Psychosocial interventions for reducing injection and sexual risk behaviour for preventing HIV in drug users.
Drug users (including both injection drug users and crack cocaine users), are at high levels of risk for contracting HIV. Therefore it is important to reduce the injection and/or sexual risk behaviours of these groups both for the benefit of themselves and for society as a whole. To assess the efficacy of multi-session psychosocial interventions in comparison with standard education and minimal intervention controls for the reduction of injection and sexual risk behaviour. Electronic searches were conducted of a number of bibliographic databases (including Cochrane Library, CINAHL, MEDLINE, PsycINFO). In addition, other methods of locating papers were employed including contacting various authors working in the field of HIV risk reduction and examining reference lists of applicable papers identified in the electronic search. The inclusion criteria consisted of randomised and quazi-randomised trials assessing the efficacy of psychosocial interventions in the reduction of injection and sexual risk behaviour for people who misused opiates, cocaine, or a combination of these drugs. Two authors independently assessed the eligibility of studies identified by the search strategy, quality assessed these studies and extracted the data. A total of 35 trials met the eligibility criteria of the review providing data on 11,867 participants. There were minimal differences identified between multi-session psychosocial interventions and standard educational interventions for both injection and sexual risk behaviour. Although it should be noted there were large pre-post changes for both groups suggesting both were effective in reducing risk behaviours. In addition, there was some evidence of benefit for multi-session psychosocial interventions when compared with minimal controls. Subgroup analyses suggest that people in formal treatment are likely to respond to multi-session psychosocial interventions. It also appears single-gender groups may be associated with greater benefit. There is limited support for the widespread use of formal multi-session psychosocial interventions for reducing injection and sexual risk behaviour. Brief standard education interventions appear to be a more cost-effective option. Further research is required to assess if there are particular groups of drug users more likely to respond to such interventions.


The use of growth factors in hematopoietic stem cell transplantation.
Mobilized, peripheral blood stem cells (PBSC) are increasingly used for both autologous and allogeneic transplants. Granulocyte-colony-stimulating factor is the most widely used cytokine for mobilization. Several different mechanisms of stem cell mobilization have been proposed including protease-dependent and non-protease- dependent mechanisms. In autologous transplants, the addition of chemotherapy to mobilization can enhance the yield of PBSC collected but with substantial adverse effects, and not necessarily faster engraftment. In allogeneic transplants, the use of mobilized PBSC is associated with faster engraftment and donor chimerism compared to bone marrow. In the majority of studies, the rate of acute graft-versus-host disease (GVHD) has not been shown to be significantly higher with PBSC, but the rate of chronic GVHD appears to be increased. Several different strategies have been proposed for patients and donors who fail initial mobilization, including the use of novel agents. AMD3100 (Plerixafor) works by directly inhibiting the interaction between stromal cell-derived factor-1 and its receptor CXCR4, and mobilizes hematopoietic stem cells within hours. It is being studied alone or in conjunction with growth factors for PBSC mobilization in both autologous and allogeneic settings. Although the use of growth factors after PBSC transplantation results in faster neutrophil engraftment its impact on treatment-related mortality and survival does not appear significant. Here, we review the biology and methods of PBSC mobilization, the effect of growth factors on normal donors and the controversies of growth factor use in the post-transplant setting. We also review the data on novel agents for mobilization of stem cells.


BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.
Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond independently to environmental signals, or require interactions with each other to do so? We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues. Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness. Importantly, tissue-autonomous Bmal1 partially sustains homeostasis in otherwise arrhythmic and prematurely aging animals. Our results therefore support a two-branched model for the daily synchronization of tissues: an autonomous response branch, whereby light entrains circadian clocks without any commitment of other Bmal1-dependent clocks, and a memory branch using other Bmal1-dependent clocks to "remember" time in the absence of external cues.


Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals.
Neuroligin-1 is a potent trigger for the de novo formation of synaptic connections, and it has recently been suggested that it is required for the maturation of functionally competent excitatory synapses. Despite evidence for the role of neuroligin-1 in specifying excitatory synapses, the underlying molecular mechanisms and physiological consequences that neuroligin-1 may have at mature synapses of normal adult animals remain unknown. By silencing endogenous neuroligin-1 acutely in the amygdala of live behaving animals, we have found that neuroligin-1 is required for the storage of associative fear memory. Subsequent cellular physiological studies showed that suppression of neuroligin-1 reduces NMDA receptor-mediated currents and prevents the expression of long-term potentiation without affecting basal synaptic connectivity at the thalamo-amygdala pathway. These results indicate that persistent expression of neuroligin-1 is required for the maintenance of NMDAR-mediated synaptic transmission, which enables normal development of synaptic plasticity and long-term memory in the amygdala of adult animals.


MRI and MRV in cerebral venous thrombosis.
Although Cerebral venous thrombosis is an uncommon cause of stroke among the young, it is being increasingly recognised. A prothrombotic risk factor is identified in the majority of the patients. In most instances it is seen in women in the post-partum period and those on oral contraceptives. Magnetic Resonance Imaging (MRI) has improved our ability to diagnose this condition however the variability of radiological and clinical presentation remains a challenge. MR in combination with MR venography (MRV) is the single most sensitive diagnostic technique. The MR appearance of the thrombus within the dual sinus or cortical vein is variable and is largely dependent on its age. The loss of the normal flow void on spin echo T2 images is a sensitive parameter. Thrombus on MRV is seen as loss of high flow signal from the sinus. Focal parenchymal changes occur in approximately 50% of cases and are due to oedema and infarction, with or without haemorrhage. Appearances of these lesions too are dependent on their age. Diffuse changes of raised intracranial pressure with gyral effacement may also be present.


Rare Anterior Segment Retinoblastoma Masquerading as Corneal Endotheliitis.
We present a unique case involving a 6-year-old female with a unilateral corneal endotheliitis-like finding, who was ultimately found to have a form of anterior diffuse infiltrating retinoblastoma with no evidence of retinal involvement. The patient's presumed endotheliitis was initially treated with topical dexamethasone and oral acyclovir without improvement. She then underwent multiple fine-needle aspirations of anterior chamber fluid, which were negative for abnormal findings of viral polymerase chain reaction, viral cultures, and flow cytometry. Months after initial presentation, an anterior chamber angle mass developed and a biopsy identified retinoblastoma cells. The patient underwent plaque radiotherapy of the cornea and systemic chemotherapy. The patient regained good vision and is tumor-free at 13 months. Anterior inflammation is a rare form of masquerade syndrome associated with retinoblastoma; however, it tends to be associated with diffuse posterior segment retinoblastoma when it does occur. Diffuse anterior retinoblastoma is a rare form of retinoblastoma with no apparent focus in the retina. Ultimately, our patient developed an anterior chamber angle lesion, which was biopsied and proven to be retinoblastoma. Unusual corneal endotheliitis-like findings in children that are not responsive to conventional treatment should raise the clinician's suspicion of malignancy, even when no retinal lesion is detected.


Bias between the left and right inverted repeats during IS911 targeted insertion.
IS911 is a bacterial insertion sequence composed of two consecutive overlapping open reading frames (ORFs [orfA and orfB]) encoding the transposase (OrfAB) as well as a regulatory protein (OrfA). These ORFs are bordered by terminal left and right inverted repeats (IRL and IRR, respectively) with several differences in nucleotide sequence. IS911 transposition is asymmetric: each end is cleaved on one strand to generate a free 3'-OH, which is then used as the nucleophile in attacking the opposite insertion sequence (IS) end to generate a free IS circle. This will be inserted into a new target site. We show here that the ends exhibit functional differences which, in vivo, may favor the use of one compared to the other during transposition. Electromobility shift assays showed that a truncated form of the transposase [OrfAB(1-149)] exhibits higher affinity for IRR than for IRL. While there was no detectable difference in IR activities during the early steps of transposition, IRR was more efficient during the final insertion steps. We show here that the differential activities between the two IRs correlate with the different affinities of OrfAB(1-149) for the IRs during assembly of the nucleoprotein complexes leading to transposition. We conclude that the two inverted repeats are not equivalent during IS911 transposition and that this asymmetry may intervene to determine the ordered assembly of the different protein-DNA complexes involved in the reaction.


Understanding decisions made about hepatitis C treatment by couples who inject drugs.
Efforts to increase the number of people having hepatitis C virus (HCV) treatment require understanding how to best deliver services to meet consumers' needs. The general health literature has examined the role that partners can play in supporting health outcomes. This study examines the experiences of couples who inject drugs in relation to knowledge of, decisions about and management of HCV treatment. This is a qualitative interview study of people who inject drugs in couples. Participants were recruited from harm reduction services in two major Australian cities. Couples were interviewed separately. Data were examined using the couple as the unit of analysis and to identify patterns of experience related to the HCV serostatus of couples. Knowledge of HCV and HCV treatment was low and variable but showed some relationship to serostatus. Decisions about HCV treatment were deeply informed by concerns regarding treatment side effects. Positive concordant couples considered 'staging' treatment to ensure that each partner could (in turn) care for the other. People with HCV in serodiscordant relationships may need specific support regarding HCV treatment information. Within positive concordant partnerships, our data indicated the need to support the HCV-positive 'carer' during their partner's treatment. Changing treatment regimens, and their anticipated lower side effect profiles, will need to be actively promoted to ensure that couples understand how these changes affect their treatment options.


Body mass index in young adulthood, obesity trajectory, and premature mortality.
Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40-79 years and were followed through December, 2011. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years of follow-up. Participants who reported being overweight or obese as young adults had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95% confidence interval: 52, 78) higher, respectively, than those of their normal weight counterparts. The results did not significantly differ by race or sex. Participants who reported being obese in young adulthood only or in both young and middle adulthood experienced mortality rates that were 40%-90% higher than those of participants who were nonobese at either time. These results suggest that obesity in young adulthood is associated with higher mortality risk regardless of race, sex, and obesity status in later life.


CO2 and carbonate as substrate for the activation of the microbial community in 180 m deep bedrock fracture fluid of Outokumpu Deep Drill Hole, Finland.
Microbial communities in deep subsurface environments comprise a large portion of Earth's biomass, but the metabolic activities in these habitats are largely unknown. Here the effect of CO2 and carbonate on the microbial community of an isolated groundwater fracture zone at 180 m depth of the Outokumpu Deep Scientific Drill Hole (Finland) was tested. Outokumpu groundwater at 180 m depth contains approximately 0.45 L L-1 dissolved gas of which methane contributes 76%. CO2, on the other hand, is scarce. The number of microbial cells with intracellular activity in the groundwater was low when examined with redox staining. Fluorescence Assisted Cell Sorting (FACS) analyses indicated that only 1% of the microbial community stained active with the redox sensing dye in the untreated groundwater after 4 weeks of starvation. However, carbon substrate and sulfate addition increased the abundance of fluorescent cells up to 7%. CO2 and CO2 + sulfate activated the greatest number of microbes, especially increasing the abundance of Pseudomonas sp., which otherwise was present at only low abundance in Outokumpu. Over longer exposure time (2 months) up to 50% of the bacterial cells in the groundwater were shown to incorporate inorganic carbon from carbonate into biomass. Carbon recapture is an important feature in this ecosystem since it may decrease the rate of carbon loss in form of CO2 released from cellular processes.


The prohibition of kidney sales and organ markets should remain.
There is an ongoing vigorous debate regarding the wisdom of the current prohibition of organ sales in the United States. We argue that this prohibition must remain in place. We discuss the current international realities regarding organ vending in order to show that even a so-called 'regulated' market brings with it danger to the welfare of transplant donors, their recipients, and potential recipients of nonrenal organs. We counter the specific arguments made in favor of organ sales while recommending multiple measures that can serve to remove disincentives to noncommercial organ donation. We encourage the investment in innovative healthy transplant practice for the benefit of all. In 'natural experiments' performed in developing countries the outcome for kidney vendors, in terms of both their medical and psychosocial health, has been shown to be poor. A high incidence of serious infections has been reported in recipients of vended organs. Commercialization of living kidney donation does not serve the interests of the donors, endangers the health of recipients, and undermines the healthy development of the international transplant endeavor.


Motor-related cortical activity after cervical spinal cord injury: multifaceted EEG analysis of isometric elbow flexion contractions.
Electroencephalographic (EEG) studies have well established that motor cortex (M1) activity ~20 Hz decreases during muscular contraction and increases as soon as contraction stops, which are known as event-related desynchronization (ERD) and event-related synchronization (ERS), respectively. ERD is supposed to reflect M1 activation, sending information to recruited muscles, while the process underlying ERS is interpreted either as active cortical inhibition or as processing of sensory inputs. Investigation of the process behind ERD/ERS in people with spinal cord injury (SCI) would be particularly relevant since their M1 remains effective despite decreased sensorimotor abilities. In this study, we recorded net joint torque and EEG in 6 participants with cervical SCI and 8 healthy participants who performed isometric elbow flexion at 3 force levels. Multifaceted EEG analysis was introduced to assess ERD/ERS according to their amplitude, frequency range and duration. The results revealed that net joint torque increased with the required force level for all participants and time to contraction inhibition was longer in the SCI group. At the cortical level, ERD/ERS frequency ranges increased with the required force level in all participants, indicating that the modulation of cortical activity with force level is preserved after SCI. However, ERS amplitude decreased only in SCI participants, which may be linked to delayed contraction inhibition. All in all, cortical modulation of frequency range and amplitude could reflect two different kinds of neural communication.


Intraspecific variation in juvenile tree growth under elevated CO2 alone and with O3: a meta-analysis.
Atmospheric carbon dioxide (CO2) concentrations are expected to increase throughout this century, potentially fostering tree growth. A wealth of studies have examined the variation in CO2 responses across tree species, but the extent of intraspecific variation in response to elevated CO2 (eCO2) has, so far, been examined in individual studies and syntheses of published work are currently lacking. We conducted a meta-analysis on the effects of eCO2 on tree growth (height, stem biomass and stem volume) and photosynthesis across genotypes to examine whether there is genetic variation in growth responses to eCO2 and to understand their dependence on photosynthesis. We additionally examined the interaction between the responses to eCO2 and ozone (O3), another global change agent. Most of the published studies so far have been conducted in juveniles and in Populus spp., although the patterns observed were not species dependent. All but one study reported significant genetic variation in stem biomass, and the magnitude of intraspecific variation in response to eCO2 was similar in magnitude to previous analyses on interspecific variation. Growth at eCO2 was predictable from growth at ambient CO2 (R(2) = 0.60), and relative rankings of genotype performance were preserved across CO2 levels, indicating no significant interaction between genotypic and environmental effects. The growth response to eCO2 was not correlated with the response of photosynthesis (P > 0.1), and while we observed 57.7% average increases in leaf photosynthesis, stem biomass and volume increased by 36 and 38.5%, respectively, and height only increased by 9.5%, suggesting a predominant role for carbon allocation in ultimately driving the response to eCO2 Finally, best-performing genotypes under eCO2 also responded better under eCO2 and elevated O3 Further research needs include widening the study of intraspecific variation beyond the genus Populus and examining the interaction between eCO2 and other environmental stressors. We conclude that significant potential to foster CO2-induced productivity gains through tree breeding exists, that these programs could be based upon best-performing genotypes under ambient conditions and that they would benefit from an increased understanding on the controls of allocation.


[Changes in bacterial meningitis in French children resulting from vaccination].
For the past 20 years, three vaccines against the three main bacterial species implicated in meningitis in children have been included in the French vaccine calendar: Haemophilus influenzae b in 1993, 7-valent pneumococcal conjugate vaccine (PCV7) in 2003 (replaced by 13-valent in 2010) and Neisseria meningitidis C in 2009. The French active surveillance network from the GPIP/ACTIV monitors the change in the epidemiological, clinical, and biological features of bacterial meningitis due to vaccine use. Over a 12-year period, 233 pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of bacterial meningitis. From January 2001 to December 2012, 4808 bacterial meningitis cases were reported. Between 2001 and 2012, the number of pneumococcal meningitis (PM) cases decreased by 23.4%, and by 32.2% for children less than 2 years old. During this period, the proportion of cases attributable to PCV7 and six additional PCV13 types decreased from 63.3% to 8.1% and 83.7% to 32.4%, respectively. In 2012, the main vaccine types (accounting for 25.8% of cases) were 7F (12.2%), 19A (6.8%), and 19F (6.8%), and the most frequent non-vaccine types were 12F (14.9%), 24F (14.9%), 15B/C (6.8%), 22F (6.8%), and 10A (5.4%). In 2012, the rate of strains with decreased susceptibility to cefotaxime/ceftriaxone (MIC>0.5 μg/mL) represented less than 3% of cases, with no identified resistant strain since 2010 (MIC>2 μg/mL). Between 2001 (n=67) and 2012 (n=9), the number of NmC meningitis cases decreased by 87%. With more than 4800 bacterial meningitis cases reported in 12 years, this nationwide survey provides essential information on the microbiological and clinical characteristics of bacterial meningitis (epidemiology or resistance data). These results could lead to changing antibiotic treatment of pneumococcal meningitis before the results of antibiotic susceptibility tests.


Nuclear processing of viral high-molecular-weight RNA in cells infected with herpes simplex virus type 1.
Nuclear RNA isolated from cells infected by herpes simplex virus type 1, strain F, was fractionated on formamide-sucrose gradients into two major classes, greater and less than 45S. These two classes of labeled nuclear RNA were hybridized to viral DNA fragments generated by digestion with the restriction enzymes HindIII and BglII. Early in infection, only a few DNA fragments hybridized to RNA, with slight differences between the two classes. Late in infection, all DNA fragments hybridized, showing that all viral RNA was present in large precursor molecules greater than 14 kilobases. The fragments that correspond to late gene products hybridized more of the small RNA than the large RNA. This suggests that the mRNA corresponding to late genes accumulated after the large precursors have been cleaved. Large (greater than or equal to 45S) and small (< 45S) nuclear RNA and cytoplasmic RNA from cells late in infection were hybridized in excess to in vitro-labeled HindIII M and L fragments. More than 50% of the HIndIII M fragment annealed with the large nuclear RNA, but only 36% of it annealed with the cytoplasmic RNA. The HindIII L fragment hybridized large nuclear RNA and cytoplasmic RNA to the same extent (30% and 26%). These results suggest that RNA complementary to the HindIII M fragment, which is the template for immediate early polypeptides, was regulated in the nuclei at the posttranscriptional level. This seems to suggest that temporal regulation of RNA cleavage occurs in the nucleus.


Is a full team required for emergency management of pediatric trauma?
Pediatric trauma centers often do not meet the guidelines requiring a trauma team as recommended by the American Academy of Pediatrics (AAP). We reviewed our experience with a team consisting of a pediatric emergency physician, resident, nurse, and respiratory therapist. The surgical and pediatric critical care residents and staff were available within 5 minutes. We conducted a retrospective chart review of 146 patients (aged 8.1 +/- 4.8 years) between 1987 and 1989, with Injury Severity Scores (ISS) greater than or equal to 16 or admitted to the pediatric critical care unit. The time of presentation, surgical services consulted, and the nature of the injury were obtained from chart review. The Pediatric Trauma Score (PTS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, and Pediatric Risk of Mortality (PRISM) were used to determine the severity of insult and physiologic derangement on admission. The Modified Injury Severity Score (MISS) was determined and the Delta score for Disability Assessment was assigned at discharge. The Delta score was also determined at 3-month intervals up to one year. The probability of survival (Ps) was calculated, using the ISS and RTS. The Z statistic for this group of patients was then determined, using the Major Trauma Outcome Study (MTOS) methodology. The percentages of patients who were normal, disabled, and dead were 61%, 31.5%, and 7.5%, respectively, at 6 months follow-up. Eleven deaths were expected based on PRISM and TRISS analysis. Our mortality and morbidity figures were comparable with those of centers with teams based on AAP guidelines.(ABSTRACT TRUNCATED AT 250 WORDS)


Predicting the Emergence of Sexual Violence in Adolescence.
This study aims to report the epidemiology of sexual violence (SV) perpetration for both female and male youth across a broad age spectrum. Additionally, the etiology of SV perpetration is examined by identifying prior exposures that predict a first SV perpetration. Six waves of data were collected nationally online, between 2006 and 2012, from 1586 youth between 10 and 21 years of age. Five types of SV were assessed: sexual harassment, sexual assault, coercive sex, attempted rape, and rape. To identify how prior exposures may predict the emergence of SV in adolescence, parsimonious lagged multivariable logistic regression models estimated the odds of first perpetrating each of the five types of SV within the context of other variables (e.g., rape attitudes). Average age at first perpetration was between 15 and 16 years of age, depending on SV type. Several characteristics were more commonly reported by perpetrators than non-perpetrators (e.g., alcohol use, other types of SV perpetration and victimization). After adjusting for potentially influential characteristics, prior exposure to parental spousal abuse and current exposure to violent pornography were each strongly associated with the emergence of SV perpetration-attempted rape being the exception for violent pornography. Current aggressive behavior was also significantly implicated in all types of first SV perpetration except rape. Previous victimization of sexual harassment and current victimization of psychological abuse in relationships were additionally predictive of one's first SV perpetration, albeit in various patterns. In this national longitudinal study of different types of SV perpetration among adolescent men and women, findings suggest several malleable factors that need to be targeted, especially scripts of inter-personal violence that are being modeled by abusive parents in youths' homes and also reinforced by violent pornography. The predictive value of victimization for a subsequent first SV perpetration highlights the inter-relatedness of different types of violence involvement. Universal and holistic prevention programming that targets aggressive behaviors and violent scripts in inter-personal relationships is needed well before the age of 15 years.


Dynamic calibration of our sense of time.
An accurate sense of time contributes to functions ranging from the perception and anticipation of sensory events to the production of coordinated movements. However, accumulating evidence demonstrates that time perception is subject to strong illusory distortion. In two experiments, we investigated whether the subjective speed of temporal perception is dependent on our visual environment. By presenting human observers with speed-altered movies of a crowded street scene, we modulated performance on subsequent production of "20s" elapsed intervals. Our results indicate that one's visual environment significantly contributes to calibrating our sense of time, independently of any modulation of arousal. This plasticity generates an assay for the integrity of our sense of time and its rehabilitation in clinical pathologies.


Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia.
Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5×10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6×10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1×10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4×10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05×10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16×10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.


Intima Media Thickness Variability (IMTV) and its association with cerebrovascular events: a novel marker of carotid therosclerosis?
Increased intima-media thickness (IMT) is an early marker of atherosclerotic disease and several prospective studies have demonstrated that IMT is a strong predictor of cerebrovascular complications. In this paper we propose a novel method to assess IMT, called "intima media thickness variability" (IMTV) and evaluate its relationship with the development of cerebrovascular events. The study was approved by the local IRB. Twenty consecutive patients underwent ultrasound analysis of the carotid arteries (mean age 68 years; age range 59-81 years). The IMT and IMTV of the 40 carotid vessels was assessed. Bland-Altman statistics were employed to measure the inter-observer variability, and ROC analysis was used to assess the association with cerebrovascular events. In all cases the ROC area under the curve was higher for IMTV than IMT. There was a statistical significant association between IMTV and cerebrovascular events (P=0.018), but no relationship between IMT and events. The results for inter-observer variability showed a systematic error between 0.04 and 0.08 mm. In the Person Rho correlation analysis in no case a statistical association between IMT and symptoms was detected whereas in 2 cases (observer 1 and observer 2), a statistically significant association between IMTV and symptoms was found. Data of this preliminary study suggest that IMTV may represent a powerful method to assess carotid atherosclerotic disease with a significant association to cerebrovascular events.


Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants?
A previous study suggested an increased risk of preeclampsia among women treated with selective serotonin reuptake inhibitors (SSRIs). Using population-based health-care utilization databases from British Columbia (1997-2006), the authors conducted a study of 69,448 pregnancies in women with depression. They compared risk of preeclampsia in women using SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) between gestational weeks 10 and 20 with risk in depressed women not using antidepressants. Among prepregnancy antidepressant users, the authors compared the risk in women who continued antidepressants between gestational weeks 10 and 24 with the risk in those who discontinued. Relative risks and 95% confidence intervals were estimated. The risk of preeclampsia in depressed women not treated with antidepressants (2.4%) was similar to that in women without depression (2.3%). Compared with women with untreated depression, women treated with SSRI, SNRI, and TCA monotherapy had adjusted relative risks of 1.22 (95% confidence interval (CI): 0.97, 1.54), 1.95 (95% CI: 1.25, 3.03), and 3.23 (95% CI: 1.87, 5.59), respectively. Within prepregnancy antidepressant users, the relative risk for preeclampsia among continuers compared with discontinuers was 1.32 (95% CI: 0.95, 1.84) for SSRI, 3.43 (95% CI: 1.77, 6.65) for SNRI, and 3.26 (95% CI: 1.04, 10.24) for TCA monotherapy. Study results suggest that women who use antidepressants during pregnancy, especially SNRIs and TCAs, have an elevated risk of preeclampsia. These associations may reflect drug effects or more severe depression.


Stopping a Continuous Movement: A Novel Approach to Investigating Inhibitory Control.
Flexible, adaptive behavior is critically dependent on inhibitory control. For example, if you suddenly notice you are about to step on a tack and would prefer not to, the ability to halt your ongoing movement is critical. However, this behavior is usually not probed by current inhibitory control tasks, which often focus instead on inhibiting a movement before its initiation. To address limitations in existing approaches for studying termination of an ongoing movement, we developed a novel stop task with which we can directly observe and compare prepared and reactive termination of a continuous movement. Here, we present and evaluate our novel continuous movement stop task (CMST) and compare task performance to performance on the traditional stop signal task. Our data reveal that the CMST effectively dissociates planned and unplanned stopping behaviors. We found that participants initiated and completed stopping significantly earlier on planned compared with unplanned stop trials and that the variability for each measure was greater for planned compared with unplanned stop trials. In addition, we found that the time at which participants initiated the stopping process was more variable than the time it took participants to complete the stopping process. We also found that participants slowed before stopping significantly more on planned than unplanned stop trials. Finally, our data suggest that preparatory mechanisms may be similar between the CMST and the traditional stop signal tasks, but that the tasks were not related by any other measure. The unambiguous quantification of prepared and reactive stopping behavior provided by the CMST will help support future investigation of different kinds of stopping behavior.


Building evidence for peer-led interventions: assessing the cost of the Adolescent Asthma Action program in Australia.
Asthma is the most common chronic illness among adolescents in Australia. Aboriginal and Torres Strait Islander adolescents, in particular, face substantial inequalities in asthma-related outcomes. Triple A (Adolescent Asthma Action) is a peer-led education intervention, which aims to improve asthma self-management and reduce the uptake of smoking among adolescents. The aim of this study was to determine the cost of implementing the Triple A program in Australia. Standard economic costing methods were used. It involved identifying the resources that were utilised (such as personnel and program materials), measuring them and then valuing them. We later performed sensitivity analysis so as to identify the cost drivers and a stress test to test how the intervention can perform when some inputs are lacking. Results indicate that the estimated cost of implementing the Triple A program in five schools was $41060, assuming that the opportunity cost of all the participants and venues was accounted for. This translated to $8212 per school or $50 per target student. From sensitivity analysis and a stress test, it was identified that the cost of the intervention (in practice) was $14 per student. This appears to be a modest cost, given the burden of asthma. In conclusion, the Triple A program is an affordable intervention to implement in high schools. The potential asthma cost savings due to the program are significant. If the Triple A program is implemented nation-wide, the benefits would be substantial.


A new species of Ephemerellomyces from North America highlights its morphological plasticity and possible intergeneric similarities with other Harpellales.
During routine bioprospecting efforts in southern Idaho, we recovered a new species, Ephemerellomyces kandelii from nymphs of the mayfly genus Ephemerella (Ephemerellidae) in Dry Creek drainage, near Boise. This is the second observation of this monotypic genus since the description of Ephemerellomyces aquilonius from Norway in 2004. Ephemerellomyces was described partly on the basis of unusual developmental features at the base of the thallus. Specifically, trichospores were noted with the capacity to germinate, attach to the hindgut cuticle of the mayfly host, and produce a cell bearing a single terminal trichospore. This feature was less prominent yet noted in our collections from Idaho, but we argue that the remnant basal cell may also be a morphological feature that unites the genus and deserves further scrutinization across closely related taxa. Compared to the two Norwegian surveys, our collections extended over 1 y, a timeframe that was critical to capture the extent of the natural morphological range and plasticity of E. kandelii. Specifically, we emend the generic description to accommodate the first observation of zygospores (Type II) and E. kandelii is described with dimorphic trichospores, yet another genus of the Harpellales to include species with this feature. We also document some variability in trichospore dimensions with E. kandelii, following routine procedures, in vitro slide incubations and staining; these are discussed in light of prior reports noting morphological changes in asexual spores of certain Harpellales following such handling. Finally, we extend our discussion to include putatively closely related taxa of gut fungi in other Ephemeroptera.


Structure of pressinoic acid: the cyclic moiety of vasopressin.
Arginine vasopressin consists of a 20-membered, disulfide-linked macrocyclic ring system called pressinoic acid to which is attached a COOH-terminal tripeptide. The molecular conformation of pressinoic acid has been determined from single crystal x-ray diffraction data. The 20-membered macrocyclic ring, stabilized by two intramolecular hydrogen bonds, has a type I beta-bend centered on Gln4 and Asn5 and a highly distorted type II' bend centered on Phe3 and Gln4. In vasopressin the Asn5 side chain extends away from the macrocyclic ring system and hydrogen bonds to the terminal tripeptide, but in pressinoic acid the Asn5 side chain lies over the molecule and forms a strong hydrogen bond to the nitrogen of Tyr2. The absence of pressor activity in pressinoic acid may be a result of both the loss of the COOH-terminal tripeptide and the incorrect orientation of the Asn5 side chain. Whether this class of hormones has pressor or oxytocic activity is determined by the orientation of the Tyr2 side chain, that is, whether it is extended away from or over the ring system, respectively. In pressinoic acid, the Tyr2 side chain is in the expected "pressor conformation," that is, extended away from the ring system, and is stabilized through a hydrophobic interaction with the Phe3 side chain. Thus, the conformation of the pressinoic acid molecule partly explains the activity of vasopressin-like hormones.


Cloning and sequence analysis of desmosomal glycoproteins 2 and 3 (desmocollins): cadherin-like desmosomal adhesion molecules with heterogeneous cytoplasmic domains.
Desmosomal glycoproteins 2 and 3 (dg2 and 3) or desmocollins have been implicated in desmosome adhesion. We have obtained a 5.0-kb-long clone for dg3 from a bovine nasal epidermal lambda gt11 cDNA library. Sequence analysis of this clone reveals an open reading frame of 2,517 bases encoding a polypeptide of 839 amino acids. The sequence consists of a signal peptide of 28 amino acids, a precursor sequence of 104 amino acids, and a mature protein of 707 amino acids. The latter has the characteristics of a transmembrane glycoprotein with an extracellular domain of 550 amino acids and a cytoplasmic domain of 122 amino acids. The sequence of a partial clone from the same library shows that dg2 has an alternative COOH terminus that is extended by 54 amino acids. Genomic DNA sequence data show that this arises by splicing out of a 46-bp exon that encodes the COOH-terminal 11 amino acids of dg3 and contains an in-frame stop codon. The extracellular domain of dg3 shows 39.4% protein sequence identity with bovine N-cadherin and 28.4% identity with the other major desmosomal glycoprotein, dg1, or desmoglein. The cytoplasmic domain of dg3 and the partial cytoplasmic domain of dg2 show 23 and 24% identity with bovine N-cadherin, respectively. The results support our previous model for the transmembrane organization of dg2 and 3 (Parrish, E.P., J.E. Marston, D.L. Mattey, H.R. Measures, R. Venning, and D.R. Garrod. 1990. J. Cell Sci. 96:239-248; Holton, J.L., T.P. Kenny, P.K. Legan, J.E. Collins, J.N. Keen, R. Sharma, and D.R. Garrod. 1990. J. Cell Sci. 97:239-246). They suggest that these glycoproteins are specialized for calcium-dependent adhesion in their extracellular domains and, cytoplasmically, for the molecular interactions involved in desmosome plaque formation. Moreover this represents the first example of alternative splicing within the cadherin family of cell adhesion molecules.


Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.
To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥2.0; average HER2 copy number <4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.


In Situ Analysis of Small Populations of Adherent Mammalian Cells Using Laser Ablation Electrospray Ionization Mass Spectrometry in Transmission Geometry.
Most cultured cells used for biomedical research are cultured adherently, and the requisite detachment prior to biochemical analysis might induce chemical changes. This is especially crucial if accurate metabolic measurements are desired, given the rapid turnover of metabolites in living organisms. There are only a few methods available for the nontargeted in situ analysis of small adherent cell populations. Here we show that laser ablation electrospray ionization (LAESI) mass spectrometry (MS) can be used to analyze adherent cells directly, while still attached to the culture surface. To reduce the size of the analyzed cell population, the spot size constraints of conventional focusing in reflection geometry (rg) LAESI had to be eliminated. By introducing transmission geometry (tg) LAESI and incorporating an objective with a high numerical aperture, spot sizes of 10-20 μm were readily achieved. As few as five adherent cells could be specifically selected for analysis in their culturing environment. The importance of in situ analysis was highlighted by comparing the metabolite composition of adherent versus suspended cells. For example, we observed that cells analyzed adherently yielded higher values for the adenylate energy charge (0.90 ± 0.09 for adherent cells vs 0.09 ± 0.03 for suspended cells). Additionally, due to the smaller focal spot size, tg-LAESI enabled the analysis of ∼20 times smaller cell populations compared to rg-LAESI.


Depression in patients with hypertrophic cardiomyopathy: is there any relation with the risk factors for sudden death?
The aim of this study was to investigate whether depressive symptoms are related to the risk factors for sudden death in patients with hypertrophic cardiomyopathy (HCM). 121 patients diagnosed as having HCM were assessed for depressive symptomatology using the Beck Depression Inventory and the Center for Epidemiological Studies Depression Scale (CES-D) and followed up for a period of 2 years. For the interview, the authors used the Structured Clinical Interview for DSM-III/DSM-III-R. A multidimensional longitudinal study was carried out with both somatic and psychological symptoms and signs taken into consideration. SPSS was used for the statistical analysis. (1) Patients with HCM are more depressed than the general population. (2) There is no positive correlation between the occurrence of depressive symptoms and the risk factors for sudden death in patients with HCM. (3) Patients at high risk for sudden death are not more depressed than the others. (4) Time from diagnosis of the cardiac disease is not related to the presence and severity of depressive symptoms. Patients with HCM are more depressed than the general population. The authors suggest that depressive symptoms and risk factors for sudden death in these patients are not related. It is important to screen for mood disorders in this patient population in order to provide an early diagnosis and treatment of the psychiatric disease.


[Correction of congenital malformations by custom-made silicone implants: Contribution of computer-aided design. Experience of 611 cases].
Modern techniques of computer-aided design and tridimensional prototyping for manufacturing silicone elastomer custom implants are growing. They have widely modified the surgical indications in our unit. By presenting their experience of 611 cases managed between 1993 and 2016, the authors describe the method of conception from CT-scans, the virtual image of the body and the manufacture of the custom-made implant perfectly adapted to the anatomy of each one. The operative techniques are described for the three main indications: the funnel chest or pectus excavatum (474 cases) according to a modified CHIN classification is corrected simply and very satisfactorily. This approach may render thoracic surgery techniques obsolete. Indeed, these operations remain risky and of doubtful functional utility; Poland syndrome (116 cases), where the use of a custom-made implant for compensation of muscle volume is frequently used, but can be improved by a transfer of adipose tissue or a classic breast implant; the leg atrophies (21 cases) receive custom elastomer implants introduced in a sub-fascial plane. The results are excellent for pectus excavatum but more difficult to optimize for the other two indications, requiring sometimes complementary techniques. Complications are rare and often benign, implants endure for life. Quality of life, psychological comfort and self-esteem have been improved with low morbidity and without having undergone a painful surgical experience. Reconstructive procedures of congenital malformations by custom-made silicone implants open a new field of activity for our surgical specialty with vast opportunities.


Long-term white matter changes after severe traumatic brain injury: a 5-year prospective cohort.
Extensive white matter damage has been documented in patients with severe traumatic brain injury, yet how this damage evolves in the long term is not well understood. We used DTI to study white matter changes at 5 years after traumatic brain injury. There were 8 healthy control participants and 13 patients with severe traumatic brain injury who were enrolled in a prospective observational study, which included clinical assessment and brain MR imaging in the acute setting (< 6 weeks) and 2 years and 5 years after injury. Only subjects with mild to moderate disability or no disability at 1 year were included in this analysis. DTI parameters were measured in 20 different brain regions and were normalized to values obtained in an age-matched control group. In the acute setting, fractional anisotropy was significantly lower in the genu and body of the corpus callosum and in the bilateral corona radiata in patients compared with control participants, whereas radial diffusivity was significantly (P < .05) higher in these tracts. At 2 years, fractional anisotropy in these tracts had further decreased and radial diffusivity had increased. No significant changes were detected between 2 and 5 years after injury. The baseline radial diffusivity and fractional anisotropy values in the anterior aspect of the brain stem, genu and body of the corpus callosum, and the right and left corona radiata were significantly (P < .05) associated with neurocognitive sequelae (including amnesia, aphasia, and dyspraxia) at year 5. DTI changes in major white matter tracts persist up to 5 years after severe traumatic brain injury and are most pronounced in the corpus callosum and corona radiata. Limited structural change is noted in the interval between 2 and 5 years.


Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice.
Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized 5'-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy.


Designing theoretically-informed implementation interventions.
Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area.


Case Report: Sudden death related to unrecognized cardiac hydatid cyst.
Echinococcosis, also known as hydatid disease, is a common parasitic human infestation found in sheep-breeding areas. It is caused by the larvae stage of Echinococcus granulosus, and cysts develop mostly in the lungs and the liver. Cardiac involvement is unusual and silent until acute complications or a fatal outcome occurs. Herein, we report an autopsy case of a young healthy adult who died suddenly. The autopsy revealed an external bulging on the right heart ventricle outlet with a fluid-filled cystic cavity discovered on sectioning. Dissection of other organs did not reveal other cyst locations. Histological examination ascertained the diagnosis of hydatid cyst, and death was attributed to cardiac arrhythmias. Pathologists should keep in mind that hydatid cysts can develop anywhere in the body. Solitary cardiac cyst is rare and can simulate a "silent bomb". Unfortunately, sudden death remains the frequent manner of revelation of this disease in endemic areas.


Clinical effects of raloxifene hydrochloride in women.
To review clinical data on raloxifene hydrochloride, a selective estrogen receptor modulator that was recently approved for the prevention of osteoporosis in postmenopausal women. English-language articles published from 1980 to May 1998 were identified through MEDLINE searches. Bibliographies, book chapters, and meeting abstracts were reviewed for additional relevant publications. Publications that contained information on the background of development, structure, mechanism of action, tissue-selective effects, and adverse effects of raloxifene hydrochloride were included. Data in selected articles were reviewed, and relevant clinical information was extracted. Raloxifene hydrochloride was developed in an effort to find a treatment for breast cancer and osteoporosis. It binds to the estrogen receptor and shows tissue-selective effects; thus, it belongs to a class of drugs recently described as selective estrogen receptor modulators. Tissue selectivity of raloxifene may be achieved through several mechanisms: the ligand structure, interaction of the ligand with different estrogen receptor subtypes in various tissues, and intracellular events after ligand binding. Raloxifene has estrogen-agonistic effects on bone and lipids and estrogen-antagonistic effects on the breast and uterus. An increase in bone mineral density at the spine, total hip, and total body has been reported with raloxifene but seems to be less than that seen with estrogen or alendronate therapy. Raloxifene has been shown to produce a reduction in total and low-density lipoprotein cholesterol concentrations similar to that produced by estrogen therapy, but high-density lipoprotein cholesterol and triglyceride concentrations do not increase during raloxifene therapy. In the uterus, raloxifene does not stimulate the endometrium. Long-term data on the effects of raloxifene in reduction of risk for fracture; prevention of cardiovascular events; cognitive function; and the incidence of breast, ovarian, and uterine cancer are not available. The most common adverse effect of raloxifene is hot flashes. Raloxifene has been shown to have beneficial effects in selected organs in postmenopausal women. Although estrogen remains the drug of choice for hormonal therapy in most postmenopausal women, raloxifene may be an alternative in certain groups of women at risk for osteoporosis.


Living with Cancer: an Educational Intervention in Cancer Patients Can Improve Patient-Reported Knowledge Deficit.
A cancer diagnosis requires significant information to facilitate health care decision making, understand management options, and health care system navigation. Patient knowledge deficit can decrease quality of life and health care compliance. Surveys were distributed to attendees of the Mayo Clinic "Living with and Surviving Cancer" patient symposium January 2015. Follow-up survey was sent to participants 3 months after the symposium. Surveys included demographic data and patient-reported disease comprehension, symptom burden, desired information, and quality-of-life assessment. Demographics: 113 patients completed the pre-intervention survey. Average age was 64.7 years. Disease types included hematologic (N = 50) and solid malignancies (N = 77). Most patients self-reported adequate baseline understanding of their disease (80 %), screening tests (74 %), and monitoring tools (72 %). Lowest knowledge topics were legal issues (13 %) and pain management (35 %). Pre- and post-analysis: 79 of the initial 113 participants completed both surveys. In the post-symposium setting, durable knowledge impact was noted in disease understanding (pre 80 % vs post 92 %), treatment options (pre 60 % vs post 76 %), nutrition (pre 68 % vs post 84 %), and legal issues (pre 15 % vs post 32 %). Most patients desired increased understanding regarding disease, screening tests, nutrition, and stress and fatigue management. The level of desired information for these topics decreased in the post-symposium setting, statistically significant decrease noted in 4 of 5 topics assessed. Knowledge needs and deficit in cancer care range from disease-specific topics, social stressors, and health care navigation. A cancer patient-centered symposium can improve patient-reported knowledge deficit, with durable responses at 3 months, but patient needs persist.


U.S. Army Physical Demands Study: Differences in Physical Fitness and Occupational Task Performance Between Trainees and Active Duty Soldiers.
Canino, MC, Foulis, SA, Zambraski, EJ, Cohen, BS, Redmond, JE, Hauret, KG, Frykman, PN, and Sharp, MA. U.S. Army Physical Demands Study: Differences in physical fitness and occupational task performance between trainees and active duty soldiers. J Strength Cond Res 33(7): 1864-1870, 2019-U.S. Army initial entry training (IET) is designed to prepare trainees for the military environment and subsequent training, including specific programs to increase physical fitness to perform job-specific tasks to the minimal acceptable performance standard (MAPS). The aim of this study was to compare physical fitness and occupational task performance of trainees at the end of IET to that of active duty soldiers. One hundred seventy-nine male combat arms trainees at the end of IET and 337 male combat arms active duty soldiers performed a sandbag carry (SBC), casualty drag (CD), and move under direct fire (MUF). Physical fitness was assessed using Army Physical Fitness Test scores. A questionnaire was administered to determine frequency of task performance. Active duty soldiers compared with trainees were older (p < 0.01) and performed more push-ups (p < 0.01) and sit-ups (p < 0.01). Trainees performed the 2-mile run faster (p < 0.01). Ninety-four percent of trainees and 99% of active duty soldiers performed the 3 tasks to the MAPSs. Active duty soldiers performed significantly faster on both the SBC (p < 0.01) and CD (p < 0.01) and reported a higher task frequency on the SBC (p = 0.03) and CD (p < 0.01). No difference in MUF performance (p = 0.16) and task frequency (p = 0.13) was detected. Initial entry training seems to provide sufficient physical training as most trainees were able to meet the MAPSs; however, performance differences were still apparent between trainees and active duty soldiers. Additional practice performing the physically demanding tasks may help maximize performance on the physically demanding job requirements.


Lexical Stress and Linguistic Predictability Influence Proofreading Behavior.
There is extensive evidence that the segmental (i.e., phonemic) layer of phonology is routinely activated during reading, but little is known about whether phonological activation extends beyond phonemes to subsegmental layers (which include articulatory information, such as voicing) and suprasegmental layers (which include prosodic information, such as lexical stress). In three proofreading experiments, we show that spelling errors are detected more reliably in syllables that are stressed than in syllables that are unstressed if comprehension is a goal of the reader, indicating that suprasegmental phonology is both active during silent reading and can influence orthographic processes. In Experiment 1, participants received instructions to read for both errors and comprehension, and we found that the effect of lexical stress interacted with linguistic predictability, such that detection of errors in more predictable words was aided by stress but detection of errors in less predictable words was not. This finding suggests that lexical stress patterns can be accessed prelexically if an upcoming word is sufficiently predictable from context. Participants with stronger vocabularies showed decreased effects of stress on task performance, which is consistent with previous findings that more skilled readers are less swayed by phonological information in decisions about orthographic form. In two subsequent experiments, participants were instructed to read only for errors (Experiment 2) or only for comprehension (Experiment 3); the effect of stress disappeared when participants read for errors and reappeared when participants read for comprehension, reconfirming our hypothesis that predictability is a driver of lexical stress effects. In all experiments, errors were detected more reliably in words that were difficult to predict from context than in words that were highly predictable. Taken together, this series of experiments contributes two important findings to the field of reading and cognition: (1) The prosodic property of lexical stress can influence orthographic processing, and (2) Predictability inhibits the detection of errors in written language processing.


Is performance status associated with symptom scores? A population-based longitudinal study among cancer outpatients.
Symptom scores and performance status are both important measures for patients with cancer. However, since performance status is not often part of routinely collected data, there is interest in exploring whether it can be calculated from symptom scores. This was a population-based longitudinal study of cancer outpatients in Ontario, Canada in the year following their cancer diagnosis and among the subset of patients during the last year of their lives. In the first year after diagnosis, there was a significant relationship between performance status and fatigue and appetite; fatigue and well-being had a significant association with performance status in the last year of life. In both periods, the associations, although statistically significant, were not large enough to be clinically meaningful. Performance status is an important measurement that cannot be substituted or captured with symptom scores; it is important for healthcare providers to record performance scores on a regular basis.


Predictors of histological activity and fibrosis in chronic Hepatitis C infection: a study from North India.
The role of hepatitis C virus (HCV) genotypes in the severity of liver disease is still debatable and there is an occasional published report from India. The aim of this study is to assess the role of HCV genotypes in severity of liver disease in Indian patients. An attempt has also been made to perform a multivariate analysis to identify the predictors of severity of liver disease in chronic HCV infection. In this study, 31 newly diagnosed cases of chronic HCV infection over a period of two years were included. Age, sex and serum alanine transaminase (ALT) levels were recorded for each patient. HCV genotypes were identified using Line Probe assay (INNO-LiPA HCV II kit, Innogenetics, Belgium). Histological activity was graded and fibrosis was staged. Univariate and multivariate analysis was done to identify predictors of histological severity and fibrosis. By univariate analysis, age of the patient, serum ALT levels and absence of genotype 3 (i.e., presence of HCV genotype other than genotype 3) showed association with histological activity score; whereas age and histological activity score showed association with fibrosis. However, on multivariate analysis, only serum ALT levels and absence of genotype 3 correlated well with activity score; while only activity score remained a significant predictor of stage of fibrosis. This study emphasizes the significant correlation of HCV genotype with severity of liver disease in chronic HCV infection. The stage of fibrosis showed correlation only with activity score as an independent factor. These results would further help in outlining algorithms for therapeutic stratification of patients with HCV infection.


Assessment of calcitonin response to experimentally induced hypercalcemia in cats.
To characterize the dynamics of calcitonin secretion in response to experimentally induced hypercalcemia in cats. 13 healthy adult European Shorthair cats. For each cat, the calcitonin response to hypercalcemia (defined as an increase in ionized calcium concentration > 0.3 mM) was investigated by infusing calcium chloride solution and measuring circulating calcitonin concentrations before infusion (baseline) and at various ionized calcium concentrations. Calcitonin expression in the thyroid glands of 10 of the cats was investigated by immunohistochemical analysis. Preinfusion baseline plasma calcitonin concentrations were very low in many cats, sometimes less than the limit of detection of the assay. Cats had a heterogeneous calcitonin response to hypercalcemia. Calcitonin concentrations only increased in response to hypercalcemia in 6 of 13 cats; in those cats, the increase in calcitonin concentration was quite variable. In cats that responded to hypercalcemia, calcitonin concentration increased from 1.3 ± 0.3 pg/mL at baseline ionized calcium concentration to a maximum of 21.2 ± 8.4 pg/mL at an ionized calcium concentration of 1.60 mM. Cats that did not respond to hypercalcemia had a flat calcitonin-to-ionized calcium concentration curve that was not modified by changes in ionized calcium concentration. A significant strong correlation (r = 0.813) was found between the number of calcitonin-positive cells in the thyroid gland and plasma calcitonin concentrations during hypercalcemia. Healthy cats had very low baseline plasma calcitonin concentrations. A heterogeneous increase in plasma calcitonin concentration in response to hypercalcemia, which correlated with the expression of calcitonin-producing cells in the thyroid, was identified in cats.


Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.
Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment. The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed. Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability. miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.


The continuous Wagon wheel illusion and the 'when' pathway of the right parietal lobe: a repetitive transcranial magnetic stimulation study.
A continuous periodic motion stimulus can sometimes be perceived moving in the wrong direction. These illusory reversals have been taken as evidence that part of the motion perception system samples its inputs as a series of discrete snapshots -although other explanations of the phenomenon have been proposed, that rely on the spurious activation of low-level motion detectors in early visual areas. We have hypothesized that the right inferior parietal lobe ('when' pathway) plays a critical role in timing perceptual events relative to one another, and thus we examined the role of the right parietal lobe in the generation of this "continuous Wagon Wheel Illusion" (c-WWI). Consistent with our hypothesis, we found that the illusion was effectively weakened following disruption of right, but not left, parietal regions by low frequency repetitive transcranial magnetic stimulation (1 Hz, 10 min). These results were independent of whether the motion stimulus was shown in the left or the right visual field. Thus, the c-WWI appears to depend on higher-order attentional mechanisms that are supported by the 'when' pathway of the right parietal lobe.


Chimeric brain: theoretical and clinical aspects.
Using xeno-transplantation, interactions of neural tissues of vertebrates and insects were studied. Ventral neurogenic primordium of Notch Drosophila melanogaster embryos was transplanted into neural tube of amphibian and mammalian embryos with the aid of microhydrofeeding. Embryos of four different amphibian species, random bred mice and rats were used as graft recipients. It was concluded that there is a possibility to incorporate nerve cells of insects into the brain of vertebrates. Morphological and functional contacts can be established between the transplanted cells and host brain tissues. Transplanted Drosophila cells preserve their viability for a long time, so that a prolonged influence of the transplant upon the recipient can be predicted, which may be used in medical practice. A mixture of human fetal brain and Notch Drosophila melanogaster neural embryonic tissues were transplanted into the ventro-lateral nucleus of the thalamus of the patients of Parkinson' disease. As a result, tremor and constrained movements disappeared. Post-operation patients have been observed within 13-38 months. No side effects were noted during this time.


Nonlinear distortion generated by semiconductor optical amplifier boosters in analog optical systems.
Closed-form theoretical expressions for the second- and third-order harmonic distortions generated by a semi-conductor optical amplifier (SOA) operating under slight saturation conditions are derived for what is believed to be the first time. The distortion results provided by these expressions agree very well with those obtained by means of simulation and experiments, showing that one should carefully adjust the optical power launched into the SOA to obtain both the good linearity and high dynamic range required by analog optical systems.


Amnioinfusion and Bed Rest May Effectively Improve the Insufficient Circulation of the Umbilical Cord in Pregnant Women With Hyper-Coiled Cord and Oligohydramnios.
We experienced two cases with hyper-coiled cord in which fetal-umbilical-placental circulation was improved after amnioinfusion or bed rest. Therefore, amnioinfusion and bed rest to reduce the compression of the vulnerable umbilical cord in cases of hyper-coiled cord might improve the pathologic fetal-umbilical-placental circulation.


Anti-TNF-alpha therapies do not increase early postoperative complications in patients with inflammatory bowel disease. An Italian single-center experience.
The impact of preoperative use of TNF-alpha inhibitors on postoperative complications in patients with inflammatory bowel disease (IBD) undergoing abdominal surgery is controversial. The aim of this study was to evaluate the 30-day postoperative outcomes for IBD patients treated with these drugs prior to surgery. We analyzed retrospectively the incidence of short-term postoperative complications. Statistical analyses were performed to reveal the independent variables that influenced postoperative complications and the role of preoperative medical therapy with anti-TNF drugs within 12 weeks prior to surgery. One hundred fourteen patients (76 with Crohn's disease (CD) and 38 ulcerative colitis (UC)) underwent abdominal surgery for IBD. Fifty-four patients were treated with anti-TNF-alpha within 12 weeks prior to surgery (anti-TNF group). Postoperative mortality and morbidity were 0% and 21%, respectively. The infection rate was 15%. A significantly higher incidence of postoperative complications was found in patients treated with high-dose steroids (58% vs. 17%; p = 0.003) after univariate analysis. The infection rate was significantly higher in patients treated with high-dose corticosteroids (50% vs. 11%; p = 0.002) and concomitant anti-TNF-alpha (60% vs. 13%; p = 0.023). Multivariate analysis revealed that only therapy with high-dose corticosteroids was significantly associated with cumulative (p = 0.017) and infective postoperative complications (p = 0.046). No significant differences were found between the anti-TNF group and the control group. High-dose corticosteroids increased the risk of short-term postoperative cumulative and infective complications. Anti-TNF drugs within 12 weeks prior to abdominal surgery in patients with IBD did not appear to increase the rate of postoperative complications.


Thriving within the host: Candida spp. interactions with phagocytic cells.
Certain Candida spp. (e.g. C. albicans, C. tropicalis, C. parapsilosis and C. glabrata) are not only well-adapted fungal commensals of humans, but are also able to cause superficial mucosal infections or even systemic disease. Professional phagocytes (neutrophils, macrophages and dendritic cells) constitute the first line of defence against Candida spp. Here, we review the interactions of phagocytes with pathogenic Candida spp., focusing on macrophages and neutrophils. We discuss the mechanisms involved in recognition, uptake and killing of these fungi. We go on to analyse the cellular responses of these yeasts towards phagocyte-imposed stresses, including metabolic flexibility, robust oxidative stress response and ability to cope with nitrosative stress. Finally, we address strategies that allow these opportunistic pathogens to thrive within the host, evading and escaping from the phagocyte attack.


An intercalation-locked parallel-stranded DNA tetraplex.
DNA has proved to be an excellent material for nanoscale construction because complementary DNA duplexes are programmable and structurally predictable. However, in the absence of Watson-Crick pairings, DNA can be structurally more diverse. Here, we describe the crystal structures of d(ACTCGGATGAT) and the brominated derivative, d(AC(Br)UCGGA(Br)UGAT). These oligonucleotides form parallel-stranded duplexes with a crystallographically equivalent strand, resulting in the first examples of DNA crystal structures that contains four different symmetric homo base pairs. Two of the parallel-stranded duplexes are coaxially stacked in opposite directions and locked together to form a tetraplex through intercalation of the 5'-most A-A base pairs between adjacent G-G pairs in the partner duplex. The intercalation region is a new type of DNA tertiary structural motif with similarities to the i-motif. (1)H-(1)H nuclear magnetic resonance and native gel electrophoresis confirmed the formation of a parallel-stranded duplex in solution. Finally, we modified specific nucleotide positions and added d(GAY) motifs to oligonucleotides and were readily able to obtain similar crystals. This suggests that this parallel-stranded DNA structure may be useful in the rational design of DNA crystals and nanostructures.


Optimal contrast concentration for CT-guided epidural steroid injections.
Contrast is used in CT-guided epidural steroid injections to ensure proper needle placement. Once injected, undiluted contrast often obscures the needle, hindering subsequent repositioning. The purpose of this investigation was to establish the optimal contrast dilution for CT-guided epidural steroid injections. This investigation consisted of an initial phantom study, followed by a prospective, randomized, single-center trial assessing a range of contrast dilutions. In the phantom study, a phantom housing a chamber containing a 22-gauge needle and various dilutions of contrast was scanned, and images were evaluated for needle visibility. On the basis of these results, concentrations of 66, 100, 133, and 150 mg/mL iodine were selected for evaluation in a clinical study. Patients presenting for CT-guided epidural steroid injections were randomly assigned to a contrast dilution, and images from the procedure were evaluated by 2 readers blinded to the contrast assignment. Needle visibility was scored by use of a 5-point scale. In the phantom study, the needle was not visible at contrast concentrations of ≥133 mg/mL. In the clinical study, needle visibility was strongly associated with contrast concentration (P < .0001). Significant improvements in visibility were found in 66 mg/mL and 100 mg/mL compared with higher iodine concentrations; no difference was found comparing 66 mg/mL with 100 mg/mL iodine. Neither injection location (cervical versus lumbar) nor technique (interlaminar versus transforaminal) influenced visibility scores. For CT-guided epidural steroid injections, the optimal contrast concentration is 66-100 mg/mL iodine. Because these concentrations are not commercially available, proceduralists must dilute their contrast for such procedures.


Pharmacists as a Source of Advice on Medication Use for Athletes.
Background: The World Anti-Doping Agency (WADA) specifies substances that competitive sportspersons are not allowed to take. Some of these substances are contained in common medicines used in everyday medical practice and could be used by athletes by accident. Objectives: This study aimed to explore pharmacists' knowledge and confidence in guiding athletes about the use of medicines in professional sport. Methods: Registered pharmacists in Australia were invited to participate in an online survey. The survey had five domains and aimed to identify pharmacists' demographic information, interest in sport, familiarity with WADA guidelines, knowledge on prohibited drug classes, and their opinion about the role of pharmacists in educating athletes on medication use. Descriptive statistics were provided and where appropriate, Chi-square, Mann-Whitney and independent t-test were used to identify potential associations and difference between means. Results: One hundred and thirty-five pharmacists (response rate of 10.6%) completed the survey, with the majority indicating that they were not confident in advising athletes on medication use. Although most respondents believed that pharmacists have a role in the education of athletes to help avoid unintentional doping, only about a quarter indicated that they had sufficient knowledge to advise athletes. About one-half of the respondents could provide fully correct answers when asked to identify the WADA status of some commonly used drugs. Conclusions: The results of the survey indicate that upskilling is required to enable pharmacists in Australia to provide accurate medication advice to professional athletes.


An immunohistochemical evaluation of podoplanin expression in oral leukoplakia and oral squamous cell carcinoma to explore its potential to be used as a predictor for malignant transformation.
Oral leukoplakia (OL) is a potentially malignant disorder with increased risk for the development of oral squamous cell carcinoma (OSCC). Many cases of OSCC arise from the malignant transformation of preexisting OL. However, the risk of progression into OSCC and the possible prediction of malignant potential of OL remain inconclusive. Recent studies have shown that podoplanin, a mucin-like transmembrane glycoprotein specifically expressed in lymphatic endothelial cells, is expressed in various neoplasms including OSCC, indicating its possible biologic role in tumor cells. In this study, an evaluation of podoplanin expression in OL and OSCC has been carried out to assess its potential role as a biomarker to predict the possibility of malignant transformation in OL cases. To assess the usefulness of podoplanin as a potential biomarker for predicting the risk of malignant transformation in OL, by comparing its immunohistochemical expression in OL and OSCC. Archival paraffin-embedded blocks of 25 OL cases with varying grades of dysplasia and 30 OSCC cases showing its varying grades were selected. Sections were subjected to immunohistochemical staining for podoplanin and compared with the control group for evaluation of results in the three groups. A statistically significant increase in podoplanin expression was observed from normal mucosa through OL to OSCC. In the OL cases, the podoplanin staining score progressively increased from mild dysplasia to carcinoma in situ, whereas in OSCC, well-differentiated group showed the maximum expression of podoplanin. The progressive increase in podoplanin expression through the increasing grades of dysplasia in OL is suggestive of an increased risk for malignant transformation with increased expression of podoplanin in OL cases. A high podoplanin expression in the well-differentiated OSCC may indicate a vital role for podoplanin in the early stages of tumorigenesis.


Brewer's spent grain, serum lipids and fecal sterol excretion in human subjects with ileostomies.
A crossover design studying lipid and apoprotein levels in serum and excretion of sterol, nitrogen and fat in ileostomy effluent was performed in 10 subjects fed diets with or without supplementation with brewer's spent grain, which is the residue of barley after the brewing of beer. More cholesterol, nitrogen, fat and energy were excreted in the ileostomy effluents when the subjects consumed a brewer's spent grain supplemented, high fiber diet than when they consumed a low fiber diet. No significant change was found in the daily net sterol excretion. The six subjects with low daily excretion of bile acids (less than 1000 mg/24 h) had increased cholesterol and net cholesterol and decreased bile acid excretion per day, and lowered serum LDL-cholesterol and apoprotein B levels after supplementation with brewer's spent grain. We propose that subjects with low daily bile acid excretion are suitable models for studying the effect of dietary changes on sterol excretion and serum lipid levels. Increased fecal cholesterol excretion is suggested to be the primary mechanism for the serum LDL-cholesterol lowering effect of brewer's spent grain.


CadA negatively regulates Escherichia coli O157:H7 adherence and intestinal colonization.
Adherence of pathogenic Escherichia coli strains to intestinal epithelia is essential for infection. For enterohemorrhagic E. coli (EHEC) serotype O157:H7, we have previously demonstrated that multiple factors govern this pathogen's adherence to HeLa cells (A. G. Torres and J. B. Kaper, Infect. Immun. 71:4985-4995, 2003). One of these factors is CadA, a lysine decarboxylase, and this protein has been proposed to negatively regulate virulence in several enteric pathogens. In the case of EHEC strains, CadA modulates expression of the intimin, an outer membrane adhesin involved in pathogenesis. Here, we inactivated cadA in O157:H7 strain 86-24 to investigate the role of this gene in EHEC adhesion to tissue-cultured monolayers, global gene expression patterns, and colonization of the infant rabbit intestine. The cadA mutant did not possess lysine decarboxylation activity and was hyperadherent to tissue-cultured cells. Adherence of the cadA mutant was nearly twofold greater than that of the wild type, and the adherence phenotype was independent of pH, lysine, or cadaverine in the media. Additionally, complementation of the cadA defect reduced adherence back to wild-type levels, and it was found that the mutation affected the expression of the intimin protein. Disruption of the eae gene (intimin-encoding gene) in the cadA mutant significantly reduced its adherence to tissue-cultured cells. However, adherence of the cadA eae double mutant was greater than that of an 86-24 eae mutant, suggesting that the enhanced adherence of the cadA mutant is not entirely attributable to enhanced expression of intimin in this background. Gene array analysis revealed that the cadA mutation significantly altered EHEC gene expression patterns; expression of 1,332 genes was downregulated and that of 132 genes was upregulated in the mutant compared to the wild-type strain. Interestingly, the gene expression variation shows an EHEC-biased gene alteration including intergenic regions. Two putative adhesins, flagella and F9 fimbria, were upregulated in the cadA mutant, suggestive of their association with adherence in the absence of the Cad regulatory mechanism. In the infant rabbit model, the cadA mutant outcompeted the wild-type strain in the ileum but not in the cecum or mid-colon, raising the possibility that CadA negatively regulates EHEC pathogenicity in a tissue-specific fashion.


Snoring and excessive daytime somnolence among Polish middle-aged adults.
There is considerable interest in the association of snoring and health consequences that have been linked to more severe sleep-disordered breathing, including obstructive sleep apnoea syndrome. The goal of this investigation was to assess the independent association of heavy, habitual snoring and daytime sleepiness. For this, a cross-sectional, population based study of snoring, sleepiness and other factors was conducted using the Warsaw sample of the Multinational Monitoring of Trends and Determinants of Cardiovascular Diseases (MONICA) study, a population-based multicentre study of cardiovascular disease. The well-defined MONICA sample of middle-aged males and females also allowed estimation of age- and sex-specific prevalences of habitual snoring in Polish adults. Data on self-reported snoring frequency and loudness, and daytime sleepiness using the Epworth Sleepiness Scale (ESS) and other questions, were collected with a postal questionnaire. Seventy-nine per cent of the MONICA sample completed the questionnaire, yielding a total of 1,186 participants. Of the total sample, 27% of the females and 48% of the males reported habitual snoring ("often" or "always"). There was an independent association of habitual snoring and excessive daytime sleepiness (EDS), sleepiness that interfered with work and with increasing ESS scores. Habitual snorers were 5.8 and 3.1 times more likely to report EDS in active and passive situations, respectively, compared to nonsnorers (all p<0.01). It is concluded that habitual snorers, most of whom are probably unlikely to have frank sleep apnoea syndrome, are at substantial risk for daytime sleepiness. These findings add support to the hypothesis that simple snoring is not benign and underscores the need for further research on health outcomes associated with this prevalent condition.


Prevalence of dental caries in Sri Lankan aboriginal Veddha children.
To evaluate the cares status of Sri-Lankan Veddha children in relation to the traditional risk factors. Prevalence of dental caries is still high in certain populations, studies of which may shed additional light on the complex aetiology of caries. Using the NIDR criteria for caries diagnosis, the Strip Mutans technique (Dentocult SM), and a questionnaire administered by a native speaker, 39 children between the ages of 2-17 years were examined in a cross-sectional study. Of the 2-9-year-olds, 33% were caries free in the primary dentition and 72% of 5-17-year-olds were caries free in the permanent dentition (mean dft = 2.7; SE = 0.61 and mean DMFT = 0.9; SE = 0.41). There was no correlation between caries and mutans streptococci levels. Excessive consumption of sugar or honey was significantly correlated with the mean dft levels (P = 0.007). The mother was the primary caregiver for all but two children and the children were breast-fed for an average of 2.8 years (SD = 0.82). The duration of breast-feeding was not correlated with the caries experience. Lack of professional and home care and unfavourable dietary practices may be related to the high prevalence of caries observed in this population.


Emerging Tuberculosis Pathogen Hijacks Social Communication Behavior in the Group-Living Banded Mongoose (Mungos mungo).
An emerging Mycobacterium tuberculosis complex (MTC) pathogen, M. mungi, infects wild banded mongooses (Mungos mungo) in Northern Botswana, causing significant mortality. This MTC pathogen did not appear to be transmitted through a primary aerosol or oral route. We utilized histopathology, spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), quantitative PCR (qPCR), and molecular markers (regions of difference [RDs] from various MTC members, including region of difference 1 [RD1] from M. bovis BCG [RD1(BCG)], M. microti [RD1(mic)], and M. pinnipedii [RD1(seal)], genes Rv1510 [RD4], Rv1970 [RD7], Rv3877/8 [RD1], and Rv3120 [RD12], insertion element IS1561, the 16S RNA gene, and gene Rv0577 [cfp32]), including the newly characterized mongoose-specific deletion in RD1 (RD1(mon)), in order to demonstrate the presence of M. mungi DNA in infected mongooses and investigate pathogen invasion and exposure mechanisms. M. mungi DNA was identified in 29% of nasal planum samples (n = 52), 56% of nasal rinses and swabs (n = 9), 53% of oral swabs (n = 19), 22% of urine samples (n = 23), 33% of anal gland tissue (n = 18), and 39% of anal gland secretions (n = 44). The occurrence of extremely low cycle threshold values obtained with qPCR in anal gland and nasal planum samples indicates that high levels of M. mungi can be found in these tissue types. Histological data were consistent with these results, suggesting that pathogen invasion occurs through breaks in the nasal planum and/or skin of the mongoose host, which are in frequent contact with anal gland secretions and urine during olfactory communication behavior. Lesions in the lung, when present, occurred only with disseminated disease. No environmental sources of M. mungi DNA could be found. We report primary environmental transmission of an MTC pathogen that occurs in association with social communication behavior. Organisms causing infectious disease evolve modes of transmission that exploit environmental and host conditions favoring pathogen spread and persistence. We report a novel mode of environmental infectious disease transmission that occurs in association with olfactory secretions (e.g., urine and anal gland secretions), allowing pathogen exposure to occur within and between social groups through intricate social communication behaviors of the banded mongoose host. The presence of M. mungi in these environmentally deposited secretions would effectively circumvent natural social barriers (e.g., territoriality), facilitating between-group pathogen transmission in the absence of direct physical contact, a rare occurrence in this highly territorial species. This work identifies an important potential mechanism of pathogen transmission of epidemiological significance in social species. We also provide evidence of a novel mechanism of pathogen transmission for the MTC complex, where pathogen movement in the environment and host exposure dynamics are driven by social behavior.


Cancer risks among iron and steel workers in Anshan, China, Part I: Proportional mortality ratio analysis.
A standardized proportional mortality ratio (SPMR) study of 8,887 deaths during 1980-1989 among male workers in a large integrated iron-steel complex in Anshan, China, was conducted to provide clues to occupational risk factors. Accidents and cancer accounted for a higher proportion of deaths among the iron-steel workers than among the general male population (SPMR = 1.21; 95% CI = 1.12-1.31 and 1.14; 95% CI = 1.10-1.18, respectively). Among all workers, SPMRs were significantly elevated for stomach, lung, and colorectal cancers (SPMR = 1.37, 1.37, 1.38, respectively), but not other cancers. Risks of stomach cancer appeared to be highest among workers employed in jobs with exposure to iron and coal dust, whereas significant increases in colorectal cancer were seen for loading and other dusty jobs and for administrative and sedentary jobs without dust exposure. Risks of lung cancer appeared increased for a variety of jobs throughout the complex, especially those with probable high levels of exposure to polycyclic hydrocarbons and asbestos. Risk of esophageal cancer was significantly elevated for fire-resistant brick makers, and risk of nonmalignant respiratory disease was significantly elevated for those employed as furnace workers, foundry workers, and fire-resistant brick makers.


Mirex incorporation in the environment: in situ decomposition of fire ant bait and its effects on two soil macroarthropods.
The decomposition rate of fire ant baits and the consequent leaching of the pesticide mirex from the bait were investigated for one year in three types of environments (i.e., on the ground, in the soil, and in the pond) by means of the nylon litter bag method. There was no significant difference in the decomposition rates between toxic and non-toxic baits. The bait proved to be stable and slow to decay. After one year of exposure in the field, about 75% of bait material remained in the bags that were deployed on the ground, 60% in the soil, and 25% in the pond. The removal of mirex from the bait was due to leaching from, and natural decay of the bait. The loss of mirex from the bait to the environment varied significantly among the three habitats. At the end of 12 months, mirex disappearance from baits exposed on the ground was 41.1%, in the soil 56.3%, and in the pond 83.9%. The rate of mirex loss was slower during fall and winter. The toxicities of the bait decomposed in situ for different lengths of time (12, 9, 6, 3, and 0 months) to the land isopod Armadillidium vulgare and the soil millipede oxidus gracilis were higher than the undecomposed baits. This indicated that weathered mirex baits left in the field have greater biological impact than freshly applied baits, at least on the two soil animals tested.