Familial colorectal cancertype X in central Iran: A new clinicopathologic description

Background: Familial colorectal cancer type X (FCCX) is a subtype of mismatchrepair (MMR)-proficient colorectal cancerin whichthe patients are clinicallyat risk for Lynch syndrome (LS), a common hereditary cancer predisposing syndrome.In this study, we describeda new clinicopathological feature of the condition in central Iran. Subjects and Methods: We designed a descriptive, retrospective study to screenat-riskcolorectal cancer (CRC) patients,usingAmsterdam II criteria and Molecular analysis in Isfahan (central Iran) throughout 2000-2013 period. Results: 219 early-onset (≤ 50 years) CRC patients of 1659 were selected for the evaluation. Amsterdam II criteria were positive in 45 families; of whom 31 were finally analyzed by molecular testing. MMR deficiency was detected in 7/31 probands (22.6%) as affected to LS, so 24 families (77.4%) were identified as FCCX. The mean age of the probands at diagnosis among FCCX families was 45.3 years (range 24-69) versus 38.0 years (range 31-50) in LS families.The frequency of CRC among FCCX and LS families was calculated 27.9% and 67.5%, respectively. Also, the most frequent extracolonic cancer among both FCCX and LS families was stomach by 25.5% and 30.8%, respectively. Tumor site was proximal to the splenic flexure in 20.8% and 57.1% of index CRC patients in FCCX and LS families, respectively. Conclusion: Given the relative high frequency of FCCXand its different phenotype among Iranian populations, we need to set up more advanced molecular studies for exploration of unknown molecular pathways leading to tumorigenesis in this class of CRC patients

Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran

Background. Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis in patients with congenital hypothyroidism (CH). In this study, the prevalence of TPO gene mutations in patients with thyroid dyshormonogenesis in Isfahan was investigated. Methods. In this cross-sectional study, genomic DNA of 41 patients with permanent CH due to thyroid dyshormonogenesis was extracted using the salting out method. The 17 exonic regions of the TPO gene were amplified. SSCP technique was performed for scanning of the exonic regions of the TPO gene, except exon 8. DNA sequencing was performed for those with different migration patterns in SSCP by chain termination method. Exon 8 was sequenced directly in all patients. In 4 patients, all fragments were also sequenced. Results. One missense mutation c.2669G>A (NM_000547.5) at exon 15 (14th coding exon) in one patient in homozygous form and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11, and 15 of TPO gene. Conclusion. The TPO gene mutations among CH patients with dyshormonogenesis in Isfahan were less frequent in comparison with other similar studies. It may be due to the presence of other unknown gene mutations which could not be detected by SSCP and sequencing methods

Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library

53 p.-7 fig.-1 tab.-1 schem.-1 graph. abst.Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine.We are also grateful to the Iran National Science Foundation (INSF, grant number 98026465) for financial support of this project and Shahid Beheshti University Research Council for providing facilities of to conduct this study. This work was supported by CSIC PIE 201920E111 (MAO).Peer reviewe

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

An overview of production of hydrogen and carbon nanomaterials via thermocatalytic decomposition of methane

The ever-increasing global demand for energy and functional materials, coupled with the growing threat of global warming, necessitates the development of new technologies for the large-scale production of green energy carriers and materials. ThermoCatalytic Decomposition (TCD) of methane is an environmentally and economically favorable approach to produce hydrogen and valuable carbon nanomaterials simultaneously, without direct greenhouse gas emissions. The chemical kinetics of TCD can be captured by considering the maximum reaction rate and deactivation factor. However, additional studies are required to obtain a deeper understanding of the deactivation mechanisms that limit catalyst performance over time. Moreover, the development of sustainable catalysts that align with the desired application of the carbon product is essential. In order to advance the development of TCD reactors and processes, further research is urgently needed. The challenges that need to be addressed include the impact of catalyst particle growth on the reaction and reactor performance. Fluidized bed reactors (FBRs) are considered the most viable units for TCD, but require comprehensive experimental and modeling studies to assess and overcome the design and operational challenges. Numerical modeling is crucial for designing, optimizing, and evaluating TCD reactors and processes. Coupled Computational Fluid Dynamics–Discrete Element Method models with intraparticle models such as MultiGrain Model, can provide a more representation view of the complex multiscale phenomena of TCD in FBRs, enabling researchers and engineers to explore effectively different reactor concepts and designs.</p

Nanocomposites in food packaging applications and their risk assessment for health

Nanotechnology has shown many advantages in different fields. As the uses of nanotechnology have progressed, it has been found to be a promising technology for the food packaging industry in the global market. It has proven capabilities that are valuable in packaging foods, including improved barriers; mechanical, thermal, and biodegradable properties; and applications in active and intelligent food packaging. Examples of the latter are anti-microbial agents and nanosensors, respectively. However, the use of nanocomposites in food packaging might be challenging due to the reduced particle size of nanomaterials and the fact that the chemical and physical characteristics of such tiny materials may be quite different from those of their macro-scale counterparts. In order to discuss the potential risks of nanoparticles for consumers, in addition to the quantification of data, a thorough investigation of their characteristics is required. Migration studies must be conducted to determine the amounts of nanomaterials released into the food matrices. In this article, different applications of nanocomposites in food packaging, migration issues, analyzing techniques, and the main concerns about their usage are discussed briefl

Comparison of the effect of heparin, reteplase, and taurolock in the prevention of thrombosis in hemodialysis catheters

Abstract Background and Aim One of the complications of using catheters is the occurrence of thrombosis, which can be dangerous for patients. The main objective of this study is to compare the effect of heparin, reteplase, and taurolock in the prevention of thrombosis in hemodialysis catheters. Methods The present study is a clinical trial, in which the effect of three drugs, heparin, reteplase, and taurolock, in the prevention of thrombosis in hemodialysis catheters, has been investigated. The research units were studied in two intervention and control groups. The stratified random allocation method was used to assign patients to five groups (control, Heparin 50, Heparin 1000, reteplase, and taurolock), with strata based on the patient's age (20–70 years), gender, and duration of dialysis. Within each stratum, patients were also assigned to groups using the randomized block permutation method and a random number table tool. To prevent bias, this study is triple‐blinded. This means that the patient, the thrombosis assessor, and the statistical analyst are unaware of the type of intervention received by the patient. Results Gender (p < 0.999), age distribution (p = 0.774), and duration of dialysis (p = 0.875) showed no statistically significant relationship with thrombosis. However, significant differences were observed among the five groups regarding thrombosis incidence. The relative risk of thrombosis in the Heparin 50, Heparin 1000, reteplase, and taurolock groups compared to the control group was 92.5%, 92.2%, 98.2%, and 89% lower, respectively. Conclusion Our study underscores the efficacy of heparin, reteplase, and taurolock in preventing thrombosis in hemodialysis catheters. While all three drugs demonstrated efficacy, the Heparin 50 group exhibited the highest relative risk reduction. These findings suggest that heparin, particularly at a low dose, should be considered a standard prophylactic treatment in hemodialysis patients