The new pelagic Operational Observatory of the Catalan Sea (OOCS) for the multisensor coordinated measurement of atmospheric and oceanographic conditions.
The new pelagic Operational Observatory of the Catalan Sea (OOCS) for the coordinated multisensor measurement of atmospheric and oceanographic conditions has been recently installed (2009) in the Catalan Sea (41°39'N, 2°54'E; Western Mediterranean) and continuously operated (with minor maintenance gaps) until today. This multiparametric platform is moored at 192 m depth, 9.3 km off Blanes harbour (Girona, Spain). It is composed of a buoy holding atmospheric sensors and a set of oceanographic sensors measuring the water conditions over the upper 100 m depth. The station is located close to the head of the Blanes submarine canyon where an important multispecies pelagic and demersal fishery gives the station ecological and economic relevance. The OOCS provides important records on atmospheric and oceanographic conditions, the latter through the measurement of hydrological and biogeochemical parameters, at depths with a time resolution never attained before for this area of the Mediterranean. Twenty four moored sensors and probes operating in a coordinated fashion provide important data on Essential Ocean Variables (EOVs; UNESCO) such as temperature, salinity, pressure, dissolved oxygen, chlorophyll fluorescence, and turbidity. In comparison with other pelagic observatories presently operating in other world areas, OOCS also measures photosynthetic available radiation (PAR) from above the sea surface and at different depths in the upper 50 m. Data are recorded each 30 min and transmitted in real-time to a ground station via GPRS. This time series is published and automatically updated at the frequency of data collection on the official OOCS website (http://www.ceab.csic.es/~oceans). Under development are embedded automated routines for the in situ data treatment and assimilation into numerical models, in order to provide a reliable local marine processing forecast. In this work, our goal is to detail the OOCS multisensor architecture in relation to the coordinated capability for the remote, continuous and prolonged monitoring of atmospheric and oceanographic conditions, including data communication and storage. Accordingly, time series of measurements for a number of biological parameters will be presented for the summer months of 2011. Marine hindcast outputs from the numerical models implemented for simulating the conditions over the study area are shown. The strong changes of atmospheric conditions recorded in the last years over the area have altered the marine conditions of living organisms, but the dimension of the impact remains unclear. The OOCS multisensor coordinated monitoring has been specifically designed to address this issue, thus contributing to better understand the present environmental fluctuations and to provide a sound basis for a more accurate marine forecast system.


Quantitative sectioning and noise analysis for structured illumination microscopy.
Structured illumination (SI) has long been regarded as a nonquantitative technique for obtaining sectioned microscopic images. Its lack of quantitative results has restricted the use of SI sectioning to qualitative imaging experiments, and has also limited researchers' ability to compare SI against competing sectioning methods such as confocal microscopy. We show how to modify the standard SI sectioning algorithm to make the technique quantitative, and provide formulas for calculating the noise in the sectioned images. The results indicate that, for an illumination source providing the same spatially-integrated photon flux at the object plane, and for the same effective slice thicknesses, SI sectioning can provide higher SNR images than confocal microscopy for an equivalent setup when the modulation contrast exceeds about 0.09.


HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation.
MicroRNAs (miRs) are an abundant class of small non-coding RNAs (~22 nt) that reprogram gene expression by targeting mRNA degradation and translational disruption. An emerging concept implicates miR coupling with transcription factors in myeloid cell development and function, thus contributing to host defense and inflammation. The important role that these molecules play in the pathogenesis of HIV-1 is only now emerging. We provide evidence that exposure of monocyte-derived dendritic cells (MDDCs) to recombinant HIV-1 R5 gp120, but not to CCR5 natural ligand CCL4, influences the expression of a panel of miRs (i.e., miR-21, miR-155 and miR-181b) regulated by STAT3 and potentially targeting genes belonging to the STAT3 signaling pathway. The blockage of gp120-induced STAT3 activation impairs gp120 capacity to modulate the expression level of above mentioned miRs. Predictive analysis of miR putative targets emphasizes that these miRs share common target genes. Furthermore, gene ontology and pathway enrichment analysis outline that these genes mainly belong to biological processes related to regulation of transcription, in a complex network of interactions involving pathways relevant to HIV-DC interaction. Overall, these results point to gp120-triggered modulation of miR expression via STAT3 activation as a novel molecular mechanism exploited by HIV-1 to affect DC biology and thus modulate the immune response through complex regulatory loops involving, at the same time, miRs and transcription factors.


[Langer-Giedion syndrome with 8q23.1-q24.12 deletion diagnosed by comparative genomic hybridization].
The Langer-Giedion syndrome, also known as trichorhinophalangeal syndrome type II, is a hereditary multisystemic disease part of the group of contiguous gene deletion syndromes. The cause of this syndrome is a heterozygous deletion that involves the chromosomal region 8q23.3-q24.11 and mainly affects genes TRPS1, RAD21, and EXT1. This syndrome is characterized by the presence of multiple osteochondromas in limbs, hypertrichosis, and facial phenotype that includes sparse scalp hair, large laterally protruding ears, a long nose with a bulbous tip. We report the case of a Colombian patient with finding of an 8q23.1-q24.12 deletion by comparative genomic hybridization array technique and classical clinical findings, being the first case reported in Colombia.


Sequential Monte Carlo with transformations.
This paper examines methodology for performing Bayesian inference sequentially on a sequence of posteriors on spaces of different dimensions. For this, we use sequential Monte Carlo samplers, introducing the innovation of using deterministic transformations to move particles effectively between target distributions with different dimensions. This approach, combined with adaptive methods, yields an extremely flexible and general algorithm for Bayesian model comparison that is suitable for use in applications where the acceptance rate in reversible jump Markov chain Monte Carlo is low. We use this approach on model comparison for mixture models, and for inferring coalescent trees sequentially, as data arrives.


Primary Care Medication Safety Surveillance with Integrated Primary and Secondary Care Electronic Health Records: A Cross-Sectional Study.
The extent of preventable medication-related hospital admissions and medication-related issues in primary care is significant enough to justify developing decision support systems for medication safety surveillance. The prerequisite for such systems is defining a relevant set of medication safety-related indicators and understanding the influence of both patient and general practice characteristics on medication prescribing and monitoring. The aim of the study was to investigate the feasibility of linked primary and secondary care electronic health record data for surveillance of medication safety, examining not only prescribing but also monitoring, and associations with patient- and general practice-level characteristics. A cross-sectional study was conducted using linked records of patients served by one hospital and over 50 general practices in Salford, UK. Statistical analysis consisted of mixed-effects logistic models, relating prescribing safety indicators to potential determinants. The overall prevalence (proportion of patients with at least one medication safety hazard) was 5.45 % for prescribing indicators and 7.65 % for monitoring indicators. Older patients and those on multiple medications were at higher risk of prescribing hazards, but at lower risk of missed monitoring. The odds of missed monitoring among all patients were 25 % less for males, 50 % less for patients in practices that provide general practitioner training, and threefold higher in practices serving the most deprived compared with the least deprived areas. Practices with more prescribing hazards did not tend to show more monitoring issues. Systematic collection, collation, and analysis of linked primary and secondary care records produce plausible and useful information about medication safety for a health system. Medication safety surveillance systems should pay close attention to patient age and polypharmacy with respect to both prescribing and monitoring failures; treat prescribing and monitoring as different statistical processes, rather than a combined measure of prescribing safety; and audit the socio-economic equity of missed monitoring.


Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin.
Recent studies and experience suggest that cefazolin might be equally as effective as antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA), with a better safety profile and lower cost. The objective of these meta-analyses was to compare the safeties of antistaphylococcal penicillins and cefazolin. The PubMed, Embase, and International Pharmaceutical Abstracts databases and websites for clinical trial registries through 23 June 2017 were searched. In addition, recent abstracts from infectious disease and pharmacy conferences were reviewed. We estimated Peto odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models. One analysis focused on hospitalized patients, and the other focused on outpatients. Eleven retrospective studies of hospitalized patients and three retrospective studies of outpatients were included. In hospitalized patients, lower rates of nephrotoxicity (Peto OR, 0.225; 95% CI, 0.127 to 0.513), acute interstitial nephritis (Peto OR, 0.189; 95% CI, 0.053 to 0.675), hepatotoxicity (Peto OR, 0.160; 95% CI, 0.066 to 0.387), and drug discontinuation due to adverse reactions (Peto OR, 0.192; 95% CI, 0.089 to 0.414) were found with cefazolin. In outpatients, lower rates of nephrotoxicity (Peto OR, 0.372; 95% CI, 0.192 to 0.722), hepatotoxicity (Peto OR, 0.313; 95% CI, 0.156 to 0.627), and hypersensitivity reactions (Peto OR, 0.372; 95% CI, 0.201 to 0.687) were observed with cefazolin. Compared to antistaphylococcal penicillins, cefazolin was associated with significant reductions in nephrotoxicity and hepatotoxicity in hospitalized patients and outpatients. Additionally, cefazolin was associated with lower likelihoods of discontinuation due to side effects in hospitalized patients and hypersensitivity reactions in outpatients. Cefazolin should be considered a first-line option for patients with MSSA infections for which efficacy is presumed to be similar to that of antistaphylococcal penicillin therapy.


Novel players in coeliac disease pathogenesis: role of the gut microbiota.
Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause-effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host-microbial interactions can influence host responses to gluten.


Climate oscillation during the Quaternary associated with landscape heterogeneity promoted allopatric lineage divergence of a temperate tree Kalopanax septemlobus (Araliaceae) in East Asia.
We investigated the biogeographic history of Kalopanax septemlobus, one of the most widespread temperate tree species in East Asia, using a combined phylogeographic and palaeodistribution modelling approach. Range-wide genetic differentiation at nuclear microsatellites (G'(ST) = 0.709; 2205 samples genotyped at five loci) and chloroplast DNA (G(ST) = 0.697; 576 samples sequenced for 2055 bp at three fragments) was high. A major phylogeographic break in Central China corresponded with those of other temperate species and the spatial delineation of the two temperate forest subkingdoms of East Asia, consistent with the forests having been isolated within both East and West China for multiple glacial-interglacial cycles. Evidence for multiple glacial refugia was found in most of its current range in China, South Japan and the southernmost part of the Korean Peninsula. In contrast, lineage admixture and absence of private alleles and haplotypes in Hokkaido and the northern Korean Peninsula support a postglacial origin of northernmost populations. Although palaeodistribution modelling predicted suitable climate across a land-bridge extending from South Japan to East China during the Last Glacial Maximum, the genetic differentiation of regional populations indicated a limited role of the exposed sea floor as a dispersal corridor at that time. Overall, this study provides evidence that differential impacts of Quaternary climate oscillation associated with landscape heterogeneity have shaped the genetic structure of a wide-ranging temperate tree in East Asia.


Coordinating Cytoskeleton and Molecular Traffic in T Cell Migration, Activation, and Effector Functions.
Dynamic localization of receptors and signaling molecules at the plasma membrane and within intracellular vesicular compartments is crucial for T lymphocyte sensing environmental cues, triggering membrane receptors, recruiting signaling molecules, and fine-tuning of intracellular signals. The orchestrated action of actin and microtubule cytoskeleton and intracellular vesicle traffic plays a key role in all these events that together ensure important steps in T cell physiology. These include extravasation and migration through lymphoid and peripheral tissues, T cell interactions with antigen-presenting cells, T cell receptor (TCR) triggering by cognate antigen-major histocompatibility complex (MHC) complexes, immunological synapse formation, cell activation, and effector functions. Cytoskeletal and vesicle traffic dynamics and their interplay are coordinated by a variety of regulatory molecules. Among them, polarity regulators and membrane-cytoskeleton linkers are master controllers of this interplay. Here, we review the various ways the T cell plasma membrane, receptors, and their signaling machinery interplay with the actin and microtubule cytoskeleton and with intracellular vesicular compartments. We highlight the importance of this fine-tuned crosstalk in three key stages of T cell biology involving cell polarization: T cell migration in response to chemokines, immunological synapse formation in response to antigen cues, and effector functions. Finally, we discuss two examples of perturbation of this interplay in pathological settings, such as HIV-1 infection and mutation of the polarity regulator and tumor suppressor adenomatous polyposis coli (Apc) that leads to familial polyposis and colorectal cancer.


Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6.
Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis.


Relation between serum anti-p53 antibodies and microvessel density in bladder cancer patients.
Etiology of serum anti-p53 antibodies in bladder cancer patients is still unknown. In this study we evaluated the relationship between serum anti-p53 antibodies and microvessel density in bladder cancer patients. Seventy-six patients with transitional cell carcinoma of the urinary bladder were assessed prospectively (18 Ta, 30 T1, 28 T2>or =). Serum anti-p53 antibodies were detected by enzyme-linked immunosorbent assay. Tumor p53 overexpression was assessed by immunohistochemical staining. Vessels were stained immunohistochemically using an antibody against platelet endothelial cell-adhesion molecule CD31. Spearman correlation test and t test were used for statistical analysis. Serum anti-p53 antibodies were positive in 25 (60%) of 41 tumor p53-positive patients. While the mean (SD, range) microvessel density was found to be 43 (7.59, 8-99) in patients who had positive serum anti-p53 antibodies, it was found to be 23 (4.53, 6-98) in patients who had negative serum anti-p53 antibodies. There was a good correlation between serum anti-p53 antibodies and microvessel density (p<0.05). No correlation was found between tumor p53 expression and microvessel density (p>0.05). We found that there is a significant correlation between the microvessel density and serum anti-p53 antibodies. This result may show the role of angiogenesis in the etiology of serum anti-p53 antibodies in bladder cancer patients.


Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus.
To investigate a putative link between genetically determined variations in Toll-like receptor 2 (TLR2) and the occurrence of severe Staphylococcus aureus infection, the functional Arg753Gln single-nucleotide polymorphism and the GT repeat microsatellite in the TLR2 gene were examined in a large case-control study. No associations with disease or mortality attributable to these features were found.


Prevalence of Migraine Headache in Taif City, Saudi Arabia.
Migraine is a public health problem and it is the third most common cause of disability among individuals below the age of 50. In spite of the multiplicity of the studies concerned with exploring the disease epidemiology and nature worldwide, data from Saudi Arabia are lacking. The aim of this study was to study the prevalence of migraine in Taif city, Saudi Arabia. This was a cross-sectional study conducted on 354 individuals in Taif city. Data were collected via a self-administered questionnaire including demographic variables, clinical variables, and therapeutic variables. Data were fed into the computer and analyzed using SPSS software. Among the 354 recruited participants, 54% were females, and 46% were males. Migraine occurred in 89.9% of urban inhabitants. About 24% of migraineurs were unemployed, and 16% were non-working students. Headache occurred in 86.9% of females and 71.6% of males (P = 0.002). Gender was significantly correlated with migraine prevalence (odds ratio (OR) = 0.28). About 47% reported pain score of 4 - 6. Seeking medical advice was encountered in 32.4% of females and 26.6% of males. Nausea occurred in more than one-third of patients before and during headache. Only 31.4% of participants knew about migraine triggers. Family history was found in 64% of participants. Migraine is prevalent in Taif city. It is more prevalent among females, and among urban areas. Migraine is associated with high rates of unemployment. Most Saudi migraineurs encounter throbbing, moderately severe headache, that does not awake them from sleep. Females report more severe headaches, whereas more men take medications. Nausea is the most common associated symptom with migraine. Only one-third of Saudi migraineurs know about migraine triggers. Family history of migraine is very common among Saudi migraineurs.


Physician-Patient Communication is Associated With Hepatocellular Carcinoma Screening in Chronic Liver Disease Patients.
Patients with chronic liver disease are at high risk for developing liver cancer. Factors associated with screening awareness and doctor-patient communication regarding liver cancer were examined. Four hundred sixty-seven patients with chronic liver disease at a tertiary-care clinic participated in a phone survey regarding awareness of cancer screening, doctor-patient communication, and health behaviors. Medical records were retrospectively reviewed for data on liver disease etiology and dates of liver imaging tests. Seventy-nine percent of patients reported awareness of liver cancer screening, and 50% reported talking to their doctor about liver cancer. Patients with higher education, abstinence from alcohol, and liver cirrhosis were more likely to be aware of liver cancer screening (P=0.06, 0.005, <0.0001). Whites, patients with higher education, and those with cirrhosis were more likely to talk to their doctor about liver cancer (P=0.006; P=0.09, <0.0001). Awareness of liver cancer screening (79%) was similar to that of colorectal cancer screening (85%), lower than breast cancer screening (91%), and higher than prostate cancer screening (66%). Patients who were aware of liver cancer screening and reported talking to their doctor about liver cancer were significantly more likely to receive consistent liver surveillance (odds ratio, 4.81; 95% confidence interval, 2.62-8.84 and odds ratio, 1.97; 95% confidence interval, 1.19-3.28, respectively). Our study demonstrates the importance of effective physician communication with chronic liver disease patients on the risks of developing liver cancer and the importance of regular screening, especially among nonwhites and patients with lower education.


Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis.
Experimental studies have suggested that constant intravenous infusion would be preferable to conventional intermittent bolus administration of beta-lactam antibiotics for serious Gram-negative infections. Severe melioidosis (Burkholderia pseudomallei infection) carries a mortality over 40% despite treatment with high dose ceftazidime. The aim of this study was to measure the pharmacokinetic and pharmacodynamic effects of continuous infusion of ceftazidime vs intermittent bolus dosing in septicaemic melioidosis. Patients with suspected septicaemic melioidosis were randomised to receive ceftazidime 40 mg kg(-1) 8 hourly by bolus injection or 4 mg kg(-1) h(-1) by constant infusion following a 12 mg kg(-1) priming dose and pharmacokinetic and pharmacodynamic parameters were compared. Of the 34 patients studied 16 (59%) died. Twenty patients had cultures positive for B. pseudomallei of whom 12 (60%) died. The median MIC90 of B. pseudomallei was 2 mg l(-1), giving a minimum target concentration (4*MIC) of 8 mg l(-1). The median (range) estimated total apparent volume of distribution, systemic clearance and terminal elimination half-lives of ceftazidime were 0.468 (0.241-0. 573) l kg(-1), 0.058 (0.005-0.159) l kg(-1) h(-1) and 7.74 (1.95-44.71) h, respectively. Clearance of ceftazidime and creatinine clearance were correlated closely (r = 0.71; P < 0.001) and there was no evidence of significant nonrenal clearance. Simulations based on these data and the ceftazidime sensitivity of the B. pseudomallei isolates indicated that administration by constant infusion would allow significant dose reduction and cost saving. With conventional 8 h intermittent dosing to patients with normal renal function, plasma ceftazidime concentrations could fall below the target concentration but this would be unlikely with a constant infusion. Correction for renal failure, which is common in patients with meliodosis is Clearance = k(*) creatinine clearance where k = 0.72. Calculation of a loading dose gives median (range) values of loading dose, DL of 18.7 mg kg(-1) (9.5-23) and infusion rate I = 3.5 mg k(-1) h(-1) (0.4-13) (which equals 84 mg kg(-1) day(-1)). A nomogram for adjustment in renal failure is given.


Fertility-preserving options for cervical cancer.
Childbearing is one of the most important life goals for many women, and fertility preservation is a very important factor in the overall quality of life of cancer survivors. Cervical cancer frequently affects young women; because some women tend to delay childbearing, fertility preservation must be considered when treatment options are discussed. Over the past decade, the radical trachelectomy procedure has become a well established fertility-preserving option for young women with early-stage cancer; this procedure is associated with low morbidity, good oncologic outcome, and a high proportion of pregnancies that reach the third trimester and babies that are delivered at term. This article will review available literature on the vaginal radical trachelectomy procedure and data from other surgical approaches, such as the abdominal radical trachelectomy. In addition, the potential future application of neoadjuvant chemotherapy followed by fertility-preserving surgery in patients with locally advanced cervical cancer will be examined. Finally, ultraconservative surgical approaches (eg, conization alone with or without laparoscopic lymphadenectomy) in very early-stage disease will be discussed.


Cost-benefit analysis of the introduction of mass vaccination against hepatitis B in Italy.
The aim of the study was to evaluate the costs and benefits of introducing mass vaccination against hepatitis B in Italy, given the announcement of compulsory vaccination of all newborn babies from 1991. Benefits were calculated by summarizing the clinical course of hepatitis B in Italy and projecting its incidence rates to the next 30 years using Brown's exponential smoothing technique. Incidence rates were then applied to the survivors of a cohort of newborns in 1992, and the total number of cases avoidable through vaccination was derived. Direct and indirect marginal costs were estimated for these cases. The marginal costs of the vaccination campaign were estimated. Cost and benefits were compared for 99 years following the introduction of the vaccination, using an 8 per cent discount rate and a sensitivity analysis. Despite difficulties in data gathering, susceptibility to discounting and estimating costs, results show an unfavourable cost-benefit ratio which is influenced by a declining incidence of the disease. Vaccination of high-risk groups is probably more efficient.


Endotracheal intubation versus supraglottic airway insertion in out-of-hospital cardiac arrest.
To simplify airway management and minimize cardiopulmonary resuscitation (CPR) chest compression interruptions, some emergency medical services (EMS) practitioners utilize supraglottic airway (SGA) devices instead of endotracheal intubation (ETI) as the primary airway adjunct in out-of-hospital cardiac arrest (OHCA). We compared the outcomes of patients receiving ETI with those receiving SGA following OHCA. We performed a secondary analysis of data from the multicenter Resuscitation Outcomes Consortium (ROC) PRIMED trial. We studied adult non-traumatic OHCA receiving successful SGA insertion (King Laryngeal Tube, Combitube, and Laryngeal Mask Airway) or successful ETI. The primary outcome was survival to hospital discharge with satisfactory functional status (Modified Rankin Scale ≤3). Secondary outcomes included return of spontaneous circulation (ROSC), 24-h survival, major airway or pulmonary complications (pulmonary edema, internal thoracic or abdominal injuries, acute lung injury, sepsis, and pneumonia). Using multivariable logistic regression, we studied the association between out-of-hospital airway management method (ETI vs. SGA) and OHCA outcomes, adjusting for confounders. Of 10,455 adult OHCA, 8487 (81.2%) received ETI and 1968 (18.8%) received SGA. Survival to hospital discharge with satisfactory functional status was: ETI 4.7%, SGA 3.9%. Compared with successful SGA, successful ETI was associated with increased survival to hospital discharge (adjusted OR 1.40; 95% CI: 1.04, 1.89), ROSC (adjusted OR 1.78; 95% CI: 1.54, 2.04) and 24-h survival (adjusted OR 1.74; 95% CI: 1.49, 2.04). ETI was not associated with secondary airway or pulmonary complications (adjusted OR 0.84; 95% CI: 0.61, 1.16). In this secondary analysis of data from the multicenter ROC PRIMED trial, ETI was associated with improved outcomes over SGA insertion after OHCA.


Immunity protein release from a cell-bound nuclease colicin complex requires global conformational rearrangement.
Nuclease colicins bind their target receptor BtuB in the outer membrane of sensitive Escherichia coli cells in the form of a high-affinity complex with their cognate immunity proteins. The release of the immunity protein from the colicin complex is a prerequisite for cell entry of the colicin and occurs via a process that is still relatively poorly understood. We have previously shown that an energy input in the form of the cytoplasmic membrane proton motive force is required to promote immunity protein (Im9) release from the colicin E9/Im9 complex and colicin cell entry. We report here that engineering rigidity in the structured part of the colicin translocation domain via the introduction of disulfide bonds prevents immunity protein release from the colicin complex. Reduction of the disulfide bond by the addition of DTT leads to immunity protein release and resumption of activity. Similarly, the introduction of a disulfide bond in the DNase domain previously shown to abolish channel formation in planar bilayers also prevented immunity protein release. Importantly, all disulfide bonds, in the translocation as well as the DNase domain, also abolished the biological activity of the Im9-free colicin E9, the reduction of which led to a resumption of activity. Our results show, for the first time, that conformational flexibility in the structured translocation and DNase domains of a nuclease colicin is essential for immunity protein release, providing further evidence for the hypothesis that global structural rearrangement of the colicin molecule is required for disassembly of this high-affinity toxin-immunity protein complex prior to outer membrane translocation.


[Chronic urticaria with alterations of the thyroid function and thyroid peroxidase antibodies].
Chronic urticaria is a frequent pathology, characterized by the presence of hives and/or angioedema lasting longer than 6 weeks. In an important number of patients it behaves as an autoimmune illness, frequently associated with alterations in thyroid function and thyroid antibodies. We herein describe a consecutive series of 70 patients with a diagnosis of chronic urticaria. Seven (10%) had a diagnosis of thyroid illness previous to their first consultation. Thyroid function and thyroid antibodies were studied in the remaining 63 patients by measuring the level of serum thyrotropin and the titer of peroxidase antibodies. Abnormal thyrotropin levels were detected in 11 (17%) patients, who in conjunction with the 7 patients with previous thyroid illness, add up to 18 (26%) with altered thyroid function. From 61 patients who were tested for thyroid peroxidase antibodies, 22 (36%) were positive. Of 57 patients without a diagnosis of previous thyroid disease, in whom both the levels of serum thyrotropin and the presence of thyroid peroxidase antibodies had been studied, 24 (42%) presented at least one altered study. Given the high percentage of thyroid alterations in our series of patients, it seems clinically relevant to study the thyroid function and the presence of thyroid peroxidase antibodies in patients with chronic urticaria.


Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation.
The goal of this study was to assess the efficacy of sirolimus in lung-transplant recipients. The study was designed as a single center, consecutive case study of lung-transplant recipients treated with sirolimus, tacrolimus, and prednisone. All study subjects also received an HMG-CoA reductase inhibitor, and prophylaxis for cytomegalovirus and Pneumocystis carinii. A total of 15 subjects were enrolled in the study. Within 6 months, significant airway complications occurred in four subjects, three of whom died. At that point, the investigators terminated enrollment in the study. The study population was compared retrospectively with a group of 83 consecutive lung recipients treated with cyclosporine (n=64) or tacrolimus (n=19), mycophenolate mofetil, and prednisone. This confirmed an increased incidence of airway dehiscence and reduced survival in the sirolimus-treated patients. Sirolimus-treated patients had a low incidence of acute rejection. No significant differences were noted in the incidence of bacterial or fungal bronchopulmonary infections. We observed an unexpectedly high incidence of postoperative airway dehiscence in lung-transplant recipients treated with sirolimus, in combination with tacrolimus, prednisone, and an HMG-CoA inhibitor. Further studies will be needed to determine the safety and efficacy of using sirolimus after complete airway healing has occurred.


Heteroatom incorporation effect in σ- and π-electron systems: the sEDA(II) and pEDA(II) descriptors.
The effect of heteroatom or heteroatomic group incorporation into unsaturated five- and six-membered cyclic systems was studied by means of DFT/B3LYP/aug-cc-pVDZ calculations. Two descriptors of the incorporation effect, sEDA(II) and pEDA(II), reflecting the influence of the incorporated atom or group on the population of the σ and π valence electrons, were constructed on the basis of natural bond orbital analysis. The sEDA(II) and pEDA(II) descriptors were shown to be linearly independent; the former correlated very well with electronegativity scales, whereas the latter correlated with NICS(1)(ZZ) and HOMA(CC) aromaticity indices. The two descriptors seem to be universal tools for analyzing different chemical and physicochemical effects occurring in unsaturated heterocyclic systems.


Vitamin B12 concentrations in pregnant Colombian women: analysis of nationwide data 2010.
Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence and socio-demographic factors associated with vitamin B12 deficiency in a representative sample of pregnant women in Colombia. We used data from the cross-sectional, nationally representative survey (ENSIN, 2010). A total of 1.781, (13-49 years old) pregnant women were enrolled. Serum Vitamin B12 a concentration was determined by chemiluminescence and sociodemographic date was assessed by computer-assisted personal interview technology. Multivariate analyses using unordered multinomial logistic regression models were conducted in the main analysis. Vitamin B12 concentrations ranged from 45 to 1000 pg/mL (mean 299.2 pg/mL, 95% CI 290.6 to 303.7 pg/mL). A total of 18.6% of pregnant women had vitamin B12 concentrations below 200 pg/mL and 41.3% had concentrations between 200 and 300 pg/mL. Being of indigenous ethnicity, living in the east and living in a rural area showed the lowest mean values (273.2 pg/mL, 270.8 pg/mL and 290.1 pg/mL, respectively). The multivariate logistic regression shows that pregnant women belonging to the indigenous ethnic group OR 2.2, (95% CI 1.1 to 4.3), living in the pacific region (west) OR 4.4, (95% CI 2.8 to 6.9), or national territories (south) OR 2.3, (95% CI 1.4 to 3.7) were associated with a higher probability of serum vitamin B12 deficiency. The prevalence of vitamin B12 deficiency in Colombian pregnant women is substantial. Factors associated with depletion among pregnant women should be considered for future interventions in countries experiencing nutritional transition.


Effects of Game Characteristics and Player Positions on Concussion Incidence and Severity in Professional Football.
Increasing efforts have been made to reduce the incidence and severity of concussion in high-contact sports. Despite these efforts, a relative lack of knowledge is available regarding modulating factors affecting concussion injury. To analyze the potential influence of game characteristics and outcomes on concussion incidence and severity in professional football. Descriptive epidemiology study. PBS Frontline Concussion Watch was used to collect concussion injury data from regular-season games of 32 National Football League (NFL) teams from 2012 to 2015. Game characteristic variables such as rushing and passing attempts, turnovers, and margin of victory were collected from ESPN. Analysis included descriptive statistics, analysis of variance, t tests, and correlation tests. Away teams demonstrated a significantly greater concussion incidence per game than home teams. Losing teams had a significantly greater concussion incidence per game than winning teams. Being both the away team and the losing team appeared to have an additive effect. The home-versus-away and win-versus-loss effects were significant for offensive but not defensive positions. Within individual positions, significantly greater concussion incidence was associated with tight ends, running backs, wide receivers, and cornerbacks. When running versus passing positions were compared, passing positions (wide receiver, tight end, cornerback, safety) had significantly greater concussion incidence. A total of 626 games were missed as a result of reported concussions. Away teams had significantly more games missed due to concussion when they lost. Play time did not significantly differ before or after concussion injury. Other game characteristic variables did not significantly affect concussion frequency or intensity. Position, game location, and game outcome affect concussion incidence for professional football players. In a subset of analyses, the number of games missed aligned with concussion incidence, but this appeared to be an imperfect measure. These findings highlight new factors that may modulate concussion incidence and merit further study on how they may influence concussion evaluation.


Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice.
The p38 mitogen-activated protein kinase (MAPK) pathway, like the c-Jun N-terminal kinase (JNK) MAPK pathway, is activated in response to cellular stress and inflammation and is involved in many fundamental biological processes. To study the role of the p38 MAPK pathway in vivo, we have used homologous recombination in mice to inactivate the Mkk3 gene, one of the two specific MAPK kinases (MAPKKs) that activate p38 MAPK. Mkk3(-/-) mice were viable and fertile; however, they were defective in interleukin-12 (IL-12) production by macrophages and dendritic cells. Interferon-gamma production following immunization with protein antigens and in vitro differentiation of naive T cells is greatly reduced, suggesting an impaired type I cytokine immune response. The effect of the p38 MAPK pathway on IL-12 expression is at least partly transcriptional, since inhibition of this pathway blocks IL-12 p40 promoter activity in macrophage cell lines and IL-12 p40 mRNA is reduced in MKK3-deficient mice. We conclude that the p38 MAP kinase, activated through MKK3, is required for the production of inflammatory cytokines by both antigen-presenting cells and CD4(+) T cells.


Receptor-mediated endocytosis of human transferrin and its cell surface receptor.
We have studied the process of transferrin endocytosis in human erythromyeloid cell line K562 using fluorescein (FL) and rhodamine (RD) labeled iron-saturated transferrin (FeTF), and a fluorescein labeled monoclonal antibody to the transferrin receptor (FL-mAB). Because the antireceptor antibody and FeTF bind to different sites on the TF receptor molecule, it is possible to simultaneously and independently follow receptor and ligand. We have measured the relative amounts of transferrin or antireceptor antibody bound in the presence or absence of proteolytic enzymes using a cell sorter. At 4 degrees C almost all of the FL-TF and the FL-mAB is surface bound in a diffuse pattern. Within minutes of elevating the temperature to 37 degrees C surface aggregates form and the FL-TF is internalized. At this time about one sixth of the transferrin is still surface bound and accessible to papain digestion. The remainder localizes in a perinuclear cluster of vesicles. Monoclonal antibody binds to the cell surface transferrin receptor but is not internalized at 4 degrees C or 37 degrees C. When unlabeled diferric transferrin is added, it promotes the uptake of the Fl-mAB. The addition of goat anti-mouse immunoglobulin also promotes FL-mAB uptake. These studies support the concept that a specific trigger is required for transferrin receptor endocytosis.


Intravenous Vitamin C Administration Improved Blood Cell Counts and Health-Related Quality of Life of Patient with History of Relapsed Acute Myeloid Leukaemia.
A 52-year-old female presented to Integrated Health Options Clinic in October 2014 with a history of relapsed acute myeloid leukaemia (AML, diagnosed in 2009 and relapsed in 2014). Intravenous(IV) vitamin C therapy was initiated (in 2014) following completion of chemotherapy as an alternative to haematopoietic stem cell transplantation. IV vitamin C was administered twice weekly at a dose of 70 g/infusion. Within 4 weeks of initiation of IV vitamin C therapy, there was a dramatic improvement in the patient's blood indices with platelet cell counts increasing from 25 × 10⁸/L to 196 × 10⁸/L and white blood cell counts increasing from 0.29 × 10⁸/L to 4.0 × 10⁸/L, with further improvements observed over the next 18 months. Furthermore, there was a clear and sustained improvement in the patient's health-related quality of life scores assessed using a validated questionnaire. She has remained healthy and in complete remission until the present day. This case study highlights the benefits of IV vitamin C as a supportive therapy for previously relapsed AML.


Oleoresin capsicum (pepper) spray and "in-custody deaths".
Increasing use of oleoresin capsicum (OC) spray devices (i.e., pepper spray, pepper mace, OC, capsaicin) by law enforcement agencies as a means of sublethal force to control suspects has brought into question whether exposure to this noxious irritant (capsaicin) can cause or contribute to unexpected in-custody deaths. Capsaicin stimulates nociceptors in exposed mucous membranes to produce intense pain, particularly involving the conjunctiva, and generates systemic physiologic and behavioral responses consonant with such extreme discomfort. We describe two cases of in-custody death, both associated temporally with the use of pepper spray, to illustrate salient investigative considerations. As with any other in-custody death, a thorough autopsy and toxicologic analysis, coupled with evaluation of the premortem chain of events, postexposure symptomatology, and the extent of natural disease processes, will help to reveal the role of oleoresin capsicum spray as unrelated, contributory, or causative.


The telomere-specific non-LTR retrotransposons SART1 and TRAS1 are suppressed by Piwi subfamily proteins in the silkworm, Bombyx mori.
The telomere structures in Bombyx mori are thought to be maintained mainly by the transposition of the specialized telomeric retroelements SART and TRAS. The silkworm genome has telomeric TTAGG repeats and telomerase, but this telomerase displays little or no activity. Here, we report that the transcription of the telomeric retroelements SART1 and TRAS1 is suppressed by the silkworm Piwi subfamily proteins BmAgo3 and Siwi. The silkworm Piwi subfamily was found to be expressed predominantly in the gonads and early embryo, as in other model organisms, but in BmN4 cultured cells, these proteins formed granules that were separate from the nuage, which is a different behaviour pattern. The expression of TRAS1 was increased in BmN4 cells when BmAgo3 or Siwi were silenced by RNAi. Our results suggest that B. mori Piwi proteins are involved in regulating the transposition of telomeric retroelements, and that the functional piRNA pathway is conserved in BmN4 cultured cells.


The Umeå University Database of Facial Expressions: a validation study.
A set of face stimuli, called the Umeå University Database of Facial Expressions, is described. The set consists of 30 female and 30 male models aged 17-67 years (M = 30.19, SD = 10.66). Each model shows seven different facial expressions (angry, surprised, happy, sad, neutral, afraid, and disgusted). Most models are ethnic Swedes but models of Central European, Arabic, and Asian origin are also included. Creating and validating a new database of facial expressions that can be used for scientific experiments. The images, presented in random order one at a time, were validated by 526 volunteers rating on average 125 images on seven 10-point Likert-type scales ranging from "completely disagree" to "completely agree" for each emotion. The proportion of the aggregated results that were correctly classified was considered to be high (M = 88%). The results lend empirical support for the validity of this set of facial expressions. The set can be used freely by the scientific community.


Cyclin E expression is associated with high levels of replication stress in triple-negative breast cancer.
Replication stress entails the improper progression of DNA replication. In cancer cells, including breast cancer cells, an important cause of replication stress is oncogene activation. Importantly, tumors with high levels of replication stress may have different clinical behavior, and high levels of replication stress appear to be a vulnerability of cancer cells, which may be therapeutically targeted by novel molecularly targeted agents. Unfortunately, data on replication stress is largely based on experimental models. Further investigation of replication stress in clinical samples is required to optimally implement novel therapeutics. To uncover the relation between oncogene expression, replication stress, and clinical features of breast cancer subgroups, we immunohistochemically analyzed the expression of a panel of oncogenes (Cyclin E, c-Myc, and Cdc25A,) and markers of replication stress (phospho-Ser33-RPA32 and γ-H2AX) in breast tumor tissues prior to treatment (n = 384). Triple-negative breast cancers (TNBCs) exhibited the highest levels of phospho-Ser33-RPA32 (P < 0.001 for all tests) and γ-H2AX (P < 0.05 for all tests). Moreover, expression levels of Cyclin E (P < 0.001 for all tests) and c-Myc (P < 0.001 for all tests) were highest in TNBCs. Expression of Cyclin E positively correlated with phospho-RPA32 (Spearman correlation r = 0.37, P < 0.001) and γ-H2AX (Spearman correlation r = 0.63, P < 0.001). Combined, these data indicate that, among breast cancers, replication stress is predominantly observed in TNBCs, and is associated with expression levels of Cyclin E. These results indicate that Cyclin E overexpression may be used as a biomarker for patient selection in the clinical evaluation of drugs that target the DNA replication stress response.


Effects of a mass media campaign to increase physical activity among children: year-1 results of the VERB campaign.
To determine the effects of a mass media campaign on the levels of physical activity among children 9 to 13 years of age. A prospective, longitudinal, quasi-experimental design was used. A baseline survey was conducted in April to June 2002, before the launch of VERB advertising. Random-digit-dialing methods were used to survey a nationally representative sample of children and parents. The follow-up survey was repeated with the same cohort of children and parents in April to June 2003. Propensity scoring was used to determine the campaign's effects on awareness and physical activity behaviors. United States. A total of 3120 parent-child dyads. Intervention. The VERB campaign is a multiethnic campaign that combines paid advertisements with school and community promotions and Internet activities to encourage children 9 to 13 years of age to be physically active every day. Launched in 2002 by the Centers for Disease Control and Prevention, VERB uses commercial marketing methods to advertise being physically active as cool, fun, and a chance to have a good time with friends. Using the VERB brand, paid advertising ran nationally from June 2002 through June 2003, targeting 9- to 13-year-old youths. Children's awareness of the campaign and self-reported estimates of free-time and organized physical activity sessions during nonschool hours in the week before the interview. After 1 year, 74% of children surveyed were aware of the VERB campaign. Levels of reported sessions of free-time physical activity increased for subgroups of children 9 to 13 years of age. A pattern of effects across 2 measures was observed for younger children (9-10 years of age), girls, children whose parents had less than a high school education, children from urban areas that were densely populated, and children who were low active at baseline. These subgroups engaged in more median weekly sessions of free-time physical activity than did children who were unaware of VERB and, as the children's level of VERB awareness was incrementally higher, the children engaged in incrementally more free-time physical activity sessions. The average 9- to 10-year-old youth engaged in 34% more free-time physical activity sessions per week than did 9- to 10-year-old youths who were unaware of the campaign. A pattern of effects for organized activity was found only for children classified as low active at baseline. The VERB campaign achieved high levels of awareness in 1 year. Higher levels of physical activity were reported for subgroups of US children. Promoting physical activity with child-focused commercial advertising shows promise.


Treatment of abdominal pain in irritable bowel syndrome.
Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.


Splicing factor mutations in the myelodysplastic syndromes: Role of key aberrantly spliced genes in disease pathophysiology and treatment.
Mutations of splicing factor genes (including SF3B1, SRSF2, U2AF1 and ZRSR2) occur in more than half of all patients with myelodysplastic syndromes (MDS), a heterogeneous group of myeloid neoplasms. Splicing factor mutations lead to aberrant pre-mRNA splicing of many genes, some of which have been shown in functional studies to impact on hematopoiesis and to contribute to the MDS phenotype. This clearly demonstrates that impaired spliceosome function plays an important role in MDS pathophysiology. Recent studies that harnessed the power of induced pluripotent stem cell (iPSC) and CRISPR/Cas9 gene editing technologies to generate new iPSC-based models of splicing factor mutant MDS, have further illuminated the role of key downstream target genes. The aberrantly spliced genes and the dysregulated pathways associated with splicing factor mutations in MDS represent potential new therapeutic targets. Emerging data has shown that IRAK4 is aberrantly spliced in SF3B1 and U2AF1 mutant MDS, leading to hyperactivation of NF-κB signaling. Pharmacological inhibition of IRAK4 has shown efficacy in pre-clinical studies and in MDS clinical trials, with higher response rates in patients with splicing factor mutations. Our increasing knowledge of the effects of splicing factor mutations in MDS is leading to the development of new treatments that may benefit patients harboring these mutations.


'Active' sugar transport in eukaryotes.
Sugar transporters in prokaryotes and eukaryotes belong to a large family of membrane proteins containing 12 transmembrane alpha-helices. They are divided into two classes: one facilitative (uniporters) and the other concentrative (cotransporters or symporters). The concentrative transporters are energised by either H+ or Na+ gradients, which are generated and maintained by ion pumps. The facilitative and H(+)-driven sugar transporters belong to a gene family with a distinctive secondary structure profile. The Na(+)-driven transporters belong to a separate, small gene family with no homology at either the primary or secondary structural levels. It is likely that the Na(+)- and H(+)-driven sugar cotransporters share common transport mechanisms. To explore these mechanisms, we have expressed cloned eukaryote Na+/sugar cotransporters (SGLT) in Xenopus laevis oocytes and measured the kinetics of sugar transport using two-electrode voltage-clamp techniques. For SGLT1, we have developed a six-state ordered model that accounts for the experimental data. To test the model we have carried out the following experiments. (i) We measured pre-steady-state kinetics of SGLT1 using voltage-jump techniques. In the absence of sugar, SGLT1 exhibits transient carrier currents that reflect voltage-dependent conformational changes of the protein. Time constants for the carrier currents give estimates of rate constants for the conformational changes, and the charge movements, integrals of the transient currents, give estimates of the number and valence of SGLT1 proteins in the plasma membrane. Ultrastructural studies have confirmed these estimates of SGLT1 density. (ii) We have perturbed the kinetics of the cotransporter by site-directed mutagenesis of selected residues.(ABSTRACT TRUNCATED AT 250 WORDS)


Impaired emotional categorisation in young people at increased familial risk of depression.
Negative biases in emotional information processing are characteristic of patients with acute depression and may persist after clinical recovery. It is not clear, however, whether such biases are present before the onset of the depressive disorder. The aim of the present study was to examine whether young people at risk of depression, by virtue of having a depressed biological parent (FH+), demonstrate negative biases in tasks of emotional facial recognition and emotional categorization. We also assessed whether task performance and the influence of parental depression are modified by allelic variation in the serotonin transporter (5HTT) gene. We found that the FH+ participants did not show evidence of negative biases relative to matched controls. They were, however, significantly slower to perform a task of emotional categorization. 5HTT genotype did not influence emotional processing significantly. We conclude that negative biases in emotional processing do not appear to be present in people with a family history of depression. However, impairment in emotional categorization could identify a high-risk phenotype and may indicate that people at genetic risk of depression have difficulty in using "mood as information".


R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions.
Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia, an inherited disorder of cortisol biosynthesis. All mutations thus far characterized that cause this disorder appear to result from recombinations between the gene encoding the enzyme, CYP21B (CYP21), and the adjacent pseudogene, CYP21A (CYP21P). These are either deletions caused by unequal crossing-over during meiosis or apparent transfers of deleterious sequences from CYP21A to CYP21B, a phenomenon termed gene conversion. However, a small percentage of alleles do not carry such a mutation. We analyzed DNA from a patient with the mild, nonclassic form of 21-hydroxylase deficiency, who carried one allele that had no gene conversions detectable by hybridization with oligonucleotide probes. Sequence analysis revealed that this allele carried two missense mutations, R339H and P453S, neither of which has been previously observed in CYP21A or CYP21B. Each of these mutations was introduced into CYP21 cDNA which was then expressed in COS1 cells using a vaccinia virus system. Each mutation reduced the ability of the enzyme to 21-hydroxylate 17-hydroxyprogesterone to 50% of normal and the ability to metabolize progesterone to 20% of normal. Thus, each of these mutations represents a potential nonclassic 21-hydroxylase deficiency allele that is not the result of an apparent gene conversion.


Changes in brain glioma incidence and laterality correlates with use of mobile phones--a nationwide population based study in Israel.
Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor's laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups--low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals. A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03). We found a statistically significant decrease in LGG's over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.


Mantle shear-wave velocity structure beneath the Hawaiian hot spot.
Defining the mantle structure that lies beneath hot spots is important for revealing their depth of origin. Three-dimensional images of shear-wave velocity beneath the Hawaiian Islands, obtained from a network of sea-floor and land seismometers, show an upper-mantle low-velocity anomaly that is elongated in the direction of the island chain and surrounded by a parabola-shaped high-velocity anomaly. Low velocities continue downward to the mantle transition zone between 410 and 660 kilometers depth, a result that is in agreement with prior observations of transition-zone thinning. The inclusion of SKS observations extends the resolution downward to a depth of 1500 kilometers and reveals a several-hundred-kilometer-wide region of low velocities beneath and southeast of Hawaii. These images suggest that the Hawaiian hot spot is the result of an upwelling high-temperature plume from the lower mantle.


Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.
In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 μg of chloroquine or 7.99 μg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.


An evaluation of patients' quality of life before, 6 weeks and 6 months after total hip replacement surgery.
Annually, throughout the world, more than 800,000 primary total hip replacement surgery procedures are performed on patients suffering from hip joint arthrosis. Since 1991, approximately 11,000 of these procedures are performed annually in Sweden. This study aimed to investigate any changes in the patients' life quality 6 weeks and 6 months after their total hip replacement surgery had been performed, compared to that immediately prior to the operation. It also aimed to examine the reason for surgery, the types of prostheses used, postoperative pain, complications and the actual usage of ambulation support. The Sickness Impact Profile self-appraisal instrument, together with personal patient interviews have been used as the basis of the research. A total of 51 patients responded to the quality of life instrument prior to their operation, 47 of these participated 6 weeks after the operation, and 40 patients 6 months after the operation. Significant differences in patients' total, physical and psychosocial quality of life 6 months postoperatively compared to the situation prior to the operation were found, but not between the situation before and 6 weeks after the total hip replacement surgery. The majority of patients were of the opinion that it was more important that the pain had disappeared or decreased, than any overall increase in the quality of life. Postoperative complications occurred within 6 weeks, and even after 6 months some patients still suffered from these.


Assessment of changes in total body water in patients undergoing renal dialysis using bioelectrical impedance analysis.
This study aimed to assess whether changes in fluid can be accurately predicted from the change in whole-body impedance with an appropriate correction for the conductor length (i.e. height). Eight studies to measure changes in impedance were performed on six patients during dialysis. The measured loss of fluid from the beginning to the end of dialysis (1174+/-706ml) agreed well with the change in body weight (1188+/-768kg). The regression lines of the plot of change in height(2)/impedance versus loss of fluid for each subject had correlation coefficients ranging from 0.880-0.999, but there was a four-fold variation in the slopes of the different curves. The mean +/- SD change in height(2)/impedance during the removal of 0.5, 1 and 2l of water was 1.75+/-0.96, 3.41+/-1.55 and 6.72+/-2.91 m(2)/ohms respectively. The total change in body water, calculated by a variety of prediction equations, overestimated the loss of fluid by a mean of between 86 and 100%. The lack of a fixed relationship between changes in impedance and changes in body water precludes the use of the impedance technique as a means of accurately assessing small fluid changes in this patient group.


Does Nissen fundoplication improve deglutition in children?
Soyer T, Yalçın Ş, Demir N, Karhan AN, Saltık-Temizel İN, Demir H, Tanyel FC. Does Nissen fundoplication improve deglutition in children? Turk J Pediatr 2017; 59: 28-34. A prospective study was performed to evaluate the effect of Nissen fundoplication (NF) on deglutition in children. Children who underwent NF between 2011-2015 were evaluated for demographic features, clinical findings, diagnostic methods for gastroesophageal reflux (GER) and indications for NF. Penetration aspiration scale (PAS), functional oral intake scale (FOIS) and esophageal functions were evaluated by videoflouroscopy (VFS). Preoperative and postoperative VFS findings were compared to evaluate the effect of NF on clinical findings and deglutition. Twenty-three children with a mean age of 5.08 ± 3.7 years were included. Female to male ratio was 15:8. Recurrent respiratory infections (RTI) (n: 14, 60.8%), swallowing dysfunction (n:13, 56.5%) and vomiting (n:10, 43.4%) were the most common symptoms. Preoperatively GER was diagnosed with barium swallowing study (BSS) contrast graphs (n:20, 87%) and with 24-hour esophageal pH monitorization (n:8, 34.8%). In 39.1% of patients, medical treatment for GER was used with a mean duration of 8 ± 5.8 months. Indications for NF were swallowing dysfunction (n: 18, 78%), GER complications (n:6, 26%), associated anatomical problems (n:4, 17.3%) and unresponsiveness to medical treatment (n: 3, 13%). Postoperative barium swallowing study and 24-hour esophageal pH monitorization showed no GER after NF in 95% of patients. Number of RTI were significantly decreased after NF (preoperative vs postoperative infection rate 4.21 vs 1.6 respectively, p < 0.05). VFS findings showed that PAS was significantly decreased after NF during both liquid and semi-liquid swallowing (p < 0.05). After NF, upper esophageal opening (UEO) was decreased when compared to preoperative VFS findings (p < 0.05 Esophageal cleaning, esophageal motility, esophageal backflow and lower esophageal sphincter narrowing did not alter after NF (p > 0.05). FOIS were significantly improved after NF (p < 0.05). VFS findings showed that penetration and aspiration were significantly decreased after NF and children had less RTI. Although, esophageal motility evaluated by VFS did not changed after NF, functional oral intake significantly improved in children.


Aspects of genetic susceptibility to human infectious diseases.
Host genetic factors play a major role in determining differential susceptibility to major infectious diseases of humans, such as malaria, HIV/AIDS, tuberculosis, and invasive pneumococcal disease. Progress in identifying the relevant genetic loci has come from a variety of approaches. Most convincing associations have been identified by case-control studies assessing biologically plausible candidate genes. All six of the genes that have a major effect on infectious disease susceptibility in humans have been identified in this way. However, recently genome-wide linkage analysis of affected sibling pairs has identified susceptibility loci for chronic infections such as leprosy and chronic hepatitis B virus persistence. Other approaches used successfully have included assessment in humans of the homologues of susceptibility genes mapped and identified in murine models. However, the great majority of susceptibility loci remain to be identified and the advent of large-scale genome-wide association scans offers a new approach to defining many of these.


Taste-related activity in the human dorsolateral prefrontal cortex.
Taste remains one of the least-explored human senses. Cortical taste responses were investigated using neuroimaging in 40 subjects tasting a range of different taste stimuli compared to a neutral tasteless control. Activation was found in the anterior insula/frontal opercular taste cortex and caudal orbitofrontal cortex, both areas established as taste cortical areas by neuronal recordings in primates. A novel finding in this study was a highly significant response to taste in the dorsolateral prefrontal cortex. This may reflect an effect of taste on cognitive processing to help optimise or modify behavioural strategies involved in executive control; or it could reflect the engagement of this region in attentional processing by a taste input.


Assembly and diploid architecture of an individual human genome via single-molecule technologies.
We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.


Requirements for the activation of protein kinase C: comparison of the molecular geometries of phorbol and diacylglycerol.
MM2 calculations have been performed on a number of derivatives of phorbol and diacylglycerol (DAG) to establish the molecular features required for the activation of protein kinase C by a detailed comparison of the molecular geometries in these two classes of compounds. For DAG, a dihedral angle of about -60 degrees appears to be required for the oxygens at C2 and C3 because that angle is fixed at this value in phorbols. There is good agreement between the computed Boltzmann distribution for the O1-C1-C2-O2 dihedral angle and NMR results for the same angle in phospholipids, as obtained by others. A conformer of DAG is identified with dihedral angles corresponding to those of beta-phorbols. This conformer, however, is 3.2 kcal/mol above the global minimum found for DAG. The molecular geometry of this conformer is consistent with that of a number of active and inactive rigid analogues of DAG. The preferred conformation in beta-phorbol diesters is found to be stabilized by an antiparallel stacking of the ester carbonyl groups. The lack of activity of alpha-phorbol esters appears to be due to differences in a portion of the molecule containing the five-membered/seven-membered rings, which are far from the DAG-like end of the phorbol molecule. It is proposed that some of the biological activities of phorbol diesters may be due to this portion of the beta-phorbol molecule, which might represent a second active region, distinct from that resembling DAG.


Hemoglobin-Based Oxygen Carrier for the Reconstitution of Canine Freeze-Dried Plasma in an In Vitro Model of Resuscitation.
Military working dogs (MWDs) are force multipliers that are at risk for severe trauma when employed on the battlefield. When in severe hemorrhagic shock, MWDs require both oxygen- carrying capacity and replacement of vascular volume and coagulation factors. The objective of this study was to evaluate the hemostatic capacity of canine freeze-dried plasma (cFDP) with a Food and Drug Administration (FDA)-approved hemoglobin- based oxygen carrier (HBOC) in an in vitro model of resuscitation. Whole blood (WB) was collected from 10 MWDs, and these samples were diluted by 10%, 25%, or 40% with either cFDP (reconstituted with water), HBOC, cFDP (reconstituted with HBOC), or an equal volume of a 1:1 ratio of cFDP (reconstituted with water) and HBOC. Hemostatic parameters were minimally changed based on evaluation of prothrombin time, activated partial thromboplastin time, fibrinogen and thromboelastography at the 10% and 25% dilutions, and parameters consistent with a hypocoagulability were seen at dilutions of 40%. Based on the results of this study, additional research is warranted to determine if cFDP reconstituted with HBOC is a viable resuscitation product in canine trauma.


Automated co-culture system for spatiotemporal analysis of cell-to-cell communication.
We present a microfluidic co-culture system that generates localized and precisely formulated immune signals among a population of cells, enabling spatiotemporal analysis of paracrine signal transmission between different cell types. The automated system allows us to create temporally modulated chemical inputs that can be delivered to single signal-transmitting and receiving cells in a highly controlled way. Using this system we stimulated a single macrophage with brief pulses of bacterial LPS and observed the macrophage transmitted TNF signal propagating in a population of fibroblasts via NF-κB activation. The signal receiving fibroblasts transformed the TNF signal into a spatiotemporally distributed NF-κB output, recapitulating the initiation of immune response to bacterial infection.


Magnetic resonance imaging and deep brain stimulation.
To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems.


The Society of Thoracic Surgeons Intermacs Database Annual Report: Evolving Indications, Outcomes, and Scientific Partnerships.
The Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), a joint effort among the National Heart, Lung, and Blood Institute, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and others, was established in 2005 at the University of Alabama at Birmingham. The registry examined clinical outcomes and quality-of-life metrics of patients who received an Food and Drug Administration-approved durable mechanical circulatory support (MCS) device to treat advanced heart failure. On January 1, 2018, the Intermacs Database became part of The Society of Thoracic Surgeons National Database, providing additional resources for quality assessment and improvement and scientific advancement. The Intermacs Database Annual Report summarizes outcomes in patients (≥19 years of age) who underwent durable MCS implant between June 23, 2006, and December 31, 2017. Outcomes are presented for patients who underwent isolated continuous flow left ventricular assist device (CF LVAD) support, CF LVAD support with concomitant right ventricular assist device (RVAD) implant, or total artificial heart implant. Analyses of patients with CF LVADs are stratified by axial flow and centrifugal flow configurations. Because of the association of era with outcomes, the survival analyses are restricted to isolated CF LVADs implanted in the 2012 to 2016 era. There were 25,145 adult patients with MCS reported to Intermacs, of whom 18,539 (74%) received CF LVADs, 667 (2.6%) had an RVAD with CF LVAD, 339 received a total artificial heart (1.3%), and 20 (0.07%) received an isolated RVAD. Of the CF LVADs, mean age was 57 ± 1 years, 26% were listed for transplantation, and 51% were in cardiogenic shock (profile 1 to 2) preoperatively. CF LVADs included 14,527 axial flow (78%) and 4,012 centrifugal flow (22%) devices. Intermacs patient phenotype has evolved over time to include more patients with profile 3 (26% in 2006 to 2011 versus 35% in 2012 to 2016) and fewer patients with profile 2 (40% versus 35%), patients with better markers of preoperative renal and hepatic function, and more patients who received implants for destination therapy (29% versus 48%) indication. In 2017, centrifugal flow implants (51%) approximated that of axial flow devices (49%). Mean CF LVAD support duration was 20 months (31,563 patient-years). One-year survival for isolated CF LVADs was 83% and 5-year survival was 46%. One-year survivals for centrifugal versus axial flow devices were 85% and 84%, respectively. Patients who required concomitant RVAD support had 1- and 5-year survivals of 58% and 28%, respectively. Freedom from all-cause readmission was 70% at 1 month and 20% at 1 year. At 1 year, stroke occurred in 20% of patients on centrifugal flow and 13% of patients on axial flow support (p < 0.001), gastrointestinal bleeding affected 20% of patients with centrifugal flow devices and 25% of patients with axial flow devices (p < 0.001), and pump-related infection occurred in 28% of patients with centrifugal flow devices versus 25% of patients with axial flow devices (p = 0.01). Neurologic dysfunction (19% of deaths) and multisystem organ dysfunction (15%) were the most common causes of death. With the evolution of MCS, patient phenotype and outcomes are also changing over time. CF LVAD support is increasingly being used in the less ill patient phenotype and more patients are supported for destination therapy. Mean survival is now approaching 5 years, but adverse events, especially neurologic events, continue to have a detrimental impact on the success of CF LVAD support.


Predictors and Outcomes of Surgery in Peritoneal Mesothelioma: an Analysis of 2000 Patients from the National Cancer Database.
Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignancy associated with poor outcomes. Recent reports have shown longer survival with radical surgery, usually combined with intraperitoneal chemotherapy. However, surgical interventions in these patients have not been extensively studied at a population level. The objective of this retrospective cohort study is to assess the prevalence of surgical and nonsurgical interventions for DMPM patients, the influence of surgery on survival outcomes, and the associations between demographic and clinical factors with treatments and outcomes. This study included adult patients diagnosed with DMPM from 2003 to 2014 and registered in the National Cancer Database (NCDB). The primary outcome was overall survival. Histologically confirmed mesothelioma was defined using International Classification of Diseases (ICD)-3 codes 9050/3, 9051/3, 90523, and 9053/3 and peritoneum as primary affected organ using ICD codes C17-19, C22-24, C26, C42, C48, and C76. Relationships between demographic and clinical variables, surgical treatments, and survival outcomes were evaluated using logistic and Cox modeling and log-rank tests. A total of 2062 patients were identified, of whom 1055 (51%) did not receive any surgery while 701 (34%) received radical surgery. Patients receiving radical surgery had overall survival of 38.4 months compared with 7.1 months for patients without surgery (p < 0.001) and 41.8 months in patients who received both radical surgery and systemic chemotherapy. Patients selected for and treated with radical surgery had significantly better overall survival compared with those receiving nonsurgical treatment. Patients newly diagnosed with DMPM should be evaluated for the possibility of receiving radical surgery.


Influence of shock waves on laser-driven proton acceleration.
The influence of shock waves, driven by amplified spontaneous emission (ASE), on laser-accelerated proton beams is investigated. A local deformation, produced by a cold shock wave launched by the ablation pressure of the ASE pedestal, can under oblique laser irradiation significantly direct the proton beam toward the laser axis. This can be understood in the frame of target normal sheath acceleration as proton emission from an area of the target where the local target normal is shifted toward the laser axis. Hydrodynamic simulations and experimental data show that there exists a window in laser and target parameter space where the target can be significantly deformed and yet facilitate efficient proton acceleration. The dependence of the magnitude of the deflection on target material, foil thickness, and ASE pedestal intensity and duration is experimentally investigated. The deflection angle is found to increase with increasing ASE intensity and duration and decrease with increasing target thickness. In a comparison between aluminum and copper target foils, aluminum is found to yield a larger proton beam deflection. An analytic model is successfully used to predict the proton emission direction.


Evaluation of the antibacterial activity of selected Pakistani honeys against multi-drug resistant Salmonella typhi.
The development of resistance to conventional anti-typhoid drugs and the recent emergence of fluoroquinolone resistance have made it very difficult and expensive to treat typhoid fever. As the therapeutic strategies become even more limited, it is imperative to investigate non-conventional modalities. In this context, honey is a potential candidate for combating antimicrobial resistance because it contains a broad repertoire of antibacterial compounds which act synergistically at multiple sites, thus making it less likely that the bacteria will become resistant. The in vitro antibacterial activity of 100 unifloral honey samples against a blood culture isolate of multi-drug resistant (MDR) Salmonella typhi were investigated. All honey samples were evaluated for both total (acidity, osmolarity, hydrogen peroxide and non-peroxide activity) and plant derived non-peroxide antibacterial activity by agar well diffusion assay at 50% and 25% dilution in sterile distilled water and 25% in catalase solution. Manuka (Unique Manuka Factor-21) honey was used for comparison. The phenol equivalence of each honey sample from 2% to 7% (w/v) phenol was obtained from regression analysis. The antibacterial potential of each honey sample was expressed as its equivalent phenol concentration. The honey samples which showed antibacterial activity equivalent to or greater than manuka honey were considered therapeutically active honeys. Nineteen honey samples (19%) displayed higher hydrogen peroxide related antibacterial activity (16-20% phenol), which is more than that of manuka honey (21-UMF). A total of 30% of the honey samples demonstrated antibacterial activity between 11 and 15% phenol similar to that of manuka honey while 51% of the honey samples did not exhibit any zone of inhibition against MDR-S. typhi at 50% (w/v) dilution. None of the indigenous honey samples displayed non-peroxide antibacterial activity. Only manuka honey showed non-peroxide antibacterial activity at 25% dilution (w/v) in catalase solution. The honey samples which displayed antibacterial activity equal to or greater than manuka honey may be useful in the clinical conditions where higher hydrogen peroxide related antibacterial activity is required. Manuka honey, which is known to possess non-peroxide antibacterial activity, warrants further evaluation in a suitable typhoid animal model.


Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction.
To analyse the treatment outcome of patients with ankylosing spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total period of 8 years with specific focus on dosage and the duration of intervals between infliximab infusions. EASIC included patients with AS who had received infliximab for 2 years as part of the ASSERT trial. After that period, rheumatologists were free to change the dose or the intervals of infliximab. Clinical data were status at baseline, end of ASSERT and for a total of 8 years of follow-up. Of the initially 71 patients with AS from EASIC, 55 patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF) treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean infusion interval increased slightly from 6 to 7.1±1.5 weeks, while 45.8% patients had increased the intervals up to a maximum of 12 weeks. The mean infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean infusion interval increased to 7.0±1.2 weeks. In total, the mean cumulative dose per patient and per year decreased from 3566.30 to 2973.60 mg. We could observe that over a follow-up of 8 years of treatment with infliximab, >85% patients still remained on the same treatment, without any major safety events. Furthermore, both the infusion intervals and also the mean infliximab dose were modestly reduced in ≥70% of the patients without the loss of clinical efficiency.


Low Second-To-Fourth Digit Ratio Has High Explosive Power? A Prepubertal Study.
Hsu, CC, Fong, TH, Chang, HM, Su, B, Chi, CP, Kan, NW, and Hsu, MC. Low second-to-fourth digit ratio has high explosive power? A prepubertal study. J Strength Cond Res 32(7): 2091-2095, 2018-A recent study reported that lower limb explosive power had no correlation with the index finger: ring finger (2D:4D) ratio. However, many studies hypothesized that a lower 2D:4D ratio (reflecting a relative higher testosterone exposure) predicts higher physical fitness. The aim of this study was to replicate the study of explosive power and the 2D:4D ratio in a sample of Taiwanese children. A total of 541 Taiwanese prepubertal children (257 girls and 284 boys aged 9-10 years) participated in this study. This study analyzed the relationship between the 2D:4D ratio and explosive power. Explosive power of the lower limbs was assessed using the standing long jump (SLJ) test. The lengths of the second and fourth fingers of the right hand were measured to calculate the 2D:4D ratio. The SLJ length was correlated with the 2D:4D ratios (r = -0.144, p = 0.015) in boys. After controlling for age and the body mass index, this correlation remained significant (r = -0.134, p = 0.024). For girls, 2D:4D ratios were not significantly correlated with SLJ scores. These results indicate that the SLJ distance was negatively correlated with the 2D:4D ratio in boys, but not in girls. These findings might suggest that prenatal testosterone exposure is negatively correlated with the explosive power in men, but not in women.


Depression, anxiety, and compulsive sexual behaviour among men in residential treatment for substance use disorders: The role of experiential avoidance.
Nearly one-third of individuals in treatment for substance use disorders endorse at-risk levels of compulsive sexual behaviours (CSBs). Untreated sexual compulsivity may facilitate relapse for treatment-seeking men. Previous research and theory suggest that CSBs are maintained by efforts to escape or alter negative affect (e.g., depression and anxiety). However, this hypothesis has not been examined within a sample of men in treatment for substance use disorders. In an effort to better understand CSBs within a population of men with substance use disorders, the present study is the first to examine experiential avoidance as one potential mechanism underlying the relation between men's symptoms of depression and anxiety and their use of CSBs. The present study reviewed medical records of 150 men in residential treatment for substance use disorders. Structural equation modelling was used to examine pathways from men's depression and anxiety symptoms to CSBs directly and indirectly through experiential avoidance while controlling for alcohol/drug problems and use. Results revealed significant indirect effects of both depression and anxiety symptoms on CSB through experiential avoidance. These results support and extend existing research on CSB in a treatment population. Findings suggest that intervention efforts for CSB may benefit by targeting men's avoidance of painful internal events. Compulsive sexual behaviour is related to symptoms of depression and anxiety amongst men in residential treatment for substance use disorders. Experiential avoidance is positively related to compulsive sexual behaviour amongst men with substance use disorders. For men in treatment for substance use disorders, the relation between symptoms of depression and anxiety and compulsive sexual behaviour is explained, in part, by experiential avoidance. Helping men with substance use disorders develop more adaptive methods of processing aversive experiences, as opposed to escaping them, may reduce their use of compulsive sexual behaviours when faced with aversive affect.


Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition.
A diet rich in vegetables and fruit is generally considered healthy because of a high content of phytochemicals, vitamins, and fiber. The phytochemical indole-3-carbinol (I3C), a derivative of glucobrassicin, is sold as a dietary supplement promising diverse health benefits. I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. Here, we investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition. For this, we used AhR repressor (AhRR)-reporter mice as a tool to study AhR activation in the intestine following dietary I3C-supplementation in comparison with AhR ligand-deprived diets, including a high fat diet. AhRR expression in intestinal immune cells was mainly driven by dietary AhR ligands and was independent of microbial metabolites. A lack of dietary AhR ligands caused enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis and correlated with the expansion of Enterobacteriaceae, whereas Clostridiales, Muribaculaceae, and Rikenellaceae were strongly reduced. I3C supplementation largely reverted this effect. Comparison of I3C-induced changes in microbiota composition using wild-type (WT), AhRR-deficient, and AhR-deficient mice revealed both AhR-dependent and -independent alterations in the microbiome. Overall, our study demonstrates that dietary AhR ligand supplementation has a profound influence on Ahrr expression in intestinal immune cells as well as microbiota composition.


A transcriptional sketch of a primary human breast cancer by 454 deep sequencing.
The cancer transcriptome is difficult to explore due to the heterogeneity of quantitative and qualitative changes in gene expression linked to the disease status. An increasing number of "unconventional" transcripts, such as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been associated with the tumoral state. Massively parallel sequencing techniques provide a framework for exploring the transcriptional complexity inherent to cancer with a limited laboratory and financial effort. We developed a deep sequencing and bioinformatics analysis protocol to investigate the molecular composition of a breast cancer poly(A)+ transcriptome. This method utilizes a cDNA library normalization step to diminish the representation of highly expressed transcripts and biology-oriented bioinformatic analyses to facilitate detection of rare and novel transcripts. We analyzed over 132,000 Roche 454 high-confidence deep sequencing reads from a primary human lobular breast cancer tissue specimen, and detected a range of unusual transcriptional events that were subsequently validated by RT-PCR in additional eight primary human breast cancer samples. We identified and validated one deletion, two novel ncRNAs (one intergenic and one intragenic), ten previously unknown or rare transcript isoforms and a novel gene fusion specific to a single primary tissue sample. We also explored the non-protein-coding portion of the breast cancer transcriptome, identifying thousands of novel non-coding transcripts and more than three hundred reads corresponding to the non-coding RNA MALAT1, which is highly expressed in many human carcinomas. Our results demonstrate that combining 454 deep sequencing with a normalization step and careful bioinformatic analysis facilitates the discovery and quantification of rare transcripts or ncRNAs, and can be used as a qualitative tool to characterize transcriptome complexity, revealing many hitherto unknown transcripts, splice isoforms, gene fusion events and ncRNAs, even at a relatively low sequence sampling.


The interrelationship between phagocytosis, autophagy and formation of neutrophil extracellular traps following infection of human neutrophils by Streptococcus pneumoniae.
Neutrophils play an important role in the innate immune response to infection with Streptococcus pneumoniae, the pneumococcus. Pneumococci are phagocytosed by neutrophils and undergo killing after ingestion. Other cellular processes may also be induced, including autophagy and the formation of neutrophil extracellular traps (NETs), which may play a role in bacterial eradication. We set out to determine how these different processes interacted following pneumococcal infection of neutrophils, and the role of the major pneumococcal toxin pneumolysin in these various pathways. We found that pneumococci induced autophagy in neutrophils in a type III phosphatidylinositol-3 kinase dependent fashion that also required the autophagy gene Atg5. Pneumolysin did not affect this process. Phagocytosis was inhibited by pneumolysin but enhanced by autophagy, while killing was accelerated by pneumolysin but inhibited by autophagy. Pneumococci induced extensive NET formation in neutrophils that was not influenced by pneumolysin but was critically dependent on autophagy. While pneumolysin did not affect NET formation, it had a potent inhibitory effect on bacterial trapping within NETs. These findings show a complex interaction between phagocytosis, killing, autophagy and NET formation in neutrophils following pneumococcal infection that contribute to host defence against this pathogen.