Investigational and emerging gastric inhibitory polypeptide (GIP) receptor-based therapies for the treatment of obesity.

INTRODUCTION: One billion people live with obesity. The most promising medications for its treatment are incretin-based therapies, based on enteroendocrine peptides released in response to oral nutrients, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The mechanisms by which GLP-1 receptor agonism cause weight reduction are becoming increasingly understood. However, the mechanisms by which GIP receptor-modulating medications cause weight loss remain to be clarified. AREAS COVERED: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of 'biased agonism' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction. EXPERT OPINION: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.

Predictors of Extended Length of Stay after Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND OBJECTIVES: Despite their asymptomatic occurrence, unruptured intracranial aneurysms (UIAs) account for a significant proportion of hospital charges and healthcare resource utilization in the United States. Hospital length of stay (LOS) is a reimbursement metric utilized to incentivize value-based care. Our study identifies predictors of extended LOS (eLOS) after elective treatment of UIAs. METHODS: This was a retrospective study of 525 patients who underwent elective treatment of an unruptured intracranial aneurysm (UIA) at a single institution. Data was collected with regard to demographics, clinical presentation, treatment characteristics and post-operative outcomes. The primary outcome, eLOS, was defined as hospital stay in the upper quartile of the median (≥75th percentile). Univariate and multivariate analyses was performed to identify factors predictive of eLOS in this cohort. RESULTS: The average age of the cohort was 61.40, standard deviation (SD)= 11.41. 77.3% of the cohort was female. The median duration of LOS was 2 days (interquartile range (IQR): 1-5). 11.6% experienced eLOS (≥5 days). Multivariate logistic regression identified age (OR: 1.04, 95% confidence interval (CI): 1.01- 1.07), co-existent vascular pathology (OR: 21.33, 95% CI: 8.06- 56.39), open surgery (OR: 3.93, 95% CI: 1.85- 8.34) and post-operative stroke (OR: 11.72, 95% CI: 3.18- 43.18) as independent predictors of eLOS. CONCLUSION: Our study identified predictors of eLOS that could help promote risk stratification prior to treatment of UIAs. Future research that identifies predictors of long term outcomes based on treatment modality could help identify ways to improve healthcare resource utilization in this cohort.

The Predictors of Surgery for Symptomatic, Atraumatic Full-Thickness Rotator Cuff Tears Change Over Time: Ten-Year Outcomes of the MOON Shoulder Prospective Cohort.

BACKGROUND: A prospective cohort study was conducted to assess the predictors of failure of nonoperative treatment, defined as the patient undergoing surgery for symptomatic, atraumatic full-thickness rotator cuff tears. We present the 10-year follow-up data of this population to determine if predictors for surgery change over time, and secondarily we report the outcomes of the cohort. METHODS: At the time of enrollment, demographic, symptom, rotator cuff anatomy, and patient-reported outcome data were collected in patients with symptomatic, atraumatic full-thickness rotator cuff tears. Patients underwent a standard physical therapy protocol for 6 to 12 weeks. Patient data were then collected at 1, 2, 5, 7, and 10 years. Failure of nonoperative treatment was defined as the patient electing to undergo surgery. RESULTS: Of the 452 patients in the original cohort, 20 patients (5%) withdrew from the study, 37 (9%) died before 10 years, and 40 (9%) were otherwise lost to follow-up. A total of 115 patients (27.0%) underwent a surgical procedure at some point during the 10-year follow-up period. Of these patients, 56.5% underwent surgery within 6 months of enrollment and 43.5%, between 6 months and 10 years. Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery. Workers' Compensation status and activity level were more important predictors of later surgery. Patient-reported outcome measures all improved following physical therapy. For patients who did not undergo a surgical procedure, patient-reported outcome measures did not decline over the 10-year follow-up period. CONCLUSIONS: Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery, whereas Workers' Compensation status and activity level were predictors of later surgery. Physical therapy was successful in >70% of patients with symptomatic, atraumatic full-thickness rotator cuff tears at 10 years. Outcome measures improved with physical therapy and did not decline over the 10-year follow-up period. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

A Reliable System for Quantitative G-Protein Activation Imaging in Cancer Cells.

Fluorescence resonance energy transfer (FRET) biosensors have proven to be an indispensable tool in cell biology and, more specifically, in the study of G-protein signalling. The best method of measuring the activation status or FRET state of a biosensor is often fluorescence lifetime imaging microscopy (FLIM), as it does away with many disadvantages inherent to fluorescence intensity-based methods and is easily quantitated. Despite the significant potential, there is a lack of reliable FLIM-FRET biosensors, and the data processing and analysis workflows reported previously face reproducibility challenges. Here, we established a system in live primary mouse pancreatic ductal adenocarcinoma cells, where we can detect the activation of an mNeonGreen-Gαi3-mCherry-Gγ2 biosensor through the lysophosphatidic acid receptor (LPAR) with 2-photon time-correlated single-photon counting (TCSPC) FLIM. This combination gave a superior signal to the commonly used mTurquoise2-mVenus G-protein biosensor. This system has potential as a platform for drug screening, or to answer basic cell biology questions in the field of G-protein signalling.

Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

BACKGROUND: Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. OBJECTIVE: To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. MATERIALS AND METHODS: Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40 minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. RESULTS: Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). CONCLUSION: This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene lowering a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNASOD1 extended survival in SOD1-G93A ALS mice, surpassing survival previously seen in these mice by ASO modalities, slowed disease progression, and prevented ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.

2024 Update of The Society of Thoracic Surgeons Short-Term Esophagectomy Risk Model: More Inclusive and Improved Calibration.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) previously reported short-term risk models for esophagectomy for esophageal cancer. We sought to update existing models using more inclusive contemporary cohorts, with consideration of additional risk factors based on clinical evidence. METHODS: The study population consisted of adult patients in the STS-GTSD who underwent esophagectomy for esophageal cancer between January 2015 and December 2022. Separate esophagectomy risk models were derived for three primary endpoints: operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used with predictors retained in models if p<0.10. All derived models were validated using 9-fold cross validation. Model discrimination and calibration were assessed for the overall cohort and specified subgroups. RESULTS: A total of 18,503 patients from 254 centers underwent esophagectomy for esophageal cancer. Operative mortality, morbidity, and composite morbidity or mortality rates were 3.4%, 30.5% and 30.9%, respectively. Novel predictors of short-term outcomes in the updated models included body surface area and insurance payor type. Overall discrimination was similar or superior to previous GTSD models for operative mortality [C-statistic = 0.72] and for composite morbidity or mortality [C-statistic = 0.62], Model discrimination was comparable across procedure- and demographic-specific sub-cohorts. Model calibration was excellent in all patient sub-groups. CONCLUSIONS: The newly derived esophagectomy risk models showed similar or superior performance compared to previous models, with broader applicability and clinical face validity. These models provide robust preoperative risk estimation and can be used for shared decision-making, assessment of provider performance, and quality improvement.

Controlled Synthesis of Terbium-Doped Colloidal Gd2O2S Nanoplatelets Enables High-Performance X-ray Scintillators.

Terbium-doped gadolinium oxysulfide (Gd2O2S:Tb3+), commonly referred to as Gadox, is a widely used scintillator material due to its exceptional X-ray attenuation efficiency and high light yield. However, Gadox-based scintillators suffer from low X-ray spatial resolution due to their large particle size, which causes significant light scattering. To address this limitation, we report the synthesis of terbium-doped colloidal Gadox nanoplatelets (NPLs) with near-unity photoluminescence quantum yield (PLQY) and high radioluminescence light yield (LY). In particular, our investigation reveals a strong correlation between PLQY, LY, particle size, and Tb3+concentration. Our synthetic approach allows precise control over the lateral size and thickness of the Gadox NPLs, resulting in a LY of 50,000 photons/MeV. Flexible scintillating screens fabricated with the solution-processable Gadox NPLs exhibited a 20 lp/mm X-ray spatial resolution, surpassing commercial Gadox scintillators. These high-performance and flexible Gadox NPL-based scintillators enable enhanced X-ray imaging capabilities in medicine and security. Our work provides a framework for designing nanomaterial scintillators with superior spatial resolution and efficiency through precise control of dimensions and dopant concentration.

Hard Candy Production and Quality Parameters: A review.

Hard candies are sugar confections comprising mainly water and sucrose. Corn syrup, colorants and flavors are also usually added to hard candy formulations. The production of hard candy requires heating of the ingredients to very high temperatures to reduce moisture content and subsequent cooling to obtain a solid matrix. Cooling of the mixtures achieves the final, well known glassy state of the products. In this glassy state, the system is kinetically stable and molecular mobility is restricted, providing longer shelf life to hard candies. There are, however, several factors affecting the final quality and consumer acceptance of hard candies. Production methods and parameters, initial formulations as well as storage conditions all play a crucial role in the physicochemical, textural and sensory properties of hard candies. Addition of colorants and flavors also plays a vital role in the final quality. Although hard candy production is a simple process with few production stages, even small changes in the method of production and process parameters may induce substantial changes in the final product characteristics. Additionally, storage conditions such as temperature and humidity can change the product properties leading to graining and stickiness which are the two major problems for hard candies during storage. Both production and storage conditions should therefore be carefully chosen and controlled for desirable hard candy properties. This review addresses the general production methods and considers process parameters and quality parameters of hard candy products. Moreover, a comprehensive review of the related hard candy literature is also presented. The majority of hard candy reviews focus on specific methods and processes, but this review will present a more general frame on the subject.

Obesity is associated with muscle atrophy in rotator cuff tear.

Objective: The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears. Methods: This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis. Results: A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2 increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01-1.81) increased odds among individuals with full-thickness tear. Conclusions: Higher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients. Level of Evidence: III.

Identification and characterization of a skin microbiome on Caenorhabditis elegans suggests environmental microbes confer cuticle protection.

In the wild, C. elegans are emersed in environments teeming with a veritable menagerie of microorganisms. The C. elegans cuticular surface serves as a barrier and first point of contact with their microbial environments. In this study, we identify microbes from C. elegans natural habitats that associate with its cuticle, constituting a simple "skin microbiome." We rear our animals on a modified CeMbio, mCeMbio, a consortium of ecologically relevant microbes. We first combine standard microbiological methods with an adapted micro skin-swabbing tool to describe the skin-resident bacteria on the C. elegans surface. Furthermore, we conduct 16S rRNA gene sequencing studies to identify relative shifts in the proportion of mCeMbio bacteria upon surface-sterilization, implying distinct skin- and gut-microbiomes. We find that some strains of bacteria, including Enterobacter sp. JUb101, are primarily found on the nematode skin, while others like Stenotrophomonas indicatrix JUb19 and Ochrobactrum vermis MYb71 are predominantly found in the animal's gut. Finally, we show that this skin microbiome promotes host cuticle integrity in harsh environments. Together, we identify a skin microbiome for the well-studied nematode model and propose its value in conferring host fitness advantages in naturalized contexts. IMPORTANCE: The genetic model organism C. elegans has recently emerged as a tool for understanding host-microbiome interactions. Nearly all of these studies either focus on pathogenic or gut-resident microbes. Little is known about the existence of native, nonpathogenic skin microbes or their function. We demonstrate that members of a modified C. elegans model microbiome, mCeMbio, can adhere to the animal's cuticle and confer protection from noxious environments. We combine a novel micro-swab tool, the first 16S microbial sequencing data from relatively unperturbed C. elegans, and physiological assays to demonstrate microbially mediated protection of the skin. This work serves as a foundation to explore wild C. elegans skin microbiomes and use C. elegans as a model for skin research.

Caspase-8 promotes scramblase-mediated phosphatidylserine exposure and fusion of osteoclast precursors.

Efficient cellular fusion of mononuclear precursors is the prerequisite for the generation of fully functional multinucleated bone-resorbing osteoclasts. However, the exact molecular factors and mechanisms controlling osteoclast fusion remain incompletely understood. Here we identify RANKL-mediated activation of caspase-8 as early key event during osteoclast fusion. Single cell RNA sequencing-based analyses suggested that activation of parts of the apoptotic machinery accompanied the differentiation of osteoclast precursors into mature multinucleated osteoclasts. A subsequent characterization of osteoclast precursors confirmed that RANKL-mediated activation of caspase-8 promoted the non-apoptotic cleavage and activation of downstream effector caspases that translocated to the plasma membrane where they triggered activation of the phospholipid scramblase Xkr8. Xkr8-mediated exposure of phosphatidylserine, in turn, aided cellular fusion of osteoclast precursors and thereby allowed generation of functional multinucleated osteoclast syncytia and initiation of bone resorption. Pharmacological blockage or genetic deletion of caspase-8 accordingly interfered with fusion of osteoclasts and bone resorption resulting in increased bone mass in mice carrying a conditional deletion of caspase-8 in mononuclear osteoclast precursors. These data identify a novel pathway controlling osteoclast biology and bone turnover with the potential to serve as target for therapeutic intervention during diseases characterized by pathologic osteoclast-mediated bone loss. Proposed model of osteoclast fusion regulated by caspase-8 activation and PS exposure. RANK/RANK-L interaction. Activation of procaspase-8 into caspase-8. Caspase-8 activates caspase-3. Active capase-3 cleaves Xkr8. Local PS exposure is induced. Exposed PS is recognized by the fusion partner. FUSION. PS is re-internalized.

The impact of the Woven EndoBridge device on the treatment of anterior circulation wide-neck bifurcation aneurysms: a single-center experience.

OBJECTIVE: The paucity of literature comparing Woven EndoBridge (WEB) embolization to microsurgical clipping for anterior circulation wide-neck bifurcation aneurysms (WNBAs) underscores the need for further investigation into the optimal management of this patient subpopulation. The objective of this study was to compare the rate of endovascular and microsurgical treatment of WNBAs before and after the introduction of the WEB device. In addition, the authors performed a comparison of demographics, aneurysm characteristics, and treatment outcomes in patients before and after the introduction of the WEB device. METHODS: This study was a retrospective review of the usage rate of different treatment modalities for WNBAs before and after the WEB device was approved by the US FDA on September 27, 2018. RESULTS: The study cohort comprised 235 patients with anterior circulation WNBAs treated at the authors' institution, including 127 aneurysms treated pre-WEB and 108 treated post-WEB. Generally, the rate of endovascular treatment of anterior circulation WNBAs was significantly higher post-WEB (86.1% vs 46.5%, p < 0.001), while the rate of clipping was significantly lower (13.9% vs 53.5%, p < 0.001). During follow-up, the rate of adequate aneurysm occlusion (Raymond-Roy occlusion classification [RROC] grades 1 and 2) was nonsignificantly higher in the post-WEB cohort (83.9% vs 78.5%, p = 0.34), while the rate of RROC grade 3 was nonsignificantly higher in the pre-WEB cohort (21.5% vs 16.1%, p = 0.34). Additionally, and although nonsignificant, the rates of recurrence (pre-WEB 25.3% vs post-WEB 14.9%, p = 0.12) and retreatment (pre-WEB 22.8% vs post-WEB 14.9%, p = 0.22) were higher in the pre-WEB cohort. Recurrence was assessed before retreatment. CONCLUSIONS: After the introduction of the WEB device, the rate of endovascular treatment of WNBAs increased while the rate of microsurgical clipping decreased. It is essential for neurointerventionalists to become familiar with the indications, advantages, and shortcomings of all these different techniques to be able to match the right patient with the right technique to produce the best outcome.

Utility of thromboelastography with platelet mapping (TEG-PM) for monitoring platelet transfusion in qualitative platelet disorders.

BACKGROUND: Patients with pathogenic variants in RASGRP2 (inherited platelet disorder (IPD)-18) have normal platelet counts but show impaired platelet aggregation due to diminished activation of αIIbß3 integrin. This defect results in moderate to severe bleeding episodes, especially following surgical procedures, which require patients to be transfused with platelets and/or pro-hemostatic agents. We recently demonstrated that hemostatic efficacy of transfused platelets is limited by dysfunctional endogenous platelets in a mouse model of IPD-18 (Rasgrp2-/- mice), as dysfunctional platelets were recruited to the forming hemostatic plug but did not participate in clot contraction. Consequently, higher amounts of transfused platelets were required to outcompete these dysfunctional cells and to reverse bleeding. OBJECTIVE: We here studied the usefulness of thromboelastography with platelet mapping (TEG-PM), a method to evaluate platelet-dependent clot contraction, for ex vivo monitoring of the hemostatic potential in Rasgrp2-/- mice transfused with various amounts of wild-type (WT) platelets. RESULTS: Rasgrp2-/- whole blood samples did not contract in TEG-PM, consistent with a critical role of this protein in αIIbß3 activation. Addition of WT platelets improved TEG parameters (K time, α-angle, MA) in a ratio dependent manner, consistent with our recent in vivo studies showing impaired hemostasis at a 5:1, but not at a 2:1 ratio of mutant to WT platelets. K and α values were identified as better predictors of transfusion efficacy than MA, the most platelet-dependent TEG parameter. CONCLUSION: This proof-of-concept study supports the use of TEG-PM to monitor platelet transfusion ratios and hemostatic potential in IPD-18 and potentially other platelet disorders.

De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis.

PURPOSE OF REVIEW: Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk-benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. RECENT FINDINGS: Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

Unraveling PTSD: Symptom cluster change during and 1 year after veterans' residential PTSD treatment.

OBJECTIVE: Although treatment of posttraumatic stress disorder (PTSD) is effective in reducing symptom severity, remission rates are low. One potential underlying reason for treatment ineffectiveness is differential response of specific PTSD symptom clusters. Using data from a national Veterans Affairs (VA) residential PTSD treatment cohort, we conducted a longitudinal study to examine changes in Diagnostic and Statistical Manual of Mental Disorders, fifth edition PTSD symptom clusters from admission to 1-year follow-up. METHOD: PTSD symptom data were analyzed from a national cohort of veterans who completed VA PTSD residential treatment between October 2019 and September 2020 (n = 1,648; 13% women; median age 44.2 years). Endorsement (%) and severity (M[SD]) of PTSD clusters and individual symptoms were compared at admission, discharge, 4-month and 1-year follow-ups. RESULTS: Large magnitude reductions in all four PTSD symptom clusters were observed from admission to discharge and both follow-ups; however, endorsement of all symptom clusters remained high. Intrusions (Cluster B) were the most highly endorsed at discharge and follow-up, whereas avoidance symptoms (Cluster C) were the least highly endorsed. Differential patterns of change were observed among the 20 individual PTSD symptoms; for example, flashbacks decreased during treatment, but increased to near admission levels by 1-year postdischarge. CONCLUSIONS: Results suggest that intrusive symptoms may be more resistant to residential treatment for PTSD and contribute to lower likelihood of treatment success. Future work is needed to examine differential treatment response for PTSD clusters, to inform the improvement of current and creation of novel treatment interventions, and to better address intrusive symptoms to maximize PTSD treatment gains. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Era of Radial-Specific Catheters: A Multicenter Comparison of the Armadillo and RIST Catheters in Transradial Procedures.

BACKGROUND AND OBJECTIVES: As the radial approach is gaining popularity in neurointervention, new radial-specific catheters are being manufactured while taking into consideration the smaller size of the radial artery, different trajectories of angles into the great vessels from the arm, and subsequent force vectors. We compared outcomes of transradial procedures performed using the Armadillo catheter (Q'Apel Medical Inc.) and the RIST radial guide catheter (Medtronic). METHODS: This is a retrospective multicenter study comparing outcomes of transradial neuroendovascular procedures using the Armadillo and RIST catheters at 2 institutions between 2021 and 2024. RESULTS: The study comprised 206 patients, 96 of whom underwent procedures using the Armadillo and 110 using the RIST. Age and sex were comparable across cohorts. In most procedures, 1 target vessel was catheterized (Armadillo: 94.8% vs 89.1%, P = .29) with no significant difference between cohorts. The use of an intermediate catheter was minimal in both cohorts (Armadillo 5.2% vs RIST: 2.7%, P = .36), and the median number of major vessel catheterization did not significantly differ between cohorts (Armadillo: 1 [1-4] vs RIST: 1 [0-6], P = .21). Failure to catheterize the target vessel was encountered in 1 case in each cohort (Armadillo: 1.0% vs RIST: 0.9%, P = .18), and the rate did not significantly differ between cohorts. Similarly, the rate of conversion to femoral access was comparable between cohorts (Armadillo: 2.1% vs RIST: 1.8%, P = .55). There was no significant difference in access site complications (Armadillo: 1% vs RIST: 2.8%, P = .55) or neurological complications (Armadillo: 3.1% vs RIST: 5.5%, P = .42) between cohorts. CONCLUSION: No significant difference in successful catheterization of target vessels, procedure duration, triaxial system use, complication rates, or the need for transfemoral cross-over was observed between both catheters. Both devices offer high and comparable rates of technical success and low morbidity rates.

Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.

Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.