Beta cell regeneration upon magainin and growth hormone treatment as a possible alternative to insulin therapy.

Insulin therapy, pancreas transplantation and ß cell regeneration are among the suggested treatment strategies for type 1 diabetes. It has been shown that some antimicrobial peptides have the potential to increase insulin release and to improve glucose tolerance, although the mechanism by which they promote the regeneration of damaged pancreatic cells to functional ß-like cells remains unknown. To answer this question, we evaluated the in vivo effects of magainin-AM2 and growth hormone (GH) on the regeneration of streptozotocin (STZ)-damaged mouse pancreas. Treatment with magainin-AM2 and GH ameliorated the effects of STZ on fasting blood glucose and glucose tolerance test values, and also resulted in a significant increase in total cell counts (α and ß) and the number of insulin+ and glucagon+ cells per islet and a decrease in the number of T and B cells. In addition, we observed a 1.43- and 2.21-fold increase in expression of paired box 4, one of the main factors for α to ß-like cell conversion, in normal- and diabetes-treated mice, respectively. Similarly, expression of P-S6 and extracellular signal-regulated kinases 1 and 2, required for cell proliferation/differentiation, increased by 3.27- and 2.19-fold among the diabetes-treated and control diabetic mice, respectively. Furthermore, in all experiments, amelioration of the effects of STZ were greatest upon Mag treatment followed by GH administration. The present in vivo data provide evidence in support of the possibility of pharmaceutical induction of α cell production and their trans-differentiation to functional ß-like cells.

Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021. METHODS: The literature search was based on keywords including "chronic fatigue syndrome and HHV 6," "chronic fatigue syndrome and HHV-6," "chronic fatigue syndrome and HHV6," "chronic fatigue syndrome and Herpes virus 6," and "chronic fatigue syndrome and Herpesvirus6" in MEDLINE (PubMed), Web of Science, and EMBASE. RESULTS: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger's test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies. DISCUSSION: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

Imaging Features of Vessels and Leakage Patterns Predict Extended Interval Aflibercept Dosing Using Ultra-Widefield Angiography in Retinal Vascular Disease: Findings From the PERMEATE Study.

Diabetic Macular Edema (DME) and macular edema secondary to retinal occlusion (RVO) are the two most common retinal vascular causes of visual impairment and leading cause of worldwide vision loss. The blood-retinal barrier is the key barrier for maintaining fluid balance within the retinal tissue. Vascular Endothelial Growth Factor (VEGF) has a significant role in the permeability of the blood-retinal barrier, which also leads to appearance of leakage foci. Intravitreal anti-VEGF therapy is the current gold standard treatment and has been demonstrated to improve macular thickening, improve vision acuity and reduce vascular leakage. However, treatment response and required dosing interval can vary widely across patients. Given the role of the blood-retinal barrier and vascular leakage in the pathogenesis of these disorders, the goal of this study was to present and evaluate new computer extracted features relating to morphology, spatial architecture and tortuosity of vessels and leakages from baseline ultra-widefield fluorescein angiography (UWFA) images. Specifically, we sought to evaluate the role of these computer extracted features from baseline UWFA images. Notably, these UWFA images were obtained from IRB-approved PERMEATE clinical trial [1], [2] to distinguish eyes tolerating extended dosing intervals (n = 16) who are referred to as non-rebounders and those who require more frequent dosing (n = 12) and are called rebounders based on visual acuity loss with extended dosing challenges. A total of 64 features encapsulating different morphological and geometrical attributes of leakage patches including the anatomical (shape, size, density, area, minor and major axis, orientation, area, extent ratio, perimeter, radii) and geometrical characteristics (the proximity of each leakage foci to main vessels, to other leakage foci and to optical disc) as well as 54 tortuosity features (tortuosity of whole vessel network, local tortuosity of vessels in the vicinity of leakage foci) were extracted. The most significant and predictive biomarkers related to treatment response were proximity of leakage nodes to major and minor eye vessels as well as local vasculature tortuosity in the vicinity of the leakages. The imaging features were then used in conjunction with a Linear Discriminant Analysis (LDA) classifier to distinguish rebounders from non-rebounders. The 3-fold cross-validated Area Under Curve (AUC) was found to be 0.82 for the morphological based features and 0.85 for the tortuosity based features. Our findings suggest higher variation in leakage node proximity to retinal vessels in eyes tolerating extended interval dosing. In contrast, eyes with increased local vascular tortuosity demonstrated less tolerance of increased dosing interval. Moreover, a class activation map generated by a deep learning model identified regions that corresponded to regions of leakages proximal to the vessels, providing confirmation of the validity of predictive image features extracted from these regions in this study.

Environmental exposure to endotoxin and its health outcomes: A systematic review.

Exposure to endotoxin occurs environmentally and occupationally. There are several differences between them in terms of the variety and severity of health outcomes, possible exposed groups and type and route of exposure. Occupational exposures caused adverse health outcomes in almost all cases, but there is disparity in the incidence of significant health outcomes due to environmental exposure to endotoxin. This study has therefore endeavoured to investigate health outcomes from environmental exposure to endotoxin. A systematic review was conducted of three databases and non-occupational studies reporting the environmental concentration of endotoxin, and observed health outcomes in exposed groups were included in the review (n = 27). The studies showed that first exposure to endotoxin occurs in infancy by the inhalation route. Inhalation is the only exposure route that can induce inflammation as the main symptom of exposure to endotoxin. The studies included were conducted using four approaches: molecular immunology, measurement of lung volumes, clinical sensitisation test and diagnosis of asthmatic and respiratory symptoms such as wheezing. By the immunological approach, all the included studies reported that environmental exposure to endotoxin, especially at a younger age, has a protective effect on the incidence of asthma in adolescence. The main disparity observed was in studies using the approach of diagnosed asthma. Overall, however, they confirm the protective effect of exposure to endotoxin although, in the case of children with non-atopic asthma, the results could be different.

The Frequency and Importance of Common α-globin Gene Deletions Among ß-Thalassemia Carriers in an Iranian Population.

[This retracts the article on p. 196 in vol. 9, PMID: 29090069.].

The Frequency and Importance of Common α-globin Gene Deletions Among ß-Thalassemia Carriers in an Iranian Population.

BACKGROUND: ß-thalassemia is the most common monogenic disorder in Iran, and one of the challenges in the screening of the carriers is the coinheritance of α-thalassemia mutations. In the view of high prevalence of α-thalassemia mutations in many parts of the country, the aim of this study was to determine the carrier frequency of common alpha deletions, as a secondary modifier in clinical manifestations of beta thalassemia, in known beta-thalassemia carriers and some hematology parameter changes. METHODS: The study included families referred from different primary health care centers with microcytic hypochromic anemia [MCV<80fl; MCH<27 pg] and A2>3.4%]. Genomic DNA was extracted from peripheral blood leukocytes by salting out method. For common ß-globin gene mutation analysis, amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) and for rare ß-thal alleles, DNA sequencing were used. Also, for investigation of common α-globin gene cluster deletions (-α3.7, -α4.2, --MED and -α20.5), multiplex Gap-PCR was performed. RESULTS: Among 227 ß-thalassemia minor individuals studied, α-globin gene deletions were found in 43 cases: 37 heterozygote -α3.7 (16.3%), 5 homo -α3.7 (2.2%) and 1 --MED (0.44%). Also, the co-inheritance of α-globin gene deletion and triplication was not found in the studied individuals. CONCLUSION: Although it is highly recommended that physicians and genetic counselors involved in the screening program of beta-thal major in the country consider this phenomenon because of high prevalence of this coinheritance, hematologic indices changes are very slight.

Role of Epigenetics in Biology and Human Diseases.

For a long time, scientists have tried to describe disorders just by genetic or environmental factors. However, the role of epigenetics in human diseases has been considered from a half of century ago. In the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurodegenerative and psychological disorders. This review first explains the history and classification of epigenetic modifications, and then the role of epigenetic in biology and connection between the epigenetics and environment are explained. Furthermore, the role of epigenetics in human diseases is considered by focusing on some diseases with some complicated features, and at the end, we have given the future perspective of this field. The present review article provides concepts with some examples to reveal a broad view of different aspects of epigenetics in biology and human diseases.

The WHO score predicts treatment outcome in low risk gestational trophoblastic neoplasia patients treated with weekly intramuscular methotrexate.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) includes a spectrum of disease ranging from hydatidifrom mole to choriocarcinoma. Low risk GTN is defined as persistent molar pregnancy with a WHO score lower than seven. The optimal chemotherapeutic regimen still remains controversial. AIM: The objectives of this study was to determine efficacy and safety of weekly intramuscular methotrexte in the treatment of low risk gestational trophoblastic neoplasia.(LRGTN) and also identify prognostic factors associated with treatment failure, necessitating second line chemotherapy. MATERIALS AND METHODS: Sixty-six women with LRGTN from 2001 to 2009 were treated with weekly intramuscular methotrexate at 40 mg/m 2 as first line therapy.Monitoring of treatment was done with weekly checking of ßhCG level. Three consecutive negative ßhCG measurements showed complete response. After first negative ßhCG measurement, one additional dose was administered for consolidation. RESULTS: Of 66 patients, who started the treatment five continued their treatment in other medical centres and were excluded from final analysis for treatment evaluation, and seven discontinued first line therapy because of hepatotoxicity. Of the remaining 54, complete remission occurred in 43 (79.6%) and eleven were resistant to first line therapy. Mean WHO score prior to starting chemotherapy was significantly different between two groups of response and resistance according to our data. Change of treatment to second line Actinomycin-D was necessary in eighteen cases because of resistance to first line in eleven and liver enzyme elevation in seven patients. Sixteen of these 18 responded to Actinomycin-D as second line and one needed hysterectomy for complete response. One patient received multiagent chemotherapy for complete remission. CONCLUSION: We recommend this effective and safe method of chemotherapy for women with LRGTN. According to our data, lower mean WHO score predicts a better outcome for this regimen.