bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Microcirculatory Disturbances in Acute Pancreatitis
Authors: Antkowiak Ryszard , Bialecki Jacek , Chabowski Mariusz , Domoslawski Pawel
Published: August 2022

Acute pancreatitis is a serious inflammatory condition. Research has shown an increase in the number of pancreatitis-associated hospitalizations, with a marked decline in the mortality rates down to 0.79% in patients with acute pancreatitis and 0.26% in patients with exacerbation of chronic pancreatitis. Up to one-third of patients develop pancreatic tissue necrosis, with a mortality rate of 30%. One of the mechanisms is the disturbances in pancreatic microcirculation due to the release of endothelin, a long-acting vasoconstrictor. The development of pancreatitis causes the release of other inflammatory mediators, which reduce blood flow in the microcirculation. The activation of intracellular trypsinogen initiates a cascade of mechanisms in pancreatitis. There is no specific treatment for acute pancreatitis. Protease inhibitors are not effective in treating severe acute pancreatitis. There is an important role of low-molecular-weight heparin in attenuating necrosis and restoring perfusion of the pancreas. Other drugs used are endothelin receptor antagonists, antagonist of interleukin-1 and interleukin-6 receptors, α-tocopherol, tumor necrosis factor-α and platelet-activating factor inhibitors, acetylsalicylic acid, and local intra-arterial injection of lidocaine. The prophylactic use of antibiotics is not recommended. The treatment outcome of acute pancreatitis is still unsatisfactory.
Glucocorticosteroid and Silicone Gel During Patch Application Without Clinical Scar Improvement After Central Venous Catheter Removal: A Randomized Trial
Authors: Nissen Ida Bo , Handrup Mette Møller , Bang Karen , Hasle Henrik
Published: August 2022

Introduction:

We studied whether glucocorticosteroid during patch occlusion has a beneficial effect on scar outcome in children and adolescents treated for cancer.

Methods:

A double-blinded placebo-controlled randomized clinical trial was performed. The main outcome was the Vancouver Scar Scale. Secondary outcomes were scar width and scar quality measured using the Patient and Observer Scar Assessment Scale. The patients were divided into an intervention groups and a control group. The intervention group was randomized into active and placebo group. The active treatment consisted of cream with glucocorticosteroid and fusidic acid. The placebo treatment consisted of cream with fusidic acid. Both groups received silicone gel patch after central venous catheter removal. The control group received no specific skin care.

Results:

Assessment at 12 months showed that the intervention group had a significantly lower Vancouver Scar Scale and a smaller scar (0,1 cm) compared with the control group (P=0.00, P=0.02) but no benefit of glucocorticosteroid. The Patient and Observer Scar Assessment Scale showed no significant difference between the intervention and control groups (P=0.84, P=0.36).

Conclusions:

Silicone gel sheet alone or in combination with application of glucocorticosteroid during sheet occlusion does not clinically improve scar outcome after removal of central venous catheter in children treated for neoplastic diseases.
Redesigning a Clinical Advancement Program to Promote and Strengthen Competencies of Clinical Nurses
Authors: Tomaszczuk Kate C. , Nichols Emily , Mandrell Belinda N.
Published: August 2022

Clinical advancement programs (CAPs) benefit direct care nursing staff, patients, and healthcare institutions. As standards in nursing practice and workforce evolve, changes in CAPs are necessary. In this quality improvement project, nursing leadership and a 15-member nurse committee redesigned a CAP using Benner's Novice to Expert Model. Changes included self-selection of specialty tracks by shadowing senior nurses in direct patient care, education, and leadership. CAPs increase satisfaction, collaboration, and generation of innovative knowledge.
Skin Tensioning Concept in Rhinoplasty Using a Semifixed Support Mechanism
Authors: Cabbarzade Cavid
Published: August 2022

Background:

As the skin on the nose shows outwardly, if we do not consider the volume of skin on the nose that is reduced, the results may be unsatisfactory. Although redraping the skin over a wide area may help, excess skin cannot be adequately controlled in some cases.

Materials and Methods:

During skin tensioning, a semifixed support mechanism was applied to keep the nasal tip stable and maintain its position while simultaneously allowing stretching and mobility in accordance with its normal function. The dorsal and infratip/columellar skin was stretched by using the support of the most projected part of the nasal tip. The skin was pulled posteriorly to obtain sufficient tensioning and excised at the columellar incision line.

Results:

Of the 94 patients who underwent skin tensioning, 82 were women, and 12 were men. The ages of the patients ranged from 18 to 59 years. Ninety-one patients were primary rhinoplasty patients, and 3 patients were secondary rhinoplasty patients. Skin tensioning was performed in 31 patients with overprojection, 24 patients with thick skin, 17 patients with low skin elasticity, 12 patients with excessive skin elasticity, 7 patients with an advanced long nose, and 3 patients with scar tissue due to previous surgery. No serious complications, either functional or aesthetic, related to skin tensioning was encountered.

Conclusion:

The skin tensioning technique using a semifixed support mechanism helped to achieve a required reduction with a sufficiently defined appearance of the nose in patients with difficult skin.
Sociodemographic Disparities in Access to Cleft Rhinoplasty
Authors: Phillips Sarah , Hauc Sacha C. , Sasson Daniel C. , Khetpal Sumun , Ihnat Jacqueline M. , Boroumand Sam , Rodriguez Jennifer , Prassinos Alexandre , Lopez Joseph , Steinbacher Derek M.
Published: August 2022

Various sociodemographic factors affect patient access to care. This study aims to assess how factors such as government-funded insurance and socioeconomic status impact the ability of adolescents with cleft lip–associated nasal deformities to access secondary rhinoplasty procedures. Patients older than 13 years old with a history of cleft lip/palate were identified in the National Inpatient Sample database from 2010 to 2012. Those who received a secondary rhinoplasty were identified using the International Classification of Diseases, Ninth Revision (ICD-9) procedural codes. A multivariate logistic regression model with post hoc analyses was performed to analyze if insurance status, socioeconomic status, and hospital-level variables impacted the likelihood of undergoing rhinoplasty. Of the 874 patients with a cleft lip/palate history, 154 (17.6%) underwent a secondary rhinoplasty. After controlling for various patient-level and hospital-level variables, living in a higher income quartile (based on zip code of residence) was an independent predictor of receiving a secondary cleft rhinoplasty (odds ratio=1.946, P=0.024). Patients had lower odds of receiving a cleft rhinoplasty if care occurred in a private, nonprofit hospital compared with a government-owned hospital (odds ratio=0.506, P=0.030). Income status plays a significant role in cleft rhinoplasty access, with patients from lower income households less likely to receive a secondary cleft rhinoplasty. Hospital-specific factors such as geographic region, bed size, urbanization, and teaching status may also create barriers for patients and their families in accessing surgical care for cleft lip nasal deformities.
Preoperative Transfusion and Surgical Outcomes for Children with Sickle Cell Disease
Authors: Salvi Pooja S , Solomon Daniel G , Cowles Robert A
Published: August 2022

BACKGROUND:

Current guidelines recommending preoperative transfusion to a hemoglobin level of 9 to 10 g/dL for patients with sickle cell disease (SCD) are based on imperfect evidence. The benefit of preoperative transfusion in children specifically is not known. This study aimed to evaluate whether preoperative RBC transfusion is associated with different rates of sickle cell crisis and surgical complications, compared with no preoperative transfusion, among children with SCD undergoing common abdominal operations.

STUDY DESIGN:

The NSQIP-Pediatrics database (2013 to 2019) was queried. Patients who underwent cholecystectomy, splenectomy, or appendectomy with a preoperative Hct level of less than 30% were included. The primary outcome was 30-day readmission for sickle cell crisis. Secondary outcomes were 30-day surgical complications and hospital length of stay. Propensity score matching methods were used to obtain two statistically similar cohorts of patients comprised of those who were preoperatively transfused and those who were not.

RESULTS:

Among 357 SCD patients, 200 (56%) received preoperative transfusion. In the matched cohort of 278 patients (139 per group), there was no statistically significant difference in 30-day readmission for sickle cell crisis in the transfused and non-transfused groups (5.8% vs 7.2%, p = 0.80). The rate of 30-day surgical complications did not differ between matched groups (10.8% vs 9.4%, p = 0.84). Subgroups defined by presenting Hct levels of 27.3% or greater or less than 27.3%, American Society of Anesthesiologists classification, wound class, and index operation were not associated with an altered risk of sickle cell crisis or surgical complications after preoperative transfusion compared with no transfusion.

CONCLUSIONS:

Preoperative transfusion for children with SCD undergoing semi-elective abdominal operations was not associated with improved outcomes. Prospective investigation is warranted to strengthen guidelines and minimize unnecessary perioperative transfusions in this population.
Surgeons and Professionalism: Where We Are and Where We Need to Go
Authors: Olortegui Kinga Skowron , Angelos Peter
Published: August 2022

Surgeons are famously decisive, assertive, and confident. Unfortunately, we also often have a reputation for being blunt, harsh, and unprofessional. Unprofessional behaviors are unacceptable, and we believe that they are a symptom of surgeon distress and burnout. Unprofessional behaviors should be prevented, but equally importantly, so should the stressors that drive them. This is critically important for the future of our profession.
Effect of Background Music in the Operating Room on Surgical Outcomes: A Prospective Single-Blinded Case-Control Study
Authors: Co Michael , Fong Sze Man , Lau Yik Ching Christy
Published: August 2022

BACKGROUND:

The effect of playing background music on surgical outcomes has been controversial. This prospective case-control study aims to evaluate the impact of music tempo in general surgical settings.

STUDY DESIGN:

Six hundred consecutive patients with nonmetastatic breast cancer receiving breast cancer surgery have been recruited since April 2017. Patients were then assigned to 3 arms in consecutive order. The surgeon operated without music in study arm A; the surgeon operated with slow music in study arm B; and in study arm C, the surgeon operated with fast background music. Patients’ clinical records were reviewed by an independent blinded assessor.

RESULTS:

Baseline demographic data were comparable among the 3 study arms. Seven (3.5%) patients from study arm A developed minor complications (Clavien-Dindo class I and II); none developed major complications (Clavien-Dindo class III or above). Six (3.0%) patients from study arm B and C, respectively (slow/fast music groups), developed minor complications; none developed a major complication. Mean blood loss was also similar among the 3 study arms (5.1, 5.1, and 5.2 mL, respectively; p > 0.05). Operating time was significantly shorter in study arm C: 115 minutes (90–145), compared with 125 minutes (100–160) in study arm A (p < 0.0001) and 120 minutes (95–155) in study arm B (p = 0.0024). After a median follow-up of 40 months (3–56), 40 months (3–56), and 39.5 months (3–56), the local recurrence rates were 1.5%, 1%, and 1%, respectively (p > 0.05).

CONCLUSION:

Playing music in the operating room is safe in general surgical settings in experienced hands.
Outcomes of the Early Specialization Program in Vascular Operation
Authors: Potts John R , Buyske Jo , Klingensmith Mary E
Published: August 2022

BACKGROUND:

The Early Specialization Program (ESP) in vascular surgery (VS) began as a “pilot program” in 2003. There is only one published report on ESP outcomes.

STUDY DESIGN:

The general surgery (GS) and VS programs of all institutions using the ESP were contacted. Data gathered included demographics of ESP enrollees, participants’ case logs (CLs), and CLs of participants’ residency graduating classmates. National CLs, program and institutional data, and participants’ certification status were publicly available.

RESULTS:

Nine institutions have enrolled 34 participants. Four withdrew, and four are in the GS component. Of 26 who have completed ESP, residency CLs were available for 20. Participants’ percentile rankings among national contemporaries were lower than 13th for surgeon–junior cases (SJCs), higher than 73rd for surgeon–chief cases (SCCs), and 49th for total major cases (TMCs). They were lower than the 40th percentile in all domains except operative trauma (52; SD 23.8) and vascular (84.7; SD 22.1). As a percentage of the mean (% mean) for their own graduating classes, participants performed 91.8% (SD 16.5) as many SJCs, 143.7% (SD 45.1) as many SCCs, and 105% (SD 11.4) as many TMCs. Participants performed more than 79 % mean in every domain, including 213.4% (SD 82.4) as many vascular cases. As fellows, they ranked higher than the 50th percentile nationally in all but two categories. Twenty-four of 26 certified in GS. GS certification has lapsed for 5, 17 remain initially certified, and 2 have re-certified. All have current VS certification.

CONCLUSION:

Although infrequently employed, ESP remains an effective option for those who seek both GS and VS certification.
Dexamethasone for Postoperative Nausea and Vomiting in Papillary Thyroid Carcinoma Patients: A Randomized Clinical Trial
Authors: Chen Wenjie , Li Genpeng , Jiang Ke , Song Jinen , Du Runzi , Yang Hui , Gou Juxiang , Li Zhihui , Zhu Jingqiang , Lei Jianyong
Published: August 2022

BACKGROUND:

Postoperative nausea and vomiting (PONV) frequently occur after thyroidectomy. Previous studies have investigated the effects of preoperative dexamethasone for alleviating PONV in various cancers, but studies focused on papillary thyroid carcinoma (PTC) were limited. This study aimed to determine the efficacy of a single preoperative dose of dexamethasone to prevent PONV in patients with PTC.

METHODS:

This single-center, parallel-group, double-blind, placebo-controlled clinical trial was conducted on patients with PTC in West China Hospital. Patients were randomized 1:1 into Group Dex (preoperative 8-mg dexamethasone) or Group Control (0.9% NaCl as control). The primary outcome was the incidence and severity of PONV. The secondary outcomes included postoperative pain, vocal dysfunction, and adverse events.

RESULTS:

Six hundred participants were recruited and randomized. The total incidence of PONV was 33.3% (200 of 600 patients; 95% CI, 29.6–37.1). In the intention-to-treat analysis, PONV occurred in 81 of 300 patients (27.0%; 95% CI, 21.9–32.1) in Group Dex and in 119 of 300 patients (39.7%; 95% CI, 34.1–45.2) in Group Control (p = 0.001), and the absolute risk reduction was 12.7% (95% CI, 5.1–20.0). Patients in Group Dex reported fewer antiemetic requirements than those in Group Control (p = 0.004). Multivariate analysis indicated that dexamethasone administration (OR = 0.546; 95% CI, 0.383–0.777; p = 0.001) was associated with a reduced rate of PONV. Dexamethasone treatment also contributed to alleviating postoperative pain and improving subjective vocal dysfunction, with no increase in adverse events.

CONCLUSIONS:

A single dose of dexamethasone is effective and safe for preventing PONV in PTC patients.
Duganella dendranthematis sp. nov. and Massilia forsythiae sp. nov., isolated from flowers
Authors: Heo Jun , Won Miyoung , Lee Daseul , Han Byeong-Hak , Hong Seung-Beom , Kwon Soon-Wo
Published: August 2022

Two aerobic, Gram-stain-negative, motile, mesophilic, rod-shaped and catalase-positive bacterial strains designated AF9R3T and GN2-R2T were isolated from flowers collected in the Republic of Korea. Strain AF9R3T grew at 4–33 °C, pH 4.0–9.0 and with 0–1 % NaCl (w/v), and strain GN2-R2T grew at 10–33 °C, pH 4.0–9.0 and with 0–1 % NaCl (w/v). Phylogenetic analysis on the basis of 16S rRNA gene sequences indicated that strains AF9R3T and GN2-R2T belonged to the genera

Duganella

and

Massilia

, respectively, showing high sequence similarity to

Duganella levis

CY42WT (99.4 %) and

Massilia putida

6 NM-7T (98.0 %), respectively. Both strains contained summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c) and C16 : 0 as the major fatty acids, and ubiquinone Q-8 as the predominant quinone. Strain AF9R3T had diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and strain GN2-R2T comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid as the major polar lipids. Orthologous average nucleotide identity and digital DNA–DNA hybridization values of strain AF9R3T to its closest relative

D. levis

CY42WT were 92.6 and 56.5 %, and those of strain GN2-R2T to its closest relative

M. putida

6 NM-7T were 81.4 and 24.8 %. Based on genotypic and phenotypic data, strains AF9R3T and GN2-R2T are considered to represent novel species of the genus

Duganella

and

Massilia

, respectively, for which the names Duganella dendranthematis sp. nov. (type strain AF9R3T=KACC 21258T=NBRC 114510T) and Massilia forsythiae sp. nov. (type strain GN2-R2T=KACC 21261T=NBRC 114511T) have been proposed.
False-positive detection of Group B Streptococcus (GBS) in chromogenic media (Strep B Carrot Broth) due to presence of Enterococcus faecalis in High Vaginal swabs
Authors: Singh Abhishek , Husein Atahar , Singh Salomi , Ghattargi Vikas , Dhotre Dhiraj , Shouche Yogesh S. , Colaco Stacy , Abhyankar Vivek , Patekar Suyash , Chhabria Karisma , Kumar Sushil , Urhekar A. D. , Modi Deepak
Published: August 2022

Introduction. Vaginal colonization of Group B

Streptococcus

(GBS) is associated with preterm births and neonatal sepsis. Thus routine screening of GBS in prenatal care is recommended.

Hypothesis. Chromogenic media (carrot broth) aids in specific and rapid detection of GBS.

Aim. To investigate the efficiency of Strep B Carrot Broth for detection of GBS in high vaginal swabs from pregnant women.

Methods. In this study 201 vaginal swab samples were collected from pregnant women. Swabs were inoculated in chromogenic media (Strep B Carrot Broth). The positive and negative cultures were inoculated on blood agar and crome agar plates. The colonies were subjected to 16S rRNA sequencing and gene-specific PCR for confirmation. The Christie Atkins Munch Peterson (CAMP) and bile esculin agar (BEA) tests were used for biochemical confirmation. PCR was performed on genomic DNA isolated from uncultured vaginal swabs.

Results. It was found that 20/201 (9.9 %) vaginal swab samples were positive in the Strep B Carrot Broth and 17/20 (85 %) and 19/20 (95 %) of these samples yielded colonies on blood agar and crome agar, respectively. Of the 181 carrot broth-negative samples, 1 (0.5 %) and 38 (20.9 %) yielded colonies on blood agar and crome agar plates, respectively. However, 16 s rRNA sequencing revealed that none of the 20 carrot broth-positive cultures were GBS and had sequence similarities to

Enterococcus faecalis

. This was also confirmed by using gene-specific PCR and BEA positivity. Furthermore,

E. faecalis

was detected by PCR in DNA isolated from 57 uncultured vaginal swabs samples, GBS could only be detected by PCR in four samples.

Conclusion. Carrot broth-based culture can lead to false-positive detection due to the presence of

E. faecalis

. Thus GBS-positive results in carrot broth must be confirmed by the other molecular and biochemical tests before making a final diagnosis.
CRISPR arrays as high-resolution markers to track microbial transmission during influenza infection
Authors: Zhang Lingdi , Rahman Jahan , Lashua Lauren , Gordon Aubree , Balmaseda Angel , Kuan Guillermina , Bonneau Richard , Ghedin Elodie
Published: August 2022

Background

The microbial community present in the respiratory tract can be disrupted during influenza virus infection, leading to functional effects on the microbial ecology of the airways and potentially impacting transmission of bacterial pathogens. Determining the transmission of airway commensals, which can carry antibiotic resistance genes that could in turn be transferred to bacterial pathogens, is of public health interest. Metagenomic-type analyses of the microbiome provide the resolution necessary for microbial tracking and functional assessments in the airways.

Results

We obtained 221 respiratory samples that were collected from 54 individuals at 4 to 5 time points across 10 households, with and without influenza infection, in Managua, Nicaragua. From these samples we generated metagenomic (whole genome shotgun sequencing) and metatranscriptomic (RNA sequencing) datasets to profile microbial taxonomy and gene orthologous groups. Overall, specific bacteria and phages were differentially abundant between influenza positive households and control (no influenza infection) households, with bacterial species like Moraxella catarrhalis and bacteriophages like Chivirus significantly enriched in the influenza positive households. Some of the bacterial taxa found to be differentially abundant were active at the RNA level with genes involved in bacterial physiology differentially enriched between influenza positive and influenza negative samples, primarily for Moraxella. We identified and quantified CRISPR arrays detected in the metagenomic sequence reads and used these as barcodes to track bacteria transmission within and across households. We detected a clear sharing of bacteria commensals and pathobionts, such as Rothia mulcilaginosa and Prevotella bacteria, within and between households, indicating community transmission of these microbes. Antibiotic resistance genes that mapped to Rothia and Prevotella were prevalent across our samples. Due to the relatively small number of households in our study we could not determine if there was a correlation between increased bacteria transmission and influenza infection.

Conclusion

This study shows that microbial composition and ecological disruption during influenza infection were primarily associated with Moraxella in the households sampled. We demonstrated that CRISPR arrays can be used as high-resolution markers to study bacteria transmission between individuals. Although tracking of antibiotic resistance transmission would require higher resolution mapping of antibiotic resistance genes to specific bacterial genomes, we observed that individuals connected by shared bacteria had more similar antibiotic resistance gene profiles than non-connected individuals from the same households.
Modelling vaccination and control strategies of outbreaks of monkeypox at gatherings
Authors: Yuan Pei , Tan Yi , Yang Liu , Aruffo Elena , Ogden Nicholas H. , Bélair Jacques , Arino Julien , Heffernan Jane , Watmough James , Carabin Hélène , Zhu Huaiping
Published: August 2022

Background

Monkeypox cases keep soaring in non-endemic’s countries and areas in the last few months, leading to the WHO declaring a Public Health Emergency of International Concern. The ongoing and coming festivals, parties and holidays gathering events are causing increased concerns about possible outbreaks.

Methods

We considered a hypothetical metropolitan city and modelled the transmission of monkeypox virus in humans in high-risk (HRG) and low-risk groups (LRG) using a Susceptible-Exposed-Infectious-Recovered (SEIR) model and incorporated gathering events. Model simulations assessed how the current vaccination strategy combined with other public health measures can contribute to mitigating or halting outbreaks from mass gathering events.

Results

The risk of a monkeypox outbreak remains high on the occasion of mass gathering events in the absence of public health control measures. However, the outbreaks can be well controlled by cutting off transmission by isolating confirmed cases and inoculating their close contacts. Also, Post Exposure Prophylaxis is more effective for containment in the summer gatherings than a broad vaccination campaign in HRG, considering the time needed for developing the immune response and the availability of vaccine. The number of attendees and effective contacts during the gathering are the factors that need more attention by public health authorities to prevent a burgeoning outbreak. Moreover, restricting attendance through vaccination requirements can help secure mass gathering events.

Conclusion

Gathering events can be made safe with some restrictions of either the number and density of attendees in the gathering, or vaccination requirements. The ring vaccination strategy inoculating close contacts of confirmed cases may not be enough to prevent potential outbreaks, however, mass gatherings can be rendered safe if that strategy is combined with public health measures, including rigorous contact tracing, testing, identifying and isolating cases. Compliance of the community and promotion of awareness are also indispensable to the containment.
BNT162b2 induced neutralizing and non-neutralizing antibody functions against SARSCoV-2 diminish with age
Authors: Bates Timothy A. , Lu Pei , Kang Ye jin , Schoen Devin , Thornton Micah , McBride Savannah K. , Park Chanhee , Kim Daehwan , Messer William B. , Curlin Marcel E. , Tafesse Fikadu G. , Lu Lenette L.
Published: August 2022

Each novel SARS-CoV-2 variant renews concerns about decreased vaccine efficacy caused by evasion of vaccine induced neutralizing antibodies. However, accumulating epidemiological data show that while vaccine prevention of infection varies, protection from severe disease and death remains high. Thus, immune responses beyond neutralization could contribute to vaccine efficacy. Polyclonal antibodies function through their Fab domains that neutralize virus directly, and Fc domains that induce non-neutralizing host responses via engagement of Fc receptors on immune cells. To understand how vaccine induced neutralizing and non-neutralizing activities synergize to promote protection, we leverage sera from 51 SARS-CoV-2 uninfected health-care workers after two doses of the BNT162b2 mRNA vaccine. We show that BNT162b2 elicits antibodies that neutralize clinical isolates of wildtype and five variants of SARS-CoV-2, including Omicron BA.2, and, critically, induce Fc effector functions. FcγRIIIa/CD16 activity is linked to neutralizing activity and associated with post-translational afucosylation and sialylation of vaccine specific antibodies. Further, neutralizing and non-neutralizing functions diminish with age, with limited polyfunctional breadth, magnitude and coordination observed in those ≥65 years old compared to <65. Thus, studying Fc functions in addition to Fab mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations such as the elderly against SARS-CoV-2 and novel variants.
Paraoxonase 1 status is a major Janus-faced component of mild and moderate acute ischemic stroke and consequent disabilities
Authors: Brinholi Francis F. , Michelin Ana Paula , Matsumoto Andressa K. , Semeão Laura de O. , Almulla Abbas F. , Supasitthumrong Thitiporn , Tunvirachaisakul Chavit , Barbosa Decio S. , Maes Michael
Published: August 2022

Aims

This study aims to examine the associations between paraoxonase 1 (PON)1 status and acute ischemic stroke (AIS) and consequent disabilities.

Methods

This study recruited 122 patients with AIS and 40 healthy controls and assessed the Q192R gene variants, arylesterase (AREase) and chloromethyl phenylacetate (CMPAase) activities, and high-density lipoprotein cholesterol (HDL) in baseline conditions. AREase and CMPAase were measured 3 months later. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin score (mRS) were assessed at baseline and 3 and 6 months later.

Results

Reduced CMPAase and increased AREase activities are significantly associated with AIS and mRS and NIHSS scores (baseline and 3 and 6 months later). The best predictor of AIS/disabilities was a decrease in the z-unit-based composite zCMPAase-zAREase score. Serum high density lipoprotein cholsterol (HDL) was significantly correlated with CMPAase, but not AREase, activity and a lowered zCMPAase+zHDL score was the second best predictor of AIS/disabilities. Regression analysis showed that 34.7% of the variance in baseline NIHSS was explained by zCMPAase-zAREase and zCMPAase+zHDL composites, HDL, and hypertension. Neural network analysis showed that stroke was differentiated from controls with an area under the ROC curve of 0.975 using both new composite scores, PON1 status, hypertension, dyslipidemia, previous stroke as body mass index. The PON1 Q192R genotype has many significant direct and mediated effects on AIS/disabilities, however, its overall effect was not significant.

Discussion

PON1 status and the CMPAase-HDL complex play key roles in AIS and its disabilities at baseline and 3 and 6 months later.
D-cycloserine (DCS) is Not Susceptible to Self-administration, unlike S-ketamine Using an Intravenous Self-administration Model in Naive and Ketamine-habituated Sprague-Dawley Rats
Authors: Javitt Daniel C. , Javitt Jonathan C.
Published: August 2022

OBJECTIVE

N-methyl D-aspartate Receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested in its efficacy in substituting for ketamine in ketamine-dependent rats.

METHODS

A standard Intravenous self-administration study was conducted in Male adult Sprague-Dawley rats. model to study compounds’ abuse liability. Potential for self-administration was assessed in ketamine-habituated subjects. Subjects were trained to press a lever to obtain food, prior to connection of the lever to intravenous drug administration apparatus. DCS was provided for self-infusion by test subjects at doses of 1.5, 5.0, and 15mg/kg per lever press.

RESULTS

S-Ketamine was seen to substitute for ketamine and to result in self-administration at the same frequency. DCS was not seen to result in any self-administration at any of the test doses. The self-infusion behavior of DCS was the same as that of saline.

CONCLUSION

C-cycloserine, an a mixed agonist/antagonist of the NMDAR glycine site, which has been shown to have antidepressant and anti-suicidal properties in clinical studies has no apparent potential for abuse liability in a standard rodent self-administration model.
Effects of metformin use in pregnant women on maternal and infant outcomes: protocol for a systematic review and meta-analysis
Authors: Wang Kezhang , Pan Rui , Wang Yu
Published: August 2022

Introduction

Metformin has been considered for use in women who are overweight or obese and with pre-existing type 2 diabetes(T2DM) or gestational diabetes mellitus(GDM). Nevertheless, few studies have weighed the pros and cons of maternal metformin use on offspring and women’s perinatal health. We determined to ascertain whether the insulin sensitiser metformin improves fetal and maternal outcomes in Pregnant women with type 2 diabetes or with a BMI no less than 24 kg/m2

Methods and analysis

The protocol was formulated according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Exhaustive literature searches of electronic bibliographic databases will be conducted in PubMed, EMBASE, Cochrane Library, Web of Sciences, Scopus, ClinicalTrial, OvidSP and ScienceDirect. We used a predefined data extraction table to perform data extraction, and publication bias measurement for each study will be accomplished through the Cochrane Collaboration Tool.

The statistical analyses will be performed using RevMan (5.4.1; The Cochrane Collaboration) and STATA (17). Heterogeneity will be assessed using the Q and I2 test, with a value of I2 > 50% being considered substantial. The extent of publication bias will be investigated by visual assessment of a funnel plot and using Egger’s test, Begg’s test, and Harbord’s test if ten or more trials are pooled.

Ethics and dissemination

Patients’ consent and Ethical approval are not requisites. The complete analysis will be published in an international open-access journal and translational articles to disseminate the results to clinical internists.

PROSPERO registration number: CRD42022347084

Strengths and limitations of this study

▸

This review will comprehensively assess published English-language studies without period or geographical restrictions.

▸

This system review plan strictly follows preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P)

▸

Included studies will be limited to RCTs, which have a high degree of internal consistency and are not representative of the real world.

▸

As is the case with most meta-analyses, there may be significant and unexplained heterogeneity in this study.
The C-terminus of the cargo receptor Erv14p affects COPII vesicle formation and cargo delivery
Authors: Lagunas-Gomez Daniel , Yañez-Dominguez Carolina , Zavala-Padilla Guadalupe , Barlowe Charles , Pantoja Omar
Published: August 2022

The endoplasmic reticulum (ER) is the start site of the secretory pathway, where newly synthesized secreted and membrane proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Little is known about how post-translational modification events regulate packaging of cargo into COPII vesicles. Erv14/Cornichon belongs to a conserved family of cargo receptors required for the selection and ER export of transmembrane proteins. In this work, we show the importance of a phosphorylation consensus site (Serine-134) at the C-terminus of Erv14. Mimicking phosphorylation of S134 (S134D) prevents the incorporation of Erv14 into COPII vesicles, delays cell growth, exacerbates growth of sec mutants, modifies ER structure, and affects localization of several plasma membrane transporters. In contrast, the dephosphorylated mimic (S134A) had less deleterious effects, but still modifies ER structure and slows cell growth. Our results suggest that a possible cycle of phosphorylation and dephosphorylation is important for the correct functioning of Erv14p.

Summary statement

Erv14 C-terminus regulates COPII formation and cargo delivery
Secondary findings in a large Pakistani cohort tested with whole genome sequencing
Authors: Skrahin Aliaksandr , Cheema Huma Arshad , Hussain Maqbool , Rana Nuzhat Noureen , Rehman Khalil Ur , Kumar Raman , Oprea Gabriela , Ameziane Najim , Rolfs Arndt , Skrahina Volha
Published: August 2022

Background

Studies in the field of genomic secondary findings (SF) are diverse regarding participants’ characteristics; sequencing methods; versions of the ACMG SF gene list.

Aim and methods

Based on whole genome sequencing (WGS) and version 3.1 of ACMG SF list (ACMG SF), we studied SF in 863 individuals from Pakistan: 62% males; 80% had consanguineous parents. In addition to the ACMG SF we have generated a list of gene-disease pairs that have a clear epidemiological and medically actionable value (non-ACMG SF) in Pakistan.

Results

The total rate of SF was 4.6%, with rates of ACMG SF – 2.7% and non-AGMG SF – 1.9%. 75.0% of ACMG SF were related to cardiovascular diseases (CVD); cancer predisposition syndromes accounted for 16.7%. Among non-ACMG SF 18.8% belong to eye diseases, followed by neuromuscular – 12.5%, metabolic – 12.5%, and urinary system diseases – 12.5%; CVD accounted for 6.3%. We found high proportion of biallelic mutations among both ACMG (4.2%) and non-ACMG (50%) SF.

Conclusions

The frequency of ACMG SF is within the range reported in most studies. High proportion of CVD can be explained by inclusion of additional CVD in the ACMG v3.1 SF list. 1.9% of non-ACMG SF and high proportion of biallelic variants are relevant to epidemiology of Pakistan as a country with high rate of consanguineous marriages. In such countries the ACMG criteria for SF can be expanded, and our list of non-ACMG SF is one example. Our findings may help guide the development of standards of practice in genomic medicine and drive future research.
Cost-Benefit Analysis of a Distracted Pedestrian Intervention
Authors: Rahim Md Jillur , Schwebel David C. , Hasan Ragib , Griffin Russell , Sen Bisakha
Published: August 2022

Objective

Cellphone ubiquity has increased distracted pedestrian behavior and contributed to growing pedestrian injury rates. A major barrier to large-scale implementation of prevention programs is unavailable information on potential net monetary benefits. We evaluated net economic benefits of StreetBit, a program that reduces distracted pedestrian behavior by sending warnings from intersection-installed Bluetooth beacons to distracted pedestrians’ smartphones.

Methods

Three data sources were used: (1) fatal, severe, non-severe pedestrian injury rates from Alabama’s electronic crash-reporting-system; (2) expected costs per fatal, severe, non-severe pedestrian injury – including medical cost, value of statistical life, work-loss cost, quality-of-life cost – from CDC; and (3) prevalence of distracted walking from extant literature. We computed and compared estimated monetary costs of distracted walking in Alabama and monetary benefits from implementing StreetBit to reduce pedestrian injuries at intersections.

Results

Over 2019-2021, Alabama recorded an annual average of 31 fatal, 83 severe, and 115 non-severe pedestrian injuries in intersections. Expected costs/injury were $11 million, $339,535, and $93,877, respectively. The estimated range of distracted walking prevalence is 25%-40%, and StreetBit demonstrates 19.1% (95%CI: 1.6%-36.0%) reduction. These figures demonstrate potential annual cost savings from using interventions like StreetBit statewide ranging from $18.1-$29 million. Potential costs range from $3,208,600 (beacons at every-fourth urban intersection) to $6,359,200 (every other intersection).

Conclusions

Even under the most parsimonious scenario (25% distracted pedestrians; densest beacon placement), StreetBit yields $11.8 million estimated net annual benefit. Existing data sources can be leveraged to predict net monetary benefits of distracted pedestrian interventions like StreetBit and facilitate large-scale intervention adoption.

What is already known in this topic

Smartphone-related distraction is a likely contributing factor to the increasing rate of pedestrian fatalities and injuries in the US. However, interventions to reduce pedestrian distraction have not been widely adapted.

What this study adds

One barrier to widespread adaption is lack of information on benefits versus costs. This study examines the economic costs and benefits of an intervention that reduces distracted walking to increase pedestrian safety, and provides a template showing how existing data sources can be leveraged to do similar analyses for other interventions designed to reduce pedestrian safety.

How this study might affect research, practice or policy

The template developed in this study can facilitate large-scale implementation of any intervention designed to prevent pedestrian fatalities and injuries by providing policymakers information on net benefits of the intervention.
Syncytial nerve net in a ctenophore sheds new light on the early evolution of nervous systems
Authors: Burkhardt Pawel , Medhus Astrid , Digel Leonid , Naumann Benjamin , Soto-Àngel Joan J , Nordmann Eva-Lena , Sachkova Maria Y , Kittelmann Maike
Published: August 2022

A fundamental breakthrough in neurobiology has been the formulation of the neuron doctrine by Santiago Ramón y Cajal, which states that the nervous system is composed of discrete individual cells. Electron microscopy later confirmed the doctrine and allowed the identification of synaptic connections. Here we use volume electron microscopy and 3D reconstructions to characterize the nerve net of a cydippid-phase ctenophore, belonging to one of the earliest-branching animal lineages. We found that neurons of its subepithelial nerve net do not follow Cajal’s neuron doctrine but instead show a continuous plasma membrane forming a syncytium. This is more similar to the reticulate theory of the nervous system put forward by Camillo Golgi. Additionally, we were able to identify new sensory cell types and describe simple neuro-sensory circuits for cydippid-phase ctenophores. Together with the ctenophore-specific synaptic architecture and the presence of an extensive repertoire of lineage-specific neuropeptides our morphological data provide substantial evidence for the independent evolution of the nervous system of ctenophores and the remaining animals.
Local RNA Structure, Ion Hydration Shell and the Energy Barrier for Water Exchange from the Ion Hydration Shell Determine the Mechanism of Ion Condensation on Specific RNA Sites
Authors: Halder Antarip , Kumar Sunil , Habibullah Sk , Reddy Govardhan
Published: August 2022

RNA folding and functioning require the binding of metal ions in specific cavities of the folded structure. This property is critical to the functioning of riboswitches that especially regulate the metal ions concentration in bacteria. However, the fundamental principles governing the specific binding of metal ions in RNA are unclear. We probed the condensation mechanism of biologically relevant alkali (Na+ and K+), alkaline earth (Mg2+ and Ca2+), and transition metals (Mn2+, Co2+, Ni2+ and Zn2+) on a part of the Ni2+ and Co2+ (NiCo) sensing riboswitch aptamer domain using computer simulations. The selected structure has multiple secondary structural elements and a single site for the specific binding of a metal ion. We show that three factors primarily determine the binding of a metal ion to an RNA site - (1) The varying structural constraints from different RNA secondary structural elements strongly influence the metal ion binding. The mode of ion binding depends on the local structure around the RNA’s ion-binding pocket. (2) The arrangement of water molecules in the ion hydration shell, and (3) the energy barrier for the ion to lose a water molecule from its hydration shell and transition from an outer to an inner shell interaction, which is primarily influenced by the metal ion charge density. These results have implications for designing biocompatible sensors using riboswitches to probe the concentration of intracellular metal ions.
Disease decreases variation in host community structure in an old-field grassland
Authors: Grunberg Rita L. , Halliday Fletcher W. , Heckman Robert W. , Joyner Brooklynn N. , O’Keeffe Kayleigh R. , Mitchell Charles E.
Published: August 2022

Disease may modulate variation in host community structure by modifying the interplay of deterministic and stochastic processes. For instance, deterministic processes like ecological selection can benefit species less impacted by disease. When disease consistently selects for certain host species, this can reduce variation in host community composition. On the other hand, when host communities are less impacted by disease and selection is weaker, stochastic processes (e.g., drift, dispersal) may play a bigger role in host community structure, which can increase variation in structure among communities. While effects of disease on host community structure have been quantified in field experiments, few have addressed the role of disease in modulating variation in structure among host communities. To address this, we conducted a field experiment spanning three years, using a tractable system: foliar fungal pathogens in an old-field grassland community dominated by the grassLolium arundinaceum, tall fescue. We reduced foliar fungal disease burden in replicate host communities (experimental plots in intact vegetation) in three fungicide regimens that varied in the duration of fungicide exposure and included a fungicide-free control. We measured host diversity, biomass, and variation in community structure among replicate communities. Disease reduction generally decreased plant richness and increased aboveground biomass relative to communities experiencing ambient levels of disease. Despite changes in structure of the plant communities over the experiment’s three years, the effects of disease reduction on plant richness and biomass were consistent across years. However, disease reduction did not reduce variation in host community structure, providing little evidence for ecological selection by competition or other deterministic processes. Instead, disease reduction tended to amplify variation in host community structure among replicate communities (i.e., within fungicide treatment groups), suggesting that disease diminished the degree to which host communities were structured by stochastic processes. These results of experimental disease reduction both highlight the potential importance of stochastic processes in plant communities and reveal the potential for disease to regulate variation in host community structure.
Deep Learning-based Phenotype Imputation on Population-scale Biobank Data Increases Genetic Discoveries
Authors: An Ulzee , Pazokitoroudi Ali , Alvarez Marcus , Huang Lianyun , Bacanu Silviu , Schork Andrew J. , Kendler Kenneth , Pajukanta Päivi , Flint Jonathan , Zaitlen Noah , Cai Na , Dahl Andy , Sankararaman Sriram
Published: August 2022

Biobanks that collect deep phenotypic and genomic data across large numbers of individuals have emerged as a key resource for human genetic research. However, phenotypes acquired as part of Biobanks are often missing across many individuals, limiting the utility of these datasets. The ability to accurately impute or “fill-in” missing phenotypes is critical to harness the power of population-scale Biobank datasets. We propose AutoComplete, a deep learning-based imputation method which can accurately impute missing phenotypes in population-scale Biobank datasets. When applied to collections of phenotypes measured across ≈ 300K individuals from the UK Biobank, AutoComplete improved imputation accuracy over existing 2 methods (average improvement in r2 of 18% for all phenotypes and 42% for binary phenotypes). We explored the utility of phenotype imputation for improving the power of genome-wide association studies (GWAS) by applying our method to a group of five clinically relevant traits with an average missigness rate of 83% (67% to 94%) leading to an an increase in effective sample size of ≈2-fold on average (0.5 to 3.3-fold across the phenotypes). GWAS on the resulting imputed phenotypes led to an increase in the total number of loci significantly associated to the traits from four to 129. Our results demonstrate the utility of deep-learning based imputation to increase power for genetic discoveries in existing biobank data sets.