Diffuse alveolar haemorrhage in children hospitalised in a tertiary­level hospital: A retrospective descriptive study.

Background: Diffuse alveolar haemorrhage (DAH) is considered a rare condition in children. There is no consensus on the management of DAH syndromes in Africa or other low- and middle-income countries. In this brief report, the clinical characteristics, management and outcomes of children treated for DAH in the Chris Hani Baragwanath Academic Hospital paediatric pulmonology unit in Johannesburg, South Africa are described. Fifteen children were included in this case series, of whom 11 (73.3%) presented with severe microcytic anaemia. Of the 11 children who had bronchoalveolar lavage, 9 (81.8%; 60.0% of the total) had haemosiderin-laden macrophages on microscopy. Only 5 children had a lung biopsy, of whom 3 (60.0%) had capillaritis. All the children were started on oral prednisone at presentation, and 11 (73.3%) received additional complementary treatment. Nine children (60.0%) had normal haemoglobin levels 1 year after initiation of treatment. Our series supports previous reports that DAH is uncommon in children. A large proportion of our patients responded well to treatment despite some resource limitations. What the study adds: The study provides additional data on children presenting with diffuse alveolar haemorrhage in a South African tertiary hospital. What are the implications of the findings: There is a need for South African pulmonologists to come together and conduct a national audit of these patients in different hospitals to determine the incidence in our country, as well as to inform a management plan in the presence or absence of specialised tests.

When are bacteria really gazelles? Comparing patchy ecologies with dimensionless numbers.

From micro to planetary scales, spatial heterogeneity-patchiness-is ubiquitous in ecosystems, defining the environments in which organisms move and interact. However, most large-scale models still use spatially averaged 'mean fields' to represent natural populations, while fine-scale spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grünbaum (2012, Interface Focus 2: 150-155) introduced a heuristic, based on three dimensionless ratios quantifying movement, reproduction and resource consumption, to characterise patchy ecological interactions and identify when mean-field assumptions are justifiable. We calculated these dimensionless numbers for 33 interactions between consumers and their resource patches in terrestrial, aquatic and aerial environments. Consumers ranged in size from bacteria to whales, and patches lasted from minutes to millennia, with separation scales from mm to hundreds of km. No interactions could be accurately represented by naive mean-field models, though 19 (58%) could be partially simplified by averaging out movement, reproductive or consumption dynamics. Clustering interactions by their non-dimensional ratios revealed several unexpected dynamic similarities. For example, bacterial Pseudoalteromonas exploit nutrient plumes similarly to Mongolian gazelles grazing on ephemeral steppe vegetation. We argue that dimensional analysis is valuable for characterising ecological patchiness and can link widely different systems into a single quantitative framework.

The global lake area, climate, and population dataset.

An increasing population in conjunction with a changing climate necessitates a detailed understanding of water abundance at multiple spatial and temporal scales. Remote sensing has provided massive data volumes to track fluctuations in water quantity, yet contextualizing water abundance with other local, regional, and global trends remains challenging by often requiring large computational resources to combine multiple data sources into analytically-friendly formats. To bridge this gap and facilitate future freshwater research opportunities, we harmonized existing global datasets to create the Global Lake area, Climate, and Population (GLCP) dataset. The GLCP is a compilation of lake surface area for 1.42 + million lakes and reservoirs of at least 10 ha in size from 1995 to 2015 with co-located basin-level temperature, precipitation, and population data. The GLCP was created with FAIR (findable, accessible, interoperable, reusable) data principles in mind and retains unique identifiers from parent datasets to expedite interoperability. The GLCP offers critical data for basic and applied investigations of lake surface area and water quantity at local, regional, and global scales.

Serum IL-36α, IL-36ß, and IL-36γ levels in patients with hidradenitis suppurativa: association with disease characteristics, smoking, obesity, and metabolic syndrome.

Hidradenitis Suppurativa (HS) is a chronic, inflammatory, and relapsing skin disease. Pathogenesis of the disease is not well understood, but many studies revealed the potential role of cytokines and interleukins. IL-36 expression was increased in tissue samples of HS patients with conflicting result regarding serum levels. To investigate serum IL-36 levels in HS patients and evaluate their relation to disease characteristics, 44 patients diagnosed with HS and 44 age and sex-matched healthy controls were included in the study. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum IL-36 concentrations. Serum levels of IL-36α, IL-36ß, and IL-36γ were significantly elevated in HS patients compared to healthy controls (all three p < 0.001). IL-36α, IL-36ß, and IL-36γ levels were significantly higher in current smokers compared to non-smokers and positively correlated with number of packs/year (p = 0.002, r = 0.402; p = 0.042, r = 0.242 and p = 0.001, r = 0.391, respectively). IL-36α, IL-36ß, and IL-36γ levels were also elevated in obese patients and patients with metabolic syndrome (p = 0.007, < 0.001, 0.038, 0.004, 0.006, and 0.048, respectively). After stratified and restricted analyses for smoking, obesity, and metabolic syndrome IL-36α, IL-36ß, and IL-36γ increased the risk of HS 11.0, 1.79, and 4.5 time, respectively (95% CI 1.7-71.28, p < 0.001; 95% CI 1.04-3.06, p = 0.005 and, 95% CI 1.007-20.106, p = 0.040, respectively). Elevated serum IL-36 levels may contribute to pathogenesis of HS and may be a candidate for future biological treatment of the disease.

Role of serum 25-hydroxyvitamin D levels and vitamin D receptor gene polymorphisms in patients with rosacea: a case-control study.

BACKGROUND: Vitamin D has significant effects on the immune system and thereby on the pathogenesis of rosacea. However, there is a lack of information on the vitamin D status and vitamin D receptors (VDRs) of patients with rosacea. AIM: To evaluate the role of vitamin D in rosacea susceptibility. METHODS: A case-control study was conducted, enrolling patients with rosacea and healthy controls (HCs). Five VDR gene single nucleotide polymorphisms (SNPs) (Cdx2, FokI, ApaI, BsmI and TaqI) and serum 25-hydroxyvitamin D3 [25(OH)D3 ] levels were compared between patients and HCs. RESULTS: The study enrolled 60 patients (M/F: 14/46) and 60 age- and sex-matched HCs (M/F: 14/46). Age (mean ± SD) was 48 ± 11 years for both groups. The serum 25(OH)D3 levels (median ± interquartile range) were higher in patients with rosacea (12.9 ± 6.8 ng/mL) than in HCs (10.5 ± 3.7 ng/mL) (P < 0.001). Subjects with high serum 25(OH)D3 levels had a 1.36-fold increased risk of rosacea (95% CI 1.17-1.58). Heterozygous and mutant ApaI polymorphisms increased rosacea risk by 5.26-fold (95% CI 1.51-18.35) and 3.69-fold (95% CI 1.19-11.48), respectively, whereas mutant TaqI polymorphisms decreased the risk by 4.69 times (95% CI 1.37-16.67). Heterozygosity for Cdx2 alleles increased rosacea risk, whereas wildtype ApaI and mutant TaqI alleles decreased it. CONCLUSIONS: The present study suggests that an increase in vitamin D levels may contribute to the development of rosacea. ApaI and TaqI polymorphisms, and heterozygous Cdx2, wildtype ApaI and mutant TaqI alleles were significantly associated with rosacea. These results indicate a possible role of vitamin D and VDR pathways in the pathogenesis of rosacea, although causality could not be assessed.

The prevalence of HIV seropositivity and associated cytopenias in full blood counts processed at an academic laboratory in Soweto, South Africa.

BACKGROUND: The HIV epidemic in South Africa (SA) has had a substantial impact on laboratory services, at least partially owing to the well-described propensity to cytopenias in HIV-positive patients. OBJECTIVES: (i) To formally gauge the impact of HIV infection on the state sector haematology services in SA by determining the HIV seropositivity rate among full blood counts (FBCs) performed at a large academic state sector laboratory; and (ii) to document the prevalence of cytopenias among HIV-positive patients in this setting. METHODS: Randomly selected FBCs submitted to the National Health Laboratory Service laboratory at Chris Hani Baragwanath Academic Hospital, Johannesburg, were extracted from the laboratory information system (LIS) and retrospectively reviewed. HIV test results and other pertinent information in the LIS were documented, as was the presence of any cytopenias. RESULTS: HIV status was documented in 561 of 1 006 samples (55.8%), with 307 (54.7%) of these being HIV-positive. Of the HIV-positive patients, 63.2% had one or more cytopenia/s. Anaemia was present in 183/307 (59.6%) of the HIV-positive patients, and was severe (haemoglobin <8 g/dL) in 32/307 (10.4%). Multivariate linear regression analysis showed significant independent associations between the presence of anaemia and both immunological AIDS (iAIDS) (p<0.0001) and male sex (p<0.025), but not HIV viral load (VL) (p=0.33) or antiretroviral therapy (ART) exposure (p=0.70). Thrombocytopenia and neutropenia were present in 37/307 (12.1%) and 11/51 (21.6%) of the HIV-positive patients, respectively, with no statistically significant association between either of these cytopenias and iAIDS, exposure to ART or VL. CONCLUSIONS: The findings reflect the substantial impact of the HIV epidemic on state sector laboratory resources, particularly the haematology service.

Refining peripheral blood smear review rules for neonatal inpatients in a South African academic laboratory.

INTRODUCTION: Peripheral blood smear review (PBSR) is a labour-intensive test, and skilled morphologists are in short supply. It is therefore helpful for laboratories to establish rules for PBSR to improve laboratory efficiency. Previously published guidelines in this regard are useful, but make few recommendations specific to neonates. Neonatal blood is characterized by several peculiarities which would be considered pathological if present in adults. Consequently, smear review rules (SRR) are often triggered in neonates without significant value being added on review. This study aimed to assess and fine-tune the SRR triggered in neonatal samples in order to improve laboratory efficiency. METHODS: Full blood counts collected from 188 neonatal inpatients of the Chris Hani Baragwanath Academic Hospital in South Africa were retrospectively reviewed, the triggered rules documented, and the value added on PBSR determined. RESULTS: Smear review rules were triggered in 148 (78.7%) samples, with significant morphological abnormalities identified in 84 (54.4%), and a false-positive rate of 34.0%. In patients with unhelpful review, the commonest rules triggered were the flags querying the presence of abnormal lymphocytes, blasts or nucleated red blood cells. When one or more of these flags were triggered in the absence of any other SRR, PBSR was always noncontributory. Disregarding these flags in the current cohort would reduce both the review and the false-positive rates by >20% without increasing the false-negative rate. CONCLUSION: False-positive smear review is common in neonates, and minor modifications to SRR can substantially reduce the smear review rate without increasing the false-negative rate.

A conserved MADS-box phosphorylation motif regulates differentiation and mitochondrial function in skeletal, cardiac, and smooth muscle cells.

Exposure to metabolic disease during fetal development alters cellular differentiation and perturbs metabolic homeostasis, but the underlying molecular regulators of this phenomenon in muscle cells are not completely understood. To address this, we undertook a computational approach to identify cooperating partners of the myocyte enhancer factor-2 (MEF2) family of transcription factors, known regulators of muscle differentiation and metabolic function. We demonstrate that MEF2 and the serum response factor (SRF) collaboratively regulate the expression of numerous muscle-specific genes, including microRNA-133a (miR-133a). Using tandem mass spectrometry techniques, we identify a conserved phosphorylation motif within the MEF2 and SRF Mcm1 Agamous Deficiens SRF (MADS)-box that regulates miR-133a expression and mitochondrial function in response to a lipotoxic signal. Furthermore, reconstitution of MEF2 function by expression of a neutralizing mutation in this identified phosphorylation motif restores miR-133a expression and mitochondrial membrane potential during lipotoxicity. Mechanistically, we demonstrate that miR-133a regulates mitochondrial function through translational inhibition of a mitophagy and cell death modulating protein, called Nix. Finally, we show that rodents exposed to gestational diabetes during fetal development display muscle diacylglycerol accumulation, concurrent with insulin resistance, reduced miR-133a, and elevated Nix expression, as young adult rats. Given the diverse roles of miR-133a and Nix in regulating mitochondrial function, and proliferation in certain cancers, dysregulation of this genetic pathway may have broad implications involving insulin resistance, cardiovascular disease, and cancer biology.

Prevalence and causes of thrombocytopenia in an academic state-sector laboratory in Soweto, Johannesburg, South Africa.

BACKGROUND: Causes of thrombocytopenia range from laboratory errors to life-threatening pathological conditions. To establish the cause, appropriate laboratory investigation is required. OBJECTIVES: To determine the prevalence and causes of platelet counts <100 × 10(9)/L in state health facilities in Johannesburg, South Africa, as well as the quality of the subsequent laboratory work-up in this setting. METHODS: Full blood counts (FBCs) performed on 7 randomly selected days at the National Health Laboratory Service laboratory at Chris Hani Baragwanath Academic Hospital were retrospectively reviewed. Samples with platelet counts <100 × 109/L were identified, and pertinent information was extracted from the laboratory database. RESULTS: Of 4 456 FBCs included, 381 (8.6%) had a platelet count of <100 × 10(9)/L. Thrombocytopenia prevalence rates were high in haematology/oncology wards (34.4%), intensive care units (20.5%) and medical wards (18.7%) and among neonatal inpatients (16.5%), and were lowest in outpatient clinics (1-2%). A cause was apparent in ~60% of patients, the commonest causes being chemotherapy and sepsis (each comprising >20% of the recognised causes). Spurious thrombocytopenia, disseminated tuberculosis, aplastic anaemia, immune thrombocytopenia and malignant marrow infiltration each accounted for 5 - 10% of the causes, while malaria, thrombotic thrombocytopenic purpura, HIV effect and liver disease were each identified in <5% of cases. HIV status was documented in ~70% of the patients, of whom ~50% tested positive. The quality of the laboratory work-up showed differences between specialties within the hospital setting, and was poorest in the primary healthcare clinic sector. CONCLUSION: Thrombocytopenia is common in hospitalised patients in the Johannesburg academic state sector. Differences in the quality of the laboratory work-up emphasise the need for a standardised approach to thrombocytopenia investigation and increased awareness among clinicians.

Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Signal-dependent fra-2 regulation in skeletal muscle reserve and satellite cells.

Activator protein-1 (AP-1) is a ubiquitous transcription factor that paradoxically also has some tissue-specific functions. In skeletal muscle cells, we document that the AP-1 subunit, Fra-2, is expressed in the resident stem cells (Pax7-positive satellite cells) and also in the analogous undifferentiated 'reserve' cell population in myogenic cultures, but not in differentiated myofiber nuclei. Silencing of Fra-2 expression enhances the expression of differentiation markers such as muscle creatine kinase and myosin heavy chain, indicating a possible role of Fra-2 in undifferentiated myogenic progenitor cells. We observed that Fra-2 is a target of cytokine-mediated extracellular signal-regulated kinase-1/2 signaling in cultured muscle cells, and extensive mass spectrometry and mutational analysis identified S320 and T322 as regulators of Fra-2 protein stability. Interestingly, Fra-2 S320 phosphorylation occurs transiently in activated satellite cells and is extinguished in myogenin-positive differentiating cells. Thus, cytokine-mediated Fra-2 expression and stabilization is linked to regulation of myogenic progenitor cells having implications for the molecular regulation of adult muscle stem cells and skeletal muscle regeneration.

Effect of reading on surface electromyogram recordings in patients with blepharospasm.

PURPOSE: To compare the surface electromyogram recordings between patients with benign essential blepharospasm and controls while maintaining primary gaze and reading in downgaze. METHODS: A university-based, prospective case series of 7 benign essential blepharospasm patients and 7 normal patients. Bilateral lower eyelid preseptal orbicularis oculi muscle potentials were recorded via surface electromyogram and video while performing a standardized 60-second task that was divided in 3 equal 20-second subtasks. Specifically, patients were asked to maintain primary gaze for the first 20-second interval, to read quietly for the second interval, and again maintain primary gaze for the third 20-second interval. Fourteen trials capturing bilateral recordings were performed in each group; qualitative and quantitative analysis of the surface electromyogram recordings was performed and compared both between patient groups and between subtasks. Blepharospasm patients were also asked to describe the effect of reading on their spasms. Specifically, they were asked before the study if reading lessened or worsened their spasms and then were asked poststudy if their symptoms lessened or worsened during the reading task. RESULTS: The mean surface electromyogram potential of the orbicularis muscle was significantly less in normal eyes when compared with blepharospasm eyes for each task. Furthermore, the mean surface electromyogram potential during the reading task was significantly reduced when compared with the primary gaze task in all eyes. Only blepharospasm patients noticed this reduction subjectively. CONCLUSIONS: Although conventional wisdom regarding blepharospasm suggests that reading is an exacerbating factor, short durations of reading seem to relieve spasms. This may be due to the effect of downgaze on the blink reflex and may offer possible areas of investigation for novel blepharospasm treatments.

The functional role of nuclear factor kappa-kappaB1 -94 ins/del ATTG promotor gene polymorphism in Behçet's disease: an exploratory study.

Behçet's Disease (BD) is a systemic immunoinflammatory disease. The pathogenesis of BD is unknown, although raised levels of several pro-inflammatory cytokines have been reported. Nuclear factor kappa B (NF-kappaB) is a family of critical transcriptional factors involved in the regulation of a large variety of inflammatory responses and apoptosis. In this study we investigated the -94 insertion/deletion ATTG promoter polymorphism of the NF-kappaB1 gene (NFKB1) in 86 patients with BD and 100 healthy controls. The frequency of the -94ins ATTG (I) allele was 61.6% in patients with BD and 59% in controls and the frequency of the -94 del ATTG (D) allele was 38.4% in patients with BD and 41% in controls. The frequency of the -94ins ATTG (I) allele was significantly higher in patients with ocular involvement (P = 0.03). In the genotype study, the overall frequencies of II, ID and DD were 40.7%, 41.9%, and 17.4% in the patient group and 30%, 58% and 12% in the control group (P: 0.08). The II genotype was significantly higher in patients with ocular involvement, genital ulcers or papulopustular lesions. The frequency of the II, ID and DD genotypes showed no marked difference in patients with erythema nodosum, pathergy positivity, arthritis or vascular involvement. No difference was found for gender, positive family history or age at disease onset. This study provides evidence that the -94ins/del ATTG promoter polymorphism of NFKB1 may have functional consequences in BD, especially in patients with ocular involvement.

Bonbon toffee sign: a new dermatoscopic feature for sebaceous hyperplasia.

INTRODUCTION: Sebaceous hyperplasia is a benign proliferation of the sebaceous gland. In this study, we tried to define the dermatoscopic features of sebaceous hyperplasia, which will help to minimize misdiagnoses. MATERIAL AND METHOD: Seventeen patients with 30 sebaceous hyperplasia lesions were included in the study. All the lesions were evaluated dermatoscopically. RESULTS: Cumulus sign, crown vessels, and milia-like cysts were detected in 100%, 86.6%, 53.3% of the lesions, respectively. In 80% of the lesions, the bonbon toffee sign was detected. CONCLUSION: During this study, we observed a feature with central umbilication surrounded by cumulus sign in 80% of our cases, and we named this entity as the 'Bonbon toffee sign', which resembled us 'bonbon toffee'. We think the 'bonbon toffee sign' is a simple and easily recognizable phrase, and it can be used as a new terminology in dermatoscopic diagnosis of sebaceous hyperplasia.