Notes

Ellagic Chemical p from Terminalia arjuna Fruit Shields Against Chromium and also Cobalt Poisoning in Principal Man Lymphocytes.
Current anaerobic digestion (AD) design methods rely on crude empirical models or sophisticated anaerobic digestion models (like ADM1) requiring a large number of parameters which are difficult to obtain experimentally. A simplified model for simulating AD was developed in this work. The model requires knowledge of CH4/CO2 ratio in biogas or indigestible fraction in substrate and batch biomethane potential (BMP) data for estimating three kinetic parameters (maximum specific growth rate, half velocity constant and cell death rate). Reported lab scale BMP data of sugarcane bagasse and spent wash were used to first estimate the kinetics and then to simulate corresponding largescale AD. Simulated results of specific methane yield and digester performance were consistent with available largescale AD data. The potential of the model to simulate single and multi-stage AD were illustrated. The presented approach and model will be useful for effectively valorising a variety of complex biomass substrates to biogas.Cigarette smoking is a risk factor for the development of head and neck squamous cell carcinoma (HNSCC), partially due to tobacco-induced large-scale chromosomal copy-number alterations (CNAs). Identifying CNAs caused by smoking is essential in determining how gene expression from such regions impact tumor progression and patient outcome. We utilized The Cancer Genome Atlas (TCGA) whole genome sequencing data for HNSCC to directly identify amplified or deleted genes correlating with smoking pack-year based on linear modeling. Internal cross-validation identified 35 CNAs that significantly correlated with patient smoking, independent of human papillomavirus (HPV) status. The most abundant CNAs were chromosome 11q13.3-q14.4 amplification and 9p23.1/9p24.1 deletion. Evaluation of patient amplicons reveals four different patterns of 11q13 gene amplification in HNSCC resulting from breakage-fusion-bridge (BFB) events. . Predictive modeling identified 16 genes from these regions that denote poorer overall and disease-free survival with increased pack-year use, constituting a smoking-associated expression signature (SAES). Patients with altered expression of signature genes have increased risk of death and enhanced cervical lymph node involvement. The identified SAES can be utilized as a novel predictor of increased disease aggressiveness and poor outcome in smoking-associated HNSCC.The ALK inhibitors are promising therapeutic agents against lung cancer harboring ALK fusion genes and are currently under development up to the third generation. However, its therapeutic effects are reported to be affected by differences in ALK variants and co-occurrent mutations. Materials and Methods; We experienced an autopsy case of an ALK-positive lung cancer patient who showed primary resistance to three generations of ALK inhibitors. The poor survival time of the case was 14 months. To reveal the mechanism of primary resistance to three generations of ALK inhibitors, we performed next generation sequencing for 12 specimes obtained from an autopsy with covering whole exons of 53 significantly mutated, lung cancer-associated genes and amplicon-based target RNA sequenceing for the ALK fusion gene. The NGS analysis revealed a rare variant.3 of ALK fusion, in which 30 bp of base was inserted at the end of ALK intron.19 and was associated with EML exon.6 [E6_ins30A20] and a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. Structural analysis of the fusion protein ALK [E6_ins30A20] showed no interferance with the binding of ALK inhibitors to the kinase domain. The NGS analysis of primary and metastatic lesions obtained from an autopsy revealed a co-occurrent oncogenic PIK3CA E542K mutation in all specimens. The constitutive activation of PI3K-Akt signal by PIK3CA E542K mutation occurred downstream of ALK signaling pathway, could lead to primary resistance to ALK inhibitors in all generations.
Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).

Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).

Patients received monotherapy based on 5-FU (n=1068), a cytotoxic doublet (n=395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n=727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0-1 (OR 2.57; 95% CI [1.16, 5.73]; p=0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p=0.02), alkaline phosphatase>300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p<0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p=0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80-0.96]; p=0.004).

ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.
ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.
Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations existbetween its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them.

Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P<0.0001) whilst increasing diarrhoea severity (P=0.0007) and treatment-related mortality (P=0.0045). Importantly, thte the acute and chronic complications caused by disruption of the gastrointestinal microenvironment. learn more Translation of this new knowledge should focus on stabilising and strengthening the gut microbiome before chemotherapy and developing new microbial approaches to accelerate recovery of the mucosa. By controlling the depth and duration of mucosal injury, secondary consequences of gastrointestinal toxicity may be avoided.
The Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire is a validated patient-reported outcome measure (PROM) capturing the impacts of vaginal symptoms in postmenopausal women.

We aimed to psychometrically validate the German version of the DIVA questionnaire.

Data was collected online and by paper-pencil. We ran confirmatory factor analyses to confirm the a priori four-factor structure of the DIVA. Internal consistency was calculated using Cronbach's alpha. Correlations with other outcome measures such as the Patient Health Questionnaire-4 (PHQ-4), the SF-12 SOEP (socio-economic panel) version and self-created anchor questions were calculated regarding convergent validity. Known groups regarding age, home country and disease severity were analyzed. Test-retest reliability after 1 week and responsiveness after 4 weeks were only descriptively assessed due to low sample sizes.

The DIVA questionnaire, the Menopause Rating Scale (MRS II), the PHQ-4 and the SF-12 SOEP version were the main outcome meaidation of the German Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire in Peri- and Postmenopausal Women. Sex Med 2021;9100382.
This study supports the excellent structural validity, internal consistency and construct validity of the German version of the DIVA questionnaire. It can be recommended for the assessment of the impacts of vaginal symptoms in postmenopausal women in future clinical GSM trials. Gabes M, Stute P, Apfelbacher C. Validation of the German Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire in Peri- and Postmenopausal Women. Sex Med 2021;9100382.We investigated connections between antimicrobial use (AMU), biosecurity, and the numbers of pigs and staff in ten Finnish farrow-to-finish herds. Data on AMU in each herd were collected for 12 months. AMU was quantified as treatment incidences per 1000 days at risk (TI) using the consensus defined daily dose calculation. Biosecurity was scored using the Biocheck.UGent™ system. We also examined antimicrobial resistance patterns of indicator E. coli isolated from faeces of selected pigs. In each herd, two groups of five pigs were formed 1) antimicrobial treatment group (ANT at least one pig in the litter was identified as sick and treated with antimicrobials) and 2) non-antimicrobial treatment group (NON the litter was not medicated). Faecal samples were taken from these pigs at 5 and 22 weeks of age, cultured, and indicator E. coli isolates were tested for antimicrobial susceptibilities. The AMU varied considerably between the herds. Altogether, most of the antimicrobial treatment courses were assigned to weaned piglets. When AMU was quantified as TIs, suckling piglets had the highest TI (mean 46.6), which was significantly higher (P 0.05). We found few connections enhanced external biosecurity levels found in the large herds co-occurred with lower use of antimicrobials and herds with low biosecurity scores - especially in the internal subcategories - appeared to have higher proportions of resistant isolates. Conclusively, we suggest that enhancing internal biosecurity might contribute to a reduction in the spreading of antimicrobial resistance in pig herds.The present study provides a noninvasive method to estimate the body volume of sharks (Elasmobranchii, Selachii) using a computational geometric model. This method allows the volume of sharks to be estimated from lateral and ventral photographs assuming an elliptical body cross-sectional geometry. A comparison of the estimated and actual body volumes of several shark species showed that the estimation error was less then 0.5%. The accuracy of the model decreased if photographs that were inclined to the orthogonal plane were used, although this error was on average less then 2.3% if the inclination angle was 10° or less. Applying this model to captive whale sharks (Rhincodon typus) that were 8.0 and 8.8 m in total length revealed that their body volumes were 3.5 and 4.5 m3, respectively. These estimates allowed for the quantitative evaluation of our hypothesis, that the whale shark uses suctioned air for buoyancy control during vertical feeding-a behavior unique to this species among elasmobranchs. The volume estimates of the captive whale sharks, together with the density estimates from their liver proportions, revealed that the air occupying a part of oro-pharyngeal and branchial cavities can help the whale sharks to keep their body floating.
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