Translational Gap between Guidelines and Clinical Medicine: The Viewpoint of Italian General Practitioners in the Management of IBS

Irritable bowel syndrome (IBS) guidelines are generally developed by experts, with the possibility of a translational gap in clinical medicine. The aim of our study was to assess an Italian group of general practitioners (GPs) for their awareness and use of criteria for the diagnosis and management of IBS. For this purpose, a survey was carried out involving 235 GPs, divided into two groups according to their years of activity: 65 “junior general practitioners” (JGPs) (≤10 years) and 170 “senior general practitioners” (SGPs) (>10 years). JGPs were more familiar with the Rome IV Criteria and Bristol Scale than SGPs. Abdominal pain, bowel movement frequency and bloating were the symptoms most frequently used to make a diagnosis. The most probable causes of IBS were reported to be abnormal gastrointestinal motility and psychological triggers. SGPs reported more frequently than JGPs that challenging management and patient’s request were motivations for a gastroenterological consultation. The practice of clinical medicine is still far from the guidelines provided by the specialists. Abdominal pain related to defecation and changes in bowel frequency are considered to be the more important symptoms for IBS diagnosis, but most GPs, both JGPs and SGPs, like to consider abdominal bloating as another useful symptom. Involving both gastroenterologists and GPs in developing shared guidelines would be highly desirable in order to improve IBS management strategies in everyday clinical practice

Lifelong exposure to a low-dose of the glyphosate-based herbicide RoundUp® causes intestinal damage, gut dysbiosis, and behavioral changes in mice

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world’s leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1–positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders

Eficácia de herbicidas pré-emergentes no controle de caruru resistente ao glifosato e efeito carryover sobre azevém em sucessão.

O objetivo do trabalho foi investigar o efeito residual de herbicidas pré-emergentes no controle de caruru e o efeito carryover sobre azevém em sucessão ao cultivo de soja

EP-1156: Radiotherapy for ductal carcinoma in situ: patterns of recurrence and risk factors stratification

n/

Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas

Fatigue strength of common tibial intramedullary nail distal locking screws

Premature failure of either the nail and/or locking screws with unstable fracture patterns may lead to angulation, shortening, malunion, and IM nail migration. Up to thirty percent of all unreamed nail locking screws can break after initial weight bearing is allowed at 8–10 weeks if union has not occurred. The primary problem this presents is hardware removal during revision surgery. The purposes of our study was to evaluate the relative fatigue resistance of distal locking screws and bolts from representative manufacturers of tibial IM nail systems, and develop a relative risk assessment of screws and materials used. Evaluations included quantitative and qualitative measures of the relative performance of these screws

Notulae to the Italian alien vascular flora: 1

In this contribution, new data concerning the Italian distribution of alien vascular flora are presented. It includes new records, exclusions, and confirmations for Italy or for Italian administrative regions for taxa in the genera Agave, Arctotheca, Berberis, Bidens, Cardamine, Catalpa, Cordyline, Cotoneaster, Dichondra, Elaeagnus, Eragrostis, Impatiens, Iris, Koelreuteria, Lamiastrum, Lantana, Ligustrum, Limnophila, Lonicera, Lycianthes, Maclura, Mazus, Paspalum, Pelargonium, Phyllanthus, Pyracantha, Ruellia, Sorghum, Symphyotrichum, Triticum, Tulbaghia and Youngia

The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer

The availability of bromodomain and extra-terminal inhibitors (BETi) has enabled translational epigenetic studies in cancer. BET proteins regulate transcription by selectively recognizing acetylated lysine residues on chromatin. BETi compete with this process leading to both downregulation and upregulation of gene expression. Hypoxia enables progression of triple negative breast cancer (TNBC), the most aggressive form of breast cancer, partly by driving metabolic adaptation, angiogenesis and metastasis through upregulation of hypoxia-regulated genes (for example, carbonic anhydrase 9 (CA9) and vascular endothelial growth factor A (VEGF-A). Responses to hypoxia can be mediated epigenetically, thus we investigated whether BETi JQ1 could impair the TNBC response induced by hypoxia and exert anti-tumour effects. JQ1 significantly modulated 44% of hypoxia-induced genes, of which two-thirds were downregulated including CA9 and VEGF-A. JQ1 prevented HIF binding to the hypoxia response element in CA9 promoter, but did not alter HIF expression or activity, suggesting some HIF targets are BET-dependent. JQ1 reduced TNBC growth in vitro and in vivo and inhibited xenograft vascularization. These findings identify that BETi dually targets angiogenesis and the hypoxic response, an effective combination at reducing tumour growth in preclinical studies