Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO) : 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group

Background: Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. Methods: The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Recommendations: Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. Discussion: This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited.Peer reviewe

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Cartographie des directions dominantes des vents au Benin : Outil de conception et de dimensionnement des ouvrages

La présente étude a pour objet de déterminer les directions dominantes du vent et d'établir une carte région-vent du Bénin. Pour ce faire, nous avons, après la collecte des informations météorologiques, procédé : - à l’analyse des données (directions) des six stations météorologiques principales conformément aux méthodes statistiques. Ces données couvrent une période de 23 ans ; - au moyen des techniques numériques, à l’analyse des variations des directions ; - à l’analyse selon la norme AFNOR de l’influence du relief et de la végétation sur les directions. A l’issue de cette étude, nous avons établi des cartes régions appropriées. The present study aims to determine dominant directions of the wind and to establish a wind-region map of Benin. In order to do that, we have after the collection of meteorological information carried out: - the analysis of data (directions) of the six main meteorological stations in accordance with statistical methods. These data cover a period of 23 years; - the analysis of the variations of directions by means of numerical techniques; - the analysis of the influence of the relief and the vegetation on directions according to AFNOR norms. At the end of this study, we established appropriate regions maps

Dosimetrie et radioprotection des patients lors des examens tomodensitomtriques au Chu Sylvanus Olympio (CHU-SO) de Lomé (Togo)

Méthodologies : Etude rétrospective des rapports de doses de 660 scanners de la tête,du thorax, de l’abdomen et du pelvis des adultes de plus 15 ans réalisés au pavillonscanner du CHU-SO de juillet à décembre 2011.Résultats : La tête était la région la plus explorée (565), suivie de thorax (43), del’abdomen (33) et enfin du pelvis (19). On notait une prédominance masculine avec unratio de 1,5 homme pour une femme. La tranche d’âge la plus représentée était latranche 46-51 ans. Les CTDI vol moyens étaient de 61,5 mGy pour les scanners de latête, 8,7mGy pour le thorax, 70,9 mGy pour l’abdomen et 2,8 mGy pour le pelvis. LesDLP moyens étaient de 1850mGy/cm pour les scanners de la tête, 281,8 mGy/cm pourle thorax, 476,2 mGy/cm pour l’abdomen et 351,6 pour le pelvis. Quatre cent quarantequatrescanners (78,58%) de la tête avaient une dose supérieure à 2,2 mSv. Pour lesscanners du thorax, 4 (9,30%) dépassaient les 8,5 mSv, 24,24% (8/33) des scanners del’abdomen dépassaient 9,8 mSv et 47,37%(9/19) des scanners du pelvis avaient uneexposition supérieure à 7,2 mSv.Conclusion : Il ressort de notre étude que les doses délivrées aux patients lors desexamens TDM sont supérieurs aux NRD françaises et européennes, surtout pour la tête.Mots clés : Dosimétrie, radioprotection, tomodensitométrie, crâne, Lomé.ABSTRACTMethodology: A retrospective study doses reports of 660 scans of the head, thorax,abdomen and pelvis of adults over 15 years made in the CHU-SO from July toDecember 2011.Results: The head was the most explored region (565), followed by chest (43), abdomen(33) and the pelvis (19). We noted a male predominance with a male ratio of 1.5 for awoman. The most represented age group was the 46-51 year bracket. The CTDI volmeans were 61.5 mGy for scanners of the head, thorax 8,7mGy, 70.9 mGy for theabdomen and 2.8 mGy for the pelvis. The DLP means were 1850mGy / cm for scannersof the head, 281,8mGy / cm for the thorax, 476,2mGy / cm, and 351.6 for the abdomenand pelvis. Four hundred forty-four scanners (78.58%) of the head had a dose higherthan 2.2 mSv. For scanners chest, 4 (9.30%) exceeded 8.5 mSv, 24.24% (8/33) of theabdomen scanners exceeded 9.8 mSv and 47.37% (9/19) of pelvic scanners were greaterthan 7,2mSv exposure.Conclusion: Our study shows that patient dose during CT examinations are superior tothe French and European DRLs, especially for the head.Keywords: Dosimetry, radioprotection, CT, head, Lome

Progress from morbidity control to elimination as a public health problem of schistosomiasis and the status of soil-transmitted helminth infection in Togo: a second impact assessment after ten rounds of mass drug administration

Abstract Background Due to the burden of schistosomiasis (SCH) and soil-transmitted helminths (STH), Togo Ministry of Health launched a program for Preventive Chemotherapy Neglected Tropical Diseases (PC-NTDs) in 2009, initiating integrated mass drug administration (MDA) the following year for the three PC-NTDs: SCH, STH and onchocerciasis. Significant reduction of infection across the country was noted in 2015 during the first impact assessment, following 5 years of high-coverage MDA implemented at the sub-district level for SCH and district level for STH. After another 5 years of effective MDA, a second survey was conducted in 2021 to re-evaluate the situation of SCH and STH. Methods A cross-section of school-aged children was taken across ten districts of Togo. A total of 302 schools in 92 sub-districts were sampled, with 24 school-aged children per school resulting in 7248 children surveyed. Urine samples were tested by haemastix® for Schistosoma haematobium, with urine filtration for the presence of eggs conducted on haematuria-positive samples. Stool samples were collected in a subset of 34 sub-districts in seven out of the ten surveyed districts, where STH and Schistosoma mansoni endemicity was high during the 2015 impact assessment. Duplicate (two) Kato-Katz analysis was performed for each stool sample. Sociodemographic and school-level water, sanitation and hygiene information was also collected. Results Overall, SCH prevalence was 5.90% (95% CI: 5.4–6.5), with 5.09% (95% CI: 4.64–5.67) for S. haematobium and 2.56% (95% CI: 1.98–3.29) for S. mansoni. STH prevalence was 19.7% (95% CI: 18.2–21.4), with 19.6% (95% CI: 18.1–21.3) hookworm, 0.08% (95% CI: 2.2–5.8) Trichuris trichiura and 0.04% (95% CI: 0.01–0.33) Ascaris lumbricoides. Compared to baseline, a significant reduction in both SCH (22.2% to 5.90%) and STH (29.2% t0 19.7%) prevalence was observed. Children aged 5–9 years were less infected than older peers aged 10–14 years: 4.76% vs. 7.53% (P < 0.01) for SCH and 17.2% vs. 23.0% (P < 0.01) for STH. Conclusions After 10 years of high coverage integrated MDA, Togo has achieved low prevalence SCH infection through the sub-district MDA implementation with considerable infection heterogeneity within sub-districts. As STH infection has not reached a level where the infections are not a public health problem, the sub-district treatment strategy could also be adopted in addition to improvement of treatment coverage among preschool age children and hygiene and sanitation practices. Graphical Abstrac