bluuebunny/crossref_metadata_2025 huggingface dataset:
New Pigmentation After Medical Treatment Suggests Increased Efficacy of Dermabrasion and Noncultured Epidermal Cell Suspension Techniques in Stable Vitiligo
Authors: Chen Cheng , Yu Nanze , Liu Zhifei , Tao Yong , Liu Bin
Published: October 2020

BACKGROUND

Stable vitiligo has been treated by dermabrasion and noncultured epidermal cell suspension (NCES) effectively. However, not all patches respond well.

OBJECTIVE

To investigate the efficacy of new pigmentation after medical treatment in the therapy of stable vitiligo.

MATERIALS AND METHODS

Medical records were retrospectively reviewed from October 2016 to March 2019, and 134 patients with stable vitiligo after medical therapy were further treated with NCES. They were divided into 2 groups: 70 patients in Group 1 had new pigmentation, whereas 64 patients in Group 2 did not. Repigmentation and satisfaction of patients and third-party assessors were evaluated at 3 and 6 months postoperatively.

RESULTS

Repigmentation was scored as excellent (≥76%), good (51%–75%), fair (26%–50%), or poor (≤25%). Repigmentation of the 2 groups at 6 months postoperatively was excellent in 82.9% versus 23.4%, good in 10.0% versus 15.6%, fair in 7.1% versus 13.0%, and poor in 0% versus 48.4%, respectively. A positive correlation between satisfaction and repigmentation was found.

CONCLUSION

New pigmentation after medical treatment suggests increased efficacy of NCES in treating stable vitiligo.
Interim Guidance on the Preparticipation Physical Examination for Athletes During the SARS-CoV-2 Pandemic
Authors: Diamond Alex B. , Narducci Dusty Marie , Roberts William O. , Bernhardt David T. , LaBella Cynthia R. , Moffatt Kody A. , Nuti Rathna , Powell Amy P. , Rooks Yvette L. , Zaremski Jason L.
Published: October 2020

The American Medical Society for Sports Medicine (AMSSM) convened a writing group to address the current evidence and knowledge gaps regarding preparticipation evaluation of athletes during the SARS-CoV2 pandemic. The writing group held a series of meetings beginning in April 2020. The task force reviewed the available literature and used an iterative process and expert consensus to finalize this guidance statement that is intended to provide clinicians with a clinical framework to return athletes of all levels to training and competition during the pandemic. The statement is not intended to address treatment, infection control principles, or public health issues related to SARS-CoV2. The AMSSM task force acknowledges the clinical uncertainty, evolving public health objectives, and the limited data currently available to create this guidance statement.
Antibiotic stewardship: Improving patient-centered right care in urgent care using a shared decision aid and 5 Ds tool
Authors: Forrest Cynthia L. , Verzone Ana
Published: October 2020

Background:

Overuse of antibiotics leads to antibiotic resistance, costing $35 billion and causing approximately 23,000 deaths in the United States annually. Antibiotic stewardship is important in urgent care centers to prevent antibiotic resistance.

Local problem:

Providers prescribed antibiotics to 80% of patients with viral conditions at this urgent care center. The aim of this quality improvement (QI) project was to improve right care for patients of 65 years and younger with upper respiratory infections and/or head, ears, nose, or throat viral illnesses presenting to urgent care from 36.2% to 80% within 90 days.

Methods:

Four rapid Plan-Do-Study-Act cycles were performed every two weeks. Four concurrent focus areas were used for team and patient engagement, antibiotic prescribing, and tracking right care.

Interventions:

There were four core interventions. These included biweekly team meetings, a shared decision aid (SDA), an antibiotic prescribing 5 Ds tool, and a case management log.

Results:

Use of the SDA improved patient engagement from 33% to 93%. The 5 Ds tool improved proper prescribing from 20% to 95%. Pediatric acute otitis media had the greatest improvement, with the proper diagnosis and the use of watchful waiting, delaying the filling of an antibiotic prescription.

Conclusion:

Antibiotic stewardship and standardization of prescribing were improved in urgent care with the use of the 5 Ds tool. This QI project can be replicated for use in urgent care centers for compliance with the Joint Commission standards required.
Novel clinical features and pleiotropic effect in three unrelated patients with LMNA variant
Authors: Turkyilmaz Ayberk , Geçkinli Bilgen Bilge , Alavanda Ceren , Ates Esra Arslan , Arman Ahmet
Published: October 2020

LMNA gene encodes A-type lamins and the encoded proteins join the structure of the nuclear lamina and affect the processes of nuclear homeostasis, DNA replication, repair, transcription, and apoptosis. LMNA variants cause a heterogeneous group of diseases known as laminopathies. Phenotypes associated with LMNA variants mainly affect the heart, skeleton, skin, bones, and nervous system. The affected tissues may vary depending on the site of the variant on the gene and the variation type. Complex phenotypes may also occur in some cases, in which findings of premature aging, cardiomyopathy, mandibuloacral dysplasia, lipodystrophy, renal involvement, metabolic involvement, and myopathy coexist. The pleiotropic effect of LMNA variants can result in heterogeneous phenotypes. In this study, we aimed to describe atypical phenotypic characteristics in a patient with familial partial lipodystrophy type 2 associated with LMNA variant, another with mandibuloacral dysplasia, and a third patient with a complex phenotype as well as discuss them in the context of their relationship with the genotype.
Predictors of Out-of-Class Mindfulness Practice Adherence During and After a Mindfulness-Based Intervention
Authors: Canby Nicholas K. , Eichel Kristina , Peters Sarah I. , Rahrig Hadley , Britton Willoughby B.
Published: October 2020

Objective

Out-of-class mindfulness meditation practice is a health behavior that is considered to be a crucial ingredient in mindfulness-based interventions (MBIs), yet participant adherence to practice recommendations is often inconsistent. Furthermore, MBIs may enhance factors that lead to greater adherence to medical regimens in other contexts. This study examined baseline factors previously found to relate to adherence to medical regimen, MBI-related changes in these baseline factors, and treatment-related factors as predictors of meditation adherence in an 8-week MBI.

Methods

Baseline traits (personality, depressive symptoms, and executive function) were entered into regression models (n = 96) to predict intervention and postintervention out-of-class meditation adherence. Trait changes and treatment-related factors were entered into models to predict postintervention meditation adherence.

Results

Baseline conscientiousness (β = 0.33, p = .002), openness (β = 0.23, p = .019), and depressive symptoms (β = 0.19, p = .042) predicted intervention meditation adherence, whereas conscientiousness (β = 0.21, p = .044) and depressive symptoms (β = 0.22, p = .020) predicted postintervention meditation adherence. Although all trait variables except for agreeableness changed significantly pre-to-post intervention, these changes did not predict postintervention meditation adherence. Retreat attendance (β = 0.38, p = .029) and instructor/group-related therapeutic factors collectively predicted postintervention meditation adherence (R
2 = 0.21, p = .019).

Conclusions

The identified baseline trait factors could be used to increase adherence in these interventions as a method of increasing their effectiveness. An emphasis on the MBI retreat and social factors during the intervention may be important for participant out-of-class practice postintervention.

Trial Registration:
ClinicalTrials.gov
NCT01831362.
Minimally Invasive Treatment With a Patient Specific Implant in Reconstruction of Isolated Anterior Wall Fracture of the Frontal Sinus
Authors: Helmers Renée , Klop Cornelis , Schreurs Ruud , de Lange Jan , Dubois Leander
Published: October 2020

Isolated fractures of the anterior wall of the frontal sinus are most often treated through a coronal approach. Although the coronal approach is a relatively easy procedure, the size of the incision is causing more problems related to patient morbidity and recovery time than smaller approaches. A novel, minimal invasive procedure for reconstruction of the anterior wall fracture of the frontal sinus is presented in this article. An endoscopic assisted approach to camouflage the defect of the anterior wall and restore the contour of the frontal bone with a titanium patient specific implant is described in 2 patients. The aim of this procedure is to evaluate the effect on the operating time, recovery time, length of hospital stay and facial scarring compared to the conventional coronal approach. Postoperative evaluation was performed by superimposing pre and postoperative 3D stereophotographs and computed tomography scans. A distance map demonstrated an accurate reconstruction of the preoperatively planned contour. Postoperative recovery of both patients was quick and uneventful with no complications. The use of endoscopically inserted patient specific implant for contour reconstruction in anterior wall fractures of the frontal sinus seems to offer a predictable and minimal invasive alternative to the conventional approach.
Testosterone, HIV, and cardiovascular disease risk
Authors: Grant Jelani K. , Loyd Quentin , Martinez Claudia
Published: October 2020

There has been a recent increase in the use of testosterone supplementation among young adults in the United States, despite the controversy of testosterone replacement therapy (TRT) and cardiovascular safety. The lower testosterone levels and earlier age of TRT use in persons living with HIV (PLHIV) is of particular relevance for this population because cardiovascular disease (CVD) comorbidities are known to be increased among PLHIV. There is very limited data on TRT in PLHIV, as such, in this article, we sought to compile current evidence regarding the diagnosis and management of testosterone deficiency and its link to CVD risk including among PLHIV.
Surgical counts in open abdominal and pelvic surgeries in a university hospital: a best practice implementation project
Authors: Gomes Eduardo T. , Galvão Mayana C.B. , Shimoda Gilcéria T. , de Oliveira Larissa B. , de Araújo Püschel Vilanice A.
Published: October 2020

Introduction:

Counting of accountable items used during surgery, frequently called ’the count’, is a fundamental practice to ensure that items such as surgical instruments, sponges and sharps are not forgotten within patients. Although inadvertently leaving behind a sponge or instrument at the end of an operation is a rare event, it is an error that may have serious implications.

Objectives:

The aim of this evidence implementation project was to contribute to promoting evidence-based practice in surgical counts in open abdominal and pelvic surgeries and thereby improving the outcomes of the surgical patients at a surgical centre of a university hospital.

Methods:

The current evidence implementation project used the JBI Practical Application of Clinical Evidence System and Getting Research into Practice (GRiP) audit and feedback tool. The JBI Practical Application of Clinical Evidence System and GRiP framework for promoting evidence-based healthcare involves three phases of activity: first, establishing a project team and undertaking a baseline audit based on evidence-informed criteria; second, reflecting on the results of the baseline audit and designing and implementing strategies to address non-compliance found in the baseline audit informed by the JBI GRiP framework; third, conducting a follow-up audit to assess the outcomes of the interventions implemented to improve practice, and identify future practice issues to be addressed in subsequent audits. These three phases were performed over a period of 6 months, from August 2017 to March 2018.

Results:

The baseline audit revealed deficits between old and best practice in all criteria. Barriers for implementation of a protocol for surgical counts were identified, and strategies were implemented. The postimplementation (follow-up) audit showed improvement in compliance with best practice in six of the audit criteria selected except two, a multidisciplinary team approach to decrease retained surgical items, and limited staff hand-offs during surgical procedures to ensure the same team is present in all counting episodes.

Conclusion:

The main achievements of the study included substantial increases in compliance with best practice. However, registration and report and commitment of all members of surgical team to apply the entire protocol, avoiding to skip any step, persist as challenges.
Aliikangiella coralliicola sp. nov., a bacterium isolated from coral Porites lutea, and proposal of Pleioneaceae fam. nov. to accommodate Pleionea and Aliikangiella
Authors: Wang Guanghua , Dang Ge , Xu Shuailiang , Liu Jianfeng , Su Hongfei , Liang Jiayuan , Huang Wen , Wang Yinghui , Yu Kefu
Published: October 2020

A novel Gram-stain-negative, non-endospore-forming, motile, and aerobic bacterial strain, M105T, was isolated from coral Porites lutea, and was subjected to a polyphasic taxonomic study. Global alignment based on 16S rRNA gene sequences indicated that M105T shares the highest sequence identity of 94.5 % with

Aliikangiella marina

GYP-15T. The average nucleotide identity (ANI) and average amino acid identity (AAI) between M105T and

A. marina

GYP-15T was 69.8 and 71.6 %, respectively. On the basis of the results of phenotypic, chemotaxonomic, phylogenetic, phylogenomic, and comparative genomic analyses, it is concluded that M105T should represent a novel species in the genus

Aliikangiella

, for which the name Aliikangiella coralliicola sp. nov. is proposed. The type strain is M105T (=MCCC 1K03773T= KCTC 72442T). Furthermore, the family

Kangiellaceae

was classified into two families on the basis of phylogenetic, phylogenomic, polar lipid profile and motility variations. The novel family Pleioneaceae fam. nov. is proposed to accommodate the genera

Aliikangiella

and

Pleionea

.
Transcriptomic Analyses Throughout Chili Pepper Fruit Development Reveal Novel Insights into Domestication Process
Authors: Martínez Octavio , Arce-Rodríguez Magda L. , Hernández-Godínez Fernando , Escoto-Sandoval Christian , Cervantes-Hernández Felipe , Hayano-Kanashiro Corina , Ordaz-Ortiz José J. , Reyes-Valdés M. Humberto , Razo-Mendivil Fernando G. , Garcés-Claver Ana , Ochoa-Alejo Neftalí
Published: October 2020

Chili pepper (Capsicumspp.) is both an important crop and a model for domestication studies. Here we performed a time course experiment to estimate standardized gene expression profiles across fruit development for six domesticated and four wild chili pepper ancestors. We sampled the transcriptome every 10 days, from flower to fruit at 60 Days After Anthesis (DAA), and found that the mean standardized expression profile for domesticated and wild accessions significantly differed. The mean standardized expression was higher and peaked earlier for domesticated vs. wild genotypes, particularly for genes involved in the cell cycle that ultimately control fruit size. We postulate that these gene expression changes are driven by selection pressures during domestication and show a robust network of cell cycle genes with a time-shift in expression which explains some of the differences between domesticated and wild phenotypes.
AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci
Authors: Roberts Genevieve H.L. , Park Danny S. , Coignet Marie V. , McCurdy Shannon R. , Knight Spencer C. , Partha Raghavendran , Rhead Brooke , Zhang Miao , Berkowitz Nathan ,   AncestryDNA Science Team, Haug Baltzell Asher K. , Guturu Harendra , Girshick Ahna R. , Rand Kristin A. , Hong Eurie L. , Ball Catherine A.
Published: October 2020

Human infection with SARS-CoV-2, the causative agent of COVID-19, leads to a remarkably diverse spectrum of outcomes, ranging from asymptomatic to fatal. Recent reports suggest that both clinical and genetic risk factors may contribute to COVID-19 susceptibility and severity. To investigate genetic risk factors, we collected over 500,000 COVID-19 survey responses between April and May 2020 with accompanying genetic data from the AncestryDNA database. We conducted sex-stratified and meta-analyzed genome-wide association studies (GWAS) for COVID-19 susceptibility (positive nasopharyngeal swab test,ncases=2,407) and severity (hospitalization,ncases=250). The severity GWAS replicated associations with severe COVID-19 nearABOandSLC6A20(P<0.05). Furthermore, we identified three novel loci withP<5×10−8. The strongest association was nearIVNS1ABP, a gene involved in influenza virus replication1, and was associated only in males. The other two novel loci harbor genes with established roles in viral replication or immunity:SRRM1and the immunoglobulin lambda locus. We thus present new evidence that host genetic variation likely contributes to COVID-19 outcomes and demonstrate the value of large-scale, self-reported data as a mechanism to rapidly address a health crisis.
Post-operative serum procalcitonin vs C reactive Protein as a marker of post-operative infectious complications in pancreatic surgery – A systemic review and meta-analysis
Authors: Vasavada Bhavin , Patel Hardik
Published: October 2020

Aim of Study

Aim of this meta-analysis was to compare diagnostic accuracy of C reactive Protein and Procalcitonin between postoperative day 3 to 5 in predicting infectious complications post pancreatic surgery.

Methods

Systemic literature search was performed using MEDLINE, EMBASE and SCOPUS to identify studies evaluating the diagnostic accuracy of Procalcitonin (PCT) and C-Reactive Protein (CRP) as a predictor for detecting infectious complications between postoperative days (POD) 3 to 5 following pancreatic surgery. A meta-analysis was performed using random effect model and pooled predictive parameters. Geometric means were calculated for PCT cut offs. The work has been reported in line with PRISMA guidelines.

Results

After applying inclusion and exclusion criteria 15 studies consisting of 2212 patients were included in the final analysis according to PRISMA guidelines. Pooled sensitivity, specificity, Area under curve and diagnostic odds ratio (DOR)for day 3 C-reactive protein was respectively 62%,67% 0.772 and 6.54. Pooled sensitivity, specificity, Area under curve and diagnostic odds ratio (DOR)for day 3 procalcitonin was respectively 74%,79%,0.8453 and 11.03. Sensitivity, specificity, Area under curve, and Diagnostic odds ratio for day 4 C-reactive protein was respectively 60%,68%, 0.8022 and 11.90. Pooled Sensitivity, specificity and Diagnostic odds ratio of post-operative day 5 procalcitonin level in predicting infectious complications were respectively 83%,70% and 12.9. Pooled Sensitivity, specificity, AUROC and diagnostic odds ratio were respectively 50%,70%, 0.777 and 10.19.

Conclusion

Post-operative procalcitonin is better marker to predict post-operative infectious complications after pancreatic surgeries and post-operative day 3 procalcitonin has highest diagnostic accuracy.
Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun
Authors: Wagstaff Laura J. , Gomez-Sanchez Jose A. , Fazal Shaline V. , Otto Georg W. , Kilpatrick Alastair M. , Michael Kirolos , Wong Liam Y.N. , Ma Ki H. , Turmaine Mark , Svaren John , Gordon Tessa , Arthur-Farraj Peter , Velasco-Aviles Sergio , Cabedo Hugo , Benito Cristina , Mirsky Rhona , Jessen Kristjan R
Published: October 2020

After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during the chronic denervation that results from the slow growth of axons. This impairs axonal regeneration and causes a significant clinical problem. In mice, we find that repair cells express reduced c-Jun protein as the regenerative support provided by these cells declines in aging animals and during chronic denervation. In both cases, genetically restoring Schwann cell c-Jun levels restores regeneration to that in controls. We identify potential gene candidates mediating this effect and implicate Shh in the control of Schwann cell c-Jun levels. This establishes that a common mechanism, reduced c-Jun in Schwann cells, regulates the success and failure of nerve repair both during aging and chronic denervation. This provides a molecular framework for addressing important clinical problems, and suggests molecular pathways that can be targeted to promote repair in the PNS.
Implementation of an ERAS program in patients undergoing thoracic surgery at a third-level university hospital. An ambispective cohort study
Authors: Bellas-Cotán Soledad , Casans-Francés Rubén , Ibáñez Cristina , Muguruza Ignacio , Muñoz-Alameda Luis E.
Published: October 2020

Objetive

To analyze the effects of the implementation of an ERAS program in patients undergoing pulmonary resection in a tertiary university hospital on the rates of complications and readmission and the length of stay.

Methods

ambispective cohort study, with a prospective arm of patients undergoing thoracic surgery within an ERAS program versus a retrospective arm of patients before the implementation of the protocol. We recluited 50 patients per arm. The primary outcome was the number of patients with 30-day surgical complications. Secondary outcome included ERAS adherence, no-surgical complications, mortality, readmission, reintervention rates, pain and hospital lenght of stay. We performed a multivariate logistic analysis to study the association of coutcomes with ERAS adherence.

Results

We found no difference between the two groups in surgical complications [Standard 18 (36%) vs 12 (24%], p =0.19]. ERAS group was significantly lower only in its readmission rate [Standard 15 (30%) vs 6 (12%], p =0.03]. In multivariate analyses, ERAS adherence was the only factor associated with a reduction in surgical complications [OR (95%CI) = 0.02 (0.00, 0.59), p = 0.03] and length of stay [HR (95%CI) = 18.5 (4.39, 78.4), p < 0.001].

Conclusions

ERAS program was able to decrease the readmission rate at our centre significantly. The adherence to the ERAS protocol influenced the reduction of surgical complications and length of stay.
Machine Learning Directed Interventions Associate with Decreased Hospitalization Rates in Hemodialysis Patients
Authors: Chaudhuri Sheetal , Han Hao , Usvyat Len , Jiao Yue , Sweet David , Vinson Allison , Steinberg Stephanie Johnstone , Maddux Dugan , Belmonte Kathleen , Brzozowski Jane , Bucci Brad , Kotanko Peter , Wang Yuedong , Kooman Jeroen P. , Maddux Franklin W , Larkin John
Published: October 2020

Background

An integrated kidney disease company uses machine learning (ML) models that predict the 12-month risk of an outpatient hemodialysis (HD) patient having multiple hospitalizations to assist with directing personalized interdisciplinary interventions in a Dialysis Hospitalization Reduction Program (DHRP). We investigated the impact of risk directed interventions in the DHRP on clinic-wide hospitalization rates.

Methods

We compared the hospital admission and day rates per-patient-year (ppy) from all hemodialysis patients in 54 DHRP and 54 control clinics identified by propensity score matching at baseline in 2015 and at the end of the pilot in 2018. We also used paired T test to compare the between group difference of annual hospitalization rate and hospitalization days rates at baseline and end of the pilot.

Results

The between group difference in annual hospital admission and day rates was similar at baseline (2015) with a mean difference between DHRP versus control clinics of −0.008±0.09 ppy and −0.05±0.96 ppy respectively. The between group difference in hospital admission and day rates became more distinct at the end of follow up (2018) favoring DHRP clinics with the mean difference being −0.155±0.38 ppy and - 0.97±2.78 ppy respectively. A paired t-test showed the change in the between group difference in hospital admission and day rates from baseline to the end of the follow up was statistically significant (t-value=2.73, p-value<0.01) and (t-value=2.29, p-value=0.02) respectively.

Conclusions

These findings suggest ML model-based risk-directed interdisciplinary team interventions associate with lower hospitalization rates and hospital day rate in HD patients, compared to controls.
Reliability and limits of transport-ventilators to safely ventilate severe patients in special surge situations
Authors: Savary Dominique , Lesimple Arnaud , Beloncle François , Morin François , Templier François , Broc Alexandre , Brochard Laurent , Richard Jean-Christophe , Mercat Alain
Published: October 2020

Background

Several Intensive Care Units (ICU) have been overwhelmed by the surge of COVID-19 patients thus necessitating to extend ventilation capacity outside the ICU where air and oxygen pressure are not always available. Transport ventilators requiring only O2 source may be used to deliver volume-controlled ventilation.

Objective

To evaluate the performances of four transport ventilators compared to an ICU ventilator simulating severe respiratory conditions.

Materials and methods

Two pneumatic transport ventilators, (Oxylog 3000, Draeger; Osiris 3, Air Liquide Medical Systems) and two turbine transport ventilators (Elisee 350, ResMed; Monnal T60, Air Liquide Medical Systems) were compared to an ICU ventilator (Engström Carestation – GE Healthcare) using a Michigan training test lung. We tested each ventilator with different set volumes Vtset (350, 450, 550 ml) and different compliances (20 or 50 ml/cmH2O) and a resistance of 15 cmH2 0/L/sec based on values recently described in COVID-19 Acute Respiratory Distress Syndrome. Volume error was measured, as well as the trigger time delay during assist-control ventilation simulating spontaneous breathing activity with a P0.1 of 4 cmH20.

Results

Grouping all conditions, the volume error was 2.9 ± 2.2 % for Engström Carestation; 3.6 ± 3.9 % for Osiris 3; 2.5 ± 2.1 % for Oxylog 3000; 5.4 ± 2.7 % for Monnal T60 and 8.8 ± 4.8 % for Elisee 350. Grouping all conditions, trigger delay was 42 ± 4 ms, 65 ± 5 ms, 151 ± 14 ms, 51 ± 6 and 64 ± 5 ms for Engström Carestation, Osiris 3, Oxylog 3000, Monnal T60 and Elisee 350, respectively.

Conclusions

In special surge situations such as COVID-19 pandemic, most transport ventilators may be used to safely deliver volume-controlled ventilation in locations where only oxygen pressure supply is available with acceptable volume accuracy. Performances regarding triggering function are generally acceptable but vary across ventilators.
Enhanced skin permeation of a novel peptide via structural modification, chemical enhancement, and microneedles
Authors: Chen Jungen , Bian Junxing , Hantash Basil M. , Hibbs David E. , Wu Chunyong , Kang Lifeng
Published: October 2020

Hyperpigmentation is a common skin condition with serious psychosocial consequences. Decapeptide-12, a novel peptide, has been found to be safer than hydroquinone in reducing content of melanin, with efficacy up to more than 50% upon 16 weeks of twice daily treatment. However, the peptide suffers from limited transcutaneous penetration due to its hydrophilicity and large molecular weight. Therefore, decapeptide-12 was modified by adding a palmitate chain in an attempt to overcome this limitation. We also tested the effects of chemical penetration enhancers and microneedles to deliver two peptides through skin. Enhanced skin permeation was found using anin vitrohuman skin permeation model. Moreover, we examined peptide retention of different formulations in skin. Our data showed that palm-peptides in microneedle patch was the most effective.
Remote Learning Barriers and Opportunities for Graduate Student and Postdoctoral Learners in Career and Professional Skill Development: A Case Study
Authors: Gardner Margery Evans , Bodiya Elizabeth C , Subramanian Shoba
Published: October 2020

Career and professional development competencies are critical for biomedical PhD and postdoctoral training. In the current educational landscape, programs that meet these competencies are offered and attended in an ad hoc manner. During the COVID-19 pandemic and the accompanying switch to virtual learning, our team observed a surge in interest for our weekly non-sequential programs. In this study, we surveyed our learners to better understand motivators for attending these programs during the pandemic and to identify barriers for participating in such events before and during Work-From-Home. Our data indicate that conflict with research responsibilities, time spent to get to the event location, and planning time to attend are all significant barriers to engagement. Notably, feelings of being overwhelmed, which increased slightly during the pandemic, stood out as an identified barrier. Per our results, the virtual format was an attraction. While 58% of respondents would prefer to access professional development programs virtually in the future, almost 42% indicated a preference for in-person events when normalcy resumes as the physical presence of an instructor and of peers result in a deeper engagement. Our collective analysis here suggests that learners will benefit from a hybrid or combination of synchronous and asynchronous career and professional development programming in the future, even post-pandemic, to reduce identified barriers. Alongside hybrid learning engagements, we strongly recommend structured time for learners to enhance their professional competencies, enabled by a commitment from departments and faculty mentors to enable equity in professional skill building and fostering lifelong growth mindset.
α-Endosulfine regulates amyloid β 42 via the modulation of neprilysin activity
Authors: Watamura Naoto , Kakiya Naomasa , Nilsson Per , Tsubuki Satoshi , Kamano Naoko , Takahashi Mika , Hashimoto Shoko , Sasaguri Hiroki , Saito Takashi , Saido Takaomi C.
Published: October 2020

The neuropeptide somatostatin (SST) regulates amyloid β peptide (Aβ) catabolism by enhancing neprilysin (NEP)-catalyzed proteolytic degradation. However, the mechanism by which SST regulates NEP activity remains unclear. Here we report the identification by differential proteomics of α-endosulfine (ENSA), an endogenous ligand of the ATP-sensitive potassium (KATP) channel, as a negative regulator of NEP activity downstream of SST signaling. Genetic deficiency of ENSA resulted in enhanced NEP activity and decreased Aβ deposition in the brains of wild-type and Alzheimer’s disease (AD) model mice. Pharmacological intervention to increase the probability of KATPchannel opening reduced Aβ deposition in AD model mice. Our findings provide new insights into possible mechanisms to prevent AD.
Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia
Authors: Borghesani V. , Dale C. L. , Lukic S. , Hinkley L. B. N. , Lauricella M. , Shwe W. , Mizuiri D. , Honma S. , Miller Z. , Miller B. , Houde J. F. , Gorno-Tempini M.L. , Nagarajan S. S.
Published: October 2020

Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g.,it has eight legs) to conceptual (e.g.,venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing.

Impact Statement

Following anterior temporal lobe neurodegeneration, defective semantic representations are compensated via enhanced perceptual processing and associated with a dysregulation of the semantic control system.
Better expression profile of CD8 and CD4 gene in uterus of pregnant ewe in comparison to non-pregnant - a novel report
Authors: Islam Md Mofijul , Pal Aruna , Das Partha , Banerjee Samiddha
Published: October 2020

CD8 and CD4 T cells play a central role in the immune response to viruses and intracellular pathogens as well as functions for the maintenance of both the mother and fetus. The present study was conducted to explore the differential gene expression profile for CD8 and CD4 present in the uterus with reference to the gravid and non-gravid Garole sheep and confirmation through immuno histochemical studies. Better CD8 and CD4 gene expression was observed in the mid uterus of pregnant ewes compared to that of non-pregnant ewes, where CD8 expression was better to that of CD4. Gene expression profiling of CD8 and CD4 are reported here for the first time in sheep. CD8 and CD4 expression may be regarded as the useful factor for maintenance of pregnancy. The current observations demonstrate that during pregnancy in ewe the immune system may respond to changes in the maternal environment to maintain the size and function of the CD8 and CD4 T-cell compartment. CD8 and CD4 expression may be employed as marker for pregnancy detection in sheep, which remains always a challenge for sheep breeders.
A Spectral Theory for Wright’s Inbreeding Coefficients and Related Quantities
Authors: François Olivier , Gain Clément
Published: October 2020

Wright’s inbreeding coefficient,FST, is a fundamental measure in population genetics. Assuming a predefined population subdivision, this statistic is classically used to evaluate population structure at a given genomic locus. With large numbers of loci, unsupervised approaches such as principal component analysis (PCA) have, however, become prominent in recent analyses of population structure. In this study, we describe the relationships between Wright’s inbreeding coefficients and PCA for a model ofKdiscrete populations. Our theory provides an equivalent definition ofFSTbased on the decomposition of the genotype matrix into between and within-population matrices. The average value of Wright’sFSTover all loci included in the genotype matrix can be obtained from the PCA of the between-population matrix. Assuming that a separation condition is fulfilled and for reasonably large data sets, this value ofFSTapproximates the proportion of genetic variation explained by the first (K– 1) principal components accurately. The new definition ofFSTis useful for computing inbreeding coefficients from surrogate genotypes, for example, obtained after correction of experimental artifacts or after removing adaptive genetic variation associated with environmental variables. The relationships between inbreeding coefficients and the spectrum of the genotype matrix not only allow interpretations of PCA results in terms of population genetic concepts but extend those concepts to population genetic analyses accounting for temporal, geographical and environmental contexts.

Author’s summary

Principal component analysis (PCA) is the most-frequently used approach to describe population genetic structure from large population genomic data sets. In this study, we show that PCA not only estimates ancestries of sampled individuals, but also computes the average value of Wright’s inbreeding coefficient over the loci included in the genotype matrix. Our result shows that inbreeding coefficients and PCA eigenvalues provide equivalent descriptions of population structure. As a consequence, PCA extends the definition of this coefficient beyond the framework of allelic frequencies. We give examples on howFSTcan be computed from ancient DNA samples for which genotypes are corrected for coverage, and in an ecological genomic example where a proportion of genetic variation is explained by environmental variables.
Multi-modal imaging of a single mouse brain over five orders of magnitude of resolution
Authors: Foxley Sean , Sampathkumar Vandana , De Andrade Vincent , Trinkle Scott , Sorokina Anastasia , Norwood Katrina , La Riviere Patrick , Kasthuri Narayanan
Published: October 2020

Mammalian neurons operate at length scales spanning five orders of magnitude; micron-scale-diameter myelinated axons project millimeters across brain regions, ultimately forming nanometer scale synapses on individual post-synaptic neurons. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities (e.g. MRI, electron microscopy, etc.). Translating between the different modalities, however, requires imaging thesamebrain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micron-scale synchrotron x-ray tomography (μCT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brain’s multi-scaled organization as well as a vehicle for studying the brain’s multi-scale pathologies.
Criteria for effective fallow field eco schemes for farmland birds during non-breeding
Authors: Rieger Mirjam , Mailänder Sarah , Stier Lea , Staggenborg Julia , Anthes Nils
Published: October 2020

Farmland eco schemes implemented under the current Common Agricultural Policy (CAP) of the European Union are often considered ineffective in halting farmland bird declines. Fallow fields, often seeded with dedicated seed mixtures, rate among the more beneficial eco scheme types. Yet, the CAP currently defines no minimum criteria for fallow fields to qualify as eco scheme, likely jeopardizing their potential biodiversity benefits.

We investigated the attractiveness of four fallow field types established under CAP eco schemes and dedicated bird conservation programs in Southern Germany. Our 2-year surveys on > 100 fields focused on the non-breeding season, where food limitation can become particularly problematic. We modelled bird incidences also in response to vegetation structure and adjacent landscape features to derive minimum criteria for effective fallow field eco schemes.

Fallow field types varied only mildly in overall species richness but showed striking differences in the attracted species. Finches in particular tended to preferentially visit 1-year fallow fields, while buntings tended towards 2-year and older field types. 1-year CAP fallows, however, are typically removed before mid-winter, and thus potentially act as a trap to farmland birds and other wildlife.

The investigated species consistently preferred larger fallow fields with a more differentiated vegetation structure. Placement close to woods and hedgerows positively affected birds inhabiting woodland ecotones, while classic farmland species showed higher incidences on fallow fields embedded in open landscapes.

‘Policy implications’Our findings call for the ongoing CAP revisions to specify minimum requirements that qualify fallow fields as eco schemes. These should include an at least biennial cycle, a diversification of seed mixtures, standards for fallow field size, and criteria for their placement in the landscape matrix.
Fibrillin 2 interacts with other proteins to protect photosystem II against abiotic stress inArabidopsis thaliana
Authors: Torres-Romero Diego , Gómez-Zambrano Ángeles , Serrato Antonio Jesús , Sahrawy Mariam , Mérida Ángel
Published: October 2020

Fibrillins (FBNs) are plastidial proteins found in photosynthetic organisms, from cyanobacteria to higher plants. The function of most FBNs is largely unknown. We focused on the subgroup formed by FBN1a, −1b, and −;2, which has been proposed to be involved in the photoprotection of photosystem II (PSII), though their mechanism of action has not yet been characterized. We show that FBN2 interacts with FBN1a and with other FBN2 polypeptides, potentially forming a network around the plastoglobule surface. Both FBN2 and FBN1 interact with the allene oxide synthase, and the elimination of any of these FBNs results in a delay in jasmonate-mediated anthocyanin accumulation in response to a combination of moderate-high light and low temperature. FBN2 also interacts with other proteins involved in different metabolic processes. Mutants lacking FBN2 demonstrate less photoprotection of PSII, alterations that are not found infbn1a-fbn1bmutants. We also show that FBN2 interacts with Acclimation of Photosynthesis to Environment 1 (APE1), and gene co-expression analysis suggests that both proteins are involved in the same metabolic process. The elimination of APE1 leads to lesions in PSII under abiotic stress similar to observations infbn2mutants, with lower maximum and effective quantum yield. However, a reduction in non-photochemical quenching is observed exclusively infbn2mutants, suggesting that other FBN2-interacting proteins are responsible for this alteration. We propose that FBN2 facilitates accurate positioning of different proteins involved in distinct metabolic processes, and its elimination leads to dysfunction in those proteins.

One sentence summary

Fibrillin 2 protects photosynthesis against abiotic stresses by facilitating the accurate positioning of different proteins involved in distinct processes, and its elimination leads to dysfunction in those proteins
Neonicotinoid exposure affects foraging, nesting, and reproductive success of ground-nesting solitary bees
Authors: Willis Chan D. Susan , Raine Nigel E.
Published: October 2020

Despite their indispensable role in food production1,2, insect pollinators are threatened by multiple environmental stressors, including pesticide exposure2-4. Although honeybees are important, most pollinating insect species are wild, solitary, ground-nesting bees1,4-6that are inadequately represented by honeybee-centric regulatory pesticide risk assessment frameworks7,8. Here, for the first time, we evaluate the effects of realistic exposure to systemic insecticides (imidacloprid, thiamethoxam or chlorantraniliprole) on a ground-nesting bee species in a semi-field experiment. Hoary squash bees (Eucera(Peponapis)pruinosa) provide essential pollination services to North American pumpkin and squash crops9-14and commonly nest within cropping areas10, placing them at risk of exposure to pesticides in soil8,10, nectar and pollen15,16. Hoary squash bees exposed to an imidacloprid-treated crop initiated 85% fewer nests, left 84% more pollen unharvested, and produced 89% fewer offspring than untreated controls. We found no measurable impact on squash bees from exposure to thiamethoxam- or chlorantraniliprole-treated crops. Our results demonstrate important sublethal effects of field-realistic exposure to a soil-applied neonicotinoid (imidacloprid) on the behaviour and reproductive success of a ground-nesting solitary bee. To prevent potential declines in ground-nesting bee populations and associated impoverishment of crop pollination services, soil must be considered a possible route of pesticide exposure for bees, and restrictions on soil-applied insecticides may be justified.
Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care setting
Authors: Dziopa K , Asselbergs F W , Gratton J , Chaturvedi N , Schmidt A F
Published: October 2020

Objective

To compare performance of general and diabetes specific cardiovascular risk prediction scores in type 2 diabetes patients (T2DM).

Design

Cohort study.

Setting

Scores were identified through a systematic review and included irrespective of predicted outcome, or inclusion of T2DM patients. Performance was assessed using data from routine practice.

Participants

A contemporary representative sample of 203,172 UK T2DM patients (age ≥ 18 years).

Main outcome measures

Cardiovascular disease (CVD i.e., coronary heart disease and stroke) and CVD+ (including atrial fibrillation and heart failure).

Results

We identified 22 scores: 11 derived in the general population, 9 in only T2DM patients, and 2 that excluded T2DM patients. Over 10 years follow-up, 63,000 events occurred. The RECODE score, derived in people with T2DM, performed best for both CVD (c-statistic 0.731 (0.728,0.734), and CVD+ (0.732 (0.729,0.735)). Overall, neither derivation population, nor original predicted outcome influenced performance. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95%CI 0.37;0.39) to 1.05 (95%CI 1.03;1.07). A simple, population specific recalibration process considerably improved performance, ranging between 0.98 and 1.03. Risk scores performed badly in people with pre-existing CVD (c-statistic ∼0.55). Scores with more predictors did not perform scores better: for CVD+ QRISK3 (19 variables) c-statistic 0.69 (95%CI 0.68;0.69), compared to CHD Basic (8 variables) 0.71 (95%CI 0.70; 0.71).

Conclusions

CVD risk prediction scores performed well in T2DM, irrespective of derivation population and of original predicted outcome. Scores performed poorly in patients with established CVD. Complex scores with multiple variables did not outperform simple scores. A simple population specific recalibration markedly improved score performance and is recommended for future use.