Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.

Introduction: Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized.

Methods: Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified.

Altered Cell Clusters and Upregulated Aqp1 in Connexin 50 Knockout Lens Epithelium.

Purpose: To characterize the heterogeneity and cell clusters of postnatal lens epithelial cells (LECs) and to investigate the downstream targets of connexin 50 (Cx50) in the regulation of lens homeostasis and lens growth. To determine differentially expressed genes (DEGs) in the connexin 50 knockout (Cx50KO) lens epithelial cells that shed light on novel mechanism underlying the cataract and small size of the Cx50KO lenses.

Methods: Single-cell RNA sequencing (scRNA-seq) of lens epithelial cells isolated from one-month-old Cx50KO and wild-type (WT) mice were performed.

Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes.

Aims: This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).

Methods: Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms).

Normal and malaligned talonavicular fusion alters cadaveric foot pressure and kinematics.

Talonavicular (TN) fusion is a common treatment for TN arthritis or deformity correction. There is incongruous evidence regarding remaining motion at the talocalcaneal and calcaneocuboid joints after TN fusion. Additionally, the effects of a malaligned TN fusion are not well understood and alignment of the fusion may be important for overall foot integrity.

Genetic retargeting of E3 ligases to enhance CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapies are medical breakthroughs in cancer treatment. However, treatment failure is often caused by CAR T cell dysfunction. Additional approaches are needed to overcome inhibitory signals that limit anti-tumor potency.

Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis.

Importance: Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research comparing different PNI patterns on patient outcomes is limited.

Objective: To compare 4 assessments of PNI in CSCC, their associations with poor outcomes, and implications for their inclusion in the Brigham and Women's Hospital (BWH) staging system.

Persistence of long-term insulin independence after islet transplantation and two subsequent pregnancies.

Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence.

Adrenergic nerves regulate intestinal regeneration through IL-22 signaling from type 3 innate lymphoid cells.

The intestinal epithelium has high intrinsic turnover rate, and the precise renewal of the epithelium is dependent on the microenvironment. The intestine is innervated by a dense network of peripheral nerves that controls various aspects of intestinal physiology. However, the role of neurons in regulating epithelial cell regeneration remains largely unknown.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together.

Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals.

Localised chronic fibrosing vasculitis versus erythema elevatum diutinum.

A woman in her 70s was referred for a painless plaque on the shin, present for 2 years and progressing in thickness. Examination revealed a large erythematous to violaceous indurated plaque with cobblestone appearance. Biopsy revealed an inflammatory infiltrate of neutrophils with scattered histiocytes, lymphocytes, eosinophils and plasma cells interspersed with areas of lamellar fibrosis and focal areas of vascular damage, suggestive of a localised chronic fibrosing vasculitis of the skin.

Unsupervised Phenotype-Based Clustering of Clinicopathologic Features in Cutaneous Melanoma.

Pathogenic phenotypes in cutaneous melanoma have been vastly cataloged, although these classifications lack concordance and are confined to either morphological or molecular contexts. In this study, we perform unsupervised k-medoids clustering as a machine learning technique of 2,978 primary cutaneous melanomas at Mass General Brigham and apply this information to elucidate computer-defined subsets within the clinicopathologic domain. We identified five optimally separated clusters of melanoma that occupied two distinct clinicopathologic subspaces: a lower-grade partition associated with common or dysplastic nevi (i.

Improving timeliness in the neglected tropical diseases preventive chemotherapy donation supply chain through information sharing: A retrospective empirical analysis.

Background: Billions of doses of medicines are donated for mass drug administrations in support of the World Health Organization's "Roadmap to Implementation," which aims to control, eliminate, and eradicate Neglected Tropical Diseases (NTDs). The supply chain to deliver these medicines is complex, with fragmented data systems and limited visibility on performance. This study empirically evaluates the impact of an online supply chain performance measurement system, "NTDeliver," providing understanding of the value of information sharing towards the success of global health programs.

Novel gel bolus to improve impedance-based measurements of esophageal cross-sectional area during primary peristalsis.

Introduction: Intraluminal esophageal impedance (ILEE) has the potential to measure esophageal luminal distension during swallow-induced peristalsis in the esophagus. A potential cause of inaccuracy in the ILEE measurement is the swallow-induced air in the bolus.

Aim: Compare a novel gel bolus to the current alternatives for the measurement of impedance-based luminal distension (cross-sectional area, CSA) during primary peristalsis.

Associations of Endometriosis and Hormone Therapy With Risk of Hyperlipidemia.

Using claims data from the universal health insurance program of Taiwan, we conducted a retrospective cohort study to investigate whether endometriosis and hormone therapy are associated with the risk of developing hyperlipidemia. We selected 9,155 women aged 20-55 years with endometriosis diagnosed during the period 2000-2013 and 212,641 women without endometriosis with a median follow-up time of 7 years. Among patients with endometriosis, 86% of cases were identified on the basis of diagnosis codes with an ultrasound claim, and 14% were defined by diagnostic laparoscopy or surgical treatments.

PROMISE international; a clinical post marketing trial investigating the percutaneous deep vein arterialization (LimFlow) in the treatment of no-option chronic limb ischemia patient.

Background: Critical limb ischemia (CLI) is the clinical end stage of peripheral artery disease and is associated with high amputation, mortality rates and poor quality of life. For CLI patients with no revascularization options, venous arterialization could be an alternative technique for limb salvage. A systematic review and meta-analysis published in 2017 concluded that venous arterialization may be considered a viable alternative.

Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas.

Importance: Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships.

Objective: To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing.

Clinical spectrum of cutaneous melanoma morphology.

Background: Melanoma can mimic other cutaneous lesions, but the full spectrum and prevalence of these morphologic variants remain largely unknown.

Objective: To classify nonacral cutaneous melanomas into distinct morphologic clusters and characterize clusters' clinicopathologic features.

Methods: All pathologic melanoma diagnoses (occurring during 2011-2016) were reviewed for routine prebiopsy digital photographs (n = 400).

Sustainable access to deworming drugs in a changing landscape.

The global effort to control and eliminate soil-transmitted helminthiasis (STH) currently depends on donations of albendazole and mebendazole, which reached more than 530 million children in 2016. As we approach 2020, the WHO goal of eliminating STH as a public health problem will not be met in most endemic countries, and ongoing treatment will be necessary. Additionally, the volume of drugs required might increase because global strategies for STH aim to interrupt transmission.

A 25-Year-Old Male with Orogenital Ulcers, Rash, and Difficulty Swallowing.

A 25-year-old otherwise healthy male presented with new-onset odynophagia, rash, and orogenital ulcers. Despite treatment with antibiotics for presumed bacterial pharyngitis, the patient remained symptomatic, with abnormal vital signs and laboratory values. Upon dermatology consultation and histopathologic correlation, he was diagnosed with Behçet disease.

Faculty and resident perspectives on ambulatory care education: A collective case study of family medicine, psychiatry, and surgery.

Background: Ambulatory care (AC) experiences within medical education are garnering increasing attention. We sought to understand how faculty and residents' describe their experiences of AC and ambulatory care education (ACEduc) within, between, and across disciplinary contexts.

Methods: We designed a Stakian collective case study, applying constructivist grounded theory analytic methods.

hace1 Influences zebrafish cardiac development via ROS-dependent mechanisms.

Background: In this study, we reveal a previously undescribed role of the HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) tumor suppressor protein in normal vertebrate heart development using the zebrafish (Danio rerio) model. We examined the link between the cardiac phenotypes associated with hace1 loss of function to the expression of the Rho small family GTPase, rac1, which is a known target of HACE1 and promotes ROS production via its interaction with NADPH oxidase holoenzymes.

Results: We demonstrate that loss of hace1 in zebrafish via morpholino knockdown results in cardiac deformities, specifically a looping defect, where the heart is either tubular or "inverted".