastair , David John
Published: June 2021

Amaryllidaceae is a widespread and distinctive plant family contributing both food and ornamental plants. Here we present an initial survey of plastomes across the family and report on both structural rearrangements and gene losses. Most plastomes in the family are of similar gene arrangement and content however some taxa have shown gains in plastome length while in several taxa there is evidence of gene loss. Strumaria truncata shows a substantial loss of ndh family genes while three other taxa show loss of cemA, which has been reported only rarely. Our sparse sampling of the family has detected sufficient variation to suggest further sampling across the family could be a rich source of new information on plastome variation and evolution.
Quantification of RNA Polymerase I transcriptional attenuation at the active VSG expression site in Trypanosoma brucei
Authors: Weisert Nadine , Thein Klara , Reis Helena , Janzen Christian J.
Published: June 2021

The cell surface of the extracellular pathogen Trypanosoma brucei consists of a dense coat of variant surface glycoprotein (VSG), which enables the parasite to evade the immune system of the vertebrate host. Only one VSG gene from a large repertoire is expressed from a so-called bloodstream form expression site (BES) at a given timepoint. There are several BES in every parasite but only one is transcriptionally active. Other BES are silenced by transcriptional attenuation. Periodic activation of a previously-silenced BES results in differential VSG transcription and escape from the immune response. A process called antigenic variation. In contrast to gene transcription in other eukaryotes, the BES is transcribed by RNA polymerase I (Pol I). It was proposed that this highly-processive polymerase is needed to provide a sufficiently high transcription rate at the VSG gene. Surprisingly, we discovered a position-dependent Pol I activity and attenuation of transcriptional elongation also at the active BES. Transcription rates at the VSG gene appear to be comparable to Pol II-mediated transcription of house-keeping genes. Although these findings are in contradiction to the long-standing concept of continuously high transcription rates at the active BES in Trypanosoma brucei, they are complementary to recent groundbreaking findings about transcriptional regulation of VSG genes.
Magnetic modes compatible with the symmetry of crystals
Authors: Fabrykiewicz Piotr , Przeniosło Radosław , Sosnowska Izabela
Published: June 2021

A classification of magnetic point groups is presented which gives an answer to the question: which magnetic groups can describe a given magnetic mode? There are 32 categories of magnetic point groups which describe 64 unique magnetic modes: 16 with a ferromagnetic component and 48 without. This classification focused on magnetic modes is helpful for finding the magnetic space group which can describe the magnetic symmetry of the material.