Quality of post-treatment surveillance of early stage breast cancer in Texas.
Only annual mammography and physical examination are recommended for the post-treatment surveillance of early stage breast cancer. We used Texas Cancer Registry-Medicare linked data (2001-2007) to identify physician visits and use of mammography, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) CT in patients ≥ 66 years old with ductal carcinoma in situ and stage I-III ductal carcinoma who underwent curative-intent operations. We also evaluated the trends in use of recommended and nonrecommended tests. We identified 8,598 patients with resected ductal carcinoma in situ (37.3%) or invasive ductal cancer (62.7%). Breast-conserving therapy was performed in 59%. Only 55% saw a physician twice a year for 2 years and underwent annual mammography for 2 consecutive years in the surveillance period. Mammography use decreased from 81% in 2001 to 75% in 2007 (P < .0001), and breast MRI use rose from 0.5% to 7.0% (P < .0001). For asymptomatic patients, the use of CT/MRI of the abdomen, chest, and head was 27%, 23%, and 22%, and this slightly increased during the study period. There was a significant increase in PET/PET CT use, from 2% in 2001 to 9% in 2007 (P < .0001). There was a concomitant decrease in bone scan use from 21% in 2001 to 13% in 2007 (P < .0001). Adherence to evidence-based guidelines has been substandard and the use of nonrecommended tests has persisted over the study period. The rise in PET use and attendant decrease in bone scan implicates a population receiving PET scan in lieu of bone scan for surveillance of asymptomatic metastatic disease. In an elderly population of breast cancer patients in Texas, these findings imply both underuse and overuse.


A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity.
Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women. Here we investigated the sex-specific effects of the CACNA1C variant rs1024582 on psychiatry-related traits, brain activity during tasks and rest, and brain volume in 1207 normal male and female subjects. After correcting for multiple comparisons, there were significant interaction effects between sex and the minor allele of this polymorphism on the hostile behavior subscale scores of the Coronary-Prone Type Scale mediated by higher scores in female carriers of the minor allele. Imaging analyses revealed significant interaction effects between sex and the minor allele on fractional amplitude of low-frequency fluctuations in the right dorsolateral prefrontal cortex and on brain activity during the 2-back task in areas of the right posterior cingulate cortex, right thalamus, and right hippocampus, which were all mediated by reduced activity in female carriers of the minor allele. Our results demonstrated that the rs1024582 risk variant of CACNA1C is associated with reduced activity in the frontolimbic regions at rest and during a working memory task as well as with greater hostility in females in the healthy population.


Protein Kinase D-Dependent Downregulation of Immediate Early Genes through Class IIA Histone Deacetylases in Acute Lymphoblastic Leukemia.
Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related death in children and adolescents, and cure rates for relapsed/refractory ALL remain dismal, highlighting the need for novel targeted therapies. To identify genome-wide metabolic-stress regulated genes, we used RNA-sequencing in ALL cells treated with AICAR, an AMPK activator. RNA-sequencing identified the immediate early genes (IEGs) as a subset of genes downregulated by AICAR. We show that AICAR-induced IEGs downregulation was blocked by an adenosine uptake inhibitor indicating AICAR was responsible for IEGs reprogramming. Using pharmacologic and genetic models we established this mechanism was AMPK-independent. Further investigations using kinase assays, PKD/PKC inhibitors and rescue experiments, demonstrated that AICAR directly inhibited PKD kinase activity and identified PKD as responsible for IEGs downregulation. Mechanistically, PKD inhibition suppressed phosphorylation and nuclear export of class IIa HDACs, which lowered histone H3 acetylation and decreased NFκB(p65) recruitment to IEGs promoters. Finally, PKD inhibition induced apoptosis via DUSP1/DUSP6 downregulation eliciting a DNA damage response. More importantly, ALL patient cells exhibited the same PKD-HDACs-IEGs-mediated mechanism. As proof of principle of the therapeutic potential of targeting PKD, we established the in vivo relevance of our findings using an NSG ALL mouse model. In conclusion, we identified a previously unreported PKD-dependent survival mechanism in response to AICAR-induced cellular stress in ALL through regulation of DUSPs and IEGs' expression. IMPLICATIONS: PKD mediates early transcriptional responses in ALL cells as an adaptive survival mechanism to overcome cellular stress.


Three-dimensional optical sensing network written in fused silica glass with femtosecond laser.
A single-step fast-writing method of burst ultrafast laser modification was applied to form a mesh network of multi-wavelength Bragg grating waveguides in bulk fused silica glass. Strain-optic and thermo-optic responses of the laser-written internal sensors are reported for the first time. A dual planar layout provided independent temperature- and strain-compensated characterization of temperature and strain distribution with coarse spatial resolution. The grating responses were thermally stable to 500 masculineC. To our best knowledge, the grating network represents the first demonstration of 3D distributed optical sensing network in a bulk transparent medium. Such 3D grating networks open new directions for strain and temperature sensing in optical circuits, optofluidic, MEMS or lab-on-a-chip microsystems, actuators, and windows and other large display or civil structures.


Force-generating capacities and fatigability of the quadriceps femoris in relation to different exercise modes.
In this study, we examined whether different exercise modes provoke functional differences in maximal and explosive force-generating capacities and fatigability of the quadriceps femoris (QF). Additionally, the interaction of different functional capacities was studied in competitive athletes. Ten competitive tennis players and 10 endurance athletes participated in the study. Pre-exercise force-generating capacities were determined during maximal voluntary isometric knee extensions (MVC). Fatigability of the QF was studied using sustained isometric contractions with target loads of 20% and 40% of pre-exercise MVC. Postexercise MVCs were conducted 20 seconds, 1 minute, and 3 minutes post task failure. Muscle activation of the QF during the fatiguing exercises and postexercise MVCs was estimated using surface electromyography. Higher explosive force-generating capacities, but no differences in absolute moments, were detected in tennis players compared with endurance athletes. Fatigability of the QF during both fatiguing tasks was approximately the same in both athletic populations. This was indicated by minor group differences in endurance time, postexercise MVC production, and electromyography (EMG)-estimated muscle activation during fatigue. Variability in endurance time was not significantly associated with pre-exercise force-generating capacities in these competitive athletes. In both athletic populations, recovery of MVC was significantly slower after the fatiguing contraction with 20% of MVC compared with that with 40% of MVC. These results may enhance understanding of plasticity of the neuromuscular system and yield interesting information for the optimization of athletic training programs. Explosive strength training might enhance endurance athletes' explosiveness without decreasing muscle fatigue resistance. The exercise profile of competitive tennis is suggested to act as a sufficient trigger to reach high neuromuscular fatigue resistance but may be inadequate to cause significant gains in absolute muscle strength.


Multimorbidity and Functional Limitation in Individuals with Heart Failure: A Prospective Community Study.
To characterize the individual and combined effects of multimorbidity and functional limitation on healthcare use and mortality in a large, community cohort of individuals with heart failure (HF). Prospective cohort study. Eleven southeastern Minnesota counties. Individuals (mean age 74, 54% male) with a first-ever HF code (International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code I50) between January 1, 2013 and March 31, 2016 (N=2,692). Eight activities of daily living measured using a survey on a Likert scale (1=without any difficulty, 5=unable to do; median=8). Participants with a score greater than 8 were categorized as having functional limitation. Multimorbidity was defined as having 2 or more noncardiac comorbidities. Twenty-five percent of participants had neither multimorbidity nor functional limitation, 35% had multimorbidity, 9% had functional limitation, and 31% had both. After adjustment, participants with multimorbidity and functional limitation had greater risks of all outcomes (death: hazard ratio (HR)=4.92, 95% confidence interval (CI)=3.03-8.00; emergency department (ED) visit: HR=3.67, 95% CI=2.94-4.59; hospitalization: HR=3.66, 95% CI=2.85-4.70; outpatient visit: HR=1.73, 95% CI=1.52-1.96) than those with neither. Participants with functional limitation alone had greater risks of death (HR=4.84, 95% CI=2.78-8.43), ED visits (HR=2.35, 95% CI=1.75-3.16), and hospitalizations (HR=2.10, 95% CI=1.52-2.88) but not outpatient visits. Those with multimorbidity alone had similar risks of ED visits and hospitalizations as those with functional limitation alone but were more likely to have outpatient visits (HR=1.50, 95% CI=1.34-1.67). Individuals with both multimorbidity and functional limitation have the highest risk of death and healthcare use. Individuals with only functional limitation have similar rates of hospitalizations and ED visits as those with only multimorbidity, underscoring the need to consider both when managing individuals with HF.


Chemotherapy-induced ovarian damage and protective strategies.
More than 9.2 million women worldwide suffer from cancer, and about 5% of them are at reproductive age. Chemotherapy-induced impairment of fertility affects the quality of life of these women. Several chemotherapeutic agents have been proven to cause apoptosis and autophagy by inducing DNA damage and cellular stress. Injuries to the ovarian stroma and micro-vessel network are also considered as pivotal factors resulting in ovarian dysfunction induced by chemotherapeutic agents. Primordial follicle pool over-activation may also be the mechanism inducing damage to the ovarian reserve. Although many studies have explored the mechanisms involved in chemotherapy-induced reproductive toxicity, the exact molecular mechanisms have not been elucidated. It is essential to understand the mechanisms involved in ovarian damage, in order to develop potential protective treatments to preserve fertility. In this article, we reviewed the current knowledge on the mechanism of chemotherapy-induced ovarian damage and possible protective strategies that prevent the ovary from such damages.


The effect of thymoquinone coating on adhesive properties of polypropylene mesh.
An incisional hernia is a common complication following abdominal surgery. Polypropylene mesh is frequently used in the repair of such defects and has nearly become the standard surgical treatment modality. Though they are very effective in reducing recurrence, mesh materials exhibit a strong stimulating effect for intraabdominal adhesion. The thymoquinone (TQ) extracted from Nigella sativa seeds has potential medical properties. TQ has anti-inflammatory, antioxidant and antibacterial properties. The aim of this study is to coat polypropylene mesh with TQ in order to investigate the effect of surface modification on intraabdominal adhesions. TQ-coated polypropylene mesh material was tested for cytotoxicity, contact angle, surface spectroscopy, TQ content, sterility, and electron microscopic surface properties. An experimental incisional hernia model was created in study groups, each consisting of 12 female Wistar rats. The defect was closed with uncoated mesh in control group, with polylactic acid (PLA) coated mesh and PLA-TQ coated mesh in study groups. Adhesion scores and histopathologic properties were evaluated after sacrifice on postoperative 21th day. Granuloma formation, lymphocyte and polymorphonuclear leukocyte infiltration, histiocyte fibroblast and giant cell formation, capillary infiltration, collagen content were significantly reduced in the PLA-TQ coated mesh group (p < 0.05). Though not statistically significant, likely due to the limited number of study animals, adhesion formation was also reduced in the PLA-TQ coated mesh group (p: 0.067). TQ coated mesh is shown to reduce adhesion formation and TQ is a promising coating material for mesh surface modification.


Defining duodenitis: quantitative histological study of mucosal responses and their correlations.
Biopsies from 56 patients with endoscopically normal duodenal bulbs, duodenitis, or duodenal ulceration were studied for counts of plasma cells, polymorphs, and eosinophils and extent of gastric metaplasia, villous atrophy, and mucosal oedema. A correlation matrix showed that the counts of different types of plasma cells were closely correlated with each other and that there was also a close correlation between the presence of intraepithelial polymorphs, villous atrophy, and gastric metaplasia. Cluster and discriminant analysis indicated that the histological changes could be grouped by their statistical association into three simple categories: normal, which includes many cases incorrectly labelled in some classification systems as mild or chronic duodenitis; histologically defined mild duodenitis, characterised by an appreciable plasma cell response and oedema usually with intraepithelial polymorph infiltration and gastric metaplasia; and severe duodenitis, with an appreciable polymorph response and villous atrophy but decreased plasma cells. Decreased plasma cells may be an important indication of peptic ulceration.


Solubilization of functional calcitonin receptors.
Calcitonin (CT) binding activity has been extracted from a membrane fraction of human placenta using the zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulphonic acid (Chaps). Approximately two-thirds of the available binding sites were extracted using 5 mM-Chaps. The binding characteristics of 125I-labelled salmon CT(125I-sCT) to the solubilized extract were similar to those obtained previously with placental membranes and other targets such as osteoclasts, renal cells and certain human cancer cell lines. 125I-sCT binding was saturable (Bmax. 75 +/- 6 fmol/mg of protein, n = 3) and Scatchard analysis revealed a single class of high-affinity binding sites (Kd 165 +/- 28 pM, n = 3). In competitive-binding studies, various species-specific CTs and CT analogues showed the same rank order of potencies as seen in CT bioassays and several unrelated peptides did not compete at high doses. A biologically active CT analogue, [Arg11,18, Lys14]sCT, derivatized with the photoreactive phenylazide cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate, was used to identify receptor components of Mr approximately 88,000 and approximately 71,000 in both particulate placental membranes and the solubilized extract. Receptor components of Mr 85-90,000 have been identified in other CT target cells previously using chemical- and photoaffinity-labelling techniques. These results demonstrate the first successful solubilization of the CT receptor in a form which purification.


A highly sensitive and low-background fluorescence assay for pesticides residues based on hybridization chain reaction amplification assisted by magnetic separation.
Due to the concern over food safety, it is important to detect the pesticides residues in agricultural products. Here, a highly sensitive and low background fluorescent strategy for the detection of pesticides residues has been developed. The fluorescence intensity of N-methyl mesoporphyrin IX (NMM) binding G-quadruplex could be turn off because of inhibiting effect of the pesticides on the acetylcholinesterase (AChE) activity. For that, four single-stranded DNAs (named linker, trigger, H1 and H2, respectively) are rational designed and T-Hg-T mismatches duplex DNAs as a recognizer combined with the separation of magnetic beads. The design of hybridization chain reaction (HCR) amplification strategy assisted by magnetic separation has been adopted to improve the detection sensitivity. In the presence of pesticides, the amount of the thiol group generated by hydrolysis reaction of acetylcholine (ACh) is reduced, lead to release of less trigger DNA. Therefor subsequent HCR process is retarded with decreased fluorescence intensity. The reduced fluorescence intensity has a quantitative relationship with the pesticide concentration. The limit of detection of chlorpyrifos was estimated to be 2.0 ng ml-1. It has been applied to detect the pesticides residues in real samples.


Repulsive guidance molecule acts in axon branching in Caenorhabditis elegans.
Repulsive guidance molecules (RGMs) are evolutionarily conserved proteins implicated in repulsive axon guidance. Here we report the function of the Caenorhabditis elegans ortholog DRAG-1 in axon branching. The axons of hermaphrodite-specific neurons (HSNs) extend dorsal branches at the region abutting the vulval muscles. The drag-1 mutants exhibited defects in HSN axon branching in addition to a small body size phenotype. DRAG-1 expression in the hypodermal cells was required for the branching of the axons. Although DRAG-1 is normally expressed in the ventral hypodermis excepting the vulval region, its ectopic expression in vulval precursor cells was sufficient to induce the branching. The C-terminal glycosylphosphatidylinositol anchor of DRAG-1 was important for its function, suggesting that DRAG-1 should be anchored to the cell surface. Genetic analyses suggested that the membrane receptor UNC-40 acts in the same pathway with DRAG-1 in HSN branching. We propose that DRAG-1 expressed in the ventral hypodermis signals via the UNC-40 receptor expressed in HSNs to elicit branching activity of HSN axons.


[Mechanisms of membrane transport of ascorbic acid].
The paper deals with modern ideas concerning molecular mechanisms of the biosynthesis, metabolism and function of ascorbic acid as with as with its transport through the membrane structures of different extent of organization. It is emphasized that under physiological conditions a quickly saturated mechanism of ascorbic acid active transport through the biomembranes is an effective system of maintaining the acid steady-state intracellular homeostasis in animal tissues.


Accuracy of TrUE-Net in comparison to established white matter hyperintensity segmentation methods: an independent validation study.
White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the established relationship between WMH burden and age. We found that TrUE-Net was highly reliable at identifying WMH regions with low false positive rates, when compared to semi-manual segmentation as the reference standard. TrUE-Net performed similarly or favorably when compared to the other automated techniques. Moreover, TrUE-Net was able to detect relationships between WMH and age to a similar degree as the reference standard semi-manual segmentation at both the global and regional level. These results support the use of TrUE-Net for identifying WMH at the global or regional level, including in large, combined datasets.


Growing up with interfering neighbours: the influence of time of learning and vocabulary knowledge on written word learning in children.
Evidence suggests that new vocabulary undergoes a period of strengthening and integration offline, particularly during sleep. Practical questions remain, however, including whether learning closer to bedtime can optimize consolidation, and whether such an effect varies with vocabulary ability. To examine this, children aged 8-12-years-old (n 59) were trained on written novel forms (e.g. BANARA) in either the morning (long delay) or the evening (short delay). Immediately after training and the next day, lexical competition (a marker of integration) was assessed via speeded semantic decisions to neighbouring existing words (e.g. BANANA); explicit memory was measured via recognition and recall tasks. There were no main effects indicating performance changes across sleep for any task, counter to studies of spoken word learning. However, a significant interaction was found, such that children with poorer vocabulary showed stronger lexical competition on the day after learning if there was a short delay between learning and sleep. Furthermore, while poorer vocabulary was associated with slower novel word recognition speed before and after sleep for the long delay group, this association was only present before sleep for the short delay group. Thus, weak vocabulary knowledge compromises novel word acquisition, and when there is a longer period of post-learning wake, this disadvantage remains after a consolidation opportunity. However, when sleep occurs soon after learning, consolidation processes can compensate for weaker encoding and permit lexical integration. These data provide preliminary suggestion that children with poorer vocabulary may benefit from learning new words closer to bedtime.


A real world study of cough burden and quality of life of UK patients who have undergone evaluation for chronic cough.
Treatment options for adults with chronic cough (CC) are limited. This study reports on the health status and experiences of patients with recent healthcare evaluation for CC. This prospective, UK, cross-sectional study surveyed adults with a CC evaluation within the previous 12 months. All were never smokers (or ex-smokers for ≥12 months). Subjects completed five validated patient-reported outcome measures: cough visual analogue scale (VAS), EuroQoL 5 dimension, 5 level (EQ-5D-5L), EQ-5D VAS, Leicester Cough Questionnaire (LCQ), and Work Productivity and Activity Impairment (WPAI) questionnaire. A total of 101 participants were recruited: 71% were female, mean age was 54.9 ± 15.2 years. Median (IQR) CC duration was 36 (11, 120) months. Mean self-reported CC severity (Cough-VAS) was 51.3 ± 22.9 over the previous 2 weeks and 62.9 ± 23.7 on the worst day of coughing. EQ-5D values were lower for CC patients than population norms. Subanalyses revealed that EQ-5D and LCQ scores were significantly impacted by CC duration and the number of healthcare providers (HCPs) visited. WPAI analysis showed a 27.6% work time impairment because of participants' CC. The number of HCP attendances ranged from 1 to 10 (3.3 ± 2.8) before diagnosis was confirmed. Treatment was being prescribed to 87% of participants and comprised mainly steroids (nasal [19%] and inhaled [25%]), beta agonists (24%), and proton pump inhibitors (21%); 44% of patients were dissatisfied with treatment efficacy. Real-world data from a nationally representative UK population show significant unmet needs associated with CC, including multiple healthcare visits and limited treatment effectiveness, resulting in inadequate cough control and impaired health status.


A Self-Compassion Group Intervention for Patients Living With Chronic Medical Illness: Treatment Development and Feasibility Study.
Self-compassion is a psychological skill associated with good mental health and adjustment to illness in the second half of life, but to date, few self-compassion-based interventions have been developed specifically for use in midlife and older adult cohorts. The purpose of this study was to develop and test the feasibility of a 4-week group self-compassion-based intervention designed to improve self-report and biological markers of well-being in midlife and older adult patients living with chronic illness. Treatment development drew on existing literature, expert input, and qualitative interview data. Eight patients in outpatient treatment for a chronic illness were recruited from a rehabilitation hospital (during September and October 2017 and again during February and March 2018) to test feasibility. Participants attended a 1-hour group self-compassion-based intervention once per week for 4 weeks. Feasibility was assessed on 6 domains. Measures of well-being and heart rate variability (HRV), an index of nervous system functioning, were also collected. Recruitment was feasible and occurred within the expected time frame. Attendance at sessions was high (84.4%), with no dropouts. Participants found that the intervention was acceptable, rating sessions as enjoyable (6.8/7) and relevant to daily life (6.6/7). There were no adverse events. Secondary analysis revealed pre-post improvements for some well-being outcomes, such as a significant reduction in depressive symptoms (Hedges' g = -1.18, 95% CI, -0.18 to -2.16). A 4-session group self-compassion-based intervention was found to be feasible and acceptable to midlife and older adult patients in treatment for a chronic illness. A larger, randomized pilot trial is needed to explore the efficacy of this intervention. Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12619000709145.


Rapid and combined detection of Mycoplasma pneumoniae, Epstein-Barr virus and human cytomegalovirus using AllGlo quadruplex quantitative PCR.
Acute respiratory infections (ARIs) cause substantial morbidity and mortality worldwide. The causes of ARI are dynamic, and co-infections of Mycoplasma pneumoniae, Epstein-Barr virus and human cytomegalovirus are recently developed causes of ARI. Here, we established a quadruplex quantitative PCR (qPCR) method to rapidly identify and simultaneously detect a single infection or co-infection of these three pathogens and an internal control in a single tube using AllGlo probes. The analysis demonstrated a wide linear range of detection from 101 to 108 copies per test and a low coefficient of variation of less than 5 %. The amplification efficiencies were all close to 1, and the correlation coefficients (r2) were all greater than 0.99. We found no significant difference in a comparative reagent test (P >0.05). Moreover, the results of tests on clinical samples using AllGlo quadruplex qPCR and TaqMan uniplex qPCR were in near-perfect agreement (κ =0.97). Clinically, the availability of this method will enable better differential diagnosis, disease surveillance and controlled outcomes.


Declines in physical functioning attributable to hip fracture among older people: a follow-up study of case-control participants.
To identify declines in physical functioning, directly attributable to the effects of hip fracture. A follow-up study of participants in a case-control study was conducted in Auckland, New Zealand, between 1993 and 1996. Nine hundred and eleven randomly selected older people with a hip fracture at the time of the initial interview (cases) and 910 randomly selected older people, without hip fracture (controls), were invited to participate in the study. Two year changes in physical functioning, defined in terms of self-reported mobility, functional dependence and physical activity were examined. Data from the survivors (572 cases and 756 controls) showed that, after controlling for pre-existing chronic medical conditions and disabilities, cases were 4.2 times more likely than controls to be community immobile (95% confidence interval (CI) 2.8-6.2, p < 0.001) and 2.6 times more likely to be functionally dependent (95% CI 1.7-4.1, p < 0.001). Cases were also spending less hours per day on their feet (2.9) compared with controls (3.5) (F1,1211 = 55.7, p < 0.001). Hip fractures are associated with dramatic declines in physical functioning at two years, independent of the effects of increasing age, pre-existing medical conditions and disabilities.


Autoimmune lymphoproliferative syndrome (ALPS) in a patient with a new germline Fas gene mutation.
Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder characterized by chronic lymphoproliferation, autoimmune manifestations and expansion of TCRalphabeta+CD4-CD8- lymphocytes. The main pathogenic factor is a defective Fas-mediated apoptosis generally caused by mutations in the Fas gene. This report describes a new heterozygous Fas gene mutation in a boy with clinical and immunological features of ALPS. In vitro, T-cell blasts from the patient are completely resistant to the effects on the anti-Fas cytotoxic mAb CH-11, they also have a higher proliferation rate than T cells from healthy donors, while PHA-induced AICD is normal. The location of the mutation (I246S) found in the intracytoplasmic death domain, and the conservation of that residue in four different species from human suggest that I246 is an essential amino acid for Fas function. The patient has inherited the mutation from his father who also shows defective Fas-mediated apoptosis but the clinical and immunological manifestations are much less severe. These results provide evidence that the penetrance of genetic defects in Fas is variable and that other factors may influence the phenotype of the disease.


[The study of 4 cases of myeloid neoplasm with t (5;12) (q33;p13) and the literatures review].
To report clinical and laboratory features of 4 cases of myeloid neoplasm with t (5;12) (q33;p13). Cytogenetic examination of bone marrow cells obtained from patients was performed by 24 h culture method. R banding technical was used for karyotype analysis. PDGFRβ gene rearrangement was detected by FISH using dual color break apart PDGFRβ probe. ETV6-PDGFRβ fusion genes were detected by multiple-reverse transcription polymerase chain reaction (RT-PCR). Direct sequencing analysis was performed on the PCR products in case 1. Immunophenotype analysis was carried out by flow cytometry. Four cases were treated with imatinib (IM) and followed up. The diagnoses included 3 MPN and 1 AML-M2. The t (5;12) (q33;p13) was a primary abnormality in 3 cases of MPN and a secondary abnormality in 1 case of AML-M2. PDGFRβ gene rearrangement and ETV6-PDGFRβ fusion genes were detected by FISH and multiple-RT-PCR in 4 cases, respectively. The immunophenotypical analysis of leukemia cells showed positive for CD13, CD33 and CD34. Two cases obtained MMR after the treatment of IM, one case complete hematologic and complete cytogenetic response. ETV6-PDGFRβ was negative detected by multiple-RT-PCR after the treatment of IM, but relapsed and died soon in case 4. The t (5;12) myeloid neoplasm was a subtype with unique features. The t (5;12) maybe a primary chromosome abnormality in MPN and a secondary in AML. MPN with t (5;12) could benefit from IM, but not for AML. Dual-FISH was a reliable tool for detecting PDGFRβ rearrangement.


[Breast cancer and axillary area: state of the art and perspectives].
A therapeutic surgical de-escalation has been observed since many years with an actual prolongation for axillary lymph node area treatment. Axillary lymph node dissection (ALND) omission has been studied before and after validation of sentinel node (SN) biopsy procedure. A non-inferiority of ALND omission has been reported in case of non-involved SN. ALND omission has been studied in case of SN involvement without consensus in relation with scientific level of proof and with selective indications. The purpose of this work is to make a synthesis of the experiences on this subject then to envisage the current and future perspectives.


Cut-off values of body mass index, waist circumference, and waist-to-height ratio to identify excess abdominal fat: population-based screening of Japanese school children.
School-based screening and prevention programs for adiposity generally target school children in grades 4 and 6 (age 9-11 years). The aims of this study were to evaluate the validity of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in identifying abdominal adiposity in fifth-grade Japanese school children and to determine optimal cut-off values for anthropometric measures. The target population was fifth-grade school children enrolled in 2 schools in Shizuoka, Japan between 2008 and 2010; 422 of the 466 children participated in the present study. Abdominal adiposity was defined as percent trunk fat in the 95th percentile or higher, as determined by dual-energy x-ray absorptiometry (DXA). We analyzed the validity of BMI, WC, and WHtR using receiver operating characteristic (ROC) curve analysis. The Youden index was used to determine cut-off values of BMI, WC, and WHtR that identify excess abdominal fat. Optimal cut-off values to identify abdominal adiposity were 20.8 kg/m(2) (BMI), 76.5 cm (WC), and 0.519 (WHtR) for boys, and 19.6 kg/m(2) (BMI), 73.0 cm (WC), and 0.499 (WHtR) for girls. Areas under the ROC curve were 0.983 (BMI), 0.987 (WC), and 0.981 (WHtR) for boys, and 0.981 (BMI), 0986 (WC), and 0.992 (WHtR) for girls. BMI, WC, and WHtR successfully identified a high proportion of children with excess abdominal fat as measured by DXA, demonstrating that these measures are useful indices for school screening.


Inter/intramolecular Cherenkov radiation energy transfer (CRET) from a fluorophore with a built-in radionuclide.
The Cherenkov radiation (CR) from [(18)F]-FDG, [(177)Lu]-LuCl3 and [(90)Y]-YCl3 was detected and CR energy transfer (CRET) to several fluorophores was examined. Subsequent fluorescence emission was found to be a function of the position of absorption bands with respect to the CR peak, energy of emitted particles, radionuclide/fluorophore loading, and fluorophore brightness. A variant of the best fluorophore with a built-in radionuclide was synthesized to achieve inter- and intra-molecular CRET.


[Microflora of the gastroduodenal zone and morphological characteristics of phases of recurrent peptic ulcer].
The studies conducted for 126 patients with stomach and duodenal ulcers revealed that at the acute state of recurrent ulcer activation of the microflora displaying pathogenetic signs and corresponding to the third or fourth degree of dysbacteriosis takes place in the ulcerous defect zone along with microcirculatory disorders, necrotic inflammatory processes and reduction of the lysozyme content in tissues. This allows comparing ulcers of the gastroduodenal zone to an infected wound. At the sub-acute phase of recurrent ulcer (next one or two weeks) microbiological changes in the per-ulcer zone reduce to dysbacteriosis of the second or third degree as inflammatory and necrotic processes cease, an at the phase of cicatrisation and epithelization they are similar to normal biocenosis.


Helicobacter Pylori infection is a significant risk for modified lipid profile in Japanese male subjects.
Helicobacter Pylori infection was associated with the risk of cardiovascular disease; however, the relation between Helicobacter Pylori infection and the lipid profile has not been fully established. We measured anti-Helicobacter Pylori antibody concentration and lipid profiles in 6,289 Japanese subjects aged 21-64 years (5,077 male and 1,212 female). The prevalence of Helicobacter Pylori-seropositive subjects was 46.8% and 39.6% in men and women, respectively. Adjusted mean values of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in men were significantly higher and lower in Helicobacter Pylori-seropositive than-negative subjects, respectively, (LDL-cholesterol: 129.0±0.8 vs. 125.3±0.7 mg/dL, p< 0.001, HDL-cholesterol: 54.6±0.3 vs. 56.6±0.3 mg/dL, p< 0.01), whereas these associations were not significant in female subjects. Moreover, the odds ratio of Helicobacter Pylori infection for high LDL-cholesteremia and low HDL-cholesteremia in male subjects was 1.23 (95% CI (confidence interval): 1.08-1.40, p< 0.05) and 1.29 (95% CI: 1.03-1.59, p< 0.05), respectively. Female subjects did not have such associations. The present study demonstrates that Helicobacter Pylori infection is significantly associated with high LDL-cholesteremia and low HDL-cholesteremia in Japanese male subjects.


[Continuing medical education and the Social Balance Sheet].
The social balance sheet is an instrument used to obtain a clear and transparent account, that helps to develop an analysis of the budget from the point of view of the stakeholders; this is not all that is required by law, but it takes into account the ability of the health institutions to obtain a collaboration with the neighboring environment and with the social issues that enter into the relationship. This could be a valuable tool also for educational purposes; it is an useful task to be performed by the health workers, and an opportunity to redefine the information needs through the analysis of the results achieved.


[Preparation of autologous platelet-rich gel for diabetic refractory dermal ulcer and growth factors analysis from it].
To compare the platelet enrichment ratio of platelet-rich plasma (PRP) prepared by different centrifuge methods and to compare the concentration of growth factors released from autologous platelet-rich gel (APG) with the whole blood. Thirteen diabetic patients with refractory skin lesions were enrolled in APG treatment. (1) Three kinds of centrifuge methods were selected for PRP by 11 diabetic patients: A (n = 6): 529 x g for 4 minutes in the first centrifuge and 854 x g for 6 minutes in the second centrifuge; B (n = 5): 313 x g for 4 minutes in the first centrifuge and 1,252 x g for 6 minutes in the second centrifuge; C (n = 5): 176 x g for 5 minutes in the first centrifuge and 1,252 x g for 5 minutes in the second centrifuge. Platelet counted on the whole blood and PRP was determined. The APG, produced by combining the PRP with thrombin and calcium gluconate (10:1) was used by patients. (2) PDGF-BB, TGF-beta1, VEGF, EGF, and IGF-1 were measured in the APG and the whole blood using the enzyme-linked immunosorbent assay method. (1) The average platelet concentration was higher in group B [(1,363.80 +/- 919.74) x 10(9)/L] than in groups A [(779.67 +/- 352.39) x 10(9)/L)] and C [(765.00 +/- 278.78) x 10(9)/L] and the platelet recovery rate was 75.2% +/- 21.0% in group B. (2) The concentration of growth factors all increased with the increasing platelet number. On average, for the whole blood as compared with APG, the PDGF-BB concentration increased from (145.94 +/- 133.24) pg/mL to (503.81 +/- 197.86) pg/mL (P < 0.05); TGF-beta1 concentration increased from (3.31 +/- 2.27) ng/mL to (5.67 +/- 4.80) ng/mL (P < 0.05); IGF-1 concentration increased from (14.54 +/- 35.34) ng/mL to (110.56 +/- 84.36) ng/mL (P < 0.05); and EGF concentration increased from (160.73 +/- 71.10) pg/mL to (265.95 +/- 138.43) pg/mL (P < 0.05). No increase was found for VEGF (P > 0.05). (3) There was positive correlation between the platelet concentration and PDGF-BB and TGF-beta1 (r = 0.627, r = 0.437, P < 0.05). (4) Thirteen diabetic repractory dermal ulcers received APG treatment for 18 times, 9 ulcers (69.2%) and 10 sinuses (88.3%) were cured at the end of 12-week treatment. The method of group B is the best centrifuge method. A variety of growth factors are detected and released from the platelets at significant levels in APG. There is positive correlation between the platelet concentration and PDGF-BB and TGF-beta1.


Intracellular metabolism of 5,10-dideazatetrahydrofolic acid in human leukemia cell lines.
5,10-Dideazatetrahydrofolic acid (DDATHF) is a new potent antitumor agent that specifically inhibits purine biosynthesis, primarily through inhibition of glycinamide ribonucleotide transformylase, the first of the tetrahydrofolate-requiring enzymes in the de novo synthesis pathway. DDATHF has been shown to be an excellent substrate for mouse liver folylpolyglutamate synthetase in vitro, suggesting that intracellular conversion to polyglutamates could play an important role in the action of this antifolate. In this report, metabolic studies of the 6R-diastereomer of DDATHF in the cultured human leukemia cell lines CCRF-CEM and HL-60 are presented. At both 1 and 10 microM (6R)-DDATHF was rapidly converted to polyglutamates in both cell lines. DDATHF(Glu)5 and DDATHF(Glu)6 were the main intracellular metabolites. After incubation in drug-free medium, (6R)-DDATHF polyglutamates were better retained intracellularly with increasing glutamate chain length. (6R)-DDATHF showed reduced cytotoxicity toward a folylpolyglutamate synthetase-deficient cell line, CCRF-CEM30/6 related to a dramatically diminished accumulation of polyglutamates. The activity of (6R)-DDATHF in CCRF-CEM30/6 cells was decreased after both short and prolonged exposures. These results suggest that polyglutamylation of (6R)-DDATHF not only represents a mechanism for trapping the drug inside the cells but also produces a more potent inhibitor of the target enzyme.


[Endoscopic drainage of the biliary system].
Endoscopic biliary drainage, with nasobiliary catheter or biliary prostheses, changed the treatment of biliary problems. The first indication for endoscopic drainage with biliary prostheses ware malignant diseases and then, benign diseases, and recently, the use of metallic autoexpandable prostheses in malignant and benign diseases to avoid stent occlusion. At the same time, the nasobiliary catheter for biliary drainage began to be used first in benign pathologies with good results and low morbidity-mortality. This article reviews the indications for biliary endoscopic drainage, with nasobiliary catheter or biliary prostheses, and the results for endoscopic management employing both treatments.


Adaptation of a patient activation measure (PAM) into Turkish: reliability and validity test.
Patient activation is a central concept in chronic illness care model. Activated patients have ability and willingness to manage their health. Aim of this study was to test the reliability and validity of a Patient Activation Measure. Research sample consisted of 130 patients who had diabetes, hypertension or rheumatoid arthritis. Data was collected through socio-demographic information form and a Patient Activation Measure (PAM). Reliability and validity of PAM were analyzed. Internal consistency reliability coefficient of the PAM was α: .81. Correlation coefficients between item and total scale scores varied from .38 to .66. Result of explanatory factor analysis Kaiser Meyer Olkin coefficient was .75 and Barlett test was x2: 646.870; p: 0. 000. Result of confirmatory factor analysis, model fit indexes were x2/df: 1.59, RMSEA: 0.071, CFI: 0.96, NNFI: 0.95. The result of Rasch analysis, reliability coefficient varied from 0.83 to 0.87 and in validity assesment, item fit statistics for INFIT varied from 0.68 to 1.53 and for OUTFIT varied from 0.65 to 1.54. PAM has enough validy and reliability for use in determining activation scores and level of the patients in Turkey. It could be used in planing appropriate interventions for the activation level and help to improve self management.


Alexithymia influences brain activation during emotion perception but not regulation.
Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.


Phenotyping the effect of diet on non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and progression of NAFLD. In general, saturated fat and fructose seem to stimulate hepatic lipid accumulation and progression into NASH, whereas unsaturated fat, choline, antioxidants, and high-protein diets rich in isoflavones seem to have a more preventive effect. Knowledge of the underlying mechanisms by which diet affects NAFLD is expanding, not in the least due to innovative techniques, such as genomics tools that provide detailed comprehensive information on a large high-throughput scale. Although most nutrients seem to interfere with the balance between hepatic de novo lipogenesis (endogenous synthesis of fatty acids) and lipid oxidation (burning fat for energy), there are also indications that diet can trigger or prevent hepatic lipid accumulation by influencing the interaction between liver, gut, and adipose tissue. This review now gives a current detailed overview of diet-mediated mechanisms underlying NAFLD development and progression and summarizes recent results of genomics (transcriptomics, proteomics and metabolomics) studies that contribute to improved staging, monitoring and understanding of NAFLD pathophysiology.


Evidence for the involvement of serine transhydroxymethylase in serine and glycine interconversions in Salmonella typhimurium.
Salmonella typhimurium can normally use glycine as a serine source to support the growth of serine auxotrophs. This reaction was presumed to occur by the reversible activity of the enzyme, serine transhydroxymethylase (E. C. 2. 1. 2. 1; L-serine: tetrahydrofolic-5, 10 transhydroxymethylase), which is responsible for glycine biosynthesis. However, this enzyme had not been demonstrated to be solely capable of synthesizing serine from glycine in vivo. The isolation and characterization of a mutant able to convert serine to glycine but unable to convert glycine to serine supports the conclusion that a single enzyme is involved in this reversible interconversion of serine and glycine. The mutation conferring this phenotype was mapped with other mutations affecting serine transhydroxymethylase (glyA) and assays demonstrated reduced activities of this enzyme in the mutant.


Antigen heterogeneity of human B and T lymphocytes.
Rhesus monkeys were immunized with normal human lymphoid cells, cultured lymphoid cells, and chronic leukemic lymphocytes. Antisera were analyzed by cytotoxicity and immunofluorescence techniques to study the antigenic characteristics of human lymphocytes. In an attempt to obtain a reagent specifically reactive with T (thymus-derived) lymphocytes, an antispleen antiserum was absorbed with cellf from five B- (bone marrow-derived) cell lines. After absorption, the antiserum killed 60-75% of peripheral blood lymphocytes and 40-50% of tonsil cells, so that there was a relationship between the percentage of killed cells and the proportion of T lymphocytes. However, when cells after cytotoxic treatment were assayed for rosette formation with sheep erythrocytes (a T-cell marker) 5-20% of viable rosette-forming lymphocytes were found. Therefore, this antiserum was cytotoxic for only 75-90% of T cells. From studies performed with antisera prepared against spleen and B-cell lines, we conclude that lymphoblastoid cells are antigenically different and deficient in comparison to normal B lymphocytes. In addition, cultured B-cell lines appear to be antigenically heterogenous, as shown by the cytotoxic activity remaining in antispleen and anti-B-cell lines sera after absorption with various numbers and types of lymphoid cell lines. After absorption with normal lymphocytes, an antiserum produced against chronic lymphatic leukemia cells had specific activity associated with 12 chronic lymphatic leukemia cells tested. Absorption of the same antiserum with leukemic cells from two patients showed that a certain degree of antigenic heterogeneity also exists among chronic leukemic lymphocytes.


Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer.
In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)-induced or TNBS-induced models of colitis. High-dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS-induced CAC model. It also decreased the expression of pro-inflammatory cytokines, such as IL-13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll-like receptor 4 (TLR4)/NF-κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF-κB signalling-mediated inflammatory responses and disruption of the intestinal microbiotal structure.


Characterization of Sarcocystis from four species of hawks from Georgia, USA.
During 2001 to 2004, 4 species of hawks (Buteo and Accipiter spp.) from Georgia were surveyed for Sarcocystis spp. infections by examining intestinal sections. In total, 159 of 238 (66.8%) hawks examined were infected with Sarcocystis spp. Samples from 10 birds were characterized by sequence analysis of a portion of the 18S rRNA gene (783 base pairs). Only 3 of the 10 sequences from the hawks were identical; the remainder differed by at least 1 nucleotide. Phylogenetic analysis failed to resolve the position of the hawk Sarcocystis species, but they were closely related several Sarcocystis species from raptors, rodents, and Sarcocystis neurona. The high genetic diversity of Sarcocystis suggests that more than 1 species infects these 4 hawk species; however, additional molecular or experimental work will be required to determine the speciation and diversity of parasites infecting these avian hosts. In addition to assisting with determining species richness of Sarcocystis in raptors, molecular analysis should be useful in the identification of potential intermediate hosts.


Differences in coronary heart disease, stroke and cancer mortality rates between England, Wales, Scotland and Northern Ireland: the role of diet and nutrition.
Introduction It is unclear how much of the geographical variation in coronary heart disease (CHD), stroke and cancer mortality rates within the UK is associated with diet. The aim of this study is to estimate how many deaths from CHD, stroke and cancer would be delayed or averted if Wales, Scotland and Northern Ireland adopted a diet equivalent in nutritional quality to the English diet. Methods Mortality data for CHD, stroke and 10 diet-related cancers for 2007-2009 were used to calculate the mortality gap (the difference between actual mortality and English mortality rates) for Wales, Scotland and Northern Ireland. Estimates of mean national consumption of 10 dietary factors were used as baseline and counterfactual inputs in a macrosimulation model (DIETRON). An uncertainty analysis was conducted using a Monte Carlo simulation with 5000 iterations. Results The mortality gap in the modelled scenario (achieving the English diet) was reduced by 81% (95% credible intervals: 62% to 108%) for Wales, 40% (33% to 51%) for Scotland and 81% (67% to 99%) for Northern Ireland, equating to approximately 3700 deaths delayed or averted annually. For CHD only, the mortality gap was reduced by 88% (69% to 118%) for Wales, 58% (47% to 72%) for Scotland, and 88% (70% to 111%) for Northern Ireland. Conclusion Improving the average diet in Wales, Scotland and Northern Ireland to a level already achieved in England could have a substantial impact on reducing geographical variations in chronic disease mortality rates in the UK. Much of the mortality gap between Scotland and England is explained by non-dietary risk factors.


Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation.
The human immunodeficiency virus type 1 (HIV-1) envelope (Env) trimer evades antibody recognition by adopting a closed prefusion conformation. Here, we show that two conserved tyrosines (Y173, Y177) within the second variable (V2) loop of the gp120 Env glycoprotein are key regulators of the closed, antibody-protected state of the trimer by establishing intramolecular interaction with the base of the third variable (V3) loop. Mutation of Y177 and/or Y173 to phenylalanine or alanine dramatically altered the susceptibility of diverse HIV-1 strains to neutralization, increasing sensitivity to weakly and nonneutralizing antibodies directed against diverse Env regions, consistent with the adoption of an open trimer configuration. Conversely, potent broadly neutralizing antibodies (bNAbs) against different supersites of HIV-1 vulnerability exhibited reduced potency against V2 loop tyrosine mutants, consistent with their preferential targeting of the closed trimer. Mutation of V3 loop residues predicted to interact with the V2 loop tyrosines yielded a similar neutralization phenotype. Sera from chronically HIV-1-infected patients contained very high titers of antibodies capable of neutralizing V2 loop tyrosine mutants but not wild-type viruses, indicating that the bulk of antibodies produced in infected hosts are unable to penetrate the protective shield of the closed trimer. These results identify the tyrosine-mediated V2-V3 loop complex at the trimer apex as a key structural constraint that facilitates HIV-1 evasion from the bulk of host antibodies.IMPORTANCE The extraordinary ability of human immunodeficiency virus type 1 (HIV-1) to evade host immunity represents a major obstacle to the development of a protective vaccine. Thus, elucidating the mechanisms whereby HIV-1 protects its external envelope (Env), which is the sole target of virus-neutralizing antibodies, is an essential step toward vaccine design. We identified a key structural element that maintains the HIV-1 Env trimer in a closed, antibody-resistant conformation. A major role is played by two conserved tyrosines at the apex of the Env spike, whose mutation causes a global opening of the trimer structure, exposing multiple concealed targets for neutralizing antibodies. We also found that HIV-infected individuals produce very large amounts of antibodies that neutralize the open Env form; however, the bulk of these antibodies are unable to penetrate the tight defensive shield of the native virus. This work may help to devise new strategies to overcome the viral defensive mechanisms and facilitate the development of an effective HIV-1 vaccine.


Late complications of childhood female genital mutilation.
Canada's immigrants are increasingly from non-English-speaking countries with different medical issues. Female genital mutilation (FGM) is a procedure performed for non-medical reasons that is not traditionally encountered in Canada and that has serious health implications for women. A 36-year-old woman, who underwent FGM at the age of four, presented to our colposcopy unit with increasing swelling of the vulva. Examination revealed a large cystic mass in the midline of the vulva, and MRI identified two well-defined cystic lesions. The mass was excised, and histologic examination confirmed an epidermal inclusion cyst. An epidermal inclusion cyst can develop as a long-term consequence of FGM. Although it grows slowly and usually without symptoms, it may require excision because of inflammation, secondary infection, or, in rare cases, malignancy developing within the cyst.


Teenage pregnancy prevention: the role of young men.
Although teenage pregnancy is declining in many parts of the world, it remains associated with considerable social, health, and economic outcomes. Pregnancy prevention efforts focus primarily on young women, with minimal attention to young men. This review highlights recent literature pertaining to the role of young men in pregnancy prevention. Young men have varying views on contraception as well as which partner(s) should be responsible for its use. Limited contraception knowledge reduces young men's sexual health communication as well as their contraception use. Healthcare providers play a major role as one of the main sources of sexual health information for young men, but there are gaps in young men's sexual health care so new guidelines have emerged. Recent literature highlights young men's range of views on contraception as well as their low sexual health knowledge and sexual health communication. To address teenage pregnancy and improve young men's overall wellness, healthcare providers should routinely address sexual health. Healthcare providers may use our newly proposed acronym, HIS BESTT, (Hello. Initiate. Sexual health assessment. Both condoms and female dependent methods. Examine genitals. STI screening. Talking to partner(s). Talking to parent(s) or guardians), to incorporate current clinical recommendations.


Differential temporal evolution of post-training changes in regional brain glucose metabolism induced by repeated spatial discrimination training in mice: visualization of the memory consolidation process?
The present study analyses the effects of the stage of learning on the spatial patterns and time-course of [14C]glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight-arm radial maze. Our particular approach was designed to follow, during the post-training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C]glucose uptake was assessed at three post-training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham-conditioned animals placed in the same experimental environment. The results indicated that numerous subcortical and cortical brain regions exhibit metabolic alterations following the acquisition of the spatial discrimination task. These alterations, which were specifically related to learning since they did not appear in sham-conditioned animals, were functions both of the post-training interval studied and of the degree of mastery of the task. On Day 1, a progressive, time-dependent and sequential increase in labelling was found from subcortical (5 min post-training) to cortical regions (3 h post-training). On Day 4, a peak of cortical metabolic activation was identified at 1 h post-training. In contrast, on Day 9, maximum labelling was found 5 min post-training in all subcortical and cortical regions followed by a general monotonic decline at 1 and 3 h post-training. These findings, which show widely distributed changes of metabolic activity in the brain, are consistent with the hypothesis that learning involves distributed neural networks. The sequential activation from subcortical to cortical regions seems to indicate a general mechanism whose function would ultimately be to store cortical memory representations. The acquisition-dependent shifts in the patterns of post-training metabolic labelling observed as a function of task mastery may be taken to represent a visualization of the spatio-temporal evolution of the networks of brain structures actively engaged in the memory consolidation process. In particular, the present data suggest that the duration of post-acquisition memory processing is a function of the quantity of new information which has to be dealt with by the central nervous system.


Real-ear acoustical characteristics of impulse sound generated by golf drivers and the estimated risk to hearing: a cross-sectional study.
This study investigated real-ear acoustical characteristics in terms of the sound pressure levels (SPLs) and frequency responses in situ generated from golf club drivers at impact with a golf ball. The risk of hearing loss caused by hitting a basket of golf balls using various drivers was then estimated. Cross-sectional study. The three driver clubs were chosen on the basis of reflection of the commonality and modern technology of the clubs. The participants were asked to choose the clubs in a random order and hit six two-piece range golf balls with each club. The experiment was carried out at a golf driving range in South Wales, UK. 19 male amateur golfers volunteered to take part in the study, with an age range of 19-54 years. The frequency responses and peak SPLs in situ of the transient sound generated from the club at impact were recorded bilaterally and simultaneously using the GN Otometric Freefit wireless real-ear measurement system. A swing speed radar system was also used to investigate the relationship between noise level and swing speed. Different clubs generated significantly different real-ear acoustical characteristics in terms of SPL and frequency responses. However, they did not differ significantly between the ears. No significant correlation was found between the swing speed and noise intensity. On the basis of the SPLs measured in the present study, the percentage of daily noise exposure for hitting a basket of golf balls using the drivers described above was less than 2%. The immediate danger of noise-induced hearing loss for amateur golfers is quite unlikely. However, it may be dangerous to hearing if the noise level generated by the golf clubs exceeded 116 dBA.


Programmable comprehensive controller for multi-color 3D confocal spinning-disk image scanning microscope.
This paper introduces a compact, portable, and highly accurate triggering control system for a 3D confocal spinning-disk image scanning microscope (CSD-ISM). Building upon on our previously published research, we expanded the hardware of the controller and synchronized it with a sub-micron translator which scans the object in the z-direction. As well as expanding the hardware, the software also was extended from previously published work similarly as it is stated for hardware while allowing full control over the 3D movement. We showed a clear and smooth 3D image made up of a collection of 2D images at different heights.


[Seroprevalence anti-Ehrlichia canis antibodies in dogs of Cuiabá, Mato Grosso].
Canine ehrlichiosis is a disease transmitted by ticks Rhipicephalus sanguineus and caused by Ehrlichia canis, obligatory intracellular bacteria. The present study examined the prevalence of anti-E. canis in 254 dogs from four administrative regions of Cuiabá, Mato Grosso, by indirect immunofluorescence assay. There was a prevalence of 42.5% (108/254) without significant difference between the studied regions. The variables age, breed, sex, habitat, access to rural and ticks were analyzed. The antibody titers ranged from 1:40 to 1:2,560. Only 32 (29.63%) seropositive dogs were infested with ticks, all R. sanguineus. The results confirm that do not have breed, sex or age predisposition to ehrlichiosis due E. canis, while the lowest occurrence of reactive dogs indoors probably related to low tick infestation, although no significant difference between dogs with or without infestation with the tick vector.


Thrombotic microangiopathy associated with intravenous injection of extended-release oxycodone.
We describe the case of a 35-year-old man presenting with thrombotic microangiopathy (TMA) and renal impairment following, as he later disclosed, intravenous injection of oral formulation tamper-resistant extended-release oxycodone hydrochloride (Oxycontin). Recurrent misuse of this agent was associated with relapsing TMA despite treatment with terminal complement inhibitor eculizumab. Cases of TMA have been reported in the USA in association with intravenous misuse of extended-release oxymorphone (Opana ER) after the introduction of a new non-crushable formulation in 2012. There are two reported accounts of TMA associated with tamper-resistant Oxycontin, which became available in Australia in 2014. This is the first documented case in which eculizumab was used. This case illustrates the practical diagnostic challenges in identifying TMA disorders, and the importance of a detailed drug history. It also highlights the need to clarify what role, if any, eculizumab therapy has in cases of drug-associated TMA.


Evidence for the Factorial and Construct Validity of a Self-Report Concussion Symptoms Scale.
OBJECTIVE: To evaluate the factorial and construct validity of the Head Injury Scale (HIS) among a sample of male and female collegiate athletes. DESIGN AND SETTING: Using a cross-sectional design, we established the factorial validity of the HIS scale with confirmatory factor analysis and the construct validity of the HIS with Pearson product moment correlation analyses. Using an experimental design, we compared scores on the HIS between concussed and nonconcussed groups with a 2 (groups) x 5 (time) mixed-model analysis of variance. SUBJECTS: Participants (N = 279) in the cross-sectional analyses were predominately male (n = 223) collegiate athletes with a mean age of 19.49 +/- 1.63 years. Participants (N = 33) in the experimental analyses were concussed (n = 17) and nonconcussed control (n = 16) collegiate athletes with a mean age of 19.76 +/- 1.49 years. MEASUREMENTS: All participants completed baseline measures for the 16-item HIS, neuropsychological testing battery, and posturography. Concussed individuals and paired controls were evaluated on days 1, 2, 3, and 10 postinjury on the same testing battery. RESULTS: Confirmatory factor analysis indicated that a theoretically derived, 3-factor model provided a good but not excellent fit to the 16-item HIS. Hence, the 16-item HIS was modified on the basis of substantive arguments about item-content validity. The subsequent analysis indicated that the 3-factor model provided an excellent fit to the modified 9-item HIS. The 3 factors were best described by a single second-order factor: concussion symptoms. Scores from the 16-item HIS and 9-item HIS were strongly correlated, but there were few significant correlations between HIS scores and scores from the neuropsychological and balance measures. A significant group-by-day interaction was noted on both the 9-item HIS and 16-item HIS, with significant differences seen between groups on days 1 and 2 postconcussion. CONCLUSIONS: We provide evidence for the factorial and construct validity of the HIS among collegiate athletes. This scale might aid in return-to-play decisions by physicians and athletic trainers.


The endocannabinoid system and multiple sclerosis.
Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish "quality of life" and have prompted some patients to self-medicate with and perceive benefit from cannabis. Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system. Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects. In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion. In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults. Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.


Consumption of green tea epigallocatechin-3-gallate enhances systemic immune response, antioxidative capacity and HPA axis functions in aged male swiss albino mice.
The present investigation assessed the potential of green tea phytochemical epigallocatechin-3-gallate (EGCG) in alleviating age-associated aberrations in immunity, hypothalamus-pituitary-adrenal (HPA) axis and redox homeostasis using 16 months old male Swiss albino mice. Four groups of animals (n = 6 per group) were supplemented with either aqueous EGCG at 25, 50 and 100 mg/kg/animal or vehicle control for 6 weeks. A concurrent analysis of CD4+ and CD8+ lymphocytes in splenocytes, differential leucocyte population, T cell differentiation markers in peripheral blood mononuclear cells (PBMCs), neutrophil functions, immunoglobulins profile in intestine, circulatory HPA axis hormonal levels as well as inflammatory and oxidative stress in the liver was performed. We observed a remarkable increase in plasma dehydroepiandrosterone (DHEA) levels of 100 mg EGCG fed animals while eosinophils and monocytes counts in blood increased. EGCG consumption increased the fraction of CD3+CD8+ cells in splenocytes and CD28 expression on PBMCs. The immunoglobulins profile revealed decreased production of secretory IgA, IgE and IgG1/IgG2a ratio. Liver extracts showed increase in superoxide dismutase activity and total antioxidant capacity while lipid peroxidation along with inflammatory markers (IL-6 and TNF-α) decreased. Our results collectively show that EGCG consumption during aging strengthens systemic immunity by enhancing cellular immune response and simultaneously attenuating antibody response aided by an increase in adrenal DHEA production. Thus, consumption of green tea may be beneficial in alleviating some of the deleterious aspects of aging and immunosenescence in elderly.


1alpha-Hydroxyvitamin D2: a potent synthetic analog of vitamin D2.
A hydroxy analog of vitamin D(2), 1alpha-hydroxyvitamin D(2), has been synthesized and tested for biological activity. This vitamin derivative is active in stimulating intestinal calcium transport and bone calcium mobilization in the rat and exhibits antirachitic activity. Its biopotency is comparable to that of the corresponding vitamin D(3) analog, 1alpha-hydroxyvitamin D(3).


Korean self-report version of the yale-brown obsessive-compulsive scale: factor structure, reliability, and validity.
Although several self-report versions of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) have been developed and used widely, few psychometric studies have established the construct validity of this measure. Therefore, we developed Korean self-report version of the Y-BOCS and evaluated its factor structure, reliability, and validity. A non-clinical student sample (n=206) and a clinical OCD sample (n=199) completed the Korean self-report version and other measures of obsessive-compulsive disorder (OCD), depression, and anxiety. Consistent with the originally proposed structure, confirmatory factor analyses supported a factor structure comprised of Obsessions and Compulsions factors in the Korean self-report version. Two subscale scores and the total score of the Korean self-report version showed good internal consistency and convergent validity, but relatively poor discriminant validity. Applying a cutoff score of 16, 84% of OCD patients and 93% of the non-clinical sample were classified correctly. Korean self-report version of the Y-BOCS is a psychometrically sound and valid measure for assessing OCD symptoms as compared with the clinician-administered version. The originally proposed division of OCD severity into obsessions and compulsions appears accurate in the Korean self-report version. The cutoff score for the Korean self-report version needs adjustment based on further researches.


Unilateral lichen planus pigmentosus mimicking acral lentiginous melanoma.
The authors report a case of a Latin American woman who developed progressive pigmentation primarily involving two digits of her right hand. She was scheduled for amputation based on a presumptive histologic diagnosis of melanoma with regression. Dermatology consultation with repeat biopsies disclosed a lichenoid tissue reaction with marked pigment incontinence and no evidence of melanoma. This report should prompt physicians to include lichen planus pigmentosus in the differential diagnosis of acral lentiginous melanoma.


[Ophthalmological symptoms following extrathoracal reanimation (author's transl)].
In patients with cardiac arrest and extrathorakal reanimation, hyposphagma, vitreous and retinal hemorrhages, fat embolism in the retinal arteries as well as fluffy exudates of the fundus were observed. Pathogenesis and connections with Purtscher's traumatic angiopathic retinopathy are discussed.


Nonlinear absorption: intraocular microsurgery and laser lithotripsy.
The paper reviews the principles of nonlinear absorption with reference to the present major clinical applications of plasma-mediated effects: intraocular microsurgery and laser lithotripsy. Emphasis is laid on the analysis of the working mechanisms, sources of collateral damage, and on strategies for both the optimization of efficacy and the minimization of side effects.


Note: An automated image analysis method for high-throughput classification of surface-bound bacterial cell motions.
We present a Single-Cell Motion Characterization System (SiCMoCS) to automatically extract bacterial cell morphological features from microscope images and use those features to automatically classify cell motion for rod shaped motile bacterial cells. In some imaging based studies, bacteria cells need to be attached to the surface for time-lapse observation of cellular processes such as cell membrane-protein interactions and membrane elasticity. These studies often generate large volumes of images. Extracting accurate bacterial cell morphology features from these images is critical for quantitative assessment. Using SiCMoCS, we demonstrated simultaneous and automated motion tracking and classification of hundreds of individual cells in an image sequence of several hundred frames. This is a significant improvement from traditional manual and semi-automated approaches to segmenting bacterial cells based on empirical thresholds, and a first attempt to automatically classify bacterial motion types for motile rod shaped bacterial cells, which enables rapid and quantitative analysis of various types of bacterial motion.


HIV-1 and HIV-2 Vif interact with human APOBEC3 proteins using completely different determinants.
Human APOBEC3 (A3) restriction factors provide intrinsic immunity against zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs to inhibit viral replication. To overcome these restriction factors, Vif binds to the A3 proteins in viral producer cells to target them for ubiquitination and proteasomal degradation, thus preventing their packaging into assembling virions. Therefore, the Vif-A3 interactions are attractive targets for novel drug development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of simian immunodeficiency viruses from chimpanzees and sooty mangabeys, respectively, and Vifs from these viruses have limited homology. To gain insights into the evolution of virus-host interactions that led to successful cross-species transmission of lentiviruses, we characterized the determinants of the interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced degradation. Alanine-scanning mutational analysis of the first 62 amino acids of Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F are completely distinct from these regions in Vif1, as are the determinants in A3G and A3F that are critical for Vif2-induced degradation. These observations suggest that distinct Vif-A3 interactions evolved independently in different SIVs and their nonhuman primate hosts and conservation of the A3 determinants targeted by the SIV Vif proteins resulted in successful zoonotic transmission into humans. Primate APOBEC3 proteins provide innate immunity against invading pathogens, and Vif proteins of primate lentiviruses have evolved to overcome these host defenses by interacting with them and inducing their proteasomal degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and elucidating interactions between their Vif proteins and human A3 proteins could facilitate the development of novel antiviral drugs. Furthermore, understanding Vif-A3 interactions can provide novel insights into the cross-species transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of host-virus interactions. We carried out mutational analysis of the N-terminal 62 amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained antiviral activity to identify the determinants of the Vif2 and A3 interaction. Our results show that the Vif2-A3 interactions are completely different from the Vif1-A3 interactions, suggesting that these interactions evolved independently and that conservation of the A3 determinants resulted in successful zoonotic transmission into humans.


'Going green' in food services: Can health care adopt environmentally friendly practices?
Sustainability and the environment are issues influencing individual and organizational choices on purchasing, waste management, and energy-saving practices. The food service industry and related stakeholders have reported active pursuit of initiatives to reduce environmental impacts. We examine reported environmentally friendly practices being implemented in the food service industry and consider ways in which health care or hospital food services can adopt some of these programs. Building and equipment, waste management, food, and non-food supplies and procurement are considered. Suggestions are made for small changes to start the green initiative in each of these areas. A health care food service department is a large consumer of resources, and therefore food service workers, managers, dietitians, and administrators can make a significant difference by supporting and adopting environmentally friendly practices. Further studies are needed to determine which practices are currently being implemented in health care facilities in Canada, as well as perceived facilitators and barriers to these practices in the food service area.


Concentric Circular Grating Generated by the Patterning Trapping of Nanoparticles in an Optofluidic Chip.
Due to the field enhancement effect of the hollow-core metal-cladded optical waveguide chip, massive nanoparticles in a solvent are effectively trapped via exciting ultrahigh order modes. A concentric ring structure of the trapped nanoparticles is obtained since the excited modes are omnidirectional at small incident angle. During the process of solvent evaporation, the nanoparticles remain well trapped since the excitation condition of the optical modes is still valid, and a concentric circular grating consisting of deposited nanoparticles can be produced by this approach. Experiments via scanning electron microscopy, atomic force microscopy and diffraction of a probe laser confirmed the above hypothesis. This technique provides an alternative strategy to enable effective trapping of dielectric particles with low-intensity nonfocused illumination, and a better understanding of the correlation between the guided modes in an optical waveguide and the nanoparticles in a solvent.


Metabolomic profile of acute myeloid leukaemia parallels of prognosis and response to therapy.
The heterogeneity of acute myeloid leukemia (AML), a complex hematological malignancy, is caused by mutations in myeloid cells affecting their differentiation and proliferation. Thus, various cytogenetic alterations in AML cells may be characterized by a unique metabolome and require different treatment approaches. In this study, we performed untargeted metabolomics to assess metabolomics differences between AML patients and healthy controls, AML patients with different treatment outcomes, AML patients in different risk groups based on the 2017 European LeukemiaNet (ELN) recommendations for the diagnosis and management of AML, AML patients with and without FLT3-ITD mutation, and a comparison between patients with FLT3-ITD, CBF-AML (Core binding factor acute myelogenous leukemia), and MLL AML (mixed-lineage leukemia gene) in comparison to control subjects. Analyses were performed in serum samples using liquid chromatography coupled with mass spectrometry (LC-MS). The obtained metabolomics profiles exhibited many alterations in glycerophospholipid and sphingolipid metabolism and allowed us to propose biomarkers based on each of the above assessments as an aid for diagnosis and eventual classification, allowing physicians to choose the best-suited treatment approach. These results highlight the application of LC-MS-based metabolomics of serum samples as an aid in diagnostics and a potential minimally invasive prognostic tool for identifying various cytogenetic and treatment outcomes of AML.


Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience.
Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC) is a rare phenotype. We aimed to assess patients with UC-PSC or UC alone and describe differences in clinical and phenotypic characteristics, antitumor necrosis factor (TNF) therapy, and long-term clinical outcomes. This retrospective multicenter cohort study included patients who received a diagnosis of UC from 1962 through 2015. We evaluated clinical factors associated with UC-PSC vs UC alone and assessed associations by using multivariable logistic regression models. Among 522 patients with UC, 56 (10.7%) had PSC. Compared with UC alone, patients with UC-PSC were younger (younger than 20 years) at diagnosis (odds ratios [OR], 2.35; adjusted P = 0.02) and had milder UC severity (adjusted P = 0.05), despite having pancolonic involvement (OR, 7.01; adjusted P < 0.001). In the biologics era (calendar year 2005 to 2015), patients with UC-PSC less commonly received anti-TNF therapy compared with patients with UC (OR, 0.38; adjusted P = 0.009), but their response rates were similar. Fewer patients with UC-PSC received corticosteroids (OR, 0.24; adjusted P = 0.005) or rectal 5-aminosalicyte acid (OR, 0.26; adjusted P < 0.001). Other differences were identified that were not statistically significant in a multivariable model: patients with UC-PSC more commonly were male, had lower rates of smoking, and had higher rates of colorectal cancer and colectomy. This study identified a unique phenotype of UC with concurrent PSC, which had different clinical behavior compared with UC only. These phenotypic characteristics can help identify high-risk patients with UC before PSC is diagnosed and guide different management and monitoring strategies.


Urinary tract infection in infancy is a risk factor for chronic abdominal pain in childhood.
Adverse early life events are key factors for development of functional gastrointestinal disorders (FGIDs). Urinary tract infection (UTI) is associated with chronic pelvic pain in adults, a finding that has been recapitulated in murine models, but the relation between UTI and chronic pelvic and abdominal pain has not been studied in children. We hypothesized that UTI in infancy increases the risk of FGIDs and chronic abdominal pain (CAP) in childhood. The present study included children, ages 4 to 18 years, with a single UTI in the first year of life and their siblings with no history of UTI. Parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-III) by telephone. Children meeting QPGS-III criteria for FGIDs but with pain less than once weekly were considered to have CAP. A total of 57 patients with UTI and 58 sibling controls were identified. Mean age at UTI was 4.8 months, and mean time since UTI was 9.3 years. At the time of survey, mean age of patients was 9.7 years (5-16 years, 40% boys) and that of controls was 9.6 years (range 4-17 years, 57% boys). FGIDs were diagnosed in 6 of 57 (11%) patients, and 1 of 58 (2%) controls (P = 0.06). CAP was identified in 10 of 57 (18%) patients and 2 of 58 (3%) controls (P = 0.02). Predominant sex (female), infecting organism (E coli), and treatment (third-generation cephalosporin) were similar in patients with UTI with and without CAP. We show for the first time that UTI is associated with CAP in childhood. We speculate that pelvic organ sensory convergence explains our findings.


Substance use and risk of death in young offenders: a prospective data linkage study.
Young offenders are at increased risk of preventable death after release from custody, but risk factors for death in this population are poorly understood. Despite their poor health profiles, no studies have examined mortality outcomes in young people who have served community-based orders. The aims of this study were to describe the causes and identify risk factors for death in a cohort of young offenders in Victoria, Australia. We interviewed young people serving a custodial (n = 273) or community-based order (n = 242) in Victoria, Australia in 2002-2003. Measures included demographics and family history, offence history, experience of victimisation, mental illness, self-harm and substance use. Deaths up to 31 December 2011 were identified through a probabilistic linkage with the National Death Index. The all-cause crude mortality rate was 4.2 (95% confidence interval 2.7-6.8) per 1000 person years and was not significantly different for those who had served custodial and community-based orders. Most deaths were due to drug overdose, traffic accidents or suicide. Adjusting for age, sex and order type, risk factors for death from the baseline interview included weekly use of opioids, sleeping pills or painkillers, polydrug use and injecting drug use. Young people who have served community-based and custodial orders are at an increased risk of preventable death. Those engaging in risky substance use, particularly injecting drug use and use of multiple central nervous system depressants, are at greatest risk. There is an urgent need to develop and rigorously evaluate preventive interventions.


Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation.
The role of interleukin 4 (IL-4) (previously called B-cell stimulatory factor 1) in the response of T helper (TH) cells to antigen presented by antigen-specific B cells or splenic adherent cells was investigated. Antigenic stimulation of either a keyhole-limpet-hemocyanin-specific TH-cell line or two keyhole-limpet-hemocyanin-specific T-cell clones resulted in the secretion of IL-4 but not interleukin 2 (IL-2). The secretion of IL-4 was first detected in the culture supernatant 6-8 hr after antigenic stimulation. Induction of IL-4 secretion was antigen specific and major histocompatibility complex restricted. Antigenic stimulation also resulted in increased responsiveness of the TH cells to exogenously added or endogenously produced IL-4. The antigen-induced proliferation of the TH cells could be inhibited by an anti-IL-4 antibody but not by an anti-IL-2-receptor antibody. These results suggest that IL-4 mediates the proliferation of some TH cells by an antigen-induced autocrine mechanism. Taken together with past results, these data indicate that, during T-cell-B-cell interactions involving some soluble protein antigens, IL-4 and not IL-2 is the critical lymphokine for activating resting B cells and inducing proliferation of the TH cells.


Spontaneous and mutator-induced reversions of an Escherichia coli auxotroph. II. Acetylornithinase activity associated with the different revertant types.
Bacon, Donald F. (Yale University, New Haven, Conn.), and Henry P. Treffers. Spontaneous and mutator-induced reversions of an Escherichia coli auxotroph. II. Acetylornithinase activity associated with the different revertant types. J. Bacteriol. 82:48-53. 1961.-In a preceding communication it was shown that three principal groups of spontaneous revertants from an ornithine-requiring strain of Escherichia coli could be distinguished on the basis of their growth characteristics. They were designated as fast (F) (identical with the wild type), slow-48 (S(48)), and slow-72 (S(72)). The present paper presents data on the acetylornithinase activities as well as precursor accumulations of typical revertants from each group. The enzymatic activity associated with extracts of F revertants did not differ significantly from those of the wild type; the mean activity of extracts from the wild-type and F revertants was 23 units per mg of protein; the mean activity of S(48) revertant extracts was 0.4 units per mg of protein and, similarly, that of the S(72) revertant extracts was 0.06 units per mg of protein. These are, respectively, 1/50 and 1/350 of the wild-type activity. It was estimated that an S(48) culture in minimal broth accumulated 16 mug of N(alpha)-acetylornithine per ml and that an S(72) culture accumulated 60 mug per ml of this compound. Accumulation of this precursor in an F revertant culture was not detected by the assay procedure employed. In an earlier communication we reported that both the S(48) and S(72) revertant types exhibited increasing rates of growth when the growth in minimal broth was followed photometrically Supplements of N(alpha)-acetylornithine and of a sterile supernatant from an S(48) revertant culture which were incorporated into minimal broth failed to modify the unusual curvilinear nature of the growth curve. The data on the enzymatic activities and precursor accumulations support the original classification of revertant groups on the basis of growth rates. The total information at hand is consistent with the notion that reversion from an auxotrophic requirement may result in at least three distinct revertant types, each characterized by a unique growth rate, enzymatic activity, and precursor accumulation.


Dependence of EEG spectral power density on the meaning of stimuli.
Spectrum analysis of event-related brain activity periods was done in the 2-32 Hz frequency band. Three tests were performed in which the flash acted as an attention requiring stimulus or as a negative or a positive reinforcement. EEG was recorded from 8 scalp leads on 24 human subjects. During the performance-adapted time conditioning task, with the flash acting as a negative reinforcer, there was a marked increase of densities for frequencies 2-7 Hz and a decrease for 8-13 Hz in the fronto-centro-parietal leads. Power shifts are discussed in relation to the different meaning of the flashes.


Deoxycholic acid activates protein kinase C and phospholipase C via increased Ca2+ entry at plasma membrane.
Secondary bile acids like deoxycholic acid (DCA) are well-established tumor promoters that may exert their pathologic actions by interfering with intracellular signaling cascades. We evaluated the effects of DCA on Ca2+ signaling in BHK-21 fibroblasts using fura-2 and mag-fura-2 to measure cytoplasmic and intraluminal internal stores [Ca2+], respectively. Furthermore, green fluorescent protein (GFP)-based probes were used to monitor time courses of phospholipase C (PLC) activation (pleckstrin-homology [PH]-PLCdelta-GFP), and translocation of protein kinase C (PKC) and a major PKC substrate, myristolated alanine-rich C-kinase substrate (MARCKS). DCA (50-250 micromol/L) caused profound Ca2+ release from intracellular stores of intact or permeabilized cells. Correspondingly, DCA increased cytoplasmic Ca2+ to levels that were approximately 120% of those stimulated by Ca2+-mobilizing agonists in the presence of external Ca2+, and approximately 60% of control in Ca2+-free solutions. DCA also caused dramatic translocation of PH-PLCdelta-GFP, and conventional, Ca2+/diacylglycerol (DAG)-dependent isoforms of PKC (PKC-betaI and PKC-alpha), and MARCKS-GFP, but only in Ca2+-containing solutions. DCA had no effect on localization of a novel (PKCdelta) or an atypical (PKCzeta) PKC isoform. Data are consistent with a model in which DCA directly induces both Ca2+ release from internal stores and persistent Ca2+ entry at the plasma membrane. The resulting microdomains of high Ca2+ levels beneath the plasma membrane appear to directly activate PLC, resulting in modest InsP 3 and DAG production. Furthermore, the increased Ca2+ entry stimulates vigorous recruitment of conventional PKC isoforms to the plasma membrane.


Building the evidence base on the HIV programme in India: an integrated approach to document programmatic learnings.
The Knowledge Network project was launched in 2010 to build evidence on the HIV epidemic by using the data generated by HIV programme implementing organisations in India. This paper describes the implementation of the programme and the strategies adopted to enhance the capacity of individuals to document and publish HIV prevention programme learnings. Further, it discusses the outcomes of the initiative. A multipronged approach was adopted, where a group of experts were brought together to collaborate with programme implementing organisations, review available data, develop research questions and guide peer-reviewed publications. Further, scientific writing courses were conducted to support individuals from HIV programme implementing organisations as well as educational and government organisations (mentees) to build the documentation capacity of individuals leading programme implementation and current and future researchers. The impact and quality of evidence generated was measured by examining the number of papers published, the number of citations, and the number of papers with at least 10 citations. Additionally, course participants' responses to open-ended questions in the anonymous course evaluation questionnaires are presented as verbatim quotes. Overall, 99 papers on HIV programmatic learnings from India were finalised under the programme, of which 95 have been published. In all, 67 papers were co-authored by mentees. Most papers were published in high-impact factor (1 or more) journals and 72% were cited at least once in the literature. The main themes documented include key populations' HIV risk, HIV risk of general population groups, HIV/STI service delivery models and community mobilisation interventions. The study demonstrates that an integrated approach, involving partnership, capacity-building and mentorship, can maximise the use of available data and build the evidence base on HIV programmatic learnings. The capacity-building model adopted in the programme can be used to build scientific writing and documentation capacity in other public health programmes that are implemented at scale.


Inflammatory osteoarthritis which was precipitated by Arimidex and resolved with tamoxifen.
We report the case of a 51-year-old woman who presented with an inflammatory flare of osteoarthritis of the small joints of her hands occurring in a temporal relationship with the commencement of Arimidex, prescribed to reduce systemic oestrogen levels to treat breast cancer. Following the cessation of Arimidex and the initiation of tamoxifen, a specific oestrogen receptor antagonist, this flare resolved. It has long been observed that during the menopause, as oestrogen levels decline, many women develop osteoarthritis or experience progression of the disease. However, this theory of oestrogen-dependent osteoarthritis has not been consistently demonstrated in animal models. As far as the authors are aware, this is the first case in which systemic oestrogen reduction has resulted in a severe osteoarthritis flare but targeted oestrogen receptor blockade led to a resolution of symptoms. These findings may inform the pathophysiological process underlying oestrogen-dependent osteoarthritis, although further series are needed.