Inflammatory Cytokines Are Associated with Cognitive Dysfunction and Depressive State during Acute Bacterial Infections and the Recovery Phase.

During a bacterial infection, individuals may present with behavioral changes referred to as sickness behavior, which has been suggested is induced by the inflammatory markers that are released because of the infective immunological challenge. However, few studies have explored this multidimensional phenomenon in naturally occurring conditions. A longitudinal observational study was conducted to explore the role of inflammatory cytokines in mediating the sickness behavior during a bacterial infection. There were 13, 11 and 37 participants in the infection, hospital control and healthy groups, respectively. They were all followed up for 6 weeks and their inflammatory markers were quantified throughout those weeks. Cognitive function and depressive state were assessed by means of the Mini-Mental State Examination (MMSE) and Cornell Scale for Depression in Dementia (CSDD). Reductions in proinflammatory markers C-Reactive protein (CRP), interleukin - 6 (IL6) and tumor necrosis factor-α (TNFα) and increments in anti-inflammatory markers (interleukin - 4 (IL4)) were associated with an improvement in CSDD and MSEE in patients recovering from a bacterial infection. The correlation between inflammatory makers and CSDD was statistically significant for the CRP (r = 0.535, p = 0.001), the IL6 (r = 0.499, p < 0.001), the TNFα (r = 0.235, p = 0.007) and the IL4 (r = -0.321, p = 0.018). Inflammatory cytokines may mediate sickness behavior during acute illness. These results may enhance the understanding of the pathophysiology and potential treatment strategies to palliate this sickness behavior.

Dchs1-Fat4 regulation of osteogenic differentiation in mouse.

In human, mutations of the protocadherins FAT4 and DCHS1 result in Van Maldergem syndrome, which is characterised, in part, by craniofacial abnormalities. Here, we analyse the role of Dchs1-Fat4 signalling during osteoblast differentiation in mouse. We show that Fat4 and Dchs1 mutants mimic the craniofacial phenotype of the human syndrome and that Dchs1-Fat4 signalling is essential for osteoblast differentiation. In Dchs1/Fat4 mutants, proliferation of osteoprogenitors is increased and osteoblast differentiation is delayed. We show that loss of Dchs1-Fat4 signalling is linked to increased Yap-Tead activity and that Yap is expressed and required for proliferation in osteoprogenitors. In contrast, Taz is expressed in more-committed Runx2-expressing osteoblasts, Taz does not regulate osteoblast proliferation and Taz-Tead activity is unaffected in Dchs1/Fat4 mutants. Finally, we show that Yap and Taz differentially regulate the transcriptional activity of Runx2, and that the activity of Yap-Runx2 and Taz-Runx2 complexes is altered in Dchs1/Fat4 mutant osteoblasts. In conclusion, these data identify Dchs1-Fat4 as a signalling pathway in osteoblast differentiation, reveal its crucial role within the early Runx2 progenitors, and identify distinct requirements for Yap and Taz during osteoblast differentiation.

Identification of European isolates of the lager yeast parent Saccharomyces eubayanus.

Lager brewing first occurred in Bavaria in the 15th century, associated with restrictions of brewing to colder months. The lager yeast, Saccharomyces pastorianus, is cold tolerant. It is a hybrid between Saccharomyces cerevisiae and Saccharomyces eubayanus, and has been found only in industrial settings. Natural isolates of S. eubayanus were first discovered in Patagonia 11 years ago. They have since been isolated from China, Tibet, New Zealand, and North America, but not from Europe. Here, we describe the first European strains UCD646 and UCD650, isolated from a wooded area on a university campus in Dublin, Ireland. We generated complete chromosome level assemblies of both genomes using long- and short-read sequencing. The UCD isolates belong to the Holarctic clade. Genome analysis shows that isolates similar to the Irish strains contributed to the S. eubayanus component of S. pastorianus, but isolates from Tibet made a larger contribution.

Evaluating the 'cost of generating force' hypothesis across frequency in human running and hopping.

The volume of active muscle and duration of extensor muscle force well explain the associated metabolic energy expenditure across body mass and velocity during level-ground running and hopping. However, if these parameters fundamentally drive metabolic energy expenditure, then they should pertain to multiple modes of locomotion and provide a simple framework for relating biomechanics to metabolic energy expenditure in bouncing gaits. Therefore, we evaluated the ability of the 'cost of generating force' hypothesis to link biomechanics and metabolic energy expenditure during human running and hopping across step frequencies. We asked participants to run and hop at 85%, 92%, 100%, 108% and 115% of preferred running step frequency. We calculated changes in active muscle volume, duration of force production and metabolic energy expenditure. Overall, as step frequency increased, active muscle volume decreased as a result of postural changes via effective mechanical advantage (EMA) or duty factor. Accounting for changes in EMA and muscle volume better related to metabolic energy expenditure during running and hopping at different step frequencies than assuming a constant EMA and muscle volume. Thus, to ultimately develop muscle mechanics models that can explain metabolic energy expenditure across different modes of locomotion, we suggest more precise measures of muscle force production that include the effects of EMA.

Survey showed that very few paediatric residents in Southwest Nigeria were interested in specialising in gastroenterology.

AIM: Paediatric gastroenterology remains an under-recognised sub-speciality in Africa. We determined the preferred sub-specialities among paediatric residents in Southwest Nigeria and what influenced whether they chose paediatric gastroenterology. METHODS: This was a cross-sectional survey of paediatric residents in seven teaching hospitals in Southwest Nigeria. A self-administered questionnaire was used to obtain information on their socio-demographics, educational attainment, choice of sub-speciality and the factors influencing that choice. RESULTS: Of 144 eligible paediatric residents, 124 (86.1%) completed the survey. Their mean age was 35.0 ± 1.7 years, and 83 (66.9%) were females. The majority (94.4%) had already chosen their sub-speciality, and nearly two-thirds (65.0%) made the decision during training. The most popular sub-speciality was neonatology (30.6%), and only three (2.4%) residents chose gastroenterology. Factors influencing the choice of sub-speciality were perceived ability (85.3%) and academic experience (83.8%). Financial reasons were less frequent (32.5%). Lack of diagnostic equipment (30.6%) and role models (21.0%) were the most frequent reasons for residents being disinterested in paediatric gastroenterology. CONCLUSION: Few residents were interested in paediatric gastroenterology and there is a need to encourage interest in this subject at an early stage in their training and provide more diagnostic equipment and greater mentorship.

Factors impacting-stillbirth and neonatal death audit in Malawi: a qualitative study.

BACKGROUND: Over one million babies are stillborn or die within the first 28 days of life each year due to preventable causes and poor-quality care in resource-constrained countries. Death audit may be a valuable tool for improving quality of care and decreasing mortality. However, challenges in implementing audit and their subsequent action plans have been reported, with few successfully implemented and sustained. This study aimed to identify factors that affect stillbirth and neonatal death audit at the facility level in the southern region of Malawi. METHODS: Thirty-eight semi-structured interviews and seven focus group discussions with death audit committee members were conducted. Thematic analysis was guided by a conceptual framework applied deductively, combined with inductive line-by-line coding to identify additional emerging themes. RESULTS: The factors that affected audit at individual, facility and national level were related to training, staff motivation, power dynamics and autonomy, audit organisation and data support. We found that factors were linked because they informed each other. Inadequate staff training was caused by a lack of financial allocation at the facility level and donor-driven approaches to training at the national level, with training taking place only with support from funders. Staff motivation was affected by the institutional norms of reliance on monetary incentives during meetings, gazetted at the national level so that audits happened only if such incentives were available. This overshadowed other benefits and non-monetary incentives which were not promoted at the facility level. Inadequate resources to support audit were informed by limited facility-level autonomy and decision-making powers which remained controlled at the national level despite decentralisation. Action plan implementation challenges after audit meetings resulted from inadequate support at the facility level and inadequate audit policy and guidelines at the national level. Poor documentation affected audit processes informed by inadequate supervision and promotion of data usage at both facility and national levels. CONCLUSIONS: Given that the factors that facilitate or inhibit audits are interconnected, implementers, policymakers and managers need to be aware that addressing barriers is likely to require a whole health systems approach targeting all system levels. This will require behavioural and complex intervention approaches.

Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study.

BACKGROUND: In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. METHODS AND FINDINGS: This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. CONCLUSIONS: Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201770.

A four-helix bundle stores copper for methane oxidation.

Methane-oxidizing bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase. Certain methanotrophs are also able to switch to using the iron-containing soluble methane monooxygenase to catalyse methane oxidation, with this switchover regulated by copper. Methane monooxygenases are nature's primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and methane monooxygenases have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. Here we discover and characterize a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for particulate methane monooxygenase. Csp1 is a tetramer of four-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realized. Cytosolic homologues of Csp1 are present in diverse bacteria, thus challenging the dogma that such organisms do not use copper in this location.

Load Carriage During Walking Increases Dynamic Stiffness at Distal Lower Limb Joints.

The addition of a load during walking requires changes in the movement pattern. The investigation of the dynamic joint stiffness behavior may help to understand the lower limb joints' contribution to these changes. This study aimed to investigate the dynamic stiffness of lower limb joints in response to the increased load carried while walking. Thirteen participants walked in two conditions: unloaded (an empty backpack) and loaded (the same backpack plus added mass corresponding to 30% of body mass). Dynamic stiffness was calculated as the linear slope of the regression line on the moment-angle curve during the power absorption phases of the ankle, knee, and hip in the sagittal plane. The results showed that ankle (P = .002) and knee (P < .001) increased their dynamic stiffness during loaded walking compared with unloaded, but no difference was observed at the hip (P = .332). The dynamic stiffness changes were different among joints (P < .001): ankle and knee changes were not different (P < .992), but they had a greater change than hip (P < .001). The nonuniform increases in lower limb joint dynamic stiffness suggest that the ankle and knee are critical joints to deal with the extra loading.

Differences in postural sway among healthy adults are associated with the ability to perform steady contractions with leg muscles.

Upright standing involves small displacements of the center of mass about the base of support. These displacements are often quantified by measuring various kinematic features of the center-of-pressure trajectory. The plantar flexors have often been identified as the key muscles for the control of these displacements; however, studies have suggested that the hip abductor and adductors may also be important. The purpose of our study was to determine the association between the force capabilities of selected leg muscles and sway-area rate across four balance conditions in young (25 ± 4 years; 12/19 women) and older adults (71 ± 5 years; 5/19 women). Due to the marked overlap in sway-area rate between the two age groups, the data were collapsed, and individuals were assigned to groups of low- and high-sway area rates based on a k-medoid cluster analysis. The number of participants assigned to each group varied across balance conditions and a subset of older adults was always included in the low-sway group for each balance condition. The most consistent explanatory variable for the variance in sway-area rate was force control of the hip abductors and ankle dorsiflexors as indicated by the magnitude of the normalized force fluctuations (force steadiness) during a submaximal isometric contraction. The explanatory power of the regression models varied across conditions, thereby identifying specific balance conditions that should be examined further in future studies of postural control.

Probiotics for treating acute infectious diarrhoea.

BACKGROUND: Probiotics may be effective in reducing the duration of acute infectious diarrhoea. OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. SEARCH METHODS: We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. SELECTION CRITERIA: Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. MAIN RESULTS: We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster-randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta-analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate-certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low-certainty evidence). Effect size was similar and marked heterogeneity persisted in pre-specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered. For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD -18.03 hours, 95% CI -27.28 to -8.78, random-effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants). No serious adverse events were attributed to probiotics. AUTHORS' CONCLUSIONS: Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.

Steep (30°) uphill walking vs. running: COM movements, stride kinematics, and leg muscle excitations.

PURPOSE: We sought to biomechanically distinguish steep uphill running from steep uphill walking and explore why athletes alternate between walking and running on steep inclines. METHODS: We quantified vertical center of mass (COM) accelerations and basic stride parameters for both walking and running at a treadmill speed of 1.0 m/s on the level and up a 30° incline. We also investigated how electromyography (EMG) of the gluteus maximus (GMAX), vastus medialis (VM), medial gastrocnemius (MG), and soleus (SOL) muscles differ between gaits when ascending steep hills. RESULTS: The vertical COM accelerations for steep uphill walking exhibited two peaks per step of magnitude 1.47 ± 0.23 g and 0.79 ± 0.10 g. In contrast, steep running exhibited a single peak per step pattern with a magnitude of 1.81 ± 0.15 g. Steep uphill running exhibited no aerial phase, 40% faster stride frequency, and 40% shorter foot-ground contact time compared to steep uphill walking but similar leg swing times. SOL showed 36% less iEMG per stride during steep uphill running versus steep uphill walking, but all other EMG comparisons between steep running and walking were not significantly different. CONCLUSIONS: Multiple biomechanical variables clearly indicate that steep uphill running is a distinctly different gait from steep uphill walking and is more similar to level running. The competing desires to minimize the energetic cost of locomotion and to avoid exhaustion of the SOL may be a possible explanation for gait alternation on steep inclines.

A cost-of-illness analysis of ß-Thalassaemia major in children in Sri Lanka - experience from a tertiary level teaching hospital.

BACKGROUND: Sri Lanka has a high prevalence of ß-thalassaemia major. Clinical management is complex and long-term and includes regular blood transfusion and iron chelation therapy. The economic burden of ß-thalassaemia for the Sri Lankan healthcare system and households is currently unknown. METHODS: A prevalence-based, cost-of-illness study was conducted on the Thalassaemia Unit, Department of Paediatrics, Kandy Teaching Hospital, Sri Lanka. Data were collected from clinical records, consultations with the head of the blood bank and a consultant paediatrician directly involved with the care of patients, alongside structured interviews with families to gather data on the personal costs incurred such as those for travel. RESULTS: Thirty-four children aged 2-17 years with transfusion dependent thalassaemia major and their parent/guardian were included in the study. The total average cost per patient year to the hospital was $US 2601 of which $US 2092 were direct costs and $US 509 were overhead costs. Mean household expenditure was $US 206 per year with food and transport per transfusion ($US 7.57 and $US 4.26 respectively) being the highest cost items. Nine (26.5%) families experienced catastrophic levels of healthcare expenditure (> 10% of income) in the care of their affected child. The poorest households were the most likely to experience such levels of expenditure. CONCLUSIONS: ß-thalassaemia major poses a significant economic burden on health services and the families of affected children in Sri Lanka. Greater support is needed for the high proportion of families that suffer catastrophic out-of-pocket costs.

The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka.

In hereditary hemochromatosis, iron overload is associated with homozygosity for the p.C282Y mutation. A second mutation, p.H63D, occurs at significant frequencies in Europe, North Africa, the Middle East and Asia. Early studies in Sri Lanka indicated that the variant had arisen independently, suggesting that it had been the subject of selective pressure. However, its role in iron absorption is unclear. In a survey of 7526 Sri Lankan secondary school students, we determined hemoglobin genotype and measured red cell indices, serum ferritin, transferrin receptor, iron zinc protoporphyrin and hepcidin. These variables were compared according to the presence or absence of the p.H63D variant in a subset of 1313 students for whom DNA samples were available. Students were classified as having low red cell indices if they had an MCV <80 fl and/or MCH <27 pg. Hetero and/or homozygosity for the p.H63D variant was more common in students with normal than low red cell indices (16.4% and 11.9% respectively; p = 0.019). Iron biomarkers and red cell indices were greater in children with the p.H63D variant than in normal and this was statistically significant for MCV (p = 0.046). Our findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant.

Growth in early life and physical and intellectual development at school age: a cohort study.

The associations between growth during early life and subsequent cognitive development and physical outcomes are not widely known in low-resource settings. We examined postnatal weight and height gain through early life and related these measurements to the nutritional status and intellectual development of the same children when they were between 7 and 9 years old. Mothers had enrolled in an randomised controlled trial to evaluate the effect of prenatal micronutrient supplementation on birth weight. Their children were born in 2004, their height and weight were measured at 6, 12, 18 and 24 months of age and were followed up between October 2012 and September 2013 (at ages 7-9 years, n 650). Height-for-age, weight-for-age and BMI-for-age were used to describe the nutritional status, and the Wechsler Intelligence Scale for Children fourth edition was used to measure the intellectual function. Multilevel linear and logistic modelling was used to estimate the association between early growth and subsequent growth and intellectual function. After adjustment, weight gain from 6 to 12 months of age was associated with Full-scale Intelligence Quotient, Verbal Comprehension Index, Working Memory Index and Perceptual Reasoning Index. Weight gain during early life was associated with subsequent nutritional status. For every 1 kg increase in weight during the 0- to 6-month period, the OR for underweight, thinness and stunting at 7-9 years of age were 0·19 (95 % CI 0·09, 0·37), 0·34 (95 % CI 0·19, 0·59) and 0·40 (95 % CI 0·19, 0·83), respectively. Weight gain during the periods of 6-12 months of age and 18-24 months of age was also associated with a lower risk of being underweight. Weight gain during early life was associated with better growth outcomes and improved intellectual development in young school-aged children.

Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey.

Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.

Manufacturing of novel low-cost adsorbent: Co-granulation of limestone and coffee waste.

Limestone and coffee waste were used during the wet co-granulation process for the production of efficient adsorbents to be used in the removal of anionic and cationic dyes. The adsorbents were characterized using different analytical techniques such as XRD, SEM, FTIR, organic elemental analysis, the nitrogen adsorption method, with wettability, strength and adsorption tests. The adsorption capacity of granules was determined by removal of methylene blue (MB) and orange II (OR) from single and mixed solutions. In the mixed solution, co-granules removed 100% of MB and 85% of OR. The equilibria were established after 6 and 480 h for MB and OR, respectively.

A prospective observational study of outcomes from rehabilitation of elderly patients with moderate to severe cognitive impairment.

OBJECTIVES: To evaluate rehabilitation outcomes in patients with moderate to severe cognitive impairment. DESIGN: Prospective observational cohort study. SETTING: Rehabilitation unit for older people. SUBJECTS: A total of 116 patients (70F) mean age (SD) 86.3 (6.4). Group 1: 89 patients with moderate cognitive impairment (Mini-Mental State Examination 11-20); and Group 2: 27 patients with severe cognitive impairment (Mini-Mental State Examination 0-10). INTERVENTION: A personalised rehabilitation plan. MAIN MEASURES: Barthel Activity of Daily Living score on admission and discharge, length of stay and discharge destination. RESULTS: Of 116 patients, 64 (55.2%) showed an improvement in Barthel score. Mini-Mental State Examination was significantly higher in those who improved, 15.4 (SD 3.7) vs.13.2 (SD 5.1): p = 0.01. The mean Barthel score improved in both groups; Group 1 - 14.7 (SD 19.1) vs. Group 2 - 9.3 (SD 16.3): p = 0.17. Of 84 home admissions in Group 1, more patients returning home showed improvements of at least 5 points in the Barthel score compared with nursing/residential home discharges (32/37 - 86.5% vs. 10/28 - 35.7%: p = 0.0001). In Group 2 of 17 home admissions, 6/6 (100%) home discharges showed improvement compared with 3/7 (42.8%) discharges to nursing/residential home (p = 0.07). In Group 1, a discharge home was associated with significantly greater improvement in number of Barthel items than a nursing/residential home discharge (3.27 (SD 2.07) vs. 1.86 (SD 2.32): p = 0.007). A similar non-significant pattern was noted for severe cognitive impairment patients (3.5 (3.06) vs. 1.14 (1.06); p = 0.1). CONCLUSION: Patients with moderate to severe cognitive impairment demonstrated significant improvements in Barthel score and Barthel items showing that such patients can and do improve with rehabilitation.

Using international human rights law to improve child health in low-income countries: a framework for healthcare professionals.

BACKGROUND: The Committee on Economic, Social and Cultural Rights states that the right to health is closely related to, and dependent upon, the realization of other human rights, including the right to food, water, education and shelter which are important determinants of health. Children's healthcare workers in low income settings may spend the majority of their professional lives trying to mitigate deficiencies of these rights but have little influence over them. In order to advocate successfully at a local level, we should be aware of the proportion of children living in our catchment population who do not have access to their basic rights. In order to carry out a rights audit, a framework within which healthcare workers could play their part is required, as is an agreed minimum core of rights, a timeframe and a set of indicators. DISCUSSION: A framework to assess how well states and their developmental partners are adhering to human rights principles is discussed, including the role that a healthcare worker might optimally play. A minimum core of economic and social rights seeks to establish a legal minimum set of protections, which should be available with immediate effect and applicable to all nations despite very different resources. Minimum core rights and the impact that progressive realisation may have had on the right to health is discussed, including what they should include from the perspective of children's health. A set of absolute rights are suggested, based on physiological needs and aligned with the corresponding articles of the United Nations Convention on the Rights of the Child. The development indicators which are likely to be used to monitor progress towards the Sustainable Development Goals is suggested as a way to monitor rights. We consider the ways in which the healthcare worker could use a rights audit to advocate with, and for their community. These audits could achieve several objectives. They may legitimise healthcare workers' interests in the determinants of health and, as they are often highly respected by their community, this may facilitate them to be agents for change at a local level. This may raise awareness on basic human rights and their importance to health and contribute to a needed change in mind-set from one of development needs to absolute rights. The results may catalyse colleagues to analyse further the upstream reasons why children, and the families in which they live, are not having their rights met.

Comparison of the next-generation Xpert MRSA/SA BC assay and the GeneOhm StaphSR assay to routine culture for identification of Staphylococcus aureus and methicillin-resistant S. aureus in positive-blood-culture broths.

A bloodstream infection with Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is a serious condition that carries a high mortality rate and is also associated with significant hospital costs. The rapid and accurate identification and differentiation of methicillin-susceptible S. aureus (MSSA) and MRSA directly from positive blood cultures has demonstrated benefits in both patient outcome and cost-of-care metrics. We compare the next-generation Xpert MRSA/SA BC (Xpert) assay to the GeneOhm StaphSR (GeneOhm) assay for the identification and detection of S. aureus and methicillin resistance in prospectively collected blood culture broths containing Gram-positive cocci. All results were compared to routine bacterial culture as the gold standard. Across 8 collection and test sites, the Xpert assay demonstrated a sensitivity of 99.6% (range, 96.4% to 100%) and a specificity of 99.5% (range, 98.0% to 100%) for identifying S. aureus, as well as a sensitivity of 98.1% (range, 87.5% to 100%) and a specificity of 99.6% (range, 98.3% to 100%) for identifying MRSA. In comparison, the GeneOhm assay demonstrated a sensitivity of 99.2% (range, 95.2% to 100%) and a specificity of 96.5% (range, 89.2% to 100%) for identifying S. aureus, as well as a sensitivity of 94.3% (range, 87.5% to 100%) and a specificity of 97.8% (range, 96.1% to 100%) for identifying MRSA. Five of six cultures falsely reported as negative for MRSA by the GeneOhm assay were correctly identified as positive by the Xpert assay, while one culture falsely reported as negative for MRSA by the Xpert assay was correctly reported as positive by the GeneOhm assay.