Frequency and characteristics of goal attainment following BoNT-A injection for management of spasticity.
To determine which Goal Attainment Scale (GAS) goals are commonly achieved in patients with upper limb and/or lower limb spasticity following Botulinum Neurotoxin Type A (BoNT-A) injection. Adults who attended a Spasticity Management Clinic for upper and/or lower limb BoNT-A injection were included in this prospective cohort study. Goals were set by participants and/or carers in conjunction with the therapist using the GAS, prior to injection and reviewed at one month following the injection. Three out of the five categories of goals were passive. Goals were categorised into: mobility/transfers, pain/comfort, upper limb use, hygiene, and cosmesis. The number of responders for the GAS total score, and in each of the GAS categories, was calculated. Sixty-seven participants were recruited (mean age 51 ± 16 years; range 18-85), 70% had a stroke. Responders for mobility and transfer goals were further post injury or disease onset than non-responders (median 5.9 vs. 1.2 years, p = 0.03). Clients with stroke were less likely than other participants to achieve mobility and transfer goals (p = 0.02). There was a trend for those who achieved mobility and transfer goals to be younger (mean 49 years vs. 55 years, p = 0.06). Although active goals are more commonly identified, passive goals were more likely to be achieved. Although active goals are commonly identified by people with spasticity, passive goals were more likely to be achieved following BoNT-A injection. A long duration of spasticity does not preclude patients from achieving mobility and transfer goals. Non-stroke participants were more likely to achieve mobility and transfer goals. Implications for Rehabilitation Patients with chronic spasticity should be considered for BoNT-A as clinically meaningful outcomes can be achieved. When spasticity is present in multiple muscles, the GAS can be an assistive tool to guide clinicians in determining which muscles are a priority for injection, because the client will be more motivated to improve those specific goals. Although carers and patients are more willing to set active goals, these are more difficult to achieve possibly because follow up intervention or independent practise is required.


Associations Between Personality Traits and Cognitive Resilience in Older Adults.
The goal of this paper was to examine associations between personality traits and resilience to neuropathologic burden. Using data from the Religious Orders Study and the Rush Memory and Aging Project, we identified a total of 1,375 participants with personality, cognitive, and post-mortem neuropathology data. We regressed cognition onto pathology and extracted the residuals as an indicator of cognitive resilience. We then modeled the effect of Big Five personality traits on cognitive resilience, adjusting for demographics, APOE status, medical comorbidities, and cognitive activity. The analytic plan was preregistered prior to data access or analysis, and all scripts and outputs are available online. Higher neuroticism was associated with greater vulnerability to pathology. Results from exploratory analyses suggest that higher conscientiousness was associated with less cognitive decline relative to the amount of pathology, or greater resilience. Education and cognitive activity did not moderate these associations. Personality may have a pathoplastic effect on neuropathology, as low neuroticism and high conscientiousness are associated with better function despite neuropathologic burden.


Protective immunity evoked by locally administered group A streptococcal vaccines in mice.
The present studies were undertaken to determine the pathogenicity of group A streptococci introduced intranasally (i.n.) into mice in an attempt to mimic mucosal infections in humans and to determine the efficacy of streptococcal vaccines administered via the mucosal route. The LD50 of type 24 streptococci (M24 strep) administered i.n. was 3 x 10(4) CFU. Throat cultures were performed in M24 strep-inoculated mice. Of 11 mice that died, 9 had positive throat cultures 3 or 4 days after i.n. challenge, and of 9 mice that survived, only 1 had a positive throat culture, indicating an association between mucosal infection and death. Postmortem examination performed on 35 mice that died after i.n. challenge showed that all had evidence of disseminated infections, and group A streptococci were recovered from the cervical lymph nodes, blood, spleen, liver, and brain. To determine vaccine efficacy, heat-killed M24 strep or pep M24 were administered i.n. to groups of mice. Whole, heat-killed streptococci and pep M24 administered locally protected mice against death from i.n. challenge infections with homologous M24 strep. The whole cell vaccine also protected against i.n. challenge infections with heterologous type 6 streptococci. Our data suggest that streptococcal vaccines administered locally evoke protective immunity against streptococcal infections.


Endoscopic sclerotherapy for the treatment of weight regain after Roux-en-Y gastric bypass: outcomes, complications, and predictors of response in 575 procedures.
Weight regain after Roux-en-Y gastric bypass (RYGB) is common. Endoscopic sclerotherapy is increasingly used to treat this weight regain. To report safety, outcomes, durability, and predictors of response to sclerotherapy in a large prospective cohort. Retrospective analysis of a prospective cohort study of patients with weight regain after RYGB. A total of 231 consecutive patients undergoing 575 sclerotherapy procedures between September 2008 and March 2011. Single or multiple sclerotherapy procedures to inject sodium morrhuate into the rim of the gastrojejunal anastomosis. We report weight loss, complications, and predictors of response. We also used Kaplan-Meier survival analysis and log-rank test to compare time to continuation of weight regain after sclerotherapy in patients undergoing a single versus multiple sclerotherapy procedures. At 6 and 12 months from the last sclerotherapy procedure, weight regain stabilized in 92% and 78% of the cohort, respectively. Those who underwent 2 or 3 sclerotherapy sessions had significantly higher rates of weight regain stabilization than those who underwent a single session (90% vs 60% at 12 months; P = .003). The average weight loss at 6 months from the last sclerotherapy session for the entire cohort was 10 lb (standard deviation 16), representing 18% of the weight regained after RYGB. A subset of 73 patients (32% of the cohort) had greater weight loss at 6 months (26 lb, standard deviation 12), representing 61% of the weight regained. Predictors of a favorable outcome included greater weight regain and the number of sclerotherapy procedures. Bleeding was reported in 2.4% of procedures and transient diastolic blood pressure increases in 15%, without adverse health outcomes. No GI perforations were reported. Endoscopic sclerotherapy appears to be a safe and effective tool for the management of weight regain after RYGB.


Information technology systems in public sector health facilities in developing countries: the case of South Africa.
The public healthcare sector in developing countries faces many challenges including weak healthcare systems and under-resourced facilities that deliver poor outcomes relative to total healthcare expenditure. Global references demonstrate that information technology has the ability to assist in this regard through the automation of processes, thus reducing the inefficiencies of manually driven processes and lowering transaction costs. This study examines the impact of hospital information systems implementation on service delivery, user adoption and organisational culture within two hospital settings in South Africa. Ninety-four interviews with doctors, nurses and hospital administrators were conducted in two public sector tertiary healthcare facilities (in two provinces) to record end-user perceptions. Structured questionnaires were used to conduct the interviews with both qualitative and quantitative information. Noteworthy differences were observed among the three sample groups of doctors, nurses and administrators as well as between our two hospital groups. The impact of automation in terms of cost and strategic value in public sector hospitals is shown to have yielded positive outcomes with regard to patient experience, hospital staff workflow enhancements, and overall morale in the workplace. The research provides insight into the reasons for investing in system automation, the associated outcomes, and organisational factors that impact the successful adoption of IT systems. In addition, it finds that sustainable success in these initiatives is as much a function of the technology as it is of the change management function that must accompany the system implementation.


Ten-Year Trends of Clinicopathologic Features and Surgical Treatment of Lung Cancer in China.
Lung cancer has changed significantly during the past 2 decades in its epidemiology and treatment. This retrospective analysis used data from 7 major areas of China over 10 years to evaluate clinicopathologic and surgical treatment trends of lung cancer in China during the past decade. Data from 7184 patients with primary lung cancer who were treated between 2005 and 2014 in 8 provinces of China were retrospectively collected. Their clinicopathologic features and surgical treatment information were recorded. Simple linear regression models and the Cochrane-Armitage trend test were used to assess temporal trends. The proportion of female patients (from 57.4% to 59.6%; P < .001) and nonsmoking patients (from 37.1% to 48.9%; P < .001) and of patients with a family history of malignant tumors (from 7.0% to 11.5%; P < .001) increased significantly. The percentage of adenocarcinomas increased significantly (from 36.4% to 53.5%; P < .001), with a decrease in squamous cell carcinomas (from 45.4% to 34.4%; P < .001). After 2008, the application of minimally invasive surgery significantly increased in China (from 2.4% in 2008 to 34.4% in 2014; P < .001), with a decline in the rate of conversion to open operation (from 14.3% in 2008 to 4.8% in 2014; P = .146) and an increase in the proportion of systematic mediastinal lymph node dissection (from 50.0% in 2008 to 84.1% in 2014; P = .001). This study investigated recent 10-year trends in the clinicopathologic features and surgical treatment of lung cancer in China and found significant important changes. These findings provide valuable information and evidence for the future control of the disease in China.


Conditionally positive effect of the TetR-family transcriptional regulator AtrA on streptomycin production by Streptomyces griseus.
AtrA, a transcriptional activator for actII-ORF4, encoding the pathway-specific transcriptional activator of the actinorhodin biosynthetic gene cluster in Streptomyces coelicolor A3(2), has been shown to bind the region upstream from the promoter of strR, encoding the pathway-specific transcriptional activator of the streptomycin biosynthetic gene cluster in Streptomyces griseus [Uguru et al. (2005) Mol Microbiol 58, 131-150]. The atrA orthologue (atrA-g) in S. griseus was constitutively transcribed throughout growth from a promoter located about 250 nt upstream of the translational start codon, as determined by S1 nuclease mapping. DNase I footprinting showed that histidine-tagged AtrA-g bound an inverted repeat located upstream of strR at positions -117 to -142 relative to the transcriptional start point of strR as +1. This AtrA-g-binding site was between two AdpA-binding sites at approximately nucleotide positions -270 and -50. AdpA is a central transcriptional activator in the A-factor regulatory cascade and essential for the transcription of strR. AtrA-g and AdpA simultaneously bound the respective binding sites. In contrast to AdpA, AtrA-g was non-essential for strR transcription; an atrA-g-disrupted strain produced streptomycin on routine agar media to the same extent as the wild-type strain. However, the atrA-g-disrupted strain tended to produce a smaller amount of streptomycin than the wild-type strain under some conditions, for example, on Bennett agar containing 1 % maltose and on a minimal medium. Therefore, AtrA-g had a conditionally positive effect on streptomycin production, as a tuner, probably by enhancing the AdpA-dependent transcriptional activation of strR in a still unknown manner.


Initial experience of bedaquiline use in a series of drug-resistant tuberculosis patients from India.
Drug-resistant tuberculosis (DR-TB) is a major problem both in India and worldwide. Newer drugs such as TMC-207 (bedaquiline) may have an important role to play in making up an effective drug regimen in such cases. There have been a few reports of bedaquiline use in a non-trial setting from Europe. Our series of five patients is the first series of DR-TB patients from India to receive bedaquiline. All five patients showed striking improvement, with microbiological conversion and an absence of notable adverse effects (e.g., prolonged QTcF), indicating the potential impact of this drug in such a population.


Freezing fertility or freezing false hope? A content analysis of social egg freezing in U.S. print media.
In 2012, the American Society for Reproductive Medicine (ASRM) lifted the experimental label on oocyte preservation, but cautioned against women using it to avoid age-related infertility, known as social egg freezing (SEF). In 2014, Facebook and Apple announced that they would offer SEF as a workplace benefit. Within the context of a rapidly growing market for SEF, we were interested in how these two decisions affected media discussions, given that such discourse can strongly influence public perceptions and behaviors. We used a content analysis methodology to code 138 articles published in U.S. newspapers and magazines between 2012 and 2015. Focusing on a financial concern over the cost of SEF and the lack of insurance for SEF, we found that media portrayals of SEF pivot away from the ethical principle of nonmaleficence centered in the ASRM decision to discourage SEF. Instead, they highlight an issue of justice that can be remedied through the offer of SEF as a workplace benefit. Overall, media portrayals of SEF paint a simplistic and rosy picture that more options, especially more reproductive and economic options, automatically enhance women's autonomy.


Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach.
Cognitive decline is a key outcome of clinical studies in Alzheimer's disease (AD). To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.


Reducing the rehospitalization risk after a manic episode: A population based cohort study of lithium, valproate, olanzapine, quetiapine and aripiprazole in monotherapy and combinations.
Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited. We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors. The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy). Register data does not provide information on all clinical parameters affecting treatment choices. One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode.


Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice.
Aging is a strong risk factor for atherosclerosis and induces accumulation of memory CD8+ T cells in mice and humans. Biological changes that occur with aging lead to enhanced atherosclerosis, yet the role of aging on CD8+ T cells during atherogenesis is unclear. In this study, using femle mice, we found that depletion of CD8+ T cells attenuated atherogenesis in aged, but not young, animals. Furthermore, adoptive transfer of splenic CD8+ T cells from aged wild-type, but not young wild-type, donor mice significantly enhanced atherosclerosis in recipient mice lacking CD8+ T cells. We also characterized T cells in healthy and atherosclerotic young and aged mice by single-cell RNA sequencing. We found specific subsets of age-associated CD8+ T cells, including a Granzyme K+ effector memory subset, that accumulated and was clonally expanded within atherosclerotic plaques. These had transcriptomic signatures of T cell activation, migration, cytotoxicity and exhaustion. Overall, our study identified memory CD8+ T cells as therapeutic targets for atherosclerosis in aging.


Is survival in myeloid malignancies really improving? A retrospective 15-year population-based study.
Myeloid malignancies (MMs) are heterogeneous groups of diseases which present different prognoses. Using data from the population-based Girona Cancer Registry, we estimated the relative survival (RS) rates and relative excess risk of death among patients with MMs in the province of Girona between 1994 and 2008. The 5-year RS rate was 49.7%, ranging from 20.2% for acute myeloid leukemia (AML) to 75.3% for myeloproliferative neoplasms (MPN). Marked differences in RS were observed when the age of patients was considered: an increase in RS was mainly found in younger patients with myelodysplastic syndromes and MPN. Furthermore, cases of chronic myeloid leukemia treated with imatinib had a significantly better outcome compared with those that were untreated. Despite the slight improvement in the survival rate of younger patients with AML, RS remained stable for 15 years, as no significant improvements were made in the management of the disease during that period.


Geriatric evaluation of oncological elderly patients.
Cancer has a high prevalence in older age. The management of cancer in the older aged person is an increasingly common problem. Age may be construed as a progressive loss of stress tolerance, due to decline in functional reserve of multiple organ systems, high prevalence of comorbid conditions, limited socioeconomic support, reduced cognition, and higher prevalence of depression. In the elderly, the comorbidities and physiological changes in the pharmacokinetics reduce the prospective for therapy and suggest the importance of a multidimensional assessment of cancer patients as well as the formulation of predictive models of risk, in order to estimate the life expectancy and tolerance to treatment. The pharmacological changes of age include decreased renal excretion of drugs and increased susceptibility to myelosuppression, mucositis, cardio toxicity and neurotoxicity. The chemotherapy in patients older than 75 years is very limited. The geriatric assessment is considered a valid tool in geriatric medical. It is important for two main reasons: first of all, for the need to distinguish the features linked to the geriatric syndromes from those ones which are strictly connected to the cancer pathology; secondly, for its potential prognostic value.


Quantum resonances and regularity islands in quantum maps
We study analytically as well as numerically the dynamics of a quantum map near a quantum resonance of an order q. The map is embedded into a continuous unitary transformation generated by a time-independent quasi-Hamiltonian. Such a Hamiltonian generates at the very point of the resonance a local gauge transformation described by the unitary unimodular group SU(q). The resonant energy growth is attributed to the zero Liouville eigenmodes of the generator in the adjoint representation of the group while the nonzero modes yield saturating with time contribution. In a vicinity of a given resonance, the quasi-Hamiltonian is then found in the form of power expansion with respect to the detuning from the resonance. The problem is related in this way to the motion along a circle in a (q2 - 1)-component inhomogeneous "magnetic" field of a quantum particle with q intrinsic degrees of freedom described by the SU(q) group. This motion is in parallel with the classical phase oscillations near a nonlinear resonance. The most important role is played by the resonances with the orders much smaller than the typical localization length q << l. Such resonances master for exponentially long though finite times the motion in some domains around them. Explicit analytical solution is possible for a few lowest and strongest resonances.


Supporting facial transplantation with the pillars of bioethics.
Facial transplantation has recently been offered to patients with severely disfigured faces not amenable to functional reconstruction with autologous tissues. Arguments against this procedure include risks of immunosuppression, the concern that it will be done for cosmesis, the belief that acceptable reconstruction can be achieved with autologous tissues, the potential impact on the patient of graft failure, and the concern that the procedure may be adopted by unqualified centers. If we look to bioethics to help us dissect the question of whether or not facial transplantation should be performed, we see that the majority of the arguments have been proscriptive rather than prescriptive. There are valid arguments in favor of facial transplantation based on the prescriptive pillars of bioethics: autonomy, justice, and beneficence. This article attempts to reframe the dialogue in a prescriptive manner.


The coupling relationship and driving mechanism between urbanization and ecosystem services in the Yellow River Basin from a multi-spatial scale perspective.
Rapid urbanization has led to ecological destruction and associated issues. Macro policies wield substantial influence over urbanization and its relationship with the environment. Without considering the differences in scale, macro policies may be ineffective at addressing urbanization's adverse impacts on the environment, and even worsen this relationship. We used data on 622 counties, 76 prefectures, and 7 urban agglomerations in the Yellow River Basin to examine the development level, coupling coordination degree, and spatial patterns of urbanization and ecosystem services at three scales during 2000-2020. Further, we explored the driving mechanisms in the relationship between urbanization and ecosystem services. We found that: First, the coupling coordination was relatively low but showed an upward trend. A sizeable spatiotemporal difference existed, with higher (lower) coordination in the east (west). Second, the coupling coordination of each scale exhibited significant spatial positive correlations. The low-value heterogeneous region was embedded around the agglomeration region, and polarization was significant. The larger the scale, the stronger the agglomeration effect. Further, the coupling coordination spatial agglomeration effect of each scale gradually weakened over time. Third, the spatial and temporal distributions of coupling coordination and its agglomeration characteristics at different scales differed. The urban agglomeration scale showed significant overall coordination or agglomeration characteristics, and prefecture and county regions showed local and unique characteristics within urban agglomerations. Fourth, the dominant factors influencing the spatial patterns of the coupling coordination at the county, prefecture, and urban agglomeration scales differed. The interaction and factor detection showed linear and double-factor enhancements. We find that economic development, government policies, environmental protection, and natural factors are the combined effects of urbanization and ecosystem services. Our research method can provide a reference for other river basins, and the results can help governments in formulating policies for sustainable development at different spatial scales.


Self-Assembled Multilayered Coatings with Multiple Cyclic Self-Healing Capability, Bacteria Killing, Osteogenesis and Angiogenesis Properties on Magnesium Alloys.
Self-healing coatings improve the durability of magnesium (Mg) implants but rapid corrosion still poses a challenge in healing stage. Moreover, Mg-based materials with acceptable bacteria killing, osteogenic and angiogenic properties are challenging in biomedical applications. Herein, the self-healing polymeric coatings are fabricated on Mg alloys using the spin-assisted layer-by-layer (SLbL) assembly of hyaluronic acid (HA) and branched polyethyleneimine (bPEI) followed by chemical crosslinking treatment. The self-healing coatings show excellent adhesion strength and structure stability. The corrosion resistance is improved due to the physical barrier of polymer coatings, which also promote the formation of hydroxyapatite during degradation for further protection of Mg substrate. Owing to the dynamic reversible hydrogen bonds existing between HA and bPEI, the crosslinked multilayered coatings possess fast, substantial, and cyclic self-healing capabilities leading to restoration of the original structure and functions. In vitro investigations reveal that the self-healing coatings have multiple functionalities pertaining to bacteria killing, cytocompatibility, osteogenesis, as well as angiogenesis. In addition, the self-healing coatings stimulate alkaline phosphatase activity, extracellular matrix mineralization, and the expression of osteogenesis-related genes of mBMSCs and HUVECs. This study reveals a feasible strategy to design and prepare versatile self-healing coatings on Mg implants for biomedical applications. This article is protected by copyright. All rights reserved.


Interprofessional education in health professions education programmes in the Arab world: a scoping review protocol.
Interprofessional education is a relatively new addition to health professional education curricula in the Arab world. To understand current practice in this area, a scoping review will enable reporting of essential elements for the implementation of interprofessional education. The objective of this scoping review is to report on the implementation components, including presage, process and product, of interprofessional education in prelicensure health professions education programmes in the Arab world. A comprehensive and systematic search for literature will be conducted using eight electronic databases from their inception to September 2022. A presearch was devised in PubMed, Scopus and CINAHL using a combination of terms related to population, context and concept. The Covidence Systematic Review tool will be used for blind screening, selection and conflict resolution. Data will be presented in tabular format and as a narrative synthesis and will include elements that support the implementation of interprofessional education. This review will be presented according to the Joanna Briggs Institute methodology.Studies conducted with students and/or faculty in prelicensure health professions education programmes will be included. The concept to be explored is interprofessional education. The context is the region commonly known as the Arab world, which includes 18 countries, sharing many common social and cultural traditions and where Arabic is the first language.Excluded will be studies conducted on collaborative practice of health professionals and postlicensure interprofessional education. No ethical approval was required. Findings will be disseminated in conference presentations and peer-reviewed articles.


In utero polychlorinated biphenyl exposures in relation to fetal and early childhood growth.
Polychlorinated biphenyls (PCBs) are industrial chemicals that were used widely for approximately 50 years. Now banned, they are still ubiquitous because of their persistence in the environment, the food chain, and human fatty tissue. High in utero exposures cause developmental deficits accompanied by growth retardation. Studies examining intrauterine growth at lower exposures have been inconsistent, with most such investigations having relied on surrogate exposure indicators such as consumption of fish from contaminated bodies of water. In the 1960s, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at -20 degrees C. At 5 years of age, detailed anthropometric measurements were made on children born in the years 1964-1967. We measured PCBs in specimens from 399 mothers using gas chromatography/electron capture detection. We conducted multiple linear regression to examine the relationship between these organochlorine concentrations and both intrauterine and 5-year growth, with adjustment for medical, lifestyle, sociodemographic, and specimen characteristics. In male infants, higher total in utero PCB exposure was associated with reduced birth weight, head circumference, and weight-for-gestational age. An increase from the 10th to 90th percentile in total PCBs was related to 290 g lower birth weight, a 0.7-cm decrease in head circumference, and for weight for gestational age, a reduction in z-score of 0.6. In girls, smaller head circumference and shorter gestations were observed. In contrast, prenatal PCBs were associated with greater growth in 5-year-old girls, with no apparent effect in 5-year-old boys. Maternally mediated exposure to PCBs may be detrimental to fetal growth, particularly in boys. These effects apparently are not persistent. Interpretation of greater childhood growth of girls is unclear.


Evaluation of risk factors in patients with vulvovaginal candidiasis and the value of chromID Candida agar versus CHROMagar Candida for recovery and presumptive identification of vaginal yeast species.
Vulvovaginal candidiasis (VVC), particularly the recurrent form, remains an intractable problem for clinicians, microbiologists, and patients. It is essential to confirm the clinical diagnosis by mycological methods and avoid empirical therapy. The recovery of yeast in fungal culture, such as on Sabouraud dextrose agar, remains the gold standard for diagnosis. In this investigation, we examined 474 participants, including 122 (25.7%) with acute VVC cases, 249 (52.5%) who had recurrent VVC (RVVC) cases, and 103 (21.7%) healthy controls. We also administered a questionnaire to obtain information on patient lifestyle and medical, gynecological, and sexual history. In addition, we compared the performance of chromID Candida agar (CAN2) to CHROMagar Candida (CAC) and Sabouraud dextrose agar with gentamicin and chloramphenicol (SGC2). The yeasts were identified by conventional methods including the germ tube test, microscopic morphology on cornmeal-Tween 80 agar, and the commercial API 20C AUX system. We detected yeasts in 60 of 122 (49.2%) patients with acute VVC cases, 110 of 249 (44.2%) with RVVC cases, and in 35 of 103 (34%) healthy controls (P = 0.07). A total of 205 samples were found to be positive for fungi (43.2%), of which 176 (85.9%) were monofungal, and 29 (14.1%) were polyfungal. In addition, 198 of these samples (96.6%) were positive on CAN2, 195 (95.1%) on CAC, 189 (92.2%) on SGC2, and 183 (89.3%) samples on all three (P = 0.17). The 234 yeast isolates recovered were C. albicans (n = 118), C. glabrata (n = 82), C. kefyr (n = 11), C. krusei (n = 9), C. lipolytica (n = 3), C. colliculosa (n = 2), C. parapsilosis (n = 2), C. pelliculosa (n = 2), C. tropicalis (n = 2), and other species of Candida (n = 3). Of the 29 polyfungal populations, 28 (96.6%) were detected in CAN2, 25 in (86.2%) CAC, and 25 (86.2%) on both (P = 0.35). Notably, we detected the high predominance of C. albicans+C. glabrata (86.2%) in polyfungal populations. Briefly, the detection of C. albicans after 24 h of incubation was easier on CAN2 (64.4%) than on CAC (25.4%). This study showed that CAN2 is a rapid and reliable medium for immediate identification of C. albicans and for detecting polyfungal populations in vaginal specimens. We observed that the use of antibiotics, intrauterine devices, as well as, perineal laceration, short anovaginal distance (< 3 cm), and genital epilation in common areas are predisposing factors for RVVC (P < 0.001). In addition, we detected that the use of menstrual pad, using an (IUD), and having a history of childbirth increased the risk of both acute and recurrent VVC (P < 0.01), whereas the use of a daily pad and walking daily significantly decreased the risk of both acute and recurrent VVC (P < 0.01).


Chloride-inducible transient apoplastic alkalinizations induce stomata closure by controlling abscisic acid distribution between leaf apoplast and guard cells in salt-stressed Vicia faba.
Chloride stress causes the leaf apoplast transiently to alkalize, an event that is presumed to contribute to the ability of plants to adapt to saline conditions. However, the initiation of coordinated processes downstream of the alkalinization is unknown. We hypothesize that chloride-inducible pH dynamics are a key chemical feature modulating the compartmental distribution of abscisic acid (ABA) and, as a consequence, affecting stomata aperture. Apoplastic pH and stomata aperture dynamics in intact Vicia faba leaves were monitored by microscopy-based ratio imaging and porometric measurements of stomatal conductance. ABA concentrations in leaf apoplast and guard cells were compared with pH dynamics by gas-chromatography-mass-spectrometry (GC-MS) and liquid-chromatography-tandem-mass spectrometry (LC-MS/MS). Results demonstrate that, upon chloride addition to roots, an alkalizing factor that initiates the pH dynamic propagates from root to leaf in a way similar to xylem-distributed water. In leaves, it induces a systemic transient apoplastic alkalinization that causes apoplastic ABA concentration to increase, followed by an elevation of endogenous guard cell ABA. We conclude that the transient alkalinization, which is a remote effect of chloride stress, modulates the compartmental distribution of ABA between the leaf apoplast and the guard cells and, in this way, is instrumental in inducing stomata closure during the beginning of salinity.


Quantification and three-dimensional imaging of the insulitis-induced destruction of beta-cells in murine type 1 diabetes.
The aim of this study was to refine the information regarding the quantitative and spatial dynamics of infiltrating lymphocytes and remaining beta-cell volume during the progression of type 1 diabetes in the nonobese diabetic (NOD) mouse model of the disease. Using an ex vivo technique, optical projection tomography (OPT), we quantified and assessed the three-dimensional spatial development and progression of insulitis and beta-cell destruction in pancreata from diabetes-prone NOD and non-diabetes-prone congenic NOD.H-2b mice between 3 and 16 weeks of age. Together with results showing the spatial dynamics of the insulitis process, we provide data of beta-cell volume distributions down to the level of the individual islets and throughout the pancreas during the development and progression of type 1 diabetes. Our data provide evidence for a compensatory growth potential of the larger insulin(+) islets during the later stages of the disease around the time point for development of clinical diabetes. This is in contrast to smaller islets, which appear less resistant to the autoimmune attack. We also provide new information on the spatial dynamics of the insulitis process itself, including its apparently random distribution at onset, the local variations during its further development, and the formation of structures resembling tertiary lymphoid organs at later phases of insulitis progression. Our data provide a powerful tool for phenotypic analysis of genetic and environmental effects on type 1 diabetes etiology as well as for evaluating the potential effect of therapeutic regimes.


A characterization and an exposure risk assessment of microplastics in settled house floor dust in Istanbul, Turkey.
The presence of microplastics in the indoor environment presents growing environmental and human health risks because of their physicochemical and toxic characteristics. Therefore, we aimed to isolate, identify, and characterize plastic debris in settled house floor dusts. This study is a rare study which assess the risks of plastic debris in settled house dust through multiple approaches including the estimated daily intake, pollution loading index, and polymer hazard index. The results indicated that polyethylene and polypropylene were the predominate polymer type of plastic debris in settled house dust with various shapes and colors. The risk assessment results also indicated the serious impact of microplastics in terms of extremely dangerous contamination as well as the fact that they present a polymer hazard. Results indicated that humans have a higher risk of exposure to microplastics via ingestion rather than inhalation. In addition, infants had a higher risk of potential intake compared to other age groups.


Update on calcium antagonists and the kidney.
The treatment of hypertension has been proven to reduce cardiovascular and renal risk. The role of long-acting calcium channel antagonists in the management of hypertension has been confused in the past because of a lack of controlled clinical trials on people with hypertension and in subpopulations including those with diabetes and renal disease. The year 2002 saw the publication of the results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, the largest ever prospective drug-treatment trial, which involved 33 357 people with hypertension and included a calcium-antagonist group of 9048 individuals. Major publications on blood pressure control in people with kidney disease include the African American Study of Kidney Disease and Hypertension, and publications on people with diabetes include the results of the normotensive arm of the Appropriate Blood Pressure Control in Diabetes trial. The main finding, from the studies reported in the last year, is that blood pressure control can be achieved using one or more of the first-line agents, including diuretics, calcium antagonists and angiotensin-converting enzyme inhibitors. On the basis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, diuretics make clinical and economic sense as initial therapy for those with hypertension. Calcium antagonists are well tolerated and effective and should be considered as the initial drug therapy when diuretics are not tolerated or when multiple drug therapy is indicated. Angiotensin-converting enzyme inhibitors should be used in people with nephropathy, and, in these patients, will nearly always need to be part of multiple drug therapy to achieve blood pressure control. When blood pressure control can be achieved in largely non-nephropathic populations, there is further evidence that the drug class used as initial therapy may not be important. One of the main themes coming from the literature in the last year is that renal function is increasingly being recognized as an important outcome measure and marker of cardiovascular risk. The focus in blood pressure management must now be on identifying those with hypertension and bringing their blood pressure to target. For the majority of those with hypertension and renal disease, multiple drug therapy will be required, and, to achieve blood pressure targets, calcium antagonists are an appropriate part of this regimen. Particular attention is needed for nephropathic patients because of their higher risk of progression and the need for combination therapy; this group is likely to be the focus of future research and publications.


Factors Significantly Associated with Postoperative Neck Pain Deterioration after Surgery for Cervical Ossification of the Posterior Longitudinal Ligament: Study of a Cohort Using a Prospective Registry.
Postoperative neck pain has been reported as an unsolved postoperative complication of surgery for cervical ossification of the posterior longitudinal ligament (OPLL). The aim of the present study was to elucidate factors having a significant association with postoperative deterioration of neck pain in cervical OPLL patients. We studied a cohort of patients in a prospective registry of 478 patients who had undergone cervical spine surgery for cervical OPLL. We excluded those without evaluation of preoperative neck pain. Therefore, 438 patients were included in the present study. Neck pain was evaluated with the visual analogue scale (VAS, 0-100 mm). Postoperative neck pain deterioration was defined as a ≥20 mm increase of VAS neck pain. Patient factors, neurological status, imaging factors and surgical factors were assessed. Univariate analyses followed by multivariate analysis using stepwise logistic regression was performed. Six months after surgery, 50 (11.6%) patients showed postoperative neck pain deterioration and 76 (17.4%) patients showed postoperative neck pain deterioration 2 years after surgery. Six months after surgery, the rate of neck pain deterioration was significantly higher in patients who had undergone posterior surgery. Two years after surgery, the number of levels fused was significantly correlated with neck pain deterioration.


Waist-What? Can a single sensor positioned at the waist detect parameters of gait at a speed and distance reflective of older adults' activity?
One of the problems facing an ageing population is functional decline associated with reduced levels of physical activity (PA). Traditionally researcher or clinician input is necessary to capture parameters of gait or PA. Enabling older adults to monitor their activity independently could raise their awareness of their activitiy levels, promote self-care and potentially mitigate the risks associated with ageing. The ankle is accepted as the optimum position for sensor placement to capture parameters of gait however, the waist is proposed as a more accessible body-location for older adults. This study aimed to compare step-count measurements obtained from a single inertial sensor positioned at the ankle and at the waist to that of a criterion measure of step-count, and to compare gait parameters obtained from the sensors positioned at the two different body-locations. Step-count from the waist-mounted inertial sensor was compared with that from the ankle-mounted sensor, and with a criterion measure of direct observation in healthy young and healthy older adults during a three-minute treadmill walk test. Parameters of gait obtained from the sensors at both body-locations were also compared. Results indicated there was a strong positive correlation between step-count measured by both the ankle and waist sensors and the criterion measure, and between ankle and waist sensor step-count, mean step time and mean stride time (r = .802-1.0). There was a moderate correlation between the step time variability measures at the waist and ankle (r = .405). This study demonstrates that a single sensor positioned at the waist is an appropriate method for the capture of important measures of gait and physical activity among older adults.


[Secondary impingement syndrome in athletes].
Dysfunction of the shoulder joint is based not only on anatomic conditions. The consideration of the special kinesiology of the shoulder helps to understand the shoulder pathology. This mainly applies to young "overhead athletes" like swimmers, handball-, basketball-, volleyball-, and racketplayers. These disciplines cause stress on the anterior joint structures (capsule, ligaments, labrum, subscapularis tendon) and lead to anterior instability. This includes anterior subluxation or even dislocation. Finally, an impingement syndrome with the typical symptoms can frequently result from these conditions. The impingement-syndrome of the elderly must be considered as a primary disease, whereas the young overhead athlete suffers from the impingement syndrome as a secondary disease and does not take the first place in therapy. The first step in therapy should to be treat the muscular imbalance of the shoulder. To gain a regular pattern of motion the rotator cuff must be strengthened. This regimen is likely to be successful in 80-90% of the cases. If the conservative therapy fails the surgical treatment may come into consideration. Arthroscopic surgery has the advantage not to affect the proprioceptivity. To retain the previous level of performance an adequate rehabilitation programme is essential for the athlete.


Induction of mutants with altered DNA composition: effect of ultraviolet on Bacterium paracoli 5099.
The culture of Bacterium paracoli 5099 represents a favorable system for induction of mutants with altered DNA base composition. The frequency of induction of these mutants by ultraviolet radiation is strongly dose-dependent, and has a peak at the ultraviolet exposure equal to 860 ergs. On both sides of this maximum the rate of appearance of mutants decreases, and with the exposures less than 350 and more than 1900 ergs per square millimeter, mutants with altered DNA base composition do not appear at all.


Influenza-attributable deaths, Canada 1990-1999.
The number of deaths attributable to influenza is believed to be considerably higher than the number certified by vital statistics registration as due to influenza. Weekly mortality data for Canada from the 1989/1990 to the 1998/1999 influenza seasons were analysed by cause of death, age group, and place of death to estimate the impact of influenza on mortality. A Poisson regression model was found to accurately predict all-cause, as well as cause-specific mortality, as a function of influenza-certified deaths, after controlling for seasonality, and trend. Influenza-attributable deaths were calculated as predicted less baseline-predicted deaths. In summary, throughout the 1990s there were on average just under 4000 deaths attributable to influenza annually (for an influenza-attributable mortality rate of 13/100,000 persons), varying from no detectable excess mortality for the 1990/1991 influenza season, to 6000-8000 influenza-attributable deaths for the more severe influenza seasons of 1997/1998 and 1998/1999. On average, 8% (95% CI 7-10) of influenza-attributable deaths were certified as influenza, although this percentage varied from 4% to 12% from year to year. Only 15% of the influenza-attributable deaths were certified as pneumonia, and for all respiratory causes, 40%. Deaths were distributed over most causes. The weekly pattern of influenza-certified deaths was a good predictor of excess all-cause mortality.


Opportunistic insights into occupational health hazards associated with waterpipe tobacco smoking premises in the United Kingdom.
Smokefree laws aim to protect employees and the public from the dangers of secondhand smoke. Waterpipe premises have significantly increased in number in the last decade, with anecdotal reports of poor compliance with the smokefree law. The literature is bereft of information pertaining to waterpipe premise employees. This study aimed to opportunistically gather knowledge about the occupational health hazards associated with working in waterpipe premises in London, England. Employees from seven convenience-sampled, smokefree-compliant waterpipe premises in London were observed for occupational activities. Opportunistic carbon monoxide (CO) measurements were made among those with whom a rapport had developed. Observations were thematically coded and analysed. Occupational hazards mainly included environmental smoke exposure. Waterpipe-serving employees were required to draw several puffs soon after igniting the coals, thereby providing quality assurance of the product. Median CO levels were 27.5 ppm (range 21-55 ppm) among these employees. Self-reported employee health was poor, with some suggestion that working patterns and smoke exposure was a contributory factor. The smokefree law in England does not appear to protect waterpipe premise employees from high levels of CO. Continued concerns surrounding chronic smoke exposure may contribute to poor self-reported physical and mental wellbeing.


Who needs innate ability to succeed in math and literacy? Academic-domain-specific theories of intelligence about peers versus adults.
Individuals' implicit theories of intelligence exist on a spectrum, from believing intelligence is fixed and unchangeable, to believing it is malleable and can be improved with effort. A belief in malleable intelligence leads to adaptive responses to challenge and higher achievement. However, surprisingly little is known about the development of academic-domain-specific theories of intelligence (i.e., math vs. reading and writing). The authors examined this in a cross-section of students from 1st grade to college (N = 523). They also examined whether students hold different beliefs about the role of fixed ability in adult jobs versus their own grade. The authors' adult-specific beliefs hypothesis states that when children learn societally held beliefs from adults, they first apply these beliefs specifically to adults and later to students their own age. Consistent with this, even the youngest students (1st and 2nd graders) believed that success in an adult job requires more fixed ability in math than reading and writing. However, when asked about students in their own grade, only high school and college students reported that math involves more fixed ability than reading and writing. High school and college students' math-specific theories of intelligence were related to their motivation and achievement in math, controlling for reading and writing-specific theories. Reading and writing-specific theories did not predict reading and writing-specific motivations or achievement, perhaps because students perceive reading and writing as less challenging than math. In summary, academic-domain-specific theories of intelligence develop early but may not become self-relevant until adolescence, and math-specific beliefs may be especially important targets for intervention. (PsycINFO Database Record


Passive and Active Tobacco Exposure and Children's Lipid Profiles.
Despite reductions in smoking rates, exposure to cigarette smoke remains common among US children and adolescents. In adults, active smoking and secondhand smoke (SHS) exposure have been linked to adverse changes in lipid profiles and increases in inflammatory markers. Evidence that such changes are present before adulthood remains limited, and the extent to which active smoking and SHS exposure affect these cardiovascular measures in children has not been thoroughly assessed. We employed data from 2008 individuals aged 12-19 years from the 2005-2010 National Health and Nutrition Examination Survey. Comparisons of the lipid and inflammatory marker levels among active smokers, those exposed to SHS (as determined by serum cotinine levels), and those unexposed to tobacco smoke were made using linear regression with multiple propensity score adjustment. Compared to unexposed children, lipid and inflammatory marker profiles did not differ among those exposed to SHS exposure. Among active smokers, differences compared to unexposed children were observed in triglyceride levels ( β=8.5 mg/dL, P = .01), the ratio of triglycerides to high-density lipoprotein ( β=0.2, P = .045), and low-density lipoprotein cholesterol ( β=-4.1 mg/dL , P = .03), though these did not reach levels of confirmatory statistical significance. After accounting for sociodemographic characteristics and medical comorbidities, serum lipids and markers of systemic inflammation were not associated with SHS exposure. Tobacco smoke exposure in children may require longer durations of compounded effect before serum lipid abnormalities are detected. This paper adds detail to the study of secondhand smoke's effects on lipid profiles of children and adolescents. Prior research on this topic for these age groups has been limited, and this study provides national, cross-sectional data to show that both secondhand smoke and active smoking in childhood and adolescence is not associated with changes in lipid profiles or markers of inflammation. Tobacco smoke exposure may require longer durations of compounded effect before abnormalities are detected.


[Nosocomial infections in surgical patients. Problems of measuring and comparing results].
What is striking when studying the frequency of nosocomial infection (NI) is the variability of the study data. Different frequency indicators and infection criteria are used for estimates and these make it difficult to compare works. The aim of this work is to estimate the frequency of hospital infection by using different indicators to compare the results. A market study was carried out including patients admitted to four surgical units over the period of one year. The following indicators were used: proportion of patients infected, cumulative number of cases of infection and density of number of cases. The infections were detected through active search and included those acquired in Intensive Care Units and those diagnosed after patients had been discharged from hospital. A total of 14.5% of the patients suffered NI and 5% of the infections were diagnosed after discharge from hospital. In 38.5% of the cases of infection a microbiological study was not requested. The General Surgery Unit had the highest figures for the three indicators. Nevertheless, the magnitude of the differences between services was modified in line with the indicator used. The real percentage of patients with NI is higher than the values given by the usual monitoring systems. Given the trend witnessed over recent years whereby the length of hospital stays is being reduced and early discharge programmes promoted with the aim of increasing efficiency, densities for the number of cases should be estimated and these should include the NI cases diagnosed after hospital discharge in order to make valid comparisons between different institutions and periods of time.


Bimodal redistribution of surface transmembrane glycoproteins during Ca2+-dependent secretion (acrosome reaction) in boar spermatozoa.
We used the acrosome reaction of boar sperm cells to study the dynamics of surface transmembrane glycoproteins (TMG) during a secretory process. The acrosome reaction is the Ca2+-dependent fusion of a large cytoplasmic vesicle (the acrosome) with the overlying segment of the plasma membrane (acrosomal cap) that leads to the release of the acrosomal enzymes. After triggering the acrosome reaction in vitro (2 mM-CaCl2 in the presence of 10 microM-A23187), we used freeze-fracture electron microscopy to follow the topographical rearrangement of a population of acrosomal-cap large intramembrane particles that correspond to transmembrane proteins that bind wheat germ agglutinin. We found that these TMG move in the direction of either one of two opposite poles, proximal and distal, of the acrosomal cap. This bimodal movement of the TMG reorganizes the acrosomal cap into three extensive domains. The first two, on the apical rim and on the equator, are membrane domains to which the TMG are directed and where they accumulate. The third, a large in-between area of protein clearing, corresponds to the region from which TMG were preferentially located before displacement induced by the Ca2+ effect. The topography of these new membrane domains of the acrosomal cap becomes coincident with that of the structural domains of the subjacent acrosomal membrane. Mirroring of the acrosomal membrane by the plasma membrane is followed by fusion between the two membranes, formation of an exquisite labyrinth of hybrid-membrane tubules, followed by fission and release of the acrosomal contents through intertubular fenestrae.


A Clinical and Ethical Dilemma: Expectant Management for Ectopic Pregnancy with a Vital Fetus in a Low-Resource Setting.
Guidelines recommend the prompt surgical removal of any ectopic pregnancy (EP) in the presence of a vital embryo. This treatment impacts future fertility, particularly in low-resource settings where access to assisted reproductive techniques is limited. In addition, growing evidence is reporting live births after conservative management of initially undiagnosed abdominal pregnancies. Therefore, the discussion on the acceptability of expectant management in selected cases has been recently raised. We present and discuss the case of a woman with vital first trimester EP who refused surgical treatment at Princess Christian Maternity Hospital, Freetown, Sierra Leone. She was initially diagnosed with a 12 week pregnancy located in the left adnexal region without hemoperitoneum. She refused both surgical treatment and hospital admission and did not come back to the hospital for antenatal care until 26 weeks of gestational age. Therefore, she was admitted and finally delivered, at 34 weeks of gestation, a 1.9 kg healthy baby which was alive. To disentangle the potential conflict between the ethical principles of medical treatment's beneficence and the patient's autonomy, we provide an update on counselling for a patient with early vital EP in a resource-limited setting and discuss the knowledge gap in this area. Limited access to fertility treatment in low- and middle-income countries may justify the discussion of expectant management as an option in selected cases of uncomplicated vital EP.


Charge transport in DNA duplex/quadruplex conjugates.
DNA conjugates containing adjacent duplex and guanine quadruplex assemblies have been designed to explore charge transport into quadruplex architectures. The quadruplex assemblies have been characterized structurally using circular dichroism and by assaying for chemical protection. Using an intercalating rhodium photooxidant, noncovalently bound or tethered to the duplex end, oxidizing radicals are found to be trapped in the folded quadruplex. Damage is observed almost exclusively at the external tetrads of the quadruplex. Little damage of the center tetrad is observed, due most likely to lowered efficiency of radical trapping within the quadruplex core. This pattern of damage is distinct from that observed for repetitive G sequences within duplex DNA. The data indicate, furthermore, that in the conjugates examined, the guanine quadruplex provides a more effective trap than a 5'-GG-3' guanine doublet within duplex DNA. Within these assemblies, sufficient base-base overlap must exist at the duplex/quadruplex junction to allow for charge migration. This funneling of damage to the quadruplex, as well as the unique pattern of damage within the quadruplex, requires consideration with respect to the analysis of oxidative DNA damage within the cell.


Accurate lattice extraction in integral images.
Integral imaging is one of the most promising techniques for delivering three-dimensional content. Most processing tasks usually require prior knowledge of the size and positions of the elemental images that comprise an integral image. In this paper we propose an automated method for calibrating the acquisition setup, by applying a preprocessing stage to an acquired integral image. The skew angle is extracted and the size and positions of the elemental images are accurately determined. For these purposes a method is developed to automatically identify an elemental image lattice that best matches the acquired integral image.


BCL10 gene mutation in lymphoma.
BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas. No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas. High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%). Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule. (Blood. 2000;95:3885-3890)


Secondary alcohol dehydrogenase as a marker of the conversion between progestagens and androgens in the rat testis.
Supraphysiological doses of LHRH-Analogue blocked the C21 to C19 steroid conversion in the mature Wistar rats testis. It was associated with inhibition of the NAD-dependent secondary alcohol-dehydrogenase (A-D II) histochemical reaction in the Leydig cells. Under this condition the treated group exhibited lower testis, seminal vesicle and prostate weights, intratesticular (IT) and plasmatic (PL) increased progesterone (P4) and decreased testosterone (T) concentrations. We also observed a decrease in the IT androstenedione (delta 4) concentration without pregnenolone (P5) change. All these data confirm a chemical castration pointing to a blockade at the level of the P450C21scc (17 alpha-hydroxylase/17-20 desmolase) enzyme complex. After hCG administration there is no difference in sexual gland weights, while steroid's biosynthesis are stimulated and all IT and PL steroid concentrations increase. A-D II showed a lower optical density in the LHRH-A treated groups and no differences in the hCG rats. The hydroxylase or lyase activity of the P450C21scc may change under certain hormonal conditions as occurs in adrenarche, probably due to conformational changes in the active site of the enzyme system since it is encoded by only one gene. We suppose that the secondary alcohol itself and not the coenzyme reacts with the enzyme active site inhibited by the LHRH-A, since the NAD dependent 3 beta, hydroxysteroid-dehydrogenase (3 beta HOST-D) is affected in the opposite sense. This study shows A-D II reaction as a marker of the mediated P450C21scc enzyme complex activity in the rat testis Leydig cells.


Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord Contusion Injury.
Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping platelet-derived growth factor receptor α (PDGFRα), Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for de novo ensheathment of ∼30% of myelinated spinal axons at injury epicenter 3 months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration. OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited contribution. These findings reveal that PDGFRα+ cells perform diverse roles in CNS repair, as multipotential progenitors that generate both classes of myelinating cells. This endogenous repair might be exploited as a therapeutic target for CNS trauma and disease.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to profound functional deficits, though substantial numbers of axons often survive. One possible explanation for these deficits is loss of myelin, creating conduction block at the site of injury. SCI leads to oligodendrocyte death and demyelination, and clinical trials have tested glial transplants to promote myelin repair. However, the degree and duration of myelin loss, and the extent and mechanisms of endogenous repair, have been contentious issues. Here, we use genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous oligodendrocyte precursors is much more robust than previously recognized. These findings are relevant to many types of CNS pathology, raising the possibility that CNS precursors could be manipulated to repair myelin in lieu of glial transplantation.


Modeling the impact of smoking-cessation treatment policies on quit rates.
Smoking-cessation treatment policies could yield substantial increases in adult quit rates in the U.S. The goals of this paper are to model the effects of individual cessation treatment policies on population quit rates, and to illustrate the potential benefits of combining policies to leverage their synergistic effects. A mathematical model is updated to examine the impact of five cessation treatment policies on quit attempts, treatment use, and treatment effectiveness. Policies include: (1) expand cessation treatment coverage and provider reimbursement; (2) mandate adequate funding for the use and promotion of evidence-based, state-sponsored telephone quitlines; (3) support healthcare system changes to prompt, guide, and incentivize tobacco treatment; (4) support and promote evidence-based treatment via the Internet; and (5) improve individually tailored, stepped-care approaches and the long-term effectiveness of evidence-based treatments. The annual baseline population quit rate is 4.3% of all current smokers. Implementing any policy in isolation is projected to increase the quit rate to between 4.5% and 6%. By implementing all five policies in combination, the quit rate is projected to increase to 10.9%, or 2.5 times the baseline rate. If fully implemented in a coordinated fashion, cessation treatment policies could reduce smoking prevalence from its current rate of 20.5% to 17.2% within 1 year. By modeling the policy impacts on the components of the population quit rate (quit attempts, treatment use, treatment effectiveness), key indicators are identified that need to be analyzed in attempts to improve the effect of cessation treatment policies.


Nocardioides flavus sp. nov., isolated from marine sediment.
A Gram-stain-positive, aerobic, non-motile, non-spore-forming and short rod-shaped actinomycete strain, Y4T, was isolated from a sediment sample collected from the Western Pacific. This isolate grew in the presence of 0-10 % (w/v) NaCl and at pH 6.0-9.0 and 4-40 °C; optimum growth was observed with 1 % (w/v) NaCl and at pH 7.0 and 35-37 °C. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain Y4T belonged to the genus Nocardioides and was most closely related to the type strains Nocardioides ganghwensis JC2055T (98.0 %) and Nocardioides exalbidus RC825T (98.0 %), followed by Nocardioides alpinus Cr7-14T (97.9 %), Nocardioides oleivorans DSM 16090T (97.9 %), Nocardioides furvisabuli SBS-26T (97.4 %) and Nocardioides hwasunensis HFW-21T (97.4 %). Sequence similarities between strain Y4T and the other related species of the genus Nocardioides were less than 96.3 %. Strain Y4T had MK-8(H4) and MK-7(H4) as the predominant respiratory quinones and C17 : 1ω8c, iso-C16 : 0 and C17 : 0 as major fatty acids. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unknown phospholipid, two unknown glycolipids and one unknown lipid. The DNA G+C content was 70.4 mol%. The diagnostic diamino acid in the cell-wall peptidoglycan was ll-diaminopimelic acid. Strain Y4T could be differentiated from recognized Nocardioides species based on phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA hybridization data. Thus, strain Y4T is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioides flavus sp. nov. is proposed. The type strain is Y4T (=MCCC 1A09944T=LMG 28100T=JCM 19770T=CGMCC 1.12791T).


Analyzing the Impact of Demographic Variables on Spreading and Forecasting COVID-19.
The aim of this study is to analyse the coronavirus disease 2019 (COVID-19) outbreak in Bangladesh. This study investigates the impact of demographic variables on the spread of COVID-19 as well as tries to forecast the COVID-19 infected numbers. First of all, this study uses Fisher's Exact test to investigate the association between the infected groups of COVID-19 and demographical variables. Second, it exploits the ANOVA test to examine significant difference in the mean infected number of COVID-19 cases across the population density, literacy rate, and regions/divisions in Bangladesh. Third, this research predicts the number of infected cases in the epidemic peak region of Bangladesh for the year 2021. As a result, from the Fisher's Exact test, we find a very strong significant association between the population density groups and infected groups of COVID-19. And, from the ANOVA test, we observe a significant difference in the mean infected number of COVID-19 cases across the five different population density groups. Besides, the prediction model shows that the cumulative number of infected cases would be raised to around 500,000 in the most densely region of Bangladesh, Dhaka division.


Normobaric hyperoxia delays perfusion/diffusion mismatch evolution, reduces infarct volume, and differentially affects neuronal cell death pathways after suture middle cerebral artery occlusion in rats.
Normobaric hyperoxia (NBO) has been shown to extend the reperfusion window after focal cerebral ischemia. Employing diffusion (DWI)- and perfusion (PWI)-weighted magnetic resonance imaging (MRI), the effect of NBO (100% started at 30 mins after middle cerebral artery occlusion (MCAO)) on the spatiotemporal evolution of ischemia during and after permanent (pMCAO) and transient suture middle cerebral artery occlusion (tMCAO) was investigated (experiment 3). In two additional experiments, time window (experiment 1) and cell death pathways (experiment 2) were investigated in the pMCAO model. In experiment 1, NBO treatment reduced infarct volume at 24 h after pMCAO by 10% when administered for 3 h (P>0.05) and by 44% when administered for 6 h (P<0.05). In experiment 2, NBO acutely (390 mins, P<0.05) reduced in situ end labeling (ISEL) positivity in the ipsilesional penumbra but increased contralesional necrotic as well as caspase-3-mediated apoptotic cell death. In experiment 3, CBF characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the apparent diffusion coefficient (ADC)-derived lesion volume essentially stopped progressing during NBO treatment, resulting in a persistent PWI/DWI mismatch that could be salvaged by delayed (3 h) reperfusion. In conclusion, NBO (1) acutely preserved the perfusion/diffusion mismatch without altering CBF, (2) significantly extended the time window for reperfusion, (3) induced lasting neuroprotection in permanent ischemia, and (4) although capable of reducing cell death in hypoperfused tissue it also induced cell death in otherwise unaffected areas. Our data suggest that NBO may represent a promising strategy for acute stroke treatment.


Anatomical development of urinary bladder during the fetal period.
The aim of this study was to determine the development, location, and size of the urinary bladder during the fetal period. The study was performed on 149 human fetuses between 9 and 40 weeks of gestation. The location of the urinary bladder with respect to transverse plane between the highest point of pubic symphysis and the sacral promontory and median sagittal plane was first determined. The dimensions and the angle of the urinary bladder were measured, and bladder shapes were determined. In addition, the edges of the vesical trigone were measured. There was no significant difference between sexes for any of the parameters (P > 0.05). A significant correlation was observed between all parameters and gestational age (P < 0.001). The urinary bladder was located above the transverse plane in most of the cases (83%) and in the median sagittal plane in every case. It was determined that the angle of bladder did not change and the mean value of the angle was 151 degrees during the fetal period. Bladder was categorized into four different shapes (ellipsoid, round, cuboid, and triangular), and the most common shape found during the fetal period was cuboid. The vesical trigone was an isosceles triangle during the fetal period. The new data provided by this study will enable evaluation of the development of the fetal urinary bladder, and should be useful in several fields such as anatomy, fetopathology, medical imaging, obstetrics, and pediatric urology.


Educational and Vocational Issues in Traumatic Brain Injury.
This article describes some of the current issues related to return to school and employment for individuals with traumatic brain injury. A strong, collaborative partnership between an individual's health care providers and key stake holders is essential to a smooth transition back to school or work. Ways to improve current practices and ensure more timely and appropriate educational and employment services and supports for individuals with traumatic brain injury are described. Some recommendations on areas for future research are also offered.


Expression of oncogenic K-ras from its endogenous promoter leads to a partial block of erythroid differentiation and hyperactivation of cytokine-dependent signaling pathways.
When overexpressed in primary erythroid progenitors, oncogenic Ras leads to the constitutive activation of its downstream signaling pathways, severe block of terminal erythroid differentiation, and cytokine-independent growth of primary erythroid progenitors. However, whether high-level expression of oncogenic Ras is required for these phenotypes is unknown. To address this issue, we expressed oncogenic K-ras (K-ras(G12D)) from its endogenous promoter using a tetracycline-inducible system. We show that endogenous K-ras(G12D) leads to a partial block of terminal erythroid differentiation in vivo. In contrast to results obtained when oncogenic Ras was overexpressed from retroviral vectors, endogenous levels of K-ras(G12D) fail to constitutively activate but rather hyperactivate cytokine-dependent signaling pathways, including Stat5, Akt, and p44/42 MAPK, in primary erythroid progenitors. This explains previous observations that hematopoietic progenitors expressing endogenous K-ras(G12D) display hypersensitivity to cytokine stimulation in various colony assays. Our results support efforts to modulate Ras signaling for treating hematopoietic malignancies.


Metal accumulation by bacteria with particular reference to dissimilatory sulphate-reducing bacteria.
Dissimilatory sulphate-reducing bacteria, genera Desulfovibrio and Desulfotomaculum, exhibit a superior ability, over assimilatory organisms, to extract three amounts of metals from culture media. This property does not appear to be solely a function of the presence of H2S. In media containing elevated amounts of Fe, electron dense particles, provisionally identified as FeS, are deposited within the cells of dissimilatory bacteria.


Plasma-Induced Exfoliation Provides Onion-Like Graphene-Surrounded MoS2 Nanosheets for a Highly Efficient Hydrogen Evolution Reaction.
With the goal of obtaining sustainable earth-abundant electrocatalyst materials displaying high performance in the hydrogen evolution reaction (HER), here we propose a facile one-pot plasma-induced electrochemical process for the fabrication of new core-shell structures of ultrathin MoS2 nanosheets engulfed within onion-like graphene nanosheets (OGNs@MoS2). The resultant OGNs@MoS2 structures not only increased the number of active sites of the semiconducting MoS2 nanosheets but also enhanced their conductivity. Our OGNs@MoS2 composites exhibited high HER performance, characterized by a low overpotential of 118 mV at a current density of 10 mA cm-2, a Tafel slope of 73 mV dec-1, and long-time stability of 105 s without degradation; this performance is much better than that of the sheet-like graphene-wrapped MoS2 composite GNs@MoS2 (182 mV, 82 mV dec-1) and is among the best ever reported for composites involving MoS2 and graphene nanosheets prepared through a simple one-batch process and using a low temperature and a short time for the HER. This approach appears to be an effective and simple strategy for tuning the morphologies of composites of graphene and transition metal dichalcogenide materials for a broad range of energy applications.


Nutritional interventions for optimizing healthy body composition in older adults in the community: an umbrella review of systematic reviews.
Optimizing body composition for healthy aging in the community is a significant challenge. There are a number of potential interventions available for older people to support both weight gain (for those who are underweight) and weight loss (for overweight or obese people). While the benefits of weight gain for underweight people are generally clearly defined, the value of weight loss in overweight or obese people is less clear, particularly for older people. This umbrella review aimed to measure the effectiveness of nutritional interventions for optimizing healthy body composition in older adults living in the community and to explore theirqualitative perceptions. The participants were older adults, 60 years of age or older, living in the community. The review examinedsix types of nutritional interventions: (i) dietary programs, (ii) nutritional supplements, (iii) meal replacements, (iv) food groups, (v) food delivery support and eating behavior, and (vi) nutritional counselling or education. This umbrella review considered any quantitative systematic reviews and meta-analyses of effectiveness, or qualitative systematic reviews, or a combination (i.e. comprehensive reviews). The quantitative outcome measures of body composition were: (i) nutritional status (e.g. proportion of overweight or underweight patients); (ii) fat mass (kg), (iii) lean mass or muscle mass (kg), (iv) weight (kg) or BMI (kg/m), (v) bone mass (kg) or bone measures such as bone mineral density, and (vi) hydration status. The phenomena of interestwere the qualitative perceptions and experiences of participants. We developed an iterative search strategy for nine bibliometric databases and gray literature. Critical appraisal of 13 studies was conducted independently in pairs using standard Joanna Briggs Institute tools. Six medium quality and seven high quality studies were identified. Data was extracted independently in pairs from all 13 included studies using the standard Joanna Briggs Institute data extraction tool. Only quantitative studies of effectiveness were included. The strength of evidence assessing the effectiveness of interventionswas graded using a traffic light system (green, amber, red). An overall assessment of the quality of the evidence for each comparison was undertaken. More systematic reviews investigating weight gain than those investigating weight loss were included. Studies onweight gain showed improved body composition for oral nutritional supplements on its own, for oral nutritional supplements in combination with resistance exercise training, and for oral nutritional supplements in combination with nutrition counselling. Studies on weight loss showed that diet in combination with exercise, diet in combination with exercise and nutrition counselling, and nutrition counselling on its own all can lead to reduced weight in older people. The outcomes of lean mass and weight/BMI were responsive to nutritional interventions, but fat mass did not vary. There were no qualitative reviews identified. Although effective interventions for weight gain and weight loss to optimize body composition of older people in the community were identified,making long term, clinically relevant changes in body composition is difficult. Multiple interventions are more effective than single interventions.


Enhanced fluid transport across gallbladder mucosa in experimental cholelithiasis.
Fluid transport of the gallbladder has been studied in two models of experimental cholelithiasis: dihydrocholesterol-induced gallstones in the rabbit and lincomycin-induced gallstones in the guinea pig. Using the noneverted explained gallbladder of the rabbit and the guinea pig, the transport of luminal to serosal fluid has been quantitated before, during, and after stone formation. The everted gallbladder preparation of the rabbit has also been used to measure fluid transport before and during gallstone formation. In both models, an increased fluid transport was observed in the phase of gallstone induction and a return to normal after stones were formed. This abnormality preceded the appearance of conventional histological features of cholecystitis. There was also a coincidental increase in glycoprotein production from and cell proliferation of the gallbladder epithelium. This enhancement of fluid transfer may play a contributing role in the genesis of gallstones.


Coordination of a step with a reach.
Although natural reaching behavior can easily include forward body movement, most laboratory studies of reaching have constrained the body to be stationary. Recently, however, it has been shown that normal subjects exhibit a different pattern of errors when attempting to pinpoint remembered target locations, depending on whether or not the reach includes a step. In the study of Flanders et al., these errors appeared to be due to the strategy of eye/head/hand coordination which normally comes into play when the body is moving toward the target. Since the spatial positioning of the head was found to partially explain the errors in hand placement, the present study examined the movements of patients with bilateral vestibular deficits in order to further analyze the whole-body coordination. Somewhat surprisingly, the patients exhibited the same pattern of head movement and the same errors in hand placement as did the control subjects. Nevertheless, the patients' movements clearly exhibited evidence for an abnormal decomposition of elbow extension and trunk rotation. Furthermore the patients' (spatial) hand paths were significantly more curved than those of control subjects and, only in the patients, paths to remembered targets were significantly more curved than paths to visible targets. Thus for movements to remembered targets, the patients tended to move the hand to the same incorrect spatial positions as control subjects but spatiotemporal aspects of the arm and body movement differed. The results are consistent with the idea that vestibular patients are overly dependent upon visual cues, and support the hypothesis that this stepping and reaching behavior is largely dependent upon a visual reference signal.


Children's and adults' use of fictional discourse and semantic knowledge for prediction in language processing.
Using real-time eye-movement measures, we asked how a fantastical discourse context competes with stored representations of real-world events to influence the moment-by-moment interpretation of a story by 7-year-old children and adults. Seven-year-olds were less effective at bypassing stored real-world knowledge during real-time interpretation than adults. Our results suggest that children privilege stored semantic knowledge over situation-specific information presented in a fictional story context. We suggest that 7-year-olds' canonical semantic and conceptual relations are sufficiently strongly rooted in statistical patterns in language that have consolidated over time that they overwhelm new and unexpected information even when the latter is fantastical and highly salient.


Events at the cardiac sarcolemma: localization and movement of contractile-dependent calcium.
At present there is a controversy about the appropriate model for excitation-contraction (E-C) coupling in mammalian heart muscle. There is an apparent conflict between the data derived from voltage clamp experiments and data derived from isotopic exchange studies. The maximum transsarcolemmal Ca influx as derived from voltage clamp studies is not more than 10 mumoles/kg wet weight heart per beat. This is barely enough to achieve 10% activation of contractile force. It has been proposed, therefore, that the remainder of the required Ca is derived from intracellular sites. However, ionic exchange studies, using specific E-C uncouplers such as lanthanum, indicate that the major source of coupling Ca is external to the sarcolemma. Its movement, during E-C coupling, would then have to be nonelectrogenic since influx of this quantity of Ca is not discerned with voltage clamp experiments. It is proposed that on excitation, Ca moves across the cardiac sarcolemma by two routes: 1) a small amount through a pore or channel and 2) a much larger amount via an electroneutral carrier. Movement through the pore would be electrogenic and therefore measurable with the voltage clamp whereas movement via the carrier would not be evident with the clamp. The model is consistent with the proposal that the immediate source of contractile-dependent Ca in mammalian heart is derived from sites external to the sarcolemmal (and T tubular) membrane.


[Intraoperative identification of the supplementary motor area in neurooncological surgery].
The main objective of the present work was to identify, by means of intraoperative electrical stimulation, the supplementary motor area (SMA) region which is implicated in complex motor function. The functional prognostic relevance of the surgical preservation of this area was also analyzed. Fifteen patients with tumors infiltrating the premotor cortex were selected. All patients were operated under awake conditions. Primary motor cortex was identified with intraoperative electrical stimulation (IES). To identify the SMA, patients were asked to do a finger opposition motor task with their hand contralateral to the lesion, that was blocked by electrically stimulating the premotor cerebral cortex. SMA was identified in all patients with IES. Complete surgical resection was achieved in 13 patients (86.6%) and subtotal in 2 patients (13.3%). SMA function was preserved in 14 patients (93.3%). In only one patient the SMA was partially resected because of tumor infiltration (6.6%). In the immediate postoperative period, 8 patients (53.3%) did not show changes in comparison to their preoperative clinical status, and 2 patients improved. At 6 months follow up, 5 patients (33.3%) were asymptomatic and 10 patients showed permanent deficits. In this last group, five patients (33.3%) showed mild deficits that did not interfere with a normal life. In the other 5 patients (33.3%), permanent deficits interfered with daily life activities: two patients presented severe hemiparesis 3/5 (same similar to their preoperative status with no improvement), one patient had motor aphasia, and two other patients (13.3%) showed permanent left SMA syndrome. In two patients with severe postoperative hemiparesis, tumor infiltration of primary motor cortex and piramidal pathway was observed; severe preoperative motor deficit (KPS <70) was associated with poor functional outcome. Intraoperative electrical cortical stimulation is useful to identify the SMA. Once identified, SMA preservation decreases the risk of postoperative symptoms and permanent SMA syndrome. When SMA is infiltrated by the tumor, radical resection may cause permanent neurological deficits, specially in the dominant hemisphere. Severe preoperative motor deficit was associated with poor outcome.


Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE.
Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant. A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points. A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively). Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.


Structural integrity of centromeric chromatin and faithful chromosome segregation requires Pat1.
The kinetochore (centromeric DNA and associated protein complex) is essential for faithful chromosome segregation and maintenance of genome stability. Here we report that an evolutionarily conserved protein Pat1 is a structural component of Saccharomyces cerevisiae kinetochore and associates with centromeres in a NDC10-dependent manner. Consistent with a role for Pat1 in kinetochore structure and function, a deletion of PAT1 results in delay in sister chromatid separation, errors in chromosome segregation, and defects in structural integrity of centromeric chromatin. Pat1 is involved in topological regulation of minichromosomes as altered patterns of DNA supercoiling were observed in pat1Δ cells. Studies with pat1 alleles uncovered an evolutionarily conserved region within the central domain of Pat1 that is required for its association with centromeres, sister chromatid separation, and faithful chromosome segregation. Taken together, our data have uncovered a novel role for Pat1 in maintaining the structural integrity of centromeric chromatin to facilitate faithful chromosome segregation and proper kinetochore function.


Global analysis of the small RNA transcriptome in different ploidies and genomic combinations of a vertebrate complex--the Squalius alburnoides.
The Squalius alburnoides complex (Steindachner) is one of the most intricate hybrid polyploid systems known in vertebrates. In this complex, the constant switch of the genome composition in consecutive generations, very frequently involving a change on the ploidy level, promotes repetitive situations of potential genomic shock. Previously in this complex, it was showed that in response to the increase in genome dosage, triploids hybrids could regulate gene expression to a diploid state. In this work we compared the small RNA profiles in the different genomic compositions interacting in the complex in order to explore the miRNA involvement in gene expression regulation of triploids. Using high-throughput arrays and sequencing technologies we were able to verify that diploid and triploid hybrids shared most of their sequences and their miRNA expression profiles were high correlated. However, an overall view indicates an up-regulation of several miRNAs in triploids and a global miRNA expression in triploids higher than the predicted from an additive model. Those results point to a participation of miRNAs in the cellular functional stability needed when the ploidy change.


The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line.
Cytokines belonging to the TNF superfamily play a relevant role in neurodegenerative processes. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), released during neuronal injury, has proven to potently mediate and sustain neurotoxic processes leading to neuronal death. Similarly to TRAIL, the cytokine Glucocorticoid-induced TNF receptor ligand (GITRL) is able to transduce proapoptotic signals. In spite of the array of reports suggesting relationships between TRAIL and other cytokines, scanty data are, so far, available about a GITRL/TRAIL crosstalk. Here, we investigated possible interactions between TRAIL and the GITRL system in an in vitro model of neurodegeneration, using the human cortical neuronal cell line HCN-2. Cultured HCN-2 neurons were incubated at different times with GITRL and/or TRAIL, and thereafter nucleic acid and protein expression were measured. Real-time PCR analysis showed that the human cortical neuronal cell line HCN-2 does not express GITRL mRNA, but the latter is induced after treatment with TRAIL. In addition, HCN-2 cells did not express the GITRL receptor GITR mRNA, neither in control cultures, nor after treatment with TRAIL. All mRNA data were confirmed by western blot analysis of proteins. Cell viability assay showed that TRAIL, when associated to GITRL, was able to exert additive toxic effects. A counterproof was provided in experiments performed blocking GITRL, in which TRAIL-mediated toxicity appeared significantly reduced. Results suggest that GITRL/TRAIL redundancy during neurodegenerative processes implies extended potentiation of detrimental effects of both cytokines on neurons, eventually leading to larger cell damage and death. Finally, characterization of novel molecular targets within the TRAIL/GITRL interplay may represent a platform for innovative therapy of neurodegenerative disorders.


The unhappy postdoc: a survey based study.
Background: The emerging public discourse about the "broken" postdoc system is mostly conceptual. The current work offers an attempt to quantify postdocs' perceptions, goals, and well-being. Methods: A survey of 190 postdocs in North America. Results: This article first reveals a surprisingly unhappy postdoc community with low satisfaction with life scores. Second, it demonstrates how over the course of the fellowship many postdocs lose interest in the goal of pursuing a tenure track academic position (~20%) or in recommending the postdoc track to others (~30%). Finally, we find that among a large number of factors that can enhance satisfaction with life for postdocs (e.g., publication productivity, resources available to them) only one factor stood out as significant: the degree to which atmosphere in the lab is pleasant and collegial. Conclusions: Our findings can stimulate policy, managerial, and career development improvements in the context of the postdoc system.