Reproductive toxicity of manganese dioxide in forms of micro- and nanoparticles in male rats

Background: Manganese Dioxide (MnO2) has long been used in industry, and its application has recently been increasing in the form of nanoparticle. Objective: The present study was an attempt to assess the effects of MnO2 nanoparticles on spermatogenesis in male rats. Materials and Methods: Micro- and nanoparticles of MnO2 were injected (100 mg/kg) subcutaneously to male Wistar rats (150 ± 20 gr) once a week for a period of 4 weeks, and the vehicle group received only normal saline (each group included 8 rats). The effect of these particles on the bodyweight, number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes, testosterone, estrogen, follicle stimulating factor, and the motility of sperms were evaluated and then compared among the control and vehicle groups as the criteria for spermatogenesis. Results: The results showed that a chronic injection of MnO2 nanoparticles caused a significant decrease in the number of sperms, spermatogonia, spermatocytes, diameter of seminiferous tubes (p < 0.001) and in the motility of sperms. However, no significant difference was observed in the weight of prostate, epididymis, left testicle, estradiol (p = 0.8) and testosterone hormone (p = 0.2). Conclusion: It seems that the high oxidative power of both particles was the main reason for the disturbances in the function of the testis. It is also concluded that these particles may have a potential reproductive toxicity in adult male rats. Further studies are thus needed to determine its mechanism of action upon spermatogenesis

Prognostic Value of KI6 Biomarker to Predict Short Term Prognosis of Low Grade Cervical Intraepithelial Neoplasia in Human Papilloma Virus Negative and Positive Patients

Background: Cervical cancer is the most common gynecologic cancer in developing countries. Although this malignancy is preventable, problems exist with screening this cancer. Numerous studies have researched immunohistochemistry methods, such as the KI-67 biomarker as a proliferation marker, to improve screening for cervical intraepithelial neoplasia as the precancerous phase of cervical cancer. These studies mostly screened cytological samples. In the current study, we sought to analyze the correlation between the KI-67 proliferative biomarker and HPV infection in order to predict short-time prognosis in cervical intraepithelial neoplasia as an alternative or ancillary method to current screening methods. Our assessment was based on histologic samples from a different geographic population. Methods: This descriptive cohort prospective study included 40 patients diagnosed with low grade cervical intraepithelial neoplasia based on cervical punch biopsy samples after colposcopy examination. We enrolled patients who referred to the Department of Gynecology- Oncology of an academic hospital of Mashhad University of Medical Sciences from 2016 to 2017. All low grade cervical intraepithelial neoplasia samples were investigated for HR-HPV DNA with the Cobas test and immunostaining for the KI-67 biomarker. After a one-year follow-up, we evaluated the prognosis for all patients based on liquid based cytology and HRHPV test. Data were analyzed by SPSS version 23.0 and the Mann-Whitney U and Fisher's exact tests. A P-value < 0.05 was considered significant. Results:We observed a significant difference between HR-HPV positive and negative tests in KI-67 expression (P<0.001), but there were no significant differences in reactivity level of cervical epithelium (P=0.5) and in KI-67 expressions in metaplastic and non-metaplastic epithelium (P=0.88). After one year, most low grade cervical intraepithelial neoplasia cases in group A that had a low staining KI-67 biomarker had evidence of regression. On the contrary, all cases with high grade KI-67 expression didn’t persist or progressed necessarily. Conclusion: The KI-67 biomarker is recommended as a complementary screening test, but not an alternative for triage of high-risk patients with low grade cervical intraepithelial neoplasia. Patients with low grade cervical intraepithelial neoplasia/HR-HPV positive cervical samples and low staining KI-67 antigen could be offered a less aggressive follow-up protocol

Evaluation of Cause of Deaths' Validity Using Outcome Measures from a Prospective, Population Based Cohort Study in Tehran, Iran

OBJECTIVE: The aim of this study was to evaluate the validity of cause of death stated in death certificates in Tehran using outcome measures of the Tehran Lipid and Glucose Study (TLGS), an ongoing prospective cohort study. METHODS: The cohort was established in 1999 in a population of 15005 people, 3 years old and over, living in Tehran; 3551 individuals were added to this population three years later. As part of cohort's outcome measures, deaths occurring in the cohort are investigated by a panel of medical specialists (Cohort Outcome Panel--COP) and underlying cause of death is determined for each death. The cause of death assigned in a deceased's original death certificate was evaluated against the cause of death determined by COP and sensitivity and positive predictive values (PPV) were determined. In addition, determinants of assigning accurate underlying cause of death were determined using logistic regression model. RESULT: A total of 231 death certificates were evaluated. The original death certificates over reported deaths due to neoplasms and underreported death due to circulatory system and transport accidents. Neoplasms with sensitivity of 0.91 and PPV of 0.71 were the most valid category. The disease of circulatory system showed moderate degree of validity with sensitivity of 0.67 and PPV of 0.78. The result of logistic regression indicated if the death certificate is issued by a general practitioner, there is 2.3 (95% CI 1.1, 5.1) times chance of being misclassified compared with when it is issued by a specialist. If the deceased is more than 60 years, the chance of misclassification would be 2.5 times (95% CI of 1.1, 5.9) compared with when the deceased is less than 60 years

Estimating the incidence of lung cancer attributable to occupational exposure in Iran

<p>Abstract</p> <p>Objective</p> <p>The aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos.</p> <p>Methods</p> <p>Nationwide exposure to each of the mentioned carcinogens was estimated using workforce data from the Iranian population census of 1995, available from the International Labor Organization (ILO) website. The prevalence of exposure to carcinogens in each industry was estimated using exposure data from the CAREX (CARcinogen EXposure) database, an international occupational carcinogen information system kept and maintained by the European Union. The magnitude of the relative risk of lung cancer for each carcinogen was estimated from local and international literature. Using the Levin modified population attributable risk (incidence) fraction, lung cancer incidence (as estimated by the Tehran Population-Based Cancer Registry) attributable to workplace exposure to carcinogens was estimated.</p> <p>Results</p> <p>The total workforce in Iran according to the 1995 census identified 12,488,020 men and 677,469 women. Agriculture is the largest sector with 25% of the male and 0.27% of female workforce. After applying the CAREX exposure estimate to each sector, the proportion exposed to lung carcinogens was 0.08% for male workers and 0.02% for female workers. Estimating a relative risk of 1.9 (95% CI of 1.7–2.1) for high exposure and 1.3 (95% CI 1.2–1.4) for low exposure, and employing the Levin modified formula, the fraction of lung cancer attributed to carcinogens in the workplace was 1.5% (95% CI of 1.2–1.9) for females and 12% (95% CI of 10–15) for males. These fractions correspond to an estimated incidence of 1.3 and 0.08 cases of lung cancer per 100,000 population for males and females, respectively.</p> <p>Conclusion</p> <p>The incidence of lung cancer due to occupational exposure is low in Iran and, as in other countries, more lung cancer is due to occupational exposure among males than females.</p

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Photodegradation of methylene blue by phytosynthesized Ag–ZnO nanocomposites

With the use of pomegranate (Punica granatum) peel extract in the present study, a safe and affordable method of biosynthesizing Ag–ZnO nanocomposites has been developed that follows all green chemistry principles. Different analytical techniques, including X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray (EDX), UV–Vis spectroscopy, and Fourier Transform Infrared (FTIR) Spectroscopy, were utilized to identify the unique properties of synthesized nanocomposites. Based on the characterization results, these nanocomposites have a spherical shape with dimensions ranging from 40 to 77 ​nm and a wurtzite structure with hexagonal facets. Considering the upcoming water crises and the importance of treating water contaminated with industrial and organic dyes, this study investigates how biosynthesized nanocomposites using ultraviolet lamps and sunlight can be used to remove one of the most common organic dyes, methylene blue. In order to identify the most optimal conditions for removing methylene blue from polluted water, this study used two light sources, different nanocatalyst concentrations, and various pH value ranging from 2 to 10. When the ideal conditions for this reaction are met, the prepared nanocomposites can catalyze the pollutant dye within 14 and 50 ​min, when exposed to ultraviolet light and sunlight. In this study, it was determined that plant wastes are biogenic sources capable of providing active ingredients (AI) for the biosynthesis of metal nanocomposites for applications such as decomposition and degradation of organic dyes

The cost effectiveness of rotavirus vaccination in Iran

Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. Effective vaccines have recently been approved and successful vaccination program implemented. The aim of this study was to evaluate the cost effectiveness of mass rotavirus vaccination program in Iran. We developed a Markov model that reflects key features of rotavirus natural history. Parameters of the model were assessed by field study or developed through literature search and published data. We applied the model to the 2009 Iranian birth cohort and evaluated the cost-effectiveness of including the rotavirus vaccine (Rotarix®) into Iranian expanded immunization program (EPI). With an estimated hospitalization rate of 0.05 and outpatient rate of 0.23 cases per person-year, vaccinating cohort of 1231735 infants in Iran with 2 doses of (Rotarix®), would prevent 32092 hospitalizations, 158750 outpatient visits, and 1591 deaths during 5 y of follow-up. Under base-case assumption of 10 cost per course of vaccine, the vaccination would incur an extra cost of 1,019,192 from health care perspective and would avert 54680 DALYs. From societal perspective, there would be 15,192,568 saving for the society with the same averted DALYs. The incremental cost effectiveness ratio showed a cost of 19 US dollars per averted DALY from health care perspective and a saving of 278 US dollars for each averted DALY from societal perspective. Introducing rotavirus vaccine into EPI program would be highly cost-effective public health intervention in Iran. © 2016, Taylor & Francis

The sensitivity and positive predictive values of validity for the death certificates (major grouping).

<p>*Expressed as number. Categories with less than 5 events were omitted.</p

Misclassification matrix (expressed as number) for major grouping of ICD10^*.

<p>*Categories with less than 5 events were eliminated.</p