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Steroidogenic factor 1 (SF1) expressing neurons in the ventromedial hypothalamus (VMH) have been directly implicated in whole-body metabolism and in the onset of obesity. The co-chaperone FKBP51 is abundantly expressed in the VMH and was recently linked to type 2 diabetes, insulin resistance, adipogenesis, browning of white adipose tissue (WAT) and bodyweight regulation. We investigated the role of FKBP51 in the VMH by conditional deletion and virus-mediated overexpression of FKBP51 in SF1-positive neurons. Baseline and high fat diet (HFD)-induced metabolic- and stress-related phenotypes in male and female mice were obtained. In contrast to previously reported robust phenotypes of FKBP51 manipulation in the entire mediobasal hypothalamus (MBH), selective deletion or overexpression of FKBP51 in the VMH resulted in only a moderate alteration of HFD-induced bodyweight gain and body composition, independent of sex. Overall, this study shows that animals lacking and overexpressing Fkbp5 in Sf1 -expressing cells within the VMH display only a mild metabolic phenotype compared to an MBH-wide manipulation of this gene, suggesting that FKBP51 in SF1 neurons within this hypothalamic nucleus plays a subsidiary role in controlling whole-body metabolism. • Loss of FKBP51 in SF1 neurons of the VMH induces a mild metabolic phenotype. • Male and female mice develop similar metabolic responses to the loss of FKBP51. • VMH-specific overexpression of FKBP51 induces phenotypes comparable to knockout. • FKBP51 in the VMH mediates whole-body metabolism in a U-shaped manner. [ABSTRACT FROM AUTHOR]

• There is an increase in the MS relapse incidence after COVID-19 infection. • There is a mild increase in the MS relapse incidence after COVID-19 vaccination. • Lower age was associated with MS relapse after vaccination or infection. • The results in NMOSD patients were broadly consistent with those of MS patients. COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality. [ABSTRACT FROM AUTHOR]

The indication for primary surgical resection or neoadjuvant therapy in lower and middle rectal cancers is often disputable. The aim of the study was to evaluate the occurrence of local recurrence of rectal cancer as for a period of at least 4 years after radical resection. The second aim was to evaluate and compare the results of preoperative magnetic resonance (MR) staging with definitive histology.From September 2013 to December 2017, we, at the 3rd Surgical Department Comenius University, Bratislava, prospectively evaluated patients with lower and middle rectal cancers with the distal tumor border being in a 12-cm distance from the anal verge. All patients underwent MR examination at the same MRI department and were operated on at the 3rd Surgical Department, Comenius University, Bratislava. Inclusion criteria included parameters based on MRI examination, i.e., T-staging of T1-T3b, negative extramural vascular infiltration (EMVI), negative circumferential margin (CRM), no mesorectal fascia infiltration with a distance of more than 2 mm. We did not take lymph node staging into account in the indication for primary surgical resection. We performed a radical primary resection procedure (R0 resection) in all patients. The group consisted of 87 patients, of whom 49 were men and 38 were women. The mean age of the patients was 66 years (min. 36 - max. 86 years). Our study also shows significant differences in preoperative T and N staging as compared to definitive histology. The incidence of local recurrence during a period of at least 4 years after surgery was 6.76 %. Study also shows that the indication for preoperative radiotherapy for lower and middle rectal cancers based on N status is inaccurate and leads to unnecessary indications for preoperative radiotherapy which may decrease the patients´ quality of life and increase the post‑operative complications. We have also shown that leaving out the N-based radiotherapy from indications does not lead to an increase in the number of local recurrences in lower and middle rectal cancers (Tab. 1, Fig. 5, Ref. 22). Text in PDF www.elis.sk Keywords: rectal cancer, neoadjuvant therapy, local recurrence.