bluuebunny/crossref_metadata_2025 huggingface dataset:
Gab1 Overexpression Alleviates Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis Through PI3K/Akt Signaling Pathway
Authors: Zhang Zhaoxia , Shen Caijie , Wu Nan , Wang Jian , Du Weiping , Chen Xiaomin
Published: July 2022

Grb2-associated binding protein 1 (Gab1), an intracellular scaffolding adaptor, was involved in several cardiovascular diseases. However, the role of Gab1 in doxorubicin (DOX)-induced cardiotoxicity remains largely unknown. The present study investigated whether Gab1 protected against DOX-induced cardiotoxicity and the underlying mechanism. We overexpressed Gab1 in the hearts using an adeno-associated virus 9 system through tail vein injection. C57BL/6 mice were subjected to DOX (15 mg/kg/d, i.p.) to generate DOX-induced cardiotoxicity. Echocardiography, histological analysis, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) kits, Western blotting, and quantitative real-time polymerase chain reaction (PCR) evaluated DOX-induced cardiotoxicity and the underlying mechanisms. Myocardial Gab1 protein and messenger RNA (mRNA) levels were markedly decreased in DOX-administered mice. Overexpression of Gab1 in myocardium significantly improved cardiac function and attenuated cardiac oxidative stress, inflammatory response, and apoptosis induced by DOX. Mechanistically, we found that PI3K/Akt signaling pathway was downregulated after DOX treatment, and Gab1 overexpression activated PI3K/Akt signaling pathway, whereas PI3K/Akt signaling pathway inhibition abolished the beneficial effect of Gab1 overexpression in the heart. Collectively, our results indicated that Gab1 is essential for cardioprotection against DOX-induced oxidative stress, inflammatory response, and apoptosis by mediating PI3K/Akt signaling pathway. And cardiac gene therapy with Gab1 provides a novel therapeutic strategy against DOX-induced cardiotoxicity.
Long-term risk of suture breakage after scleral fixation of late in-the-bag intraocular lens dislocation with a polypropylene 10-0 suture
Authors: Medin Helle , Kure Ingeborg Slørdahl Hjort , Dalby Marius , Drolsum Liv , Kristianslund Olav
Published: July 2022

Purpose:

To investigate the long-term risk of suture breakage after scleral fixation with a polypropylene 10-0 suture in eyes with late in-the-bag intraocular lens (IOL) dislocation.

Setting:

Oslo University Hospital, Oslo, Norway.

Design:

Retrospective case series.

Methods:

Patients operated with scleral suturing of late in-the-bag IOL dislocation from 2007 to 2016. 192 eyes (176 patients) operated with scleral suture (polypropylene 10-0 suture) fixation of a dislocated IOL-capsule complex were identified; 91 patients (47%) were men.

Results:

The mean follow-up after the operation was 6.2 (95% CI, 5.7-6.7) years, and 98 patients (56%) deceased during the study. 11 eyes (6%) (11 patients) had suture breakage that required reoperation with a mean time of 5.5 (3.4-7.6) years after IOL repositioning surgery. These patients had a mean age of 73.5 (67.9-79.2) years at the time of the operation for late in-the-bag IOL dislocation vs 81.3 (79.8-82.9) years for patients who did not experience this complication (P = .004). No cases of late endophthalmitis were registered.

Conclusions:

The long-term risk of suture breakage was quite low after scleral fixation of late in-the-bag IOL dislocation, particularly in the oldest patients. Hence, the polypropylene 10-0 suture seems to be a safe option for scleral fixation in this patient group.
Cutaneous Manifestations of Systemic Lupus Erythematosus
Authors: Panikkath Deepa Ragesh , Sandhu Vaneet Kaur
Published: July 2022

Inflammation driven by immune-mediated mechanisms can lead to a wide variety of skin manifestations. Cutaneous lupus erythematosus (CLE), for example, is an autoimmune connective tissue disease that may be limited to the skin or be part of the widespread multiorgan involvement seen in systemic lupus erythematosus. Clinical findings are divided into lupus-specific (acute, subacute, and chronic) and nonspecific skin lesions. The diagnosis of CLE requires a thorough physical examination and, in some cases, skin biopsy and laboratory evaluation for any underlying systemic involvement. CLE treatment is dependent on the cutaneous manifestations and severity of disease. In addition to lifestyle measures, particularly avoidance of sunlight, topical and systemic therapies have proven beneficial. Prognosis is varied by disease severity, although chronic CLE notoriously results in cosmetic damage. Early recognition and management of CLE is important as it may also be the presenting manifestation of systemic lupus erythematosus. Patient care includes education and close collaboration with primary care providers, dermatologists, and rheumatologists.
Translucent Cyst Around the Eyelid
Authors: Hassan Oyindayo M. , Medepalli Vidya M. , Zieman Daniel P. , Ortego Joshua R. , Brodell Robert T. , Nahar Vinayak K.
Published: July 2022

A translucent cyst adjacent to the left lateral canthus enlarged slowly over 2 years in a 48-year-old woman. Readers will be challenged to choose the correct diagnosis based on case presentation, history, and symptoms. The differential diagnosis of translucent, cystic lesions on the face requires a careful assessment because both benign and malignant lesions must be considered.
Innovation in Pediatric Clinical Education: The Development of a Clinical Instructor Toolkit
Authors: Birkmeier Marisa , Emmel Lauren A. , Manning Rhonda A. , Nesbit Kathryn C.
Published: July 2022

Introduction/Literature Review:

Clinical education (CE) experiences are essential components of physical therapist assistant (PTA) and professional physical therapist education requiring qualified clinical instructors (CIs). The 2014 CE Summit recognized the need for CI development. The Academy of Pediatric Physical Therapy Academic and Clinical Educators special interest group assembled a task force to address the need for pediatric CI resources. The purposes of this study are to describe the process used to create a pediatric CI Toolkit and describe the results of the task force's work as a mechanism to meet the needs of CIs to facilitate clinical teaching.

Participants:

Pediatric PTAs and physical therapists (PTs) engaged in physical therapy CE were included in the needs assessment survey. The target population of the survey also represented the intended users of the created CI Toolkit.

Method:

A task force composed of individuals with diverse pediatric subspecialties, geographic regions, and roles in CE convened to create the CI Toolkit. The task force completed a literature search and online CE resources search to assist with survey development and with guidance in the development of the CI Toolkit. A needs assessment survey was created and deployed to gather information from pediatric PTAs and PTs. The task force developed the structure of the CI Toolkit and collected resources to populate the online tool.

Results:

An online CI Toolkit was created and contained 160 resources organized into topics, settings, and descriptors. Tools include resources for clinical reasoning, student assignments, general resources, weekly objectives, and CI development. A four-person committee was created to review proposed additions to the CI Toolkit.

Discussion and Conclusion:

The CI Toolkit is a model for accessible CI professional development for clinical teaching and learning. Health professions educators interested in creating resources for clinical educators will benefit from the lessons learned in the creation of the CI Toolkit.
Under and overtreatment with thyroid hormone replacement during pregnancy
Authors: Peng Carol Chiung-Hui , Maraka Spyridoula , Pearce Elizabeth N.
Published: July 2022

Purpose of review

Among pregnant women on thyroid hormone replacement therapy undertreatment is common, while overtreatment is rare. Both deficient and excessive maternal thyroid hormone have been related to adverse maternofetal and long-term offspring outcomes, although studies’ results are inconsistent. This review aims to discuss recent evidence regarding the effects of under- and overtreatment with thyroid hormone replacement during pregnancy and how current practices could be improved.

Recent findings

Whether or not thyroid hormone therapy needs to be initiated for maternal subclinical hypothyroidism remains unclear, but recent meta-analyses have confirmed associations between adverse maternal, neonatal, and offspring outcomes in both overt and subclinical hypothyroidism. Subclinical hyperthyroidism in pregnancy is related to fewer adverse outcomes. Current adherence to levothyroxine during pregnancy and medication counseling by healthcare providers are suboptimal.

Undertreatment of maternal hypothyroidism may increase risks for adverse maternofetal and offspring effects more than overtreatment does. If thyroid hormone replacement therapy is indicated and initiated in pregnancy, frequent thyroid function monitoring is required to avoid under- or overtreatment. Effective communication between clinicians and patients is imperative to increase medication adherence.
Efficacy and safety of medical and nutritional management of gastroesophageal reflux in formula-fed infants: a narrative review
Authors: Barbieur Jana , Levy Elvira Ingrid , Vandenplas Yvan
Published: July 2022

Purpose of review

The prescription of proton pump inhibitors has an increasing trend, despite that guidelines recommend nutritional management as first-line management. A thickened antiregurgitation formula is recommended in formula-fed infants. In this review we focus on the novel insights in management of formula-fed infants with gastroesophageal reflux disease (GERD).

Recent findings

New data are limited. Concerning thickened antiregurgitation formula, locust bean gum has been the most studied and has limited adverse effects. However, positive results were also obtained with pectin. The effect of pro- and prebiotics on regurgitation is unclear. The overlap between cow's milk allergy and gastroesophageal reflux remains a challenge.

Very limited new data were published during the last 18 months. Thickened antiregurgitation formula is the first-line approach in formula-fed infants with GERD. No specific thickening agent can be recommended because of lack of comparative trials. Proton pump inhibitors are over prescribed in infants.
Effects of the complement system on antibody formation and function: implications for transplantation
Authors: Cumpelik Arun , Heeger Peter S.
Published: July 2022

Purpose of review

In antibody-mediated allograft rejection, donor-reactive antibodies cause transplant injury in part via complement activation. New mechanistic insights indicate complement also modulates development of humoral immune responses. Herein we review recent data that describes how complement affects antibody formation and we discuss therapeutic implications.

Recent findings

Extravasating T cells interacting with integrins express and activate intracellular complement that drives immune-metabolic adaptations vital for CD4+ helper cells. Marginal zone B cells can acquire intact major histocompatibility complexes from dendritic cells via complement-dependent trogocytosis for presentation to T cells. Activated B cells in germinal centers receive co-stimulatory signals from T-helper cells. These germinal center B cells undergo coordinate shifts in surface complement regulator expression that permit complement receptor signaling on the germinal center B cells required for affinity maturation. The positively selected, high-affinity B cells can differentiate into plasma cells that produce donor-HLA-reactive antibodies capable of ligating endothelial, among other, graft cells. Subsequent sublytic complement attack can stimulate endothelial cells to activate CD4+ and CD8+ T cells, promoting cellular and humoral rejection. Newly developed complement inhibitors are being tested to prevent/treat transplant rejection.

The complement system influences T-cell, B-cell and endothelial-cell activation, and thereby contributes allograft injury. Emerging therapeutic strategies targeting complement activation have the potential to prevent or abrogate transplant injury and improve transplant outcomes.
Major heritable renal cell carcinoma syndromes: novel treatment options and future perspectives
Authors: Naidoo Vishen , Perera Marlon , Adam Ahmed
Published: July 2022

Purpose of review

To provide an overview of diagnosis, genetic abnormalities, clinical signs and treatment options for the major heritable renal cell carcinoma (RCC) syndromes.

Recent findings

RCC in major hereditary syndromes are disorders which are typically autosomal dominant. They predispose patients to early onset of RCC and may exhibit other extrarenal manifestations. Early recognition of these diseases allows correct screening at appropriate ages as well as early detection of RCC. Moreover, expedient identification may optimize the management of extra renal manifestations as well as allow for genetic testing and screening of at-risk relatives.

The risk of RCC in these major heritable syndromes is higher than sporadic disease. They occur at earlier age groups and can be multifocal or bilateral. Tumours are observed until at least 3 cm before any intervention, while nephron sparing surgery is widely considered as the treatment of choice except for hereditary leiomyomatosis with renal cell cancer, of which radical nephrectomy is treatment of choice. Intervention should be timeous as there is a highly reported incidence of early metastasis. Molecular therapies have been used in the setting of patients with metastasis, some of which show favourable outcomes.
Blood Purification for Hypertriglyceridemia-Induced Acute Pancreatitis
Authors: Zhang Yaqiong , Lin Jueying , Wu Lijun , Lin Juexin , Liang Yawei
Published: July 2022

Objectives

The purpose of our study is to investigate the efficacy and safety of blood purification (BP) therapy in hypertriglyceridemia-induced acute pancreatitis.

Methods

We searched PubMed, Embase, Cochrane Library, and Web of Science databases for articles published.

Results

The analysis included 13 studies with 934 patients (263 in BP group, 671 in control group). There was no difference in efficacy and safety between the BP group and the control group (all P > 0.05). Compared with conventional treatment, BP had shorter hospital stay (mean difference, −4.96; 95% confidence interval [CI], −8.81 to −1.11; P = 0.01) in the case of similar mortality and complications. Meanwhile, insulin treatment showed similar mortality to BP, but fewer local complications (odds risk, 2.18; 95% CI, 1.13–4.20; P = 0.02) and shorter hospital stay (mean difference, 5.46; 95% CI, 0.64–10.29; P = 0.03).

Conclusions

In the treatment of hypertriglyceridemia-induced acute pancreatitis, BP methods are effective in accelerating triglyceride level reduction and shortening hospital stay but do not affect the efficacy or reduce mortality significantly compared with conventional treatment. Insulin therapy has the same effect as BP but decreases incidence of complications and cost.
The Impact of Generation on Nurse Manager Job Satisfaction
Authors: Keith Angela C. , Warshawsky Nora , Neff Donna , Loerzel Victoria , Parchment Joy , Grandfield Elizabeth
Published: July 2022

OBJECTIVE

The aim of this study was to determine the effects of generational membership on nurse managers' (NMs') perception of their practice environment and job satisfaction using the Nurse Manager Practice Environment Scale (NMPES).

BACKGROUND

Boomers, Generation Xers, and millennials make up the NM workforce. Each has specific perceptions and expectations for their practice environment and job satisfaction. Little is known about these differences.

METHODS

A secondary analysis of NM survey data was conducted using descriptive statistics and multiple regression to identify the impact of generation on NMs' perception of their practice environment and satisfaction.

RESULTS

Generational membership did not significantly impact NMPES or job satisfaction scores, but the practice environment was a strong predictor of these outcomes.

CONCLUSION

Generational membership did not impact NMs' satisfaction for this sample, but the practice environment did. Further research is needed to examine additional factors that influence NM satisfaction and retention.
The Healthy Disruption of Anger
Authors: Bailey K. David , Prestia Angela S.
Published: July 2022

During the COVID-19 pandemic, information related to the virus changed so rapidly, and anxiety among healthcare workforce mounted exponentially. The reality of the situation was fluid; leadership had a challenging time communicating even short-term strategies. What evolved was a scared, tired, angry healthcare workforce. Association for Leadership Science in Nursing authors explore leaderships' opportunity to acknowledge, harness, and transform this anger into healthy disruption.
Functional Neurological Disorders
Authors: Mishra Anumeha , Pandey Sanjay
Published: July 2022

Background:

Functional neurological disorders (FNDs) are common but often misdiagnosed.

Review Summary:

The incidence of FNDs is between 4 and 12 per 100,000, comparable to multiple sclerosis and amyotrophic lateral sclerosis, and it is the second most common diagnosis in neurology clinics. Some clues in the history are sudden onset, intermittent time course, variability of manifestation over time, childhood trauma, and history of other somatic symptoms. Anxiety and depression are common, but not necessarily more than in the general population. Although there are no tests currently capable of demonstrating whether symptoms are willfully produced, there may not be a clear categorical difference between voluntary and involuntary symptoms. The prognosis of an FND is linked to early diagnosis and symptom duration, but unfortunately, the majority of the patients are diagnosed after considerable delays.

Conclusions:

A positive diagnosis of FNDs can be made on the basis of history and neurological signs without reliance on psychological stressors. Past sensitizing events and neurobiological abnormalities contribute to the pathogenesis of FNDs. Physical rehabilitation and psychological interventions alone or in combination are helpful in the treatment.
Combined limited internal fixation and multiplanar external fixation for immediate weight bearing of fractures around the foot and ankle
Authors: Sen Milan K.
Published: July 2022

Treatment of fractures around the foot and ankle can be challenging in patients who are unable to remain non weight bearing on their lower extremity. Traditional implants are not sufficient to resist loads incurred during weight bearing and can also lead to complications related to wound healing and infection. We describe a technique for fracture fixation of the foot and ankle that uses low profile implants to minimize soft tissue insult combined with multiplanar external fixation to allow for immediate weight bearing.
Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates From Peru, 2018 and 2019
Authors: Jorge-Berrocal Ana , Vargas-Herrera Natalia , Benites Carlos , Salazar-Quispe Fabiola , Mayta-Barrios Maritza , Barrios-Cárdenas Yuli J. , Melano Roberto G. , Yagui Martin ,   Neisseria gonorrhoeae Surveillance Working Group
Published: July 2022

Background

Currently, in Latin America, including Peru, the treatment of gonorrhea is still empiric and information regarding antimicrobial resistance is scarce in some countries because of the limited resources, which can contribute to the rising rates of reported multidrug-resistant gonococcal strains. In that context, it is mandatory to continuously monitor and report antimicrobial resistance in N. gonorrhoeae to update treatment recommendations.

Methods

This descriptive study analyzed genital and anal samples from symptomatic patients who attended 15 sexually transmitted infections health facilities from 8 different regions in Peru during the years 2018 to 2019 within the framework of Sentinel Surveillance. After establishing the presumptive diagnosis, the isolates were sent to the Laboratory of Sexually Transmitted Bacteria of the National Institute of Health of Peru in Lima where the species were confirmed (N = 165) and susceptibility profiles were determined.

Results

Among the 165 isolates, 95.2% corresponded to male patients, between 18 and 22 years of age (40.6%), half reported having a sexual partner and being heterosexual. Clinically, 89.7% manifested the presence of urethral exudate. Microbiology showed 95.2% of the isolates resistant to ciprofloxacin and 9.1% non-susceptible to azithromycin. Reduced susceptibility to ceftriaxone and cefixime was observed in 1.2% and 3.6% of the isolates respectively. All strains tested were susceptible to spectinomycin.

Conclusions

This study demonstrated that in Peru, fluoroquinolones should not be recommended or used in N. gonorrhoeae infections due to the high percentage of resistant strains. In addition, nationwide access to gonococcal resistance testing, molecular diagnostics and antimicrobial stewardship should be implemented to control the spread of gonococcal antimicrobial resistance.
Test-of-Cure After Treatment of Pharyngeal Gonorrhea in Durham, North Carolina, 2021–2022
Authors: Jenks Jeffrey D. , Hester Lizeth , Ryan Emily , Stancil Candy , Hauser Quinn , Zitta John-Paul , Mortiboy Marissa , Rayner Malkia , Stevens Elizabeth , Carrico Savannah , Jenkins Rodney
Published: July 2022

Background

In December 2020, the Centers for Disease Control and Prevention updated its treatment guidelines for gonococcal infection and, for the first time, recommended universal test-of-cure for all individuals treated for pharyngeal gonorrhea. After the release of these guidelines, data are lacking on rates of return for the test-of-cure, particularly in populations other than men who have sex with men.

Methods

We analyzed the demographic characteristics, clinical characteristics, rate of return for the recommended test-of-cure, and percent positivity for Neisseria gonorrhoeae on repeat pharyngeal specimens at a local public health department in Durham, NC.

Results

Of 101 individuals treated for pharyngeal gonorrhea between March 2021 and April 2022, 54.5% were men, 71.2% Black or African American, and 58.4% between the ages of 20 and 29 years. Most identified as either women who have sex with men (38.6%), men who have sex with men (24.8%), or men who have sex with women (22.8%). Of these individuals, 41 (40.6%) returned for a test-of-cure, with LGBTQ+ individuals more likely to return than men who have sex with women and women who have sex with men. Of those who returned for the test-of-cure, 4.9% of pharyngeal samples were equivocal and 2.4% positive for N. gonorrhoeae by nucleic acid amplification testing, likely reflecting false-positive tests.

Conclusion

Despite recommendations to perform a test-of-cure 7 to 14 days after treatment of pharyngeal gonorrhea, rates of return continue to be low. Alternative strategies should be investigated to increase test-of-cure rates.
Sexually Transmitted Infection Testing Among Unstably Housed, Sexually Active Persons With Human Immunodeficiency Virus in the United States, 2018–2019
Authors: Marcus Ruthanne , Tie Yunfeng , Dasgupta Sharoda , Crim Stacy M. , Beer Linda , Williams Samantha P. , Weiser John
Published: July 2022

Unstably housed sexually active people with human immunodeficiency virus experience both a high incidence of sexually transmitted infections (STI) and barriers to annual STI screening recommended by Centers for Disease Control and Prevention guidelines. We used Medical Monitoring Project data to describe STI testing among unstably housed people with human immunodeficiency virus by attendance at Ryan White HIV/AIDS Program–funded facilities.
Sexually Transmitted Infections Diagnosed Among Sexual and Gender Minority Communities During the First 11 Months of the COVID-19 Pandemic in Midwest and Southern Cities in the United States
Authors: Nyitray Alan G. , Quinn Katherine G. , John Steven A. , Walsh Jennifer L. , Schim van der Loeff Maarten F. , Wu Ruizhe , Eastwood Daniel , McAuliffe Timothy L.
Published: July 2022

Background

The COVID-19 pandemic adversely affected sexual health services. Given the burden of sexually transmitted infections (STIs) on sexual and gender minorities (SGMs), we estimated incidence of self-reported STI diagnoses and factors associated with STI diagnoses among SGMs during the pandemic's first year.

Methods

A cohort of 426 SGM persons, 25 years or older, recruited in Chicago, Milwaukee, Detroit, Minneapolis, and Houston completed 5 online surveys from April 2020 to February 2021. Persons self-reported on each survey all health care provider STI diagnoses. Kaplan-Meier was used to estimate the cumulative risk of STI diagnoses, stratified by human immunodeficiency virus (HIV) status. Factors associated with STI diagnoses were assessed with a longitudinal negative binomial regression.

Results

Median age was 37 years, and 27.0% were persons living with HIV (PLH). Participants reported 63 STIs for a cumulative incidence for PLH and HIV-negative persons of 0.19 (95% confidence interval [CI], 0.13–0.29) and 0.12 (95% CI, 0.09–0.17), respectively. Regardless of HIV, a younger age and changes in health care use were associated with STI diagnoses. Among HIV-negative persons, the rate of STI diagnoses was higher in Houston than the Midwest cities (adjusted relative risk, 2.37; 95% CI, 1.08–5.20). Among PLH, a decrease in health care use was also associated with STI diagnoses (adjusted relative risk, 3.53; 95% CI, 1.01–12.32 vs no change in health care services), as was Hispanic ethnicity and using a dating app to meet a sex partner.

Conclusions

Factors associated with STI diagnoses during the COVID-19 pandemic generally reflected factors associated with STI incidence before the pandemic like geography, HIV, age, and ethnicity.
Comparison of a Voluntary Safety Reporting System to a Global Trigger Tool for Identifying Adverse Events in an Oncology Population
Authors: Samal Lipika , Khasnabish Srijesa , Foskett Cathy , Zigmont Katherine , Faxvaag Arild , Chang Frank , Clements Marsha , Rossetti Sarah Collins , Dalal Anuj K. , Leone Kathleen , Lipsitz Stuart , Massaro Anthony , Rozenblum Ronen , Schnock Kumiko O. , Yoon Catherine , Bates David W. , Dykes Patricia C.
Published: July 2022

Objective

There is a lack of research on adverse event (AE) detection in oncology patients, despite the propensity for iatrogenic harm. Two common methods include voluntary safety reporting (VSR) and chart review tools, such as the Institute for Healthcare Improvement’s Global Trigger Tool (GTT). Our objective was to compare frequency and type of AEs detected by a modified GTT compared with VSR for identifying AEs in oncology patients in a larger clinical trial.

Methods

Patients across 6 oncology units (from July 1, 2013, through May 29, 2015) were randomly selected. Retrospective chart reviews were conducted by a team of nurses and physicians to identify AEs using the GTT. The VSR system was queried by the department of quality and safety of the hospital. Adverse event frequencies, type, and harm code for both methods were compared.

Results

The modified GTT detected 0.90 AEs per patient (79 AEs in 88 patients; 95% [0.71–1.12] AEs per patient) that were predominantly medication AEs (53/79); more than half of the AEs caused harm to the patients (41/79, 52%), but only one quarter were preventable (21/79; 27%). The VSR detected 0.24 AEs per patient (21 AEs in 88 patients; 95% [0.15–0.37] AEs per patient), a large plurality of which were medication/intravenous related (8/21); more than half did not cause harm (70%). Only 2% of the AEs (2/100) were detected by both methods.

Conclusions

Neither the modified GTT nor the VSR system alone is sufficient for detecting AEs in oncology patient populations. Further studies exploring methods such as automated AE detection from electronic health records and leveraging patient-reported AEs are needed.
Obstetrical Outcomes After Implementation of Laborist Model During the COVID-19 Pandemic
Authors: Prasannan Lakha , Gerber Rachel , Gulersen Moti , Shan Weiwei , Blitz Matthew J. , Rochelson Burton
Published: July 2022

Objective

The COVID-19 pandemic prompted labor and delivery units to establish ways to decrease viral exposure to healthcare workers while continuing to deliver optimal patient care. A laborist model was implemented to improve safety at our tertiary care hospital in Long Island. The aim of the study is to determine whether implementation of a laborist model during the COVID-19 pandemic is associated with a change in the frequency of cesarean birth.

Methods

The retrospective cohort study included patients who delivered at a single tertiary center during March 2019 to May 2019 and March 2020 to May 2020 when our laborist model was initiated. The primary outcome compared the frequency of a cesarean delivery between both models. Secondary outcomes were the frequency of adverse obstetrical complications, which included intensive care unit admission, shoulder dystocia, intra-amniotic infection, hemorrhage, and need for blood transfusion. Statistical analysis included multivariable regression to adjust for potential confounders.

Results

A total of 1506 patients were included. Baseline characteristics were similar between the 2 groups. After adjusting for potential confounders, there was no significant difference in the frequency of cesarean births between both models (37% versus 35%; adjusted odds ratio, 1.003; 95% confidence interval, 0.46–2.89). Similarly, there were no significant differences in adverse outcomes between the study populations (adjusted odds ratio, 1.064; 95% confidence interval, 0.68–1.59).

Conclusions

A change in practice behavior during a pandemic was not associated with an increase in frequency of cesarean births or adverse obstetrical outcomes.
High-dose radiation exposure of cold-stored whole blood does not affect hemostatic function
Authors: Becerra Sandra C. , Darlington Daniel N. , Abaasah Isaac E. , Herzig Maryanne C. , Bynum James A. , Christy Barbara A.
Published: July 2022

BACKGROUND

Whole blood (WB) transfusion is routinely used to resuscitate severely injured military trauma patients. Blood can be stored refrigerated while still maintaining reasonable function but is susceptible to environmental influences, including radiation exposure. Immune-compromised patients are transfused with irradiated blood to inactivate donor lymphocyte function (25 Gy per Association for the Advancement of Blood and Biotherapies [AARB] standard 5.7.3.2). However, there is limited information on function of WB exposed to high radiation doses.

OBJECTIVE

This study aimed to determine if stored irradiated WB still retains function. This will be important if the stored blood supply is exposed to radiation in a combat situation or mass casualty incident when the need for blood will be high.

METHODS

Whole blood collected from healthy donors was irradiated at 0, 25, or 75 Gy and stored at 4°C. Blood cell count, blood gas chemistry, thromboelastometry, platelet aggregation, and reactive oxygen species were measured before irradiation and at 1, 7, and 14 days of storage. Irradiated WB was compared with nonirradiated WB controls.

RESULTS

Irradiated WB stored for up to 14 days was not significantly different than nonirradiated WB in most of the parameters measured. Stored blood showed expected changes associated with functional decline at longer storage times, but irradiation did not hasten the decline. There was a significant change in potassium and sodium ion concentrations after irradiation, but the functional relevance is not clear.

CONCLUSION

High-dose irradiation had little effect on stored WB. Although there were changes in plasma sodium and potassium levels, there was little to no effect on hemostasis and blood cell viability. This suggests that stored blood subjected to a radiation event generating at least a dose of 75 Gy is still suitable for transfusion, which could be particularly important in the event of a mass casualty event where a large amount of blood is needed.
Historical development and contemporary use of neuromodulation in human spinal cord injury
Authors: Harkema Susan , Angeli Claudia , Gerasimenko Yury
Published: July 2022

Purpose of review

There is a long history of neuromodulation of the spinal cord after injury in humans with recent momentum of studies showing evidence for therapeutic potential. Nonrandomized, mechanistic, hypothesis-driven, small cohort, epidural stimulation proof of principle studies provide insight into the human spinal circuitry functionality and support the pathway toward clinical treatments.

Recent findings

Individuals living with spinal cord injury can recover motor, cardiovascular, and bladder function even years after injury using neuromodulation. Integration of continuous feedback from sensory information, task-specific training, and optimized excitability state of human spinal circuitry are critical spinal mechanisms. Neuromodulation activates previously undetectable residual supraspinal pathways to allow intentional (voluntary) control of motor movements. Further discovery unveiled the human spinal circuitry integrated regulatory control of motor and autonomic systems indicating the realistic potential of neuromodulation to improve the capacity incrementally, but significantly for recovery after severe spinal cord injury.

The discovery that both motor and autonomic function recovers with lumbosacral spinal cord placement of the electrode reveals exciting avenues for a synergistic overall improvement in function, health, and quality of life for those who have been living with the consequences of spinal cord injury even for decades.
Nonparaneoplastic Anti-GAD Limbic Encephalitis: Seizure Outcome and Long-term Neuropsychological Follow-up After Immunotherapy
Authors: Spilioti Martha , Kiryttopoulos Andreas , Panou Theodora , Simos Panagiotis , Alexopoulos Haris , Karafyles Georgios , Geroukis Triantafillos , Kalevrosoglou Ioannis , Kimiskidis Vasilios
Published: July 2022

Antibodies against glutamate decarboxylase (GAD-Abs), especially GAD65 antibodies, are associated with limbic encephalitis (LE) manifested by temporal lobe epilepsy and neuropsychological deficits. We present the case of a 42-year-old Greek woman with nonparaneoplastic anti-GAD LE, discussing the therapeutic management and highlighting the role of neuropsychological assessment. The patient underwent functional and structural brain studies and was investigated longitudinally over a 6-year period with a battery of neuropsychological tests that were designed to document her intellectual function and verbal and visual memory. The patient suffered from refractory temporal-impaired awareness seizures and memory impairment that was mediated by autoimmune nonparaneoplastic LE and comorbid autoimmune disorders (ie, Hashimoto thyroiditis and vitiligo). Neuroimaging studies demonstrated hyperintensities in the medial temporal lobes bilaterally on T2WI MRI sequences. Serial EEGs showed bitemporal intermittent delta activity as well as epileptiform discharges. Tumor blood markers and onconeural antibodies were negative. Immunological screening revealed extremely high GAD-Abs titers in both serum and CSF, as well as the presence of CSF oligoclonal bands. Neuropsychological testing revealed anterograde amnesia with relative preservation of more remote, premorbid memories. The patient underwent first-line immunotherapy followed by immunosuppressive maintenance treatment that led to a reduction of seizures, EEG improvement, and a significant decline in GAD-Abs titers. Neuropsychological evaluations at 5 months, 1 year, and 6 years posttreatment demonstrated improvement, particularly in recent memory and everyday functionality. In this case of anti-GAD LE, the long-term seizure reduction and the improvement of neuropsychological deficits were most likely related to the immunotherapy.
The mental health of healthcare workers during the COVID-19 pandemic: a narrative review
Authors: De Kock Johannes H. , Latham Helen Ann , Cowden Richard G.
Published: July 2022

Purpose of review

Mental health (MH) problems among healthcare workers (HCWs) have the potential to impact negatively on the capacity of health systems to respond effectively to COVID-19. A thorough understanding of the factors that degrade or promote the MH of HCWs is needed to design and implement suitable intervention strategies to support the wellbeing of this population.

Recent findings

MH problems among HCWs were elevated prior to the COVID-19 pandemic. Accumulating evidence indicates that this public health crisis has had a disproportionately negative impact on the MH of specialised populations, including HCWs. Literature from prior health pandemics suggests that the adverse effects of the COVID-19 pandemic on the MH of HCWs are likely to persist in the aftermath of the public health crisis. Primary and secondary risk factors for adverse MH outcomes have been identified and should be considered when implementing interventions to protect the MH of HCWs.

The MH of HCWs has been negatively impacted by the COVID-19 pandemic, which is having a detrimental influence on the public health response to COVID-19. Protecting the MH of HCWs both during and beyond this public health crisis should remain a top priority, with particular emphasis on multifaceted interventions that aim to balance the psychological needs of individual HCWs with organisational-level strategies that could be targeted to promote their wellbeing.
Methods to study folding of alpha-helical membrane proteins in lipids
Authors: Harris Nicola J. , Pellowe Grant A. , Blackholly Laura R. , Gulaidi-Breen Samuel , Findlay Heather E. , Booth Paula J.
Published: July 2022

How alpha-helical membrane proteins fold correctly in the highly hydrophobic membrane interior is not well understood. Their folding is known to be highly influenced by the lipids within the surrounding bilayer, but the majority of folding studies have focused on detergent-solubilized protein rather than protein in a lipid environment. There are different ways to study folding in lipid bilayers, and each method has its own advantages and disadvantages. This review will discuss folding methods which can be used to study alpha-helical membrane proteins in bicelles, liposomes, nanodiscs or native membranes. These folding methods include
in vitro
folding methods in liposomes such as denaturant unfolding studies, and single-molecule force spectroscopy studies in bicelles, liposomes and native membranes. This review will also discuss recent advances in co-translational folding studies, which use cell-free expression with liposomes or nanodiscs or are performed
in vivo
with native membranes.
A high-performance Ni-CeO
2
/Ni/Ni-Y
2
O
3
·ZrO
2
three-layer anode for direct iso-octane feeding of solid oxide fuel cells
Authors: Sasaki Kazuya , Takahashi Ikuma , Kuramoto Kodai , Shin-mura Kiyoto
Published: July 2022

Solid oxide fuel cells (SOFCs) directly fed with iso-octane are expected to be power sources for mobile devices and automobiles. However, the conventional anode catalysts nickel (Ni) or cerium oxide (CeO
2
) used for direct feeding of iso-octane do not suppress carbon deposition or generate high power. In this study, we investigated the Ni-CeO
2
/Ni/Ni-yttria-stabilized-zirconia (YSZ) three-layer anode to establish the suppression of carbon deposition and high-power generation in the SOFC. The anode consists of a Ni-CeO
2
catalyst layer as the top layer, an Ni catalyst layer as the second layer, and a Ni-YSZ catalyst layer as the third layer on top of the electrolyte. The concept of the three-layer anode is as follows: fuel reforming occurs in the Ni-CeO
2
layer, the reformed H
2
or CO is electrochemically oxidized in the Ni-YSZ catalyst layer, and the Ni catalyst middle layer prevents the reaction between YSZ and CeO
2
. Scanning electron microscopy and electrochemical characterization confirmed carbon deposition suppression and improved power generation. The anode showed no carbon deposition and generated high-power, 600 mA cm
−2
and 150 mW cm
−2
, at 950°C and a steam/carbon ratio of 3.0. Additionally, we discuss the fuel reforming reactions on the three-layer electrode by the results of exhaust gas analysis.
Individual reference intervals in practice: A guide to personalise clinical and omics level data with IRIS
Authors: Pusparum Murih , Thas Olivier , Ertaylan Gökhan
Published: July 2022

Reference intervals (RI) are the best-established methodology used for the interpretation of numerical clinical level data in healthcare and clinical practice. As the test results are interpreted by comparing with the (population-derived) reference intervals, the quality of the calculation and implementation of reference intervals play a major role in decision-making process at the subject level. Here we describe the IRIS workflow to compute Individual Reference Intervals (IRI) based on multiple “healthy” data points from the same subjects and also utilising peers’ test results. We have improved the IRI models so they allow for covariate adjustments, such as sex and age. The IRI is expected to play pivotal roles in i) early detection of disease transition in chronic diseases by facilitating the detection of small deviations in clinical measurements, ii) monitoring personal disease progression, either using the standard clinical biochemistry test results or the omics level data. We demonstrate the utility of IRI in clinical and omics level data (proteomics and metabolomics) from two different longitudinal studies, including prior data processing and data quality check procedures. We have created an integrated application IRIS incorporating all described steps in an easy-to-use tool in research and/or clinical practice. We compute the IRI estimates in a healthy population to demonstrate its diagnostic utility in chronic diseases and from a diseased cohort to demonstrate its potential in disease monitoring.
The fidelity of genetic information transfer with aging skeletal muscle segregates according to biological processes
Authors: Sivakumar Sruthi , LeFebre Ryan , Menichetti Giulia , IIjima Hirotaka , Mugler Andrew , Ambrosio Fabrisia
Published: July 2022

Maintenance of organismal function requires tightly regulated biomolecular communication. However, with aging, communication deteriorates, thereby disrupting effective information flow. Using information theory applied to skeletal muscle single cell RNA-seq data from young, middle-aged, and aged animals, we quantified the loss of communication efficiency over time. We considered communication channels between transcription factors (TF; input message) and corresponding target genes (TG; output message). Mutual information (MI), defined as the information effectively transmitted between TFs and TGs, declined with age. This decline was attributed to escalating biological noise and loss of precision with which TFs regulate TGs (i.e., channel capacity). When we ranked TF:TG pairs by MI, pairs associated with fatty acid oxidation displayed the greatest loss of communication with aging, while the system preserved communication between pairs related to RNA synthesis. These data suggest ineffective communication with aging against a backdrop of resource reallocation to support essential cellular functions.
Characterizations of enhanced infectivity and antibody evasion of Omicron BA.2.75
Authors: Cao Yunlong , Song Weiliang , Wang Lei , Liu Pan , Yue Can , Jian Fanchong , Yu Yuanling , Yisimayi Ayijiang , Wang Peng , Wang Yao , Zhu Qianhui , Deng Jie , Fu Wangjun , Yu Lingling , Zhang Na , Wang Jing , Xiao Tianhe , An Ran , Wang Jing , Liu Lu , Yang Sijie , Niu Xiao , Gu Qingqing , Shao Fei , Hao Xiaohua , Jin Ronghua , Wang Youchun , Xie Xiaoliang Sunney , Wang Xiangxi
Published: July 2022

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a local growth advantage over BA.2.38, BA.2.76 and BA.5 in India. The underlying mechanism of BA.2.75’s enhanced infectivity, especially compared to BA.5, remains unclear. Here, we show that BA.2.75 exhibits substantially higher ACE2-binding affinity than BA.5. Also, BA.2.75 spike shows decreased thermostability and increased “up” RBD conformation in acidic conditions, suggesting enhanced low-pH-endosomal cell-entry pathway utilization. BA.2.75 is less humoral immune evasive than BA.4/BA.5 in BA.1/BA.2 breakthrough-infection convalescents; however, BA.2.75 shows heavier neutralization evasion in Delta breakthrough-infection convalescents. Importantly, plasma from BA.5 breakthrough infection exhibit significantly weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct RBD and NTD-targeting antibody escaping pattern from BA.4/BA.5. Additionally, Evusheld and Bebtelovimab remain effective against BA.2.75, and Sotrovimab recovered RBD-binding affinity. Together, our results suggest BA.2.75 may prevail after the global BA.4/BA.5 wave, and its increased receptor-binding capability could allow further incorporation of immune-evasive mutations.
Neurophysiological markers of successful learning in healthy aging
Authors: Strzelczyk Dawid , Popov Tzvetan , Kelly Simon P. , Langer Nicolas
Published: July 2022

The capacity to learn and memorize is a key determinant for the quality of life, but is known to decline to varying degrees with age. Previous ERP research methods had the limitation that their design did not allow to track the gradual memory formation process. Thus, the neural mechanisms underlying memory formation and the critical features that determine the extent to which aging affects learning are still unknown. By using a visual sequence learning task, which consists of the repeated presentation of a simple sequence of tokens, we are able to track the progress of gradual memory formation through both neurophysiological and behavioral markers. On a neurophysiological level, we focused on two learning related centroparietal ERP components: the P300 and broad positivity.

Our results revealed that although both age groups showed significant learning progress, young individuals learned faster and remembered more stimuli than older participants. Successful learning was directly linked to a decrease of P300 amplitude. However, young participants showed larger P300 amplitude with a sharper decrease during the memory formation process. The P300 amplitude predicted learning success in both age groups, was associated with increased fronto-parietal brain network activation and showed good test-retest reliability. Highly, similar results were found for the broad positivity component, which raises the questions if the BP is a distinct component or just a prolonged P300. In a series of analyses, including topographic analysis of variance (TANOVA), equivalence testing and source reconstruction analysis, we addressed the unresolved questions. These analyses revealed concordant distributed brain activation patterns within parietal circuits. Thus, there is no evidence (rather evidence for equivalence) for distinct underlying neural generators for the two components.

Taken together, the results highlight the importance of the P300 as a neurophysiological marker of learning and may enable the development of preventive measures for age-related impeded learning.