Morphological connectivity differences in Alzheimer's disease correlate with gene transcription and cell-type.
Alzheimer's disease (AD) is one of the most prevalent forms of dementia in older individuals. Convergent evidence suggests structural connectome abnormalities in specific brain regions are linked to AD progression. The biological basis underpinnings of these connectome changes, however, have remained elusive. We utilized an individual regional mean connectivity strength (RMCS) derived from a regional radiomics similarity network to capture altered morphological connectivity in 1654 participants (605 normal controls, 766 mild cognitive impairment [MCI], and 283 AD). Then, we also explored the biological basis behind these morphological changes through gene enrichment analysis and cell-specific analysis. We found that RMCS probes of the hippocampus and medial temporal lobe were significantly altered in AD and MCI, with these differences being spatially related to the expression of AD-risk genes. In addition, gene enrichment analysis revealed that the modulation of chemical synaptic transmission is the most relevant biological process associated with the altered RMCS in AD. Notably, neuronal cells were found to be the most pertinent cells in the altered RMCS. Our findings shed light on understanding the biological basis of structural connectome changes in AD, which may ultimately lead to more effective diagnostic and therapeutic strategies for this devastating disease.


Brain natriuretic peptide and impedance cardiography to assess volume status in peritoneal dialysis patients.
Assessment of volume status in patients with end-stage renal disease has long been a problem. Objective tools for estimating dry weight are necessary. The present study was designed to determine if better assessment of volume status could be achieved by measuring brain natriuretic peptide (BNP) and thoracic fluid content (TFC) by bioimpedance. We prospectively surveyed 51 medically stable peritoneal dialysis (PD) patients during their routine visits to our PD facility. There were no exclusion criteria. Clinical volume status was assessed by the attending nephrologist as hypovolemic, euvolemic, or hypervolemic. Once the clinical assessment was complete, plasma BNP concentration was measured. The TFC was determined by bioimpedance cardiography measured in the supine position. Of 51 patients, 19 (37.3%) were considered hypervolemic, 30 (58.8%) euvolemic, and 3 (5.9%) hypovolemic by clinical assessment. As defined by systolic blood pressure > or = 130 mmHg or diastolic pressure > or = 80 mmHg (or both), 57% were hypertensive. The hypovolemic group was excluded from the statistical analysis because of the small sample size. Logistic regression analysis did not show a significant correlation between clinical assessment of volume and BNP (p = 0.76) or TFC (p = 0.39). Our data demonstrate the limitations of BNP and thoracic impedance in helping with the clinical evaluation of volume status in a cohort of chronic PD patients.


Role of ERα in Mediating Female Uterine Transcriptional Responses to IGF1.
Estrogen (E2) signaling through its nuclear receptor, E2 receptor α (ERα) increases insulinlike growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor. Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERαUtcKO) mice, which selectively lack ERα in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERα expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERα binding sites in uterine chromatin using chromatin immunoprecipitation sequencing. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERα-mediated and ERα-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife.


[Formation and repair of DNA breaks in bone marrow cells of the irradiated rat].
The method of sedimentation was used to study the induction and repair of DNA breaks in irradiated rat bone marrow cells. It was shown that a total population of bone marrow cells did not differ from that of cultured L5178Y cells with regard to the yield of single-strand breaks and the ratio between double- and single-strand breaks. The absence of double-strand breaks and incomplete repair of single-strand breaks (70%) were noted with doses ranging from 20 to 100 Gy. The quantity of unrepaired single-strand breaks did not correlate with that of double-strand breaks, induced by the same radiation doses. This is indicative of the capacity of bone marrow cells for repair in a short-term culture.


Developmental changes in serum ferritin concentration of dairy calves.
Serum ferritin concentration of nursing calves was measured by a two-site immunoradiometric assay to assess developmental changes and to evaluate relationships of serum ferritin with iron-related blood characteristics. Serum ferritin concentration of calves was low at birth and elevated slightly at 3 days of age. From 1 wk of age onward, serum ferritin concentration of untreated calves and calves fed only whole milk for 4 wk decreased and remained low throughout the nursing period. This finding almost coincided with hematological characteristics. However, that nearly normal hematological measures and weight gain persisted and that they did not develop any anemic symptom indicate that serum ferritin concentration is more sensitive than other hematological characteristics to iron depletion. However, serum ferritin concentration of calves administered 130 mg of ferrous fumarate (40 mg iron) daily from 3 to 22 days of age or injected with 4 ml of iron-dextran intramuscularly (400 mg iron) at 3 days and 2 wk of age increased sharply just after treatment and persisted high for 2 to 6 wk of age. However, there was large variation between animals for serum ferritin concentration. Thus, it seems likely that serum ferritin concentration is an index for monitoring prelatent iron deficiency of calves.


GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population.
d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A>G) were similar in healthy Siberian women (n=136) and cancer patients (n=129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR=1.76; 95% CI=1.04-1.90; P(Y)=0.035 χ2=4.44). Heterozygous AG genotype was associated with tumour size (OR=3.67, P(Y)=0.004), ER-negative tumours (OR=3.25, P(Y)=0.0028), triple-negative tumours (OR=4.94, P(Y)=0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER+PR+ luminal A breast cancer (OR=0.25, P(Y)=0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes.


Early atherosclerosis and autoantibodies to heat-shock proteins and oxidized LDL in systemic sclerosis.
Autoimmune diseases are characterized by enhanced atherosclerosis. Humoral immune responses to mycobacterial HSP-65, human HSP-60, and to oxLDL have been established in a number of human autoimmune diseases and are considered to be associated with atherosclerosis. The aim of this study was to evaluate carotid artery intima-media thickness (IMT) in patients having systemic sclerosis (SSc) and to find out whether early atherosclerosis is associated with these autoantibodies. Forty-four patients having SSc underwent clinical evaluation and carotid artery IMT measurement. Several autoantibodies were tested among patients and a control group. The antibodies against human HSP-60 were measured by antihuman (IgG/IgM) HSP-60 ELISA kit. IgGs and IgMs antimycobacterial HSP-65 were determined using an ELISA with mycobacterial recombinant HSP-65 antigens. Similarly, anti-oxLDL antibodies were measured by an ELISA kit. Abnormal IMT levels were significantly more common in SSc patients compared with control subjects. Age was found as the sole most significant clinical parameter associated with carotid artery IMT in SSc. Disease duration, type of SSc, lung function tests, and cardiovascular risk factors were not associated with IMT in these patients. Levels of HSP-60, HSP-65, and oxLDL autoantibodies were similar among patients compared with controls, and in patients having "positive" IgM anti-HSP-65, higher IMT values were found. Abnormal carotid IMT is more prevalent in SSc than in normal subjects. Age rather than other clinical parameters is associated with early atherosclerotic changes in SSc. Autoantibodies to oxLDL, HSP-60, and HSP-65 are not elevated in SSc and there is only a borderline association with carotid artery IMT.


[Lateralisation of aldosterone-producing adenoma in primary aldosteronism].
Four lateralizing methods were carried out in 14 patients with primary aldosteronism (PA): ultrasonography, CT scan, adrenal scintiscan and determination of adrenal venous aldosterone levels. In all cases, unilateral aldosterone-producing adenomas were verified by surgery. Of four lateralizing methods, determination of adrenal venous aldosterone, in spite of high diagnostic value, has two big problems: difficulty in selective catheterization of right adrenal vein and dilution of adrenal vein efflux from non-adrenal sources. To solve these problems, cortisol (C, micrograms/dl) levels along with aldosterone (A, ng/dl) were determined in samples from the left adrenal vein (LAV) and the inferior vena cava (IVC) in 8 patients with PA, and the (LAV A/C)/(IVC A/C) ratio was calculated. That ratio was also obtained in 7 patients with other types of hypertension for comparison. Accuracy of lateralisation by ultrasonography, CT scan and adrenal scintiscan was 23%, 64% and 69% respectively, in the first studies. Those rates changed to 23%, 93% and 85% when the second studies were performed. Venous blood was obtained from both adrenal veins in 46% (6/13), while lateralisation of adenoma was also predicted in 46% (6/13) by the measurement of aldosterone concentrations alone. On the other hand, (LAV A/C)/(IVC A/C) ratios were 3.54-6.98 in the cases of left APA, 0.15-0.98 in those of right APA and 1.10-2.86 in cases of other types of hypertension. There was no overlap of ratios among the three groups, resulting in correct prediction of lateralisation in all cases (8/8) of APA.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of parenteral fish oil lipid emulsion in parenteral nutrition supplementation combined with enteral nutrition support in patients undergoing pancreaticoduodenectomy.
The effect of parenteral fish oil lipid emulsion in parenteral nutrition (PN) supplementation combined with enteral nutrition (EN) support on pancreaticoduodenectomy (PD) was investigated with a randomized controlled clinical trial at the Affiliated Drum Tower Hospital. Seventy-six patients who underwent PD in the Department of Hepatobiliary Surgery were randomly divided into 2 groups: the polyunsaturated fatty acid (PUFA) group (n = 38) and control group (n = 38). Patients in the PUFA group received parenteral fish oil lipid emulsion supplementation combined with early EN support for 5 days after PD. Venous blood samples were obtained for assay on the day before surgery and on day 6 after surgery. Compared with the results of the control group, a significant difference was seen in the extent of the decrease in total protein and prealbumin in the PUFA group (P < .05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were significantly decreased on day 6 in the PUFA group (P < .01), and a significant difference was seen in the extent of decrease in ALT, AST, and LDH in the PUFA group (P < .05). The ratio of infectious complications in the PUFA group was significantly decreased, as well as the postoperative hospital stay (P < .05), and there was no hospital mortality in this study. Parenteral fish oil lipid emulsion in PN supplementation combined with EN support can greatly improve the nutrition state and liver function of patients, decrease the incidence of infectious morbidities, and shorten the postoperative hospital stay.


A case of ST elevation myocardial infarction secondary to heparin-induced thrombocytopaenia with thrombosis.
A 54 year-old woman with Noonan Syndrome presented with an acute anterolateral ST elevation myocardial infarction two weeks post septal myectomy and heparin exposure, on the background of known normal coronary arteries. Coronary angiography revealed acute thrombosis of the left main, left anterior descending and left circumflex arteries, which was successfully treated by percutaneous coronary intervention with overlapping bare metal stents. A positive heparin induced platelet antibody test and dramatic fall in platelet count confirmed the diagnosis of heparin induced thrombocytopaenia with thrombosis (HITTS) as the underlying diagnosis. This represents the first documented case of HITTS induced left main coronary artery thrombosis and occlusion.


Transient human auditory cortex activation during volitional attention shifting.
While strong activation of auditory cortex is generally found for exogenous orienting of attention, endogenous, intra-modal shifting of auditory attention has not yet been demonstrated to evoke transient activation of the auditory cortex. Here, we used fMRI to test if endogenous shifting of attention is also associated with transient activation of the auditory cortex. In contrast to previous studies, attention shifts were completely self-initiated and not cued by transient auditory or visual stimuli. Stimuli were two dichotic, continuous streams of tones, whose perceptual grouping was not ambiguous. Participants were instructed to continuously focus on one of the streams and switch between the two after a while, indicating the time and direction of each attentional shift by pressing one of two response buttons. The BOLD response around the time of the button presses revealed robust activation of the auditory cortex, along with activation of a distributed task network. To test if the transient auditory cortex activation was specifically related to auditory orienting, a self-paced motor task was added, where participants were instructed to ignore the auditory stimulation while they pressed the response buttons in alternation and at a similar pace. Results showed that attentional orienting produced stronger activity in auditory cortex, but auditory cortex activation was also observed for button presses without focused attention to the auditory stimulus. The response related to attention shifting was stronger contralateral to the side where attention was shifted to. Contralateral-dominant activation was also observed in dorsal parietal cortex areas, confirming previous observations for auditory attention shifting in studies that used auditory cues.


Safety and Clinical Utility of Flexible Bronchoscopic Cryoextraction in Patients With Non-neoplasm Tracheobronchial Obstruction: A Retrospective Chart Review.
Airway obstruction from blood clots, airway secretions, and foreign bodies is a potentially life-threatening condition. Optimal management of this problem, whether by rigid or flexible bronchoscopy, has not been well studied. We report our single-center experience on the safety and clinical utility of cryoprobe extraction for this indication. We performed a retrospective chart review from January 2006 to November 2014 of all subjects aged 18 and older who underwent flexible bronchoscopic cryoprobe extraction. Subjects with obstruction due to benign or malignant neoplasm or airway stenosis were excluded. A total of 38 cryotherapy sessions performed on 30 subjects were identified for inclusion. Cryoprobe extraction was successful in reestablishing airway patency in 32/38 (84%) sessions overall and in 24/26 (92%) for blood clots, 4/6 (67%) for mucous plugging, 2/4 (50%) for foreign bodies, and 2/2 (100%) for plastic bronchitis. Twenty-one of 31 (68%) sessions resulted in improvement in oxygenation or ventilation. There was 1 complication related to sedation. We conclude that flexible bronchoscopic cryoprobe extraction of blood clots, mucous secretions, plastic bronchitis, and foreign bodies is a safe and effective option. It can be safely performed at the bedside and in many cases eliminates the need for rigid bronchoscopy.


Cortical responses to tone and phoneme mismatch as a predictor of dyslexia? A systematic review.
Evidence from event-related-potential (ERP) studies has repeatedly shown differences in the perception and processing of auditory stimuli in children with dyslexia compared to control children. The mismatch negativity (MMN) - an ERP component reflecting passive auditory change detection ability - has been found to be reduced, not only in children with a diagnosis of dyslexia, but also in infants and preschool children at risk of developing dyslexia. However, the results are controversial due to the different methods, age of the children and stimuli used. The aim of the present review is to summarize and evaluate the MMN research about at-risk children in order to identify risk factors that discriminate between children with and without dyslexia risk and to analyze if the MMR (the abbreviation refers to positive and negative mismatch responses) correlates with later reading and spelling ability. A literature search yielded 17 studies reporting MMR to speech or non-speech stimuli in children at risk of dyslexia. The results of the studies were inconsistent. Studies measuring speech MMR often found attenuated amplitudes in the at-risk group, but mainly in very young children. The results for older children (6-7years) and for non-speech stimuli are more heterogeneous. A moderate positive correlation of MMR amplitude size with later reading and spelling abilities was consistently found. Overall, the findings of this review indicate that the MMR can be a valuable part of early dyslexia identification, which can enable efficient support and intervention for a child before the first problems appear.


Cardiometabolic Risk Factors and Health-Related Quality of Life in Adolescents with Obesity.
A number of research studies have demonstrated a decrease in health-related quality of life (HRQL) measures among obese children. Moreover, the causes of HRQL impairments are not completely clear. Adolescent obesity is oftentimes associated with other cardiometabolic risk factors (CRFs); hence, the aim of our research was to estimate the frequency of CRFs and to determine whether there is an association between CRFs and HRQL scores among obese adolescents. Our research included 92 treatment-seeking obese adolescents (11-17 years), 34 males. We looked at medical records and performed physical examinations, including anthropometry and laboratory evaluations. PedsQL™ 4.0 was used to assess the HRQL score. Logistic regression models were used to identify CRFs associated with worse HRQL scores, both in total and in each domain. The vast majority (70.6%) of adolescents had at least one CRF in addition to obesity. A cluster of three to four CRFs was found in 23.3% and was associated with males more than with the degree of obesity [odds ratio (OR) 4; confidence interval (95% CI) 1.3-11.6, p = 0.01]. HRQL scores in emotional functioning domain and scores of HRQL total were directly associated with waist circumference Z-score (OR 4.1; 95% CI 1.1-14.9, p = 0.03 and OR 3.4; 95% CI 1-11.6, p = 0.049). Hypertension was associated with worsening HRQL scores in school functioning domain (OR 3.3; 95% CI 1-10.9, p = 0.049). Obesity in adolescents is associated with a high frequency of associated CRFs and decreased HRQL scores. Although CRFs have an influence on reducing adolescents' HRQL, they are not a determining factor.


Parents' motivation for seeing a physician.
To explore situations in which parents with an ill child consult a physician and to identify trigger factors for consultation. Qualitative interviews with parents of young children. Parents were asked to describe the situation in which the decision to contact the physician was made. A total of 20 families selected from a birth cohort from Frederiksborg County. The cohort numbered 194 of 389 children born between 1 and 28 February 2001. The cohort was followed prospectively from the age of 9 to 12 months by diary (January-April), and retrospectively from birth to the age of 9 months by questionnaire. Families were chosen on the basis of information provided in a questionnaire, diary illness pattern and a telephone conversation. Nine trigger factors associated with physician contacts were identified. Parents' answers demonstrated how their feelings and logical reasoning while caring for an ill child led them to consult the physician. The main reasons for consultation were children's protracted or aggravated symptoms. Parents initially tried to handle the situation but when unsuccessful information and advice was sought by consulting a physician. Parents consult the physician when they feel overtaxed, afraid, or inadequately prepared to care for their ill child. They considered seriously whether to consult a physician or not.


Can Optical Coherence Tomography Be Used to Guide Treatment Decisions in Adult or Pediatric Multiple Sclerosis?
With the recognition that neurodegeneration represents the principal substrate of disability in multiple sclerosis (MS), there has been increased strives towards identifying biomarkers for accurately quantifying and tracking neurodegeneration during the disease course. The retina provides an opportune "window" into the central nervous system (CNS) in MS, with retinal changes in MS reflecting not only local, but also global aspects of neurodegeneration and inflammation operative in the disease. Optical coherence tomography (OCT) is a rapid, inexpensive, reproducible, high-resolution imaging technique allowing accurate quantification of discrete retinal layers. OCT determined thinning of inner retinal layers such as the retinal nerve fiber layer (RNFL) and in particular the composite of the ganglion cell and inner plexiform (GCIP) layers, predominantly related to optic neuropathy, have been shown to not only correlate with high and low contrast visual function in MS, but also global MS disability scores, as well as whole brain and particularly gray matter volumes. Rates of GCIP thinning have been shown to be accelerated among MS patients exhibiting inflammatory activity outside of the visual pathways, as well as disability progression during follow-up. Moreover, baseline RNFL thickness in MS has been shown to have utility for predicting future disability accumulation. On the other hand, thickening of the inner nuclear layer (INL) in MS, the pathophysiologic basis of which remains to be elucidated, has been found to predict the development of clinical and radiological inflammatory activity, as well as subsequent disability progression in MS. Given the potential for OCT to provide insight into neurodegeneration and inflammation occurring in MS, this review focuses on the potential utility of OCT within the clinical setting to influence treatment decisions for MS patients. The evolution of spectral domain-OCT technology, with improved resolution and reproducibility allowing intra-retinal layer segmentation, has facilitated the determination that the OCT derived measure GCIP thickness is a highly accurate measure for quantifying and tracking neurodegeneration, and conversely neuroprotection, in MS. The strong relationships between rates of GCIP and brain atrophy across MS subtypes over time underpin the insight derived regarding the global MS disease process from OCT and highlight OCT as an excellent complementary tool to magnetic resonance imaging (MRI) for tracking MS patients. More recently, longitudinal studies are emerging which support the utility of OCT for monitoring the differential effects of disease-modifying therapies (DMTs) in MS. Although further work is required, there is mounting evidence supporting the utility of OCT in the clinical setting to monitor disease course in individual patients with MS and to aid in the prediction of disease course. As pharmacological treatment options in MS expand to also include potentially neuroprotective and/or remyelinating or neurorestorative drugs, OCT as a biomarker of neurodegeneration and neuroprotection (and neuroinflammation to a lesser degree) may become an invaluable tool in both the research and clinical settings.


Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos.
Microtubule remodeling is critical for cellular and developmental processes underlying morphogenetic changes and for the formation of many subcellular structures. Katanins are conserved microtubule severing enzymes that are essential for spindle assembly, ciliogenesis, cell division, and cellular motility. We have recently shown that a related protein, Katanin-like 2 (KATNAL2), is similarly required for cytokinesis, cell cycle progression, and ciliogenesis in cultured mouse cells. However, its developmental expression pattern, localization, and in vivo role during organogenesis have yet to be characterized. Here, we used Xenopus embryos to reveal that Katnal2 (1) is expressed broadly in ciliated and neurogenic tissues throughout embryonic development; (2) is localized to basal bodies, ciliary axonemes, centrioles, and mitotic spindles; and (3) is required for ciliogenesis and brain development. Since human KATNAL2 is a risk gene for autism spectrum disorders, our functional data suggest that Xenopus may be a relevant system for understanding the relationship of mutations in this gene to autism and the underlying molecular mechanisms of pathogenesis.


Influences of hydration force and elastic strain energy on the stability of solid film in a very thin solid-on-liquid structure.
Since hydration forces become very strong at short range and are particularly important for determining the magnitude of the adhesion between two surfaces or interaction energy, the influences of the hydration force and elastic strain energy due to hydration-induced layering of liquid molecules close to a solid film surface on the stability of a solid film in a solid-on-liquid (SOL) nanostructure are studied in this paper. The liquid of this thin SOL structure is a kind of water solution. Since the surface forces play an important role in the structure, the total free energy change of SOL structures consists of the changes in the bulk elastic energy within the solid film, the surface energy at the solid-liquid interface and the solid-air interface, and highly nonlinear volumetric component associated with interfacial forces. The critical wavelength of one-dimensional undulation, the critical thickness of the solid film, and the critical thickness of the liquid layer are studied, and the stability regions of the solid film have been determined. Emphasis is placed on calculation of critical values, which are the basis of analyzing the stability of the very thin solid film.


Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.
Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differentiate into myocytes. To address the unique cellular and temporal context of hiPSC differentiation, we perform a longitudinal comparison of the transcriptomic profiles of three hiPSC lines that display differential myogenic specification, one robust and two blunted. We detail temporal differences in mechanisms that lead to robust myogenic specification. We show gene expression signatures of putative cell subpopulations and extracellular matrix components that may support myogenesis. Furthermore, we show that targeted knockdown of ZIC3 at the outset of differentiation leads to improved myogenic specification in blunted hiPSC lines. Our study suggests that β-catenin transcriptional cofactors mediate cross-talk between multiple cellular processes and exogenous cues to facilitate specification of hiPSCs to mesoderm lineage, leading to robust myogenesis.


The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats.
Hydrogen sulfide (H2S) can protect the liver against ischemia-reperfusion (I/R) injury. However, it is unknown whether H2S plays a role in the protection of hepatic I/R injury in both young and old patients. This study compared the protective effects of H2S in a rat model (young and old animals) of I/R injury and the mechanism underlying its effects. Young and old rats were assessed following an injection of NaHS. NaHS alone reduced hepatic I/R injury in the young rats by activating the nuclear erythroid-related factor 2 (Nrf2) signaling pathway, but it had little effect on the old rats. NaHS pretreatment decreased miR-34a expression in the hepatocytes of the young rats with hepatic I/R. Overexpression of miR-34a decreased Nrf-2 and its downstream target expression, impairing the hepatoprotective effect of H2S on the young rats. More importantly, downregulation of miR-34a expression increased Nrf-2 and the expression of its downstream targets, enhancing the effect of H2S on hepatic I/R injury in the old rats. This study reveals the different effects of H2S on hepatic I/R injury in young and old rats and sheds light on the involvement of H2S in miR-34a modulation of the Nrf-2 pathway.


Work-related musculoskeletal disorders with reference to the revised occupational diseases list.
Due to the different compensation schemes, compensated musculoskeletal disorders vary widely between countries. In Italy, following the Constitutional Court Decision no.179/1988, these disorders were treated as "non-listed" diseases and workers must prove their occupational origin by submitting a compensation claim for musculoskeletal disorders to INAIL. The Italian Workers Compensation Agency (INAIL) supplied guidelines for the management of these claims. Recently, a new occupational diseases list has been submitted to the Labour Ministry for approval. This list includes musculoskeletal disorders of the upper limb, back and knee.


Ab initio study of the effect of Si on the phase stability and electronic structure of γ- and α-Al2O3.
Using density functional theory, the effect of Si on the stability and electronic structure of γ- and α-Al2O3 has been investigated. The concentration range from 0 to 5 at.% is probed and the additive is positioned at different substitutional sites in the γ-phase. The calculations for (Al,Si)2O3 predict a trend towards spontaneous decomposition into α-/γ-Al2O3 and SiO2. Therefore, the formation of the metastable γ-(Al,Si)2O3 phase can only be expected during non-equilibrium processing where the decomposition is kinetically hindered. The Si-induced changes in stability of this metastable solid solution may be understood based on the electronic structure. As the Si concentration is increased, stiff silicon-oxygen bonds are formed giving rise to the observed stabilization of the γ-phase.


Low-dose cranial boost in high-risk adult acute lymphoblastic leukemia patients undergoing bone marrow transplant.
Acute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high-risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high-dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of central nervous system (CNS) recurrence. However, the use of CB has fallen out of favor because of toxicity concerns. In high-risk adults undergoing transplant at our institution, we have used a low-dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains. The safety, efficacy, and utility of a low-dose CB in adults are poorly studied; herein, we report their outcomes and toxicity. We identified all high-risk ALL patients undergoing total body irradiation as part of their conditioning regimen. Those who received 6 Gy CB or no CB were included (55 total). Their charts were reviewed and statistical analyses were completed with R, version 2.15.2. In patients undergoing CB, 3-year CNS disease-free survival and overall survival were 94.7% and 62.7%. In those not undergoing CBs, survivals were 81.8% and 51.5%. Notably, within the CB cohort, patients without prior CNS involvement had no CNS failures. In contrast, in the non-CB cohort, there were 2 CNS failures in patients with no history of CNS involvement. In the CB cohort, the only notable acute toxicity was parotitis (2.8%). Late toxicity in the CB cohort included 1 instance of cataracts (2.8%) without any evidence of cognitive impairment or potential radiation induced secondary malignancy. A dose of 6 Gy CB is well-tolerated in the adult ALL population as part of a radiation-based conditioning regimen. Low-dose CB may be considered in adult patients with high-risk ALL without prior CNS involvement to reduce the likelihood of recurrence.


[A cross-sectional study of cataract in residents with type 2 diabetes living in Xinjing Town, Shanghai].
Objective: To investigate the prevalence, subtypes and risk factors of cataract in type 2 diabetic individuals. Methods: Geographically defined cluster sampling method was used in this population-based, cross-sectional study. There were 7 756 type 2 diabetes individuals in Xinjing Town with a residential population of 88 864. The type 2 diabetic individuals were randomly selected from 20 basic sample units in Xinjing Town of Changning District from April to June 2016. All participants received visual acuity measurement and eye examination. The standard of lens opacity assessment was according to the Lens Opacities Classification SystemⅡ(LOCSⅡ). The prevalence of cataract in diabetic individuals was calculated with LOCS≥2. Multivariate Logistic regression analysis was used to explore the relevant factors of cataract in type 2 diabetic individuals. Results: A total of 1 719 type 2 diabetic individuals were included in the analysis. There were 682 men (39.67%) and 1 037 women (60.33%) in this population. There were 434 cataract individuals and the prevalence of cataract was 25.25%. There were 269 cases of nuclear type (15.7%), 38 cases of cortical type (2.2%), 2 cases of posterior subcapsular type (0.12%) and 42 cases of mixed type (2.4%) in the 1 719 individuals. Multivariate Logistic regression analysis showed that age (P<0.001), duration of diabetes (P<0.001), education (P=0.005), fasting blood glucose (P(6.1-7.7mmol/L)=0.025, P(7.8-24.3mmol/L)=0.022, compared with 3.6-6.0 mmol/L of fasting blood glucose), and ocular axial length (P<0.001) were associated with cataract. Conclusion: Cataract is a common ophthalmic disease in adults with type 2 diabetes in Xinjing Town. Regular screening of diabetes in the high risk population and intensive control of both glucose and blood pressure in diabetic patients are recommended to prevent and delay the development of cataract. (Chin J Ophthalmol, 2017, 53: 489-494).


Community Emergency Response Training.
My assessment of my Community Emergency Response Training experience is this: the training was excellent, and the experience was extremely valuable. That said, I would add that the one weakness that could be addressed in the program's design is the role of CERT teams in a biological attack by an infectious agent.


The Link between Health Complaints and Wind Turbines: Support for the Nocebo Expectations Hypothesis.
The worldwide expansion of wind energy has met with opposition based on concerns that the infrasound generated by wind turbines causes health problems in nearby residents. In this paper, we argue that health complaints are more likely to be explained by the nocebo response, whereby adverse effects are generated by negative expectations. When individuals expect a feature of their environment or medical treatment to produce illness or symptoms, then this may start a process where the individual looks for symptoms or signs of illness to confirm these negative expectations. As physical symptoms are common in healthy people, there is considerable scope for people to match symptoms with their negative expectations. To support this hypothesis, we draw an evidence from experimental studies that show that, during exposure to wind farm sound, expectations about infrasound can influence symptoms and mood in both positive and negative directions, depending on how expectations are framed. We also consider epidemiological work showing that health complaints have primarily been located in areas that have received the most negative publicity about the harmful effects of turbines. The social aspect of symptom complaints in a community is also discussed as an important process in increasing symptom reports. Media stories, publicity, or social discourse about the reported health effects of wind turbines are likely to trigger reports of similar symptoms, regardless of exposure. Finally, we present evidence to show that the same pattern of health complaints following negative information about wind turbines has also been found in other types of environmental concerns and scares.


InterAtrial Shunt Device (IASD®) implantation - a novel treatment method for heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) is a condition with complex pathophysiology and clinical profile. No treatment has been proven to reduce mortality or reduce morbidity in a meaningful way. In the era of percutaneous cardiac interventions, a novel method of reducing left atrial pressure by creating an iatrogenic interatrial shunt has been introduced. We present a report of implantation of InterAtrial Shunt Device (IASD®) in three consecutive patients.


[Relationship between serum homocysteine level and oxidative stress in patients with obstructive sleep apnea-hypopnea syndrome].
To explore the relationship between serum homocysteine (Hcy) level and oxidative stress in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Patients undergoing overnight full polysomnography (PSG) were selected from Sleep Disorders Center at First Affiliated Hospital between June 2008 and December 2013. A total of 117 OSAHS patients were recruited and divided into 3 groups of mild (n = 41), moderate (n = 40) and severe (n = 36). And they were compared with the controls (n = 33). The PSG variables were recorded and the contents of Hcy, malonaldehyde (MDA) and glutathione (GSH) detected after sleep. Serum Hcy was measured by cyclophorase. And MDA and GSH were measured by spectrophotometer. The concentrations of MDA in severe group were higher than those in the other three groups ((7.3 ± 1.0) vs (4.6 ± 0.9), (5.4 ± 1.3), (6.8 ± 0.7) µmol/L, all P < 0.05). The concentrations of GSH in mild and moderate groups were both higher than the controls ((6.5 ± 2.1), (7.5 ± 1.5) vs (4.2 ± 1.4) mg/L, all P < 0.05). However there was no significant difference between severe group ((4.6 ± 1.4) mg/L) and controls (P > 0.05). The Hcy level in mild and moderate groups were both higher than the controls ((10.3 ± 2.0), (13.3 ± 2.6) vs (8.7 ± 0.7) µmol/L, all P < 0.05). However there was no significant difference between severe group ((9.5 ± 1.8) µmol/L) and controls (P > 0.05). When severe group was removed, multielement linearity regression analysis indicated that there was a statistically significant relationship between Hcy concentration and age, MDA, GSH, apnea hypopnea index (AHI) and oxygen desaturation index (ODI) (P = 0.011, 0.005, 0.008, 0.001, 0.016 respectively). The change of marker levels in oxidative stress is not entirely consistent with the antioxidant levels in OSAHS patients at different stages of disease. The change of Hcy level is proportional to GSH level, but not proportional to severity in OSAHS patients. The mechanism of serum Hcy change may be oxidative stress in OSAHS patients.


Vortex velocity probability distributions in phase-ordering kinetics.
The calculation of the point vortex velocity probability distribution function (VVPDF) is extended to a larger class of systems beyond the nonconserved time-dependent Ginzburg-Landau (TDGL) model treated earlier. The range is extended to include certain anisotropic models and the conserved order parameter case. The VVPDF still satisfies scaling with large velocity tails as for the nonconserved isotropic case. It is shown that the average vortex speed can be self-consistently expressed in terms of correlation functions associated with a Gaussian auxiliary field. In the conserved order parameter case the average vortex speed decays as t(-1) compared to the t(-1/2) decay for the nonconserved case.


New and old GFR equations: a European perspective.
Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI2009) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimate GFR of adults aged 18-30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.


Applications of three-dimensional printing in orbital diseases and disorders.
To comprehensively review the applications of advanced three-dimensional printing technology in the management of orbital abnormalities. Three-dimensional printing has added value in the preoperative planning and manufacturing of patient-specific implants and surgical guides in the reconstruction of orbital trauma, congenital defects and tumor resection. In view of the costs and time, it is reserved as strategy for large and complex craniofacial cases, in particular those including the bony contour. There is anecdotal evidence of a benefit of three-dimensional printing in the manufacturing of prostheses for the exenterated and anophthalmic socket, and in the fabrication of patient-specific boluses, applicators and shielding devices for orbital radiation therapy. In addition, three-dimensional printed healthy and diseased orbits as phantom tangible models may augment the teaching and learning process of orbital surgery. Three-dimensional printing allows precision treatment tailored to the unique orbital anatomy of the patient. Advancement in technology and further research are required to support its wider use in orbital clinical practice.


Reversed cephalic vein: a lifeboat in head and neck free-flap reconstruction.
Free flaps always followed surgical resection in head and neck cancer patients as a means of reconstruction. Problems may be encountered in recurrent patients who have received postoperative cervical irradiation, since finding a good, healthy vein for microanastomosis is sometimes difficult. The internal jugular vein, with or without vein grafting, as the recipient vessel may solve the problem. However, we encountered two patients in whom the internal jugular vein was very fibrotic as a result of irradiation. A long vein graft to the nonirradiated, healthy area was the only choice in this condition. A new method in which a reversed cephalic vein is used as the recipient vessel was designed. It seems that the reversed cephalic vein can play the role of lifeboat as recipient vein and solve the most difficult problem encountered in head and neck free-flap surgery.


Radiation doses in the UK trial of breast screening in women aged 40-48 years.
Although data have been published on the radiation doses involved in screening women in the UK in the age range 50-64 years, data have not been published for the screening of younger women, when one might expect higher doses and a different risk benefit balance. Therefore, data on the radiation doses arising from screening younger women (age range 40-48 years) as part of the UK age trial have been collected and reviewed. Each of the screening centres participating in the trial was asked to submit measurements of doses for samples of approximately 50 or 100 women. The doses for 2296 women were received. The dose estimates were corrected to take account of variations in composition with age and breast thickness and in the spectra used. The average received dose was 2.5 mGy per oblique film and 2.0 mGy per craniocaudal film. Although these doses are about 7% higher than those calculated for the screening of older women, this was owing to differences in equipment rather than age of the women. Age itself was not found to be a significant factor affecting the dose to screened women aged over or under 50 years. An identifiable sub-group of women with larger breasts who were screened using higher dose systems received doses that were about 4.2 times the average, and should be considered in any risk benefit analysis. Where modern mammography systems with automatic beam quality selection and alternative target and filter materials had been introduced, there was a 15% reduction in average received dose and up to a 50% reduction in received dose for large breasts.


Pulmonary rhabdomyosarcoma with isolated small bowel metastasis. A report of a case with immunohistochemical and ultrastructural studies.
A unique case of pulmonary rhabdomyosarcoma with an isolated, symptomatic small bowel metastasis is presented. The tumor affected the middle lobe, and was treated with a right pneumonectomy. Eleven months after the operation, an isolated small bowel metastasis, which produced intestinal obstruction, was resected. The patient is currently alive, 11 months after operation. The myogenous nature of the tumor was confirmed by the immunohistochemical demonstration of myoglobin in the pulmonary and enteric lesion by the ultrastructural findings of poorly developed sarcomeres.


The human external auditory canal, secretory system--an ultrastructural study.
Human external auditory canal skin, with a special emphasis on the secretory system, was studied by light, transmission electron and scanning electron microscopy. Two types of secretory glands were observed: modified apocrine (ceruminous) and sebaceous. The sebaceous secretory cellere homogeneous; on the other hand, modified apocrine secretory cells contained heterogeneous secretory granules. They were ither dark granules or light granules. Evidence to support both the apocrine as well as the eccrine mode of secretion was noted in the modified apocrine gland. This finding is partly in agreement with early reports based on light microscopy with suggested only an apocrine mode and data based on transmission electron microscopy which showed only the eccrine mode. Significance of the secretion by the external ear canal and its role in a local immune defense system is discussed.


Noise and hospital stay.
Length of hospital stay for simple cataract surgery was compared retrospectively for a period of construction noise and for two similar periods without construction noise. Hospital stay was significantly longer during the period of construction.


[Hemorrhagic fever with renal syndrome due to Hantaan virus or a serologically related virus].
Seven cases of acute renal failure consecutive to haemorrhagic fever with renal syndrome (HFRS) due to the Hantaan virus or to a serologically related virus are reported. These cases were observed in north-eastern France between March, 1983 and January, 1984. All patients were of rural origin and had been in contact with field mice. The predominant initial clinical symptoms were signs of infection and diffuse muscle pain, without evidence of haemorrhage. However, massive proteinuria was noted, and acute anuric renal failure unaccompanied by oedema or arterial hypertension developed. Renal biopsy performed in 2 patients showed tubular and interstitial nephritis but no glomerular or vascular lesions. Two patients only required haemodialysis. All patients recovered within 2 to 8 weeks without sequelae. Antibodies directed against the Hantaan virus were detected by indirect immunofluorescence tests, and seroconversion could be demonstrated in 2 patients seen at a sufficiently early stage. The risk of epidemics suggested by this small outbreak of HFRS can only be evaluated after an exhaustive epidemiological study.


Moving beyond Stylized Economic Network Models: The Hybrid World of the Indian Firm Ownership Network.
A central theme of economic sociology has been to highlight the complexity and diversity of real world markets, but many network models of economic social structure ignore this feature and rely instead on stylized one-dimensional characterizations. Here, the authors return to the basic insight of structural diversity in economic sociology. Using the Indian interorganizational ownership network as their case, they discover a composite-or "hybrid"-model of economic networks that combines elements of prior stylized models. The network contains a disconnected periphery conforming closely to a "transactional" model; a semiperiphery characterized by small, dense clusters with sporadic links, as predicted in "small-world" models; and finally a nested core composed of clusters connected via multiple independent paths. The authors then show how a firm's position within the mesolevel structure is associated with demographic features such as age and industry and differences in the extent to which firms engage in multiplex and high-value exchanges.


Prenatal Diagnosis of a Retroesophageal Left Brachiocephalic Vein: Two Case Reports.
A retroesophageal left brachiocephalic vein is an extremely rare anomaly and has only been reported in 6 postnatal cases. Two prenatally diagnosed cases are reported. On the 3-vessel view, the vein appears as an aberrant vessel transversely coursing behind the aorta and trachea, which subsequently drains into the superior vena cava, giving rise to a U-shaped configuration. On color Doppler sonography, the U sign is bicolored. This anomaly should prompt the sonographer to carefully assess for other congenital heart defects, suggest consideration for genetic testing, and alert the cardiologist because it could affect central line procedures and cardiac interventions after delivery.


Five-year outcomes from a trial of three limus-eluting stents with different polymer coatings in patients with coronary artery disease: final results from the ISAR-TEST 4 randomised trial.
Both biodegradable polymer sirolimus-eluting stents and permanent polymer everolimus-eluting stents offer potential for enhanced late outcomes in comparison with earlier-generation permanent polymer sirolimus-eluting stents. However, long-term comparative efficacy data among these devices remain a scientific gap. We aimed to compare the efficacy and safety of biodegradable polymer sirolimus-eluting stents (Yukon Choice PC) versus permanent polymer everolimus-eluting stents (XIENCE) versus permanent polymer sirolimus-eluting stents (CYPHER) at five-year follow-up. Overall, 2,603 patients were randomised to treatment with the Yukon Choice PC (n=1,299), XIENCE (n=652) or CYPHER (n=652) stents. The primary endpoint was the device-oriented composite of cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularisation (TLR). The main secondary endpoint was definite/probable stent thrombosis (ST). Follow-up was performed up to five years. Concerning the primary endpoint, there was no significant difference between Yukon Choice PC and XIENCE stents (20.5% vs. 19.5%, HR=1.04, 95% CI: 0.84-1.29; p=0.71) or between CYPHER and XIENCE stents (23.5% vs. 19.5%, HR=1.21, 95% CI: 0.95-1.53; p=0.12). In terms of safety, rates of ST were similar with both Yukon Choice PC and XIENCE (1.2% vs. 1.4%; HR=0.83, 95% CI: 0.37-1.91; p=0.67) but numerically higher with CYPHER as compared to XIENCE (2.4% vs. 1.4%, HR=1.67, 95% CI: 0.73-3.82; p=0.22). Biodegradable polymer Yukon Choice PC and permanent polymer XIENCE stents showed comparable clinical outcomes at five years. Permanent polymer CYPHER stents showed numerically higher rates of device-related adverse events. Trials registration: ClinicalTrials.gov (identifier: NCT00598676).


Structure parameters of synaptic vesicles quantified by small-angle x-ray scattering.
Synaptic vesicles (SVs) are small, membrane-bound organelles that are found in the synaptic terminal of neurons, and which are crucial in neurotransmission. After a rise in internal [Ca(2+)] during neuronal stimulation, SVs fuse with the plasma membrane releasing their neurotransmitter content, which then signals neighboring neurons. SVs are subsequently recycled and refilled with neurotransmitter for further rounds of release. Recently, tremendous progress has been made in elucidating the molecular composition of SVs, as well as putative protein-protein interactions. However, what is lacking is an empirical description of SV structure at the supramolecular level-which is necessary to enable us to fully understand the processes of membrane fusion, retrieval, and recycling. Using small-angle x-ray scattering, we have directly investigated the size and structure of purified SVs. From this information, we deduced detailed size and density parameters for the protein layers responsible for SV function, as well as information about the lipid bilayer. To achieve a convincing model fit, a laterally anisotropic structure for the protein shell is needed, as a rotationally symmetric density profile does not explain the data. Not only does our model confirm many of the preexisting ideas concerning SV structure, but also for the first time, to our knowledge, it indicates structural refinements, such as the presence of protein microdomains.


Cangrelor reduces the risk of ischemic complications in patients with single-vessel and multi-vessel disease undergoing percutaneous coronary intervention: Insights from the CHAMPION PHOENIX trial.
To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD). Cangrelor, an intravenous, rapidly acting P2Y12 inhibitor, is superior to clopidogrel in reducing ischemic events among patients receiving percutaneous coronary intervention (PCI). We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial. The primary efficacy outcome was the composite of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), and stent thrombosis (ST) at 48hours. The key safety outcome was non-coronary artery bypass grafting GUSTO severe bleeding at 48hours. Among 10,921 patients, 5,220 (48%) had SVD and 5,701 (52%) had MVD. MVD patients were older and more often had diabetes, hyperlipidemia, hypertension, prior stroke, and prior MI. After adjustment, MVD patients had similar rates of 48-hour death/MI/IDR/ST (6.3% vs 4.2%, adjusted odds ratio [OR] 1.6 [95% CI 0.42-6.06]) and GUSTO severe bleeding (0.1% vs 0.2%, P=.67) compared with SVD patients. Consistent with overall trial findings, cangrelor use reduced ischemic complications in patients with both SVD (3.9% vs 4.5%; OR 0.86, 95% CI 0.65-1.12) and MVD (5.5% vs 7.2%; OR 0.74, 95% CI 0.6-0.92, P-interaction=.43). GUSTO severe bleeding outcomes were not significantly increased with cangrelor or clopidogrel in either SVD or MVD patients. In the CHAMPION PHOENIX trial, MVD and SVD patients had similar ischemic outcomes at 48hours and 30days. Cangrelor consistently reduced ischemic complications in both SVD and MVD patients without a significant increase in GUSTO severe bleeding. CLINICAL PERSPECTIVES.


Survey of the use of crisis intervention centers by the black population.
In an attempt to determine the extent to which crisis centers meet the needs of black communities, questionnaires were sent to 12 centers. Responses were received from six. Only two centers, in Nashville and Washington, D.C., had statistics of callers identified by race. The findings from these two centers indicate that there are differences between the white and black callers with regard to age, marital status, and type of problem. As an example, the typical black male caller was older and more concerned about his job and financial problems than were white males. This kind of information suggests a need for expanded services within the crisis center framework, possibly for a more preventive approach. More data gathering concerned the black community using crisis centers is urged in order better to identify the needs of this population and the methods to be used for meeting those needs.


A purple acidophilic di-ferric DNA ligase from Ferroplasma.
We describe here an extraordinary purple-colored DNA ligase, LigFa, from the acidophilic ferrous iron-oxidizing archaeon Ferroplasma acidiphilum, a di-ferric enzyme with an extremely low pH activity optimum. Unlike any other DNA ligase studied to date, LigFa contains two Fe(3+)-tyrosinate centers and lacks any requirement for either Mg(2+) or K(+) for activity. DNA ligases from closest phylogenetic and ecophysiological relatives have normal pH optima (6.0-7.5), lack iron, and require Mg(2+)/K(+) for activity. Ferric iron retention is pH-dependent, with release resulting in partial protein unfolding and loss of activity. Reduction of the Fe(3+) to Fe(2+) results in an 80% decrease in DNA substrate binding and an increase in the pH activity optimum to 5.0. DNA binding induces significant conformational change around the iron site(s), suggesting that the ferric irons of LigFa act both as structure organizing and stabilizing elements and as Lewis acids facilitating DNA binding at low pH.


MEMS and FOG Technologies for Tactical and Navigation Grade Inertial Sensors-Recent Improvements and Comparison.
In the following paper, we present an industry perspective of inertial sensors for navigation purposes driven by applications and customer needs. Microelectromechanical system (MEMS) inertial sensors have revolutionized consumer, automotive, and industrial applications and they have started to fulfill the high end tactical grade performance requirements of hybrid navigation systems on a series production scale. The Fiber Optic Gyroscope (FOG) technology, on the other hand, is further pushed into the near navigation grade performance region and beyond. Each technology has its special pros and cons making it more or less suitable for specific applications. In our overview paper, we present latest improvements at NG LITEF in tactical and navigation grade MEMS accelerometers, MEMS gyroscopes, and Fiber Optic Gyroscopes, based on our long-term experience in the field. We demonstrate how accelerometer performance has improved by switching from wet etching to deep reactive ion etching (DRIE) technology. For MEMS gyroscopes, we show that better than 1°/h series production devices are within reach, and for FOGs we present how limitations in noise performance were overcome by signal processing. The paper also intends a comparison of the different technologies, emphasizing suitability for different navigation applications, thus providing guidance to system engineers.


Utilizing multilevel partnerships to build the capacity of community-based organizations to implement effective HIV prevention interventions in Michigan.
The Michigan Department of Community Health (MDCH), utilizing the expertise of public and private, federal, state, and local partners, increased the proportion of state health department-funded community-based organizations implementing effective behavioral interventions (EBIs) from .05 (1:18) in 2002 to .78 (14:18) in 2004. As the stewards of nearly two thirds of the HIV prevention funds awarded annually by the Centers for Disease Control and Prevention, state health departments occupy an important position in diffusing the science of EBIs to their grantees. This article describes the strategies and partners employed by Michigan's state health department to build the capacity of community-based providers to implement effective behavioral interventions. Additionally, lessons learned by the MDCH are highlighted and challenges to the long-term sustainability of these interventions are also discussed.


Reduction of serum testosterone levels during chronic glucocorticoid therapy.
The effect of chronic glucocorticoid therapy on serum testosterone levels was studied in men aged 67 +/- 4 (SD) years with chronic pulmonary disease. The serum testosterone level was reduced in 14 of 16 patients to a mean value of 211 +/- 93 ng/dL, compared with 449 +/- 111 ng/dL in 11 age- and disease-matched control patients (p less than 0.001). The corticosteroid dosage and the serum testosterone level were inversely related (r = -0.78). Testosterone binding to serum proteins was not significantly affected. Basal gonadotrophin levels were not elevated while their secretory responses to exogenous gonadotrophin-releasing hormone (GnRH) were intact. We conclude that glucocorticoid therapy commonly reduces serum testosterone levels in older men due to alteration of hypothalamic GnRH secretion.


Quantitative characterization of vascular endothelial cell morphology and orientation using Fourier transform analysis.
Fourier Transform methods were used to quantify mean elongation, mean orientation, and standard deviation of orientations of cultured vascular endothelial cells. Images of cell populations, which had been subjected to 11 and 20 hours of shear stress at 30 dynes/cm2 and 20 hours of no shear, were analyzed by Fourier Transform methods. Measurements of cell morphology and orientation characteristics were also obtained using a manual method for comparison purposes. The results of the study showed that mean cell orientation can be determined accurately with the Fourier Transform methods. Attempts to determine the standard deviation of cell orientations, however, resulted in poorer estimates of mean elongation and standard deviation of orientations except in the case of exposure of endothelial cells to 20 hours of shear, where the actual standard deviation of orientations was low. When the value for standard deviation of orientations was constrained to zero, a minimum possible mean elongation was determined reliably using the Fourier Transform methods. Use of the Fourier Transform methods in determining morphological and orientation characteristics of cell monolayers is fast and objective and may provide a basis for identifying other characteristics of cell shape.


An assessment of reliability and validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 among breast cancer patients in Qatar.
Breast cancer has been the most common cancer type that affects women worldwide and subsequent treatment is often associated with considerable psychological and quality of life (QoL). This study aimed to assess psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer (EORTC) general QoL questionnaire (QLQ-C30) for breast cancer patients in Qatar. This is a cross-sectional hospital-based study conducted on 678 breast cancer patients using Arabic version of the EORTC QLQ-C30 tool. The mean age of women was 47.7 ± 10.2 years and 33.4% of women had consanguineous parents. Six subscales out of the nine met the standards of reliability with coefficients ranging from 0.55 to 0.89. The mean score of all functioning scales was high >55. Advanced breast cancer stages of III-IV had higher symptomatic scores significantly than those in early stages for the physical function, cognitive, fatigue, insomnia, appetite loss, constipation, and financial difficulties. Correlation coefficients between each item ranged from -0.113 to 0.960, and item 21 (tense) and item 23 (irritable) had strongest negative correlations with their corresponding emotional functioning subscale, whereas items 29 (physical condition) and 30 (overall QoL) had the strongest positive correlation with Global Health/QoL subscale. Item 6 (limited work) showed a higher correlation with fatigue (r = 0.749). Likewise, item 19 (pain interfered with daily activities) of the pain subscale had higher correlations with physical functioning, role functioning, and fatigue subscales. Qatari Arabic version of the EORTC QLQ-C30 showed acceptable psychometric properties, which is a reliable and valid instrument, that can be used by oncologists.


Fast electrical control of a quantum dot strongly coupled to a photonic-crystal cavity.
The resonance frequency of an InAs quantum dot strongly coupled to a GaAs photonic-crystal cavity was electrically controlled via the quadratic quantum confined Stark effect. Stark shifts up to 0.3 meV were achieved using a lateral Schottky electrode that created a local depletion region at the location of the quantum dot. We report switching of a probe laser coherently coupled to the cavity up to speeds as high as 150 MHz, limited by the RC constant of the transmission line. The coupling strength g and the magnitude of the Stark shift with electric field were investigated while coherently probing the system.


Electrochromic Metallo-Organic Nanoscale Films: Fabrication, Color Range, and Devices.
In this study, we demonstrate a versatile approach for the formation of electrochromic nanoscale assemblies on transparent conductive oxides on both rigid and flexible substrates. Our method is based on the application of alternating spin-coated layers of well-defined metal polypyridyl complexes and a palladium(II) salt to form electrochemically addressable films with a high chromophore density. By varying the central metal ion of the polypyridyl complexes (Os, Ru, and Fe) and their ligands and by mixing these complexes, coatings with a wide range of colors can be achieved. These coatings cover a large area of RGB color space. The coloration intensities of these nanoscale films can be tuned by the number of deposition steps. The materials have very attractive ON/OFF ratios, electrochemical stabilities, and coloration efficiencies. Reversible color-to-colorless and color-to-color transitions were demonstrated, and the films were further integrated into sandwich cells.


Estimating potential environmental loadings of Cryptosporidium spp. and Campylobacter spp. from livestock in the Grand River Watershed, Ontario, Canada.
Exposure to waterborne pathogens in recreational or drinking water is a serious public health concern. Thus, it is important to determine the sources of pathogens in a watershed and to quantify their environmental loadings. The natural variability of potentially pathogenic microorganisms in the environment from anthropogenic, natural, and livestock sources is large and has been difficult to quantify. A first step in characterizing the risk of nonpoint source contamination from pathogens of livestock origin is to determine the potential environmental loading based on animal prevalence and fecal shedding intensity. This study developed a probabilistic model for estimating the production of Cryptosporidium spp. and Campylobacter spp. from livestock sources within a watershed. Probability density functions representing daily pathogen production rates from livestock were simulated for the Grand River Watershed in southwestern Ontario. The prevalence of pathogenic microorganisms in animals was modeled as a mixture of beta-distributions with parameters drawn from published studies. Similarly, gamma-distributions were generated to describe animal pathogen shedding intensity. Results demonstrate that although cattle are responsible for the largest amount of manure produced, other domesticated farm animals contribute large numbers of the two pathogenic microorganisms studied. Daily pathogen production rates are highly sensitive to the parameters of the gamma-distributions, illustrating the need for reliable data on animal shedding intensity. The methodology may be used for identifying source terms for pathogen fate and transport modeling and for defining and targeting regions that are most vulnerable to water contamination from pathogenic sources.


[SUMO-specific protease 1 and cancer].
Post-translational modifiers of the small ubiquitin-like modifier protein (SUMO) family have emerged as key regulators of protein function and localization. SUMO modification is a dynamic process, catalyzed by SUMO-specific E1, E2, and E3 enzymes and reversed by a family of SUMO-specific proteases (SENPs). Although six human SENPs have been identified, each with different cellular locations and substrate specificities, the precise roles of SENPs in cellular processes involved has not been well-defined. This brief review will focus on recent advances about the identified targets of SENP1 and its potential role in tumorigenesis.


Biological investigation of resinous endodontic sealers containing calcium hydroxide.
The purpose of this study was to evaluate, in vivo, the biocompatibility, biomineralization, collagen maturation and the in vitro antibacterial and cytotoxicity of resinous endodontic sealers containing calcium hydroxide. Forty rats were implanted with polyethylene tubes containing Sealer 26, Sealer Plus, Dia-ProSeal and an empty tube, examined after 7, 15, 30 and 60 days. Antimicrobial activity was evaluated against Enterococcus faecalis by Agar Diffusion Test (ADT) through inhibition zones. For cytotoxicity, undifferentiated pulp cells (OD-21) were cultured and assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, exposed to dilution of serial extracts at 6, 24, 48h. Cytotoxicity was analyzed by two-way ANOVA and Bonferroni correction. Kruskal-Wallis test followed by Dunn test was performed for nonparametric data (p<0.05). MTT assay revealed cell proliferation affected by sealers extract in all periods (p<0.0001), except for Dia-Proseal and Sealer Plus ⅛ dilution. Subcutaneous analysis showed at day 7th moderate inflammatory infiltration. After 30 days, Sealer 26 still showed moderate inflammatory infiltrate compared to mild inflammation from control and Dia-ProSeal (p = 0.006). At day 60th, all groups showed similar mild inflammatory infiltrate (p>0.05). Sealer 26 induced more biomineralization than other sealers in all periods. At 7 and 15 days, all sealers had significant percentage of immature collagen fibers. After 60 days Sealer 26 showed more mature fibers compared to other sealers (p<0.001). All sealers had a smaller zone of inhibition than chlorhexidine, but with no significant difference among any group (p>0.05). All sealers showed satisfactory biological responses with in vitro/in vivo biocompatibility and antimicrobial activity against planktonic bacteria. Sealer 26 induced more biomineralization than Sealer Plus and Dia-ProSeal.


Risk of transmitting the human immunodeficiency virus, cytomegalovirus, and hepatitis B virus to health care workers exposed to patients with AIDS and AIDS-related conditions.
This prospective cohort study was designed to evaluate the risk of occupational transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and cytomegalovirus (CMV) to health care workers with intensive exposure to HIV-infected patients. Seventy-five percent of the 270 subjects had been exposed to patients with AIDS and AIDS-related conditions (ARC) for at least one year before enrollment, 18% worked in specialized AIDS units, and 35% sustained a total of 342 accidental parenteral exposures to HIV-infected body fluids. At the time of enrollment, none had antibody to HIV, and none of the 175 subjects retested 10 months later had acquired antibody. No evidence of increased risk of acquiring CMV or HBV was obtained. These results indicate that health care workers are at minimal risk for HIV, CMV, and HBV transmission from occupational exposure to patients with AIDS or ARC, even when intensively exposed for prolonged periods of time.


Infrared crystallographic investigation of T-state hemoglobin.
Polarized IR measurements on single crystals of human hemoglobin, grown under low salt conditions that stabilize the T quaternary structure, allow spectral features to be associated with individual sites within the molecule. Differences between the a- and c-polarized IR spectra in the sulfhydryl stretching region distinguish the contributions of individual Cys residues to the S-H band and lead to an evaluation of possible H-bonding partners for Cys beta-112. Successful modelling of both crystal and solution S-H spectra with component bands having identical frequencies and bandwidths, supports the use of the X-ray structure as a model for the low affinity T-state in solution. Polarization analysis of a crystal partially saturated with CO reveals comparable occupancy of the alpha- and beta-hemes. In the T-state crystal, the C-O bands are broader and lower in frequency than in the R-state solution, and 20% of the CO-ligated beta-subunits adopt an alternate conformation with a 1967 cm(-1) C-O frequency. The latter observation reflects an energetically significant disruption of the distal heme pocket upon CO binding to beta-hemes in the low affinity T-state.


Evidence for kappa- and mu-opioid receptor expression in C6 glioma cells.
The astrocytoma cell line rat C6 glioma has been used as a model system to study the mechanism of various opioid actions. Nevertheless, the type of opioid receptor(s) involved has not been established. Here we demonstrate the presence of high-affinity U69,593, endomorphin-1, morphine, and beta-endorphin binding in desipramine (DMI)-treated C6 cell membranes by performing homologous and heterologous binding assays with [3H]U69,593, [3H]morphine, or 125I-beta-endorphin. Naive C6 cell membranes displayed U69,593 but neither endomorphin-1, morphine, nor beta-endorphin binding. Cross-linking of 125I-beta-endorphin to C6 membranes gave labeled bands characteristic of opioid receptors. Moreover, RT-PCR analysis of opioid receptor expression in control and DMI-treated C6 cells indicate that both kappa- and mu-opioid receptors are expressed. There does not appear to be a significant difference in the level of mu nor kappa receptor expression in naive versus C6 cells treated with DMI over a 20-h period. Collectively, the data indicate that kappa- and mu-opioid receptors are present in C6 glioma cells.


A Previously Unreported Arterial Variant of the Suboccipital Region Based on Cadaveric Dissection.
Introduction Several arterial variants have been reported to occur around the posterior arch of the atlas. Understanding the various anomalies and diagnosing them preoperatively can dramatically reduce the risk of surgical insult during neurosurgical procedures. Herein we report a case of an arterial variant found just below the posterior arch of C1. Case Report During the routine dissection of the suboccipital region via a posterior approach, an unusual bulge was identified just inferior to the inferior capitis oblique muscle. With further dissection, the structure was identified as a tortuous internal carotid artery. Conclusion Arterial variants around the posterior arch of C1 are surgically significant and can result in catastrophic injuries if unappreciated. Most of these variants will be related to the vertebral artery. To our knowledge, an arterial variant of the internal carotid artery in this location, as reported herein, has not been previously reported.


Pan-Arctic sea ice-algal chl a biomass and suitable habitat are largely underestimated for multiyear ice.
There is mounting evidence that multiyear ice (MYI) is a unique component of the Arctic Ocean and may play a more important ecological role than previously assumed. This study improves our understanding of the potential of MYI as a suitable habitat for sea ice algae on a pan-Arctic scale. We sampled sea ice cores from MYI and first-year sea ice (FYI) within the Lincoln Sea during four consecutive spring seasons. This included four MYI hummocks with a mean chl a biomass of 2.0 mg/m2 , a value significantly higher than FYI and MYI refrozen ponds. Our results support the hypothesis that MYI hummocks can host substantial ice-algal biomass and represent a reliable ice-algal habitat due to the (quasi-) permanent low-snow surface of these features. We identified an ice-algal habitat threshold value for calculated light transmittance of 0.014%. Ice classes and coverage of suitable ice-algal habitat were determined from snow and ice surveys. These ice classes and associated coverage of suitable habitat were applied to pan-Arctic CryoSat-2 snow and ice thickness data products. This habitat classification accounted for the variability of the snow and ice properties and showed an areal coverage of suitable ice-algal habitat within the MYI-covered region of 0.54 million km2 (8.5% of total ice area). This is 27 times greater than the areal coverage of 0.02 million km2 (0.3% of total ice area) determined using the conventional block-model classification, which assigns single-parameter values to each grid cell and does not account for subgrid cell variability. This emphasizes the importance of accounting for variable snow and ice conditions in all sea ice studies. Furthermore, our results indicate the loss of MYI will also mean the loss of reliable ice-algal habitat during spring when food is sparse and many organisms depend on ice-algae.


Synthesis and disassembly of an organometallic polymer comprising redox-active Co4S4 clusters and Janus biscarbene linkers.
Here, we show for the first time that main-chain organometallic polymers (MCOPs) can be prepared from Janus N-heterocyclic carbene (NHC) linkers and polynuclear cluster nodes. The crosslinked framework Co4S4-MCOP is synthesized via ligand displacement reactions and undergoes reversible electron transfer in the solid state. Discrete molecular cluster species can be excised from the framework by digesting the solid in solutions of excess monocarbene. Finally, we demonstrate a synthetic route to monodisperse framework particles via coordination modulation.


Spontaneous osteochondrosis in rats.
143 Sprague Dawley rats, ranging from 19-63 weeks of age, were examined pathologically for the occurrence of spontaneous joint lesions. Macroscopically, a white round plaque was observed in the caudocentral portion of the medial femoral condyle or humeral head and sometimes it had a partially detached margin. Microscopic examination revealed a local thickening of the articular cartilage protruding into the subchondral bone, which suggested cessation of endochondral ossification and retention of cartilage. As the lesion advanced there was fissure formation in the thickened cartilage and proliferation of fibrous tissue beneath the fissure. Formation of a cartilage flap and extensive fibrosis with large cysts were also observed in the most advanced cases. Total incidence of the lesion in the distal femur was 22.2% in male and 2.8% in female rats. The change detected in the rats was identical with pathologic descriptions of osteochondrosis in domestic animals.


Association of Parasite Load Levels in Amniotic Fluid With Clinical Outcome in Congenital Toxoplasmosis.
To correlate neonatal and infant clinical outcome with parasite load in amniotic fluid (AF). We conducted a retrospective cohort study of 122 children whose mothers had toxoplasmosis during pregnancy. The children were monitored from birth to 12 months old. Stored AF samples were obtained at maternal diagnosis and tested by quantitative polymerase chain reaction. Gestational age at maternal infection, quantitative polymerase chain reaction results, neonatal anti-Toxoplasma gondii immunoglobulin (Ig) M, and clinical outcome at 12 months were correlated. Maternal infection occurred in 18 of 122 (14.7%) and 104 of 122 (85.2%) women in the first and second trimesters, respectively. At birth, IgM was present in 107 of 122 (87.7%) neonates and 36 (29.5%) were symptomatic. Of these, half occurred in the first and the other half in the second trimester and 6 of 36 had severe infections (16.7% of symptomatic, 4.9% of total), all infected in the first trimester. Parasite load levels were highly variable (median 35 parasites/mL, range 2-30,473). Logistic regression correlated symptomatic infection with gestational age (odds ratio [OR] 0.47, CI 0.31-0.73) and parasite load (OR 2.04, CI 1.23-3.37), but not with positive IgM (OR 6.81, CI 0.86-53.9). Negative correlations were found between gestational age and parasite load (rs -0.780, CI -0.843 to -0.696), gestational age and symptoms (rs -0.664, CI -0.755 to -0.547), but not gestational age and IgM (rs -0.136, CI -0.311 to 0.048). Parasite load levels distributed by percentile showed that all symptomatic patients appeared from the 75th percentile and all severe infections from the 95th percentile. Load rankings showed doubled the OR for each 20 parasite/mL increment. Parasite load was associated with symptomatic infections (area under the curve 0.959, CI 0.908-0.987) as well as gestational age (area under the curve 0.918, CI 0.855-0.960) and both parameters combined (area under the curve 0.969, CI 0.920-0.992). Parasite load in AF is associated with the clinical outcome in congenital toxoplasmosis, irrespective of gestational age at maternal infection.


Iliopsoas abscess: analysis and perspectives from an endemic region of Eastern Nepal.
To evaluate the clinical profile and outcome in patients with iliopsoas abscess. A descriptive study was carried out in B.P. Koirala Institute of Health Science, Dharan, Nepal from February 2005 to March 2006. The medical records of all thirty six patients admitted in surgery ward with diagnosis of iliopsoas abscess during the study period were analyzed. Thirty six patients were included the study. There were 22 (61.1%) males and 14 (38.9%) females with a mean age of 24.33 +/-19.19 years. Demographic distribution of the patients revealed the highest number 13 (36.1%) from Sunsari district, eastern part of the country. Right sided unilateral involvement was the most common presentation and only 2 cases had bilateral involvement. In none of our patients the dorsolumbar spine radiograph revealed any involvement of the bone. The most common complaints were pain in lower abdomen and lump in iliac fossa with flexion deformity at hip joint. All the patients underwent open surgical drainage and their outcomes were analyzed in term of cure, morbidity and mortality. Staphylococcus aureus was the most common organism 24 (61.5%) isolated. Twenty two (91.66%) of Staphylococcus aureus samples were sensitive to ciprofloxacin. There was one mortality in the group who died of septicaemia secondary to necrotizing fascitis. Six patients had wound infection, which were cured by regular dressing. On the basis of our experience and review of available relevant literature, we can conclude that a high index of suspicion and awareness of the varying clinical picture are required to diagnose this condition properly. Ultrasonography should still be the preferred imaging modality as it is cheap, safe, cost effective and readily available. Ciprofloxacin should be used as a first line drug. Image guided aspiration may be practical in selected cases having little pus and traditional open drainage should be considered without hesitation.


The interplay between retinoic acid receptor-related orphan receptors and human diseases.
The retinoic acid receptor-related orphan receptors (RORs) are an important subfamily of transcriptional regulators of the nuclear receptors superfamily. Their discovery over a decade ago by gene cloning strategy have revealed three major isoforms of these orphan receptors in animals. Generation and analyses of isoform-specific ROR null mice have provided revealed-vital roles for the RORs in animals. The RORs undoubtedly participate in a host of biological functions such a metabolism, immunity, development and differentiation, angiogenesis, circadian clock, xenobiotic/drug metabolism and other tissue physiologies for optimal animal survival. Moreover, intense work in the last one decade also revealed a host of human diseases being modulated by the RORs. A number of diseases, such as cancer, autoimmune diseases, inflammation, osteoporosis, metabolic syndrome etc., strongly support the involvement of RORs in their onset and progression. By involving in such diseases, the RORs are indeed a critical factor for optimal cell function and are being intensely investigated as novel targets for drug interventions in the treatment of various diseases. This review focuses on the current knowledge and status about RORs in a number of human disease conditions.


Funding for continuing professional education: time to stop moaning.
The issue of funding for continuing professional education (CPE) has generated much debate recently. Continued negative comments about funding may create a pessimistic psychological environment with respect to CPE. Practitioners and educators must work together in presenting their case so that the logic of CPE is obvious to business managers.


Changing the Antibiotic Prescribing of general practice registrars: the ChAP study protocol for a prospective controlled study of a multimodal educational intervention.
Australian General Practitioners (GPs) are generous prescribers of antibiotics, prompting concerns including increasing antimicrobial resistance in the community. Recent data show that GPs in vocational training have prescribing patterns comparable with the high prescribing rate of their established GP supervisors. Evidence-based guidelines consistently advise that antibiotics are not indicated for uncomplicated upper respiratory tract infections (URTI) and are rarely indicated for acute bronchitis. A number of interventions have been trialled to promote rational antibiotic prescribing by established GPs (with variable effectiveness), but the impact of such interventions in a training setting is unclear. We hypothesise that intervening while early-career GPs are still developing their practice patterns and prescribing habits will result in better adherence to evidence-based guidelines as manifested by lower antibiotic prescribing rates for URTIs and acute bronchitis. The intervention consists of two online modules, a face-to-face workshop for GP trainees, a face-to-face workshop for their supervisors and encouragement for the trainee-supervisor dyad to include a case-based discussion of evidence-based antibiotic prescribing in their weekly one-on-one teaching meetings. We will use a non-randomised, non-equivalent control group design to assess the impact on antibiotic prescribing for acute upper respiratory infections and acute bronchitis by GP trainees in vocational training. Early-career GPs who are still developing their clinical practice and prescribing habits are an underutilized target-group for interventions to curb the growth of antimicrobial resistance in the community. Interventions that are embedded into existing training programs or are linked to continuing professional development have potential to increase the impact of existing interventions at limited additional cost. Australian New Zealand Clinical Trials Registry, ACTRN12614001209684 (registered 17/11/2014).


Dissipative rogue waves induced by long-range chaotic multi-pulse interactions in a fiber laser with a topological insulator-deposited microfiber photonic device.
We reported on the generation of dissipative rogue waves (DRWs) induced by long-range chaotic multi-pulse interactions in a fiber laser based on a topological insulator (TI)-deposited microfiber photonic device. By virtue of the simultaneous saturable absorption effect and high nonlinearity provided by the TI-deposited microfiber, a localized, chaotic multi-pulse wave packet with strong long-range nonlinear interactions could be obtained, which gives rise to the formation of DRWs. The results might enhance the understanding of DRWs in optical systems, and further demonstrated that the TI-deposited microfiber could be considered as an excellent photonic device with both saturable absorption and highly nonlinear effects for the application field of nonlinear optics.


Repeated use of L-asparaginase in multi-drug therapy of childhood leukemia.
The capacity of 1-asparaginase in two separate schedules (consecutive and intermittent), along with vincristine and prednisone to produce multiple responses, was evaluated in previously treated children with acute leukemia in relapse. The response rates varied inversely with previous 1-asparaginase exposure. A history of prior resistance to prednisone and vincristine appeared to reduce the response rate. Hypersensitivity reactions occurred in 14%.


Complex Trauma Care Pathway: Results of a 12-Month Pilot.
Sustained, developmentally adverse experiences in childhood put survivors at risk for posttraumatic stress disorder and impairments in biological, affective, cognitive, and intra/interpersonal domains. Complex trauma symptoms are often treated in isolation without addressing their common root cause. The trauma-focused phased Complex Trauma Care Pathway (CTCP) was developed to address this care gap. We piloted the CTCP in 2 medical centers for 12 months among 46 therapist-referred adults. Outcome measures collected every 3 months included standardized scales assessing anxiety, depression, suicidal thoughts, and disorders of extreme stress not otherwise specified (DESNOS). Statistically significant improvements occurred in mean scores for anxiety (p = 0.003), total DESNOS scores (p < 0.001), and 5 DESNOS domains: alterations in regulation of affect and impulses, alterations in regulation of attention or consciousness, alterations in self-perception, alterations in relationships with others (p < 0.001 for all), and alterations in systems of meaning (p = 0.006). In contrast, decreases in symptoms of somatization, depression, substance use, and suicidal thoughts were not statistically significant. Participant feedback was very positive. Many trials evaluate phased interventions for posttraumatic stress disorder, but much less evidence exists about effective interventions for complex trauma. Our study fills a knowledge gap. The CTCP shows promising clinical efficacy and should be evaluated using a more rigorous design. Further research should also explore the relationship between the CTCP or similar interventions and chronic disease management, overall healthcare utilization, and suicide risk.


Cell subpopulations in the paracortical area of the normal human lymphnode defined by monoclonal antibodies.
The cell subpopulations of normal human lymphnode were studied by immunohistochemical and immunoelectronmicroscopy techniques carried out by using monoclonal antibodies. OKT3 positive cells were demonstrated overwhelming in comparison to both OKT4 positive cells and OKT8 positive cells; furthermore la positive cells, dendritic in shape, were observed. Our results, compared to literature data, confirm that paracortex of limphnode is a T-dependent area. Moreover a possible role of the la positive dendritic cells in the immunological education of T helper-inducer lymphocytes was hypotised. Finally, our immunoelectronmicroscopic findings prove that OKT4 positive cells and OKT8 positive cells show different ultrastructural patterns.


Sorghum extracellular leucine-rich repeat protein SbLRR2 mediates lead tolerance in transgenic Arabidopsis.
A sorghum pathogen-inducible gene predicted to encode a simple extracellular leucine-rich repeat (LRR) protein SbLRR2 was previously isolated. LRR was the only domain identified in SbLRR2 and its homologous sequences. Phylogenetic analysis revealed that they are distinct from the simple extracellular LRR proteins reported previously. Agrobacterium-mediated transient expression in tobacco leaf cells demonstrated that the SbLRR2-EYFP (enhanced yellow fluorescent protein) fusion protein was targeted to the extracellular space. Transgenic analysis of SbLRR2 revealed its role in enhancing lead [Pb(II)] tolerance in Arabidopsis. Consequently, SbLRR2-overexpressing lines were found to show alleviated Pb(II)-induced root inhibition, lower levels of Pb(II) accumulation and enhanced transcription of AtPDR12 which encodes a plasma membrane ATP-bind cassette (ABC)-type transporter formerly shown to contribute to Pb(II) detoxification. However, all the Pb(II) tolerance responses were abolished when SbLRR2 was overexpressed in an atpdr12 T-DNA insertion line. The extracellular localization of SbLRR2 was also shown to be essential for the Pb(II) phenotypes and AtPDR12 up-regulation. Taken together, SbLRR2 appears to mediate Pb(II) tolerance through the elevation of AtPDR12 expression in transgenic Arabidopsis, thus activating a glutathione-independent mechanism for detoxification. Further investigations revealed the Pb(II)-induced transcriptional activation of SbLRR2 and several highly conserved AtPDR12 homologs in sorghum seedlings, suggesting the possibility of a common molecular mechanism for Pb(II) tolerance in diverse plant species.


Update on the Native Kidney Biopsy: Core Curriculum 2019.
The kidney biopsy is an invaluable tool that has become the gold standard for the diagnosis of pathologic kidney diseases since the early 1950s. Throughout the years, immunohistologic and ultrastructural microscopy techniques have improved and provide more information on the cause and classification of kidney diseases than that available from simple light microscopy alone. Kidney biopsy has become a preferred method to obtain critical information that can be used in conjunction with serologic, urinary, and genetic testing to diagnose a variety of kidney diseases, both acute and chronic. The kidney biopsy procedure carries relatively low risk and yields substantial information. Potential complications include bleeding requiring transfusion, gross hematuria, arteriovenous fistula formation, and perinephric hematoma, among others. Percutaneous kidney biopsies are typically performed using real-time ultrasound or computed tomographic imaging. This Core Curriculum briefly outlines the history of the kidney biopsy, then discusses indications, complications, and specific procedural aspects.


Identification of a bipartite nuclear localization signal in the silkworm Masc protein.
The silkworm Masculinizer (Masc) gene encodes a CCCH-tandem zinc finger protein that controls both masculinization and dosage compensation. Masc protein is a nuclear protein, but the mechanism underlying the transport of this protein into the nucleus has not yet been elucidated. Here, we identified a functional bipartite nuclear localization signal (NLS) located between residues 274 and 290 of the Masc protein. Sequence comparison revealed that this bipartite NLS is evolutionarily conserved in Masc proteins from other lepidopteran insects. Furthermore, we showed that the degree of nuclear localization is not associated with the masculinizing activity of the Masc protein.


Distal Bypass to the Deep Palmar Arch for Treatment of a Unique Presentation of Digital Ischemia.
Radial artery occlusion leading to hand ischemia is a serious problem that may require prompt surgical intervention. Due to the rarity of these events, consensus on the most effective surgical approach has not yet been reached. There is even scarce literature on appropriate management of symptomatic radial occlusion in patients with a congenital variation in hand vasculature. We report on a case of a 38-year-old woman with radial artery occlusion who underwent a successful distal radial artery bypass to the deep palmar arch due to a diminutive ulnar artery and the absence of a superficial palmar arch. Radial artery bypass to the deep palmar arch using a reversed vein graft is a viable treatment option for preventing further digital ischemia or necrosis in patients with a compromised vasculature of the hand.