Soft robotic sleeve supports heart function.
There is much interest in form-fitting, low-modulus, implantable devices or soft robots that can mimic or assist in complex biological functions such as the contraction of heart muscle. We present a soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device. The sleeve does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current ventricular assist devices, such as clotting and infection. Our approach used a biologically inspired design to orient individual contracting elements or actuators in a layered helical and circumferential fashion, mimicking the orientation of the outer two muscle layers of the mammalian heart. The resulting implantable soft robot mimicked the form and function of the native heart, with a stiffness value of the same order of magnitude as that of the heart tissue. We demonstrated feasibility of this soft sleeve device for supporting heart function in a porcine model of acute heart failure. The soft robotic sleeve can be customized to patient-specific needs and may have the potential to act as a bridge to transplant for patients with heart failure.


Optical and electrical study of core-shell silicon nanowires for solar applications.
In this work, we report a CMOS comparable fabrication process of core-shell SiNW solar cell from single-crystalline p-type Si(100) test wafers. Optical lithography defined plasma etching was used to form highly ordered vertical SiNW arrays, which display a drastic reduction in optical reflectance over a wide range of wavelengths. BF(2) and P ion implantations were employed for producing a sharp and shallow radial p-n junction. Under AM 1.5G illumination, the device demonstrates a short circuit current density (Jsc) of 14.2 mA/cm(2), an open circuit voltage (Voc) of 0.485 V and a fill factor (FF) of 42.9%, giving a power conversion efficiency (PCE) of 2.95%. The Jsc observed is 52% higher than that in the control device with planar Si p-n junction, indicating significant enhancement in carrier generation and collection efficiency from the core-shell structure. Impact of series resistance (Rs) is also studied, highlighting potential improvement of PCE to 4.40% in the absence of Rs. With top contact optimized, PCE could further increase to 6.29%.


Prunella vulgaris suppresses HG-induced vascular inflammation via Nrf2/HO-1/eNOS activation.
Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.


Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study.
Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytoBOM) for patients with intermediate- and high-grade non-Hodgkin's lymphomas was tested by the Southwest Oncology Group (SWOG) to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimens in a cooperative group setting. On day 1, cyclophosphamide, doxorubicin, and etoposide were administered, followed by cytarabine, bleomycin, vincristine and methotrexate with leucovorin given on day 8. There were 51 complete remissions (CRs) among 78 previously untreated patients (65%) having clinical stage II-IV disease. The median length of follow-up is 37.9 months with 57% of patients alive at 3 years and 50% of CR patients free of disease at 3 years. Patients with diffuse large-cell lymphoma have the best survival (63% at 3 years) and relapse-free survival (RFS; 68% at 3 years with no relapses seen after 14 months). Administration of ProMACE-CytoBOM is feasible and safe in a cooperative group setting with 84% of 537 courses of treatment given exactly according to schedule and fatal toxicities seen in five patients (6%). ProMACE-CytaBOM may represent improved treatment for diffuse large-cell lymphoma, but the modest differences compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) indicate the need for a prospective randomized comparative trial.


Self-reported loss of smell without nasal obstruction to identify COVID-19. The multicenter Coranosmia cohort study.
To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period. Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19. i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)). Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts.


Cultural, contextual, and gender differences in peer talk: a comparative study.
The study focused on cultural, contextual, and gender differences in children's peer talk. Same-sex dyads of Estonian (n = 38), Finnish (n = 38), and Swedish (n = 34) preschool age children were videotaped during unstructured and structured play settings. We found only one gender difference in children's talkativeness and in the use of regulatory speech: during free play, Swedish boys used more imperatives per directives than Swedish girls. At the same time there were significant cultural and contextual differences. Estonian children were most directive and Swedish children were least directive. Finnish children were less directive than Estonian children but more directive than Swedish children. It was concluded that cultural and contextual factors strongly influence the likelihood, extent, and nature of gender differences in peer talk.


Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead.
To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. Case-control study. Information on parents was obtained by home interview. Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. 109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth.


Doppler-angle measurement in highly scattering media.
We describe a dual-channel optical low-coherence reflectometer for accurate measurement of Doppler angles in highly scattering media. Accurate fluid-flow velocity estimation requires measurement of the Doppler shift and angle. Estimated values of the Doppler angle and average fluid-flow velocity from experimental data are in good agreement with preset values.


Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages.
Pterostilbene, an active constituent of blueberries, is known to possess anti-inflammatory activity and also to induce apoptosis in various types of cancer cells. Here, we investigated the inhibitory effects of pterostilbene on the induction of NO synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and real-time polymerase chain reaction (PCR) analyses demonstrated that pterostilbene significantly blocked the protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with pterostilbene resulted in the reduction of LPS-induced nuclear translocation of the nuclear factor-kappaB (NFkappaB) subunit and the dependent transcriptional activity of NFkappaB by blocking phosphorylation of inhibitor kappaB (IkappaB)alpha and p65 and subsequent degradation of IkappaB alpha. Transient transfection experiments using NFkappaB reporter constructs indicated that pterostilbene inhibits the transcriptional activity of NFkappaB in LPS-stimulated mouse macrophages. We found that pterostilbene also inhibited LPS-induced activation of PI3K/Akt, extracellular signal-regulated kinase 1/2 and p38 MAPK. Taken together, these results show that pterostilbene down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation of PI3K/Akt/IKK and MAPK. These results have an important implication for using pterostilbene toward the development of an effective anti-inflammatory agent.


Physicians' perceptions and practices regarding patient reports of multiple chemical sensitivity.
Ninety physicians practicing in the state of Virginia USA completed a mail survey regarding Multiple Chemical Sensitivity (MCS). Survey questions addressed demographics; familiarity with MCS; etiology; overlapping conditions; accommodations made for patients and practices regarding evaluation, treatment, and referral. A little over half of respondents were familiar with MCS. Under a third had received any medical training regarding chemical sensitivity, only 7% were "very satisfied" with their knowledge, and 6% had a treatment protocol for the condition. Participants cited a range of etiologies and overlapping conditions including asthma, Reactive Airway Dysfunction Syndrome (RADS), Sick Building Syndrome (SBS), Chronic Fatigues Syndrome (CFS), and Fibromyalgia. Physicians infrequently considered chemicals as a cause of illness when seeing new patients. Evaluation techniques included interviews, blood work, immune profiles, and allergy testing. Interventions recommended included chemical avoidance, alterations in the home environment, diet restrictions, the use of air filters, and referrals to outside specialists.


Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
The anaphase-promoting complex/cyclosome (APC) ubiquitin ligase is activated by Cdc20 and Cdh1 and inhibited by Mad2 and the spindle assembly checkpoint complex, Mad2B, and the early mitotic inhibitor Emi1. Mad2 inhibits APC(Cdc20), whereas Mad2B preferentially inhibits APC(Cdh1). We have examined the mechanism of APC inhibition by Emi1 and find that unlike Mad2 proteins, Emi1 binds and inhibits both APC(Cdh1) and APC(Cdc20). Also unlike Mad2, Emi1 stabilizes cyclin A in the embryo and requires zinc for its APC inhibitory activity. We find that Emi1 binds the substrate-binding region of Cdc20 and prevents substrate binding to the APC, illustrating a novel mechanism of APC inhibition.


Improvement in 3-month patient-reported gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients.
The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both P<0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was -0.74 overall (cyclosporine: -0.73 and tacrolimus: -0.74; all P<0.0001 versus baseline), with a slight further improvement (-0.79) at month 3 (cyclosporine: -0.82 and tacrolimus: -0.78; all P<0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all P<0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.


Heterogeneity in coal composition and implications for lung cancer risk in Xuanwei and Fuyuan counties, China.
Xuanwei and Fuyuan counties in Yunnan Province, China have among the highest lung cancer rates in the country. This has been associated with the domestic combustion of bituminous coal (referred to as "smoky" coal). Additionally, significant geographical variation in cancer rates among smoky coal users has been observed, suggesting heterogeneity in fuel source composition and/or combustion characteristics. Research thus far has indicated that smoky coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains high concentrations of fine grained crystalline quartz, however, much of this research is limited in terms of sample size and geographic scope. In order to more fully characterise geochemical and elemental compositions of smoky and smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure assessment study in households in this region. Fuel samples representing smoky and "smokeless" (anthracite, the major alternative coal type in the region) coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS, XRF analysis and electron microscopy were used to establish hydrocarbon content (to represent volatile organic compounds), major and trace element composition and mineral composition respectively. Heterogeneity in coal characteristics between and within coal types was assessed by the Kruskal-Wallis test. 145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically significant differences between smoky and smokeless coals with regard to hydrocarbon content, sulfur, trace elements and mineral composition were observed. Of note, smoky coal contained between 5 and 15 times the amount of volatile organic matter and twice the amount of quartz (including respirable quartz) than smokeless coal. Smoky coal generally had lower levels of trace elements (plus aluminium) than smokeless coal. Significant variation was also observed between smoky coal samples from different geographical areas with regard to hydrocarbon content and elemental composition (including aluminium and silicon). This paper has identified compositional differences between and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A decreased ratio of aluminium to silicon in smoky coal suggests elevated free silica, a finding consistent with observed higher levels of quartz. Elevated volatile organic matter content in smoky coal (when compared to smokeless coal) is consistent with the geochemical expectations for smoky and smokeless coals. These findings also reflect previous observations of elevated volatile compound emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity in coal composition between and within coal types may provide leads to the observed heterogeneity in cancer risk observed in this area.


Impact of Coping Strategies on Nurses' Well-Being and Practice.
To examine the mechanisms of coping strategies on nurses' psychological well-being, practice environments and safety attitudes. A cross-sectional study design was used. Structural equation modeling was performed to analyze the results. Five hundred clinical nurses were randomly selected from a large group of 1,500 from a medical center with 1,350 beds in Taipei, Taiwan, from July to October 2015. Self-report questionnaires were administered to measure coping strategies (Brief COPE), psychological well-being (Ryff's Psychological Well-being Scale), nurses' practice environments (Practice Environment Scale of the Nursing Work Index), and safety attitudes (Safety Attitudes Questionnaire). Of the 500 participants who gave written consent, 474 (94.8%) filled out the questionnaire. Results showed that using more approach-oriented coping strategies and fewer avoidant coping strategies was associated with greater psychological well-being. Psychological well-being was directly associated with quality of nurses' practice environments and safety attitudes. The impact of psychological well-being on safety attitudes was mediated significantly by the quality of the practice environment. The use of approach-oriented coping strategies was significantly predictive of positive psychological well-being, a good practice environment, and good safety attitudes. This study found a distinct pathway for the relationships between clinical nurses' psychological well-being, practice environment, and safety attitudes. Psychological well-being in clinical nurses was higher for those with more approach-oriented coping strategies. Psychological well-being directly impacted safety attitudes, which mediated nurses' practice environments. The practical implications of the results suggest that interventions designed to promote positive psychological well-being may help improve nurses' practice environments, which, in turn, may result in better safety attitudes and nursing care outcomes.


Malaria and related outcomes in patients with intestinal helminths: a cross-sectional study.
The effects of helminth co-infection on malaria in humans remain uncertain. This study aimed to evaluate the nature of association of intestinal helminths with prevalence and clinical outcomes of Plasmodium infection. A cross-sectional study involving 1,065 malaria suspected febrile patients was conducted at Dore Bafeno Health Center, Southern Ethiopia, from December 2010 to February 2011. Plasmodium and intestinal helminth infections were diagnosed using Giemsa-stained blood films and Kato-Katz technique, respectively. Haemoglobin level was determined using a haemocue machine. Among 1,065 malaria suspected febrile patients, 28.8% were positive for Plasmodium parasites (P. falciparum =13.0%, P. vivax =14.5%, P. falciparum and P. vivax =1.3%). Among 702 patients who provided stool samples, 53.8%, 31.6% and 19.4% were infected with intestinal helminths, Plasmodium alone and with both Plasmodium and intestinal helminths, respectively. The prevalence of infections with Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), Schistosoma mansoni (S. mansoni) and hookworm (9.8%) were 35.9%, 15.8%, 11.7% and 9.8%, respectively. Out of the 222 (31.6%) Plasmodium infected cases, 9 (4.1%) had severe malaria. P. falciparum infection was more common in febrile patients infected with A. lumbricoides alone (21.3%), T. trichiura alone (23.1%) and S. mansoni alone (23.1%) compared to those without intestinal helminth infections (9.3%) (p<0.001 for all). Prevalence of non-severe malaria was significantly higher in individuals infected with intestinal helminths than in those who were not infected with intestinal helminths (adjusted OR=1.58, 95% CI=1.13-2.22). The chance of developing non-severe P. falciparum malaria were 2.6, 2.8 and 3.3 times higher in individuals infected with A. lumbricoides alone, T. trichiura alone and S. mansoni alone, respectively, compared to intestinal helminth-free individuals (p<0.05 for all). The odds ratio for being infected with non-severe P. falciparum increased with the number of intestinal helminth species (p<0.001). Mean Plasmodium density among intestinal helminth infected individuals was significantly increased with the number of intestinal helminths species (p=0.027). Individuals who were co-infected with different species of intestinal helminths and Plasmodium showed lower mean haemoglobin concentration than individuals who were infected only with Plasmodium. Infections with A. lumbricoides, T. trichiura and S. mansoni were positively associated with P. falciparum infection. However, further studies are required to investigate how these helminths could contribute to increased prevalence of P. falciparum infection.


Selective Antagonism of A1 Adenosinergic Receptors Strengthens the Neuromodulation of the Sensorimotor Network During Epidural Spinal Stimulation.
Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the capacity of electrical and pharmacological interventions to synergistically increase the engagement of spinal sensorimotor networks and regain motor function after SCI. This study explored whether selective pharmacological antagonism of the adenosine A1 receptor subtype synergizes with ESS, thereby increasing motor response. We hypothesized that selective pharmacological antagonism of A1 receptors during ESS would produce facilitatory effects in spinal sensorimotor networks detected as an increased amplitude of spinally-evoked motor potentials and sustained duration of ESS induced activity. Terminal experiments were performed in adult rats using trains of stereotyped pulses at 40 Hz delivered at L5 with the local administration to the cord of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We demonstrated that ESS combined with the blockage of A1 receptors increased the magnitude of the endogenous modulation and postponed the decay of responses that occur during ESS alone. Although DPCPX significantly increased the yield of repetitive stimulation in intact spinal cords, the effects of A1 antagonism on motor evoked responses after an acute spinal transection was not detected. These studies support the future investigation of the optimal dosage, methods of delivery, and systemic effects of the synergistic application of A1 antagonists and spinal stimulation in the intact and injured spinal cord.


Microbial Indicator Profiling of Fresh Produce and Environmental Samples from Farms and Packing Facilities in Northern Mexico.
To compare microbiological indicator and pathogen contamination among different types of fresh produce and environmental samples along the production chain, 636 samples of produce (rinsates from cantaloupe melons, jalapeño peppers, and tomatoes) and environmental samples (rinsates from hands of workers, soil, and water) were collected at four successive steps in the production process (from the field before harvest through the packing facility) on 11 farms in northern Mexico during 2011 and 2012. Samples were assayed for enteric pathogens (Escherichia coli O157:H7, other Shiga toxigenic E. coli, Salmonella, and Listeria monocytogenes) and microbial indicators (coliforms, other E. coli strains, and Enterococcus spp.). Salmonella was the only pathogen detected; it was found in one preharvest jalapeño sample (detection limits: 0.0033 CFU/ml in produce and hand samples, 0.0013 CFU/ml in water, and 0.04 CFU/g in soil). Microbial indicator profiles for produce, worker hands, and soil from jalapeño and tomato farms were similar, but cantaloupe farm samples had higher indicator levels (P < 0.05 for all comparisons) on fruit (6.5, 2.8, and 7.2 log CFU per fruit) and hands (6.6, 3.1, and 7.1 log CFU per hand) for coliforms, E. coli, and Enterococcus, respectively, and lower E. coli levels in soil (<1 CFU/g). In water from tomato farms, E. coli indicators were significantly more prevalent (70 to 89% of samples were positive; P = 0.01 to 0.02), and geometric mean levels were higher (0.3 to 0.6 log CFU/100 ml) than those in cantaloupe farm water (32 to 38% of samples were positive, geometric mean <1 CFU/100 ml). Microbial indicators were present during all production steps, but prevalence and levels were generally highest at the final on-farm production step (the packing facility) (P < 0.03 for significant comparisons). The finding that microbial contamination on produce farms is influenced by produce type and production step can inform the design of effective approaches to mitigate microbial contamination.


The relationship of internal conductance and membrane capacity to mitochondrial volume.
A study was made of the effect of mitochondrial size on the electrical properties of the membrane and the internal conductivity of mitochondria. The dielectric constant and electrical conductivity of suspensions of guinea pig heart mitochondria were examined in the frequency range 5 x 10(5) to 2.5 x 10(8)C.P.S. Membrane capacity was calculated to be 1.1 to 1.3 microf./cm.(2) and was virtually the same in mitochondria whose surface area was made to vary by a factor of 4 by osmotic means. This finding suggested that some mechanism must exist for the transfer of mitochondrial material into membrane structure during fluctuations in mitochondrial size. The electrical capacity of the membrane was unaffected by a 33-fold change in potassium chloride concentration. The internal conductance of swollen mitochondria was 2 to 3 times lower than that of the external medium. In shrunken mitochondria the internal conductance was virtually independent of the conductivity of the external medium. These results were discussed in relation to current concepts of mitochondrial structure.


Cutting edge: Guillain-Barre syndrome-associated IgG responses to gangliosides are generated independently of CD1 function in mice.
CD1 molecules present a variety of microbial glycolipids and self-glycolipids to T cells, but their potential role in humoral responses to glycolipid Ags remains to be established. To address this issue directly, we used GM1/GD1a-deficient mice, which, upon immunization with heat-killed Campylobacter jejuni, develop Guillain-Barré syndrome-associated IgG Abs against the GM1/GD1a sugar chain epitopes of bacterial lipo-oligosaccharides (LOS). Our results showed that anti-ganglioside Abs of the IgG1, IgG2b, and IgG3 isotypes were produced in the absence of group 2 CD1 (CD1d) expression. Unlike mouse and human group 2 CD1 molecules that specifically bound LOS, none of the group 1 CD1 molecules (CD1a, CD1b, and CD1c in humans) were capable of interacting with LOS. Thus, these results indicate CD1-independent pathways for anti-ganglioside Ab production.


Stroke and nursing home care: a national survey of nursing homes.
Although stroke is recognised as a major factor in admission to nursing home care, data is lacking on the extent and nature of the disabilities and dependency in nursing homes arising from stroke. A national study conducted in nursing homes can quantify the number of residents with stroke in nursing homes, their disability and levels of dependency. A cross-sectional survey research design was used. A total of 572 public and private nursing homes were identified nationally and a stratified random selection of 60 nursing homes with 3,239 residents was made. In half of the nursing homes (n = 30) efforts were made to interview all residents with stroke Survey instruments were used to collect data from residents with stroke and nursing home managers on demography, patient disability, and treatment. Across all nursing homes (n = 60), 18% (n = 570) of the residents had previously had a stroke. In homes (n = 30), where interviews with residents with stroke (n = 257), only 7% (n = 18) residents were capable of answering for themselves and were interviewed. Data on the remaining 93% (n = 239) residents were provided by the nursing home manager. Nurse Managers reported that 73% of residents with stroke had a high level of dependency. One in two residents with stroke was prescribed antidepressants or sedative medication. Only 21% of stroke residents were prescribed anticoagulants, 42% antiplatelets, and 36% cholesterol lowering medications. Stroke rehabilitation guidelines were lacking and 68% reported that there was no formal review process in place. This study provides seminal findings on stroke and nursing home services in Ireland. We now know that one in six nursing home residents in a national survey are residents with a stroke, and have a wide range of disabilities. There is currently little or no structured care (beyond generic care) for stroke survivors who reside in nursing homes in Ireland.


Colloidal spirals in nematic liquid crystals.
One of the central experimental efforts in nematic colloids research aims to explore how the interplay between the geometry of particles along with the accompanying nematic director deformations and defects around them can provide a means of guiding particle self-assembly and controlling the structure of particle-induced defects. In this work, we design, fabricate, and disperse low-symmetry colloidal particles with shapes of spirals, double spirals, and triple spirals in a nematic fluid. These spiral-shaped particles, which are controlled by varying their surface functionalization to provide tangential or perpendicular boundary conditions of the nematic molecular alignment, are found inducing director distortions and defect configurations with non-chiral or chiral symmetry. Colloidal particles also exhibit both stable and metastable multiple orientational states in the nematic host, with a large number of director configurations featuring both singular and solitonic nonsingular topological defects accompanying them, which can result in unusual forms of colloidal self-assembly. Our findings directly demonstrate how the symmetry of particle-generated director configurations can be further lowered, or not, as compared to the low point group symmetry of solid micro-inclusions, depending on the nature of induced defects while satisfying topological constraints. We show that achiral colloidal particles can cause chiral symmetry breaking of elastic distortions, which is driven by complex three-dimensional winding of induced topological line defects and solitons.


Deep learning in ophthalmology: The technical and clinical considerations.
The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally.


Development of a PtSn bimetallic catalyst for direct fuel cells using bio-butanol fuel.
Pt and PtSn catalysts were studied for n-butanol electro-oxidation at various temperatures. PtSn showed a higher activity towards butanol electro-oxidation compared to Pt in acidic media. The onset potential for n-butanol oxidation on PtSn is ∼520 mV lower than that found on Pt, and significantly lower activation energy was found for PtSn compared with that for Pt.


Encoding Active Device Elements at Nanowire Tips.
Semiconductor nanowires and other one-dimensional materials are attractive for highly sensitive and spatially confined electrical and optical signal detection in biological and physical systems, although it has been difficult to localize active electronic or optoelectronic device function at one end of such one-dimensional structures. Here we report a new nanowire structure in which the material and dopant are modulated specifically at only one end of nanowires to encode an active two-terminal device element. We present a general bottom-up synthetic scheme for these tip-modulated nanowires and illustrate this with the synthesis of nanoscale p-n junctions. Electron microscopy imaging verifies the designed p-Si nanowire core with SiO2 insulating inner shell and n-Si outer shell with clean p-Si/n-Si tip junction. Electrical transport measurements with independent contacts to the p-Si core and n-Si shell exhibited a current rectification behavior through the tip and no detectable current through the SiO2 shell. Electrical measurements also exhibited an n-type response in conductance versus water-gate voltage with pulsed gate experiments yielding a temporal resolution of at least 0.1 ms and ∼90% device sensitivity localized to within 0.5 μm from the nanowire p-n tip. In addition, photocurrent experiments showed an open-circuit voltage of 0.75 V at illumination power of ∼28.1 μW, exhibited linear dependence of photocurrent with respect to incident illumination power with an estimated responsivity up to ∼0.22 A/W, and revealed localized photocurrent generation at the nanowire tip. The tip-modulated concept was further extended to a top-down/bottom-up hybrid approach that enabled large-scale production of vertical tip-modulated nanowires with a final synthetic yield of >75% with >4300 nanowires. Vertical tip-modulated nanowires were fabricated into >50 individually addressable nanowire device arrays showing diode-like current-voltage characteristics. These tip-modulated nanowire devices provide substantial opportunity in areas ranging from biological and chemical sensing to optoelectronic signal and nanoscale photodetection.


First Report of Little Cherry Disease from Sweet Cherry (Prunus avium) and Sour Cherry (P. cerasus) in the Czech Republic.
Little cherry disease (LChD), a virus disease of sweet (Prunus avium) and sour cherries (P. cerasus), is caused by members of the Closteroviridae family. Symptoms are especially visible on fruits and leaves. Leaves become red or bronze in late summer and fall. Fruit are small, angular, and pointed. Fruits are unmarketable due to a characteristic bitter flavor. LChD also causes reduction of yield (1). Sweet and sour cherries are the second (after apples) most often grown fruit species in the Czech Republic. Since LChD occurred in Germany (1) and Poland (2) in 2007 and 2008, sweet and sour cherry trees with LChD symptoms were surveyed in orchards in the East Bohemia Region of the Czech Republic. The presence of LChD was determined by reverse transcription (RT)-PCR and woody indicator plants, as recommended by the European and Mediterranean Plant Protection Organization (EPPO). Different parts of plants were taken from trees with suspicious symptoms to observe the dynamics of virus infection during the 2009 growing season. Total RNA was isolated from young leaves, blossoms, fruits, and fully developed leaves with a CONCERT Plant RNA Purification Reagent (Invitrogen, Carlsbad, CA) (3). RT-PCR was performed with a QIAGEN OneStep RT-PCR Kit (Qiagen, Hilden, Germany) and oligonucleotides previously described (4). Oligonucleotide LCV3EC (5'-GCTCTAGAGGCACCTTTTATTTTTTATATATGC-3'), complementary to position 16910 to 16934 (GenBankAccession No. Y10237) (with the addition of eight nonviral nucleotides to introduce an XbaI site), was used as a negative-sense primer in RT reactions and PCR. Oligonucleotide LCV16659 (5'-GTTATAGAATTCACTGCAAGTG-3') was used as a positive-sense primer for PCR amplification. The program used for cDNA synthesis was 50°C for 30 min, followed by denaturation for 10 min at 95°C, 35 cycles of 45 s at 94°C, 45 s at 58°C, and 45 s at 72°C. A final incubation was at 72°C for 5 min (1). The finished PCR products (430 bp) were analyzed on 1% agarose gels (stained with SYBR green). According to the preliminary results, young leaves from buds (67% of samples of selected trees with LChD were positive), blossoms (67% positive), and leaves taken in autumn (67% positive) were optimal for the detection of LChD by RT-PCR. The trial with woody indicator plant species was established in the field. Indicators P. avium cv. Sam and P. avium cvs. Bing, F12/1, and Canindex (4) were inoculated with buds from LChD-infected trees and observed for 2 years. Woody indicators remained symptomless throughout the first year of observation, but the indicators showed red coloration of leaves in late summer of the second year. P. avium cv. Canindex seems to be the best woody indicator for testing of LChD in the climatic conditions of the Czech Republic. To our knowledge, this is the first report of LChD in the Czech Republic. References: (1) W. Jelkmann et al. Acta Hortic. 781:321, 2008. (2) B. Komorowska and M. Cieślińska. Plant Dis. 92:1366, 2008. (3) J. Matoušek et al. Biol.Chem. 388:1, 2007. (4) M. Vitushkina et al. Eur. J. Plant Pathol. 103:803, 1997.


The effect of bovine colostrum supplementation in older adults during resistance training.
Bovine colostrum is the first milk secreted by cows after parturition and has high levels of protein, immunoglobulins, and various growth factors. We determined the effects of 8 weeks of bovine colostrum supplementation versus whey protein during resistance training in older adults. Males (N = 15, 59.1 ± 5.4 y) and females (N = 25, 59.0 ± 6.7 y) randomly received (double-blind) 60 g/d of colostrum or whey protein complex (containing 38 g protein) while participating in a resistance training program (12 exercises, 3 sets of 8-12 reps, 3 days/ week). Strength (bench press and leg press 1-RM), body composition (by dual energy x-ray absorptiometry), muscle thickness of the biceps and quadriceps (by ultrasound), cognitive function (by questionnaire), plasma insulin-like growth factor-1 (IGF-1) and C-reactive protein (CRP, as a marker of inflammation), and urinary N-telopeptides (Ntx, a marker of bone resorption) were determined before and after the intervention. Participants on colostrum increased leg press strength (24 ± 29 kg; p < .01) to a greater extent than participants on whey protein (8 ± 16 kg) and had a greater reduction in Ntx compared with participants on whey protein (-15 ± 40% vs. 10 ± 42%; p < .05). Bench press strength, muscle thickness, lean tissue mass, bone mineral content, and cognitive scores increased over time (p < .05) with no difference between groups. There were no changes in IGF-1 or CRP. Colostrum supplementation during resistance training was beneficial for increasing leg press strength and reducing bone resorption in older adults. Both colostrum and whey protein groups improved upper body strength, muscle thickness, lean tissue mass, and cognitive function.


Virtual rehabilitation in an activity centre for community-dwelling persons with stroke. The possibilities of 3-dimensional computer games.
The main purpose of this study was to place a virtual reality (VR) system, designed to assess and to promote motor performance in the affected upper extremity in subjects after stroke, in a nonhospital environment. We also wanted to investigate if playing computer games resulted in improved motor function in persons with prior stroke. The intervention involved 11 patients after stroke who received extra rehabilitation by training on a computer 3 times a week during a 4-week period. The control group involved 11 patients after stroke who continued their previous rehabilitation (no extra computer training) during this period. The mean age of all was 68 years (range = 47-85) and the average time after stroke 66 months (range = 15-140). The VR training consisted of challenging games, which provided a range of difficulty levels that allow practice to be fun and motivating. An additional group of 11 right-handed aged matched individuals without history of neurological or psychiatric illnesses served as reference subjects. All the participants reported that they were novel computer game players. After an initial introduction they learned to use the VR system quickly. The treatment group demonstrated improvements in motor outcome for the trained upper extremity, but this was not detected in real-life activities. The results of this research suggest the usefulness of computer games in training motor performance. VR can be used beneficially not only by younger participants but also by older persons to enhance their motor performance after stroke.


Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells.
Murine Lyme borreliosis is characterized by arthritis and carditis that are most severe at 2 to 3 wk, then regress during the course of persistent infection. Borrelia burgdorferi-specific Abs and CD4+ T cells have been implicated in the resolution phase of arthritis. Therefore, MHC class II transactivator (CIITA)-deficient mice that do not express conventional class II molecules and lack the normal CD4 repertoire were used to investigate the role of MHC class II-mediated responses in Lyme disease. The development of arthritis and carditis, and the resolution of arthritis, were similar in CIITA-deficient and control C57/BL6 mice. In contrast, the resolution of carditis was delayed in CIITA-deficient animals compared with controls. Moreover, CIITA-deficient mice developed B. burgdorferi-specific IgG2b Abs, and sera from these animals passively protected naive C3H/HeN mice from challenge inoculation and cleared B. burgdorferi from 2 day-infected C.B.17 SCID mice. These data suggest that CD4+ T cells and MHC class II-mediated responses are not required for the generation of protective Abs or the regression of arthritis, but may be important in the resolution of Lyme carditis in mice.


The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction.
Lysosomal storage diseases (LSDs) are a family of disorders that result from inherited gene mutations that perturb lysosomal homeostasis. LSDs mainly stem from deficiencies in lysosomal enzymes, but also in some non-enzymatic lysosomal proteins, which lead to abnormal storage of macromolecular substrates. Valuable insights into lysosome functions have emerged from research into these diseases. In addition to primary lysosomal dysfunction, cellular pathways associated with other membrane-bound organelles are perturbed in these disorders. Through selective examples, we illustrate why the term "cellular storage disorders" may be a more appropriate description of these diseases and discuss therapies that can alleviate storage and restore normal cellular function.


Euros vs. yuan: comparing European and Chinese fishing access in West Africa.
We compare the performance of European Union (EU) and Chinese fisheries access agreements with West African countries in terms of illegal and unreported fishing, economic equity, and patterns of exploitation. Bottom-up re-estimations of catch reveal that the EU (1.6 million t•year(-1)) and China (2.3 million t•year(-1)) report only 29% and 8%, respectively, of their estimated total catches (including estimated discards whenever possible) from West African countries between 2000 and 2010. EU catches are declining, while Chinese catches are increasing and are yet to reach the historic maximum level of EU catches (3 million t•year(-1) on average in the 1970s-1980s). The monetary value of EU fishing agreements, correlated in theory with reported catches, is straightforward to access, in contrast to Chinese agreements. However, once quantified, the value of Chinese agreements is readily traceable within the African economy through the different projects they directly cover, in contrast to the funds disbursed [to host governments] by the EU. Overall, China provides resources equivalent to about 4% of the ex-vessel value [value at landing] of the catch taken by Chinese distant-water fleets from West African waters, while the EU pays 8%. We address the difficulties of separating fees directly related to fishing from other economic or political motivations for Chinese fees, which could introduce a bias to the present findings as this operation is not performed for EU access fees officially related to fishing. Our study reveals that the EU and China perform similarly in terms of illegal fishing, patterns of exploitation and sustainability of resource use, while under-reporting by the EU increases and that by China decreases. The EU agreements provide, in theory, room for improving scientific research, monitoring and surveillance, suggesting a better performance than for Chinese agreements, but the end-use of the EU funds are more difficult, and sometime impossible to ascertain.


[Guidelines for the sociomedical assessment of performance in patients suffering from breast cancer].
The following guidelines were developed for the medical assessment services of the German Pension Insurance Federal Institution. Starting from day-to-day practice, criteria and attributes to guide decisions for a systemisation of the sociomedical assessment of performance in breast cancer were compiled. The guidelines aim at standardising the sociomedical assessment of performance and help to make the decision-making process more transparent, e. g., for the assessment of applications for decreased earning capacity benefits. The guidelines summarise typical manifestations of breast cancer and describe the necessary medical information for the sociomedical assessment of performance. Relevant assessment criteria for the medical history, clinical examination, and for diagnostic tests are illustrated. The assessment of the individual's capacity is outlined, taking occupational factors into account. Following the determination of dysfunctions, the remaining abilities and disabilities, respectively, are deduced and compared with occupational demands. Finally, inferences are drawn regarding the occupational capacity of the individual.


Genotyping coronaviruses associated with feline infectious peritonitis.
Feline coronavirus (FCoV) infections are endemic among cats worldwide. The majority of infections are asymptomatic or result in only mild enteric disease. However, approximately 5 % of cases develop feline infectious peritonitis (FIP), a systemic disease that is a frequent cause of death in young cats. In this study, we report the complete coding genome sequences of six FCoVs: three from faecal samples from healthy cats and three from tissue lesion samples from cats with confirmed FIP. The six samples were obtained over a period of 8 weeks at a single-site cat rescue and rehoming centre in the UK. We found amino acid differences located at 44 positions across an alignment of the six virus translatomes and, at 21 of these positions, the differences fully or partially discriminated between the genomes derived from the faecal samples and the genomes derived from the tissue lesion samples. In this study, two amino acid differences fully discriminated the two classes of genomes: these were both located in the S2 domain of the virus surface glycoprotein gene. We also identified deletions in the 3c protein ORF of genomes from two of the FIP samples. Our results support previous studies that implicate S protein mutations in the pathogenesis of FIP.


PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer.
The purpose of this work was to determine whether there are differences in PIK3CA mutation status and PTEN protein expression between primary and matched metastatic breast tumors as this could influence patient management. Paraffin sections of 50 μm were used for DNA extraction and slides of 3 μm for immunohistochemistry (IHC) and FISH. Estrogen receptor, progesterone receptor, and HER2 IHC were repeated in a central laboratory for both primary tumors and metastases. PTEN levels were assessed by IHC and phosphoinositide 3-kinase (PI3K) pathway mutations were detected by a mass spectroscopy-based approach. Median age was 48 years (range: 30-83 years). Tumor subtype included 72% hormone receptor positive/HER2 negative, 20% HER2-positive, and less than 7.8% triple receptor negative. Tissues were available for PTEN IHC in 46 primary tumors and 52 metastases. PTEN was lost in 14 (30%) primary tumors and 13 (25%) metastases. There were five cases of PTEN loss and eight cases of PTEN gain from primary tumors to metastases (26% discordance). Adequate DNA was obtained from 46 primary tumors and from 50 metastases for PIK3CA analysis. PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases. There were five cases of PIK3CA mutation loss and four cases of mutation gain (18% discordance). There was an increase of the level of PIK3CA mutations in four cases and decrease in one case from primary tumors to metastases. There is a high level of discordance in PTEN level, PIK3CA mutations, and receptor status between primary tumors and metastases that may influence patient selection and response to PI3K-targeted therapies.


The Bathyclarias-Clarias species flock. A new model to understand rapid speciation in African great lakes.
Phylogenetic relationships between seven species of the catfish species flock from Lake Malawi (genus Bathyclarias) and other Clariid catfish have been investigated using cytochrome b partial sequences. Here we demonstrate that this species flock originated from a widespread, generalist species, Clarias gariepinus, still occurring in the lake. Bathyclarias species and their ancestor C. gariepinus form a simple model that can be used to understand the mechanisms of adaptation and rapid speciation in African Great lakes.


Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study.
To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). Cohort study with logistic regression analysis to combine predictors and treatment modality. Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models. Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale. Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort. The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.


BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging.
Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [(11)C]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.


Autism spectrum disorder and the cerebellum.
The cerebellum has been long known for its importance in motor learning and coordination. Recently, anatomical, clinical, and neuroimaging studies strongly suggest that the cerebellum supports cognitive functions, including language and executive functions, as well as affective regulation. Furthermore, the cerebellum has emerged as one of the key brain regions affected in autism. Here, we discuss our current understanding of the role of the cerebellum in autism, including evidence from genetic, molecular, clinical, behavioral, and neuroimaging studies. Cerebellar findings in autism suggest developmental differences at multiple levels of neural structure and function, indicating that the cerebellum is an important player in the complex neural underpinnings of autism spectrum disorder, with behavioral implications beyond the motor domain.


Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women.
High salt intake is a well-recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross-over trial consisting of four successive 5-wk periods of controlled dietary intervention, each separated by a minimum 4-wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western-style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.


Mode competition in high power fiber amplifiers.
Using a beam propagation model of Yb3+ doped, CW fiber amplifiers we show that gain saturation by a strong fundamental mode significantly suppresses the growth of higher order modes with parallel polarization, but enhances the growth of higher order modes with perpendicular polarization. We quantify this effect in straight and bent fibers, with full core or restricted area doping.


Tarsorrhaphy: clinical experience from a cornea practice.
To evaluate indications, success rate, and complications of tarsorrhaphy in a cohort of cornea and external disease patients. In this study, charts of patients who underwent tarsorrhaphies from January 1, 1995, to September 30, 2000, were retrospectively evaluated. Information reviewed included patient age and sex, indication for tarsorrhaphy, duration of signs and symptoms before tarsorrhaphy, time to epithelial healing after tarsorrhaphy, type of tarsorrhaphy (temporary/permanent), complications, timing of tarsorrhaphy removal, recurrence of signs and symptoms after complete or partial opening of the tarsorrhaphy, number of tarsorrhaphies needed to be replaced or extended, and duration of follow up. Seventy-seven patients were included in this study. Indications for a tarsorrhaphy were persistent epithelial defects or other ocular surface problems associated with neurotrophic ulcers, penetrating keratoplasty (PK), postinfection, exposure keratopathy, surgery other than PK, dry eye syndrome, radiation keratopathy, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, entropion, and application of tissue adhesive. The epithelial defects in 70 (90.9%) of the 77 eyes completely resolved. Overall, the mean duration of signs and symptoms before tarsorrhaphy was 89.8 +/- 27.8 days, and time-to-healing after tarsorrhaphy was 18.0 +/- 2.0 days. The difference between the duration of the signs and symptoms before tarsorrhaphy and time-to-healing after tarsorrhaphy was statistically significant ( p = 0.01). Of the 77 tarsorrhaphies, 24 (31.2%) were temporary and 53 (68.8%) were permanent. Complications after tarsorrhaphy included trichiasis, adhesion between upper and lower lids after tarsorrhaphy lysis, premature opening of the temporary tarsorrhaphy, pyogenic granuloma, and keloid formation of the eyelid. Tarsorrhaphy is a very effective and safe procedure in the management of nonhealing epithelial defects and other surface problems, with a 90.9% success rate and only minor complications.


[Development skills in children with congenital hypothyroidism: focus on communication].
congenital hypothyroidism may cause alterations in the child's global development. to outline the development profile in children with congenital hypothyroidism, focusing on communication, and to verify the influence of clinical history on the outlined profile. 35 children, with ages between 2 to 36 months, with congenital hypothyroidism detected by neonatal screening, and who were in treatment for at least one month using hormonal replacement were assessed using the Early Language Milestone Scale (ELM) and the Portage Operation Inventory (POI). The clinical history was obtained in an interview with the family and from the analysis of medical records. in the ELM, eleven children presented a poor performance in the expressive auditory function, two in the visual function and one in the receptive auditory function. In the POI, seven children presented a poor performance in the language section, five in cognitive section, four in the motor and social sections and three in the self-care section. There was no correlation between the results obtained in the assessments and the clinical history. most of the children presented adequate performances in the evaluated skills. For the children with altered performance, larger deficits were observed in the language section, for the expressive aspects, and in the cognitive section. The influence of clinical history on the development profile was not confirmed. However, a tendency for an adequate performance was observed in those children who underwent neonatal screening, received an early diagnosis and treatment for the congenital hypothyroidism and who received higher doses of thyroxine at the beginning of treatment. The importance of a speech-language follow-up for communication development in this population is highlighted.


Determination of granule size distribution in a UASB reactor.
Granular sludge is the key factor for an efficient operation of an upflow anaerobic sludge blanket (UASB) reactor. In order to monitor the granularity of anaerobic sludge, the determination of the granule size distribution is of vital importance. For this reason, several techniques have been proposed; however, they are either tedious, imprecise or expensive and hardly applicable in full-scale treatment plants. There was then the need for a simple and low-cost technique. This technique involves the determination of the settling velocities of a sludge sample and of extrapolating the corresponding diameters using a mathematical algorithm. In the proposed algorithm, the granules density was calculated, the flow regime was examined and finally the granule size distribution was obtained. Two very important correlations were suggested by the experimental results. The granule density and diameter were strongly correlated with the VSS/TSS ratio.


Pulmonary embolism mimicking left-ventricular hypertrophy on ECG.
Patients with pulmonary embolism (PE) can show changes on the ECG. Here, we report the case of a 48-year-old man who initially presented with calf discomfort and swelling. He was discharged with no anticoagulation after a negative complex duplex venous ultrasonography for deep vein thrombosis (DVT). He presented 4 days later with shortness of breath and pleuritic chest pain. Multiple pulmonary emboli were found on CT pulmonary angiogram. His ECGs showed left-ventricular strain which is unusual for PE. He was anticoagulated and discharged. Despite presenting 2 days later with PE-related complications, he eventually recovered well.


Exploring new 129Xe chemical shift ranges in HXeY compounds: hydrogen more relativistic than xenon.
Among rare gases, xenon features an unusually broad nuclear magnetic resonance (NMR) chemical shift range in its compounds and as a non-bonded Xe atom introduced into different environments. In this work we show that (129)Xe NMR chemical shifts in the recently prepared, matrix-isolated xenon compounds appear in new, so far unexplored (129)Xe chemical shift ranges. State-of-the-art theoretical predictions of NMR chemical shifts in compounds of general formula HXeY (Y = H, F, Cl, Br, I, -CN, -NC, -CCH, -CCCCH, -CCCN, -CCXeH, -OXeH, -OH, -SH) as well as in the recently prepared ClXeCN and ClXeNC species are reported. The bonding situation of Xe in the studied compounds is rather different from the previously characterized cases as Xe appears in the electronic state corresponding to a situation with a low formal oxidation state, between I and II in these compounds. Accordingly, the predicted (129)Xe chemical shifts occur in new NMR ranges for this nucleus: ca. 500-1000 ppm (wrt Xe gas) for HXeY species and ca. 1100-1600 ppm for ClXeCN and ClXeNC. These new ranges fall between those corresponding to the weakly-bonded Xe(0) atom in guest-host systems (δ < 300 ppm) and in the hitherto characterized Xe molecules (δ > 2000 ppm). The importance of relativistic effects is discussed. Relativistic effects only slightly modulate the (129)Xe chemical shift that is obtained already at the nonrelativistic CCSD(T) level. In contrast, spin-orbit-induced shielding effects on the (1)H chemical shifts of the H1 atom directly bonded to the Xe center largely overwhelm the nonrelativistic deshielding effects. This leads to an overall negative (1)H chemical shift in the range between -5 and -25 ppm (wrt CH(4)). Thus, the relativistic effects induced by the heavy Xe atom appear considerably more important for the chemical shift of the neighbouring, light hydrogen atom than that of the Xe nucleus itself. The predicted NMR parameters facilitate an unambiguous experimental identification of these novel compounds.


Preparation of hydrophobic epoxy-polydimethylsiloxane-graphene oxide nanocomposite coatings for antifouling application.
Epoxy-polydimethylsiloxane-graphene oxide (EPG) nanocomposite coatings were successfully developed by loading different wt% of graphene oxide nanosheets (GNs) into an epoxy-hydroxy-terminated-polydimethylsiloxane (EP-hPD) matrix via a facile in situ preparation technique. The inclusion of GNs into EPN led to an increase in modulus of elasticity and tensile strength up to 1570.46 MPa and 31.54 MPa, respectively, in the case of 1 wt% loading of GNs in the EP-hPD matrix. Also, an increase in the water contact angle from 90.1° to 115.2°, 104.5° and 101.7° was discerned at 1, 3 and 5 wt% loadings of GNs respectively. Taber abrasion results demonstrated a decrease in abrasion loss by 33.3% at 1 wt% loading of GNs in comparison to the unreinforced coating. An improvement in the glass transition temperature (Tg) was observed from 63.5 °C for the neat sample to 77.6 °C, 76.3 °C and 71.6 °C for the 1, 3 and 5 wt% EPG nanocomposites, respectively. An inevitable enhancement in the properties of the nanocomposites was affirmed due to the synergistic effect of GNs dispersed within the EP-hPD blend matrix. The prominent findings of this work include a minimum corrosion rate of 0.73 × 10-2 mm per year and upgradation in the antifouling performance of the nanocomposite coatings in comparison to the neat coating.


Adherence to dietary and physical activity guidelines among shift workers: associations with individual and work-related factors.
Shift work is associated with adverse effects on the health and lifestyle behaviours of employees. This study aimed to examine factors associated with adherence among shift workers to selected indicators of dietary and physical activity guidelines. A cross-sectional study was conducted on 1300 shift workers. Data were collected using a 15 minute telephone-administered questionnaire. Logistic regression methods were used for data analysis. Male shift workers (p<0.001, OR=0.55, 95% CI 0.40 to 0.74) and those of lower socioeconomic status (p=0.046, OR=0.75, 95% CI 0.57 to 0.99) were significantly less likely to consume five or more daily servings of fruits and vegetables. Shift workers with access to workplace vending machines were significantly more likely to consume soft drinks at least weekly (p=0.003, OR=1.64, 95% CI 1.18 to 2.27). Middle-aged shift workers (p=0.012, OR=0.65, 95% CI 0.46 to 0.91) and those reporting insufficient break times at work (p=0.026, OR=0.69, 95% CI 0.49 to 0.96) were significantly less likely to be sufficiently active. Individual, work schedule and workplace environment related factors were independently associated with selected indicators of adherence to dietary and physical activity guidelines in this cohort of shift workers.


A high aggression strategy for smaller males.
Male-male conflict is common among animals, but questions remain as to when, how and by whom aggression should be initiated. Factors that affect agonistic strategies include residency, the value of the contested resource and the fighting ability of the two contestants. We quantified initiation of aggression in a fish, the desert goby, Chlamydogobius eremius, by exposing nest-holding males to a male intruder. The perceived value of the resource (the nest) was manipulated by exposing half of the residents to sexually receptive females for two days before the trial. Resident male aggression, however, was unaffected by perceived mating opportunities. It was also unaffected by the absolute and relative size of the intruder. Instead resident aggression was negatively related to resident male size. In particular, smaller residents attacked sooner and with greater intensity compared to larger residents. These results suggest that resident desert goby males used set, rather than conditional, strategies for initiating aggression. If intruders are more likely to flee than retaliate, small males may benefit from attacking intruders before these have had an opportunity to assess the resident and/or the resource.


The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus.
Hibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no change in either skeletal muscle size or contractile performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3 months of hibernation on contractile performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer (active) animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than in summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than in summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from torpid animals compared with summer controls. These findings in hindlimb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance.


Institutionalising global health: a call for ethical reflection.
We describe a global health course and pedagogy that highlights the moral ambiguity and many ethical compromises that have emerged as the discipline has increasingly become institutionalised. We encourage students to reflect on how the oft-declared aspiration for global health equity still remains seriously contested as a normative and political matter, especially in settings like the USA. We further encourage students to reflect on how authentic concern for social justice, health equity and human rights are consistently undermined by unconscious and/or intentional fealty to standard operating procedures within hierarchical structures and systems. Lastly, we encourage students to openly question and critique the dominant socioeconomic and institutional paradigms that influence practitioner ways of thinking about global health. Our aim is to provide a learning space for students to at least imagine, if not demand, more daring modes of engagement. We also encourage our colleagues in the global health education community to be forthright that the process of institutionalising global health reliably favours our own interests more than those we claim to be most concerned about. If the ideal of global health is to build a bridge to human solidarity, we see substantial risk that current popularised approaches might never yield a structural tipping point.


Development of decision tree models for substrates, inhibitors, and inducers of p-glycoprotein.
In silico classification of new compounds for certain properties is a useful tool to guide further experiments or compound selection. Interaction of new compounds with the efflux pump P-glycoprotein (P-gp) is an important drug property determining tissue distribution and the potential for drug-drug interactions. We present three datasets on substrate, inhibitor, and inducer activities for P-gp (n = 471) obtained from a literature search which we compared to an existing evaluation of the Prestwick Chemical Library with the calcein-AM assay (retrieved from PubMed). Additionally, we present decision tree models of these activities with predictive accuracies of 77.7 % (substrates), 86.9 % (inhibitors), and 90.3 % (inducers) using three algorithms (CHAID, CART, and C4.5). We also present decision tree models of the calcein-AM assay (79.9 %). Apart from a comprehensive dataset of P-gp interacting compounds, our study provides evidence of the efficacy of logD descriptors and of two algorithms not commonly used in pharmacological QSAR studies (CART and CHAID).


A Decade Revisited - Forensic and Clinical Applications of Hair Testing.
Hair testing for metals in clinical and forensic applications began in the 1950s whereas drugs of abuse testing in hair did not begin until the early 1980s. Hair testing has continued to develop as indicated by the publication of more than 300 scientific manuscripts focusing on applications of hair analysis in the past 10 years alone. This review describes many disciplines of hair testing cited in journals and books over the past decade including forensic drug screening, clinical testing, death investigations, and the potential use of newer applications such as reinstatement of driving privileges, detection of doping agents, and testing for drugs used in a criminal act. Each discipline is explained and further details are then illustrated through actual case studies and investigational resultss.


Use of simulated sputum specimens to estimate the specificity of laboratory-diagnosed tuberculosis.
Cross-contamination is not uncommon in mycobacteriology laboratories of high-income countries, as documented by bacterial genotyping. The extent of this problem in low-income countries is largely unknown, where this method is impractical. To estimate the rate of cross-contamination in a high-volume tuberculosis (TB) laboratory in South Africa. Simulated sputum specimens labelled with false names were sent from a TB clinic, interspersed with patient samples, and processed for culture and microscopy. Results were interpreted in the context of the observed proportion of samples with positive microscopy and culture results. With microscopy, 6/190 (3.2%) simulated specimens were positive (estimated specificity = 96.8%). Considering the 881 positive microscopy results in 6093 clinical samples, we extrapolate that 19.3% (95%CI 7.0-42.8) of positive smears were false-positives. On culture, 2/190 (1.1%) of the simulated specimens were positive for Mycobacterium tuberculosis (estimated specificity = 98.9%). Considering the 1862 positive cultures from 6093 clinical samples, we estimate that 2.4% (95%CI 0.3-8.8) of positive cultures were false-positives. Simulated specimens offer a simple means of estimating the proportion of false-positive results, providing information on all sources of potential error from the clinic, through the laboratory and to reporting of results.


Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis.
To assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change. A systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/). Randomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6 months. Outcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes. 27,984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6 months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI -0.11 to 0.56, z=1.30 (p=0.19) I(2) statistic of 85%). Subgroup analysis of 6-12 month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I(2) of 66%). Arthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12 months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up.


Synthesis and characterization of divalent manganese, iron, and cobalt complexes in tripodal phenolate/N-heterocyclic carbene ligand environments.
Two novel tripodal ligands, (BIMPN(Mes,Ad,Me))(-) and (MIMPN(Mes,Ad,Me))(2-), combining two types of donor atoms, namely, NHC and phenolate donors, were synthesized to complete the series of N-anchored ligands, ranging from chelating species with tris(carbene) to tris(phenolate) chelating arms. The complete ligand series offers a convenient way of tuning the electronic and steric environment around the metal center, thus, allowing for control of the complex's reactivity. This series of divalent complexes of Mn, Fe, and Co was synthesized and characterized by (1)H NMR, IR, and UV/vis spectroscopy as well as by single-crystal X-ray diffraction studies. Variable-temperature SQUID magnetization measurements in the range from 2 to 300 K confirmed high-spin ground states for all divalent complexes and revealed a trend of increasing zero-field splitting |D| from Mn(II), to Fe(II), to Co(II) complexes. Zero-field (57)Fe Mössbauer spectroscopy of the Fe(II) complexes 3, 4, 8, and 11 shows isomer shifts δ that increase gradually as carbenes are substituted for phenolates in the series of ligands. From the single-crystal structure determinations of the complexes, the different steric demand of the ligands is evident. Particularly, the molecular structure of 1-in which a pyridine molecule is situated next to the Mn-Cl bond-and those of azide complexes 2, 4, and 6 demonstrate the flexibility of these mixed-ligand derivatives, which, in contrast to the corresponding symmetrical TIMEN(R) ligands, allow for side access of, e.g., organic substrates, to the reactive metal center.


Senescence of primary amniotic cells via oxidative DNA damage.
Oxidative stress is a postulated etiology of spontaneous preterm birth (PTB) and preterm prelabor rupture of the membranes (pPROM); however, the precise mechanistic role of reactive oxygen species (ROS) in these complications is unclear. The objective of this study is to examine impact of a water soluble cigarette smoke extract (wsCSE), a predicted cause of pregnancy complications, on human amnion epithelial cells. Amnion cells isolated from fetal membranes were exposed to wsCSE prepared in cell culture medium and changes in ROS levels, DNA base and strand damage was determined by using 2'7'-dichlorodihydro-fluorescein and comet assays as well as Fragment Length Analysis using Repair Enzymes (FLARE) assays, respectively. Western blot analyses were used to determine the changes in mass and post-translational modification of apoptosis signal-regulating kinase (ASK1), phospho-p38 (P-p38 MAPK), and p19(arf). Expression of senescence-associated β-galectosidase (SAβ-gal) was used to confirm cell ageing in situ. ROS levels in wsCSE-exposed amnion cells increased rapidly (within 2 min) and significantly (p<0.01) at all-time points, and DNA strand and base damage was evidenced by comet and FLARE assays. Activation of ASK1, P-p38 MAPK and p19(Arf) correlated with percentage of SAβ-gal expressing cells after wsCSE treatment. The antioxidant N-acetyl-L-cysteine (NAC) prevented ROS-induced DNA damage and phosphorylation of p38 MAPK, whereas activation of ASK1 and increased expression of p19(Arf) were not significantly affected by NAC. The findings support the hypothesis that compounds in wsCSE induces amnion cell senescence via a mechanism involving ROS and DNA damage. Both pathways may contribute to PTB and pPROM. Our results imply that antioxidant interventions that control ROS may interrupt pathways leading to pPROM and other causes of PTB.


Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy.
Introduction. Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P = 0.35). Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P = 0.97). Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.


Construct validity of the G-CPAQ and its mediating role in pain interference and adjustment.
The Chronic Pain Acceptance Questionnaire (CPAQ) is a measure of pain acceptance comprised of pain willingness (PW) and activity engagement (AE; McCracken et al., 2004). Concerns about the factorial structure of the CPAQ exist, as it is not yet clear whether PW and AE constitute 2 independent constructs or 1, pain acceptance. Concerns also exist about the internal and predictive validity of test score interpretations of this measure. This study also presents that the choice of predictor variables has contributed to theoretical confusion regarding the impact of pain acceptance on pain-related adjustment. The purpose of this study was: (a) to examine the psychometric properties of both the long (20 items) and short (8 items) versions of the Greek-Chronic Pain Acceptance Questionnaire (G-CPAQ); (b) to examine the utility of a 2-factor solution in predicting psychosocial adjustment to pain using confirmatory factor analysis; and (c) to explore the mediating effects of pain acceptance and cognitive defusion, comprising the "open" response style to pain, between pain interference and pain related outcomes. One hundred and sixty chronic pain patients completed a questionnaire packet including pain indexes, pain acceptance, cognitive fusion, avoidance, and emotional distress. Confirmatory factor analyses supported the 2-factor solution, though a general good model fit was achieved only for the short G-CPAQ version. Structural equation modeling showed that PW and AE coupled with cognitive defusion partially mediated the influence of pain interference on pain severity, emotional distress, and avoidance of pain. (PsycINFO Database Record


The role of a novel decision aid to support informed decision making process in patients with a symptomatic non - lower pole renal stone < 20 mm in diameter: a prospective randomized study.
To evaluate the efficacy of a novel decision aid (DA) in improving the patients' level of knowledge and decreasing decisional conflicts while deciding for SWL vs. RIRS in case of a symptomatic renal stone < 2 cm. In this prospective randomized study patients were randomized to receive either standard informing process (group 1, n=57) or DA (group 2, n=58). Level of knowledge was assessed with a questionnaire of 10 questions before and after patient informing process. Level of decisional conflict was assessed with a previously validated scoring system. Logistic regression analysis was performed to identify factors associated with adequate level of knowledge. Level of knowledge increased significantly in both groups after patient informing process. The increase was significantly more prominent in group 2 (p=0.045). Percentage of patients with adequate knowledge was also higher in group 2 (56.1%vs.74.1%, p=0.04). Mean decisional conflict scale score (higher score indicates higher decisional conflict level) was also significantly higher in group1 (14.7±14.5 vs. 10.1±13.7, p=0.045). Multivariate logistic regression analysis revealed higher education level (college degree) and use of DA as factors associated with adequate level of knowledge. In the current study, The DA was shown to have a positive impact on level of knowledge and diminish the level of decisional conflict for patients with a symptomatic non-lower pole renal stone < 20 mm. We recommend development and use of DAs for particular clinic scenarios to aid in education of patients and shared decision making process in stone disease clinics.


Successive epidemic waves of cholera in South Sudan between 2014 and 2017: a descriptive epidemiological study.
Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting. In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports. The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016-17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1-2·3) higher attack rates than those where vaccination occurred before the peak. Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging. The Bill & Melinda Gates Foundation.


A structured handoff program for interns.
To develop, teach, and supervise a structured process for handing off patient care and to evaluate its effect on interns' knowledge, skills, and attitudes toward handoffs. The authors developed a formal process for interns on the medicine ward services to hand off patient care at their teaching hospital. In July 2006, attending physicians began to teach and supervise the process. To evaluate the entire structured handoff program (the process, teaching, and supervision), interns were surveyed on the first day and during the last week of each of their month long rotations. From June through December 2006, the authors obtained 137 of 144 surveys (95% response) they had administered to 72 consecutive interns rotating through the hospital. During the first three months of the academic year, first-year interns had little confidence in their ability to hand off patients, make contingency plans, or perform read-backs when they began their rotations, but after exposure to the handoff program, their perceptions of these abilities increased (all P < .05). Eighty-five percent of the interns felt that attending supervision of the handoff process was useful or extremely useful, but only 51% viewed the lecture/small-group session about handoffs as useful. The structured handoff program improved the participating interns' perceptions of their knowledge of the handoff process and their ability to transfer the care of their patients effectively. The formal program for teaching handoffs, that included attendings' supervision of the process, was well received.


Novel Endorna-like viruses, including three with two open reading frames, challenge the membership criteria and taxonomy of the Endornaviridae.
Viruses associated with wild orchids and their mycorrhizal fungi are poorly studied. Using a shotgun sequencing approach, we identified eight novel endornavirus-like genome sequences from isolates of Ceratobasidium fungi isolated from pelotons within root cortical cells of wild indigenous orchid species Microtis media, Pterostylis sanguinea and an undetermined species of Pterostylis in Western Australia. They represent the first endornaviruses to be described from orchid mycorrhizal fungi and from the Australian continent. Five of the novel endornaviruses were detected from one Ceratobasidium isolate collected from one Pterostylis plant. The partial and complete viral replicases shared low (9-30%) identities with one another and with endornaviruses described from elsewhere. Four had genome lengths greater than those of previously described endornaviruses, two resembled ascomycete-infecting endornaviruses, and unlike currently described endornaviruses, three had two open reading frames. The unusual features of these new viruses challenge current taxonomic criteria for membership of the family Endornaviridae.


A deacetylase-deficient SIRT1 variant opposes full-length SIRT1 in regulating tumor suppressor p53 and governs expression of cancer-related genes.
SIRT1 is an NAD-dependent deacetylase and epigenetic regulator essential for normal mammalian development and homeostasis. Here we describe a human SIRT1 splice variant, designated SIRT1-Δ2/9, in which the deacetylase coding sequence is lost due to splicing between exons 2 and 9. This work aimed to determine if SIRT1-Δ2/9 is a novel functional product of the SIRT1 gene. Endogenous SIRT1-Δ2/9 protein was identified in human cell lysate by immunoblotting and splice variant-specific RNA interference (RNAi). SIRT1-Δ2/9 mRNA is bound by CUGBP2, which downregulates its translation. Using pulldown assays, we demonstrate that SIRT1-Δ2/9 binds p53 protein. SIRT1-Δ2/9 maintains basal p53 protein levels and supports p53 function in response to DNA damage, as evidenced by RNAi-mediated depletion of SIRT1-Δ2/9 prior to damage. In turn, basal p53 downregulates SIRT1-Δ2/9 RNA levels, while stress-activated p53 eliminates SIRT1-Δ2/9. Loss of wild-type (wt) p53 has been correlated with overexpression of SIRT1-Δ2/9 in a range of human cancers. Exogenous SIRT1-Δ2/9 protein associates with specific promoters in chromatin and can regulate cancer-related gene expression, as evidenced by chromatin immunoprecipitation analysis and RNAi/genomic array data. SIRT1 is of major therapeutic importance, and potential therapeutic drugs are screened against SIRT1 deacetylase activity. Our discovery of SIRT1-Δ2/9 identifies a new, deacetylase-independent therapeutic target for SIRT1-related diseases, including cancer.