Erbin interacts with c-Cbl and promotes tumourigenesis and tumour growth in colorectal cancer by preventing c-Cbl-mediated ubiquitination and down-regulation of EGFR.
The epidermal growth factor receptor (EGFR) is implicated in many types of cancer, including colorectal cancer (CRC), and has become one of the most common candidates for targeted therapy. Here, we found that Erbin, a member of the leucine-rich repeat and PDZ domain (LAP) family, plays a key role in EGFR signalling. Erbin inhibited EGFR ubiquitination and stabilized the EGFR protein by interacting with c-Cbl. Moreover, the PDZ domain of Erbin was critical for the interaction between Erbin and c-Cbl and EGFR ubiquitination. Interestingly, Erbin expression was elevated in tumour samples from CRC patients, increased in advanced clinical stage disease and correlated with EGFR expression. In vivo studies using mouse xenograft models of CRC showed that Erbin promotes tumour growth, and that the effects of Erbin on tumour growth are mainly related to the regulatory effects of Erbin on EGFR. The azoxymethane (AOM)-induced colon carcinogenesis model in Erbin(ΔC) (/) (ΔC) mice, with the PDZ domain of Erbin deleted, demonstrated that the PDZ domain of Erbin and its regulation of EGFR signalling are necessary for the tumourigenesis and tumour growth of CRC. We found that Erbin promotes tumourigenesis and tumour growth in CRC by stabilizing EGFR. Our study sheds light on developing Erbin, especially its PDZ domain, as a potential target for CRC treatment.


Functional and histologic changes in the lacrimal gland after botulinum toxin injection.
The purpose of this study was to evaluate changes in tear volume, epidermal growth factor (EGF), and histology of the rabbit lacrimal gland after intraglandular application of botulinum toxin. Ten New Zealand rabbits were separated into 3 groups. Eight rabbits received botulinum toxin injection (2.5 U per 0.1 mL) into the right lacrimal gland and saline injection (0.1 mL) into the left lacrimal gland as a sham control. Two rabbits were untreated to serve as normal controls. Tear volume was measured using cotton thread every 2 weeks, and 4 rabbits were killed after 2 and 4 weeks. The lacrimal glands were surgically excised and sectioned or lysed for gene expression analysis. Epidermal growth factor expression and concentration were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay; morphometric and histologic analyses were performed. The rabbits that were killed 2 weeks after the injection showed decreased tear volume and increased EGF expression and concentration, but differences were not statistically significant. The rabbits that were killed 4 weeks after the injection exhibited similar results. When all 8 rabbits were considered, we detected a significant decrease in tear volume and increased EGF expression and concentration (P = 0.012, P = 0.011, and P = 0.012, respectively). The EGF level was not significantly correlated with the tear volume. There were no prominent histologic changes between the glands, and the lumen versus fibrosis ratio in the interlobular ducts showed no statistically significant difference. The use of botulinum toxin in patients with epiphora is effective, safe, and repeatable because it reduces tear volume and increases the EGF level to prevent corneal damage while causing no histologic changes.


Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.
Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population.


Uncertainty and agreement regarding the role of flow diversion in the management of difficult aneurysms.
The role of flow diversion in the management of aneurysms remains unknown. We sought to evaluate the community agreement regarding indications for flow diversion. A portfolio of 35 difficult aneurysm cases was sent to 40 clinicians with varying backgrounds and experience. Responders were asked whether they considered flow diversion a treatment option, whether other options were possible, whether recruitment in a randomized trial would be considered, and to select their final choice. Agreement was studied by using κ statistics. Decisions for flow diversion were more frequent (n = 300, 39%) than decisions to coil (n = 163, 21.2%), to observe (n = 121, 15.7%), to occlude the parent vessel (n = 102, 13.2%), or to clip (n = 66, 8.6%). Sidewall aneurysm morphology was associated with flow diversion as the final choice (P = .001). Interjudge agreement was fair at best (κ <0.3) for all cases and all judges, despite high certainty levels (range, 7.2-8.9 ± 2.0 on a 0-10 scale). Agreement was no better within specialties or with more experience. All patients were judged to have other treatment options. Judges were willing to offer trial participation in 417 of 741 (56.3%) scenarios, more frequently when the aneurysm was sidewall (P = .001) or in the anterior circulation (P = .028). Individuals did not agree regarding the indications for flow diversion. There is sufficient uncertainty to justify trials designed to protect patients from the potential risks of premature adoption of an innovation.


Effects of PEG hydrogel crosslinking density on protein diffusion and encapsulated islet survival and function.
The rational design of immunoprotective hydrogel barriers for transplanting insulin-producing cells requires an understanding of protein diffusion within the hydrogel network and how alterations to the network structure affect protein diffusion. Hydrogels of varying crosslinking density were formed via the chain polymerization of dimethacrylated PEG macromers of varying molecular weight, and the diffusion of six model proteins with molecular weights ranging from 5700 to 67,000 g/mol was observed in these hydrogel networks. Protein release profiles were used to estimate diffusion coefficients for each protein/gel system that exhibited Fickian diffusion. Diffusion coefficients were on the order of 10(-6)-10(-7) cm(2)/s, such that protein diffusion time scales (t(d) = L(2)/D) from 0.5-mm thick gels vary from 5 min to 24 h. Adult murine islets were encapsulated in PEG hydrogels of varying crosslinking density, and islet survival and insulin release was maintained after two weeks of culture in each gel condition. While the total insulin released during a 1 h glucose stimulation period was the same from islets in each sample, increasing hydrogel crosslinking density contributed to delays in insulin release from hydrogel samples within the 1 h stimulation period.


Determining RBE for development of lung fibrosis induced by fractionated irradiation with carbon ions utilizing fibrosis index and high-LET BED model.
Carbon ion radiotherapy (CIRT) with raster scanning technology is a promising treatment for lung cancer and thoracic malignancies. Determining normal tissue tolerance of organs at risk is of utmost importance for the success of CIRT. Here we report the relative biological effectiveness (RBE) of CIRT as a function of dose and fractionation for development of pulmonary fibrosis using well established fibrosis index (FI) model. Dose series of fractionated clinical quality CIRT versus conventional photon irradiation to the whole thorax were compared in C57BL6 mice. Quantitative assessment of pulmonary fibrosis was performed by applying the FI to computed tomography (CT) data acquired 24-weeks post irradiation. RBE was calculated as the ratio of photon to CIRT dose required for the same level of FI. Further RBE predictions were performed using the derived equation from high-linear energy transfer biologically effective dose (high-LET BED) model. The averaged lung fibrosis RBE of 5-fraction CIRT schedule was determined as 2.75 ± 0.55. The RBE estimate at the half maximum effective dose (RBEED50) was estimated at 2.82 for clinically relevant fractional sizes of 1-6 Gy. At the same dose range, an RBE value of 2.81 ± 0.40 was predicted by the high-LET BED model. The converted biologically effective dose (BED) of CIRT for induction of half maximum FI (BEDED50) was identified to be 58.12 Gy3.95. In accordance, an estimated RBE of 2.88 was obtained at the BEDED50 level. The LQ model radiosensitivity parameters for 5-fraction was obtained as αH = 0.3030 ± 0.0037 Gy-1 and βH = 0.0056 ± 0.0007 Gy-2. This is the first report of RBE estimation for CIRT with the endpoint of pulmonary fibrosis in-vivo. We proposed in present study a novel way to mathematically modeling RBE by integrating RBEmax and α/βL based on conventional high-LET BED conception. This model well predicted RBE in the clinically relevant dose range but is sensitive to the uncertainties of α/β estimates from the reference photon irradiation (α/βL). These findings will assist to eliminate current uncertainties in prediction of CIRT induced normal tissue complications and builds a solid foundation for development of more accurate in-vivo data driven RBE estimates.


Expression of immediate early genes in brain reward circuitries: Differential regulation by psychostimulant and opioid drugs.
Although some of the clinical manifestations of substance use disorders might be superficially similar, it is highly likely that different classes of abused drugs including opioids (heroin, morphine, and oxycodone, other opioids) and psychostimulants (cocaine and amphetamines) cause different neuroadaptations in various brain regions dependent in the distribution and concentration of their biochemical sites of actions. In fact, different molecular networks are indeed impacted by acute and chronic administration of addictive substances. Some of the genes whose expression is influenced by the administration of these substances are immediate-early genes (IEGs). IEGs include classes of low expression genes that can become very highly induced within seconds or minutes of activation by endogenous or exogenous stimuli. These IEGs might play important roles in activating target genes that regulate adaptations implicated in the behavioral manifestations diagnosed as addiction. Therefore, the purpose of this review is to provide an overview of recent data on the effects of psychostimulants and opioids on IEG expression in the brain. The review documents some contrasting effects of these classes of drugs on gene expression and indicates that further studies are necessary to identify the specific effects of each drug class when trying to predict clinical responses to therapeutic agents.


The effect of tree nut, peanut, and soy nut consumption on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials.
Although several studies have assessed the effects of nut consumption (tree nuts, peanuts, and soy nuts) on blood pressure (BP), the results are conflicting. The aim was to conduct a systematic review and meta-analysis of published randomized controlled trials (RCTs) to estimate the effect of nut consumption on BP. The databases MEDLINE, SCOPUS, ISI Web of Science, and Google Scholar were searched for RCTs carried out between 1958 and October 2013 that reported the effect of consuming single or mixed nuts (including walnuts, almonds, pistachios, cashews, hazelnuts, macadamia nuts, pecans, peanuts, and soy nuts) on systolic BP (SBP) or diastolic BP (DBP) as primary or secondary outcomes in adult populations aged ≥18 y. Relevant articles were identified by screening the abstracts and titles and the full text. Studies that evaluated the effects for <2 wk or in which the control group ingested different healthy oils were excluded. Mean ± SD changes in SBP and DBP in each treatment group were recorded for meta-analysis. Twenty-one RCTs met the inclusion criteria. Our findings suggest that nut consumption leads to a significant reduction in SBP in participants without type 2 diabetes [mean difference (MD): -1.29; 95% CI: -2.35, -0.22; P = 0.02] but not in the total population. Subgroup analyses of different nut types suggest that pistachios, but not other nuts, significantly reduce SBP (MD: -1.82; 95% CI: -2.97, -0.67; P = 0.002). Our study suggests that pistachios (MD: -0.80; 95% CI: -1.43, -0.17; P = 0.01) and mixed nuts (MD: -1.19; 95% CI: -2.35, -0.03; P = 0.04) have a significant reducing effect on DBP. We found no significant changes in DBP after the consumption of other nuts. Total nut consumption lowered SBP in participants without type 2 diabetes. Pistachios seemed to have the strongest effect on reducing SBP and DBP. Mixed nuts also reduced DBP.


CCL5 via GPX1 activation protects hippocampal memory function after mild traumatic brain injury.
Traumatic brain injury (TBI) is a prevalent head injury worldwide which increases the risk of neurodegenerative diseases. Increased reactive oxygen species (ROS) and inflammatory chemokines after TBI induces secondary effects which damage neurons. Targeting NADPH oxidase or increasing redox systems are ways to reduce ROS and damage. Earlier studies show that C-C motif chemokine ligand 5 (CCL5) has neurotrophic functions such as promoting neurite outgrowth as well as reducing apoptosis. Although CCL5 levels in blood are associated with severity in TBI patients, the function of CCL5 after brain injury is unclear. In the current study, we induced mild brain injury in C57BL/6 (wildtype, WT) mice and CCL5 knockout (CCL5-KO) mice using a weight-drop model. Cognitive and memory functions in mice were analyzed by Novel-object-recognition and Barnes Maze tests. The memory performance of both WT and KO mice were impaired after mild injury. Cognition and memory function in WT mice quickly recovered after 7 days but recovery took more than 14 days in CCL5-KO mice. FJC, NeuN and Hypoxyprobe staining revealed large numbers of neurons damaged by oxidative stress in CCL5-KO mice after mTBI. NADPH oxidase activity show increased ROS generation together with reduced glutathione peroxidase-1 (GPX1) and glutathione (GSH) activity in CCL5-KO mice; this was opposite to that seen in WT mice. CCL5 increased GPX1 expression and reduced intracellular ROS levels which subsequently increased cell survival both in primary neuron cultures and in an overexpression model using SHSY5Y cell. Memory impairment in CCL5-KO mice induced by TBI could be rescued by i.p. injection of the GSH precursor - N-acetylcysteine (NAC) or intranasal delivery of recombinant CCL5 into mice after injury. We conclude that CCL5 is an important molecule for GPX1 antioxidant activation during post-injury day 1-3, and protects hippocampal neurons from ROS as well as improves memory function after trauma.


Meditation training for people with amyotrophic lateral sclerosis: a randomized clinical trial.
Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population. A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life. Adults who received a diagnosis of ALS within 18 months were randomly assigned either to usual care or to an 8-week meditation training based on the original mindfulness-based stress reduction programme and tailored for people with ALS. Quality of life, assessed with the ALS-Specific Quality of Life Revised scale, represented the primary outcome, whilst secondary outcomes included anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, and specific quality of life domains. Participants were assessed at recruitment and after 2, 6 and 12 months. The efficacy of the treatment was assessed on an intention-to-treat basis of a linear mixed model. A hundred participants were recruited between November 2012 and December 2014. Over time, there was a significant difference between the two groups in terms of quality of life (β = 0.24, P = 0.015, d = 0.89). Significant differences between groups over time were also found for anxiety, depression, negative emotions, and interaction with people and the environment. An ALS-specific meditation programme is beneficial for the quality of life and psychological well-being of people with ALS.


Measuring Meaningful Benefit-Risk Tradeoffs to Promote Patient-Focused Drug Development in Prader-Willi Syndrome: A Discrete-Choice Experiment.
Background. Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder causing quality of life impairments such as insatiable hunger (hyperphagia) and obesity. We explored caregivers' willingness to assume treatment risk in exchange for reduced hyperphagia according to a PWS-validated observer-reported outcome measure. Methods. We partnered with PWS patient organizations to develop a discrete-choice experiment exploring caregivers' benefit-risk tradeoffs for emerging PWS treatments. The treatment benefit was a reduction in hyperphagia (as measured by a 0-, 5-, or 10-point change on the Hyperphagia Questionnaire for Clinical Trials [HQ-CT]). Treatment risks included weight gain (none, 5%, 10%), added risk of skin rash (none, 10%, 20%), and risk of liver damage (none, 1 in 1000, 10 in 1000). Preference models were estimated using mixed logistic regression and maximum acceptable risk. We explored differences in preferences across familial caregivers of patients with and without hyperphagia. Results. Four hundred sixty-eight caregivers completed the online survey. The majority of caregivers reported that patients experienced hyperphagia (68%) and half of patients experienced obesity (52%). Caregivers of patients without hyperphagia were willing to accept greater weight gain (16.4% v. 8.1%, P = 0.004) and a higher risk of skin rash (11.7% v. 6.2% P = 0.008) as compared to caregivers of patients with hyperphagia. Caregivers of patients with hyperphagia would accept a higher risk of liver damage as compared to caregivers of patients without hyperphagia (11.9 out of 1000 v. 6.4 out of 1000, P = 0.04). Conclusions. This research demonstrates that caregivers are willing to accept risk in exchange for a five-point improvement on the HQ-CT, a smaller marginal improvement than had been previously classified as meaningful. Patient experience with hyperphagia is a modifier in how much risk caregivers will accept.


Subjective health complaints in older adolescents are related to perceived stress, anxiety and gender - a cross-sectional school study in Northern Sweden.
Negative trends in adolescent mental and subjective health are a challenge to public health work in Sweden and worldwide. Self-reported mental and subjective health complaints such as pain, sleeping problems, anxiety, and various stress-related problems seem to have increased over time among older adolescents, especially girls. The aim of this study has therefore been to investigate perceived stress, mental and subjective health complaints among older adolescents in Northern Sweden. Data were derived from a cross-sectional school-based survey with a sample consisting of 16-18 year olds (n = 1027), boys and girls, in the first two years of upper secondary school, from different vocational and academic programmes in three public upper secondary schools in a university town in northern Sweden. Prevalence of perceived stress, subjective health complaints, general self-rated health, anxiety, and depression were measured using a questionnaire, including the Hospital Anxiety and Depression Scale (HADS). A large proportion of both girls and boys reported health complaints and perceived stress. There was a clear gender difference: two to three times as many girls as boys reported subjective health complaints, such as headache, tiredness and sleeping difficulties and musculoskeletal pain, as well as sadness and anxiety. High pressure and demands from school were experienced by 63.6% of girls and 38.5% of boys. Perceived stress in the form of pressure and demands correlated strongly with reported health complaints (r = 0.71) and anxiety (r = 0.71). The results indicate that mental and subjective health complaints are prevalent during adolescence, especially in girls, and furthermore, that perceived stress and demands may be important explanatory factors. Future studies should pay attention to the balance between gender-related demands, perceived control and social support, particularly in the school environment, in order to prevent negative strain and stress-related ill-health. The gender gap in subjective adolescent health needs to be further explored.


Lower Radiation Dosing in Cardiac Computed Tomographic Angiography: the CONVERGE Registry.
Intro: Coronary artery disease is the leading cause for morbidity and mortality. Tools have been developed to accurately diagnose and evaluate coronary artery disease. Coronary computed tomographic angiography (CCTA) scans provide detailed imaging along with analysis to in order to deliver precise analysis and prognostic information. We sought to evaluate the radiation doses of the 256 detector CT scanner to a 64 slice scanner across a similar profile of patients. Methods: Consecutive patients were screened, enrolled, and consented for the Converge Registry study, in accordance with the Institutional Review Board (IRB) approved protocol. 110 patients underwent CCTA using the GE Revolution 256 detector CT scanner. We matched patients by age, gender and body mass index (BMI) who underwent 64 slice CT scanning. Results: We compared 110 patients in each group. We found that mean dose length product (DLP, presented also in the tables below in millisieverts (mSv)) was significantly lower in the Revolution 256 detector group compared to the 64 slice control group (p<0.05). The radiation dose was reduced 32% with use of Revolution 256 detector scanner for BMI between 18.5 and 24.9 (DLP = 111.2 vs 76.1; 1.56 vs 1.07 mSv; p<0.05). For each BMI subgroup, there was a significant decrease in dose. Regression analysis found that with the increase in BMI both scanners experienced a significant increase in DLP. Conclusion: We are able to demonstrate that the 256 slice CT scanner is able to provide CCTA scans at significantly lower radiation doses compared to the 64 row scanner at different BMI groups, with all other variables accounted for. Lower radiation exposures along with lower contrast requirements can provide quality imaging with high diagnostic accuracy and less risk to the patient.


Association of Kidney Function Tests with a Cardio-Ankle Vascular Index in Community-Dwelling Individuals with a Normal or Mildly Decreased Estimated Glomerular Filtration Rate.
Background and objectives: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). Previous studies reported controversial results about the independence of CKD as a risk factor for atherosclerosis. In this study, we tried to determine whether the estimated glomerular filtration rate (eGFR) and other renal function tests are independent factors associated with arterial stiffness in community-dwelling individuals with a normal (≥90) or slightly decreased eGFR (60-90). Materials and Methods: Data of 164 community individuals were analyzed, and demographic information, related disease history, atherosclerosis risk factors, certain laboratory tests, the estimated eGFR, and urine albumin creatinine ratio (UACR) were recorded for each individual. Results: The age, systolic blood pressure (SBP), hypertension (HTN), and cardio-ankle vascular index (CAVI) significantly differed between individuals with a normal and those with a slightly decreased eGFR. Blood urea nitrogen (BUN), glycated hemoglobin (HBA1c), and the eGFR significantly differed between the high- and low-CAVI groups and were also significantly correlated with the CAVI. The relationship between the eGFR and CAVI was shown to be independent of other atherosclerosis risk factors in a multiple linear regression model. Conclusions: We concluded that evaluations of the eGFR, HTN, body-mass index, and SBP can be used in a model for arterial stiffness risk assessments for community-dwelling individuals with a normal or slightly decreased eGFR.


Regional Examination for Nurse Registration, Commonwealth Caribbean.
In 1990, a Regional Examination for Nurse Registration was approved by the Conference of Ministers Responsible for Health in the Commonwealth Caribbean. The examination allows for standardization and improvement of nursing education, as well as reciprocity and ease-of-movement for Registered Nurses among the countries of the region. A Planning Committee and a Blueprint Committee were established to develop the examination process. Committee membership included the Principal/Chief Nursing Officers, Nurse Tutors, and General Nursing Council representatives of each country, as well as educators from the two universities of the region. The accepted model, based on mutually agreed competencies for the Registered Nurse to practice in the region, forms the basis for the elaboration of the blueprint and the administrative manuals. The treatment of test items, assembling and conducting the examinations, which consist of four papers, as well as scoring the examination results, and notifying students of the results, are the responsibility of each General Nursing Council. The 13 General Nursing Councils with responsibility for Schools of Nursing meet annually as a regional committee to prepare the examinations, using a different country for each meeting; countries are rotated alphabetically. There is no permanent site for the administration of the examination. Membership to the regional committee, known as the Regional General Nursing Councils (RGNCs), is for 3 years. This staggering of membership allows for continuity.


Daylight saving time can decrease the frequency of wildlife-vehicle collisions.
Daylight saving time (DST) could reduce collisions with wildlife by changing the timing of commuter traffic relative to the behaviour of nocturnal animals. To test this idea, we tracked wild koalas (Phascolarctos cinereus) in southeast Queensland, where koalas have declined by 80% in the last 20 years, and compared their movements with traffic patterns along roads where they are often killed. Using a simple model, we found that DST could decrease collisions with koalas by 8% on weekdays and 11% at weekends, simply by shifting the timing of traffic relative to darkness. Wildlife conservation and road safety should become part of the debate on DST.


Biochemical changes in the pancreas of rats with chronic renal failure.
Chronic renal failure (CRF) was produced in female Sprague-Dawley rats by 7/8 nephrectomy. Creatinine clearance was depressed significantly (P less than 0.005) and blood urea nitrogen (BUN) increased in CRF rats when compared with the sham-operated (S) controls. CRF caused no apparent change in body weight but significantly increased pancreatic weight as well as increased DNA, RNA, and protein content. Pancreatic protein-to-DNA and RNA-to-DNA ratios were also found to be significantly higher in CRF rats than in the S controls. Trypsin-like activity and immunoreactive cationic trypsinogen levels were both increased in the pancreas of CRF rats, but not in their serum. On the other hand, protease inhibitory activity in the pancreas and serum was significantly decreased by CRF. The ability of the dispersed pancreatic acini isolated from CRF rats to incorporate [3H]-leucine into protein, in the absence and presence of 0.25 nM cholecystokinin octapeptide (CCK-8), was found to be lower than in the controls. Furthermore, discharge of both trypsinogen and chymotrypsinogen induced by CCK-8 was markedly reduced from acini of CRF rats as compared with the S controls. In contrast, lactate dehydrogenase (LDH) was released more readily from pancreatic acini of CRF. It is concluded that mild CRF produces hyperplasia and hypertrophy of the pancreas and lowers the responsiveness of acini to CCK-8 with respect to synthesis and secretion of proteins.


Coordinated regulation of multiple flagellar motors by the Escherichia coli chemotaxis system.
Escherichia coli cells swim toward a favorable environment by chemotaxis. The chemotaxis system regulates the swimming behavior of the bacteria by controlling the rotational direction of their flagellar motors. Extracellular stimuli sensed by chemoreceptors are transduced to an intracellular signal molecule, phosphorylated CheY (CheY-P), that switches the rotational direction of the flagellar motors from counterclockwise (CCW) to clockwise (CW) or from CW to CCW. Many studies have focused on identifying the proteins involved in the chemotaxis system, and findings on the structures and intracellular localizations of these proteins have largely elucidated the molecular pathway. On the other hand, quantitative evaluations of the chemotaxis system, including the process of intracellular signaling by the propagation of CheY-P and the rotational switching of flagellar motor by binding of CheY-P molecules, are still uncertain. For instance, scientific consensus has held that the flagellar motors of an E. coli cell switch rotational direction asynchronously. However, recent work shows that the rotational switching of any two different motors on a single E. coli cell is highly coordinated; a sub-second switching delay between motors is clearly correlated with the relative distance of each motor from the chemoreceptor patch located at one pole of the cell. In this review of previous studies and our recent findings, we discuss the regulatory mechanism of the multiple flagellar motors on an individual E. coli cell and the intracellular signaling process that can be inferred from this coordinated switching.


Military Deployments and Mental Health Utilization Among Spouses of Active Duty Service Members.
Since the onset of the wars in Iraq and Afghanistan attention has increased on the importance of mental health with military service members. An integral component, although far less studied, are the ties between mental health and military spouses. Military deployments place considerable stress on military families. This study analyzed the mental health utilization of military spouses of active duty service members assigned to an aircraft carrier between 2011 and 2014. A negative binomial generalized estimating equation was used to examine the rate of change in mental health utilization over time against various deployment phases. Associations emerged between select deployment phases (i.e., deployment 1, between deployments, deployment 2) with increases in mental health utilization ranging between 12% and 20% for military spouses. This study demonstrated, for military spouses, the in between deployment phase has associations with mental health utilization rates similar to actual deployed periods. As a result, military leaders should continue to monitor the well-being of their service members' families throughout all deployment phases.


The association between parenting and attachment security is moderated by a polymorphism in the mineralocorticoid receptor gene: evidence for differential susceptibility.
Maternal sensitive responsiveness and extreme insensitivity only partly explain the variance in attachment security. Differences in attachment security may well be rooted in the interplay of genetic variations and environmental factors. The association between parenting (observed sensitive responsiveness and extreme insensitivity) and attachment security (assessed with the Strange Situation Procedure) was hypothesized to be moderated by genes involved in the regulation of the stress response: the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) genes. A significant G×E interaction was found: infants carrying the minor MR allele (G) were significantly more securely attached if their mothers showed more sensitive responsiveness and significantly less securely attached if their mothers showed more extremely insensitive behaviors. These associations were not significant for carriers of the AA genotype of MR. Findings are discussed from a differential susceptibility perspective.


Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats.
Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress.


Association between the body mass index, waist circumference, and body fat percentage with erosive esophagitis in adults with obesity after sleeve gastrectomy.
Background: High anthropometric indexes before sleeve gastrectomy (SG) are associated with an increased risk of erosive esophagitis (EE) in bariatric surgery candidates. Reasons that explain how these indexes influence the development of esophageal pathology after surgery remains unclear. Objectives: To assess the association between the body mass index (BMI), waist circumference (WC), and body fat percentage (BFP) with the development of EE in adults with obesity three months after SG. Setting: Clínica Avendaño, Lima, Peru. Methods: Retrospective cohort using a database including adults with obesity who underwent SG during 2017-2020. All the patients included had an endoscopy before and after the surgery. Sociodemographic, clinical and laboratory characteristics were compared according to BMI, WC and BFP, as well as by the development of de novo esophagitis. The association was evaluated by crude and adjusted generalized linear models with the log-Poisson family. Results: From a total of 106 patients, 23 (21.7%) developed EE. We did not find significant differences in sociodemographic, clinical and laboratory characteristics between patients with de novo EE compared to those who did not develop EE. After adjustment, BMI (aRR = 0.59, 95% CI = 0.18-1.40), BFP (aRR = 0.41, 95% CI = 0.15-1.19) and WC (aRR = 0.91, 95% CI = 0.69-1.16) were not associated with the development of EE three months post SG. Conclusions: We found no association between preoperative anthropometric indexes and the development of de novo EE; therefore, morbid obesity should not be a criterion to exclude the patients to undergo SG as primary surgery because of the risk of developing EE.


Insect Responses to Linearly Polarized Reflections: Orphan Behaviors Without Neural Circuits.
The e-vector orientation of linearly polarized light represents an important visual stimulus for many insects. Especially the detection of polarized skylight by many navigating insect species is known to improve their orientation skills. While great progress has been made towards describing both the anatomy and function of neural circuit elements mediating behaviors related to navigation, relatively little is known about how insects perceive non-celestial polarized light stimuli, like reflections off water, leaves, or shiny body surfaces. Work on different species suggests that these behaviors are not mediated by the "Dorsal Rim Area" (DRA), a specialized region in the dorsal periphery of the adult compound eye, where ommatidia contain highly polarization-sensitive photoreceptor cells whose receptive fields point towards the sky. So far, only few cases of polarization-sensitive photoreceptors have been described in the ventral periphery of the insect retina. Furthermore, both the structure and function of those neural circuits connecting to these photoreceptor inputs remain largely uncharacterized. Here we review the known data on non-celestial polarization vision from different insect species (dragonflies, butterflies, beetles, bugs and flies) and present three well-characterized examples for functionally specialized non-DRA detectors from different insects that seem perfectly suited for mediating such behaviors. Finally, using recent advances from circuit dissection in Drosophila melanogaster, we discuss what types of potential candidate neurons could be involved in forming the underlying neural circuitry mediating non-celestial polarization vision.


Cervical positional effects on snoring and apneas.
We examined the effects of cervical position on the Obstructive Sleep Apnea Syndrome (OSAS) through the use of a custom-designed cervical pillow which promoted neck extension. Twelve subjects with OSAS were recruited from a tertiary sleep disorder clinic population. Of the twelve subjects, three had mild cases of OSAS, four had moderate cases, and the remaining five had severe cases. The subjects used their usual pillows during two consecutive recorded baseline nights in our laboratory. The subjects then used the cervical pillow for five days at home, and returned for two consecutive recorded nights at our laboratory while using the cervical pillow. During the nights in our laboratory, the subjects completed questionnaires, were videotaped to record head and body position, and had their breathing parameters recorded during sleep. Subjects with mild OSAS cases had a non-significant improvement in the severity of their snoring and a significant improvement in their respiratory disturbance index with the cervical pillow, while subjects with moderate OSAS cases showed no improvement in these parameters. Subjects with severe OSAS cases showed slight improvement in some measures of their abnormal respiratory events during the experimental period.


Antenatal risk factors for child maltreatment: Linkage of data from a birth cohort study to child welfare records.
Understanding the risk factors for child maltreatment is critical to efforts to reduce its prevalence. This study investigated the association between characteristics and circumstances of mothers during pregnancy and the subsequent identification of concerns about child maltreatment. The study drew on two data sets: (i) data from questionnaires administered to the expectant mothers of 11,332 children born in a deprived multi-ethnic local authority in England between 2007 and 2011, for a birth cohort study, and (ii) administrative data on children referred to child welfare services. The linkage of these two pre-existing data sets enabled the prospective study of risk factors for child maltreatment. A range of factors captured during the antenatal period were associated with an increased likelihood of subsequent recorded child maltreatment concerns, including: younger maternal age (HR=0.96; p < .001), lower maternal education level (HR=1.36; p < .001), maternal mental illness (HR=1.17; p = .001), maternal smoking in pregnancy (HR=1.69; p < .001), single motherhood (HR=1.41; p = .022), larger family size (HR=1.13; p < .001), multiple deprivation (HR=1.01; p = .011), social housing (HR=1.72; p < .001), paternal unemployment (HR=1.79; p < .001), and the receipt of means-tested welfare benefits (HR=1.43; p < .001). A greater total number of risk factors during pregnancy also increased the risk of subsequent maltreatment concerns (HR=1.45; p < .001). The identification of multiple risk factors in this study supports claims that single targeted interventions are unlikely to be successful in preventing or reducing child maltreatment due to its multifactorial nature, and that multidimensional interventions are required.


Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes.
E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD. This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers. The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ≥18 years of age who had smoked ≥15 cigarettes/day for ≥2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels. Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend β = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (-0.529 m/s; 95% CI: -0.946 to -0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe. TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298).


What is the Sugar Code?
A code is defined by the nature of the symbols, which are used to generate information-storing combinations (e. g. oligo- and polymers). Like nucleic acids and proteins, oligo- and polysaccharides are ubiquitous, and they are a biochemical platform for establishing molecular messages. Of note, the letters of the sugar code system (third alphabet of life) excel in coding capacity by making an unsurpassed versatility for isomer (code word) formation possible by variability in anomery and linkage position of the glycosidic bond, ring size and branching. The enzymatic machinery for glycan biosynthesis (writers) realizes this enormous potential for building a large vocabulary. It includes possibilities for dynamic editing/erasing as known from nucleic acids and proteins. Matching the glycome diversity, a large panel of sugar receptors (lectins) has developed based on more than a dozen folds. Lectins 'read' the glycan-encoded information. Hydrogen/coordination bonding and ionic pairing together with stacking and C-H/π-interactions as well as modes of spatial glycan presentation underlie the selectivity and specificity of glycan-lectin recognition. Modular design of lectins together with glycan display and the nature of the cognate glycoconjugate account for the large number of post-binding events. They give an entry to the glycan vocabulary its functional, often context-dependent meaning(s), hereby building the dictionary of the sugar code.


Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation.
Elg1, the major subunit of a Replication Factor C-like complex, is critical to ensure genomic stability during DNA replication, and is implicated in controlling chromatin structure. We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication. Measurement of Okazaki fragment length and the micrococcal nuclease sensitivity of newly replicated DNA revealed a defect in nucleosome organization in the absence of Elg1. Using a proteomic approach to identify Elg1 binding partners, we discovered that Elg1 interacts with Rtt106, a histone chaperone implicated in replication-coupled nucleosome assembly that also regulates transcription. A central role for Elg1 is the unloading of PCNA from chromatin following DNA replication, so we examined the relative importance of Rtt106 and PCNA unloading for chromatin reassembly following DNA replication. We find that the major cause of the chromatin organization defects of an ELG1 mutant is PCNA retention on DNA following replication, with Rtt106-Elg1 interaction potentially playing a contributory role.


Emended descriptions of the genus Micrococcus, Micrococcus luteus (Cohn 1872) and Micrococcus lylae (Kloos et al. 1974).
Nine yellow-pigmented, spherical bacterial strains isolated from a medieval wall painting (strain D7), from indoor air (strains 3, 6, 7, 13C2, 38, 83 and 118) and from an activated-sludge plant (strain Ballarat) were classified by a polyphasic approach. Analyses of the 16S rRNA gene sequences of three representatives (strains D7, 118 and Ballarat) indicated that they all belong to the genus Micrococcus. The three isolates shared the highest sequence similarities with Micrococcus luteus DSM 20030T (97.9-98%), Micrococcus antarcticus AS 1.2372T (97.9-98.3%) and Micrococcus lylae DSM 20315T (97.5-97.9%). DNA-DNA reassociation studies clearly demonstrated that all nine isolates belong to the species M. luteus. However, neither their chemotaxonomic features nor their physiological and biochemical properties were consistent with those of M. luteus DSM 20030T. In contrast to M. luteus DSM 20030T, all isolates investigated possessed MK-8(H2) as the major respiratory quinone, and strain Ballarat had an A4alpha peptidoglycan type. On the basis of analyses of their Fourier transform-infrared spectroscopy spectra, isolates D7, 3, 6, 7, 13C2, 38, 83 and 118 could be grouped into a single cluster separate from M. luteus DSM 20030T, strain Ballarat and M. lylae DSM 20315T. In addition, all these isolates could be distinguished from M. luteus DSM 20030T by their ability to assimilate D-maltose, D-trehalose, DL-3-hydroxybutyrate, DL-lactate, pyruvate and L-histidine and to hydrolyse casein. Strains D7, 3, 6, 7, 13C2, 38, 83 and 118 differed from both M. luteus DSM 20030T and strain Ballarat by their ability to assimilate acetate, L-phenylalanine, L-serine and phenylacetate. Furthermore, REP-PCR fingerprinting yielded one common band for these strains, whereas this band was not observed for M. luteus DSM 20030T, strain Ballarat or M. lylae DSM 20315T. On the basis of these data, the species M. luteus can be divided into three biovars that are distinguished by several chemotaxonomic and biochemical traits: biovar I, represented by M. luteus DSM 20030T; biovar II, represented by strains D7 (= DSM 14234 = CCM 4959), 3, 6, 7, 13C2, 38, 83 and 118; and biovar III, represented by strain Ballarat (= DSM 14235 = CCM 4960). On the basis of the results generated in this study, emended descriptions of the genus Micrococcus and the species M. luteus and M. lylae are given.


New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes.
To elucidate etiologies, treatment, functional and neurocognitive outcomes of children with new-onset refractory status epilepticus. A single-center retrospective study. A tertiary care children's hospital. All patients between 1 month and 21 years old admitted with new-onset refractory status epilepticus between January 2004 and July 2017. None. Clinical presentation, laboratory data, imaging studies, and treatments were collected during hospitalization. Outcomes were assessed at hospital discharge and follow-up in the outpatient neurology clinic based on functional and neurocognitive outcomes as well as development of epilepsy. A total of 674 unique patients presented with status epilepticus of which 40 had new-onset refractory status epilepticus. Patients were classified into either refractory status epilepticus or super-refractory status epilepticus. The etiology of most children with new-onset refractory status epilepticus remained cryptogenic. The most common identified etiology was viral (20%). None of the patients had a contributory positive neuronal antibody test. Several treatments were tried including immunotherapy which was used in half of the patients. Five patients died (12.5%) during the acute phase of their disease, with four lost to follow-up. Twenty out of the remaining 31 patients (65%) developed epilepsy and 18 (58%) had persistent neurocognitive impairment. There was no statistical significant difference in various outcome measures and various etiologies, patients' characteristics, and treatments. In this single-center cohort, more than half of the children with new-onset refractory status epilepticus did not have an identifiable etiology. Unlike adult patients, the presence of positive neuronal antibody syndrome was rare. There was no difference in outcome between those with or without an identifiable etiology. As expected, patients with super-refractory status epilepticus had worse functional and neurocognitive outcomes. More standardized diagnostic and treatment algorithms are needed along with prospective multicenter studies.


Control of an outbreak of pandrug-resistant Acinetobacter baumannii colonization and infection in a neonatal intensive care unit.
To investigate the potential reservoir and mode of transmission of pandrug-resistant (PDR) Acinetobacter baumannii in a 7-day-old neonate who developed PDR A. baumannii bacteremia that was presumed to be the iceberg of a potential outbreak. Outbreak investigation based on a program of prospective hospital-wide surveillance for nosocomial infection. A 24-bed neonatal intensive care unit in a 2,200-bed major teaching hospital in Taiwan that provides care for critically ill neonates born in this hospital and those transferred from other hospitals. Samples from 33 healthcare workers' hands and 40 samples from the environment were cultured. Surveillance cultures of anal swab specimens and sputum samples were performed for neonates on admission to the neonatal intensive care unit and every 2 weeks until discharge. The PDR A. baumannii isolates, defined as isolates resistant to all currently available systemic antimicrobials except polymyxin B, were analyzed by pulsed-field gel electrophoresis. Control measures consisted of implementing contact isolation, reinforcing hand hygiene adherence, cohorting of nurses, and environmental cleaning. One culture of an environmental sample and no cultures of samples from healthcare workers' hands grew PDR A. baumannii. The positive culture result involved a sample obtained from a ventilation tube used by the index patient. During the following 2 months, active surveillance identified PDR A. baumannii in 8 additional neonates, and isolates from 7 had the same electrokaryotype. Of the 9 neonates colonized or infected with PDR A. baumannii, 1 died from an unrelated condition. Reinforcement of infection control measures resulted in 100% adherence to proper hand hygiene protocol. The outbreak was stopped without compromising patient care. In the absence of environmental contamination, transient hand carriage by personnel who cared for neonates colonized or infected with PDR A. baumannii was suspected to be the mode of transmission. Vigilance, prompt intervention and strict adherence to hand hygiene protocol were the key factors that led to the successful control of this outbreak. Active surveillance appears to be an effective measure to identify potential transmitters and reservoirs of PDR A. baumannii.


Henneguya ghaffari sp. n. (Myxozoa: Myxosporea), infecting the Nile perch Lates niloticus (Teleostei: Centropomidae).
Light microscopical description is presented for a new myxozoan species, Henneguya ghaffari, which infects the Nile perch Lates niloticus (Linnaeus, 1758) in Lake Wadi El-Raiyan in Egypt. The spore is characterized by a triangular thickening at the base of the caudal processes. The relatively long caudal processes run adherent to each other for two-thirds of their length, then bifurcate to very fine processes. Prevalence of infection was 34.6% and peaked during winter and early spring. The infection was concentrated along the intestinal tract, and in severe cases gills and gill rakers were also infected. Histology revealed that, in contrast to findings of previously published works on related species, intralamellar plasmodia did not develop inside the blood capillaries of the gills. Intestinal plasmodia were very pathogenic due to their large number and size. These plasmodia caused atrophy of the muscularis layer, and replaced and distended the submucosal and mucosal layers. The validity of some Henneguya species in Africa is discussed.


Brain imaging of attentional networks in normal and pathological states.
The ability to image the human brain has provided a new perspective for neuropsychologists in their efforts to understand, diagnose, and treat insults to the human brain that might occur as the result of stroke, tumor, traumatic injury, degenerative disease, or errors in development. These new findings are the major theme of this special issue. In our article, we consider brain networks that carry out the functions of attention. We outline several such networks that have been studied in normal and pathological states. These include networks for orienting to sensory stimuli, for maintaining the alert state, and for orchestrating volitional control. There is evidence that these networks have a certain degree of anatomical and functional independence, but that they also interact in many practical situations. Damage to each of these networks, irrespective of the source, produces distinctive neuropsychological deficits. We consider the links between the etiology of the injury and changes in cognition and behavior and examine the role of brain imaging in the study of rehabilitation.


A pilot study of atomoxetine in young children with attention-deficit/hyperactivity disorder.
The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds. Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit. Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p < 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p < 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p < 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children's Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p < 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p < 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy. Atomoxetine was generally effective for reducing core ADHD symptoms in the 5 and 6 year olds in this open-label study.


Completing a worldwide picture: preliminary evidence of lead exposure in a scavenging bird from mainland Australia.
Lead toxicity from ammunition has been shown to be a threat to scavenging birds across the globe. Despite decades of research in Europe, North and South America, Asia and Africa, there have been no studies to investigate this phenomenon in Australia despite that continent having many species of scavenging birds and widespread shooting practices. We present preliminary evidence of lead exposure in Australia's largest bird of prey, the wedge-tailed eagles (Aquila audax) through analysis of bone and eggshell samples from south-western Australia. From 11 bone samples, three birds (27%) had lead levels exceeding literature thresholds for elevated levels (>6.75 ppm). From 36 eggshell samples, no samples had lead levels >0.5 ppm, suggesting some limitations for this matrix as an indicator of lead exposure. Isotope ratios suggested ammunition as a likely source of the lead found in bone samples with elevated lead levels but other potential sources of lead require further investigation. Our preliminary results demonstrate that lead exposure is occurring in scavenging birds in Australia, and like the rest of the world, is likely to be derived from ammunition. This study supports an urgent call for further research into this worldwide phenomenon in Australia.


Positive effect of a simplified diet on blood phenylalanine control in different phenylketonuria variants, characterized by newborn BH4 loading test and PAH analysis.
Until today, the mainstay of phenylketonuria (PKU) treatment is a phenylalanine (Phe)-restricted diet. Strict dietary treatment decreases flexibility and autonomy and still has a major impact on patients and their families. Compliance is often poor, particularly in adolescence. The aim of this study was to investigate the effect of the intake of fruits and vegetables containing Phe less than 100 mg/100g ('simplified diet'), as recommended by WHO for all individuals, instead of classical totally restricted diet on the course and treatment control of the disease in a well-characterized PKU cohort (n=80). All individual blood Phe measurements of each patient (1992-2009) were statistically analyzed before and after diet switch. Epidemiological data, age at diagnosis, PAH mutations, BH(4) responsiveness, as well as Phe control measurements and detailed diet information were tabulated in a local database. 62.5% had BH4 loading test and 40% had PAH analysis; 50/80 switched from classical to simplified diet, including 26 classical PKU, 13 moderate PKU, 7 mild PKU and 4 mild hyperphenylalaninemia (HPA). Median Phe levels on a simplified diet did not differ significantly to the median Phe levels on classical diet in all disease groups. Our results indicate that a simplified diet has no negative effect on blood Phe control in patients with hyperphenylalaninemia, independent of severity of the phenotype or the age at diet switch, over the period of 3 years. Thus, a simpler approach to dietary treatment of PKU available to all HPA patients is more likely to be accepted and adhered by patients and might also increase quality of life.


Designing a laser scanning picoprojector. Part 2: laser-safety-related issues.
Laser scanning picoprojectors present a new challenge in the field of laser safety with methods of calculating accessible emission limits still in their infancy. We present a laser safety analysis and a calculation of an example picoprojector. We show that, due to its scanning operation, a picoprojector should be considered an extended laser source, and we also show that a picoprojector with two separate one-axis microelectromechanical systems mirrors offers a higher safe power limit than a projector with a single scanning mirror. Finally, a safety analysis is done under conditions of mirror failure. We show that, if the projector fails to scan in just one of the axes, the ocular hazard rises sharply, highlighting the need for a fail-safe system to be built into laser scanning picoprojectors.


Multiplex real-time PCR using temperature sensitive primer-supplying hydrogel particles and its application for malaria species identification.
Real-time PCR, also called quantitative PCR (qPCR), has been powerful analytical tool for detection of nucleic acids since it developed. Not only for biological research but also for diagnostic needs, qPCR technique requires capacity to detect multiple genes in recent years. Solid phase PCR (SP-PCR) where one or two directional primers are immobilized on solid substrates could analyze multiplex genetic targets. However, conventional SP-PCR was subjected to restriction of application for lack of PCR efficiency and quantitative resolution. Here we introduce an advanced qPCR with primer-incorporated network (PIN). One directional primers are immobilized in the porous hydrogel particle by covalent bond and the other direction of primers are temporarily immobilized at so-called 'Supplimers'. Supplimers released the primers to aqueous phase in the hydrogel at the thermal cycling of PCR. It induced the high PCR efficiency over 92% with high reliability. It reduced the formation of primer dimers and improved the selectivity of qPCR thanks to the strategy of 'right primers supplied to right place only'. By conducting a six-plex qPCR of 30 minutes, we analyzed DNA samples originated from malaria patients and successfully identified malaria species in a single reaction.


Landscape of NAT2 polymorphisms among breast cancer.
The prevalence of phenotypes of Arylamine N-acetyltransferase-2(NAT2) gene (i.e. fast, intermediate and slow acetylators) among ethnic groups, as well as the association studies regarding NAT2 polymorphisms and risk of breast cancer produced inconsistent results. This meta-analysis aimed to clarify whether the selected NAT2 phenotypes have an effect on the susceptibility to breast cancer. After aggregating the frequencies of fast, intermediate and slow phenotypes of NAT2 in breast cancer subjects, the odds ratio and relevant 95% confidence intervals were examined using combined data from all published 36 articles. Overall, our results did not produce statistical significance for the proposed association, suggesting that there is no association between the selected phenotypes of NAT2 polymorphisms and breast cancer. In subgroup analyses, it was revealed that, as compared with the fast phenotype, intermediate acetylator is protective of the vulnerable White population to breast cancer. In addition, an obvious ethnic/geographic difference was found in the prevalence of fast, intermediate and slow acetylators among world-wide populations. Although ethnic and geographic differences in NAT2 polymorphisms were present, this was not associated with the risk of breast cancer in general. Intermediate acetylator is protective for particular ethnic groups, a finding which should be carefully viewed and confirmed in the future studies.


Vortex statistics in turbulent rotating convection.
The vortices emerging in rotating turbulent Rayleigh-Bénard convection in water at Rayleigh number Ra=6.0×10{8} are investigated using stereoscopic particle image velocimetry and by direct numerical simulation. The so-called Q criterion is used to detect the vortices from velocity fields. This criterion allows distinguishing vorticity- and strain-dominated regions in the flow by decomposing the velocity gradient tensor into symmetric and antisymmetric parts. Vortex densities, mean vortex radii and mean vortex circulations are calculated at two horizontal cross-sections of the cylindrical flow domain and at several rotation rates, described by the Taylor number which takes values between 3.0×10{8} and 7.7×10{10} . Separate statistics are calculated for cyclonic and anticyclonic vortices. Vortex densities and mean vortex radii are mostly independent of the Taylor number except very close to the bottom and top plates where more vortices are detected when the Taylor number is raised (rotation increases). The vortex population close to the plate consists mostly of cyclones while further into the bulk of the domain a similar amount of cyclones and anticyclones is found. The cyclonic vortices contain more circulation than the anticyclones. The same vortex analysis of the simulation results at additional vertical positions revealed that the vortices are formed in a boundary layer on the plate with a thickness of approximately two Ekman lengths.


Oral morphine versus ibuprofen administered at home for postoperative orthopedic pain in children: a randomized controlled trial.
Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain. We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale - Revised, for the first dose. Secondary outcomes included additional analgesic requirements, adverse effects, unplanned health care visits and pain scores for doses 2 to 8. We analyzed data for 77 participants in each of the morphine and ibuprofen groups. Both interventions decreased pain scores with no difference in efficacy. The median difference in pain score before and after the first dose of medication was 1 (interquartile range 0-1) for both morphine and ibuprofen (p = 0.2). For doses 2 to 8, the median differences in pain score before and after the dose were not significantly different between groups. Significantly more participants taking morphine reported adverse effects (45/65 [69%] v. 26/67 [39%], p < 0.001), most commonly drowsiness (31/65 [48%] v. 15/67 [22%] in the morphine and ibuprofen groups, respectively; p = 0.003). Morphine was not superior to ibuprofen, and both drugs decreased pain with no apparent difference in efficacy. Morphine was associated with significantly more adverse effects, which suggests that ibuprofen is a better first-line option after minor surgery. ClinicalTrials.gov, no. NCT01686802.


High-performance Mo-Si multilayer coatings for extreme-ultraviolet lithography by ion-beam deposition.
An ion-beam deposition system has been used to fabricate Mo-Si multilayer coatings for masks and imaging optics to be used for extreme-ultraviolet lithography. In addition to high reflectivity and excellent profile control, ion-beam deposition has the capability to smooth rough substrates. For example, we achieved reflectivity of 66.8% on a substrate with 0.39-nm roughness. Smoothing can be further enhanced with a second ion source directed at the multilayer coating. The smoothing capabilities relax the requirement on the finish of the mirror and the mask substrates and could dramatically reduce the cost of these components. Thickness profile control is in the +/-0.01% range, and the figure error added to the mirror substrate by errors in the multilayer thickness is less than 0.1 nm. Peak reflectivities obtained on smooth substrates are 67.5-68.6%.


[Episiotomy as a risk factor for early perineal trauma].
To assess the association between medio-lateral episiotomy and early perineal trauma. A prospective observational cohort study of 667 consecutive vaginal deliveries was conducted over a 10-week period. On the day following delivery, all women were examined for the extent of early perineal trauma (swelling, oedema, haematoma), in addition to the episiotomy or lacerations. The demographic and clinical variables (age, parity, gestational age, birthweight, length of second stage, operative delivery, epidural, seniority of the obstetrical provider, episiotomy) and the post-partum treatment given for the perineum were retrieved from the hospital records. The overall episiotomy rate was 37.6%. Significant early perineal trauma was found in 9.9% of the women, more so in the episiotomy group (17.1% vs 5.5%, p < 0.001). In the episiotomy group, a larger number of women received more than routine treatment for the perineum (6.4% vs 2.9%, p < 0.05). Episiotomy was found to be the major independent predictor for perineal trauma (OR: 4.5, 95% CI: 2.4-8.5, p < 0.001), followed by epidural analgesia (OR: 2.4, CI: 1.3-4.3, p < 0.05) and birth weight >3700 g (OR: 2.1, CI: 1.1-4.1, p < 0.05). Episiotomy does not prevent immediate postpartum perineal trauma; rather, it is a major independent risk factor associated with significant early perineal trauma.


Diversity of plant methionine sulfoxide reductases B and evolution of a form specific for free methionine sulfoxide.
Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological conditions. Organisms evolved two distinct methionine sulfoxide reductase families (MSRA & MSRB) to repair oxidized methionine residues. We found that 5 MSRB genes exist in the soybean genome, including GmMSRB1 and two segmentally duplicated gene pairs (GmMSRB2 and GmMSRB5, GmMSRB3 and GmMSRB4). GmMSRB2 and GmMSRB4 proteins showed MSRB activity toward protein-based MetO with either DTT or thioredoxin (TRX) as reductants, whereas GmMSRB1 was active only with DTT. GmMSRB2 had a typical MSRB mechanism with Cys121 and Cys 68 as catalytic and resolving residues, respectively. Surprisingly, this enzyme also possessed the MSRB activity toward free Met-R-O with kinetic parameters similar to those reported for fRMSR from Escherichia coli, an enzyme specific for free Met-R-O. Overexpression of GmMSRB2 or GmMSRB4 in the yeast cytosol supported the growth of the triple MSRA/MSRB/fRMSR (Δ3MSRs) mutant on MetO and protected cells against H2O2-induced stress. Taken together, our data reveal an unexpected diversity of MSRBs in plants and indicate that, in contrast to mammals that cannot reduce free Met-R-O and microorganisms that use fRMSR for this purpose, plants evolved MSRBs for the reduction of both free and protein-based MetO.


Bicarbonate induces sensitization of cyclic AMP accumulation by intact 1321N1 human astrocytoma cells.
Preincubation of 1321N1 human astrocytoma cells in medium buffered with bicarbonate induced 50 to 100% increases in subsequent stimulation of cyclic AMP accumulation by the beta adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, compared to cells incubated in buffered medium without bicarbonate. This "bicarbonate-induced sensitization" of cyclic AMP accumulation occurred rapidly, was rapidly reversible and was bicarbonate concentration-dependent. Although protein kinase C activation also induces sensitization in these cells, sensitization by bicarbonate does not appear to involve protein kinase C, because neither protein kinase C down-regulation nor the kinase inhibitor staurosporine prevented sensitization. Pertussis toxin neither mimicked nor prevented the sensitization by bicarbonate, suggesting that pertussis toxin-sensitive guanine nucleotide-binding proteins are not involved. The effect of bicarbonate appears to be on synthesis of cyclic AMP rather than degradation, inasmuch as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine did not prevent expression of sensitization and because cyclic AMP degradation rates were not altered after bicarbonate incubation. However, increased adenylyl cyclase activity was not retained in broken cell preparations from cells incubated with bicarbonate. These results suggest the occurrence of a novel mechanism through which bicarbonate exposure can regulate adenylyl cyclase activity in intact cells.


Summarizing cellular responses as biological process networks.
Microarray experiments can simultaneously identify thousands of genes that show significant perturbation in expression between two experimental conditions. Response networks, computed through the integration of gene interaction networks with expression perturbation data, may themselves contain tens of thousands of interactions. Gene set enrichment has become standard for summarizing the results of these analyses in terms functionally coherent collections of genes such as biological processes. However, even these methods can yield hundreds of enriched functions that may overlap considerably. We describe a new technique called Markov chain Monte Carlo Biological Process Networks (MCMC-BPN) capable of reporting a highly non-redundant set of links between processes that describe the molecular interactions that are perturbed under a specific biological context. Each link in the BPN represents the perturbed interactions that serve as the interfaces between the two processes connected by the link.We apply MCMC-BPN to publicly available liver-related datasets to demonstrate that the networks formed by the most probable inter-process links reported by MCMC-BPN show high relevance to each biological condition. We show that MCMC-BPN's ability to discern the few key links from in a very large solution space by comparing results from two other methods for detecting inter-process links. MCMC-BPN is successful in using few inter-process links to explain as many of the perturbed gene-gene interactions as possible. Thereby, BPNs summarize the important biological trends within a response network by reporting a digestible number of inter-process links that can be explored in greater detail.


Differences in Symptom Severity and Quality of Life among Patients with Cancer Using Conventional Therapies with/without Herbal Medicines in Uganda: A Cross-Sectional Study.
Patients with cancer experience numerous symptoms related to cancer and treatment side effects that reduce their quality of life (QOL). Although herbal medicine (HM) is used to manage such symptoms by patients in sub-Saharan Africa, data on patients' perceived clinical outcomes are limited. We compared differences in QOL and symptom severity between patients with cancer using HM plus conventional therapies (i.e., chemotherapy, hormonal therapy, radiotherapy, surgery) and those using conventional therapies alone. This cross-sectional study included patients with cancer aged >18 years who were consecutively sampled and completed a researcher-administered questionnaire between December 2022 and January 2023. Specifically, data was collected using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MD Anderson Symptom Inventory for Traditional Chinese Medicine (MDASI-TCM). Data were analyzed using descriptive statistics and chi-square and logistic regression analyses. Of 400 participants (67.5% female), 49% (n=195) used HM plus conventional therapies and 51% (n=205) used conventional therapies alone. Most participants were aged >38 years (73.3%; median age 47 years). A univariate analysis showed the HM plus conventional therapies group had better mean scores for most QOL and symptom severity measures than the conventional therapies alone group. However, only role functioning significantly differed (p=0.046) in the bivariate analysis. There were no statistically significant differences between the two groups after confounder adjustment for all others measures of symptom severity and QOL. HM plus conventional therapies may offer minimal benefits or differences for clinical outcomes among patients with cancer. However, our findings have clinical, research, and public health implications for Uganda and other sub-Saharan African settings.


Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting.
Adequate zinc nutrition is essential for adequate growth, immunocompetence and neurobehavioral development, but limited information on population zinc status hinders the expansion of interventions to control zinc deficiency. The present analyses were conducted to: (1) estimate the country-specific prevalence of inadequate zinc intake; and (2) investigate relationships between country-specific estimated prevalence of dietary zinc inadequacy and dietary patterns and stunting prevalence. National food balance sheet data were obtained from the Food and Agriculture Organization of the United Nations. Country-specific estimated prevalence of inadequate zinc intake were calculated based on the estimated absorbable zinc content of the national food supply, International Zinc Nutrition Consultative Group estimated physiological requirements for absorbed zinc, and demographic data obtained from United Nations estimates. Stunting data were obtained from a recent systematic analysis based on World Health Organization growth standards. An estimated 17.3% of the world's population is at risk of inadequate zinc intake. Country-specific estimated prevalence of inadequate zinc intake was negatively correlated with the total energy and zinc contents of the national food supply and the percent of zinc obtained from animal source foods, and positively correlated with the phytate: zinc molar ratio of the food supply. The estimated prevalence of inadequate zinc intake was correlated with the prevalence of stunting (low height-for-age) in children under five years of age (r = 0.48, P<0.001). These results, which indicate that inadequate dietary zinc intake may be fairly common, particularly in Sub-Saharan Africa and South Asia, allow inter-country comparisons regarding the relative likelihood of zinc deficiency as a public health problem. Data from these analyses should be used to determine the need for direct biochemical and dietary assessments of population zinc status, as part of nationally representative nutritional surveys targeting countries estimated to be at high risk.


Sex-lethal interacts with splicing factors in vitro and in vivo.
The Drosophila sex determination gene Sex-lethal controls its own expression and the expression of downstream target genes such as transformer by regulating RNA splicing. Genetic and molecular studies have established that Sxl requires the product of another gene, snf, to autoregulate the splicing of its own transcripts. snf has recently been shown to encode a Drosophila U1 and U2 small nuclear ribonucleoprotein particle protein. In the work reported here, we demonstrate that the Sxl and Snf proteins can interact directly in vitro and that these two proteins are part of an RNase-sensitive complex in vivo which can be immunoprecipitated with the Sxl antibody. Unlike bulk Snf protein, which sediments slowly in sucrose gradients, the Snf protein associated with Sxl is in a large, rapidly sedimenting complex. Detailed characterization of the Sxl-Snf complexes from cross-linked extracts indicates that these complexes contain additional small nuclear ribonucleoprotein particle proteins and the U1 and U2 small nuclear RNAs. Finally, consistent with the RNase sensitivity of the Sxl-Snf complexes, Sxl transcripts can also be immunoprecipitated by Sxl antibodies. On the basis of the physical interactions between Sxl and Snf, we present a model for Sxl splicing regulation. This model helps explain how the Sxl protein is able to promote the sex-specific splicing of Sxl transcripts, utilizing target sequences that are distant from the regulated splice sites.


The assessment of deviant sexual arousal as a function of intelligence, instructional set and alcohol ingestion.
Sexual offenders who had been referred for a forensic evaluation were assessed in terms of their deviant sexual arousal by means of standard penile plethysmographic procedures. The sample was divided into Rapist and Nonrapist groups according to their sexual history and criminal charges. Penile circumference responses (PCR) and self-reported arousal to consenting sex, sexual assault, and physical assault were monitored. The assessments were repeated following subject instructions to suppress their arousal and following the ingestion of alcohol. The overall correlation between PCR and self-reported arousal was .65. An Alcohol-by-Offender Type interaction revealed that the lowering effect of alcohol on PCR occurred only among the Nonrapists. The suppression instruction increased Rapists' PCRs to Rape and Physical Assault presentations relative to consenting sexual narrations. When the data were examined in relation to intelligence, low IQ Rapists displayed greater responses to rape than high IQ Rapists. Under the influence of alcohol, low IQ Rapists displayed greater arousal regardless of the stimulus, while high IQ Rapists showed no change, and Nonrapists responded less than they did without alcohol. Comments concerning the accurate assessment of deviant sexual arousal and the identification of precursors to deviant sexual behaviour are made in view of the current findings.


Does duration of stenting increase the risk of clinical infection?
We investigated when an indwelling ureteral catheter should be withdrawn for infection and evaluated the importance of urinary cultures in identifying colonized microorganisms and define the bacterial flora encountered in the study. Moreover, this study tried to determine the clinical role of stent culture in clinical practice. The study was conducted between June 2018 and February 2019. Patients with ureteral stent implantation after endoscopic ureteral stone treatment were divided into two groups and each group consisted of 45 patients. Ureteral catheter was removed 15 and 30 days after ureteral stone treatment in group 1 and 2, respectively, and transferred for microbiological examination. The urine culture was obtained before and after ureteral stent implantation. The groups were compared in terms of demographics, urine and catheter cultures results. Urine analysis and catheter culture results were also compared. Demographic data of patients were similar in both groups. 3 patients in group 1 and 12 patients in group 2 had positive urine culture before catheter retraction; 2 of 45 and 6 of 45 patients had positive catheter culture in group 1 and 2, respectively. Although 2 patients in group 1 and 4 patients in group 2 had urine culture sterile, they had growth in catheter culture. In Group 1, 1 of the microorganisms was E. fecalis and 1 was E. coli. In Group 2, 2 cases were E. fecalis, 3 were E. coli and 1 was MRSE. There was no significant difference between the urine analysis results of the patients before catheter retraction and catheter culture positivity. Pre-operative urine culture does not exclude catheter colonization, and the prolonged duration of the catheter associated with greater colonization and may be associated urinary tract infection. Ureteral catheter should be removed as early as possible.


Oxygen Self-Sufficient Amphiphilic Polypeptide Nanoparticles Encapsulating BODIPY for Potential Near Infrared Imaging-guided Photodynamic Therapy at Low Energy.
Near infrared (NIR) imaging-guided photodynamic therapy (PDT) is remarkable for its high-efficiency in "see and treat" field. However, hypoxia of cancer cell limits PDT dues to the low singlet oxygen yield. Here MnO2 conjugated multifunctional polypeptide nanoparticles encapsulating photosensitizer BODIPY has been prepared via a one-step reaction, which can generate oxygen in cancer cytoplasm where rich of H2O2, following singlet oxygen by photosensitizer under NIR light irradiation. In vitro studies on HepG2 and 4T1 cancer cells revealed that the as-prepared nanoparticles obviously increase the cell suppression rate under hypoxia conditions, even exposed to an extremely low light energy density (25 mW/cm2). Meanwhile, excellent NIR fluorescence property of BODIPY enabled the nanoparticles to light up the cancer cells for real-time imaging. These results suggest the promises of biocompatible and biodegradable nanoparticles has potential application on efficient NIR imaging-guided photodynamic therapy.


Effect of magnesium supplementation and depletion on the onset and course of acute experimental pancreatitis.
High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis. Pancreatic acini were incubated with up to 10 mM magnesium; [Ca(2+)](i) (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (<300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg(2+) 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated. Increasing extracellular Mg(2+) concentration significantly reduced [Ca(2+)](i) peaks and frequency of [Ca(2+)](i) oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow-even with low caerulein concentrations that normally cause no damage. Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca(2+)](i) signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis.


Vulnerability and knowledge of sexually transmitted infections among female traders of reproductive age in enugu, Nigeria.
Sexually transmitted infections (STIs) constitute major public health concern and enigma. A comprehensive knowledge of the modes of transmission is necessary to evolve an effective preventive strategy. The aim of the study is to assess the vulnerability, knowledge and prevention of STIs among female traders of reproductive age in Enugu, Southeast Nigeria. This was a cross-sectional descriptive study carried out on female traders aged 15-49 years at Ogbete Main Market, Enugu, Southeast Nigeria. Data was analyzed using Epi-Info 2000 version 3.3.1 Centers for Disease Control and Prevention Atlanta USA) was used to analyze the data and results were presented in tabular form. A total of 200 female traders of reproductive age participated in the study. The mean (standard deviation) age was 26 (7.4) years. 16% (32/200) were adolescents. Knowledge of specific STIs was highest for human immunodeficiency virus/acquired immune deficiency syndrome 90% (130/200). Parents were poor sources of information as only 28.5% (57/200) respondents heard about STIs from their parents compared with 46% (92/200) from friends and peers. Risk factors identified were multiple sexual partners 75.5% (151/200), non-use of condoms 62% (124/200) and early debut 58% (116/200). Majority 67.5% (135/200) were aware that STIs could be treated by a visit to the doctor while 21.5% (43/200) preferred traditional/herbal healers. The inclusion of health education in schools' curricula to ensure that adolescents are adequately aware of STIs, their modes of transmission, prevention and treatment before embarking on any vocation out-of-school is advocated.


Identification of UDP-glucuronosyltransferases involved in the human hepatic metabolism of GV150526, a novel glycine antagonist.
The major metabolic pathway for elimination of GV150526 is by glucuronidation exerted by glucuronosyl transferases (UGTs). Potential exists for the modification of GV150526 pharmacokinetics by drugs capable of inhibiting the glucuronidation of GV150526. Using human liver microsomes, 44 compounds were screened for inhibition of GV150526 glucuronidation. These compounds were selected because they are extensively glucuronidated themselves or are used as concomitant medication in the treatment of acute stroke. For 11 compounds out of the 44, full inhibition kinetics were performed to determine their Ki-value and mechanism of inhibition. To predict possible in vivo drug-drug interactions, the theoretical percentage of inhibition (i) was determined, based on in vitro determined Ki-values, and the expected Cmax plasma levels of GV150526 and the inhibitor. Of the 11 compounds examined, only propofol had an i-value of 6.6; for all other compounds i-values were lower than 2.1. These results indicate that although in vitro inhibition is observed, the likelihood of in vivo drug-drug metabolic interactions occurring is low. The inhibition results suggest that in addition to UGT1A1, also UGT1A3, UGT1A8/9, and UGT2B4 are involved in the glucuronidation of GV150526. The involvement of UGT1A1 and UGT1A8/9 was confirmed from studies using cDNA expressed human UGT cell lines.


In situ and in vitro antioxidant activity of sweetpotato anthocyanins.
Anthocyanins from a variety of fruits and vegetables have been shown to possess potent antioxidant activity in vitro, but scavenging of free radicals by anthocyanins has only been demonstrated in situ in the leaves of certain plants. We report on a new sweetpotato that exhibits mottled purple flesh attributable to high concentrations of anthocyanins. By perfusing transverse sweetpotato sections with the reactive oxygen species H(2)O(2), followed by the H(2)O(2) sensitive fluorochrome scopletin, we show that anthocyanins act as antioxidants in situ within the sweetpotato storage roots. We also demonstrate in vitro antioxidant activity by sweetpotato anthocyanins, where an additive effect with hydroxycinnamic acids is observed. Anthocyanic foods have been shown to offer protection against a variety of degenerative disease processes. Given that sweetpotato can be eaten several hundred grams at a time and as a staple, these data are consistent with the possibility of superior health protection by anthocyanic varieties of sweetpotato in comparison to most common fruits and vegetables.


[Trends in socioeconomic inequalities in mortality over a twenty-two-year period in the city of Barcelona (Spain)].
To analyze the trend in socioeconomic inequalities in all-cause mortality in Barcelona from 1983 to 2004. We performed an ecological study of trends over 4 cross-sections (1983-1988, 1989-1994, 1995-1999 and 2000-2004), with the basic health area (BHA) as the unit of analysis. The study population consisted of men and women aged 20 years or more living in Barcelona. The information sources were the mortality registry, the municipal census and the census of inhabitants and dwellings. The age- and sex-specific mortality rate (ASMR) for all causes was used as the dependent variable. As the independent variable, a composite index of socioeconomic deprivation of the BHA was calculated; BHAs were grouped in quartiles according to the values on the index. Poisson models were adjusted to estimate the relative risk of mortality from all causes in the 4 groups of BHA, stratified by age groups and sex. In all the study periods, inequalities in mortality were found, depending on the BHA of residence, both for men and for women: the ASMR of the most deprived BHAs were greater than those of less deprived BHA, and were greater among men than among women. Likewise, relative risks in the youngest age groups were higher than in the oldest age groups. However, from the second to fourth study periods, inequalities decreased in absolute and relative terms, especially among men. Inequalities in mortality persist in BHA in Barcelona but have decreased over the last 2 decades. Public policies should take this information into account when tackling inequalities among BHA.


Matching spiracle opening to metabolic need during flight in Drosophila.
The respiratory exchange system of insects must maximize the flux of respiratory gases through the spiracles of the tracheal system while minimizing water loss. This trade-off between gas exchange and water loss becomes crucial when locomotor activity is increased during flight and metabolic needs are greatest. Insects that keep their spiracles mostly closed during flight reduce water loss but limit the flux of oxygen and carbon dioxide into and out of the tracheal system and thus attenuate locomotor performance. Insects that keep their spiracles completely open allow maximum gas exchange but face desiccation stress more quickly. Experiments in which water vapor was used as a tracer gas to track changes in the conductance of the respiratory system indicated that flying fruit flies minimize potential water loss by matching the area of the open spiracles to their gas exchange required for metabolic needs. This behavior maintained approximately constant pressure for carbon dioxide (1.35 kilopascals) and oxygen (19.9 kilopascals) within the tracheal system while reducing respirometric water loss by up to 23% compared with a strategy in which the spiracles are held wide open during flight. The adaptive spiracle-closing behavior in fruit flies has general implications for the ecology of flying insects because it shows how these animals may cope with environmental challenges during high locomotor performance.


Behavioral effects mediated by the modulatory glycine site of the NMDA receptor in the anterodorsal striatum and nucleus accumbens.
The striatum and the nucleus accumbens are the main input structures of the basal ganglia (BG). They contribute differently to motor behavior controlled by the BG in rats, e.g., stereo-typed behavior, catalepsy, and locomotion. Whereas the striatum is predominantly involved in the control of sniffing behavior and catalepsy, the nucleus accumbens contributes to control of locomotion. To test whether the allosteric glycine site of the NMDA receptor complex modulates these behavioral variables, we injected the glycine-site antagonist 7-chlorokynurenate and the glycine-site agonist D-serine into the anterodorsal striatum and the nucleus accumbens and studied their influence on stereotypical snout contacts and locomotion. Additionally, the effects of intrastriatal injections of 7-chlorokynurenate on haloperidol- and SCH 23390-induced catalepsy were investigated. 7-Chlorokynurenate enhanced stereotypical snout contacts in the anterodorsal striatum and in the nucleus accumbens but did not change spontaneous locomotion in either of these structures. Haloperidol- but not SCH 23390-induced catalepsy was attenuated by intrastriatally administered 7-chlorokynurenate. The glycine-site agonist D-serine had no effect on stereotypical snout contacts and locomotion. The results suggest that motor behavior mediated by the striatopallidal output pathway is modulated by the glycine site, whereas motor behavior mediated by the accumbopallidal and striatonigral output pathway is not.


"Candidatus Mesenet longicola": Novel Endosymbionts of Brontispa longissima that Induce Cytoplasmic Incompatibility.
Intracellular bacteria that are mainly transmitted maternally affect their arthropod hosts' biology in various ways. One such effect is known as cytoplasmic incompatibility (CI), and three bacterial species are known to induce CI: Wolbachia, Cardinium hertigii, and a recently found alphaproteobacterial symbiont. To clarify the taxonomic status and provide the foundation for future studies to reveal CI mechanisms and other phenotypes, we investigated genetic and morphological properties of the third CI inducer that we have previously reported inducing CI in the coconut beetle Brontispa longissima. The draft genome of the bacteria was obtained from the oocytes of two isofemale lines of B. longissima infected with the bacteria: one from Japan (GL2) and the other from Vietnam (L5). Genome features of the symbionts (sGL2 and sL5) were highly similar, showing 1.3 Mb in size, 32.1% GC content, and 99.83% average nucleotide sequence. A phylogenetic study based on 43 universal and single-copy phylogenetic marker genes indicates that they formed a distinct clade in the family Anaplasmataceae. 16S rRNA gene sequences indicate that they are different from the closest known relatives, at least at the genus level. Therefore, we propose a new genus and species, "Candidatus Mesenet longicola", for the symbionts of B. longissima. Morphological analyses showed that Ca. M. longicola is an intracellular bacterium that is ellipsoidal to rod-shaped and 0.94 ± 0.26 μm (mean ± SD) in length, and accumulated in the anterior part of the oocyte. Candidates for the Ca. M. longicola genes responsible for CI induction are also described.