Fine Structure of A: Autonomic Nerve Fibers and Terminals in Human Myocardium; and B: Myocardial Changes in Congenital Heart Disease

In a histological and fine structural study of right atrial biopsy specimens from 31 patients with rheumatic heart disease (RHD), aged 7 to 46 years, and 11 patients with congenital heart disease (CHD), aged 3 to 36 years, nerve fibers or endings were seen by electron microscopy in 11 specimens. There was concurrence of ordinary axons along with terminals bearing pale cholinergic or dark adrenergic synaptic vesicles. Smaller and denser cholinergic vesicles suggested proliferation followed by exhaustion of such nerve endings. The closest proximity of nerve terminal to muscle fiber was about 100 nm. In one RHD specimen a “specific terminal cell” was present between a nerve ending and muscle fiber; in another a possible neuromuscular contact was developing at the surface of a regenerating small muscle fiber with a few myofilaments. Unmyelinated axons amidst increased subendocardial and subepicardial collagen, with prominent fibroblasts and depleted muscle fibers, were seen more frequently in specimens of CHD. Loss of myofibrils and accumulation of mitochondria, with infrequent formation of lipofuscin bodies, characterized degenerating muscle fibers in CHD also, although to a lesser degree than in RHD (reported earlier, 1985). The myocardial blood vessels in CHD tended to have pale swollen endothelial cells and narrowed lumen. The most severely affected cases of CHD were those with (1) a very wide atrial septal defect (ASD), (2) ventricular septal defect (VSD) with vegetations near the defect, (3) 1 infundibular pulmonary stenosis, and (4) Fallot's tetralogy.     

Urine and Plasma Metabolome of Healthy Adults Consuming the DASH (Dietary Approaches to Stop Hypertension) Diet: A Randomized Pilot Feeding Study

We aimed to identify plasma and urine metabolites altered by the Dietary Approaches to Stop Hypertension (DASH) diet in a post-hoc analysis of a pilot feeding trial. Twenty adult participants with un-medicated hypertension consumed a Control diet for one week followed by 2 weeks of random assignment to either Control or DASH diet. Non-missing fasting plasma (n = 56) and 24-h urine (n = 40) were used to profile metabolites using untargeted gas chromatography/mass spectrometry. Linear models were used to compare metabolite levels between the groups. In urine, 19 identifiable untargeted metabolites differed between groups at p < 0.05. These included a variety of phenolic acids and their microbial metabolites that were higher during the DASH diet, with many at false discovery rate (FDR) adjusted p < 0.2. In plasma, eight identifiable untargeted metabolites were different at p < 0.05, but only gamma-tocopherol was significantly lower on DASH at FDR adjusted p < 0.2. The results provide insights into the mechanisms of benefit of the DASH diet.     

Etiology of Severe Acute Respiratory Infections,Bangladesh, 2017

In April 2017, surveillance detected a surge in severe acute respiratory infections (SARI) in Bangladesh. We collected specimens from SARI patients and asymptomatic controls for analysis with multipathogen diagnostic tests. Influenza A(H1N1)pdm09 was associated with the SARI epidemic, suggesting that introducing vaccines and empiric antiviral drugs could be beneficial.     

It May Seem Inflammatory,but Some T Cells Are Innately Healing to the Bone

Among the most significant developments to have taken place in osteology over the last few decades is an evolution from treating and viewing bone disorders primarily through an endocrine lens to instead seeing them as metabolic disorders that interface at the molecular and cellular level with the immune system. Osteoimmunology was officially born in response to accumulating evidence that the immune system is integrally involved in bone remodeling, but much of the early work focused on the role of conventional αβ T cells in driving bone loss. There is, however, emerging data indicating that innate lymphocytes, in particular γδ T cells, may in fact be important for bone regeneration. We first observed that bisphosphonate‐associated osteonecrosis of the jaw (ONJ), a rare but serious adverse drug effect characterized by nonhealing necrotic bone tissue of the mandible or maxilla, was linked to a deficiency in a subset of γδ T cells found in human peripheral blood. Patients who developed ONJ while on bisphosphonate therapy not only lacked the main subset of circulating γδ T cells, but they also all had underlying conditions that compromised their immune integrity. A number of recent studies have unraveled the role of γδ T cells (and lymphocytes sharing their characteristics) in bone regeneration—particularly for fracture healing. These findings seem to contradict the prevailing view of such “inflammatory” T cells as being bone degenerative rather than restorative. This viewpoint melds together the emerging evidence of these so‐called inflammatory T cells in bone remodeling and healing—showing that they are not in fact “all bad to the bone.” © 2016 American Society for Bone and Mineral Research.     

Intermittent pneumatic compression therapy improves functional and dynamic balance and neuropathy severity in neuropathic patients with type 2 diabetes

Diabetic neuropathy is a common complication of diabetes which increases risk of falling. Reduction in neural blood flow is one proposed theory for this etiology of diabetic neuropathy. Intermittent pneumatic compression (IPC) is a treatment method that increases nutritional supplies for the peripheral nervous system. The current study aims at evaluating the effects of IPC therapy on two aspects of balance dysfunction as one of the most important clinical signs of diabetic neuropathy. This study is a single-blind, randomized, controlled clinical trial that involved 39 patients with diabetic peripheral neuropathy. In this analysis, patients aged 40–75 years (with a mean age of 58.82 years) were randomly divided into intervention (n = 20) and control groups (n = 19). In the first session, all tests of neuropathy severity (using Valk and Michigan diabetic neuropathy questionnaires) and stability (functional and dynamic balance) were performed for both groups. The subjects in intervention group underwent 10 sessions of IPC treatment. At last, balance and neuropathy examinations were carried out in the final session. P < 0.05 was chosen as statistical significance level. Implementation of IPC interventions for 10 sessions significantly decreased APSI and OSI of Biodex balance system in level 6 (P < 0.05). The subjects in intervention group showed significant increases in standing time with their eyes either open or closed by performing functional balance tests. Additionally, Valk and Michigan neuropathy screening scores significantly decreased after 10 sessions of IPC therapy. This study showed that IPC has a positive effect on diabetic neuropathy and balance.

     

Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) in BPH and PCa. ERβ agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNFα knock-out mice fail to respond to ERβ agonist, demonstrating the requirement for TNFα signaling. In human tissues, ERβ agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133⁺ enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ERβ causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ERβ agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ERβ agonist for treatment of PCa and/or BPH with or without androgen withdrawal.     

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.