Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

BACKGROUND: Randomised controlled trials of typhoid conjugate vaccines among children in Africa and Asia have shown high short-term efficacy. Data on the durability of protection beyond 2 years are sparse. We present the final analysis of a randomised controlled trial in Malawi, encompassing more than 4 years of follow-up, with the aim of investigating vaccine efficacy over time and by age group. METHODS: In this phase 3, double-blind, randomised controlled efficacy trial in Blantyre, Malawi, healthy children aged 9 months to 12 years were randomly assigned (1:1) by an unmasked statistician to receive a single dose of Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) or meningococcal capsular group A conjugate (MenA) vaccine. Children had to have no previous history of typhoid vaccination and reside in the study areas for inclusion and were recruited from government schools and health centres. Participants, their parents or guardians, and the study team were masked to vaccine allocation. Nurses administering vaccines were unmasked. We did surveillance for febrile illness from vaccination until follow-up completion. The primary outcome was first occurrence of blood culture-confirmed typhoid fever. Eligible children who were randomly assigned and vaccinated were included in the intention-to-treat analyses. This trial is registered at ClinicalTrials.gov, NCT03299426. FINDINGS: Between Feb 21, 2018, and Sept 27, 2018, 28 130 children were vaccinated; 14 069 were assigned to receive Vi-TT and 14 061 to receive MenA. After a median follow-up of 4·3 years (IQR 4·2-4·5), 24 (39·7 cases per 100 000 person-years) children in the Vi-TT group and 110 (182·7 cases per 100 000 person-years) children in the MenA group were diagnosed with a first episode of blood culture-confirmed typhoid fever. In the intention-to-treat population, efficacy of Vi-TT was 78·3% (95% CI 66·3-86·1), and 163 (129-222) children needed to be vaccinated to prevent one case. Efficacies by age group were 70·6% (6·4-93·0) for children aged 9 months to 2 years; 79·6% (45·8-93·9) for children aged 2-4 years; and 79·3% (63·5-89·0) for children aged 5-12 years. INTERPRETATION: A single dose of Vi-TT is durably efficacious for at least 4 years among children aged 9 months to 12 years and shows efficacy in all age groups, including children younger than 2 years. These results support current WHO recommendations in typhoid-endemic areas for mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first 2 years of life. FUNDING: Bill & Melinda Gates Foundation.

Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children.

BACKGROUND: Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa. METHODS: We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up. RESULTS: The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture-confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination. CONCLUSIONS: Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture-confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426.).

Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins.

Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins.

A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic.

Oxidative stress, DNA, and membranes targets as modes of antibacterial and antibiofilm activity of facile synthesized biocompatible keratin-copper nanoparticles against multidrug resistant uro-pathogens.

Escherichia coli and Enterococcus faecalis are two of the most prevalent uro-pathogens and are difficult to treat as they acquire multidrug-resistant traits. In this study, the main objective was to develop biocompatible copper nanoparticles using chicken feather keratin protein (CuNPs-K) and to investigate their impact on multidrug-resistant (MDR) uro-pathogens, E. coli and E. faecalis, under both single and mixed culture conditions. CuNPs-K were characterised by UV-Vis spectroscopy, dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, and docking experiments. The MIC values of CuNPs-K against single and mixed planktonic cultures were 50 µg/ml and 75 µg/ml, respectively. CuNPs-K efficiently disrupted the biofilm of single and mixed uro-pathogen cultures by eliminating sessile cells. This biofilm disruption may be attributed to a decline in the production of extracellular polymeric substances in both single and mixed bacterial cultures treated with CuNPs-K. Moreover, selective antimicrobial activity was determined by selectivity assays using T24 cells. CuNPs-K targets both the bacterial membrane and DNA with elevated reactive oxygen species (ROS) as their bactericidal mode of action. This comprehensive antimicrobial activity of CuNPs-K was further confirmed in vivo by using the zebra fish model. In this study, CuNPs-K effectively reduced bacterial load with increased survivability of infected zebrafish. All these results suggest that CuNPs-K can be explored as an exceptional antibacterial agent against MDR uro-pathogenic E. coli and E. faecalis.

A capture and release method based on noncovalent ligand cross-linking and facile filtration for purification of lectins and glycoproteins.

Glycan-binding proteins such as lectins are ubiquitous proteins that mediate many biological functions. To study their various biological activities and structure-function relationships, researchers must use lectins in their purest form. Conventional purification techniques, especially affinity column chromatography, have been instrumental in isolating numerous lectins and glycoproteins. These approaches, however, are time-consuming, consist of multiple steps, and often require extensive trial-and-error experimentation. Therefore, techniques that are relatively rapid and facile are needed. Here we describe such a technique, called capture and release (CaRe). The strength of this approach is rooted in its simplicity and accuracy. CaRe purifies lectins by utilizing their ability to form spontaneous noncovalently cross-linked complexes with specific multivalent ligands. The lectins are captured in the solution phase by multivalent capturing agents, released by competitive monovalent ligands, and then separated by filtration. CaRe does not require antibodies, solid affinity matrices, specialized detectors, a customized apparatus, controlled environments, or functionalization or covalent modification of reagents. CaRe is a time-saving procedure that can purify lectins even from a few milliliters of crude protein extracts. We validated CaRe by purifying recombinant human galectin-3 and five other known lectins and also tested CaRe's ability to purify glycoproteins. Besides purifying lectins and glycoproteins, CaRe has the potential to purify other glycoconjugates, including proteoglycans. This technique could also be used for nonlectin proteins that bind multivalent ligands. Given the ubiquity of glycosylation in nature, we anticipate that CaRe has broad utility.

Usability of Electronic Health Record-Generated Discharge Summaries: Heuristic Evaluation.

BACKGROUND: Obtaining accurate clinical information about recent acute care visits is extremely important for outpatient providers. However, documents used to communicate this information are often difficult to use. This puts patients at risk of adverse events. Elderly patients who are seen by more providers and have more care transitions are especially vulnerable. OBJECTIVE: This study aimed to (1) identify the information about elderly patients' recent acute care visits needed to coordinate their care, (2) use this information to assess discharge summaries, and (3) provide recommendations to help improve the quality of electronic health record (EHR)-generated discharge summaries, thereby increasing patient safety. METHODS: A literature review, clinician interviews, and a survey of outpatient providers were used to identify and categorize data needed to coordinate care for recently discharged elderly patients. Based upon those data, 2 guidelines for creating useful discharge summaries were created. The new guidelines, along with 17 previously developed medical documentation usability heuristics, were applied to assess 4 simulated elderly patient discharge summaries. RESULTS: The initial research effort yielded a list of 29 items that should always be included in elderly patient discharge summaries and a list of 7 "helpful, but not always necessary" items. Evaluation of 4 deidentified elderly patient discharge summaries revealed that none of the documents contained all 36 necessary items; between 14 and 18 were missing. The documents each had several other issues, and they differed significantly in organization, layout, and formatting. CONCLUSIONS: Variations in content and structure of discharge summaries in the United States make them unnecessarily difficult to use. Standardization would benefit both patients, by lowering the risk of care transition-related adverse events, and outpatient providers, by helping reduce frustration that can contribute to burnout. In the short term, acute care providers can help improve the quality of their discharge summaries by working with EHR vendors to follow recommendations based upon this study. Meanwhile, additional human factors work should determine the most effective way to organize and present information in discharge summaries, to facilitate effective standardization.

Comparison of peritubal infiltration and single level T10 paravertebral block in percutaneous nephrolithotomy (PCNL).

Background and Aims: In percutaneous nephrolithotomy (PCNL), distension of renal capsule, pelvicalyceal system and nephrostomy tube causes intense postoperative pain. The present study was done to compare the efficacy of peritubal infiltration of Ropivacaine with Dexmedetomidine and ultrasound guided single level T10 paravertebral block for post-operative analgesia in patients undergoing PCNL. Material and Methods: A prospective, double blind study was conducted on 60 American Society of Anesthesiologists (ASA) I and II patients of either gender between 18-65 years undergoing PCNL who were randomized into 3 groups. Group PV [n = 20] received paravertebral block at T 10 level with 20 ml of 0.25% Ropivacaine plus 0.25 mcg/kg Dexmedetomidine. Group PT [n = 20] received peritubal infiltration along nephrostomy tube with 20 ml of 0.25% Ropivacaine plus 0.25 mcg/kg Dexmedetomidine. Group C [n = 20] control group received intravenous Tramadol 1mg/kg. Postoperative pain scores, opioid consumption and side effects if any were recorded for 24 hrs. Statistical analysis was done using ANOVA test, Chi-square test. P value <0.05 was considered significant. Results: Demographic data were comparable. Reduced dynamic VAS score was noted for first 8hrs in peritubal infiltration compared to paravertebral group. Dynamic VAS scores were significantly lower in paravertebral group at 8th, 12th and 24th hr as compared to peritubal infiltration (P < 0.05). During all time intervals peritubal infiltration and paravertebral group had significantly lower VAS scores as compared to control group. Opioid requirement was more in control group compared to study groups. Conclusion: In PCNL, peritubal infiltration and single level paravertebral block produces effective postoperative analgesia without significant side effects.

Early Insights From Clinical Trials of Typhoid Conjugate Vaccine.

Clinical trials of typhoid conjugate vaccine (TCV) are ongoing in 4 countries. Early data confirm safety, tolerability, and immunogenicity of typhoid conjugate vaccine, and early efficacy results are promising. These data support World Health Organization recommendations and planned country introductions. Forthcoming trial data will continue to inform programmatic use of typhoid conjugate vaccine.

Knowledge, attitude, and practices of medical clinicians regarding food allergy and anaphylaxis in Hyderabad, India.

BACKGROUND: Food allergy (FA) is a chronic condition of emerging global concern. Surveys have been conducted in numerous countries to assess physician knowledge, attitude, and practices (KAP) pertaining to FA and anaphylaxis, and substantial deficits in their KAP were identified. OBJECTIVE: To assess the KAP of medical clinicians in Hyderabad, India, with respect to FA and anaphylaxis. METHODS: A regionally representative sample of 570 physicians including 113 general practitioners, 123 pediatricians, 110 pulmonologists, 113 dermatologists, and 111 gastroenterologists were recruited from all major institutions in Hyderabad, India. A validated questionnaire was used to assess their KAP. RESULTS: Overall, 90% of questions were correctly answered and differences emerged with respect to specific items, namely the following: (1) the lateral thigh being the preferred location for epinephrine administration (P = .001); (2) a positive skin prick test or radioallergosorbent test is sufficient for FA diagnosis (P = .04); and (3) the appropriate epinephrine dose for a 27-kg child (P = .006). Approximately 95% of the participants in each group were confident in their ability to care for patients with FA, yet 91% desired additional periodic FA training sessions. CONCLUSION: Survey findings suggest that although FA knowledge among South Indian clinicians seems high across all major specialties who care for patients with FA, there are differences in the level of knowledge among them, which in turn reflects the differences in attitude and approach toward their patients. These FA care providers still desire to further participate in continuing medical education efforts in the field of food allergy. Efforts to provide periodic training and education for all FA clinical care providers remain vital in South India.

Grading systems of oral cavity pre-malignancy: a systematic review and meta-analysis.

PURPOSE: Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. METHODS: This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. RESULTS: Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18-15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386-0.723) and 12.7% (95% CI - 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640-0.740) and 0.388 (95% CI 0.195-0.552), respectively. CONCLUSION: Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs.

Compounding Benefits of Sentinel Lymph Node Biopsy for Perineal Melanoma: A Population-Based Retrospective Cohort Analysis.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) in the treatment of melanoma is known to provide valuable prognostic information. However, there is no literature describing an overall or disease-specific survival (DDS) benefit of SLNB. In the perineum, melanoma is often more advanced at presentation with current treatment guidelines translated from nonanatomic specific melanoma. As a result, there is little understanding surrounding the role of SLNB in melanoma of the perineum. Our objective is to better understand the therapeutic benefits of SLNB in perineal melanoma. METHODS: The Surveillance, Epidemiology, and End Results program is a large population-based cancer registry including survival data from millions of patients in the United States. The registry was used to generate patient data for analysis from 2004 to 2016. Inclusion criteria included melanoma of the perineum; Breslow depth of 0.80 mm or greater and less than 0.80 mm with ulceration; SLNB or no intervention; clinically negative nodal disease; and available overall survival data. RESULTS: For 879 patients from 2004 to 2016 with perineal melanoma, significant predictors of reduced survival include older than 75 years, Clark level IV-V, Breslow depth of greater than 4.00 mm, positive ulceration status, regional and distant nodal micrometastases, and clinically positive nodes on presentation. Aggregates for overall survival (OS) and disease-specific survival (DSS) were improved with implementation of SLNB. The 5-year survival rates with SLNB versus no SLNB were 54.0% and 43.0% for OS (P = 0.001) and 57.8% and 53.1% for DSS (P = 0.044). Stratification by Breslow depth yielded significant OS and DSS advantage for greater than 1.00 to 2.00 mm (21.3% benefit, P =0.021, and 16.8% benefit, P = 0.044) and greater than 4.00 mm (30.3% benefit, P = 0.005, and 21.0% benefit, P = 0.007) Breslow depths. CONCLUSIONS AND RELEVANCE: Sentinel lymph node biopsy may provide therapeutic benefits in addition to prognostic information for melanoma of the perineum through an increase in 5-year OS.

Effect of Different Cavity Disinfectants on Marginal Sealing Ability of a Seventh-generation Dentin Bonding Agent: An In Vitro Study.

AIM: To determine the effect of three different cavity disinfectants (2% chlorhexidine gluconate, 2.5% sodium hypochlorite, and 2% iodine solution) on microleakage in a seventh-generation dentin-bonding system. MATERIALS AND METHODS: Class V cavity was prepared on 50 extracted molars (n = 50). The respective experimental groups were treated with cavity disinfectants and Adper Easy One Bond. Preparations without cavity disinfectants worked as negative control and those with neither disinfectant nor dentin-bonding resin application worked as positive controls. After the cavity preparations were restored with resin composite (Filtek™ Z 350), the teeth were then subjected to dye leakage tests. Microleakage was assessed for both occlusal and gingival margins, using a stereomicroscope. Data were analyzed using (ANOVA; Kruskal-Wallis) test. RESULTS: No statistically significant differences were observed among 2% chlorhexidine gluconate, 2.5% sodium hypochlorite, and 2% iodine and also no statistically significant differences were observed between occlusal and gingival margins of groups. CONCLUSION: (1) 2% chlorhexidine gluconate, 2.5% sodium hypochlorite, and 2% iodine produced significantly higher microleakage when used with seventh-generation dentin-bonding agent. (2) 2% chlorhexidine gluconate produced lesser microleakage in comparison with 2.5% sodium hypochlorite and 2% iodine. (3) The gingival margins exhibited greater microleakage than occlusal margins. CLINICAL SIGNIFICANCE: The application of cavity disinfectants on prepared tooth before the application of dentin-bonding agent could help to reduce the potential risk of residual caries and postoperative sensitivity.

Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation.

Cognitive deficits are commonly reported by patients following treatment with chemotherapeutic agents. Anthracycline-containing chemotherapy regimens are associated with cognitive impairment and reductions in neuronal connectivity in cancer survivors, and doxorubicin (Dox) is a commonly used anthracycline. Although it has been reported that Dox distribution to the central nervous system (CNS) is limited, considerable Dox concentrations are observed in the brain with co-administration of certain medications. Additionally, pro-inflammatory cytokines, which are overproduced in cancer or in response to chemotherapy, can reduce the integrity of the blood-brain barrier (BBB). Therefore, the aim of this study was to evaluate the acute neurotoxic effects of Dox on hippocampal neurons. In this study, we utilized a hippocampal cell line (H19-7/IGF-IR) along with rodent hippocampal slices to evaluate the acute neurotoxic effects of Dox. Hippocampal slices were used to measure long-term potentiation (LTP), and expression of proteins was determined by immunoblotting. Cellular assays for mitochondrial complex activity and lipid peroxidation were also utilized. We observed reduction in LTP in hippocampal slices with Dox. In addition, lipid peroxidation was increased as measured by thiobarbituric acid reactive substances content indicating oxidative stress. Caspase-3 expression was increased indicating an increased propensity for cell death. Finally, the phosphorylation of signaling molecules which modulate LTP including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and Akt were increased. This data indicates that acute Dox exposure dose-dependently impairs synaptic processes associated with hippocampal neurotransmission, induces apoptosis, and increases lipid peroxidation leading to neurotoxicity.

Role of Adiponectin in Central Nervous System Disorders.

Adiponectin, the most abundant plasma adipokine, plays an important role in the regulation of glucose and lipid metabolism. Adiponectin also possesses insulin-sensitizing, anti-inflammatory, angiogenic, and vasodilatory properties which may influence central nervous system (CNS) disorders. Although initially not thought to cross the blood-brain barrier, adiponectin enters the brain through peripheral circulation. In the brain, adiponectin signaling through its receptors, AdipoR1 and AdipoR2, directly influences important brain functions such as energy homeostasis, hippocampal neurogenesis, and synaptic plasticity. Overall, based on its central and peripheral actions, recent evidence indicates that adiponectin has neuroprotective, antiatherogenic, and antidepressant effects. However, these findings are not without controversy as human observational studies report differing correlations between plasma adiponectin levels and incidence of CNS disorders. Despite these controversies, adiponectin is gaining attention as a potential therapeutic target for diverse CNS disorders, such as stroke, Alzheimer's disease, anxiety, and depression. Evidence regarding the emerging role for adiponectin in these disorders is discussed in the current review.

Coping With Staff Burnout and Work-Related Posttraumatic Stress in Intensive Care.

OBJECTIVES: To examine the associations with symptoms of 1) burnout and 2) work-related posttraumatic stress, in adult and pediatric intensive care staff, focusing on the particular contributions of resilience and coping strategies. DESIGN: Point prevalence cross-sectional study. SETTING: Three adult ICUs and four PICUs. SUBJECTS: Three hundred seventy-seven ICU staff. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Brief Resilience Scale, abbreviated Maslach Burnout Inventory, Trauma Screening Questionnaire, and Hospital Anxiety and Depression Scale. Prevalence of burnout (defined as high emotional exhaustion or high depersonalization) was 37%. Prevalence of clinically significant posttraumatic stress symptoms was 13%. There was a degree of overlap between burnout and other measures of distress, most notably for anxiety (odds ratio, 10.56; 95% CI, 4.12-27.02; p < 0.001). Hierarchical logistic regression demonstrated that self-reported resilience was strongly associated with decreased likelihood of meeting criteria for both forms of work-related distress (burnout: odds ratio, 0.52; 95% CI, 0.36-0.74; p < 0.001 and posttraumatic stress: odds ratio, 0.28; 95% CI, 0.16-0.46; p < 0.001) and that physicians were twice as likely as nurses to be at risk of reporting burnout (odds ratio, 2.11; 95% CI, 1.18-3.78; p = 0.012). After controlling for resilience, profession, and setting, the following coping strategies were independently associated with outcomes: attending debriefing reduced risk of burnout (odds ratio, 0.45; 95% CI, 0.21-0.95; p = 0.036), whereas the odds of posttraumatic stress were less if staff used talking to seniors (odds ratio, 0.43; 95% CI, 0.20-0.92; p = 0.029) or hobbies (odds ratio, 0.46; 95% CI, 0.23-0.93; p = 0.030) to cope with stress at work. Venting emotion (odds ratio, 1.92; 95% CI, 1.12-3.31; p = 0.018) and using alcohol (odds ratio, 2.30; 95% CI, 1.26-4.20; p = 0.006) were associated with a doubling in risk of reporting burnout. CONCLUSIONS: The use of particular coping strategies was systematically associated with symptoms of burnout and work-related posttraumatic stress in this group of intensive care staff, even after controlling for resilience and other factors. More research on how best to promote adaptive coping is needed in these challenging settings.

Does Combination Therapy with Tamsulosin and Tolterodine Improve Ureteral Stent Discomfort Compared with Tamsulosin Alone? A Double-Blind, Randomized, Controlled Trial.

PURPOSE: Ureteral stent discomfort is a significant postoperative problem for many patients. Despite the use of narcotics and α-blockers patients often experience bothersome lower urinary tract symptoms and pain, which impair daily activities. We compared combination therapy with an α-blocker and an anticholinergic to monotherapy with an α-blocker. MATERIALS AND METHODS: A double-blind, randomized, controlled trial was performed from December 2012 to April 2014. A total of 80 patients were randomized, including 44 to the combination group (tamsulosin 0.4 mg and tolterodine early release 4 mg) and 36 to the monotherapy group (tamsulosin 0.4 mg and placebo). Patients with preexisting ureteral stent placement or current anticholinergic therapy were excluded from study. Patients completed USSQ (Urinary Stent Symptom Questionnaire) before stent placement on the day of surgery, the day after stent placement, the morning of stent removal and the day after stent removal. The questionnaire included questions regarding urinary symptoms, general health, body pain, and work and sexual history. RESULTS: A total of 80 patients (40 males and 40 females) were studied. Mean age was 51.5 vs 51.3 years (p = 0.95) and mean body mass index was 33.6 vs 31.9 kg/m(2) (p = 0.44) in monotherapy group 1 vs combination therapy group 2. Between the 2 groups there was no significant difference in urinary symptoms, body pain and activities of daily living from baseline to just before stent removal (p = 0.95, 0.40 and 0.95, respectively). Although there was no difference between the groups, both showed improvement in urinary symptoms from the time of initial stent insertion to just prior to stent removal (difference -0.50 for combination therapy and -0.40 for monotherapy). The mean stent indwelling time of 9.6 and 8.7 days in the combination and monotherapy groups, respectively, did not differ (p = 0.67). On ANOVA it had no significant impact on results (p = 0.64). CONCLUSIONS: Combination therapy with tamsulosin and tolterodine does not appear to improve urinary symptoms, bodily pain or quality of life in patients after ureteral stent placement for nephrolithiasis compared to tamsulosin alone. Both groups experienced worse urinary symptoms, pain and quality of life with a stent, suggesting that further research is necessary to improve stent discomfort.

Implications of Volume Exclusion: A Look at Thermodynamic Perspective of DNA-Hemoglobin Complexes and Their Reconstitutes Under Macromolecular Crowding.

Live cells contain high concentrations of macromolecules, but almost all experimental biochemical data have been generated from dilute solutions that do not reflect conditions in vivo. To understand biomolecular behavior in vivo, properties studied in vitro are extrapolated to conditions in vivo. Another significant factor which is overlooked is the effects of macromolecular crowding and its consequences in the actual biochemical and physiological environment. Such influences of crowding, its modification and physiological parameters have been reported. The present study investigates the effect of molecular crowding on binding characteristics of Salmon sperm DNA with Bovine hemoglobin and their reconstitutes in presence of molecular crowders viz., Poly ethylene glycol (PEG) and Dextran of different molecular weight by fluorescence, UV visible spectroscopic technique at different temperatures. The results showed that BHb fluorescence was quenched by sDNA through static quenching mechanism which is enhanced in presence of polymers. The number of binding sites 'n' and binding constants 'K' were determined at different temperatures based on fluorescence quenching. The thermodynamic parameters namely ∆H°, ∆G°, T∆S° were studied at different temperatures and the results indicate that hydrophobic forces are predominant in the sDNA-BHb complex. Negative ∆G° values imply that the binding process is spontaneous.

Analysis of electron-vibrational interaction in interconfigurational 5d➔4f transition of Eu2+ ions in Na5 Ca4 (PO4 )4 F.

In this paper, the photoluminescence properties of Eu2+ -activated greenish-blue-emitting halophosphate phosphor Na5 Ca4 (PO4 )4 F were studied to estimate electron-vibrational interaction (EVI) parameters such as the Huang-Rhys factor, effective phonon energy, Stokes shift and zero phonon line (ZPL) position for various concentrations of dopant. The validity of the results was established by modeling the emission spectra, which was found to be in good agreement with the experimental photoluminescence spectra. Copyright © 2016 John Wiley & Sons, Ltd.