Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

May Measurement Month (MMM) 2017: an analysis of blood pressure screening results in Bangladesh-South Asia

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. Based on the findings of the non-communicable disease Risk Factors Survey Bangladesh 2010, the prevalence of hypertension in adults 25 years or older in Bangladesh is 20.1%. The Bangladesh Demographic Health Survey, 2011 showed that approximately 50% of those affected are unaware of their hypertensive condition. The May Measurement Month 2017 (MMM17) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP. We participated in MMM17 to raise awareness of hypertension screening and identify those with elevated BP who were unaware, and those on treatment with still uncontrolled hypertension. Following the standard protocol designed by the ISH, we participated in MMM17, an opportunistic cross-sectional survey of volunteers aged ≥18. It was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. Data were collected from 35 screening sites in 33 districts in Bangladesh. Personnel from several government and non-government organizations volunteered in this huge event. A total of 11 418 individuals were screened during MMM17, of which 5401 (47.3%) were found to have hypertension. Of 8365 individuals not receiving anti-hypertensive medication, 2348 (28.1%) were hypertensive. Of 3053 individuals receiving anti-hypertensive medication, 1594 (52.2%) had uncontrolled BP. MMM17 was the largest BP screening campaign undertaken in Bangladesh. This study suggests that opportunistic screening can identify significant numbers of people with raised BP. A periodic public health programme at a national level needs to be initiated to increase hypertension detection and control rate and thus for the prevention of cardiovascular diseases

Chylous ascites following radical nephrectomy: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Incidence of re-amputation following partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy: a systematic review.

Diabetes mellitus with peripheral sensory neuropathy frequently results in forefoot ulceration. Ulceration at the first ray level tends to be recalcitrant to local wound care modalities and off-loading techniques. If healing does occur, ulcer recurrence is common. When infection develops, partial first ray amputation in an effort to preserve maximum foot length is often performed. However, the survivorship of partial first ray amputations in this patient population and associated re-amputation rate remain unknown. Therefore, in an effort to determine the actual re-amputation rate following any form of partial first ray amputation in patients with diabetes mellitus and peripheral neuropathy, the authors conducted a systematic review. Only studies involving any form of partial first ray amputation associated with diabetes mellitus and peripheral sensory neuropathy but without critical limb ischemia were included. Our search yielded a total of 24 references with 5 (20.8%) meeting our inclusion criteria involving 435 partial first ray amputations. The weighted mean age of patients was 59 years and the weighted mean follow-up was 26 months. The initial amputation level included the proximal phalanx base 167 (38.4%) times; first metatarsal head resection 96 (22.1%) times; first metatarsal-phalangeal joint disarticulation 53 (12.2%) times; first metatarsal mid-shaft 39 (9%) times; hallux fillet flap 32 (7.4%) times; first metatarsal base 29 (6.7%) times; and partial hallux 19 (4.4%) times. The incidence of re-amputation was 19.8% (86/435). The end stage, most proximal level, following re-amputation was an additional digit 32 (37.2%) times; transmetatarsal 28 (32.6%) times; below-knee 25 (29.1%) times; and LisFranc 1 (1.2%) time. The results of our systematic review reveal that one out of every five patients undergoing any version of a partial first ray amputation will eventually require more proximal re-amputation. These results reveal that partial first ray amputation for patients with diabetes and peripheral sensory neuropathy may not represent a durable, functional, or predictable foot-sparing amputation and that a more proximal amputation, such as a balanced transmetatarsal amputation, as the index amputation may be more beneficial to the patient. However, this remains a matter for conjecture due to the limited data available and, therefore, additional prospective investigations are warranted

Cut off values of waist circumference & associated cardiovascular risk in egyptians

<p>Abstract</p> <p>Background</p> <p>Recent guidelines stressed the need to adopt different values of waist circumference (WC) measurements to define abdominal obesity in different ethnic groups. The aim of this study is to identify WC cutoff points in normotensive and hypertensive subjects which are diagnostic of abdominal obesity in a Middle Eastern population and the prevalence of abdominal obesity in a nationwide sample.</p> <p>Methods</p> <p>Data were collected during phase-2 of the Egyptians National Hypertension Project survey. Blood pressure, anthropometric measurements and laboratory studies were performed according to a standardized protocol by trained personnel. To derive the cutoff points for WC, we applied the factor analysis on CV risk factors: diabetes mellitus, decrease in HDL-C and increase in LDL-C, triglycerides and left ventricular mass index by echocardiography.</p> <p>Results</p> <p>The sample included 2313 individuals above the age of 25 years. WC values (mean ± SD) were 88 ± 14 cm and 95 ± 14 cm for normotensive (NT) and hypertensive (HT) men respectively, and 89.6 ± 14.7 cm and 95.7 ± 15.9 cm for NT and HT women respectively. Applying factor analysis, the weighted average cutoff points were 93.5 cm for both NT and HT men and 91.5 and 92.5 cm for NT and HT women respectively. Based on these thresholds, the prevalence of abdominal obesity was 48% in men and 51.5% in women.</p> <p>Conclusion</p> <p>This is the first report of specific abdominal obesity cutoff points in a Middle Eastern country. The cutoff points were different from the Europid standards. There is a high prevalence rate of abdominal obesity among Egyptians which is associated with increased prevalence of cardiometabolic risk factors.</p

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer.

Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism