Abstract

The exposure of the developing foetal heart to hyperglycaemia in mothers with diabetes mellitus is a major risk factor for foetal cardiac complications that lead to heart failure. We studied the effects of hyperglycaemia on the layout of cardiac myofilament proteins in stem cell-derived cardiomyocytes and their possible underlying mechanisms. Mouse embryonic stem cells (mESCs) were differentiated into cardiac-like cells and cultured in media containing baseline- or high glucose concentrations. Cellular biomarkers were detected using Western blot analysis, immunocytochemistry, 5–ethynyl–2-deoxyuridine (EdU) cell proliferation assay, and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. High glucose decreased the proportion of cardiac troponin T and α-actinin 2 positive mESCs as well as disrupted the α-actinin 2 striated pattern and the distribution of the cardiac myosin heavy chain α- and β isoforms. However, there was no alteration of the cellular EdU uptake nor the expression of the receptor of advanced glycation end-product (RAGE). High glucose also increased the presence of the oxidative stress marker nitrotyrosine as well as the number of TUNEL-stained nuclei in cardiaclike cells. Treatment with the antioxidant N-acetyl cysteine decreased the number of TUNEL-stained cells in high glucose and improved the α-actinin 2 striated pattern. Hyperglycaemia negatively impacted the expression and cellular organisation of cardiac myofilament proteins in mESC-derived cardiomyocytes through oxidative stress. The results add further insights into the pathophysiological mechanisms of cardiac contractile dysfunction in diabetic cardiac developmental disease.

Abstract

Hyperglycaemia, a key metabolic abnormality in diabetes mellitus, is implicated in pathological cardiogenesis during embryological development. However, the underlying mechanisms and potential therapeutic targets remain unknown. We, therefore, studied the effect of hyperglycaemia on mouse embryonic stem cell (mESC) cardiac differentiation. The mESCs were differentiated via embryoid body (EB) formation and cultured under conditions with baseline (25 mM) or high (50 mM) glucose. Time-lapse microscopy images of pulsatile mESCs and Ca2+ntransients were recorded. Biomarkers of cellular changes were detected using immunocytochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and Western blot analyses. Differentiated, spontaneously beating mESCs stained positive for cardiac troponin T, α-actinin 2,nmyosin heavy chain, and connexin 43. Hyperglycaemia decreased the EB diameter and number of beating EBs as well asnthe cellular amplitude of contraction, the Ca2+ transient, and the contractile response to caffeine (1 mM), but had no effect. on the expression of the sarco-endoplasmic reticulum calcium transport ATPase 2 (SERCA 2). Furthermore, hyperglycaemia decreased the expression of B cell lymphoma 2 (Bcl-2) and increased the expression of cytoplasmic cytochrome c and the number of TUNEL-positive cells, but had no effect on the expression of one of the mitochondrial fusion regulatory proteins, optic atrophy protein 1 (OPA1). Overall, hyperglycaemia suppressed the mESC cardiomyocyte-like differentiation and induced contractile dysfunction. The results are consistent with mechanisms involving abnormal Ca2+ handling and mitochondrial-dependent apoptosis, factors which represent potential therapeutic targets in developmental diabetic cardiac disease.

Abstract

Objective: Chronic diabetes mellitus is associated with detrimental cardiovascular complications and electrolyte imbalances such as hypomagnesaemia. We investigated the effect of magnesium (Mg2+) on cardiac function and the possible role of histological and electrical alterations in chronic, streptozotocin-induced diabetic rats.

Methods: Wistar rats were treated once intraperitoneally with streptozotocin or citrate, and then daily with MgSO4 or saline for four weeks. Cardiac contractile and electrocardiographic parameters were measured on Langendorff-perfused hearts. Other hearts were histologically stained or immunoblotted for the mitochondrial ATP synthase (ATP5A).

Results: In diabetic hearts, Mg2+ prevented a diabetes-induced decrease in left ventricular developed pressure and improved contractility indices, as well as attenuated the reduction in heart rate and prolongation of QT interval, but not the QT interval corrected for heart rate (QTc). Histologically, there

were neither differences in cardiomyocyte width nor interstitial collagen. The expression of ATP5A was not different among the treatment groups.

Conclusion: Mg2+ supplementation improved cardiac contractile activity in chronic diabetic hearts via mechanisms unrelated to electrocardiographic or histologically detectable myocardial alterations.

Abstract Introduction: Abdominal wall defects (AWD) are a common problem that can become difficult to manage, especially when the defect is large and resources are limited (silo and TPN). Methods: Retrospectively, 85 medical records of patients who have been admitted to TMC over a decade (2005 - 2015) were studied. The defects have been categorized into three groups: omphalocele minor, omphalocele major and gastroschisis. The aim is compare the outcomes within these three groups between developed and developing nations. Results: Out of 85 neonates with abdominal wall defects, 50 are males and 35 are females. 58 patients had omphalocele minor, 16 omphalocele major and 11 with gastroschisis. Associated congenital anomalies are reported in 45% of omphalocele groups (1 and 2) and in 27% of gastroschisis group. Post-operative morbidity rate among the omphalocele groups (1 and 2) is 27.37%, and 54.54% among gastroschisis group. Mortality rate among the group one is 3.45%, group two 12.5%, and group three 27.27%. The mortality rate among the two patients who received devices was 50%. Conclusion: Omphalocele can be treated effectively in the developing world; however, gastroschisis cases need more sophisticated supportive measures to reach the reported rates.

Libya is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) in Libya. Objective: Evaluate drug resistance of bacteria isolated from equipment placed close to patients in an Intensive Care Unit of a Central hospital in Gharian.

DNA, RNA, and protein are represented as strings in bioinformatics for this reason string processing is the cornerstone in the field of bioinformatics and these problems take a variety of manifestations each of which has a specific meaning. This topic will shed some light on some traditional string problems such as: local sequence alignment problem, global sequence alignment problem, exact pattern matching problem, approximate pattern matching problem, finding all maximal palindromes problem, finding all tandem repeats problem, finding all tandem arrays problem, etc. There are quite rich researches for these problems. This paper, will propose the major algorithms in this respect which implemented in BioQt.

BACKGROUND AND PURPOSE: A thorough knowledge of fetal growth and development is key to understanding both the normal and abnormal fetal MR imaging findings. We investigated the size and signal intensity of the normal pituitary gland and the intrasphenoidal ossification around the Rathke pouch in formalin-fixed fetuses on MR imaging.

MATERIALS AND METHODS: Thirty-two fetuses with undamaged brains were included in this study (mean age, 19.93 weeks; age range, 12–31 weeks). Visual inspection of the pituitary and ossification around the Rathke pouch in the sphenoid bone or the postsphenoid ossification was conducted. The extent of pituitary and postsphenoid ossification, pituitary/pons signal ratio, and postsphenoidal ossification/sphenoid bone signal ratio was compared according to gestational age.

RESULTS: The pituitary gland was identified as a hyperintense intrasellar structure in all cases, and postsphenoid ossification was identified as an intrasphenoidal hyperintense area in 27 of the 32 cases (84%). The mean pituitary/pons signal ratio was 1.13 ± 0.18 and correlated weakly with gestational age (R2 = 0.243), while the mean postsphenoid ossification/sphenoid bone signal ratio was 2.14 ± 0.56 and did not show any increase with gestational age (R2 = 0.05). No apparent change in the size of pituitary hyperintensity was seen with gestational age (R2 = 0.001). Postsphenoid ossification showed an increase in size with gestational age (R2 = 0.307).

CONCLUSIONS: The fetal pituitary gland was hyperintense on T1-weighted images and the pituitary/pons ratio and extent of postsphenoid ossification correlated weakly with gestational age.

Bioinformatics is a multi-disciplinary science focusing on the applications of computational methods and mathematical statistics to molecular biology. Choosing bioinformatics as specialization gives an opportunity to get involved with the most interesting computational techniques dealing with biological data to contribute to cure and diagnose some of genetic disorders that affect biological machines. The purpose of this library (which defines namespace BioQt), is to provide a set of routines for handling biological sequence data for Qt/C++ users (the full source code available on https://github.com/alrawab/BioQt). This thesis will shed the light on some modules of BioQt SDK such as exact string matching problem, Microsatellite Repeats, Palindromic sequences and sequence alignment algorithms (Longest Common Subsequence, Needleman-Wunsch and Smith-Waterman). This thesis examines and evaluates these challenging problems in bioinformatics by using Qt/C++.

Objective: We qualitatively evaluated the differences among susceptibility-weighted (SWI), magnitude (MAG), and high pass filtered phase (PHA) images in depicting interlobar differences in the appearance of the signal of the corticomedullary junction (CMJ). We conducted quantitative evaluation to validate the qualitative results.

Materials and Methods: We obtained SWI images from 25 preoperative brain tumor patients (12 men, 13 women, aged 19 to 82 years, mean, 52 years). Two trained neuroradiologists evaluated MAG, PHA, and SWI images. Qualitative evaluation of the CMJ signal and quantitative calculation of the relative signal ratio (RSR) percentages between the CMJ and deep white matter (WM) were conducted at 3 different slice levels of the brain independently for 4 different lobes (frontal, parietal, temporal, and occipital) and compared among MAG, PHA, and SWI. The extent of the area of the CMJ signal was graded on a 4-point scale (Grade 3, >75%; Grade 2, 50 to 75%; Grade 1, 25 to 50%; Grade 0, <25%). Data were statistically analyzed using a nonparametric Friedman test.

Results: The Kappa coefficients between the qualitative and quantitative grades were 0.002 for MAG, 0.0047 for PHA, and 0.050 for SWI. Qualitatively, on the PHA images and SWI, grades of the occipital lobes were significantly higher than those of the other lobes (P < 0.005). Quantitatively, PHA images showed statistically significant interlobar differences in RSR percentage values of the CMJ (P = 0.025).

Conclusion: Qualitatively, the appearance of the CMJ differed significantly among the different lobes of the brain on SWI and underlying PHA images but not on MAG images. Quantitatively, only PHA images showed significant interlobar differences in the RSR. PHA images are most sensitive to the CMJ signal contrast due to local paramagnetic iron content.