Increasing Neonatal Mortality among Palestine Refugees in the Gaza Strip

Background

The United Nations Relief and Works Agency for Palestine refugees in the Near East (UNRWA) has periodically estimated infant mortality rates among Palestine refugees in Gaza. These surveys have recorded a decline from 127 per 1000 live births in 1960 to 20.2 in 2008.

Methods

We used the same preceding-birth technique as in previous surveys. All multiparous mothers who came to the 22 UNRWA health centres to register their last-born child for immunization were asked if their preceding child was alive or dead. We based our target sample size on the infant mortality rate in 2008 and included 3128 mothers from August until October 2013. We used multiple logistic regression analyses to identify predictors of infant mortality.

Findings

Infant mortality in 2013 was 22.4 per 1000 live births compared with 20.2 in 2008 (p = 0.61), and this change reflected a statistically significant increase in neonatal mortality (from 12.0 to 20.3 per 1000 live births, p = 0.01). The main causes of the 65 infant deaths were preterm birth (n = 25, 39%), congenital anomalies (n = 19, 29%), and infections (n = 12, 19%). Risk factors for infant death were preterm birth (OR 9.88, 3.98–24.85), consanguinity (2.41, 1.35–4.30) and high-risk pregnancies (3.09, 1.46–6.53).

Conclusion

For the first time in five decades, mortality rates have increased among Palestine refugee newborns in Gaza. The possible causes of this trend may include inadequate neonatal care. We will estimate infant and neonatal mortality rates again in 2015 to see if this trend continues and, if so, to assess how it can be reversed.     

Bovine Norovirus: Carbohydrate Ligand,Environmental Contamination,and Potential Cross-Species Transmission via Oysters

Noroviruses (NoV) are major agents of acute gastroenteritis in humans and the primary pathogens of shellfish-related outbreaks. Previous studies showed that some human strains bind to oyster tissues through carbohydrate ligands that are similar to their human receptors. Thus, based on presentation of shared norovirus carbohydrate ligands, oysters could selectively concentrate animal strains with increased ability to overcome species barriers. In comparison with human GI and GII strains, bovine GIII NoV strains, although frequently detected in bovine feces and waters of two estuaries of Brittany, were seldom detected in oysters grown in these estuaries. Characterization of the carbohydrate ligand from a new GIII strain indicated recognition of the alpha-galactosidase (α-Gal) epitope not expressed by humans, similar to the GIII.2 Newbury2 strain. This ligand was not detectable on oyster tissues, suggesting that oysters may not be able to accumulate substantial amounts of GIII strains due to the lack of shared carbohydrate ligand and that they should be unable to contribute to select GIII strains with an increased ability to recognize humans.Environmental sources of animal pathogens and, most specifically, of RNA viruses may constitute substantial risk factors for cross-species transmission to humans (14). In this context, noroviruses (NoVs) infecting cattle could be of importance owing to the high densities of cows bred in areas of human activities. The ability of shellfish to concentrate pathogens released in seawater raises questions about the transmission of animal NoVs to humans through oyster consumption, but so far very few studies have compared water and shellfish contamination. One of the first such studies, conducted more than 30 years ago, comparing the presence of enterovirus by cell culture in water and oysters yielded about the same frequency of positive water (59%) and shellfish samples (35%) (12). More recently, phages of Bacteroides fragilis and Salmonella detected in sewage effluents were also detected in receiving waters and oysters (6). Human NoVs were detected in 75% of river water samples and in 60% of oyster beds (38). Only one study reported the detection of porcine norovirus in 15% of shellfish collected from the U.S. market but no information from the surrounding water was available (8).NoVs are small nonenveloped viruses approximately 30 nm in diameter with a positive-sense, single-stranded RNA genome. They belong to the Caliciviridae family, and in humans they are the most frequent cause of diarrhea outbreaks in all age groups (11, 28). They are classified in five genogroups, with human strains belonging to genogroups I, II, and IV, GIII strains infecting cattle, and murine strains classified in GV (45). Recently, two new genogroups (VI and VII) infecting animals have been proposed (29). Based on analysis of the open reading frame 2 (ORF2) sequence encoding the capsid protein, high diversity has been observed, with the result that genogroups have been subdivided into clusters, including up to 19 for GII strains. Porcine NoVs have been classified into three clusters of GII (GII.11, GII.18, and GII.19) while all bovine strains of NoV described so far belong to GIII (25, 29, 41, 45). The first bovine strain, Bo/Newbury2/1976/UK (NB2), was isolated in the United Kingdom from calves with diarrhea (43). Later, another distinct genotype of bovine NoV, Bo/Jena/1978/GER, was identified in Germany (21). These two strains represent the prototypes of the GIII.2 and GIII.1 genotypes, respectively.Although many gaps persist in our understanding of human NoV infections and pathogenesis, recent advances demonstrated a genetically determined host susceptibility based on histo-blood group antigen diversity. Various human NoV strains attach to distinct carbohydrates of the ABH and Lewis histo-blood group family, and evidence accumulated from volunteer studies and outbreaks indicates that binding to these carbohydrates is required for infection (19, 35). In addition, it was recently shown that the prototype bovine GIII.2 strain binds to a related carbohydrate structure which is absent from human tissues (44). Similarly, it was also demonstrated that some strains of either GI or GII specifically attach to oysters tissues through recognition of histo-blood group antigens (HBGAs) (17, 22, 36). This finding could help explain other observations, such as the rapid contamination of oysters, long persistence of viral particles, and, consequently, shellfish-borne outbreaks (3, 16). It additionally suggests that oysters may not merely act as passive filters randomly accumulating virus particles but, instead, may also act as selective filters specifically concentrating strains by recognition of carbohydrate epitopes shared with humans. As shellfish are grown in coastal waters frequently exposed to contamination from bovine in neighboring fields, they may be contaminated by these animal strains. This raises the issue of the potential role of oysters in the emergence of bovine NoVs into the human population.The aim of our study is to provide quantitative data on the presence of GIII NoV strains in comparison with GI and GII strains in bovine feces, rivers, or estuarine waters as well as shellfish from an area of both high cattle density and high-density oyster breeding. The possibility of GIII strain-specific binding to carbohydrate ligands of oyster tissues that may be shared with cows and humans is additionally examined. The results are discussed in the context of the environmental data in order to provide a first appreciation of the risk of GIII NoV transmission to humans through oyster consumption.     

Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: relevance to dopamine pathology in schizophrenia

Deleterious effects of dopamine (DA) involving mitochondrial dysfunction have an important role in DA-associated neuronal disorders, including schizophrenia and Parkinson's disease. DA detrimental effects have been attributed to its ability to be auto-oxidized to toxic reactive oxygen species. Since, unlike Parkinson's disease, schizophrenia does not involve neurodegenerative processes, we suggest a novel mechanism by which DA impairs mitochondrial function without affecting cell viability. DA significantly dissipated mitochondrial membrane potential (delta psi m) in SH-SY5Y cells. Bypassing complex I prevented the DA-induced depolarization. Moreover, DA inhibited complex I but not complex II activity in disrupted mitochondria, suggesting complex I participation in DA-induced mitochondrial dysfunction. We further demonstrated that intact mitochondria can accumulate DA in a saturated manner, with an apparent Km=122.1+/-28.6 nM and Vmax=1.41+/-0.15 pmol/mg protein/min, thereby enabling the interaction between DA and complex I. DA accumulation was an energy and Na+-dependent process. The pharmacological profile of mitochondrial DA uptake differed from that of other characterized DA transporters. Finally, relevance to schizophrenia is demonstrated by an abnormal interaction between DA and complex I in schizophrenic patients. These results suggest a non-lethal interaction between DA and mitochondria possibly via complex I, which can better explain DA-related pathological processes observed in non-degenerative disorders, such as schizophrenia.     

Functional Trait Changes,Productivity Shifts and Vegetation Stability in Mountain Grasslands during a Short-Term Warming

Plant functional traits underlie vegetation responses to environmental changes such as global warming, and consequently influence ecosystem processes. While most of the existing studies focus on the effect of warming only on species diversity and productivity, we further investigated (i) how the structure of community plant functional traits in temperate grasslands respond to experimental warming, and (ii) whether species and functional diversity contribute to a greater stability of grasslands, in terms of vegetation composition and productivity. Intact vegetation turves were extracted from temperate subalpine grassland (highland) in the Eastern Pyrenees and transplanted into a warm continental, experimental site in Lleida, in Western Catalonia (lowland). The impacts of simulated warming on plant production and diversity, functional trait structure, and vegetation compositional stability were assessed. We observed an increase in biomass and a reduction in species and functional diversity under short-term warming. The functional structure of the grassland communities changed significantly, in terms of functional diversity and community-weighted means (CWM) for several traits. Acquisitive and fast-growing species with higher SLA, early flowering, erect growth habit, and rhizomatous strategy became dominant in the lowland. Productivity was significantly positively related to species, and to a lower extent, functional diversity, but productivity and stability after warming were more dependent on trait composition (CWM) than on diversity. The turves with more acquisitive species before warming changed less in composition after warming. Results suggest that (i) the short-term warming can lead to the dominance of acquisitive fast growing species over conservative species, thus reducing species richness, and (ii) the functional traits structure in grassland communities had a greater influence on the productivity and stability of the community under short-term warming, compared to diversity effects. In summary, short-term climate warming can greatly alter vegetation functional structure and its relation to productivity.     

Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells

The flavanone hesperetin is known to decrease basal glucose uptake, although the inhibitory mechanism is largely unknown. Here, we used MDA‐MB‐231 breast cancer cells to investigate the molecular pathways affected by hesperetin. The results indicate that the suppression of glucose uptake is caused by the down‐regulation of glucose transporter 1 (GLUT1). Hesperetin was also found to inhibit insulin‐induced glucose uptake through impaired cell membrane translocation of glucose transporter 4 (GLUT4). In addition, the phosphorylation of the insulin receptor‐beta subunit (IR‐beta) and Akt was suppressed. Hesperetin also decreased cellular proliferation, which is likely due to the inhibition of glucose uptake. Cancer cells are highly dependent on glucose and hesperetin may, therefore, have potential application as an anticancer agent. Copyright © 2012 John Wiley & Sons, Ltd.     

Modulation of GluK2a Subunit-containing Kainate Receptors by 14-3-3 Proteins

Kainate receptors (KARs) are one of the ionotropic glutamate receptors that mediate excitatory postsynaptic currents (EPSCs) with characteristically slow kinetics. Although mechanisms for the slow kinetics of KAR-EPSCs are not totally understood, recent evidence has implicated a regulatory role of KAR-associated proteins. Here, we report that decay kinetics of GluK2a-containing receptors is modulated by closely associated 14-3-3 proteins. 14-3-3 binding requires PKC-dependent phosphorylation of serine residues localized in the carboxyl tail of the GluK2a subunit. In transfected cells, 14-3-3 binding to GluK2a slows desensitization kinetics of both homomeric GluK2a and heteromeric GluK2a/GluK5 receptors. Moreover, KAR-EPSCs at mossy fiber-CA3 synapses decay significantly faster in the 14-3-3 functional knock-out mice. Collectively, these results demonstrate that 14-3-3 proteins are an important regulator of GluK2a-containing KARs and may contribute to the slow decay kinetics of native KAR-EPSCs.     

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population

Abstract

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting.

Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians.

Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III.

Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III.

Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.