Rethinking Unacceptable Thoughts: Validation of an Expanded Version of the Dimensional Obsessive-Compulsive Scale.

The Dimensional Obsessive-Compulsive Scale (DOCS) is widely used to measure obsessive-compulsive disorder (OCD) severity across four broad symptom dimensions (i.e., contamination, responsibility for harm, unacceptable thoughts, symmetry). Despite its proven utility, there is reason to suspect that the unacceptable thoughts subscale conflates different types of unacceptable thoughts that are meaningfully distinct from one another. In the current study, we first evaluated the psychometric properties of a newly developed DOCS violent and/or aggressive thoughts subscale. We then examined the factor structure, psychometric properties, and diagnostic sensitivity of a seven-factor version of the DOCS that includes the four original DOCS subscales and three more-specific versions of the unacceptable thoughts scale (i.e., sexually intrusive thoughts, violent and/or aggressive thoughts, and scrupulous or religious thoughts). The sample included 329 residential and intensive outpatients, the majority of which had a diagnosis of OCD (75.2%). The new unacceptable thoughts subscales demonstrated convergent and discriminant validity with unique associations between the subscales and depression, suicide, and perceived threat from emotions that were not present in the broader unacceptable thoughts subscale. The seven-factor version of the DOCS demonstrated slightly lower levels of diagnostic sensitivity than the original DOCS. Thus, the four-factor version of the DOCS is recommended for screening purposes. A score of 40 or higher on the seven-factor version of the DOCS best predicted a diagnosis of OCD. Overall, the three additional unacceptable thoughts subscales appear to be distinct factors that have potential value in research and clinical settings.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for the Mitigation of Complications of Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to October 2023. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.

INTRODUCTION: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines. RESEARCH DESIGN AND METHODS: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications. RESULTS: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m2, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes. CONCLUSIONS: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events. TRIAL REGISTRATION NUMBER: NCT04049149.

Sociodemographic representation in randomized controlled trials for anxiety-related disorders in the U.S.: A systematic review (1993-2023).

Cognitive behavioral therapies have been identified as evidence-based treatments for anxiety-related disorders. However, data supporting the effectiveness of these treatments have been largely collected from participants with majoritized identities, potentially limiting the extent to which they can be considered "evidence-based" for clients from minoritized groups. The current review examined sociodemographic representation and quality of sociodemographic reporting in randomized controlled trials for anxiety-related disorders in the U.S. between 1993 and 2023. We conducted a systematic literature review of U.S.-based randomized controlled trials of cognitive behavioral therapies for anxiety-related disorders, extracted data on sociodemographic variables, and rated quality of reporting. Data from 55 eligible studies (N = 4492) indicated that white and female identities were overrepresented relative to the U.S. population, with variables like disability status, sexual orientation, and religious identification consistently ignored. In addition, quality of reporting was generally poor (mean = 3.6 out of 10), with many studies failing to account for demographic variables in their analyses or description of study limitations. Publication year, sample size, and NIH funding status did not significantly predict gender representation (% women), ethnoracial representation (% white), or quality of reporting. These findings underscore the importance of critically evaluating to whom "evidence-based" treatments apply and increasing diversity of clinical samples, to ensure that evidence-based treatments are inclusive. Recommendations for future research, clinical implications, and limitations are discussed.

Analysis of Hip Preservation Questions on the Orthopaedic In-Training Examination Over the Past 20 Years.

Background: The orthopaedic in-training examination (OITE) is a 275-question test for orthopaedic residents administered annually. As the field of orthopaedics changes, the OITE evolves its content. The incidence of hip preservation-related procedures has increased substantially over the past decade; nonetheless, an analysis of the trends of hip preservation questions on the OITE has not yet been performed. Purpose/Hypothesis: The purpose of the study was to evaluate the number and type of questions on the OITE related to hip preservation to determine whether trends over time paralleled the increases in hip-related care in clinical practice. It was hypothesized that the frequency of hip preservation questions on the OITE would increase with time. Study Design: Cross-sectional study. Methods: Each OITE between 2002 and 2021 was reviewed for questions related to hip preservation. The types of questions included under "hip preservation" were those related to femoroacetabular impingement (FAI), athletic soft tissue injuries of the hip, acetabular labral tears, hip arthroscopy, and surgical management of adult hip dysplasia-excluding arthroplasty. Questions were quantified and categorized by topic, taxonomy level, associated imaging, and cited sources. Results: There were 30 hip preservation-related questions between 2002 and 2021. Of these, 77% occurred within the past 10 years. Also, 14 questions (47%) had associated images in the question stem-the most common being radiographs (n = 8 questions). The most commonly tested subcategories were FAI (n = 11 questions [37%]), athletic injuries (n = 7 questions [23%]), and anatomy (n = 7 questions [23%]). Over the last 10 years, 97.9% of citations were from journal articles-the most common being the Journal of the American Academy of Orthopaedic Surgeons, Clinical Orthopedics and Related Research, and the American Journal of Sports Medicine. Conclusion: The frequency of hip preservation-related questions on the OITE has increased with time, reflecting trends in clinical practice.

Effects of mindfulness-based cognitive therapy for Chinese adults with PTSD symptoms: protocol for a randomised controlled trial.

INTRODUCTION: Emerging evidence supports mindfulness as a potential psychotherapy for post-traumatic stress disorder (PTSD). Individuals with subthreshold PTSD experience significant impairment in their daily life and functioning due to PTSD symptoms, despite not meeting the full diagnostic criteria for PTSD in DSM-5. Mindfulness skills, including non-judgmental acceptance, attentional control and openness to experiences may help alleviate PTSD symptoms by targeting characteristics such as intensified memory processing, dysregulated hyperarousal, avoidance, and thought suppression. This trial aims to test the effects of mindfulness-based cognitive therapy (MBCT) when compared to an active control. METHOD AND ANALYSIS: This 1:1 randomised controlled trial will enroll 160 participants with PTSD symptoms in 2 arms (MBCT vs. Seeking Safety), with both interventions consisting of 8 weekly sessions lasting 2 h each week and led by certified instructors. Assessments will be conducted at baseline (T0), post-intervention (T1), and 3 months post-intervention (T2), with the primary outcome being PTSD symptoms measured by the PTSD checklist for DSM-5 (PCL-5) at T1. Secondary outcomes include depression, anxiety, attention, experimental avoidance, rumination, mindfulness, and coping skills. Both intention-to-treat and per-protocol analyses will be performed. Mediation analysis will investigate whether attention, experimental avoidance, and rumination mediate the effect of mindfulness on PTSD symptoms. DISCUSSION: The proposed study will assess the effectiveness of MBCT in improving PTSD symptoms. The findings are anticipated to have implications for various areas of healthcare and contribute to the enhancement of existing intervention guidelines for PTSD. TRIAL REGISTRATION NUMBER: ChiCTR2200061863.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer.

BACKGROUND: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer. MATERIAL AND METHODS: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study. The study endpoint was lympopenia, defined as the reduction in absolute lymphocytes and graded lymphopenia after RT. The dose-volume histogram (DVH) data of related critical structures and clinical factors were taken into account for the development of dense neural network (DNN) predictive models. The developed DNN models were validated using external patient cohorts. RESULTS: A total of 918 consecutive patients with invasive breast cancer enrolled. The training, testing, and external validating datasets consisted of 589, 203, and 126 patients, respectively. Treatment volumes at nearly all dose levels of the DVH were significant predictors for lymphopenia following RT, including volumes at very low-dose 1 Gy (V1) of organs at risk (OARs) including lung, heart and body, especially ipsilateral-lung V1. A final DNN model, combining full DVH dosimetric parameters of OARs and three key clinical factors, achieved a predictive accuracy of 75 % or higher. CONCLUSION: This study demonstrated and externally validated the significance of full dosimetric data, particularly the volume of low dose at as low as 1 Gy of critical structures on lymphopenia after radiation in patients with breast cancer. The significance of V1 deserves special attention, as modern VMAT RT technology often has a relatively high value of this parameter. Further study is warranted for RT plan optimization.

The Relationship Between Transfusion in Cardiac Surgery Patients and Adverse Outcomes.

OBJECTIVES: To understand if red blood cell (RBC) transfusions are independently associated with a risk of mortality, prolonged intubation, or infectious, cardiac, or renal morbid outcomes. DESIGN: A retrospective review. SETTING: A single-institution university hospital. PARTICIPANTS: A total of 2,458 patients undergoing coronary bypass artery graft and/or valvular surgery from July 2014 through January 2018. INTERVENTIONS: No interventions were done. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of an adverse event or prolonged intubation. Infectious, cardiac, and renal composite outcomes were also defined. These composites, along with mortality, were analyzed individually and then combined to form the "any adverse events" composite. Preoperative demographic and intraoperative parameters were analyzed as univariate risk factors for adverse outcomes. Logistic regression was used to screen variables, with a p value criterion of p < 0.05 for entry into the model selection procedure. A backward selection algorithm was used with variable entry and retention criteria of p < 0.05 to select the final multivariate model. Multivariate logistic regression models were used to determine whether there was an association between the volume of RBC transfusion and the defined adverse event after adjusting for covariates. A p value < 0.01 was considered statistically significant in the final model of each aim to adjust for multiple comparisons. The final logistic models for each of the following outcomes indicate an increased risk of that outcome per each additional unit of RBC transfused. For prolonged intubation, the odds ratio (OR) was 1.493 (p < 0.0001), OR = 1.358 (p < 0.0001) for infectious composite outcomes, OR = 1.247 (p < 0.0001) for adverse renal outcomes, and OR = 1.467 (p < 0.0001) for any adverse event. CONCLUSIONS: The authors demonstrated a strong independent association between RBC transfusion volume and adverse outcomes after cardiac surgery. Efforts should be undertaken, such as preoperative anemia management and control of coagulopathy, in order to minimize the need for RBC transfusion.

Storylines of family medicine III: core principles-primary care, systems and family.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'III: core principles-primary care, systems, and family', authors address the following themes: 'Continuity of care-building therapeutic relationships over time', 'Comprehensiveness-combining breadth and depth of scope', 'Coordination of care-managing multiple realities', 'Access to care-intersectional, systemic, and personal', 'Systems theory-a core value in patient-centered care', 'Family-oriented practice-supporting patients' health and well-being', 'Family physician as family member' and 'Family in the exam room'. May readers develop new understandings from these essays.

Electrophoresis of a weakly charged dielectric fluid droplet in a cylindrical pore.

Electrophoresis of a weakly charged dielectric droplet with constant surface charge density in a chargeless cylindrical pore is investigated theoretically in this study, focusing on the boundary confinement effect of the double layer, which in turn determines the ultimate motion of the droplet. A patched pseudo-spectral method based on the Chebyshev polynomial is adopted to solve the resulting governing fundamental electrokinetic equations. Mobility reversal, among other interesting phenomena, is observed when the droplet is in a narrow cylindrical pore. No such observation was made in the corresponding motion of a rigid particle. The droplet with a thick double layer may even move against the prediction based on the Coulomb electrostatic law, for instance, a positively charged droplet may move against the electric field. The significant enhancement of the motion-deterring double layer polarization due to the severe steric boundary confinement within a narrow cylindrical pore is found to be responsible for this seemingly peculiar phenomenon. Moreover, smaller droplets may move in the opposite direction of the larger ones. The results are useful in capillary electrophoresis involving droplets in particular and migration of droplets through narrow channels in general.

HoloCamera: Advanced Volumetric Capture for Cinematic-Quality VR Applications.

High-precision virtual environments are increasingly important for various education, simulation, training, performance, and entertainment applications. We present HoloCamera, an innovative volumetric capture instrument to rapidly acquire, process, and create cinematic-quality virtual avatars and scenarios. The HoloCamera consists of a custom-designed free-standing structure with 300 high-resolution RGB cameras mounted with uniform spacing spanning the four sides and the ceiling of a room-sized studio. The light field acquired from these cameras is streamed through a distributed array of GPUs that interleave the processing and transmission of 4K resolution images. The distributed compute infrastructure that powers these RGB cameras consists of 50 Jetson AGX Xavier boards, with each processing unit dedicated to driving and processing imagery from six cameras. A high-speed Gigabit Ethernet network fabric seamlessly interconnects all computing boards. In this systems paper, we provide an in-depth description of the steps involved and lessons learned in constructing such a cutting-edge volumetric capture facility that can be generalized to other such facilities. We delve into the techniques employed to achieve precise frame synchronization and spatial calibration of cameras, careful determination of angled camera mounts, image processing from the camera sensors, and the need for a resilient and robust network infrastructure. To advance the field of volumetric capture, we are releasing a high-fidelity static light-field dataset, which will serve as a benchmark for further research and applications of cinematic-quality volumetric light fields.

'Long-term outcomes after endoscopic submucosal dissection for relative indication early gastric cancer in non-surgical candidates'.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is effective in treating early gastric cancer (EGC). It's role in the comorbid with more advanced disease is unknown. We sought to evaluate this in a large Western cohort. METHODS: Consecutive patients who underwent ESD for EGC in a single tertiary Western endoscopy centre over 10 years were prospectively analyzed. The primary outcomes were long term overall survival (OS) and disease-free survival (DFS) up to 5 years. Secondary outcomes were efficacy and serious adverse events (SAE). RESULTS: ESD for 157 EGC in 149 patients were performed in an elderly and comorbid cohort with mean age 73.7 years and age-adjusted Charleson Comorbidity Index 4.2. Over a median follow-up period of 51.6 months, there was no significant difference in 5-year OS (88.9% vs 77.9%, P = 0.290) and DFS (83.2% vs 75.1%, P = 0.593) between absolute indication (AI) EGC and relative indication (RI) EGC. AI EGC cohort achieved higher en bloc (96.3% vs 87.5%, P = 0.069) and R0 resection rate (93.6% vs 62.5%, P <0.001) when compared to RI EGC. There were no significant differences in SAE (7.3% vs 12.5%, P = 0.363). No mortality or surgical resection ensued from ESD complications. CONCLUSION: ESD safely confers DFS in poor surgical candidates with RI EGC in a large Western cohort. Patients who are elderly and comorbid or decline surgical resection may benefit from ESD and avoid the risks of surgery and its long-term sequelae.

Design of a symmetry-broken tetrahedral protein cage by a method of internal steric occlusion.

Methods in protein design have made it possible to create large and complex, self-assembling protein cages with diverse applications. These have largely been based on highly symmetric forms exemplified by the Platonic solids. Prospective applications of protein cages would be expanded by strategies for breaking the designed symmetry, for example, so that only one or a few (instead of many) copies of an exterior domain or motif might be displayed on their surfaces. Here we demonstrate a straightforward design approach for creating symmetry-broken protein cages able to display singular copies of outward-facing domains. We modify the subunit of an otherwise symmetric protein cage through fusion to a small inward-facing domain, only one copy of which can be accommodated in the cage interior. Using biochemical methods and native mass spectrometry, we show that co-expression of the original subunit and the modified subunit, which is further fused to an outward-facing anti-GFP DARPin domain, leads to self-assembly of a protein cage presenting just one copy of the DARPin protein on its exterior. This strategy of designed occlusion provides a facile route for creating new types of protein cages with unique properties.

Type 2 diabetes associated with areca nut usage: A systematic review and meta-analysis.

AIMS/HYPOTHESIS: This study aimed to evaluate the potential association between chewing areca nuts and the occurrence of type 2 diabetes and to investigate whether chewing status (current chewers or ex-chewers) affects this association. METHODS: We searched The Cochrane Library, PubMed, and EMBASE databases for relevant studies up to May 21, 2023, using predefined inclusion and exclusion criteria. Three population-based studies conducted in Taiwan were included in the systematic review and meta-analysis. RESULTS: When combined current or ex-chewers were more likely to develop diabetes (Odds Ratio [OR] = 1.45; 95% confidence interval [CI]: 1.30-1.62) compared to the never chewers. Ex-chewers had a higher risk of diabetes (OR: 1.53, 95% CI: 1.45-1.62) compared to never chewers. However, there was no evidence that current chewers were associated with a higher risk of diabetes compared to never chewers. Male current and ex-chewers were associated with higher risk of diabetes compared with never chewers (OR: 1.55, 95% CI: 1.49-1.61). For females there was insufficient evidence. CONCLUSIONS/INTERPRETATION: Existing evidence suggests a link between chewing areca nuts and the development of type 2 diabetes. Therefore, areca chewers should monitor diabetes-related biomarkers.

A simplified algorithm to evaluate the risk of submucosal invasive cancer in large (≥20 mm) nonpedunculated colonic polyps.

BACKGROUND: Recognition of submucosal invasive cancer (SMIC) in large (≥20 mm) nonpedunculated colonic polyps (LNPCPs) informs selection of the optimal resection strategy. LNPCP location, morphology, and size influence the risk of SMIC; however, currently no meaningful application of this information has simplified the process to make it accessible and broadly applicable. We developed a decision-making algorithm to simplify the identification of LNPCP subtypes with increased risk of potential SMIC. METHODS: Patients referred for LNPCP resection from September 2008 to November 2022 were enrolled. LNPCPs with SMIC were identified from endoscopic resection specimens, lesion biopsies, or surgical outcomes. Decision tree analysis of lesion characteristics identified in multivariable analysis was used to create a hierarchical classification of SMIC prevalence. RESULTS: 2451 LNPCPs were analyzed: 1289 (52.6%) were flat, 1043 (42.6%) nodular, and 118 (4.8%) depressed. SMIC was confirmed in 273 of the LNPCPs (11.1%). It was associated with depressed and nodular vs. flat morphology (odds ratios [ORs] 35.7 [95%CI 22.6-56.5] and 3.5 [95%CI 2.6-4.9], respectively; P<0.001); rectosigmoid vs. proximal location (OR 3.2 [95%CI 2.5-4.1]; P<0.001); nongranular vs. granular appearance (OR 2.4 [95%CI 1.9-3.1]; P<0.001); and size (OR 1.12 per 10-mm increase [95%CI 1.05-1.19]; P<0.001). Decision tree analysis targeting SMIC identified eight terminal nodes: SMIC prevalence was 62% in depressed LNPCPs, 19% in nodular rectosigmoid LNPCPs, and 20% in nodular proximal colon nongranular LNPCPs. CONCLUSIONS: This decision-making algorithm simplifies identification of LNPCPs with an increased risk of potential SMIC. When combined with surface optical evaluation, it facilitates accurate lesion characterization and resection choices.

The Effect of Anti-Depressants on Dental Implant Failure: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this systematic review and meta-analysis is to analyze the risk of dental implant failure for patients who had a history of anti-depressant use. MATERIALS AND METHODS: An electronic search was performed up to June 2023 in three databases, including PubMed/MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials with data on comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at the patient level and implant level were performed. RESULTS: Eleven clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% confidence interval= 1.75 to 3.39, p< 0.0001) and 2.44 (95% CI= 1.73 to 3.46, p< 0.0001) for the implant failure at the patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other type of anti-depressants had a higher risk of implant failure than those who were not on any anti-depressants. CONCLUSIONS: The current review demonstrates the use of anti-depressants, such as SSRIs, may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to warrant this finding.

Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws.

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the distal limb during chronic diabetes. In 21-week-old Leprdb/db mice, increases were seen in mast cells/basophils, dermal γδ T cells, heterogeneous T cells, and Type 2 innate lymphoid cells. In addition, macrophages represented the largest cluster of immune cells and showed the greatest increase in genes associated with immune-specific pathways. Sub-clustering of macrophages revealed a bias toward angiogenic Lyve1+MHCIIlo macrophages in the hindpaws of 21-week-old diabetic mice, which corresponded to an increase in Lyve1+ macrophages in the hindpaws of 21-week-old diabetic mice on histology. Our results show that in Type 2 diabetes, the immunological function and phenotype of multiple immune cell types shift not only with metabolic disturbance, but also with duration of disease, which may explain the increased susceptibility to pathologies of the distal limb in patients with more chronic diabetes.

Optimization of direct cortical stimulation using tibial versus median nerve sensory mapping during midline brain tumor resection: illustrative case.

BACKGROUND: During brain tumor resection, neurophysiological mapping and monitoring help surgeons locate, characterize, and functionally assess eloquent brain areas in real time. The selection of mapping and monitoring targets has implications for successful surgery. Here, the authors compare direct cortical stimulation (DCS) as suggested by median nerve (MN) with posterior tibial nerve (PTN) cortical sensory mapping (SM) during mesial lesion resection. OBSERVATIONS: Recordings from a 6-contact cortical strip served to generate an MN and a PTN sensory map, which indicated the strip was anterior to the central sulcus. Responses exhibited an amplitude gradient with no phase reversal (PR). DCS, elicited through a stimulus probe or contact(s) of the strip, yielded larger responses from the corresponding sensory mapped limb; that is, PTN SM resulted in larger lower limb muscle responses than those suggested by MN SM. LESSONS: SM of the MN and PTN is effective for localizing eloquent cortical areas wherein the PTN is favored in surgery for mesial cortical tumors. The recorded amplitude of the cortical somatosensory evoked potential is a valuable criterion for defining the optimal location for DCS, despite an absent PR. The pathway at risk dictates the specifics of SM, which subsequently defines the optimal location for DCS.

Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program.

Importance: Although poorly controlled diabetes is associated with a higher incidence of dementia, few studies have examined the association of diabetes management interventions with dementia incidence. Objective: To examine the association of receiving a multidisciplinary diabetes management program (the Risk Assessment and Management Program-Diabetes Mellitus [RAMP-DM]) that enables better glycemic control with subsequent risk of dementia incidence and the association of dementia with glycemic control. Design, Setting, and Participants: This territory-wide, retrospective, matched cohort study with more than 8 years of follow-up was conducted using electronic health care records from all the patients who used public health care services in Hong Kong from 2011 to 2019. Eligible participants included all patients with type 2 diabetes (T2D) who were managed in primary care settings. Patients who received RAMP-DM were matched in a 1:1 ratio with patients who received usual care only. Data analysis occurred from April 2023 to July 2023. Exposures: Diagnosis of T2D, hemoglobin A1C (HbA1C) level, and attendance at a general outpatient clinic or family medicine clinic. Patients received either RAMP-DM or usual care. Main Outcomes and Measures: Incidence of all-cause dementia and subtypes of dementia were compared between the RAMP-DM and usual care participants using a Cox proportional hazard model with other baseline characteristics, biomarkers, and medication history adjusted. HbA1C levels were measured as a secondary outcome. Results: Among the 55 618 matched participants (mean [SD] age, 62.28 [11.90] years; 28 561 female [51.4%]; 27 057 male [48.6%]), including the 27 809 patients in the RAMP-DM group and 27 809 patients in the usual care group, patients had been diagnosed with T2D for a mean (SD) of 5.90 (4.20) years. During a median (IQR) follow-up period of 8.4 (6.8-8.8) years, 1938 patients in the RAMP-DM group (6.97%) and 2728 patients in the usual care group (9.81%) received a diagnosis of dementia. Compared with those receiving usual care, RAMP-DM participants had a lower risk of developing all-cause dementia (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.68-0.77; P < .001), Alzheimer disease (aHR, 0.85; 95% CI, 0.76-0.96; P = .009), vascular dementia (aHR, 0.61; 95% CI, 0.51-0.73; P < .001), and other or unspecified dementia (aHR, 0.71; 95% CI, 0.66-0.77; P < .001). Compared with having a mean HbA1C level during the first 3 years after cohort entry between 6.5% and 7.5%, a higher risk of dementia incidence was detected for patients with a 3-year mean HbA1C level greater than 8.5% (aHR, 1.54; 95% CI, 1.31-1.80]), between 7.5% and 8.5% (aHR, 1.33; 95% CI, 1.19-1.48), between 6% and 6.5% (aHR, 1.17; 95% CI, 1.07-1.29), and 6% or less (aHR, 1.39; 95% CI, 1.24-1.57). Conclusions and Relevance: In this cohort study of patients with T2D, the findings strengthened evidence of an association of glycemic control with dementia incidence, and revealed that a multidisciplinary primary care diabetes management program was associated with beneficial outcomes for T2D patients against dementia and its major subtypes. A moderate glycemic control target of HbA1C between 6.5% and 7.5% was associated with lower dementia incidence.