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Background: Patients with progressive familial intrahepatic cholestasis (PFIC) experience cholestasis-associated symptoms, including severe pruritus. Odevixibat is an ileal bile acid transporter inhibitor indicated for treatment of PFIC in the European Union and for the treatment of pruritus in PFIC in the United States. The aim of the current study was to characterize the real-world effectiveness and safety of odevixibat in patients with PFIC. Methods: This retrospective study included 9 patients with PFIC treated with odevixibat in a single center in Tübingen, Germany. Data were recorded using case report forms. Results: Of the 9 patients (PFIC1, n = 2; PFIC2, n = 7), 5 had improved serum bile acid levels, pruritus, liver function tests, and sleep with odevixibat treatment. Two siblings with periodic relapses of PFIC symptoms also had improved pruritus and sleep within 4 months of treatment. Two siblings with complete loss of bile salt export pump (BSEP) protein did not respond to treatment; both underwent liver transplantation (indications: hepatocellular carcinoma [HCC] manifestation [n = 1] and severe failure to thrive and refractory pruritus [n = 1]). Four patients reported abdominal complaints that were transient or responded to dose reduction; no other safety issues were reported. Conclusions: In this case series, clinical benefits were observed in most patients with PFIC1 and PFIC2 treated with odevixibat. In patients with periodic relapse of PFIC symptoms, ≥3 months of treatment with odevixibat may be required for symptom control. Patients with complete loss of BSEP did not have consistent symptom relief and require careful monitoring. Effectiveness and feasibility results from our cohort demonstrate potential for long-term benefits with odevixibat in real-world treatment of patients with PFIC.

When choosing between rewards that differ in temporal proximity (inter-temporal choice), human preferences are typically stable, constituting a clinically-relevant transdiagnostic trait. Here we show in patients undergoing deep brain stimulation (DBS) of the anterior limb of the internal capsule / nucleus accumbens region for treatment-resistant obsessivecompulsive disorder (OCD), that long-term chronic (but not phasic) DBS disrupts inter-temporal preferences. Hierarchical Bayesian modeling accounting for temporal discounting behavior across multiple time points allowed us to assess both short-term and long-term reliability of inter-temporal choice. In controls, temporal discounting was highly reliable, both long-term (6 months) and short-term (1 week). In contrast, in patients undergoing DBS, short-term reliability was high, but long-term reliability (6 months) was severely disrupted. Control analyses confirmed that this effect was not due to range restriction, the presence of OCD symptoms or group differences in choice stochasticity. Model-agnostic between- and within-subject analyses confirmed this effect. These findings provide initial evidence for long-term modulation of cognitive function via DBS and highlight a potential contribution of the human nucleus accumbens region to inter-temporal preference stability over time.Competing Interest StatementJ.K. has occasionally received honoraria from AstraZeneca, Lilly, Lundbeck, and Otsuka Pharma for lecturing at conferences and financial support to travel. He received financial support for investigator-initiated trials from Medtronic Europe SARL (Meerbusch, Germany). The remaining authors reported no biomedical financial interests or potential conflicts of interests.Footnotes* - Major update of all modeling procedures: data across time points are now modeled via multivariate gaussian distributions - Reliability analyses now based on posterior distributions of test-retest correlation coefficients drawn from these generative models - All control analyses and single-subject data plots now included in the main text - Included links for open data and code

Chronic skin wounds place a high burden on patients and health care systems. The use of angiogenic and mitogenic growth factors (GF) can facilitate the healing but GF are quickly inactivated by the wound environment if added exogenously. Here, free-standing multilayer films (FSF) are fabricated from chitosan (CHI) and alginate (ALG) as opposing polyelectrolytes in an alternating manner using layer-by-layer technique (LbL). One hundred bilayers form an about 450 µm thick, detachable free-standing film (N-FSF) that is subsequently crosslinked by either ethyl (dimethylaminopropyl) carbodiimide (EDC) combined with N-hydroxysuccinimide (NHS) (E-FSF) or genipin (G-FSF). The characterization of swelling, oxygen permeability and crosslinking density shows reduced swelling and oxygen permeability for both crosslinked films compared to N-FSF. Loading of fibroblast growth factor 2 (FGF2) into the films results in a sustained release of GF from crosslinked in comparison to N-FSF. Biocompatibility studies in vitro with human dermal fibroblasts (HDF) cultured underneath the films demonstrate increased cell growth and cell migration for all films with and without FGF2. Especially G-FSF loaded with FGF2 greatly increases cell proliferation and migration. In vivo biocompatibility studies by subcutaneous implantation in mice show that E-FSF causes a strong inflammatory response while G-FSF is of high biocompatibility. N-FSF also represents a biocompatible film but shows early degradation. All FSF possess antibacterial properties against gram+ and gram-bacteria demonstrated by an agar diffusion disc assay. In summary, FSF made of ALG and CHI crosslinked with genipin can act as a reservoir for the sustained release of FGF2, possessing high biocompatibility in vitro and in vivo. Moreover, G-FSF promotes growth and migration of HDF and has antibacterial properties which makes it an interesting candidate for bioactive wound dressings.