The inhibitory anti-beta1 integrin monoclonal antibody 13 recognizes an epitope that is attenuated by ligand occupancy. Evidence for allosteric inhibition of integrin function.
Integrin-ligand binding causes conformational changes in the integrin, as evidenced by the increased expression of epitopes known as ligand-induced binding sites. Some monoclonal antibodies (mAbs) that recognize ligand-induced binding sites stimulate ligand binding, possibly by stabilizing the ligand-occupied conformation of the integrin. Here we have investigated the effect of ligand recognition by alpha5beta1 on the binding of a mAb that inhibits beta1 integrin function (mAb 13). Ligand (fibronectin fragment or GRGDS peptide) decreased the binding of mAb 13 to alpha5beta1. Analysis of this inhibition showed that at high ligand concentrations, approximately 50% of the total integrin bound mAb 13 with >50-fold lower affinity than in the absence of ligand. The concentration of ligand required for half-maximal inhibition of antibody binding was independent of antibody concentration, suggesting that ligand acts as an allosteric inhibitor of mAb 13 binding. Hence, ligand and mAb 13 did not appear to compete directly for binding to alpha5beta1. The stimulatory anti-beta1 mAb 9EG7 was found to increase the maximum level of ligand binding approximately 2-fold, indicating that up to 50% of the total integrin could not bind ligand without 9EG7 stimulation. Analysis of mAb 13 binding in the presence of 9EG7 and ligand (i.e. maximal ligand occupancy) demonstrated that essentially all of the integrin bound mAb 13 with very low or zero affinity. Our results demonstrate that mAb 13 recognizes an epitope that is dramatically attenuated in the ligand-occupied form of alpha5beta1. Hence, since mAb 13 preferentially recognizes the unoccupied conformation of the integrin, the antibody may inhibit ligand binding by stabilizing the unoccupied state of alpha5beta1. In addition, we present evidence that the binding of mAb 13 to ligand-occupied alpha5beta1 may also induce a conformational change in the integrin, resulting in the displacement of ligand.


Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I.
Patients with the autoimmune polyendocrine syndrome I (APS I) have high titers of neutralizing IgG autoantibodies against type I interferons (IFNs), in particular IFN-omega. Until now, the most specific assay has been the antiviral interferon neutralizing assay (AVINA), which has the drawbacks of requiring a cytolytic virus, being cumbersome and difficult to standardise. We have developed a fast and reliable immunoassay based on radiolabelled IFN-omega for quantifying anti-IFN-omega antibodies. Sera from 48 APS I patients were analysed together with those from 5 control groups. All sera from APS I patients were positive for anti-IFN-omega, while, except one serum, all sera from the controls were negative. This method has the advantage over bioassays that it is readily adapted to high throughput. It provides an alternative, sensitive and specific diagnostic test for APS I, and an ideal screening tool to precede mutational analyses of the AIRE gene in suspected APS I cases.


Social brain circuitry and social cognition in infants born preterm.
Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention.


Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.
High concentrations of oxygen can induce pulmonary toxicity and cause injury to alveolar epithelial and endothelial cells. The present study was performed to determine whether the potent epithelial and endothelial fibroblast growth factor 1 (FGF-1) protected against hyperoxia-induced lung injury. Recombinant adenovirus carrying the gene encoding human secreted FGF-1 (Ad. FGF1) increased the proliferation of lung epithelial cells in vitro. Ad.FGF1 or control vector with an empty expression cassette (Ad.V152) was administered intratracheally to Wistar rats. With Ad.FGF1 (10(9), 5 x 10(9), 10(10), or 5 x 10(10) viral particles [VP]), FGF-1 protein was found in bronchoalveolar lavage fluid 4 days postinfection at levels proportional to the viral dose and was detected in plasma after doses of 10(10) VP or more were administered. Histological examination of the lungs showed intense proliferation and apoptosis of alveolar and bronchial epithelial cells, with few inflammatory cells. The alveolar architecture returned to normal within 17 days. Rats pretreated with Ad.FGF1 (10(9) or 5 x 10(9) VP) 2 days before exposure to hyperoxia (95% O2) survived, whereas rats pretreated with Ad.V152 died within 3 days. In conclusion, adenovirus-mediated FGF-1 overexpression in the lungs causes epithelial cell proliferation and has beneficial effects in hyperoxic lung injury.


Quercetin induces p53-independent apoptosis in human prostate cancer cells by modulating Bcl-2-related proteins: a possible mediation by IGFBP-3.
Quercetin, a flavonoid found in onion, grapes, green vegetables, etc., has been shown to possess potent antiproliferative effects against various malignant cells. We report insulin-like growth factor-binding protein-3 (IGFBP-3) as an effector of quercetin-induced apoptosis in human prostate cancer cell lines in a p53-independent manner. We evaluated the production of IGFBP-3 in quercetin-treated cells. Apoptosis was studied in quercetin-treated cells to study the IGFBP-3-mediated role with flow cytometry and DNA fragmentation. Protein expressions of Bcl-2, Bcl-x(L), and Bax were studied by Western blot. Increased production of IGFBP-3 was associated with the increased ratio of proapoptotic to antiapoptotic members of the Bcl-2 family. In quercetin-treated PC-3 cells, an increase in Bax protein expression and a decrease in Bcl-x(L) protein and Bcl-2 protein were observed. As PC-3 is a p53-negative cell line, these modulations of proapoptotic proteins and induction of apoptosis were independent of p53. The level of IGFBP-3 on the response of PC-3 cells to quercetin was examined. There was a twofold increase in IGFBP-3 level in conditioned media of 100 microM quercetin-treated cells. Quercetin also brought a peak at sub-G1 in PC-3 cells. Thus, increased level of IGFBP-3 was associated with increased proapoptotic proteins and apoptosis in response to quercetin, suggesting it may be a p53-independent effector of apoptosis in prostate cancer cells via its modulation of the Bax/Bcl-2 protein ratio.


Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome.
Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.


Response of renal and femoropopliteal arteries to Palmaz stent implantation assessed with intravascular ultrasound.
To establish the processes responsible for late lumen loss in renal and femoropopliteal Palmaz stents using intravascular ultrasound (IVUS). The first 7 consecutive patients treated with stents for renal (n = 4) and femoropopliteal (n = 3) arterial occlusive disease were studied with IVUS immediately after angiographically successful stent placement (< 10% residual stenosis) and periodically during follow-up. Images of both stent edges and the most stenotic site inside the stent at followup were matched to the same cross sections captured immediately after stent placement for quantitative analysis. Late lumen loss in renal artery stents at 5 to 34 months was considerably less than in femoropopliteal stents (17% versus 62%, respectively). In the renal location, late lumen loss (3.0 +/- 1.3 mm2) was due to neointimal hyperplasia, whereas stent area remained unchanged (3% decrease). Late lumen loss (7.4 +/- 8.2 mm2) in femoropopliteal stents was due to neointimal hyperplasia and stent area reduction (26%). Overall, in both types of arteries, neointimal development and stent area reduction were larger at the most stenotic site than at the stent edges. These data suggest that there may be differences between renal and femoropopliteal arteries in the extent of hyperplastic response to stents.


Transoral robotic surgery for base of tongue neoplasms.
Surgery to the base of tongue (BOT) in the presence of neoplasm is a challenging topic for head and neck surgeons. This area is difficult to access and includes important neurovascular structures such as the hypoglossal nerve and lingual artery. The pivotal role of the tongue base in swallowing makes planning the surgical approach more challenging. The surgical approaches vary from open neck/mandibulotomy to transoral laser surgery (TLS) which have significant disadvantages. After introduction of transoral robotic surgery (TORS) to otolaryngology practice with the da Vinci Surgical system, we have in our armamentarium a new approach to the BOT. The improved exposure with new retractors, 3-dimensional (3-D) visualization and magnification and advanced motion capacity allow for increased ease to perform surgery in this difficult area. In recent years, several articles published the data about safety and feasibility of TORS for various conditions. This article presents our approach to the BOT for neoplasms including malignant and benign lesions.


Use of a "Super-child" Approach to Assess the Vitamin A Equivalence of Moringa oleifera Leaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children.
Background: Worldwide, an estimated 250 million children <5 y old are vitamin A (VA) deficient. In Mexico, despite ongoing efforts to reduce VA deficiency, it remains an important public health problem; thus, food-based interventions that increase the availability and consumption of provitamin A-rich foods should be considered.Objective: The objectives were to assess the VA equivalence of 2H-labeled Moringa oleifera (MO) leaves and to estimate both total body stores (TBS) of VA and plasma retinol kinetics in young Mexican children.Methods: β-Carotene was intrinsically labeled by growing MO plants in a 2H2O nutrient solution. Fifteen well-nourished children (17-35 mo old) consumed puréed MO leaves (1 mg β-carotene) and a reference dose of [13C10]retinyl acetate (1 mg) in oil. Blood (2 samples/child) was collected 10 times (2 or 3 children each time) over 35 d. The bioefficacy of MO leaves was calculated from areas under the composite "super-child" plasma isotope response curves, and MO VA equivalence was estimated through the use of these values; a compartmental model was developed to predict VA TBS and retinol kinetics through the use of composite plasma [13C10]retinol data. TBS were also estimated with isotope dilution.Results: The relative bioefficacy of β-carotene retinol activity equivalents from MO was 28%; VA equivalence was 3.3:1 by weight (0.56 μmol retinol:1 μmol β-carotene). Kinetics of plasma retinol indicate more rapid plasma appearance and turnover and more extensive recycling in these children than are observed in adults. Model-predicted mean TBS (823 μmol) was similar to values predicted using a retinol isotope dilution equation applied to data from 3 to 6 d after dosing (mean ± SD: 832 ± 176 μmol; n = 7).Conclusions: The super-child approach can be used to estimate population carotenoid bioefficacy and VA equivalence, VA status, and parameters of retinol metabolism from a composite data set. Our results provide initial estimates of retinol kinetics in well-nourished young children with adequate VA stores and demonstrate that MO leaves may be an important source of VA.


Proteomic characterization of human multiple myeloma bone marrow extracellular matrix.
The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM, are critical to the pathogenesis of the disease and the development of drug resistance. Nevertheless, composition of the ECM in MM and its role in supporting MM pathogenesis has not been reported. We have applied a novel proteomic-based strategy and defined the BM ECM composition in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed and relapsed MM compared with healthy donor-derived BM ECM. In this study, we show that the tumor ECM is remodeled at the mRNA and protein levels in MGUS and MM to allow development of a permissive microenvironment. We further demonstrate that two ECM-affiliated proteins, ANXA2 and LGALS1, are more abundant in MM and high expression is associated with a decreased overall survival. This study points to the importance of ECM remodeling in MM and provides a novel proteomic pipeline for interrogating the role of the ECM in cancers with BM tropism.


Parent involvement in school: English speaking versus Spanish speaking families.
The purpose of the present study was to explore the relationships between three predictor variables (attitude toward school, parent-child communication, and school commitment action) and the criterion variable (parent involvement) in a representative sample and to examine if these relationships were consistent across three groups (English speaking Caucasian family, English speaking Latino family, and Spanish speaking Latino families). Using a national database (N = 9.841), multi-group SEM analyses were conducted to investigate the relationship between three predictor variables and the criterion variable in three family groups. While all three predictor variables significantly predicted parent involvement in English speaking Caucasian and Latino families, only two variables (parent-child communication and school commitment actions), significantly predicted parent involvement in Spanish speaking Latino families. The results of this study suggest that when administrators, teachers and counselors in school strive to share specific school-related information with Latino families, Spanish speaking families are more likely to become involved with schools.


The neuropsychology of face perception: beyond simple dissociations and functional selectivity.
Face processing relies on a distributed, patchy network of cortical regions in the temporal and frontal lobes that respond disproportionately to face stimuli, other cortical regions that are not even primarily visual (such as somatosensory cortex), and subcortical structures such as the amygdala. Higher-level face perception abilities, such as judging identity, emotion and trustworthiness, appear to rely on an intact face-processing network that includes the occipital face area (OFA), whereas lower-level face categorization abilities, such as discriminating faces from objects, can be achieved without OFA, perhaps via the direct connections to the fusiform face area (FFA) from several extrastriate cortical areas. Some lesion, transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) findings argue against a strict feed-forward hierarchical model of face perception, in which the OFA is the principal and common source of input for other visual and non-visual cortical regions involved in face perception, including the FFA, face-selective superior temporal sulcus and somatosensory cortex. Instead, these findings point to a more interactive model in which higher-level face perception abilities depend on the interplay between several functionally and anatomically distinct neural regions. Furthermore, the nature of these interactions may depend on the particular demands of the task. We review the lesion and TMS literature on this topic and highlight the dynamic and distributed nature of face processing.


Zap it track it: the application of Lean Six Sigma methods to improve the screening system of low-grade mucinous neoplasms of the appendix in an acute hospital setting.
To improve the number of patients receiving annual computed tomography (CT) scan and tumour markers, who are diagnosed with low-grade mucinous neoplasms (LAMN). A pre-/post-intervention design was employed using Lean Six Sigma methods to identify gaps in the screening system and to develop and implement solutions for a more robust, auditable screening programme. The patients diagnosed with LAMN of the appendix referred to the acute hospital and are enrolled in the screening service. Consultant colorectal surgeons, cancer nurse specialist, colorectal medical team and quality improvement staff. Diagnostic tools identified gaps in the current process. A set of improvements were implemented to standardize the pathway for referral and surveillance of patients, provide information on the condition and treatment and standardize and track information received by patients and their referring hospital. Pre and post-intervention outcome measures were taken for the number of patients who receive an annual CT of thoracic, abdomen and peritoneum and tumour markers and number of patients who receive information and contact details. At baseline, of the 28 patients that met the inclusion criteria only 61% had a correct follow-up. Following the implementation of improvements, 78% of patients had correct follow-up and 90% had received information. Gaps in the current cancer screening system were identified and improvements implemented a reduced number of patients having an incorrect follow-up. Findings are applicable across all precancerous screening systems irrespective of the type of malignancy. The methods used empowered patients and fostered an interdisciplinary team approach to care.


Reproductive and hormonal factors and lung cancer risk in the NIH-AARP Diet and Health Study cohort.
Lung cancer exhibits unique patterns among women including high adenocarcinoma rates among nonsmokers. Inconsistent findings about hormonal factors on risk may reflect incomplete control for confounding, misclassification of exposures, or insufficient attention to variation by histology. Among 185,017 women, ages 50 to 71 years, recruited during 1995 and 1996 for the NIH-AARP (American Association of Retired Persons) Diet and Health Study, we identified 3,512 incident lung cancers (including 276 in never smokers) in follow-up through December 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% CIs for self-reported hormonally related risk factors. After adjustment for smoking and other confounders, subjects with late menarche were at reduced risk, with the association specific for adenocarcinomas (RR = 0.72 for menarche 15+ vs. <11, P(trend) < 0.01). Subjects with early ages at ovarian cessation (either from natural menopause or bilateral oophorectomy) were at an increased risk for adenocarcinomas and squamous cell tumors, but the associations were strongest for smokers, suggesting either residual confounding or an enhanced effect of menopausally related factors among subjects with decreased endogenous estrogens. In contrast, we saw no relationships of risk with either parity, age at first birth, or exogenous hormone use. Elevated levels of hormones may adversely affect lung function early in life while assisting with cellular and immunologic responses later in life. Additional attention toward the role of hormonal factors may further our understanding of lung carcinogenesis. Our findings provide some support for a role of hormonal factors in the etiology of lung cancer, although the mechanisms appear complicated.


Cost-saving effects of olanzapine as long-term treatment for bipolar disorder.
Promoters of new medications often argue that using newer drug can reduce use of non-drug medical services and therefore reduce total healthcare spending. This cost-offset argument is plausible both in theory and in practice, but rigorous research on specific drugs or drug categories is needed to make targeted and efficient policy and management decisions. I examined the drug-offset hypothesis for bipolar disorder, an important yet under-studied clinical condition where effective medication treatments can service as substitutes for non-drug medical treatments. I compared two first line long-term treatments, a new atypical antipsychotic medication, olanzapine, and a traditional mood stabilizer, lithium. I used private sector insurance claims data collected from a nationally representative sample of U.S. health plans between January 1998 and December 2001. I first selected a cohort of patients with bipolar disorder who were continuously enrolled for at least two years. I then used a propensity-score method to match individuals taking each drug on observed variables that are known to affect medication choices. The central challenge for estimation is that drug treatments are not randomly assigned among patients with bipolar disorder. To identify a causal link between choice of drugs and non-drug medical spending, I employed three different advanced econometrics techniques to assess the robustness of findings; namely interrupted time series, differencing strategies, and an instrumental variables approach. I found that compared to similar lithium users, olanzapine users spent approximately $330 more on monthly average non-drug medical services during the first year after initiation of drug treatment. The higher spending for olanzapine users was accounted for by both higher rates of re-hospitalization and more outpatient visits. In addition, olanzapine cost $153 per month while lithium cost $16 per month. Including the direct cost of the drugs, compared to similar patients taking lithium, patients with bipolar disorder taking olanzapine spent $5,600 more annually on health care services. These findings do not support the hypothesis that new drugs "pay for themselves" by reducing the need for other health care services in the case of olanzpine for bipolar disorder. This does not mean that the new drug is not "cost-effective" because increased "benefits" associated with the drug in terms of the improved quality of life may be worth the increased costs. However the findings do indicate that "cost-offsets" must be measured and not taken for granted. Incorporating such drug-offset evidence into policy and business decisions can facilitate appropriate clinical practices and improve efficiency of resource allocation. The methods used in this study to test for cost-offsets can be applied to other clinical areas and drug classes.


Pattern of acute poisonings in children below 15 years--a study from Mangalore, South India.
Acute poisoning in children is a problem ubiquitous in distribution and is an important paediatric emergency. The present research was aimed to study the pattern and outcome of childhood poisoning under the age of 15 years at a tertiary care centre in South India to characterize the problem of acute paediatric poisoning among the children in different age group in the region. Medical records of all poisoning patients admitted during 2010 and 2011 were reviewed, and the information relating to the sociodemographic and clinical profile of the patients was recorded. Acute poisoning was reported in 81 children aged below 15 years during the study period. 50.6% were boys (n = 41) and 49.4% girls (n = 40). The mean age of the study sample was 6.8 years. Mean age was observed to be higher in females than males. The maximum number of cases were observed in the below 5 years age group (n = 45). A male predominance was evident in the below 5 years age group, while a female predominance in the age group between 10 and 15 years. Kerosene (n = 23, 28.4%) and organophosphate compounds (n = 16, 19.8%) were the most common agents responsible for poisoning in children. The majority of the poisoning cases were reported to the hospital within 12 h of the incident (n = 65, 83.3%). The mortality in paediatric poisoning was observed to be 7.4%. The majority of the children (n = 68, 84.0%) recovered, while seven patients had left the hospital against medical advice (8.6%). The study reports agrochemicals and hydrocarbons to be the most commonly implicated agents in paediatric poisoning. The cause of paediatric poisonings varies in different age groups and hence, preventive strategies should be planned accordingly.


Serotonin and 5-HT3 receptors sensitize human skin cells to direct irradiation cell death but not to soluble radiation-induced bystander signals.
Ionizing radiation (IR) is an environmental carcinogen and the biological damages it elicits are mechanistically distinct between high and low doses. Non-targeted effects occurring in nonirradiated cells such as the radiation-induced bystander effect predominate at low doses of IR. However, the role of non-targeted effects in environmental radiation protection is often overlooked because the governing mechanisms are complex and multifactorial. An improved understanding of the signaling molecules and their capacity to sensitize specific cell types are essential in establishing environmental IR risks. In particular, serotonin (5-HT) has been identified to exacerbate both direct irradiation and bystander-induced cell death (CD) in certain cell types, although not all cell types are responsive to 5-HT in this respect. In this study, we further characterize the role of 5-HT and 5-HT receptors (5-HTR) in the amplification of CD following IR exposure in human keratinocytes. We examined the survival of HaCaT cells treated with 5-HT and the 5-HTR antagonists ketanserin (5-HT2A) and ondansetron (5-HT3) following exposure to direct IR and irradiated cell condition medium (ICCM). Nonirradiated cell survival was consistent with the vehicle control among 5-HT concentrations ranging from 0.001 to 100 μM. Significant 5-HT concentration-dependent increases in CD occurred following direct IR exposure. Nonirradiated ICCM-recipient CD was not altered by 5-HT (0.001-100 μM) when present during donor cell irradiation among all IR doses. Increases in direct irradiation CD evoked by 5-HT were significantly attenuated by ondansetron, blocking the effect of 5-HT, whereas ketanserin did not alter CD. Western blotting of these target 5-HTRs revealed protein expression of the 5-HT3 receptor, while the 5-HT2A receptor was not detected. We have demonstrated a definitive role for 5-HT in the exacerbation of CD following direct IR exposure and identified the 5-HT3 receptor as a potential target for ameliorating radiation damage in keratinocytes.


A randomized, rater-blinded, parallel trial of intensive speech therapy in sub-acute post-stroke aphasia: the SP-I-R-IT study.
There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT) treatment in sub-acute post-stroke aphasia. Consecutive patients with aphasia, within 3 months of a left hemisphere ischemic stroke, were randomized to IT (2 h per day × 5 days per week, 10 weeks) or RT (2 h per week × 50 weeks). Evaluations took place at 10, 50 and 62 weeks. Primary outcome was the frequency of responders, defined by 15% increase of Aphasia Quotient (AQ) from the baseline to 50 weeks. Secondary outcomes were changes from the baseline in AQ and functional communication profile (FCP) at 50 and 62 weeks and improvement stability between 50 and 62 weeks. Thirty patients were randomized and 18 completed the study. No significant differences were found between groups in primary or secondary outcomes, although IT patients (N = 9) obtained higher scores in language measures between 10 and 62 weeks in per protocol analysis. The number of non-completions was identical between groups. This study suggests that, in the sub-acute period following stroke and controlling for the number of hours of SLT provided, there is a trend for a greater improvement in language and functional communication measures with IT compared with RT. The lack of statistical significance in results was probably due to the small sample size.


Attitudes towards abortion and decision-making capacity of pregnant adolescents: perspectives of medicine, midwifery and law students in Accra, Ghana.
Objectives: Because medical, midwifery and law students in Ghana constitute the next generation of health care and legal practitioners, this study aimed to evaluate their attitudes towards abortion and their perceptions of the decision-making capacity of pregnant adolescents.Methods: We conducted a cross-sectional survey among 340 medical, midwifery and law students. A pretested and validated questionnaire was used to collect relevant data on respondents' sociodemographic characteristics, attitudes towards abortion and the perceived capacity and rationality of pregnant adolescents' decisions. The χ2 test of independency and Fischer's exact test were used where appropriate.Results: We retained 331 completed questionnaires for analysis. Respondents' mean age was 21.0 ± 2.9 years and the majority (95.5%) were of the Christian faith. Women made up 77.9% (n = 258) of the sample. Most students (70.1%) were strongly in favour of abortion if it was for health reasons. More than three-quarters (78.0%) of the students strongly disagreed on the use of abortion for the purposes of sex selection. Most respondents (89.0%) were not in favour of legislation to make abortion available on request for pregnant adolescents, with medical students expressing a more negative attitude compared with law and midwifery students (p < 0.001). Over half of the midwifery students (52.6%) believed that adolescents should have full decision-making capacity regarding their pregnancy outcome, compared with law and medical students (p < 0.001).Conclusion: Tensions between adolescent reproductive autonomy, the accepted culture of third party involvement (parents and partners), and the current abortion law may require keen reflection if an improvement in access to safe abortion services is envisioned.


Growth and health status of Pacific white shrimp, Litopenaeus vannamei, exposed to chronic water born cobalt.
Cobalt (Co) is an important component of vitamin B12, but is toxic to aquatic animals at a high level. In this study, the Pacific white shrimp, Litopenaeus vannamei were exposed to three Co concentrations (0, 100, and 1000 μg/L) for 4 weeks. The survival and condition factor in shrimp exposed to the Co treatments were not different from the control, but the shrimp exposed to 100 μg Co/L gained more weight than in other two groups, and the shrimp exposed to 1000 μg Co/L gained less weight than in other groups. The SOD and GSH-PX activities were higher in shrimp exposed to 100 μg Co/L, but lower in the shrimp exposed to 100 μg Co/L compared with the control, respectively. The MDA contents in the hepatopancreas decreased in the 100 μg Co/L, but increased in the 1000 μg Co/L. The serum lysozyme decreased with ambient cobalt, was lower in the shrimp exposed to 1000 μg Co/L than in other two groups. The expression of C-type lectin 3 was down-regulated by Co concentrations. The Toll and immune deficiency in shrimp exposed to 100 μg Co/L was higher than in other two groups. The mucin-1 was lower in the 1000 μg Co/L group than in other two groups, but mucin-2 and mucin-5AC were higher in the 1000 μg Co/L group than in the control. With increasing Co concentration, Shannon and Simpson indexes of the intestinal microbial communities were decreased. The abundance of pathogenic bacteria (Ruegeria and Vibrio) increased in both Co groups. This study indicates that chronic exposure to waterborne cobalt could affect growth, cause oxidative stress, stimulate the immune response, damage intestinal histology, and reshape intestinal microbiota community L. vannamei.


Safety in long-term EEG/video monitoring.
The goal of epilepsy monitoring is to capture several seizures, utilizing continuous electroencephalography (EEG)/video for later analysis. Various provocative techniques, such as withdrawing antiepileptic drugs or sleep deprivation are used to precipitate seizures. Patients run a higher risk of injuries due to having an increase in seizure frequency and/or intensity or a change in seizure type. Evaluating the potential for, and preventing injuries is an important part of risk management. However, very little information has been published regarding safety issues in an epilepsy monitoring unit (EMU). Several types of safety issues have been identified during monitoring: uncontrolled behavior (ictal and post-ictal aggression, self injurious behavior, psychosis); seizure related injuries (falls, status epilepticus); problems related to electrodes (pulling out scalp and surgically implanted electrodes); and specific concerns regarding children in the EMU. Use of restraints and sitters in selected patients, appropriate medication for psychosis, shock absorbing carpet and "child-proofing" rooms for the young are among the preventative actions discussed. Central to risk management is the education of the staff in the assessment of each patient's potential for injury and use the appropriate interventions. Consideration should be given to balancing the need to avert harm, with an unrestricted environment.


[Sporadic case of non-progressive neurogenic muscular atrophy localized in both calf muscles].
A 60-year-old woman was admitted to our hospital because of difficulty in standing on her toes. Neurological examination showed muscle weakness in both calf muscles. Her serum creatine kinase (CK) level was slightly elevated. MRI revealed hyper-intense signals localized in both the gastrocnemius and soleus muscles. Histological examinations of biopsied muscle specimens showed a marked variation in fiber size, small angular fibers, and hypertrophic and splitting fibers, but no muscle fiber necrosis or regeneration or inflammatory cell infiltration. ATPase stained sections showed small grouped atrophy of type 1 fibers. NADH-TR stained sections showed target/targetoid fibers predominantly in type 1 fibers. Dysferlin immunoreactivity was normal. Follow-up clinical evaluation for one year showed no progression. This patient was diagnosed as having an unknown type of spinal muscular atrophy or benign calf amyotrophy. Sporadic cases characterized by elderly-onset, neurogenic muscular atrophy localized in both calf muscles, and non-progressive course are extremely rare in Japan.


Volume of mammographic density and risk of breast cancer.
Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area. We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume. After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5-4.3) for percent dense area, 2.9 (95% CI: 1.7-4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3-7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer. Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area. Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models.