Pediatric surgical site infection in the developing world: a Kenyan experience

Background  

The purpose of the current study was to determine the incidence of pediatric surgical site infections (SSIs) at an academic children’s hospital in rural sub-Saharan Africa and to identify potentially modifiable risk factors.     

The prevalence of cigarette smoking and its relation to certain risk predictors of cardiovascular diseases in central-Slovakian Roma children and adolescents

The objective of the study was to determine some Cardiovascular Disease (CVD) risk factors in relation to cigarette smoking in 174 Roma children and adolescents (88 males and 86 females) and 131 non-Roma probands (males and females) aged 7-18 in central Slovakia. In this biethnic study, 26.4% of the Roma children and adolescents (more than twice contrary to the control group) were smokers. Among the studied ethnicities, the majority of smokers was Roma (79.3%, 46 subjects). Smoking Roma have higher means of TG, Lp(a) and WHR compared with non-smoking non-Roma. The most frequent CVD risk predictors of smoking Roma probands was low serum levels HDL-C, apo A (the Fisher test confirmed a significant relationship between cigarette smoking and HDL-C, apo A; p < 0.01). The results of the research should help to develop an effective preventative health education programs focused on Roma education (who live in a higher-risk environment compared to the majority population) in order to stem the spread of CVD as well as morbidity and mortality in this ethnic group living in Slovakia.     

Cardiovascular risk predictors in central Slovakian Roma children and adolescents: regional differences

The objective of the study was to determine some Cardiovascular Disease (CVD) risk factors in 174 Roma children and adolescents (88 males and 86 females) aged 7-18 in 3 Central Slovakian cities (44 from Zilina, 39 from Bansk, Bystrica and 91 from Rimavská Sobota). Venous blood samples were drawn in the morning, after a 12 hour overnight fast for biochemical analysis. Total cholesterol (TC) and triglycerides (TG) were determined enzymatically. HDL-cholesterol (HDL-C) after selective precipitation lipoproteins containing apolipoprotein B and LDL-cholesterol (LDL-C) was calculated by the Friedewald Formula. Serum levels of apolipoproteins (apo A, apo B) were analyzed immunochemically. Concentration of lipoprotein a [Lp(a)] was analyzed by immunonephelometric method (Beckman-Coulter System). Anthropometric measurements, including weight, height, waist and hip circumference were used to calculate the sum of the body mass index (BMI) and waist to hip ratio (WHR). Measured blood pressure (BP) was used to classify for hypertension. Significant differences were determined in serum levels of LDL-C (p < 0.05; by Tukey HSD test multiple comparison more significant difference was determined between Zilina and Rimavská Sobota p < 0.046), TG (p = 0.008), apo A (p < 0.001), Lp(a) (p = 0.042), WHR (p < 0.001), BMI (p < 0.001), sBP (p < 0.001) and dBP (p = 0.012) in Roma individuals of all locality groups. The Roma population from Rimavsk, Sobota had (in comparison to the examined populations) statistically higher values of TC, TG, LDL-C, lower HDL-C. The population showed significant relation of TG and stress at home (p = 0.03) and at school (p = 0.01), HDL-C and cigarette smoking (p = 0.004), apo A and cigarette smoking (p = 0.02) and socioeconomic status (p = 0.006), WHR and cigarette smoking (p = 0.02). Risk values of WHR, apo B and Lp(a) were mostly determined in Zilina's population (WHR significantly connected with family history CVD p = 0.03, cigarette smoking p = 0.02 and leisure time physical activity p < 0.001) and BMI, apo A and BP in Banská Bystrica. WHR was positively correlated to BP and negatively to HDL-C and TG only in Roma participants from Rimavská Sobota. BMI was positively correlated to systolic BP in populations from Banská Bystrica and Rimavská Sobota. The results of the study should improve the paediatric health treatment and prevention of CVD risk predictors for Roma from different cities.     

KRAS,NRAS and BRAF mutations in colorectal cancer and melanoma

Cancers are the group of diseases, which arise because of the uncontrolled behavior of some of the genes in our cells. There are possibilities of gene amplifications, overexpressions, deletions and other anomalies which might lead to the development and spread of cancer. One of the most dangerous ways to the cancers is the mutations of the genes. The mutated genes can start unstoppable proliferation of cells, their uncontrolled motility, protection from apoptosis, the DNA mutation enhancement as well as other anomalies, leading to the cancer. This review focuses on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF.     

Plasma membrane phospholipid signature recruits the plant exocyst complex via the EXO70A1 subunit

Polarized exocytosis is essential for many vital processes in eukaryotic cells, where secretory vesicles are targeted to distinct plasma membrane domains characterized by their specific lipid–protein composition. Heterooctameric protein complex exocyst facilitates the vesicle tethering to a target membrane and is a principal cell polarity regulator in eukaryotes. The architecture and molecular details of plant exocyst and its membrane recruitment have remained elusive. Here, we show that the plant exocyst consists of two modules formed by SEC3–SEC5–SEC6–SEC8 and SEC10–SEC15–EXO70–EXO84 subunits, respectively, documenting the evolutionarily conserved architecture within eukaryotes. In contrast to yeast and mammals, the two modules are linked by a plant-specific SEC3–EXO70 interaction, and plant EXO70 functionally dominates over SEC3 in the exocyst recruitment to the plasma membrane. Using an interdisciplinary approach, we found that the C-terminal part of EXO70A1, the canonical EXO70 isoform in Arabidopsis, is critical for this process. In contrast to yeast and animal cells, the EXO70A1 interaction with the plasma membrane is mediated by multiple anionic phospholipids uniquely contributing to the plant plasma membrane identity. We identified several evolutionary conserved EXO70 lysine residues and experimentally proved their importance for the EXO70A1–phospholipid interactions. Collectively, our work has uncovered plant-specific features of the exocyst complex and emphasized the importance of the specific protein–lipid code for the recruitment of peripheral membrane proteins.

The plasma membrane (PM) of eukaryotic cells is spatially segregated into distinct domains with diverse functions, composition, and scales, a feature essential for many vital processes, including cell polarity regulation, signaling, and interactions with microorganisms (1, 2). Localized exocytosis is a fundamental process contributing to the establishment and maintenance of cellular polarity. An arsenal of small GTPases orchestrates the exocytosis through multiple effectors. Octameric protein complex exocyst is the small GTPase effector that facilitates the fusion of secretory vesicles with the PM (3, 4). The exocyst consists of eight subunits, Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84, that are evolutionarily conserved across eukaryotes (5).The plant exocyst complex is crucial for targeted secretion in cellular processes including the tip growth of root hairs and pollen tubes (6–9); hypocotyl elongation (10); cell wall maturation in xylem, endodermis, and trichomes (11–13); pectin secretion in seed coats (14); recycling of PIN auxin transporters (15); and plant–microbe interactions (16, 17). The exocyst is also important for cell plate initiation and maturation during plant cytokinesis (18–20). At the outer lateral PM of plant epidermal cells, the exocyst controls the secretion of polarly localized cargo proteins (21). Notably, exocyst accumulates at the outer lateral PM in dynamic foci that are distinct from sites of endocytosis (22).While the Exo70 subunit is encoded by a single gene in yeast and animals, many EXO70 isoforms exist in angiosperm plants. Such multiplication enables the existence of diverse, functionally specific exocyst complexes even within one cell (23, 24). Particular EXO70 isoforms are involved in highly localized domain-specific secretion at the PM as documented in pollen tubes and trichomes (8, 13, 25). Some EXO70 isoforms even acquired diverged functions in autophagy regulation (26) or as negative regulators of tip growth (27, 28).In Arabidopsis, housekeeping secretory processes in most sporophytic tissues involve the EXO70 isoform EXO70A1 (29, 30). On the other hand, these processes employ the closely related EXO70A2 isoform in the male gametophyte (9). Mutant plants lacking EXO70A1, unlike other studied EXO70 mutants, are severely morphologically affected and show secretory defects similarly to several mutants in other exocyst subunits (14, 15, 29, 31, 32). Moreover, among the multiple plant EXO70 isoforms, EXO70A1 is sequentially and structurally the most similar to the yeast and animal Exo70 (24, 29, 33). Hence, we focused on the EXO70A1 function in the plant exocyst architecture and PM recruitment in this study.Molecular mechanisms of the exocyst function reside in mediating the first contact of secretory vesicles with the PM and facilitating the subsequent fusogenic SNARE complex formation, leading to a vesicle–PM fusion (34, 35). An emerging model of the exocyst complex based on partially solved structures of several exocyst subunits, protein interaction mapping, fluorescent microscopy, and cryogenic electron microscopy indicates that interlaced rod-like exocyst subunits align longitudinally at the core of the complex with distant parts being flexible and available for concomitant molecular interactions bridging vesicles and the PM (36). In yeast, the Sec15p subunit binds secretory vesicles via interaction with Rab GTPase Sec4p (37), while Sec3p and Exo70p subunits interact with the PM and serve as landmarks for the exocyst recruitment (38–40). Both Sec3p and Exo70p bind the PM-specific phosphatidylinositol 4,5-bisphosphate (PIP₂) (39–41) and protein interactors such as Rho GTPases (42, 43). In animal cells, the exocyst membrane recruitment depends on the direct interaction of Exo70 with PIP₂ (44). In yeast and animals, PIP₂-dependent recruitment represents a general mechanism governing the localization of peripheral membrane proteins to the PM (45). In contrast, other anionic phospholipids, namely phosphatidic acid (PA), phosphatidylserine (PS), and phosphatidylinositol 4-phosphate (PI4P), seem to be more important than PIP₂ in constituting the PM phospholipid signature in plants (46–48).In this study, we analyzed the overall Arabidopsis exocyst architecture and described the subunit connectivity map. Although the general architecture of the exocyst is evolutionary conserved, the PM recruitment mechanism represents a unique feature of the plant complex. By combining genetics, live-cell imaging, biochemistry, protein structure modeling, and molecular dynamics simulations, we demonstrated that the EXO70A1 subunit plays an essential role in PM–lipid signature recognition and dominates in the plant exocyst–PM recruitment to the PM.     

Epidemiology of hepatitis B virus infection in Albania

AIM： To assess the prevalence and socio-demographic distribution of hepatitis B virus （HBV） infection in Albania. METHODS： Blood samples from 410 unselected schoolboys, 666 students, 500 military personnel, 1286 casual blood donors, 378 voluntary blood donors and 640 pregnant women （total 3880 non-vaccinated residents of rural and metropolitan areas from all over Albania; 2354 （60.7%） male and 1526 （39.3%） female; mean age of 26.3 years） were tested during 2004-2006 for hepatitis B surface antigen （HBsAg） and antibodies to hepatitis B virus （anti-HBs） by ELISA. RESULTS： The HBsAg and anti-HBs prevalence were 9.5% and 28.7%, respectively. The highest HI3sAg prevalence was evident in the younger age group, such as in schoolchildren （11.8%） and the military （10.6%）. Consequently, the anti-HBs prevalence increased with age, from 21.2% in schoolchildren （mean age： 15.7 years）, to 36.3% in pregnant women （mean age： 26.3 years） and 29.7% in voluntary blood donors （mean age： 40.1 years）. There were no significant differences between males and females. CONCLUSION： Despite the estimated two-fold reduction of HBsAg prevalence in the general population from about 18%-19% to 9.5%, Albania remains a highly endemic country （i.e. over 8% of HBsAg prevalence rate）.     

Indoor protection against mosquito and sand fly bites: a comparison between citronella, linalool, and geraniol candles

The repellent effect of 3 essential-oil-based candles was evaluated in a high biting pressure environment in Israel. In human landing assays, the repellency rate of 5% citronella candles against mosquitoes was 29.0%, of 5% linalool candles was 71.1%, and of 5% geraniol candles was 85.4%. The candles with geraniol were about twice as effective as those with linalool and were about 5 times as effective as citronella candles in protecting a person from being bitten indoors by mosquitoes. The repellency rate of 5% citronella candles towards sand flies was 24.7%, of 5% linalool candles was 55.2%, and of 5% geraniol candles was 79.7%. A geraniol candle was almost 5 times as effective as a citronella candle and about twice as effective as a linalool candle in protecting a person from being bitten indoors by sand flies.     

Comparison of 18F-FDG-PET and standard procedures for the pretreatment staging of children and adolescents with Hodgkin’s disease

Purpose The aim of this study was to perform a prospective, blinded comparison of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and conventional staging methods (CSMs) for initial staging of children and adolescents with Hodgkin’s disease (HD). Methods Over a period of 4 years, 55 children and adolescents with HD (mean age 15.5 years, range 3.9–18.9 years) were prospectively recruited into the study. They underwent 61 FDG-PET studies using a dedicated whole-body PET scanner as a part of their initial staging work-up. PET findings were correlated with the results of CSMs, including computed tomography (CT), ultrasound, bone scanning and bone marrow examination. Discordant findings were resolved by magnetic resonance imaging or clinical follow-up (range 2–47 months). Results PET correctly changed the staging in 15% of patients (seven upstagings, two downstagings). Only two out of 61 patients (3%) were not accurately staged by PET; in these children, PET missed small lymphoma nodules detected on lung CT. The sensitivity of PET and CSMs for pretreatment staging was 96.5% and 87.5%, respectively; specificity was 100% and 60%, and accuracy, 96.7% and 85.2%, respectively. Upon combination of FDG-PET and lung CT, the diagnostic accuracy reached 100% in our series. Conclusion Our study showed that whole-body FDG-PET is an efficient and useful method for the initial staging of children with HD. FDG-PET in combination with lung CT should be recommended as a screening method prior to other conventional imaging modalities to plan a rational staging protocol. Large multicentre prospective studies are necessary to verify this conclusion.