Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Determination of genetic diversity in Acacia modesta germplasm using SDS-PAGE.

Biochemical markers such as protein are very important to determine genetic diversity among plant species in a given population which in turn is very important for breeders and farmers as they can then easily select the most appropriate variety to grow in a given locality. In this connection, the present study is aimed to evaluate genetic diversity in Acacia modesta germplasm through Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (SDS-PAGE) technique. About 40 genotypes were subjected to SDS-PAGE analysis where a total of 12 polypeptide bands were observed in electrophoretogram. Out of which 16.67% were monomorphic while the remaining 83.33% were polymorphic. Variation found in B-2, 4, 5, 6, 7, 8, 9, 10, 11 and 12, were 20, 22.50, 32.50, 10, 2.50, 22.50, 15, 5, 2.50 and 75% respectively. Locus contribution toward genetic disagreement was 83.33%. Cluster analysis sorted all the genotypes into 9 clusters. The genotypes in one cluster were identical regarding protein profiling and showed less intra-specific genetic variation whereas differences were find from other genotypes.

Design and Development of a Solar Water Purification System with Graphene-Plasmonic Based Hybrid Nanocomposites: A Review.

Harvesting solar energy for water treatments has been considered a promising solution for a global community. The shortage of water is a great challenge for scientists due to the increased demand of the population-however, the low efficiency of absorber materials obstacles in practical applications. In addition, state-of-the-art conventional technologies require optical concentrators and multiple component-based systems, leading to lower efficiency and higher cost. In this review, a low-cost, more reliable, less energy-intensive, and more eco-friendly solar water purification system based on graphene-plasmonic hybrid nanocomposite has been demonstrated. Graphene-plasmonic-based hybrid nanocomposite has been utilized to achieve pure water from wastewater. Such hybrid nanocomposites have the ability to clean polluted water very efficiently due to their excellent properties such as higher surface area, low concentration, and working ability. Furthermore, the development of a solar water purification system has been achieved through optimized hybrid nanocomposites.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Lung ultrasound patterns in paediatric pneumonia in Mozambique and Pakistan.

OBJECTIVE: Improved pneumonia diagnostics are needed, particularly in resource-constrained settings. Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing pneumonia. The objective was to explore LUS patterns associated with paediatric pneumonia. METHODS: We conducted a prospective, observational study among children aged 2 to 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at two district hospitals in Mozambique and Pakistan. We assessed LUS and chest radiograph (CXR) examinations, and viral and bacterial nasopharyngeal carriage, and performed a secondary analysis of LUS patterns. RESULTS: LUS demonstrated a range of distinctive patterns that differed between children with and without pneumonia and between children in Mozambique versus Pakistan. The presence of LUS consolidation or interstitial patterns was more common in children with chest-indrawing pneumonia than in those without pneumonia. Consolidations were also more common among those with only bacterial but no viral carriage detected (50.0%) than among those with both (13.0%) and those with only virus detected (8.3%; p=0.03). LUS showed high interrater reliability among expert LUS interpreters for overall determination of pneumonia (κ=0.915), consolidation (κ=0.915) and interstitial patterns (κ=0.901), but interrater reliability between LUS and CXR for detecting consolidations was poor (κ=0.159, Pakistan) to fair (κ=0.453, Mozambique). DISCUSSION: Pattern recognition was discordant between LUS and CXR imaging modalities. Further research is needed to define and standardise LUS patterns associated with paediatric pneumonia and to evaluate the potential value of LUS as a reference standard.

Associations between Household-Level Exposures and All-Cause Diarrhea and Pathogen-Specific Enteric Infections in Children Enrolled in Five Sentinel Surveillance Studies.

Diarrheal disease remains a major cause of childhood mortality and morbidity causing poor health and economic outcomes. In low-resource settings, young children are exposed to numerous risk factors for enteric pathogen transmission within their dwellings, though the relative importance of different transmission pathways varies by pathogen species. The objective of this analysis was to model associations between five household-level risk factors-water, sanitation, flooring, caregiver education, and crowding-and infection status for endemic enteric pathogens in children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000 stool samples were tested for 16 specific enteropathogens using qPCR. Risk ratios for pathogen- and taxon-specific infection status were modeled using generalized linear models along with hazard ratios for all-cause diarrhea in proportional hazard models, with the five household-level variables as primary exposures adjusting for covariates. Improved drinking water sources conferred a 17% reduction in diarrhea risk; however, the direction of its association with particular pathogens was inconsistent. Improved sanitation was associated with a 9% reduction in diarrhea risk with protective effects across pathogen species and taxa of around 10-20% risk reduction. A 9% reduction in diarrhea risk was observed in subjects with covered floors, which were also associated with decreases in risk for zoonotic enteropathogens. Caregiver education and household crowding showed more modest, inconclusive results. Combining data from diverse sites, this analysis quantified associations between five household-level exposures on risk of specific enteric infections, effects which differed by pathogen species but were broadly consistent with hypothesized transmission mechanisms. Such estimates may be used within expanded water, sanitation, and hygiene (WASH) programs to target interventions to the particular pathogen profiles of individual communities and prioritize resources.

Early arthritis clinic is cost-effective, improves outcomes and reduces biologic use.

There is good evidence that dedicated early arthritis clinics (EACs) improve referral lag time and reduce delay in establishing disease-modifying therapy. However, it remains arguable whether such clinics improve relevant disease outcomes. Nationally, only 57% of units have dedicated EACs. Our rheumatology department established a centralised, patient-focused and multidisciplinary EAC to achieve key financial and clinical outcome targets the department was failing to meet. The EAC aimed to increase the department's capacity to accommodate referrals from general practitioners (GPs) and other sources, decrease the time between diagnosis and starting therapy, establish standardised treatment algorithms and reduce biologic use. The EAC was established in January 2016 and comprised the introduction of a dedicated referral pro forma and an EA educational programme for GPs, pooling of all sources of referral, running of six EACs per week with availability of ultrasound and introduction of a standardised approach to the early initiation of therapy and timely review of treatment outcomes. The introduction of the EAC was associated with improved clinical outcomes (EA patients achieving a Disease Activity Score 28 (DAS28) < 3.2 in 2015, 38.0% [N = 113] vs. 78.5% [N = 220] in 2016) and overall patient experience (mean waiting time for EA patients' first appointment in 2015: 12 weeks vs. 2.5 weeks in 2016; 94% [N = 167] of patients recommended the rheumatology service in 2016 vs. 74% [N = 100] in 2015). The total costs associated with introducing the EAC were ~ £201,362. Use of biologics decreased from 26.0 to 5.6% between 2015 and 2016, resulting in a cost saving of ~ £394,942. Other cost savings associated with the EAC included reductions in the overall cost/patient seen (2015, £198.88; 2016, £74.98) and not running any premium rate initiative clinics (saving ~ £26,500 in 2016) to meet waiting list targets. Efficiency gains from the introduction of the EACs have improved patients' health and overall satisfaction with their treatment, whilst saving costs for healthcare.

Early arthritis clinic is effective for rheumatoid and psoriatic arthritides.

INTRODUCTION: Early arthritis clinics (EACs) have been well established since 1980s. Most of the data for their effectiveness comes from rheumatoid arthritis (RA) management and is largely limited to process outcomes. There is little evidence that such clinics improve clinical outcomes particularly for psoriatic arthritis (PsA). We examined whether EACs provide better outcomes irrespective of final arthritis diagnosis. METHODS: A 52-week prospective observational study of all inflammatory arthritis patients presenting to early arthritis service at our secondary care hospital in 2016 was undertaken. A protocolised approach to the early initiation of therapy (within 3 weeks) and 6-weekly review of treatment outcomes was embedded irrespective of the arthritis diagnosis. Statistical analysis was undertaken using Mann-Whitney U test for disease activity scores to ascertain the significance of outcomes. RESULTS: Of 1884 patients referred, 482 (25.5%) were triaged into EACs based on set criteria. 159 (64.3%) had RA, 55 (22%) with PsA and 33 had other inflammatory arthritides. Mean DAS28 for RA at first visit was 4.65 (0.6-8.0). Treating to target achieved DAS28 remission for 84 (53.5%) and low disease activity (LDA) for a further 44 (34%). Median time to achieve remission or LDA was 20 weeks (0-52 weeks). Mean tender (TJ) and swollen joint (SJ) counts for PsA at first visit were 8.2 (1-35) and 3.5 (0-14), respectively [n = 55]. The patient (PtGA) and physician (PhGA) global assessments mean were 3.0 and 2.9 (1-5). Target [TJ and SJ ≤ 2] was achieved for 38 patients (69%) and good PsARC response for a further four (7%). Median time to achieve the target or good response was 22 weeks (0-48 weeks). Final TJ and SJ mean was significantly better at 1.2 (0-4) and 0.3 (0-2) [p < 0.0001] with similar improvement in PtGA [mean 1.8 (1-4)] and PhGA [mean 1.6 (1-3)]. CONCLUSION: Dedicated EACs help achieve good clinical outcomes in majority of patients with RA and PsA. Nearly 80% of our cohort attained the target or good disease response in less than 6 months. This was despite a significant delay in patients presenting to their GPs and moderately high disease activity.

Optimization of the blood culture pathway: a template for improved sepsis management and diagnostic antimicrobial stewardship.

Laboratory processing of blood cultures has remained static over the past 30 years, despite increasing antibiotic resistance and advances in analyser design. At the study hospital, siting the blood culture analyser in the blood sciences laboratory and optimizing the pre-analytical and analytic phases of blood culture management resulted in a reduction in the time taken to detect most blood culture isolates to <12h. Fifty percent of positive blood cultures containing Escherichia coli were definitively reported with antibiotic susceptibilities in <24h. More than 85% of blood cultures positive for E. coli had antibiotic susceptibilities reported within 36h of collection, compared with 66h at a comparator hospital.

Spontaneous coronary artery dissection in the context of positive anticardiolipin antibodies and clinically undiagnosed systemic lupus erythematosus.

Spontaneous coronary artery dissection (SCAD) is an extremely uncommon condition that can lead to fatal acute myocardial infarction. There have been very few case reports of SCAD in patients with systemic lupus erythematosus (SLE) and even fewer in association with antiphospholipid antibodies - mainly postpartum. This is the first reported case of SCAD in a patient who was confirmed to have SLE and tested positive for anticardiolipin antibody and lupus anticoagulant. This case demonstrates the importance of carefully considering the differential diagnoses of SCAD at presentation. It also highlights the need for further research to explore the link between SLE, antiphospholipid antibodies and SCAD.

Linkage of a RAPD marker with powdery mildew resistance.

The aim of this study was to investigate the inheritance of powdery mildew disease and to tag it with a DNA marker to utilize for the marker-assisted selection (MAS) breeding program. The powdery mildew resistant genotype Fallon(er) and susceptible genotype 11760-3ER were selected from 177 genotypes by heavy infestation of germplasm with Erysiphe pisi through artificial inoculation. The F1 plants of the cross Fallon/11760-3 indicated the dominance of the susceptible allele, while F2 plants segregated in 3 : 1 ratio (susceptible : resistant) that fit for goodness of fitness by chi2 (P > 0.07), indicating monogenic recessive inheritance for powdery mildew resistance in Pisum sativum. A novel RAPD marker OPB18 (5'-CCACAGCAGT-3') was linked to the er-1 gene with 83% probability with a LOD score of 4.13, and was located at a distance of 11.2 cM from the er-1 gene.

Phenotypic variation in the agronomic and morphological traits of Pisum sativum L. germplasm obtained from different parts of the world.

A total of 286 genotypes were collected from 39 countries of the world and were evaluated to determine the phenotypic diversity for 17 quantitative traits. Higher degree of coefficient of variation were recorded for grain yield(-5) (52.46%), biomass(-5) (45.73%), fresh pod width(-10) (47.24%), dry pod weight(-1) (40.33%), plant height(-1) (35.25%), harvest index (32.70%) and number of branches(-5). Cluster-II clearly reflected that late genotypes were having lightest pods weight, shortest pod width, and pod length; low grain yield, biomass and harvest index. While genotypes in Cluster-III were in contrast to Cluster-II having heaviest pods weight, longest pods width and length, highest grain yield, biomass and harvest index. Higher PC(-1) values have been determined for days to flower initiation which consequently were contributing weighed positive to days to pods picking, days to flower completion, days to dry pod appearance, days to plant harvesting while negatively contributed to yield producing traits, indicating that late flowering pea germplasm emphasizes more on the vegetative growth and was low yielding. However, higher PC(-2) values have been obtained for number of branches(-5), grain yield and biomass while lower values for days to flowering, days to pods picking, days to flower completion, days to dry pod appearance and days to plant harvesting confirming the fact that early genotypes were high yielding.

First proteomic assay of Pakistani Pisum sativum L. germplasm relation to geographic pattern.

Proteomic assay was carried out to asses genetic diversity in relation to geographic pattern in 97 genotypes of Pisum sativum L., collected from all over Pakistan. In total 34 bands were observed and among these, 26.7% bands were monomorphic, while 73.5% bands showed polymorphism. Based on both Province Wise Analysis (PWA) and Agro-ecological Zones (AEZ) the genotypes collected from Punjab, North West Frontier Province (NWFP) exhibited 70.6%, and 64.7% variation respectively. The germplasm collected from Azad Kashmir showed the lowest level of genetic diversity. Cluster analysis exhibited, moderate level of association, between genetic diversity and geographic pattern of the genotypes.

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used. RESULTS: Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect. CONCLUSION: Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

Antinociceptive and antipyretic activities of the Zizyphus oxyphylla Edgew. leaves.

A methanol extract of Zizyphus oxyphylla Edgew leaves has been investigated for its analgesic and antipyretic activities in Adult Wistar and Swiss albino mice of either sex at 50, 100 and 200 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract demonstrated significant peripheral analgesic effect in the acetic acid-induced writhing test in mice. The phytochemical tests revealed that the extract contained alkaloids, anthraquinones, flavonoids, glycosides, phenols, resins, saponins and tannins using standard procedures. In conclusion, the present study suggests that the methanol extract of Zizyphus oxyphylla Edgew leaves possesses potent antipyretic and antinociceptive activities and thus validates its use in the treatment of pain and fever.

Inhibition activities of Colchicum luteum baker on lipoxygenase and other enzymes.

In vitro enzymes inhibition activities of the crude methanolic extract and various fractions of Colchicum luteum Baker (Liliaceae) including chloroform, ethyl acetate, n-butanol and aqueous were carried out against actylcholinesterase, butyrylcholinesterase, lipoxygenase and urease enzymes. A significant enzyme inhibition activity (89%) is shown by the crude methanolic extract and its fractions against lipoxygenase, while low to significant activity (32-75%) was evident against butyrylcholinesterase. The crude methanolic extract and its various fractions demonstrated low activity (29-61%) against acetylcholinesterase and no activity against urease.

Phytochemical study of Salvia moorcroftiana.

Four known flavonoids were isolated from the aerial parts of Salvia moorcroftiana.

Oral corticosteroid trials in the management of stable chronic obstructive pulmonary disease.

Although recent guidelines for managing chronic obstructive pulmonary disease (COPD) recommend a trial of oral corticosteroids in the initial assessment, its prognostic value remains unclear. We prospectively studied 127 adults (64% men) with stable COPD (FEV1/FVC < 60%) over 1 year. At entry, we measured lung volumes, gas transfer factor, respiratory symptoms (by questionnaire), and peripheral blood eosinophil count. Skin-prick testing was done, and spirometry after nebulized 5 mg salbutamol and, after 2 weeks, oral prednisolone. Physician A gave all patients inhaled beclomethasone dipropionate (800 mcg/day), whereas physician B prescribed this only to those with a positive oral corticosteroid trial. At 1 year, spirometry and respiratory questionnaire were repeated, with an estimate of overall symptom severity on a visual analogue scale. Follow-up data were available in 104 (82%) patients. Of these, 32 (31%) were unresponsive to salbutamol and prednisolone; 48 (46%) were responsive to beta agonists but not to corticosteroids, and 24 (23%) responded to corticosteroids and salbutamol. Patients in all groups were comparable, except that the prednisolone responders had a higher mean eosinophil count (p < 0.001) and more were ex-smokers (p < 0.001). Only the response to oral prednisolone correlated with the change in prebronchodilator FEV1 over 1 year. Oral prednisolone responders had higher FEV1 at 1 year (p < 0.02) and significantly lower symptom scores (p < 0.02). In COPD, corticosteroid trials contribute information additional to that gained from nebulized bronchodilator reversibility testing. Patients with a positive response to a corticosteroid trial are more likely to have improved symptomatically and spirometrically at 1 year.