Different Surgical Approaches to the Treatment of Cleft Palate Fistulae as Perceived by Cleft Surgeons.

OBJECTIVE: Palatal fistulas after palatoplasty could pose difficulties for both patients and surgeons. Numerous surgical approaches are available to treat palatal fistulas. In this manuscript, we investigate surgical treatment options for palatal fistula repair looking at the different anatomical locations, and we create a summary of surgical approaches to facilitate the decision-making process for palatal fistulae repair. DESIGN: In this cross-sectional survey, nine anonymized patient cases with palatal fistulae that differed in severity and anatomical location were presented to participants from the International Cleft Master Course in Amsterdam about "Palatal Fistulas". Participants were invited to participate in this survey. A total of 141 participants reported their preferred surgical treatment options for fistula repair at different anatomical locations. RESULTS: We created different options for fistula treatment, catalogued by fistula location. This overview gives the surgeon possible approaches for each location. If the soft palate is involved, this overview underscores the importance of including velopharyngeal insufficiency management into the fistula repair. For hard palate involvement, our overview lists techniques available for nasal lining repair and for oral lining repair in each region. CONCLUSIONS: We provide a comprehensive overview of potential surgical approaches to repair palatal fistulae. This inventory of techniques is grouped per location to support surgeons in their decision-making process when confronted with a palatal fistula.

Virtual Reality as an Adjunct to Traditional Patient Counseling in Patients With Newly Diagnosed Localized Prostate Cancer.

OBJECTIVE: To determine the utility of a virtual reality (VR) model constructed using patient-derived clinical imaging to improve patient understanding of localized prostate cancer (PCa) diagnosis and surgical plan. METHODS: Patients undergoing robotic radical prostatectomy were selected and demographic data recorded. Patients completed a questionnaire to assess baseline knowledge of their diagnosis after consultation and shared-decision making with their surgeon. A trained non-clinical staff member then guided the patient through a VR experience to view patient-specific anatomy in a 3-dimensional space. Patients then completed the same questionnaire, followed by an additional post-VR questionnaire evaluating patient satisfaction. Questions 1-7 (patient understanding of prostate cancer and treatment plan) and 11-17 (patient opinion of VR) used a standard Likert scale and Questions 8-10 were multiple choice with 1 correct answer. RESULTS: In total, 15 patients were included with an average age of 64.1 years. 6 of 7 questions showed an improvement after VR (P <.001). The percentage of correct responses on Questions 8-10 was higher after VR but not statistically significant (P >.13). Mean responses range from 4.3 to 4.8 (Likert scale, 1 through 5) for the post-VR questionnaire, with a mean total of 31.9 out of 35. CONCLUSION: This small preliminary investigation of a novel technology to improve the patient experience showed potential as an adjunct to traditional patient counseling. However, due the small sample size and study design, further research is needed to determine the value VR adds to prostate cancer surgical counseling.

Trifecta Outcomes After Use of 3-Dimensional Digital Models for Planning of Robotic Prostatectomy: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Planning complex operations such as robotic-assisted laparoscopic radical prostatectomy (RALP) requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) scans to understand 3-dimensional (3D) patient anatomy. Three-dimensional digital models for planning RALP may allow better understanding of patient anatomy and may lead to better patient outcomes, although data are currently limited. Objective: To determine surgical outcomes after RALP when surgeons reviewed 3D digital models during operative planning. Design, Setting, and Participants: This study was a planned secondary analysis of a multicenter, single-blind, randomized clinical trial conducted at 6 large teaching hospitals in the US. The study was conducted between January 1, 2019, and December 31, 2022, and included patients undergoing RALP. Patients were assessed and recruited at the time of surgical consultation. Final data analysis was conducted between August and December 2023. Intervention: Patients were randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and multiparametric MRI only or to an intervention group in which imaging and biopsy results were supplemented with a 3D digital model. This model was viewed on the surgeon's mobile phone in 3D format and picture-in-picture on the robotic console screen. Main Outcomes and Measures: The primary outcome measure for the overall study was oncologic outcomes after RALP, measured as prostate-specific antigen (PSA) detectability. Secondary outcomes were sexual function and urinary function, measured with Sexual Health Inventory for Men (SHIM) scores and rates of urinary incontinence, respectively, as well as use of salvage or adjuvant radiation therapy (RT) or androgen deprivation therapy (ADT). Trifecta outcomes were defined as undetectable PSA without RT or ADT, SHIM score categorically the same or greater than preoperatively, and complete continence. Univariate analysis was performed to compare outcomes between groups. Results: This trial included 92 patients undergoing RALP (51 in the control group and 41 in the intervention group). Their mean (SD) age was 62 (7.4) years; 10 patients (10.9%) were Black and 67 (72.8%) were White. At 18 months postsurgery, the intervention group had lower rates of biochemical recurrence (PSA level >0.1 ng/mL, 0 vs 7 [17.9%]; absolute difference, 17.9% [95% CI, 1.8% to 31.8%]; P = .01) and were significantly less likely to undergo adjuvant or salvage RT (1 [3.1%] vs 12 [31.6%]; absolute difference, 28.5% [95% CI, 10.1% to 46.7%]; P = .002) compared with the control group. Sexual function at 18 months postsurgery was significantly better in the intervention group (mean [SD] SHIM score, 16.8 [8.7] vs 9.8 [7.7]; absolute difference, 7.0 [95% CI, 2.6 to 11.4]; P = .002) and urinary function was unchanged (total continence, 22 [78.6%] vs 29 [80.6%]; absolute difference, 2.0% [95% CI, -17.9% to 21.9%]; P = .84) compared with the control group. Trifecta outcomes were achieved for 12 (48.0%) patients in the intervention group and 3 patients (10.0%) in the control group (absolute difference, 38.0% [95% CI, 14.4% to 61.6%]; P = .002). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, patients whose surgical planning of RALP involved 3D digital models had better oncologic and functional outcomes. Further work should assess the effect of 3D models in a broader set of patients, physicians, and hospital settings. Trial Registration: ClinicalTrials.gov Identifier: NCT03943368.

N-Glycan Branching Regulates BTLA Opposite to PD-1 to Limit T Cell Hyperactivity Induced by Branching Deficiency.

N-glycan branching is a potent and multifaceted negative regulator of proinflammatory T cell and B cell function. By promoting multivalent galectin-glycoprotein lattice formation at the cell surface, branching regulates clustering and/or endocytosis of the TCR complex (TCR+CD4/CD8), CD45, CD25, BCR, TLR2 and TLR4 to inhibit T cell and B cell activation/proliferation and proinflammatory TH1 and TH17 over TH2 and induced T regulatory cell responses. In addition, branching promotes cell surface retention of the growth inhibitory receptor CTLA-4. However, the role of N-glycan branching in regulating cell surface levels of other checkpoint receptors such as BTLA (B and T lymphocyte attenuator) and PD-1 (programmed cell death protein 1) is unknown. In this study, we report that whereas branching significantly enhances PD-1 cell surface expression by reducing loss from endocytosis, the opposite occurs with BTLA in both T cells and B cells. T cell hyperactivity induced by branching deficiency was opposed by BTLA ligation proportional to increased BTLA expression. Other members of the BTLA/HVEM (herpesvirus entry mediator) signaling axis in T cells, including HVEM, LIGHT, and CD160, are largely unaltered by branching. Thus, branching-mediated endocytosis of BTLA is opposite of branching-induced inhibition of PD-1 endocytosis. In this manner, branching deficiency-induced upregulation of BTLA appears to serve as a checkpoint to limit extreme T cell hyperactivity and proinflammatory outcomes in T cells with low branching.

Leveraging the One Health concept for arsenic sustainability.

Arsenic (As) is a naturally occurring chemical element widely distributed in the Earth's crust. Human activities have significantly altered As presence in the environment, posing significant threats to the biota as well as human health. The environmental fates and adverse outcomes of As of various species have been extensively studied in the past few decades. It is imperative to summarize these advances as a whole to provide more profound insights into the As cycle for sustainable development. Embracing the One Health concept, we systematically reviewed previous studies in this work and explored the following three fundamental questions, i.e., what the trends and associated changes are in As contamination, how living organisms interact and cope with As contamination, and most importantly what to do to achieve a sustainable future with As. By focusing on one critical question in each section, this review aims to provide a full picture of the complexity of environmental As. To tackle the significant research challenges and gaps in As pollution and mitigation, we further proposed a One Health framework with potential coping strategies, guiding a coordinated agenda on dealing with legacy As in the environment and ensuring a sustainable As future.

IN Esketamine and IV Ketamine: Results of a multi-site observational study assessing the effectiveness and tolerability of two novel therapies for treatment-resistant depression.

Intravenous (IV) ketamine and intranasal (IN) esketamine are novel therapies to manage treatment resistant depression within major depressive disorder (MDD-TRD). This is a multi-site observational study aiming to assess the real-world effectiveness and tolerability of these novel therapies in the management of MDD-TRD. 53 patients were referred to receive IV ketamine (n = 26, 69.23 % female, 52.81 ± 14.33 years old) or IN esketamine (n = 27, 51.85 % female, 43.93 ± 13.57 years old). Treatment effectiveness was assessed using the Montgomery and Åsberg Depression Rating Scale (MADRS) for depression severity and item 10 of the MADRS for suicidal ideation (SI). Tolerability was assessed by systematically tracking side effects and depersonalization using the 6-item Clinician administered dissociative symptom scale (CADSS-6). The data was analyzed using descriptive statistics, risk ratio and effect size. Both IV ketamine and IN esketamine significantly reduced depressive symptoms and suicidal ideation by treatment endpoint. Patients receiving IN esketamine, and patients receiving IV ketamine had a similar risk of developing side effects. All side effects reported were mild and transient. These results suggested that both IV ketamine and IN esketamine are effective in the management of depressive symptoms and were well tolerated. Therefore, the results of this study could serve to inform clinical practice.

Changes in higher order cognitive function between four watch keeping schedules.

Maritime industries utilize many different watch keeping schedules to maintain vigilance and crew safety around the clock. These schedules can be fatiguing, negatively impacting vigilant attention. This has led to the consideration of schedules that might allow for more sleep time, but how these schedules impact higher order cognitive function remains unclear. These schedules require assessment with tasks that are relevant to real-world operations on maritime vessels. This study investigated the effect of four schedules on higher order cognitive function. N = 27 (16 female) participants were recruited to a 10-day laboratory study, comparing four schedules. The schedules investigated were eight-on/eight-off/four-on/four-off (8/8/4/4) with sleep from 09:30 to 16:00 (condition A); six-on/six-off (6/6) with sleep from 08:30 to 12:30 and 21:30 to 00:00 (condition B); four-on/four-off (4/4/4/4/4/4) with sleep from 18:00 to 00:30 (condition C); and four-on/four-off (4/4/4/4/4/4) with sleep from 01:30 to 08:00 (condition D). Higher order cognitive function was assessed 2-3× daily whilst "on watch" using tests of visual scanning, learning, working memory, mental flexibility, and visuomotor control. Conditions were ranked and stability of performance on watch was compared between conditions using Kruskal-Wallis tests. Cognitive function within condition B was ranked the worst for most of the tasks. However, the stability of higher order cognitive function was poorest across the waking day within condition A. These findings highlight the variability in cognitive capacities during different watch keeping schedules.

Small towns limit dispersal and reduce genetic diversity in populations of Texas horned lizards.

There is a general expectation that urban populations will be fragmented and the movement of individuals will be restricted leading to low effective population sizes, low genetic diversity, higher inbreeding, and higher differentiation than populations living in more continuous habitat. In this study, we compare the genetic diversity and differentiation of Texas horned lizards that are found in four small towns (Kenedy, Karnes City, Rockdale, and Smithville) in Texas and at Tinker Air Force Base, Oklahoma to populations that occur in 16 natural areas and to an introduced population in South Carolina. We also present more detailed spatial genetic data and home range data for several of the towns. Texas horned lizards (Phrynosoma cornutum) living in small towns have lower genetic diversity, higher differentiation, and smaller effective population sizes than populations located in more natural areas. There was evidence for human-mediated movement of lizards into town; however, it has not been enough to counteract the effects of drift. Home range size is smaller in town than in more natural areas. Genetic patterns suggest dispersal occurs over short distances and is inhibited across areas with a high percent of impervious surface and major roads. These data suggest that effective planning to maintain suitable habitat and corridors to facilitate movement is critical to maintaining small terrestrial species like the Texas horned lizard and must be integrated into the early stages of urban development.

Comparison of the Efficacy Between Standard Measurement-Base Care (MBC) and Enhanced MBC for Major Depressive Disorder: A Pilot Study.

Purpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder. Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points. Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up. Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.

Racial, ethnic, and socioeconomic disparities in rates of stage IV prostate cancer after USPSTF category "D" recommendation against prostate-specific antigen screening: a retrospective cohort study.

Background: In 2012 the United States Preventative Services Task Force (USPSTF) changed its prostate-specific antigen (PSA) screening recommendation to a category "D". The purpose of this study is to examine racial, ethnic, and socioeconomic differences in risk of presentation with metastatic prostate cancer (mPCa) at time of diagnosis before and after the 2012 USPSTF category "D" recommendation. Methods: This is a population-based cohort study. We identified patients with mPCa at diagnosis within the National Cancer Database from 2004-2017. Logistic regression models were used to examine associations of mPCa with age, race, ethnicity, geographic location, education level, income, and insurance status. Linear regression models assuming underlying binomial distribution were fitted to annual percentage of mPCa at diagnosis for years 2012-2017 to evaluate the post category "D" recommendation era. Results: From 2004 to 2017, 88,987 patients presented with mPCa. A higher percentage of mPCa was noted post-USPSTF category "D" recommendation, with a disproportionately greater increase observed among Hispanics and non-Hispanic Blacks [Δslope/year: Hispanics (0.0092), non-Hispanic Blacks (0.0073) and non-Hispanic Whites (0.0070)]. Insurance status impacts race/ethnicity differently: uninsured Hispanics were 3.66 times more likely to present with mPCa than insured Hispanics, while uninsured non-Hispanic Blacks were 2.62 times more likely to present with mPCa than insured non-Hispanic Blacks. Household income appears to be associated with differences in mPCa, particularly among non-Hispanic Blacks. Those earning <$30,000 were more likely to present with mPCa compared to higher income brackets. Conclusions: Since the USPSTF grade "D" recommendation against PSA screening, the percentage of mPCa at diagnosis has increased, with a higher rate of increase among Hispanic and non-Hispanic Blacks compared to non-Hispanic Whites.

External RF-EMF alters cell number and ROS balance possibly via the regulation of NADPH metabolism and apoptosis.

The influence of weak radio-frequency electromagnetic field (RF-EMF) on living organisms raises new concern because of the Industrial, Scientific, and Medical (ISM) frequency band at 6.78 MHz being promoted by the AirFuel Alliance for mid-range wireless power transfer (WPT) applications and product development. Human exposure to the RF-EMF radiation is unavoidable. In this study, we employed in vitro cell culture and molecular biology approach coupled with integrated transcriptomic and proteomic analyses to uncover the effects of RF-EMF on cells at molecular and cellular levels. Our study has demonstrated that weak RF-EMF is sufficient to exert non-thermal effects on human umbilical vein endothelial cells (HUVEC). Exposure of weak RF-EMF promotes cell proliferation, inhibits apoptosis and deregulates ROS balance. Alteration of several signaling pathways and key enzymes involved in NADPH metabolism, cell proliferation and ferroptosis were identified. Our current study provide solid evidence for the first time that the present safety standards that solely considered the thermal effect of RF-EMF on cell tissue are inadequate, prompt response and modification of existing Guidelines, Standards and Regulation are warranted.

Mechanisms of action of microbicides commonly used in infection prevention and control.

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

Alpha Angle and Anterior Femoral Neck Offset Identify Different Cohorts of Cam Morphology: An Osteologic Study.

PURPOSE: To explore differences in cam morphology defined by alpha angle (AA) and anterior femoral neck offset (AFNO) in the context of other anthropometric parameters in an osteologic collection to further elucidate whether each measurement tool is identifying the same underlying pathology. METHODS: Anthropometric measurements of 992 cadaveric hips from the Hamann-Todd Osteological Collection were analyzed. Femurs with cam morphology were identified by AA >55° or AFNO <7 mm. Anthropometric parameters stratified by cam morphology were assessed with Wilcoxon rank-sum and Pearson χ2 tests. Multivariate logistic regressions were performed on significant variables in univariate analysis to examine the predictive ability of anthropometric variables to cam morphology. RESULTS: Cam morphology was identified in 242 hips via AA, 344 hips via AFNO, and 123 hips via both measures. Multivariate logarithmic regression analysis demonstrated that sex negatively predicted AA (females with less pathology, ß = -0.14, P = .04), race negatively predicted AA (Blacks with less pathology, ß = -0.21, P < .01), and proximal femoral osteoarthritis was positively associated with AA (ß = 0.16, P = .02), while none of these were associated with AFNO. On the other hand, right-side specimens were associated with AA (ß = 0.15, P = .02) and AFNO (ß = 0.25, P < .01), whereas the combined version was unassociated with both measures. CONCLUSIONS: In conclusion, cam morphology was identified in a modest percentage of osteologic specimens by both AA and AFNO in our study. Further, associations of multiple demographic, anthropometric, and anatomical parameters to AA and AFNO suggest they may identify different subsets of cam morphology. CLINICAL RELEVANCE: Cam morphology identified by AA versus AFNO may represent 2 different pathologic entities. Future studies should assess differences between these measures in a clinical cohort and determine whether these 2 definitions of cam morphology identify different clinical populations.

Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

DeepComBat: A statistically motivated, hyperparameter-robust, deep learning approach to harmonization of neuroimaging data.

Neuroimaging data acquired using multiple scanners or protocols are increasingly available. However, such data exhibit technical artifacts across batches which introduce confounding and decrease reproducibility. This is especially true when multi-batch data are analyzed using complex downstream models which are more likely to pick up on and implicitly incorporate batch-related information. Previously proposed image harmonization methods have sought to remove these batch effects; however, batch effects remain detectable in the data after applying these methods. We present DeepComBat, a deep learning harmonization method based on a conditional variational autoencoder and the ComBat method. DeepComBat combines the strengths of statistical and deep learning methods in order to account for the multivariate relationships between features while simultaneously relaxing strong assumptions made by previous deep learning harmonization methods. As a result, DeepComBat can perform multivariate harmonization while preserving data structure and avoiding the introduction of synthetic artifacts. We apply this method to cortical thickness measurements from a cognitive-aging cohort and show DeepComBat qualitatively and quantitatively outperforms existing methods in removing batch effects while preserving biological heterogeneity. Additionally, DeepComBat provides a new perspective for statistically motivated deep learning harmonization methods.

How Prominent Are Gender Bias, Racial Bias, and Score Inflation in Orthopaedic Surgery Residency Recommendation Letters? A Systematic Review.

INTRODUCTION: Letters of recommendation are considered an important factor in the holistic ranking of orthopaedic residency applications. The standardized letter of recommendation (SLOR) was introduced in 2017 in response to the inherent bias and limited comparative value of traditional LORs. It includes standardized questions about an applicant's orthopaedic qualifications, designed to enable fair comparisons among candidates. However, disparate and inconsistent findings have made it difficult to draw meaningful conclusions from individual studies on the SLOR and narrative letter of recommendation. QUESTION/PURPOSES: In this systematic review we asked: (1) What is the distribution of applicant SLOR rating among nine domains and summative scores? (2) Are there applicant characteristics associated with SLOR ratings? (3) Is there gender and racial bias in the SLOR and narrative letter of recommendation? METHODS: PubMed, EBSCO, and Google Scholar electronic databases were queried on March 20, 2023, to identify all studies evaluating SLOR and narrative letter of recommendations between January 1, 2017, and March 20, 2023. Articles that evaluated orthopaedic SLOR or narrative LORs were included. Systematic reviews, case reports, duplicate studies between databases, and grey literature such as abstracts and articles on preprint servers were excluded. Eight studies including 6179 applicants and 18,987 letters of recommendation were included in the final analysis. The applicant classes ranged from years 2014 to 2020. Two reviewers independently evaluated the quality of the included studies using the Joanna Briggs Institute (JBI) tool for cross-sectional studies. The mean JBI score of included studies was 7.4 out of a maximum of 8, with higher scores indicating better quality. The primary outcome was to determine the distribution of applicant SLOR rankings in their summative score. Summative scores were separated into ranked to match, top one-third, middle one-third, lower one-third, and not a fit. Four studies reported the summative SLOR scores of applicants. Our secondary study goal was to assess applicant characteristics associated with SLOR summative scores and assess any bias present in the SLOR or narrative recommendation. Five studies compared SLOR ratings across applicant characteristics including gender, race, USMLE Step 1 score, USMLE Step 2 score, Alpha Omega Alpha (AΩA) membership, clerkship grades, and publications. Gender and racial bias were also assessed across five studies. Four studies utilized a linguistic analysis software to search letters of recommendation for differences in word category use by gender and race. RESULTS: Studies consistently found that a higher percentage of candidates were identified in the top percentile blocks than is mathematically possible. For example, the two studies that tallied the proportion of candidates ranking in the top 10% of applicants found that 36% and 42% were rated as being in the top 10%. Similarly, articles found more than 87% of applicants scored in the top one-third. Studies had mixed results, but in general, they suggested that AΩA status, higher Step 1 scores, and more research publications have a slightly positive association with increased SLOR scores. We found no evidence of gender bias against women, and in fact, most studies evaluating word choices found word choices for women candidates generally were stronger. Similarly, no consistent disparities were identified in word categories utilized in SLORs based on applicant race. CONCLUSION: Most notably, a mathematically impossible proportion of applicants were counted in the top percentiles in letters of recommendation. This compromises readers' abilities to differentiate candidates. Factors like AOA status and research publications displayed a modest positive correlation with SLOR scores. Gender bias against women or candidates from racial minority groups was not evident. CLINICAL RELEVANCE: We suggest that group SLOR authorship, with a consensus assessment by clerkship or residency directors, should be considered. We also recommend the incorporation of mean and SD scores for each letter writer (or group) alongside their letters. Furthermore, studies indicate that submitting all four SLOR letters can substantially improve an applicant's chances of success. We advise students to choose strategically and submit the maximum allowable number of SLORs.

Osteocalcin: A novel biomarker of adolescent psychopathology.

Osteocalcin is a bone-derived hormone implicated in the acute stress response and recently linked to adult depression. Yet it is unclear whether osteocalcin is a biomarker of other forms of psychopathology and whether osteocalcin-psychopathology associations emerge during developmentally sensitive periods earlier in life. Thus, in the current pilot study we examined salivary osteocalcin and psychiatric symptoms and disorders among 48 early adolescents during a period of stress. A logistic regression indicated lower osteocalcin was associated with meeting criteria for a psychiatric disorder, OR = 0.43, 95 % CI [.002,.924], and showed moderate-to-large cross-sectional associations with a range of elevated psychopathology symptoms, Bs ≥ |-3.44|, ps ≤.034. Multilevel linear growth models indicated that low osteocalcin prospectively predicted an even greater range of psychopathology symptoms at one-year follow-up as well as increases in some symptoms over time, Bs ≥ |-1.83|, ps ≤.021. Findings introduce osteocalcin as a biomarker of diverse forms of psychopathology in youth. Osteocalcin is a potential transdiagnostic mechanism through which dysregulated responses to stress could cause or exacerbate various types of psychopathology, highlighting a promising target for clinical assessment and early intervention.

(Cost-)effectiveness of personalised multimodal physiotherapy compared to surgery in patients with cervical radiculopathy: A systematic review.

RATIONALE: Cervical radiculopathy is initially typically managed conservatively. Surgery is indicated when conservative management fails or with severe/progressive neurological signs. Personalised multimodal physiotherapy could be a promising conservative strategy. However, aggregated evidence on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with/without post-operative physiotherapy is lacking. AIM/OBJECTIVES: To systematically summarise the literature on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with or without post-operative physiotherapy in patients with cervical radiculopathy. METHODS: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched from inception to 1st of March 2023. Primary outcomes were effectiveness regarding costs, arm pain intensity and disability. Neck pain intensity, perceived recovery, quality of life, neurological symptoms, range-of-motion, return-to-work, medication use, (re)surgeries and adverse events were considered secondary outcomes. Randomised clinical trials comparing personalised multimodal physiotherapy versus surgical approaches with/without post-operative physiotherapy were included. Two independent reviewers performed study selection, data-extraction, and risk of bias assessment using the Cochrane RoB 2 and Consolidated Health Economic Evaluation Reporting Standards statement. Certainty of the evidence was determined using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: From 2109 records, eight papers from two original trials, with 117 participants in total were included. Low certainty evidence showed there were no significant differences on arm pain intensity and disability, except for the subscale 'heavy work' related disability (12 months) and disability at 5-8 years. Cost-effectiveness was not assessed. There was low certainty evidence that physiotherapy improved significantly less on neck pain intensity, sensory loss and perceived recovery compared to surgery with/without physiotherapy. Low certainty evidence showed there were no significant differences on numbness, range of motion, medication use, and quality of life. No adverse events were reported. CONCLUSION: Considering the clinical importance of accurate management recommendations and the current low level of certainty, high-quality cost-effectiveness studies are needed.