NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46

Interleukin-2 (IL-2)-activated polyclonal or clonal NK cells lysed autologous antigen presenting cells (APC) through the engagement of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. NK cell-mediated cytolysis of APC correlated with the surface density of these NCR. Indeed, NK cell clones bearing low amounts of NKp30 and NKp46 did not lyse autologous APC, whereas NK cell clones with bright expression of these NCR efficiently killed autologous APC. Upon masking of NKp30 or NKp46 by specific monoclonal antibodies a strong reduction (by 50%) of APC lysis could be detected and the complete inhibition was achieved by the simultaneous masking of these NCR. Interestingly, NK cell-mediated APC lysis was impaired by the phosphatidylinositol 3-kinase (PI-3 K) inhibitors LY294002 or wortmannin. Similarly, these drugs strongly reduced NK cell activation triggered by NKp30 or NKp46 in a re-directed killing assay as well as the activation of Akt/PKB, substrate of PI-3 K, induced by the engagement of these receptors. Altogether, these findings strongly suggest that NCR are responsible for the killing of autologous APC through the activation of PI-3 K.     

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women

OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.     

A novel mutation of varicella-zoster virus associated to fatal hepatitis.

BACKGROUND: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. OBJECTIVES: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. RESULTS: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. CONCLUSIONS: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.     

Rapid,Full-Scale Change to Virtual PCIT During the COVID-19 Pandemic: Implementation and Clinical Implications

Health agencies call for the immediate mobilization of existing interventions in response to numerous child and family mental health concerns that have arisen as result of the COVID-19 pandemic. Answering this call, this pilot study describes the rapid, full-scale change from a primarily clinic-based Parent–Child Interaction Therapy (PCIT) model to a virtual service model (i.e., I-PCIT) in an academic and community-based program in Miami, Florida. First, we describe the virtual service training model our program developed and its implementation with 17 therapists (M_Age?=?32.35, 88.2% female, 47.1% Hispanic) to enable our clinic to shift from providing virtual services to a small portion of the families served (29.1%) to all of the families served. Second, we examine the effect of I-PCIT on child and caregiver outcomes during the 2-month stay-at-home period between March 16, 2020, and May 16, 2020, in 86 families (M_ChildAge?=?4.75, 71% Hispanic). Due to the rapid nature of the current study, all active participants were transferred to virtual services, and therefore there was no comparison or control group, and outcomes represent the most recently available scores and not treatment completion. Results reveal that I-PCIT reduced child externalizing and internalizing problems and caregiver stress, and increased parenting skills and child compliance with medium to large effects even in the midst of the COVID-19 pandemic. Finally, the study examined components of our virtual service training model associated with the greatest improvements in child and caregiver outcomes. Preliminary findings revealed that locally and collaboratively developed strategies (e.g., online communities of practice, training videos and guides) had the strongest association with child and caregiver outcomes. Implications for virtual service delivery, implementation, and practice in the midst of the COVID-19 pandemic are discussed.

     

Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description

Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used...     

Left ventricular mass index and ventricular contractility improvement in patients with severe obesity following rapid weight loss after bariatric surgery

BackgroundObesity is a well-known risk factor for heart disease, resulting in a broad spectrum of cardiovascular changes. Left ventricular mass (LVM) and contractility are recognized markers of cardiac function.ObjectivesTo determine the changes of LVM and contractility after bariatric surgery (BaS).SettingUniversity hospital, United StatesMethodsTo determine the cardiac changes in ventricular mass, ventricular contractility, and left ventricular shortening fraction (LVSF), we retrospectively reviewed the 2-dimensional echocardiographic parameters of patients with obesity who underwent BaS at our institution. We compared these results before and after BaS.ResultsA total of 40 patients met the inclusion criteria. The majority were females (57.5%; n = 23), with an average age of 63.5 ± 12.1. The excess body mass index (BMI) lost at 12 months was 48.9 ± 28.9%. The percent total weight loss after BaS was 16.46 ± 9.9%. The left ventricular mass was 234.9 ± 88.1 grams before and 181.5 ± 52.7 grams after BaS (P = .002). The LVM index was 101.3 ± 38.3 g/m² before versus 86.7 ± 26.6 g/m² after BaS (P = .005). The LVSF was 31% ± 8.8% before and 36.3% ± 8.2% after BaS (P = .007). We found a good correlation between the decrease in LVM index and the BMI after BaS (P = .03).ConclusionRapid weight loss results in a decrease of the LVM index, as well as improvement in the left ventricular muscle contractility. Our results suggest that there is left ventricular remodeling and an improvement of heart dynamics following bariatric surgery. Further studies are needed to better assess these findings.     

Endoscopic internal drainage for the management of leak,fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.     

Peyronie’s disease may negatively impact the sexual experience of a couple and female sexual function: a single center study

BackgroundPeyonie’s disease (PD) mostly affects males in the fifth decade of life, with a prevalence in the general population ranging between 0.5% and 20.3%. The pathology of PD is characterized by fibrosis of the tunic albuginea of the cavernous bodies of the penis, with the presence of pain in the erection and penile deformity. This is associated with decreased sexual function for both participants. The objective of the study was to investigate the influence of PD pathology on both male patients’ and their female partners’ sexual spheres, and analyze changes in sexual function and perception following penile correction surgery.MethodsProspective study, we included male patients with PD and their female partner sexually active. Patients underwent corporoplasty with multiple plications. The male and female sexuality was evaluated before surgery and three months after male treatment by the Female sexual Function Index (FSFI); International Index of Erectile Function (IIEF); Visual Analogical Scale (VAS).ResultsFrom January 2018 to November 2019 we included 35 couple. The female subjects before partner’s surgery presented dyspareunia, loss of sexual desire, inability to achieve orgasm, and sexual dissatisfaction. At three months after surgical treatment there was an improvement of sexual function in both male patients and female partners (desire P<0.0001, arousal P<0.0001, lubrification P<0.0001, orgasm P<0.0001, satisfaction P<0.0001, pain P<0.0001). As regarding male patients the pain decreased significantly (VAS score from 6 to 2.5), while there was no statistically significant improvement in erectile function (P=0.05).ConclusionsOur findings suggest that a viable approach to treatment of PD patients that involves their partners could lead to better functional and psychological results.     

Optimization of the future remnant liver: review of the current strategies in Europe

Liver resection still represent the treatment of choice for liver malignancies, but in some cases inadequate future remnant liver (FRL) can lead to post hepatectomy liver failure (PHLF) that still represents the most common cause of death after hepatectomy. Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL, reducing the risk of post hepatectomy liver failure. Portal vein embolization, portal vein ligation, and ALLPS are the most popular techniques historically adopted up to now. The liver venous deprivation and the radio-embolization are the most recent promising techniques. Despite even more precise tools to calculate the relationship among volume and function, such as scintigraphy with ^99mTc-mebrofenin (HBS), no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery, complexity of the pathology and quality of liver parenchyma. The aim of this article is to analyse these different strategies to achieve sufficient FRL.