Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting

Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti?an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate?after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions

New insight into the structural, electrochemical and biological aspects of macrocylic Cu(II) complexes derived from S-substituted dithiocarbazate Schiff bases

Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7

Rationale, design and population baseline characteristics of the PERFORM Vascular Project: an ancillary study of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) trial

<p><b>Purpose</b></p> <p>PERFORM is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke or transient ischemic attacks (TIAs). The PERFORM Vascular Project will evaluate the effect of terutroban on progression of atherosclerosis, as assessed by change in carotid intima-media thickness (CIMT) in a subgroup of patients.</p> <p><b>Methods and results</b></p> <p>The Vascular Project includes structural (CIMT, carotid plaques) and functional (carotid stiffness) vascular studies in all patients showing at least one carotid plaque at entry. Expected mean follow-up is 36 months. Primary endpoint is rate of change of CIMT. Secondary endpoints include emergent plaques and assessment of carotid stiffness. 1,100 patients are required for 90% statistical power to detect treatment-related CIMT difference of 0.025 mm. The first patient was randomized in April 2006.</p> <p><b>Conclusions</b></p> <p>The PERFORM Vascular Project will investigate terutroban’s effect on vascular structure and function in patients with a history of ischemic stroke or TIAs.</p&gt

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal

Synthesis, characterization and biological activity of Cu(II), Zn(II) and Re(I) complexes derived from S-benzyldithiocarbazate and 3-acetylcoumarin.

International audienc

Conjugation of a New Series of Dithiocarbazate Schiff Base Copper(II) Complexes with Vectors Selected to Enhance Antibacterial Activity.

International audienceA new series of six Schiff bases derived from S-methyldithiocarbazate and S-benzyldithiocarbazate with methyl levulinate, levulinic acid and 4-carboxybenzaldehyde were reacted with copper(II), producing complexes of general formula ML2 (M = Cu(II), L = ligand). All compounds were characterized using established physico-chemical and spectroscopic methods. Crystal structures were determined for most of the Schiff bases and two Cu(II) complexes. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. The parent ligands and their respective copper(II) complexes exhibited moderate antibacterial activity against both Gram-negative and Gram-positive bacteria. The most active ligand and its analogous S-methyl derivative were conjugated with various vector moieties: polyarginines (R1, R4, R9 and RW9), oligoethylene glycol (OEG) and an efflux pump blocker, phenylalanine-arginine-β-naphthylamide (PAβN). Among the conjugates, nonarginine (R9) derivatives showed the most encouraging synergistic effect upon conjugation and complexation with copper ion with enhanced water solubility, bacteria cell membrane permeability and bioactivity. These Cu(II)-R9 derivatives display remarkable antibacterial activity against a wide spectrum of bacteria and in particular, are highly efficacious against Staphylococcus aureus with minimum inhibition concentration (MIC) values of 1-0.5 µM. This pioneer study clearly indicates that the conjugation of cell-penetrating peptides (CPPs) to dithiocarbazate compounds greatly enhances their therapeutic potential

Conjugation of a New Series of Dithiocarbazate Schiff Base Copper(II) Complexes with Vectors Selected to Enhance Antibacterial Activity

A new series of six Schiff bases derived from S-methyldithiocarbazate (SMDTC) and S-benzyldithiocarbazate (SBDTC) with methyl levulinate (SMML, SBML), levulinic acid (SMLA, SBLA), and 4-carboxybenzaldehyde (SM4CB, SB4CB) were reacted with copper­(II), producing complexes of general formula ML₂ (M = Cu­(II), L = ligand). All compounds were characterized using established physicochemical and spectroscopic methods. Crystal structures were determined for three Schiff bases (SMML, SBML, SBLA) and two Cu­(II) complexes (Cu­(SMML)₂ and Cu­(SMLA)₂). In order to provide more insight into the behavior of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. The parent ligands and their respective copper­(II) complexes exhibited moderate antibacterial activity against both Gram-negative and Gram-positive bacteria. The most active ligand (SB4CB) and its analogous S-methyl derivative (SM4CB) were conjugated with various vector moieties: polyarginines (R1, R4, R9, and RW9), oligoethylene glycol (OEG), and an efflux pump blocker, phenylalanine-arginine-β-naphthylamide (PAβN). Nonaarginine (R9) derivatives showed the most encouraging synergistic effects upon conjugation and complexation with copper ion including enhanced water solubility, bacteria cell membrane permeability, and bioactivity. These Cu­(II)-R9 derivatives display remarkable antibacterial activity against a wide spectrum of bacteria and, in particular, are highly efficacious against Staphylococcus aureus with minimum inhibitory concentration (MIC) values of 0.5–1 μM. This pioneer study clearly indicates that the conjugation of cell-penetrating peptides (CPPs) to dithiocarbazate compounds greatly enhances their therapeutic potential