Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells.
A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the ATRX-DAXX chromatin-remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of ATRX and telomerase in a telomerase-positive adenocarcinoma cell line. Inactivating mutations in ATRX were introduced using CRISPR-cas9 nickase into two prostate cancer cell lines, LAPC-4 (derived from a lymph node metastasis) and CWR22Rv1 (sourced from a xenograft established from a primary prostate cancer). In LAPC-4, but not CWR22Rv1, abolishing ATRX was sufficient to induce multiple ALT-associated hallmarks, including the presence of ALT-associated promyelocytic leukemia bodies (APB), extrachromosomal telomere C-circles, and dramatic telomere length heterogeneity. However, telomerase activity was still present in these ATRXKO cells. Telomerase activity was subsequently crippled in these LAPC-4 ATRXKO cells by introducing mutations in the TERC locus, the essential RNA component of telomerase. These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance. IMPLICATIONS: These prostate cancer cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.


Arginine recycling in endothelial cells is regulated BY HSP90 and the ubiquitin proteasome system.
Despite the saturating concentrations of intracellular l-arginine, nitric oxide (NO) production in endothelial cells (EC) can be stimulated by exogenous arginine. This phenomenon, termed the "arginine paradox" led to the discovery of an arginine recycling pathway in which l-citrulline is recycled to l-arginine by utilizing two important urea cycle enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). Prior work has shown that ASL is present in a NO synthetic complex containing hsp90 and endothelial NO synthase (eNOS). However, it is unclear whether hsp90 forms functional complexes with ASS and ASL and if it is involved regulating their activity. Thus, elucidating the role of hsp90 in the arginine recycling pathway was the goal of this study. Our data indicate that both ASS and ASL are chaperoned by hsp90. Inhibiting hsp90 activity with geldanamycin (GA), decreased the activity of both ASS and ASL and decreased cellular l-arginine levels in bovine aortic endothelial cells (BAEC). hsp90 inhibition led to a time-dependent decrease in ASS and ASL protein, despite no changes in mRNA levels. We further linked this protein loss to a proteasome dependent degradation of ASS and ASL via the E3 ubiquitin ligase, C-terminus of Hsc70-interacting protein (CHIP) and the heat shock protein, hsp70. Transient over-expression of CHIP was sufficient to stimulate ASS and ASL degradation while the over-expression of CHIP mutant proteins identified both TPR- and U-box-domain as essential for ASS and ASL degradation. This study provides a novel insight into the molecular regulation l-arginine recycling in EC and implicates the proteasome pathway as a possible therapeutic target to stimulate NO signaling.


Automatic personality assessment through social media language.
Language use is a psychologically rich, stable individual difference with well-established correlations to personality. We describe a method for assessing personality using an open-vocabulary analysis of language from social media. We compiled the written language from 66,732 Facebook users and their questionnaire-based self-reported Big Five personality traits, and then we built a predictive model of personality based on their language. We used this model to predict the 5 personality factors in a separate sample of 4,824 Facebook users, examining (a) convergence with self-reports of personality at the domain- and facet-level; (b) discriminant validity between predictions of distinct traits; (c) agreement with informant reports of personality; (d) patterns of correlations with external criteria (e.g., number of friends, political attitudes, impulsiveness); and (e) test-retest reliability over 6-month intervals. Results indicated that language-based assessments can constitute valid personality measures: they agreed with self-reports and informant reports of personality, added incremental validity over informant reports, adequately discriminated between traits, exhibited patterns of correlations with external criteria similar to those found with self-reported personality, and were stable over 6-month intervals. Analysis of predictive language can provide rich portraits of the mental life associated with traits. This approach can complement and extend traditional methods, providing researchers with an additional measure that can quickly and cheaply assess large groups of participants with minimal burden.


Dogs ≥ five years of age at the time of congenital extrahepatic portosystemic shunt diagnosis have better long-term outcomes with surgical attenuation than with medical management alone.
To determine the outcome in dogs diagnosed with congenital extrahepatic portosystemic shunts (EHPSS) at ≥ 5 years of age treated with medical management only (M) or with surgical attenuation (S). The hypothesis was that dogs undergoing surgical attenuation would have a longer survival time than dogs undergoing medical management only. 351 dogs definitively diagnosed with EHPSS at ≥ 5 years of age. Medical records from 2009 to 2019 at 16 veterinary teaching hospitals were evaluated. Data collected included signalment, clinical signs at diagnosis, clinicopathologic data, surgical and medical treatments, shunt morphology, clinical signs and medical treatments at 6 to 12 months after diagnosis, and survival time. 351 dogs (M, 119 [33.9%]; S, 232 [66.1%]) were included in the study. Survival time was longer with surgery than medical management (hazard ratio, 4.2; M, 3.4 years; S, 10.9 years). Continued clinical signs at 6 to 12 months after diagnosis were more common with medical management (M, 40% [33/88]; S, 14% [21/155]). Continued medical treatments at 6 to 12 months after diagnosis were more common in the medical management group (M, 78% [69/88]; S, 34% [53/155]). Perioperative mortality rate was 7.3%. Dogs diagnosed at ≥ 5 years of age with EHPSS have significantly better survival times and fewer clinical signs with surgical attenuation, compared with medical management. Older dogs have similar surgical mortality rates to dogs of all ages after surgical EHPSS attenuation.


Computational approaches to the in vitro antibacterial activity of Allium hirtifolium Boiss against gentamicin-resistant Escherichia coli: focus on ribosome recycling factor.
Persian shallot, Allium hirtifolium Boiss. (AH), is an Iranian native medicinal plant belongs to Alliaceae family. Here, we investigated in vitro antibacterial activity of hydro-alcoholic extract derived from bulbs of AH. We also employed in silico molecular docking to decipher mechanisms of its antibacterial effects. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) against E. coli ATCC 25922 were determined. Molecular docking was performed for major phytochemicals of AH against ribosome recycling factor (RRF). E. coli ATCC 25922 was gentamicin-resistant while AH showed MIC (42 ± 18 μg/ml) and MBC (106 ± 36 μg/ml) against E. coli. In silico results reported all phytochemicals of AH shown acceptable negative binding affinity (kcal/mol) with RRF. In essence, the binding affinities of alliogenin (-11.6), gitogenin (-11.6), kaempferol (-10.2), linoleic acid (-8.4), oleic acid (-8.0), palmitic acid (-7.4), palmitoleic acid (-8.4), quercetin (-10.8), and shallomin (-13.4) with RRF were comparable to that of gentamicin (-12.6). In sum, hydro-alcoholic extract of bulbs of AH could be considered as a commercial phytobiotics if in-depth antibacterial assays employed in future studies. More interestingly, shallomin showed more promising binding affinity with RRF and can be considered as lead molecule for future drug discovery.


Grouped-coordinate ascent algorithms for penalized-likelihood transmission image reconstruction.
This paper presents a new class of algorithms for penalized-likelihood reconstruction of attenuation maps from low-count transmission scans. We derive the algorithms by applying to the transmission log-likelihood a version of the convexity technique developed by De Pierro for emission tomography. The new class includes the single-coordinate ascent (SCA) algorithm and Lange's convex algorithm for transmission tomography as special cases. The new grouped-coordinate ascent (GCA) algorithms in the class overcome several limitations associated with previous algorithms. 1) Fewer exponentiations are required than in the transmission maximum likelihood-expectation maximization (ML-EM) algorithm or in the SCA algorithm. 2) The algorithms intrinsically accommodate nonnegativity constraints, unlike many gradient-based methods. 3) The algorithms are easily parallelizable, unlike the SCA algorithm and perhaps line-search algorithms. We show that the GCA algorithms converge faster than the SCA algorithm, even on conventional workstations. An example from a low-count positron emission tomography (PET) transmission scan illustrates the method.


The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice.
We sought to determine if the histone deacetylase inhibitor (HDI), trichostatin A (TSA), would alter systemic lupus erythematosus (SLE) in NZB/W mice. Fourteen to sixteen-week-old female NZB/W F1 mice were given TSA (1.0mg/kg body weight (BW)) intraperitonealy (i.p.) daily, TSA (1.0mg/kg BW) i.p.+anti-CD25 (250mg/mouse) i.p. every third day, only anti-CD25 (250mg/mouse) i.p., DMSO or isotype IgG. Disease progression was assessed as they aged. Mice were sacrificed at 26 or 38 weeks of age, tissues collected and evaluated. At 36 weeks, TSA-treated animals had decreased anti-double stranded DNA (dsDNA) autoantibodies and decreased protein excretion compared to controls. Spleen size and the percentage of CD4+CD69+ cells were decreased, with an increase in CD4+CD25+ T cells in the TSA-treated mice. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis of T cells showed a decrease in IL-6 production but an increase in TGF-beta1 and Foxp3 in the TSA-treated animals. Kidney analysis showed a decrease in IgG and C3 deposition, decrease in pathologic glomerular disease and renal MCP-1, MMP-9, and IL-6 mRNA expression. Anti-CD25-treated mice euthanized at 26 weeks of age showed decreased Foxp3+CD4+CD25+ T cells compared to TSA-treated mice. These data suggest TSA administration modulates lupus-like disease, in part, by increasing T regulatory cells.


Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography.
2-Deoxy-2[18F]fluoro-D-glucose positron emission tomography performed in human infants during development revealed progressive changes in local cerebral glucose utilization. In infants 5 weeks of age and younger, glucose utilization was highest in the sensorimotor cortex, thalamus, midbrain-brainstem, and cerebellar vermis. By 3 months, glucose metabolic activity had increased in the parietal, temporal, and occipital cortices and the basal ganglia, with subsequent increases in frontal and various association regions occurring by 8 months. These functional changes measured with positron emission tomography are in agreement with behavioral, neurophysiological, and anatomical alterations known to occur during infant development.


Model-Free Robust Optimal Feedback Mechanisms of Biological Motor Control.
Sensorimotor tasks that humans perform are often affected by different sources of uncertainty. Nevertheless, the central nervous system (CNS) can gracefully coordinate our movements. Most learning frameworks rely on the internal model principle, which requires a precise internal representation in the CNS to predict the outcomes of our motor commands. However, learning a perfect internal model in a complex environment over a short period of time is a nontrivial problem. Indeed, achieving proficient motor skills may require years of training for some difficult tasks. Internal models alone may not be adequate to explain the motor adaptation behavior during the early phase of learning. Recent studies investigating the active regulation of motor variability, the presence of suboptimal inference, and model-free learning have challenged some of the traditional viewpoints on the sensorimotor learning mechanism. As a result, it may be necessary to develop a computational framework that can account for these new phenomena. Here, we develop a novel theory of motor learning, based on model-free adaptive optimal control, which can bypass some of the difficulties in existing theories. This new theory is based on our recently developed adaptive dynamic programming (ADP) and robust ADP (RADP) methods and is especially useful for accounting for motor learning behavior when an internal model is inaccurate or unavailable. Our preliminary computational results are in line with experimental observations reported in the literature and can account for some phenomena that are inexplicable using existing models.


The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors.
Numerous studies have linked severe stress to the development of major depressive disorder (MDD) and suicidal behaviors. Furthermore, recent preclinical studies from our laboratory and others have demonstrated that in rodents, chronic stress and the stress hormone cortisol cause oxidative damage to mitochondrial function and membrane lipids in the brain. Mitochondria play a key role in synaptic neurotransmitter signaling by providing adenosine triphosphate (ATP), mediating lipid and protein synthesis, buffering intracellular calcium, and regulating apoptotic and resilience pathways. Membrane lipids are similarly essential to central nervous system (CNS) function because cholesterol, polyunsaturated fatty acids, and sphingolipids form a lipid raft region, a special lipid region on the membrane that mediates neurotransmitter signaling through G-protein-coupled receptors and ion channels. Low serum cholesterol levels, low antioxidant capacity, and abnormal early morning cortisol levels are biomarkers consistently associated with both depression and suicidal behaviors. In this review, we summarize the manner in which nutrients can protect against oxidative damage to mitochondria and lipids in the neuronal circuits associated with cognitive and affective behaviors. These nutrients include ω3 fatty acids, antioxidants (vitamin C and zinc), members of the vitamin B family (Vitamin B12 and folic acid), and magnesium. Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors. A growing body of studies suggests the intriguing possibility that regular consumption of these nutrients may help prevent the onset of mood disorders and suicidal behaviors in vulnerable individuals, or significantly augment the therapeutic effect of available antidepressants. These findings have important implications for the health of both military and civilian populations.


Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease.
Although new therapeutic strategies have been developed to control Crohn's disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohn's disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6 years) outcome in three patients. Three patients (two male, one female) with active severe Crohn's disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine. Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4 g/m(2), followed on day 4 by subcutaneous injections with G-CSF 5 μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4 days), antithymocyte globulin 30 mg/kg/day (3 days) and prednisolone 500 mg (3 days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed. All three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6 years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohn's disease for which we are now reconsidering conditioning and transplantation. Autologous HSCT appears to be safe and can be an alternative strategy for Crohn's disease patients with severe and therapy resistant disease.


Novel role of interleukin 7 in myelopoiesis: stimulation of primitive murine hematopoietic progenitor cells.
Interleukin 7 (IL-7) has been demonstrated to be an important regulator of the growth of B and T cell precursors as well as mature T cells, whereas IL-7 has been reported to have no direct myeloproliferative effects. Here we show that IL-7 potently and directly enhances colony stimulating factor-induced myeloid colony formation from Lin-Sca-1+ murine bone marrow progenitor cells, increasing the cloning frequency up to ninefold and cell numbers up to 50-fold, without affecting their ability to differentiate along the myeloid lineages In contrast, IL-7 has no effect on proliferation of committed Lin- myeloid progenitors. Thus, in addition to its established lymphopoietic potential, this study implicates a novel role of IL-7 in early myelopoiesis.


Pathological effects of prenatal exposure to a 900 MHz electromagnetic field on the 21-day-old male rat kidney.
We investigated the effects on kidney tissue of 900 megahertz (MHz) EMF applied during the prenatal period. Pregnant rats were exposed to 900 MHz EMF, 1 h/day, on days 13-21 of pregnancy; no procedure was performed on control group pregnant rats or on mothers or newborns after birth. On postnatal day 21, kidney tissues of male rat pups from both groups were examined by light and electron microscopy. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione levels also were investigated. Light microscopy revealed some degenerative changes in the tubule epithelium, small cystic formations in the primitive tubules and large cysts in the cortico-medullary or medullary regions in the experimental group. Electron microscopy revealed a loss of peritubular capillaries and atypical parietal layer epithelial cells in the experimental group. Biochemical analysis showed significantly increased MDA levels in the experimental group and decreased SOD and CAT levels. EMF applied during the prenatal period can caused pathological changes in kidney tissue in 21-day-old male rats owing to oxidative stress and decreased antioxidant enzyme levels.


Streptokinase treatment for femoral artery thrombosis after arterial cardiac catheterisation in infants and children.
Data on 205 children who underwent retrograde arterial catheterisation were studied to assess the frequency of femoral artery thrombosis and the safety and efficacy of systemic streptokinase treatment for this complication. In 29 (14%) a transarterial balloon dilatation was performed. In 15 (7.3%) patients impaired arterial perfusion due to vascular spasm with or without thrombus formation was seen in the cannulated leg after catheterisation. Despite heparinisation, signs of impaired arterial circulation persisted in nine patients (4.4% of the total). In these patients femoral artery thrombosis was strongly suspected. Six (53%) of these had undergone a balloon dilatation. Therefore in this study the risk of femoral artery thrombosis developing was 12 times greater after transarterial balloon dilatation than after arterial catheterisation without dilatation (20.6% v 1.7%). Systemic infusion of streptokinase was started in all patients with femoral artery thrombosis. Arterial perfusion became normal in all patients, though in one this was delayed. Haematological monitoring showed lengthening of the thrombin time and a decrease of the fibrinogen concentration during streptokinase treatment. There were no serious complications. Systemic infusion of streptokinase is a safe and useful treatment in children with persistent femoral artery thrombosis after arterial cardiac catheterisation.


Myocyte repolarization modulates myocardial function in aging dogs.
Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.


The somatosensory representation of the human clitoris: an fMRI study.
We studied the central representation of pudendal afferents arising from the clitoral nerves in 15 healthy adult female subjects using electrical dorsal clitoral nerve stimulation and fMRI. As a control body region, we electrically stimulated the right hallux in eight subjects. In a block design experiment, we applied bilateral clitoral stimulation and unilateral (right) hallux stimulation. Activation maps were calculated for the contrasts 'electrical dorsal clitoral nerve stimulation versus rest' and 'electrical hallux stimulation versus rest'. A random-effect group analysis for the clitoral stimulation showed significant activations bilateral in the superior and inferior frontal gyri, insulae and putamen and in the postcentral, precentral and inferior parietal gyri (including the primary and secondary somatosensory cortices). No activation was found on the mesial surface of the postcentral gyrus. For the hallux, activations occurred in a similar neuronal network but the activation in the primary somatosensory cortex was localized in the inter-hemispheric fissure. The results of this study demonstrate that the central representation of pudendal afferents arising from the clitoral nerves and sensory inputs from the hallux can be studied and distinguished from each other by fMRI. From the somatotopic order described in the somatosensory homunculus one would expect for electrical clitoral nerve stimulation activation of the mesial wall of the postcentral gyrus. In contrast, we found activations on the lateral surface of the postcentral gyrus.


An efficient protocol for perennial ryegrass mesophyll protoplast isolation and transformation, and its application on interaction study between LpNOL and LpNYC1.
Perennial ryegrass (Lolium perenne L.) is an important temperate grass used for turf and forage purposes. With the increasing accumulation of genomic and transcriptomic data of perennial ryegrass, an efficient protoplast and transient gene expression protocol is highly desirable for in vivo gene functional studies in its homologous system. In this report, a highly efficient protoplast isolation (5.6 × 107 protoplasts per gram of leaf material) and transient expression (plasmid transformation efficiency at 55.2%) was developed and the detailed protocol presented. Using this protocol, the subcellular locations of two ryegrass proteins were visualized in chloroplasts and nuclei, respectively, and protein-protein interaction between two chlorophyll catabolic enzymes (LpNOL and LpNYC1) was recorded in its homologous system for the first time. This efficient protoplast isolation and transformation protocol is sufficient for studies on protein subcellular localization and protein-protein interaction, and shall be suitable for many other molecular biology applications where the mesophyll protoplast system is desirable in perennial ryegrass.


Disclosure of incidental constituents of psychotherapy as a moral obligation for psychiatrists and psychotherapists.
Informed consent to medical intervention reflects the moral principle of respect for autonomy and the patient's right to self-determination. In psychotherapy, this includes a requirement to inform the patient about those components of treatment purported to cause the therapeutic effect. This information must encompass positive expectancies of change and placebo-related or incidental constituent therapy effects, which are as important as specific intervention techniques for the efficacy of psychotherapy. There is a risk that informing the patient about possible incidental constituents of therapy may reduce or even completely impede these effects, with negative consequences for overall outcome. However, withholding information about incidental constituents of psychotherapy would effectively represent a paternalistic action at the expense of patient autonomy; whether such paternalism might in certain circumstances be justified forms part of the present discussion.


An expert panel delphi consensus statement on patient selection and management for transitioning between oral and inhaled treprostinil.
Treprostinil, a prostacyclin analogue used in the treatment of pulmonary arterial hypertension (PAH), is available for administration by parenteral, oral, or inhaled routes. Transitioning between routes may be beneficial for appropriate patients; however, there is little published data on transitions between oral and inhaled treprostinil. We used a modified Delphi process to develop expert consensus recommendations on transitions between these formulations. Three questionnaires were used to develop statements about relevant aspects of transition management, which the panelists rated, using a Likert scale, from -5 (strongly disagree) to +5 (strongly agree). Eleven physicians with expertise in PAH treatment modalities, participated in the panel. Of the 492 statements evaluated, consensus was reached on 215 (43.7%). Key consensus recommendations included (1) accurately defining successful transition, as stable or improved PAH with good tolerability and adherence, and (2) patients with stable, low-risk PAH showing insufficient response or tolerability to their existing treprostinil therapy (and due to restrictions in up titration of dosing), as appropriate candidates for transitions between treprostinil formulations. Panelists did not reach consensus for an overall strategy for performing these transitions, mainly because of variability in their practice parameters. Consensus was also achieved on recommendations for adverse event management, including reassurance, administration of oral treprostinil 3 times daily with food, and dosing inhaled treprostinil at intervals ≥3 hours apart. The Delphi process aided in developing expert consensus recommendations that may provide clinically useful guidance for transitioning between treprostinil formulations. However, additional data from centers with high volumes of PAH patients undergoing treprostinil transitions would be optimal for defining more complete and robust strategies to facilitate successful transition.


Periodic sampling errors in terahertz time-domain measurements.
An extensive investigation of the origin and the impact of periodic sampling errors of terahertz time-domain spectroscopy systems is given. We present experimental findings and compare them to a theoretical model which is developed in this work. Special attention is given to the influence on the extraction of the refractive index from measurements. It can be shown that even distortions of the spectrum at frequencies higher than the used bandwidth can have a significant impact on the extracted refractive index.


Quality of life changes during the pre- to postdiagnosis period and treatment-related recovery time in older women with breast cancer.
Health care providers have little population-based evidence about health-related quality of life (HRQOL) changes, from the pre- to postdiagnosis period, and treatment-related recovery time for women aged 65 years and older diagnosed with breast cancer. Older women with and without breast cancer completed self-reports of HRQOL at baseline and 2 years later as part of annual Medicare Health Outcomes Surveys (MHOS). MHOS was linked to Surveillance, Epidemiology, and End Results registries, which were used to categorize women with breast cancer by treatment type (breast-conserving surgery, breast-conserving surgery plus radiation, mastectomy) and time since diagnosis at follow-up. Each cancer case diagnosed in 1998 through 2007 (N = 542) was matched to 5 women without cancer (N = 2710) using propensity score matching. Analysis of covariance models examined changes in HRQOL, adjusting for demographics and initial functioning. Older women within 6 months of diagnosis had greater declines than women without cancer in SF-36 Physical (-5.8 vs -1.8) and Mental (-3.6 vs -0.7) Component Summary scores, General Health (-12.3 vs -4.6), Vitality (-11.0 vs -2.2), Bodily Pain (-8.5 vs -2.1), Social Functioning (-15.1 vs -3.3), Role-Physical (-26.5 vs -3.9), and Role-Emotional (-13.1 vs -3.1) scores (all P < .05). By approximately 1 year, women with and without breast cancer had similar HRQOL. Comparable declines in Physical Component Summary and Role-Physical occurred across treatment types. Women aged 65 years and older diagnosed with breast cancer should be counseled that survivors within 6 months of diagnosis are vulnerable to HRQOL declines, compared to women without breast cancer, but that decrements generally wane after 12 months.


Cognitive behavioural therapy: from face to face interaction to a broader contextual understanding of change.
Cognitive behavioural therapy (CBT) is increasingly used to address the emotional and interpersonal problems of people with ID. There is a limited but promising evidence base supporting this activity. However, these individuals face real and continuing challenges in their lives that have implications for their self and interpersonal perceptions. These adversities have implications for the adaptation of CBT. First, it may mean that characteristically negative perceptions may be more common and may be the result of a complex interaction with a truly aversive environment and should not simply be considered as cognitive distortions. Secondly, clients may have limited control over their everyday lives, with limited opportunity to negotiate change with their informal and formal sources of support. This review suggests that it is important to consider the interpersonal context of therapy both to ensure effective work within sessions and to enable real change in clients' everyday lives. The review draws upon Vygotsky's theory of the zone of proximal development and ecological models of change to consider the challenges of establishing collaborative relationships and the potential to use CBT within a broad psychosocial model. The aim is to offer a helpful framework for practitioners and to identify directions for future research.


Perioperative Detection of Circulating Tumor Cells in Radical or Partial Nephrectomy for Renal Cell Carcinoma.
The current study was conducted to clarify the frequency of systemic circulating tumor cells (CTCs) appearing after surgery for renal cell carcinoma and to evaluate the differences in postoperative CTCs between different surgical procedures. This prospective, cohort study included 60 consecutive patients who underwent laparoscopic radical nephrectomy (RN) (n = 22), laparoscopic partial nephrectomy (PN) (n = 19), open RN (n = 8), or open PN (n = 11). In this study CTCs were measured by the FISHMAN-R system, and CTCs drawn from a peripheral artery were collected just before and immediately after surgery. The number of pre- and postoperative CTCs and the perioperative changes in CTCs were measured for each surgical method. Six patients were excluded from the current analyses. Preoperative CTCs did not differ significantly by surgical approach (laparoscopic RN: 3.4 ± 4.2; laparoscopic PN: 3.4 ± 4.1; open RN: 7.7 ± 6.8; open PN: 6.0 ± 7.6; P = 0.19). Open RN resulted in a significantly greater number of postoperative CTCs (laparoscopic RN: 4.8 ± 3.7; laparoscopic PN: 7.9 ± 9.1; open RN: 22.5 ± 26.3; open PN: 6.4 ± 6.3; P < 0.001) and perioperative changes in CTCs (laparoscopic RN: 1.3 ± 5.3; laparoscopic PN: 4.5 ± 9.6; open RN: 14.7 ± 25.0; open PN: 0.4 ± 6.3; P < 0.001). No significant differences in these were observed among the three groups except in the open RN group. In the multivariate analysis, the surgical approach was significantly correlated with the number of postoperative CTCs (P = 0.016) and the perioperative change in CTCs (P = 0.01). This proof-of-concept study indicated that after surgery, more cancer cells can be expelled into the bloodstream, especially after open RN. Sufficient and careful follow-up assessment for the emergence of distant metastases is needed for patients undergoing open RN.


A random control trial of contrast baths and ice baths for recovery during competition in U/20 rugby union.
Players in team sports must recover in a relatively short period of time to perform at optimal levels. To enhance recovery, cryotherapy is widely used. To date, there are limited scientific data to support the use of cryotherapy for recovery. Players (n = 26) from a premier rugby club volunteered to participate in a random control trial (RCT) using contrast baths, ice baths, and no recovery. Statistical analysis, between group and within group, with repeated measures was conducted along with determination of effect sizes in 2 field tests. Pre and postfield tests including a 300-m test and a phosphate decrement test and subjective reports were conducted during the RCT. No significant difference was identified between base tests and retests in the phosphate decrement test or the 300-m tests. Effect size calculations identified a medium to large effect (d = 0.72) for 300-m tests for contrast baths against control. Trivial effects were identified for ice baths (d = 0.17) in the 300-m test against control. Effect size calculations in the phosphate decrement test showed a trivial effect (d = 0.18) contrast baths and a negative effect (d = -0.62) for ice baths. Treatment-treatment analysis identified a large effect for contrast baths (d = 0.99) in the phosphate decrement test and a medium effect for contrast baths (d = 0.53) in the 300-m test. Effect scores across contrast baths, ice baths, and passive recovery along with subjective reports indicate a trend toward contrast baths benefiting recovery in rugby. The continued use of 5-minute ice baths for recovery should be reconsidered based on this research because trends suggest a detrimental effect.


Multichannel NIRS analysis of brain activity during semantic differential rating of drawing stimuli containing different affective polarities.
We used 24-channel near-infrared spectroscopy (NIRS) to measure activity in the temporal, parietal, and frontal regions of the brain in eight Japanese women while the participants rated line drawings using semantic differential scales. Participants rated the seven line drawings on 15 bipolar semantic scales, each of which belonged to one of three semantic classes: Evaluation, Activity, or Potency. Suzuki et al. [M. Suzuki, J. Gyoba, Y. Sakuta, Multichannel near-infrared spectroscopy analysis of brain activities during semantic differential rating of drawings, Tohoku Psychologica Folia 62 (2003) 86-98.] had reported previously that the right superior temporal gyrus and the right inferior parietal lobule are associated with Activity rating, while the brain regions around the central fissure were related to Potency rating. Based on these suggestions, we investigated the brain activity in these regions during rating of stimuli containing different affective polarities. When drawings were reported as 'static' or 'calm', oxyhemoglobin concentration was higher around the right superior temporal gyrus as compared to when they were considered 'noisy' or 'excitable'. Oxyhemoglobin concentrations around the central fissure were also higher when drawings were rated as 'soft', 'smooth', or 'blunt' compared to 'hard', 'rough', or 'sharp'. Any characteristic oxyhemoglobin changes were not found during the ratings on the evaluation scales. Our results suggest that activation patterns of the temporal and parietal regions are significantly modified by semantic polarities of Activity and Potency.


Examining the epidemiology of work-related traumatic brain injury through a sex/gender lens: analysis of workers' compensation claims in Victoria, Australia.
To provide an overview of the epidemiology of work-related traumatic brain injury (wrTBI) in the state of Victoria, Australia. Specifically, we investigated sex differences in incidence, demographics, injury characteristics, in addition to outcomes associated with wrTBI. This study involved secondary analysis of administrative workers' compensation claims data obtained from the Victorian WorkCover Authority for the period 2004-2011. Sex-specific and industry-specific rates of wrTBI were calculated using denominators derived from the Australian Bureau of Statistics. A descriptive analysis of all variables was conducted for the total wrTBI population and stratified by sex. Among 4186 wrTBI cases identified, 36.4% were females. The annual incidence of wrTBI was estimated at 19.8/100 000 workers. The rate for males was 1.43 (95% CI 1.35 to 1.53) times that for females, but the gap between the two sexes appeared to have narrowed over time. Compared to males, females were older at time of injury and had lower preinjury income. Males had higher rates than females across most industry sectors, with the exception of education/training (RR 0.77, 95% CI 0.64 to 0.93) and professional/scientific/technical services (RR 0.64, 95% CI 0.44 to 0.93). For both sexes, the most common injury mechanism was struck by/against, followed by falls. WrTBI among males was associated with longer duration of work disability and higher claim costs compared to females. This study found significant sex differences in various risk factors and outcomes of wrTBI. Sex/gender should be taken into consideration in future research and prevention strategies.


Rapid thinning of parts of the southern greenland ice sheet
Aircraft laser-altimeter surveys over southern Greenland in 1993 and 1998 show three areas of thickening by more than 10 centimeters per year in the southern part of the region and large areas of thinning, particularly in the east. Above 2000 meters elevation the ice sheet is in balance but thinning predominates at lower elevations, with rates exceeding 1 meter per year on east coast outlet glaciers. These high thinning rates occur at different latitudes and at elevations up to 1500 meters, which suggests that they are caused by increased rates of creep thinning rather than by excessive melting. Taken as a whole, the surveyed region is in negative balance.


The prevalence and risk factors of group B streptococcus colonization in Iranian pregnant women.
Group B Streptococcus (GBS) is a leading cause of serious neonatal infections. Although great progress has been made in preventing prenatal GBS, its colonization rate in different regions of Iran remains unknown. To determine GBS colonization prevalence and its risk factors among Iranian pregnant women. This prospective cross-sectional study was performed on 186 pregnant women, who attended Boo-Ali hospital which is affiliated with Islamic Azad University in Tehran, Iran, from March 2014 to June 2015. The demographic, obstetric and gynecological data were gathered. A recto-vaginal culture was taken from each patient, with a sterile swab, in lithotomy position without using speculum, and vaginal pH was measured. Patients with positive GBS received IV antibiotic therapy during labor (penicillin G 3 gram at first dose then 1.5 gram Q/4h until delivery). Data were analyzed by statistical software SPSS version 21. Statistical tests for differences were performed by Chi-square test. Potential confounding was assessed by logistic regression. Level of significance was set at p<0.05. Twenty-two (11.8%) patients had positive recto-vaginal colonization. No significant differences between colonized and GBS-negative women with regard to age, obstetrics history and socio-economic factor were noticed. In contrast, smoking, history of previous infection with HPV, presence of vulvitis and a vaginal pH>4.5 were associated with GBS colonization (p≤0.05). With a relatively low prevalence and few significantly correlated factors, it is hardly possible to define a high risk group of pregnant women for GBS colonization. Therefore, thorough measures should be taken in order to prevent infection complications in mothers and neonates in the Iranian population.


A community level syphilis prevention programme: outcome data from a controlled trial.
This study investigated the impact of a small media campaign to reduce syphilis through testing, treatment, and condom use in two urban predominantly African-American communities with high syphilis rates. Data were collected from intervention and comparison zip codes using cross sectional street intercept interviews at baseline and 2 years later (n = 1630) following a small media syphilis prevention campaign with role model story posters, billboards, and other merchandise. Community businesses and a community based organisation served as partners, distributing condoms and small media. Comparing intervention with comparison zip codes, there were significant increases in condom use in last sexual act, and some aspects of knowledge of syphilis. However, there was significant cross contamination of media impact, with respondents in the comparison zip code seeing an average of two media items compared with three in the intervention zip code. Media exposure was associated with significant increases in knowledge of syphilis, testing, and condom use. Targeted community based small media interventions using community partners for distribution are effective in increasing syphilis knowledge, testing, and condom use.


Treatment of reflux esophagitis resulting in massive esophageal bleeding.
The complications that occur secondary to sliding hiatal hernia are reflux esophagitis with ulceration, stricture formation, and hemorrhage. We have treated seven patients for massive esophageal bleeding secondary to reflux esophagitis. All had endoscopic evidence of reflux esophagitis and a negative work-up for other sources of bleeding. All underwent Nissen fundoplication as the only mode of therapy for the bleeding esophagitis. No patient has bled again; healing of the esophagitis was evident six weeks after operation, as observed by gastrointestinal endoscopy. This operation prevents reflux, has minimal side-effects, and gives consistent results in the hands of the average trained gastrointestinal surgeon.


Fully Inkjet-Printed CuO Sensor on Flexible Polymer Substrate for Alcohol Vapours and Humidity Sensing at Room Temperature.
This work focuses on an inkjet-fabricated sensor based on copper oxide nanostructured particles on polymer flexible substrate for the sensing of alcohol vapours and humidity at room temperature. Nanoparticles were prepared by a microwave-assisted solvothermal sealed vessel synthesis method. The ink composition was developed on the basis of viscosity and surface tension optimization by the addition of polymeric steric surfactant and dispersant. The printing process was optimized with the help of non-dimensional criteria. Silver nanoink was used for the printing of an interdigitated pattern on a PET substrate which was overprinted by the copper oxide ink, thus obtaining a flexible flat sensor. Material design and all fabrication steps of the sensor respected the temperature limitation given by the thermal stability of the polymer substrate. Printed layers and motifs were characterized microscopically and by resistance measurement. The effectiveness of the prepared sensor was demonstrated and studied by measuring the response to saturated vapours at room temperature. The sensing layer showed the opposite resistance response to stimuli than expected for the well-known p-type sensing mechanism of CuO sensors operated at high temperatures. In addition to vapour sorption, condensation and desorption influencing electron, proton and ionic conductivity, manifestation of another mechanism was observed and an explanation suggested in terms of the electrochemical mechanism.


Neural representation of natural images in visual area V2.
Area V2 is a major visual processing stage in mammalian visual cortex, but little is currently known about how V2 encodes information during natural vision. To determine how V2 represents natural images, we used a novel nonlinear system identification approach to obtain quantitative estimates of spatial tuning across a large sample of V2 neurons. We compared these tuning estimates with those obtained in area V1, in which the neural code is relatively well understood. We find two subpopulations of neurons in V2. Approximately one-half of the V2 neurons have tuning that is similar to V1. The other half of the V2 neurons are selective for complex features such as those that occur in natural scenes. These neurons are distinguished from V1 neurons mainly by the presence of stronger suppressive tuning. Selectivity in these neurons therefore reflects a balance between excitatory and suppressive tuning for specific features. These results provide a new perspective on how complex shape selectivity arises, emphasizing the role of suppressive tuning in determining stimulus selectivity in higher visual cortex.


A school-based intervention to reduce overweight and inactivity in children aged 6-12 years: study design of a randomized controlled trial.
Effective interventions to prevent overweight and obesity in children are urgently needed especially in inner-city neighbourhoods where prevalence of overweight and inactivity among primary school children is high. A school based intervention was developed aiming at the reduction of overweight and inactivity in these children by addressing both behavioural and environmental determinants. The main components of the intervention (Lekker Fit!) are the re-establishment of a professional physical education teacher; three (instead of two) PE classes per week; additional sport and play activities outside school hours; fitness testing; classroom education on healthy nutrition, active living and healthy lifestyle choices; and the involvement of parents. The effectiveness of the intervention is evaluated through a cluster randomized controlled trial in 20 primary schools among grades 3 through 8 (6-12 year olds). Primary outcome measures are BMI, waist circumference and fitness. Secondary outcome measures are assessed in a subgroup of grade 6-8 pupils (9-12 year olds) through classroom questionnaires and constitute of nutrition and physical activity behaviours and behavioural determinants. Multilevel regression analyses are used to study differences in outcomes between children in the intervention schools and in control schools, taking clustering of children within schools into account. Hypotheses are that the intervention results in a lower prevalence of children being overweight and an improved mean fitness score, in comparison with a control group where the intervention is not implemented. The results of our study will contribute to the discussion on the role of physical education and physical activity in the school curriculum. [ISRCTN84383524].


Effect of increased intra-abdominal pressure on hepatic arterial, portal venous, and hepatic microcirculatory blood flow.
The effects of increased intra-abdominal pressure (IAP) on hepatic perfusion were studied in five anesthetized pigs. Doppler flow probes were used to measure hepatic artery blood flow (HABF) and portal venous blood flow (PVBF), and laser Doppler flowmetry was used to assess changes in hepatic microvascular blood flow (HMVBF). Hepatic blood flow responses to 10, 20, 30 and 40 mm Hg increases in IAP were assessed while the mean arterial BP (MAP) was maintained at baseline levels with IV crystalloid infusions. Although cardiac output and MAP were normal, HABF and HMVBF fell significantly with 10 mm IAP, and at 20 mm Hg IAP, HABF was 45% of the control value, PVBF was 65% of the control value, and HMVBF was 71% of the control value (p less than 0.05). At 30 and 40 mm Hg, hepatic blood flow was reduced even more. Thus, modest increases in IAP can cause significant impairment of hepatic perfusion despite a normal BP and cardiac output.


Imaging molecular adsorption and desorption dynamics on graphene using terahertz emission spectroscopy.
Being an atomically thin material, graphene is known to be extremely susceptible to its environment, including defects and phonons in the substrate on which it is placed as well as gas molecules that surround it. Thus, any device design using graphene has to take into consideration all surrounding components, and device performance needs to be evaluated in terms of environmental influence. However, no methods have been established to date to readily measure the density and distribution of external perturbations in a quantitative and non-destructive manner. Here, we present a rapid and non-contact method for visualizing the distribution of molecular adsorbates on graphene semi-quantitatively using terahertz time-domain spectroscopy and imaging. We found that the waveform of terahertz bursts emitted from graphene-coated InP sensitively changes with the type of atmospheric gas, laser irradiation time, and ultraviolet light illumination. The terahertz waveform change is explained through band structure modifications in the InP surface depletion layer due to the presence of localized electric dipoles induced by adsorbed oxygen. These results demonstrate that terahertz emission serves as a local probe for monitoring adsorption and desorption processes on graphene films and devices, suggesting a novel two-dimensional sensor for detecting local chemical reactions.


Fluorescence lifetime of Rhodamine B in aqueous solutions of polysaccharides and proteins as a function of viscosity and temperature.
Rhodamine B (RhB) is a well known dye extensively used in thermometric studies, either considering the decrease in the fluorescence intensity or the lifetime (τ) with temperature. Lifetime measurements are preferred over intensity ones as they are more robust. In order to expand microscopy thermometry to complex food fluids, the effect of solutes on the τ of RhB was studied using fluorescence lifetime imaging microscopy (FLIM) in a two-photon microscope. Polysaccharides of different molecular weights (glucose, lactose, dextran, maltodextrin, and sodium alginate), as well as whey proteins, were considered as typical model food ingredients. A linear increase in τ with the concentration is observed in most polysaccharides, highlighting that it is not due to an increase in the macroscopic viscosity, but in maltodextrins a Langmuir-like concentration dependence is observed. There are extensive interactions between RhB and whey proteins at small concentrations that quickly increase τ up to saturation at >10 wt% proteins, with τ modelled well using an adsorption Langmuir model. Therefore, the effect of solutes on RhB τ is not related to changes in the macroscopic viscosity. The temperature sensitivity of τ, quantified using apparent activation energies, decreases at high solute contents.


Lumbar spine intervertebral disc gene delivery: a pilot study in lewis rats.
Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc. This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery. Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure. Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation. The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.


Expression of epidermal keratins and filaggrin during human fetal skin development.
The major structural proteins of epithelia, the keratins, and the keratin filament-associated protein, filaggrin, were analyzed in more than 50 samples of human embryonic and fetal skin by one-dimensional SDS PAGE and immunoblotting with monoclonal and polyclonal antibodies. Companion samples were examined by immunohistochemistry and electron microscopy. Based on structural characteristics of the epidermis, four periods of human epidermal development were identified. The first is the embryonic period (before 9 wk estimated gestational age), and the others are within the fetal period: stratification (9-14 wk), follicular keratinization (14-24 wk), and interfollicular keratinization (beginning at approximately 24 wk). Keratin proteins of both the acidic (AE1-reactive, type I) and the basic (AE3-reactive, type II) subfamilies were present throughout development. Keratin intermediate filaments were recognized in the tissue by electron microscopy and immunohistochemical staining. Keratins of 50 and 58 kD were present in the epidermis at all ages studied (8 wk to birth), and those of 56.5 and 67 kD were expressed at the time of stratification and increased in abundance as development proceeded. 40- and 52-kD keratins were present early in development but disappeared with keratinization. Immunohistochemical staining suggested the presence of keratins of 50 and 58 kD in basal cells, 56.5 and 67 kD in intermediate cells, and 40 and 52 kD in the periderm as well as in the basal cells between the time of stratification and birth. Filaggrin was first detected biochemically at approximately 15 wk and was localized immunohistochemically in the keratinizing cells that surround hair follicles. It was identified 8-10 wk later in the granular and cornified cell layers of keratinized interfollicular epidermis. These results demonstrate the following. An intimate relationship exists between expression of structural proteins and morphologic changes during development of the epidermis. The order of expression of individual keratins is consistent with the known expression of keratins in simple vs. stratified vs. keratinized epithelia. Expression of keratins typical of stratified epithelia (50 and 58 kD) precedes stratification, and expression of keratins typical of keratinization (56.5 and 67 kD) precedes keratinization, which suggests that their expression marks the tissue commitment to those processes. Because only keratins that have been demonstrated in various adult tissues are expressed during fetal development, we conclude that there are no "fetal" keratins per se.(ABSTRACT TRUNCATED AT 400 WORDS)


Ultrasound-guided interventional procedures around the shoulder.
Ultrasound is an established modality for shoulder evaluation, being accurate, low cost and radiation free. Different pathological conditions can be diagnosed using ultrasound and can be treated using ultrasound guidance, such as degenerative, traumatic or inflammatory diseases. Subacromial-subdeltoid bursitis is the most common finding on ultrasound evaluation for painful shoulder. Therapeutic injections of corticosteroids are helpful to reduce inflammation and pain. Calcific tendinopathy of rotator cuff affects up to 20% of painful shoulders. Ultrasound-guided treatment may be performed with both single- and double-needle approach. Calcific enthesopathy, a peculiar form of degenerative tendinopathy, is a common and mostly asymptomatic ultrasound finding; dry needling has been proposed in symptomatic patients. An alternative is represented by autologous platelet-rich plasma injections. Intra-articular injections of the shoulder can be performed in the treatment of a variety of inflammatory and degenerative diseases with corticosteroids or hyaluronic acid respectively. Steroid injections around the long head of the biceps brachii tendon are indicated in patients with biceps tendinopathy, reducing pain and humeral tenderness. The most common indication for acromion-clavicular joint injection is degenerative osteoarthritis, with ultrasound representing a useful tool in localizing the joint space and properly injecting various types of drugs (steroids, lidocaine or hyaluronic acid). Suprascapular nerve block is an approved treatment for chronic shoulder pain non-responsive to conventional treatments as well as candidate patients for shoulder arthroscopy. This review provides an overview of these different ultrasonography-guided procedures that can be performed around the shoulder.


Partner notification in the context of HIV: an interest-analysis.
Codes of confidentiality play an essential role in the intimate discourses in many learned professions. Codes with various prescriptions exist. The Hippocratic Oath for example, prescribes rewards to the secret keeper, for keeping secret what ought to be kept secret, and punishments for failing. In public health practice, partner notification, arguably is one endeavor that tests the durability of this secret keeping doctrine of the health professional. We present an interest-analysis of partner notification in the context of HIV service rendition. Using principles-based analysis, the interests of the individual, the state/public health, and the bioethicist's are discussed. The public health interests in partner notification, which are usually backed by state statutes and evidence, are premised on the theory that partners are entitled to knowledge. This theory posits that knowledge empowers individuals to avoid continuing risks; knowledge of infection allows for early treatment; and that knowledgeable partners can adapt their behavior to prevent further transmission of infection to others. However, persons infected with HIV often have counter interests. For instance, an infected person may desire to maintain the privacy of their health status from unnecessary disclosure because of the negative impacts of disclosure, or because notification without a matching access to HIV prevention and treatment services is detrimental. The interest of the bioethicist in this matter is to facilitate a resolution of these conflicted interests. Our analysis concludes that governmental interests are not absolute in comparison with the interests of the individual. We reiterate that any effort to morally balance the benefits of partner notification with its burdens ought to first recognize the multivalent nature of the interests at play.


Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.
We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at <37 weeks gestation (P = 0·01) and their babies were more likely to have reduced birth weight. Delivery at <34 weeks was increased in both HbSS and HbSC women (5·9% vs. 4·6%) compared to national data. This study confirms a high rate of maternal and fetal complications in mothers with SCD, even in women with HbSC, which has previously been considered to have a more benign phenotype in pregnancy.


Rectal dosimetry in intracavitary brachytherapy by HDR at rural center of Maharashtra: Comparison of two methods.
The purpose of this study was to calculate the radiation dose at the anterior rectal wall as per the International Commission on Radiation Units and Measurements (ICRU 38) recommendations and compare it with the dose calculated by the commonly used intrarectal catheter. Dose delivery by brachytherapy to the cervix is limited by the critical structure of the bladder and rectum. In this study the ICRU-38 rectal point was derived by using a radio-opaque gauze piece on the posterior vaginal wall, and the intrarectal point was derived by inserting a rubber catheter with a wire, inside the rectum. A total of 146 applications were performed in 81 patients. Rectal doses were compared for complementary rectal points R1 and R5, R2 and R6, R3 and R7, and R4 and R8, obtained by both methods. The rectal doses at each complementary pair were compared with each other. The average dose at R1 was 5% higher than at R5 (60.57% vs. 55.57%). The average dose at R2 was 1% higher than at R6 (58% vs. 57%). The average dose at R3 was 1.29% higher than at R7 (52.71% vs. 51.42%), and the average dose at R4 was 1.15% higher than at R8 (43% vs. 41.85%). There were many instances where the rectal dose exceeded by more than 15%, from the R1 to R4 points (43, 22, 21, and 11 times, respectively, for R1-R5, R2-R6, R3-R7, and R4-R8 pairs). The difference in dose between R1 and R5 was significant as seen on the statistical tests, i.e., Pair T test, Wilcoxan Signed Ranks test, and Sign test (p value 0.002). The rectal dose obtained by the intrarectal wire method underestimates the actual dose to the rectum when compared to the ICRU-38 method. Thus ICRU-38 recommendations should be strictly adhered to, to reduce late complications.


Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland.
Basic research and our previous studies have suggested that mercury exposure enhances lipid peroxidation and the risk of myocardial infarction, but there are no studies concerning the association between mercury accumulation and atherosclerosis. We therefore investigated whether high hair mercury content is associated with accelerated progression of carotid atherosclerosis, determined by ultrasonographic assessment of common carotid intima-media thickness (IMT), in a prospective study among 1014 men aged 42-60 years. In a linear regression model adjusting for other atherosclerotic risk factors, high hair mercury content was one of the strongest predictors of the 4-year increase in the mean IMT (P2.81 microg/g (fifths) had an IMT increase of 0.105, 0.102, 0.113, 0.107 and 0.140 mm/4 years, respectively (P=0.041 for heterogeneity between groups). The IMT increase was 0.034 mm/4 years (31.9%) greater in the highest fifth than in the other fifths (P<0.05 for the difference). These findings suggest that mercury accumulation in the human body is associated with accelerated progression of carotid atherosclerosis.


Species Distinction in the Trichophyton rubrum Complex.
The Trichophyton rubrum species complex comprises commonly encountered dermatophytic fungi with a worldwide distribution. The members of the complex usually have distinct phenotypes in culture and cause different clinical symptoms, despite high genome similarity. In order to better delimit the species within the complex, molecular, phenotypic, and physiological characteristics were combined to reestablish a natural species concept. Three groups, T. rubrum, T. soudanense, and T. violaceum, could be distinguished based on the sequence of the internal transcribed spacer (ITS) ribosomal DNA barcode gene. On average, strains within each group were similar by colony appearance, microscopy, and physiology, but strains between groups showed significant differences. Trichophyton rubrum strains had higher keratinase activity, whereas T. violaceum strains tended to be more lipophilic; however, none of the phenotypic features were diagnostic. The results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and amplified fragment length polymorphism (AFLP) were partially consistent with the ITS data but failed to distinguish the species unambiguously. Despite their close similarity, T. violaceum, T. soudanense, and T. rubrum can be regarded as independent species with distinct geographical distributions and clinical predilections. Trichophyton soudanense is pheno- and genotypically intermediate between T. rubrum and T. violaceum For routine diagnostics, ITS sequencing is recommended.


Mass Spectrometry Imaging and Integration with Other Imaging Modalities for Greater Molecular Understanding of Biological Tissues.
Over the last two decades, mass spectrometry imaging (MSI) has been increasingly employed to investigate the spatial distribution of a wide variety of molecules in complex biological samples. MSI has demonstrated its potential in numerous applications from drug discovery, disease state evaluation through proteomic and/or metabolomic studies. Significant technological and methodological advancements have addressed natural limitations of the techniques, i.e., increased spatial resolution, increased detection sensitivity especially for large molecules, higher throughput analysis and data management. One of the next major evolutions of MSI is linked to the introduction of imaging mass cytometry (IMC). IMC is a multiplexed method for tissue phenotyping, imaging signalling pathway or cell marker assessment, at sub-cellular resolution (1 μm). It uses MSI to simultaneously detect and quantify up to 30 different antibodies within a tissue section. The combination of MSI with other molecular imaging techniques can also provide highly relevant complementary information to explore new scientific fields. Traditionally, classical histology (especially haematoxylin and eosin-stained sections) is overlaid with molecular profiles obtained by MSI. Thus, MSI-based molecular histology provides a snapshot of a tissue microenvironment and enables the correlation of drugs, metabolites, lipids, peptides or proteins with histological/pathological features or tissue substructures. Recently, many examples combining MSI with other imaging modalities such as fluorescence, confocal Raman spectroscopy and MRI have emerged. For instance, brain pathophysiology has been studied using both MRI and MSI, establishing correlations between in and ex vivo molecular imaging techniques. Endogenous metabolite and small peptide modulation were evaluated depending on disease state. Here, we review advanced 'hot topics' in MSI development and explore the combination of MSI with established molecular imaging techniques to improve our understanding of biological and pathophysiological processes.


64Cu-Labeled multifunctional dendrimers for targeted tumor PET imaging.
We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with 64Cu for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5·NHAc dendrimers were then radiolabeled with 64Cu via the DOTA chelation. We show that the FA modification renders the dendrimers with targeting specificity to cancer cells overexpressing FR in vitro. Importantly, the radiolabeled 64Cu-DOTA-FA-FI-G5·NHAc dendrimers can be used as a nanoprobe for specific targeting of FR-overexpressing cancer cells in vitro and targeted microPET imaging of the FR-expressing xenografted tumor model in vivo. The developed 64Cu-labeled multifunctional dendrimeric nanoprobe may hold great promise to be used for targeted PET imaging of different types of FR-expressing cancer.


The characterization and optimization of injectable silicone resin particles in conjunction with dermal fibroblasts and growth factors: an in vitro study.
Minimally invasive subdermal injection of liquid silicone has been used clinically to augment the soft tissue of the foot to mitigate high pressures that cause diabetic foot ulcers. However, implant migration has been a clinical issue. The objective of this study was to assess the effects of three specific concentrations of silicone resin particles (12 mum average diameter) in conjunction with either platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor (bFGF) on fibroblast cell proliferation, collagen synthesis, cell morphology, and migration through in vitro assays and a monolayer scratch wound model. PDGF and bFGF enhanced the proliferation of fibroblasts 5.7-fold and fivefold, respectively, while the addition of silicone particles had no significant effect on proliferation. Collagen production was increased approximately twofold with the addition of bFGF and the medium concentration of particles over bFGF without particles and the PDGF groups. The addition of silicone particles had no significant effect on collagen production compared with control groups without particles. Fibroblast migration was enhanced by the addition of both PDGF and bFGF compared to controls, although slower scratch wound closure rates were observed in the presence of particles compared to controls without particles. Cell morphology suggested that particles induced cellular aggregation encircling silicone particles postwounding as well as migration into the wound area. These results suggest that silicone particles in combination with a growth factor might enhance fibroblast aggregation and implant stability, and could promote connective tissue ingrowth and implant encapsulation in the soft tissue of the diabetic foot.


Critical evaluation of the usability of augmented reality ophthalmoscopy for the training of inexperienced examiners.
To measure the value of augmented reality technology usage to teach the medical students performing binocular indirect ophthalmoscopy. Thirty-seven medical students were randomly assigned to the training of binocular indirect ophthalmoscopy either in the conventional way or with augmented reality ophthalmoscopy (ARO). For testing student's skills, they had to examine a real person using a conventional ophthalmoscopy system and draw the optic disk. They also had to fill out a questionnaire. Subjective and objective evaluations were performed. Thirty-seven students were randomly assigned to two groups. Eighteen students were trained with conventional ophthalmoscopy and 19 students with ARO. The questionnaires showed no differences. Performing an objective analysis, the median ophthalmoscopy training score for the conventional ophthalmoscopy group was 1.2 (range, 0.67-2) and showed a significant difference (P < 0.0033) to the ARO group (median 2; range, 0.67-2). The study provides evidence that a single ARO training is efficient to improve ophthalmoscopy skills. As the objective analysis showed, the ARO group had a significantly superior performance. Our study also indicates that subjective evaluation of the fundus drawings without systematic analysis is prone to errors.


Predictors of interleukin-33 and thymic stromal lymphopoietin levels in cord blood.
The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers. This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels. Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21). Maternal allergy, heavy street traffic, and elevated birth weight were significantly associated with jointly elevated TSLP and IL-33 levels, whereas maternal age and female infant sex were inversely associated with elevated IgE. In this population of Canadian women and infants, TSLP and IL-33 were detectable in cord blood, more strongly correlated with each other than with IgE, and associated with maternal characteristics indicative of inflammatory responses. This study motivates investigation into the value of cord blood IL-33 and TSLP levels as childhood allergy predictors and raises interesting questions regarding in utero coordinated regulation of these cytokines.


Increased UV resistance in xeroderma pigmentosum group A cells after transformation with a human genomic DNA clone.
Xeroderma pigmentosum (XP) is an autosomal recessive disease in which the major clinical manifestation is a 2,000-fold enhanced probability of developing sunlight-induced skin tumors, and the molecular basis for the disease is a defective DNA excision repair system. To clone the gene defective in XP complementation group A (XP-A), cDNA clones were isolated by a competition hybridization strategy in which the corresponding mRNAs were more abundant in cells of the obligately heterozygous parents relative to cells of the homozygous proband affected with the disease. In this report, a human genomic DNA clone that contains this cDNA was transformed into two independent homozygous XP-A cell lines, and these transformants displayed partial restoration of resistance to the killing effects of UV irradiation. The abundance of mRNA corresponding to this cDNA appears to correlate well with the observed UV cell survival. The results of unscheduled DNA synthesis after UV exposure indicate that the transformed cells are repair proficient relative to that of the control XP-A cells. However, using this same genomic DNA, transformation of an XP-F cell line did not confer any enhancement of UV survival or promote unscheduled DNA synthesis after UV exposure.


Long noncoding RNA profiles reveal three molecular subtypes in glioma.
Gliomas are the most lethal type of primary brain tumor in adult. Long noncoding RNAs (lncRNAs), which are involved in the progression of various cancers, may offer a potential gene therapy target in glioma. We first classified gliomas into three molecular subtypes (namely LncR1, LncR2 and LncR3) in Rembrandt dataset using consensus clustering. Survival analysis indicated that LncR3 had the best prognosis, while the LncR1 subtype showed the poorest overall survival rate. The results were further validated in an independent glioma dataset GSE16011. Additionally, we collected and merged data of the two databases (Rembrandt and GSE16011 dataset) and analyzed prognosis of each subtype in WHO II, III and IV gliomas. The similar results were obtained. Gene Set Variation Analysis (GSVA) demonstrated that LncR1 subtype enriched cultured astroglia's gene signature, while LncR2 subtype was characterized by neuronal gene signature. Oligodendrocytic was rich in LncR3. In addition, IDH1 mutation and 1p/19q LOH were found rich with LncR3, and EGFR amplification showed high percentage in LncR1 in GSE16011 dataset. We report a novel molecular classification of glioma based on lncRNA expression profiles and believe that it would provide a potential platform for future studies on gene treatment for glioma and lead to more individualized therapies to improve survival rates.


Apelin-13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism.
Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM) cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+)-activated K(+) (BKCa) channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BK(Ca) channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM) caused concentration-dependent inhibition of BK(Ca) in VSM cells. Apelin-13 (0.1 µM) significantly decreased BK(Ca) current density from 71.25 ± 8.14 pA/pF to 44.52 ± 7.10 pA/pF (n=14 cells, P<0.05). This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 (0.1 µM) decreased the open-state probability (NPo) of BK(Ca) channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 (0.1 µM) did not alter the NPo of BK(Ca) channels, suggesting that the inhibitory effect of apelin-13 on BKCa is not mediated by a direct action on BK(Ca). In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BK(Ca current density. In addition, treatment of arteries with apelin-13 (0.1 µM) significantly increased the ratio of phosphorylated-Akt/total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BK(Ca) channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.


E2F1 inhibits circulating cholesterol clearance by regulating Pcsk9 expression in the liver.
Cholesterol accumulation in the liver is an early event in nonalcoholic fatty liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1-/- mice display reduced total plasma cholesterol levels and increased cholesterol content in the liver. In this study, we show that E2f1 deletion in cellular and mouse models leads to a marked decrease in Pcsk9 expression and an increase in LDLR expression. In addition to the upregulation of LDLR, we report that E2f1-/- hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter. Interestingly, E2f1-/- mice fed a high-cholesterol diet (HCD) display a fatty liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in the liver. Collectively, these data indicate that E2F1 regulates cholesterol uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in the liver and the development of fibrosis in response to an HCD.


Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.
Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial. In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed. After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component. Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.


Making C-H bonds with CO2: production of formate by molecular electrocatalysts.
Molecular approaches to the electrocatalytic reduction of CO2 to formate are varied and versatile in their methods. We discuss recent efforts to catalyse this reaction including significant progress made in the last 5 years. This Feature Article begins with a survey of molecular electrocatalysts that produce CO or H2, but have been observed under certain conditions to afford some formate. These examples are included because they provide valuable mechanistic insight for design of catalysts that produce hydrogenated products selectively from CO2. The subsequent discussion describes catalyst properties that favour C-H bond formation with CO2 and this is followed by recent advances that have been made in developing these catalysts. The focus on specific catalyst systems includes recently reported Ir PCP-type pincer complexes and Fe carbonyl clusters, such as [Fe4N(CO)12](-), that selectively produce formate from CO2 in aqueous solution. A discussion of the relevant thermochemical properties of the catalysts in the context of formate production is included.


Investigating the pro-cognitive and anti-depressant efficacy of metformin: A systematic review and meta-analysis of randomised controlled trials.
The preclinical and clinical data regarding the efficacy of metformin as a pro-cognitive and anti-depressant therapy is mixed. We conducted a systematic review and meta-analysis of randomised controlled trials investigating the effects of metformin on cognition and depressive symptoms. The study was conducted in accordance with PRISMA guidelines (PROSPERO identifier: CRD42020184547). PubMed and Web of Science were searched (inception through to May 6, 2020) for trials which measured the effects (change from baseline to end-of-treatment) of metformin on cognition and depressive symptoms, compared to either placebo or other oral antidiabetic therapies. When feasible, pooled meta-analytic estimates were provided using a random-effects model. Eight studies met the inclusion criteria: four assessed only cognition, three assessed only depressive symptoms, and one study assessed both cognition and depressive symptoms. Results suggested that metformin was significantly superior to placebo in improving cognitive function in patients suffering with clinical conditions associated with cognitive impairment (SMD: 0.80; 95%CI: 0.46 to 1.15; p < 0.001; N = 2 studies; I2 = 0.0%). One study reported an association between improved cognition and depressive symptoms in a cohort of patients with type 2 diabetes mellitus and depression. Two studies investigating metformin versus pioglitazone showed a superior, but not significant, effect of pioglitazone on depressive symptoms (SMD: 1.56; 95%CI: -0.52 to 3.56; p = 0.13;I2 = 94.9%; N = 2 studies). Assessment of risk of bias identified two studies as having "some concerns". Our findings suggest that metformin might be re-purposed for the treatment of cognitive deficits in select clinical conditions.


Sparse-exposure technique in holographic two-photon polymerization.
Holographic two-photon polymerization is based on a high-speed, low-loss parallel laser irradiation technique inside photosensitive materials using a computer-generated hologram displayed on a liquid crystal spatial light modulator. We demonstrated a sparse exposure technique combining parallel exposure and scanning exposure to improve the fabrication throughput and to achieve simultaneous fabrication of linear structures with different widths. We also demonstrated fabrication of space-variant structures by changing a CGH, as well as parallel fabrication of voxel structures with single femtosecond laser pulse irradiation.


Effectiveness, relapse prevention and mechanisms of change of cognitive therapy vs. interpersonal therapy for depression: Study protocol for a randomised controlled trial.
Major depression is a common mental disorder that substantially impairs quality of life and has high societal costs. Although psychotherapies have proven to be effective antidepressant treatments, initial response rates are insufficient and the risk of relapse and recurrence is high. Improvement of treatments is badly needed. Studying the mechanisms of change in treatment might be a good investment for improving everyday mental health care. However, the mechanisms underlying therapeutic change remain largely unknown. The objective of the current study is to assess both the effectiveness of two commonly used psychotherapies for depression in terms of reduction of symptoms and prevention of relapse on short and long term, as well as identifying underlying mechanisms of change. In a randomised trial we will compare (a) Cognitive Therapy (CT) with (b) Interpersonal therapy (IPT), and (c) an 8-week waiting list condition followed by treatment of choice. One hundred eighty depressed patients (aged 18-65) will be recruited in a mental health care centre in Maastricht (the Netherlands). Eligible patients will be randomly allocated to one of the three intervention groups. The primary outcome measure of the clinical evaluation is depression severity measured by the Beck Depression Intenvory-II (BDI-II). Other outcomes include process variables such as dysfunctional beliefs, negative attributions, and interpersonal problems. All self-report outcome assessments will take place on the internet at baseline, three, seven, eight, nine, ten, eleven, twelve and twenty-four months. At 24 months a retrospective telephone interview will be administered. Furthermore, a rudimentary analysis of the cost-effectiveness will be embedded. The study has been ethically approved and registered. By comparing CT and IPT head-to-head and by investigating multiple potential mediators and outcomes at multiple time points during and after therapy, we hope to provide new insights in the effectiveness and mechanisms of change of CT and IPT for depression, and contribute to the improvement of mental health care for adults suffering from depression. The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (ISRCTN67561918).


Preference of goats (Capra hircus L.) for tanniniferous browse species available in semi-arid areas in Ethiopia.
The objectives were to determine browse species preference of goats using dry matter intake (DMI) as a proxy, to compare preference when offered in combination with polyethylene glycol (PEG) and to establish relationships between browse species intake and chemical compositional data. Air-dried leaves of Acacia etbaica, Cadaba farinosa, Capparis tomentosa, Dichrostachys cinerea, Dodonaea angustifolia, Euclea racemosa, Maerua angolensis, Maytenus senegalensis, Rhus natalensis and Senna singueana were used. Two cafeteria trials, each lasting 10 days, were conducted using four local mature male goats of 2-2.5 years receiving a daily ration of grass hay (4% of body weight) and 200 g wheat bran. In trial 1, goats were offered 25 g of each browse species for a total of 30 min with intake, time spent on consumption and the number of visits to specific browse species recorded at 10-min intervals. In trial 2, the same procedure was followed except that 25 g of PEG 4000 was added to the daily wheat bran ration. Crude protein and neutral detergent fibre in browse species ranged from 69.0-245.5 to 159.8-560.6 g/kg dry matter (DM) respectively. Total phenols and total tannins contents ranged between 3.7-70.6 and 2.5-68.1 mg tannic acid equivalent/g DM, respectively, and condensed tannins 1.7-18.4 Abs550 nm /g DM. Preference indicators measured in the first 10 min of browse species intake differed significantly among browse species and with PEG (p < 0.0001). Principal components explained 69.9% of the total variation in browse species DMI. Despite the high tannin levels, D. cinerea, R. natalensis and A. etbaica were the most preferred species regardless of PEG presence. Tannin levels at the observed browse species DMI did not determine preference, instead, preference appeared to be based on hemicellulose. Determining browse species preference is essential to exploit them to improve nutrient utilization and control parasites in goats.


Bio-organic compounds and glassy microparticles in lunar fines and other materials.
Acid hydrolyzates of aqueous extracts indicated: glycine, alanine, glutamic acid, serine, aspartic acid, threonine, and I-diaminopropionic acid. The sources of these amino acids may be terrestrial contaminants, fuel exhaust products, or indigenous lunar material. The lunar particles found in the sample include: (i) spherules, rotational ellipsoids, dumbbells, tear-drops, rings, and crescents which have (ii) diameters of 0.1 to 500 microns; (iii) budlike features on the particles; and (iv) chemical inhomogeneity (electron probe). Some of the processes and results inferred for the moon have been simulated by the electron beam and low pressure of the electron microscope. Basalt (Kilauea-lki) and chondrite (Orgueil) have been found to behave similarly.


Variability among Capsicum baccatum accessions from Goiás, Brazil, assessed by morphological traits and molecular markers.
Capsicum peppers are native to the Americas, with Brazil being a significant diversity center. Capsicum baccatum accessions at Instituto Federal (IF) Goiano represent a portion of the species genetic resources from central Brazil. We aimed to characterize a C. baccatum working collection comprising 27 accessions and 3 commercial cultivars using morphological traits and molecular markers to describe its genetic and morphological variability and verify the occurrence of duplicates. This set included 1 C. baccatum var. praetermissum and 29 C. baccatum var. pendulum with potential for use in breeding programs. Twenty-two morphological descriptors, 57 inter-simple sequence repeat, and 34 random amplified polymorphic DNA markers were used. Genetic distance was calculated through the Jaccard similarity index and genetic variability through cluster analysis using the unweighted pair group method with arithmetic mean, resulting in dendrograms for both morphological analysis and molecular analysis. Genetic variability was found among C. baccatum var. pendulum accessions, and the distinction between the two C. baccatum varieties was evident in both the morphological and molecular analyses. The 29 C. baccatum var. pendulum genotypes clustered in four groups according to fruit type in the morphological analysis. They formed seven groups in the molecular analysis, without a clear correspondence with morphology. No duplicates were found. The results describe the genetic and morphological variability, provide a detailed characterization of genotypes, and discard the possibility of duplicates within the IF Goiano C. baccatum L. collection. This study will foment the use of this germplasm collection in C. baccatum breeding programs.


The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats.
In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320mg/kg body wt.), crocin (100, 200 and 400mg/kg body wt.), safranal (0.1, 0.2 and 0.4ml/kg), sildenafil (60mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.


Sildenafil citrate-restored eNOS and PDE5 regulation in sickle cell mouse penis prevents priapism via control of oxidative/nitrosative stress.
Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.