Effectiveness of β-Lactam Monotherapy vs Macrolide Combination Therapy for Children Hospitalized With Pneumonia.
β-Lactam monotherapy and β-lactam plus macrolide combination therapy are both common empirical treatment strategies for children hospitalized with pneumonia, but few studies have evaluated the effectiveness of these 2 treatment approaches. To compare the effectiveness of β-lactam monotherapy vs β-lactam plus macrolide combination therapy among a cohort of children hospitalized with pneumonia. We analyzed data from the Etiology of Pneumonia in the Community Study, a multicenter, prospective, population-based study of community-acquired pneumonia hospitalizations conducted from January 1, 2010, to June 30, 2012, in 3 children's hospitals in Nashville, Tennessee; Memphis, Tennessee; and Salt Lake City, Utah. The study included all children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia and who received β-lactam monotherapy or β-lactam plus macrolide combination therapy. Data analysis was completed in April 2017. We defined the referent as β-lactam monotherapy, including exclusive use of an oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate. Use of a β-lactam plus an oral or parenteral macrolide (azithromycin or clarithromycin) served as the comparison group. We modeled the association between these groups and patients' length of stay using multivariable Cox proportional hazards regression. Covariates included demographic, clinical, and radiographic variables. We further evaluated length of stay in a cohort matched by propensity to receive combination therapy. Logistic regression was used to evaluate secondary outcomes in the unmatched cohort, including intensive care admission, rehospitalizations, and self-reported recovery at follow-up. Our study included 1418 children (693 girls and 725 boys) with a median age of 27 months (interquartile range, 12-69 months). This cohort was 60.1% of the 2358 children enrolled in the Etiology of Pneumonia in the Community Study with radiographically confirmed pneumonia in the study period; 1019 (71.9%) received β-lactam monotherapy and 399 (28.1%) received β-lactam plus macrolide combination therapy. In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs 59 hours; adjusted hazard ratio, 0.87; 95% CI, 0.74-1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes. Empirical macrolide combination therapy conferred no benefit over β-lactam monotherapy for children hospitalized with community-acquired pneumonia. The results of this study elicit questions about the routine empirical use of macrolide combination therapy in this population.


Multisensory Convergence of Visual and Vestibular Heading Cues in the Pursuit Area of the Frontal Eye Field.
Both visual and vestibular sensory cues are important for perceiving one's direction of heading during self-motion. Previous studies have identified multisensory, heading-selective neurons in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP). Both MSTd and VIP have strong recurrent connections with the pursuit area of the frontal eye field (FEFsem), but whether FEFsem neurons may contribute to multisensory heading perception remain unknown. We characterized the tuning of macaque FEFsem neurons to visual, vestibular, and multisensory heading stimuli. About two-thirds of FEFsem neurons exhibited significant heading selectivity based on either vestibular or visual stimulation. These multisensory neurons shared many properties, including distributions of tuning strength and heading preferences, with MSTd and VIP neurons. Fisher information analysis also revealed that the average FEFsem neuron was almost as sensitive as MSTd or VIP cells. Visual and vestibular heading preferences in FEFsem tended to be either matched (congruent cells) or discrepant (opposite cells), such that combined stimulation strengthened heading selectivity for congruent cells but weakened heading selectivity for opposite cells. These findings demonstrate that, in addition to oculomotor functions, FEFsem neurons also exhibit properties that may allow them to contribute to a cortical network that processes multisensory heading cues.


Influence of Ukrain on the nuclear thyroid hormone receptors after short-term gamma-irradiation.
The ability of Ukrain, a semi-synthetic alkaloid thiophosphoric acid derivative (NSC-631579), to influence thyroid hormone levels in plasma and nuclear thyroid hormone receptors in female rat liver, as well as to modify the effects of short-term whole body gamma-irradiation on nuclear thyroid-hormone receptors in the liver was evaluated after intraperitoneal administration of the drug at 0.4 mg/kg body weight. Ukrain had no effect on the concentration of thyroid hormones in rat blood and increased the concentration of thyroid hormone receptors in the liver of intact rats during the first 2 months after administration. Ukrain normalized the level of nuclear thyroid hormone receptors influenced by short-term whole body gamma-irradiation of rats with 1 Gy, beginning from the first day after administration of the drug. Thus, Ukrain can minimize the consequences of irradiation in the endocrine system of experimental animals.


Effect of a Rapid Response Team on the Incidence of In-Hospital Mortality.
Approximately half of the life-limiting events, such as cardiopulmonary arrests or cardiac arrhythmias occurring in hospitals, are considered preventable. These critical events are usually preceded by clinical deterioration. Rapid response teams (RRTs) were introduced to intervene early in the course of clinical deterioration and possibly prevent progression to an event. An RRT was introduced at the Cleveland Clinic in 2009 and transitioned to an anesthesiologist-led system in 2012. We evaluated the association between in-hospital mortality and: (1) the introduction of the RRT in 2009 (primary analysis), and (2) introduction of the anesthesiologist-led system in 2012 and other policy changes in 2014 (secondary analyses). We conducted a single-center, retrospective analysis using the medical records of overnight hospitalizations from March 1, 2005, to December 31, 2018, at the Cleveland Clinic. We assessed the association between the introduction of the RRT in 2009 and in-hospital mortality using segmented regression in a generalized estimating equation model to account for within-subject correlation across repeated visits. Baseline potential confounders (demographic factors and surgery type) were controlled for using inverse probability of treatment weighting on the propensity score. We assessed whether in-hospital mortality changed at the start of the intervention and whether the temporal trend (slope) differed from before to after initiation. Analogous models were used for the secondary outcomes. Of 628,533 hospitalizations in our data set, 177,755 occurred before and 450,778 after introduction of our RRT program. Introduction of the RRT was associated with a slight initial increase in in-hospital mortality (odds ratio [95% confidence interval {CI}], 1.17 [1.09-1.25]; P < .001). However, while the pre-RRT slope in in-hospital mortality over time was flat (odds ratio [95% CI] per year, 1.01 [0.98-1.04]; P = .60), the post-RRT slope decreased over time, with an odds ratio per additional year of 0.961 (0.955-0.968). This represented a significant improvement (P < .001) from the pre-RRT slope. We found a gradual decrease in mortality over a 9-year period after introduction of an RRT program. Although mechanisms underlying this decrease are unclear, possibilities include optimization of RRT implementation, anesthesiology department leadership of the RRT program, and overall improvements in health care delivery over the study period. Our findings suggest that improvements in outcome after RRT introduction may take years to manifest. Further work is needed to better understand the effects of RRT implementation on in-hospital mortality.


Electrophysiological effects of a novel, short-acting and potent ester derivative of amiodarone, ATI-2001, in guinea pig isolated heart.
In this study the acute effects of ATI-2001, a recently developed ester derivative of amiodarone, on heart rate, atrioventricular conduction and frequency-dependent prolongation of ventricular conduction, repolarization and refractoriness were investigated in guinea pig isolated heart. Compared with amiodarone, an equimolar concentration of ATI-2001 (1 microM) caused significantly greater slowing of heart rate, depression of atrioventricular and intraventricular conduction and prolongation of ventricular repolarization. Unlike amiodarone, the effects of ATI-2001 were significantly reversed during washout of the drug. ATI-2001 exhibited frequency-independent effects on ventricular repolarization and refractoriness. It prolonged base-line ventricular monophasic action potential duration by 10%, 8%, 9% and 9% and ventricular effective refractory period by 24%, 20%, 22% and 26% at cycle lengths of 350, 300, 250 and 200 msec, respectively. Thus, ATI-2001 (1 microM) increased the ventricular effective refractory period/action potential duration ratio, suggesting both time- and voltage-dependent prolongation of ventricular refractoriness. In addition, ATI-2001 lengthened ventricular conduction times (QRS interval and basic conduction time) significantly more at shorter cycle lengths. Conversely, d-sotalol, a pure class III antiarrhythmic agent, had no effect on ventricular conduction times and exhibited a reverse frequency-dependent effect on ventricular repolarization. In summary, the electrophysiological effects of ATI-2001 were greater and more rapidly reversible than those of amiodarone. The lack of reverse frequency-dependent effects on ventricular repolarization and refractoriness suggests that ATI-2001 may be more efficacious than d-sotalol or other pure class III drugs in treating ventricular tachycardias and less likely to become proarrhythmic at normal or slow heart rates.


A new algorithm for use in computer identification.
On 9 May 1987, a Soviet-made IL-62M Polish airliner, LOT Flight 5055, crashed, exploded, and burned, killing the crew and 183 passengers. A forensic science team from the Armed Forces Institute of Pathology, comprised of 6 dental officers, 3 forensic pathologists, and 3 medical photographers, worked in concert with the Polish forensic science team. The small number of antemortem records and the extreme fragmentation of the remains presented a new scenario for computer use. Typically, the Computer-Assisted Postmortem Identification (CAPMI) software is used to compare remains against an antemortem database. Results are listed by the number of tooth-to-tooth matches based on restorative or other characteristics or both. The Polish disaster confounded this approach to some degree, however, and suggested a reconsideration of the theory on which the sort is made, that is, that the cases with maximum number of matches to preexisting dental records would be the most likely identification (ID) match. A hypothesis was constructed that, if searches were accomplished for fragments with a minimum number of mismatches, the correct matches would appear higher in the rank order. Six antemortem records (that had all dental information) were sorted against one hundred and twelve postmortem fragmented records. The resulting report was reordered so that records were listed by minimum number of mismatches. There was significant improvement in rank placement for all of the records. Thus it was accepted that in the situation of highly fragmented remains a different sorting based on the number of mismatches is indicated. Programming changes to make this option available have been implemented in the new version of CAPMI.


Preimplantation genetic diagnosis: choosing the "good enough" child.
Preimplantation genetic diagnosis (PGD) raises serious moral questions concerning the parent-child relationship. Good parents accept their children unconditionally: they do not reject/attack them because they do not have the features they want. There is nothing wrong with treating a child as someone who can help promote some other worthwhile end, providing the child is also respected as an end in him or herself. However, if the child's presence is not valued in itself, regardless of any further benefits it brings, the child is not being treated as an end in the full sense of the term, in this paper, I argue that these principles apply to human embryos, as well as to born human offspring: the human moral subject is a bodily being, whose interests and rights begin with the onset of his or her bodily life. The rights of the living, bodily human individual include a righ not to be attacked/abandoned because of his or her genetic profile. PGD is harmful to the parent-child relationship, and we give mixed messages to parents by expecting them to show unconditional commitment to offspring after birth, while inviting them to take a very different approach at the prenatal stage.


Visually Grounded Meaning Representations.
In this paper we address the problem of grounding distributional representations of lexical meaning. We introduce a new model which uses stacked autoencoders to learn higher-level representations from textual and visual input. The visual modality is encoded via vectors of attributes obtained automatically from images. We create a new large-scale taxonomy of 600 visual attributes representing more than 500 concepts and 700 K images. We use this dataset to train attribute classifiers and integrate their predictions with text-based distributional models of word meaning. We evaluate our model on its ability to simulate word similarity judgments and concept categorization. On both tasks, our model yields a better fit to behavioral data compared to baselines and related models which either rely on a single modality or do not make use of attribute-based input.


Highly syntenic regions in the genomes of soybean, Medicago truncatula, and Arabidopsis thaliana.
Recent genome sequencing enables mega-base scale comparisons between related genomes. Comparisons between animals, plants, fungi, and bacteria demonstrate extensive synteny tempered by rearrangements. Within the legume plant family, glimpses of synteny have also been observed. Characterizing syntenic relationships in legumes is important in transferring knowledge from model legumes to crops that are important sources of protein, fixed nitrogen, and health-promoting compounds. We have uncovered two large soybean regions exhibiting synteny with M. truncatula and with a network of segmentally duplicated regions in Arabidopsis. In all, syntenic regions comprise over 500 predicted genes spanning 3 Mb. Up to 75% of soybean genes are colinear with M. truncatula, including one region in which 33 of 35 soybean predicted genes with database support are colinear to M. truncatula. In some regions, 60% of soybean genes share colinearity with a network of A. thaliana duplications. One region is especially interesting because this 500 kbp segment of soybean is syntenic to two paralogous regions in M. truncatula on different chromosomes. Phylogenetic analysis of individual genes within these regions demonstrates that one is orthologous to the soybean region, with which it also shows substantially denser synteny and significantly lower levels of synonymous nucleotide substitutions. The other M. truncatula region is inferred to be paralogous, presumably resulting from a duplication event preceding speciation. The presence of well-defined M. truncatula segments showing orthologous and paralogous relationships with soybean allows us to explore the evolution of contiguous genomic regions in the context of ancient genome duplication and speciation events.


Bacterial Communities in Multiple Tissues Across the Body Surface of Three Coastal Shark Species.
Bacteria are known to have explicit roles within the microbiomes of host tissues, therefore examining these communities may prove useful in assessing host health and responses to environmental change. The present study contributes to the emerging, yet understudied, field of microbiome research in elasmobranchs. We provide a screening of the culturable bacteria communities found on multiple tissue sites on the body surface of blacktip (Carcharhinus limbatus), bull (Carcharhinus leucas), and tiger (Galeocerdo cuvier) sharks near Miami, Florida. Tissue sites include mouth, gills, skin, and any visible wounds. The study adds to our understanding of the diversity of bacteria present on sharks in comparison to their natural environment. We also compare bacterial groups found within wounds in shark skin to healthy tissue sites on the same individual. Results indicate that wounds on an individual may allow for opportunistic bacteria to invade or overgrow where they would not normally be found, which may have potential health consequences for sharks that become wounded due to fishing practices. Identified bacteria belonged to the Actinobacteria, Firmicutes, and Proteobacteria phyla, known to be prominent bacterial groups associated with marine organisms. Results indicate shark species-specific differences in bacterial communities, including the presence of bacteria belonging to Planococcaceae exclusively on the skin of tiger sharks. To our knowledge, this is the first report of this family in any elasmobranch. While most tissue sites displayed commensal bacteria identified in similar studies, known pathogens belonging to Vibrionaceae and Staphylococcaceae were identified in the wounds of blacktip and bull sharks. Some bacteria may be normal residents, but the loss of protective dermal denticles due to a wound may allow colonization by pathogens. Continued research is needed to explore microbial communities associated with sharks and their influence on host health.


Neuroimaging of Early Life Epilepsy.
We assessed the adherence to neuroimaging guidelines and the diagnostically relevant yield of neuroimaging in newly presenting early life epilepsy (ELE). There were 775 children with a new diagnosis of epilepsy (<3 years old at onset) who were recruited through the ELE study at 17 US pediatric epilepsy centers (2012-2015) and managed prospectively for 1 year. The data were analyzed to assess the proportion of children who underwent neuroimaging, the type of neuroimaging, and abnormalities. Of 725 children (93.5%) with neuroimaging, 714 had an MRI (87% with seizure protocols) and 11 had computed tomography or ultrasound only. Etiologically relevant abnormalities were present in 290 individuals (40%) and included: an acquired injury in 97 (13.4%), malformations of cortical development in 56 (7.7%), and other diffuse disorders of brain development in 51 (7.0%). Neuroimaging was abnormal in 160 of 262 (61%) children with abnormal development at diagnosis versus 113 of 463 (24%) children with typical development. Neuroimaging abnormalities were most common in association with focal seizure semiology (40%), spasms (47%), or unclear semiology (42%). In children without spasms or focal semiology with typical development, 29 of 185 (16%) had imaging abnormalities. Pathogenic genetic variants were identified in 53 of 121 (44%) children with abnormal neuroimaging in whom genetic testing was performed. Structural abnormalities occur commonly in ELE, and adherence to neuroimaging guidelines is high at US pediatric epilepsy centers. These data support the universal adoption of imaging guidelines because the yield is substantially high, even in the lowest risk group.


Sub-pg mass sensing and measurement with an optomechanical oscillator.
Mass sensing based on mechanical oscillation frequency shift in micro/nano scale mechanical oscillators is a well-known and widely used technique. Piezo-electric, electronic excitation/detection and free-space optical detection are the most common techniques used for monitoring the minute frequency shifts induced by added mass. The advent of optomechanical oscillator (OMO), enabled by strong interaction between circulating optical power and mechanical deformation in high quality factor optical microresonators, has created new possibilities for excitation and interrogation of micro/nanomechanical resonators. In particular, radiation pressure driven optomechanical oscillators (OMOs) are excellent candidates for mass detection/measurement due to their simplicity, sensitivity and all-optical operation. In an OMO, a high quality factor optical mode simultaneously serves as an efficient actuator and a sensitive probe for precise monitoring of the mechanical eigen-frequencies of the cavity structure. Here, we show the narrow linewidth of optomechanical oscillation combined with harmonic optical modulation generated by nonlinear optical transfer function, can result in sub-pg mass sensitivity in large silica microtoroid OMOs. Moreover by carefully studying the impact of mechanical mode selection, device dimensions, mass position and noise mechanisms we explore the performance limits of OMO both as a mass detector and a high resolution mass measurement system. Our analysis shows that femtogram level resolution is within reach even with relatively large OMOs.


A Rare Presentation of Mycosis Fungoides Mimicking Psoriasis Vulgaris.
Mycosis fungoides (MF) is an uncommon primary cutaneous lymphoma with a wide spectrum of clinicopathological manifestations. Diagnosis can be difficult in its early stages given the considerable overlap with more common benign dermatoses. We report an unusual case of MF in a 52-year-old male presenting with psoriasiform plaques on the palms and the soles who rapidly developed additional lesions on the scalp, limps and trunk. Punch biopsy of the face was obtained for routine histology and immunohistochemical stains. Chest X-ray, total body computed tomography scanning and excisional biopsy of the inguinal lymph node were performed. Review of the face biopsy revealed a diffuse dermal infiltrate containing a high number of atypical lymphocytes showing a CD3+, CD4+, CD45RO+, CD8-, CD20- immunophenotype and epidermotropism. Findings were consistent with tumor stage MF (stage IIB, T3 N1 M0). We report a rare presentation of MF mimicking psoriasis vulgaris.


Differential influence of family history of hypertension and premature myocardial infarction on systolic blood pressure and left ventricular mass trajectories in youth.
To examine the influence of genetic susceptibility to essential hypertension (EH) and the genetic susceptibility to premature myocardial infarction (MI) on longitudinal development of systolic blood pressure (SBP) and left ventricular mass (LVM) in youth. Individual SBP and LVM growth curves across age were created for a sample of 745 subjects (age range: 4.9-27.5 years) and a sample of 687 subjects (age range: 8.2-27.5 years), respectively. Each sample had an approximately equal proportion of African American and European American males and females, with annual assessments over a 10-year period. Family history (FH) of EH and FH of premature MI were used as measures of genetic susceptibility to EH and to premature MI, respectively. Positive FH (FH(+)) of EH and of premature MI were defined, respectively, as verified EH in 1 or both biological parents, and verified MI in any biological parent or grandparent before 55 years of age. Subjects with an FH(+) of EH had higher SBP levels and stronger increases in SBP over time than subjects with a negative FH (FH(-)) of EH. Subjects with an FH(+) of EH also showed higher LVM levels than subjects with an FH(-) of EH. In addition, the effect of an FH(+) of EH on LVM was stronger in females than males. The effects of FH of EH on SBP and LVM could not be explained by differences in socioeconomic status, but the effect on LVM was no longer significant after adjustment for BMI. FH of MI had no significant effects on SBP or LVM. Effects of genetic susceptibility to EH on SBP and LVM trajectories were observed in childhood, whereas no such effects were found for FH of MI. Genetic markers of EH may improve the understanding of individual differences in susceptibility to develop hypertension and LV hypertrophy.


Are Manipulation Checks Necessary?
Researchers are concerned about whether manipulations have the intended effects. Many journals and reviewers view manipulation checks favorably, and they are widely reported in prestigious journals. However, the prototypical manipulation check is a verbal (rather than behavioral) measure that always appears at the same point in the procedure (rather than its order being varied to assess order effects). Embedding such manipulation checks within an experiment comes with problems. While we conceptualize manipulation checks as measures, they can also act as interventions which initiate new processes that would otherwise not occur. The default assumption that manipulation checks do not affect experimental conclusions is unwarranted. They may amplify, undo, or interact with the effects of a manipulation. Further, the use of manipulation checks in mediational analyses does not rule out confounding variables, as any unmeasured variables that correlate with the manipulation check may still drive the relationship. Alternatives such as non-verbal and behavioral measures as manipulation checks and pilot testing are less problematic. Reviewers should view manipulation checks more critically, and authors should explore alternative methods to ensure the effectiveness of manipulations.


Molecular architecture of adenovirus DNA polymerase and location of the protein primer.
Adenovirus (Ad) DNA polymerase (pol) belongs to the distinct subclass of the polalpha family of DNA pols that employs the precursor terminal protein (pTP) as primer. Ad pol forms a stable heterodimer with this primer, and together, they bind specifically to the core origin in order to start replication. After initiation of Ad replication, the resulting pTP-trinucleotide intermediate jumps back and pTP starts to dissociate. Compared to free Ad pol, the pTP-pol complex shows reduced polymerase and exonuclease activities, but the reason for this is not understood. Furthermore, the interaction domains between these proteins have not been defined and the contribution of each protein to origin binding is unclear. To address these questions, we used oligonucleotides with a translocation block and show here that pTP binds at the entrance of the primer binding groove of Ad pol, thereby explaining the decreased synthetic activities of the pTP-pol complex and providing insight into how pTP primes Ad replication. Employing an exonuclease-deficient mutant polymerase, we further show that the polymerase and exonuclease active sites of Ad pol are spatially distinct and that the exonuclease activity of Ad pol is located at the N-terminal part of the protein. In addition, by probing the distances between both active sites and the surface of Ad pol, we show that Ad pol binds a DNA region of 14 to 15 nucleotides. Based on these results, a model for binding of the pTP-pol complex at the origin of replication is proposed.


Thiopurine drugs azathioprine and 6-mercaptopurine inhibit Mycobacterium paratuberculosis growth in vitro.
The in vitro susceptibility of human- and bovine-origin Mycobacterium paratuberculosis to the thioupurine drugs 6-mercaptopurine (6-MP) and azathioprine (AZA) was established using conventional plate counting methods and the MGIT 960 ParaTB culture system. Both 6-MP and AZA had antibacterial activity against M. paratuberculosis; isolates from Crohn's disease patients tended to be more susceptible than were bovine-origin isolates. Isolates of Mycobacterium avium, used as controls, were generally resistant to both AZA and 6-MP, even at high concentrations (> or =64.0 microg/ml). Among rapidly growing mycobacteria, Mycobacterium phlei was susceptible to 6-MP and AZA whereas Mycobacterium smegmatis strains were not. AZA and 6-MP limited the growth of, but did not kill, M. paratuberculosis in a dose-dependent manner. Anti-inflammatory drugs in the sulfonamide family (sulfapyridine, sulfasalazine, and 5-aminosalycilic acid [mesalamine]) had little or no antibacterial activity against M. paratuberculosis. The conventional antibiotics azithromycin and ciprofloxacin, used as control drugs, were bactericidal for M. paratuberculosis, exerting their killing effects on the organism relatively quickly. Simultaneous exposure of M. paratuberculosis to 6-MP and ciprofloxacin resulted in significantly higher CFU than use of ciprofloxacin alone. These data may partially explain the paradoxical response of Crohn's disease patients infected with M. paratuberculosis to treatment with immunosuppressive thiopurine drugs, i.e., they do not worsen with anti-inflammatory treatment as would be expected with a microbiological etiologic pathogen. These findings also should influence the design of therapeutic trials to evaluate antibiotic treatments of Crohn's disease: AZA drugs may confound interpretation of data on therapeutic responses for both antibiotic-treated and control groups.


Depression and Anxiety Change from Adolescence to Adulthood in Individuals with and without Language Impairment.
This prospective longitudinal study aims to determine patterns and predictors of change in depression and anxiety from adolescence to adulthood in individuals with language impairment (LI). Individuals with LI originally recruited at age 7 years and a comparison group of age-matched peers (AMPs) were followed from adolescence (16 years) to adulthood (24 years). We determine patterns of change in depression and anxiety using the Child Manifest Anxiety Scale-Revised (CMAS-R) and Short Moods and Feelings Questionnaire (SMFQ). In addition to examining associations with gender, verbal and nonverbal skills, we use a time-varying variable to investigate relationships between depression and anxiety symptoms and transitions in educational/employment circumstances. The results show that anxiety was higher in participants with LI than age matched peers and remained so from adolescence to adulthood. Individuals with LI had higher levels of depression symptoms than did AMPs at 16 years. Levels in those with LI decreased post-compulsory schooling but rose again by 24 years of age. Those who left compulsory school provision (regardless of school type) for more choice-driven college but who were not in full-time employment or study by 24 years of age were more likely to show this depression pathway. Verbal and nonverbal skills were not predictive of this pattern of depression over time. The typical female vulnerability for depression and anxiety was observed for AMPs but not for individuals with LI. These findings have implications for service provision, career/employment advice and support for individuals with a history of LI during different transitions from adolescence to adulthood.


Insomnia severity is an indicator of suicidal ideation during a depression clinical trial.
Insomnia has been linked to suicidal ideas and suicide death in cross-sectional and longitudinal population-based studies. A link between insomnia and suicide has not been previously examined in the setting of a clinical trial. Herein we describe the relationship between insomnia and suicidal thinking during the course of a clinical trial for depression with insomnia. Sixty patients aged 41.5±12.5 years (2/3 women) with major depressive episode and symptoms of insomnia received open-label fluoxetine for 9 weeks and also received blinded, randomized eszopiclone 3mg or placebo at bedtime after the first week of fluoxetine. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI), and suicidal ideation was assessed with The Scale for Suicide Ideation (SSI). Depression symptoms were assessed with the depressed mood item and the anhedonia item from the Hamilton Rating Scale for Depression-24 (HRSD24), as well as a sum score for all non-sleep and non-suicide items from the HRSD (HRSD20). Measurements were taken at baseline and weeks 1, 2, 4, 6, and 8. SSI was examined by generalized linear mixed models for repeated measures as the outcome of interest for all 60 participants with ISI and various mood symptoms as independent variables, with adjustment for age, gender, treatment assignment, and baseline SSI. Higher levels of insomnia corresponded to significantly greater intensity of suicidal thinking (p<0.01). The depressed mood item of the HRSD, and the sum of the HRSD20, both corresponded to greater suicidal thinking (p<0.001). The anhedonia item did not correspond with suicidal thinking. When both ISI and the depressed mood item, or ISI and the anhedonia item, were included together in the same model, the ISI remained an independent predictor of suicidal thinking. The results support the concept that insomnia may be a useful indicator for suicidal ideation and now extend this idea into clinical trials. Insomnia remains an independent indicator of suicidal ideation, even taking into account the core symptoms of depression such as depressed mood and anhedonia. The complaint of insomnia during a depression clinical trial might indicate that more direct questioning about suicide is warranted.


Transmission pathways for sporadic Shiga-toxin producing E. coli infections: A systematic review and meta-analysis.
Shiga-toxin E. coli infections remain a public health concern because of the severity of the gastrointestinal illness and associated complications. Transmission pathways are typically elucidated from outbreaks, with foodborne transmission the primary source. However, most STEC cases are sporadic. This systematic review aimed to identify the most common pathways for sporadic STEC transmission and quantify their importance. We systematically reviewed epidemiological studies of sporadic (non-outbreak) STEC cases that investigated potential risk factors. Searches were run in Medline, EMBASE, and Scopus. Included studies needed to confirm STEC infection and investigate ≥20 cases. 31 studies were included, of which 25 were case-control or case-case studies. 62.5% found consumption of undercooked/raw meat associated with STEC infection while 70.4% found contact with animals or their environment a risk factor. Random-effects meta-analysis provided pooled odds ratios and population attributable fraction (PAF). The PAF was 19% for undercooked/raw meat, followed by person to person transmission at 15%. Contact with animals and visiting farm environments had PAFs of 14% and 12% respectively. Out of potential sources for STEC exposure, undercooked meat and contact with animals and their environment were the most frequently found transmission routes. Decreasing the chances of acquiring the bacteria by these methods would additionally cut down on the other major transmission route, person-to-person spread.


MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men.
Excess production of reactive oxygen species (ROS) from the mitochondria can promote mitochondrial dysfunction and has been implicated in the development of a range of chronic diseases. As such there is interest in whether mitochondrial-targeted antioxidant supplementation can attenuate mitochondrial-associated oxidative stress. We investigated the effect of MitoQ and CoQ10 supplementation on oxidative stress and skeletal muscle mitochondrial ROS levels and function in healthy middle-aged men. Skeletal muscle and blood samples were collected from twenty men (50 ± 1 y) before and following six weeks of daily supplementation with MitoQ (20 mg) or CoQ10 (200 mg). High-resolution respirometry was used to determine mitochondrial respiration and H2O2 levels, markers of mitochondrial mass and antioxidant defences were measured in muscle samples and oxidative stress markers in urine and blood samples. Both MitoQ and CoQ10 supplementation suppressed mitochondrial net H2O2 levels during leak respiration, while MitoQ also elevated muscle catalase expression. However, neither supplement altered urine F2-isoprostanes nor plasma TBARS levels. Neither MitoQ nor CoQ10 supplementation had a significant impact on mitochondrial respiration or mitochondrial density markers (citrate synthase, mtDNA/nDNA, PPARGC1A, OXPHOS expression). Our results suggest that neither MitoQ and CoQ10 supplements impact mitochondrial function, but both can mildly suppress mitochondrial ROS levels in healthy middle-aged men, with some indication that MitoQ may be more effective than CoQ10.


Reducing inequalities in access to health care: developing a toolkit through action research.
Healthcare organisations are expected both to monitor inequalities in access to health services and also to act to improve access and increase equity in service provision. Locally developed action research projects with an explicit objective of reducing inequalities in access. Eight different health care services in the Yorkshire and Humber region, including community based palliative care, general practice asthma care, hospital based cardiology clinics, and termination of pregnancy services. Changes in service provision, increasing attendance rates in targeted groups. Local teams identified the population concerned and appropriate interventions using both published and grey literature. Where change to service provision was achieved, local data were collected to monitor the impact of service change. A number of evidence based changes to service provision were proposed and implemented with variable success. Service uptake increased in some of the targeted populations. Interventions to improve access must be sensitive to local settings and need both practical and managerial support to succeed. It is particularly difficult to improve access effectively if services are already struggling to meet current demand. Key elements for successful interventions included effective local leadership, identification of an intervention which is both evidence based and locally practicable, and identification of additional resources to support increased activity. A "toolkit" has been developed to support the identification and implementation of appropriate changes.


Glucocorticoid Regimens in the Treatment of Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.
Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [e.g., biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (17OHP) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower 17OHP and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.


Admission pattern and outcome in critical care obstetric patients.
We undertook a six-year retrospective study to determine the pattern of admission and outcome for obstetric patients admitted to the intensive care unit of the University of Nigeria Teaching Hospital, Enugu. The hospital records (case notes and intensive care unit records) were used to extract the necessary data. A total of 816 patients were admitted to the intensive care unit during the period under review. Eighteen (2.2%) were obstetric patients. Nine (50%) were preeclamptic and eclamptic patients. Four patients (22.2%) had obstetric haemorrhage. Five others presented with the following: asthma, postoperative respiratory distress, cervical incompetence, gestational diabetes and hypertension, and caesarean section for terminal carcinoma of the breast. There were six deaths (mortality rate 33.3%). Preeclampsia/eclampsia accounted for four deaths (44% mortality rate amongst preeclamptics/eclamptics), while two deaths accounted for a 50% mortality rate in the obstetric haemorrhage group. This study confirmed similar reports from the advanced nations and Asia that preeclampsia/eclampsia and obstetric haemorrhage are the leading causes of admission to the intensive care unit. The mortality rate in this study is however higher.


Oxidation kinetics of YBaCo4O7+δ and substituted oxygen carriers.
In this paper, the relaxation kinetics of the oxidation process of the YBaCo4O7+δ , Y0.95Ti0.05BaCo4O7+δ and Y0.5Dy0.5BaCo4O7+δ oxygen carriers is studied with isothermal reaction data. XRD analysis for fresh samples shows that all the samples have YBaCo4O7+δ structure. Scanning electron microscopy images of samples show that the samples consist of porous agglomerates of primary particles. Isothermal TG experiments are conducted with temperatures of 290°C, 310°C, 330°C and 350°C, respectively. It is found that the Avrami-Eroféev model describes solid-phase changes in the oxygen absorption process adequately. The results show that the distributed activation energies of the oxidation process obtained by the Avrami-Eroféev model are 42.079 kJ mol-1, 42.944 kJ mol-1 and 41.711 kJ mol-1 for the YBaCo4O7+δ , Y0.95Ti0.05BaCo4O7+δ and Y0.5Dy0.5BaCo4O7+δ oxygen carriers, respectively. The kinetic model was obtained to predict the oxygen carrier conversion of oxygen absorption for different time durations. The kinetic parameters obtained here are quite vital when this material is used in reactors.


CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival.
Defects of CIB2, calcium- and integrin-binding protein 2, have been reported to cause isolated deafness, DFNB48 and Usher syndrome type-IJ, characterized by congenital profound deafness, balance defects and blindness. We report here two new nonsense mutations (pGln12* and pTyr110*) in CIB2 patients displaying nonsyndromic profound hearing loss, with no evidence of vestibular or retinal dysfunction. Also, the generated CIB2-/- mice display an early onset profound deafness and have normal balance and retinal functions. In these mice, the mechanoelectrical transduction currents are totally abolished in the auditory hair cells, whilst they remain unchanged in the vestibular hair cells. The hair bundle morphological abnormalities of CIB2-/- mice, unlike those of mice defective for the other five known USH1 proteins, begin only after birth and lead to regression of the stereocilia and rapid hair-cell death. This essential role of CIB2 in mechanotransduction and cell survival that, we show, is restricted to the cochlea, probably accounts for the presence in CIB2-/- mice and CIB2 patients, unlike in Usher syndrome, of isolated hearing loss without balance and vision deficits.


Sound Categories: Category Formation and Evidence-Based Taxonomies.
Five evidence-based taxonomies of everyday sounds frequently reported in the soundscape literature have been generated. An online sorting and category-labeling method that elicits rather than prescribes descriptive words was used. A total of N = 242 participants took part. The main categories of the soundscape taxonomy were people, nature, and manmade, with each dividing into further categories. Sounds within the nature and manmade categories, and two further individual sound sources, dogs, and engines, were explored further by repeating the procedure using multiple exemplars. By generating multidimensional spaces containing both sounds and the spontaneously generated descriptive words the procedure allows for the interpretation of the psychological dimensions along which sounds are organized. This reveals how category formation is based upon different cues - sound source-event identification, subjective-states, and explicit assessment of the acoustic signal - in different contexts. At higher levels of the taxonomy the majority of words described sound source-events. In contrast, when categorizing dog sounds a greater proportion of the words described subjective-states, and valence and arousal scores of these words correlated with their coordinates along the first two dimensions of the data. This is consistent with valence and arousal judgments being the primary categorization strategy used for dog sounds. In contrast, when categorizing engine sounds a greater proportion of the words explicitly described the acoustic signal. The coordinates of sounds along the first two dimensions were found to correlate with fluctuation strength and sharpness, consistent with explicit assessment of acoustic signal features underlying category formation for engine sounds. By eliciting descriptive words the method makes explicit the subjective meaning of these judgments based upon valence and arousal and acoustic properties, and the results demonstrate distinct strategies being spontaneously used to categorize different types of sounds.


Nationwide practice patterns in the use of recombinant human bone morphogenetic protein-2 in pediatric spine surgery as a function of patient-, hospital-, and procedure-related factors.
Current national patterns as a function of patient-, hospital-, and procedure-related factors, and complication rates in the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an adjunct to the practice of pediatric spine surgery have scarcely been investigated. The authors conducted a cross-sectional study using data from the Healthcare Cost and Utilization Project Kids' Inpatient Database. Univariate and multivariate logistic regression were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals, and p values < 0.05 were considered to be statistically significant. The authors identified 9538 hospitalizations in pediatric patients 20 years old or younger who had undergone spinal fusion in the US in 2009; 1541 of these admissions were associated with rhBMP-2 use. By multivariate logistic regression, the following factors were associated with rhBMP-2 use: patient age 15-20 years; length of hospital stay (adjusted odds ratio [aOR] 1.01, p = 0.017); insurance status (private [aOR 1.49, p < 0.001] compared with Medicaid); hospital type (nonchildren's hospital); region (Midwest [aOR 2.49, p = 0.008] compared with Northeast); spinal refusion (aOR 2.20, p < 0.001); spinal fusion approach/segment (anterior lumbar [aOR 1.73, p < 0.001] and occipitocervical [aOR 1.86, p = 0.013] compared with posterior lumbar); short segment length (aOR 1.42, p = 0.016) and midlength (aOR 1.44, p = 0.005) compared with long; and preoperative diagnosis (Scheuermann kyphosis [aOR 1.56, p < 0.017] and spondylolisthesis [aOR 1.93, p < 0.001]). Use of BMP in pediatric spine procedures now comprises more than 10% of pediatric spinal fusion. Patient-related (age, insurance type, diagnosis); hospital-related (children's hospital vs general hospital, region in the US); and procedure-related (redo fusion, anterior vs posterior approach, spinal levels, number of levels fused) factors are associated with the variation in BMP use in the US.


Molecular approaches to sarcoma therapy.
Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed.


Trans-fatty acid intake and increased risk of advanced prostate cancer: modification by RNASEL R462Q variant.
Previous studies have examined the role of higher trans-fatty acid consumption on prostate cancer risk, but the results remain unclear. Any potential association may be modified by variants in genes involved with immune and inflammatory responses. To investigate this, we undertook a case-control study (N = 1012) of the association between trans-fatty acid intake and advanced prostate cancer, and evaluated whether this effect was modified by a functional polymorphism in the RNASEL gene (R462Q). Among Caucasians (N = 834), we observed that each type of trans-fatty acid and total trans-fatty acid intake showed a statistically significant positive association with prostate cancer, but only weakly increased risk for the isomers of cis-fatty acids. Compared with the lowest quartile of total trans-fatty acid consumption, the higher quartiles gave odds ratios (ORs) equal to 1.58 [95% confidence interval (CI): 1.00, 2.48], 1.95 (95% CI: 1.20, 3.19) and 2.77 (95% CI: 1.60, 4.79) (P-trend = 0.0003); this effect was modified by the RNASEL R462Q polymorphism (P(interaction) = 0.01). Among men with the QQ/RQ genotype, the association between total trans-fatty acid intake and prostate cancer was substantially stronger [ORs of higher quartiles equal to 2.93 (95% CI: 1.62, 5.30), 3.13 (95% CI: 1.64, 5.98) and 4.80 (95% CI: 2.29, 10.08), respectively]. For men with the RR genotype, total trans-fatty acid intake was not associated with disease. This suggests that among Caucasians, positive association between higher trans-fatty acid consumption and prostate cancer may be modified by the functional RNASEL variant R462Q.


Is hesperidin essential for prophylaxis and treatment of COVID-19 Infection?
SARS-CoV-2 or COVID-19 is representing the major global burden that implicated more than 4.7 million infected cases and 310 thousand deaths worldwide in less than 6 months. The prevalence of this pandemic disease is expected to rise every day. The challenge is to control its rapid spread meanwhile looking for a specific treatment to improve patient outcomes. Hesperidin is a classical herbal medicine used worldwide for a long time with an excellent safety profile. Hesperidin is a well-known herbal medication used as an antioxidant and anti-inflammatory agent. Available shreds of evidence support the promising use of hesperidin in prophylaxis and treatment of COVID 19. Herein, we discuss the possible prophylactic and treatment mechanisms of hesperidin based on previous and recent findings. Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection. Anti-viral activity of hesperidin might constitute a treatment option for COVID-19 through improving host cellular immunity against infection and its good anti-inflammatory activity may help in controlling cytokine storm. Hesperidin mixture with diosmin co-administrated with heparin protect against venous thromboembolism which may prevent disease progression. Based on that, hesperidin might be used as a meaningful prophylactic agent and a promising adjuvant treatment option against SARS-CoV-2 infection.


Isolation and characterization of temperature sensitive mutants of Broadhaven virus, a Kemerovo group orbivirus (family, Reoviridae).
Eighteen stable temperature sensitive (ts) mutants of Broadhaven virus were isolated without the aid of mutagens. Spontaneous mutants were detected using 41 degrees C as the nonpermissive temperature and 36 degrees C as the permissive temperature. High frequency pairwise recombination defined five recombination groups. Four mutants belonged to group I, three to group II, six to group III, two to group IV, and two to group V. ts 7 was a possible double mutant representing lesions corresponding to those of groups III and V mutants. This is the first reported isolation of temperature sensitive mutants of a tick-borne orbivirus.


[Clinical finding and follow-up of chronic constrictive pericarditis].
The aim of this study was to describe the etiology, clinical findings, diagnostic methods, treatment, outcome and long-term prognosis of 35 patients with chronic constrictive pericarditis (CCP) that were prospectively analyzed according to a pericardial disease protocol performed in our Institution. Etiology of CCP was idiopathic in 24 patients (68%), and specific in 11 (32%). The majority (34 patients, 97%) underwent pericardiectomy. Perioperative mortality was 12% (4/33) no deaths were registered among patients with idiopathic CCP. Median follow-up was 5.6 years (percentile 25-75: 2.4-7.4 years). The cumulative actuarial survival probability was 97% at 1 year (confidence interval [CI] 80% to 99%); 83% at 5 years, (95% CI 65% to 93%); 78% at 7 years, (95% CI 60% to 90%), and 69% at 10 years (95% CI 50% to 84%). In conclusion, nowadays CCP is generally an idiopathic disease with late diagnosis. The clinical course of the disease produces severe symptoms of congestive heart failure. In a 10 years follow-up 2/3 of patients are alive and improved their quality of life. Idiopathic form of pericarditis did not show mortality during early postoperative period.


Effect of radiation on the Notch signaling pathway in osteoblasts.
Notch signaling has been shown to be important in osteoblast differentiation. Therapeutic radiation has been shown to alter the skeletal system, yet little information is available on the changes in Notch signaling in irradiated osteoblasts. The purpose of this study was to analyze the effect of radiation therapy with 2 and 4 Gy on Notch signaling in osteoblasts. In order to assess the radiation damage on osteoblast differentiation, total RNA and protein were collected three days after exposure to radiation. The effects of radiation on Notch signaling at the early and terminal stages of osteoblastic MC3T3-E1 cell differentiation was analyzed by qRT-PCR and western blot analysis. Our study applied a previously established method to induce MC3T3-E1 cell differentiation into osteoblasts and osteoblast precursors. Our results showed that the expression of Notch receptors (Notch1-4), ligands (Jagged1, Jagged2 and Delta1), target of Notch signaling (Hes1) and markers (ALP, M-CSF, RANKL and OPG) were altered following 2 and 4 Gy of irradiation. The present research did not indicate a strong relationship between Notch1 regulation and suppression of osteoblast differentiation. We found Hes1 may play a role in the radiation effect on osteoblast differentiation. Our results indicate that radiated osteoblast precursors and osteoblasts promoted osteoclast differentiation and proliferation.


Evaluation of arbitrarily primed PCR analysis and pulsed-field gel electrophoresis of large genomic DNA fragments for identification of enterococci important in human medicine.
The increasing problems encountered with enterococcal nosocomial infections and the intrinsic and acquired resistance of the enterococci to different antimicrobial compounds highlight the need for a rapid identification technique. Enterococcus faecalis is readily identified by biochemical tests, but species differentiation within the Enterococcus faecium and Enterococcus gallinarum species groups is less well established. In the present study, 66 strains representing the most prevalent human enterococci were used to develop a PCR-based species-specific identification protocol. Whole-cell protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used as a reference method for species identification. In addition, the genomic SmaI macro-restriction fragment distribution of all of the strains was examined by pulsed-field gel electrophoresis (PFGE). Oligonucleotide D11344-primed PCR was as discriminative as whole-cell protein analysis and resulted in more easily interpreted band patterns. This PCR-based technique allowed identification of clinical isolates by visual examination of the DNA profiles obtained. The inability of both methods to discriminate between Enterococcus casseliflavus and Enterococcus flavescens brought into question the species status of E. flavescens. PFGE did not result in species-discriminative DNA bands or band patterns, but proved to be superior for interpretation of interstrain relationships.


Learning tactical human behavior through observation of human performance.
It is widely accepted that the difficulty and expense involved in acquiring the knowledge behind tactical behaviors has been one limiting factor in the development of simulated agents representing adversaries and teammates in military and game simulations. Several researchers have addressed this problem with varying degrees of success. The problem mostly lies in the fact that tactical knowledge is difficult to elicit and represent through interactive sessions between the model developer and the subject matter expert. This paper describes a novel approach that employs genetic programming in conjunction with context-based reasoning to evolve tactical agents based upon automatic observation of a human performing a mission on a simulator. In this paper, we describe the process used to carry out the learning. A prototype was built to demonstrate feasibility and it is described herein. The prototype was rigorously and extensively tested. The evolved agents exhibited good fidelity to the observed human performance, as well as the capacity to generalize from it.


Predictors of quality-of-life improvement following pulmonary resection due to lung cancer.
There is increasing involvement of health professionals in organizing protocols to determine the impact of lung surgery on functional state and activities of daily living, with the aim of improving quality of life (QoL). The objective of this study was to investigate predictors of QoL improvement among patients undergoing parenchyma resection due to lung cancer. Prospective study, at teaching hospital of Universidade Estadual de Campinas (Unicamp). 36 patients with lung cancer diagnosis were assessed before surgery and on the 30th, 90th and 180th days after surgery. The Short-Form Health Survey (SF-36) was used as the dependent variable. The independent variables were the Hospital Anxiety and Depression (HAD) scale, a six-minute walking test (6-MWT), a visual analogue scale for pain, forced vital capacity (FVC), type of surgery and use of radiotherapy and chemotherapy. Generalized estimation equations (GEE) were utilized. The median age for these 20 men and 16 women was 55.5 +/- 13.4 years. Both FVC and 6-MWT were predictors of improvement in the physical dimensions of QoL (p = 0.011 and 0.0003, respectively), as was smaller extent of surgical resection (p = 0.04). The social component of QoL had improved by the third postoperative month (p = 0.0005). The predictors that affected QoL positively were better FVC and 6-MWT results and less extensive lung resection. Three months after the surgery, an improvement in social life was already seen.


Exchange interaction of strongly anisotropic tripodal erbium single-ion magnets with metallic surfaces.
We present a comprehensive study of Er(trensal) single-ion magnets deposited in ultrahigh vacuum onto metallic surfaces. X-ray photoelectron spectroscopy reveals that the molecular structure is preserved after sublimation, and that the molecules are physisorbed on Au(111) while they are chemisorbed on a Ni thin film on Cu(100) single-crystalline surfaces. X-ray magnetic circular dichroism (XMCD) measurements performed on Au(111) samples covered with molecular monolayers held at temperatures down to 4 K suggest that the easy axes of the strongly anisotropic molecules are randomly oriented. Furthermore XMCD indicates a weak antiferromagnetic exchange coupling between the single-ion magnets and the ferromagnetic Ni/Cu(100) substrate. For the latter case, spin-Hamiltonian fits to the XMCD M(H) suggest a significant structural distortion of the molecules. Scanning tunneling microscopy reveals that the molecules are mobile on Au(111) at room temperature, whereas they are more strongly attached on Ni/Cu(100). X-ray photoelectron spectroscopy results provide evidence for the chemical bonding between Er(trensal) molecules and the Ni substrate. Density functional theory calculations support these findings and, in addition, reveal the most stable adsorption configuration on Ni/Cu(100) as well as the Ni-Er exchange path. Our study suggests that the magnetic moment of Er(trensal) can be stabilized via suppression of quantum tunneling of magnetization by exchange coupling to the Ni surface atoms. Moreover, it opens up pathways toward optical addressing of surface-deposited single-ion magnets.


Hypothalamic sites of leptin action linking metabolism and reproduction.
A critical amount of energy reserve is necessary for puberty initiation, for normal sexual maturation and maintenance of cyclicity and fertility in females of most species. Therefore, the existence of circulating metabolic cues which directly modulate the hypothalamus-pituitary-gonad axis is predictable. The adipocyte-derived hormone leptin is one of these cues having been studied extensively in the context of regulating the reproductive physiology. Humans and mice lacking leptin (ob/ob) or leptin receptor (LepR, db/db) are infertile. Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility. LepR is expressed in brain, pituitary gland and gonads, but studies using genetically engineered mouse models determined that the brain plays a major role. Recently, it has been made clear that leptin acts indirectly on gonadotropin-releasing hormone (GnRH)-secreting cells via actions on interneurons. However, the exact site(s) of leptin action has been difficult to determine. In this review, we discuss the recent advances in the field focused on the identification of potential site(s) or specific neuronal populations involved in leptin's effects in the neuroendocrine reproductive axis.


Projection-type dual-view three-dimensional display system based on integral imaging.
A dual-view display system provides two different images in different directions. Most of them only present two-dimensional images for observers. In this paper, we propose a projection-type dual-view three-dimensional (3D) display system based on integral imaging. To assign directivities to the images, a projection-type display and dual-view screen with lenticular lenses are implemented. The lenticular lenses split the collimated image from the projection device into two different directions. The separated images are integrated by a single lens array in front of the screen, and full-parallax 3D images are observed in two different viewing regions. The visibility of the reconstructed 3D images can be improved by using high-density lenticular lenses and a high numerical aperture lens array. We explain the principle of the proposed method and verify the feasibility of the proposed system with simulations and experimental results.


Miniature diamond-anvil cells for FTIR-microspectroscopy of small quantities of biosamples.
Fourier transform infrared (FTIR) spectroscopy techniques and data analyses have become widely available, are easy to use, and are convenient for studies of various biosamples, especially in biomedical science. Yet, cultivation of cells and purification of cell components are costly, often methodically challenging, and time and labor consuming. Therefore, reduction of the sample amount is of high value. Here we propose a novel method for the analysis of small quantities of biosamples by FTIR-microscopy of dry films using a diamond-anvil cell (DAC). This approach allows us to decrease the sample volume at least a hundred times compared to that for a high-throughput screening device (HTS-XT, Bruker, Germany), while still obtaining homogeneous films, acquiring qualitative spectra, and using a conventional 15× objective instead of an ATR-objective. Both FTIR methods were applied for analyses of human colorectal cancer cell lines SW480 and SW620 cultured under hypoxic conditions to estimate the strengths and weaknesses of each approach. FTIR absorption spectra acquired by both methods were compared and no significant spectral differences were detected. It was shown that FTIR-microscopy of films on the DAC can be used for evaluation, screening, discrimination and identification of biochemical markers in biosamples like cells. We conclude that the DAC can be transferred to other biosamples like tissues, biofluids, their components and extracellular matrix, and is especially valuable when the available quantities of biosamples are limited.


Intracellular transport of mouse kidney -glucuronidase induced by gonadotrophin.
1. The response of renal beta-glucuronidase with time to the injection of gonadotrophin was investigated in each submicrosomal fraction of rough and smooth microsomal fractions of mouse kidney homogenate. 2. The increase in beta-glucuronidase activity appeared initially in membranes of the rough microsomal fraction, 24h after injection. 3. Afterwards the newly synthesized enzyme appeared in the contents of the rough microsomal fraction and was subsequently found in the smooth microsomal fraction, reaching a maximum concentration in this fraction at 72h. 4. At this juncture, a decrease in the enzyme activity was observed in rough microsomal contents whereas the lysosomal fraction had reached its maximum value. 5. The time-course of the appearance of beta-glucuronidase in the submicrosomal fractions after the gonadotrophin stimulation suggests that the newly synthesized enzyme at the site of membrane-bound ribosomes is transferred across the membrane into cisternae of the rough endoplasmic reticulum, and then is transported into lysosomes via the smooth endoplasmic reticulum. 6. The properties of microsomal and lysosomal beta-glucuronidases were compared.


Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies.
Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. We investigated these associations in a pooled analysis of 18 cohort studies. Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.


Evaluation of the Achilles Ankle Exoskeleton.
This paper evaluates the Achilles exoskeleton. The exoskeleton is intended to provide push-off assistance for healthy subjects during walking. The assistance is provided by a series elastic actuator that has been optimized to provide maximal push-off power. The paper presents the control method of the exoskeleton and the evaluation of the exoskeleton.


Simulation based teamwork training for emergency department staff: does it improve clinical team performance when added to an existing didactic teamwork curriculum?
To determine if high fidelity simulation based team training can improve clinical team performance when added to an existing didactic teamwork curriculum. Level 1 trauma center and academic emergency medicine training program. Emergency department (ED) staff including nurses, technicians, emergency medicine residents, and attending physicians. ED staff who had recently received didactic training in the Emergency Team Coordination Course (ETCC) also received an 8 hour intensive experience in an ED simulator in which three scenarios of graduated difficulty were encountered. A comparison group, also ETCC trained, was assigned to work together in the ED for one 8 hour shift. Experimental and comparison teams were observed in the ED before and after the intervention. Single, crossover, prospective, blinded and controlled observational study. Teamwork ratings using previously validated behaviorally anchored rating scales (BARS) were completed by outside trained observers in the ED. Observers were blinded to the identification of the teams. There were no significant differences between experimental and comparison groups at baseline. The experimental team showed a trend towards improvement in the quality of team behavior (p = 0.07); the comparison group showed no change in team behavior during the two observation periods (p = 0.55). Members of the experimental team rated simulation based training as a useful educational method. High fidelity medical simulation appears to be a promising method for enhancing didactic teamwork training. This approach, using a number of patients, is more representative of clinical care and is therefore the proper paradigm in which to perform teamwork training. It is, however, unclear how much simulator based training must augment didactic teamwork training for clinically meaningful differences to become apparent.


Behavioral responses of streamer F mutants of Dictyostelium discoideum: effects of cyclic GMP on cell motility.
Streamer F (stmF) mutants have a prolonged increase in intracellular cGMP in response to addition of the chemoattractant cAMP. The speed of movement and area of stmF cells were quantitated as the cells were stimulated with a rapid, uniform increase in extracellular cAMP. The speed of stmF cells rapidly drops as does that of the wild-type, but then requires about 300 seconds to recover. In contrast, the speed of the parental strain, XP55, recovers within 60-70 seconds. This prolonged drop in speed correlates with the time during which intracellular cGMP remains high, suggesting that intracellular cGMP induces this prolonged reduction in speed. Mutants from other streamer complementation groups do not show this altered response. Area measurements indicate that stmF cells do not cringe or round up as XP55 does, but spread with the same kinetics as XP55. Chemotactic orientation of the stmF cells in stable spatial gradients is similar to or slightly greater than that of the wild-type. Tracking of cells moving during aggregation indicates that the stmF cells show large drops in speed between pulses, resulting in the banding pattern seen in streams. The cells can still respond to new pulses, resulting in an aggregation time that is similar to that of XP55.


Genetic structure analysis of three Hispanic populations from Costa Rica, Mexico, and the southwestern United States using Y-chromosome STR markers and mtDNA sequences.
Two hundred seventeen male subjects from Costa Rica, Mexico, and the Hispanic population of the southwestern United States were studied. Twelve Y-chromosome STRs and the HVSI sequence of the mtDNA were analyzed to describe their genetic structure and to compare maternal and paternal lineages. All subjects are part of two NIMH-funded studies to localize schizophrenia susceptibility genes in Hispanic populations of Mexican and Central American ancestry. We showed that these three populations are similar in their internal genetic characteristics, as revealed by analyses of mtDNA and Y-chromosome STR diversity. These populations are related through their maternal lineage in a stronger way than through their paternal lineage, because a higher number of shared haplotypes and polymorphisms are seen in the mtDNA (compared to Y-chromosome STRs). These results provide evidence of previous contact between the three populations and shared histories. An analysis of molecular variance revealed no genetic differentiation for the mtDNA for the three populations, but differentiation was detected in the Y-chromosome STRs. Genetic distance analysis showed that the three populations are closely related, probably as a result of migration between close neighbors, as indicated by shared haplotypes and their demographic histories. This relationship could be an important common feature for genetic studies in Latin American and Hispanic populations.


Unraveling the protein targets of vancomycin in living S. aureus and E. faecalis cells.
Vancomycin is a potent glycopeptide antibiotic that has evolved to specifically bind to the D-Ala-D-Ala dipeptide termini of nascent peptidoglycans. Although this mode of action is well established, several studies indicate that vancomycin and analogues exploit noncanonical target sites. In order to address all vancomycin targets in clinically relevant Staphylococcus aureus and Enterococcus faecalis strains we developed a series of small-molecule photoaffinity probes based on vancomycin. Proteomic profiling revealed the specific labeling of two previously unknown vancomycin targets that are likely to contribute to its antibiotic activity. The specific inhibition of the major staphylococcal autolysin Atl confirms previous observations that vancomycin alters S. aureus cell morphology by interaction with the autolytic machinery. Moreover, in E. faecalis the vancomycin photoprobe specifically binds to an ABC transporter protein, which likely impedes the uptake of essential nutrients such as sugars and peptides. The labeling of these two prominent membrane targets in living cells reveals a thus far unexplored mode of vancomycin binding and inhibition that could allow a rational design of variants with improved activity.


[Qualitative Evaluation of the Implementation of Group Psychoeducation for Bipolar Disorder in Clinical Settings in Quebec].
Objectives Bipolar disorder is a chronic condition which significantly impacts the functioning and quality of life of patients with the disorder. Recognized efficacious psychological interventions, such as group psychoeducation, can help better address some of the limitations observed when pharmacotherapy is used alone in the management of bipolar disorder. However, access to these evidence-based interventions seems to be limited for most patients. Indeed, the translation of knowledge acquired through research towards actual clinical settings poses a significant challenge. Assessing the implementation of these efficacious interventions in clinical practice is thus a priority. The objective of this study is to describe the implementation of a psychoeducative intervention, the Life Goals Program (LGP), for the treatment of bipolar disorder in community mental health settings in Quebec City. Methods The LGP was implemented in three different clinical settings located in Quebec City. Fifteen healthcare service providers chosen by their respective clinical site were trained to deliver the intervention. They delivered the treatment to 73 patients with a diagnosis of bipolar disorder. Healthcare service providers filled a log book after each group session, in order to assess whether they had properly delivered the content of the program. At the end of the study, they also participated in a group interview in order to get a better understanding of their experience delivering the intervention and their appreciation of the research process. Results Following qualitative content analysis, four main categories of factors that could influence the implementation of the intervention were identified: 1) healthcare service providers' characteristics (academic training, clinical experience, personality, knowledge of the program, and dynamic between animators); 2) participants' characteristics; 3) organizational context (physical and material environment, staff stability, administrative management and research requirements); and 4) facilitation (perception of research, research team support, and facilitation tools). These categories derived from data analysis coincide with those observed in the literature. The following factors seemed to have had the most impact in the differences observed between sites in the implementation of the LGP: the support offered by the research team; staff stability; and the academic training of healthcare services providers. Conclusion Dissemination and implantation studies can not only help determine factors that are important to consider when implementing a program, but can also help improve and adapt these programs in order to increase acceptability and effectiveness in real world clinical settings.


A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system development.
Epidemiological studies have suggested that the encounter with commensal microorganisms during the neonatal period is essential for normal development of the host immune system. Basic research involving gnotobiotic mice has demonstrated that colonization at the age of 5 weeks is too late to reconstitute normal immune function. In this study, we examined the transcriptome profiles of the large intestine (LI), small intestine (SI), liver (LIV), and spleen (SPL) of 3 bacterial colonization models-specific pathogen-free mice (SPF), ex-germ-free mice with bacterial reconstitution at the time of delivery (0WexGF), and ex-germ-free mice with bacterial reconstitution at 5 weeks of age (5WexGF)-and compared them with those of germ-free (GF) mice. Hundreds of genes were affected in all tissues in each of the colonized models; however, a gene set enrichment analysis method, MetaGene Profiler (MGP), demonstrated that the specific changes of Gene Ontology (GO) categories occurred predominantly in 0WexGF LI, SPF SI, and 5WexGF SPL, respectively. MGP analysis on signal pathways revealed prominent changes in toll-like receptor (TLR)- and type 1 interferon (IFN)-signaling in LI of 0WexGF and SPF mice, but not 5WexGF mice, while 5WexGF mice showed specific changes in chemokine signaling. RT-PCR analysis of TLR-related genes showed that the expression of interferon regulatory factor 3 (Irf3), a crucial rate-limiting transcription factor in the induction of type 1 IFN, prominently decreased in 0WexGF and SPF mice but not in 5WexGF and GF mice. The present study provides important new information regarding the molecular mechanisms of the so-called "hygiene hypothesis".


Caregiver emotional distress: external open-behaviour signs.
To determine whether specific external signs of emotional distress (ESED) can be an indirect measure of emotional distress in caregivers. A cross-sectional multicentre design was used. 148 primary caregivers of advanced cancer patients attended in four Spanish palliative care units participated in this study. The emotional distress of caregivers was measured using both the Emotional Distress of Caregivers Scale and a psychological interview. Health professionals collected data using a standard clinical interview process after a brief training period. More than half the caregivers (60%) presented with emotional distress. A positive correlation (r=0.566) was found between the intensity of ESED and emotional distress per se. Caregivers who presented emotional distress showed more ESED than those that did not (p<0.01). The study found significant differences for the categories 'visible signs of sadness, fear, crying, feeling overwhelmed' (p<0.001), 'difficulty in separating from the patient: family refuses to let the patient make decisions and insists on care' (p<0.001) and 'visible signs of anger, irritability or frequent disagreement with therapeutic measures' (p<0.001). No significant differences were found with respect to gender. The set of items to measure these external signs presented an adequate reliability assessed using Cronbach's alpha (α=0.773). The assessment of ESED in caregivers could serve as a useful method to assess their emotional distress. Incorporating the systematic assessment of these external signs as part of the assessment of the emotional distress of primary caregivers could improve the overall assessment and treatment provided to these caregivers.


Protein localization in Escherichia coli cells: comparison of the cytoplasmic membrane proteins ProP, LacY, ProW, AqpZ, MscS, and MscL.
Fluorescence microscopy has revealed that the phospholipid cardiolipin (CL) and FlAsH-labeled transporters ProP and LacY are concentrated at the poles of Escherichia coli cells. The proportion of CL among E. coli phospholipids can be varied in vivo as it is decreased by cls mutations and it increases with the osmolality of the growth medium. In this report we compare the localization of CL, ProP, and LacY with that of other cytoplasmic membrane proteins. The proportion of cells in which FlAsH-labeled membrane proteins were concentrated at the cell poles was determined as a function of protein expression level and CL content. Each tagged protein was expressed from a pBAD24-derived plasmid; tagged ProP was also expressed from the chromosome. The osmosensory transporter ProP and the mechanosensitive channel MscS concentrated at the poles at frequencies correlated with the cellular CL content. The lactose transporter LacY was found at the poles at a high and CL-independent frequency. ProW (a component of the osmoregulatory transporter ProU), AqpZ (an aquaporin), and MscL (a mechanosensitive channel) were concentrated at the poles in a minority of cells, and this polar localization was CL independent. The frequency of polar localization was independent of induction (at arabinose concentrations up to 1 mM) for proteins encoded by pBAD24-derived plasmids. Complementation studies showed that ProW, AqpZ, MscS, and MscL remained functional after introduction of the FlAsH tag (CCPGCC). These data suggest that CL-dependent polar localization in E. coli cells is not a general characteristic of transporters, channels, or osmoregulatory proteins. Polar localization can be frequent and CL independent (as observed for LacY), frequent and CL dependent (as observed for ProP and MscS), or infrequent (as observed for AqpZ, ProW, and MscL).


The Effects of Tempur Insoles on Ground Reaction Forces and Loading Rates in Running.
Runners often experience over-use injuries. Ground reaction force (GRFs) patterns have been associated with these over-use injuries; however, it is not solely the magnitude of GRFs, but also the rate at which they are applied that lead to lower extremity injury. Many recreational runners will use over-the-counter insoles as a method of treating or preventing injury. Therefore, the purpose of this study was to examine the efficacy of two insoles on peak GRFs and loading rates. It was hypothesized that no differences in peak GRFs or loading rates would exist with the addition of two insoles during running. Twelve subjects (7 females; 5 males) performed seven running trials in each of the following conditions: no insoles (NORM), over-the-counter insoles (OTC) and memory-foam insoles (TEMPUR). GRFs were recorded using a force plate (1440Hz; AMTI) while subjects ran across a 15 meter lab. A 2 x 3 (gender x insole) repeated measures ANOVA was used to compare the effects of insoles on loading rate and ground reaction forces. Alpha level was set at p <0.05. The current study found no statistical differences in loading rate or GRFs between the insole and no insole conditions. Furthermore, there was no gender effect in any condition. The findings of the current study suggest that insoles do not attenuate shock or decrease loading rate. The lack of shock attenuation associated with insoles suggests they do not protect the lower extremity from injury.


Risk factors for falling in older Mexican Americans.
To estimate the prevalence of falls and the risk factors associated with falls in Mexican-American men and women aged 72 and older, from the Hispanic Established Population for the Epidemiological Study of the Elderly. A 2-year cohort study. Five Southwestern states: Texas, New Mexico, Colorado, Arizona, and California. Data on sociodemographic characteristics, health status, cognitive function, affective function, functional status, body mass index, and summary performance measures of lower body function, were obtained (1998-1999). Two years later (2000-2001), falls in the previous 12 months were assessed by self-report. Chi-square, univariate statistics, and multivariate logistic regression analyses were used. Of the 1,391 participants, 31.8% fell one or more times, and 14.2% reported 2 or more falls. In the logistic regression analysis, aged > or = 80 years (adjusted odds ratio [OR]=1.52, 95% confidence interval [CI]=1.17-1.98), being female (OR=1.45, 95% CI 1.13-1.86), having diabetes (OR=1.37, 95% CI 1.06-1.77), having arthritis (OR=1.32, 95% CI 1.04-1.68), experiencing impairment of instrumental activities of daily living (OR=1.05, 95% CI 1.01-1.10), and exhibiting high depressive symptoms (OR=1.59, 95% CI 1.16-2.19), were significant (P<.05) independent risk factors for one or more falls. The risk of falling increased linearly with the number of risk factors, from 14% with none, to 41% with 3 or more risk factors (P<.001). Prevalence of falls among older Mexican Americans was similar to that reported in non-Hispanic Caucasians. Potential modifiable conditions, such as functional deficits, arthritis, diabetes, and depressive symptoms were independent risk factors for falls in this population.


Study protocol: longitudinal study of the transition of young people with complex health needs from child to adult health services.
Young people with complex health needs have impairments that can limit their ability to carry out day-to-day activities. As well as coping with other developmental transitions, these young people must negotiate the transfer of their clinical care from child to adult services. The process of transition may not be smooth and both health and social outcomes may suffer.Increasingly, policy-makers have recognised the need to ensure a smoother transition between children's and adult services, with processes that are holistic, individualised, and person-centred; however, there is little outcome data to support proposed models of care. This study aims to identify the features of transitional care that are potentially effective and efficient for young people with complex health needs making their transition. Longitudinal cohort study. 450 young people aged 14 years to 18 years 11 months (with autism spectrum disorder and an additional mental health problem, cerebral palsy or diabetes) will be followed through their transition from child to adult services and will contribute data at baseline, 12, 24 and 36 months. We will collect data on: health and wellbeing outcomes (participation, quality of life, satisfaction with services, generic health status (EQ-5D-Y) and condition specific measure of disease control or management); exposure to proposed beneficial features of services (such as having a key worker, appropriate involvement of parents); socio-economic characteristics of the sample; use of condition-related health and personal social services; preferences for the characteristics of transitional care.We will us regression techniques to explore how outcomes vary by exposure to service features and by characteristics of the young people. These data will populate a decision-analytic model comparing the costs and benefits of potential alternative ways of organising transition services.In order to better understand mechanisms and aid interpretation, we will undertake qualitative work with 15 young people, including interviews, non-participant observation and diary collection. This study will evaluate the effect of service components of transitional care, rather than evaluation of specific models that may be unsustainable or not generalisable. It has been developed in response to numerous national and international calls for such evaluation.


[The treatment of phimosis in childhood without circumcision: plastic repair of the prepuce].
To device a new surgical technique of preputial plasty for the treatment of phimosis, as an alternative to circumcision, easy to perform, which preserves the normal function of the prepuce. The new technique consists of three lengthwise incisions of the stenosing wase and their diagonal suture, the triple incision preputial plasty, described by others, modified adding frenulotomy and two more incisions between the previous ones, which are left to heal spontaneously. This technique has been applied on 22 children over a period of 24 months, with a follow-up of six-twenty-four months. The technique is easy to perform. All check-ups show good cosmetic results, no recurrence, normal preputial anatomy and function. It is important to continue "preputial gymnastics" until stabilization. The devised technique fully succeeds in preserving a normal prepuce, it is easier to perform and safer than other preputial plasties and it may be carried out in all cases of phimosis in pediatrics. The good results achieved encourage us to continue along this path, hoping that the technique will be largely applied.


From the Frontline: Strengthening Surveillance and Response Capacities of the Rural Workforce in the Asia-Pacific Region. How Can Grass-Roots Implementation Research Help?
Health systems in the Asia-Pacific region are poorly prepared for pandemic threats, particularly in rural/provincial areas. Yet future emerging infectious diseases are highly likely to emerge in these rural/provincial areas, due to high levels of contact between animals and humans (domestically and through agricultural activities), over-stretched and under-resourced health systems, notably within the health workforce, and a diverse array of socio-cultural determinants of health. In order to optimally implement health security measures at the frontline of health services where the people are served, it is vital to build capacity at the local district and facility level to adapt national and global guidelines to local contexts, including health systems, and community and socio-cultural realities. During 2017/18 James Cook University (JCU) facilitated an implementation research training program (funded by Australian Department of Foreign Affairs and Trade) for rural/provincial and regional health and biosecurity workers and managers from Fiji, Indonesia, Papua New Guinea (PNG), Solomon Islands and Timor-Leste. This training was designed so frontline health workers could learn research in their workplace, with no funding other than workplace resources, on topics relevant to health security in their local setting. The program, based upon the WHO-TDR Structured Operational Research and Training IniTiative (SORT-IT) consists of three blocks of teaching and a small, workplace-based research project. Over 50 projects by health workers including surveillance staff, laboratory managers, disease control officers, and border security staff included: analysis and mapping of surveillance data, infection control, IHR readiness, prevention/response and outbreak investigation. Policy briefs written by participants have informed local, provincial and national health managers, policy makers and development partners and provided on-the-ground recommendations for improved practice and training. These policy briefs reflected the socio-cultural, health system and disease-specific realities of each context. The information in the policy briefs can be used collectively to assess and strengthen health workforce capacity in rural/provincial areas. The capacity to use robust but simple research tools for formative and evaluative purposes provides sustainable capacity in the health system, particularly the rural health workforce. This capacity improves responses to infectious diseases threats and builds resilience into fragile health systems.


Vesicular transport systems in fungi.
Canonical and unconventional mechanisms of secretion in many eukaryotic cells are relatively well known. In contrast to the situation in animal cells, mechanisms of secretion in fungi must include the capacity for trans-cell wall passage of macromolecules to the extracellular space. Although these mechanisms remain somewhat elusive, several studies in recent years have suggested that vesicular transport is required for trans-cell wall secretion of large molecules. Several fungal molecules, including proteins, lipids, polysaccharides and pigments, are released to the extracellular space in vesicles. In pathogenic fungi, a number of these vesicular components are associated with fungal virulence. Indeed, extracellular vesicles produced by fungi can interfere with the immunomodulatory activity of host cells. Fungal vesicles share many functional aspects with mammalian exosomes and extracellular vesicles produced by bacteria, plants and protozoa, but their cellular origin remains unknown. Here, we discuss the involvement of vesicular transport systems in fungal physiology and pathogenesis, making parallels with the mammalian, bacterial, protozoan and plant cell literature.


Patient preferences for emergency department-initiated tobacco interventions: a multicenter cross-sectional study of current smokers.
The emergency department (ED) visit provides a great opportunity to initiate interventions for smoking cessation. However, little is known about ED patient preferences for receiving smoking cessation interventions or correlates of interest in tobacco counseling. ED patients at 10 US medical centers were surveyed about preferences for hypothetical smoking cessation interventions and specific counseling styles. Multivariable linear regression determined correlates of receptivity to bedside counseling. Three hundred seventy-five patients were enrolled; 46% smoked at least one pack of cigarettes per day, and 11% had a smoking-related diagnosis. Most participants (75%) reported interest in at least one intervention. Medications were the most popular (e.g., nicotine replacement therapy, 54%), followed by linkages to hotlines or other outpatient counseling (33-42%), then counseling during the ED visit (33%). Counseling styles rated most favorably involved individualized feedback (54%), avoidance skill-building (53%), and emphasis on autonomy (53%). In univariable analysis, age (r=0.09), gender (average Likert score=2.75 for men, 2.42 for women), education (average Likert score=2.92 for non-high school graduates, 2.44 for high school graduates), and presence of smoking-related symptoms (r=0.10) were significant at the p<0.10 level and thus were retained for the final model. In multivariable linear regression, male gender, lower education, and smoking-related symptoms were independent correlates of increased receptivity to ED-based smoking counseling. In this multicenter study, smokers reported receptivity to ED-initiated interventions. However, there was variability in individual preferences for intervention type and counseling styles. To be effective in reducing smoking among its patients, the ED should offer a range of tobacco intervention options.