Tertiary conformational transition constant of guinea pig haemoglobin determined from the reaction of 5,5′-dithiobis (2-nitrobenzoate) with CysF9[93]β and CysH3[125]β

We have determined Kequ, the equilibrium constant for the reaction of 5,5′-dithiobis(2-nitrobenzoate) — DTNB — with the CysF9*93+β and CysH3*125+β sulphydryl groups of various derivatives of guinea pig haemoglobin at 25oC. In the pH range 5.6 to 9, Kequ decreases almost 50-fold: from a mean of 3.45 ± 0.2 to a mean of 0.073 ± 0.01. Quantitative analyses of the pH dependence profiles of Kequ enable the determination of Krt, the equilibrium constant for the rt tertiary conformational transition of haemoglobin. The t isomer population is 53.9 (± 2)%. In the r conformation the pKas of the amino acid residues whose ionisations are coupled to the reaction of DTNB with the sulphydryl groups are 5.74 ± 0.02 — for a combination of HisNA2*2+β and HisH21*143+β) — and 7.74 ± 0.2 for ValNA1*1+β); in the t conformation they are 5.88 ± 0.05 and 8.23 ± 0.1, respectively.Keywords --- guinea pig haemoglobin; sulphydryl groups; 5,5′-dithiobis(2-nitrobenzoate); equilibrium constants; tertiary conformational transition

Nutritional Evaluation of Honey Bee Slum gum Meal as Replacement for Maize in the Feed of Growing Rabbits

As part of the efforts in developing alternative feed ingredients for feeding rabbits a feeding trial was conducted to investigate the nutritional potential of Honey Bee slum gum meal (HBSM) on the performance characteristics of growing rabbit. Thirty (30) growing rabbit of 7 weeks of age were weight-balanced and divided into three (3) dietary treatment groups of 10 rabbit each in a completely randomized designed experiment. Diet 1 had 0% inclusion of HBSM while 25 and 50% maize in diets 2 and 3 were replaced by HBSM respectively. Rabbits received feed and water ad libitum during the 12 weeks of the experiment. The final weights decrease linearly (P<0.05) as the level of inclusion increases (1663.20g 1630.00g and 1458.40g for rabbits on treatments 1, 2 and 3 respectively). Rabbit on diets 1 and 2 had higher (P<0.05) daily weight gains (13.59g and 13.15 respectively) compared with rabbits on diet 3 (11.1g). The digestibility of nutrients were not affected (P>0.05) by the dietary treatments. The values obtained for final weight, carcass weight, abdominal fat, kidney, liver and lungs were significantly (P<0.05) affected by dietary treatment. HBSM can be used as an alternative for substituting maize in growing rabbits diets up of 25% beyond which depression in performance is observed. Key words: Honey slum gum meal, Digestibility, Final weight, growing rabbits

Community pharmacists' management of minor ailments in developing countries: A systematic review of types, recommendations, information gathering and counselling practices

Aims: To conduct a systematic review of the management of minor ailments by community pharmacists in developing countries, and to identify the specific minor ailments encountered, the medications recommended or requested and the information gathering and counselling practices. Method: Observational studies from developing countries published in English language from inception to 2019 and report the management of minor ailments by community pharmacists were systematically searched in PubMed, ScienceDirect and Cochrane Library. Results: Thirty full-text studies, out of 7876 retrieved and screened, were included in the systematic review. Minor ailment-induced encounters by patients with community pharmacists are generally pervasive and involve mainly verbal request for specific medicines by name (60%). The most frequent minor ailments reported were respiratory, gastrointestinal and musculoskeletal conditions, and the most common medicines recommended or requested for were cough/cold preparations, antimotility and oral rehydration preparation, and analgesic/antipyretic. Inappropriate recommendation of antibiotics were reported for acute diarrhoea and cough/colds (40%) (10/25). Community pharmacists encountered 11-30 customers with minor ailments per day, with an average of about 4.8 (1.3-20.5) minutes per encounter. None of the studies reported the availability and/or use of a specific protocol to guide the management of minor ailments. There was wide variation in the type and depth of information gathered and used for the management of minor ailments; and the counselling information provided by community pharmacists, and there was no evidence of the documentation activities related to the management of minor ailments. Conclusions: Community pharmacists' encounter with and management of minor ailments appear extensive in developing countries and probably present an opportunity to contribute significantly to reduce disease burden and enhance public health. However, the management process is currently unstructured, unguided by a specific protocol and vary in the quality of recommendations, information gathering and counselling practices.Qatar National Research Fund, UREP24-147-3043; Open Access funding provided by the Qatar National Library

Thrombosis, major bleeding, and survival in COVID-19 supported by VV- ECMO in the first vs second wave- multicentre observational study in the UK

BACKGROUND: Bleeding and thrombosis are major complications of veno-venous extracorporeal membrane (VV-ECMO). OBJECTIVES: To assess thrombosis, major bleeding (MB) and 180-day in patients supported by VV-ECMO between first (1st March-31st May 2020) and second (1st June 2020-30th June 2021) waves of the COVID-19 pandemic. PATIENTS/METHODS: Observational study of 309 consecutive patients (≥18years) with severe COVID-19 supported by VV-ECMO in four nationally commissioned ECMO centres, UK. RESULTS: Median age was 48 (19-75)years and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8%(123/309) and 30%(93/309). In multivariate analysis, age >55 years (HR 2.29 [1.33-3.93],p=0.003) and elevated creatinine (HR 1.91 [1.19-3.08],p=0.008) were associated with increased mortality. Corrected for duration of VV-ECMO support, arterial thrombosis alone (HR 3.0 [95% CI1.5-5.9], P= 0.002) or circuit thrombosis alone (HR 3.9 [95% 2.4-6.3], P<0.001), but not venous thrombosis, increased mortality. MB during ECMO had 3-fold risk (95% CI 2.6-5.8, P<0.001) of mortality. The first wave cohort had more males (76.7% vs 64%, p=0.014), higher 180-day survival (71.1% vs 53.3% p=0.003), more venous thrombosis alone (46.4% vs 29.2%, p=0.02) and lower circuit thrombosis (9.2% vs 28.1%, p<0.001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%], p<0.0001) and Tocilizumab (20/150 [13.3%] vs 4/159 [2.5%] p=0.005). CONCLUSIONS: MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality whilst venous thrombosis alone had no effect. MB during ECMO support increased mortality 3.9-fold

Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\alpha}1{\beta}2 and {\alpha}2{\beta}1 interface.Comment: Reprinted (adapted) with permission from J. Phys. Chem. B DOI:10.1021/jp3022908. Copyright (2012) American Chemical Societ

Patient characteristics associated with COVID-19 positivity and fatality in Nigeria: retrospective cohort study

Objective: Despite the increasing disease burden, there is a dearth of context-specific evidence on the risk factors for COVID-19 positivity and subsequent death in Nigeria. Thus, the study objective was to identify context-specific factors associated with testing positive for COVID-19 and fatality in Nigeria. Design Retrospective cohort study. Setting: COVID-19 surveillance and laboratory centres in 36 states and the Federal Capital Territory reporting data to the Nigeria Centre for Disease Control. Participants: Individuals who were investigated for SARSCoV-2 using real-time PCR testing during the study period 27 February–8 June 2020. Methods: COVID-19 positivity and subsequent mortality. Multivariable logistic regression analyses were performed to identify factors independently associated with both outcome variables, and findings are presented as adjusted ORs (aORs) and 95% CIs. Results: A total of 36 496 patients were tested for COVID-19, with 10 517 confirmed cases. Of 3215 confirmed cases with available clinical outcomes, 295 died. Factors independently associated with COVID-19 positivity were older age (p value for trend<0.0001), male sex (aOR 1.11, 95%CI 1.04 to 1.18) and the following presenting symptoms: cough (aOR 1.23, 95% CI 1.13 to 1.32), fever (aOR 1.45, 95% CI 1.45 to 1.71), loss of smell (aOR 7.78, 95% CI 5.19 to 11.66) and loss of taste (aOR 2.50, 95% CI 1.60 to 3.90). An increased risk of mortality following COVID-19 was observed in those aged ≥51 years, patients in farming occupation (aOR 7.56, 95% CI 1.70 to 33.53) and those presenting with cough (aOR 2.06, 95% CI 1.41 to 3.01), breathing difficulties (aOR 5.68, 95% CI 3.77 to 8.58) and vomiting (aOR 2.54, 95% CI 1.33 to 4.84). Conclusion: The significant risk factors associated with COVID-19 positivity and subsequent mortality in the Nigerian population are similar to those reported in studies from other countries and should guide clinical decisions for COVID-19 testing and specialist care referrals

Thombosis, major bleeding, and survival in COVID-19 supported by veno-venous extracorporeal membrane oxygenation in the first vs second wave: a multicenter observational study in the United Kingdom

Background Bleeding and thrombosis are major complications of veno-venous (VV) extracorporeal membrane oxygenation (ECMO). Objectives To assess thrombosis, major bleeding (MB), and 180-day survival in patients supported by VV-ECMO between the first (March 1 to May 31, 2020) and second (June 1, 2020, to June 30, 2021) waves of the COVID-19 pandemic. Methods An observational study of 309 consecutive patients (aged ≥18years) with severe COVID-19 supported by VV-ECMO was performed in 4 nationally commissioned ECMO centers in the United Kingdom. Results Median age was 48 (19-75) years, and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8% (123/309), and 30% (93/309), respectively. In multivariate analysis, an age of >55 years (hazard ratio [HR], 2.29; 95% CI, 1.33-3.93; P = .003) and an elevated creatinine level (HR, 1.91; 95% CI, 1.19-3.08; P = .008) were associated with increased mortality. Correction for duration of VV-ECMO support, arterial thrombosis alone (HR, 3.0; 95% CI, 1.5-5.9; P = .002) or circuit thrombosis alone (HR, 3.9; 95% CI, 2.4-6.3; P < .001) but not venous thrombosis increased mortality. MB during ECMO had a 3-fold risk (95% CI, 2.6-5.8, P < .001) of mortality. The first wave cohort had more males (76.7% vs 64%; P = .014), higher 180-day survival (71.1% vs 53.3%; P = .003), more venous thrombosis alone (46.4% vs 29.2%; P = .02), and lower circuit thrombosis (9.2% vs 28.1%; P < .001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%]; P < .0001) and tocilizumab (20/150 [13.3%] vs 4/159 [2.5%]; P = .005). Conclusion MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality, while venous thrombosis alone had no effect. MB during ECMO support increased mortality by 3.9-fold. Keywords: COVID-19; extracorporeal membrane oxygenation; hemorrhage; mortality; thrombosi

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30