Extraocular Muscle Imbalance and Outcomes of Scleral Buckling Surgery for Primary Rhegmatogenous Retinal Detachment

Objective: The objective was to study the muscle imbalance, restrictive motility in unlike gazes and the outcomes of the scleral buckling surgery for rhegmatogenous retinal detachment. Study design: Prospective follow-up study Settings and duration: The study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from Aug 2015 to Jan 2016. Methodology: The patients were checked prior to surgery and two follow up visits were done afterwards. Thorough history was taken along with full orthoptic assessment and ocular motility in all four main gazes including elevation, depression, adduction and abduction. Vision, type and position of explants, site of detachment, and risk factors of detachment were also observed. Results: A total of 48 eyes of 46 patients were taken. Mean age of the study participants was 37.16±20.37 years. Horizontal, vertical and combined deviations were observed in study population. Exo deviation was most common deviation among patients. Most reported risk factors of retinal detachment included trauma, pseudophakia, aphakia and myopia. Motility limitations of all four gazes was observed and it was found out that after buckling the squint and restriction is been increased up till two months. Conclusion: Ocular restriction among the patients was observed over a period of 2 months and it depicted that encircling with sclera buckling elicited an increase in restrictive ocular motility from pre-operative to 1 week and 2 months after surgery

Whipple's pancreaticoduodenectomy: perioperative outcomes in a tertiary care hospital in Dhaka, Bangladesh

Background: Pancreaticoduodenectomy is one of the most complex surgery with significant mortality and morbidity. Though the mortality rate has steadily improved, morbidity continues to be high. The aim of this study was to demonstrate the perioperative outcome following this procedure at our hospital.Methods: This retrospective study was conducted in the department of Surgery, Sir Salimullah medical college and Mitford hospital from July 2018 to December 2019. A total of 29 patients who undergone pancreaticoduodenectomy were included in the study. Preoperative, intra-operative and post-operative data were analyzed with emphasis on the morbidity and mortality rates. None of the operated patients received any types of neoadjuvant therapy.Results: Out of 29 patients who underwent PD, 18 (62.1%) were male and 11 (37.9%) were female with a median age of 53.7 years. The most common (34.5%) age group of the patients were 51-60 years. Jaundice was the commonest (89.7%) presenting symptoms followed by anorexia (75.9%) and abdominal pain (48.3%). Overall complications occurred in 37.9% patients, including wound infections (31.0%) and post-operative pancreatic fistula (6.9%). The post-operative mortality rate was 6.9%.Conclusions: PD still causes considerable morbidity and mortality. With careful patient selection, adequate preoperative preparation, surgical technique, excellent critical care management PD can be performed safely. At our center we have a reasonable volume and our data are comparable to literature data.

Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia. METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, - 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO(2)/FiO(2) = 101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04345614

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention

Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC

A streptococcus pneumoniae lineage usually associated with pneumococcal conjugate vaccine (PCV) serotypes is the most common cause of serotype 35B invasive disease in South Africa, following routine use of PCV

Pneumococcal serotype 35B is an important non-conjugate vaccine (non-PCV) serotype. Its continued emergence, post-PCV7 in the USA, was associated with expansion of a pre-existing 35B clone (clonal complex [CC] 558) along with post-PCV13 emergence of a non-35B clone previously associated with PCV serotypes (CC156). This study describes lineages circulating among 35B isolates in South Africa before and after PCV introduction. We also compared 35B isolates belonging to a predominant 35B lineage in South Africa (GPSC5), with isolates belonging to the same lineage in other parts of the world. Serotype 35B isolates that caused invasive pneumococcal disease in South Africa in 2005-2014 were characterized by whole-genome sequencing (WGS). Multi-locus sequence types and global pneumococcal sequence clusters (GPSCs) were derived from WGS data of 63 35B isolates obtained in 2005-2014. A total of 262 isolates that belong to GPSC5 (115 isolates from South Africa and 147 from other countries) that were sequenced as part of the global pneumococcal sequencing (GPS) project were included for comparison. Serotype 35B isolates from South Africa were differentiated into seven GPSCs and GPSC5 was most common (49 %, 31/63). While 35B was the most common serotype among GPSC5/CC172 isolates in South Africa during the PCV13 period (66 %, 29/44), 23F was the most common serotype during both the pre-PCV (80 %, 37/46) and PCV7 period (32 %, 8/25). Serotype 35B represented 15 % (40/262) of GPSC5 isolates within the global GPS database and 75 % (31/40) were from South Africa. The predominance of the GPSC5 lineage within non-vaccine serotype 35B, is possibly unique to South Africa and warrants further molecular surveillance of pneumococci

Reconstructing the infrared spectrum of a peptide from representative conformers of the full canonical ensemble

Leucine enkephalin (LeuEnk), a biologically active endogenous opioid pentapeptide, has been under intense investigation because it is small enough to allow efficient use of sophisticated computational methods and large enough to provide insights into low-lying minima of its conformational space. Here, we reproduce and interpret experimental infrared (IR) spectra of this model peptide in gas phase using a combination of replica-exchange molecular dynamics simulations, machine learning, and ab initio calculations. In particular, we evaluate the possibility of averaging representative structural contributions to obtain an accurate computed spectrum that accounts for the corresponding canonical ensemble of the real experimental situation. Representative conformers are identified by partitioning the conformational phase space into subensembles of similar conformers. The IR contribution of each representative conformer is calculated from ab initio and weighted according to the population of each cluster. Convergence of the averaged IR signal is rationalized by merging contributions in a hierarchical clustering and the comparison to IR multiple photon dissociation experiments. The improvements achieved by decomposing clusters containing similar conformations into even smaller subensembles is strong evidence that a thorough assessment of the conformational landscape and the associated hydrogen bonding is a prerequisite for deciphering important fingerprints in experimental spectroscopic data.</p

Multi-insecticide resistant malaria vectors in the field remain susceptible to malathion, despite the presence of Ace1 point mutations

Insecticide resistance in Anopheles mosquitoes is seriously threatening the success of insecticide-based malaria vector control. Surveillance of insecticide resistance in mosquito populations and identifying the underlying mechanisms enables optimisation of vector control strategies. Here, we investigated the molecular mechanisms of insecticide resistance in three Anopheles coluzzii field populations from southern Cote d'Ivoire, including Agboville, Dabou and Tiassale. All three populations were resistant to bendiocarb, deltamethrin and DDT, but not or only very weakly resistant to malathion. The absence of malathion resistance is an unexpected result because we found the acetylcholinesterase mutation Ace1-G280S at high frequencies, which would typically confer cross-resistance to carbamates and organophosphates, including malathion. Notably, Tiassale was the most susceptible population to malathion while being the most resistant one to the pyrethroid deltamethrin. The resistance ratio to deltamethrin between Tiassale and the laboratory reference colony was 1,800 fold. By sequencing the transcriptome of individual mosquitoes, we found numerous cytochrome P450-dependent monooxygenases - including CYP6M2, CYP6P2, CYP6P3, CYP6P4 and CYP6P5 - overexpressed in all three field populations. This could be an indication for negative cross-resistance caused by overexpression of pyrethroid-detoxifying cytochrome P450s that may activate pro-insecticides, thereby increasing malathion susceptibility. In addition to the P450s, we found several overexpressed carboxylesterases, glutathione S-transferases and other candidates putatively involved in insecticide resistance