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Background: [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with 177 Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival., Methods: Adults with progressive post androgen receptor pathway inhibitor and taxane prostate-specific membrane antigen (PSMA)-positive mCRPC received 177 Lu-PSMA-617 plus protocol-permitted standard of care (SoC) or SoC alone. In this post hoc analysis, multivariable Cox proportional hazards models of overall survival (OS) and radiographic progression-free survival (rPFS), and a logistic regression model of prostate-specific antigen response (≥50% decline; PSA50) were constructed and evaluated using C-index or receiver operating characteristic (ROC) analyses with bootstrapping validation. Nomograms were constructed for visualisation., Findings: Patients were randomised between June 2018 and October 2019. Data from all 551 patients in the 177 Lu-PSMA-617 arm were analysed in multivariable modelling. The OS nomogram (C-index, 0.73; 95% confidence interval [CI], 0.70-0.76) included whole-body maximum standardised uptake value (SUV max ), time since diagnosis, opioid analgesic use, aspartate aminotransferase, haemoglobin, lymphocyte count, presence of PSMA-positive lesions in lymph nodes, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and neutrophil count. The rPFS nomogram (C-index, 0.68; 0.65-0.72) included SUV max , time since diagnosis, opioid analgesic use, lymphocyte count, presence of liver metastases by computed tomography, LDH, and ALP. The PSA50 nomogram (area under ROC curve, 0.72; 95% CI, 0.68-0.77) included SUV max , lymphocyte count and ALP. Performances of the OS and rPFS models were maintained when they were reconstructed excluding SUV max ., Interpretation: These models of outcomes with 177 Lu-PSMA-617 are the first built using prospective phase 3 data. They show that a combination of pretreatment laboratory, clinical, and imaging parameters, reflecting both patient and tumour status, influences outcomes. These models are important for aiding treatment selection, patient management, and clinical trial design., Funding: Novartis., Competing Interests: KH reports receiving grants or contracts from Boston Scientific, Janssen, and Novartis; consulting fees from Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, Novartis, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, and ymabs; and stock or other ownership in AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences. JSdB reports receiving grants or contracts from Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi Aventis; consulting or advisory fees from Astellas, AstraZeneca, Bayer, Daiichi-Sankyo, Genentech/Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Orion, Pfizer, Sanofi Aventis, and Taiho; payment or honorarium from Astellas, AstraZeneca, Bayer, Cellcentric, Crecendo, Daiichi, Genentech, Genmab, GlaxoSmithKline, Janssen, Merck Serono, Mycrix, MSD, Orion, Pfizer, Sanofi Aventis, and Taiho; being an inventor on patent 8,822,438; participating on a data safety monitoring or advisory board for Amgen, AstraZeneca, Bayer, Bioxcel Therapeutics, Crescendo, Daiichi-Sankyo, Endocyte, Genentech/Roche, GlaxoSmithKline, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Oncternal, Pfizer, and Sanofi Aventis; and receiving institutional royalties or licenses related to abiraterone, PARP inhibitor, and PI3K/AKT. OS reports receiving support for the present manuscript from Novartis; institutional grants or contracts from Amgen, AstraZeneca, Bayer, Endocyte, Invitae, Janssen, Lantheus, Merck, Novartis, Progenics, and Tenebio; consulting fees from ARTBIO, AstraZeneca, Bayer, Blue Earth Diagnostics, Clarity Pharmaceuticals, Fusion, Isotopen Technologien Muenchen, Janssen, Merck, Myovant, Myriad, Noria Therapeutics, NorthStar, Novartis, Pfizer, POINT Biopharma, Sanofi, Telix, and Tenebio; travel and accommodation expenses from Lantheus, NorthStar, and Novartis; participation on a data safety monitoring or advisory board for AstraZeneca, Merck, and Pfizer; and stock or stock options in ARTBIO, Clarity Pharmaceuticals, Convergent, Fusion, Lilly, Pfizer, Ratio, and Telix. KNC reports receiving grants or contracts from AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche; and consulting fees from Astellas, AstraZeneca, Bayer, Janssen, Merck, Novartis, Pfizer, POINT Biopharma, and Roche. BJK reports receiving consultant or advisory fees from Bayer, Isotope Technologies Munich, and Novartis; and research funding from Novartis. KR reports receiving consultant fees from ABX, ABX-CRO, Amgen, Bayer Healthcare, Janssen Cilag, Novartis, and Sirtex; and lecture payments from AstraZeneca, Bayer Healthcare, Novartis, and Siemens Healthcare. STT reports receiving institutional fees from AbbVie, Ambrx, Amgen, Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Clarity, Clovis, Endocyte, Genentech, Gilead, Inovio, Janssen, Karyopharm, Medivation, Merck, Newlink, Novartis, POINT Biopharma, Rexahn, Sanofi, and Seattle Genetics; and consultant fees from AbbVie, Aikido Pharma, Ambrx, Amgen, Astellas, Bayer, Blue Earth, Clarity Pharma, Clovis, Convergent Therapeutics, Daiichi Sankyo, Eisai, EMD Serono, Genentech, Genomic Health, Janssen, Medivation, Merck, Myovant, Novartis, Pfizer, POINT Biopharma, Regeneron, Sanofi, Seattle Genetics, Telix, Tolmar, and TransThera. JC reports stock or other ownership interest in Sofie Biosciences, Inc., and Trethera; acting as an uncompensated founder for Trethera; and an uncompensated adviser for Amgen, Atkis Oncology, Jubilant Radiopharma, Novartis, POINT Biopharma, and RayzeBio. GEH reports receiving consultant fees from Bayer HealthCare, Boston Scientific Corporation, NorthStar Medical Radioisotopes, Novartis, and Terumo; and stock ownership in Johnson and Johnson. CCW reports employment and stock ownership with Novartis. ZZ reports previous employment and current stock ownership with Novartis. CW reports employment and stock ownership with Novartis. OM reports employment and stock ownership with Novartis. MJM reports receiving consulting or advisory fees from Amgen, AstraZeneca, Blue Earth Diagnostics, Clarity Pharmaceuticals, Convergent Therapeutics, Daiichi, ITM Isotope Technologies Munich, Lantheus Medical Imaging, Pfizer, POINT Biopharma, Progenics, Telix Pharmaceuticals, and Z-Alpha; stock and other ownership in Doximity; travel, accommodations, and expenses from APCCC, AstraZeneca, and Memorial Sloan-Kettering Cancer Center; institutional research funding from Astellas Pharma, Bayer, Celgene, Corcept Therapeutics, Janssen, Novartis, Progenics, and Roche/Genentech; patents pending with Novartis; and royalties from Telix. KF reports receiving institutional honorarium or payments to Gustave Roussy Institute from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, and Sanofi; institutional participation on data safety monitoring or advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, and Sanofi; and personal participation on a data safety monitoring or advisory board for Arvinas, CureVac, Macrogenics, Orion. No other potential conflict of interest relevant to this article was reported., (© 2024 The Authors.)

Rapamycin (sirolimus) is an FDA approved drug with immune modulating properties that is being prescribed off-label in adults as a preventative therapy to maintain healthspan. We recently published one of the first reports on 333 adults with a history of off-label rapamycin use. Along with presenting evidence that rapamycin can be used safely in adults of normal health status, we discovered that about 26% of rapamycin users also reported oral health changes. Given the recent evidence highlighting the potential benefits of rapamycin and its derivatives in enhancing oral health, we conducted a secondary data analysis to profile the oral health of off-label rapamycin users, the true incidence of mouth sores, and present specific case studies of periodontal bone loss quantification using an FDA-approved artificial intelligence platform. Contrary to expected findings and previous literature, dimensions of rapamycin usage (such as length of use, dosage, and interval) were not found to be related to the incidence of mouth ulcers in rapamycin users. Notably, among rapamycin users, the most deleterious forms of ulcers were found to be infrequent and not statistically linked to rapamycin usage, with most rapamycin users having a common transient form of mouth ulcers. Additionally, we describe the general oral health outcomes of off-label rapamycin users and provide recommendations for individuals engaging in off-label rapamycin to be regularly checked by a dentist or an oral health care provider. This report was limited by being a secondary data analysis taken from survey data that focused on a more holistic health model. Future studies will use a focused survey that collects data on more dimensions of oral health outcomes while including questions on oral health for non-rapamycin-using participants., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Objective: Our primary objective was to determine if there was a difference in success of cardiac visualization by focused transthoracic echocardiography (TTE) location (subxiphoid, parasternal, or apical) during chest compression interruptions among cardiac arrest patients. Secondarily, we sought to determine whether there were differences in chest compression interruption times with the focused TTE locations., Methods: We conducted a retrospective cohort study of video-recorded, adult, cardiac arrest resuscitations in a quaternary care Emergency Department from 11/2018 to 11/2023. Focused TTE was successful if 1) cardiac visualization was seen on video review, or 2) cardiac visualization was discussed in the recording. A chi-squared test was used to assess differences in success and ANOVA was used to assess differences in interruption times based on TTE locations. Repeated measures multivariable regression models were constructed to control for clinically relevant variables for the primary and secondary objectives., Results: 136 patients and 365 focused TTE attempts were included in the study (241 subxiphoid, 101 parasternal, and 23 apical). There was no difference in the success rate: subxiphoid 83.4%, parasternal 88.1%, and apical 95.7% (p = 0.190) or in multivariable regression analysis (p = 0.189). There was no difference in the mean chest compression interruption time for each site: subxiphoid 15 sec. (IQR 12-23 sec.), parasternal 17 sec. (IQR 11-22 sec.), and apical 19 sec. (IQR 15-25 sec., p = 0.446) or in multivariable logistic regression analysis (p = 0.803). Sonographers with ≥ 50 quality assured focused TTEs had higher success than those without (94.4% vs. 75.1%; p < 0.001)., Conclusions: In cardiac arrest, the parasternal and apical TTE locations had similar success of cardiac visualization and similar compression interruption times to the more commonly used subxiphoid location., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Articular masses comprise various disease entities including benign or malignant proliferative processes and other non-neoplastic processes such as infection, deposition diseases, vascular malformations, and other lesions. Many diseases that lead to intra-articular or para-articular masses have distinct imaging features, particularly on MRI. Radiologists can localize masses to the joint space by knowing the articular anatomy and can reach a suggested diagnosis by looking at precise imaging findings. In this review article, we first define the concept of articular space (intraarticular, para-articular) and the normal joint anatomy and histology. We provide a general and comprehensive approach for evaluation of articular lesions on MRI. We then describe specific imaging and histologic features of typical benign and malignant soft tissue articular neoplasms and some non-neoplastic mimickers; and provide a radio-pathologic correlation of the different described entities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Individuals with posttraumatic stress disorder (PTSD) face an increased risk of cardiovascular disease, but the mechanisms linking PTSD to cardiovascular disease remain incompletely understood. We used a co-twin control study design to test the hypothesis that individuals with PTSD exhibit augmented peripheral and systemic vasoconstriction during a personalized trauma recall task., Methods: In 179 older male twins from the Vietnam Era Twin Registry, lifetime history of PTSD and current (last month) PTSD symptoms were assessed. Participants listened to neutral and personalized trauma scripts while peripheral vascular tone (Peripheral Arterial Tone ratio) and systemic vascular tone (e.g., total vascular conductance) were measured. Linear mixed-effect models were used to assess the within-pair relationship between PTSD and vascular tone indices., Results: The mean age of participants was 68 years, and 19% had a history of PTSD. For the Peripheral Arterial Tone ratio analysis, 32 twins were discordant for a history of PTSD, and 46 were discordant for current PTSD symptoms. Compared with their brothers without PTSD, during trauma recall, participants with a history of PTSD had greater increases in peripheral (β = -1.01, 95% CI [-1.72, -0.30]) and systemic (total vascular conductance: β = -1.12, 95% CI [-1.97, -0.27]) vasoconstriction after adjusting for cardiovascular risk factors. Associations persisted after adjusting for antidepressant medication use and heart rate and blood pressure during the tasks. Analysis of current PTSD symptom severity showed consistent results., Conclusions: PTSD is associated with exaggerated peripheral and systemic vasoconstrictor responses to traumatic stress reminders, which may contribute to elevated risk of cardiovascular disease., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Rationale : Evaluating the long-term safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumors (mNETs) who have undergone prior bland hepatic transarterial embolization (TAE). Methods : Retrospective review of mNET patients who received PRRT with 177 Lu-DOTATATE between 4/2018 and 02/2022 with and without prior TAE. The most recent clinical, imaging, and laboratory findings, including hepatic Common Terminology Criteria for Adverse Events v5.0, were compared to pre-PRRT. Results : 171 patients (95 M, 76 F, median age = 66) with mNET of different primary sites (9 foregut, 100 midgut, 9 hindgut, 44 pancreas, 9 unknown) received at least 1 cycle of PRRT with at least 6 months of follow-up, 110 of whom were embolization-naïve and 61 who had prior TAE. The median follow up was 22 months (range: 6-43). Patients with prior TAE had higher liver tumor burden on average than patients without prior TAE; however, the difference was not statistically significant ( p = 0.06). There was no significant difference in the rates of G3 or G4 hepatotoxicity ( p = 0.548 and p = 0.999, respectively) in patients who underwent prior TAE and those who were TAE-naïve. The hepatic progression-free survival was 22.9 months in TAE-naïve patients and 25.7, 20.2, and 12.8 months in patients with 1, 2, and 3 prior TAE treatments, respectively. Conclusion : Peptide receptor radionuclide therapy following transarterial bland embolization for mNET is safe and effective.

This article provides a thorough overview of the practice and multistep approach of hepatic radioembolization. The current literature on hepatic radioembolization in primary or metastatic liver tumors as well as future perspectives are discussed., Competing Interests: Disclosure A.J.A.T. Braat is a consultant for Boston Scientific and Terumo and receives research support from Ariceum Therapeutics. M.L.J. Smits is a consultant for Terumo and has received speaking fees for Medtronic and Philips. G. El-Haddad is a consultant for Boston Scientific, Terumo, Novartis, Bayer, and NorthStar Medical Radioisotopes. M.G.E.H. Lam is a consultant for Boston Scientific and Terumo and receives research support from Novartis, Boston Scientific and Terumo. The UMC Utrecht receives research support and royalties from Terumo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas., Methods: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use., Results: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed., Discussion: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred., (© 2024. Springer Nature B.V.)

Background: Malignant soft tissue spinal canal tumors compromise 20% of all spinal neoplasms. They may be primary or metastatic lesions, originating from a diverse range of tissues within and surrounding the spinal canal. These masses can present as diverse emergencies such as secondary cauda equina syndrome, vascular compromise, or syringomyelia. Interpretation of malignant soft tissue spinal canal tumors imaging is an essential for non-radiologists in the setting of emergencies. This task is intricate due to a great radiologic pattern overlap among entities., Methods: We present a step-by-step strategy that can guide nonradiologists identify a likely malignant soft tissue lesion in the spinal canal based on imaging features, as well as a review of the radiologic features of malignant soft tissue spinal canal tumors., Results: Diagnosis of soft tissue spinal canal malignancies starts with the identification of the lesion's spinal level and its relationship to the dura and medulla. The second step consists of characterizing it as likely-malignant based on radiological signs like a larger size, ill-defined margins, central necrosis, and/or increased vascularity. The third step is to identify additional imaging features such as intratumoral hemorrhage or cyst formation that can suggest specific malignancies. The physician can then formulate a differential diagnosis. The most encountered malignant soft tissue tumors of the spinal canal are anaplastic ependymomas, anaplastic astrocytomas, metastatic tumors, lymphoma, peripheral nerve sheath tumors, and central nervous system melanomas. A review of the imaging features of every type/subtype of lesion is presented in this work. Although magnetic resonance imaging remains the modality of choice for spinal tumor assessment, other techniques such as dynamic contrast agent-enhanced perfusion magnetic resonance imaging or diffusion-weighted imaging could guide diagnosis in specific situations., Conclusions: In this review, diagnostic strategies for several spinal cord tumors were presented, including anaplastic ependymoma, metastatic spinal cord tumors, anaplastic and malignant astrocytoma, lymphoma, malignant peripheral nerve sheath tumors , and primary central nervous system melanoma. Although the characterization of spinal cord tumors can be challenging, comprehensive knowledge of imaging features can help overcome these challenges and ensure optimal management of spinal canal lesions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2-positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2-low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2-low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2-low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (Copyright © 2024 Georges El Haddad et al.)

Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse cardiovascular outcomes in individuals with coronary artery disease, but the mechanisms underlying this phenomenon are unknown. We examined the relationship between stress-induced autonomic dysfunction, measured by low heart rate variability (HRV) in response to stress, and MSIMI in patients with stable coronary artery disease. We hypothesized that stress-induced autonomic dysfunction is associated with higher odds of MSIMI., Methods: In 735 participants with stable coronary artery disease, we measured high- and low-frequency HRV in 5-minute intervals before and during a standardized laboratory-based speech stressor using Holter monitoring. HRV at rest and stress were categorized into low HRV (first quartile) versus high HRV (second to fourth quartiles); the low category was used as an indicator of autonomic dysfunction. Multivariable logistic regression models were used to examine the association of autonomic dysfunction with MSIMI., Results: The mean age was 58 (SD, ±10) years, 35% were women, 44% were Black participants, and 16% developed MSIMI. Compared with high HRV during stress, low HRV during stress (both high and low frequencies) was associated with higher odds of MSIMI after adjusting for demographic and clinical factors (odds ratio for high-frequency HRV, 2.1 [95% CI, 1.3-3.3]; odds ratio for low-frequency HRV, 2.1 [95% CI, 1.3-3.3]). Low-frequency HRV at rest was also associated with MSIMI but with slightly reduced effect estimates., Conclusions: In individuals with coronary artery disease, mental stress-induced autonomic dysfunction may be a mechanism implicated in the causal pathway of MSIMI., Competing Interests: Disclosures None.

Background: Colistin (Polymyxin E) has reemerged in the treatment of MDR Gram-negative infections. Traditional Colistin AST methods have long turnaround times and are cumbersome for routine use. We present a SEM-AST technique enabling rapid detection of Colistin resistance through direct observation of morphological and quantitative changes in bacteria exposed to Colistin., Methods: Forty-four Gram-negative reference organisms were chosen based on their Colistin susceptibility profiles. Bacterial suspensions of ∼10 7  CFU/mL were exposed to Colistin at EUCAST-ECOFF, with controls not exposed, incubated at 37°C, and then sampled at 0, 15, 30, 60, and 120 minutes. Phosphotungstic Acid (PTA) staining was applied, followed by SEM imaging using Hitachi TM4000PlusII-Tabletop-SEM at ×2000, ×5000 and ×7000 magnifications. Bacterial viability analysis was performed for all conditions by quantifying viable and dead organisms based on PTA-staining and morphologic changes., Results: We identified a significant drop in the percentage of viable organisms starting 30 minutes after exposure in susceptible strains, as compared to nonsignificant changes in resistant strains across all tested organisms. The killing effect of Colistin was best observed after 120 minutes of incubation with the antibiotic, with significant changes in morphologic features, including bacterial inflation, fusion, and lysis, observed as early as 30 minutes. Our observation matched the results of the gold standard-based broth microdilution method., Conclusions: We provide an extended application of the proof of concept for the utilization of the SEM-AST assay for Colistin for a number of clinically relevant bacterial species, providing a rapid and reliable susceptibility profile for a critical antibiotic., Competing Interests: The authors would like to declare that DR was a consultant in microbiology for Hitachi High-Tech Corporation from March 2018 until March 2021. YO is employed by Hitachi High-Tech Corporation. AH and EM are employed by Hitachi, Ltd. Personal fees for GH, SB, and JBK are paid through a collaborative contract from the Hitachi High-Tech Corporation. OZ and RI declare no relevant competing interests. A patent application for this methodology is pending (PCT/FR2021/052468)., (Copyright © 2024 Omar Zmerli et al.)

Objective: To investigate the prevalence of obesity in patients with dysphonia and the association between Body Mass Index (BMI) and the Voice Handicap Index-10 (VHI-10)., Material and Methods: This is a retrospective study that included 304 patients who visited the senior author's Otolaryngology practice between the years 2018 and 2020. Patients were divided into two groups, those presenting for dysphonia and those presenting for other otolaryngologic complaints (Controls). Patients were also stratified as Normal weight (BMI < 25 kg/m2) vs. Overweight (BMI between 25-30 kg/m2), vs. Obese (BMI ≥ 25 kg/m2). The VHI-10 was used as a subjective outcome measure reported by patients with dysphonia., Results: A total of 304 patients included in this study, 203 presenting with dysphonia and 101 with other otolaryngologic complaint. Within the dysphonia group, a significantly higher percentage of patients had a BMI ≥ 25 (70.4%) as compared to the control group (57.4%). The odds ratio were 1.76, meaning that obese patients were 1.76 times more likely to present with dysphonia. There was a weak negative correlation between overweight, obesity, and VHI-10 scores (r=-0.007 and r=-0.039, respectively)., Conclusion: There was a significantly higher prevalence of overweight and obesity in patients with dysphonia vs. patients with no dysphonia. Although there was a weak correlation between BMI and VHI, our results demonstrate that overweight and obese patients are more likely to have dysphonia., Competing Interests: Conflict of Interest There is no conflict of interest or financial support in relation to this paper., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to examine the association between financial wellbeing and somatization, in addition to the mediating effect of anxiety, depression and stress. To test such hypotheses, a cross-sectional study was carried out between September and October 2021; 403 participants (264 females; age = 32.76 ± 13.24 years) were recruited. Depression mediated the association between financial wellbeing and somatization. A worse financial wellbeing was significantly associated with more depression, which was associated with more somatization. Moreover, a worse financial wellbeing was significantly and directly associated with more somatization. Our study adds to the narrow body of research revolving around the relationship between financial wellbeing and somatization in Lebanese adults. Understanding that the effects of, depression are aggravated in a country such as Lebanon would help establish more preventative guidelines and mental health awareness campaigns. Identifying the correlates of somatization can also be translated into improved interventions.

Research into the neonatal Fc receptor (FcRn) has increased dramatically ever since Simister and Mostov first purified a rat version of the receptor. Over the years, FcRn has been shown to function not only as a receptor that transfers immunity from mother to fetus but also performs an array of different functions that include transport and recycling of immunoglobulins and albumin in the adult. Due to its important cellular roles, several clinical trials have been designed to either inhibit/enhance FcRn function or develop of non-invasive therapeutic delivery system such as fusion of drugs to IgG Fc or albumin to enhance delivery inside the cells. Here, we report the accidental identification of several FcRn alternatively spliced variants in both mouse and human cells. The four new mouse splice variants are capable of binding immunoglobulins' Fc and Fab portions. In addition, we have identified FcRn-specific vesicles in which immunoglobulins and albumin can be stored and that are involved in the endosomal-lysosomal system. The complexity of FcRn functions offers significant potential to design and develop novel and targeted therapeutics.

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends the scope of our understanding of human biology and diseases. Brain organoids especially open an opportunity for human brain research and modeling many human neurological diseases, which have lagged due to the inaccessibility of human brain samples and lack of similarity with other animal models. Brain organoids can be generated through various protocols and mimic whole brain or region-specific. To provide an overview of brain organoid technology, we summarize currently available protocols and list several factors to consider before choosing protocols. We also outline the limitations of current protocols and challenges that need to be solved in future investigation of brain development and pathobiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao and Haddad.)

Most well-differentiated neuroendocrine tumors (NETs) express high levels of somatostatin receptors, particularly subtypes 2 and 5. Somatostatin analogs (SSAs) bind to somatostatin receptors and are used for palliation of hormonal syndromes and control of tumor growth. The long-acting SSAs octreotide long-acting release and lanreotide are commonly used in the first-line metastatic setting because of their tolerable side effect profile. Radiolabeled SSAs are used both for imaging and for treatment of NETs. 177 Lu-DOTATATE is a β-emitting radiolabeled SSA that has been proven to significantly improve progression-free survival among patients with progressive midgut NETs and is approved for treatment of metastatic gastroenteropancreatic NETs. A key question in management of patients with gastroenteropancreatic and lung NETs is the sequencing of 177 Lu-DOTATATE in relation to other systemic treatments (such as everolimus) or liver-directed therapies. This question is particularly complicated given the heterogeneity of NETs and the near absence of randomized trials comparing active treatment options. This state-of-the-art review examines the evidence supporting use of somatostatin-receptor-targeted treatments within the larger landscape of NET therapy and offers insights regarding optimal patient selection, assessment of benefit versus risk, and treatment sequencing., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Human lice are the only hematophagous ectoparasites specific to human hosts. They transmit epidemic typhus, trench fever and relapsing fever, diseases which have already caused millions of deaths worldwide. In order to further investigate lice vectorial capacities, laboratory-controlled live lice colonies are essential. Previously developed lice-rearing methods significantly advanced research on louse-borne diseases and louse biology. In this study, we aimed to develop a rearing technique for the Orlando (Or) strain of body lice on an artificial membrane. We tested two systems, namely the Hemotek feeding system and a Petri dish with the lice being fed through a Parafilm membrane. Lice longevity and development were drastically affected by the blood anticoagulant. Additionally, heparinised human blood on a Petri dish was the best candidate when compared to the control group (reared on a rabbit). Therefore, this strategy was applied to 500 lice. Development into adulthood was recorded after 21 days (17 days for the rabbits), and 52 eggs were deposited (240 for the rabbits). In this study, we were able to maintain one generation of body lice on an artificial membrane with comparable feeding and longevity rates to those fed on live rabbits. However, lice fecundity decreased on the artificial membrane. In vitro lice-rearing experiments will enable pathogen infection assays and pesticide bioassays to be carried out in accordance with animal welfare requirements.

The strains Marseille-Q7072 T (= CSUR Q7072 T  = CECT 30604  T ) and Marseille-Q7826 T (= CSUR Q7826 T  = CECT 30727  T ) were isolated from vaginal samples. As MALDI-TOF mass spectrometry failed to identify them, their genomes were directly sequenced to determine their taxogenomic identities. Both strains are anaerobic without any oxidase and catalase activity. C 16:0 is the most abundant fatty acid for both strains. Strain Marseille-Q7072 T is non-spore-forming, non-motile, Gram-stain-positive, and coccus-shaped, while strain Marseille-Q7826 T is non-spore-forming, motile, Gram-stain-variable, and curved rod-shaped. The genomic comparison of the Marseille-Q7072 T and Marseille-Q7826 T strains showed that all digital DNA-DNA hybridisation (dDDH) and mean orthologous nucleotide identity (OrthoANI) values were below published species thresholds (70% and 95-96%, respectively) with other closely related species with standing in nomenclature. Thus, we conclude that both strains are new bacterial species. Strain Marseille-Q7072 T is a new member of the Bacillota phylum, for which the name Peptoniphilus genitalis sp. nov. is proposed, while the Marseille-Q7826 T strain is a new member of the Actinomycetota phylum, for which the name Mobiluncus massiliensis sp. nov. is proposed., (© 2024. The Author(s).)

Background: Psychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear., Objectives: The purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction., Methods: Pooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years., Results: In both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved., Conclusions: Among patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

Background: Lebanese adults have been crippled for years by several crises, including the lately COVID-19 pandemic. These massive civilian traumas have increased the risk of post-traumatic stress disorder (PTSD) in this population. Extensive literature pointed to the association between PTSD and somatization; however, the nature of this relationship remains unknown. We sought to contribute further to work in this area by testing the moderating role of emotion regulation in the relationship between COVID-19- related PTSD and somatization. As a secondary objective, we aimed to examine the psychometric properties of an Arabic translation of the somatization measure Patient Health Questionnaire-15 (PHQ-15) in terms of factorial validity and internal consistency before its use in the present study., Methods: This cross-sectional study was conducted between September and October 2021. A total of 403 Lebanese adults residing in Lebanon were recruited. Eligible participants received an online link to the survey. The Patient Health Questionnaire-15 was used to assess somatization, PTSD Checklist-Civilian Version for PTSD and Emotion Regulation Questionnaire for emotion regulation., Results: The results of the exploratory factor analysis (EFA) revealed a three-factor solution explaining 48.79% of the common variance. Confirmatory Factor Analysis results of the three-factor model obtained in the EFA indicated a good fit with a significant CFI of 0.98, TLI 0.98 and a GFI of .97, a RMSEA of .04 [90% CI .01, .06]. Higher PTSD symptoms were associated with somatization. In addition, we found that one specific ER component, i.e. expressive suppression, significantly moderated the relationship between PTSD from the COVID pandemic and somatization. In particular, the interaction PTSD from the COVID-19 pandemic by expressive suppression was significantly associated with somatization; at low, medium and high levels of expressive suppression, higher PTSD from the COVID-19 pandemic was significantly associated with higher somatization scores. As for our secondary objective, findings revealed that the Arabic version of the PHQ-15 exhibited good psychometric properties. In particular, the scale yielded a three-factor structure, and good internal consistency (Cronbach's alpha = 0.87)., Conclusion: The moderating role of expressive suppression on the link between PTSD and somatization presents a novel finding in the field of trauma. Additionally, making a psychometrically sound Arabic version of the PHQ-15 available is a valuable addition to the literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nehme et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The neonatal Fc receptor (FcRn) was initially discovered as the receptor that allowed passive immunity in newborns by transporting maternal IgG through the placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life and in many different cell types. Beyond passive immunity, FcRn is necessary for intrinsic albumin and IgG recycling and is important for antigen processing and presentation. Given its multiple important roles, FcRn has been utilized in many disease treatments including a new class of agents that were developed to inhibit FcRn for treatment of a variety of autoimmune diseases. Certain cell populations within the kidney also express high levels of this receptor. Specifically, podocytes, proximal tubule epithelial cells, and vascular endothelial cells have been found to utilize FcRn. In this review, we summarize what is known about FcRn and its function within the kidney. We also discuss how FcRn has been used for therapeutic benefit, including how newer FcRn inhibiting agents are being used to treat autoimmune diseases. Lastly, we will discuss what renal diseases may respond to FcRn inhibitors and how further work studying FcRn within the kidney may lead to therapies for kidney diseases.