Patient-related post-ERCP pancreatitis (PEP) risk factors between two groups of patients: Prophylactic pancreatic stent and rectal indomethacin

Background: Pancreatitis is one of the most crucial complications following endoscopic retrograde cholangiopancreatography (ERCP). The purpose of the current study was to investigate patient-related post-ERCP pancreatitis (PEP) risk factors in two groups of patients: prophylactic pancreatic stent and rectal indomethacin. Methods: Two different prophylactic modalities were planned and complications were assessed based on the defined inclusion criteria. In this study, the patients were evaluated for the procedure and patient-related risk factors in post-ERCP pancreatitis in the recipient groups of the prophylactic pancreatic stent and rectal indomethacin. Results: Pancreatitis was confirmed in 27 of all 170 selected patients after ERCP. By univariate analysis, two variables were significant with the development of PEP. Regarding the patient-related risk factors, unique subjects with common bile duct (CBD) dilated 10mm were more exposed to an increased chance of PEP (P=0. 015); meanwhile, other factors did not correlate with the increased possibility of PEP in both groups. The only procedure-related risk factor for PEP was the deep cannulation of the pancreatic duct in both groups during the procedure with an incremental significant incidence of pancreatitis (P=0.005). Comparison of prophylactic pancreatic stent and rectal indomethacin showed no effects in term of post ERCP pancreatitis reduction. Additionally, there was no significant difference between these two strategies in the rate of PEP. Conclusion: Prophylactic pancreatic duct stents and administration of rectal indomethacin cannot have particular approaches for reducing the possible occurrence of PEP. The increase in time of deep cannulation and the presence of CBD dilation <10mm could be considered as important risk factors. &#160

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Quantitative structure activity relationship study of p38α MAP kinase inhibitors

The quantitative structure activity relationship (QSAR) of the novel pyrazole derivatives as inhibitors of p38α mitogen activated protein (MAP) kinase was studied. The suitable set of the molecular descriptors was calculated and the important descriptors using the variable selections of the stepwise (SW) and the genetic algorithm (GA) were selected. The predictive quality of the QSAR models was tested for an external set of nine compounds, randomly chosen out of 44 compounds. A comparison between the attained results indicated the superiority of the genetic algorithm over the stepwise method in the feature selection. The genetic algorithm-multiple linear regression (GA-MLR) model with six selected descriptors was obtained. The accuracy of the proposed model is illustrated using the following evaluation techniques: cross-validation, validation through an external test set, applicability domain, and Y-randomization. The analyses may be used to design more potent pyrazole derivatives and predict their activity prior to synthesis

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging

Abstract Background Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99mTc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. Methods The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99mTc using tricine/EDDA co-ligand. The cellular specific binding of 99mTc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. Results Radiochemical purity for 99mTc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (Kd) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99mTc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99mTc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. Conclusions The 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells

Evaluation of anti-tumor potential of lactobacillus acidophilus atcc4356 culture supernatants in mcf-7 breast cancer

Background: The anti-cancer activity of some lactic acid bacterial strains is well documented in several kinds of literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. Materials and Methods: The anti-cancer effects of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. Results: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR (~ 0.009 fold) and Bcl-2 (~ 0.5 fold) and upregulation of p53 (~ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated a reduction in tumor weight and volume by both 24h and 48h supernatants (2 mg/kg) after 15 days. According to the99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (2mg/kg) led to a significant decrease in tumor uptake compared with the control group. Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer

Application of Artificial Neural Networks and Adaptive Neuro-Fuzzy Inference Systems to Predict Activated Carbon Properties for Methane Storage

BET surface area and micropore volume are important factors for improving methane storage in activated carbons (ACs). Specification and optimization of carbon structures are vastly examined by different researchers. However, because of complex relations between independent and dependent variables, the proposed statistical and mathematical models are not satisfactory. In this paper, the specifications of some ACs synthesized by chemical activation methods are predicted. The effects of parameters such as agent type, activation time, activation temperature, impregnation ratio and heating rate on the BET surface areas and micropore volumes of ACs are also analyzed. Two models of artificial neural networks and adaptive neuro-fuzzy interference systems are used. Later on, a number of data on other ACs reported by several researchers are used for the model validation. The obtained results from these two models are found to be satisfactory. The coefficients of determination for these models were 0.982 and 0.984, respectively. Through this modelling of AC production process, which was the main purpose of this study, the specifications of ACs may be obtained without spending extra time and expenses