Fructose-1,6-bisphosphatase deficiency with confirmed molecular diagnosis: An important cause of hypoglycemia in children

Objectives:To draw attention towards fructose-1,6-bisphosphatase (FBPase) deficiency as an important cause of hypoglycemia and lactic acidosis and to implement preventive strategies.Methods:This observational, cross-sectional study was conducted on 7 Saudi patients with genetically confirmed FBPase deficiency from 2008 to 2018 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia.Results:Participants ranged in age from 1-10 years, and all presented with recurrent hypoglycemia. All but one had associated severe metabolic acidosis, and 3 patients (42.9%) presented with hypoglycemia and severe acidosis since birth. The mean duration from presentation to diagnosis was 39.4 months, as other diagnoses, like glycogen storage diseases and mitochondrial diseases needed to be ruled out. Development was normal apart from speech delay in one patient with a novel variant of the FBP1 gene. All patients have homozygous variants in the FBP1 gene.Conclusion:Fructose-1,6-bisphosphatase is an important cause of hypoglycemia and acidosis; therefore, it is important to offer early molecular diagnostics in any child presenting with these symptoms. Molecular diagnostics should always be undertaken to confirm the diagnosis and for further preventive strategies.     

IL-17A and IL-17F genes variants and susceptibility to childhood asthma in Tunisia

Objectives: IL-17A and IL-17F are new pro-inflammatory cytokines implicated in neutrophilic inflammation and thus, involved in the pathogenesis of asthma. We investigated the possible association among asthma and IL-17A -197G/A (rs2275913), IL-17F 7488A/G (rs763780) and IL-17F 7383A/G (rs2397084).

Methods: The study was performed in 171 patients with asthma (mean age 9.5?years, 105 boys, and 66 girls) and 171 healthy individuals matched with patients in age and sex. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect genes’ polymorphisms.

Results: IL-17A -197G/A and IL-17F 7383A/G were associated with asthma in children (p?=?0.008, p?=?0.001, respectively). No association was found with IL-17F 7488A/G polymorphism. Haplotype analysis revealed a significant association between GA and AG haplotypes and asthma (p?=?0.004, p?=?0.02). When patients were stratified according to the atopic status, no significant association was detected with any of the three studied variants.

Conclusion: Our results suggested that SNPs in IL-17A and IL-17F confer susceptibility to childhood asthma in Tunisia.     

Efficacy and mechanism of action of the proteasome inhibitor PS-341 in T-cell lymphomas and HTLV-I associated adult T-cell leukemia/lymphoma

HTLV-I associated adult T-cell leukemia (ATL) and HTLV-I-negative peripheral T-cell lymphomas are associated with poor prognosis. Using pharmacological concentrations of the proteasome inhibitor PS-341, we demonstrate inhibition of cell proliferation and induction of apoptosis in fresh ATL cells, HTLV-I transformed and HTLV-I-negative malignant T cells, while normal resting or activated T lymphocytes were resistant. Combination of PS-341 and doxorubicin or etoposide resulted in an additive growth inhibition. In HTLV-I-negative malignant cells, PS-341 treatment significantly downregulated the antiapoptotic protein X-IAP and to a lesser extent c-IAP-1 and bcl-X(L) and resulted in caspase-dependent apoptosis. In HTLV-I transformed cells, the inhibition of the proteasomal degradation of Tax by PS-341 likely explains the relative protection of HTLV-I infected cells against caspase-dependent apoptosis. PS-341 treatment of these cells stabilized IkappaBalpha, IkappaBbeta, IkappaBvarepsilon, p21, p27 and p53 proteins and selectively inhibited Rel-A DNA binding NF-kappaB complexes. In both HTLV-I-positive and -negative cells, PS-341 treatment induced ceramide accumulation that correlated with apoptosis. We conclude that PS-341 affects multiple pathways critical for the survival of HTLV-I-positive and -negative malignant T cells supporting a potential therapeutic role for PS-341 in both ATL and HTLV-I-negative T-cell lymphomas, whether alone or in combination with chemotherapy.     

Co-introgression of Y-chromosome haplogroups and the sickle cell gene across Africa's Sahel

The Sahel that extends from the Atlantic Ocean to the Ethiopian highland is a historical reservoir of Africa's cultures and grandest populations and a known arena of ancient and recent migrations. We are interested in the issue whether such migrations were also carriers of genetic traits and whether this introgression could be associated with population genetic markers. Based on analysis of Y-chromosome haplogroups, we present evidence that the sickle gene, one of the major protective polymorphisms known in malaria, has in fact found its way only recently to the gene pool of the populations in eastern Sahel. We discuss the possible dynamics of the process and give estimates of the age of the introduction of the S allele into eastern Sahel.     

Cervical dynamic screening in spinal clearance: now redundant

BACKGROUND: The safest and most effective method of early cervical spine clearance in unconscious patients is the subject of intense debate. We hypothesize that helical computed tomography (CT) is a sufficiently sensitive investigation to render dynamic screening redundant. METHOD: We retrospectively reviewed the records of 839 trauma patients admitted to the intensive care unit under the orthopedic surgeons from April 1994 to September 2004. Our protocol for cervical spinal clearance in the unconscious patient involves plain radiographs, CT scanning, and dynamic screening. We recorded the presence of any unstable cervical spine injury and any cases that were missed by CT but detected by dynamic screening. RESULTS: There were 87 patients with an unstable cervical spine. Of these, 85 were detected by CT. Two cases were missed by CT (sensitivity 97.7%, specificity 100%). In one of these patients, dynamic screening detected an unstable spine and in the other patient dynamic screening missed an atlanto-occipital dislocation (sensitivity 98.8%, specificity 100%). Critical analysis of this case revealed that a powers ratio calculation on the CT scan would have detected the injury. There were no complications as a result of dynamic screening. CONCLUSION: Dynamic screening is a safe procedure but has no real advantage over helical CT. Power's ratio calculation is essential to reduce the chance of a missing an upper cervical injury. The cervical spine can be reliably cleared using helical CT alone.     

Malettinins B-D: new polyketide metabolites from an unidentified fungal colonist of Hypoxylon Stromata (NRRL 29110)

Malettinins B-D (2-4), three new antimicrobial polyketide-derived metabolites related to the previously reported malettinin A (1), have been obtained from nonsporulating cultures of an isolate of Mycelia sterilia MYC-155 (= NRRL 29110) collected from colonies of Hypoxylon stromata. Malettinins B (2) and C (3) are partially reduced analogues of malettinin A and were identified by analysis of NMR and MS data. Malettinin D (4) is biogenetically similar, but possesses a new ring system, and the structure of 4 was established by single-crystal X-ray diffraction analysis.     

A capillary cytometer method to quantitate viable virus particles based on early detection of viral antigens and cellular events within single cells

The traditional plaque forming and TCID(50) methods to determine replication competent virus titres rely on several cycles of replication and infection to generate a plaque with an incubation period of 24-72 h post-infection typically required. We developed a method to quantify infective viral particles based on early detection of cellular events by capillary cytometry. The method uses a capillary cytometer as a precise cell counter that can discriminate infected from non-infected cells. The general protocol was developed using a Guava PCA, genetically modified HSV-1 virus and polyclonal antibodies against antigens expressed on the cell membrane. Infection was detected after 1 h incubation and a plateau in the number of infected cells was observed between 7 and 9 h. A good correlation between titres obtained by the plaque forming method and the proposed method was observed for a ratio of infected to total cells between 0.5 and 0.05. The rapid and automated analysis (10 s/1000 events acquired per sample) makes the method particularly useful for high-throughput applications. The proposed method can be extended easily to determine the titre of other viruses providing a powerful tool for virology and antiviral screening.