Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

<p>Abstract</p> <p>Background</p> <p>Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against <it>Anopheles culicifacies </it>and <it>Anopheles stephensi </it>for its possible use in vector control.</p> <p>Methods</p> <p>Efficacy of chlorfenapyr against <it>An. culicifacies </it>and <it>An. stephensi </it>was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of <it>An. culicifacies</it>.</p> <p>Results</p> <p>A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of <it>An. culicifacies </it>species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible <it>An. culicifacies </it>species A (0.41 and 2.0% respectively) and <it>An. stephensi </it>strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m²on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against <it>An. culicifacies </it>and up to 34 weeks against <it>An. stephensi</it>. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of <it>An. stephensi </it>and field-caught <it>An. culicifacies. </it>Potentiation studies demonstrated the antagonistic effect of PBO.</p> <p>Conclusion</p> <p>Laboratory studies with susceptible and resistant strains of <it>An. culicifacies </it>and <it>An. stephensi</it>, coupled with limited field studies with multiple insecticide-resistant <it>An. culicifacies </it>have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.</p

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Transcatheter pulmonary valve perforation using chronic total occlusion wire in pulmonary atresia with intact ventricular septum

Background: Perforation of pulmonary valve using radiofrequency ablation in pulmonary atresia with intact ventricular septum (PA IVS) is a treatment of choice. However, significant cost of the equipment limits its utility, especially in the developing economies. Objective: To assess the feasibility, safety, and efficacy of perforation of pulmonary valve using chronic total occlusion (CTO) wires in patients with PA IVS as an alternative to radiofrequency ablation. Methods: This is a single.center, nonrandomized, retrospective study conducted during June 2008 to September 2015. Twenty-four patients with PA IVS were selected for the procedure during the study period. The median age and weight of the study population were 8. days and 2.65 kg, respectively. Four patients were excluded after right ventricular angiogram as they showed right ventricular-dependent coronary circulation. The pulmonary valve perforation was attempted using various types of CTO wires based on the tip load with variable penetrating characteristics. Results: The procedure was successful in 16 of twenty patients using CTO wires: Shinobi in nine, Miracle in four, CROSS-IT in two, and Conquest Pro in one. Two patients had perforation of right ventricular outflow tract (RVOT). Pericardiocentesis was required in one patient to relieve cardiac tamponade. Later, the same patient underwent successful hybrid pulmonary valvotomy. The other patient underwent ductus arteriosus. (DA) stenting. Balloon atrial septostomy was needed in three cases with systemic venous congestion. Desaturation was persistent in five cases necessitating DA or RVOT stenting to augment pulmonary blood flow. There were two early and two late deaths. The mean follow-up was 22.66. ± 16 months. Three patients underwent one and half ventricle repair and one Blalock-Taussig shunt during follow-up. Conclusion: Perforation of the pulmonary valve can be done successfully using CTO wires in selected cases of pulmonary atresia with intact ventricular septum

Diagnosis and management of aorto-left ventricular tunnel

Background: Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel with progressive left ventricular dilatation needs early correction. Materials and Methods: This is a report of diagnosis and management of aorto-left ventricular tunnel (ALVT) over a period of 11 years from a single institution. Seven patients (age range: 7 days-45 years) presented with heart failure. The diagnosis of ALVT was made by transthoracic echocardiogram in all cases. Results: Treatment was refused by two patients who died during follow-up. Surgical closure of the tunnel was done in four cases, of which one needed Bentall procedure. Two patients had residual leak after the surgery. Transcatheter closure using Amplatzer muscular device was performed in two cases (for postoperative residual leak in one and primary procedure in the other). Significant hemolysis developed in one of them, necessitating the removal of the device and closed surgically. This child underwent aortic valve replacement two years later. All the remaining patients were doing well during the median follow-up of 30 months (range: 1.5-9 years). Conclusion: ALVT is a rare and potentially fatal anomaly that is ideally managed surgically. Catheter closure has a limited role

Evaluation of hepatoprotective and antioxidant activity of Ichnocarpus frutescens (Linn.) R.Br. on paracetamol-induced hepatotoxicity in rats

Purpose: The entire plant including the flowers, of Ichnocarpus frutescens R.Br. (Apocynaceae) has been used for the treatment of cancer, skin infections, diabetes and liver disorder. The present study is aimed at evaluating the hepatoprotective effect of chloroform and methanol extract (CEIF and MEIF) of whole plant of I. frutescens (Linn.) by paracetamol-induced liver damage in rats. Methods: The chloroform and methanolic extracts of I. frutescens (CEIF and MEIF) were studied for their hepatoprotective and antioxidant effects on paracetamol (750mg/kg) induced acute liver damage on Wistar albino rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin and total protein. Further, the effects of both extracts on lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were estimated. Results: CEIF and MEIF at a dose level of 250mg/kg and 500mg/kg produce significant (P<0.05) hepatoprotection by decreasing the activity of serum enzymes, bilirubin, and lipid peroxidation, while they significantly increased the levels of Glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in a dose dependent manner. The effects of CEIF and MEIF were comparable to that of standard drug, Silymarin. Conclusion: From this study, it can be concluded that the chloroform and methanol extract of I. frutescens is not only an effective hepatoprotective agent, but also possesses significant (p<0.05) antioxidant activity

Vertical Distribution of Available Nutrients in Boudh Block of Boudh District Catena

An investigation was conducted to analyse the distribution of available plant nutrients and to examine the relationships between soil properties and available nutrient status in soil profiles of Eastern India. Three soil profiles were exposed under three different topographic positions. In all the pedons, soil reaction (pH) was increasing and EC was very nominal because there is no accumulation of dissolved salts in the soil pedons. The status of available N was decreasing with soil depth and phosphorus (P) was increased with depth of soil, Organic carbon (OC) was unevenly distributed with the depth of soil, sulphur was also unevenly distributed with depth of soil which is comparable with the (OC). There is similar trend between pH and P