bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation
Authors: Smith Ley Cody , Abramova Elena , Vayas Kinal , Rodriguez Jessica , Gelfand-Titiyevksiy Benjamin , Roepke Troy A , Laskin Jeffrey D , Gow Andrew J , Laskin Debra L
Published: June 2024

Macrophages play a key role in ozone-induced lung injury by regulating both the initiation and resolution of inflammation. These distinct activities are mediated by pro-inflammatory and anti-inflammatory/proresolution macrophages which sequentially accumulate in injured tissues. Macrophage activation is dependent, in part, on intracellular metabolism. Herein, we used RNA-sequencing (seq) to identify signaling pathways regulating macrophage immunometabolic activity following exposure of mice to ozone (0.8 ppm, 3 h) or air control. Analysis of lung macrophages using an Agilent Seahorse showed that inhalation of ozone increased macrophage glycolytic activity and oxidative phosphorylation at 24 and 72 h post-exposure. An increase in the percentage of macrophages in S phase of the cell cycle was observed 24 h post ozone. RNA-seq revealed significant enrichment of pathways involved in innate immune signaling and cytokine production among differentially expressed genes at both 24 and 72 h after ozone, whereas pathways involved in cell cycle regulation were upregulated at 24 h and intracellular metabolism at 72 h. An interaction network analysis identified tumor suppressor 53 (TP53), E2F family of transcription factors (E2Fs), cyclin-dependent kinase inhibitor 1A (CDKN1a/p21), and cyclin D1 (CCND1) as upstream regulators of cell cycle pathways at 24 h and TP53, nuclear receptor subfamily 4 group a member 1 (NR4A1/Nur77), and estrogen receptor alpha (ESR1/ERα) as central upstream regulators of mitochondrial respiration pathways at 72 h. To assess whether ERα regulates metabolic activity, we used ERα−/− mice. In both air and ozone-exposed mice, loss of ERα resulted in increases in glycolytic capacity and glycolytic reserve in lung macrophages with no effect on mitochondrial oxidative phosphorylation. Taken together, these results highlight the complex interaction between cell cycle, intracellular metabolism, and macrophage activation which may be important in the initiation and resolution of inflammation following ozone exposure.
Perianal Ulcers from Antihemorrhoidal Ointment: A Case Report and Literature Review
Authors: García-Irigoyen Alejandro , Guzmán-Bucio Simón , Molina-López Juan Francisco , Vega-Memije María Elisa , Platonoff Adriana Lozano
Published: June 2024

Perianal ulcers (PAUs) related to antihemorrhoidal product use have been recently reported in the literature through a few case reports. However, other etiologies of PAU must be ruled out, including infectious disease, inflammatory disease, malignancy, pressure injuries, radiotherapy, and other topical drugs. In this report, the authors describe two cases of PAUs due to an antihemorrhoidal ointment. In case 1, a 68-year-old woman with a history of hemorrhoids presented with PAUs after using an antihemorrhoidal ointment for 2 months. The ulcers were assessed through a histopathologic study and treated with calcium alginate dressings, with complete re-epithelialization occurring after 2 months. In case 2, a 58-year-old woman with a history of hemorrhoids developed painful PAUs while using an antihemorrhoidal ointment for 2 months. No other probable cause was found, and the ulcers were treated by discontinuing the ointment. The ulcers showed marked improvement, and complete re-epithelialization occurred after 6 weeks without additional treatment.
Impact of Lymphedema on Foot-Health-Related Quality of Life: A Case-Control Investigation
Authors: Monteiro Ana Júlia , de Labra Carmen , Losa-Iglesias Marta Elena , Dias Adriano , Becerro-de-Bengoa-Vallejo Ricardo , Silva-Migueis Helena , Nuno Sérgio Loureiro , López-López Daniel , Gómez-Salgado Juan
Published: June 2024

OBJECTIVE

To evaluate the foot-health-related quality of life in individuals with versus without lower-limb lymphedema.

METHODS

A case-control study was carried out in an academic clinic in Lisbon, Portugal. Eighty participants (40 controls and 40 with lymphedema) were included in the study. The researchers examined sociodemographic and clinical data and foot-health-related quality of life in both groups. In the group with lymphedema, lower-limb lymphedema was also characterized.

RESULTS

Individuals with lower-limb lymphedema had significantly lower scores on all dimensions of the Foot Health Status Questionnaire in comparison with the control group.

CONCLUSIONS

Individuals with lower-limb lymphedema appear to have a poorer foot-health-related quality of life than the general population.
Repairing Exposed Tendon Wounds with Absorbable Gelatin Sponges and Autologous Split-Thickness Skin Grafts: A Case Series
Authors: Jing Gang , Wang LinLin
Published: June 2024

Conventional flap repair surgery has several drawbacks, including operational complexity, donor site damage, and high risk. In this case series, the authors explored an alternative approach for repairing exposed tendon wounds caused by trauma using absorbable gelatin sponges (AGSs) and autologous thigh skin grafts. This report presents two cases of lower-extremity skin necrosis with tendon exposure following wound debridement. The treatment approach involved early debridement, negative-pressure wound therapy, and wound irrigation with 0.9% sodium chloride. Upon achieving controlled wound infection, AGSs were applied to the exposed tendon to prevent degeneration and promote wound healing. Subsequently, areas where granulation tissue failed to cover the tendon were repaired using AGSs and 0.25-mm-thick autologous mesh skin grafts harvested from the thigh. Complete wound healing was achieved in both cases, on the 20th and 12th day after skin grafting, respectively. The proposed method proved successful in repairing exposed tendon wounds, effectively preventing infection and necrosis.
Is YouTube a Useful Source of Information on Pressure Injuries? A Content, Reliability, and Quality Analysis
Authors: Dünya Cansu Polat , Kara Öykü , Yiğitoğlu Eylem Toğluk
Published: June 2024

OBJECTIVE

To evaluate the comprehensiveness, reliability, and quality of YouTube videos related to pressure injuries.

METHODS

The authors searched YouTube for relevant videos using the keywords “pressure injury”, “pressure ulcer”, “bedsore”, “pressure injury etiology”, “pressure injury classification”, “pressure injury prevention”, “pressure injury risk assessment”, and “pressure injury management”. Of the 1,023 videos screened, 269 met the inclusion criteria and were included in the study. For each video, the authors recorded the number of views, likes, and comments; the length; and the video upload source. The Comprehensiveness Assessment Tool for Pressure Injuries, the Quality Criteria for Consumer Health Information score, and the Global Quality Score were used to evaluate the comprehensiveness, reliability, and quality of the videos.

RESULTS

The mean length of the 269 videos was 6.22 ± 4.62 minutes (range, 0.18-19.47 minutes). Only 14.5% of the videos (n = 39) were uploaded by universities or professional organizations. Most videos included information about PI prevention (69.5%), followed by PI management (27.9%). The mean comprehensiveness score was 2.33 ± 1.32 (range, 1-5). Nearly half of the videos (49.1%) were not reliable. However, the quality of 43.9% of the videos was somewhat useful. The Quality Criteria for Consumer Health Information mean scores of universities/professional organizations (P < .001), nonprofit healthcare professionals (P = .015), and independent health information channel videos (P = .026) were higher than the mean score of medical advertising/profit companies channel videos.

CONCLUSIONS

This study draws attention to the need for more comprehensive, high-quality, and reliable videos about PIs. It is important that videos on YouTube provide comprehensive and reliable information for patients, caregivers, students, or providers seeking information on PI prevention, assessment, and management.
Prevalence, number of fractures, and hospital characteristics among the pediatric population with osteogenesis imperfecta: results from the nationwide registry of Türkiye
Authors: Görgün Bariş , Yaşar Niyazi Erdem , Bingöl İzzet , Dumlupinar Ebru , Ata Naim , Ülgü M. Mahir , Birinci Şuayip , Bayram Sinem , Özdemir Güzelali
Published: June 2024

Objective

Osteogenesis imperfecta is a rare connective tissue disorder with an estimated number of 4–20 cases per 100 000 inhabitants. Although the prevalence differs among regions, there are only a few number of national registry studies published previously. The aim of this study was to determine the prevalence of osteogenesis imperfecta among the pediatric age group in Türkiye, together with the patient and hospital characteristics.

Methods

Via the e-health database of the Turkish Ministry of Health, we collected and retrospectively evaluated the medical records of the patients who were under 18 years of age with the diagnosis of osteogenesis imperfecta between 2016 and 2022. Total number of fractures, treatment modalities, and the hospital characteristics were also recorded. Two thousand seven hundred forty patients were extracted with a mean age of 9.77 ± 4.81 years.

Results

The prevalence of osteogenesis imperfecta in Türkiye among the pediatric population was calculated as 11.6 per 100 000 individuals. The median annual incidence was 31.5 per 100 000 live births between 2016 and 2022. There were 17.4 hospital admissions per patient per year. The mean age at the time of in-hospital mortality was 4.08 ± 5.03 years. The fracture rate per patient per year was 0.56 and conservative treatment was the most commonly preferred modality for all ages.

Conclusion

This is the first registry-based nationwide study of osteogenesis imperfecta patients in Türkiye, providing important characteristics of the disease. Together with the help of the ongoing development of national health database systems, precision in patient identification would yield substantial benefits in terms of management of osteogenesis imperfecta.
Wilms’ Tumor 1-Associating Protein Promotes Nonsmall-Cell Lung Cancer Through the Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5
Authors: Liu Changjiang , Gao Feng , Yang Jie , Liu Chengang , Tian Ziqiang
Published: June 2024

Objective:

This study aimed to analyze the functional roles and molecular mechanism of Wilms’ tumor 1-associating protein (WTAP) in the tumorigenesis of nonsmall-cell lung cancer (NSCLC).

Methods:

Retrospective analysis was used. Tumor tissues and surrounding nontumor tissues of 150 patients with NSCLS who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2016 to January 2018 were selected. The expression of WTAP in NSCLC tissues was detected by immunohistochemistry. Clinicopathologic parameters were then subjected to univariate and multivariate Cox regression analysis in purpose of uncovering the independent risk factors for overall survival time. MTS (3-[4,5-dimethylthiazol-zyl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazoliuzolium, inner salt) assay, colony formation assay, and transwell assays were performed to estimate cell proliferation, migration, and invasion. Meanwhile, the relationship between WTAP and the cell migration and invasion marker-related proteins were evaluated by Western blot analysis and RT-qPCR. WTAP expression was knocked-down in cell lines by shRNA, and RNA-Seq was performed to investigate the pathways regulated by WTAP.

Results:

In NSCLC patients, WTAP was highly expressed in tumor tissues and the higher expression was significantly associated with poor overall survival (OS) (P<0.01). Compared with the control group in vitro, the overexpression of WTAP could significantly promote cell proliferation, migration, and invasion (P<0.01), while knock-down WTAP significantly reduces the above effects (P<0.01). In a mouse orthotopic implantation model, higher WTAP abundance could significantly promote tumor enlargement compared with the control group (P<0.01). Compared with the control group, the knock-down of WTAP significantly inhibit the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in cell lines (P<0.01). Besides, in NSCLC, knocked-down CEACAM5 significantly reduced the impact of WTAP on cell proliferation, migration, and invasion compared with the control group (P<0.05).

Conclusions:

This study suggests that high expression of WTAP was associated with poor clinical outcomes. CEACAM5 may play a synergistic role with WTAP to jointly promote NSCLC progression by enhancing cell proliferation, invasion, and migration.
Real-world Implications of Botulinum Neurotoxin A Immunoresistance for Consumers and Aesthetic Practitioners: Insights from ASCEND Multidisciplinary Panel
Authors: Corduff Niamh , Park Je-Young , Calderon Pacifico E. , Choi Hosung , Dingley Mary , Ho Wilson W. S. , Martin Michael U. , Suseno Lis S. , Tseng Fang-Wen , Vachiramon Vasanop , Wanitphakdeedecha Rungsima , Yu Jonathan N. T.
Published: June 2024

Background:

As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals’ (HCPs’) perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient’s viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey.

Methods:

A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants’ BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey.

Results:

Aesthetic BoNT-A patients’ depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed.

Conclusion:

These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.
Fragility Index and Fragility Quotient in Statistically Significant Randomized Controlled Trials in Plastic Breast Surgery
Authors: Skorochod Ron , Gronovich Yoav
Published: June 2024

Background:

The fragility index (FI) was conceived as an adjunct to the P value, signifying the strength of statistically significant results. The index states the minimal number of patients whose outcome must be changed from “event” to “nonevent” for the results to be statistically nonsignificant. The FI was applied in various medical specialties to assess the robustness of results presented in studies. We aim to assess the robustness of statistically significant results in studies on plastic surgery of the breast and determine factors correlated with studies deemed fragile.

Methods:

A systematic literature review of PubMed databases using designated keywords was performed. Background characteristics were extracted from the studies, alongside the significance of outcomes. FI and fragility quotient were calculated for each analyzed outcome and correlated with various baseline characteristics.

Results:

FI and fragility quotient were both significantly correlated only with the P value of the analyzed outcomes. However, grouping studies based on the P value into three categories did not demonstrate a difference in FI. Comparisons of fragile and robust studies did not demonstrate a statistically significant change in terms of baseline variables, except for the mean P value of the outcome.

Conclusion:

Statistically significant results of randomized controlled trials in plastic surgery of the breast suffer from extensive fragility, and researchers should critically implement their conclusions in their practice.
Subclinical valve leaflet thrombosis following bioprosthetic aortic valve replacement
Authors: Giuliani Carlos , Zanuttini Antonela , Salaun Erwan , Côté Nancy , Clavel Marie Annick , Pibarot Philippe
Published: June 2024

Purpose of review

Subclinical leaflet thrombosis (SLT) is often an incidental finding characterized by a thin layer of thrombus involving one, two or three leaflets, with typical appearance on multi-detector computed tomography (MDCT) of hypo-attenuating defect at the aortic side of the leaflet, also called hypo-attenuating leaflet thickening (HALT). SLT may occur following both transcatheter aortic replacement (TAVR) or biological surgical aortic valve replacement (SAVR). The aim of this review is to present an overview of the current state of knowledge on the incidence, diagnosis, clinical impact, and management of SLT following TAVR or SAVR.

Recent findings

SLT occurs in 10–20% of patients following TAVR and is somewhat more frequent than following SAVR (5–15%). SLT may regress spontaneously without treatment in about 50% of the cases but may also progress to clinically significant valve thrombosis in some cases. Oral anticoagulation with vitamin K antagonist is reasonable if SLT is detected by echocardiography and/or MDCT during follow-up and is generally efficient to reverse SLT. SLT is associated with mild increase in the risk of stroke but has no impact on survival. SLT has been linked with accelerated structural valve deterioration and may thus impact valve durability and long-term outcomes.

SLT is often an incidental finding on echocardiography or MDCT that occurs in 10–20% of patients following TAVR or 5–15% following biological SAVR and is associated with a mild increase in the risk of thrombo-embolic event with no significant impact on mortality but may be associated with reduced valve durability.
Challenges in the Treatment of Psychotic Bipolar Depression
Authors: Cintrón Pastrana Maité A. , Irizarry Flores Jessica C. , Rothschild Anthony J.
Published: June 2024

Background

Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration–approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD.

Methods

We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD.

Findings

PBD is a complex disorder, with 50%–75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary.

Conclusion

PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.
Deutetrabenazine Provides Long-Term Benefit for Tardive Dyskinesia Regardless of Underlying Condition and Dopamine Receptor Antagonist Use
Authors: Hauser Robert A. , Barkay Hadas , Fernandez Hubert H. , Jimenez-Shahed Joohi , Factor Stewart A. , Gross Nicholas , Marinelli Leslie , Gordon Mark Forrest , Barash Steve , Finkbeiner Stacy , Chaijale Nayla , Anderson Karen E.
Published: June 2024

Background

Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.

Methods

Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent study baseline.

Results

Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this study baseline to week 145 were −6.3 (4.53), −7.1 (4.92), −6.1 (4.42), and −7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05).

Conclusions

Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.
Celiac disease and nonceliac enteropathies
Authors: Doyle John B. , Lebwohl Benjamin
Published: June 2024

Purpose of review

This review highlights recent research in the field of celiac disease.

Recent findings

Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition.

Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies.
Dyspnea and Palliative Care in Advanced Chronic Obstructive Pulmonary Disease
Authors: Miller Sarah N. , Higgins Elizabeth , Cain Joan , Coyne Patrick , Peacock Robert , Logan Ayaba , Fasolino Tracy , Lindell Kathleen Oare
Published: June 2024

Dyspnea is the most common and activity-limiting symptom for those with chronic obstructive pulmonary disease (COPD). Treatment is complex, palliative care (PC) dyspnea relief interventions are poorly understood, and PC remains underutilized in COPD despite national guidelines and recommendations. The purpose of this rapid review was to explore the concept of dyspnea and role of PC through the lens of providers, caregivers, and patients with COPD. A systematic approach for synthesis was used to identify 13 articles published between January 2018 and October 2023. Team members compared data via visualization and theme clustering to identify key conclusions describing operationalization of dyspnea, management, and PC implications. Dyspnea operationalization was challenging, with inconsistent measurement and terminology. Dyspnea was a significant burden in COPD and contributed to complexity of treatment. Opioids were used most often to treat dyspnea, but provider perspectives and biases can influence treatment decisions and perceptions of opioid therapy by the patient and caregiver. Evidence-based clinical practice guidelines and policies are needed to clarify the use of opioid therapy for dyspnea management to reduce stigmatization and barriers to treatment. Provider education should emphasize a multipronged approach to treatment of dyspnea in COPD with integration of PC early in the care continuum.
Evaluating the Impact of Self-Care Strategies Incorporated in Undergraduate and Graduate Nursing Curricula
Authors: Fairchild Roseanne Moody , Tully Salena
Published: June 2024

Background:

Evidence demonstrates professional nurses’ vital need for self-care, underscoring the necessity to support the integration of self-care behaviors in nursing education.

Purpose:

The aim was to synthesize the impact of self-care strategies in nursing curricula to evaluate students’ experiential, evidence-based outcomes.

Methods:

A systematic review was conducted to examine interventional self-care studies in undergraduate and graduate nursing curricula published in the English language from 2018 to 2023. Searches were conducted between June 1, 2023, and July 12, 2023, in MEDLINE, PsycINFO, CINAHL, ProQuest, and PubMed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, yielding 20 peer-reviewed articles. Studies were evaluated for quality utilizing Medical Education Research Study Quality Instrument scoring; each author examined results independently to ensure rigor and mitigate bias.

Results:

Notable increases were observed regarding students’ recognition of self-care needs across a variety of curricular methodologies and self-care strategies.

Conclusions:

Evidence is mounting to substantiate curricular integration of self-care strategies in nursing education; further research of a robust nature is needed to refine curricular approaches.
Development and Validation of the GAASThyriC Model for Predicting Patients with Suboptimal Clinical Response After Laparoscopic Sleeve Gastrectomy and a Practical Calculator: A Retrospective Cohort Study
Authors: Demirpolat Muhammed Taha , İslam Mehmet Muzaffer
Published: June 2024

Background:

It might not be possible to achieve the desired outcome in every patient following bariatric surgery, even though every patient is thoroughly examined before surgery. This study aimed to develop a regression model based on parameters that affect weight loss success in patients scheduled for laparoscopic sleeve gastrectomy (LSG) and thus preoperatively predict whether the patients will have an optimal clinical response in terms of weight loss at the end of the first year.

Materials and Methods:

Between January 2018 and August 2022, patients who underwent LSG were analyzed retrospectively. Age, sex, comorbidities, smoking status, alcohol use status, preoperative weight, preoperative body mass index (BMI), preoperative laboratory data, weight, and total weight loss (TWL)% values at the end of the first year were recorded. At the end of the first year following LSG, patients with TWL% above 20% were defined as having an optimal clinical response in terms of weight loss. This study is designed, conducted, and reported regarding the “transparent reporting of a multivariable prediction model for individual prognosis or diagnosis” (TRIPOD) statement. The final model was used to construct an Excel-based calculator.

Results:

Four hundred thirty-eight patients underwent the sleeve gastrectomy procedure, and 38 of them were excluded from the study because of a lack of 1-year follow-up information, resulting in 400 eligible patients for our study. Age, glucose, thyroid stimulating hormone (TSH), alcohol consumption, systemic immune inflammation index (SII), and tobacco were the independent predictors of optimal clinical response (P<0.001, P<0.001, P<0.001, P=0.011, P=0.039, P=0.045, respectively). The model was called the GAASThyriC score. When the final model was tested in the validation cohort, the AUC was 0.875 (95% CI, 0.742-0.999), the sensitivity was 83.3% (95% CI, 51.6-97.9), specificity was 86.4% (95% CI, 77.4-92.8), negative likelihood ratio was 0.19 (95% CI, 0.05-0.68), and accuracy was 86% (95% CI, 77.6-92.1) when the cutoff value was set to the optimal threshold (logit = 0.8451).

Conclusion:

The GAASThyriC score can be used as an effective auxiliary tool to predict the patient population with suboptimal clinical response in terms of TWL% at the end of the first year after LSG.
Free-listing and Semantic Knowledge: A Tool for Detecting Alzheimer Disease?
Authors: Ulep Maileen G. , Liénard Pierre
Published: June 2024

Background:

Impairment in semantic knowledge contributes to Alzheimer disease (AD)-related decline. However, the particulars of the impact AD has on specific domains of knowledge remain debatable.

Objective:

To investigate the impact of AD on specific semantic categories that are integral to daily functions—living things and man-made objects.

Method:

We administered a free-listing task (written version) to 19 individuals with AD and 15 cognitively normal older adults and assessed the task’s relationship with other cognitive and functional tests in clinical use. We compared the contents of the lists of salient concepts generated by the AD and control groups.

Results:

Group membership (AD or control), after controlling for age, sex, formal education, and an estimate of premorbid intellectual ability, predicted the groups’ performance on the free-listing task across two categories. Functional status was inversely related to performance on the free-listing task, holding demographic variables constant. Based on a comparison of the contents of the free lists that were generated by the two groups, it was possible to conclude that, in individuals with AD, conceptual knowledge central to the respective categories was well preserved, whereas the peripheral conceptual material showed evidence of degradation.

Conclusion:

The free-listing task, which is an easy-to-administer and cost-effective tool, could aid in the preliminary detection of semantic knowledge dysfunction, revealing concepts that are better preserved and, possibly, the characterization of AD. Cognitive assessment tools that can be applied across cultures are needed, and the free-listing task has the potential to address this gap.
Group A streptococcus isolated in Guyana with reduced susceptibility to β-lactam antibiotics
Authors: Kalladeen Melissa , Cheddie Paul , Akpaka Patrick Eberechi
Published: June 2024

Introduction.
Streptococcus pyogenes [group A streptococci (GAS)] is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS), and necrotising fasciitis. Although the prevalence of GAS infections globally remains high, necessitating the widespread use of β-lactam antibiotics, GAS have remained largely susceptible to these agents. However, there have been several reports of GAS with reduced susceptibility harbouring mutations in genes for penicillin-binding proteins (PBPs). The objectives of this study were to examine the in vitro β-lactam susceptibility patterns of group A streptococci, determine the prevalence of drug resistance, and ascertain whether such resistance could be attributed to mutations in specific PBP genes.

Methods. In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from patients that required inpatient and outpatient care that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips.

Results. While there were no documented cases of reduced susceptibility to penicillin or amoxicillin, 13 isolates had reduced susceptibility to cefazolin. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first-generation cephalosporins.

Conclusion. Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.
Trends and antibiotic susceptibility patterns of diarrhoeal pathogens - an experience of fourteen years in Southern India
Authors: Mohanty Ankita , Lakra Nayannika , Mandal Jharna
Published: June 2024

INTRODUCTION:
Enteric pathogens contribute largely to morbidity in a developing country like India. Early and prompt diagnosis of diarrhoeal diseases can reduce the mortality rate, particularly in children.  The pattern of sensitivity to antimicrobials for the common pathogens can vary from time to time. The present study was conducted to study the pathogen distribution and antimicrobial susceptibility pattern during the study period (January 2010 to December 2023).
HYPOTHESIS/GAP STATEMENT: Studying the changing trend in the antimicrobial sensitivity pattern of diarrhoeal pathogens over a decade can help to plan future treatment options.
AIM: This study was undertaken to provide insight into the changing pattern of pathogen distribution and antimicrobial susceptibility of enteric pathogens over 14 years.
METHODS: A retrospective observational cohort analysis was conducted on all the stool pathogens isolated from the samples received in the Microbiology department of a tertiary care hospital from the year 2010 to 2023. The demographic details, stool microscopy, culture reports, and antimicrobial susceptibility patterns were noted.
RESULTS:  A total of 18336 stool specimens were received in the Microbiology laboratory between January 2010 to December 2023, of which 1354 specimens had diarrhoeal pathogens grown in culture. Out of these 1354 specimens, 591(44%)had Salmonella, 471 (35%) Shigella,181 (13%)Vibrio cholerae, and 80(6%) had Aeromonas species. Among these pathogens, susceptibility to Ceftriaxone was seen in 93% (552 isolates) of Salmonella species, 89% (420 isolates) of Shigella species, and in 95 %(171 isolates) of Vibriocholerae; 91%(73 isolates) of Aeromonas species were susceptible to Chloramphenicol. Some major parasites were also observed on microscopy.
CONCLUSION: Timely diagnosis of diarrhoeal pathogens can be life-saving for patients belonging to extremes of age. Pathogens can exhibit a changing susceptibility pattern to antibiotics which should be regularly observed to plan future therapy.
Gut-resident C. perfringens impedes rotavirus vaccine efficacy
Authors: Ngo Vu L. , Wang Yanling , Shi Zhenda , Ramani Sasirekha , Jiang Baoming , T. Gewirtz Andrew
Published: June 2024

Background & Aims

The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy.

Methods

We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.Influence of human microbiomes on RV vaccination was studied via administering germ-free mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to vaccination and challenge doses of RV.

Results

SFB administration resulted in a phenotype reminiscent of RV vaccine failure, i.e. minimal generation of RV antigens and, consequently, lack of anti-RV antibodies resulting in proneness to RV challenge once SFB levels diminished. Transplant of microbiomes from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responding children exhibited high levels of fecal RV antigen shedding and RV antibodies in response to RV vaccination and, concomitantly, were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV challenge and, accordingly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested that RV vaccine failure might involveClostridium perfringens. Oral administration of culturedC. perfringensto gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of previously-reported microbiome data found C. perfringens abundance in children associated with RV vaccine failure.

Conclusion

Microbiota composition influences RV vaccine virus infection and, consequently, protective immunity.C. perfringensmay be one, perhaps of many, bacterial species harbored in the intestine of RV-vaccine non-responders that influences RV vaccine outcomes.
Effect of Hexane and Methanol Extracts ofPiper guineense(Schum and Thonn) Seeds against the Larger grain borer (Prostephanus truncatus) in Stored Cassava Chips
Authors: Odii Emmanuel , Okonkwo Nnaemeka Joe , Uko Ibeabuchi
Published: June 2024

Methanolic and hexane extract of black pepperPiper guineenseSchum & Thonn was evaluated for its insecticidal property against the larger grain borerProstephanus truncatusin stored cassava chips. The extracts were applied at various concentrations (4000, 2000, 1000, 500, 250µl/ml) with ordinary acetone as control. The experimental setup involved placing ten unsexed adults of the test insect into petri dishes treated with each of the extracts as applicable. Also, cassava chips weighing twenty grams were treated with the different concentrations of the extracts and the control before being artificially infested withProstephanus truncatusand left for a period of thirty-three days. All of the treatments significantly reduced emergence holes and grain damage compared with the control.
Synaptic Organization-Function Relationships of Amygdala Interneurons Supporting Associative Learning
Authors: Báldi Rita , Muthuswamy Sunil , Loomba Niharika , Patel Sachin
Published: June 2024

Coordinated activity of basolateral amygdala (BLA) GABAergic interneurons (INs) and glutamatergic principal cells (PCs) is critical for associative learning, however the microcircuit organization-function relationships of distinct IN classes remain uncertain. Here, we show somatostatin (SOM) INs provide inhibition onto, and are excited by, local PCs, whereas vasoactive intestinal peptide (VIP) INs are driven by extrinsic afferents. Parvalbumin (PV) INs inhibit PCs and are activated by local and extrinsic inputs. Thus, SOM and VIP INs exhibit complementary roles in feedback and feedforward inhibition, respectively, while PV INs contribute to both microcircuit motifs. Functionally, each IN subtype reveals unique activity patterns across fear- and extinction learning with SOM and VIP INs showing most divergent characteristics, and PV INs display an intermediate phenotype parallelling synaptic data. Finally, SOM and PV INs dynamically track behavioral state transitions across learning. These data provide insight into the synaptic microcircuit organization-function relationships of distinct BLA IN classes.
The appropriateness of empirical antibiotic therapy in the management of symptomatic urinary tract infection patients-A cross sectional study in Nairobi County, Kenya
Authors: Onyango Hellen A. , Sloan Derek J , Keenan Katherine , Kesby Mike , Ngugi Caroline , Gitonga Humphrey , Hammond Robert
Published: June 2024

Background

In low- and- middle income countries, symptomatic urinary tract infection (UTI) patients are often prescribed antibiotics without microbiological confirmation. UTIs caused by antibiotic resistant bacteria are increasingly common and this heightens the risk of empirical treatment failure. This study evaluates the appropriateness of empirical antibiotic therapy to symptomatic UTI patients.

Methods

A hospital-based, cross-sectional study was conducted in Nairobi County, Kenya among symptomatic adult and child patients. UTI was defined as a monoculture growth with colony counts of ≥104. cfu/ml. Antimicrobial susceptibility testing (AST) was performed by the Kirby-Bauer disc diffusion method. Empirical therapy was considered appropriate if the pathogen isolated was susceptible to the prescribed antibiotic and inappropriate if pathogen was resistant to prescribed antibiotic.

Results

A total of 552 participants were enrolled with a median age of 29 years (IQR:24-36). The majority were female; 398 (72%). Of the 552, 274 (50%) received empirical antibiotic therapy, 95/274 (35%) were confirmed to have UTI by culture. The antibiotics most frequently prescribed were fluoroquinolones [ciprofloxacin in 80 (30%) and levofloxacin 43 (16%)], amoxicillin-clavulanic-acid in 48 (18%), and nitrofurantoin in 32 (12%). Amongst the 95 patients with bacteriological confirmation of UTI, 50 (53%) received appropriate empirical antibiotic therapy, whilst for 38 (40%) participants, the therapy was inappropriate. Appropriateness of empirical therapy to 7 (7%) patients could not be determined as the antibiotics prescribed were not in the AST panel.

Conclusion

The complexity of appropriate empirical treatment for UTIs is compounded by high levels of resistance in UTI pathogens. AMR surveillance strategies that could help in designing appropriate empirical regimens in resource constrained settings should be adopted for optimal empiric therapy.
Clinical and molecular characterization of the vinorelbine-platinum chemotherapeutic regimen in HER2(-) metastatic breast cancer
Authors: Ho I-Wei , Tseng Yi-Ru , Liu Chun-Yu , Tsai Yi-Fang , Huang Chi-Cheng , Tseng Ling-Ming , Chao Ta-Chung , Lai Jiun-I
Published: June 2024

Introduction

Despite rapidly improving therapeutics, challenges remain in treatment of advanced breast cancer. Vinorelbine, a semisynthetic vinca alkaloid, is effective and well-tolerated in breast cancer treatment. The combination of vinorelbine and platinum-combination is a well-tolerated but underreported chemotherapy regimen. Bevacizumab, a VEGF-neutralizing antibody, has shown efficacy in HER2-negative metastatic breast cancer (mBC) when combined with chemotherapy. In this study we aim to investigate the clinical and molecular effects of vinorelbine-platinum in heavily pretreated HER2-negative mBC, as well as the role of addition of bevacizumab.

Material and methods

We conducted a retrospective study at Taipei Veterans General Hospital to evaluate the effectiveness of the vinorelbine-platinum regimen in heavily pretreated HER2-negative mBC patients from 2016 to 2020, with a portion of patients receiving additional bevacizumab. To model the molecular perturbations at a cellular level, transcriptional profiling of a triple negative breast cancer cell line treated with cisplatin-vinorelbine was done by RNA-sequencing.

Results

The cohort included 54 patients. 50% of the patients received ≥ 5 lines of systemic treatment in the metastatic setting. All the patients had received anthracyclines and taxane. In patients treated with vinorelbine-platinum combination, the median progression-free survival (PFS) and overall survival (OS) were 2.3 and 7.3 months, respectively. With bevacizumab, median PFS improved to 4.1 months. Objective response rate (ORR) and disease control rate (DCR) without bevacizumab were 11.1% and 27.7%, respectively, improving to 25% and 83.3% with bevacizumab. Adverse events occurred in 37.0% of patients, with no grade IV events reported. Transcriptional profiling revealed significant downregulation of MAPK pathway, angiogenesis, and growth factor signaling related genes.

Conclusion

The vinorelbine-platinum regimen, particularly with bevacizumab, shows efficacy even in heavily pretreated HER2-negative metastatic breast cancer patients. Molecular analyses of treated cells highlight potential targets and mechanisms of action, providing a basis for future therapeutic strategies.
Quantum mechanics of composite fermions
Authors: Shi Junren
Published: June 2024

We establish the quantum mechanics of composite fermions based on the dipole picture initially proposed by Read. It comprises three complimentary components: a wave equation for determining the wave functions of a composite fermion in ideal fractional quantum Hall states and when subjected to external perturbations, a wave-function for mapping a many-body wave function of composite fermions to a physical wave function of electrons, and a microscopic approach for determining the effective Hamiltonian of the composite fermion. The wave equation resembles the ordinary Schrödinger equation but has drift velocity corrections that are not present in the Halperin-Lee-Read theory. The wave-function constructs a physical wave function of electrons by projecting a state of composite fermions onto a half-filled bosonic Laughlin state of vortices. Remarkably, Jain's wave-function can be reinterpreted as the new in an alternative wave-function representation of composite fermions. The dipole picture and the effective Hamiltonian can be derived from the microscopic model of interacting electrons confined in a Landau level, with all parameters determined. In this framework, we can construct the physical wave function of a fractional quantum Hall state deductively by solving the wave equation and applying the wave-function , based on the effective Hamiltonian derived from first principles, rather than relying on intuition or educated guesses. For ideal fractional quantum Hall states in the lowest Landau level, the approach reproduces the well-established results of the standard theory of composite fermions. We further demonstrate that the reformulated theory of composite fermions can be easily generalized for flat Chern bands.

Published by the American Physical Society
2024
Attosecond photoionization delays in molecules: The role of nuclear motion
Authors: Suñer-Rubio Adrián J. , Lemell Christoph , Bello Roger Y. , Burgdörfer Joachim , Palacios Alicia , Martín Fernando
Published: June 2024

Molecular photoionization delays are often analyzed by assuming that nuclei remain fixed during the ionization process since they move much more slowly than electrons. However, recent high-energy resolution and multicoincidence experiments have shown that nuclear motion can have a significant and visible effect on the measured ionization delays on the attosecond time scale. To analyze this behavior, we have chosen the simplest of all molecules, H2+, and performed nearly exact calculations of streaking and RABBIT (reconstruction of attosecond beatings by interferences in two-photon transitions) spectra by solving the time-dependent Schrödinger equation in full dimensionality, and retrieved the corresponding photoionization delays. We show that, when two-center effects are at play, nuclear motion is responsible for a substantial increase of the photoionization delays, in particular of the so-called continuum-continuum delays. The magnitude of such an increase is comparable to the absolute values of the measured delays.

Published by the American Physical Society
2024