Neonatal screening for absolute lymphopenia

Background: Blood counts with manual differentials could diagnose nearly all cases of severe combined immune deficiency (SCID) at birth. Objective: The aim of this study was to outline the prevalence of neonatal lymphopenia among newborns of Obstetrics and Gynecology Hospital, Ain Shams University as an entry to neonatal screening for SCID. Methods: Complete blood counting (CBC) with manual differential was performed in the cord blood of 500 newborns. Absolute lymphopenia was considered if the count was less than 2500 lymphocytes/mm3. Parents of lymphopenic infants were advised not to give them any live attenuated vaccines before doing further investigations. The lymphopenic infants were followed up by another CBC after one month. Results: In the present study, absolute lymphopenia was found in 8 (1.6%) neonates at delivery. Among our series 44.4% were primigravida and 55.6% were multigravida. Also, 84 (16.8%) experienced pre-mature rupture of membrane, 89 (17.8%) reported maternal diseases and maternal drug intake was reported in 73 (14.6%). Three neonates had congenital anomalies, one only experienced dysmorphic features and 8 (1.6%) had family history of unexplained death but these data could not be linked to the presence of lymphopenia in the studied sample. APGAR scores at 1 and 5 minutes were significantly lower in neonates with lymphopenia (p = 0.001). A significant positive correlation was elicited between the absolute lymphocyte count (ALC) and maternal age, total leukocyte count, and HCT (p = 0.003, 0.001 and 0.031 respectively). Also a significant negative correlation was found between ALC and gestational age, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (p = 0.013, 0.003 and < 0.001 respectively). Conclusion: Lymphopenia is not an uncommon finding among neonates at screening and is noted to be associated with a lower Apgar score. Serial counting and follow up is needed before considering the diagnosis of SCID. Keywords: Lymphopenia; neonatal screening; SCI

Prognostic value of FOXP3 and TGF-b expression in both peripheral blood and lymph nodes in patients with B-Non Hodgkin’s lymphoma

Foxp3 has been studied as a biomarker of Treg cells in many solid malignant diseases, although its role as an immunomodulator in B-NHL remain poorly understood and the effect of traditional chemotherapy on its expression remains unclear. In this study the role of circulating and intra-tumoral Treg and TGF-b in patients with B-NHL before and after chemotherapy was evaluated. Enumeration of Treg cells was carried out by flow cytometric staining of their cell surface markers CD4 and CD25 as well as by molecular analysis of its signature transcription factor FoxP3. Expression of FoxP3 was done using quantitative real-time PCR while TGF-b mRNA expression was semi-quantitatively assayed by the conventional reverse transcription-PCR. In addition, spontaneous versus mitogen-induced release of TGF-b by PBMCs was assessed by a short term cell culture followed by ELISA. This was done before and after six cycles of CHOP chemotherapy. The results were evaluated in relation to the clinicopathological data.A significant increase in mRNA transcripts of both Fox P3 and TGF-b as well as the percentage of CD4+/CD25+ in B-NHL patients before receiving the chemotherapy were recorded, when compared either to healthy controls or to patients after completion the treatment regimen. Interestingly 6 cycles of CHOP treatment caused significant reduction in all parameters under study, relative to the situation before treatment. A significant enhancement in spontaneous TGF-b release in B-NHL patient either before or after chemotherapy was obtained. These results strongly confirm the possible involvement of Treg cells and TGF-b in orienting the clinical course of the disease as well as the ability of targeting them in immunotherapeutic approaches. KEYWORDS FOXP3; TGF; Non Hodgkin’s lymphoma; NH

New phiocricetomyine rodents (Hystricognathi) from the Jebel Qatrani Formation, Fayum Depression, Egypt

Background The rich rodent assemblages from the Eocene–Oligocene deposits of the Jebel Qatrani Formation (Fayum Depression, Egypt) have important implications for our understanding of the origin and paleobiogeography of Hystricognathi, a diverse clade that is now represented by the Afro-Asiatic Hystricidae, New World Caviomorpha, and African Phiomorpha. Methods Here we present previously undescribed material of the enigmatic hystricognath clade Phiocricetomyinae, from two stratigraphic levels in the lower sequence of the Jebel Qatrani Formation—a new genus and species (Qatranimys safroutus) from the latest Eocene Locality 41 (~34 Ma, the oldest and most productive quarry in the formation) and additional material of Talahphiomys lavocati from that species’ type locality, early Oligocene Quarry E (~31–33.2 Ma). Results The multiple specimens of Qatranimys safroutus from L-41 document almost the entire lower and upper dentition, as well as mandibular fragments and the first cranial remains known for a derived phiocricetomyine. Specimens from Quarry E allow us to expand comparisons with specimens from Libya (late Eocene of Dur at-Talah and early Oligocene of Zallah Oasis) that have been placed in T. lavocati, and we show that the Dur at-Talah and Zallah specimens do not pertain to this species. These observations leave the Fayum Quarry E as the only locality where T. lavocati occurs

Ethnic Inequalities in Mortality: The Case of Arab-Americans

BACKGROUND: Although nearly 112 million residents of the United States belong to a non-white ethnic group, the literature about differences in health indicators across ethnic groups is limited almost exclusively to Hispanics. Features of the social experience of many ethnic groups including immigration, discrimination, and acculturation may plausibly influence mortality risk. We explored life expectancy and age-adjusted mortality risk of Arab-Americans (AAs), relative to non-Arab and non-Hispanic Whites in Michigan, the state with the largest per capita population of AAs in the US. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected about all deaths to AAs and non-Arab and non-Hispanic Whites in Michigan between 1990 and 2007, and year 2000 census data were collected for population denominators. We calculated life expectancy, age-adjusted all-cause, cause-specific, and age-specific mortality rates stratified by ethnicity and gender among AAs and non-Arab and non-Hispanic Whites. Among AAs, life expectancies among men and women were 2.0 and 1.4 years lower than among non-Arab and non-Hispanic White men and women, respectively. AA men had higher mortality than non-Arab and non-Hispanic White men due to infectious diseases, chronic diseases, and homicide. AA women had higher mortality than non-Arab and non-Hispanic White women due to chronic diseases. CONCLUSIONS/SIGNIFICANCE: Despite better education and higher income, AAs have higher age-adjusted mortality risk than non-Arab and non-Hispanic Whites, particularly due to chronic diseases. Features specific to AA culture may explain some of these findings

Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China

Background: There is accumulating evidence for an increased susceptibility to infection in patients with arthritis. We sought to understand the epidemiology of Toxoplasma gondii infection in arthritis patients in eastern China, given the paucity of data on the magnitude of T. gondii infection in these patients. Methods: Seroprevalence of T. gondii infection was assessed by enzyme-linked immunosorbent assay using a crude antigen of the parasite in 820 arthritic patients, and an equal number of healthy controls, from Qingdao and Weihai cities, eastern China. Sociodemographic, clinical and lifestyle information on the study participants were also obtained. Results: The prevalence of anti-T. gondii IgG was significantly higher in arthritic patients (18.8%) compared with 12% in healthy controls (P < 0.001). Twelve patients with arthritis had anti-T. gondii IgM antibodies comparable with 10 control patients (1.5% vs 1.2%). Demographic factors did not significantly influence these seroprevalence frequencies. The highest T. gondii infection seropositivity rate was detected in patients with rheumatoid arthritis (24.8%), followed by reactive arthritis (23.8%), osteoarthritis (19%), infectious arthritis (18.4%) and gouty arthritis (14.8%). Seroprevalence rates of rheumatoid arthritis and reactive arthritis were significantly higher when compared with controls (P < 0.001 and P = 0.002, respectively). A significant association was detected between T. gondii infection and cats being present in the home in arthritic patients (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.24 – 2.28; P = 0.001). Conclusions: These findings are consistent with and extend previous results, providing further evidence to support a link between contact with cats and an increased risk of T. gondii infection. Our study is also the first to confirm an association between T. gondii infection and arthritis patients in China. Implications for better prevention and control of T. gondii infection in arthritis patients are discussed. Trial registration: This is an epidemiological survey, therefore trial registration was not required

Identifying Schistosoma japonicum Excretory/Secretory Proteins and Their Interactions with Host Immune System

Schistosoma japonicum is a major infectious agent of schistosomiasis. It has been reported that large number of proteins excreted and secreted by S. japonicum during its life cycle are important for its infection and survival in definitive hosts. These proteins can be used as ideal candidates for vaccines or drug targets. In this work, we analyzed the protein sequences of S. japonicum and found that compared with other proteins in S. japonicum, excretory/secretory (ES) proteins are generally longer, more likely to be stable and enzyme, more likely to contain immune-related binding peptides and more likely to be involved in regulation and metabolism processes. Based on the sequence difference between ES and non-ES proteins, we trained a support vector machine (SVM) with much higher accuracy than existing approaches. Using this SVM, we identified 191 new ES proteins in S. japonicum, and further predicted 7 potential interactions between these ES proteins and human immune proteins. Our results are useful to understand the pathogenesis of schistosomiasis and can serve as a new resource for vaccine or drug targets discovery for anti-schistosome

Leishmania-Specific Surface Antigens Show Sub-Genus Sequence Variation and Immune Recognition

Single-celled Leishmania parasites, transmitted by sand flies, infect humans and other mammals in many tropical and sub-tropical regions, giving rise to a spectrum of diseases called the leishmaniases. Species of parasite within the Leishmania genus can be divided into two groups (referred to as sub-genera) that are separated by up to 100 million years of evolution yet are highly related at the genome level. Our research is focused on identifying gene differences between these sub-genera that may identify proteins that impact on the transmission and pathogenicity of different Leishmania species. Here we report the presence of a highly-variant genomic locus (OHL) that was previously described as absent in parasites of the L. (Viannia) subgenus (on the basis of lack of key genes) but is present and well-characterised (as the LmcDNA16 locus) in all members of the alternative subgenus, L. (Leishmania). We demonstrate that the proteins encoded within the LmcDNA16 and OHL loci are similar in their structure and surface localisation in mammalian-infective amastigotes, despite significant differences in their DNA sequences. Most importantly, we demonstrate that the OHL locus proteins, like the HASP proteins from the LmcDNA16 locus, contain highly variable amino acid repeats that are antigenic in man and may therefore contribute to future vaccine development

A comparative study on the effects of a pesticide (cypermethrin) and two metals (copper, lead) to serum biochemistry of Nile tilapia, Oreochromis niloticus

The present study was designed to compare the responses in freshwater fish Oreochromis niloticus exposed to a synthetic pyrethroid, cypermethrin (CYP); an essential metal, copper (Cu); and a nonessential metal, lead (Pb). Fish were exposed to 0.05 μg/l CYP, 0.05 mg/l Cu, and 0.05 mg/l Pb for 4 and 21 days, and the alterations in serum enzyme activities, metabolite, and ion levels were determined. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased in response to CYP, Cu, and Pb exposures at both exposure periods. While elevations in alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities and in cholesterol level were observed in pesticide-exposed fish at 4 and 21 days, they increased in Cu- and Pb-exposed fish at 21 days. Although metal-exposed fish showed increases in cortisol and glucose levels at 4 days followed by a return to control levels at the end of the exposure period, their levels elevated in pesticide-exposed fish at both exposure periods. Total protein levels decreased in Pb- and pesticide-exposed fish at 21 days. Na+ and Cl− levels decreased in pesticide-exposed fish at both exposure periods and in Cu- and Pb-exposed fish at 21 days. The exposures of pesticide and metals caused an elevation in K+ level at the end of the exposure period. The present study showed that observed alterations in all serum biochemical parameters of fish-treated pesticide were higher than those in fish exposed to metals

Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis

<p>Abstract</p> <p>Background</p> <p>One of the challenges facing the tuberculosis (TB) control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB). Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples are needed. This study compared the sensitivity, specificity and time to results of four direct drug susceptibility testing tests with the conventional indirect testing for detection of resistance to rifampicin and isoniazid in <it>M. tuberculosis</it>. The four direct tests included two in-house phenotypic assays – Nitrate Reductase Assay (NRA) and Microscopic Observation Drug Susceptibility (MODS), and two commercially available tests – Genotype^®MTBDR and Genotype^®MTBDR<it>plus </it>(Hain Life Sciences, Nehren, Germany).</p> <p>Methods</p> <p>A literature review and meta-analysis of study reports was performed. The Meta-Disc software was used to analyse the reports and tests for sensitivity, specificity, and area under the summary receiver operating characteristic (sROC) curves. Heterogeneity in accuracy estimates was tested with the Spearman correlation coefficient and Chi-square.</p> <p>Results</p> <p>Eighteen direct DST reports were analysed: NRA – 4, MODS- 6, Genotype MTBDR^®– 3 and Genotype^®MTBDR<it>plus </it>– 5. The pooled sensitivity and specificity for detection of resistance to rifampicin were 99% and 100% with NRA, 96% and 96% with MODS, 99% and 98% with Genotype^®MTBDR, and 99% and 99% with the new Genotype^®MTBDR<it>plus</it>, respectively. For isoniazid it was 94% and 100% for NRA, 92% and 96% for MODS, 71% and 100% for Genotype^®MTBDR, and 96% and 100% with the Genotype^®MTBDR<it>plus</it>, respectively. The area under the summary receiver operating characteristic (sROC) curves was in ranges of 0.98 to 1.00 for all the four tests. Molecular tests were completed in 1 – 2 days and also the phenotypic assays were much more rapid than conventional testing.</p> <p>Conclusion</p> <p>Direct testing of rifampicin and isoniazid resistance in <it>M. tuberculosis </it>was found to be highly sensitive and specific, and allows prompt detection of MDR TB.</p