Mental Health and Black Male Graduate Students.

The purpose of this study was to understand how masculinity and race impact mental health among Black male graduate students. A qualitative study using in-depth interviews recruited Black male graduate students enrolled at a private university in the southern United States. Data were collected over zoom and recorded. Interviews were transcribed and the data were analyzed for similar themes. Twenty-nine Black male graduate students 23 to 51 were recruited. Participants reported the three main elements that impacted their mental health were (1) expectations, (2) pressure, and (3) being strong. These findings suggest that colleges need to develop programming to help Black men learn how to handle racial discrimination in positive ways. Additionally, findings also highlight the need for culturally relevant mental health services that let Black men know seeking help is ok and is what men do.

Multiple Anomalous Coronary Arteries With Right Sinus of Valsalva Origin: A Case Report.

Coronary artery anomalies (CAA) define a wide array of congenital abnormalities that stem from the origin, course, and distribution of coronary arteries. CAAs can lead to severe complications such as arrhythmias, myocardial ischemia, and even sudden cardiac death. We describe the case of a 58-year-old female who presented to the emergency department with chest discomfort and shortness of breath and received a workup for acute coronary syndrome. She underwent a cardiac catheterization, which incidentally found an anomalous left anterior descending artery with a right sinus of Valsalva origin, an absent left circumflex coronary artery, and a dominant right coronary artery of unusually large caliber and distribution. There were no identified atherosclerotic plaques. This anomalous configuration of the coronary arteries is exceptionally rare. She required medical management with daily oral acetylsalicylic acid 81 mg, atorvastatin 80 mg, twice daily metoprolol tartrate 50 mg, and hydrocodone/acetaminophen 7.5mg/325 mg oral tablet to be taken every 4 h, as needed for severe pain. Despite optimal medical management, she continued to have chronic angina. A surgical evaluation by a cardiovascular surgeon deemed her anomaly to be inoperable.

Scleroderma Renal Crisis: Clues From the Physical Exam.

Scleroderma renal crisis (SRC) is a rare, life-threatening complication of systemic sclerosis (SSc) and can sometimes be the first manifestation of the disease.1 A 56-year-old female presented with acute encephalopathy requiring intubation and a systolic blood pressure of 230 mmHg; no information was available about her medical history.

Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder.

Background: Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies. Methods: We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =27), schizophrenia (SCZ, n =21), and bipolar disorder (BPD, n =21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants. Results: In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups. Conclusion: Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.

Paralumbar compartment syndrome, a rare sequela of deadlifting: a case report and review of current literature.

BACKGROUND: Compartment syndrome is a well-known phenomenon that is most commonly reported in the extremities. However, paralumbar compartment syndrome is rarely described in available literature. The authors present a case of paralumbar compartment syndrome after high intensity deadlifting. CASE PRESENTATION: 53-year-old male who presented with progressively worsening low back pain and paresthesias one day after high-intensity deadlifting. Laboratory testing found the patient to be in rhabdomyolysis; he was admitted for intravenous fluid resuscitation and pain control. Orthopedics was consulted, and Magnetic Resonance Imaging revealed significant paravertebral edema and loss of muscle striation. Given the patient's lack of improvement with intravenous and oral pain control, clinical and radiographic findings, there was significant concern for acute paralumbar compartment syndrome. The patient subsequently underwent urgent fasciotomy of bilateral paralumbar musculature with delayed closure. CONCLUSION: Given the paucity of literature on paralumbar compartment syndrome, the authors' goal is to promote awareness of the diagnosis, as it should be included in the differential diagnosis of intractable back pain after high exertional exercise. The current literature suggests that operative cases of paralumbar compartment syndromes have a higher rate of return to pre-operative function compared to those treated non-operatively. This case report further supports this notion. The authors recommend further study into this phenomenon, given its potential to result in persistent chronic exertional pain and irreversible tissue damage.

Risk of meningomyelocele mediated by the common 22q11.2 deletion.

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Molecular Landscape and Therapeutic Strategies against Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly due to comprehensive molecular characterization of tumors and novel therapeutic strategies. Advances in genomic and transcriptomic analyses using blood- and tumor-tissue-based sequencing have facilitated identification of distinct tumor subtypes harboring unique biological characteristics and therapeutic vulnerabilities. These insights have led to the development and incorporation of targeted therapies and immunotherapy in CRC treatment. In this review, we discuss the molecular landscape and key oncogenes/tumor suppressors contributing to CRC tumorigenesis, metastasis, and therapeutic resistance. We also discuss personalized therapeutic strategies for subsets of CRC patients and provide an overview of evolving novel treatments being evaluated in clinical trials.

Vitamin B12 status and hyperhomocysteinemia in patients with Rheumatoid arthritis treated with methotrexate and folic acid.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory arthritis in which the immune system targets synovial joints. Methotrexate serves as the mainstay of treatment for RA due to its efficacy. However, patients treated with methotrexate are uniquely at risk for vitamin B12 deficiency and hyperhomocysteinemia due to coincident disease risk factors and the fact that methotrexate use is associated with malabsorption. The objective of this study was to assess for vitamin B12 deficiency among patients with RA treated with methotrexate and folic acid. METHODS: This cross-sectional study included 50 patients with RA treated with methotrexate and folic acid and 49 patients with RA treated with other therapies. Patients were matched by age, sex, race, renal function, and disease activity. We compared plasma vitamin B12, methylmalonic acid, and homocysteine levels between these two groups utilizing quantitative and categorical analyses. RESULTS: Thirty-seven (74%) RA patients on methotrexate and folic acid had elevated plasma homocysteine levels compared with only 27 (55%) RA patients receiving other therapies (P < 0.05). The proportion of patients with low vitamin B12 and high methylmalonic acid levels did not differ between the two groups. CONCLUSIONS: Our data show high plasma homocysteine levels among RA patients treated with methotrexate and folic acid. While plasma vitamin B12 levels were similar between the two groups, high plasma homocysteine is also a sensitive marker of vitamin B12 deficiency. Additional studies should evaluate for the presence of clinical features of vitamin B12 deficiency and hyperhomocysteinemia among RA patients treated with methotrexate and folic acid.

No Difference in Pullout Strength Between a Bio-inductive Implant and a Semitendinosus Tendon Graft in a Biomechanical Study of Medial Patellofemoral Ligament Repair Augmentation.

Purpose: To compare the pullout strength of a bio-inductive implant (BI) used to augment a medial patellofemoral ligament (MPFL) repair with the pullout strength of semitendinosus graft in a biomechanical cadaveric model. Methods: Six matched pairs of cadavers (12 knees) were used in the biomechanical testing comparing semitendinosus tendon (Semi-T) versus a BI. The Semi-T was harvested from 1 of the matched pairs. A standard double-bundle technique using 2 sockets in the upper two-thirds of the patella 15 mm apart was performed. After docking of the graft into the patella, the patella was dissected free of soft tissues and potted into a fixture to allow mechanical pull parallel to the transverse axis of the patella. The construct was pulled to failure. Results: There was no statistically significant difference in pullout strength (P = .77) between the BI group (249.3 ± 36.3 N) and Semi-T group (235.0 ± 113.6 N) double-bundle constructs. In the Semi-T group, 50% of the specimens (3 of 6 knees) failed via anchor pullout and a fourth specimen failed at the suture-anchor interface (16.7%), whereas in the BI group, 16.7% of the specimens (1 of 6 knees) failed by anchor pullout. Although the Semi-T group (49.5 ± 14.1 N/mm) showed significantly greater stiffness than the BI group (13.8 ± 0.6 N/mm, P < .01), pullout strength in the Semi-T group was highly variable: 50% of the specimens (3 of 6 knees) with semitendinosus constructs failed at 5 mm of displacement or less via graft or anchor pullout. Maximum load, displacement at failure, stiffness, and load at 5 mm were compared between the augmented and non-augmented control specimens using a 2-tailed non-equal variance Student t test. For all comparisons, P < .05 was considered to indicate a statistically significant difference. Conclusions: In this biomechanical study, augmentation of an MPFL reconstruction using a common double-bundle technique with a BI had the same pullout strength as a semitendinosus graft using the same technique in cadaveric knees. Clinical Relevance: MPFL repair after a patellar dislocation may be inadequate to restore the strength of the native MPFL and prevent recurrent patellar instability. Recurrent instability of the patella can result in progressive injury to the soft tissue and articular cartilage of the patella and femur. It is important to study the techniques used for MPFL repair to continually improve patient outcomes. Further testing of these additional techniques and clinical studies are needed to evaluate the implants used to augment MPFL repairs.

Editorial Commentary: Tissue-Engineered Meniscal Scaffolds and Implants Show Promising Short-Term Outcomes While Long-Term Comparison With Meniscal Allograft Transplantation Is Pending.

Because of the prevalence of meniscal injuries and the difficulty treating irreparable tears and large defects, there has been increasing research and resultant engineering strategies over the past 20 years that have resulted in development of various meniscal scaffolds and meniscal implants. At this time, meniscal allograft transplant may be the "standard" consideration for the nonarthritis, meniscal deficient, stable, and properly aligned painful knee, but challenges include availability, preoperative planning and sizing, costs, and logistics. Newer tissue-engineered implants can minimize these concerns, and recent systematic review shows these may provide short-term improvement in knee pain and function. However, studies demonstrating long-term improvements remain pending, and it is unclear whether these implants will result in outcomes better than meniscal allograft transplant.

Correction: Low serum albumin and the risk of hospitalization in COVID-19 infection: A retrospective case-control study.

[This corrects the article DOI: 10.1371/journal.pone.0250906.].

Developmental Approaches to Chronic Pain: A Narrative Review.

Chronic pain, which can potentially develop from acute pain, subacute pain, or breakthrough pain, is generally defined as pain persisting for greater than three months with minimal relief. Chronic pain can be associated with a myriad of medical conditions. It is also one of the most common causes of disability, physical suffering, depression, and reduced quality of life. Treatment can vary depending on the underlying pathophysiology and can involve physical therapy, non-pharmaceutical approaches, pharmaceutical drugs, and invasive procedures. Currently available pharmaceutical agents have been effective for short-term management of chronic pain conditions, but few options address chronic pain with long-term efficacy. First-line pharmaceutical agents can potentially include over-the-counter (OTC) or prescription-strength non-steroidal anti-inflammatory drugs (NSAIDs), which have been linked to numerous side effects. If chronic pain persists, steroids are frequently used to provide longer relief. For more progressive or resistant chronic pain and/or in conjunction with invasive procedures, opioids have been utilized for acute treatment and for long-term maintenance. While these agents have proven to be effective for both acute and long-term use due to their modulation at various peripheral and central opioid receptors, they can be associated with numerous side effects and tied to the risk of addiction. As such, an unmet need exists to identify treatment modalities that provide opioid-like pain relief without opioid-induced adverse effects and the potential for addiction. This narrative review will provide an overview of the currently available treatment modalities for chronic pain and their adverse event profiles, as well as a review of therapies that are currently in development and/or preclinical trials for the management and treatment of chronic pain.

Human IPSC-Derived PreBötC-Like Neurons and Development of an Opiate Overdose and Recovery Model.

Opioid overdose is the leading cause of drug overdose lethality, posing an urgent need for investigation. The key brain region for inspiratory rhythm regulation and opioid-induced respiratory depression (OIRD) is the preBötzinger Complex (preBötC) and current knowledge has mainly been obtained from animal systems. This study aims to establish a protocol to generate human preBötC neurons from induced pluripotent cells (iPSCs) and develop an opioid overdose and recovery model utilizing these iPSC-preBötC neurons. A de novo protocol to differentiate preBötC-like neurons from human iPSCs is established. These neurons express essential preBötC markers analyzed by immunocytochemistry and demonstrate expected electrophysiological responses to preBötC modulators analyzed by patch clamp electrophysiology. The correlation of the specific biomarkers and function analysis strongly suggests a preBötC-like phenotype. Moreover, the dose-dependent inhibition of these neurons' activity is demonstrated for four different opioids with identified IC50's comparable to the literature. Inhibition is rescued by naloxone in a concentration-dependent manner. This iPSC-preBötC mimic is crucial for investigating OIRD and combating the overdose crisis and a first step for the integration of a functional overdose model into microphysiological systems.

Evaluating a 3D deep learning pipeline for cerebral vessel and intracranial aneurysm segmentation from computed tomography angiography-digital subtraction angiography image pairs.

OBJECTIVE: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth. METHODS: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha. RESULTS: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth. CONCLUSIONS: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.

Percutaneous Ultrasound-Guided Tenotomy of the Iliotibial Band for Trochanteric Pain Syndrome: A Longitudinal Observational Study With One-Year Durability Results.

BACKGROUND: Upper lateral hip pain is a common complaint in adults and is referred to as greater trochanteric pain syndrome (GTPS) and is more prevalent among older women. This is a debilitating condition that could result in lower physical activity and quality of life, and higher unemployment rate. GTPS is a clinical diagnosis, and many cases improve with conservative medical management (CMM). However, there is still a gap between patients not responding to CMM and those who are not good surgical candidates. Thus, percutaneous ultrasound tenotomy (PUT) may be a valuable treatment option to limit this gap. OBJECTIVES: Demonstration of the one-year pain and functional outcomes, including sit to stand. SETTING: Academic tertiary care medical center. METHODS: Forty-eight consecutive patients with refractory trochanteric pain due to iliotibial band (ITB) tendinopathy. Fifty-six hips were treated; 8 patients underwent bilateral procedures. Electronic medical record review of consecutive patients who underwent ITB TENEX® was performed at Montefiore Medical Center from December 2019 to December 2021. Institutional guidelines recommended TENEX® for greater trochanteric pain refractory to conservative treatment and ultrasound (US) confirmed ITB tendinopathy (hypoechogenicity or thickened tendon > 6 mm). Pain level, as well as sit-to-stand, side-lying, and walking tolerance levels were evaluated at baseline preprocedure visit and one-year visit. Follow-up was performed by independent practitioners and corroborated by chart review. RESULTS: Numeric Rating Scale (NRS-11) improved by 4 points across all patients. Seventy percent of patients endorsed pain relief at one-year visit. Median preprocedure NRS-11 was 9. The reported median NRS-11at one year was 5 (Wilcoxon signed rank NRS-11 demonstrated a Z score of -6.042 with P < 0.001). One-year analysis among all patients revealed 57%, 78%, and 66% improvement in side-lying, sit-to-stand, and walking tolerance levels, respectively. LIMITATIONS: We believe that our results must be confirmed with a randomized control trial with a control arm and more patients included. CONCLUSIONS: PUT of the ITB using the TENEX® tissue remodeling device could be a safe and effective treatment for ITB tendinopathy-associated GTPS.

Identification of Factors that May Predict Career Trajectory Among Neuro-Ophthalmology Fellows.

BACKGROUND: There is modest literature regarding fellowship applicant factors that may predict future career achievement. We aim to characterize neuro-ophthalmology fellows and identify and analyze characteristics that may predict future career trajectory. METHODS: Data, including demographic information, academic background, scholarly activities, and practice information, were collected using publicly available sources, on individuals who completed neuro-ophthalmology fellowships from 2015 to 2021. Summary statistics describing the cohort were calculated. Prefellowship characteristics were compared with postfellowship characteristics to evaluate which prefellowship characteristics may predict postfellowship academic productivity and career achievement. RESULTS: Data were collected on 174 individuals (41.6% men, 58.4% women). Sixty-five percent were residency-trained in ophthalmology, 31% neurology, 1.7% both, and 1.7% pediatric neurology. Fifty-eight percent completed residency in the US, 8% in Canada, 32% internationally, and 2% in multiple locations. Among those practicing in the US/Canada, 63.8% practice at academic centers, 35.3% private practice, and 0.9% at both. Thirty-one percent completed additional subspecialty training and 17.8% additional graduate degrees. Completion of additional fellowship training or graduate degrees, and publication of more papers before fellowship, correlated with later academic productivity. There were no significant correlations between completion of an additional fellowship or graduate degree with current practice environment or attainment of leadership roles. There were no significant correlations between total publishing productivity prefellowship and practice environment or leadership roles postfellowship. CONCLUSIONS: Additional graduate degrees/subspecialty training, and prefellowship academic productivity, correlated with later academic productivity among neuro-ophthalmologists, suggesting that these metrics may be helpful in predicting future academic performance among fellowship applicants.

Development of a functional human induced pluripotent stem cell-derived nociceptor MEA system as a pain model for analgesic drug testing.

The control of severe or chronic pain has relied heavily on opioids and opioid abuse and addiction have recently become a major global health crisis. Therefore, it is imperative to develop new pain therapeutics which have comparable efficacy for pain suppression but lack of the harmful effects of opioids. Due to the nature of pain, any in vivo experiment is undesired even in animals. Recent developments in stem cell technology has enabled the differentiation of nociceptors from human induced pluripotent stem cells. This study sought to establish an in vitro functional induced pluripotent stem cells-derived nociceptor culture system integrated with microelectrode arrays for nociceptive drug testing. Nociceptors were differentiated from induced pluripotent stem cells utilizing a modified protocol and a medium was designed to ensure prolonged and stable nociceptor culture. These neurons expressed nociceptor markers as characterized by immunocytochemistry and responded to the exogenous toxin capsaicin and the endogenous neural modulator ATP, as demonstrated with patch clamp electrophysiology. These cells were also integrated with microelectrode arrays for analgesic drug testing to demonstrate their utilization in the preclinical drug screening process. The neural activity was induced by ATP to mimic clinically relevant pathological pain and then the analgesics Lidocaine and the opioid DAMGO were tested individually and both induced immediate silencing of the nociceptive activity. This human-based functional nociceptive system provides a valuable platform for investigating pathological pain and for evaluating effective analgesics in the search of opioid substitutes.

Analytical characterization of broadly neutralizing antibody CAP256LS heavy chain clipping during manufacturing development.

Broadly neutralizing antibody (bNAb) CAP256-VRC26.25 (abbreviated CAP256LS), a human IgGI monoclonal antibody targeting the V1V2 site of the HIV-1 envelope, has demonstrated high therapeutic potential as a broadly neutralizing monoclonal antibody against HIV-1. During the process development, a heavy chain fragmentation (clipping) was observed, that led to a relative potency reduction. In this report, we highlighted a series of process and product mitigation strategies deployed to advance this product. We have detailed how analytical characterization tools, especially the microchip reduced capillary gel electrophoresis (CGE-SDS), played a pivotal role in identifying the development issues and in providing measurements to guide implementation of mitigation strategies.

Platelet-Rich Plasma in the Treatment of Facet Mediated Low Back Pain: A Comprehensive Review.

Background: Facet-mediated pain is a major cause of low back pain and as a result, is a significant cause of morbidity, including disability and reduced functionality. Setting: The present investigation involved a PubMed literature review between June 1, and 2021-January 1, 2022. Methods: We systematically reviewed was carried Pubmed using the search terms "platelet-rich plasma", "inflammatory mediators", "facet arthropathy", "axial back pain", and "leukoreduction". Data extraction and quality assessment were performed by 3 independent reviewers. Out of the studies analyzed 2 were retrospective, while 1 was a prospective study. Results: PRP injections for facet mediated or modulated pain are an alternative to conventional pharmacotherapies and interventional injections/radiofrequency. There are limited numbers of studies in world literature at present. Limitations: Small number of articles in the world literature and small numbers of patients in those published studies. Conclusions: At present, there are limited studies in the literature; however, larger well-designed studies are warranted to precisely understand efficacy, potential side effects and best practice techniques for PRP injections for facet mediated or modulated pain.

Managing Gout in Women: Current Perspectives.

Gout is a common inflammatory arthritis that tends to affect significantly more men than women. However, female gout patients are more likely to have comorbidities such as hypertension, diabetes mellitus, and renal dysfunction. Furthermore, they experience a greater disease burden due to gout than males. While nonbiological causes may possibly contribute to this sex discrepancy in burden, this raises questions regarding whether current gout pharmacotherapies are as efficacious in females as they are in males. In this review, we examine how the clinical profile of female gout patients differs from male patients; we then survey the literature for data on outcomes for female gout patients treated with urate-lowering therapies for chronic management of gout as well as commonly used agents for acute flares. We also discuss considerations for managing gout in women during pregnancy and lactation.