bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Long-Term Opioid Use After Hospitalization for Traumatic Injury in a Racially and Ethnically Diverse Population: A 12-Month Prospective Observational Study
Authors: Heins Sara E , Seelam Rachana , Schell Terry L , Wong Eunice C
Published: September 2022

Background

Long-term prescription opioid use is a significant risk factor for opioid morbidity and mortality, and severe traumatic injury is an important initiation point for prescription opioid use. This study examines predictors of long-term prescription opioid use among a racially and ethnically diverse population of patients hospitalized for traumatic injury.

Methods

Study participants (N= 650) from two urban Level I trauma centers were enrolled. Baseline information on demographics, injury characteristics, self-reported pre-injury substance use and mental health, and personality characteristics and attitudes was collected through interviews during the initial hospitalization. Patients were interviewed again at 3 months and 12 months and asked about prescription opioid use in the prior 7 days. Multivariable logistic regressions assessed participants’ baseline characteristics associated with opioid use at one or more follow-up interviews.

Results

Pre-injury use of prescription painkillers had the strongest association with prescription opioid use at follow-up (adjusted odds ratio: 3.10; 95% confidence interval: 1.86–5.17). Older age, health insurance coverage at baseline, length of hospitalization, higher current pain level, pre-injury post-traumatic stress disorder symptoms, and discharge to a location other than home were also associated with significantly higher odds of prescription opioid use at follow-up.

Conclusions

Providers could consider screening for past use of prescription pain relievers and post-traumatic stress disorder before hospital discharge to identify patients who might benefit from additional resources and support. However, providers should ensure that these patients’ pain management needs are still being met and avoid abrupt discontinuation of prescription opioid use among those with a history of long-term use.
PEZO-1andTRP-4mechanosensors are involved in mating behavior inCaenorhabditis elegans
Authors: Brugman Katherine I , Susoy Vladislav , Whittaker Allyson J , Palma Wilber , Nava Stephanie , Samuel Aravinthan D T , Sternberg Paul W
Published: September 2022

Male mating in Caenorhabditis elegans is a complex behavior with a strong mechanosensory component. C. elegans has several characterized mechanotransducer proteins, but few have been shown to contribute to mating. Here, we investigated the roles of PEZO-1, a piezo channel, and TRP-4, a mechanotransducing TRPN channel, in male mating behavior. We show that pezo-1 is expressed in several male-specific neurons with known roles in mating. We show that, among other neurons, trp-4 is expressed in the Post-Cloacal sensilla neuron type A (PCA) sensory neuron, which monitors relative sliding between the male and the hermaphrodite and inhibits neurons involved in vulva detection. Mutations in both genes compromise many steps of mating, including initial response to the hermaphrodite, scanning, turning, and vulva detection. We performed pan-neuronal imaging during mating between freely moving mutant males and hermaphrodites. Both pezo-1 and trp-4 mutants showed spurious activation of the sensory neurons involved in vulva detection. In trp-4 mutants, this spurious activation might be caused by PCA failure to inhibit vulva-detecting neurons during scanning. Indeed, we show that without functional TRP-4, PCA fails to detect the relative sliding between the male and hermaphrodite. Cell-specific TRP-4 expression restores PCA's mechanosensory function. Our results demonstrate new roles for both PEZO-1 and TRP-4 mechanotransducers in C. elegans mating behavior.
Exploration of Malaysian school-children’s food preferences: what do we know?
Authors: Yang Wai Yew , Ong Shu Hwa , De Lee Yi , Yen Pei Ling , Lim Kah Yen , Naumoskvi Nenad , Jani Rati
Published: September 2022

Background

Feeding practices exert a definite influence over children’s experiences. This article aims to explore parental feeding practices and investigate the prediction domain of food preference from parent–child perspectives.

Methods

Two individual studies were conducted on Malay families with children aged 7–12 years. In Study 1, mothers (n = 17) participated in semi-structured focus group interviews on their knowledge of foods and feeding practices. In Study 2, parent–child pairs (n = 14) answered a 36-item, 5-point Likert scale Food Preference Questionnaire followed by virtual structured qualitative interviews. The interviews were digitally recorded, transcribed verbatim, back-translated and analysed according to the framework analysis technique.

Results

In Study 1, mothers perceived vegetables, chicken, fish and plain water as healthy foods and drinks while discretionary options were snacks, fast foods and carbonated drinks. The mothers defined healthy foods as foods handled safely with health benefits. They used ‘healthy’ cooking methods to prepare preferred foods and overtly controlled the child’s access to discretionary food. In Study 2, the food groups reported by parent–child pair’s report were consistent for the most preferred foods [snacks, median (interquartile range), parent: 4.5 (1.0) vs. child: 4.5 (0.0), p > 0.05] and least preferred food [legumes, parent: 2.0 (1.0) vs. child: 2.0 (1.0), p > 0.05]. Parents emphasized taste as the key determinant of food preference.

Conclusion

These studies were the first to qualitatively explore parents’ perceptions of foods affecting their feeding practices among the Malaysian community to highlight the cultural contribution. Key insights into children’s food intake and factors influencing their food preferences were identified.
Bilateral parotid gland swelling
Authors: Mathe Savannah , Mate Jessica
Published: September 2022

This case report describes a 45-year-old woman with acute, bilateral parotid gland swelling caused by B-cell lymphoma. Enlarged, tender salivary glands are more commonly caused by infection, inflammation, or obstruction from salivary gland stones or tumors. This patient initially was treated for common causes of parotitis; however, her condition did not respond to the standard management and she ultimately was diagnosed with B-cell lymphoma.
The PA profession in Liberia
Authors: Oliphant John , Kennedy Jallah
Published: September 2022

In Liberia, the physician assistant (PA) profession began in the mid-1960s. PAs have had a major role in providing access to healthcare for patients, many of whom live in poverty and reside in remote areas where access to physicians may be severely limited. In 1964, representatives from UNICEF selected Agnes N. Dagbe, MS, RN, to be the first director of a new PA program to be developed at the Tubman National Institute of Medical Arts. Dagbe was sent to Russia to learn about their feldsher profession, which served as a significant source of inspiration for the newly emerging PA profession in Liberia. To date, Liberia has faced extreme shortages of physicians, the ravages of two brutal civil wars over a 14-year period (1989-2003), as well as outbreaks of the Ebola and COVID-19 viruses. Now, more than 54 years since the first class graduated, PAs are vital for the delivery of essential healthcare services for the citizens of Liberia.
Anaphylaxis in elderly people
Authors: Ventura Maria Teresa , Boni Elisa , Taborda-Barata Luis , Blain Hubert , Bousquet Jean
Published: September 2022

Purpose of review

Anaphylaxis is common in old-age adults but is insufficiently understood by physicians, and may be underdiagnosed. This review discusses the specificities of anaphylaxis in this age group and stresses the importance of adrenaline in its management.

Recent findings

Data from the European Anaphylaxis Registry on elderly patients is a major finding. Other findings include the prevention of possible anaphylactic reactions in coronavirus disease 2019 vaccination as well as some new epidemiologic data.

The most common risk factors are hymenoptera venom and food and drug allergy. Cardiovascular symptoms are the most important ones to reverse in old-age adults, especially due to the multiple comorbidities. Anaphylaxis in old-age adults has a more severe outcome than in younger ones. Polypharmacy is a specific factor to be considered. The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) algorithm is applicable in all clinical emergencies for immediate assessment and treatment, and should be considered for all patients. Adrenaline is the mainstay of the management of the condition. There are no absolute contraindications to the prescription of self-injectable adrenaline in elderly individuals at risk of anaphylaxis.
Updates of cancer hallmarks in patients with inborn errors of immunity
Authors: Wang Yating , Abolhassani Hassan
Published: September 2022

Purpose of review

The development of cancer in patients with genetically determined inborn errors of immunity (IEI) is much higher than in the general population. The hallmarks of cancer are a conceptualization tool that can refine the complexities of cancer development and pathophysiology. Each genetic defect may impose a different pathological tumor predisposition, which needs to be identified and linked with known hallmarks of cancer.

Recent findings

Four new hallmarks of cancer have been suggested, recently, including unlocking phenotypic plasticity, senescent cells, nonmutational epigenetic reprogramming, and polymorphic microbiomes. Moreover, more than 50 new IEI genes have been discovered during the last 2 years from which 15 monogenic defects perturb tumor immune surveillance in patients.

This review provides a more comprehensive and updated overview of all 14 cancer hallmarks in IEI patients and covers aspects of cancer predisposition in novel genes in the ever-increasing field of IEI.
Neurological adverse effects associated with anti-PD1 antibodies alone or in combination with ipilimumab: a multicenter case series
Authors: Smith Jessica Louise , Menzies Alexander M. , Cohen Justine V. , Mut-Lloret Margarida , Ozgun Alpaslan , Spain Lavinia , Park John , Quach Henry T. , Pallan Lalit , McQuade Jennifer , Feng Sophie , Sandhu Shahneen , Atkinson Victoria , Tsai Katy , Long Georgina V. , Larkin James , Eroglu Zeynep , Johnson Douglas B. , Sullivan Ryan , Herkes Geoffrey K. , Henderson Andrew , Carlino Matteo S.
Published: September 2022

Anti-programmed cell death protein 1 (PD1) antibodies, pembrolizumab and nivolumab, alone or in combination with ipilimumab, have become standard treatment for melanoma and multiple other malignancies. Neurological adverse effects are rare and have not been well characterized to date.

Patients who developed neurological adverse effects while being treated with PD1, alone or in combination with ipilimumab, were retrospectively identified from 10 cancer centers.

Fifty-eight patients were included, and the median time from treatment initiation to development of neurological adverse effects was 7 weeks (range, 1–86.5 weeks). Thirty-seven (64%) toxicities affected the peripheral nervous system. Fifty (86%) patients were treated with corticosteroids, with 22 (37%) patients requiring further immunomodulation including intravenous immunoglobulin (16), plasmapheresis (7), mycophenolate mofetil (4), cyclophosphamide (1), and rituximab (1). Twenty-seven (46%) had a complete resolution of their neurological symptoms, and two (4%) patients died secondary to complications from their neurological adverse effects. The response rate of the cancer to immunotherapy was 78%, and the median progression free survival was not reached.

Neurological adverse effects can occur with PD1 treatment, do not appear to impact treatment response, but may be irreversible or worsen in some patients. Management may require immunomodulation beyond corticosteroids.
A retrospective analysis of the factors associated with increased risk of readmission within 30 days after primary transurethral resection of bladder tumor
Authors: Jindal Tarun , Sarwal Ankush , Jain Prateek , Koju Rajan , Mukherjee Satyadip
Published: September 2022

Background

Transurethral resection of bladder tumor (TURBT) is associated with perioperative morbidity of 5% to 10%, which can lead to unplanned readmissions. In this study, we aimed to identify the factors that lead to an increased risk of unplanned readmissions within 30 days of primary TURBT.

Materials and methods

A retrospective study was conducted to identify patients who underwent primary TURBT at our institute from 2011 to 2019. Clinical and demographic factors, history of smoking, antiplatelet drugs intake, comorbidities, tumor size (<3 or >3 cm), multifocality, and histopathological type were abstracted. Patients who were readmitted were identified, and reasons for admission were recorded.

Results

A total of 435 patients were identified. The median age of the patients was 66 years. From 378 male patients (86.9%), 110 (25.3%) and 37 (8.5%) had a history of smoking and antiplatelet agents intake, respectively. In the cohort, 166 patients (38.2%) were diabetic, 239 (54.9%) were hypertensive, 72 (16.6%) had chronic obstructive pulmonary disease, and 78 (7.9%) had hypothyroidism. A total of 206 patients (47.4%) had a tumor >3 cm; multifocality was seen in 140 (32.2%) patients, whereas muscle invasive tumors were present in 161 patients (37%). A total of 22 patients (5.06%) had readmissions within 30 days, with hematuria being the most common etiology. On univariate and multivariate analyses, a history of smoking (p = 0.006 and p = 0.008, respectively) or antiplatelet agents intake (p < 0.001 and p < 0.001, respectively) was significantly associated with increased unplanned readmission.

Conclusions

Our study revealed smoking and antiplatelet agents intake as factors leading to an increased risk of unplanned readmissions.
Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: a large, multicentre study
Authors: Zullo Angelo , Germanà Bastianello , Galliani Ermenegildo , Iori Andrea , de Pretis Giovanni , Manfredi Guido , Buscarini Elisabetta , Ciuffi Mario , Ignomirelli Orazio , Farinati Fabio , Savarino Edoardo , Pallini Paolo , Milan Luisa , Conigliaro Rita , Grande Giuseppe , Cannizzaro Renato , Maiero Stefania , Pisani Antonio , Marangi Stefania , Manta Raffaele , Morelli Olivia , Peralta Sergio , Mantia Alessia La , Rossano Buonocore Matteo , Monica Fabio
Published: September 2022

Background

Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice.

Study design

This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis.

Results

Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P < 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device.

Conclusion

The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications.
Implications of Paneth cell dysfunction on gastrointestinal health and disease
Authors: Lee Vivian H. , Gulati Ajay S.
Published: September 2022

Purpose of review

Paneth cells are specialized, secretory epithelial cells located in the small intestine. Although their existence was first described in 1872, their precise role in the gut remained unclear for over a century. Over the past few decades, elegant studies have shown Paneth cells play a key role enhancing gut barrier function, as niche cells for the intestinal stem cell compartment and via secreting antimicrobial peptides to establish an antimicrobial barrier at the epithelial surface. This review describes what is known about Paneth cell biology from human and animal studies with a focus on their putative role in clinical gastrointestinal disease.

Recent findings

Recent work has demonstrated important associations of dysfunctional Paneth cells with several gastrointestinal disorders. These include Crohn's disease, enteric infections, graft-versus-host disease, necrotizing enterocolitis, and environmental enteric dysfunction. Ongoing studies are examining precisely how Paneth cell biology is altered in these various disease states.

By understanding the mechanisms of Paneth cell regulation – and how these processes go awry in specific gastrointestinal diseases – we set the stage for using Paneth cells as biomarkers for disease progression and developing novel therapeutics that augment Paneth cell function to treat a spectrum of gastrointestinal disorders.
Sharing Lessons From Successes
Authors: Martin Nicky , Frank Barbara , Farrell David , Brady Cathie , Dixon-Hall Janice , Mueller Jessica , Rantz Marilyn
Published: September 2022

Purpose:

To identify leadership styles and staffing strategies in Missouri long-term care (LTC) facilities that stood out among their peers as “positive deviants” with regard to COVID-19 infections and staffing shortages.

Methods:

Statewide survey of all LTC facilities to identify exemplar facilities with stable staffing and low rates of COVID-19. Interviews with senior leaders were conducted in 10 facilities in the state to understand the strategies employed that led to these “positive outliers.” A result-based educational program was designed to describe their actions and staff reactions.

Results:

Exemplar leaders used transformational leadership style. Top reasons for their success were as follows: (1) trusting and supportive staff relationships; (2) positive presence and communication; and (3) use of consistent staffing assignments. Strong statewide participation was noted in the educational programs.
Early Integration of Palliative Care in Frail Patients with Hip Fracture
Authors: Czerwinski Eileen M.
Published: September 2022

Frailty is a condition of vulnerability characterized by instability and inconsistency after a stressor event. It is associated with a range of adverse outcomes including delirium, falls, disability, mortality, and increased healthcare utilization. A subset of frail patients who are increasingly high risk for poor outcomes are older adults with hip fracture. Palliative care is a philosophy of care focused on maximizing the quality of life for seriously ill patients and their families. For frail patients with hip fracture, timely referrals to palliative care are essential to have a meaningful impact on quality of life. Recommendations for frailty screening have been offered by professional organizations; however, multiple barriers to routine preoperative frailty assessment exist. This quality improvement project evaluated the feasibility of utilizing a frailty screening tool on patients (age > 65) with hip fracture to readily identify patients with palliative care needs at the time of admission. Although nurses’ compliance with the screening tool was less than expected, having a standardized process to accurately identify this high risk population resulted in a higher percentage of appropriate palliative care referrals when compared to usual practice. Improvement in quality of life was reported in patients who received a palliative care consultation.
The Impact of Traumatic Stress, Resilience, and Threats to Core Values on Nurses During a Pandemic
Authors: Swavely Deborah , Romig Barbara , Weissinger Guy , Holtz Heidi , Alderfer Mary , Lynn Lisa , Adil Thomas , Rushton Cynda Hylton
Published: September 2022

OBJECTIVE

The aim of this study was to understand the traumatic stress and resilience of nurses who cared for patients with COVID-19.

BACKGROUND

Studies have shown a high proportion of healthcare workers are at risk for developing posttraumatic stress disorder after a pandemic. Resilience factors are believed to play an important role in the well-being of healthcare professionals.

METHODS

This was a triangulated mixed methods study; a phenomenological qualitative approach with survey data was used to triangulate the findings, and sensemaking was used as the theoretical framework.

RESULTS

Four themes emerged from the study: 1) phases of traumatic stress response to perceived threats; 2) honoring their sacrifice; 3) professional self-identity; and 4) sustaining resilience in a stressful work environment. Quantitative results on traumatic stress, general resilience, and moral resilience supported the themes.

CONCLUSIONS

The findings will help leaders understand the potential for postpandemic mental health problems and the role of resilience in maintaining well-being.
Influence of a Formal Mentor on Hospital-Based Nurse Research Resources and Outcomes
Authors: Saul Trisha , Rangel Teresa , Sperry Marietta V. , Doyle Carrie , Roney Jamie K. , Mendelson Sherri
Published: September 2022

Magnet® hospitals must conduct nursing research to maintain designation. Relationships between hospital research infrastructure, activities, and a designated nurse research mentor were explored in a large health system using survey methodology. Hospitals with a formal mentor reported more research resources (n = 23, m = 2.5) compared with those without (n = 16, m = 1.8, P < 0.001). Hospitals aspiring for Magnet may benefit from a doctorally prepared research mentor.
The Role of Patient and Parent Education in Pediatric Cast Complications
Authors: Kearney Lauren , Thompson Julie , Zychowicz Michael , Shaw Ryan , Keyes Sean
Published: September 2022

Cast immobilization remains the standard of care in managing pediatric fractures. Cast complications often result in emergency department visits, office calls and visits, or lasting patient morbidities that burden the healthcare institution from a time and economic standpoint. The purpose of this quality improvement project was to create a multimodal cast care education protocol with an aim of decreasing cast complications over a 6-week period. Qualified patients (0–18) placed in cast immobilization received a quick response (QR) code sticker on their casts linked to a custom cast care website with text, pictures, and video instructions. Incidence of cast complications, complication type, effect(s) on workflow, and patient demographics were recorded. The complication rate declined 7.6%, but it was not statistically significant. Continuous access to clinic-specific cast instructions demonstrates decreased cast complications in pediatric populations, and this approach to patient education can be easily utilized across all medical specialties.
Chronic Heart Failure
Authors: Salama Shereen , Choudhury Aeman , Kane Sean P.
Published: September 2022

Chronic heart failure affects over 6 million Americans and is the main reason that people older than 65 years get admitted to the hospital (Centers for Disease Control and Prevention, 2020). Management of heart failure requires interdisciplinary efforts involving primary care physicians, cardiologists, nurses, and pharmacists among other providers. Nurses can play a key role in identifying patients at risk for heart failure exacerbation and are often at the front lines providing education regarding medication adherence. This article summarizes the medications used in chronic heart failure and describes common side effects, dosing considerations, and counseling points that are essential for appropriate management.
Outcomes Associated With Timing of Neurologic Dysfunction Onset Relative to Pediatric Sepsis Recognition*
Authors: Alcamo Alicia M. , Weiss Scott L. , Fitzgerald Julie C. , Kirschen Matthew P. , Loftis Laura L. , Tang Swee Fong , Thomas Neal J. , Nadkarni Vinay M. , Nett Sholeen T. ,   for the Sepsis Prevalence, Outcomes and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: September 2022

OBJECTIVES:

To compare outcomes associated with timing—early versus late—of any neurologic dysfunction during pediatric sepsis.

DESIGN:

Secondary analysis of a cross-sectional point prevalence study.

SETTING:

A total of 128 PICUs in 26 countries.

PATIENTS:

Less than 18 years with severe sepsis on 5 separate days (2013–2014).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Patients were categorized as having either no neurologic dysfunction or neurologic dysfunction (i.e., present at or after sepsis recognition), which was defined as Glasgow Coma Scale score less than 5 and/or fixed dilated pupils. Our primary outcome was death or new moderate disability (i.e., Pediatric Overall [or Cerebral] Performance Category score ≥3 and change ≥1 from baseline) at hospital discharge, and 87 of 567 severe sepsis patients (15%) had neurologic dysfunction within 7 days of sepsis recognition (61 at sepsis recognition and 26 after sepsis recognition). Primary site of infection varied based on presence of neurologic dysfunction. Death or new moderate disability occurred in 161 of 480 (34%) without neurologic dysfunction, 45 of 61 (74%) with neurologic dysfunction at sepsis recognition, and 21 of 26 (81%) with neurologic dysfunction after sepsis recognition (p < 0.001 across all groups). On multivariable analysis, in comparison with those without neurologic dysfunction, neurologic dysfunction whether at sepsis recognition or after was associated with increased odds of death or new moderate disability (adjusted odds ratio, 4.9 [95% CI, 2.3–10.1] and 10.7 [95% CI, 3.8–30.5], respectively). We failed to identify a difference between these adjusted odds ratios of death or new moderate disability that would indicate a differential risk of outcome based on timing of neurologic dysfunction (p = 0.20).

CONCLUSIONS:

In this severe sepsis international cohort, the presence of neurologic dysfunction during sepsis is associated with worse outcomes at hospital discharge. The impact of early versus late onset of neurologic dysfunction in sepsis on outcome remains unknown, and further work is needed to better understand timing of neurologic dysfunction onset in pediatric sepsis.
HIV Positivity, Linkage to Medical Care, Interview for Partner Services, and Pre-Exposure Prophylaxis Awareness and Referral Among Men Who Have Sex With Men Tested in Non-healthcare Settings in the United States, 2019
Authors: Wang Guoshen , Song Wei , Rao Shubha , Heitgerd Janet , Mulatu Mesfin S. , Karch Debra , Belcher Lisa
Published: September 2022

Objectives:

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. This study reports data on HIV testing program outcomes among MSM tested for HIV in non-healthcare settings in the United States.

Methods:

We analyzed Centers for Disease Control and Prevention's National HIV Prevention Program Monitoring and Evaluation data collected in 2019. Descriptive and multivariate robust Poisson regression analyses were conducted to summarize the patterns of HIV testing program outcomes [ie, positivity, linkage to HIV medical care within 30 days of diagnosis, interview for partner services (PS), and pre-exposure prophylaxis (PrEP) awareness and referral] by demographic characteristics, HIV prevalence, and testing site type.

Results:

A total of 123,251 HIV tests were conducted among MSM; of these, 1773 (1.4%) were newly diagnosed with HIV. Among MSM newly diagnosed with HIV, 75% were linked to HIV medical care and 80% were interviewed for PS. Among MSM who tested HIV-negative, 63% were aware of PrEP and 47% of those who were eligible for PrEP were referred to PrEP providers. Referral or linkage to services varied by demographic characteristics or other factors.

Conclusions:

Linkage to HIV medical care and interview for PS among MSM newly diagnosed with HIV in non-healthcare settings were below national or funding program targets. Most MSM with risk factors for HIV infection were not referred to PrEP providers. Expanded efforts to address barriers to equitable access to services may help improve HIV-related outcomes among MSM and contribute to ending the HIV epidemic in the United States.
Risk stratification for selecting empiric antibiotherapy during and after COVID-19
Authors: Zahar Jean-Ralph , Timsit Jean-Francois
Published: September 2022

Purpose of review

SARS-CoV-2 deeply modified the risk of bacterial infection, bacterial resistance, and antibiotic strategies. This review summarized what we have learned.

Recent findings

During the COVID-19 pandemic, we observed an increase in healthcare-acquired infection and multidrug-resistant organism-related infection, triggered by several factors: structural factors, such as increased workload and ongoing outbreaks, underlying illnesses, invasive procedures, and treatment-induced immunosuppression. The two most frequently healthcare-acquired infections described in patients hospitalized with COVID-19 were bloodstream infection, related or not to catheters, health-acquired pneumonia (in ventilated or nonventilated patients). The most frequent species involved in bacteremia were Gram-positive cocci and Gram-negative bacilli in health-acquired pneumonia. The rate of Gram-negative bacilli is particularly high in late-onset ventilator-associated pneumonia, and the specific risk of Pseudomonas aeruginosa-related pneumonia increased when the duration of ventilation was longer than 7 days. A specificity that remains unexplained so far is the increase in enterococci bacteremia.

The choice of empiric antibiotimicrobials depends on several factors such as the site of the infection, time of onset and previous length of stay, previous antibiotic therapy, and known multidrug-resistant organism colonization. Pharmacokinetics of antimicrobials could be markedly altered during SARS-CoV-2 acute respiratory failure, which should encourage to perform therapeutic drug monitoring.
Evaluation of Liver and Spleen With Shear Wave Elastography in Adult Patients With Familial Mediterranean Fever
Authors: Akti Serdar , Albayrak Eda
Published: September 2022

Familial Mediterranean fever (FMF) is an autoinflammatory disease and an important health problem in countries bordering the eastern Mediterranean, including Turkey. In this study, we aimed to evaluate possible tissue stiffness changes that may develop in the liver and spleen in adult FMF patients with shear wave elastography (SWE), and its usability as an auxiliary imaging method that will be able to provide additional advantage in clinical follow-up. Seventy-five adult FMF patients and 73 adult volunteer were included in the study. Examination was performed through an intercostal space where the liver and spleen were clearly visible. The parenchymal stiffness degrees of the liver and spleen were quantified by shear modulus values in kilopascals. Differences in stiffness values of the liver and spleen between the 2 groups were examined. Liver stiffness value (LSV) was found to be statistically significantly higher in the FMF group. Although the spleen stiffness value (SSV) was found higher in the FMF group, the difference between the groups was not statistically significant. Increased LSVs in patients with FMF can be quantitatively demonstrated by the 2-dimensional SWE method, and SWE may be useful as an auxiliary imaging method in the follow-up of patients with FMF for this purpose. The LSV and SSV obtained in this study may be useful as reference stiffness values for both healthy individuals and those with FMF.
Transcranial magnetic stimulation on the dorsal premotor cortex facilitates human visuomotor adaptation
Authors: Sugiyama Taisei , Nakae Keita , Izawa Jun
Published: September 2022

The premotor cortex is traditionally known to be involved in motor preparation and execution. More recently, evidence from neuroscience research shows that the dorsal premotor cortex (PMd) is also involved in sensory error-based motor adaptation and that invasive brain stimulation on PMd can attenuate adaptation in monkeys. The present study examines if adaptation can be modulated noninvasively in humans. Twenty-five healthy volunteers participated in a motor task in which rapid arm-reaching movements were made to hit a target, whereas the online cursor feedback about the hand position was visually rotated, inducing sensory error that drove motor adaptation. Transcranial magnetic stimulation (TMS) was delivered to PMd just before experiencing a sensory error, as in the previous study on monkeys. The degree of motor adaptation was measured as the change in the hand direction in response to the experienced error. TMS was found to increase adaptation compared with control conditions. Interestingly, the direction of modulation was opposite to the previous study on monkeys, which might originate from different methods and parameters of stimulation. The effect was also location-specific and was not a mere artifact of applying TMS because the facilitatory modulation occurred when stimulating PMd but not when stimulating the ventral premotor cortex, which was known for different roles and networks from PMd. Since noninvasive neuromodulation is a promising tool for research and clinical practice, the present study demonstrates that PMd is a feasible target region of neuromodulation to understand human motor adaptation and improve motor rehabilitation.
Investigation of Molecular Weights and Pharmacokinetic Characteristics of Older and Modern Small Drugs
Authors: Fagerholm Urban
Published: September 2022

Abstract

Background

A shift towards higher molecular weight (MW) of drug candidates is anticipated to lead to changed pharmacokinetics (PK), including deteriorated absorption.

Methods

The objective of the study was to investigate changes in MW and PK of drugs over time by comparing MW and measured PK of small drugs (here MW<1500 g/mole) marketed before 2010 (n=277) and MW andin silicopredicted (data produced using the ANDROMEDA by Prosilico software) and of small drugs marketed in 2021 (n=28).

Results

Apparently, there has been a shift towards higher MW (from 355 to 551 g/mole on average). This has influenced PK-parameters such as unbound fraction (on average approximately halved), fraction excreted renally (on average approximately halved; markedly decreased contribution by active secretion), bile excretion (almost 4-fold increased appearance; now for more than every other drug) and intrinsic metabolic clearance (increased). The very high percentage of modern drugs with (according toin silicopredictions) significant renal and biliary excretion and gut-wall extraction, metabolic stability, limited passive intestinal permeability+efflux, limited gastrointestinal dissolution/solubility potential and/or a very low fuincreases complexity in predictions and places demands on predictive laboratory and computational methods.

Conclusion

Increased MW and changed PK-profiles (increased complexity) with time were observed. This shows the need for updating method set-ups for quantification and prediction of PK-parameters. ANDROMEDA has the capability to predict and optimize human clinical PK-characteristics of modern drug candidates with high accuracy.
A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta
Authors: Carter Brandon , Huang Pinghan , Liu Ge , Liang Yuejin , Lin Paulo J.C. , Peng Bi-Hung , McKay Lindsay , Dimitrakakis Alexander , Hsu Jason , Tat Vivian , Saenkham-Huntsinger Panatda , Chen Jinjin , Kaseke Clarety , Gaiha Gaurav D. , Xu Qiaobing , Griffiths Anthony , Tam Ying K. , Tseng Chien-Te K. , Gifford David K.
Published: September 2022

Clinically licensed COVID-19 vaccines ameliorate viral infection by inducing vaccinee production of neutralizing antibodies that bind to the SARS-CoV-2 Spike protein to inhibit viral cellular entry (Walsh et al., 2020; Baden et al., 2021), however the clinical effectiveness of these vaccines is transitory as viral variants arise that escape antibody neutralization (Tregoning et al., 2021; Willett et al., 2022). Vaccines that solely rely upon a T cell response to combat viral infection could be transformational because they can be based on highly conserved short peptide epitopes that hold the potential for pan-variant immunity, but a mRNA-LNP T cell vaccine has not been shown to be sufficient for effective antiviral prophylaxis. Here we show that a mRNA-LNP vaccine based on highly conserved short peptide epitopes activates a CD8+and CD4+T cell response that prevents mortality in HLA-A*02:01 transgenic mice infected with the SARS-CoV-2 Beta variant of concern (B.1.351). In mice vaccinated with the T cell vaccine, 24% of the nucleated cells in lung were CD8+T cells on day 7 post infection. This was 5.5 times more CD8+T cell infiltration of the lungs in response to infection compared to the Pfizer-BioNTech Comirnaty® vaccine. Between days 2 and 7 post infection, the number of CD8+T cells in the lung increased in mice vaccinated with the T cell vaccine and decreased in mice vaccinated with Comirnaty®. The T cell vaccine did not produce neutralizing antibodies, and thus our results demonstrate that SARS-CoV-2 viral infection can be controlled by a T cell response alone. Our results suggest that further study is merited for pan-variant T cell vaccines, and that T cell vaccines may be relevant for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.
High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike
Authors: Tan Timothy J.C. , Mou Zongjun , Lei Ruipeng , Ouyang Wenhao O. , Yuan Meng , Song Ge , Andrabi Raiees , Wilson Ian A. , Kieffer Collin , Dai Xinghong , Matreyek Kenneth A. , Wu Nicholas C.
Published: September 2022

Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we established a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrated a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, this method was applied to a region in the S2 domain that includes the first heptad repeat and central helix. Our results revealed that besides K986P and V987P, several mutations simultaneously improved expression and significantly lowered the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.
Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics
Authors: Zhang Danyang , Lape Remigijus , Shaikh Saher A. , Kohegyi Bianka K. , Watson Jake F. , Cais Ondrej , Nakagawa Terunaga , Greger Ingo H.
Published: September 2022

AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse drugs. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators.
Taxon cycles in Neotropical mangroves
Authors: Rull Valentí
Published: September 2022

The concept of taxon cycle involves successive range expansions and contractions over time through which a species can indefinitely maintain its core distribution. Otherwise, it becomes extinct. Taxon cycles have been defined mostly for tropical island faunas, examples from continental areas are scarce and similar case studies for plants remain unknown. Most taxon cycles have been identified on the basis of phylogeographic studies, and straightforward empirical evidence from fossils is lacking. Here, empirical fossil evidence is provided for recurrent Eocene to present expansion/contraction cycles in a mangrove taxon (Pelliciera), after a Neotropical-wide study of the available pollen records. This recurrent behavior is compatible with the concept of taxon cycle from biogeographical, chronological and ecological perspectives. The biotic and abiotic drivers potentially involved in the initiation and maintenance of thePellicieraexpansion/contraction cycles are analyzed, and the ecological and evolutionary implications are discussed. Whether this could be a trend toward extinction is considered under the predictions of the taxon cycle theory. The recurrent expansion and contraction cycles identified forPellicierahave strong potential for being the first empirically and unequivocally documented taxon cycles and likely the only taxon cycles documented to date for plants.
Associations of maternal prenatal emotional complaints and cortisol with neonatal meconium microbiota: A cross-sectional study
Authors: Deflorin Nadia , Ehlert Ulrike , Amiel Castro Rita T.
Published: September 2022

The gut microbiome is a complex microbial ecosystem considered as a key modulator of human health and disease. Alterations in the diversity and relative abundances of the gut microbiome have been associated with a broad spectrum of medical conditions. Maternal emotional complaints during pregnancy can impact on offspring development by altering the maternal and the foetal gut microbiome. We aimed to investigate whether self-reported maternal anxiety, depressive symptoms, and distress as well as biological stress in late pregnancy alter the bacterial composition of the infant’s meconium.

Methods

A total ofN=100 mother-infant pairs were included. Maternal emotional complaints were measured using standardised questionnaires (EPDS, PSS-10, STAI) at 34-36 weeks gestation and salivary cortisol was measured at 34-36 and 38 weeks gestation. Infant meconium samples were collected in the first five days postpartum and analysed using 16S rRNA amplicon sequencing.

Results

Correlations showed that lower alpha diversity of the meconium microbiome was significantly associated with increased maternal prenatal depressive symptoms in late gestation (τ = -0.149,p= 0.041). Increased cortisol AUCg at T2 was significantly related to higher beta diversity of the meconium samples (Pr(>F) = 0.003*).Proteobacteriawas the most abundant phylum and was associated with maternal cortisol total decline. No other associations were found.

Conclusions

Maternal prenatal depressive symptoms are associated with infant faecal microbiota alpha diversity, whereas maternal cortisol AUCg is linked to increased beta diversity and total decline related to increasedProteobacteria. Future studies are warranted to understand how these microbiota community alterations are linked to child health outcomes.

Highlights

Maternal prenatal depressive symptoms alter the meconium microbiome.

Increased biological stress during pregnancy alters the beta diversity of the meconium microbiome.

Proteobacteriais the most abundant phylum in the meconium samples.
Phase of firing does not reflect temporal order in sequence memory of humans and recurrent neural networks
Authors: Liebe Stefanie , Niediek Johannes , Pals Matthijs , Reber Thomas P. , Faber Jenny , Bostroem Jan , Elger Christian E. , Macke Jakob H. , Mormann Florian
Published: September 2022

A prominent theory proposes that the temporal order of a sequence of items held in memory is reflected in ordered firing of neurons at different phases of theta oscillations 1. We probe this theory by directly measuring single neuron activity (1420 neurons) and local field potentials (LFP, 921 channels) in the medial temporal lobe of 16 epilepsy patients performing a working memory task for temporal order. We observe theta oscillations and preferential firing of single neurons at theta phase during memory maintenance. We find that - depending on memory performance - phase of firing is related to item position within a sequence. However, in contrast to the theory, phase order did not match item order. To investigate underlying mechanisms, we subsequently trained recurrent neural networks (RNNs) to perform an analogous task. Similar to recorded neural activity, we show that RNNs generate theta oscillations during memory maintenance. Importantly, model neurons exhibit theta phase-dependent firing related to item position, where phase of firing again did not match item order. Instead, we observed a mechanistic link between phase order, stimulus timing and oscillation frequency - a relationship we subsequently confirmed in our neural recordings. Taken together, in both biological and artificial neural networks we provide validating evidence for the role of phase-of-firing in memory processing while at the same time challenging a long-held theory about the functional role of spiking and oscillations in sequence memory.
From Correlation to Communication: disentangling hidden factors from functional connectivity changes
Authors: Yu Yuhua , Gratton Caterina , Smith Derek M.
Published: September 2022

While correlations in the BOLD fMRI signal are widely used to capture functional connectivity (FC) and its changes across contexts, its interpretation is often ambiguous. The entanglement of multiple factors including local coupling of two neighbors and non-local inputs from the rest of the network (affecting one or both regions) limits the scope of the conclusions that can be drawn from correlation measures alone. Here we present a method of estimating the contribution of non-local network input to FC changes across different contexts. To disentangle the effect of task-induced coupling change from the network input change, we propose a new metric, “communication change”, utilizing BOLD signal correlation and variance. With a combination of simulation and empirical analysis, we demonstrate that 1) input from the rest of the network accounts for a moderate but significant amount of task-induced FC change; 2) the proposed “communication change” is a promising candidate for tracking the local coupling in task context-induced change. Additionally, when compared to FC change across three different tasks, communication change can better discriminate specific task types. Taken together, this novel index of local coupling may have many applications in improving our understanding of local and widespread interactions across large-scale functional networks.