Evaluation of outer retinal layers in diabetic macula edema treated with intravitreal ranibizumab

Anti-vascular endothelial growth factor (VEGF) reduces choroidal thickness by choroidal hypoperfusion in diabetic macula oedema (DME) patients. Indirect effect of anti-VEGF towards outer retinal layers (ORL) which supplied by choroidal circulation has not been well described. We evaluate the ORL thickness between retinal pigment epithelium (RPE) with inner-segment-outer-segment photoreceptor junction (IS/OS) and RPE with external limiting membrane (ELM) in pre- and postintravitreal Ranibizumab (IVR) treated eyes with central foveal diabetic macula edema. A total of 60 eyes (40 patients) were analysed. ORL thickness measured with optical coherence tomography at pre- and post-injection day 1, week 4 and week 6. Mean thickness of RPE-IS/OS was statistically significant over time (p=0.023) but not for RPE-ELM (p=0.216). Thickness ratio between RPE-IS/OS and RPE-ELM and central subfoveal thickness (CST) both showed statistically significant result over time with p=0.038 and p=0.000, respectively. We observed an initial reduction of ORL thickness at day 1 followed by increased in thickness at week 4 with subsequent reduction at week 6 was observed. ORL is an aspect that can be explore and emphasized further in patients considered for IVR injections. The long-term effects of IVR to the ORL however could not be concluded due to short follow up period

Post-partum follow-up of women with gestational diabetes mellitus: Effectiveness, determinants, and barriers

Background: Despite the recommendations for postpartum blood glucose monitoring post gestational diabetes mellitus (GDM); scientific evidence reveals that these recommendations may not be fully complied to. This study aimed to follow-up women up to 2 years post-delivery with pregnancies complicated by GDM and healthy controls to assess this fact.Methods: Women with GDM (n = 78) and normal glucose tolerant (n = 89) delivered in 2014 were followed up for 2 years. They were informed and enquired via telephone about their blood glucose screening, physical activity, postpartum complications, and current weight status of mother and baby.Results: Women with previous GDM were older and reported higher body weight 2 years post-delivery. At the 2 year follow-up, n = 11 (14.1%) participants had developed diabetes, all with previous GDM. Both weight at birth (3.8 ± 0.5 kg) and at 2-year (10.7 ± 2.3 kg) for the babies born to GDM mothers was significantly higher than the NGT group babies (2.6 ± 0.63 and 7.1 ± 1.4 kg; p \u3c .05). Only 27 women regularly opted for T2DM screening via monitoring blood glucose or HbA1c levels postpartum. The top reason for failed screening included: believing that GDM would disappear after delivery, and being occupied with the baby.Conclusions: The high incidence of T2DM in women with previous GDM is an alarming finding. Given this trend, systematic follow-up programs are needed to reduce obesity and diabetes risk

Vitamin D Levels in Asymptomatic Adults-A Population Survey in Karachi, Pakistan

Background: It is well established that low levels of 25(OH) Vitamin D (/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. Methods: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. Results: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). Conclusion: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon

Characterization of the Primo-Vascular System in the Abdominal Cavity of Lung Cancer Mouse Model and Its Differences from the Lymphatic System

Cancer growth and dissemination have been extensively studied for a long time. Nevertheless, many new observations on anatomy and histopathology of cancer events are still reported such as formation of a vasculogenic-like network inside aggressive tumors. In this research, new kinds of micro-conduits, named primo-vessels, were found inside the abdominal cavity of NCI-H460 lung cancer murine xenograft models. These vascular threads were largely distributed on the surfaces of various organs and were often connected to peritoneal tumor nodules. Histological and immunofluorescent investigations showed that the primo-vessels had characteristic features that were distinctively different from those of similar-looking lymphatic vessels. They had multiple channels surrounded with loose collageneous matrices, which is in contrast to the single-channel structure of other vascular systems. The rod-shaped nuclei aligned longitudinally along the channels were assumed to be the endothelial cells of the primo-vessels, but LYVE-1, a specific marker of lymphatics, was not expressed, which indicates a clear difference from lymphatic endothelial cells. Taken together these findings on and characterization of the novel threadlike vascular structures in cancer models may have important implications for cancer prognosis and for therapy

The Effect of a DNA Repair Gene on Cellular Invasiveness: Xrcc3 Over-Expression in Breast Cancer Cells

Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis. We assessed the effect of the DNA repair proteins known as X-ray complementing protein 3 (XRCC3) and RAD51, to the invasive behavior of the MCF-7 luminal epithelial-like and BT20 basal-like triple negative human breast cancer cell lines. We report that stable or transient over-expression of XRCC3 but not RAD51 increased invasiveness in both cell lines in vitro. Moreover, XRCC3 over-expressing MCF-7 cells also showed a higher tumorigenesis in vivo and this phenotype was associated with increased activity of the metalloproteinase MMP-9 and the expression of known modulators of cell-cell adhesion and metastasis such as CD44, ID-1, DDR1 and TFF1. Our results suggest that in addition to its' role in facilitating repair of DNA damage, XRCC3 affects invasiveness of breast cancer cell lines and the expression of genes associated with cell adhesion and invasion

CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells

Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment

Care Seeking for Neonatal Illness in Low- and Middle-Income Countries: A Systematic Review

Hadley Herbert and colleagues systematically review newborn care-seeking behaviors by caregivers in low- and middle-income countries

Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis

The aim of this study was to systematically review and meta-analyze published data on the diagnostic performance of combined 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of primary tumors in patients with cancer of unknown primary (CUP). A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Methodological quality of the included studies was assessed. Reported detection rates, sensitivities and specificities were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous. The 11 included studies, comprising a total sample size of 433 patients with CUP, had moderate methodological quality. Overall primary tumor detection rate, pooled sensitivity and specificity of FDG-PET/CT were 37%, 84% (95% CI 78–88%) and 84% (95% CI 78–89%), respectively. Sensitivity was heterogeneous across studies (P = 0.0001), whereas specificity was homogeneous across studies (P = 0.2114). Completeness of diagnostic workup before FDG-PET/CT, location of metastases of unknown primary, administration of CT contrast agents, type of FDG-PET/CT images evaluated and way of FDG-PET/CT review did not significantly influence diagnostic performance. In conclusion, FDG-PET/CT can be a useful method for unknown primary tumor detection. Future studies are required to prove the assumed advantage of FDG-PET/CT over FDG-PET alone and to further explore causes of heterogeneity

Mild Electrical Stimulation with Heat Shock Ameliorates Insulin Resistance via Enhanced Insulin Signaling

Low-intensity electrical current (or mild electrical stimulation; MES) influences signal transduction and activates phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Because insulin resistance is characterized by a marked reduction in insulin-stimulated PI3K-mediated activation of Akt, we asked whether MES could increase Akt phosphorylation and ameliorate insulin resistance. In addition, it was also previously reported that heat shock protein 72 (Hsp72) alleviates hyperglycemia. Thus, we applied MES in combination with heat shock (HS) to in vitro and in vivo models of insulin resistance. Here we show that 10-min treatment with MES at 5 V (0.1 ms pulse duration) together with HS at 42°C increased the phosphorylation of insulin signaling molecules such as insulin receptor substrate (IRS) and Akt in HepG2 cells maintained in high-glucose medium. MES (12 V)+mild HS treatment of high fat-fed mice also increased the phosphorylation of insulin receptor β subunit (IRβ) and Akt in mice liver. In high fat-fed mice and db/db mice, MES+HS treatment for 10 min applied twice a week for 12–15 weeks significantly decreased fasting blood glucose and insulin levels and improved insulin sensitivity. The treated mice showed significantly lower weight of visceral and subcutaneous fat, a markedly improved fatty liver and decreased size of adipocytes. Our findings indicated that the combination of MES and HS alleviated insulin resistance and improved fat metabolism in diabetes mouse models, in part, by enhancing the insulin signaling pathway