Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide

Muscle dysfunction in acute organophosphorus (OP) poisoning is a cause of death in human. The present study was conducted to identify the mechanism of action of OP in terms of muscle mitochondrial dysfunction. Electromyography (EMG) was conducted on rats exposed to the acute oral dose of malathion (400 mg/kg) that could inhibit acetylcholinesterase activity up to 70%. The function of mitochondrial respiratory chain and the rate of production of reactive oxygen species (ROS) from intact mitochondria were measured. The bioenergetic pathways were studied by measurement of adenosine triphosphate (ATP), lactate, and glycogen. To identify mitochondrial-dependent apoptotic pathways, the messenger RNA (mRNA) expression of bax and bcl-2, protein expression of caspase-9, mitochondrial cytochrome c release, and DNA damage were measured. The EMG confirmed muscle weakness. The reduction in activity of mitochondrial complexes and muscular glycogen with an elevation of lactate was in association with impairment of cellular respiration. The reduction in mitochondrial proapoptotic stimuli is indicative of autophagic process inducing cytoprotective effects in the early stage of stress. Downregulation of apoptotic signaling may be due to reduction in ATP and ROS, and genotoxic potential of malathion. The maintenance of mitochondrial integrity by means of artificial electron donors and increasing exogenous ATP might prevent toxicity of OPs

Narrowband Biphotons: Generation, Manipulation, and Applications

In this chapter, we review recent advances in generating narrowband biphotons with long coherence time using spontaneous parametric interaction in monolithic cavity with cluster effect as well as in cold atoms with electromagnetically induced transparency. Engineering and manipulating the temporal waveforms of these long biphotons provide efficient means for controlling light-matter quantum interaction at the single-photon level. We also review recent experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to review all features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer.</p> <p>Methods</p> <p>The medical charts of 300 male patients who underwent radical cystoprostatectomy for bladder cancer between 1997 and 2005 were retrospectively reviewed. The mean age of the patients was 62 (range 51-75) years.</p> <p>Results</p> <p>Prostate adenocarcinoma was present in 60 (20%) of 300 specimens. All were acinar adenocarcinoma. Of these, 40 (66.7%) were located in peripheral zone, 20 (33.3%) had pT2a tumor, 12 (20%) had pT2b tumor, 22(36.7%) had pT2c and, 6 (10%) had pT3a tumor. Gleason score was 6 or less in 48 (80%) patients. Surgical margins were negative in 54 (90%) patients, and tumor volume was less than 0.5 cc in 23 (38.3%) patients. Of the 60 incidentally detected cases of prostate adenocarcinoma 40 (66.7%) were considered clinically significant.</p> <p>Conclusion</p> <p>Incidentally detected prostate adenocarcinoma is frequently observed in radical cystoprostatectomy specimens. The majority are clinically significant.</p

Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999-2008

Background: In Zanzibar, the Ministry of Health and partners accelerated malaria control from September 2003 onwards. The impact of the scale-up of insecticide-treated nets (ITN), indoor-residual spraying (IRS) and artemisinin-combination therapy (ACT) combined on malaria burden was assessed at six out of seven in-patient health facilities. Methods. Numbers of outpatient and inpatient cases and deaths were compared between 2008 and the pre-intervention period 1999-2003. Reductions were estimated by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period. Results: In 2008, for all age groups combined, malaria deaths had fallen by an estimated 90% (95% confidence interval 55-98%)(p < 0.025), malaria in-patient cases by 78% (48-90%), and parasitologically- confirmed malaria out-patient cases by 99.5% (92-99.9%). Anaemia in-patient cases decreased by 87% (57-96%); anaemia deaths and out-patient cases declined without reaching statistical significance due to small numbers. Reductions were similar for children under-five and older ages. Among under-fives, the proportion of all-cause deaths due to malaria fell from 46% in 1999-2003 to 12% in 2008 (p < 0.01) and that for anaemia from 26% to 4% (p < 0.01). Cases and deaths due to other causes fluctuated or increased over 1999-2008, without consistent difference in the trend before and after 2003. Conclusions: Scaling-up effective malaria interventions reduced malaria-related burden at health facilities by over 75% within 5 years. In high-malaria settings, intensified malaria control can substantially contribute to reaching the Millennium Development Goal 4 target of reducing under-five mortality by two-thirds between 1990 and 2015

Frequency and clinical patterns of stroke in Iran - Systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Cerebrovascular disease is the second commonest cause of death, and over a third of stroke deaths occur in developing countries. To fulfil the current gap on data, this systematic review is focused on the frequency of stroke, risk factors, stroke types and mortality in Iran.</p> <p>Methods</p> <p>Thirteen relevant articles were identified by keyword searching of PubMed, Iranmedex, Iranian University index Libraries and the official national data on burden of diseases.</p> <p>Results</p> <p>The publication dates ranged from 1990 to 2008. The annual stroke incidence of various ages ranged from 23 to 103 per 100,000 population. This is comparable to the figures from Arab Countries, higher than sub-Saharan Africa, but lower than developed countries, India, the Caribbean, Latin America, and China. Similarly to other countries, ischaemic stroke was the commonest subtype. Likewise, the most common related risk factor is hypertension in adults, but cardiac causes in young stroke. The 28-day case fatality rate is reported at 19-31%.</p> <p>Conclusions</p> <p>Data on the epidemiology of stroke, its pattern and risk factors from Iran is scarce, but the available data highlights relatively low incidence of stroke. This may reflect a similarity towards the neighbouring nations, and a contrast with the West.</p

Geometric methods on low-rank matrix and tensor manifolds

In this chapter we present numerical methods for low-rank matrix and tensor problems that explicitly make use of the geometry of rank constrained matrix and tensor spaces. We focus on two types of problems: The first are optimization problems, like matrix and tensor completion, solving linear systems and eigenvalue problems. Such problems can be solved by numerical optimization for manifolds, called Riemannian optimization methods. We will explain the basic elements of differential geometry in order to apply such methods efficiently to rank constrained matrix and tensor spaces. The second type of problem is ordinary differential equations, defined on matrix and tensor spaces. We show how their solution can be approximated by the dynamical low-rank principle, and discuss several numerical integrators that rely in an essential way on geometric properties that are characteristic to sets of low rank matrices and tensors

Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy

The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell), cellular and extracellular (multicellular) events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions), whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size) were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis

The global burden of childhood and adolescent cancer in 2017: an analysis of the Global Burden of Disease Study 2017

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Accurate childhood cancer burden data are crucial for resource planning and health policy prioritisation. Model-based estimates are necessary because cancer surveillance data are scarce or non-existent in many countries. Although global incidence and mortality estimates are available, there are no previous analyses of the global burden of childhood cancer represented in disability-adjusted life-years (DALYs). Methods: Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 methodology, childhood (ages 0–19 years) cancer mortality was estimated by use of vital registration system data, verbal autopsy data, and population-based cancer registry incidence data, which were transformed to mortality estimates through modelled mortality-to-incidence ratios (MIRs). Childhood cancer incidence was estimated using the mortality estimates and corresponding MIRs. Prevalence estimates were calculated by using MIR to model survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated by multiplying age-specific cancer deaths by the difference between the age of death and a reference life expectancy. DALYs were calculated as the sum of YLLs and YLDs. Final point estimates are reported with 95% uncertainty intervals. Findings: Globally, in 2017, there were 11·5 million (95% uncertainty interval 10·6–12·3) DALYs due to childhood cancer, 97·3% (97·3–97·3) of which were attributable to YLLs and 2·7% (2·7–2·7) of which were attributable to YLDs. Childhood cancer was the sixth leading cause of total cancer burden globally and the ninth leading cause of childhood disease burden globally. 82·2% (82·1–82·2) of global childhood cancer DALYs occurred in low, low-middle, or middle Socio-demographic Index locations, whereas 50·3% (50·3–50·3) of adult cancer DALYs occurred in these same locations. Cancers that are uncategorised in the current GBD framework comprised 26·5% (26·5–26·5) of global childhood cancer DALYs. Interpretation: The GBD 2017 results call attention to the substantial burden of childhood cancer globally, which disproportionately affects populations in resource-limited settings. The use of DALY-based estimates is crucial in demonstrating that childhood cancer burden represents an important global cancer and child health concern. Funding: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities (ALSAC), and St. Baldrick's Foundation