p-Tolyl bis­(p-tolyl­amido)phosphate

In the title compound, C21H23N2O2P, the P atom exhibits tetra­hedral coordination; the P—N bond lengths are relatively short [1.6297 (13) and 1.6424 (13) Å]. In the crystal, adjacent mol­ecules are linked by N—H⋯O hydrogen bonds into a zigzag chain running along the c axis

N,N′-Dicyclo­hexyl-N′′,N′′-dimethyl­phospho­ric triamide

In the title compound, C14H30N3OP, both cyclo­hexyl groups adopt chair conformations with the NH unit in an equatorial position. The P atom adopts a slightly distorted tetra­hedral environment. In the (CH3)2NP(O) unit, the O—P—N—C torsion angles, showing the orientations of the methyl groups with respect to the phosphoryl group, are −166.6 (3) and 34.6 (4)°. The O atom of the P=O group acts as a double hydrogen-bond acceptor and is involved in two different inter­molecular N—H⋯OP hydrogen bonds, building R 2 2(8) rings that are further linked into chains running parallel to the b axis

Decay resistance of wood impregnated with monoethanolamine and sodium bisulfite pulping black liquors

The efficacy of monoethanolamine and sodium bisulfite pulping black liquors at three concentrations of 1; 1,5 and 2% on the preservation of poplar wood from white rot (Trametes versicolor) was investigated. The wood specimens were impregnated with the black liquors using a full-cell method. The black liquors enhanced the decay resistance without any reduction in mechanical strength, and a remarkable increase was observed at higher concentrations and weight gain percentage. The performance of monoethanolamine black liquor was more pronounced, probably due to lower kappa number and higher pH. The durability class of specimens impregnated with 2% monoethanolamine and sodium bisulfite black liquors improved from 5 (not durable) to 1 (very durable), and from 5 to 3 (moderately durable), respectively. Chemical analysis showed that the presence of additional lignin in wood alters the white rot. Results of anatomical studies showed that the fibers of the control and impregnated wood specimens were collapsed after 16 weeks of incubation. Leaching tests confirmed that the fixation of black liquors in wood should be examined for further studies.   PDF XM

Shigella dysentery stxA mutant (R170L-A231D-G234E) gene design and optimization of recombinant protein expression and purification

زمینه و هدف: شیگلا دیسانتری یکی از مهمترین باکتری های بیماریزا‌ی روده‌ای انسان است. شیگاتوکسین (سم این باکتری) با ورود به سلول های اپیتلیال باعث مهار سنتز پروتئین و مرگ سلولی می شود. علیرغم مطالعات فراوان جهت تولید واکسن علیه آن، هنوز ضرورت تداوم مطالعه در حصول به پروتئین نوترکیب شیگاتوکسین نوع A (stxA) وجود دارد. این مطالعه با هدف بررسی و تعیین جایگاه های مناسب جهش و طراحی ژن سینتتیک زیر واحد stxA و سپس بیان و بهینه سازی آن و در نهایت بررسی روش تخلیص آن جهت مطالعات بعدی ایمنی زایی انجام شد. روش بررسی: در این مطالعه توصیفی-آزمایشگاهی پس از طراحی و تهیه ژن صناعی pET28a/stxA موتانت (G234E– R170L -A231D)، واکنش PCR جهت کنترل صحت حضور این ژن انجام گردید. پس از انتقال این وکتور به سلول میزبان Bl21 DE3، بیان، بهینه سازی و نهایتاً تخلیص پروتئین حاصل بررسی گردید. یافته ها: نتیجه مطالعات اولیه منجر به طراحی ژن stxA موتانت گردید. نتایج واکنش PCR با استفاده از پلاسمید سنتتیک نشان از صحت ژن مورد مطالعه داشت. پس از بیان این ژن در سلول میزبان Bl21 DE3، بهینه سازی آن نیز بررسی گردید. در نتیجه تولید مقادیر زیادی از این پروتئین به شکل اجسام توده ای نشان داده شد. تخلیص انکلوژن بادی و سپس محلول سازی پروتئین های مربوطه با استفاده از روش های تلفیقی صورت گرفت. نتیجه گیری: با توجه به مکانیسم اثر شیگاتوکسین و طراحی جهش های انتخابی با آرایش جدید در این ژن، پیش بینی می شود که این پروتئین بیانی، دارای اثر سمیت کمتری نسبت به سایر موتانت های قبلی داشته باشد، در نتیجه می تواند به عنوان کاندید واکسن برتر مطرح گردد

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA (R)) to the reference product (Humira (R)) in patients with active rheumatoid arthritis

Background: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA (R), CinnaGen, Iran) to the innovator product (Humira (R), AbbVie, USA) in adult patients with active rheumatoid arthritis (RA). Methods: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA (R) or Humira (R) every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety. Results: Patients who were randomized to CinnoRA (R) or Humira (R) arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA (R) group was non-inferior to the Humira (R) group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA (R) and Humira (R) groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant. Conclusion: CinnoRA (R) was shown to be non-inferior to Humira (R) in terms of efficacy at week 24 with a comparable safety profile to the reference product

Efficiency of Constructed Wetland Vegetated with Cyperus alternifolius

The treatment of municipal wastewater from Yazd city (center of Iran) by constructed wetland vegetated with Cyperus alternifolius was assessed. Two identical wetlands with a total working volume of 60 L and 10 cm sandy layer at the bottom were used. First wetland (W1) was control and had no Cyperus alternifolius plant. Second wetland (W2) had 100 Cyperus alternifolius shrubs with 40 cm height. Influent wastewater was provided from Yazd's septic tanks effluents and after a 4-day retention time in wetlands, reactors effluent was sampled for parameters analysis. Results show that chemical oxygen demand (COD), –N, –N, and –P in W1 were reduced to 72%, 88%, 32%, and 0.8%, and in W2, these parameters were removed in values of 83%, 81%, 47%, and 10%, respectively. In both wetlands, the highest and lowest removal efficiencies were related to COD and phosphorus, respectively. Also, the removed phosphorus can be released to stream when the soil saturated or influent phosphorus decreased and when the plant died. After a 4-day-retention time, the W2 wetland showed a statistically significantly lower COD and –N in comparison with W2 wetland

Awareness, Attitude, and Performance of Residents in Using Disinfectants to Prevent COVID-19 in 2022: A Case Study in Iran

Introduction: It is essential to adopt preventive measures to reduce the prevalence and severity of COVID-19. Given the insufficient information about the use of disinfectants against the virus, which leads to various risks, this study aims to investigate awareness, performance, and attitudes of the residents of Yazd city regarding using disinfectants to prevent COVID-19. Materials and Methods: In this descriptive study, the sample consisted of 271 people residing in Yazd using convenience sampling method. The tool used was a researcher-made questionnaire, which was reliable, valid, and was divided into two parts; after that the collected data was analyzed using descriptive and analytical statistical tests. SPSS software was used for data processing, and Amos software was used for model design. Results: Most participants (51.3%) were female. The majority of participants (117 (43.2%)) aged between 30-40, and with an average age of 34.39 ± 9.6. The highest level of education attained by most participants was master's degree by 83 (30.6%) people. The mean and standard deviation for awareness (10.59 ± 2.7), attitude (40.74 ± 7.1), and performance (17.50 ± 5.1) were obtained.  Structural Equation Modeling (SEM) analysis showed that the total effect had the greatest impact on the use of disinfectants, with performance (β = 0.032) and education (β = 0.068) having the strongest effects. Increase in disinfection and having a higher level of education increased the use of disinfectants as well. Conclusion: As increasing people's awareness, attitude, and performance can help prevent the spread of COVID-19, implementing educational programs and timely comprehensive information dissemination about the use of disinfectants is recommended

Basic Occupational Health Services for Agricultural Workers in the South of Iran

The agricultural sector has by far the world’s largest labour force, there are more than one billion workers in this industry worldwide, which contains half of the total world labour force. On the other hand, agriculture is one of the most hazardous occupations, and many workers suffer occupational accidents and ill health each year. Farming and animal breeding are associated with exposure to a wide variety of risk factors, including zoonotic agents, dust, elements of the thermal environment, noise, vibration and chemicals. Although half of the world’s population are economically active and spend at least one third of their time in the workplace, only 15% of the workers have access to basic occupational health services. According to a WHO report, Iran has a well-structured health care system through which basic health care services are available to the entire population, and health indicators in Iran have consistently improved. The agricultural health program in Iran is being carried out in the cities and rural areas, and occupational health services are mainly integrated into the health network. This paper aims to describe the health care system and basic occupational health services (BOHs) available to 5,300 agricultural enterprises with 8,380 employees in the cities of Abadan, Khorramshahr and Shadegan in the Abadan region (Abadan, Khoramshahr and Shadegan districts), in the south of Iran

Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease study 2019

Introduction The current study determined the level and trends associated with the incidence, death and disability rates for bladder cancer and its attributable risk factors in 204 countries and territories, from 1990 to 2019, by age, sex and sociodemographic index (SDI; a composite measure of sociodemographic factors). Methods Various data sources from different countries, including vital registration and cancer registries were used to generate estimates. Mortality data and incidence data transformed to mortality estimates using the mortality to incidence ratio (MIR) were used in a cause of death ensemble model to estimate mortality. Mortality estimates were divided by the MIR to produce incidence estimates. Prevalence was calculated using incidence and MIR-based survival estimates. Age-specific mortality and standardised life expectancy were used to estimate years of life lost (YLLs). Prevalence was multiplied by disability weights to estimate years lived with disability (YLDs), while disability-adjusted life years (DALYs) are the sum of the YLLs and YLDs. All estimates were presented as counts and age-standardised rates per 100 000 population. Results Globally, there were 524 000 bladder cancer incident cases (95% uncertainty interval 476 000 to 569 000) and 229 000 bladder cancer deaths (211 000 to 243 000) in 2019. Age-standardised death rate decreased by 15.7% (8.6 to 21.0), during the period 1990–2019. Bladder cancer accounted for 4.39 million (4.09 to 4.70) DALYs in 2019, and the age-standardised DALY rate decreased significantly by 18.6% (11.2 to 24.3) during the period 1990–2019. In 2019, Monaco had the highest age-standardised incidence rate (31.9 cases (23.3 to 56.9) per 100 000), while Lebanon had the highest age-standardised death rate (10.4 (8.1 to 13.7)). Cabo Verde had the highest increase in age-standardised incidence (284.2% (214.1 to 362.8)) and death rates (190.3% (139.3 to 251.1)) between 1990 and 2019. In 2019, the global age-standardised incidence and death rates were higher among males than females, across all age groups and peaked in the 95+ age group. Globally, 36.8% (28.5 to 44.0) of bladder cancer DALYs were attributable to smoking, more so in males than females (43.7% (34.0 to 51.8) vs 15.2% (10.9 to 19.4)). In addition, 9.1% (1.9 to 19.6) of the DALYs were attributable to elevated fasting plasma glucose (FPG) (males 9.3% (1.6 to 20.9); females 8.4% (1.6 to 19.1)). Conclusions There was considerable variation in the burden of bladder cancer between countries during the period 1990–2019. Although there was a clear global decrease in the age-standardised death, and DALY rates, some countries experienced an increase in these rates. National policy makers should learn from these differences, and allocate resources for preventative measures, based on their country-specific estimates. In addition, smoking and elevated FPG play an important role in the burden of bladder cancer and need to be addressed with prevention programmes.publishedVersio

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions