bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychotic Experiences and Daily Functioning in Borderline Personality Disorder and Schizophrenia
Authors: Tschöke Stefan , Knauer Yvonne , Flammer Erich , Usemann Paula , Uhlmann Carmen
Published: February 2024

Psychotic experiences have been shown to be comparable in borderline personality disorder (BPD) and schizophrenia. Preliminary evidence suggests differences in the impact of psychotic experiences on daily functioning. Therefore, in this study, we aimed to investigate the role of psychotic experiences in daily functioning in BPD compared with schizophrenia. We performed post hoc analyses on data from 23 inpatients with BPD and 21 inpatients with schizophrenia, for whom results from the Psychotic Symptom Rating Scales were available. No differences were found in frequency, intensity, and disruption of life in relation to auditory verbal hallucinations and the amount of preoccupation and conviction with regard to delusions. Significant differences were found in the disruption of life due to delusions. The results emphasize that the quality of psychotic experiences in BPD and schizophrenia is comparable, but the impact of delusions on daily life is different, which may improve differential diagnosis.
Exercise Dependency and Overuse Injuries in Attention Deficit Hyperactivity Disorder
Authors: Ramji Anusha V. , Runswick Oliver R. , Dommett Eleanor J.
Published: February 2024

Attention deficit hyperactivity disorder (ADHD) is a common condition, but current medications have limitations, pushing a drive for alternative approaches. Different exercise-focused approaches have shown promise, but concern has also been raised about individuals with ADHD showing greater risk of addiction, including exercise dependency. Using an online survey, we examined current exercise practices, including exercise dependency and the presence of overuse injury, which could result from overexercising, in 114 adults with ADHD. We found that most were regularly exercising. None were classified as exercise dependent, but 38.9% were deemed symptomatic nondependent. Hyperactive-impulsive symptoms were a predictor of the level of exercise withdrawal experienced, and the co-occurrence of autism spectrum disorder was associated with greater risk of overuse injuries. The data indicate that ADHD may confer some greater risk of exercise dependency, aligning with previous studies investigating other addictions and suggesting further research is critical.
Dissociative Identity Disorder
Authors: Boysen Guy A.
Published: February 2024

Dissociative identity disorder (DID) has historically been one of the most controversial topics in the study of psychopathology. Building on a previous review of empirical research on DID from 2000 to 2010, the present review examined DID research from 2011 to 2021. The research output included 56 case studies and 104 empirical studies. Within the empirical studies, approximately 1354 new cases of DID emerged, which resulted in an average samples of approximately 20. Reanalysis of previous samples was standard in the literature with only 40% of reported cases being new. Studies emerged from dozens of countries across the world, but the majority of cases were from Western counties, especially the United States. Diagnosis primarily relied upon validated measures, but 74% of all new cases came from six research groups. Overall, research on DID is steady but methodologically limited in ways that make generalization, especially about etiology, difficult.
Social Determinants of Health and Multimorbidity Among Adults 50 Years and Older in the United States
Authors: Lee Jung Eun , Haynes Emily , DeSanto-Madeya Susan , Kim Young Man
Published: February 2024

Background

Living with two or more chronic conditions simultaneously—known as multimorbidity—has become increasingly prevalent as the aging population continues to grow. However, the factors that influence the development of multimorbidity are still not fully understood.

Objectives

The purpose of this study was to investigate the prevalence of multimorbidity among U.S. adults 50 years and older and identify associated factors with multimorbidity.

Methods

We used data from four cycles from the National Health and Nutrition Examination Survey (2011–2018) to examine the associations between social determinants of health and multimorbidity among American adults aged 50 years and older. A set of variables on socioeconomic status and health behaviors was chosen based on the social determinants of health conceptual framework developed by the World Health Organization. In our study, 4,552 participants were included. All analyses were accounted for a complex survey design and the use of survey weights. Multiple logistic regression analyses were performed to examine the associated factors with multimorbidity.

Results

The average age was 63.1 years, and 52.9% were female. The average number of chronic conditions was 2.27. The prevalence of multimorbidity was 63.8%, with high cholesterol and hypertension being the most prevalent conditions. In the adjusted model, age, gender, household income, citizenship status, health insurance, healthcare access, body mass index, and smoking status were found to be associated with living with multimorbidity.

Discussion

Our results indicate that continued efforts aimed at promoting smoking cessation and maintaining a healthy weight will be beneficial in preventing the onset of chronic conditions. Additional research is warranted to gain a deeper understanding of the interrelationships between gender, race/ethnicity, household income, citizenship status, health insurance, and healthcare access as social determinants of health in the context of multimorbidity. Further research will help us develop targeted interventions and policies to address disparities and improve health outcomes for individuals with multimorbidity.
Characterizing Interest in and Uptake of Preexposure Prophylaxis for HIV Prevention Among Men in a US State Correctional System
Authors: Ma Emily C. , Rogers Brooke G. , Chan Philip A. , Toma Emily , Almonte Alexi , Napoleon Siena , Galipeau Drew , Ahluwalia Jasjit S. , Murphy Matthew
Published: February 2024

Background

People experiencing incarceration are disproportionately impacted by HIV and are potential candidates for HIV preexposure prophylaxis (PrEP). We explored factors associated with PrEP interest and PrEP uptake and described barriers to PrEP uptake among incarcerated men in a state correctional system.

Methods

From September 2019 to July 2022, incarcerated men at the Rhode Island Department of Corrections were screened for PrEP eligibility and referred to a PrEP initiation study. We used bivariate analyses and multivariable logistic regression models to explore factors associated with PrEP interest and uptake in the screening sample.

Results

Of the men screened and determined to be eligible for PrEP, approximately half (50%) were interested in taking PrEP. Individuals identifying as men who have sex with men (adjusted odds ratio, 4.46; 95% confidence interval, 1.86–11.4) and having multiple female sex partners (adjusted odds ratio, 2.98; 95% confidence interval, 1.47–6.27) were more likely to express interest in PrEP (interested/not interested) than those not reporting these behavioral factors. Preexposure prophylaxis uptake (yes/no) was 38%. Lack of PrEP interest, low self-perceived risk of HIV acquisition, and unpredictable lengths of incarceration were the most frequently encountered barriers to PrEP uptake.

Conclusions

Men reporting sexual transmission behaviors were more interested in PrEP and had higher uptake than other men. Preexposure prophylaxis interest and HIV risk factors were both moderately high, which suggests that men experiencing incarceration should be screened for and offered PrEP as part of standard clinical care. Study findings have important implications for research and practice to adapt PrEP care to correctional systems.
Development of a Novel Fluorescent-Based Lateral Flow Assay for the Detection of Neisseria gonorrhoeae at the Point of Care
Authors: Gleeson Birgitta , Piton Jeremie , Mazzola Laura , McHugh Sean , Bender Jillian , Lear Madison , Gavrikova Tatyana , Van Der Pol Barbara , Daniels Brice , Osborn Jennifer , Dailey Peter , Ferreyra Cecilia
Published: February 2024

Background

Neisseria gonorrhoeae (NG) has acquired significant resistance, primarily due to extensive and unwarranted antibiotic utilization over several decades. This resistance has largely been associated with the syndromic management of sexually transmitted infections, particularly in low- and middle-income countries where affordable point of care tests are unavailable. To address this diagnostic gap, FIND has developed a low-cost lateral flow assay for the detection of NG at the point of care.

Methods

The early performance of the lateral flow assay was evaluated using frozen clinical samples. Limit of detection, inclusivity, and exclusivity studies were performed using well-characterized NG strains, common commensal genital microorganisms, and other Neisseria bacteria. Subsequently, clinical performance was evaluated at 2 sexual health clinics in Birmingham, Alabama.

Results

The observed limit of detection with reference NG strains was 5 × 103 CFU/mL. Inclusivity was demonstrated for 31 NG strains. Exclusivity testing showed no cross-reactivity with 28 non-Neisseria and nongonococcal Neisseria species; cross-reactivity was observed with Neisseria meningitidis, Neisseria lactamica, and Neisseria polysaccharea. The lateral flow assay demonstrated clinical sensitivity and specificity of 78.6% and 100% in female vaginal swabs and 100% and 89.7% in male urine, respectively.

Conclusions

FIND has developed a lateral flow assay that aligns with the majority of the World Health Organization Target Product Profile criteria for confirming or excluding NG infection at the point of care. The NG lateral flow assay has now achieved design freeze (final device optimization) and is ready for technology transfer to a manufacturing partner. This test has the potential to support the shift in patient management from a syndromic to an etiological approach.
Human Immunodeficiency Virus Treatment Attitudes and Bacterial Sexually Transmitted Infections Among Gay and Bisexual Men
Authors: Hart Trevor A. , Noor Syed W. , Tavangar Farideh , Zahran Adhm , Skakoon-Sparling Shayna , Tan Darrell H. S. , Lambert Gilles , Grace Daniel , Lachowsky Nathan , Sang Jordan M. , Palma Paolo A. , Zhang Terri , Dvorakova Milada , Cox Joseph , Moore David M. ,   for the Engage Study
Published: February 2024

Backgrounds

Positive attitudes toward human immunodeficiency virus (HIV) treatment, such as reduced concern about HIV transmissibility, are associated with sexual behaviors that may increase the risk of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM). We examined associations between HIV treatment attitudes and bacterial STI diagnoses among GBM in Canada's three largest cities.

Methods

We fit a structural equation model between HIV treatment attitudes and bacterial STI diagnoses via sexual behaviors in the Engage study's baseline data. We estimated direct and indirect paths between scores on HIV treatment attitudes and STIs via number of male anal sex partners, condomless anal sex, and oral sex. We conducted sub-analyses with participants stratified by HIV serostatus.

Results

Among 2449 GBM recruited in 2017 to 2019, there was a direct association between HIV treatment attitudes and current STI diagnoses (β = 0.13; 95% CI, 0.07–0.19; P < 0.001). The mediated model revealed a positive total indirect effect through 2 pathways: (1) engaging in condomless anal sex and (2) number of male anal sex partners and condomless anal sex. These 2 indirect pathways remained in the stratified mediation models for both HIV negative GBM and for GBM living with HIV.

Conclusions

The association between HIV treatment attitudes and diagnosed STIs is mediated through a higher number of male anal sex partners and condomless anal sex. The results highlight the importance of providers educating patients when providing effective STI counseling, testing, and prevention for GBM about how accurate HIV treatment attitudes may inadvertently be associated with the bacterial STI epidemic.
Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data
Authors: Michalow Julia , Jahn Andreas , Cori Anne , Boily Marie-Claude , Chimpandule Tiwonge , Mbiriyawanda Stone , Ozituosauka Washington , Nyirenda Rose , Imai-Eaton Jeffrey W.
Published: February 2024

Background

In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi.

Methods

We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021.

Results

In surveys, 11.0% (95% confidence interval, 10.7%–11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%–55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%–6.1%) for genital ulcer, 3.8% (2.0%–6.7%) for vaginal discharge, and 2.6% (1.2%–4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi.

Conclusions

Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.
Impact of work-related changes on health-related quality of life in adolescent and young adult cancer survivors
Authors: Goto Shinichi , Itani Yuki , Fujimori Maiko , Okamura Masako , Obama Kyoko , Sato Ayako , Uchitomi Yosuke
Published: February 2024

Background:

Adolescent and young adult (AYA) cancer survivors often face unique work-related challenges and poor health-related quality of life (HRQOL). This study aimed to (1) assess work-related changes after cancer diagnosis in AYA cancer survivors and (2) explore the association between work-related changes and HRQOL.

Methods:

In a cross-sectional web-based survey, AYA cancer survivors were assessed for work-related changes after cancer diagnosis and their HRQOL using the EuroQoL 5-Dimension 5-Level scale (EQ-5D-5L). The percentage of AYA cancer survivors who had experienced work-related changes was calculated. Multiple regression analysis was used to examine the association between EQ-5D-5L scores and work-related changes, demographics, and clinical variables.

Results:

The participants were 206 AYA cancer survivors (180 women) with a mean age of 33.7 years (SD 4.3, range: 22–39 years). Among them, 115 (56%) had experienced work-related changes, including 53 (25.7%) who had quit their jobs after their cancer diagnosis. The EQ-5D-5L score (mean: 0.79) was lower in the AYA cancer survivors than in the general population. Moreover, AYA cancer survivors who experienced work-related changes had significantly lower EQ-5D-5L scores compared with AYA cancer survivors who did not (0.75 vs 0.84, P < .001). Multiple regression analyses indicated that lower income, reduced working hours, and lower performance status, as measured by the Eastern Cooperative Oncology Group Scale, were associated with lower EQ-5D-5L scores.

Conclusions:

More than half of the AYA cancer survivors reported work-related changes and had lower HRQOL. Identifying potential interventions supporting AYA cancer survivors with low physical and financial status may be useful for improving their HRQOL.
Risk Factors of Convulsions in Children With Rotavirus Gastroenteritis and Construction of a Nomogram Prediction Model
Authors: Yang Jing , Sun Weiwei , Dai Shasha
Published: February 2024

Objective

This study aims to investigate and analyze the risk factors of convulsions in children with rotavirus gastroenteritis and to construct a nomogram prediction model.

Methods

A retrospective analysis was performed on 940 cases of pediatric patients with rotavirus gastroenteritis treated in our hospital from December 2017 to December 2022. Based on whether convulsions occurred during hospitalization, patients were divided into the convulsion group (n = 135) and the convulsion-free group (n = 805). Clinical information of patients in both groups was collected, logistic regression analysis was carried out to analyze the convulsion risk factors pertaining to children with rotavirus gastroenteritis, and a nomogram prediction model was constructed.

Results

The univariate analysis revealed that fever, frequency of diarrhea, white blood cell count, blood calcium level, blood glucose level, CO2CP, creatine kinase myocardial band (CK-MB), and blood pH value were all factors that display statistically significant differences at the level of P = 0.05. Then, logistic regression analysis was carried out, taking the occurrence of such convulsions as the dependent variable and the aforementioned factors as independent variables. The results show that fever, frequency of diarrhea, blood calcium, CO2CP, and CK-MB were the independent risk factors (P < 0.05), whereas the area under the receiver operating characteristic curve (area under the curve) of the constructed nomogram prediction model based on these factors was 0.842 (95% confidence interval, 0.821–0.914).

Conclusions

Frequency of diarrhea, blood calcium, CO2CP, and CK-MB are independent risk factors for the occurrence of convulsions in children with rotavirus gastroenteritis. The nomogram prediction model constructed based on these risk factors provides guidance and value in effectively preventing and controlling convulsions in children with rotavirus gastroenteritis.
POCUS for Infectious Enteritis—A Retrospective Case Series Analysis
Authors: Scheier Eric , Nachmany Aviad
Published: February 2024

Introduction

The abdominal pain associated with diarrhea can be difficult to distinguish from appendicitis. We present a case series of all children found on pediatric emergency department point-of-care ultrasound (POCUS) to have right-sided bowel wall edema.

Methods

Over the study period June 2020 through September 2023, POCUS images were collected by a pediatric emergency physician with 6 years of experience with POCUS. Children found to have small bowel wall edema on POCUS were identified, and hospital charts were reviewed.

Results

One hundred thirteen children were found on POCUS to have right-sided small bowel wall edema. Thirty-one (27%) were referred by their pediatrician or urgent care provider to evaluate for appendicitis. Seventy-eight children (69%) provided stool samples. Of those, 58% resulted Campylobacter, 8% Salmonella, and 8% Shigella. Forty (35%) were discharged after POCUS without further evaluation. One child in our case series was subsequently diagnosed with uncomplicated appendicitis. To date, no child in the series has subsequently been diagnosed with inflammatory bowel disease.

Conclusions

Enteritis can initially be difficult to distinguish on clinical grounds from acute appendicitis. Bowel wall edema on POCUS in a child without sonographic signs of appendicitis strongly suggests bacterial enteritis. Early POCUS demonstrating enteritis without signs of appendicitis may decrease hospital resource usage.
Epidemiology of Craniofacial Soft Tissue Injury in a Western Chinese Population
Authors: Mu Si-Qi , Dong Chen , Chen Jie , Liu Heng-Xin , Jin Chang-Xin , Cang Zheng-Qiang , Zhang Xi
Published: February 2024

Purpose:

Craniofacial soft tissue injuries represent a serious public health problem and their epidemiology is extremely variable. The objective of the present study was to analyze and discuss the epidemiological characteristics of 12,816 patients with craniofacial skin soft tissue injuries over a 3-year period.

Materials and Methods:

This retrospective study was conducted in emergency departments of plastic surgery at Xijing Hospitals from 2020 to 2022. Data were collected for the cause of injury, age and gender distribution, localization and frequency of soft tissue injuries, visit time, facial bone fractures, nerve injury, and treatment protocols. All the data were analyzed and performed including descriptive analysis, chi-square test, and logistic regression analyses.

Results:

A total of 13,574 soft tissue injuries were seen in 12,816 patients. A total to 94.67% (12,133) were single-site injuries, and 5.33% (683) were multiple-site injuries. The male-to-female ratio of 1.62:1. The age group 0 to 9 years accounted is the largest subgroup. The most common etiology of the trauma was collisions, accounted for 51.89%. The forehead (23.54%) was the most common site by the cheeks (14.36%). Two hundred three patients (1.58%) had associated bone fractures. May month had the highest incidence of trauma and February month had the lowest incidence. There are more visits on weekends than on weekdays. 18:00 to 24:00 is the time with the largest number of visits, but there is no statistically significant difference from other time periods. The average time interval between the accident and treatment was 6.8 hours, and the median time was 6 hours.

Conclusions:

The incidence of craniofacial soft tissue injuries is related to gender, age, and the cause of trauma. Children between 0 and 9 are the most likely group. Collisions is the main cause of craniofacial soft tissue injuries.
Use of a Space Graft in Rhinoplasty
Authors: Zhao Jiuli , Xu Xiaowen , Shan Lei
Published: February 2024

Background:

Construction of the nasal tip strut is an important part of rhinoplasty; the incidence of postoperative complications is closely related to the type of graft and the approach to cartilaginous framework construction.

Objectives:

To introduce a supplementary graft to support the cartilaginous framework.

Methods:

Forty patients (37 female and 3 male), aged from 18 to 40 years (average 29), received a rhinoplasty using a spacer graft. Of these, 12 were primary cases and the other 28 had a previous rhinoplasty procedure. Postoperatively, all patients were photographed and asked to complete a satisfaction survey. Complications were collected retrospectively.

Results:

Postoperatively, the mean nasofrontal angle was 141.92±1.26 degrees for the primary cases and 140.75±2.22 degrees for the repeat procedures; the mean nasolabial angle was 88.69±0.95 degrees for primary cases and 89.14±0.93 degrees for the repeat procedures; mean nasal length was 4.78±0.05 cm for primary cases and 4.79±0.07 cm for the repeat procedures; mean tip projection was 4.68±6.35 cm for primary cases and 2.24±0.07 cm for the repeat procedures. Self-report of the overall improvements showed a high satisfaction rate. One case (2.5%) had a postoperative complication involving a mildly deviated columellar.

Conclusions:

The spacer graft can be used as an effective supplement to the traditional methods for reconstructing the nasal tip framework; it can prevent the occurrence of postoperative complications such as the exposure of the nasal prosthesis, the downward rotation of the nasal tip, the depression of the supratip regions of the nose, and the deviation of the nasal columella.
Biomechanical Study on the Comparison of Synthetic Materials for Cranio-Orbital Fracture Repair
Authors: Zeng Xueying , Li Yang , Sun Hetian , Kikkawa Don O. , Lu Wei
Published: February 2024

Objective:

For analyzing the mechanical properties of 2 cranio-orbital repair materials under distinct external impacts by finite element analysis and evaluating the stability of various repair materials.

Methods:

Based on the computed tomography images of the patients with cranio-orbital fractures, three-dimensional models of the normal craniomaxillofacial models were established by segmenting them with Mimics 19.0, Geomagic Studio 12.0, and UG 12.0, respectively, to build the finite element models of titanium repair fixation and the poly-ether-ether-ketone repair fixation. The models were then simulated by Ansys 19.2, with divergent impact forces to analyze the stresses and displacements of the repair materials, as well as the internal fixation system, and to make a comparison on the stability of the distinct repair materials.

Results:

The titanium mesh is stable at impact forces ≤1500 N. Furthermore, the poly-ether-ether-ketone mesh and the internal fixation system are resistant to fracture and displacement at impact forces of up to 3000 N.

Conclusion:

By simulating distinct mechanical environments, the biomechanical finite element analysis method can digitally assess the mechanical properties of cranio-orbital repair materials and objectively evaluate the stability of the repair materials and the internal fixation system.
Sizeable Facial and Cervical Defect Repair using a Medial Arm Flap Combined With the Tissue Expansion Technique: Clinical Applications and Fifteen-year Follow-up
Authors: Luo Si-Si , Yang Zhe , Ma Ning , Chen Sen , Li Yang-Qun
Published: February 2024

Background:

The aim of this study was to present the 15-year clinical results using a preexpanded pedicle medial arm flap for repairing massive facial and cervical defects.

Methods:

The process of our method is divided into 3 stages. In the first stage, the rectangle-shaped tissue expander was implanted subcutaneously in the medial arm region and serially inflated for ~3 months. In the second stage, the distal portion of the flap was to cover the defects, the proximal portion was overlapped with the residual lesion flap. The pedicle was divided 3 weeks later, and the extra tissue was reinserted back to the donor site.

Results:

A total of 27 patients were retained. All donor sites were closed directly. Maximum and minimum sizes of preexpanded cervical flaps were 20

15 cm2 to 5.5

4 cm2. In 2 cases, partial necrosis occurred at the distal end of the flap, while the remaining flap survived completely. The median duration of follow-up was 7.5 years. During follow-up, 24 patients (88.9%) had satisfactory outcomes and 3 patients (11.1%) had partially satisfactory results.

Conclusion:

Using expanded pedicle medial arm flap for face or neck defects’ reconstruction showed that it was safe and effective, and had satisfying results in the long-term follow-up. The flap based on the proximal pedicle has a more reliable blood supply.
Evidence-based psychosocial interventions in schizophrenia: a critical review
Authors: Barlati Stefano , Nibbio Gabriele , Vita Antonio
Published: February 2024

Purpose of review

Schizophrenia Spectrum Disorders (SSD) are severe conditions that frequently produce significant impairment in cognitive performance, social skills and psychosocial functioning. As pharmacological treatment alone often provides only limited improvements on these outcomes, several psychosocial interventions are employed in psychiatric rehabilitation practice to improve of real-world outcomes of people living with SSD: the present review aims to provide a critical overview of these treatments, focusing on those that show consistent evidence of effectiveness.

Recent findings

Several recent systematic reviews and meta-analyses have investigated in detail the acceptability, the effectiveness on several specific outcomes and moderators of response of different psychosocial interventions, and several individual studies have provided novel insight on their implementation and combination in rehabilitation practice.

Cognitive remediation, metacognitive training, social skills training, psychoeducation, family interventions, cognitive behavioral therapy, physical exercise and lifestyle interventions, supported employment and some other interventions can be fully considered as evidence-based treatments in SSD. Psychosocial interventions could be of particular usefulness in the context of early intervention services. Future research should focus on developing newer interventions, on better understanding the barriers and the facilitators of their implementation in clinical practice, and exploring the opportunities provided by novel technologies.
No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters
Authors: Karl Sebastian , Sartorius Alexander , Aksay Suna Su
Published: February 2024

Introduction

Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality.

Methods

We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing.

Results

Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration.

Conclusions

Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.
Limited stress and tissue-specific transcriptional and translational activity of transposable elements in mosquitoes
Authors: Melo Elverson S , Wallau Gabriel L
Published: February 2024

The mobilization of transposable elements (TEs) can either negatively affect the host’s fitness or contribute to the species evolution. TE protein expression is the first stage for transposition, but organisms developed defenses to control it. The intensity of regulatory mechanisms can vary among tissues, and in response to stress, it may facilitate TE activation across different species. Using hundreds of RNA-Seq and mass spectrometry experiments we calculated TE expression on twelve mosquito species. Most mosquito TE families exhibit constitutive RNA expression with abundant lncRNA production, yet only a limited number of proteins are effectively produced, in a tissue-specific manner. Under natural conditions, TEs exhibit distinct expression in somatic and germinal tissues, notably with pronounced repression in ovaries, associated with increased PIWI and AGO3 expression. Following exposure to abiotic stress and viral infection, certain TE families undergo altered expression. However, some stressors have no effects on TEs, or cause opposite effects in distinct species. Furthermore, repression predominates over induction in most cases. These data suggest that while some proteins are synthesized, the majority of TE transcripts function in a regulatory capacity. We also propose that the conventional notion of TEs being more expressed under stress conditions may not be universally valid.

GRAPHICAL ABSTRACT
Theta-burst direct electrical stimulation remodels human brain networks
Authors: Huang Yuhao , Zelmann Rina , Hadar Peter , Dezha-Peralta Jaquelin , Richardson R. Mark , Williams Ziv M. , Cash Sydney S. , Keller Corey J. , Paulk Angelique C.
Published: February 2024

Patterned brain stimulation is a powerful therapeutic approach for treating a wide range of brain disorders. In particular, theta-burst stimulation (TBS), characterized by rhythmic bursts of 3-8 Hz mirroring endogenous brain rhythms, is delivered by transcranial magnetic stimulation to improve cognitive functions and relieve symptoms of depression. However, the mechanism by which TBS alters underlying neural activity remains poorly understood. In 10 pre-surgical epilepsy participants undergoing intracranial monitoring, we investigated the neural effects of TBS. Employing intracranial EEG (iEEG) during direct electrical stimulation across 29 stimulation cortical locations, we observed that individual bursts of electrical TBS consistently evoked strong neural responses spanning broad cortical regions. These responses exhibited dynamic changes over the course of stimulation presentations including either increasing or decreasing voltage responses, suggestive of short-term plasticity in the amplitude of the local field potential voltage response. Notably, stronger stimulation augmented the mean amplitude and distribution of TBS responses , leading to greater proportion of recording sites demonstrating short-term plasticity. TBS responses were stimulation site-specific and propagated according to the underlying functional brain architecture, as stronger responses were observed in regions with strong baseline effective (cortico-cortical evoked potentials) and functional (low frequency phase locking) connectivity. Further, our findings enabled the predictions of locations where both TBS responses and change in these responses (e.g. short-term plasticity) were observed. Future work may focus on using pre-treatment connectivity alongside other biophysical factors to personalize stimulation parameters, thereby optimizing induction of neuroplasticity within disease-relevant brain networks.
Releasable hydrogel microsphere-drug conjugates as generic prodrugs for long-acting intra-tumoral therapy
Authors: Henise Jeff , Hangasky John A. , Charych Deborah , Carreras Christopher W. , Ashley Gary W. , Santi Daniel V.
Published: February 2024

Intratumoral (IT) therapy is a powerful method of controlling tumor growth, but a major unsolved problem is the rapidity that injected drugs exit tumors, limiting on-target exposure and efficacy. We have developed a generic long acting IT delivery-system in which a drug is covalently tethered to hydrogel microspheres (MS) by a cleavable linker; upon injection the conjugate forms a depot that slowly releases the drug and “bathes” the tumor for long periods. We established technology to measure tissue pharmacokinetics and studied MSs attached to SN-38, a topoisomerase 1 inhibitor. When MS∼SN-38 was injected locally, tissues showed high levels of SN-38 with a long half-life of ∼1 week. IT MS∼SN-38 was ∼10-fold more efficacious as an anti-tumor agent than systemic SN-38. We also propose and provide an example that long-acting IT therapy might enable safe use of two drugs with overlapping toxicities. Here, long-acting IT MS∼SN-38 is delivered with concurrent systemic PARP inhibitor. The tumor is exposed to both drugs whereas other tissues are exposed only to the systemic drug; synergistic anti-tumor activity supported the validity of this approach. We propose use of this approach to increase efficacy and reduce toxicities of combinations of immune checkpoint inhibitors such asαCTLA4 andαPD-1.
Dnmt3amutations limit normal and autoreactive Tfh differentiation
Authors: Shen Yunbing , Li Zhaojun , Boddul Sanjaykumar , Kasza Zsolt , Espinosa Alexander , Klareskog Lars , Wermeling Fredrik
Published: February 2024

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation, strongly associated with the activity of autoreactive CD4+ T cells.DNMT3Amutations are the most common somatic mutations found in the hematopoietic system of patients with rheumatoid arthritis. However, the role of DNMT3A in CD4+ T cells and CD4+ T follicular helper (Tfh) cells is poorly understood. Since somatic mutations are not identified in standard genome-wide association studies, somatic mutations’ impact on the etiology of diseases could be underestimated. Here, we thoroughly characterized and used the KRN+ splenocyte transfer model of autoimmune joint inflammation and inactivatedDnmt3ausing CRISPR-Cas9 and standard Cre/loxP approaches. Experiments with competitive bone marrow (BM) chimeras identified a positive role forDnmt3ain Tfh differentiation, which was validated by comparing mice withDnmt3amutations in CD4+ cells to animals with WTDnmt3a. In conclusion, We identify thatDnmt3amutations limit normal and autoreactive Tfh differentiation.

Key findings

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Dnmt3amutations limit Tfh differentiation, which could contribute to reduced immune responses in individuals with somaticDNMT3Amutations.

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Deep characterization of the KRN+ splenocyte transfer model defines a dynamic process leading to reproducible autoimmune joint inflammation.

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The immuno-CRISPR (iCR) methodology can be used to test the role of candidate genes in disease models.
An extremely fast neural mechanism to detect emotional visual stimuli: A two-experiment study
Authors: Luis Carretié , Uxía Fernández-Folgueiras , Dominique Kessel , Guzmán Alba , Estrella Veiga-Zarza , Manuel Tapia , Fátima Álvarez
Published: February 2024

Defining the brain mechanisms underlying initial emotional evaluation is a key but unexplored clue to understand affective processing. Event-related potentials (ERPs), especially suited for investigating this issue, were recorded in two experiments (n=36 and n=35). We presented emotionally negative (spiders) and neutral (wheels) silhouettes homogenized regarding their visual parameters. In Experiment 1, stimuli appeared at fixation or in the periphery (200 trials per condition and location), the former eliciting a N40 (39 milliseconds) and a P80 (or C1: 80 milliseconds) component, and the latter only a P80. In Experiment 2, stimuli were presented only at fixation (500 trials per condition). Again, a N40 (45 milliseconds) was observed, followed by a P100 (or P1: 105 milliseconds). Analyses revealed significantly greater N40-C1P1 peak-to-peak amplitudes for spiders in both experiments, and ANCOVAs showed that these effects were not explained by C1P1 alone, but that processes underlying N40 significantly contributed. Source analyses pointed to V1 as a N40 focus (more clearly in Experiment 2). Sources for C1P1 included V1 (P80) and V2/LOC (P80 and P100). These results and their timing point to low-order structures (such as visual thalamic nuclei or superior colliculi) or the visual cortex itself, as candidates for initial evaluation structures.
Ultra-low-field paediatric MRI in low- and middle-income countries: super-resolution using a multi-orientation U-Net
Authors: Baljer Levente , Zhang Yiqi , Bourke Niall J , Donald Kirsten A , Bradford Layla E , Ringshaw Jessica E , Williams Simone R , Deoni Sean CL , Williams Steven CR ,   Khula SA Study Team, Vasa Frantisek , Moran Rosalyn J
Published: February 2024

Owing to the high cost of modern MRI systems, their use in clinical care and neurodevelopmental research is limited to hospitals and universities in high income countries. Ultra-low-field systems with significantly lower scanning costs present a promising avenue towards global MRI accessibility, however their reduced SNR compared to 1.5 or 3T systems limits their applicability for research and clinical use. In this paper, we describe a deep learning-based super-resolution approach to generate high-resolution isotropic T2-weighted scans from low-resolution paediatric input scans. We train a multi-orientation U-Net, which uses multiple low-resolution anisotropic images acquired in orthogonal orientations to construct a super-resolved output. Our approach exhibits improved quality of outputs compared to current state-of-the-art methods for super-resolution of ultra-low-field scans in paediatric populations. Crucially for paediatric development, our approach improves reconstruction of deep brain structures with the greatest improvement in volume estimates of the caudate, where our model improves upon the state-of-the-art in: linear correlation (r = 0.94 vs 0.84 using existing methods), exact agreement (Lins concordance correlation = 0.94 vs 0.80) and mean error (0.05 cm3 vs 0.36 cm3). Our research serves as proof-of-principle of the viability of training deep-learning based super-resolution models for use in neurodevelopmental research and presents the first model trained exclusively on paired ultra-low-field and high-field data from infants.
Intrinsic structural covariation links cerebellum subregions to the cerebral cortex
Authors: Wang Zilong , Diedrichsen Jörn , Saltoun Karin , Steele Christopher , Arnold-Anteraper Sheeba Rani , Yeo B.T. Thomas , Schmahmann Jeremy , Bzdok Danilo
Published: February 2024

The human cerebellum is increasingly recognized to be involved in non-motor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole-brain exploration with a unified analytical framework. Here, we characterized disso-ciable cortical-cerebellar structural covariation patterns across the brain in n=38,527 UK Bio-bank participants. Our results invigorate previous observations in that important shares of corti-cal-cerebellar structural covariation are described as i) a dissociation between the higher-level cognitive system and lower-level sensorimotor system, as well as ii) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neurosci-ence view paves the way for future studies to explore the implications of these structural covaria-tions, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.
Longitudinal study of neurochemical, volumetric and behavioral changes in Q140 & BACHD mouse models of Huntington’s disease
Authors: Zacharoff Lori , Tkac Ivan , Shapiro Alexander , Henry Pierre-Gilles , Dubinsky Janet M
Published: February 2024

Brain metabolites, detectable by magnetic resonance spectroscopy (MRS), have been examined as potential biomarkers in Huntington’s Disease (HD). In this study, the RQ140 and BACHD transgenic mouse models of HD were used to investigate the relative sensitivity of the metabolite profiling and the brain volumetry to characterize mouse HD. Magnetic resonance imaging (MRI) and 1H MRS data were acquired at 9.4 T from the transgenic mice and wild-type littermates every 3 months until death. Brain shrinkage was detectable in striatum of both mouse models at 12 months compared to littermates. In Q140 mice, increases in PCr and Gln occurred in striatum prior to cortex. Myo-inositol was significantly elevated in both regions from an early age. Lac, Ala and PE decreased in Q140 striatum. Tau increased in Q140 cortex. Metabolite changes in the BACHD cortex and striatum were minimal with a striatal decrease in Lac being most prominent, consistent with a dearth of ubiquitin and 1C2 positive aggregates detected in those regions. Binary logistical regression models generated from the Q140 metabolite data were able to predict the presence of disease in the BACHD striatal and previously published R6/2 metabolite data. Thus, neurochemical changes precede volume shrinkage and become potential biomarkers for HD mouse models

Introduction
In vivo timelapse imaging and analysis of Golgi satellite organelle distribution and movement in the neural progenitor cells of the brain
Authors: Arellano Lindsay D , Bestman Jennifer E
Published: February 2024

The dividing stem cells of the developing brain are the radial glial neural progenitor cells (NPCs), multifunctional cells that proliferate to generate all of the cells of the brain, but also act as scaffolds for their migrating neuron progeny, guideposts for pathfinding growing axons and regulators of synaptic activity. These remarkable cells perform these very different activities while remaining in contact with the inner and outer surface of the ever-growing brain. NPCs synthesize proteins locally to support the compartmentalized protein expression required for the cells to perform their specialized functions, but it is not clear how the necessary processing that normally occurs in the Golgi apparatus is achieved at locations far from the cell body. Golgi satellites, motile organelles and members of the protein maturation machinery, control protein glycosylation and maturation in polarized cells like neurons. To investigate whether NPCs also rely on Golgi satellites, we expressed a fluorescent reporter to label Golgi satellites in the NPCs in the intact brains ofXenopus laevistadpoles. Quantitative analysis ofin vivotimelapse images revealed dynamic, motile Golgi satellites that distribute throughout the cell, suggesting that NPCs have local proteostasis to support their diverse functions.
Gene–Dose–Dependent ReductionFshrExpression Improves Spatial Memory Deficits in Alzheimer’s Mice
Authors: Korkmaz Funda , Sims Steven , Sen Fazilet , Sultana Farhath , Laurencin Victoria , Cullen Liam , Pallapati Anusha , Liu Avi , Rojekar Satish , Penev George , Cheliadinova Ulliana , Vasilyeva Darya , Burganova Guzel , Macdonald Anne , Saxena Mansi , Goosens Ki , Rosen Clifford , Barak Orly , Lizneva Daria , Gumerova Anisa , Ye Keqiang , Ryu Vitaly , Yuen Tony , Frolinger Tal , Zaidi Mone
Published: February 2024

Alzheimer’s disease (AD) is a major progressive neurodegenerative disorder of the aging population. High post–menopausal levels of the pituitary gonadotropin follicle–stimulating hormone (FSH) are strongly associated with the onset of AD, and we have shown recently that FSH directly activates the hippocampalFshrto drive AD–like pathology and memory loss in mice. To establish a role for FSH in memory loss, we used female3xTg;Fshr+/+, 3xTg;Fshr+/–and3xTg;Fshr-/-mice that were either left unoperated or underwent sham surgery or ovariectomy at 8 weeks of age. Unoperated and sham–operated3xTg;Fshr-/-mice were implanted with 17β-estradiol pellets to normalize estradiol levels. Morris Water Maze and Novel Object Recognition behavioral tests were performed to study deficits in spatial and recognition memory, respectively, and to examine the effects ofFshrdepletion.3xTg;Fshr+/+mice displayed impaired spatial memory at 5 months of age; both the acquisition and retrieval of the memory were ameliorated in3xTg;Fshr-/-mice and, to a lesser extent, in3xTg;Fshr+/-mice–– thus documenting a clear gene–dose–dependent prevention of hippocampal–dependent spatial memory impairment. At 5 and 10 months, sham–operated3xTg;Fshr-/-mice showed better memory performance during the acquisition and/or retrieval phases, suggesting thatFshrdeletion prevented the progression of spatial memory deficits with age. However, this prevention was not seen when mice were ovariectomized, except in the 10–month–old3xTg;Fshr-/-mice. In the Novel Object Recognition test performed at 10 months, all groups of mice, except ovariectomized3xTg;Fshr-/-mice showed a loss of recognition memory. Consistent with the neurobehavioral data, there was a gene–dose–dependent reduction mainly in the amyloid β40 isoform in whole brain extracts. Finally, serum FSH levels <8 ng/mL in 16–month–oldAPP/PS1mice were associated with better retrieval of spatial memory. Collectively, the data provide compelling genetic evidence for a protective effect of inhibiting FSH signaling on the progression of spatial and recognition memory deficits in mice, and lay a firm foundation for the use of an FSH–blocking agent for the early prevention of cognitive decline in postmenopausal women.