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This study not only highlights the role of S776 phosphorylation to regulate ATXN1 levels throughout the brain but also suggests distinct brain region-specific disease mechanisms and demonstrates the importance of developing allele-specific therapies for maximal benefits in SCA1.Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Vorolanib molecular weight Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.

Completely obstructed anastomosis (COA) after low rectal resection (LRR) represents a rare entity difficult to manage. We herein summarize the available evidence from literature on the treatment of this condition and we report our particular experience in the management of a completely obstructed colon-anal anastomosis (CAA) with a trans-anal plus endoscopic trans-colostomy rendez-vous approach.

The Pub-Med database was inquired from inception to October 2019 about the treatment of COA after LRR reported in English literature. Article selection was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. Moreover, clinical, radiological and surgical data of our case presentation were retrieved.

Ten articles involving twelve patients and concerning the management of COA were identified. All of them reported the treatment of completely obstructed colon-rectal anastomosis. As we didn't find any article reporting the treatment of completely obstructed CAA, we also described a case of its treatment. The patient was successfully treated at our institution using a rendez-vous approach with a simultaneous trans-colostomy endoscopy, associated to a trans-anal dilatation. This combined approach, thanks to trans-illumination and to the miniature passage of CO2 coming from above, permitted to identify the correct way to surgically establish a trans-anal lumen. The post-procedural course was uneventful.

The treatment of COA after LRR can be very demanding, particularly after CAA. Few data are reported in literature to define the best approach to treat these conditions. Our described rendez-vous technique can represent a valid choice, especially after CAA.

Colorectal anastomosis, Endoscopic treatment, Low-rectal resection.

Colorectal anastomosis, Endoscopic treatment, Low-rectal resection.

Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer.

IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically.

IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P& in breast cancer therapy and prediction of prognosis.

Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.

Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.

In our surgical daily activity, we report the observation of rare tumour as Gastrointestinal Stromal Tumours (GIST). We report the incidence and behaviour of new cases of GIST operated in our Center during the last decade, from 2008 to 2018 and here we also describe the concomitant observation of a second gastroenteric tumor.

We have examined all the case files and histological examinations of patients with CD 117-positive GISTs treated in our Institute from 2008 to 2018. We have gathered data regarding clinical symptoms at the time of diagnosis, tumour site, type of surgery performed, tumour size, histopathological data and follow up data.

We have analysed 950 cases of patients who underwent surgery for gastrointestinal neoplasia in our department from 2008 to 2018. We have found 12 cases affected by GIST and in 4 cases it was also a second tumour. In two cases GIST were incidentalomas and in the others two patients a second tumour was incidentally observed in primary GIST.

Patients with GIST run the risk of developing a second neoplasm, nearly twice as high as the general population with a negative impact on survival; also, incidental GIST is often observed requiring a better molecular characterization for the high risk of developing second neoplasms with the aim of achieving an early diagnosis.

Gist, Second neoplasm, Surgery.

Gist, Second neoplasm, Surgery.