One Anastomosis Gastric Bypass (OAGB) with a 150-cm Biliopancreatic Limb (BPL) Versus a 200-cm BPL, a Systematic Review and Meta-analysis.

This is a systematic review and meta-analysis that assessed the impact of performing OAGB with a 150-cm BPL versus a 200-cm BPL concerning weight loss, comorbidities remission, and adverse nutritional effects. The analysis included studies that compared patients who underwent OAGB with a 150-cm BPL and 200-cm BPL. Eight studies were eligible for this review after searching in the EMBASE, PubMed central database, and Google scholar. The pooled analysis revealed favoring the 200-cm BPL limb length for weight loss, with a highly significant difference in the TWL% (p=0.009). Both groups showed comparable comorbidities remission. Significantly higher ferritin and folate deficiency rates were found in the 200-cm BPL group. Considering a 200-cm BPL when performing OAGB delivers a better weight loss outcome than a 150-cm BPL, which is at the expense of a more severe nutritional deficiency. No significant differences were found regarding the comorbidities' remission.

Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors.

A naturally inspired chemical library of 25 molecules was synthesised guided by 3-D dimensionality and natural product likeness factors to explore a new chemical space. The synthesised chemical library, consisting of fused-bridged dodecahydro-2a,6-epoxyazepino[3,4,5-c,d]indole skeletons, followed lead likeness factors in terms of molecular weight, C-sp3 fraction and Clog P. Screening of the 25 compounds against lung cells infected with SARS-CoV-2 led to the identification of 2 hits. Although the chemical library showed cytotoxicity, the two hits (3b, 9e) showed the highest antiviral activity (EC50 values of 3.7 and 1.4 µM, respectively) with an acceptable cytotoxicity difference. Computational analysis based on docking and molecular dynamics simulations against main protein targets in SARS-CoV-2 (main protease Mpro, nucleocapsid phosphoprotein, non-structural protein nsp10-nsp16 complex and RBD/ACE2 complex) were performed. The computational analysis proposed the possible binding targets to be either Mpro or the nsp10-nsp16 complex. Biological assays were performed to confirm this proposition. A cell-based assay for Mpro protease activity using a reverse-nanoluciferase (Rev-Nluc) reporter confirmed that 3b targets Mpro. These results open the way towards further hit-to-lead optimisations.

Novel dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses.

Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CLpro) and the papain-like protease, to generate non-structural proteins essential for the virus life cycle. Both proteases are recognized as promising drug targets for the development of anti-coronavirus chemotherapy. Aiming at identifying broad spectrum agents for the treatment of COVID-19 but also to fight emergent coronaviruses, we focused on 3CLpro that is well conserved within this viral family. Here we present a high-throughput screening of more than 89,000 small molecules that led to the identification of a new chemotype, potent inhibitor of the SARS-CoV-2 3CLpro. The mechanism of inhibition, the interaction with the protease using NMR and X-Ray, the specificity against host cysteine proteases and promising antiviral properties in cells are reported.

Hemisynthetic alkaloids derived from trilobine are antimalarials with sustained activity in multidrug-resistant Plasmodium falciparum.

Malaria eradication requires the development of new drugs to combat drug-resistant parasites. We identified bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus that are active against Plasmodium falciparum blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed to identify compound 84 that kills multi-drug resistant clinical isolates in the nanomolar range (median IC50 ranging from 35 to 88 nM). Chemical optimization led to compound 125 with significantly improved preclinical properties. 125 delays the onset of parasitemia in Plasmodium berghei infected mice and inhibits P. falciparum transmission stages in vitro (culture assays), and in vivo using membrane feeding assay in the Anopheles stephensi vector. Compound 125 also impairs P. falciparum development in sporozoite-infected hepatocytes, in the low micromolar range. Finally, by chemical pull-down strategy, we characterized the parasite interactome with trilobine derivatives, identifying protein partners belonging to metabolic pathways that are not targeted by the actual antimalarial drugs or implicated in drug-resistance mechanisms.

A clinical guide to deep venous stenting for chronic iliofemoral venous obstruction.

BACKGROUND: An increase in endovenous interventions for deep venous pathologies has been observed. This article aims to provide an overview of the role of venous stenting in the management of chronic conditions affecting the deep venous system of the lower limbs, with a focus on intervention relating to the vena cava and iliofemoral venous segments. METHODS: An overview of the literature on the minimally invasive venous stenting procedures that are being increasingly used in the management of chronic conditions affecting the deep venous system of the lower limbs. RESULTS: We discuss key areas of interest to a venous specialist practicing in this area, including diagnostic imaging in chronic deep venous disease, with a focus on the use of intravascular ultrasound examination in this context; the treatment of chronic venous outflow obstruction, including the rationale and structural indications for stenting, current guidance regarding stent placement, and fundamental points to consider during decision-making (endophlebectomy and stenting, stenting across the inguinal ligament, optimal sizing of venous stents, extension of venous stenting to beyond the common femoral vein confluence, the role of thrombolysis useful in chronic venous disease, and arteriovenous fistulae); outcomes and initial reports of stenting; and the future of venous stents. CONCLUSIONS: Deep venous stenting has become a key treatment option for chronic (thrombotic or nonthrombotic) obstructive venous disease. Dedicated venous stents and intravascular ultrasound examination represent important technological advances in the minimally invasive treatment of symptomatic chronic deep venous obstruction, which previously required open surgical reconstruction.

Clinical outcomes and overview of dedicated venous stents for management of chronic iliocaval and femoral deep venous disease.

OBJECTIVES: Venous stenting of the lower extremities has grown in popularity and is now considered a key component of the primary treatment strategy for the management of pathologically obstructive or stenotic lesions of the deep venous system. This review aims to provide an overview of the role of venous stenting in the management of chronic conditions affecting the deep venous system of the lower limbs. METHODS: An overview of venous stents design and current role of stenting procedure in individuals presenting with Chronic Venous Insufficiency (CVI) and presenting the current trials of dedicated venous stenting in management of chronic deep venous lesions. This review provides a focused insight on venous stent design, physical properties and the available dedicated venous stents selected studies with their related patency outcome based on selective literature search of the PubMed database and Cochrane library. CONCLUSIONS: Dedicated venous stent technology is advancing at a rapid pace alongside the increased undertaking of endovascular deep venous stent reconstruction in the management of iliocaval vein pathologies. The ideal design(s) for venous stents remain unknown, although it is hoped that the presence of new dedicated venous stents in clinical practice will allow the generation of experience and data to advance our understanding in this area.

Impact of Bariatric Surgery on Male Sexual Health: a Prospective Study.

BACKGROUND: Obesity is a worldwide prevalent problem which negatively affects most of the human body systems. Male sexual dysfunction is a frequent problem in obese individuals. Nowadays, bariatric surgery is the most successful way for the management of morbid obesity. Recent research has concluded that it has a significant improving effect on sexual function. AIM OF THE STUDY: This study aimed to assess the long-term effect of bariatric surgery on male sexual function. PATIENTS AND METHODS: Sixty-six male patients indicated for bariatric surgery were enrolled in this prospective study. Only forty-eight of them completed the study. Patients were invited to fill the International Index of Erectile Function (IIEF) questionnaire twice, preoperatively (T1) and 12 months postoperatively (T2). Simultaneously, patients' serum testosterone levels were assayed. RESULTS: At T2, the patients showed highly significant increase in the IIEF scores and the serum testosterone levels (p<0.001). Only weight and BMI were significant predictors of the IIEF scores. The same factors as well as the patients' age were predictors of the serum testosterone levels. CONCLUSION: Bariatric surgery improves male sexual health. It is associated with significant increase in IIEF score and serum testosterone levels.

Uniportal video assisted thoracoscopy versus open surgery for pulmonary hydatid disease-a single center experience.

BACKGROUND: Although rare in the Western world, the incidence of hydatid disease is still prevalent and strikingly endemic among the Palestinians. Until 2017, surgical treatment of lung pathologies was performed through the traditional incision (open thoracotomy). Uniportal video-assisted thoracoscopic surgery (VATS) approach has recently been applied in the cases of the pulmonary hydatid cysts with very satisfactory results. METHODS: Between January 2010 and January 2019, 39 patients with pulmonary HC disease have been surgically treated. The cases divided into two cohorts: operations performed by thoracotomy classified as group A, (n=16). Operations performed by uniportal VATS classified as group B, (n=23). Prospectively collected data was analysed retrospectively, and the results compared between both groups. RESULTS: No significant statistical differences were noticed in terms of demographics and comorbidity. Laboratory tests were similar except haemoglobin level, which was higher in group A (P=0.001). Despite that, blood transfusion was higher in group A (P=0.016). Moreover, operation time was longer in group A (P=0.000). Chest drainage remained longer in group A (P=0.077). The level of postoperative pain was significantly higher in group A certainly in POD 1 (P=0.000). Patients in group B discharged earlier from the hospital (P=0.011) and experienced lower complications (P=0.060). No significant difference in length of ICU stay. Neither recurrence nor 30-day mortality recorded in either group. CONCLUSIONS: Uniportal VATS can be safely applied for pulmonary hydatidosis. It also seems to have a preference in several aspects compared to open Thoracotomy approach.

Design and synthesis of a fragment set based on twisted bicyclic lactams.

Current fragment sets tend to be dominated by flatter molecules, and their shape diversity does not reflect that of the fragments that are theoretically possible. The design and synthesis of a set of bridged fragments containing a bridgehead nitrogen is described. Many of these fragments contain twisted lactams whose modulated electronic properties may present unusual opportunities for interaction with target proteins. The demonstrated novelty, three-dimensionality and molecular properties of the set of 22 fragments may provide valuable, and highly distinctive, starting points for fragment-based drug discovery.

Free-Radical Carbocyanation of Olefins.

The free-radical three-component carbocyanation of electron-rich olefins was investigated with p-tosyl cyanide as cyanide source. The scope and limitations of the process were established by varying the nature of the alkene and radical precursor. Carbocyanation of chiral allylsilanes was shown to occur with high diastereocontrol, leading to syn ß-silyl nitriles. The origin of the stereocontrol was rationalized by a Felkin-Anh-type transition-state model. Finally, a tin-free carbocyanation process was also devised, based on the use of a new alkylsulfonyl cyanide incorporating both carbon fragments to be added across the olefinic π system.

Total Synthesis of (±)-Eucophylline. A Free-Radical Approach to the Synthesis of the Azabicyclo[3.3.1]nonane Skeleton.

The first total synthesis of eucophylline was reported in 10 steps and 10% overall yield. The naphthyridine core of eucophylline was prepared through the coupling between a strained azabicyclo[3.3.1]nonan-2-one and a trisubstituted benzonitrile, followed by a cyclization of the corresponding amidine. This coupling reaction was shown to proceed through a stable bicyclic chloroenamine intermediate. The azabicyclo[3.3.1]nonan-2-one skeleton was in turn accessible through a straightforward sequence including a free-radical three-component olefin carbo-oximation as a key step.

Multiple left ventricular myxomas arising from the interventricular septum and ventricular trabeculae: a case report.

Myxoma is the most common tumor of the heart, with an estimated incidence of 0.5 to 1 per million per year. The majority of these tumors arise from the left atrium, and 20% arise from the right atrium with the remaining 5% arising in either the right or left ventricle. We present a rare case of multiple myxomas of the left ventricle arising from the interventricular septum and nearby ventricular trabeculae that clinically presented with an occlusion of the left axillary artery. The patient was successfully treated using cardiopulmonary bypass, during which the tumor was completely removed using a transventricular approach.