Objective and Subjective Effects of a Passive Exoskeleton on Overhead Work.
Overhead work is a frequent cause of shoulder work-related musculoskeletal disorders. Exoskeletons offering arm support have the potential to reduce shoulder strain, without requiring large scale reorganization of the workspace. Assessment of such systems however requires to take multiple factors into consideration. This paper presents a thorough in-lab assessment of PAEXO, a novel passive exoskeleton for arm support during overhead work. A list of evaluation criteria and associated performance metrics is proposed to cover both objective and subjective effects of the exoskeleton, on the user and on the task being performed. These metrics are measured during a lab study, where 12 participants perform an overhead pointing task with and without the exoskeleton, while their physical, physiological and psychological states are monitored. Results show that using PAEXO reduces shoulder physical strain as well as global physiological strain, without increasing low back strain nor degrading balance. These positive effects are achieved without degrading task performance. Importantly, participants' opinions of PAEXO are positive, in agreement with the objective measures. Thus, PAEXO seems a promising solution to help prevent shoulder injuries and diseases among overhead workers, without negatively impacting productivity.


Assessing pandemic preparedness, response, and lessons learned from the COVID-19 pandemic in four south American countries: agenda for the future.
The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths. This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers. The results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries' health agendas. We recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries' national public health agendas.


Arcuate nucleus kisspeptin response to increased nutrition in rams.
Rams respond to acute nutritional supplementation by increasing the frequency of gonadotrophin-releasing hormone (GnRH) pulses. Kisspeptin neurons may mediate the effect of environmental cues on GnRH secretion, so we tested whether the ram response to nutrition involves activation of kisspeptin neurons in the arcuate nucleus (ARC), namely kisspeptin, neurokin B, dynorphin (KNDy) neurons. Rams were given extra lupin grain with their normal ration. Blood was sampled before feeding, and continued until animals were killed for collection of brain tissue at 2 or 11h after supplementation. In supplemented rams, LH pulse frequency increased after feeding, whereas control animals showed no change. Within the caudal ARC, there were more kisspeptin neurons in supplemented rams than in controls and a higher proportion of kisspeptin cells coexpressed Fos, regardless of the time the rams were killed. There were more Fos cells in the mid-ARC and mid-dorsomedial hypothalamus of the supplemented compared with control rams. No effect of nutrition was found on kisspeptin expression in the rostral or mid-ARC, or on GnRH expression in the preoptic area. Kisspeptin neurons in the caudal ARC appear to mediate the increase in GnRH and LH production due to acute nutritional supplementation, supporting the hypothesised role of the KNDy neurons as the pulse generator for GnRH.


Functional appliances: a systematic approach.
It can be argued that all functional appliances are basically similar, using a family of common component parts. The components incorporated into a design should be chosen rationally, after consideration of the particular malocclusion to be treated. This article therefore explains functional appliances in terms of their components. It aims to give a greater understanding of the principles involved, and thus aid the practitioner in prescribing the most appropriate design for a particular clinical situation.


Development and psychometric properties of a neuropsychological battery for mild cognitive impairment with small vessel disease: the VMCI-Tuscany Study.
Vascular cognitive impairment may have a selective neuropsychological profile. We developed a battery for assessing mild cognitive impairment (MCI) in patients with small vessel disease (SVD), its applicability, and psychometric properties. Among those proposed by the 2006 NINDS-CSN Consensus Conference, we selected tests for which norms based on healthy Italians and equivalent scores methodology were available. Confirmatory factor analysis was applied to ascertain the fit of the theoretically assumed dimensions to empirical data and to derive each cognitive dimension compound measures. The entire battery was applied to 146 out of a cohort of 201 patients with MCI and SVD. Most tests showed good applicability. Fifty-five patients, who were older and cognitively more impaired, proved unable to complete the Trail Making Test part B, the Rey-Osterrieth Complex Figure, and the Stroop test, and were excluded from the analysis. Among the remaining patients, Mini-Mental State Examination proved largely normal, while Rey-Osterrieth Complex Figure, Symbol digit modalities test, and Trail Making Test part B were most frequently abnormal. Confirmatory factor analysis showed a good fit of the 4-factor theoretical model to empirical data. Praxis domain resulted in the highest percentage of abnormal performance (65%), followed by Memory and Attention/EF domains (19% and 15%), and Language (8%). Our battery proved to be comprehensive, robust, and applicable. Attention-executive dysfunction and impaired memory and visuo-constructional abilities, were the prominent features. The assessment of the Consensus Conference, that included Trial Making Test, looks poorly applicable to older and cognitively impaired patients.


Age-related impairment of autophagy in cervical motor neurons.
Neuromuscular dysfunction is common in old age. Damaged cytoplasmic structures aggregate with aging, especially in post-mitotic cells like motor neurons. Autophagy is a ubiquitous cell process that aids in the clearance of damaged aggregates. Accordingly, we hypothesized that autophagy is impaired in old age, contributing to neuromuscular dysfunction via an effect in motor neurons. Autophagy flux may be impaired as a result of deficits in the initiation, elongation or degradation phases. Changes in the expression levels of core proteins necessary for each of the autophagy phases were evaluated by Western blotting in the cervical spinal cord (segments C2-C6 corresponding to the phrenic motor pool) of adult male and female mice at 6-, 18-, and 24-months of age (reflecting 100%, 90% and 75% survival, respectively). There was no evidence of an effect of age on the expression of the autophagy markers Beclin-1 (Becn-1; initiation), ATG7 and ATG5/12 complex (elongation) or LC3 (elongation/degradation). Reduced p62 expression (a marker of degradation) was evident in the cervical spinal cord of adult mice at 18-months compared to 24-months. Accordingly, expression of LC3 and p62 in motor neurons was analyzed using immunofluorescence and confocal microscopy in separate animals. LC3 and p62 immunoreactivity was evident in the gray matter with minimal expression in the white matter across all age groups. A mixed linear model with animal as a random effect was used to compare relative LC3 and p62 expression in motor neurons to gray matter across age groups. Expression of both LC3 and p62 was higher in choline acetyl transferase (ChAT)-positive motor neurons (~2-3 fold vs. gray matter). Across age groups, there were differences in the relative expression of LC3 (F2,12 = 7.59, p < 0.01) and p62 (F2,12 = 8.00, p < 0.01) in cervical motor neurons. LC3 expression in motor neurons increased ~20% by 24-months of age in both male and female mice. p62 expression in motor neurons increased ~70% by 18-months compared to 6-months with no further changes by 24-months of age in male mice. p62 expression did not change across age groups in female mice, and was ~20% higher than in males. Our findings highlight important changes in autophagy pathways that likely contribute to the development of aging-related neuromuscular dysfunction in mice. At 18-months of age, increased autophagosome clearance (reduced p62 expression) appears to be a global effect not restricted to motor neurons. By 24-months of age, increased expression of LC3 and p62 indicates impaired autophagy with autophagosome accumulation in cervical motor neurons.


In silico Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties.
The aim of the study was to develop better anxiolytics and antidepressants. We focused on GABA A receptors and the α2δ auxiliary subunit of V-gated Ca2+ channels as putative targets because they are established as mediators of efficacious anxiolytics, antidepressants, and anticonvulsants. We further focused on short peptides as candidate ligands because of their high safety and tolerability profiles. We employed a structural bioinformatics approach to develop novel tetrapeptides with predicted affinity to GABA A receptors and α2δ. In silico docking studies of one of these peptides, LCGA-17, showed a high binding score for both GABA A receptors and α2δ, combined with anxiolytic-like properties in a Danio rerio behavioral screen. LCGA-17 showed anxiolytic-like effects in the novel tank test, the light-dark box, and the social preference test, with efficacy comparable to fluvoxamine and diazepam. In binding assays using rat brain membranes, [3H]-LCGA-17 was competed more effectively by gabapentinoid ligands of α2δ than ligands of GABA A receptors, suggesting that α2δ represents a likely target for LCGA-17. [3H]-LCGA-17 binding to brain lysates was unaffected by competition with ligands for GABAB, glutamate, dopamine, serotonin, and other receptors, suggesting specific interaction with α2δ. Dose-finding studies in mice using acute administration of LCGA-17 (i.p.) demonstrated anxiolytic-like effects in the open field test, elevated plus maze, and marble burying tests, as well as antidepressant-like properties in the forced swim test. The anxiolytic effects were effectively blocked by bicuculline. Therefore, LCGA-17 is a novel candidate anxiolytic and antidepressant that may act through α2δ, with possible synergism by GABA A receptors.


Context-Aware Time Series Imputation for Multi-Analyte Clinical Data.
Clinical time series imputation is recognized as an essential task in clinical data analytics. Most models rely either on strong assumptions regarding the underlying data-generation process or on preservation of only local properties without effective consideration of global dependencies. To advance the state of the art in clinical time series imputation, we participated in the 2019 ICHI Data Analytics Challenge on Missing Data Imputation (DACMI). In this paper, we present our proposed model: Context-Aware Time Series Imputation (CATSI), a novel framework based on a bidirectional LSTM in which patients' health states are explicitly captured by learning a "global context vector" from the entire clinical time series. The imputations are then produced with reference to the global context vector. We also incorporate a cross-feature imputation component to explore the complex feature correlations. Empirical evaluations demonstrate that CATSI obtains a normalized root mean square deviation (nRMSD) of 0.1998, which is 10.6% better than that of state-of-the-art models. Further experiments on consecutive missing datasets also illustrate the effectiveness of incorporating the global context in the generation of accurate imputations.


Patterns of childhood cancer incidence in Saudi Arabia (1999- 2008).
Although childhood cancer is a rare disease, 100,000 children younger than 15 years of age die from cancer each year, the majority of them in developing countries. More data need to be gathered and published particularly in developing countries to better understand the scale of the problem. This study aimed to describe the patterns of childhood cancers in Saudi Arabia over a period of ten years (1999-2008). This descriptive retrospective study was based on secondary data from the Saudi Cancer Registry from 1999 to 2008. All Saudi cases (both genders), under the age of 15 years, who were diagnosed with cancer during the study period, were included in this study. Childhood cancer in Saudi Arabia, in the period between 1999 and 2008, accounted for about 8% of total cancer cases. The most common encountered cancers were leukemia (34.1%), followed by lymphoma (15.2%), brain (12.4%), and kidney cancers (5.3%). The overall incidence of childhood cancers increased from 8.8 per 100,000 in 1999 to 9.8 per 100,000 in 2008. The incidence rates of cancers per 100,000 in the years 1999 and 2008 were generally higher among males, (9.4 and 11.5 in males vs. 8.3 and 8.1 in females). The highest incidence rate in the surveyed years was apparent in the birth to age 4 years group. Cancer is an important public health problem in Saudi Arabia and a major ascending contributor to mortality and morbidity in children. More studies are required to describe the patterns of childhood cancers and related risk factors in Saudi Arabia.


Alcohol consumption and liver cirrhosis mortality with and without mention of alcohol--the case of Canada.
To analyse post-war variations in per capita alcohol consumption in relation to gender-specific liver cirrhosis mortality in Canadian provinces and to assess the extent to which alcohol bears a different relation to cirrhosis deaths with mention of alcohol (alcoholic cirrhosis) compared to cirrhosis deaths without mention of alcohol (non-alcoholic cirrhosis). Annual liver cirrhosis mortality rates by 5-year age groups were converted into gender-specific and age-adjusted mortality rates. Outcome measures included total cirrhosis-the conventional measure of liver cirrhosis--alcoholic cirrhosis and non-alcoholic cirrhosis. Per capita alcohol consumption was measured by alcohol sales and weighted with a 10-year distributed lag model. A graphical analysis was used to examine the regional relationship and the Box-Jenkins technique for time-series analysis was used to estimate the temporal relationship. Geographical variations in alcohol consumption corresponded to variations in total liver cirrhosis and particularly alcoholic cirrhosis, whereas non-alcoholic cirrhosis rates were not associated geographically with alcohol consumption. In general, for all provinces, time-series analyses revealed positive and statistically significant effects of changes in alcohol consumption on cirrhosis mortality. In Canada at large, a 1-litre increase in per capita consumption was associated with a 17% increase in male total cirrhosis rates and a 13% increase in female total cirrhosis rates. Alcohol consumption had a stronger impact on alcoholic cirrhosis, which increased by fully 30% per litre increase in alcohol per capita for men and women. Although the effect on the non-alcoholic cirrhosis rate was weaker (12% for men and 7% for women) it was nevertheless statistically significant and suggests that a large proportion of these deaths may actually be alcohol-related. Some well-established findings in alcohol research were confirmed by the Canadian experience: per capita alcohol consumption is related closely to death rates from liver cirrhosis and alcohol-related deaths tend to be under-reported in mortality statistics.


Narrow line width frequency comb source based on an injection-locked III-V-on-silicon mode-locked laser.
In this paper, we report the optical injection locking of an L-band (∼1580 nm) 4.7 GHz III-V-on-silicon mode-locked laser with a narrow line width continuous wave (CW) source. This technique allows us to reduce the MHz optical line width of the mode-locked laser longitudinal modes down to the line width of the source used for injection locking, 50 kHz. We show that more than 50 laser lines generated by the mode-locked laser are coherent with the narrow line width CW source. Two locking techniques are explored. In a first approach a hybrid mode-locked laser is injection-locked with a CW source. In a second approach, light from a modulated CW source is injected in a passively mode-locked laser cavity. The realization of such a frequency comb on a chip enables transceivers for high spectral efficiency optical communication.


Significance of INHBA expression in human colorectal cancer.
Inhibin β A (INHBA) is a member of the transforming growth factor β (TGF-β) superfamily. INHBA expression is associated with several types of human cancers; however, its significance in colorectal cancer (CRC) is not fully understood. INHBA expression was studied in 126 primary CRC samples and 4 CRC cell lines. Cell growth was assessed after inhibition of INHBA expression or after exogenous overexpression of INHBA in CRC tissues. INHBA expression was significantly higher in CRC tissues when compared to that in the corresponding normal tissues (P<0.001). Patients in the high expression group showed a poorer overall survival rate when compared to those in the low expression group (P<0.001); the present study did not evaluate for an independent prognostic factor but showed the significance of lymph node metastasis as an independent prognostic factor. The present study suggests that INHBA is useful as a predictive marker for prognosis in CRC patients.


Assessing potential glycemic overtreatment in persons at hypoglycemic risk.
Although serious hypoglycemia is a common adverse drug event in ambulatory care, current performance measures do not assess potential overtreatment. To identify high-risk patients who had evidence of intensive glycemic management and thus were at risk for serious hypoglycemia. Cross-sectional study of patients in the Veterans Health Administration receiving insulin and/or sulfonylureas in 2009. Intensive control was defined as the last hemoglobin A1c (HbA1c) measured in 2009 that was less than 6.0%, less than 6.5%, or less than 7.0%. The primary outcome measure was an HbA1c less than 7.0% in patients who were aged 75 years or older who had a serum creatinine value greater than 2.0 mg/dL or had a diagnosis of cognitive impairment or dementia. We also assessed the rates in patients with other significant medical, neurologic, or mental comorbid illness. Variation in rates of possible glycemic overtreatment was evaluated among 139 Veterans Health Administration facilities grouped within 21 Veteran Integrated Service Networks. There were 652,378 patients who received insulin and/or a sulfonylurea with an HbA1c test result. Fifty percent received sulfonylurea therapy without insulin; the remainder received insulin therapy. We identified 205,857 patients (31.5%) as the denominator for the primary outcome measure; 11.3% had a last HbA1c value less than 6.0%, 28.6% less than 6.5%, and 50.0% less than 7.0%. Variation in rates by Veterans Integrated Service Network facility ranged 8.5% to 14.3%, 24.7% to 32.7%, and 46.2% to 53.4% for HbA1c less than 6.0%, less than 6.5%, and less than 7.0%, respectively. The magnitude of variation by facility was larger, with overtreatment rates ranging from 6.1% to 23.0%, 20.4% to 45.9%, and 39.7% to 65.0% for HbA1c less than 6.0%, less than 6.5%, and less than 7.0%, respectively. The maximum rate was nearly 4-fold compared with the minimum rates for HbA1c less than 6.0%, followed by 2.25-fold for HbA1c less than 6.5% and less than 2-fold for HbA1c less than 7.0%. When comorbid conditions were included, 430,178 patients (65.9%) were identified as high risk. Rates of overtreatment were 10.1% for HbA1c less than 6.0%, 25.2% for less than 6.5%, and 44.3% for less than 7.0%. Patients with risk factors for serious hypoglycemia represent a large subset of individuals receiving hypoglycemic agents; approximately one-half had evidence of intensive treatment. A patient safety indicator derived from administrative data can identify high-risk patients for whom reevaluation of glycemic management may be appropriate, consistent with meaningful use criteria for electronic medical records.


Global public-private partnerships: Part I--A new development in health?
The proliferation of public-private partnerships is rapidly reconfiguring the international health landscape. This article (part I of two on the subject) traces the changing nature of partnership, and discusses the definitional and conceptual ambiguities surrounding the term. After defining global public-private partnerships (GPPPs) for health development, we analyse the factors which have led to the convergence of public and private actors and discuss the consequences of the trend toward partnership between UN agencies (including the World Bank) and commercial entities in the health sector. Generic factors such as globalization and disillusionment with the UN, and factors specific to the health sector, such as market failure in product development for orphan diseases, are examined. Reviewed are the interests, policies, practices and concerns of the UN, the private-for-profit sector, bilateral organizations, and governments of low-income countries with respect to public-private partnership. While GPPPs bring much needed resources to problems of international health, we highlight concerns regarding this new organizational format. Part II, which will be published in the May issue of the Bulletin, presents a conceptual framework for analysing health GPPPs and explores the issues raised.


Combined transcriptome analysis of fetal human and mouse cerebral cortex exposed to alcohol.
Fetal exposure to environmental insults increases the susceptibility to late-onset neuropsychiatric disorders. Alcohol is listed as one of such prenatal environmental risk factors and known to exert devastating teratogenetic effects on the developing brain, leading to complex neurological and psychiatric symptoms observed in fetal alcohol spectrum disorder (FASD). Here, we performed a coordinated transcriptome analysis of human and mouse fetal cerebral cortices exposed to ethanol in vitro and in vivo, respectively. Up- and down-regulated genes conserved in the human and mouse models and the biological annotation of their expression profiles included many genes/terms related to neural development, such as cell proliferation, neuronal migration and differentiation, providing a reliable connection between the two species. Our data indicate that use of the combined rodent and human model systems provides an effective strategy to reveal and analyze gene expression changes inflicted by various physical and chemical environmental exposures during prenatal development. It also can potentially provide insight into the pathogenesis of environmentally caused brain disorders in humans.


[Esophageal perforations. Presentation of 23 cases].
Esophageal perforations are the most serious perforations of the digestive tract and their treatment remains controversial. The aim of this study was to analyse the outcome of patients with esophageal perforations given surgical and conservative treatment. Retrospective study of 23 patients with esophageal perforations, 8 cervical (35%) and 15 thoracic (65%). Medical treatment was indicated in patients who fulfilled Cameron's criteria (minimal signs of clinical sepsis; disruption contained in the mediastinum; drainage of the cavity back into the esophagus; minimal symptoms). The remaining patients underwent surgery. Two patients with cervical perforations (25%) met Cameron's criteria. Evolution after conservative treatment was favourable. The remaining patients (75%) were surgically treated: simple closure of the perforation was performed in four and drainage of the cervical abscess in two. Two of the patients who underwent surgery presented pleural hemorrhage, one of which was associated with pneumonia. Four patients with thoracic perforation (27%) met the criteria for conservative treatment. One presented respiratory distress syndrome during treatment and required intensive care. Evolution was favorable in all. The remaining 11 patients (73%) received surgical treatment: in five (46%) simple closure of the perforation was performed, in three (27%) bipolar exclusion was performed and in the remaining patients, other techniques were used. Morbidity was 82% (nine patients) mainly due to pneumonia and mortality was 46% (five patients). Treatment of esophageal perforation should be individualized. Conservative treatment should be considered in patients meeting Cameron's criteria as their evolution is favorable, with low morbidity and mortality and surgery is not necessary.


Buried umbilicus with inflammation due to retained rubber foreign body after liposuction: A case report.
Liposuction is one of the most widely performed aesthetic surgeries. It is mainly used for the correction of deep and superficial fat accumulations and remodeling of the body contour. We present a rare case of unusual rubber foreign body found within the periumbilical area during the reconstruction of buried umbilicus after liposuction.A 61-year-old female had undergone a liposuction surgery 10 years ago. Last year, she experienced signs of inflammation around the periumbilical area. The patient was treated with antibiotics and daily dressing at a local clinic. However, her symptoms did not improve with treatment.After admission, we decided to reconstruct the umbilicus and explore the previous operative site. During reconstruction of umbilicus, we finally discovered a rubber foreign body in the periumbilical area and buried umbilicus. Retained surgical foreign body can clinically manifest as acute reaction, such as an inflammatory response, infection, or abscess within days or weeks after the operation. Patients may complain of pain and discomfort, even months or years after the procedure.Our patient had suffered from delayed inflammation due to retained surgical foreign body after liposuction surgery. We emphasize the need for excellent communication within the surgical team to prevent the incidence of retained surgical bodies.


A chimeric adenovirus vector encoding reovirus attachment protein sigma1 targets cells expressing junctional adhesion molecule 1.
The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but a small virion-anchoring domain was fused to the N-terminal 44 aa of Ad5 fiber. This chimeric attachment protein Fibtail-T3Dsigma1 forms trimers and assembles onto Ad virions. Fibtail-T3Dsigma1 was recombined into the Ad5 genome, replacing sequences encoding wild-type fiber. The resulting vector, Ad5-T3Dsigma1, expresses Fibtail-T3Dsigma1 and infects Chinese hamster ovary cells transfected with human or mouse homologs of the reovirus receptor, junctional adhesion molecule 1 (JAM1), but not the coxsackievirus and Ad receptor. Treatment of Caco-2 intestinal epithelial cells with either JAM1-specific antibody or neuraminidase reduced transduction by Ad5-T3Dsigma1, and their combined effect decreased transduction by 95%. Ad5-T3Dsigma1 transduces primary cultures of human dendritic cells substantially more efficiently than does Ad5, and this transduction depends on expression of JAM1. These data provide strong evidence that Ad5-T3Dsigma1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector.


Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease.
Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or contributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmental microbes that are in part modulated through a series of receptors known as toll-like receptors. Endotoxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogenesis of atherosclerotic heart disease. Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in atherosclerotic disease prevention and treatment.


[Metabolic processes in the body exposed to chemical pollutants].
The paper gives the results of studying the processes of free radical and microsomal oxidation, antioxidant defense, and energy and electrolyte metabolism in the workers of OAO "Salavatnefteorgsintez", one of the leading petrochemical plants in the Republic of Bashkortostan. The metabolic processes have been found to substantially change in the persons contacting a mixture of chlorinated and aromatic hydrocarbons under industrial conditions.


[Reduction of the number of neurons in substantia nigra (Pars compacta) positively correlates with a reduction of seizure activity in WAG/Rij rats].
In WAG/Rij rats with a genetic predisposition to absence epilepsy, age-related dynamics of seizure activity in the frontal EEG was studied. In parallel, cellular content in substantia nigra was analyzed at the age of 1 and 10 months. In 10-months animals, the number of neurons in substantia nigra showed a profound decrease, whereas the number of glial calls increased. In parallel to that, the incidence of epileptic discharges and their duration significantly increased between 5 and 9 months of age. Positive correlations were revealed between the incidence of epileptic discharges and the number of neurons in substantia nigra suggesting that animals with lower number of neurons in SN expressed fewer absence seizures, and vice versa. It was suggested that reduction of neurons in substantia nigra is an adaptive process to prevent progressive development of absence seizures.


Superior mesenteric artery syndrome in intellectually disabled children.
Superior mesenteric artery syndrome (SMAS) is a rare cause of small intestinal obstruction in pediatric patients. Children with intellectual disabilities are a challenging patient population in which to make this diagnosis. The goal of this study was to determine the frequency, presenting symptoms, and outcomes of SMAS in intellectually disabled and non-intellectually disabled children. Retrospective chart review of pediatric patients with SMAS admitted to Penn State Hershey Children's Hospital between January 1999 and July 2010. Sixteen children with SMAS were identified. The majority were male (n = 9) and more than two thirds had an intellectual disability (n = 11). Presenting symptoms were similar between groups, but 78% (7/9) of intellectually disabled patients who had a gastrostomy tube presented with feeding intolerance. Although intellectually disabled patients had a higher number of comorbidities and the number of health care visits before diagnosis was higher, this did not reach statistical significance. There were also no significant differences in length of symptoms before diagnosis and amount of weight loss. However, the weight-for-age percentiles in intellectual disabled children were significantly lower in those without an intellectual disability (9.09 [20.31] vs 48 [20.19], respectively, P ≤ 0.001). Seventy-five percent of patients responded favorably to conservative treatment, but 36% (4/11) of intellectually disabled patients required multiple treatments before there was an improvement in their condition. Superior mesenteric artery syndrome was found more often in children with an intellectual disability. These data highlight the need to consider SMAS if there is difficulty tolerating gastrostomy tube feedings in patients with weight-for-age percentiles less than 5%.


[Escherichia-erythrocyte diagnostic agents].
The conditions of a simple and practicable method for the preparation of effective antigenic nonprotein diagnosticums on the basis of water-phenol extracts of 23 Escherichia species have been developed. The method consists in heating the mixture of erythrocytes and the antigen in a boiling water bath for 60 minutes. The diagnosticums thus obtained are 16-30 times more sensitive in the passive hemagglutination test and 4-6 times more sensitive in the passive hemagglutination inhibition test than diagnosticums prepared with the use of tannin, rivanol, as well as by the common method for the preparation of nonprotein antigens. The minimum concentration of Escherichia cells detected in the passive hemagglutination inhibition test is 0.8-1.2 million cells/ml.


Lifetime Video Game Consumption, Interpersonal Aggression, Hostile Sexism, and Rape Myth Acceptance: A Cultivation Perspective.
Although previous research has investigated relationships between media consumption, sexism, and rape myth acceptance (RMA), limited research has investigated video games despite their emergence as one of the most popular forms of media entertainment globally. Given that video games typically feature even less diverse and more objectified representations of women than traditional mainstream media, we predicted that there would be relationships between video game consumption and negative beliefs and attitudes about women. In this study, we conducted a survey (N = 351) of male and female adults and used structural equation modeling to analyze relationships among video game consumption, trait interpersonal aggression, ambivalent sexism, and first-order (percentage of false rape accusations) and second-order cultivation effects (RMA). We found support for the hypothesized cultivation model, indicating a relationship between video game consumption and RMA via interpersonal aggression and hostile sexism. Although these findings cannot be interpreted causally, we discuss the implications of these associations and future directions for research.


Tissue-specific effects of starvation and refeeding on the disposal of oral [1-14C]triolein in the rat during lactation and on removal of litter.
1. The effects of starvation and refeeding on the disposal of oral [14C]triolein between 14CO2 production and 14C-lipid accumulation in tissues of virgin rats, lactating rats and lactating rats with pups removed were studied. 2. Starvation (24 h) increased 14CO2 production in lactating rats and lactating rats with pups removed to values found in virgin rats. This increase was accompanied by decreases in 14C-lipid accumulation in mammary gland and pups of lactating rats and in white and brown adipose tissue of lactating rats with pups removed. 3. Short-term (2 h) refeeding ad libitum decreased 14CO2 production in lactating rats and lactating rats with pups removed, and restored the 14C-lipid accumulation in mammary glands plus pups and in white and brown adipose tissue respectively 4. Insulin deficiency induced with mannoheptulose inhibited the restoration of 14C-lipid accumulation in white adipose tissue on refeeding of lactating rats with pups removed, but did not prevent the restoration of 14C-lipid accumulation in mammary gland. 5. Changes in the activity of lipoprotein lipase in mammary gland and white adipose tissue paralleled the changes in 14C-lipid accumulation in these tissues. 6. It is concluded that 14C-lipid accumulation in mammary gland may not be affected by changes in plasma insulin concentration and that it is less sensitive to starvation than is lipogenesis or lactose synthesis. This has the advantage that the milk lipid content can still be maintained from hepatic very-low-density lipoprotein for a period after withdrawal of food. The major determinant of the disposal of oral 14C-triolein appears to be the total tissue activity of lipoprotein lipase. When this is high in mammary gland (fed lactating rats) or white adipose tissue (fed lactating rats with pups removed), less triacylglycerol is available for the muscle mass and consequently less is oxidized.


Developments in xenobiotic-free culture of human keratinocytes for clinical use.
We have recently reported that irradiated human fibroblasts can be used as a feeder layer, to expand keratinocytes under serum-free conditions, on a chemically defined plasma polymer surface developed for the culture and transfer of keratinocytes for clinical use. While this is a significant advance in developing a serum-free keratinocyte culture approach, the need to irradiate fibroblasts to growth-arrest them and prevent them from overgrowing the keratinocytes introduces another small, but potential, risk for the patient. The aim of the present study was to develop conditions for the coculture of normal human keratinocytes with nonirradiated normal human fibroblasts under serum-free conditions. We examined the fibroblast/keratinocyte relationship on three separate surfaces: tissue culture plastic, non-tissue culture plastic, and a plasma polymer surface designed for clinical use. We report that it is possible to achieve rapid and successful expansion of human keratinocytes under serum-free conditions on all three surfaces providing one uses a keratinocyte-friendly media, a minimum seeding density of keratinocytes, and a ratio of fibroblasts to keratinocytes that does not exceed 1:1. These results provide us with a rapid laboratory expansion of proliferative human keratinocytes, under completely defined culture conditions, without any xenobiotic cells (mouse fibroblasts) or material (bovine serum), for the treatment of patients with extensive skin loss.


Nucleic acid delivery using magnetic nanoparticles: the Magnetofection technology.
In recent years, gene therapy has received considerable interest as a potential method for the treatment of numerous inherited and acquired diseases. However, successes have so far been hampered by several limitations, including safety issues of viral-based nucleic acid vectors and poor in vivo efficiency of nonviral vectors. Magnetofection has been introduced as a novel and powerful tool to deliver genetic material into cells. This technology is defined as the delivery of nucleic acids, either 'naked' or packaged (as complexes with lipids or polymers, and viruses) using magnetic nanoparticles under the guidance of an external magnetic field. This article first discusses the principles of the Magnetofection technology and its benefits as compared with standard transfection methods. A number of relevant examples of its use, both in vitro and in vivo, will then be highlighted. Future trends in the development of new magnetic nanoparticle formulations will also be outlined.


Optimizing Trajectories and Inverse Kinematics for Biomechanical Analysis of Markerless Motion Capture Data.
Markerless motion capture using computer vision and human pose estimation (HPE) has the potential to expand access to precise movement analysis. This could greatly benefit rehabilitation by enabling more accurate tracking of outcomes and providing more sensitive tools for research. There are numerous steps between obtaining videos to extracting accurate biomechanical results and limited research to guide many critical design decisions in these pipelines. In this work, we analyze several of these steps including the algorithm used to detect keypoints and the keypoint set, the approach to reconstructing trajectories for biomechanical inverse kinematics and optimizing the IK process. Several features we find important are: 1) using a recent algorithm trained on many datasets that produces a dense set of biomechanically-motivated keypoints, 2) using an implicit representation to reconstruct smooth, anatomically constrained marker trajectories for IK, 3) iteratively optimizing the biomechanical model to match the dense markers, 4) appropriate regularization of the IK process. Our pipeline makes it easy to obtain accurate biomechanical estimates of movement in a rehabilitation hospital.


Clinical Implications of Having Reduced Mid Forced Expiratory Flow Rates (FEF25-75), Independently of FEV1, in Adult Patients with Asthma.
FEF25-75 is one of the standard results provided in spirometry reports; however, in adult asthmatics there is limited information on how this physiological measure relates to clinical or biological outcomes independently of the FEV1 or the FEV1/FVC ratio. To determine the association between Hankinson's percent-predicted FEF25-75 (FEF25-75%) levels with changes in healthcare utilization, respiratory symptom frequency, and biomarkers of distal airway inflammation. In participants enrolled in the Severe Asthma Research Program 1-2, we compared outcomes across FEF25-75% quartiles. Multivariable analyses were done to avoid confounding by demographic characteristics, FEV1, and the FEV1/FVC ratio. In a sensitivity analysis, we also compared outcomes across participants with FEF25-75% below the lower limit of normal (LLN) and FEV1/FVC above LLN. Subjects in the lowest FEF25-75% quartile had greater rates of healthcare utilization and higher exhaled nitric oxide and sputum eosinophils. In multivariable analysis, being in the lowest FEF25-75% quartile remained significantly associated with nocturnal symptoms (OR 3.0 [95%CI 1.3-6.9]), persistent symptoms (OR 3.3 [95%CI 1-11], ICU admission for asthma (3.7 [1.3-10.8]) and blood eosinophil % (0.18 [0.07, 0.29]). In the sensitivity analysis, those with FEF25-75% <LLN had significantly more nocturnal and persistent symptoms, emergency room visits, higher serum eosinophil levels and increased methacholine responsiveness. After controlling for demographic variables, FEV1 and FEV1/FVC, a reduced FEF25-75% is independently associated with previous ICU admission, persistent symptoms, nocturnal symptoms, blood eosinophilia and bronchial hyperreactivity. This suggests that in some asthmatics, a reduced FEF25-75% is an independent biomarker for more severe asthma.


Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.
Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.


Surgery for lumbar disc herniation during pregnancy.
The case reports of three pregnant patients with lumbar disc herniation causing cauda equina syndrome or severe neurologic deficits are presented to illustrate that disc surgery during gestation is a safe method of management. To emphasize the importance of recognizing and definitively treating lumbar disc displacement causing neurologic deficits during pregnancy. The advent of magnetic resonance imaging and modern surgical techniques for treatment of lumbar disc displacement allows safe management of this condition at any stage of gestation. A review of the literature on the risks of nonobstetric surgery and the risks of delaying disc surgery until delivery shows that operating at any stage during gestation for severe neurologic deficit secondary to lumbar disc displacement is justified. A review of the literature on the use of magnetic resonance imaging scan and nonobstetric surgery during pregnancy was performed. Three case reports of the authors' patients who had lumbar disc displacement with cauda equina syndrome or severe neurologic deficit are presented. Patients were placed prone on a four-poster frame, and an epidural anesthetic agent was administered. A one-level hemilaminectomy, partial facetectomy, and disc excision were performed in all three cases. The methods used for diagnosis and surgical treatment of three patients with disc herniation during pregnancy resulted in a satisfactory outcome for both mother and child. The medical literature supports surgical intervention in pregnant patients with cauda equina syndrome and severe and/or progressive neurologic deficit(s) from lumbar disc displacement at any state of gestation. Although extremely rare, cauda equina syndrome and severe and/or progressive neurologic deficit caused by lumbar disc displacement can occur during pregnancy. The prevalence of symptomatic lumbar disc herniation during pregnancy may be on the increase because of the increasing age of patients who are becoming pregnant. These cases showed, and the literature confirms, that pregnancy at any stage is no contraindication to magnetic resonance imaging scan, epidural and/or general anesthesia, and surgical disc excision.


Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long-Term Survival After Resection for Gastric Adenocarcinoma: Results From the U.S. Gastric Cancer Collaborative.
Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien-Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. Median follow-up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer.


A direct adaptive neural-network control for unknown nonlinear systems and its application.
In this paper a direct adaptive neural-network control strategy for unknown nonlinear systems is presented. The system considered is described by an unknown NARMA model, and a feedforward neural network is used to learn the system. Taking the neural network as a neural model of the system, control signals are directly obtained by minimizing either the instant difference or the cumulative differences between a set point and the output of the neural model. Since the training algorithm guarantees that the output of the neural model approaches that of the actual system, it is shown that the control signals obtained can also make the real system output close to the set point. An application to a flow-rate control system is included to demonstrate the applicability of the proposed method and desired results are obtained.


Potentiation of the novel topoisomerase I inhibitor indenoisoquinoline LMP-400 by the cell checkpoint and Chk1-Chk2 inhibitor AZD7762.
Novel topoisomerase I (Top1) inhibitors are in clinical development to circumvent the drawbacks of camptothecins (CPT). Here, we report molecular investigations into LMP-400, an indenoisoquinoline Top1 inhibitor in phase 1 clinical trial, by itself and in combination with the cell-cycle checkpoint inhibitor AZD7762. We examined drug effects on DNA replication and killing of cancer cells and found that LMP-400 showed synergistic antiproliferative activity when combined with AZD7762 in human colon carcinoma cells. Inhibition of S-phase progression and bromodeoxyuridine incorporation were similarly induced by LMP-400 and CPT and were abrogated by AZD7762. Replication studied by single DNA molecule analyses and immunofluorescence microscopy (molecular combing) showed rapid inhibition of fork progression in response to LMP-400 treatment with subsequent recapitulation after AZD7762 addition. AZD7762 inhibited both the activation/autophosphosphorylation of Chk1 and Chk2 at nanomolar concentrations in LMP-400-treated cells. This potent dual inhibition of Chk1 and Chk2 by AZD7762 was below the drug concentrations required to abrogate cell-cycle inhibition and produce synergism with LMP-400. Also, the synergism was independent of Chk2 both in Chk2-complemented cells and Chk2 knockout cells, suggesting additional mechanisms for cell-cycle abrogation by AZD7762. Together, our findings show a rationale for combining cell-cycle checkpoint inhibitors with the novel non-CPT indenoisoquinoline Top1 inhibitors.


The dose of hydroxyethyl starch 6% 130/0.4 for fluid therapy and the incidence of acute kidney injury after cardiac surgery: A retrospective matched study.
The safety of hydroxyethyl starches (HES) is still under debate. No studies have compared different dosing regimens of HES in cardiac surgery. We analyzed whether the incidence of Acute Kidney Injury (AKI) differed taking into account a weight-adjusted cumulative dose of HES 6% 130/0.4 for perioperative fluid therapy. This retrospective cohort study included all adult patients undergoing elective or emergency cardiac surgery with or without cardiopulmonary bypass. Exclusion criteria were patients on renal replacement therapy (RRT), cardiac trauma surgery, heart transplantation, patients with ventricular assist devices, subjects who required a surgical revision for bleeding and those whose medical records were incomplete. Primary endpoint was AKI following the creatinine based RIFLE classification. Secondary endpoints were 30-day mortality and RRT. Patients were divided into 2 groups whether they had received a cumulative HES dose of < 30 mL/kg (Low HES) or ≥ 30 mL/kg (High HES) during the intra- and postoperative period. A total of 1501 patients were analyzed with 983 patients in the Low HES and 518 subjects in the High HES group. 185 (18.8%) patients in the Low HES and 119 (23.0%) patients in the High HES group developed AKI (P = 0.06). In multivariable regression analysis the dose of HES administered per weight was not associated with AKI. After case-control matching 217 patients were analyzed in each group. AKI occurred in 39 (18.0%) patients in the Low HES and 50 (23.0%) patients in the High HES group (P = 0.19). In conditional regression analysis performed on the matched groups a lower weight-adjusted dose of HES was significantly associated with a reduced incidence of AKI [(Odds Ratio (95% CI) = 0.825 (0.727-0.936); P = 0.003]. In the absence of any safety study the cumulative dose of modern HES in cardiac surgery should be kept less than 30 mL/kg.


Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition.
Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A(2) (TxA(2)) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1(Neo/Neo)) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA(2) by 98% in PGHS1(Neo/Neo) mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE(2) by 75% was associated with selectively impaired inflammatory responses. PGF(2alpha) at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1(Neo/Neo) mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function.


The role of endocannabinoid signaling in the molecular mechanisms of neurodegeneration in Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of progressive neurodegenerative disease characterized by cognitive impairment and mental disorders. The actual cause and cascade of events in the progression of this pathology is not fully determined. AD is multifaceted in nature and is linked to different multiple mechanisms in the brain. This aspect is related to the lack of efficacious therapies that could slow down or hinder the disease onset/progression. The ideal treatment for AD should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway. Recently, the endocannabinoid system emerged as a novel potential therapeutic target to treat AD. In fact, exogenous and endogenous cannabinoids seem to be able to modulate multiple processes in AD, although the mechanisms that are involved are not fully elucidated. This review provides an update of this area. In this review, we recapitulate the role of endocannabinoid signaling in AD and the probable mechanisms through which modulators of the endocannabinoid system provide their effects, thus highlighting how this target might provide more advantages over other therapeutic targets.


Review of D-dimer testing: Good, Bad, and Ugly.
D-dimer assays are commonly used in clinical practice to exclude a diagnosis of deep vein thrombosis or pulmonary embolism. More recently, they have been also been used to guide patients with unprovoked venous thromboembolism (VTE) when faced with the decision to continue or stop anticoagulation after initial treatment is complete. D-dimer assays vary widely with respect to the antibody used, method of capture, instrumentation required, and calibration standard. These differences have an important influence on the operating characteristics of the assays. Consequently, the evidence available in the literature for one assay cannot simply be extrapolated to another. In this review, we will outline the general properties of D-dimer assays, discuss the concept of raising the D-dimer threshold used in diagnosis of VTE according to pretest probability and age, and provide clinical perspective on the role of D-dimer testing in the diagnosis and prognosis of VTE.


An intrathoracic malignant peripheral nerve sheath tumor in a dog.
A 7-year-old, neutered male Labrador Retriever presented for a persistent, productive cough and regurgitation. Radiography, ultrasonography, and computed tomography confirmed a large, smoothly marginated intrathoracic mass causing tracheal compression. The mass was removed via a thoracotomy, and a malignant peripheral nerve sheath tumor, most likely originating from the ventral spinal nerve roots, was confirmed using immunohistochemistry.


Design of a new therapy for patients with chronic kidney disease: use of microarrays for selective hemoadsorption of uremic wastes and toxins to improve homeostasis.
The hypothesis proposed here would provide near to optimum homeostasis for patients with chronic kidney disease (CKD) without the need for hemodialysis. This strategy has not been described previously in the scientific literature. It involves a targeted therapy that may prevent progression of the disease and help to improve the well-being of CKD patients. It proposes a nanotechnological device, ie, a microarray-oriented homeostasis provider (MOHP), to improve homeostasis in CKD patients. MOHP would be an auxiliary kidney aid, and would improve the filtration functions that impaired kidneys cannot perform by their own. MOHP is composed of two main computer-oriented components, ie, a quantitative microarray detector (QMD) and a homeostasis-oriented microarray column (HOMC). QMD detects and HOMC selectively removes defined quantities of uremic wastes, toxins and any other metabolites which is programmed for. The QMD and HOMC would accomplish this with the help of a peristaltic blood pump that would circulate blood aseptically in an extracorporeal closed circuit. During the passage of blood through the QMD, this microarray detector would quantitatively monitor all of the blood compounds that accumulate in the blood of a patient with impaired glomerular filtration, including small-sized, middle-sized and large-sized molecules. The electronic information collected by QMD would be electronically transmitted to the HOMC, which would adjust the molecules to the concentrations they are electronically programmed for and/or receive from QMD. This process of monitoring and removal of waste continues until the programmed homeostasis criteria are reached. Like a conventional kidney machine, MOHP can be used in hospitals and homes under the supervision of a trained technician. The main advantages of this treatment would include improved homeostasis, a reduced likelihood of side effects and of the morbidity resulting from CKD, slower progression of kidney impairment, prevention of end-stage renal failure, a decreased need for hemodialysis therapy, avoidance of dialysis-related side effects later on in the patient's life, improved quality of life and increased life expectancy.


Native and Post-Repair Residual Mitral Valve Prolapse Increases Forces Exerted on the Papillary Muscles: A Possible Mechanism for Localized Fibrosis?
Recent studies have linked mitral valve prolapse to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of mitral regurgitation or hemodynamic dysfunction. The primary mechanistic theory is rooted in increased papillary muscle traction and forces due to prolapse, yet no biomechanical evidence exists showing increased forces. Our objective was to evaluate the biomechanical relationship between prolapse and papillary muscle forces, leveraging advances in ex vivo modeling and technologies. We hypothesized that mitral valve prolapse with limited hemodynamic dysfunction leads to significantly higher papillary muscle forces, which could be a possible trigger for cellular and electrophysiological changes in the papillary muscles and adjacent myocardium. We developed an ex vivo papillary muscle force transduction and novel neochord length adjustment system capable of modeling targeted prolapse. Using 3 unique ovine models of mitral valve prolapse (bileaflet or posterior leaflet prolapse), we directly measured hemodynamics and forces, comparing physiologic and prolapsing valves. We found that bileaflet prolapse significantly increases papillary muscle forces by 5% to 15% compared with an optimally coapting valve, which are correlated with statistically significant decreases in coaptation length. Moreover, we observed significant changes in the force profiles for prolapsing valves when compared with normal controls. We discovered that bileaflet prolapse with the absence of hemodynamic dysfunction results in significantly elevated forces and altered dynamics on the papillary muscles. Our work suggests that the sole reduction of mitral regurgitation without addressing reduced coaptation lengths and thus increased leaflet surface area exposed to ventricular pressure gradients (ie, billowing leaflets) is insufficient for an optimal repair.


Strain Level Streptococcus Colonization Patterns during the First Year of Life.
Pneumococcal pneumonia has decreased significantly since the implementation of the pneumococcal conjugate vaccine (PCV), nevertheless, in many developing countries pneumonia mortality in infants remains high. We have undertaken a study of the nasopharyngeal (NP) microbiome during the first year of life in infants from The Philippines and South Africa. The study entailed the determination of the Streptococcus sp. carriage using a lytA qPCR assay, whole metagenomic sequencing, and in silico serotyping of Streptococcus pneumoniae, as well as 16S rRNA amplicon based community profiling. The lytA carriage in both populations increased with infant age and lytA+ samples ranged from 24 to 85% of the samples at each sampling time point. We next developed informatic tools for determining Streptococcus community composition and pneumococcal serotype from metagenomic sequences derived from a subset of longitudinal lytA-positive Streptococcus enrichment cultures from The Philippines (n = 26 infants, 50% vaccinated) and South African (n = 7 infants, 100% vaccinated). NP samples from infants were passaged in enrichment media, and metagenomic DNA was purified and sequenced. In silico capsular serotyping of these 51 metagenomic assemblies assigned known serotypes in 28 samples, and the co-occurrence of serotypes in 5 samples. Eighteen samples were not typeable using known serotypes but did encode for capsule biosynthetic cluster genes similar to non-encapsulated reference sequences. In addition, we performed metagenomic assembly and 16S rRNA amplicon profiling to understand co-colonization dynamics of Streptococcus sp. and other NP genera, revealing the presence of multiple Streptococcus species as well as potential respiratory pathogens in healthy infants. A range of virulence and drug resistant elements were identified as circulating in the NP microbiomes of these infants. This study revealed the frequent co-occurrence of multiple S. pneumoniae strains along with Streptococcus sp. and other potential pathogens such as S. aureus in the NP microbiome of these infants. In addition, the in silico serotype analysis proved powerful in determining the serotypes in S. pneumoniae carriage, and may lead to developing better targeted vaccines to prevent invasive pneumococcal disease (IPD) in these countries. These findings suggest that NP colonization by S. pneumoniae during the first years of life is a dynamic process involving multiple serotypes and species.


Human intestinal bitter taste receptors regulate innate immune responses and metabolic regulators in obesity.
Bitter taste receptors (taste 2 receptors, TAS2Rs) serve as warning sensors in the lingual system against the ingestion of potentially poisonous food. Here, we investigated the functional role of TAS2Rs in the human gut and focused on their potential to trigger an additional host defense pathway in the intestine. Human jejunal crypts, especially those from individuals with obesity, responded to bitter agonists by inducing the release of antimicrobial peptides (α-defensin 5 and regenerating islet-derived protein 3 α [REG3A]) but also regulated the expression of other innate immune factors (mucins, chemokines) that affected E. coli growth. We found that the effect of aloin on E. coli growth and on the release of the mucus glycoprotein CLCA1, identified via proteomics, was affected by TAS2R43 deletion polymorphisms and thus confirmed a role for TAS2R43. RNA-Seq revealed that denatonium benzoate induced an NRF2-mediated nutrient stress response and an unfolded protein response that increased the expression of the mitokine GDF15 but also ADM2 and LDLR, genes that are involved in anorectic signaling and lipid homeostasis. In conclusion, TAS2Rs in the intestine constitute a promising target for treating diseases that involve disturbances in the innate immune system and body weight control. TAS2R polymorphisms may be valuable genetic markers to predict therapeutic responses.


Assessment of blood glucose predictors: the prediction-error grid analysis.
Prediction of the future blood glucose (BG) evolution from continuous glucose monitoring (CGM) data is a promising direction in diabetes therapy management, and several glucose predictors have recently been proposed. This raises the problem of their assessment. There were attempts to use for such assessment the continuous glucose-error grid analysis (CG-EGA), originally developed for CGM devices. However, in the CG-EGA the BG rate of change is estimated from past BG readings, whereas predictors provide BG estimation ahead of time. Therefore, the original CG-EGA should be modified to assess predictors. Here we propose a new version of the CG-EGA, the Prediction-Error Grid Analysis (PRED-EGA). The analysis is based both on simulated data and on data from clinical trials, performed in the European FP7-project "DIAdvisor." Simulated data are used to test the ability of the analyzed CG-EGA modifications to capture erroneous predictions in controlled situation. Real data are used to show the impact of the different CG-EGA versions in the evaluation of a predictor. Using the data of 10 virtual and 10 real subjects and analyzing two different predictors, we demonstrate that the straightforward application of the CG-EGA does not adequately classify the prediction performance. For example, we observed that up to 70% of 20 min ahead predictions in the hyperglycemia region that are classified by this application as erroneous are, in fact, accurate. Moreover, for predictions during hypoglycemia the assessments produced by the straightforward application of the CG-EGA are not only too pessimistic (in up to 60% of cases), but this version is not able to detect real erroneous predictions. In contrast, the proposed modification of the CG-EGA, where the rate of change is estimated on the predicted BG profile, is an adequate metric for the assessment of predictions. We propose a new CG-EGA, the PRED-EGA, for the assessment of glucose predictors. The presented analysis shows that, compared with the straightforward application of the CG-EGA, the PRED-EGA gives a significant reduction of the misclassification cases. A reduction by a factor of at least 4 was observed in the study. Moreover, the PRED-EGA is much more robust against uncertainty in the input and references.


Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS).
Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare, X-linked disorder caused by deficient activity of the enzyme iduronate-2-sulfatase (I2S). Treatment is available in the form of enzyme replacement therapy (ERT) with recombinant I2S. Clinical outcomes following ≥3 years of ERT with idursulfase were investigated in a broad population of patients with MPS II enrolled in the Hunter Outcome Survey (HOS). As of January 2016, 639 patients (excluding female patients, individuals who had received a bone marrow transplant and those enrolled in the phase 1/2 [TKT018] or phase 2/3 [TKT024] clinical trial) followed prospectively in the registry had received idursulfase for ≥6 months. These individuals all had data available for ≥1 clinical parameter at baseline and ≥1 additional time point following treatment initiation. Changes in clinical parameters were assessed in the subcohorts of patients with a measurement at baseline and at year 1, 2 or 3 of treatment. Safety data from patients who started treatment at or after enrollment in HOS (n = 233) were also assessed. Median (10th, 90th percentiles) age at first treatment was 6.2 (2.1, 18.2) years and median treatment duration was 56.3 (18.2, 97.6) months. Urinary glycosaminoglycan (uGAG) levels decreased from baseline to year 3 in patients with data available at this time point (median change from baseline: -201.0 [-591.4, -21.9] μg/mg creatinine [n = 121]). Improvements in the following parameters were observed at year 3 in the subcohorts: 6-min walking test (6MWT) distance, 10.6 (-33.6, 50.8)% (n = 26); left ventricular mass index (LVMI), -9.3 (-31.5, 19.7)% (n = 52); absolute forced vital capacity (FVC), 29.7 (-13.4, 66.7)% (n = 23); absolute forced expiratory volume in 1 s (FEV1), 22.8 (-15.2, 62.1)% (n = 22); palpable liver size, -54.5 (-85.7, 50.0)% (n = 53); palpable spleen size, -33.3 (-80.0, 33.3)% (n = 17). No new or unexpected safety concerns were identified in this analysis. These findings suggest that idursulfase has a positive effect on uGAG levels, 6MWT results, LVMI, FVC, FEV1 and hepatosplenomegaly after 1, 2 and 3 years treatment.


Frailty as a Predictor of Future Fracture in Older Adults: A Systematic Review and Meta-Analysis.
Studies have identified frailty as an effective predictor of fracture; however, the correlation between frailty and fracture differs between various stages of frailty. The main aim is to determine the correlation between various stages of frailty and fracture risk; a secondary purpose is to determine the correlation between subgroups (e.g., females, females with a hip fracture, or aged 65 years or older) within the stages of frailty and fracture risk. Finally, effect of frailty criteria on the association between stages of frailty and fracture risk was tested. We conducted a systematic review and meta-analysis. The inclusion criteria were as follows: (a) a prospective study design; (b) subjects aged 55 years or older; (c) a division into robust, prefrail, and frail groups; and (d) reported confidence intervals of hazard ratio. Two investigators independently assessed quality and discussed their findings to reach consensus. The quality of the literature was assessed and the level of evidence was also determined. In total, five studies included 103,783 older people and recorded 2,960 fractures. The results identified that the risk of fracture in the frail people was higher than that in both the robust people (summary HR: 1.67; 95% CI [1.46-1.91]) and prefrail people (summary HR: 1.28; 95% CI [1.16-1.40], and that the risk of fracture in the prefrail people was higher than that in the robust people (summary HR: 1.30; 95% CI [1.20-1.41]). A subgroup analysis revealed that among female adults, older females with hip fracture, or those aged 65 years or more, those who were categorized as frail showed the highest fracture risk, followed by those who were categorized as prefrail. Professional nurses caring for frail or prefrail people should actively develop fracture prevention measures to reduce the risk of death caused by fractures.


The management of preterm labour.
Preterm labour is a major cause of perinatal mortality and morbidity. The aetiology is multifactorial and attempts to predict preterm labour are unsuccessful. At the present time prophylaxis is unhelpful and the obstetrician must manage preterm labour as it arises. The management of preterm labour remains controversial because of the difficulty in conducting good clinical trials. Antepartum glucocorticoids are effective in reducing the incidence and severity of respiratory distress syndrome. The effect is dependent upon a number of factors such as race, fetal sex, gestational age, state of the membranes, fetal asphyxia and timing of delivery in relation to therapy. Tocolytics are effective in stopping contractions but this does not produce a significant prolongation of pregnancy or reduce perinatal mortality or morbidity. It is because they can suppress contractions and delay delivery for a short time that great care should be taken that this short delay is used beneficially, e.g. in-utero transfer, or steroid therapy. It is also important that this suppression does not result in an inappropriate delay where early delivery is indicated because of infection or fetal distress. Steroids, tocolytics and antibiotics are potentially hazardous although all may benefit the fetus. The particular risks versus benefits of each form of therapy should be carefully considered for the particular presentation of each individual patient. While all these agents given antenatally are of potential benefit to the fetus and neonate, prolongation of pregnancy for its own sake or for the sake of allowing time to administer such agents is no substitute for delivery of an infant in optimum condition.


Who is our cohort: recruitment, representativeness, baseline risk and retention in the "Watch Me Grow" study?
The "Watch Me Grow" (WMG) study examines the current developmental surveillance system in South West Sydney. This paper describes the establishment of the study birth cohort, including the recruitment processes, representativeness, follow-up and participants' baseline risk for future developmental risk. Newborn infants and their parents were recruited from two public hospital postnatal wards and through child health nurses during the years 2011-2013. Data was obtained through a detailed participant questionnaire and linked with the participant's electronic medical record (EMR). Representativeness was determined by Chi-square analyses of the available clinical, psychosocial and sociodemographic EMR data, comparing the WMG participants to eligible non-participants. Reasons for non-participation were also elicited. Participant characteristics were examined in six, 12, and 18-month follow-ups. The number of infants recruited totalled 2,025, with 50 % of those approached agreeing to participate. Reasons for parents not participating included: lack of interest, being too busy, having plans to relocate, language barriers, participation in other research projects, and privacy concerns. The WMG cohort was broadly representative of the culturally diverse and socially disadvantaged local population from which it was sampled. Of the original 2025 participants enrolled at birth, participants with PEDS outcome data available at follow-up were: 792 (39 %) at six months, 649 (32 %) at 12 months, and 565 (28 %) at 18 months. Participants with greater psychosocial risk were less likely to have follow-up outcome data. Almost 40 % of infants in the baseline cohort were exposed to at least two risk factors known to be associated with developmental risk. The WMG study birth cohort is a valuable resource for health services due to the inclusion of participants from vulnerable populations, despite there being challenges in being able to actively follow-up this population.


CQI strategies to reduce patient details.
The author presents a case study in which multidisciplinary teamwork, data collection, and carefully planned interventions decreased the number and expense of violent or security-related incidents in a hospital. The study was prepared in collaboration with Claude Barnes, security officer, who did much of the research and statistical analysis.


Balancing personalized medicine and personalized care.
The current description of personalized medicine by the National Institutes of Health is "the science of individualized prevention and therapy." Although physicians are beginning to see the promise of genetic medicine coming to fruition, the rapid pace of sequencing technology, informatics, and computer science predict a revolution in the ability to care for patients in the near future. The enthusiasm expressed by researchers is well founded, but the expectations voiced by the public do not center on advancing technology. Rather, patients are asking for personalized care: a holistic approach that considers physical, mental, and spiritual well-being. This perspective considers psychological, religious, and ethical challenges that may arise as the precision of preventive medicine improves. Psychological studies already highlight the barriers to single gene testing and suggest significant barriers to the predictive testing envisioned by personalized medicine. Certain religious groups will likely mount opposition if they believe personalized medicine encourages embryo selection. If the technology prompts cost-containment discussions, those concerned about the sanctity of life may raise ethical objections. Consequently, the availability of new scientific developments does not guarantee advances in treatment because patients may prove unwilling to receive and act on personalized genetic information. This perspective highlights current efforts to incorporate personalized medicine and personalized care into the medical curriculum, genetic counseling, and other aspects of clinical practice. Because these efforts are generally independent, the authors offer recommendations for physicians and educators so that personalized medicine can be implemented in a manner that meets patient expectations for personalized care.


Regulation of acetylcholine receptors on chick ciliary ganglion neurons by components from the synaptic target tissue.
Chick ciliary ganglion neurons have nicotinic acetylcholine receptors (AChRs) that mediate synaptic transmission through the ganglion. A soluble component of about 50 kDa from embryonic eye tissue, the synaptic target of the ganglion, increases the development of ACh sensitivity by the neurons 10-fold over a 1-week period in culture. The increased sensitivity does not arise from a change in agonist affinity or esterase activity. Both the basal ACh response obtained in the absence of the 50-kDa component and the elevated responses obtained with it can be inhibited by neuronal bungarotoxin (nBgt) but not by alpha-bungarotoxin (alpha Bgt). Increases of less than twofold are observed for the binding of anti-AChR monoclonal antibody 35 (mAb 35), nBgt, and alpha Bgt to the neurons under these conditions. Extract fractions containing the 50-kDa component also enable the neurons to enhance their ACh responses through a cAMP-dependent mechanism. Either the 50-kDa fraction induces the appearance of a new type of AChR regulated by cAMP, or it alters the function of existing AChRs. The 50-kDa fraction produces no change in neuronal growth but can increase GABA responses sixfold, indicating that its effects are not confined to AChRs. It is not clear whether a single molecular species is responsible for the diverse regulatory effects or whether several types of active components are present in the fraction. The component which enhances ACh sensitivity is trypsin-sensitive and heat-labile, as expected for a protein. The component may be widely distributed since the 50-kDa fraction from a number of tissues can increase the ACh response. The fraction from eye tissue, however, has a specific activity 5-10 times greater than that of the liver fraction. A wide distribution would suggest multiple targets and roles for the component during development.


Glycodendron-rhenium complexes as luminescent probes for lectin sensing.
The design, synthesis and characterization of novel glycoconjugate luminescent probes based on dinuclear rhenium(i) complexes are reported. A multivalent platform bearing different carbohydrate moieties (Glc, Gal and Man) was used to target carbohydrate-binding proteins (lectins), exploiting the unique photophysical characteristics of a Re(i) luminophore for protein sensing. Our results show that these glycoconjugates, non-luminescent in aqueous medium, are able to specifically bind different lectins (ConA and PNA) with a consequent enhancement of emission intensity. These findings suggest the use of Re(i)-based glycoconjugates as switch-on luminescent probe tools in biological applications.


Too much to handle? Pesticide dependence of smallholder vegetable farmers in Southeast Asia.
This study aimed to understand farmers' knowledge, attitudes, and practices regarding agricultural pest management and synthetic pesticide use in Southeast Asia. Data were used from 900 farm households producing leaf mustard (Brassica juncea (L.) Czern. et Coss.) and yard-long bean (Vigna unguiculata subsp. sesquipedalis (L.) Verdc.) in Cambodia, Laos and Vietnam. Farmers heavily depended on synthetic pesticides as their main method of pest control. Most farmers were aware of the adverse health effects associated with pesticide use and covered body parts while spraying, but also considered pesticides to be highly effective and indispensable farm inputs. Farmers were largely unable to distinguish between common beneficial and harmful arthropods. Greater knowledge about this was associated with less pesticide use while greater awareness of pesticide health risks was associated with fewer observed poisoning symptoms. For the average farm and while controlling for other factors, farmers who sought advice from friends and neighbors used 45% less pesticide, but those who sought advice from pesticide shopkeepers used 251% more pesticide. Pesticide use was 42% less when a woman was in charge of pest management and 31% less when farmers had adopted biopesticides. These findings suggest relevant entry points for interventions aimed at reducing pesticide dependence.


Prenatal Diagnosis of Persistent Hyperplastic Primary Vitreous: Report of 2 Cases and Review of the Literature.
Persistent hyperplastic primary vitreous is a spectrum of congenital ocular abnormalities characterized by leukocoria, microphthalmia, cataracts, extensive intravitreal hemorrhage, persistence of the hyaloid artery, glaucoma, and retinal detachment. It might be isolated or associated with congenital syndromes such as trisomy 13, Walker-Warburg syndrome, and Norrie disease. We present 2 cases of persistent hyperplastic primary vitreous diagnosed by prenatal sonography in the early third trimester. Bilateral hyperechoic lenses and retinal nonattachment were detected in the sonographic examination of the first case, whereas irregular echogenic bands between the lenses and posterior walls of the eyes were prominent in the second case. In both of the cases, ocular findings were accompanied by intracranial findings, including severe hydrocephalus, an abnormal gyral pattern, and cerebellar hypoplasia, suggesting the diagnosis of Walker-Warburg syndrome. We also present a review of the literature regarding the prenatal diagnosis of this malformation.


Quantitative analysis and prediction of G-quadruplex forming sequences in double-stranded DNA.
G-quadruplex (GQ) is a four-stranded DNA structure that can be formed in guanine-rich sequences. GQ structures have been proposed to regulate diverse biological processes including transcription, replication, translation and telomere maintenance. Recent studies have demonstrated the existence of GQ DNA in live mammalian cells and a significant number of potential GQ forming sequences in the human genome. We present a systematic and quantitative analysis of GQ folding propensity on a large set of 438 GQ forming sequences in double-stranded DNA by integrating fluorescence measurement, single-molecule imaging and computational modeling. We find that short minimum loop length and the thymine base are two main factors that lead to high GQ folding propensity. Linear and Gaussian process regression models further validate that the GQ folding potential can be predicted with high accuracy based on the loop length distribution and the nucleotide content of the loop sequences. Our study provides important new parameters that can inform the evaluation and classification of putative GQ sequences in the human genome.


Mentor vs. mentee perceptions of career mentoring partnerships and work outcomes: A multi-institutional study of faculty mentoring programs.
This article was migrated. The article was marked as recommended. Introduction: Formal mentoring programs are a professional development approach to help junior faculty develop an academic medicine career. This study investigated the perceptions of mentors versus mentees in formal career mentoring partnerships across multiple institutions. Methods: The authors implemented departmental mentoring programs for junior faculty at four academic medical centers. They collected post-program data from mentors and mentees in order to examine the predictors of mentoring satisfaction, mentee outcomes, and work-related variables. Results: The pattern of relationships between the variables differed for mentors versus mentees. Mentoring focus, mentor accessibility and mentee initiative predicted partnership satisfaction and mentee progress. Partnerships that used a mentoring agreement reported greater progress and satisfaction. There were some relationships between partnership outcomes and work-related outcomes. While partnership satisfaction predicted job and administrative/leadership satisfaction for mentors, it predicted positive perceptions of the department's mentoring culture and professional development opportunities for mentees. Conclusions: The study identified unique antecedents and consequences of mentoring partnership satisfaction and mentee outcomes. The varying perspectives of mentors versus mentees indicated a need to clearly communicate partnership expectations and desired outcomes. Overall, the positive impact of formal mentoring programs on partnership and work-related outcomes was supported with implications for future programs and research.


Styrene-induced changes in amacrine retinal cells: an experimental study in the rat.
Dopamine (DA) is synthesized in amacrine cells and released upon membrane depolarization in a calcium-dependent way. Thus, it is recognized to function as a major neurotransmitter or modulator in vertebrate retina. Owing to DA modulating activity on cone-horizontal cells transmission, depletion or dysfunction of amacrine cells could interfere with chromatic processing, accounting for the acquired dyschromatopsia described among styrene-exposed workers. The present study has been designed to test the hypothesis that amacrine cells represent a vulnerable target of styrene in subchronically exposed rats. Ten female Sprague-Dawley rats were exposed to 300 ppm styrene 6 h/day, 5 days/week, for 12 weeks; ten rats exposed to fresh air served as a control group. Whole mounted retinas were used for the morphometry of tyrosine hydroxylase (TH) immunoreactive cells (IR). DA content and TH activity were measured by HPLC and electrochemical detection and glutathione (GSH) was measured by HPLC tandem mass spectrometry (LC-MS/MS). In treated rats, morphometric analysis showed a loss of TH-IR amacrine cells (6.2/mm2 vs. 8.7/mm2 recorded in controls, p = 0.002), without any peripheral-central variation in cell loss. DA content was also lower in exposed, as compared to control animals (208.64 vs. 267.98 microg/g w.w., p = 0.004). The activity of TH in the whole retina was similar in styrene-exposed and control rats when expressed as a function of the wet weight, whereas it was much higher in styrene-exposed rats (+64%) when expressed as a function of the number of TH-IR amacrine cells (p < 0.001). Finally, retinal GSH was reduced by 30% in exposed as compared to control rats (p = 0.01). In summary, retinal TH-IR cells were sensitive to styrene exposure, which seems to cause both structural and functional changes, represented by cell loss and DA depletion, respectively. These findings confirm the vulnerability of dopaminergic systems to styrene toxicity, providing some insights on the possible mechanism of loss in chromatic discrimination recorded among workers occupationally-exposed to styrene.


Acute renal insufficiency and pancreatitis in a child with atypical Henoch-Schönlein purpura: efficacy of a single dose of cyclophosphamide.
A 9-year-old boy with petechiae on the legs and abdominal pain was unsuccessfully treated with steroids. He was admitted to our hospital for the onset of fever, ecchymosis, and arthralgia. Skin lesions suggested vasculitis, but they were not typical of Henoch-Schönlein purpura. He showed ecchymosis of the scrotal bursa, diffusion of petechiae to the trunk and arms, vomiting, severe abdominal pain, oliguria with hyponatremia, hypoalbuminemia, low C3 levels, high levels of creatinine, blood urea nitrogen, and tubular enzymes, proteinuria, and glycosuria. The urinary sediment showed macrohaematuria, and hyaline and cellular casts. Ultrasound showed polyserositis. He was treated with intravenous furosemide, albumin, and methylprednisolone. He underwent colonoscopy and gastroscopy because of development of acute pancreatitis and severe anaemia. Typical lesions of Henoch-Schönlein purpura were observed in the small intestine and colon mucosa. He received three high doses of methylprednisolone, followed by intravenous cyclophosphamide. A dramatic and persistent response was observed after these doses. A single high dose of cyclophosphamide is appropriate in Henoch-Schönlein purpura with acute renal failure and severe pancreatitis that are non-responsive to high-dose steroids.


Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury.
Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.


"Body packers" in Israel: a case series.
"Body packers" swallow multiple packets filled with illicit drugs, mainly cocaine, in order to smuggle them across international borders. In recent years, an increasing number of body packers have been hospitalized after their detention by the police upon arrival in Israel. To characterize the clinical features and outcomes of body packers hospitalized at the Sheba Medical Center. We conducted a retrospective case series of body packers hospitalized between January 2010 and October 2012 in our medical center. Electronic medical records and imaging files were reviewed to extract clinical, laboratory and radiological data as well as details on medical treatments. We identified 23 body packers (mean age 38 +/- 10 years), 20 of whom smuggled cocaine from South America. The number of packets transported ranged from 1 to 242 (median 42) and duration of hospitalization from 1 to 14 days (median 2). Two subjects required surgical intervention. All others were treated conservatively by polyethylene glycol-electrolyte lavage solution, laxatives, or watchful waiting. Ten patients underwent a urinary screen for illicit drugs, 7 of whom tested positive for cocaine and 2 for cannabinoids. Abdominal X-rays were performed in all patients at admission, and 14 had follow-up imaging, including abdominal CT scans without contrast media in 8. The main treatment goals for body packers are the rapid excretion of drug packets and early detection of complications, i.e., drug intoxication and bowel obstruction. We suggest the use of a structured treatment approach for the in-hospital management of body packers.


[Influence of the aminopeptide concentration on the growth of Haemophilus influenzae, type b, and the synthesis of its capsular polysaccharide].
The influence of the aminopeptide concentration on the growth of H. influenzae b culture and the synthesis of H. influenzae b capsular polysaccharide was determined. The maximum amount of capsular polysaccharide was accumulated at the concentration of aminopeptide in the culture fluid reaching 50 ml/l. An increase in the aminopeptide concentration led to a decreased amount of synthesized polysaccharide and an increased amount of biomass. The decrease of the aminopeptide concentration to 10 ml/l resulted in decreased amounts of both biomass and synthesized polysaccharide.


Phenotypic and genetic characterization of Paecilomyces lilacinus strains with biocontrol activity against root-knot nematodes.
Efficient selection of fungi for biological control of nematodes requires a series of screening assays. Assessment of genetic diversity in the candidate species maximizes the variety of the isolates tested and permits the assignment of a particular genotype with high nematophagous potential using a rapid novel assay. Molecular analyses also facilitate separation between isolates, allowing the identification of proprietary strains and trace biocontrol strains in the environment. The resistance of propagules to UV radiation is an important factor in the survival of a biocontrol agent. We have analyzed 15 strains of the nematophagous fungus Paecilomyces lilacinus using these principles. Arbitrarily primed DNA and allozyme assays were applied to place the isolates into genetic clusters, and demonstrated that some genetically related P. lilacinus strains exhibit widespread geographic distributions. When exposed to UV radiation, some weakly nematophagous strains were generally more susceptible than effective isolates. A microtitre tray-based assay used to screen the pathogenic activity of each isolate to Meloidogyne javanica egg masses revealed that the nematophagous ability varied between 37%-100%. However, there was no clear relationship between nematophagous ability and genetic clusters. Molecular characterizations revealed sufficient diversity to allow tracking of strains released into the environment.