Heritage Medical Research Clinic

Background: Hypertension continues to be one of the most pressing health challenges worldwide, contributing significantly to cardiovascular disease and premature death. Dietary approaches aimed at improving blood pressure control have shown promise, yet their effectiveness in real-world settings across diverse populations in the United States is not fully understood.Objective: To examine, in a cross-sectional analysis, the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and blood pressure control status among hypertensive U.S. adults using the National Health and Nutrition Examination Survey (NHANES) 2017-2020 data.Methods: This cross-sectional study analyzed 2,004 unweighted hypertensive adults representing 53,882,767 weighted U.S. adults. DASH adherence was classified into low, moderate, and high categories using the Food Patterns Equivalents Database (FPED). Survey-weighted logistic regression was applied to assess associations between DASH adherence and controlled blood pressure, adjusting for sociodemographic, behavioral, and clinical factors.Results: No significant association was observed between DASH adherence and blood pressure control (p>0.05). Predicted probabilities of control were 0.45, 0.42, and 0.43 for low, moderate, and high adherence, respectively.Conclusion: Higher DASH adherence did not significantly improve blood pressure control among U.S. adults with hypertension, highlighting the need for enhanced dietary adherence strategies in real-world settings.

Persistent anemia in older adults is commonly attributed to nutritional deficiency, chronic disease, or age-related change, particularly when routine laboratory investigations are unrevealing. However, plasma cell and lymphoplasmacytic disorders may present subtly, with anemia as the only consistent abnormality. We report two cases in which extended laboratory evaluation led to early identification of clinically significant B-cell malignancies.The first case involved a man in his early 70s with stable, asymptomatic normocytic anemia despite normal iron studies, vitamin B12 and folate levels, renal function, thyroid studies, and liver enzymes. Serum protein electrophoresis revealed a monoclonal immunoglobulin G kappa paraprotein with an abnormal serum free light-chain ratio. Bone marrow biopsy confirmed clonal plasma cell infiltration consistent with smoldering multiple myeloma, and imaging demonstrated no myeloma-defining bone disease. The patient remains under active surveillance.The second case involved a man in his late 70s with a several-year history of progressive macrocytic anemia and repeatedly normal first-line investigations. Extended testing revealed a marked immunoglobulin M lambda monoclonal gammopathy, and bone marrow biopsy confirmed Waldenström macroglobulinemia. He required treatment due to severe anemia and responded to bendamustine-rituximab therapy.These cases highlight the diagnostic value of serum protein electrophoresis, quantitative immunoglobulins, and serum free light-chain testing in patients with persistent unexplained anemia. Early use of extended investigations can facilitate timely diagnosis before end-organ damage occurs and details the critical role of primary care clinicians in recognizing patterns that warrant escalation beyond routine anemia algorithms.

The lifestyle of Vibrio cholerae is primarily environmental, yet a chance encounter with a human host can lead to cholera, a potentially lethal form of diarrhea. Strains belonging to O1 and O139 serogroups have pandemic potential, but the contribution of non-O1/non-O139 serovars towards the genesis of cholera remains unclear. Endemic V. cholerae lineages were investigated given several historical accounts describing cholera epidemics and sporadic, contemporary cholera-like outbreaks along the lower Rio Grande Delta (LRGD). Seven isolates were recovered from an urban segment of the Rio Grande and six from a rural segment where the river empties into the Gulf of Mexico. Urban isolates all encode ß-lactamase, and with one exception are phylogenetically closely related, rough (do not express O-antigen), harbor identical plasmids, exhibit a disabled Type VI Secretion System (T6SS), and decreased protease activity. In contrast, rural strains belong to distinct serogroups, are sensitive to ß-lactams, express proteases, and kill Escherichia coli in T6SS competition assays. Genome-scale phylogenetics and multilocus sequence typing indicate that urban and rural isolates belong to distinct and novel phylogroups. These results suggest that an urban niche heavily impacted by anthropogenic pressures and a downstream protected rural niche are inhabited by distinct V. cholerae phylotypes.

SummaryBackgroundPersistent fatigue is a common complaint in ANCA-vasculitis (AAV) patients and has a profound impact on patient's quality of life. The symptoms associated with this fatigue mirror those found in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia. Etiologic and pathophysiologic differences exist between PR3- and MPO-ANCA disease, yet differences in their fatigue manifestations have not been well researched. We compared fatigue and its associations in healthy controls, AAV patients and fibromyalgia controls.MethodsThe Canadian consensus criteria were used for ME/CFS diagnosis, and American College of Rheumatology criteria for fibromyalgia diagnosis. Factors such as cognitive failure, depression, anxiety, and sleep disturbances were assessed by patient reported questionnaires. Clinical factors such as BVAS, vasculitis damage index, CRP and BMI were also collected.FindingsOur AAV cohort comprised 52 patients, with a mean age of 44.7 (20–79), 57% (30/52) of the patients were female. We found 51.9% (27/52) of patients fulfilled the diagnostic criteria for ME/CFS, with 37% (10/27) of those having comorbid fibromyalgia. Rates of fatigue were higher in MPO-ANCA patients, than in PR3-ANCA patients, and their symptoms were more similar to the fibromyalgia controls. Fatigue in PR3-ANCA patients was related to inflammatory markers. These differences may be due to the varied pathophysiology of the PR3- and MPO-ANCA serotypes.InterpretationA large proportion of AAV patients suffer from debilitating fatigue consequential enough to meet the diagnostic criteria for ME/CFS. Fatigue associations were not the same between PR3- and MPO-ANCA patients, suggesting that the underlying mechanisms may be different. Future studies should consider ANCA serotype, as further research may inform different clinical treatment strategies for AAV patients suffering from ME/CFS.FundingThis manuscript was funded by the 10.13039/501100002997Dutch Kidney Foundation (17PhD01).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by severe and persistent fatigue. Along with clinical studies showing endothelial dysfunction (ED) in a subset of ME/CFS patients, we have recently reported altered ED-related microRNAs in plasma from affected individuals. Inadequate nitric oxide (NO), mainly produced by the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells (ECs), is a major cause of ED. In this study, we hypothesized that plasma from that cohort of ME/CFS patients induces eNOS-related ED in vitro. To test this, we cultured human umbilical vein endothelial cells (HUVECs) in the presence of plasma from either ME/CFS patients (ME/CFS-plasma, n = 11) or healthy controls (HC-plasma, n = 12). Then, we measured the NO production in the absence and presence of tyrosine kinase and G protein-coupled receptors agonists (TKRs and GPCRs, respectively), well-known to activate eNOS in ECs. Our data showed that HUVECs incubated with ME/CFS-plasma produced less NO either in the absence or presence of eNOS activators compared to ones in presence of HC-plasma. Also, the NO production elicited by bradykinin, histamine, and acetylcholine (GPCRs agonists) was more affected than the one triggered by insulin (TKR agonist). Finally, inhibitory eNOS phosphorylation at Thr495 was higher in HUVECs treated with ME/CFS-plasma compared to the same treatment with HC-plasma. In conclusion, this study in vitro shows a decreased NO production in HUVECs exposed to plasma from ME/CFS patients, suggesting an unreported role of eNOS in the pathophysiology of this disease.

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Aims/hypothesisThere are potential advantages to the low-temperature (−196°C) banking of isolated islets, including the maintenance of viable islets for future research. We therefore assessed the in vitro and in vivo function of islets cryopreserved for nearly 20 years.MethodsHuman islets were cryopreserved from 1991 to 2001 and thawed between 2012 and 2014. These were characterised by immunostaining, patch-clamp electrophysiology, insulin secretion, transcriptome analysis and transplantation into a streptozotocin (STZ)-induced mouse model of diabetes.ResultsThe cryopreservation time was 17.6 ± 0.4 years (n = 43). The thawed islets stained positive with dithizone, contained insulin-positive and glucagon-positive cells, and displayed levels of apoptosis and transcriptome profiles similar to those of freshly isolated islets, although their insulin content was lower. The cryopreserved beta cells possessed ion channels and exocytotic responses identical to those of freshly isolated beta cells. Cells from a subset of five donors demonstrated similar perifusion insulin secretion profiles pre- and post-cryopreservation. The transplantation of cryopreserved islets into the diabetic mice improved their glucose tolerance but did not completely normalise their blood glucose levels. Circulating human insulin and insulin-positive grafts were detectable at 10 weeks post-transplantation.Conclusions/interpretationWe have demonstrated the potential for long-term banking of human islets for research, which could enable the use of tissue from a large number of donors with future technologies to gain new insight into diabetes.