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

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Fabrication of Microbicidal Silver Nanoparticles: Green Synthesis and Implications in the Containment of Bacterial Biofilm on Orthodontal Appliances

Among various metal-based nanoparticles, silver nanoparticles (AgNPs) manifest superior inhibitory effects against several microorganisms. In fact, the AgNP-based treatment has been reported to inhibit both sensitive and resistant isolates of bacteria and other disease-causing microbes with equal propensity. Keeping this fact into consideration, we executed bio-mediated synthesis of AgNPs employing extract of flower and various other parts (such as bud and leaf) of the Hibiscus rosa-sinensis plant. The physicochemical characterization of as-synthesized AgNPs was executed employing transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy, etc. The as-synthesized AgNPs demonstrated strong antimicrobial activity against both Gram-positive and Gram-negative bacteria with equal propensity. The as-synthesized AgNPs successfully inhibited Streptococcus mutans (S. mutans), one of the main causative bacteria responsible for dental caries. Considering the fact that orthodontic appliances facilitate infliction of the oral cavity with a range of microbes including S. mutans, we determined the growth inhibitory and anti-adherence activities of AgNPs on orthodontic appliances. We performed microbiological assays employing AgNPs adsorbed onto the surface of nickel–titanium (Ni-Ti) orthodontic wires. A topographic analysis of the decontaminated Ni-Ti orthodontic wires was performed by scanning electron microscopy. In addition to antimicrobial and anti-biofilm activities against oral S. mutans, the as-fabricated AgNPs demonstrated significant inhibitory and anti-biofilm properties against other biofilm-forming bacteria such as Escherichia coli and Listeria monocytogenes

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Chondroblastoma of the cuboid with an associated aneurysmal bone cyst: a case report

We report the case of a young adult who presented with a painful foot due to chondroblastoma associated with an aneurismal bone cyst

Correlates of low birth weight in term pregnancies: a retrospective study from Iran

<p>Abstract</p> <p>Background</p> <p>Low birth weight (LBW) is considered as a major multifaceted public health concern. Seventy-two percent of LBW infants are born in Asia. An estimation of 8% LBW infants has been reported for Eastern Mediterranean region including Iran. This study investigated contributory factors of LBW in singleton term births in Tehran, Iran. Tehran is a multicultural metropolitan area and a sample from the general population in Tehran could be regarded as a representative sample of urban population in Iran.</p> <p>Methods</p> <p>This was a retrospective study using data from 15 university maternity hospitals in Tehran, Iran. Data on all singleton term births in these hospitals were extracted from case records during a one calendar year. Study variables included: maternal age, maternal educational level, history of LBW deliveries, history of preterm labor, cigarette smoking during pregnancy, number of parities, chronic diseases and residential area (Tehran versus suburbs of Tehran). In order to examine the relationship between LBW and demographic and reproductive variables the adjusted logistic regression analysis was performed.</p> <p>Results</p> <p>In all, data for 3734 term pregnancies were extracted. The mean age of women was 25.7 (SD = 5.3) years and 5.2% of term births were LBW. In addition to association between LBW and maternal age, significant risk factors for LBW were: history of LBW deliveries [adjusted odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.06–6.03], smoking during pregnancy (OR = 4.64, 95% CI = 1.97–10.95) and chronic diseases (OR for hypertension = 3.70, 95% CI = 2.25–6.06, OR for others = 2.04, 95% CI = 1.09–3.83).</p> <p>Conclusion</p> <p>The findings indicate that in addition to maternal age, history of LBW deliveries; smoking during pregnancy and chronic diseases are significant determinants of LBW in this population. This is consistent with national and international findings indicating that maternal variables and risk behaviors during pregnancy play important roles on LBW.</p

Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10-8 and 6.4 × 10-4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories

Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10-8 and 6.4 × 10-4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories

Alcoholic cirrhosis in Denmark – population-based incidence, prevalence, and hospitalization rates between 1988 and 2005: A descriptive cohort study

<p>Abstract</p> <p>Background</p> <p>Denmark has one of the highest alcohol consumption rates in Northern Europe. The overall per capita alcohol consumption has been stable in recent decades, but surveys have indicated that consumption has decreased in the young and increased in the old. However, there is no recent information on the epidemiology of alcoholic cirrhosis. We examined time trends in incidence, prevalence, and hospitalization rates of alcoholic cirrhosis in Denmark between 1988 and 2005.</p> <p>Methods</p> <p>We used data from a nationwide population-based hospital registry to identify all Danish citizens with a hospital diagnosis of alcoholic cirrhosis. We computed standardized incidence rates, prevalence and hospitalization rates of alcoholic cirrhosis within the Danish population. We also computed the number of hospitalizations per alcoholic cirrhosis patient per year.</p> <p>Results</p> <p>From 1988 to 1993, incidence rates for men and women of any age showed no clear trend, and after a 32 percent increase in 1994, rates were stable throughout 2005. In 2001–2005, the incidence rates were 265 and 118 per 1,000,000 per year for men and women, respectively, and the prevalence rates were 1,326 and 701 per 1,000,000. From 1994, incidence, prevalence, and hospitalization rates decreased for men and women younger than 45 years and increased in the older population, although the latter finding might be partly explained by changes in coding practice. Men and women born around 1960 or later had progressively lower age-specific alcoholic cirrhosis incidence rates than the generations before them. From 1996 to 2005, the number of hospitalizations per alcoholic cirrhosis patient per year increased from 1.3 to 1.5 for men and from 1.1 to 1.2 for women.</p> <p>Conclusion</p> <p>From 1988 to 2005, alcoholic cirrhosis put an increasing burden on the Danish healthcare system. However, the decreasing incidence rate in the population younger than 45 years from 1994 indicated that men and women born around 1960 or later had progressively lower incidence rates than the generations before them. Therefore, we expect the overall incidence and prevalence rates of alcoholic cirrhosis to decrease in the future.</p

Overview of Natural Inert Dust Utilization Against Stored-Product Pests as Part of Integrated Pest Management

Natural inert dust has been used as a grain protectant since the ancient Aztecs of Mexico to this modern era. Natural inert dust is divided into three groups: the first group includes sand, kaolin, paddy husk ash, wood ash, and clay; the second group includes mineral dust; and the third group includes natural silicas such as diatomaceous earth and zeolite. Natural inert dust has a unique mechanism for killing insect pests. Inert dust particles penetrate the insects’ exoskeleton, causing dehydration through the cuticle. Relative humidity is a crucial factor affecting the efficacy of inert dust application. Inert dust has been traditionally used by farmers, which impacts the insects, such as decreasing population, no insect resistance, and being environmentally friendly. Problems of using inert dust include visible residues on grain, airborne dust, reduced flowability, bulk density reduction, and adverse effects on downstream processing machinery. Moreover, inert dust is a very light product, thus it may cause human respiratory illness. The inert dust can be applied to the smaller or larger storage containers. Natural silica can be readily integrated into modern agriculture as a pest management solution