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Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders and schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap with schizophrenia. PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain.

Background Current protocols for transplantation of hematopoietic stem and progenitor cells may be limited by donor-cell availability and the long time needed to restore neutrophil and platelet counts to normal levels. Ex vivo expansion of hematopoietic cells has the potential to decrease the required harvest size, and to enhance the transplant outcome, by providing greater numbers of progenitor and post-progenitor cells. However, widespread application of ex vivo expansion in the clinical setting is complicated by sample-to-sample variability in the extent and kinetics of cell expansion. For example, the lag time before active cell expansion may vary by several days and some samples may never expand under the culture conditions employed. An early determination regarding the fate of a culture would save time and resources, and would allow corrective action to be taken if desired. Furthermore, anticipation of the onset of cell cycling should prove useful in the development of culture-feeding strategies, as well as for maximizing transduction efficiency in gene-therapy protocols that employ retroviral vectors. Methods We demonstrate that the nuclei-size distribution, which is obtained at the same time as the total nucleated cell concentration, can be used to predict the onset of cell proliferation. The formation of a second peak (with diameter > 4 μm) in the nuclei-size distribution, in addition to the smaller diameter peak (<4 μm) present for quiescent cells, precedes total cell expansion. Results In particular, 94% of all MNC and CD34 + cell cultures that we have observed to exhibit a second peak in the nuclei-size distribution have realized total cell expansion. Furthermore, only one of 67 observed cultures that did not exhibit the formation of a second peak realized total cell expansion. The formation of a second peak in the nuclei-size distribution is evident, either before or on the same day as the presence of a significant fraction of cells in the S-phase of the cell cycle. [ABSTRACT FROM AUTHOR]

A simple cobalt-catalyzed, picolinamide-directed C8-H sulfoxamination of 1-naphthalamides with NH-sulfoximines has been developed. This cross-dehydrogenative C-H/N-H coupling reaction offers a facile route to N-arylated sulfoximines, exhibiting high yields, a broad substrate scope, and excellent functional group tolerance and scalability.

Dielectric Modulated Field-Effect Transistors (DMFETs) have emerged as promising candidates for label-free bioanalyte detection. However, the inherent short-channel effects in conventional DMFETs increase their static power dissipation significantly and limit their scalability and sensitivity. Therefore, FETs based on alternate conduction mechanism such as tunneling (TFETs), which are immune to the short-channel effects, appear to be a lucrative alternative to the MOSFETs for biosensing application. In this work, we propose a novel Dual Cavity Dielectric Modulated Nanotube Tunnel FET (DCDM NTTFET)-based label-free biosensor consisting of a Ge source and nanocavities within the core as well as a shell gate stack, which not only outperforms the conventional MOSFET and advanced nanowire (NW) TFET-based biosensors in terms of energy-efficiency and scalability but also exhibits a significantly high drain current sensitivity ( S I ON = 2.9 × 10 8 ) and a threshold voltage sensitivity ( S V th = 0.85), and a considerably high selectivity of more than 6 orders of magnitude. We also perform a comprehensive design space exploration for the proposed DCDM NTTFET and provide necessary design guidelines to further improve its performance considering the practical artifacts such as steric hindrance.

Catheter-based angiography is an essential procedure for the diagnosis and treatment of vascular complications in patients. Since cerebral and coronary angiography are similar techniques that utilize the same access sites and general principles, the associated risks overlap and should be identified to help direct patient care. The purpose of this study was to determine complication rates in a combined cohort of cerebral and coronary angiography patients, as well as conduct a comparative analysis of coronary and cerebral angiography complications. The National Inpatient Sample was queried from 2008 to 2014 to identify patients who underwent coronary or cerebral angiography. After assessment of baseline characteristics, complication rates, and disposition in the combined cohort, propensity matching was utilized to create sub-cohorts of coronary and cerebral angiography patients based on demographics and comorbidities. Comparative analysis of procedural complications and disposition was then performed. A total of 3,763,651 hospitalizations were included in our study cohort (3,505,715 coronary angiographies and 257,936 cerebral angiographies). The median age was 62.9 years, with females being 46.42%. The most prevalent comorbidities in the overall cohort were hypertension (69.92%), coronary artery disease (69.48%), smoking (35.64%), and diabetes mellitus (35.13%). Propensity matching demonstrated that the cerebral angiography cohort had lower rates of acute and unspecified renal failure (5.4% vs 9.2%, OR 0.57, 95% CI, 0.53-0.61, P < 0.001), hemorrhage/hematoma formation (0.8% vs 1.3%, OR 0.63, 95% CI, 0.54-0.73, P < 0.001), and equivalent rates of retroperitoneum hematoma formation (0.03% vs 0.04%, OR 1.49, 95% CI, 0.76-2.90, P = 0.247) and arterial embolism/thrombus formation (0.3% vs 0.3%, OR 1.01, 95% CI, 0.81-1.27, P = 0.900). Our study showed both cerebral and coronary angiography have generally low rates of procedural complications. Matched cohort analysis demonstrated that cerebral angiography patients are at no greater risk for complications than coronary angiography patients., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal triage strategy for patients suspected of acute ischemic stroke due to large vessel occlusion (LVO) remains debated. We explored trends in presentation mode and their outcomes for mechanical thrombectomy (MT) hospitalizations based on the National Inpatient Sample (NIS) database., Methods: We retrospectively explored the NIS database from 2016 to 2020 for stroke hospitalizations with MT. We compared outcomes at discharge for MT hospitalizations with direct vs. transferred presentation. Outcomes comprised favorable discharge disposition (home without assistance), in-hospital mortality, and radiographic intracranial hemorrhage (ICH)., Results: This study included 100,865 patients undergoing MT, of whom 32,685 patients (32.4 %) were transferred (median age 71[60-81] years, 16775(51.2 %) women). The utilization of MT in the U.S. nearly doubled during the study period, whereas the proportion of in-hospital transfers for MT remained unchanged (32.1-33.2 %). White race, higher presenting NIHSS, hospital size, status, and location were independent predictors of transferred status. Transferred status was significantly associated with a lower likelihood of achieving favorable outcome (OR:0.80,95 % CI: [0.72,0.89],P<0.001) and a higher likelihood of ICH (OR:1.18, 95 % CI:[1.07,1.31],P=0.001), whereas no association was observed between presentation mode and in-hospital mortality (OR:1.07,95 % CI:[0.93,1.23],P=0.33)., Conclusion: Patients with direct presentation for MT after a stroke had better discharge outcomes and a lower risk of hemorrhagic transformation compared to those who were transferred from another facility. Determining the optimal triage strategy for MT following LVO stroke is an insightful area for future clinical trials., Competing Interests: Declaration of competing interest The authors declare no conflicting or competing interest in the subject matter of this manuscript, (Copyright © 2024. Published by Elsevier Inc.)

Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P. falciparum laboratory strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced anti-PfRH5 mAbs on more genetically diverse P. falciparum clinical isolates. We used mAbs previously isolated from single B cells of UK adult PfRH5 vaccinees and used ex-vivo growth inhibition activity (GIA) assays to assess their efficacy against P. falciparum clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in P. falciparum clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups: high, medium and low. Except for one isolate, our data show no significant differences in the mAb GIA profile between P. falciparum clinical isolates and the 3D7 reference strain, which harbors the vaccine allele. We also observed an additive relationship for mAb combinations, whereby the combination of GIA-low and GIA-medium antibodies resulted in increased GIA, having important implications for the contribution of specific clones within polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the pfrh5 gene, these mutations were predicted to have little or no functional impact on the antigen structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of anti-PfRH5 mAbs and constitute, to our knowledge, the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human mAbs to PfRH5., (© 2024. The Author(s).)

The Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a promising target as a next-generation blood-stage malaria vaccine and together with PCRCR complex members, the reticulocyte binding-like homologous protein 5 (PfRh5) and the Rh5-interacting protein (PfRipr), are currently being evaluated in clinical trials. PfCyRPA is essential for merozoite invasion and appears to be highly conserved within the P. falciparum parasite populations. Here, we used a targeted deep amplicon next-generation sequencing approach to assess the breadth of PfCyRPA genetic diversity in 95 P. falciparum clinical isolates from Kédougou, an area with a high seasonal malaria transmission in Senegal. Our data show the dominant prevalence of PfCyRPA wild type reference allele, while we also identify a total of 15 single nucleotide polymorphisms (SNPs). Of these, only five have previously been reported, while the majority of the SNPs were present as singletons within our sampled population. Moreover, the variant read frequency of the identified SNPs varied from 2.6 to 100%, while the majority of the SNPs were present at frequencies greater than 25% in polygenomic samples. We also applied a structure-based modelling approach to thread these SNPs onto PfCyRPA crystal structures and showed that these polymorphisms have different predicted functional impacts on the interactions with binding partner PfRH5 or neutralizing antibodies. Our prediction revealed that the majority of these SNPs have minor effects on PfCyRPA antibodies, while others alter its structure, stability, or interaction with PfRH5. Altogether, our present findings reveal conserved PfCyRPA epitopes which will inform downstream investigations on next-generation structure-guided malaria vaccine design.

Pelvic floor disorders frequently occur as the result of excessive straining from chronic constipation or the trauma of vaginal childbirth, making them more common in women. We present a 62-year-old male with bladder prolapse through the anterior rectal wall in the setting of longstanding bladder holding behavior and excessive straining to void. We performed a novel robotic-assisted laparoscopic cystoprostosacropexy by anchoring the bladder and prostate to the sacrum to prevent bladder descent. Postoperatively, the bladder prolapse resolved with return of normal urinary function. This case underscores the potential of innovative surgical techniques in managing complex pelvic floor disorders in males., (© 2024 The Authors.)

Objective: Mandibular plate reconstruction (MPR) is often indicated after tumor ablation, osteoradionecrosis excision, and traumatic bone loss to restore oral functionality and facial cosmetics. There are limited analyses identifying risk factors that lead to plate infection (PIn), exposure, and removal ("plate complications")., Study Design: Retrospective cohort study., Setting: Academic tertiary medical center., Methods: Patients who underwent MPR from 2013 to 2022 were identified. Risk factors for plate complications were analyzed based on demographic, clinical, intraoperative, and postoperative factors. Multivariable analysis was conducted with logistic regression. Survival analysis was conducted with a Cox model., Results: Of the 188 patients analyzed, 48 (25.5%) had a plate complication [infection: 22 (11.7%); exposure: 23 (12.2%); removal: 35 (18.6%)]. Multivariate analysis revealed predictive associations between at least 1 plate complication and the following variables: smoking status, soft tissue defect size, number of plates, average screw length, and various postoperative complications. Other associations approached the threshold for significance. Prior and adjuvant radiation therapy, type of free flap, stock versus custom plates, and perioperative antibiotic prophylaxis regimens were not associated with plate complications. No plate complication was independently associated with lower overall survival. PIn (hazard ratio, HR: 7.99, confidence interval, CI [4.11, 15.54]) and exposure (HR: 3.56, CI [1.79, 7.08]) were independently associated with higher rates of plate removal., Conclusion: Plate complications are relatively common after MPR. Smoking history, specific disease characteristics, hardware used during surgery, and postoperative complications may help identify higher-risk patients, but additional larger-scale studies are needed to validate our findings and resolve discrepancies in the current literature., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Occupational immunization is an integral part of institutional occupational safety and health (OSH) programs. Laboratory animal workers (LAWs) are personnel working with various small and large vertebrate animals. LAWs are at the risk of contracting a myriad of zoonotic infections as they are occupationally exposed to animals and their biological products. Immunizing employees against such zoonotic pathogens is the best way to prevent disease transmission. This review provides information on various zoonotic diseases, vaccines available to protect against such infections, and vaccination schedules. Certain sections of institutional occupational immunization programs such as risk evaluation, immunizing special categories of personnel and exemption from immunization among others are also described. Additionally, the authors have discussed various probable modes of impact through which occupational immunization of laboratory animal workers fulfills different United Nations Sustainable Development Goals.

Purpose: We know very little about Hispanic autistic children's response to intervention as, historically, Hispanic children are underrepresented in intervention studies. Pathways parent-mediated early autism intervention is one of the few naturalistic developmental behavioral interventions (NDBIs) that is contextually and linguistically responsive to Hispanic families. However, some child-centered NDBI strategies do not align with the Hispanic caregiving value of respeto. A child exhibiting respeto demonstrates affiliative obedience by displaying deference and respect toward adults. Furthermore, theories of the ontogeny of cultural learning suggest that certain levels of social development may be necessary to learn cultural values. The current study investigates (1) the relationship between Hispanic autistic children's social skills and affiliative obedience and (2) the efficacy of Pathways in improving affiliative obedience in Hispanic children., Methods: This quasi-experimental design study used preexisting standardized test data and video recordings from 26 Hispanic participants who took part in a previous Pathways efficacy study. Recordings were coded for affiliative obedience and social connectedness. Residual change variables were used to measure progress from baseline to post-intervention, and correlation and hierarchical regression analyses were conducted to analyze the data., Results: We found significant positive correlations between social skills and children's affiliative obedience for baseline and change variables. In addition, we found Pathways had a significant medium-large magnitude effect on change in affiliative obedience skills., Conclusion: This study highlights the benefits of NDBI interventions that advance social development in autistic children and support Hispanic parents in enculturating their children in the value of respeto., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade., Methods: We used data contained in the 2010-2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time., Results: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010-2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8-1.7%). Joinpoint regression showed that prevalence increased in the period 2010-2015 (APC: 2.8%, 95% CI: 1.9-3.9%) but remained stable in the period 2015-2020 (APC: -0.3%, 95% CI: -1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18-39 years (APC: 4.0%, 95% CI: 0.2-7.9%), men 40-59 years (APC: 3.4%, 95% CI: 1.9-4.9%) and women 40-59 years (APC: 4.4%, 95% CI: 2.0-6.8%). In contrast, prevalence declined in hospitalizations in women 60-79 (APC: -1.0%, 95% CI: -0.5 to -1.5%) and women ⩾ 80 years over the period 2015-2020 but plateaued in hospitalizations in similar-aged men over the same period., Conclusion: AF prevalence in AIS hospitalizations in the United States increased over the period 2010-2015, then plateaued over the period 2015-2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Kamel is an associate editor for JAMA neurology; and the principal investigator of the ARCADIA trial, testing antithrombotic strategies in patients with stroke and atrial cardiopathy; and of the ASPIRE trial, which is testing antithrombotic strategies in patients with atrial fibrillation and intracerebral hemorrhage. Dr Chaturvedi is an associate editor for the Stroke journal.

Background: The pattern of surgical treatments for Idiopathic Intracranial Hypertension (IIH) in the United States is not well-studied, specifically the trend of utilizing endovascular venous stenting (EVS) as an emerging technique., Methods: In this cross-sectional study, we aimed to explore the national trend of utilizing different procedures for the treatment of IIH including EVS, Optic Nerve Sheath Fenestration (ONSF), and CSF Shunting, with a focus on novel endovascular procedures. Moreover, we explored rates of 90-day readmission and length of hospital stay following different procedures, besides the effects of sociodemographic and clinical parameters on procedure choice., Results: 36,437 IIH patients were identified from records between 2010 and 2018. Those in the EVS group were 29 years old on average, and 93.4 % were female. Large academic hospital setting was independently associated with higher EVS utilization, while other factors were not predictive of procedure choice. The proportion of EVS use in IIH hospitalizations increased significantly from 2010 to 2018 (P < 0.001), while there was a relative decline in the frequency of shunting procedures (P = 0.001), with ONSF utilization remaining stable (P = 0.39). The rate of 90-day readmission and length of hospital stay were considerably lower following EVS compared to other procedures (Ps < 0.001)., Conclusion: This study presents novel population-level data on national trends in the frequency and outcome of EVS for IIH therapy. EVS was associated with shorter length of hospital stays and fewer readmission rates. In addition, a continuous increase in venous stenting compared to other procedures suggests an increasing role for endovascular therapies in IIH., Competing Interests: Declaration of competing interest The authors of this study declared no conflicting or competing interest in the subject matter of this paper, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Increasing an individual's ability to focus on concrete, specific detail, thus reducing the tendency toward overly broad, decontextualised generalisations about the self and world, is a target within cognitive behavioural therapy (CBT). However, empirical investigation of the impact of within-treatment specificity on treatment outcomes is scarce. We evaluated whether the specificity of patient dialogue predicted a) end-of-treatment symptoms and b) session completion for CBT for common mental health issues., Methods: This preregistered (https://osf.io/agr4t) study trained a deep learning model to score the specificity of patient dialogue in transcripts from 353,614 internet-enabled CBT sessions for common mental health disorders, delivered on behalf of UK NHS services. Data were from obtained from 65,030 participants (n = 47,308 female, n = 241 unstated) aged 18-94 years (M = 34.69, SD = 12.35). Depressive disorders were the most common (39.1 %) primary diagnosis. Primary outcome was end-of-treatment score on the Patient Health Questionnaire-9 (PHQ-9). Secondary outcome was number of sessions attended., Results: Linear mixed-effects models demonstrated that increased patient specificity significantly predicted lower post-treatment symptoms on the PHQ-9, although the size and direction of the effect varied depending on the type of therapeutic activity being completed. Effect sizes were consistently small. Higher patient specificity was associated with completing a greater number of sessions., Limitations: We are unable to infer causation from our data., Conclusions: Although effect sizes were small, an effect of specificity was observed across common mental health disorders. Further studies are needed to explore whether encouraging patient specificity during CBT may provide an enhancement of treatment attendance and treatment effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mini-screws, also known as temporary anchorage devices (TADs), offer enhanced control and versatility in orthodontic treatment by providing stable anchorage points. This clinical study aims to evaluate the effectiveness of mini-screw-supported molar intrusion in orthodontic practice. For this clinical study, a cohort of 40 orthodontic patients with various malocclusions requiring molar intrusion as part of their treatment plan was recruited. The age range of the participants spanned from 14 to 35 years, representing a diverse patient population. The intervention involved the implementation of mini-screw-supported molar intrusion on one side of the maxillary arch in each patient. To achieve this, temporary mini-screws were strategically placed, and a combination of orthodontic forces and mini-screw anchorage was employed to intrude the molars. The primary outcome measure for this study was the amount of molar intrusion achieved, which was quantified in millimeters from the initial evaluation to the final visit. Additionally, the duration of treatment required to achieve the desired molar intrusion was recorded in months. The results of this clinical study demonstrated that mini-screw-supported molar intrusion was an effective and safe orthodontic technique. On average, a significant mean molar intrusion amount of 4.8 mm (standard deviation [SD] ± 0.6) was achieved with the mini-screw-supported approach. Furthermore, the treatment duration required to attain the desired molar intrusion was relatively short, with a mean of 6.2 months (SD ± 1.1). In conclusion, this clinical study provides evidence that mini-screw-supported molar intrusion is an effective and safe approach in orthodontic practice. It offers orthodontists the advantage of enhanced control and predictability in molar intrusion procedures., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Background: Differences in treatment outcomes between community or academic centers are incompletely understood., Methods: Retrospective review of head and neck cancer patients between 2010 and 2020 in a rural health region. Kaplan-Meier curves and log-rank tests were used to evaluate survival outcomes, along with bivariate and multivariable Cox proportional hazards models. Linear regression was used for functional outcomes of tracheotomy and gastrostomy tube dependence., Results: Two hundred and forty-eight patients treated at an academic center were compared with 94 patients treated in community centers. In multivariable analysis, the risk of death (HR = 0.60, p = 0.019), and risk of recurrence were lower (HR = 0.29, p < 0.001) for patients treated in academic centers. Patients treated in community centers had longer gastrostomy tube dependence (p = 0.002)., Conclusion: Our findings suggest that treatment at an academic center was associated with a lower risk of recurrence and shorter gastrostomy tube dependence compared to treatment in the community., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: The mixed dentition stage in children is a critical period for orthodontic assessment and intervention. This study investigates the effects of interceptive orthodontics on dental and skeletal development in children with mixed dentition, aiming to evaluate the potential benefits of early orthodontic treatment., Materials and Methods: A retrospective analysis was conducted on a cohort of 150 children with mixed dentition (aged 7-11 years), who received interceptive orthodontic treatment. Dental and skeletal records, including cephalometric radiographs and dental cast models, were collected before and after treatment. A control group of 150 untreated children with mixed dentition was also assessed for comparison. Various dental and skeletal parameters, such as dental alignment, overjet (OJ), overbite (OB), and cephalometric measurements, were recorded and analyzed., Results: The results of this study indicate significant improvements in dental alignment and occlusion in the group of children who received interceptive orthodontic treatment. The average reduction in OJ was 3.5 mm, and the OB correction averaged 2.1 mm. Cephalometric analysis showed positive changes in skeletal relationships, with a mean reduction in the angle formed by point A, nasion (N) and point B. (ANB) angle of 2.8 degrees. These improvements were statistically significant compared to the control group ( P < 0.05)., Conclusion: Early orthodontic intervention, such as interceptive orthodontics, has a positive impact on dental and skeletal development in children with mixed dentition., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

A palladium-catalyzed chelation-assisted direct aldehyde C-H bond amidation of quinoline-8-carbaldehydes with an amine was developed under mild reaction conditions. A wide range of amides were obtained in good to excellent yields from aldehyde with a variety of aniline derivatives and aliphatic amines. Our methodology was successfully applied to synthesize known DNA intercalating agents and can be easily scaled up to a gram scale.

Background: Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators., Methods: This was an individual participant data meta-analysis of published and unpublished randomised studies in young people aged 6-18 years exposed to trauma. We included studies identified by the latest UK National Institute of Health and Care Excellence guidelines (completed on Jan 29, 2018) and updated their search. The search strategy included database searches restricted to publications between Jan 1, 2018, and Nov 12, 2019; grey literature search of trial registries ClinicalTrials.gov and ISRCTN; preprint archives PsyArXiv and bioRxiv; and use of social media and emails to key authors to identify any unpublished datasets. The primary outcome was post-traumatic stress symptoms after treatment (<1 month after the final session). Predominantly, one-stage random-effects models were fitted. This study is registered with PROSPERO, CRD42019151954., Findings: We identified 38 studies; 25 studies provided individual participant data, comprising 1686 young people (mean age 13·65 years [SD 3·01]), with 802 receiving CBTs-TF and 884 a control condition. The risk-of-bias assessment indicated five studies as low risk and 20 studies with some concerns. Participants who received CBTs-TF had lower mean post-traumatic stress symptoms after treatment than those who received the control conditions, after adjusting for post-traumatic stress symptoms before treatment (b=-13·17, 95% CI -17·84 to -8·50, p<0·001, τ 2 =103·72). Moderation analysis indicated that this effect of CBTs-TF on post-traumatic stress symptoms post-treatment increased by 0·15 units (b=-0·15, 95% CI -0·29 to -0·01, p=0·041, τ 2 =0·03) for each unit increase in pre-treatment post-traumatic stress symptoms., Interpretation: This is the first individual participant data meta-analysis of young people exposed to trauma. Our findings support CBTs-TF as the first-line treatment, irrespective of age, gender, trauma characteristics, or carer involvement in treatment, with particular benefits for those with higher initial distress., Funding: Swiss National Science Foundation., Competing Interests: Declaration of interests RM-S received personal payment for teaching on the delivery of cognitive therapy for post-traumatic stress disorder for children and young people at various UK universities and training bodies, and he is an unpaid council member of the UK Trauma Council. EBF received payment for contributing to a post-traumatic stress disorder manual and workbook and for post-traumatic stress disorder workshops, lectures, and meetings. JDF served as a consultant for Advanced Trauma Solutions Professionals. SK received minor side income from lecturing in a clinical training program for Narrative Exposure Therapy (University of Turku, Turku, Finland). PS received a share of royalties from Routledge publishers from publication of a cognitive therapy for post-traumatic stress disorder manual for young people; he was an unpaid member of the research committee of the Children and War Foundation (a non-profit based in Norway) and an unpaid trustee of the Children and War UK (a non-profit based in the UK). CHi received personal payment for writing an article regarding treatment of therapy for post-traumatic stress disorder in preschool-aged children from the Aeon Media Group. TD received personal payment for teaching on the delivery of cognitive therapy for post-traumatic stress disorder for children and young people at various UK universities and training bodies. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Opioid-induced constipation (OIC) is frequently undertreated in patients with advanced cancer. Our hypothesis is that the use of a stepwise treatment algorithm, supported by regular patient-reported outcome measures, should improve the management of OIC. The aim of this feasibility study was to determine whether a definitive study could be successfully completed., Methods: Patients with OIC (Rome Foundation diagnostic criteria positive), and a Bowel Function Index (BFI) score of ≥30, were recruited to the study. The study involved weekly assessments, and decisions about management were based on the current BFI score (and the tolerability of the current treatment). Management was based on a four-step treatment algorithm, developed from recent international guidelines., Results: One hundred patients entered the study, and 79 patients completed the study. Fifty-seven (72%) participants responded to treatment, with 34 (43%) participants having a 'complete' response (ie, final BFI<30) and 23 (29%) participants having a 'partial' response (ie, change in BFI≥12). In participants with a complete response, 73.5% were prescribed conventional laxatives, 12% were prescribed a peripherally acting mu-opioid receptor antagonist (PAMORA) and 14.5% were prescribed a PAMORA and conventional laxative., Discussion: The feasibility study suggests that a definitive study can be successfully completed. However, we will amend the methodology to try to improve participant recruitment, participant retention and adherence to the treatment algorithm. The feasibility study also suggests that the use of the BFI to monitor OIC, and the use of a treatment algorithm to manage OIC, can result in clinically important improvements in OIC.Trial registration number NCT04404933., Competing Interests: Competing interests: AND and CL have both received personal fees for consultancy/educational activities from Kyowa Kirin International. None of the other authors have relevant conflicts of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval ( r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

Objective: Fat-infiltrated axillary lymph nodes (LNs) are unique sites for ectopic fat deposition. Early studies showed a strong correlation between fatty LNs and obesity-related diseases. Confirming this correlation requires large-scale studies, hindered by scarce labeled data. With the long-term goal of developing a rapid and generalizable tool to aid data labeling, we developed an automated deep learning (DL)-based pipeline to classify the status of fatty LNs on screening mammograms., Methods: Our internal data set included 886 mammograms from a tertiary academic medical institution, with a binary status of the fat-infiltrated LNs based on the size and morphology of the largest visible axillary LN. A two-stage DL model training and fine-tuning pipeline was developed to classify the fat-infiltrated LN status using the internal training and development data set. The model was evaluated on a held-out internal test set and a subset of the Digital Database for Screening Mammography., Results: Our model achieved 0.97 (95% CI: 0.94-0.99) accuracy and 1.00 (95% CI: 1.00-1.00) area under the receiver operator characteristic curve on 264 internal testing mammograms, and 0.82 (95% CI: 0.77-0.86) accuracy and 0.87 (95% CI: 0.82-0.91) area under the receiver operator characteristic curve on 70 external testing mammograms., Conclusion: This study confirmed the feasibility of using a DL model for fat-infiltrated LN classification. The model provides a practical tool to identify fatty LNs on mammograms and to allow for future large-scale studies to evaluate the role of fatty LNs as an imaging biomarker of obesity-associated pathologies., Advances in Knowledge: Our study is the first to classify fatty LNs using an automated DL approach., Competing Interests: Competing interestsThe authors declare no competing interests.

Objectives: To estimate age-specific, sex-specific, and race-specific incidence of posterior reversible encephalopathy syndrome (PRES) in the United States., Methods: We conducted a retrospective cohort study using the State Inpatient Database of Florida (2016-2019), Maryland (2016-2019), and New York (2016-2018). All new cases of PRES in adults (18 years or older) were combined with Census data to compute incidence. We evaluated the generalizability of incident estimates to the entire country using the 2016-2019 National Readmissions Database (NRD)., Results: Across the study period, there were 3,716 incident hospitalizations for PRES in the selected states. The age-standardized and sex-standardized incidence of PRES was 2.7 (95% CI 2.5-2.8) cases/100,000/y. Incidence in female patients was >2 times that of male patients (3.7 vs 1.6 cases/100,000/y, p < 0.001). Incidence increased with age in both sexes ( p -trend <0.001). Similar demographic distribution of first hospitalization for PRES was also noted in the entire country using the NRD. Age-standardized and sex-standardized PRES incidence in Black patients (4.2/100,000/y) was significantly greater than in Non-Hispanic White (2.7/100,000/y) and Hispanic patients (1.2/100,000/y) ( p < 0.001 for pairwise comparisons)., Discussion: The incidence of PRES in the United States is approximately 3/100,000/y, but incidence in female patients is >2 times that of male patients. PRES incidence is higher in Black compared with non-Hispanic White and Hispanic patients., (© 2023 American Academy of Neurology.)

Depressed individuals show a wide range of difficulties in executive functioning (including working memory), which can be a significant burden on everyday mental processes. Theoretical models of depression have proposed these difficulties to be especially pronounced in affective contexts. However, evidence investigating affective working memory (WM) capacity in depressed individuals has shown mixed results. The preregistered study used a complex span task, which has been shown to be sensitive to difficulties with WM capacity in affective relative to neutral contexts in other clinical groups, to explore affective WM capacity in clinical depression. Affective WM capacity was compared between individuals with current depression ( n = 24), individuals in remission from depression ( n = 25), and healthy controls (n = 30). The results showed that, overall, WM capacity was more impaired in the context of negative distractor images, relative to neutral images. Furthermore, those with a lifetime history of depression (individuals with current depression and individuals remitted from depression), performed worse on the task, compared to healthy controls. However, there was no support for the greater disruption of WM capacity in affective compared to neutral contexts in those with a lifetime history of depression. These findings' implications for current models of depression are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Individuals with depression typically remember their past in a generalised manner, at the cost of retrieving specific event memories. This may impair engagement with cognitive behavioural therapy (CBT) tasks that use concrete episodic information to challenge maladaptive beliefs, potentially limiting their therapeutic benefit. Study 1 demonstrated that an episodic specificity induction increased detail and specificity of autobiographical memory in people with major depression, relative to control conditions (N = 88). We therefore examined whether the induction enhanced the efficacy of CBT tasks that depend on episodic memory - cognitive reappraisal (Study 2, N = 30), evidence gathering (Study 2, N = 30), and planning behavioural experiments (Study 3a, N = 30). Across all three tasks, there were no significant differences in emotion- or belief-change between the specificity and control conditions. Although the induction temporarily enhanced specificity in depressed individuals, it did not significantly augment the efficacy of CBT tasks theorised to benefit from the use of specific mnemonic information., Competing Interests: Declaration of competing interest The authors declare that there were no conflicts of interest with respect to the authorship or the publication of this article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Optic perineuritis (OPN) is a previously undescribed sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we present a case of OPN that developed several weeks after initial confirmation of the presence of novel coronavirus RNA in the nasopharynx by polymerase chain reaction assay and subsequent confirmation of SARS-CoV-2 IgG seropositivity in the absence of other systemic inflammatory or infectious markers., Case Report: An asymptomatic 71-year-old man with noninsulin-dependent diabetes mellitus (NIDDM) tested RNA positive for SARS-CoV-2 during a routine screening of patients at a skilled nursing facility. ~3 weeks after the positive SARS-CoV-2 polymerase chain reaction test, the patient developed subacute ophthalmoparesis of the left eye, horizontal diplopia, retro-orbital pain, and frontal headache. An urgent magnetic resonance imaging of the head and orbits suggested OPN. Cerebrospinal fluid studies were without evidence of other infectious, inflammatory, neoplastic, or paraneoplastic processes. He was started on a 5-day course of high-dose intravenous steroids and later transitioned to oral steroid therapy. Sixteen days after the initiation of steroid therapy, the patient had no headache or retro-orbital pain and demonstrated a marked improvement in horizontal gaze., Conclusion: SARS-CoV-2-associated neurological sequelae have been increasingly recognized during the current coronavirus disease 2019 pandemic. The present case suggests that patients with confirmed SARS-CoV-2 positivity, even without pulmonary or other classic manifestations of active infection, may manifest diverse clinical presentations including postinfectious OPN that could be related to an underlying autoimmune reactive inflammatory response., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Chronic back pain is a physically debilitating condition that affects more than 80% of adults in the United States. A recent case series highlighted how abdominoplasty with plication can offer an alternative surgical approach for treating chronic back pain. These results have been corroborated by a large prospective series. However, this study excluded male and nulliparous subjects, who may also benefit from this surgery. Our group aims to investigate the effect of abdominoplasty on back pain in a more diverse patient population., Methods: Subjects older than 18 years undergoing abdominoplasty with plication were recruited. An initial survey called the Roland-Morris Disability Questionnaire (RMQ) was administered at the preoperative visit. This questionnaire inquiries about and grades the patient's history of back pain and surgery. Demographic, medical, and social history was also obtained. A follow-up survey and RMQ was then given 6 months after surgery., Results: Thirty subjects were enrolled. Subjects had a mean age of 43.4 ± 14.3 years. Twenty-eight subjects were female and 26 were postpartum. Twenty-one subjects reported initial back pain on the RMQ scale. Of these, 19 reported a decrease in RMQ score after surgery, including male and nulliparous subjects. A significant decrease in mean RMQ score was demonstrated 6 months after surgery (2.94-0.44, P < 0.001). Further subgroup analysis of female subjects demonstrated significantly decreased final RMQ score in parous women, vaginal or cesarean section delivery, and absence of twin gestation., Conclusions: Abdominoplasty with plication significantly decreases self-reported back pain 6 months after surgery. These results support that abdominoplasty is not purely a cosmetic procedure but can also be applied therapeutically to improve functional symptoms of back pain., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: To test the hypothesis that the age and sex-specific prevalence of infectious (pneumonia, sepsis, and urinary tract infection [UTI]) and noninfectious (deep venous thrombosis [DVT], pulmonary embolism [PE], acute renal failure [ARF], acute myocardial infarction [AMI], and gastrointestinal bleeding [GIB]) complications increased after acute ischemic stroke (AIS) hospitalization in the United States from 2007 to 2019., Methods: We conducted a serial cross-sectional study using the 2007-2019 National Inpatient Sample. Primary AIS admissions in adults (aged 18 years or older) with and without complications were identified using International Classification of Diseases codes. We quantified the age/sex-specific prevalence of complications and used negative binomial regression models to evaluate trends over time., Results: Of 5,751,601 weighted admissions, 51.4% were women. 25.1% had at least 1 complication. UTI (11.8%), ARF (10.1%), pneumonia (3.2%), and AMI (2.5%) were the most common complications, while sepsis (1.7%), GIB (1.1%), DVT (1.2%), and PE (0.5%) were the least prevalent. Marked disparity in complication risk existed by age/sex (UTI: men 18-39 years 2.1%; women 80 years or older 22.5%). Prevalence of UTI (12.9%-9.7%) and pneumonia (3.8%-2.7%) declined, but that of ARF increased by ≈3-fold (4.8%-14%) over the period 2007-2019 (all p < 0.001). AMI (1.9%-3.1%), DVT (1.0%-1.4%), and PE (0.3%-0.8%) prevalence also increased ( p < 0.001), but that of sepsis and GIB remained unchanged over time. After multivariable adjustment, risk of all complications increased with increasing NIH Stroke Scale (pneumonia: prevalence rate ratio [PRR] 1.03, 95% CI 1.03-1.04, for each unit increase), but IV thrombolysis was associated with a reduced risk of all complications (pneumonia: PRR 0.80, 85% CI 0.73-0.88; AMI: PRR 0.85, 95% CI 0.78-0.92; and DVT PRR 0.87, 95% CI 0.78-0.98). Mechanical thrombectomy was associated with a reduced risk of UTI, sepsis, and ARF, but DVT and PE were more prevalent in MT hospitalizations compared with those without. All complications except UTI were associated with an increased risk of in-hospital mortality (sepsis: PRR 1.97, 95% CI 1.78-2.19)., Discussion: Infectious complications declined, but noninfectious complications increased after AIS admissions in the United States in the last decade. Utilization of IV thrombolysis is associated with a reduced risk of all complications., (© 2023 American Academy of Neurology.)

While the physical signs of opioid withdrawal are most readily observable, withdrawal insidiously drives relapse and contributes to compulsive drug use, by disrupting emotional learning circuits. How these circuits become disrupted during withdrawal is poorly understood. Because amygdala neurons mediate relapse, and are highly opioid sensitive, we hypothesized that opioid withdrawal would induce adaptations in these neurons, opening a window of disrupted emotional learning circuit function. Under normal physiological conditions, synaptic transmission between the basolateral amygdala (BLA) and the neighboring main island (Im) of GABAergic intercalated cells (ITCs) is strongly inhibited by endogenous opioids. Using patch-clamp electrophysiology in brain slices prepared from male rats, we reveal that opioid withdrawal abruptly reduces the ability of these peptides to inhibit neurotransmission, a direct consequence of a protein kinase A (PKA)-driven increase in the synaptic activity of peptidases. Reduced peptide control of neurotransmission in the amygdala shifts the excitatory/inhibitory balance of inputs onto accumbens-projecting amygdala cells involved in relapse. These findings provide novel insights into how peptidases control synaptic activity within the amygdala and presents restoration of endogenous peptide activity during withdrawal as a viable option to mitigate withdrawal-induced disruptions in emotional learning circuits and rescue the relapse behaviors exhibited during opioid withdrawal and beyond into abstinence. SIGNIFICANCE STATEMENT We find that opioid withdrawal dials down inhibitory neuropeptide activity in the amygdala. This disrupts both GABAergic and glutamatergic transmission through amygdala circuits, including reward-related outputs to the nucleus accumbens. This likely disrupts peptide-dependent emotional learning processes in the amygdala during withdrawal and may direct behavior toward compulsive drug use., (Copyright © 2023 the authors.)