Use of Endoscopic Vein Harvest Yields Improved Outcomes in Popliteal Artery Aneurysm Repair.

BACKGROUND: There is growing literature showing that endoscopic vein harvest (EVH) is safe, with excellent patency rates and decreased wound complications when treating infrainguinal occlusive disease. Our institution has performed EVH since 2003 with a dedicated team of providers specializing in endoscopic vein harvest. The purpose of this study was to evaluate major outcomes of EVH as an adjunct to standard, open operative repair of popliteal artery aneurysms. METHODS: We performed a 12-year retrospective single-institution chart review from January 2005 to December 2017, identifying all patients undergoing popliteal artery aneurysm repair with EVH. Primary outcomes were procedural technical success, operative time, wound complication, major morbidity, and freedom from amputation. RESULTS: A total 37 limbs (in 31 patients) received EVH popliteal artery aneurysm repair at an average age of 65.2 ± 10 years; 65% of the patients presented without symptoms or with claudication and 35% with rest pain or tissue loss. Coexisting aneurysm was present in 68% of patients: 49% had contralateral popliteal artery aneurysms and 19% had concurrent aortic aneurysms. Of 37 limbs, 33 (89%) were treated through a medial approach with aneurysm ligation, and 4 patients (11%) were treated through a posterior approach. The average vein size was 4.4 ± 1.1 mm, with 86% harvested by the ipsilateral great saphenous vein. Average operative time was 3.89 ± 0.82 hr, with a median hospitalization of 2 days and a median of 1 day of intravenous narcotics use. Only 2 patients (5.4%) had Szilagyi class-2 surgical site infections remedied with debridement and antibiotics. Kaplan-Meier data showed a 5-year primary patency of 82.3% and primary-assisted patency of 88.2%. Additionally, 30-day primary patency was 89.2% and primary-assisted patency of 97.3%. CONCLUSIONS: EVH for popliteal aneurysmal disease provides a safe and efficacious means of popliteal artery aneurysm repair with shorter hospitalization, lower wound complication rates, and excellent long-term patency compared to standard open technique.

Ten-year experience of infrainguinal bypass with endoscopic vein harvest.

OBJECTIVES: There is conflicting data comparing minimally invasive vein harvest (MIVH) using endoscopic technique and open vein harvest (OVH) in terms of bypass patency, wound infection incidence, and patient morbidity. Our institution has performed MIVH since 2003 for peripheral bypass procedures with a consistent team of specialized endoscopic vein harvesters. This study reviewed the major outcomes of MIVH infrainguinal bypass at our institution given a predominant cohort of critical limb ischemia. METHODS: We performed a 10-year, retrospective, single-institution review from January 2005 to December 2014, identifying all patients undergoing MIVH for obstructive infrainguinal disease. Primary outcomes were primary patency, operative time, intraoperative complications, surgical site infection (SSI), and freedom from amputation. RESULTS: A total of 289 patients (70% male) underwent MIVH infrainguinal bypass at an average age of 68 ± 12 years old, an obesity prevalence of 28%, and with critical limb ischemia in 81% of the patient cohort (20% rest pain, 61% tissue loss/gangrene). Ninety-four percent of patients had no intraoperative complications, 2.5% had adverse cardiac or technical complications, and 4.2% of patients required transfusion. Average operative time was 4.2 h. Femoral-popliteal TASC classification C and D constituted 80% of our patient cohort. At the last follow-up, toe pressures had increased from 30 ± 30 to 62 ± 40 mmHg (p < 0.0001). Primary bypass patency in the first 30 days was 95%. SSI incidence requiring surgical treatment was only 6%. Our median length of stay was 4.0 days, with median intravenous narcotic use of 1 day. In addition, 77% of patients returned to their baseline mobility at first follow-up (median 19 days), and 83% of patients had freedom from amputation at last follow-up (median 820 days). CONCLUSIONS: In a center with experience in MIVH and a consistent group of experienced endoscopic vein harvesters, MIVH bypass has excellent patency, low surgical site infection, short length of stay, and prompt return to baseline mobility.

Synthesis and evaluation of novel S-benzyl- and S-alkylphthalimide- oxadiazole -benzenesulfonamide hybrids as inhibitors of dengue virus protease.

Direct acting antiviral drugs (DAADs) are becoming therapeutics of choice for the treatment of viral infections. Successful development of anti HIV and HCV drugs by targeting the viral proteases has provided impetus for discovering newer DAADs. Dengue virus (DENV) protease, which is composed of two nonstructural proteins, NS2B and NS3pro, can be likewise exploited for discovering new anti-dengue therapeutics. In this study, we have linked together two pharmaceutically interesting motifs, namely 1,3,4-oxadiazole and benzenesulfonamide in two alternative series to develop novel S-benzylated and S-alkylphthalimidated hybrids. For the first series of hybrids, 4-aminobenzoic acid (1) was reacted with substituted benzenesulfonyl chlorides via its amino group, whereas the carboxylic acid side was elaborated to sulfonamido-1,3,4-oxadiazole-2-thiols (6a/b) in three steps. At this stage, the intermediates 6a/b were bifurcated to either S-alkylphthalimidated (8a-j) or S-benzylated (9a-c) hybrids by reacting with corresponding halides. For the alternative series of hybrids, the carboxylic acid group of probenecid (10) was similarly elaborated to sulfonamido-1,3,4-oxadiazole-2-thiols (13), and diverged to S-alkylphthalimidated (14a-f) and S-benzylated hybrids (15a-e). Bioactivity assays demonstrated that 8g and 8h are the most potent inhibitors among the synthesized analogs, exhibiting the IC50 values of 13.9 µM and 15.1 µM, respectively. Computational assessment predicted the binding of the inhibitors at an allosteric site developed in the open conformation of DENV2 NS2B/NS3pro. Taken together these findings point out that the synthesized hybrid inhibitors possess a great potential for further antiviral drug development.

Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities.

Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.

Complications after discharge predict readmission after colorectal surgery.

BACKGROUND: Health care providers, hospitals, and pay-for-performance programs are focused on strategies identifying patients at highest risk for re-admission after colorectal surgery. The study objective was to determine characteristics most associated with re-admission after elective colorectal surgery using a conceptual framework approach. METHODS: This is an observational study of Michigan Surgical Quality Collaborative clinical registry data for 8962 colorectal surgery cases between July-2012 and April-2015. Separate mixed models were fit using known re-admission risk factors aligned in categories that may impact re-admissions by different mechanisms. Overall model discrimination was evaluated using Area Under the Curve estimated on a hold-out data set and examining differences in predicted versus observed re-admission across risk quintiles. RESULTS: The overall 30-day re-admission rate was 10.5%. From Model 1 to Model 6, discrimination of re-admission was poor until Model 6 (AUC, 0.56, 0.61, 0.65, 0.63, 0.72, 0.81). Differences for observed re-admission rates comparing 'very low' versus 'very high' risk strata from Model 1 to Model 6 were 6%, 11%, 15%, 14%, 20%, and 30% respectively, and all comparisons were significant (p < 0.01). Though there were significant predictors in the first five models, most were no longer significant when additional predictors were included in subsequent models. Complications identified after discharge significantly increased the likelihood of re-admission and were the strongest predictors. CONCLUSION: Statistical models that include complications identified after discharge predict re-admission. Strategies to reduce re-admission after colorectal surgery should emphasize prevention of complications and more effective interventions to manage and ameliorate evolving complications identified after discharge.

Harnessing bio-based chelating agents for sustainable synthesis of AgNPs: Evaluating their inherent attributes and antimicrobial potency in conjunction with honey.

Greenly synthesized nanoparticles have garnered attention due to their low environmental footprint, but impurities limit their applications. A novel semi-organic method for synthesizing silver nanoparticles (AgNPs) using bio-based chelating fuels (Beta vulgaris subsp., Spinacia oleracea, and Ipomoea batatas) reduces the undesirable impurities. The study also showcases the impact of bio-based chelating fuel on various characteristics of AgNPs in comparison to synthetic chelating fuel. The antimicrobial efficacy of the synthesized AgNPs in conjunction with honey was also assessed against E. coli. The XRD analysis showed cubic structure of AgNPs. The FESEM and TEM analysis showed that the well-connected spherical-shaped AgNPs (∼3-120 nm diameter) while EDS confirmed the presence of Ag in all samples. The TEM analysis also revealed layers of carbonates in AgNPs synthesized using bio-based chelating fuels. XPS investigation confirmed the absence of any prominent impurities in prepared samples and AgNPs have not experienced oxidation on their surface. However, notable surface charging effects due to the uneven conductivity of the particles were observed. The broth dilution method showed that all mixtures containing AgNPs in combination with honey exhibited a significant bacterial growth reduction over a period of 120 h. The highest growth reduction of ∼75 % is obtained for the mixture having AgNPs (Ipomoea batatas) while the least growth reduction of ∼51 % is obtained for the mixture having AgNPs (Beta vulgaris subsp.). The findings affirm that AgNPs can be successfully synthesized using bio-based chelating fuels with negligible ecological consequences and devoid of contaminants. Moreover, the synthesized AgNPs can be employed in conjunction with honey for antibacterial purposes.

What makes for effectiveness when starting early - Learning from an integrated school-based violence and abuse prevention programme for children under 12.

BACKGROUND: Integrated programmes addressing varying forms of violence and abuse are increasingly delivered to children under 12 but uncertainty remains about what should be delivered to whom, when and in what dose. OBJECTIVE: To examine the impact of Speak Out Stay Safe (SOSS) - an integrated prevention programme for children under 12 - and whether impact varied by age, gender and context. PARTICIPANTS AND SETTING: A representative UK sample of primary schools in receipt of SOSS was matched with comparison schools not receiving SOSS. At 6 months follow-up, 1553 children from 36 schools completed the survey. METHODS: The matched control study incorporated economic and process evaluations. Survey measures included: children's knowledge and understanding of different forms of violence and abuse, readiness to seek help, knowledge of sexual abuse, perceptions of school culture and health and wellbeing. Perceptions of children, teachers, and facilitators were captured. RESULTS: At 6 months, children aged 9-10 who received SOSS retained their improved knowledge of neglect and their ability to identify a trusted adult who they would tell about violence or abuse. Children aged 6-7 receiving a shorter version of the programme were less likely to benefit and boys made fewer gains than girls. SOSS improved the knowledge of children with low knowledge of abuse. School culture was closely associated with programme impact. CONCLUSION: School-based prevention programmes deliver benefits at low cost but should acknowledge and engage with the specific school context to achieve school readiness and embed programme messages.

Synthetic flavonoids as potential antiviral agents against SARS-CoV-2 main protease.

The COVID-19 pandemic has claimed more than a million lives worldwide within a short time span. Due to the unavailability of specific antiviral drugs or vaccine, the infections are causing panic both in general public and among healthcare providers. Therefore, an urgent discovery and development of effective antiviral drug for the treatment of COVID-19 is highly desired. Targeting the main protease (Mpro) of the causative agent, SARS-CoV-2 has great potential for drug discovery and drug repurposing efforts. Published crystal structures of SARS-CoV-2 Mpro further facilitated in silico investigations for discovering new inhibitors against Mpro. The present study aimed to screen several libraries of synthetic flavonoids and benzisothiazolinones as potential SARS-CoV-2 Mpro inhibitors using in silico methods. The short-listed compounds after virtual screening were filtered through SwissADME modeling tool to remove molecules with unfavorable pharmacokinetics and medicinal properties. The drug-like molecules were further subjected to iterative docking for the identification of top binders of SARS-CoV-2 Mpro. Finally, molecular dynamic (MD) simulations and binding free energy calculations were performed for the evaluation of the dynamic behavior, stability of protein-ligand complex, and binding affinity, resulting in the identification of thioflavonol, TF-9 as a potential inhibitor of Mpro. The computational studies further revealed the binding of TF-9 close to catalytic dyad and interactions with conserved residues in the S1 subsite of the substrate binding site. Our in-silico study demonstrated that synthetic analogs of flavonoids, particularly thioflavonols, have a strong tendency to inhibit the main protease Mpro, and thereby inhibit the reproduction of SARS-CoV-2. Communicated by Ramaswamy H. Sarma.

Postharvest shelf life enhancement of peach fruit treated with glucose oxidase immobilized on ZnO nanoparticles.

For the shelf life extension of fruits, we envisioned a novel antimicrobial approach that is based on the production of a thin layer of hydrogen peroxide at the surface of food by utilizing the bioactivity of glucose oxidase (GOx). The enzyme, purified from Aspergillus Niger, was immobilized on zinc oxide nanoparticles and then suspended in a buffer to prepare a spraying solution of GOx/ZnONPs. Post-immobilization analyses indicated that immobilized enzyme showed higher activity as compared to the free enzyme. The GOx/ZnONPs spray was applied for postharvest treatment of peach. The control and treatment groups were stored at ambient conditions for fifteen days and standard quality parameters were analyzed. In contrast to the control group, the GOx/ZnONPs spray treatment was remarkably effective in maintaining the physiological appearance of fruits even more than 12 days and showed a significant reduction in the decrease of weight, firmness, TSS, and DPPH free radical scavenging activity of fruits. Thus GOx/ZnONPs is an excellent platform to extend the postharvest shelf life of peach.

B cell receptor (BCR) guided mechanotransduction: Critical hypothesis to instruct SARS-CoV-2 specific B cells to trigger proximal signalling and antibody reshaping.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, has spread around the globe with remarkable consequences for the health of millions of people. Despite the approval of mRNA vaccines to prevent the spread of infection, long-term immunity must still be monitored. Targeting and modifying virus receptor binding regions to activate B cell receptors (BCRs) is a promising way to develop long-term immunity against SARS-CoV-2. After the interaction of antigens, BCRs undergo series of signal transduction events through phosphorylation of immune receptor tyrosine activation motifs (ITAMs) to produce neutralizing antibodies against pathogens. BCRs intricate entity displays remarkable capability to translate the external mechanosensing cues to reshape the immune mechanism. However, potential investigations suggesting how SARS-CoV-2 specific B cells respond to mechanosensing cues remain obscure. This study proposes a sophisticated hypothesis explaining how B cells isolated from the CP of SARS-CoV-2 infected patients may undergo a triggered series of B cell activation, BCR dynamics, proximal signalling, and antibody production on PDMS-embedded in-vitro antigen-presenting structures (APCs). These studies could provide detailed insights in the future for the development of structural and therapeutic entanglements to fight against pathogens.

Facile Synthesis and In Vitro Activity of N-Substituted 1,2-Benzisothiazol-3(2H)-ones against Dengue Virus NS2BNS3 Protease.

Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose-response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC50 values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.

A Regional and National Database Comparison of Colorectal Outcomes.

BACKGROUND AND OBJECTIVES: The traditional open approach is still a common option for colectomy and the most common option chosen for rectal resections for cancer. Randomized trials and large database studies have reported the merits of the minimally invasive approach, while studies comparing laparoscopic and robotic options have reported inconsistent results. METHODS: This study was designed to compare open, laparoscopic, and robotic colorectal surgery outcomes in protocol-driven regional and national databases. Logistic and multiple linear regression analyses were used to compare standard 30-day colorectal outcomes in the Michigan Surgical Quality Collaborative (MSQC) and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases. The primary outcome was overall complications. RESULTS: A total of 10,054 MSQC patients (open 37.5%, laparoscopic 48.8%, and robotic 13.6%) and 80,535 ACS-NSQIP patients (open 25.0%, laparoscopic 67.1%, and robotic 7.9%) met inclusion criteria. Overall complications and surgical site infections were significantly favorable for the laparoscopic and robotic approaches compared with the open approach. Anastomotic leaks were significantly fewer for the laparoscopic and robotic approaches compared with the open approach in ACS-NSQIP, while there was no significant difference between robotic and open approaches in MSQC. Laparoscopic complications were significantly less than robotic complications in MSQC but significantly more in ACS-NSQIP. Laparoscopic 30-day mortality was significantly less than for the robotic approach in MSQC, but there was no difference in ACS-NSQIP. CONCLUSION: Minimally invasive colorectal surgery is associated with fewer complications and has several other outcomes advantages compared with the traditional open approach. Individual complication comparisons vary between databases, and caution should be exercised when interpreting results in context.

Risk Factors for Postoperative Complications Following Diverting Loop Ileostomy Takedown.

INTRODUCTION: Diverting loop ileostomies are frequently created to divert the fecal stream in an effort to protect downstream anastomoses. These are later reversed to restore intestinal continuity. The goal of this study is to evaluate risk factors for postoperative complications following diverting loop ileostomy takedown. MATERIALS AND METHODS: Patients who underwent diverting loop ileostomy takedown between January 1, 2010 and April 28, 2015 were identified in the Michigan Surgical Quality Collaborative registry. Candidate covariates were identified and a hierarchical logistic regression model was used to identify risk factors for postoperative complications. RESULTS: 1,737 patients met the inclusion criteria. Rates of postoperative complications were generally low. Mean length of stay (LOS) was 5.6 (± 4.5) days. Outcomes of interest were the following: overall morbidity, serious morbidity, extended LOS, SSI, UTI, pneumonia, readmission, reoperation, and mortality. Risk factors for these outcomes included the following: ASA class, bleeding disorder, prolonged operative time, race, tobacco use, gender, steroid use, peripheral vascular disease, weight loss, and functional status. CONCLUSIONS: Diverting loop ileostomy takedown has a complication rate of approximately 20%. Higher ASA class, longer operative times, history of bleeding disorder, and functional status were identified as risk factors for most complications.