Computer simulations show that Neanderthal facial morphology represents adaptation to cold and high energy demands, but not heavy biting.

Three adaptive hypotheses have been forwarded to explain the distinctive Neanderthal face: (i) an improved ability to accommodate high anterior bite forces, (ii) more effective conditioning of cold and/or dry air and, (iii) adaptation to facilitate greater ventilatory demands. We test these hypotheses using three-dimensional models of Neanderthals, modern humans, and a close outgroup (Homo heidelbergensis), applying finite-element analysis (FEA) and computational fluid dynamics (CFD). This is the most comprehensive application of either approach applied to date and the first to include both. FEA reveals few differences between H. heidelbergensis, modern humans, and Neanderthals in their capacities to sustain high anterior tooth loadings. CFD shows that the nasal cavities of Neanderthals and especially modern humans condition air more efficiently than does that of H. heidelbergensis, suggesting that both evolved to better withstand cold and/or dry climates than less derived Homo We further find that Neanderthals could move considerably more air through the nasal pathway than could H. heidelbergensis or modern humans, consistent with the propositions that, relative to our outgroup Homo, Neanderthal facial morphology evolved to reflect improved capacities to better condition cold, dry air, and, to move greater air volumes in response to higher energetic requirements.

Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.

BACKGROUND & AIMS: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. METHODS: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. RESULTS: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P < .0001), therapy with PEGα-2a (odds ratio = 4.7; P = .03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P = .005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P < .0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P = .002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P = .005), and lack of a sustained virologic response (HR = 3.3; P = .04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P = .04) and lack of a sustained virologic response (HR = 2.1; P = .04). CONCLUSIONS: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.

The current knowledge about the therapeutic use of endoscopic sclerotherapy and endoscopic tissue adhesives in variceal bleeding.

Introduction: The most recent guidelines vary in their approach to the management of variceal bleeding especially with the use of endoscopic sclerotherapy (ES) and endoscopic tissue adhesive (ETA). This review highlights their clinical use for variceal bleeding from different guidelines perspectives. Areas covered: A comprehensive literature review of three major guidelines including the American Association for the Study of Liver Diseases (AASLD) 2017, United Kingdom (UK) guidelines 2015 and Baveno VI Consensus workshop guidelines in 2015 on the use of ES and ETA in variceal bleeding. Expert opinion: While endoscopic band ligation (EBL) completely replaced endoscopic sclerotherapy (ES) for esophageal varices. There is a valuable use of endoscopic sclerotherapy (ES) and endoscopic tissue adhesive (ETA) especially for patients with gastroesophageal varices (GOV2) and isolated gastric varices (IGV2). The current standard of care heading toward portosystemic shunting with Trans-jugular-Intrahepatic Portosystemic Shunt (TIPS) and balloon retrograde transvenous obliteration (BRTO). However, recent advancement in endoscopic ultrasound (EUS) allowing direct injection of sclerosant and tissue adhesive into the varix bringing promising results in achieving hemostasis and lowering the risk of complications. Also, ES and ETA have great clinical value in achieving hemostasis for isolated (ectopic) varices and stomal varices.