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Mounting evidence implicates bariatric surgery as a cause of increased skeletal fragility and fracture risk. Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The main objective of this pilot randomized controlled trial (RCT; Clinical Trial No. NCT03411902) was to determine the feasibility of recruiting, treating, and following 24 older patients who had undergone sleeve gastrectomy in a 6 month RCT examining the efficacy of 150‐mg once‐monthly risedronate (versus placebo) in the prevention of surgical weight‐loss–associated bone loss. Feasibility was defined as: (i) >30% recruitment yield, (ii) >80% retention, (iii) >80% pills taken, (iv) 80% participant satisfaction. Study recruitment occurred over 17 months. Seventy participants were referred, with 24 randomized (34% yield) to risedronate (n = 11) or placebo (n = 13). Average age was 56 ± 7 years, 83% were female (63% postmenopausal), and 21% were black. The risedronate group had a higher baseline BMI than the placebo group (48.1 ± 7.2 versus 41.9 ± 3.8 kg/m2). The 10‐year fracture risk was low (6.0% major osteoporotic fracture, 0.4% hip fracture); however, three individuals (12.5%, all risedronate group) were osteopenic at baseline. Twenty‐one participants returned for 6‐month follow‐up testing (88% retention) with all (n = 3) loss to follow‐up occurring in the risedronate group. Average number of pills taken among completers was 5.9 ± 0.4 and 6.0 ± 0.0 in the risedronate and placebo groups, respectively (p = 0.21), with active participants taking >80% of allotted pills. Five AEs (3.7% AE rate) were reported; one definitely related, four not related, and none serious. All participants reported high satisfaction with participation in the study. Use of bisphosphonates as a novel therapeutic to preserve bone density in patients who had undergone a sleeve gastrectomy appears feasible and well‐tolerated. Knowledge gained from this pilot RCT will be used to inform the design of an appropriately powered trial. Clinical Trial Registration http://clinicaltrials.gov/show/NCT03411902. Weight Loss With Risedronate for Bone Health. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc 2 155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.

The influence of the hydrophobic-hydrophilic properties of bile salts (BS) on acute ethanol hepatotoxicity was investigated. Bile flow, biliary BS secretion and enzyme (LDH,AST) release in the perfusate were measured before and after exposure to low (0.1%) or high (1%) doses of ethanol in in vitro isolated livers perfused with 1 microM/min taurocholate (TCA), tauroursodeoxycholate (TUDCA) or taurodeoxycholate (TDCA). Ethanol promotes a rapid decrease of basal bile flow and BS secretion in TCA-perfused livers [-28% of basal values with 0.1% (N = 6), and -35% with 1% ethanol (N = 6)]. Bile flow and BS secretion were minimally decreased by ethanol in livers perfused with a hydrophilic BS (TUDCA) [-8% decrease of basal values with 0.1% ethanol (N = 6), and -10% with 1% ethanol (N = 9); p0.02 vs TCA-perfused livers]. In contrast, when livers were perfused with a hydrophobic BS (TDCA), ethanol showed a higher cholestatic effect than either TCA- or TUDCA-perfused livers. Enzyme release in the perfusate was not modified by 0.1% ethanol, while 1% ethanol promoted a 4-5 fold increase in LDH and AST release in the perfusate of TCA-perfused livers with respect to a mere 2-fold increase in TUDCA-perfused livers and a 6-7 fold increase in TDCA perfused livers (p0.03). In conclusion, we showed that TUDCA almost completely counteracts the cholestatic and cytolitic effects promoted by ethanol in the isolated perfused rat liver.

CD5+B cells, recently defined B-1a cells, are the main clonotype in the early B cell repertoire and persist throughout adult life. This subset is committed to the production of antibodies, defined "natural antibodies", that bind a lot of exogenous antigens, isologous and heterologous serum proteins, tissues and/or self antigens, such as hormones, nucleic acids and phospholipids. These antibodies, mostly IgM, but also IgG and IgA, are polyreactive: their role is likely that of first line of defence against invading microorganisms. Natural antibodies produced by CD5+ B cells may be involved in maintenance functions such as removal of dead cells. Because of their ability to bind self antigens, they may be important in the establishment of autoimmune phenomena. An increase of CD5+ B cells has been demonstrated in some autoimmune disorders. The authors examine the functional characteristics and the expansion of this subset in different diseases. In particular they report the increase in active Graves' disease and discuss the role of CD5+ B lymphocytes in the immune imbalance present in this thyropathy.

Stem cells in brain niches are responsible for neurogenesis and integration of new neurons into functional circuits, with inflammatory and immune system mediators playing critical roles in neurogenesis and in several diseases of the nervous system. TLR4 is known to be a master player in the development of neuroinflammation processes and to be upregulated in several animal models of neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). Nonetheless, Toll-like receptor 4 (TLR4) also plays a key role in CNS homeostasis. TLR4 is expressed in microglia, which is a master player in neuroinflammatory processes, as well as in neural cells: astrocytes, neurons, oligodendrocytes, neural progenitors (NPCs), and neural stem cells (NSCs). Here we discuss the dual role of TLR4 in brain homeostasis, suggesting that, in a translational perspective, TLR4-mediated regulation of human neural stem cells (hNSCs) needs to be deeply investigated either for the identification of novel biomarkers for rare diseases or future therapeutic approaches of aging and neurodegenerative disorders.

Unraveling the molecular basis of immune recognition still represents a challenging task for current biological sciences, both in terms of theoretical knowledge and practical implications. Here, we describe the physical-chemistry methods and computational protocols for the prediction of antibody-binding epitopes and MHC-II loaded epitopes, starting from the atomic coordinates of antigenic proteins (PDB file). These concepts are the base of the Web tool BEPPE (Binding Epitope Prediction from Protein Energetics), a free service that returns a list of putative epitope sequences and related blast searches against the Uniprot human complete proteome. BEPPE can be employed for the study of the biophysical processes at the basis of the immune recognition, as well as for immunological purposes such as the rational design of biomarkers and targets for diagnostics, therapeutics, and vaccine discovery.