Life on the Western Front of Israel Stressful Living Conditions and Adolescent Cannabis Use

Negative implications of exposure to violence on health and wellbeing of youth have been observed and studied worldwide, especially in Israel. Youth in the western Negev of the country have been exposed to missile and terror attacks for more than a decade. However, implications of such prolonged exposure have not been fully studied. This study is aimed at the implications of exposure to such conditions on youth in the town of Ofakim in the Negev. A focus group was conducted with youth following the Israeli Defense Forces’ “Protective Edge” response to continued attacks from Gaza (July–Aug. 2014). Focus group participants reported high stress levels during the operation that resulted in an increase of substance use including alcohol, tobacco, cannabis, synthetic cannabis-like substances (e.g., “Nice Guy,” “Spice” and “Black Mamba”) and changes in eating and sleeping behavior. The Ofakim resilience center served as a shelter for participants providing for them with physical and emotional comfort. Staying in the “shelter” used for protection against missile attack promoted youth resilience. Exposure to violence has a significant impact on the health and wellbeing of young people and others. A secure receptive facility that provides trust and support can serve as an important moderator of the negative impact of emergency conditions. From the results reported in this article, further research is needed to fully assess the long-term effects of stress conditions including the use of cannabis and synthetic cannabis-like substances among youth and other residents in the Western Negev.     

Age estimation of fragmented human dental remains by secondary dentin virtual analysis

International Journal of Legal Medicine - Unlike bones, teeth are remarkably resilient and can withstand severe trauma, making age assessment based on the dentition essential for forensic analysis....     

Chemokine receptor expression in peripheral blood monocytes from patients with neovascular age-related macular degeneration

Purpose. Chemokine signaling and monocytes/macrophages were implicated in the pathogenesis of AMD. We tested the association between chemokines involved in monocyte recruitment and AMD. Methods. Immunophenotyping for white blood cell (WBC) populations including CD14++CD16- and CD14+CD16+ monocytes, CD19+, CD3+, and CD16+ lymphocytes, and chemokine receptors CCR1, CCR2, CCR5, CX(3)CR1, and CXCR4 was performed on peripheral blood from treatment-na?ve neovascular AMD (NV-AMD) patients and controls. The mRNA level of chemokine receptors in monocytes was measured with quantitative-PCR. Systemic levels of major chemokine ligands CCL2, CCL5, CCL3, and CXCL10 were evaluated by ELISA. Genotyping was performed for risk SNPs for AMD in the CFH, C3, and HTRA1 genes. Results. The percentage of WBC subpopulations tested was similar between NV-AMD patients (n = 18) and controls (n = 20). CD14+CD16+ monocyte subpopulation showed a 3.5-fold increased expression of CCR1 (P = 0.039; t-test) and a 2.2-fold increased expression of CCR2 (P = 0.027) in patients compared with controls. Increased CCR1 and CCR2 expression was correlated with each other in patients (R(2) = 0.64, P < 0.0001), but not controls (R(2) = 0.02, P = 0.57). Increased mRNA levels of CCR1 (1.6-fold, P = 0.037) and CCR2 (1.6-fold, P = 0.007) were found in monocytes from NV-AMD patients. Chemokine receptor expression was not correlated with the presence of risk SNPs, and was not associated with blood chemokine levels. Conclusions. CCR1 and CCR2 are coupregulated on the CD14+CD16+ monocyte population in NV-AMD patients. These data implicate CD14+CD16+ monocytes and chemokine signaling in AMD. Additional investigation is needed to elucidate the role of these monocytes and their potential as a biomarker or therapeutic target for AMD.     

Intracellular metabolite levels shape sulfur isotope fractionation during microbial sulfate respiration

We present a quantitative model for sulfur isotope fractionation accompanying bacterial and archaeal dissimilatory sulfate respiration. By incorporating independently available biochemical data, the model can reproduce a large number of recent experimental fractionation measurements with only three free parameters: (i) the sulfur isotope selectivity of sulfate uptake into the cytoplasm, (ii) the ratio of reduced to oxidized electron carriers supporting the respiration pathway, and (iii) the ratio of in vitro to in vivo levels of respiratory enzyme activity. Fractionation is influenced by all steps in the dissimilatory pathway, which means that environmental sulfate and sulfide levels control sulfur isotope fractionation through the proximate influence of intracellular metabolites. Although sulfur isotope fractionation is a phenotypic trait that appears to be strain specific, we show that it converges on near-thermodynamic behavior, even at micromolar sulfate levels, as long as intracellular sulfate reduction rates are low enough (<<1 fmol H₂S⋅cell⁻¹⋅d⁻¹).Dissimilatory sulfate reduction is a respiratory process used by some bacteria and archaea to generate energy under anaerobic conditions. Aqueous sulfate serves as the terminal electron acceptor in this process, leading to the oxidation of organic carbon compounds and sometimes hydrogen and to the production of aqueous sulfide (1). Dissimilatory sulfate respiration was one of the first microbial metabolisms to be isotopically characterized through culture experiments (2), with ³²S-bearing sulfate shown to be consumed preferentially to ³⁴S-bearing sulfate. Early experiments identified two critical features of this dissimilatory sulfur isotope fractionation: Its magnitude correlates inversely with the sulfate reduction rate of an individual cell but correlates directly with extracellular sulfate concentrations (3–5).Through careful regulation of the environmental controls on respiration, more recent experiments have precisely calibrated these relationships and suggest that their particular form may be strain specific (6–11). All experiments, however, show a nonlinear response, where sulfur isotope fractionation increases rapidly with decreasing rate. At the low-rate limit, sulfur isotope fractionation appears to approach levels defined by thermodynamic equilibrium between aqueous sulfate and sulfide (8, 12), the initial reactant and final waste product in the respiratory processing chain.In parallel with experimental studies, theoretical work has built a broad foundation for understanding the net sulfur isotope fractionation expressed during sulfate respiration (13–17). These efforts initially dealt with sulfur flow through simplified metabolic networks (13) (Fig. 1A) and have expanded to incorporate, for example, electron supply to the reaction cycles of individual respiratory enzymes (17). The reversibility of an individual enzymatic reaction is a central theoretical concept behind these approaches, as it carries the isotopic memory of downstream steps in the pathway (Fig. 1A). Net “back flux” of sulfur from product sulfide to reactant sulfate was an early experimental observation with pure cultures of sulfate-reducing bacteria (18), supported recently by a similar demonstration in a sulfate-reducing coculture (19).Open in a separate windowFig. 1.Two illustrations of the dissimilatory sulfate respiration network. (A) Sulfur-focused representation of S-isotope fractionation. Bidirectional arrows represent reversible S transformations. In this framework the “back flux” on any one step is a phenomenological constraint. (B) Metabolite-focused representation used here to quantify back flux. Arrows indicate net flux through the individual steps of the pathway, with the ratio of backward to forward flux controlled by the relative abundances of the reactants and products for each step as well as the kinetics of their associated enzymes. Sat is sulfate adenylyl transferase. Apr is APS reductase. dSiR is dissimilatory sulfite reductase. MK_red refers to the reduced form of menaquinone (menaquinol) and MK_ox refers to the oxidized form of menaquinone. ETC stands for “electron transfer complex.” The likely identities of these complexes in sulfate-reducing microbes are discussed in the text.Here we describe a quantitative model for sulfur isotope fractionation during microbial sulfate dissimilation that explicitly links fractionation, reaction reversibility, and intracellular metabolite concentrations. Thermodynamic control over isotope fractionation at the low-rate limit is a natural consequence of this approach. It also leads to predictive relationships of fractionation with extracellular sulfate and sulfide concentrations, as well as with intracellular sulfate reduction rates. These relationships are observable characteristics of sulfate-respiring bacteria and archaea, both in the laboratory and in nature. They are the basis for interpreting fossil S-isotope fractionation patterns in the rock record in terms of ancient organisms and their environmental interactions (6, 11, 20). Both in concept and in application, then, sulfur isotope fractionation is a phenotypic trait. Its relationships with environmental metabolites and reduction rate can be thought of as a sulfur isotope phenotype. The approach we advocate here enables past and present variations of the sulfur isotope phenotype to be linked to their physiological, enzymatic, and environmental controls.     

Pulmonary hypertension in respiratory distress syndrome

Pulmonary hypertension was associated with nonresponse to surfactant in six premature infants with respiratory distress syndrome. The diagnosis was suspected on the basis of a discrepancy between the X-ray findings and the severity of the clinical status as reflected by hypoxia despite maximal ventilatory support. The diagnosis of pulmonary hypertension was made by pre- and postductal oxygen saturation differences or by echodoppler cardiography, showing suprasystemic right ventricular pressures or right to left shunts through a patent foramen ovale or the ductus arteriosus. The response to surfactant was quantified by the arterial/alveolar (a/A) ratio difference before and 1 hr after therapy (“delta a/A ratio”); the delta a/A ratio was 0 ± 0.01, which indicates a nonresponse. A single dose of 1 mg/kg tolazoline was administrated and the response assessed by a/A difference. A delta a/A ratio of 0.11 ± 0.11 (range 0.02-0.32) represented a dramatic response and enabled oxygenation in these severely ill infants. No significant side effects were observed. We conclude that pulmonary hypertension may be an important and reversible condition in certain cases of respiratory distress syndrome and has to be considered in infants who do not respond to surfactant. © 1995 Wiley-Liss, Inc.     

Translocation t(11;14) in newly diagnosed patients with multiple myeloma: Is it always favorable?

The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I‐FISH), we examined the co‐occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure. Bone marrow samples and clinical data from 212 patients with MM with t(11;14) were analyzed. At least two additional CAs were found in 35% (75/205) of patients and a strong correlation between specific CAs. The occurrence of three CAs [multiple gains of (1q) (HR = 6.94, P = 0.001), del(1p) (HR = 4.47, P = 0.008), and del(IGH) (HR = 2.38, P = 0.002)] exerted a profoundly deleterious effect on median OS when compared with patients with t(11;14) only. Del(17p) and del(13q) have also exerted a deleterious effect albeit to a lesser extent (HR = 2.05, P = 0.07 and HR = 1.81, P = 0.03, respectively). When compared with t(11;14) alone, the addition of certain CAs lead to worse outcomes. These findings may have important clinical and biological implications. Patients with coexisting adverse lesions and t(11;14) may be considered at high risk and managed accordingly. © 2016 Wiley Periodicals, Inc.     

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intra-abdominal malignancies in children—a single-institution experience

Purpose

Our purpose was to present our institutional experience with performing complete cytoreduction surgery and heated intraoperative chemotherapy (CRS-HIPEC) for children with disseminated intraabdominal malignancies, guided by a leading international center performing CRS-HIPEC in children.