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The history of social medicine in Italy between the late nineteenth and early twentieth centuries was characterised by a marked presence of gender and the consequent commitment of women of Jewish origin to the issues of early childhood education, as well as safeguarding of work and motherhood and health prevention with regard to social and cultural fragility. Some of the roles of women engaged in social medicine campaigns have been widely studied in the historiography of medicine, having recognized their roles and commitment to attempting to create a fair society through their expertise in medicine and health. However, there are some biographies and professional lives that are still unpublished and worthy of attention by historical medical research. Lucia Servadio, who was of Jewish origin (1900–2006), was the youngest Italian doctor of the first twenty years of the twentieth century. She successfully worked, despite the degrading identification of women at the time, in the field of medicine and welfare, thanks to her qualified professional, cultural and social commitment. Dr Servadio's professionalism was constantly defined by a vision of health as a right that the doctor must protect by pursuing the goal of social equity. Precisely on the basis of these principles, solidified by the practical and social activism of women's groups of the time, Dr Servadio's professional and private life was continuously shaped between medicine and social activism. However, her story is also pervaded by the ambiguity of the role played by women, often highly educated and with considerable professional standing, engaged in forms of scientific intellectual collaboration of a conjugal nature. [ABSTRACT FROM AUTHOR]

To overcome difficulties in splitting, uneven breaking and inconsistent dosing frequently reported with scored tablets, a novel punch was proposed for the manufacturing of easy breakable tablets (EBTs). In this work, the performance of the EBT punch was investigated vs. a ridged one for traditional breakable tablets (TBTs) using a furosemide powder formulation for orally disintegrating tablets (ODTs). A Face Centered Central Composite Design was applied to investigate the influence of punch type, compaction force, tablet weight and press rotation speed on the mechanical properties of ODTs, their behavior in aqueous fluids and aptitude for splitting. Mass uniformity and adequate crushing strength, friability, water uptake, disintegration and wetting times were obtained from both TBTs and EBTs. Interestingly, more favorable splitting behavior was shown by tablets manufactured by the novel punch, in view of lower mass loss and portion mass variability after breaking. The ease of breaking, accuracy of subdivision and mass loss of ODTs were also evaluated by a volunteer (n = 20) panel test. Less difficulty was found in splitting EBTs than TBTs (p < 0.05), and a larger number of tablets were properly broken into four parts. Thus, this study proved the usefulness of the EBT punch in overcoming drawbacks associated with divisible tablets.

Author(s): Wen Zheng [sup.1] , Wenjing Zhao [sup.2] [sup.3] , Meng Wu [sup.1] , Xinyang Song [sup.1] , Florence Caro [sup.3] , Ximei Sun [sup.1] , Francesca Gazzaniga [sup.1] , [...], Although maternal antibodies protect newborn babies from infection.sup.1,2, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against the maternal microbiota when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that IgG derived from breast milk was crucial for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates. Neonatal mice are protected against infection with the enteric pathogen enterotoxigenic Escherichia coli by maternally derived natural antibodies as well as by maternal commensal microbiota that induce antibodies that recognize antigens expressed by Enterobacteriaceae.

Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium, Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of chemokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identify Enterococcus faecium as a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimental in vitro platforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions.

Converging lines of evidence from diverse research domains suggest that the left and right hemispheres play distinct, yet complementary, roles in inferential reasoning. Here, we review research on split-brain patients, brain-damaged patients, delusional patients, and healthy individuals that suggests that the left hemisphere tends to create explanations, make inferences, and bridge gaps in information, while the right hemisphere tends to detect conflict, update beliefs, support mental set-shifts, and monitor and inhibit behavior. Based on this evidence, we propose that the left hemisphere specializes in creating hypotheses and representing causality, while the right hemisphere specializes in evaluating hypotheses, and rejecting those that are implausible or inconsistent with other evidence. In sum, we suggest that, in the domain of inferential reasoning, the left hemisphere strives to reduce uncertainty while the right hemisphere strives to resolve inconsistency. The hemispheres' divergent inferential reasoning strategies may contribute to flexible, complex reasoning in the healthy brain, and disruption in these systems may explain reasoning deficits in the unhealthy brain.

Telomerase canonically maintains telomeres, but recent reports have suggested that the core protein mammalian telomerase reverse transcriptase (TERT) component, together with the chromatin remodeling factor BRG1 and β-catenin, may also bind to and promote expression of Wnt target genes. However, this proposed noncanonical role of TERT in Wnt signaling has been controversial. Here, we investigated the effects of human TERT (hTERT) on Wnt signaling in human breast cancer lines and HeLa cells. We failed to find evidence for physical association of hTERT with BRG1 or β-catenin; instead, we present evidence that anti-FLAG antibody cross-reactivity properties may explain the previously reported interaction of hTERT with β-catenin. Furthermore, altering hTERT levels in four different breast cancer cell lines caused minimal and discordant effects on Wnt target and Wnt pathway gene expression. Although hTERT's role in Wnt signaling was addressed only indirectly, no significant representation of Wnt target genes was detected in chromatin immunoprecipitation-sequencing (ChIP-seq) and chromatin isolation by RNA purification and sequencing (ChIRP-seq) loci cooccupied in HeLa S3 cells by both BRG1 and hTR. In summary, our evidence fails to support the idea of a biologically consistent hTERT interaction with the Wnt pathway in human breast cancer cells, and any detectable influence of hTERT depended on cell type and experimental system.

The increasingly swift changes in the field of medicine require a reassessment of the skills necessary for the training of technically qualified doctors. Today’s physicians also need to be capable of managing the complex issue of personal relationships with patients. Recent pedagogical debates have focused on so-called “soft skills”, whose acquisition is presented in literature as a quite recent addition to medical studies. Moreover, the historical investigation of deontological texts dating from the mid-nineteenth century back to the Hippocratic Oath shows that medicine has always discussed the need to integrate technical expertise in medicine with specific personal and relationship-based skills. Debates have often circled around whether these “soft skills” could actually be taught or how they could be successfully transmitted to training physicians. The belief that defining medicine is more complex than defining other similar sciences and that the instruments to be used in the relationship with patients cannot be limited to those provided by technical aspects shows a new awareness. Today, this view is often stated as an innovative realization on the part of doctors with regard to the complexity of training and action in a delicate area in which they are entrusted with the management of the balance of the system that is the human body.

Human telomerase reverse transcriptase (hTERT; the catalytic protein subunit of telomerase) is subjected to numerous alternative splicing events, but the regulation and function of these splice variants is obscure. Full-length hTERT includes conserved domains that encode reverse transcriptase activity, RNA binding, and other functions. The major splice variant termed α+β- or β-deletion is highly expressed in stem and cancer cells, where it codes for a truncated protein lacking most of the reverse transcriptase domain but retaining the known RNA-binding motifs. In a breast cancer cell panel, we found that β-deletion was the hTERT transcript that was most highly expressed. Splicing of this transcript was controlled by the splice regulators SRSF11, HNRNPH2, and HNRNPL, and the β-deletion transcript variant was associated with polyribosomes in cells. When ectopically overexpressed, β-deletion protein competed for binding to telomerase RNA (hTR/TERC), thereby inhibiting endogenous telomerase activity. Overexpressed β-deletion protein localized to the nucleus and mitochondria and protected breast cancer cells from cisplatin-induced apoptosis. Our results reveal that a major hTERT splice variant can confer a growth advantage to cancer cells independent of telomere maintenance, suggesting that hTERT makes multiple contributions to cancer pathophysiology.

Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery. [ABSTRACT FROM AUTHOR]

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies.