Factors affecting the intestinal microbiome homeostasis

Human gut hosts a large microbial community that plays a critical role in immune maturation, energy biogenesis and synthesis of vitamins besides numerous other functions. The advent of high throughput sequencing has highlighted the link between alterations in microbiome composition and development of several complex disorders such as inflammatory bowel diseases (IBD), diabetes and several cancers. Although several reports have linked dysbiosis of gut bacteria with the etiology of diseases, their actual roles and association with risk genes are still debated. Hence, longitudinal analysis of the microbiome composition under disease mimicking and genetically susceptible conditions could help decipher the underlying mechanisms. This would also help in understanding the functional activities of the microbial component that ultimately affects host physiology and inflammatory response. The study design included: 1) analysis of human inflamed and non-inflamed appendicitis samples for identifying variations in the intestinal microbiota compositions; 2) Microbiota variations during antibiotic mediated dysbiotic event in control and Atg16l1 intestinal knock down (Atg16l1ΔIEC) mice models; 3) Microbial and functional variations during pregnancy in control and Atg16l1ΔIEC mice models. The work highlights gene-microbiome crosstalk with emphasis on Atg16l1 and its role in maintaining correct and healthy microbiota that functionally regulate metabolic pathways and inflammatory responses in the body

Comparative study on maternal morbidity in elective and emergency caeserean section at tertiary hospital

Background: The incidence of caesarean sections has significantly increased over the previous thirty years and nearly doubled in the current decade, because of more liberalisation of indications of caesarean sections. India’s caesarean section rates have surpassed the WHO cutoff point of 15%, raising serious public health issues. The prevalence of the C-section in India was 8.5% in NFHS-3 while data in NFHS-4 show that it has increased to 17.2%. Thus, almost 9% has increased over 10 years. Objective was to compare the maternal morbidity in elective and emergency caesarean section. Methods: Institution based comparative study was conducted among 108 females undergoing lower segment caesarean section at JNUIMSRC, Jaipur. After taking written informed consent patients were enrolled for the study. Once the data was collected it was analysed as per appropriate statistical analysis. Results: Incidence of emergency LSCS was 23.6% and of elective LSCS was 76.4%. the most common maternal indication was previous LSCS (38.1%) and most common fetal indication was fetal distress (13.3%) followed by malpresentation (11.4%). Incidence of intraoperative complications was 29% with most common complications being atonic PPH (12.4%) followed by traumatic PPH (5.9%), bladder and bowel injury (0.7%). Incidence of post operative complications was 51.9% with most common being anaemia (20.8%), PPH (10%), puerperal sepsis (8%). Conclusions: If performed for medical reasons, CS can save the lives of both mothers and babies. Therefore, CSs should preferably only be performed when necessary for medical reasons. Morbidity is more with emergency LSCS than elective LSCS with PPH being the most common intraoperative complication and anemia being most common post operative complication

KAP study on emergency contraception among women of reproductive age group attending JNUIMSRC OPD, Jaipur, India

Background: Unintended pregnancy, unplanned birth and unsafe abortion have been a major challenge to the reproductive health of women worldwide. Despite the availability of highly efficient contraceptive technologies, there are still many undesired pregnancies that put women at a higher risk of mortality, frequently as a result of unsafe abortion. Emergency contraceptive pills can be used to prevent these unwanted pregnancies. Aim of this study was to assess the knowledge, attitude and practice of use of emergency contraception among women of reproductive age group attending JNUIMSRC OPD, Jaipur, India. Methods: Institution based cross-sectional study was conducted among 100 females of reproductive age group attending JNUIMSRC OPD, Jaipur, India. Data was collected using pretested semi-structured questionnaire after written informed consent. Descriptive and inferential statistics were used to analyse the data generated. Results: Among respondents who were aware of ECPs, 64% had good knowledge of it, 90% had positive attitude towards ECPs and 63% have used earlier. A significant association was found between age, residence, educational level and occupational status with awareness of ECPs. Conclusions: Awareness and utilization of emergency contraceptive pills is low among females of reproductive age group attending OPD at JNUIMSRC. Thus awareness should be enhanced through formal education, communication from healthcare professionals and media that can offer trustworthy and accurate information on ECPs

Vaginal Rhabdomyosarcoma in a patient with advanced cervical cancer; a case report and review of literature

Rhabdomyosarcoma is very rare in adults accounting for less than 5% of all soft tissue tumours and less than 1% of all malignancies. Vagina is one of the least common sites for occurrence of Rhabdomyosarcoma in the genital tract. We present a case of a 53-year-old woman who is a follow up case of cervical cancer stage IIIB, managed by radiotherapy and chemotherapy. She was doing well till 5 years of her treatment for cervical cancer when she presented with complaints of pain lower abdomen and discharge per vaginum for 10 days. On examination she was found to have an abdominal mass of 18 weeks size and on local examination there was 4X4 cm fixed mass on lower third of vagina arising from left side. MRI abdomen and pelvis was done. Biopsy from the vaginal mass showed features of Rhabdomyosarcoma. Further follow up of the patient was not possible due to lockdown in view of the pandemic. She was last contacted telephonically on 25th March 2020; she said she was waiting for the lockdown to be lifted so that her further management can take place. This is just one patient; there are many more with other medical conditions all over the world who are losing their lives because of not being able to access medical care due to the present pandemic. New growth in the region of local recurrence in a known malignancy cannot necessarily be the recurrence of the primary tumour. It is important to keep our mind open to other differentials apart from the recurrence of primary malignancy, sometimes it can turn out to be a very rare tumour as we encountered in our case

A New Bioactive Compound From the Marine Sponge-Derived Streptomyces sp. SBT348 Inhibits Staphylococcal Growth and Biofilm Formation

Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients carrying surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms leads to refractory and persistent device-related infections (DRIs). Staphylococci organized in biofilms are more tolerant to antibiotics and immune responses, and thus are difficult-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm-based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal, and silicone surfaces. A bioassay-guided fractionation was performed to isolate the active compound (SKC3) from the crude SBT348 extract. Our results demonstrated that SKC3 effectively inhibits the growth (MIC: 31.25 μg/ml) and biofilm formation (sub-MIC range: 1.95–<31.25 μg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of SKC3 by heat and enzyme treatments, and mass spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258.3 Da). Cytotoxicity profiling of SKC3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria mellonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of SKC3 treated S. epidermidis RP62A has further unmasked its negative effect on central metabolism such as carbon flux as well as, amino acid, lipid, and energy metabolism. Taken together, these findings suggest a potential of SKC3 as a putative drug to prevent staphylococcal DRIs

Contribution of LTi and TH17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis

Background In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and TH17 cells in the process of B cell aggregate formation in the MP4 model. Methods We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3−CD5−CD4+RORγt+ LTi and CD3+CD5+CD4+RORγt+ TH17 cells. Myelin oligodendrocyte glycoprotein (MOG):35–55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing. Results While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3−CD5−CD4−RORγt+ innate lymphoid cells (ILCs) and TH17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35–55-induced EAE. Conclusion The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice

Sustainable Innovation in a Multi-University Master Course

Mobility, multi-locality, and transnational migration are current social developments among the population of the European Union. These social developments in society and companies, linked to the challenges of sustainability, lead to new requirements for working in the European Union. Teaching and learning in higher education needs to adapt to these requirements. As a result, new and innovative teaching and learning practices in higher education should provide competencies for transnational teamwork in the curriculum of tomorrow's engineers in order to ensure their competitiveness in the job market and advantage in their future careers. Thirteen European students from four countries participated in a new project-based course, called the "European Engineering Team". Students focused on the development of two innovative and sustainable products. The goal of this paper is to present the thermal pallet cover, which is the result of the first one-year transnational and sustainability-oriented project. This paper also aims to present the process of performing the project. It provides the overview and discussion of engineering and management tasks that students completed in the transnational environment, working remotely at their own campuses between scheduled transnational meetings. The work contributes to project-oriented learning that may constitute a basis for teaching holistic engineering courses at mechanical and industrial engineering departments

Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.

A plethora of functional and genetic studies have suggested a key role for the IL-23 pathway in chronic intestinal inflammation. Currently, pathogenic actions of IL-23 have been ascribed to specific effects on immune cells. Herein, we unveil a protective role of IL-23R signaling. Mice deficient in IL-23R expression in intestinal epithelial cells (Il23R(ΔIEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(ΔIEC) mice show impaired mucosal IL-22 induction in response to IL-23. αThy-1 treatment significantly deteriorates colitis in Il23R(ΔIEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(ΔIEC) mice by recruiting neutrophils as IL-22-producing cells, thereby restoring mucosal IL-22 levels. The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells.This work was supported by DFG Excellence Cluster Inflammation at Interfaces; the SFB877 B9, the SFB 1182 C2 project, and the BMBF IHEC DEEP project TP2.3 and 5.2 (to P.R.); the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement 260961 (to A.K.); the National Institute for Health Research Cambridge Biomedical Research Centre, ERC CoG GA 648889, and WTIA 106260-Z-14-Z (to A.K.); NIH DK53056, DK44319, and DK088199 (to R.S.B.); and the Fondation pour la Recherche Medicale (to M.C.).This is the final version of the article. It first appeared from Cell/Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.07.05

Defective ATG16L1-mediated removal of IRE1α drives Crohn's disease-like ileitis.

ATG16L1$^{T300A}$, a major risk polymorphism in Crohn's disease (CD), causes impaired autophagy, but it has remained unclear how this predisposes to CD. In this study, we report that mice with Atg16l1 deletion in intestinal epithelial cells (IECs) spontaneously develop transmural ileitis phenocopying ileal CD in an age-dependent manner, driven by the endoplasmic reticulum (ER) stress sensor IRE1α. IRE1α accumulates in Paneth cells of Atg16l1$^{ΔIEC}$ mice, and humans homozygous for ATG16L1$^{T300A}$ exhibit a corresponding increase of IRE1α in intestinal epithelial crypts. In contrast to a protective role of the IRE1β isoform, hyperactivated IRE1α also drives a similar ileitis developing earlier in life in Atg16l1;Xbp1$^{ΔIEC}$ mice, in which ER stress is induced by deletion of the unfolded protein response transcription factor XBP1. The selective autophagy receptor optineurin interacts with IRE1α, and optineurin deficiency amplifies IRE1α levels during ER stress. Furthermore, although dysbiosis of the ileal microbiota is present in Atg16l1;Xbp1$^{ΔIEC}$ mice as predicted from impaired Paneth cell antimicrobial function, such structural alteration of the microbiota does not trigger ileitis but, rather, aggravates dextran sodium sulfate-induced colitis. Hence, we conclude that defective autophagy in IECs may predispose to CD ileitis via impaired clearance of IRE1α aggregates during ER stress at this site.This study was supported by the European Research Council under the European Community’s Seventh Framework Program (grant FP7/2007-2013)/ERC, agreement no. 260961 to A. Kaser and grant HORIZON2020/ERC, agreement no. 648889 to A. Kaser), the Wellcome Trust (Investigator Award 106260/Z/14/Z to A. Kaser and Principal Research Fellowship 2008/Z/16/Z to D. Ron), the Cambridge Biomedical Research Centre (A. Kaser), a Medical Research Council PhD for clinicians training fellowship (grant MR/N001893/1 to J. Bhattacharyya), fellowships from the European Crohn’s and Colitis Organization (M. Tschurtschenthaler and T.E. Adolph), the Research Training Group Genes, Environment, and Inflammation supported by the Deutsche Forschungsgemeinschaft (grant RTG 1743/1 to P. Rosenstiel), the SFB877 subproject B9 and CLVIII ExC 306 Inflammation at Interfaces (P. Rosenstiel), and the National Institutes of Health (grants DK044319, DK051362, DK053056, and DK088199 to the Harvard Digestive Diseases Center and grant DK0034854 to R.S. Blumberg)