Early-Onset Juvenile SLE Associated With a Novel Mutation in Protein Kinase C δ

Juvenile systemic lupus erythematosus (jSLE) is rare before 5 years of age. Monogenic causes are suspected in cases of very early onset jSLE particularly in the context of a family history and/or consanguinity. We performed whole-exome sequencing and homozygosity mapping in the siblings presented with early-onset jSLE. A novel homozygous missense mutation in protein kinase C delta (c.1294G>T; p.Gly432Trp) was identified in both patients. One patient showed a marked clinical response and resolution inflammation with rituximab therapy. This report demonstrates the clinical importance of identifying monogenic causes of rare disease to provide a definitive diagnosis, help rationalize treatment, and facilitate genetic counseling

A neonatal presentation of factor V deficiency: A case report

BACKGROUND: Factor V deficiency is a rare autosomal recessive coagulation disorder. Awareness of presenting features and management is important to avoid bleeding complications associated with mortality and neurodisability. CASE PRESENTATION: A 6-day-old Pakistani boy was admitted with bleeding from the left nipple. His parents were first cousins. A coagulation screen showed a prothrombin time of 41 s (control 14 s), a partial thromboplastin time of 132 s (control 33 s) and a normal thrombin time of 15 s (control 14 s). Factor V activity was <0.01 IU/ml. Oral tranexamic acid was started. At 5 weeks of age the child presented with irritability, lethargy and reduced feeding and a drop of hemoglobin to 5.6 g/dl. A cranial computed tomography scan showed a right intra-cerebral bleed extending from the frontal lobe to the parieto-occipital region with shift of the midline to the left. A regime of 20 ml/kg of fresh frozen plasma four times a week was instituted and has prevented further bleeds up to the present age of 21 months. Neurodevelopment remained normal. CONCLUSION: This case illustrates that in an unusually bleeding newborn of consanguineous parents rare severe homozygous bleeding disorders need to be considered. Nipple bleeding may be the first presentation of a congenital bleeding disorder. In cases of factor V deficiency where factor concentrates are not available long term use of fresh frozen plasma can prevent potentially life threatening bleeding

Radioiodination via isotope exchange in pivalic acid

A variety of benzoic and aryl aliphatic mono and polyiodinated acids and esters (sterol, triglyceride) were radioiodinated in 55-99% radiochemical yield by isotope exchange with Na 125I in a melt of pivalic acid. In general, the reaction was complete in 1 h at 155[deg]C with little or no substrate decompostion. High specific activity studies afforded 125I-labeled iopanoic acid with a specific activity of over 700 Ci/mmol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26445/1/0000533.pd

Flavodiiron Proteins in Oxygenic Photosynthetic Organisms: Photoprotection of Photosystem II by Flv2 and Flv4 in Synechocystis sp. PCC 6803

BACKGROUND: Flavodiiron proteins (FDPs) comprise a group of modular enzymes that function in oxygen and nitric oxide detoxification in Bacteria and Archaea. The FDPs in cyanobacteria have an extra domain as compared to major prokaryotic enzymes. The physiological role of cyanobacteria FDPs is mostly unknown. Of the four putative flavodiiron proteins (Flv1-4) in the cyanobacterium Synechocystis sp. PCC 6803, a physiological function in Mehler reaction has been suggested for Flv1 and Flv3. PRINCIPAL FINDINGS: We demonstrate a novel and crucial function for Flv2 and Flv4 in photoprotection of photosystem II (PSII) in Synechocystis. It is shown that the expression of Flv2 and Flv4 is high under air level of CO(2) and negligible at elevated CO(2). Moreover, the rate of accumulation of flv2 and flv4 transcripts upon shift of cells from high to low CO(2) is strongly dependent on light intensity. Characterization of FDP inactivation mutants of Synechocystis revealed a specific decline in PSII centers and impaired translation of the D1 protein in Delta flv2 and Delta flv4 when grown at air level CO(2) whereas at high CO(2) the Flvs were dispensable. Delta flv2 and Delta flv4 were also more susceptible to high light induced inhibition of PSII than WT or Delta flv1 and Delta flv3. SIGNIFICANCE: Analysis of published sequences revealed the presence of cyanobacteria-like FDPs also in some oxygenic photosynthetic eukaryotes like green algae, mosses and lycophytes. Our data provide evidence that Flv2 and Flv4 have an important role in photoprotection of water-splitting PSII against oxidative stress when the cells are acclimated to air level CO(2). It is conceivable that the function of FDPs has changed during evolution from protection against oxygen in anaerobic microbes to protection against reactive oxygen species thus making the sustainable function of oxygen evolving PSII possible. Higher plants lack FDPs and distinctly different mechanisms have evolved for photoprotection of PSII

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

Predictors of Poor CD4 and Weight Recovery in HIV-Infected Children Initiating ART in South Africa

Objective: To identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa. Methods: We performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary’s hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008. We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression. Results: From the initial cohort of 901 children,10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (,400 copies/ml) were 84 % after six months of therapy and 88 % after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89 % after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58 % of children after six months of ART and 64 % after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4 % (p = 0.005), chronic diarrhe

Clinico-epidemiological profile and diagnostic procedures of pediatric tuberculosis in a tertiary care hospital of western Nepal-a case-series analysis

<p>Abstract</p> <p>Background</p> <p>Changing epidemiology and diagnostic difficulties of paediatric tuberculosis (TB) are being increasingly reported. Our aim was to describe clinico-epidemiological profile and diagnostic procedures used for paediatric TB.</p> <p>Methods</p> <p>A retrospective case-series analysis was carried out in a tertiary care teaching hospital of western Nepal. All pediatric TB (age 0-14 years) patients registered in DOTS clinic during the time period from March, 2003 to July, 2008 were included. Medical case files were reviewed for information on demography, clinical findings, investigations and final diagnosis. Analysis was done on SPSS package. Results were expressed as rates and proportions. Chi square test was used to test for statistical significance.</p> <p>Results</p> <p>About 17.2% (162/941) of TB patients were children. Common symptoms were cough, fever and lymph node swelling. The types of TB were <b/>pulmonary TB (46.3%, 75/162), followed by extra-pulmonary TB (41.4%, 67/162). Twelve patients (7.4%) had disseminated TB. Distribution of types of TB according to gender was similar. PTB was common in younger age than EPTB which was statistically significant. EPTB was mainly localized to lymph node (38, 50.7%), and abdomen (9, 12%). Five main investigations namely Mantoux test, BCG test, chest radiograph, erythrocyte sedimentation rate (ESR) and fine needle aspiration cytology (FNAC) or biopsy were carried out to diagnose TB.</p> <p>Conclusions</p> <p>Paediatric TB in both pulmonary and extrapulmonary forms is a common occurrence in our setting. Age incidence according to type of TB was significant. Diagnosis was based on a combination of epidemiological and clinical suspicion supported by results of various investigations.</p

The Influence of pCO2 and Temperature on Gene Expression of Carbon and Nitrogen Pathways in Trichodesmium IMS101

Growth, protein amount, and activity levels of metabolic pathways in Trichodesmium are influenced by environmental changes such as elevated pCO2 and temperature. This study examines changes in the expression of essential metabolic genes in Trichodesmium grown under a matrix of pCO2 (400 and 900 µatm) and temperature (25 and 31°C). Using RT-qPCR, we studied 21 genes related to four metabolic functional groups: CO2 concentrating mechanism (bicA1, bicA2, ccmM, ccmK2, ccmK3, ndhF4, ndhD4, ndhL, chpX), energy metabolism (atpB, sod, prx, glcD), nitrogen metabolism (glnA, hetR, nifH), and inorganic carbon fixation and photosynthesis (rbcL, rca, psaB, psaC, psbA). nifH and most photosynthetic genes exhibited relatively high abundance and their expression was influenced by both environmental parameters. A two to three orders of magnitude increase was observed for glnA and hetR only when both pCO2 and temperature were elevated. CO2 concentrating mechanism genes were not affected by pCO2 and temperature and their expression levels were markedly lower than that of the nitrogen metabolism and photosynthetic genes. Many of the CO2 concentrating mechanism genes were co-expressed throughout the day. Our results demonstrate that in Trichodesmium, CO2 concentrating mechanism genes are constitutively expressed. Co-expression of genes from different functional groups were frequently observed during the first half of the photoperiod when oxygenic photosynthesis and N2 fixation take place, pointing at the tight and complex regulation of gene expression in Trichodesmium. Here we provide new data linking environmental changes of pCO2 and temperature to gene expression in Trichodesmium. Although gene expression indicates an active metabolic pathway, there is often an uncoupling between transcription and enzyme activity, such that transcript level cannot usually be directly extrapolated to metabolic activity

An Evaluation of the Fe-N Phase Diagram Considering Long-Range Order of N Atoms in γ'-Fe4N1-x and ε-Fe2N1-z

The chemical potential of nitrogen was described as a function of nitrogen content for the Fe-N phases α-Fe[N], γ'-Fe4N1-x, and ε-Fe2N1-z. For α-Fe[N], an ideal, random distribution of the nitrogen atoms over the octahedral interstices of the bcc iron lattice was assumed; for γ'-Fe4N1-x and ε-Fe2N1-z, the occurrence of a long-range ordered distribution of the nitrogen atoms over the octahedral interstices of the close packed iron sublattices (fcc and hcp, respectively) was taken into account. The theoretical expressions were fitted to nitrogen-absorption isotherm data for the three Fe-N phases. The α/α + γ', α + γ'/γ', γ'/γ' + ε, and γ' + ε/ε phase boundaries in the Fe-N phase diagram were calculated from combining the quantitative descriptions for the absorption isotherms with the known composition of NH3/H2 gas mixtures in equilibrium with coexisting α and γ' phases and in equilibrium with coexisting γ' and ε phases. Comparison of the present phase boundaries with experimental data and previously calculated phase boundaries showed a major improvement as compared to the previously calculated Fe-N phase diagrams, where long-range order for the nitrogen atoms in the γ' and ε phases was not accounted for