Characteristics of the patients referred to a Hypertension Unit between 1989 and 2003

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Interspecific variations in the gastrointestinal microbiota in penguins

Despite the enormous amount of data available on the importance of the gastrointestinal (GI) microbiota in vertebrate (especially mammals), information on the GI microbiota of seabirds remains incomplete. As with many seabirds, penguins have a unique digestive physiology that enables them to store large reserves of adipose tissue, protein, and lipids. This study used quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene pyrosequencing to characterize the interspecific variations of the GI microbiota of four penguin species: the king, gentoo, macaroni, and little penguin. The qPCR results indicated that there were significant differences in the abundance of the major phyla Firmicutes, Bacteroides, Actinobacteria, and Proteobacteria. A total of 132,340, 18,336, 6324, and 4826 near full-length 16S rRNA gene sequences were amplified from fecal samples collected from king, gentoo, macaroni, and little penguins, respectively. A total of 13 phyla were identified with Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria dominating the composition; however, there were major differences in the relative abundance of the phyla. In addition, this study documented the presence of known human pathogens, such as Campylobacter, Helicobacter, Prevotella, Veillonella, Erysipelotrichaceae, Neisseria, and Mycoplasma. However, their role in disease in penguins remains unknown. To our knowledge, this is the first study to provide an in-depth investigation of the GI microbiota of penguins.<br /

The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study

Aims: To assess the risk of adverse neonatal outcomes in women with gestational diabetes (GDM) by identifying subgroups of women at higher risk to recognize the characteristics most associated with an excess of risk. Methods: Observational, retrospective, multicenter study involving consecutive women with GDM. To identify distinct and homogeneous subgroups of women at a higher risk, the RECursive Partitioning and AMalgamation (RECPAM) method was used. Overall, 2736 pregnancies complicated by GDM were analyzed. The main outcome measure was the occurrence of adverse neonatal outcomes in pregnancies complicated by GDM. Results: Among study participants (median age 36.8 years, pre-gestational BMI 24.8 kg/m2), six miscarriages, one neonatal death, but no maternal death was recorded. The occurrence of the cumulative adverse outcome (OR 2.48, 95% CI 1.59–3.87), large for gestational age (OR 3.99, 95% CI 2.40–6.63), fetal malformation (OR 2.66, 95% CI 1.00–7.18), and respiratory distress (OR 4.33, 95% CI 1.33–14.12) was associated with previous macrosomia. Large for gestational age was also associated with obesity (OR 1.46, 95% CI 1.00–2.15). Small for gestational age was associated with first trimester glucose levels (OR 1.96, 95% CI 1.04–3.69). Neonatal hypoglycemia was associated with overweight (OR 1.52, 95% CI 1.02–2.27) and obesity (OR 1.62, 95% CI 1.04–2.51). The RECPAM analysis identified high-risk subgroups mainly characterized by high pre-pregnancy BMI (OR 1.68, 95% CI 1.21–2.33 for obese; OR 1.38 95% CI 1.03–1.87 for overweight). Conclusions: A deep investigation on the factors associated with adverse neonatal outcomes requires a risk stratification. In particular, great attention must be paid to the prevention and treatment of obesity

miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1

MicroRNAs (miRNAs) with tumor-suppressor potential might have therapeutic applications in multiple myeloma (MM) through the modulation of still undiscovered molecular pathways. Here, we investigated the effects of enforced expression of miR-29b on the apoptotic occurrence in MM and highlighted its role in the context of a new transcriptional loop that is finely tuned by the proteasome inhibitor bortezomib. In details, in vitro growth inhibition and apoptosis of MM cells was induced by either transient expression of synthetic miR-29b or its stable lentivirus-enforced expression. We identified Sp1, a transcription factor endowed with oncogenic activity, as a negative regulator of miR-29b expression in MM cells. Since Sp1 expression and functions are regulated via the 26S proteasome, we investigated the effects of bortezomib on miR-29b-Sp1 loop, showing that miR-29b levels were indeed upregulated by the drug. At the same time, the bortezomib/miR-29b combination produced significant pro-apoptotic effects. We also demonstrated that the PI3K/AKT pathway plays a major role in the regulation of miR-29b-Sp1 loop and induction of apoptosis in MM cells. Finally, MM xenografts constitutively expressing miR-29b showed significant reduction of their tumorigenic potential. Our findings indicate that miR-29b is involved in a regulatory loop amenable of pharmacologic intervention and modulates the anti-MM activity of bortezomib in MM cells

Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Rational identification of a Cdc42 inhibitor presents a new regimen for long- term hematopoietic stem cell mobilization

Mobilization of hematopoietic stem cells (HSCs) from bone marrow (BM) to peripheral blood (PB) by cytokine granulocyte colony-stimulating factor (G-CSF) or the chemical antagonist of CXCR4, AMD3100, is important in the treatment of blood diseases. Due to clinical conditions of each application, there is a need for continued improvement of HSC mobilization regimens. Previous studies have shown that genetic ablation of the Rho GTPase Cdc42 in HSCs results in their mobilization without affecting survival. Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity and competitively interfere with guanine nucleotide exchange activity. CASIN inhibits intracellular Cdc42 activity specifically and transiently to induce murine hematopoietic stem/progenitor cell egress from the BM by suppressing actin polymerization, adhesion, and directional migration of stem/progenitor cells, conferring Cdc42 knockout phenotypes. We further show that, although, CASIN administration to mice mobilizes similar number of phenotypic HSCs as AMD3100, it produces HSCs with better long-term reconstitution potential than that by AMD3100. Our work validates a specific small molecule inhibitor for Cdc42, and demonstrates that signaling molecules downstream of cytokines and chemokines, such as Cdc42, constitute a useful target for long-term stem cell mobilization

Implementing a guideline for the treatment of type 2 diabetics: results of a Cluster- Randomized Controlled Trial (C-RCT)

<p>Abstract</p> <p>Background</p> <p>In Italy many diabetics still lack adequate care in general practice. We assessed the effectiveness of different strategies for the implementation of an evidence-based guideline for the management of non-complicated type 2 diabetes among General Practitioners (GPs) of Lazio region.</p> <p>Methods</p> <p>Three-arm cluster-randomised controlled trial with GPs as units of randomisation (clusters). 252 GPs were randomised either to an active strategy (training module with administration of the guideline), or to a passive dissemination (administration of the guideline only), or to usual care (control). Data on prescriptions of tests and drugs were collected by existing information systems, whereas patients' data came from GPs' databases. Process outcomes were measured at the cluster level one year after the intervention. Primary outcomes concerned the measurement of glycosilated haemoglobin and the commissioning of micro- and macrovascular complications assessment tests. In order to assess the physicians' drug prescribing behaviour secondary outcomes were also calculated.</p> <p>Results</p> <p>GPs identified 6395 uncomplicated type 2 patients with a high prevalence of cardiovascular risk factors. Data on GPs baseline performance show low proportions of glycosilated haemoglobin assessments. Results of the C-RCT analysis indicate that the active implementation strategy was ineffective relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76–1.46]; OR 1.07 [95% IC: 0.80–1.43]; OR 1.4 [95% IC:0.91–2.16]. Similarly, passive dissemination of the guideline showed no effect.</p> <p>Conclusion</p> <p>In our region compliance of GPs with guidelines was not enhanced by a structured learning programme. Implementation through organizational measures appears to be essential to induce behavioural changes.</p> <p>Trial registration</p> <p>ISRCTN80116232</p