Statistical Optimization of Xanthan Gum Production and Influence of Airflow Rates in Lab-scale Fermentor

The present study was undertaken to investigate and optimize the possibility of xanthan gum production by Xanthomonas campestris PTCC1473 in 500ml shake flasks on the second grade date palm. Using an experimental response surface methodology (RSM) coupled with a central composite design (CCD), three major independent variables (nitrogen source, phosphor source and agitation rate) were evaluated for their individual and interactive effects on biomass and xanthan gum production in submerged fermentation. The optimum conditions selected for gum production were 3.15 g.l-1 for nitrogen source, 5.03 g.l-1 for phosphor source, and 394.8 rpm for agitation rate. Reconfirmation test was conducted, and the experimental value obtained for xanthan production under optimum conditions was about 6.72±0.26 g.l-1, which was close to 6.51 g.l-1 as predicted by the model. A higher yield of biomass production was obtained at 13.74 g.l-1 for nitrogen source, 4.66 g.l-1 for phosphor source, and 387.42 rpm for agitation rate. In the next stage, scale-up from the shake flasks to the 1-L batch fermentors was carried. By using the optimum conditions for xanthan gum, the biomass and xanthan gum concentrations after 72h in three levels of air flow rate (0.5, 1 and 1.5 vvm) were obtained as 3.98, 5.31 and 6.04 g.l-1,and 11.32, 15.16 and 16.84 g.l-1, respectively. Overall, the second grade date palm seemed to exhibit promising properties that can open new pathways for the production of efficient and cost-effective xanthan gum

PI3K/Akt inhibition and down-regulation of BCRP re-sensitize MCF7 breast cancer cell line to mitoxantrone chemotherapy

Objective(s): Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy. Materials and Methods: Anticancer effects of MTX, siRNA, and LY alone and in combination were evaluated in MCF7 cells using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: MTT and apoptosis assays showed that both MTX and LY inhibited cell proliferation and induced apoptosis in MCF7 cells. Results indicated that inhibition of BCRP by siRNA or PI3K/Akt signaling pathway by LY significantly increased sensitivity of MCF7 cells to antiproliferation and apoptosis induction of MTX. Furthermore, MTX showed G2/M arrest, whereas LY induced G0/G1 arrest in cell cycle distribution of MCF7 cells. Combination of siRNA or LY with MTX chemotherapy significantly increased accumulation of MCF7 cells in the G2/M phase of cell cycle. Conclusion: Combination of MTX chemotherapy with BCRP siRNA and PI3K/Akt inhibition can overcome MDR in breast cancer cells. This study furthermore suggests that novel therapeutic approaches are needed to enhance anticancer effects of available drugs in breast cancer. © 2015, Iranian Journal of Basic Medical Sciences. All rights reserved

Association of the insulinemic potential of diet and lifestyle with risk of diabetes incident in Tehranian adults: a population based cohort study

Background: We aimed to assess the associations between insulinemic potential of diet and lifestyle and the risk of diabetes incident, using four empirical indices including the empirical dietary index for hyperinsulinemia (EDIH), the empirical dietary index for insulin resistance (EDIR), empirical lifestyle index for hyperinsulinemia (ELIH), and empirical lifestyle index for insulin resistance (ELIR). Methods: A total of 3734 individuals, aged � 20 years old, who were free of diabetes at baseline (2008�2011), were followed for 6.2 years (2015�2018) to ascertain incident diabetes. The food frequency questionnaire was used to collect dietary intakes at baseline. Odds ratio (OR) of diabetes were calculated across quartiles of EDIH, EDIR, ELIH, and ELIR using logistic regression, which controlled for confounding factors. Results: The mean ± SD age and BMI of individuals (45.1 male) were 40.9 ± 12.0 years and 27.1 ± 4.1 kg/m2, respectively. At the end of follow-up, 253 (6.8 ) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest quartile of EDIR (1.58;95 CI:1.03�2.44, P for trend = 0.025), ELIH (1.89;95 CI:1.20�2.97, P for trend = 0.004), and ELIR (1.74; 95 CI:1.11�2.72, P for trend = 0.031) had increased the risk of diabetes. However, no significant associations were found between the score of EDIH and diabetes incident. Conclusions: Higher adherence to EDIR, ELIH, and ELIR scores were associated with increased risk of diabetes, while no significant association was found between EDIH score and diabetes incident. © 2021, The Author(s)

Dietary and lifestyle inflammatory scores and risk of incident diabetes: a prospective cohort among participants of Tehran lipid and glucose study

Background: Inflammation is a precursor of chronic disease, which is affected by lifestyle and dietary habits. Recently empirical dietary inflammatory patterns (EDIP), dietary inflammation scores (DIS), and lifestyle inflammation scores (LIS) were developed to indicate lifestyle and dietary contributions in systemic inflammation. The current study aimed to investigate the associations between these indices and the incidence of diabetes among Tehranian adults. Methods: A total of 4624 individuals, aged 20�75 years, who were free of diabetes at baseline (2008�2011), were followed for 5.71 years (2014�2017) to ascertain incident diabetes. Dietary intakes were collected at baseline using the food frequency questionnaire. The hazard ratio (HR) of diabetes was calculated by Cox proportional hazards regression across quartiles of EDIP, DIS, and LIS, adjusted for potential confounders. Results: The mean ± SD for the age and BMI of the study population (45.1 male) were 40.8 ± 12.7 years and 27.1 ± 4.1 Kg.m2, respectively. At the end of the follow-up, 329 (7.1) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest compared to the lowest quartile of EDIP (HR = 0.83; 95CI:0.59�1.15, p for trend = 0.286), and LIS (HR = 2.41; 95CI:1.61�3.60, P for trend < 0.001) had increased risk of diabetes. However, no significant associations were found between the score of DIS and diabetes incidents (HR = 0.83; 95CI:0.59�1.15, p for trend = 0.286). Conclusion: Greater adherence to EDIP and LIS scores was associated with a higher risk of diabetes, while no significant association was found between the DIS score and diabetes incident. © 2021, The Author(s)

Multiple locus VNTR analysis highlights that geographical clustering and distribution of Dichelobacter nodosus, the causal agent of footrot in sheep, correlates with inter-country movements

Dichelobacter nodosus is a Gram-negative, anaerobic bacterium and the causal agent of footrot in sheep. Multiple locus variable number tandem repeat (VNTR) analysis (MLVA) is a portable technique that involves the identification and enumeration of polymorphic tandem repeats across the genome. The aims of this study were to develop an MLVA scheme for D. nodosus suitable for use as a molecular typing tool, and to apply it to a global collection of isolates. Seventy-seven isolates selected from regions with a long history of footrot (GB, Australia) and regions where footrot has recently been reported (India, Scandinavia), were characterised. From an initial 61 potential VNTR regions, four loci were identified as usable and in combination had the attributes required of a typing method for use in bacterial epidemiology: high discriminatory power (D > 0.95), typeability and reproducibility. Results from the analysis indicate that D. nodosus appears to have evolved via recombinational exchanges and clonal diversification. This has resulted in some clonal complexes that contain isolates from multiple countries and continents; and others that contain isolates from a single geographic location (country or region). The distribution of alleles between countries matches historical accounts of sheep movements, suggesting that the MLVA technique is sufficiently specific and sensitive for an epidemiological investigation of the global distribution of D. nodosus

The effect on melanoma risk of genes previously associated with telomere length.

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/dju26

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p