Sponge erosion under acidification and warming scenarios: differential impacts on living and dead coral.
Ocean acidification will disproportionately impact the growth of calcifying organisms in coral reef ecosystems. Simultaneously, sponge bioerosion rates have been shown to increase as seawater pH decreases. We conducted a 20-week experiment that included a 4-week acclimation period with a high number of replicate tanks and a fully orthogonal design with two levels of temperature (ambient and +1 °C), three levels of pH (8.1, 7.8, and 7.6), and two levels of boring sponge (Cliona varians, present and absent) to account for differences in sponge attachment and carbonate change for both living and dead coral substrate (Porites furcata). Net coral calcification, net dissolution/bioerosion, coral and sponge survival, sponge attachment, and sponge symbiont health were evaluated. Additionally, we used the empirical data from the experiment to develop a stochastic simulation of carbonate change for small coral clusters (i.e., simulated reefs). Our findings suggest differential impacts of temperature, pH and sponge presence for living and dead corals. Net coral calcification (mg CaCO3 cm(-2) day(-1) ) was significantly reduced in treatments with increased temperature (+1 °C) and when sponges were present; acidification had no significant effect on coral calcification. Net dissolution of dead coral was primarily driven by pH, regardless of sponge presence or seawater temperature. A reevaluation of the current paradigm of coral carbonate change under future acidification and warming scenarios should include ecologically relevant timescales, species interactions, and community organization to more accurately predict ecosystem-level response to future conditions.


Capacity and needs assessment of the implementation of the toddler oral health intervention at well-baby clinics.
To conduct a capacity and needs assessment identifying important factors for the successful implementation of an oral health coach (OHC) at well-baby clinics. This Toddler Oral Health Intervention (TOHI) provides oral health promotion to parents to prevent early childhood caries. A two-round Delphi study was conducted with an expert panel consisting of OHCs and paediatric staff. The survey was based on the Consolidated Framework for Implementation Research (CFIR), consisting of 39 constructs divided over 5 domains: intervention characteristics (8), inner setting (14), outer setting (4), characteristics of individuals (5) and the process of implementation (8). Constructs relating to the inner setting, outer setting and implementation process were identified as essential. Availability of resources, information on how to execute or facilitate the intervention, and the integration of the intervention into existing work tasks were also essential. Alignment and partnership between OHCs and paediatric staff, along with the prioritization of parents' and children's needs were emphasized. A formally appointed internal implementation leader within each organization, capable of transferring their enthusiasm to the team, and regular meetings for progress and experience sharing were considered essential. Specific strategies are needed in the implementation phase to increase the adoption, implementation and maintenance of the TOHI, ultimately leading to improved oral health in children. This study provides valuable insights into important factors for implementation of an oral health intervention in a public health setting.


Caffeine effects on systemic metabolism, oxidative-inflammatory pathways, and exercise performance.
Caffeine, a xanthine alkaloid compound, is consumed widely and daily by humans, as it is present in several regular beverages such as tea, coffee, soda beverages, and some drugs. Its consumption triggers arousal and alertness, improves mood, and causes the release of catecholamines, which induce beneficial effects on human behavior. Nonetheless, caffeine has been related to other beneficial effects such as antioxidant and anti-inflammatory actions that are extremely important to human health, altering the cellular redox and inflammatory status in a dose-dependent manner. Caffeine intake has also shown ergogenic effects, which are attributed to different factors, such as enhanced substrate utilization, fatigue delay, and alertness. As such, caffeine has been consumed by athletes from different sports modalities, with positive and negative effects declared. Although peripheral tissues such as the heart, skeletal muscle, and adipocytes are also impacted, there is a deficit of recognized mechanisms in systemic metabolism when compared to caffeine action in the central nervous system. This review summarizes the most relevant classical and current literature available regarding the use of caffeine in different metabolic situations, such as oxidative and inflammatory status, as well as anaerobic and aerobic physical exercises. Here, we identified the non-central nervous system caffeine mechanisms modulation, as most are still unknown or controversial, highlighting its influence in the peripheral system and its essential and crucial impacts on the human's organism adaptation.


[Endothelin receptor antagonists in pulmonary arterial hypertension].
Endothelin-1 (ET-1) is the most potent vasoconstrictor agent resulting in increased pulmonary vascular resistance and has proliferative effects on the vascular smooth muscle cells. Evidence for the relationship between increased blood levels of ET-1 and disease severity in pulmonary arterial hypertension (PAH) established the basis of specific approach targeted to endothelin pathway in PAH. The results of the observational studies and randomized controlled trials revealed that endothelin receptor antagonists (ERAs) compared with conventional medication may improve exercise tolerance and functional status, quality of life, right ventricular function and pulmonary hemodynamics and may lengthen the time to clinical worsening and survival in patients with PAH. Recently, the indications for ERAs in PAH seem to expand from class III and IV to class II symptomatology. In this review, we aimed to outline therapeutic benefits, drug-to-drug interactions and safety profile of different ERAs as specific agents of monotherapy or as a component of combination therapy in patients with PAH from the perspective of the evidence-based medicine.


Complete Talar Extrusion Treated With an Antibiotic Cement Spacer and Staged Femoral Head Allograft.
Complete talar extrusion is rare and usually associated with a high-energy mechanism of injury causing complete dissociation of the talus from the surrounding bony and soft-tissue structures with enough force to expel the talus out of the body. Treatment can be complicated by infection, osteonecrosis, posttraumatic osteoarthritis, and leg length discrepancy, which may require multiple subsequent surgeries for improved outcome and quality of life. Reimplantation of the native talus affords maintenance of joint height and favorable outcomes have been reported. Failed reimplantations have been successfully managed with arthrodesis with or without a bone allograft. We report a case of talar extrusion initially treated with a talus-shaped impregnated antibiotic spacer, followed by femoral head allograft and tibiocalcaneal fusion. This treatment resulted in radiographic evidence of bony fusion at 12 weeks without subsequent infection and good clinical outcome at 2-year follow-up.


In vivo effects of metaldehyde on Pacific oyster, Crassostrea gigas: comparing hemocyte parameters in two oyster families.
Pollutants via run-off into the ocean represent a potential threat to marine organisms, especially bivalves such as oysters living in coastal environments. These organisms filter large volumes of seawater and may accumulate contaminants within their tissues. Pesticide contamination in water could have a direct or indirect toxic action on tissues or cells and could induce alteration of immune system. Bivalve immunity is mainly supported by hemocytes and participates directly by phagocytosis to eliminate pathogens. Some studies have shown that pesticides can reduce immune defences and/or modify genomes in vertebrates and invertebrates. Metaldehyde is used to kill slugs, snails and other terrestrial gastropods. Although metaldehyde has been detected in surface waters, its effects on marine bivalves including the Pacific oyster, Crassostrea gigas, have never been studied. Given the mode of action of this molecule and its targets (molluscs), it could be potentially more toxic to oysters than other pesticides (herbicides, fungicides, insecticides, etc.). Effects of metaldehyde on oyster hemocyte parameters were thus monitored through in vivo experiments based on a short-term exposure. In this work, metaldehyde at 0.1 μg/L, which corresponds to an average concentration detected in the environment, modulated hemocyte activities of Pacific oysters after an in vivo short-term contact. Individuals belonging to two families showed different behaviours for some hemocyte activities after contamination by metaldehyde. These results suggested that effects of pollutants on oysters may differ from an individual to another in relation to genetic diversity. Finally, it appears essential to take an interest in the effects of metaldehyde on a wide variety of aquatic invertebrates including those that have a significant economic impact.


Immunohistochemical expression of PCNA and CD34 in colorectal adenomas and carcinomas using specified automated cellular image analysis system: a clinicopathologic study.
To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters. The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 μm thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer). PCNA expression was significantly increased in a sequence of normal mucosa-adenoma-carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1 cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma. PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor.


[Determination of pyrethroid pesticides in tea by accelerated solvent extraction and ultra-performance liquid chromatography-tandem mass spectrometry].
A method was developed for the determination of pyrethroid pesticides in tea by accelerated solvent extraction (ASE) combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The target compounds were extracted from tea using n-hexane and acetone (2:1, v/v) for 5 min at 10.34 MPa and 80℃ via a single cycle of accelerated solvent extraction. The extract was purified by GCB/NH2 and Florisil columns, analyzed by UPLC-MS/MS in positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) modes, and quantified by the external standard method. Regression analysis revealed that the linear relationships between mass concentration and peak area are significant for the 10 pyrethroid pesticides, and the correlation coefficients (r) are all not less than 0.9995. The limits of detection (LOD) of the 10 pyrethroid pesticides ranged from 0.5 μg/kg to 5.0 μg/kg and the limits of quantification (LOQ) ranged from 1.6 μg/kg to 16.6 μg/kg. The recoveries of all the pesticides ranged from 68.7% to 103.8% at the spiked levels of LOQ, 0.4 mg/kg and maximum residue limit (MRL) (added 1 mg/kg without MRL) with RSDs ranging from 0.8% to 13.2% (n=7). The proposed method is simple, rapid, sensitive, and accurate, and could be effective for trace analysis of pyrethroid pesticides in tea.


BACH1 regulates the differentiation of vascular smooth muscle cells from human embryonic stem cells via CARM1-mediated methylation of H3R17.
The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.


Outbreak of carbapenem-resistant enterobacteria in a thoracic-oncology unit through clonal and plasmid-mediated transmission of the bla OXA-48 gene in Southern France.
Carbapenemase-producing Enterobacteriaceae (CPE) represent an increasing threat to public health, especially in hospitals. To investigate an outbreak of CPE in a thoracic-oncology unit by using whole genome sequencing (WGS) and to describe the control measures taken to limit the epidemic, including fecal microbiota transplantation (FMT). A retrospective study between December 2016 and October 2017 was performed to investigate an outbreak of CPE in a thoracic-oncology unit at the North Hospital in Marseille, France. The isolates were identified, and antimicrobial susceptibility tests were performed. All CPE were sequenced using MiSeq and/or MinIon technologies. Nucleotide variations between plasmids and similarity within the same species were investigated. The origin of this outbreak, its spread, and the decolonization of patients in the ward were also studied. Four Citrobacter freundii, one Enterobacter cloacae and four E. hormaechei OXA-48 carbapenemase producers were isolated in eight patients hospitalized the same year in a thoracic-oncology ward. The bla OXA-48 gene was present in a Tn1999.2 transposon located in IncL/M plasmids, with single nucleotide variants (SNV) ranging from 0 to 5. All C. freundii strains belonged to the same ST22 and had more than 99.6% similarity between them. Two strains of E. hormaechei ST1007 were almost identical at 99.98%, while the others belonged to a different ST (ST98, ST114, ST133). No single source was identified. FMT resulted in decolonization in 4/6 patients. WGS demonstrated the dissemination of the bla OXA-48 gene by both clonal (C. freundii ST22 and E. hormaechei ST1007) and plasmid spread (pOXA-48 IncL/M). The origin of this outbreak appeared to be both external and internal to the ward. This evidence of cross-infection supports the urgent need for the implementation of infection control measures to prevent CPE dissemination.


Multiple Breath Washout for Diagnosing Asthma and Persistent Wheeze in Young Children.
Rationale: There is an unmet need for sensitive lung function tests for young children to aid in the diagnosis of asthma and wheezy disorders. We hypothesized that multiple breath washout (MBW) could be a valuable tool for such a purpose. Objectives: To compare the ability of MBW lung clearance index with traditional lung function measurements to discriminate between preschool children with well-controlled asthma/persistent wheeze and healthy children. Methods: We investigated 646 children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) mother-child cohort, who completed MBW testing with nitrogen, spirometry, and plethysmography before age 6 years. Asthma/persistent wheeze was prospectively diagnosed according to a validated symptom-based algorithm at the COPSAC clinic. Student's t tests and receiver operating characteristic curves were applied to analyze the discriminative ability of the lung function indices. Results: A total of 144 (22.3%) children were diagnosed with asthma/persistent wheeze during their first 6 years of life. Lung clearance index from MBW was not significantly different in children with versus those without asthma/persistent wheeze (mean standard deviation [SD] = 6.96 [1.14] vs. 6.95 [0.93], mean difference [95% confidence interval] = 0.02 [-0.18 to 0.22], P = 0.86, area under the curve [AUC] = 0.48), whereas significant differences were observed for specific airway resistance from plethysmography (1.21 kPa/s [0.31] vs. 1.14 kPa/s [0.25]; +0.07 kPa/s [0.02-0.13]; P < 0.01; AUC = 0.56) and spirometry forced expiratory volume in 1 second (FEV1) % predicted (99.4% [12.0] vs. 102.6% [12.5]; -3.2% [-5.6 to -0.9]; P < 0.01; AUC = 0.56) and forced expiratory flow at 25-75% (1.55 L/s [0.44] vs. 1.68 L/s [0.46]; -0.14 L/s [-0.22 to -0.05]; P < 0.01; AUC = 0.58). FEV1 (L/s) and FEV1/forced vital capacity ratio were not significantly different (P > 0.4). Conclusions: MBW, spirometry, and plethysmography are not sensitive tools for diagnosing mild asthmatic disease in young children.


Thrombin-Derived C-Terminal Peptide Reduces Candida-Induced Inflammation and Infection In Vitro and In Vivo.
Infections due to the opportunistic fungus Candida have been on the rise in the last decades, especially in immunocompromised individuals and hospital settings. Unfortunately, the treatments available today are limited. Thrombin-derived C-terminal peptide (TCP-25) is an antimicrobial peptide (AMP) with antibacterial and immunomodulatory effects. In this work, we, for the first time, demonstrate the ability of TCP-25 ability to counteract Candida in vitro and in vivo. Using a combination of viable count assay (VCA), radial diffusion assay (RDA), and fluorescence and transmission electron microscopy analyses, TCP-25 was found to exert a direct fungicidal activity. An inhibitory activity of TCP-25 on NF-κB activation induced by both zymosan alone and heat-killed C. albicans was demonstrated in vitro using THP-1 cells, and in vivo using NF-κB reporter mice. Moreover, the immunomodulatory property of TCP-25 was further substantiated in vitro by analyzing cytokine responses in human blood stimulated with zymosan, and in vivo employing a zymosan-induced peritonitis model in C57BL/6 mice. The therapeutic potential of TCP-25 was demonstrated in mice infected with luminescent C. albicans. Finally, the binding between TCP-25 and zymosan was investigated using circular dichroism spectroscopy and intrinsic fluorescence analysis. Taken together, our results show that TCP-25 has a dual function by inhibiting Candida as well as the associated zymosan-induced inflammation. The latter function is accompanied by a change in secondary structure upon binding to zymosan. TCP-25, therefore, shows promise as a novel drug candidate against Candida infections.


Role of neoadjuvant treatment in clinically confined prostate cancer. Takeda NHT Italian Group.
This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy. Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy. Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors. Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.


Draft Genome Sequences of Semiconstitutive Red, Dry, and Rough Biofilm-Forming Commensal and Uropathogenic Escherichia coli Isolates.
Strains of Escherichia coli exhibit diverse biofilm formation capabilities. E. coli K-12 expresses the red, dry, and rough (rdar) morphotype below 30°C, whereas clinical isolates frequently display the rdar morphotype semiconstitutively. We sequenced the genomes of eight E. coli strains to subsequently investigate the molecular basis of semiconstitutive rdar morphotype expression.


Time and timing in the acoustic recognition system of crickets.
The songs of many insects exhibit precise timing as the result of repetitive and stereotyped subunits on several time scales. As these signals encode the identity of a species, time and timing are important for the recognition system that analyzes these signals. Crickets are a prominent example as their songs are built from sound pulses that are broadcast in a long trill or as a chirped song. This pattern appears to be analyzed on two timescales, short and long. Recent evidence suggests that song recognition in crickets relies on two computations with respect to time; a short linear-nonlinear (LN) model that operates as a filter for pulse rate and a longer integration time window for monitoring song energy over time. Therefore, there is a twofold role for timing. A filter for pulse rate shows differentiating properties for which the specific timing of excitation and inhibition is important. For an integrator, however, the duration of the time window is more important than the precise timing of events. Here, we first review evidence for the role of LN-models and integration time windows for song recognition in crickets. We then parameterize the filter part by Gabor functions and explore the effects of duration, frequency, phase, and offset as these will correspond to differently timed patterns of excitation and inhibition. These filter properties were compared with known preference functions of crickets and katydids. In a comparative approach, the power for song discrimination by LN-models was tested with the songs of over 100 cricket species. It is demonstrated how the acoustic signals of crickets occupy a simple 2-dimensional space for song recognition that arises from timing, described by a Gabor function, and time, the integration window. Finally, we discuss the evolution of recognition systems in insects based on simple sensory computations.


Open removal models with temporary emigration and population dynamics to inform invasive animal management.
Removal sampling data are the primary source of monitoring information for many populations (e.g., invasive species, fisheries). Population dynamics, temporary emigration, and imperfect detection are common sources of variation in monitoring data and are key parameters for informing management. We developed two open robust-design removal models for simultaneously modeling population dynamics, temporary emigration, and imperfect detection: a random walk linear trend model (estimable without ancillary information), and a 2-age class informed population model (InfoPM, closely related to integrated population models) that incorporated prior information for age-structured vital rates and relative juvenile availability. We applied both models to multiyear, removal trapping time-series of a large invasive lizard (Argentine black and white tegu, Salvator merianae) in three management areas of South Florida to evaluate the effectiveness of management programs. Although estimates of the two models were similar, the InfoPMs generally returned more precise estimates, partitioned dynamics into births, deaths, net migration, and provided a decision support tool to predict population dynamics under different effort scenarios while accounting for uncertainty. Trends in tegu superpopulation abundance estimates were increasing in two management areas despite generally high removal rates. However, tegu abundance appeared to decline in the Core management area, where trapping density was the highest and immigration the lowest. Finally, comparing abundance predictions of no-removal scenarios to those estimated in each management area suggested significant population reductions due to management. These results suggest that local tegu population control via systematic trapping may be feasible with high enough trap density and limited immigration; and highlights the value of these trapping programs. We provided the first estimates of tegu abundance, capture probabilities, and population dynamics, which is critical for effective management. Furthermore, our models are applicable to a wide range of monitoring programs (e.g., carcass recovery or removal point-counts).


Timing of lower extremity frontal plane motion differs between female and male athletes during a landing task.
Female athletes are at a greater risk for noncontact anterior cruciate ligament injuries than male athletes. Gender differences in frontal plane kinematics (hip adduction, knee valgus, and ankle eversion) and temporal relationships that make up the components of dynamic knee valgus may explain this discrepancy. The authors hypothesized that women would reach peak frontal plane kinematic values earlier during landing compared with their male counterparts. Controlled laboratory study. Hip, knee, and ankle 3-dimensional kinematics were measured using high-speed motion capture in 10 National Collegiate Athletic Association Division I female athletes and 10 male practice squad athletes during a drop-jump landing. Independent t tests were used to analyze each dependent variable to identify differences between genders. Maximum hip adduction, knee valgus, and ankle eversion occurred earlier in women than in men (mean differences 33.7% of stance [95% CI, 20.2%-47.2%], 41.7% [95% CI, 31.5%-51.6%], 16.5% of stance [95% CI, 7.3%-25.6%], respectively). Maximum hip adduction and knee valgus occurred before maximum knee flexion in women and after in men (mean differences 0.11 seconds [95% CI, 0.05-0.18 seconds], 0.19 seconds [95% CI, 0.13-0.25 seconds], respectively). Maximum ankle eversion occurred earlier in women than in men (mean difference 0.06 seconds [95% CI, 0.01-0.11 seconds]). There was a significant difference between genders for angular velocity of knee valgus (mean difference = 25.53 deg/sec [95% CI, 8.30-42.77 deg/sec]). Frontal plane kinematic temporal relationships at the hip, knee, and ankle differ between genders. The components of dynamic knee valgus peak during the deceleration phase in women and during the acceleration phase in men during a drop-jump landing. These data suggest that men and women employ a completely different kinematic landing/jumping strategy and that women land and collapse very rapidly into valgus compared with their male counterparts. The differences in timing of the components of dynamic knee valgus between women and men may contribute to the increased risk of noncontact anterior cruciate ligament injuries in female athletes. There may be implications for neuromuscular reeducation training in those at risk for anterior cruciate ligament injury so the components of dynamic valgus occur later in the landing phase of jumping.


Bayesian isotonic density regression.
Density regression models allow the conditional distribution of the response given predictors to change flexibly over the predictor space. Such models are much more flexible than nonparametric mean regression models with nonparametric residual distributions, and are well supported in many applications. A rich variety of Bayesian methods have been proposed for density regression, but it is not clear whether such priors have full support so that any true data-generating model can be accurately approximated. This article develops a new class of density regression models that incorporate stochastic-ordering constraints which are natural when a response tends to increase or decrease monotonely with a predictor. Theory is developed showing large support. Methods are developed for hypothesis testing, with posterior computation relying on a simple Gibbs sampler. Frequentist properties are illustrated in a simulation study, and an epidemiology application is considered.


Tunable White-Light Emission in Single-Cation-Templated Three-Layered 2D Perovskites (CH3CH2NH3)4Pb3Br10-xClx.
Two-dimensional (2D) hybrid halide perovskites come as a family (B)2(A)n-1PbnX3n+1 (B and A= cations; X= halide). These perovskites are promising semiconductors for solar cells and optoelectronic applications. Among the fascinating properties of these materials is white-light emission, which has been mostly observed in single-layered 2D lead bromide or chloride systems (n = 1), where the broad emission comes from the transient photoexcited states generated by self-trapped excitons (STEs) from structural distortion. Here we report a multilayered 2D perovskite (n = 3) exhibiting a tunable white-light emission. Ethylammonium (EA+) can stabilize the 2D perovskite structure in EA4Pb3Br10-xClx (x = 0, 2, 4, 6, 8, 9.5, and 10) with EA+ being both the A and B cations in this system. Because of the larger size of EA, these materials show a high distortion level in their inorganic structures, with EA4Pb3Cl10 having a much larger distortion than that of EA4Pb3Br10, which results in broadband white-light emission of EA4Pb3Cl10 in contrast to narrow blue emission of EA4Pb3Br10. The average lifetime of the series decreases gradually from the Cl end to the Br end, indicating that the larger distortion also prolongs the lifetime (more STE states). The band gap of EA4Pb3Br10-xClx ranges from 3.45 eV (x = 10) to 2.75 eV (x = 0), following Vegard's law. First-principles density functional theory calculations (DFT) show that both EA4Pb3Cl10 and EA4Pb3Br10 are direct band gap semiconductors. The color rendering index (CRI) of the series improves from 66 (EA4Pb3Cl10) to 83 (EA4Pb3Br0.5Cl9.5), displaying high tunability and versatility of the title compounds.


Ratings of health and quality of life by young working people: are there occupational or education-based differences?
The study examines differences in self-rated health and perceived quality of life (QoL) among young working people according to occupation and education level. Subjects were extracted from a cross-sectional data set, covering questionnaire responses of people aged 20-74 years from the Swedish region of Ostergötland, and addressing individual environmental and health conditions. The emphasis was on males and females in paid employment aged 20-34 (n = 863). Differences in self-rated health items and in perceived QoL were subjected to a series of t-tests. Two measures of individual socioeconomic position were considered - occupation and education. No education-based differences were found, and there were few differences based on occupation. Among males, manual workers reported significantly higher scores with regard to pain and physical function than did non-manual workers. Male and female manual workers scored significantly lower on current perceived QoL than non-manual workers. In the case of females, the differences between manual and non-manual workers also applied to former perceived QoL. Yet, after applying the Bonferroni correction, none of the differences observed remained significant. In line with some earlier studies, it appears that -- among young working adults -- the manners in which health status and QoL are perceived are not strongly conditional on socioeconomic position.


Lobectomy in traumatic brain injury patients with intracerebral hemorrhage and delayed contusion.
TBI, standing for Traumatic Brain Injury, is a leading cause of death worldwide; nonetheless, data on its management has hitherto been sparse. In view of the fact that brain lobectomy is a contentious issue in the management of TBI, we set out the current study to assess the mortality rate and outcomes of TBI with delayed contusion or Intracerebral Hemorrhage (ICH) undergoing lobectomy. We evaluated 135 TBI patients with delayed contusion or ICH undergoing brain lobectomy from 2001 to 2013. Withal, the mortality and Glasgow Outcome Scale (GOS) and Glasgow Comma Scale (GCS) rates were assessed in these patients and the association in between was sought. The TBI patients undergoing brain lobectomy (77% male versus 23 % female) had a mean age of 43.4±20.3 years and experienced a survival rate of 62.2% (71% in females versus 60% in males). Favorable GOS was observed in 53% of male patients, compared with 27% in the females. Age was demonstrated to significantly affect the mortality rate (p=0.0001). Initial GCS score was associated with GOS as 79.1% of the survived patients with a GCS of higher than 9 on admission were discharged with favorable GOS. The evidence from the present study indicates that lobectomy can be an acceptable surgical procedure in management of TBI patients with delayed contusion or ICH.


Reliability analysis of the rank transform for stereo matching.
The rank transform is a nonparametric technique which has been recently proposed for the stereo matching problem. The motivation behind its application to this problem is its invariance to certain types of image distortion and noise, as well as its amenability to real-time implementation. This paper derives one constraint which must be satisfied for a correct match. This has been termed the rank constraint. Experimental work has shown that this constraint is capable of resolving ambiguous matches, thereby improving matching reliability. A novel matching algorithm incorporating the rank constraint has also been proposed. This modified algorithm consistently resulted in an increased percentage of correct matches, for all test imagery used. Furthermore, the rank constraint has been used to devise a method of identifying regions of an image where the rank transform, and hence matching outcome, is more susceptible to noise. Experimental results have shown that the errors predicted using this technique are consistent with the actual errors which result when images are corrupted with noise. Such a method could be used to identify matches which are likely to be incorrect and/or provide a measure of confidence in a match.


Vimentin Coordinates Protein Turnover at the Aggresome during Neural Stem Cell Quiescence Exit.
Maintaining a healthy proteome throughout life is critical for proper somatic stem cell function, but the complexities of the stem cell response to increases in damaged or aggregated proteins remain unclear. Here we demonstrate that adult neural stem cells (NSCs) utilize aggresomes to recover from disrupted proteostasis and describe a novel function for the intermediate filament vimentin in proteostasis as a spatial coordinator of proteasomes to the aggresome. In the absence of vimentin, NSCs have a reduced capacity to exit quiescence, a time when NSCs are required to clear a wave of aggregated proteins, and demonstrate an early age-dependent decline in proliferation and neurogenesis. Taken together, these data reveal a significant role of vimentin and aggresomes in the regulation of proteostasis during quiescent NSC activation.


Biosynthesis and fate of proteoglycans in cartilage and bone during development and mineralization.
Subcutaneous implantation of demineralized bone matrix in rats induces migration of host cells into the site and results in the sequential development of cartilage and bone. The biosynthesis and metabolic fate of proteoglycans in the plaques at the bone matrix implantation site were investigated by [35S]sulfate labeling in vivo. 35S-Labeled proteoglycans were extracted with 4 M guanidine HCl and purified by DEAE-Sephacel chromatography. Analysis of proteoglycans on Sepharose CL-2B chromatography showed two major peaks at Kd = 0.28 and 0.68 (peaks I and II, respectively). Peak I proteoglycan has a high buoyant density and contains chondroitin sulfate chains of average Mr = 20,000. Peak II proteoglycan has a lower average buoyant density and contains dermatan sulfate chains of average Mr = 33,000. Throughout the endochondral bone development sequence, peak II proteoglycan predominates. Peak I was low on Day 3, became prominent on Day 7 (approximately 30% of the total radioactivity), and declined after Day 9. The calculated half-lives of peak I and II proteoglycans labeled on Day 7 were about 1.8 and 2.8 days, respectively. After the initiation of osteogenesis, a species of mineral-associated proteoglycan was extracted with a 4 M guanidine HCl solvent containing 0.5 M EDTA. This proteoglycan has a small hydrodynamic size (Kd = 0.38 on Sepharose CL-6B chromatography) and shows a long half-life, about 6 days.


Garlic (Allium sativum) as an antidote or a protective agent against natural or chemical toxicities: A comprehensive update review.
Garlic (Allium sativum, Liliaceae) is used widely as a spice and medicinal herb not only in its native region (Central Asia and northeastern Iran) but also all around the world. Garlic has abundance chemical compounds such as allicin, alliin, S-allyl cysteines, thiacremonone, diallyl-disulfide, diallylsulfide, and others. This medicinal plant and its constituents offer a lot of benefits including free-radical scavenging, anti-inflammatory, anticholesterolemic, anti-gastric ulcer, antimicrobial, anticancer, and antioxidant properties. Garlic also modulates the activity of several metabolizing enzymes. This review summarizes various in vitro and animal studies on the protective effects of garlic against natural and chemical toxicities. It has been shown that garlic and its major components can ameliorate the toxicity of different agents in brain, kidney, blood, liver, embryo, spleen, pancreas, heart, reproductive system in part through radical scavenging, antioxidant effect, reducing lipid peroxidation, anti-inflammatory, chelating agent, cytoprotective activities, increase protein synthesis in damaged tissues, suppressing apoptosis, modulation of p53, phosphoinositide 3-kinase, Akt, nuclear factor (erythroid-derived 2)-like 2, antioxidant responsive element, p38 MAPK, inducible nitric oxide synthase, cyclooxygenase-2, cytosolic phospholipases A2, cleaved-caspase-9, cleaved-caspase-3 Bcl-2, Bcl-2-associated X, peroxisome proliferator-activated receptor gamma, NF-jB, nuclear factor-kappaB signaling pathways and cytochrome P450 enzymes. With controlled clinical trials, garlic may be introduced as a universal antidote or protective plant against many toxic agents.


Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.
Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS). We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723. ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score. Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.


Dose response of caffeine on 2000-m rowing performance.
To determine whether a dose-response relationship exists between caffeine and 2000-m rowing performance. In this randomized, placebo-controlled, double-blind crossover study, 10 competitive male rowers (mean +/- SD: age = 20.6 +/- 1.4 yr, body mass = 87.7 +/- 10.5 kg, height = 186.8 +/- 6.8 cm, (.)VO2peak = 5.1 +/- 0.6 L x min(-1)) consumed 2, 4, or 6 mg x kg(-1) caffeine or a placebo 60 min before completing a 2000-m time trial on a rowing ergometer. The trials were preceded by a 24-h standardized diet (including a light preexercise meal of 2 g x kg(-1) CHO), and subjects were tested preexercise for hydration, caffeine abstinence, and blood glucose concentrations. Time trial performance was not significantly different across the three caffeine doses or placebo (P = 0.249). After the three caffeine trials, postexercise plasma glucose and lactate concentrations were higher compared with the placebo trial (P < 0.05). Plasma caffeine concentrations after 60 min of ingestion were lower than the values reported previously by others following the same dose, and there was considerable interindividual variation in plasma caffeine concentrations in response to the various caffeine doses. The large interindividual response to the caffeine doses suggests that individual characteristics need to be considered when administering caffeine for performance enhancement. In addition, preexercise feeding may significantly affect plasma caffeine concentrations and the potential for caffeine to improve performance.


Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.
To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.


Intracranial anaplastic hemangiopericytoma presenting with simultaneous extra-cranial metastases: A case report and review of the literature.
Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare mesenchymal tumor with a propensity to recur and metastasize extracranially years after treatment. Accordingly, there are no reported cases of a patient presenting with a simultaneous intracranial primary and extracranial metastases. We present the case of a patient presenting with an intracranial SFT/HPC and simultaneous liver metastases and propose a treatment paradigm. A 74-year-old male smoker presented with confusion. An MRI of the brain revealed a heterogeneously enhancing left frontal extra-axial mass. Systemic workup revealed multiple small liver lesions concerning for metastases. The patient underwent gross total resection (GTR) of the intracranial lesion with adjuvant CyberKnife stereotactic radiotherapy to the resection cavity. Pathology was consistent with a WHO Grade III SFT/HPC (previously known as anaplastic HPC). The liver lesions were biopsied and confirmed to be metastases. They were subsequently treated with stereotactic body radiation therapy, temozolomide, and bevacizumab. Eighteen months postoperatively, the patient is alive with no evidence of intracranial malignancy and regression of the hepatic lesions. Several studies support GTR and adjuvant radiotherapy to treat intracranial SFT/HPC. The role of adjuvant chemotherapy is less clear. Metastatic disease is typically detected several years after the initial diagnosis, and there is no consensus regarding the optimal treatment strategy. We propose that the rare presentation of intracranial SFT/HPC with simultaneous extracranial metastases should be treated in a multidisciplinary fashion with surgical resection, adjuvant radiotherapy, and chemotherapy.


Antioxidant properties of Pelargonium graveolens L'Her essential oil on the reproductive damage induced by deltamethrin in mice as compared to alpha-tocopherol.
Exposure to the pyrethroid pesticide deltamethrin has been demonstrated to exert a wide range of effects on non-targeted organisms. The beneficial effects of geranuim essential oil (EO) as an antioxidant has been assessed in deltamethrin (DL) orally administered mice by studying whether the reprotoxicity caused by deltamethrin can be effectively combated with the geranium oil and the effects were compared to vitamin E, as the standard reference drug. Sixty male albino mice were divided into six equal groups: a control group, a group of mice was given deltamethrin (5 mg/kg b.w.), two groups were administered deltamethrin after having given geranium essential oil (67 mg/kg b.w.) or vitamin E (Vit E) (100 mg/kg b.w.), and two groups received only EO of geranium or Vit E. When compared to control, a dose of deltamethrin 5 mg/kg/day causes a decrease in the epididymal sperm count motility and viability and an increase in the number of abnormal morphology in spermatozoa. DL-exposed mice showed a significant increase of lipid peroxidation (LPP) in the testis compared to control animals. Essential oil of geranium prevented testicular oxidative damage explored by reduced LPP and improved total sperm motility, viability and morphology in mice spermatozoa. Our study showed a positive influence of geranium essential oil in the animal male reproductive system similar than that of Vit E.


Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms.
Recently, experts have warned that mass treatment with ivermectin alone may not interrupt the transmission of Onchocerca. Hence, additional drugs are needed, such as antibiotics acting on symbiotic endobacteria of the filariae, the causative agents of onchocerciasis. Based on animal experiments, human onchocerciasis was treated with doxycycline, and preliminary observations published in 2001 in The Lancet showed sterility in female worms by depletion and marked reduction in symbiotic Wolbachia endobacteria from the filariae. Here, a detailed kinetic analysis of the features of the worms, following administration or not of doxycycline to the patients is reported. Sixty-three onchocerciasis patients in Ghana were treated with 100 mg doxycycline daily for 6 weeks and 2 or 6 months later with ivermectin. Onchocercomas were extirpated 2, 6, 11 and 18 months after the onset of treatment and the filariae were examined by immunohistology and PCR. The analysis showed: (i) progressive depletion of Wolbachia from adult worms and microfilariae by doxycycline over a period of 6 months; (ii) inhibition of embryogenesis by doxycycline after 6 months with respect to all embryo stages followed by decline in microfilariae after 11 months; (iii) reduction in spermatozoa in the female genital tract by doxycycline, whereas spermiogenesis was only partly reduced after 11 and 18 months; (iv) no relevant macro- or microfilaricidal activity; (v) depletion/marked reduction in endobacteria and inhibition of embryogenesis were sustained until 18 months after doxycycline and 12 months after co-administration of ivermectin; (vi) no severe adverse side effects were seen. Due to its long-lasting inhibition of embryogenesis, doxycycline presents an additional strategy for the treatment of onchocerciasis and control of Onchocerca microfilariae transmission. Extension of the existing registration will not require much time or high cost. Treatment of individual patients can be considered immediately.


High immunogenicity of plant-produced candidate influenza vaccine based on the M2e peptide fused to flagellin.
The ectodomain of the conserved influenza matrix protein M2 (M2e) is a promising target for the development of a universal influenza vaccines. Immunogenicity of M2e could be enhanced by its fusion to bacterial flagellin, the ligand for Toll-like receptor 5. Previously we reported the transient expression in plants of a recombinant protein Flg-4M comprising flagellin fused to 4 tandem copies of the M2e. The use of self-replicating recombinant vector based on the potato virus X allowed expression of Flg-4M in Nicotiana benthaminana leaves at a very high level, up to about 1 mg/g of fresh leaf tissue. Intranasal immunization of mice with Flg-4M induced M2e-specific serum antibodies and provided protection against lethal challenge with different strains of influenza A virus. Here we show that immunization with Flg-4M not only generates a strong immune response, but also redirects the response from the carrier flagellin toward the M2e epitopes. Significant IgG response to M2e was also developed in bronchoalveolar lavages of immunized mice. Protective activity of Flg-4M upon lethal influenza challenge correlated with a decrease of virus titers in lungs relative to the control. Overall these data show the potential for the development of a plant-produced M2e-flagellin universal influenza vaccine.


Structural requirements for chelate antidotal efficacy in acute antimony(III) intoxication.
The LD50 for i.p. potassium antimonyl tartrate was determined to be 54.6 mg/kg in mice, with a 95% confidence range of 48.4 to 61.7 mg/kg. An examination of the antidotal efficacy of a number of different structural types of chelating agents showed that very few types were able to act as antidotes when potassium antimonyl tartrate was administered i.p. to mice at a level of 120 mg/kg. The most effective antidotes, by a substantial margin, were the water soluble vicinal dithiols: 2,3-dimercaptosuccinic acid and sodium 2.3-dimercaptopropane-1-sulfonate, with the first of these being significantly better than the second. Appreciably less effective, but still useful, was D-penicillamine. At this level of administration of antimony(III), BAL is not an effective antidote. Among other chelating agents which were also not effective at this level of antimony(III) are tartaric acid, EDTA, cysteine, sodium diethyldithiocarbamate and potassium dithiooxalate.


Laparoscopic surgery for melanoma metastases to the adrenal gland.
The probability of developing cutaneous melanoma is now predicted to be one in 55 for males and one in 88 for females. Although melanoma is relatively uncommon compared with other malignancies such as breast (one in seven) or prostate cancer (one in six), the incidence is growing at an alarming rate. The development of novel strategies for the management of advanced disease will become even more urgent and require continued and controlled investigations over the next 10 years. Surgery is effective for the palliation of isolated resectable metastases. However, most patients with Stage IV melanoma have widespread disease and are not cured by metastasectomy. For the few individuals with isolated adrenal metastases from melanoma, complete resection appears to confer a survival advantage. New data are emerging about the efficacy and outcome of laparoscopic adrenalectomy for malignant lesions. However, the natural history of laparoscopic surgery for these lesions is still unknown. The indications for and limitations of laparoscopic adrenalectomy for metastatic melanoma are discussed.


Survey on the use of methotrexate by pediatric rheumatologists in Canada.
To determine methotrexate (MTX) use and the degree to which Canadian pediatric rheumatologists adhere to the American College of Rheumatology (ACR) guidelines on monitoring for MTX toxicity. A 20-item questionnaire was e-mailed to 37 pediatric rheumatologists in 17 centers in Canada. A total of 28 (75.7%) responded. The oral route (PO) of administration was preferred initially by 78.6% in most cases, but for more severe cases, this fell to 42.8%. Those who chose not to start PO used the subcutaneous route (SQ). When PO was initial treatment, a switch to SQ was undertaken because of dose escalation, lack of efficacy, or GI toxicity. An initial mean dose of 0.35-0.5 mg/kg/wk was prescribed by 51.8%. For 75%, the maximum dose was 1 mg/kg/wk (up to 25 mg). Complete blood count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined by 100% at baseline and in followup; albumin and creatinine by 85.7% at baseline, but by only 71.4% and 67.8%, respectively, in followup. After a change in dose, 96.3% requested blood tests at least monthly; this was extended to every 6 to 8 weeks by 78.6% when the dose was stable. Side effects of recurrent nausea and/or vomiting were reported to occur frequently. No severe toxicity, and in particular no case of cirrhosis, was reported. Prophylactic folate supplementation was prescribed by almost all physicians. Most Canadian pediatric rheumatologists follow ACR guidelines to monitor for MTX toxicity in children with rheumatic diseases who were prescribed MTX. The variation in monitoring and response to toxicity raises the question whether specific pediatric guidelines should be developed.


Plant nucleolar DNA: Green light shed on the role of Nucleolin in genome organization.
The nucleolus forms as a consequence of ribosome biogenesis, but it is also implicated in other cell functions. The identification of nucleolus-associated chromatin domains (NADs) in animal and plant cells revealed the presence of DNA sequences other than rRNA genes in and around the nucleolus. NADs display repressive chromatin signatures and harbour repetitive DNA, but also tRNA genes and RNA polymerase II-transcribed genes. Furthermore, the identification of NADs revealed a specific function of the nucleolus and the protein Nucleolin 1 (NUC1) in telomere biology. Here, we discuss the significance of these data with regard to nucleolar structure and to the role of the nucleolus and NUC1 in global genome organization and stability.


A two-year follow-up study of the PCV2 status of a Danish pig herd that was initially assumed to be PCV2-free.
A longitudinal study was carried out to investigate whether a herd that had previously tested negative for porcine circovirus type 2 (PCV2) by polymerase chain reaction (PCR) was free of PCV2 or whether the negative profiles indicate that the level of PCV2 varies over time. In eight Danish herds that had initially tested negative for PCV2 by quantitative polymerase chain reaction (PCR), additional sampling was performed. Only one of the herds was still PCV2-negative in the additional sampling and was included in the study. The herd was a finishing herd, subclinically infected with PCV2, but vaccinated against PCV2 to improve performance. The herd was monitored by taking blood samples every seventh week over a period of two years and was not found to be continuously negative for PCV2 by PCR. The first time PCV2 was detected by PCR, in May 2010, PCV2 vaccination had been withdrawn from the herd, and at the same time the herd was infected with porcine reproductive and respiratory syndrome virus (PRRS). The PCV2-negative status, measured by PCR, was obtained in the first sampling after the PCV2 vaccination had been reintroduced. When PCV2 vaccination was withdrawn again in September 2011, the herd tested positive for PCV2 by PCR, and this time it continued to be PCV2-positive, even though PCV2 vaccination had been reintroduced. A Danish finishing herd that appeared to be PCV2-free from the start of a period of two years was not free of PCV2 during the entire period.


Pilot study of Lokomat versus manual-assisted treadmill training for locomotor recovery post-stroke.
While manually-assisted body-weight supported treadmill training (BWSTT) has revealed improved locomotor function in persons with post-stroke hemiparesis, outcomes are inconsistent and it is very labor intensive. Thus an alternate treatment approach is desirable. Objectives of this pilot study were to: 1) compare the efficacy of body-weight supported treadmill training (BWSTT) combined with the Lokomat robotic gait orthosis versus manually-assisted BWSTT for locomotor training post-stroke, and 2) assess effects of fast versus slow treadmill training speed. Sixteen volunteers with chronic hemiparetic gait (0.62 +/- 0.30 m/s) post-stroke were randomly allocated to Lokomat (n = 8) or manual-BWSTT (n = 8) 3x/wk for 4 weeks. Groups were also stratified by fast (mean 0.92 +/- 0.15 m/s) or slow (0.58 +/- 0.12 m/s) training speeds. The primary outcomes were self-selected overground walking speed and paretic step length ratio. Secondary outcomes included: fast overground walking speed, 6-minute walk test, and a battery of clinical measures. No significant differences in primary outcomes were revealed between Lokomat and manual groups as a result of training. However, within the Lokomat group, self-selected walk speed, paretic step length ratio, and four of the six secondary measures improved (p = 0.04-0.05, effect sizes = 0.19-0.60). Within the manual group, only balance scores improved (p = 0.02, effect size = 0.57). Group differences between fast and slow training groups were not revealed (p > or = 0.28). Results suggest that Lokomat training may have advantages over manual-BWSTT following a modest intervention dose in chronic hemiparetic persons and further, that our training speeds produce similar gait improvements. Suggestions for a larger randomized controlled trial with optimal study parameters are provided.


Coronary heart disease and associated risk factors in Qazvin: a population-based study.
In a cross-sectional study in Qazvin, Islamic Republic of Iran, 846 residents (425 men and 421 women) aged > or = 25 years were assessed for coronary heart disease and its associated risk factors comparing ischaemic and non-ischaemic groups. The age-adjusted prevalence of possible myocardial infarction, ischaemic ECG changes and angina pectoris were 4.2%, 36.8% and 2.2% respectively. There was no difference in the mean systolic and diastolic blood pressure and body mass index between ischaemic and non-ischaemic groups. There was a significant association between possible myocardial infarction and hypertension, type 2 diabetes, and smoking in women. There was also a significant association between ischaemic ECG changes and waist-hip ratio in women and between ischaemic ECG changes and hypertension in men.


Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.
Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33-2.94; P = 6.9 x 10(-4)) for generalized aggressive periodontitis, and 1.72 (1.06-2.76; P = 2.6 x 10(-2)) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases.


IL28B single-nucleotide polymorphism rs12979860 is associated with spontaneous HIV control in white subjects.
The single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene has been associated with the spontaneous clearance of hepatitis C virus. We sought to determine whether this SNP could be associated with the spontaneous control of human immunodeficiency virus (HIV) infection. We studied the prevalence of the IL28B CC genotype among 53 white HIV controllers, compared with the prevalence among 389 HIV-infected noncontrollers. We found that the IL28B CC genotype was independently associated with spontaneous HIV control (odds ratio [OR], 2.669; P = .017), as were female sex (OR, 7.077; P ≤ .001) and the presence of HLA-B57 and/or B27 (OR, 3.080; P = .017). This result supports the idea that common host mechanisms are involved in the spontaneous control of these 2 chronic infections.


Cost-effectiveness of intensive care for hospitalized COVID-19 patients: experience from South Africa.
Given projected shortages of critical care capacity in public hospitals during the COVID-19 pandemic, the South African government embarked on an initiative to purchase this capacity from private hospitals. In order to inform purchasing decisions, we assessed the cost-effectiveness of intensive care management for admitted COVID-19 patients across the public and private health systems in South Africa. Using a modelling framework and health system perspective, costs and health outcomes of inpatient management of severe and critical COVID-19 patients in (1) general ward and intensive care (GW + ICU) versus (2) general ward only (GW) were assessed. Disability adjusted life years (DALYs) were evaluated and the cost per admission in public and private sectors was determined. The model made use of four variables: mortality rates, utilisation of inpatient days for each management approach, disability weights associated with severity of disease, and the unit cost per general ward day and per ICU day in public and private hospitals. Unit costs were multiplied by utilisation estimates to determine the cost per admission. DALYs were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). An incremental cost-effectiveness ratio (ICER) - representing difference in costs and health outcomes of the two management strategies - was compared to a cost-effectiveness threshold to determine the value for money of expansion in ICU services during COVID-19 surges. A cost per admission of ZAR 75,127 was estimated for inpatient management of severe and critical COVID-19 patients in GW as opposed to ZAR 103,030 in GW + ICU. DALYs were 1.48 and 1.10 in GW versus GW + ICU, respectively. The ratio of difference in costs and health outcomes between the two management strategies produced an ICER of ZAR 73,091 per DALY averted, a value above the cost-effectiveness threshold of ZAR 38,465. Results indicated that purchasing ICU capacity from the private sector during COVID-19 surges may not be a cost-effective investment. The 'real time', rapid, pragmatic, and transparent nature of this analysis demonstrates an approach for evidence generation for decision making relating to the COVID-19 pandemic response and South Africa's wider priority setting agenda.


Motoneuron-driven computational muscle modelling with motor unit resolution and subject-specific musculoskeletal anatomy.
The computational simulation of human voluntary muscle contraction is possible with EMG-driven Hill-type models of whole muscles. Despite impactful applications in numerous fields, the neuromechanical information and the physiological accuracy such models provide remain limited because of multiscale simplifications that limit comprehensive description of muscle internal dynamics during contraction. We addressed this limitation by developing a novel motoneuron-driven neuromuscular model, that describes the force-generating dynamics of a population of individual motor units, each of which was described with a Hill-type actuator and controlled by a dedicated experimentally derived motoneuronal control. In forward simulation of human voluntary muscle contraction, the model transforms a vector of motoneuron spike trains decoded from high-density EMG signals into a vector of motor unit forces that sum into the predicted whole muscle force. The motoneuronal control provides comprehensive and separate descriptions of the dynamics of motor unit recruitment and discharge and decodes the subject's intention. The neuromuscular model is subject-specific, muscle-specific, includes an advanced and physiological description of motor unit activation dynamics, and is validated against an experimental muscle force. Accurate force predictions were obtained when the vector of experimental neural controls was representative of the discharge activity of the complete motor unit pool. This was achieved with large and dense grids of EMG electrodes during medium-force contractions or with computational methods that physiologically estimate the discharge activity of the motor units that were not identified experimentally. This neuromuscular model advances the state-of-the-art of neuromuscular modelling, bringing together the fields of motor control and musculoskeletal modelling, and finding applications in neuromuscular control and human-machine interfacing research.


Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction.
Acute elevation of circulating lipids, such as the postprandial state, contributes to increased cardiovascular risk. However, the effect of acutely elevated triglycerides on arterial and left ventricular function is not completely understood. We aimed to assess whether an acute increase in triglycerides affects ventricular-vascular interaction. Fifteen healthy men (age, 49 ± 8 yr) underwent blinded, randomized infusion of saline and intravenous fat emulsion to acutely raise plasma triglycerides. All subjects underwent both randomization trials, in random order on two separate days. Ventricular-vascular interaction measures were recorded by tonometry (central blood pressure) and echocardiography (left ventricular volumes, strain, and strain rate) at baseline and after 1 h infusion. Net ventricular-vascular interaction was defined by the effective arterial elastance (E(A))-to-left ventricular end-systolic elastance (E(LV)) ratio (E(A)/E(LV)). When compared with saline, the infusion of intravenous fat emulsion increased triglycerides and free fatty acids (ΔP < 0.001 for both) and improved left ventricular contractility (ΔE(LV), end-systolic volume and strain rate; P < 0.05 for all). However, arterial function was unchanged (ΔE(A), brachial and central blood pressure; P > 0.05 for all). Overall, E(A)/E(LV) was decreased by an infusion of intravenous fat emulsion (P = 0.004) but not saline (P > 0.05, P = 0.001 for Δ between trials). We conclude that intravenous fat emulsion and acute elevation of blood lipids (including triglycerides and free fatty acids) alter ventricular-vascular interaction by increasing left ventricular contractility without affecting arterial load. These findings may have implications for cardiovascular responses to parenteral nutrition.


A Department-Sponsored, Hospital-Based Pathology Education Symposium Is a Cost-Effective Method to Provide Laboratory Staff With Highly Rated Continuing Education Experiences.
Continuing education improves the quality of medical care and is a required part of most health care professions. Although a variety of educational modules are available online or at external conferences, completion of these activities can be expensive and time-consuming. In addition, externally produced modules may have limited applicability to a local practice. To assess the ability of an economically efficient, locally produced, department-wide pathology educational seminar to efficiently meet education requirements for a large number of employees in a large health system. A multiday continuing education symposium was produced annually from 2013 through 2019 at no cost to participants. Metrics related to attendance, number of educational sessions available for registration, and participant satisfaction were tabulated, trended, and compared with similar metrics tabulated from an external continuing education conference that was offered from 2011 through 2012. The production of an internal, hospital-based educational symposium increased employee attendance (mean of 635 attendees per year versus 247 at the external program; P < .001) while reducing mean annual cost per attendee ($51 versus $140, P < .001). The number of sessions produced for the internal symposium was 39 per year on average, compared with 12 per year at the external program. Technical staff, residents, fellows, and faculty all contributed to internal educational programming, helping to build a team culture in the department. Overall employee satisfaction was 96.2%. An internal educational pathology symposium led to cost-efficient distribution of continuing education credits to a large number of technical staff, with a high degree of reported employee satisfaction.


Competition for hummingbird pollination shapes flower color variation in Andean solanaceae.
One classic explanation for the remarkable diversity of flower colors across angiosperms involves evolutionary shifts among different types of pollinators with different color preferences. However, the pollinator shift model fails to account for the many examples of color variation within clades that share the same pollination system. An alternate explanation is the competition model, which suggests that color divergence evolves in response to interspecific competition for pollinators, as a means to decrease interspecific pollinator movements. This model predicts color overdispersion within communities relative to null assemblages. Here, we combine morphometric analyses, field surveys, and models of pollinator vision with a species-level phylogeny to test the competition model in the primarily hummingbird-pollinated clade Iochrominae (Solanaceae). Results show that flower color as perceived by pollinators is significantly overdispersed within sites. This pattern is not simply due to phylogenetic history: phylogenetic community structure does not deviate from random expectations, and flower color lacks phylogenetic signal. Moreover, taxa that occur in sympatry occupy a significantly larger volume of color space than those in allopatry, supporting the hypothesis that competition in sympatry drove the evolution of novel colors. We suggest that competition among close relatives may commonly underlie floral divergence, especially in species-rich habitats where congeners frequently co-occur.


Inhibition by the Landschütz ascites carcinoma of the granulomatous inflammatory response to C. parvum.
I.p. or i.v. administration of Corynebacterium parvum (CP) to MF1 mice induces a generalized inflammatory response, associated with marked hepatosplenomegaly and accompanied by a pronounced granulomatous response in the liver. Injection of the Landschütz ascites carcinoma (LAC) 24 h after CP substantially reduced the intensity of the inflammatory response, and decreased both the frequency and size of the hepatic granulomas, as revealed by morphometric analysis of histological sections. The difference in cellular composition of the granulomas between the experimental groups, as revealed by light microscopy, was further emphasized and characterized by ultrastructural studies. These revealed the predominance of macrophages within the granulomas in tumour-bearing mice, in contrast to the predominance of epithelioid cells in the lesions which developed in mice given CP alone. Our experimental findings show that the inhibitory effect of the growing LAC on granuloma formation in response to CP cannot be ascribed to (a) sequestration of the microorganism within the growing tumour, (b) a nonspecific inflammatory stimulus, (c) diversion and seqestration of mononuclear phagocytes in the growing tumour or (d) the presence of lactate dehydrogenase-elevating virus in either the host or tumour cells. The inhibition of liver granuloma formation is consistent with an effect mediated by soluble, heat-stable tumour-associated factor(s).


Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice.
B cells play an important role in the allergic response by producing allergen-specific Igs as well as by serving as antigen-presenting cells. We studied the involvement of B cells in the development of responses in a murine model of allergic airway sensitization. Normal and B cell-deficient (muMt-/-) B10.BR mice were sensitized via the airways to ovalbumin; Ig production, cytokine elaboration from local lymph node cells, development of airway hyperresponsiveness, and histological changes in the airways were evaluated. Both strains of mice had increased production of T helper 2-like cytokines and developed an accumulation of eosinophils in the bronchial tissue after airway sensitization. However, only wild-type mice produced allergen-specific antibodies and exhibited altered airway function. B cell-deficient mice reconstituted with anti-ovalbumin IgE during the course of sensitization developed increases in airway responsiveness. These results indicated that neither B cells nor IgE were necessary for the induction of a T helper 2-type cytokine response or eosinophil infiltration of the airways after allergic sensitization but that IgE was required as a second signal for the development of airway hyperresponsiveness in this model of airway sensitization.


Relationship between different species of helminths and atopy: a study in a population living in helminth-endemic area in Sulawesi, Indonesia.
The association between allergen skin sensitization and helminth infection has been debated for years. Here, we sought to estimate the prevalence of atopic sensitization of residents living in area endemic for lymphatic filariasis and intestinal helminths and to investigate the association between these different species of helminths with allergen skin test reactivity to allergens. Five hundred and eighty-three individuals living in an area endemic for Brugia malayi and for intestinal helminths were skin prick tested using 3 allergens. Microfilariae were enumerated by filtration of 1 ml nocturnally collected blood, and 442 stool samples were examined for the presence of intestinal helminth eggs. The prevalence of skin prick test positivity to any allergen was 23.5% (to cockroach 20.6%, to house dust mite 6.2% and to grass pollen 1.2%). Individuals with B. malayi infection had a significantly reduced risk for atopic reactivity to cockroach (adjusted odds ratio 0.56, 95% CI 0.35-0.88). In the same population, no association was found between the presence of intestinal helminths and any skin test reactivity. In a general population, across all ages in a rural area of Indonesia, the prevalence of skin test reactivity to house dust mite is as low as in other non-affluent countries, and infection with B. malayi appears to reduce the risk of skin reactivity to cockroach. On the other hand, we found no association between infection with intestinal helminths and skin test reactivity to aeroallergens.


Blob detection by relaxation.
A blob is a compact region lighter (or darker) than its background surrounded by a smoothly curved edge. Blobs can be detected using cooperating relaxation processes to enhance their interior and edge probabilities. A discussion of the processes working independently and together is given. The use of a pyramidal relaxation structure, the use of the closedness of contours as an additional information source, and the extension of cooperating relaxation processes to a time sequence of images are also discussed.


A review of the efficacy and tolerability of immediate-release and extended-release formulations of gepirone.
Gepirone, a 5-HT(1A) receptor agonist, has been assessed for use in the treatment of anxiety and depressive disorders. Azapirones, including gepirone, act to maintain neurotransmission at 5-HT(1A) receptors. The aim of this article was to review the pharmacology and clinical data for gepirone extended-release (ER) and immediate-release (IR) formulations for the treatment of major depressive disorder (MDD). Articles were identified by searching MEDLINE (1966 to present) using the search term gepirone. The reference list retrieved was reviewed for relevant clinical articles. Initial placebo-controlled clinical trials demonstrated that gepirone IR improved symptoms of depression; however, the short half-life of gepirone necessitated frequent administration, and high peak plasma concentrations at higher doses were associated with an increased incidence of adverse events. An ER formulation of gepirone reduced peak-to-trough fluctuations in plasma concentration while maintaining total drug exposure similar to that seen with the IR formulation; the evidence further suggested that lower peak plasma concentrations resulted in fewer adverse events. In clinical trials, both formulations significantly improved symptoms of depression. However, by permitting the use of higher doses of gepirone, the ER formulation had better efficacy and was less likely to produce adverse events (eg, lightheadedness, nausea, dizziness). Several clinical trials have suggested that gepirone ER formulations have significant antidepressant effects and better tolerability than gepirone IR formulations when used to treat MDD.


[Diabetic type of the prednisolone-glucose test as the earliest latent stage of diabetes mellitus].
Prednisolone-glucose tests (PGT) were done in 349 healthy persons and immunoreactive insulin (IRI) secretion in the time course of the glucose tolerance test (GTT) was studied in 48 persons. PGT of diabetic type was established in 33.3% of the persons with normal body mass and in 55.1% with excess body mass and GTT of boundary type. PGT of diabetic type is characterized by insulin secretion of diabetic type in response to glucose intake: the absence of the first peak of a rise of the IRI level and the second higher peak of the IRI level with a prolonged maintenance of IRI values up to the end of the test. The results suggest that PGT of diabetic type is an earlier stage of diabetes mellitus as compared to GTT of diabetic type. Therefore PGT can be used for distinguishing GTT of boundary type as one of the manifestations of diabetes mellitus and as a risk factor. Therapeutic antidiabetic measures are recommended to persons with PGT of diabetic type and prophylactic measures to persons with PGT of normal type.


A patient-specific FE-based methodology to simulate prosthesis insertion during an augmentation mammoplasty.
Breast augmentation surgery is a widespread practice for aesthetic purposes. Current techniques, however, are not able to reliably predict the desired final aspect of the breast after the intervention, whose success relies almost completely on the surgeon's skill. In this way, patient-specific methodologies capable of predicting the outcomes of such interventions are of particular interest. In this paper, a finite element biomechanical model of the breast of a female patient before an augmentation mammoplasty was generated using computer tomography images. Prosthesis insertion during surgery was simulated using the theory of finite elasticity. Hyperelastic constitutive models were considered for breast tissues and silicone implants. The deformed geometry obtained from finite element analysis was compared qualitatively and quantitatively with the real breast shape of the patient lying in supine position, with root-mean-squared errors less than 3mm. The results indicate that the presented methodology is able to reasonably predict the aspect of the breast in an intermediate step of augmentation mammoplasty, and reveal the potential capabilities of finite element simulations for visualization and prediction purposes. However, further work is required before this methodology can be helpful in aesthetic surgery planning.


Precision medicine and the principle of equal treatment: a conjoint analysis.
In precision medicine biomarkers stratify patients into groups that are offered different treatments, but this may conflict with the principle of equal treatment. While some patient characteristics are seen as relevant for unequal treatment and others not, it is known that they all may influence treatment decisions. How biomarkers influence these decisions is not known, nor is their ethical relevance well discussed. We distributed an email survey designed to elicit treatment preferences from Norwegian doctors working with cancer patients. In a forced-choice conjoint analysis pairs of hypothetical patients were presented, and we calculated the average marginal component effect of seven individual patient characteristics, to estimate how each of them influence doctors' priority-setting decisions. A positive biomarker status increased the probability of being allocated the new drug, while older age, severe comorbidity and reduced physical function reduced the probability. Importantly, sex, education level and smoking status had no significant influence on the decision. Biomarker status is perceived as relevant for priority setting decisions, alongside more well-known patient characteristics like age, physical function and comorbidity. Based on our results, we discuss a framework that can help clarify whether biomarker status should be seen as an ethically acceptable factor for providing unequal treatment to patients with the same disease.


Rib metastasis revealing hepatocellular carcinoma.
Bone metastasis infrequently appears as the first manifestation of hepatocellular calcinoma (HCC), and in any case in most patients the primary tumour is detected a few months after its development. We report the case of a patient with alcoholic liver disease, increased levels of alpha-fetoprotein, and no evidence of hepatic lesion in the different imaging modalities, in whom metastasis of HCC was detected in the ribs, whereas the primary tumour was not diagnosed until 15 months later. We believe that all patients with increased levels of alpha-fetoprotein should be tested in an intensified search for HCC and possible metastases, given that hepatic lesions may not be detected until many months alter the diagnosis of metastatic disease.


Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains.
Toll-like receptors (TLRs) play a key role in the innate immune system. The TLR7, 8, and 9 compose a family of intracellularly localized TLRs that signal in response to pathogen-derived nucleic acids. So far, there are no crystallographic structures for TLR7, 8, and 9. For this reason, their ligand-binding mechanisms are poorly understood. To enable first predictions of the receptor-ligand interaction sites, we developed three-dimensional structures for the leucine-rich repeat ectodomains of human TLR7, 8, and 9 based on homology modeling. To achieve a high sequence similarity between targets and templates, structural segments from all known TLR ectodomain structures (human TLR1/2/3/4 and mouse TLR3/4) were used as candidate templates for the modeling. The resulting models support previously reported essential ligand-binding residues. They also provide a basis to identify three potential receptor dimerization mechanisms. Additionally, potential ligand-binding residues are identified using combined procedures. We suggest further investigations of these residues through mutation experiments. Our modeling approach can be extended to other members of the TLR family or other repetitive proteins.


ErrorTracer: an algorithm for identifying the origins of inconsistencies in genome-scale metabolic models.
The number and complexity of genome-scale metabolic models is steadily increasing, empowered by automated model-generation algorithms. The quality control of the models, however, has always remained a significant challenge, the most fundamental being reactions incapable of carrying flux. Numerous automated gap-filling algorithms try to address this problem, but can rarely resolve all of a model's inconsistencies. The need for fast inconsistency checking algorithms has also been emphasized with the recent community push for automated model-validation before model publication. Previously, we wrote a graphical software to allow the modeller to solve the remaining errors manually. Nevertheless, model size and complexity remained a hindrance to efficiently tracking origins of inconsistency. We developed the ErrorTracer algorithm in order to address the shortcomings of existing approaches: ErrorTracer searches for inconsistencies, classifies them and identifies their origins. The algorithm is ∼2 orders of magnitude faster than current community standard methods, using only seconds even for large-scale models. This allows for interactive exploration in direct combination with model visualization, markedly simplifying the whole error-identification and correction work flow. Windows and Linux executables and source code are available under the EPL 2.0 Licence at https://github.com/TheAngryFox/ModelExplorer and https://www.ntnu.edu/almaaslab/downloads. Supplementary data are available at Bioinformatics online.


Transplant outcomes in acute leukemia. I.
Umbilical cord blood (UCB) has gradually emerged over the last decade as an alternative source of hematopoietic cells for transplantation in children and adults with high-risk or advanced hematologic malignancies who do not have a suitably matched related or unrelated adult donor. This increase in use of UCB is due to favorable results in children, growing availability of UCB units with large cell doses, less stringent donor-recipient HLA matching, and rapid identification and acquisition of the unit. In children with acute leukemia, the data support similar leukemia-free survival after transplantation of human leukocyte antigen (HLA)-matched and one or two HLA-mismatched UCB and HLA-matched unrelated donor bone marrow. In adults with acute leukemia, some reports suggest a survival advantage after transplantation of matched unrelated bone marrow compared to UCB, while others report similar leukemia-free survival. Work is in progress to improve hematopoietic recovery and lower early transplant-related deaths, the two major limitations to a successful outcome after UCB transplant. The importance of HLA-matching and cell dose on outcomes after UCB transplantation support the need for an even greater investment in public cord blood banks. Simultaneously searching of accredited cord blood banks and bone marrow donor registries for patients without an HLA-matched sibling thought to benefit from hematopoietic stem cell transplantation (HSCT) is encouraged.


Combining cervical cancer screening for mothers with schoolgirl vaccination during human papillomavirus (HPV) vaccine implementation in South Africa: results from the VACCS1 and VACCS2 trials.
The platform provided by human papillomavirus (HPV) vaccination for linked public health interventions to improve cervical cancer prevention remains incompletely explored. The Vaccine And Cervical Cancer Screen (VACCS) cross-sectional observation trials aimed to evaluate the efficacy of school-based HPV vaccination linked with maternal cervical cancer screening. Girls from 29 schools in two provinces in South Africa were invited in writing to receive HPV vaccination. Two approaches to informed consent were compared, namely an audiovisual presentation (VACCS1) and in written format (VACCS2). Markers of vaccine uptake and coverage were calculated, namely uptake among the invited and consented cohorts, and rates of completion and sufficient vaccination. Mothers and female guardians received educational material about cervical cancer, and either a self-sampling device or an invitation to attend existing screening facilities. Knowledge was assessed via structured questionnaires (before and after), and screening uptake was self-reported and directly assessed and compared between these approaches. Vaccine acceptance among 5137 invited girls was similar for the two methods of consent; 99.3% of consented girls received a first dose; overall completion rate was 90.5%. More girls were vaccinated using a two-dose (974/1016 (95.9%)) than a three-dose regimen (1859/2030 (91.6%)). The questionnaire (n=906) showed poor maternal knowledge which improved significantly (p<0.05) after health education; only 54% of mothers reported any previous screening. The offer of a self-sampling device (n=2247) was accepted by 43.9% of mothers, but only 26% of those invited to screen at existing facilities (n=396) reported subsequent screening. Successful linking of primary health interventions to control cervical cancer was demonstrated. School-based HPV vaccination, linked to health education, self-sampling, and molecular screening resulted in significant improvements in knowledge and screening.


The implications of lighted ureteral stenting in laparoscopic colectomy.
The placement of indwelling ureteral catheters during colorectal surgery has been recommended for prevention of ureteral injuries. With the advent of laparoscopic colectomy (LCo), the role of preoperative placement of lighted ureteral stents (LUS) has also become commonplace. We sought to evaluate the value of lighted ureteral stent placement in laparoscopic colectomy. Sixty-six patients underwent LCo with LUS inserted preoperatively. Stents were removed in the immediate postoperative period. Two surgeons performed all the colectomies; 32 patients were males and 34 were females. Fifty patients underwent sigmoid colectomy, 4 had abdominoperineal resection, 4 had right colectomy, and 1 each had transverse or subtotal colectomy. Eighteen patients had a diagnosis of cancer, 34 had diverticular disease, and 14 had neoplastic polyps. Forty patients had bilateral and 26 had unilateral stent placement. A review of the incidence of ureteral injuries, hematuria, and anuria as the cause of acute renal failure was accomplished, comparing the unilateral and bilateral stented groups. One (1.5%) patient suffered a left ureteral laceration during sigmoid colectomy. This was managed successfully with stent reinsertion. Sixty-five (98.4%) patients had gross hematuria lasting 2.93 days (1 to 6 days). The cost of bilateral stent placement was $1,504.32. A statistically significant difference occurred in the duration of hematuria (days) between patients who had unilateral (2.5 +/- 0.82) and bilateral stent placement (3.37 +/- 1.05), (P < 0.001). Four patients suffered from anuria, 2 required renal support needing hemodialysis for 3 to 6 days, 3 (75%) had bilateral stents, and 1 (25%) had a unilateral stent. We recommend the placement of lighted ureteral stents as a valuable adjunct to laparoscopic colectomy to safeguard ureteral integrity. Transient hematuria is common but requires no intervention. Reflux anuria occurs infrequently and is reversible.


Caring for Children While Working in Agriculture-The Perspectiveof Farmworker Parents.
Access to safe, off-farm childcare is often a challenge for farmworkers with young children and is likely to become an increasingly salient barrier as more agricultural workers migrate together with families and as the number of women entering the agricultural workforce increases. Agriculture is one of the most hazardous industries, and the presence of young children in the workplace puts them at risk. To better understand the current nature of childcare for farmworker families and the challenges to accessing services, this project facilitated in-person surveys with 132 parents in three communities in Florida. A convenience sample that intentionally targeted parents living and working in areas with limited access to Migrant and Seasonal Head Start facilities was used to recruit participants. Most participants reported childcare access as a challenge. They expressed a desire to work in an area based on childcare availability. These findings offer agribusiness leaders important data to consider. They also suggest that industry support of childcare may be an important workforce investment. Findings indicate that high quality, affordable off-farm childcare services could serve as a means for attracting farmworkers to regions currently experiencing labor shortages. Additional research is warranted to explore this subject in diverse geographic areas.


A Study on the Influential Factors of Stress Corrosion Cracking in C110 Casing Pipe.
In this paper, we analyze the potential factors affecting the hydrogen sulfide type of stress corrosion cracking in C110 casing pipes. In order to further study these cracking factors, the methods of material property testing, scanning electron microscopy, XRD, TEM, and 3D ultra-depth-of-field were applied in the experiments. Besides that, an HTHP autoclave was independently designed by the laboratory to simulate the actual corrosion environment, and the potential factors affecting the stress corrosion cracking of C110 casing pipes were determined. The test results showed that the chemical composition, metallographic structure, hardness, and non-metallic inclusions of the two types of C110 casing pipes were all qualified. In fact, there remains a risk of stress corrosion cracking when the two kinds of C110 casing pipes serve under long-term field-working conditions. It is considered in this paper that the precipitates on the material surface, stress damage, and pitting corrosion are all critical factors affecting the stress corrosion cracking of casing pipes.


Serious shoulder injuries in professional soccer: return to participation after surgery.
An evidence base for the management and prevention of shoulder injuries in soccer is lacking. The aim of this study was to demonstrate the type, mechanism and recovery time after surgery associated with serious shoulder injuries sustained in professional soccer to build an evidence base foundation. Fifty-two professional soccer players underwent shoulder surgery for injuries sustained during match play. Of these, 25 fulfilled the inclusion criteria. Data were collected for injury mechanism and type; clinical, radiological and surgical findings and procedures; and return to full participation. Subjects were all managed by the same surgeon. Labral injuries represented the most common injury type affecting 21 (84 %) subjects; two rotator cuff (8 %) and two combined labral/rotator cuff (8 %) injuries were less common. Fourteen (56 %) subjects sustained a high-energy trauma injury in a combined abduction and external rotation position. Six (24 %) subjects sustained a low-energy trauma mechanism in variable positions, while five (20 %) had a gradual onset of symptoms. Twenty-two (88 %) subjects reported a dislocation as a feature of their presentation. All of the subjects with high- and low-energy trauma mechanisms reported a dislocation occurring at the time of injury. Eight (32 %) subjects had sustained a previous significant shoulder injury to the ipsilateral side. Goalkeepers did not sustain low-energy trauma injuries. Outfield players returned to full participation in a mean time of 11.6 weeks, while goalkeepers did so in 11.1 weeks post-surgery. Return to participation time ranged from 7 to 24 weeks with a median of 11 weeks. Professional soccer players can expect a return to participation within 12 weeks post-surgery. The majority of serious shoulder injuries in soccer occur at a positional extreme of external rotation and abduction in high-energy situations, while a significant number occur in low-energy situations away from this position. Most serious shoulder injuries in professional soccer are dislocations. Previous shoulder injury is considered a risk factor. IV.