Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging.

Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom.

Asymptomatic bacteriuria in candidates for active treatment of renal stones: results from an international multicentric study on more than 2600 patients.

The occurrence of asymptomatic bacteriuria concomitant to urolithiasis is an issue for patients undergoing renal stone treatment. Disposing of a preoperative urine culture is essential to reduce the risk of septic events. The endpoint of the study is to report which characteristics of candidates for renal stone treatment are frequently associated with positive urine culture. 2605 patients were retrospectively enrolled from 14 centers; inclusion criteria were age > 18 and presence of a single renal stone 1-2 cm in size. The variables collected included age, gender, previous renal surgery, comorbidities, skin-to-stone distance, stone size, location, density, presence of hydronephrosis. After a descriptive analysis, the association between continuous and categorical variables and the presence of positive urine culture was assessed using a logistic regression model. Overall, 240/2605 patients (9%) had preoperative bacteriuria. Positive urine culture was more frequent in females, patients with previous renal interventions, chronic kidney disease, congenital anomalies, larger stones, increased density. Multivariate analysis demonstrated that previous renal interventions (OR 2.6; 95% CI 1.9-3.4; p < 0.001), renal-related comorbidities (OR 1.31; 95% CI 1.19-1.4; p < 0.001), higher stone size (OR 1.06; 95% CI 1.02-1.1; p = 0.01) and density (OR 1.00; 95% CI 1.0-1.00; p = 0.02) were associated with bacteriuria; male gender and lower caliceal location were inversely related to it. Beyond expected risk factors, such as female gender, other parameters are seemingly favoring the presence of positive urine culture. The awareness of variables associated with bacteriuria allows to assess which individuals are at increased risk of presenting bacteriuria and reduce the rate of septic complications.

Effect of ceftazidime/avibactam plus fosfomycin combination on 30†day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study.

Introduction: The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Materials and methods: From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ±â€Šother). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score. Results: Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ±â€Šother). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective. Conclusions: Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.

Wechsler Intelligence Scale for Adults - Fourth Edition profiles of adults with autism spectrum disorder.

AIM: In this study, we have compared 229 Wechsler Adults Intelligence Scale - Fourth Edition (WAIS-IV) cognitive profiles of different severity adults with autism spectrum disorder to verify the impact of several variables including sex, age, level of education and autism severity level in an Italian sample. Moreover, we wanted to find out the optimal cut points for the major intelligence quotients in order to discriminate autism severity levels. METHODS: Participants were recruited from two National Health System Center in two different Italian regions and were assessed with gold-standard instruments as a part of their clinical evaluation. According to DSM-5, cognitive domains were also measured with multi-componential tests. We used the Italian adaptation of WAIS-IV. We checked our hypotheses using linear regression models and receiver operating characteristics (ROC) curves. RESULTS: Our results showed that age and level of education have a strong impact on Verbal Comprehension (VCI) and Working Memory Indexes (WMI). Gender differences are relevant when considering the VCI and Processing Speed index (PSI) in which women obtained the best performance. These differences are still relevant when considering cut points of ROC because 69 resulted to be the optimal cut point for women, 65 for men. CONCLUSIONS: Few conclusions can be assumed only examining Full Scale Intelligence Quotient (FSIQ) scores as it includes many different information about broader cognitive abilities. Looking deeper at main indexes and their subtests findings are consistent with previous research on the disorder (moderate correlations of FSIQ, Perceptual Reasoning index, WMI and PSI with the participants' age), while other results are unforeseen (no effect of sex found on FSIQ score) or novel (significant effect of education on VCI and WMI). Using an algorithm predicting optimal cut point for discriminating through autism severity levels can help clinicians to better label and quantify the required help a person may need, a test cannot replace diagnostic and clinical evaluation by experienced clinicians.

Clinical course of Coronavirus Disease-19 in patients with haematological malignancies is characterized by a longer time to respiratory deterioration compared to non-haematological ones: results from a case-control study.

BACKGROUND: We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. METHODS: Retrospective, case-control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. RESULTS: Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and ≥ 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], ≥ 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. CONCLUSION: An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization.

Facilitators and Barriers to Implementation of a Childhood Tuberculosis Control Program in Bangladesh: A Mixed-Methods Study from BRAC Urban DOTS Centres in Dhaka.

The case detection rate of childhood tuberculosis in Bangladesh is 4%, far below the World Health Organization predicted rate of 10-15% for a country with a high burden of tuberculosis. A concurrent triangulation mixed-methods study was carried out in eight urban DOTS (Directly Observed Treatment, Short-course) centres to investigate the factors contributing to the diagnosis and treatment of childhood tuberculosis. Front-line health care workers (Shasthya Shebika) (n = 111) were surveyed to understand knowledge, attitude, and practice (KAP) of the diagnosis and treatment of childhood tuberculosis. In-depth interviews were conducted with field workers (n = 32) and mothers of TB cases (n = 4). Stakeholders involved in implementing the tuberculosis program (n = 9) participated in the key informant interviews. Knowledge of Shasthya Shebika was associated with the components addressed during refresher training (p = 0.02). Government stewardship, presence of specific guidelines, knowledge and capacity building of front-line health workers were identified as the key facilitators. Frequent turnover of key managerial positions in the government, stigma, delays in seeking care, lack of diagnostic facilities, and poor engagement of private practitioners were identified as major constraints. It was identified that the government should focus on improving diagnostic capacities, conduct research on childhood tuberculosis, and produce awareness materials.

A unique mode of nucleic acid immunity performed by a multifunctional bacterial enzyme.

The perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve antiphage defense. However, the prevalence and effectiveness of minimal, single-component systems that cleave DNA remain unknown. Here, we describe a unique mode of nucleic acid immunity mediated by a single enzyme with nuclease and helicase activities, herein referred to as Nhi (nuclease-helicase immunity). This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi targets and degrades phage-specific replication intermediates. Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in antiphage defense.

Multi-modal Pain Control Protocol Decreases Narcotic Consumption in an Inpatient Trauma Population.

INTRODUCTION: Opioid use after surgery or trauma has been implicated as a contributing factor to opioid dependence. The Acute Care Surgery (ACS) service at our community-based trauma center instituted an opioid-minimizing, multi-modal pain control (MMPC) protocol. The classes of pain medication included a non-opioid analgesic, a non-steroidal anti-inflammatory drug, a gabapentinoid, a skeletal muscle relaxant, and a topical anesthetic. We hypothesize that the MMPC will result in lower opioid consumption compared with the prior STP as evidenced by lower morphine milligram equivalents (MME) per day. METHODS: All adult patients (≥18 years) admitted to the ACS service from Jan 2014 to Dec 2015 and Jan 2018 to Dec 2019 were screened for inclusion. The standard pain control group (STP) and MMPC groups were defined by the year of admission. The primary outcome is opioid use per day, calculated in MME received. Secondary outcomes of the study include daily pain scores, incidence of opioid-related complications, death, ventilator days, intensive care unit length of stay, and hospital length of stay (HLOS) days. RESULTS: Multi-modal pain control protocol group was older and less injured than STP group. Daily opioid utilization was significantly less in the MMPC group (22.5 MMEs/d vs 60MMEs/d in the STP group, P < .0001). Additionally, daily pain scores were not different between groups. Secondary outcomes did not vary between the two groups. CONCLUSION: This study shows that implementation of a MMPC protocol resulted in lower opioid consumption in injured patients. Pain was equivalently controlled during the MMPC protocol period as demonstrated by similar pain scores.

Accuracy of Magnetic Resonance Cholangiopancreatography in Case of Biliary Obstruction Comparing Post-operative Findings: A Study of 50 Cases.

Complete assessment of obstructive jaundice requires the use of various imaging modalities that are required to detect the cause and level of obstruction thus helping in treatment planning. Magnetic Resonance Cholangio Pancreatography (MRCP) is a current available technology which is a non-invasive technique that visualizes the gallbladder, biliary tree and pancreatic duct and also provides information about surrounding structures. This study was done to correlate the MRCP findings with post-operative result and thereby demonstrate the specificity, sensitivity and efficacy of MRCP as an accurate investigatory tool for biliary obstruction. Total of fifty (50) patients of clinically diagnosed obstructive jaundice were studied from March 2017 to August 2017 in the Department of Radiology and Imaging, Combined Military Hospital, Dhaka, Bangladesh. In all these cases, USG was the initial screening investigation followed by MRCP. Cause and level of obstruction were evaluated using MRCP findings. MRCP results were correlated with surgical findings and few cases also with direct ERCP findings. Statistical analysis was done to see the sensitivity, specificity, accuracy, positive and negative predictive values of MRCP in diagnosis of biliary obstruction. In this study, USG detected level of obstruction in 56% (28 out of 50) cases. USG could detect causes of obstruction in 100% (02 out of 02) cases of choledocal cyst and 66.67% (02 out of 03) benign stricture, 60% (03 out of 05) cases of periampullary carcinoma, 57.70% (06 out of 14) cases of choledocholithiasis, and 42.86% (15 out of 26) cases of cholangiocarcinoma. On the other hand, MRCP detected level of obstruction in 98% (49 out of 50) cases. MRCP could detect causes of obstruction in 100% cases of cholangiocarcinoma, choledocholithiasis, benign stricture and choledocal cyst and 80% (04 out of 05) cases of periampullary carcinoma. In this study, ERCP could detect causes of obstruction in 32 cases of choledocholithiasis and benign stricture, but in case of cholangiocarcinoma ERCP was failed in 3 cases. In this study, for detection of cause of obstruction, ERCP had the highest sensitivity (97.79%); followed by MRCP (96.65%) and USG (60.25%). The overall diagnostic accuracy for detection of cause of obstruction was the highest for ERCP (95.50%); followed by MRCP (94.50%) and USG (64.50%). MRCP can be done in a short duration and is a noninvasive diagnostic modality compared to ERCP. MRCP needs to be advocated as a viable and non-invasive alternative with compararable sensitivity and specificity to ERCP.

Time-resolved relaxation and fragmentation of polycyclic aromatic hydrocarbons investigated in the ultrafast XUV-IR regime.

Polycyclic aromatic hydrocarbons (PAHs) play an important role in interstellar chemistry and are subject to high energy photons that can induce excitation, ionization, and fragmentation. Previous studies have demonstrated electronic relaxation of parent PAH monocations over 10-100 femtoseconds as a result of beyond-Born-Oppenheimer coupling between the electronic and nuclear dynamics. Here, we investigate three PAH molecules: fluorene, phenanthrene, and pyrene, using ultrafast XUV and IR laser pulses. Simultaneous measurements of the ion yields, ion momenta, and electron momenta as a function of laser pulse delay allow a detailed insight into the various molecular processes. We report relaxation times for the electronically excited PAH*, PAH+* and PAH2+* states, and show the time-dependent conversion between fragmentation pathways. Additionally, using recoil-frame covariance analysis between ion images, we demonstrate that the dissociation of the PAH2+ ions favors reaction pathways involving two-body breakup and/or loss of neutral fragments totaling an even number of carbon atoms.

A case of motor neuron involvement in Gaucher disease.

Gaucher disease (GD) is a genetic disorder characterized by an accumulation of glucosylceramide in cells in the monocyte-macrophage system. We describe a case of a 33-year-old man with a previous diagnosis of type 3 GD who displayed a progressive weakening of the limbs followed by upper motor neuron involvement. A diagnosis of definite Amyotrophic Lateral Sclerosis was made. This is the first reported case of concurrent Gaucher disease and the ALS phenotype in the same patient.

Draft Genome Sequences of Staphylococcus Podophages JBug18, Pike, Pontiff, and Pabna.

We report here the draft genome sequences of Staphylococcus bacteriophages JBug18, Pike, Pontiff, and Pabna, which infect and lyse S. epidermidis and S. aureus strains. All bacteriophages belong to the morphological family Podoviridae and constitute attractive candidates for use as whole-phage therapeutics due to their compact genomes and lytic lifestyles.

Outcome of Single Stage Correction of High Variety of Anorectal Malformation.

The standard treatment of high variety anorectal malformation (ARM) is the staged approach. A growing interest in one stage correction of high variety ARM was noted recently. The aim of this study was to examine the feasibility, safety and outcome of single stage correction of High variety ARM. This prospective study was carried out in the Department of Paediatric Surgery, Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from July 2012 to September 2013. It was conducted among 30 patients, all having high ARM. The type of ARM was diagnosed by clinical examinations and imaging studies like Invertogram and Transperineal USG. Other associated congenital anomalies were excluded. Out of 30 patients 11(36.67%) were male and 19(63.33%) were female. The age incidence ranges from 2 days to 5 months with the mean±SD age 1.70±1.63 months. The type of fistula present along with ARM in male varies from rectobulber urethral fistula, recto prostatic urethral fistula, recto vesical fistula and in one case without any fistula. Type of fistula was rectovestibular, rectovaginal and one cloacal malformation among the female patients. The treatment modalities in male patients vary in transabdominal pull through anorectoplasty and PSARP, in which the former was done more (72.73%). In case of female patients, treatment modalities vary in transabdominal pull through and anorectoplasty and transfistulous anorectoplasty, with the later done more (52.63%). Regarding post operative complications, there was 1(14.29%) wound infection in male and 1(33.33%) in female, partial wound disruption in 1(14.29%) male patient, mucosal prolapse 2(28.57%) in male and 1(33.33%) in female, anal stenosis 1(14.29%) in male and 1(33.33%) in female, perianal soiling in 1(14.29%) male patient. All the complications were treated by adopting various measures. One stage correction of High variety ARM in both male and female patients is technically feasible. The safeties of this approach depend on the adherence to strict inclusion criteria. The early post operative complications are acceptable and can be managed successfully.

Effect of time of day and daily endoscopic workload on outcomes of endoscopic mucosal resection for large sessile colon polyps.

Background: Endoscopic mucosal resection of large non-pedunculated colon polyps is challenging. Objective: To determine if the time of day or daily endoscopic workload play a role in outcomes of endoscopic mucosal resection for large non-pedunculated colon polyps greater than 20 mm. Methods: This is a retrospective study of patients who underwent endoscopic mucosal resection of large non-pedunculated colon polyps. The time of day and endoscopic workload were compared across the following outcomes: the rate of complete resection of the polyp, the rate of referral for surgery, and the rate of residual neoplasia on follow-up. Results: One hundred and three endoscopic mucosal resection procedures were performed. There were no differences in the rates of complete resection (80.8% vs. 70.0%; P = 0.25), the need for surgery (27.4% vs. 33.3%; P = 0.55), and rate of residual neoplasia (24.5% vs. 50.0%; P = 0.07) when comparing the time of day. Colon polyps greater than 40 mm were less likely to be completely resected versus polyps sized 20-39 mm (56.8% vs. 91.9%; P < 0.001). In cases with no residual neoplasia on follow-up, the mean duration for the index procedure was 45.6 minutes versus 60.7 minutes when there was residual neoplasia (P < 0.01). Conclusion: The time of day and endoscopic workload does not affect outcomes for endoscopic mucosal resection of large non-pedunculated colon polyps, but the size of large non-pedunculated colon polyps and resection times do.

CRISPR-Cas10 assisted editing of virulent staphylococcal phages.

Phages are the most abundant entities in the biosphere and profoundly impact the bacterial populations within and around us. They attach to a specific host, inject their DNA, hijack the host's cellular processes, and replicate exponentially while destroying the host. Historically, phages have been exploited as powerful antimicrobials, and phage-derived proteins have constituted the basis for numerous biotechnological applications. Only in recent years have metagenomic studies revealed that phage genomes harbor a rich reservoir of genetic diversity, which might afford further therapeutic and/or biotechnological value. Nevertheless, functions for the majority of phage genes remain unknown, and due to their swift and destructive replication cycle, many phages are intractable by current genetic engineering techniques. Whether to advance the basic understanding of phage biology or to tap into their potential applications, efficient methods for phage genetic engineering are needed. Recent reports have shown that CRISPR-Cas systems, a class of prokaryotic immune systems that protect against phage infection, can be harnessed to engineer diverse phages. In this chapter, we describe methods to genetically manipulate virulent phages using CRISPR-Cas10, a Type III-A CRISPR-Cas system native to Staphylococcus epidermidis. A method for engineering phages that infect a CRISPR-less Staphylococcus aureus host is also described. Both approaches have proved successful in isolating desired phage mutants with 100% efficiency, demonstrating that CRISPR-Cas10 constitutes a powerful tool for phage genetic engineering. The relatively widespread presence of Type III CRISPR-Cas systems in bacteria and archaea imply that similar strategies may be used to manipulate the genomes of diverse prokaryotic viruses.

Community health perceptions and human environmental exposure to chromium contamination in a small New Jersey City.

Following a 1983 chromic acid (hexavalent chromium [CrVI]) spill from a Garfield, NJ electroplating plant, CrVI-contaminated water was found in a local firehouse basement in 1993. An ATSDR public health advisory was issued for the plant site in 2010, and from 2008-2015, fourteen residential properties have required remediation to address CrVI-contaminated dust in the basements. As part of the Community Outreach and Engagement Core of the NYU NIEHS Center, seventytwo Garfield residents aged 18-65 years, participated in a community survey with the goal of identifying concerns related to environmental and community health. Thirty-two percent responded that they 'didn't know' if they were exposed to chemicals or pollutants where they live. This finding suggests a limited awareness of environmental chemical exposures, chromium contamination and/or potential exposure to CrVI. Furthermore, toenail clippings were collected from forty-seven Garfield residents and analyzed for total chromium levels to assess potential long-term exposure. On average, residents living on/inside the contaminated plume area had higher total chromium levels in their toenail clippings than residents living outside the plume area. However, chromium levels for all participants were within the range of historical normal. This study highlights the value of partnerships between environmentally-impacted community's and academic scientists working together to identify potential contaminant exposures and address public health concerns through research and environmental health education.