Positive affect dysregulation and its relation to binge eating size and frequency.

Negative affect is an established predictor of binge eating, yet less is known about positive affect. Low positive affect has been theorized to increase binge eating, but a better understanding is needed on the relationship between positive affect and binge eating frequency and size. Participants were 182 treatment-seeking adults (76% self-identified as female; 45% self-identified their race as Black and 40% as White; and 25% self-identified their ethnicity as Hispanic/Latino) with self-reported recurrent binge eating (≥12 binge episodes in the past 3 months). Participants completed the positive and negative affect schedule (PANAS) survey and the eating disorder examination to assess frequency of objective binge episodes (OBEs) and subjective binge episodes (SBEs) over the past 3 months. OBEs and SBEs also were combined to yield total binge episodes over the past 3 months. Independent t-tests and linear regression analyses were used to test associations between positive affect scores and binge episode size and frequencies, and to compare low versus higher positive affect on binge frequency. Additional exploratory models were conducted controlling for negative affect, identity characteristics, and socio-demographic variables. Lower positive affect was significantly associated with more frequent total binge episodes, but not OBEs and SBEs when assessed independently. Findings remained consistent when controlling for covariates and when comparing individuals with the lowest versus higher positive affect levels. Overall, results lend support to the theory that low positive affect is associated with binge eating. Increasing positive affect may be an important treatment consideration for those with recurrent binge eating.

Rasmussen's encephalitis: From immune pathogenesis towards targeted-therapy.

Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery. We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020. The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen.

INTRODUCTION: Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. MATERIALS AND METHODS: A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel's diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. DISCUSSION: The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. CONCLUSION: Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery.

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma.

The detection of promoter region hypermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have used a genome-wide strategy (methylated DNA immunoprecipitation (MeDIP) and whole-genome array analysis in combination with high-density expression array analysis) to identify genes that are frequently methylated and silenced in RCC. MeDIP analysis on 9 RCC tumours and 3 non-malignant normal kidney tissue samples was performed, and an initial shortlist of 56 candidate genes that were methylated by array analysis was further investigated; 9 genes were confirmed to show frequent promoter region methylation in primary RCC tumour samples (KLHL35 (39%), QPCT (19%), SCUBE3 (19%), ZSCAN18 (32%), CCDC8 (35%), FBN2 (34%), ATP5G2 (36%), PCDH8 (58%) and CORO6 (22%)). RNAi knockdown for KLHL35, QPCT, SCUBE3, ZSCAN18, CCDC8 and FBN2 resulted in an anchorage-independent growth advantage. Tumour methylation of SCUBE3 was associated with a significantly increased risk of cancer death or relapse (P=0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis.

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody.

T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti-PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1(+) MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.