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Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine
The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP-binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug-metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds
Parents and Health Care Teams Perceptions of Communication in Neonatal Intensive Care Unit
Parents experience a lot of stress in the neonatal intensive care unit (NICU). Then effective communication between parents and members of the care team is an essential component of improving the quality of care. The present study was conducted by qualitative exploratory research method for explaining parents and health care teams' perceptions of communication in NICU. We selected 39 participants by purposive sampling. We collected data through in-depth semi-structured, face-to-face interviews. The transcripts were analysed using the conventional content analysis approach. Three themes were obtained by analyzing the data included, the nature of communication, the theme of factors affecting successful communication, the theme of factor affecting continuity communication. All members of the care team should be involved in parent communication. But according to our results, nurses are more responsible for communicating with parents. Finding from the study indicates the key role of nurses in communicating in the NICU. It is necessary to teach physicians and nurses, especially physicians, how to communicate with parents. Also, health system authorities have an important role in continuing education on communication methods in the NIC
Upregulation of the long noncoding RNA GJA9‐MYCBP and PVT1 is a potential diagnostic biomarker for acute lymphoblastic leukemia
Background: Acute lymphoblastic leukemia (ALL) is the most common type of blood cancer in children. Aberrant expression of long noncoding RNAs (lncRNAs) may set stages for ALL development. LncRNAs are emerging as a novel diagnostic and prognostic biomarker for ALL. Herein, we aimed to evaluate the expression of lncRNA GJA9-MYCBP and PVT1 in blood samples of ALL and healthy individuals. Methods: As a case–control study, 40 pairs of ALL and healthy individual samples were used. The expression of MYC and each candidate lncRNA was measured using quantitative real-time PCR. Any possible association between the expression of putative noncoding RNAs and clinicopathological characteristics was also evaluated. Results: LncRNA GJA9-MYCBP and PVT1 were significantly upregulated in ALL samples compared with healthy ones. Similarly, mRNA levels of MYC were increased in ALL samples than control ones. Receiver operating characteristic curve analysis indicated a satisfactory diagnostic efficacy (p-value <.0001), suggesting that lncRNA GJA9-MYCBP and PVT1 may serve as a diagnostic biomarker for ALL. Linear regression analysis unveiled positive correlations between the expression level of MYC and lncRNA GJA9-MYCBP and PVT1 in ALL patients (p-values <.01). Conclusions: In this study, we provided approval for the clinical diagnostic significance of lncRNA GJA9-MYCBP and PVT1that their upregulations may be a diagnostic biomarker for ALL
Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021
Background: Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. Methods: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. Findings: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. Interpretation: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. Funding: Bill & Melinda Gates Foundation
Risk Factors of Pulmonary Complications in Patients with COVID-19: A Case-Control Study
Background: Pneumothorax (PTX), pneumomediastinum (PM), and subcutaneous emphysema (SE) are complications associated with COVID-19. It is crucial to study these risk factors, complications, and their prognosis for early diagnosis amidst the rising number of cases today. Methods: We conducted a case-control study involving 81 pairs of patients diagnosed with SARS-CoV-2 pneumonia complicated by Pneumothorax and pneumomediastinum, comparing them with patients who did not have these complications to assess the risk factors for and prognosis of pulmonary complications in COVID-19. Results: The demographic data and medical history of comorbid diseases did not show an association with PTX, PM, and SE in COVID-19 pneumonia (all P-values > 0.05). However, laboratory data such as white blood cell count, lymphocyte count, C-reactive protein, lactate dehydrogenase, troponin, and D-dimer levels were significantly higher in the group with complications (P < 0.05). Additionally, the length of hospital stay was significantly longer in the group with complications, and intubation further extended this duration. The mortality rate was significantly higher in the case group (70% vs. 14%, P < 0.0001), with a significant odds ratio in comparison to patients without complications in the regression model (B = 2.61, Exp(B) = 13.65 with a 95% CI of 6.28 - 29.69). Conclusions: Pulmonary complications worsen the prognosis of COVID-19. The pathophysiology of COVID-19 pneumonia can lead to mechanical barotrauma, regardless of intubation status. Ventilator settings should be adjusted below the confidence level. Acute phase reactants and certain inflammatory markers, except for the erythrocyte sedimentation rate (ESR), are elevated in patients with complications, though they do not significantly predict outcome
Unveiling the impact of siren noise exposure on cognitive function and mental health among firefighters
Firefighters reside in inherently noisy environments with sirens and emergency alarms. This noise can negatively affect the performance of firefighters and further pose a safety risk. This study investigates the relationship between siren noise exposure and its mental health disorders. In doing so, the study focuses on cognitive function among firefighters, using a Bayesian network model for the first time. This case-control study involved 92 firefighters and was conducted in 2023. Participants were categorized into case and control groups based on their exposure levels to siren noise. Noise exposures were initially measured according to ISO 9612 standards. The questionnaires covered demographic information, scales of their depression, anxiety, and stress, the Buss-Perry aggression questionnaire, and the cognitive failure questionnaire. GeNIe academic software version 2.3 was employed for Bayesian network analysis. The study results indicated a strong association that heightened siren noise exposure with a 100% probability increases depression (10%), stress (14%), anxiety (13%), and aggression (16%). In addition, each variable–noise exposure, depression, stress, anxiety, and aggression was linked to cognitive failure by 8%, 28%, 8%, and 13%, respectively. The combination of variables including noise exposure, depression, anxiety, and other mental health disorders had a 57% increase in cognitive failure. The most influence values were observed between depression and cognitive failures (0.564). The results of this study demonstrated the effect of siren noise exposure and its mental health disorders on cognitive function among firefighters. The results further highlight proper implementation of measures to mitigate these effects, and further required investigation on their effectiveness
Epidemiology and geographical patterns of common childhood cancers in Iran: Evidence from the National Cancer Registry
Introduction: Cancer is projected to become the primary cause of death in the 21st century. Although childhood cancer is relatively rare, it remains a significant contributor to mortality among children. This study examines the geographical distribution of childhood cancer incidence in Iranian provinces using data from the National Cancer Registry between 2014 and 2018. Materials and methods: This registry-based study analyzed data from 14,711 children under 20 diagnosed with common childhood cancers, sourced from the Iranian National Population-based Cancer Registry for the period 2014–2018. The age-standardized incidence rates (ASR) were calculated using direct standardization methods and reported per 1 million person-years. Spatial autocorrelation measures, including global and local indices such as Moran's I and Getis-Ord's G, were employed to identify high-risk and low-risk areas, assess overall spatial dependence, and pinpoint specific clusters and hotspots of incidence rates. Results: ASR for childhood cancer in Iran was 119.56 per 1 million individuals aged 0–19 years. Boys had a higher ASR (129.98) than girls (107.68). Childhood cancer cases increased from 2765 in 2014 to 3354 in 2018, with leukemia as the most common type, followed by brain and nervous system, lymphoma, bone, and connective and soft tissue cancers. Spatial analysis identified high-risk clusters in central Iran (Isfahan, Yazd, Tehran) and low-risk clusters in the northeast (Kermanshah, West and East Azerbaijan, Kurdistan). Conclusion: This study highlights high childhood cancer incidence in Iran, particularly among boys and in central regions, with elevated leukemia rates. These findings call for targeted prevention strategies and further research to address geographic and gender disparities and to improve care programs
Relationships between couple collaboration, well-being, and psychological health of infertile couples undergoing assisted reproductive treatment
Background: Social problems related to infertility are associated with a significant psychological burden for the involved couple. Previous studies have shown the positive effects of couple interactions on the psychological health of these couples; however, the specific conditions of participating in assisted reproductive treatments (ART) might influence the effect of couple collaboration. Therefore, the present study aimed to evaluate the relationship between couple collaboration, well-being during infertility, and the psychological indicators of infertile couples undergoing fertility treatment. Methods: This cross-sectional study was conducted on 200 ART volunteer couples. Couple collaboration and well-being during infertility were evaluated using a validated researcher-made questionnaire, and the level of depression, anxiety, and stress was evaluated using the DASS-21 questionnaire in both couples. Statistical analysis was performed using the plug-in application PROCESS macro for SPSS and AMOS software. Results: The results showed that couple collaboration was correlated with the level of depression, anxiety, and stress. Moreover, depression, anxiety, and stress levels were correlated with well-being during infertility. The direct and indirect effect of couple collaboration on the depression level was significant; however, the direct effect of couple collaboration on the level of anxiety and stress was not significant, and the effect of couple collaboration on these indicators was mediated by well-being during infertility. The fit index of the equation modelling showed a good fit of the relationship path between the variables of couple collaboration, well-being during infertility, and psychological indicators (CMIN = 4.196, p = 0.260). Conclusion: The results of this study show that the specific conditions of participating in ART may affect the direct effects of couple interaction on an infertile couple’s levels of anxiety and stress. These results suggest that in order to develop mental health programs for infertile couples, strategies based on couple collaboration that are associated with higher well-being during infertility should be developed and presented
Clinical and Laboratory Positive Predictive Value of Symptom Management of STI in Iran: A Community-Based Survey
Background: The correct diagnosis of sexually transmitted infections (STIs) is the first step in the monitoring and management of these diseases. Objectives: This study was conducted to investigate the clinical and laboratory positive predictive value (PPV) of STI symptom management in Iran. Methods: This cross-sectional study was conducted on 5986 individuals (aged 18 to 50 years) from the general population of Marovdasht (Iran) in several stages: (1) self-reported symptoms of sexually transmitted diseases, (2) evaluation by a doctor, and (3) laboratory examination. Results: Among the population sample, 686 (17.68%) individuals reported at least one of the predefined symptoms. The clinical-based PPV of syndromes in men and women were 67.74 (62.34-73.14) and 85.36 (82.76-87.96), respectively. In men and women, the highest PPV was observed for abnormal discharge from the anus 32.35 (25.35-39.35) and abnormal secretions from the cervix 59.39 (56.39-62.39), respectively. The laboratory-based PPV for men and women was 0 and 5.04 (3.04-7.4), respectively. Conclusions: The clinical and laboratory-based PPV of STI symptoms in the general population is extremely low. Accordingly, a syndromic-based screening or monitoring approach for STIs is not a reliable tool for screening or monitoring in the Iranian general population. We suggest focusing on special (core) groups for monitoring STIs using laboratory-based methods
Development of small-diameter vascular grafts using PCL/PLA/gelatin/PVA/hyaluronic acid nanofibers containing VEGF/enoxaparin
The extending demands for narrow-diameter vascular grafts to restore damaged arteries have captivated researcher's attention. The absence of appropriate vascular substitutes is due to the poor patency rate of small-caliber synthetic grafts caused by thrombosis and vessel hemodynamic mismatch that induce intimal hyperplasia. We developed small-diameter vascular grafts in two layers through electrospinning. The inner layer was fabricated by gelatin/polyvinyl alcohol (PVA)/hyaluronic acid/enoxaparin and vascular endothelial growth factor (VEGFs) and the outer layer was manufactured via polycaprolactone (PCL)/polylactic acid (PLA)/hyaluronic acid. The products were characterized by atomic force microscope (AFM), scanning electron microscope (SEM), water contact angle (WCA), attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), swelling test, mechanical test, and release rate. Blood compatibility tests including blood clotting time, hemolysis, and human platelet sedimentation were measured. The interactions of human umbilical vein endothelial cells (HUVECs) and human endometrial stem cells (hEnSCs) with nanofibrous vascular grafts were detected by SEM, viability assay, and DAPI staining. The results exhibited the produced small-diameter vascular grafts had proper antithrombotic properties due to two factors of VEGF and enoxaparin. After two months of the subcutaneous implantation of the scaffolds on the back of rats, the tubular vascular grafts lacked any macroscopic and histological signs of acute inflammation and had appropriate degradation rates. Furthermore, lumen patency was observed after 2 months. Consequently, VEGF and enoxaparin improves cell and blood compatibility in the small-diameter vascular grafts