Nerve growth factor gene therapy using adeno-associated viral vectors prevents cardiomyopathy in type 1 diabetic mice

Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or β-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2-β-Gal or AAV9-β-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in β-Gal-injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the β-Gal-injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects.     

Ermin deficiency leads to compromised myelin,inflammatory milieu,and susceptibility to demyelinating insult

Ermin is an actin‐binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although Ermin has been predicted to play a role in the formation and stability of myelin sheaths, this has not been directly examined in vivo. Here, we show that Ermin is essential for myelin sheath integrity and normal saltatory conduction. Loss of Ermin in mice caused de‐compacted and fragmented myelin sheaths and led to slower conduction along with progressive neurological deficits. RNA sequencing of the corpus callosum, the largest white matter structure in the CNS, pointed to inflammatory activation in aged Ermin‐deficient mice, which was corroborated by increased levels of microgliosis and astrogliosis. The inflammatory milieu and myelin abnormalities were further associated with increased susceptibility to immune‐mediated demyelination insult in Ermin knockout mice. Supporting a possible role of Ermin deficiency in inflammatory white matter disorders, a rare inactivating mutation in the ERMN gene was identified in multiple sclerosis patients. Our findings demonstrate a critical role for Ermin in maintaining myelin integrity. Given its near‐exclusive expression in myelinating oligodendrocytes, Ermin deficiency represents a compelling “inside‐out” model of inflammatory dysmyelination and may offer a new paradigm for the development of myelin stability‐targeted therapies.     

Perceptions and uses of plants for reproductive health among traditional midwives in Ecuador: Moving towards intercultural pharmacological practices

Despite the fact that plants have played an important role in midwifery in many cultures, there are very few in-depth studies on the plants traditionally used by midwives. The aim of this study is to analyse the perceptions and the uses of medicinal plants for reproductive health among indigenous midwives in the city of Otavalo, Ecuador. The article also aims to analyse the perceptions of traditional midwives regarding allopathic drugs for reproductive health and their possible overlapping uses of medicinal plants and allopathic drugs. The data are drawn from an ethnographic study carried out in Ecuador. In total, 20 traditional midwives have been interviewed. Individual and in-depth interviews also took place with a sample of 35 women as well as with five nurses and two doctors working at San Luis Hospital in Otavalo.     

Distribution of paresthesias in Carpal Tunnel Syndrome reflects the degree of nerve damage at wrist.

OBJECTIVE: To verify whether the distribution of paresthesias in patients with Carpal Tunnel Syndrome (CTS) is related to the degree of the neurophysiological involvement. METHODS: We performed a cross-sectional study and retrospectively evaluated 163 patients who referred to our electromyography lab and to which a clinical and electrophysiological diagnosis of CTS was made. We divided the patients into two groups: (1) patients complaining of paresthesias at the hand as a whole and (2) patients with paresthesias in the territory of the median nerve. We referred to the distribution of paresthesias at the hand as GLOVE and to the distribution in the territory of the median nerve as MEDIAN. We compared the neurophysiological impairment in GLOVE and MEDIAN distributions. Moreover, we performed multiple regression analysis to evaluate which clinical-neurophysiological variables determined GLOVE and MEDIAN distribution. RESULTS: In our sample, 70.4% of patients had GLOVE distribution and 29.6% of patients MEDIAN distribution. The risk of presenting MEDIAN distribution increases about twice (OR = 2.07; 95% IC: 1.51-2.83) for each unitary increment of neurophysiological class. CONCLUSIONS: The distribution of paresthesias reflects the degree of nerve damage at wrist; patients suffering of SEV/EXT CTS present MEDIAN distribution. SIGNIFICANCE: Our data have important clinical implications because they strongly suggest that we have to consider the possibility of a severe neurophysiological involvement of the median nerve at wrist in patients complaining of MEDIAN distribution.     

Moving Mammogram-Reluctant Women to Screening: A Pilot Study

Background  

Effective interventions are needed for women long overdue for screening mammography.     

Adverse relationship between blood transfusions and survival after colectomy for colon cancer

Random-donor blood transfusions are deliberately given before cadaver renal allografting to improve allograft survival. Since host modifications that improve the outcome of an allograft might be associated with a decreased ability of the host to control cancer growth, the relationship between blood transfusions and the outcome of 146 Dukes' stages A, B, and C colon cancers treated by resection during the years 1974 to 1979 was studied. It was found that 65 patients (45%) had been transfused and that at 5 years, overall survival was significantly better in the nontransfused patients compared to the transfused patients (0.68 and 0.51 5-year product limit survival fractions respectively; P = 0.03 for unadjusted log-rank comparison of entire survival curves). Relative risk of death due to cancer in transfused patients versus nontransfused patients was 2.3 (P = 0.05) when controlled for sex, age, stage, histologic differentiation, cancer location, and pre-resection hemoglobin level using Cox regression analysis. Thus, blood transfusion appears to be an additional important prognostic variable. The hypothesis suggested but not proven by these data that the outcome for some malignancies may be related to the immunomodulating effects of blood transfusions needs further study.