Relationship Between Cognitive Functions and Agility Performance in Elite Young Male Soccer Players.
Matlák, J, Fridvalszki, M, Kóródi, V, Szamosszegi, G, Pólyán, E, Kovács, B, Kolozs, B, Langmár, G, and Rácz, L. Relationship between cognitive functions and agility performance in elite, young, male soccer players. J Strength Cond Res 38(1): 116-122, 2024-The aim of this study was to assess the relationship between agility performance and cognitive functions measured under laboratory conditions among elite young soccer players. Twenty-five, elite, young, male soccer players (12.3 ± 0.4 years, 155.4 ± 7.6 cm, 42.6 ± 6.9 kg) completed a battery of field tests, including 5-, 10-, 20-m sprints, change of direction speed (CODS), standing long jump, and an agility test based on a human stimulus. Subjects also completed choice reaction (RT, S3) and reactive stress tolerance (DT, S1) tests on the Vienna Test System. There was a moderate significant relationship (p < 0.05) found between mean reaction time and mean motor time during the choice reaction task and decision time in the agility test. Decision time also showed a large significant correlation (p < 0.05) with total time in the agility test. No significant correlation was found between total time in the agility test and variables measured during RT and DT tests. No significant correlations were found between agility test results and results from straight line sprints, CODS, and standing long jump tests. The results of this study suggest that choice reaction time is related to decision-making speed during the agility task used in this study and can have an indirect effect on agility performance in elite young soccer players. Further studies assessing the relationship between different cognitive functions and agility performance in different sports and age categories could help in the identification of determinant cognitive functions in perceptual and decision-making factors of agility.


A model in environmental training--The University / Elementary School / Municipality Cooperation.
This study targets development of an effective training scheme model that can be implemented at elementary school level with focus on recovery and recycling of wasted papers in Turkey. For this purpose, three schools were chosen from a district within Istanbul. They were separated from one another as full intervention (FI), semi-intervention (SI) and control (C) schools. Different levels of educational activities carried out in the schools, mostly in the FI school, were directed toward being informative as regards recycling and the development of a positive attitude. Afterwards, in order to evaluate the effects of the training, paper wastes were collected in recycle bins placed at appropriate points in schools and weighed on a weekly basis. Quite a significant result was found (p = 0.0001), when the difference was calculated through the Kruskal Wallis Variance Analysis method, regarding the weekly average amount of paper in each of the three schools against per person. Furthermore, when the results were evaluated and compared as to the ones before the 2.5 months summer vacation and the ones after it, the seven measurements taken before (p = 0.001) and the eight taken afterwards (p = 0.0001), were found to have valid differences, once again, as against schools. The results show that the approach we provided to education is an effective method not only for the collection of paper wastes but also for applications in various areas of health education.


Characterizing dual atrioventricular nodal physiology in pediatric patients with atrioventricular nodal reentrant tachycardia.
Dual atrioventricular (AV) nodal physiology, defined as an AH jump > or =50 msec with a 10 msec decrease in A1A2, is the substrate for atrioventricular nodal reentrant tachycardia (AVNRT) and yet it is present in a minority of pediatric patients with AVNRT. Our objective was to characterize dual AV nodal physiology as it pertains to a pediatric population. We retrospectively reviewed invasive electrophysiology studies in 92 patients with AVNRT (age12.1 +/- 3.7 yrs) and in 46 controls without AVNRT (age 13.3 +/- 3.7 yrs). Diagnoses in controls: syncope (N = 31), palpitations (N = 6), atrial flutter (N = 3), history of atrial tachycardia with no inducible arrhythmia (N = 3), and ventricular tachycardia (N = 3). General anesthesia was used in 49% of AVNRT and 52% of controls, P = 0.86. There were no differences in PR, AH, HV, or AV block cycle length. With A1A2 atrial stimulation, AVNRT patients had a significantly longer maximum AH achieved (324 +/- 104 msec vs 255 +/- 67 msec, P = 0.001), and a shorter AVNERP (276 +/- 49 msec vs 313 +/- 68 msec P = 0.0005). An AH jump > or =50 msec was found in 42% of AVNRT versus 30% of controls (P = 0.2). Using a ROC graph we found that an AH jump of any size is a poor predictor of AVNRT. With atrial overdrive pacing, PR > or = RR was seen more commonly in AVNRT versus controls, (55/91(60%) vs 6/46 (13%) P = 0.000). Neither the common definition of dual AV nodes or redefining an AH jump as some value <50 msec are reliable methods to define dual AV nodes or to predict AVNRT in pediatric patients. PR > or = RR is a relatively good predictor of AVNRT.


Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice.
We explored the involvement of oxytocin receptor (Oxtr)/transient-receptor-potential-vanilloid-1 (TRPV1) genes and oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expressions in soleus (SOL) and tibialis anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n = 15) were divided into controls maintained at room temperature (RT = 24°C), exposed to cold stress (CS) at T = 4°C for 6 h , and 5 days. Immunohistochemical studies showed that Oxtr protein expression increased by two-fold (P = 0.01) in PVN and by 1.5-fold (P = 0.0001) in HIPP after 6 h- and 5 days of CS but decreased by 2-fold (P = 0.026) in SON in 5 days. Both Oxtr and TRPV1 gene expression increased after 6 h and 5 days of CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6 h and 5 days but not at control temperature of 24 ± 1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6 h of CS but decreased by 0.2-fold (P = 0.0141) after 5 days-CS. This is the first report that Oxtr and TRPV1 expressions are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.


Interleukin-17A Promotes Arginase-1 Production and 2,4-Dinitrochlorobenzene-Induced Acute Hyperinflammation in Human Papillomavirus E7 Oncoprotein-Expressing Skin.
Human papillomaviruses (HPVs) have evoked numerous mechanisms to subvert host innate immunity and establish a local immunosuppressive environment to facilitate persistent virus infection. Topical application of 2,4-dinitrochlorobenzene (DNCB) was speculated to overcome this immunosuppressive environment and was employed in the immunotherapy of HPV-associated lesions. We have previously shown that DNCB treatment of skin expressing HPV16.E7 protein, the major oncogenic protein expressed in HPV-associated premalignant cervical epithelium, results in a hyperinflammatory response, with an associated induction of Th2 cytokines and infiltration of myeloid cells producing arginase-1, which also contributes to the hyperinflammation. However, the molecular mechanisms underlying arginase-1 induction and arginase-mediated hyperinflammation in K14.E7 skin have not been elucidated. Here, we show that HPV16.E7 protein expression as a transgene in skin is associated with enhanced IL-17A production by macrophages exposed to DNCB. Interestingly, induction of arginase-1 by DNCB is not seen in K14.E7 animals unable to express IL-17A. Further, blockade of either IL-17A or arginase activity alleviates DNCB-induced hyperinflammation through reduced recruitment of neutrophils, as a consequence of decreased CXCL1 and CXCL5 chemokine production. Thus, our findings suggest that increased IL-17A expression by macrophages in E7-expressing skin exposed to DNCB promotes arginase-1 induction and contributes directly to the observed hyperinflammation.


Pathologic features of rhabdomyosarcoma before and after treatment: a clinicopathologic and immunohistochemical analysis.
Few studies have analyzed the relationship among pathology, therapy-induced changes, proliferative activity, and outcome for rhabdomyosarcoma (RMS), despite the challenges of histopathologic interpretation of this tumor after treatment. Although cytodifferentiation and decreased mitotic activity after treatment were documented previously, the clinical consequences of these changes are uncertain because of the small number of cases analyzed. We analyzed 16 RMSs with pre- and post-treatment specimens for clinicopathologic features, outcome, and immunohistochemical data on formalin-fixed, paraffin-embedded tissue for vimentin, smooth muscle actin, muscle-specific actin, desmin, myoglobin, p53 protein, topoisomerase II-alpha, and MIB-1 proliferative activity. Four of eight alveolar (ARMS), five of five botryoid (BRMS), and two of three nonbotryoid embryonal (ERMS) RMSs displayed varying degrees of post-therapeutic histologic maturation and expressed one or more myoid markers. The remaining five RMSs had no cytodifferentiation. Myoid marker expression did not change significantly. In BRMS, MIB-1 and topoisomerase II-alpha proliferative activity decreased after therapy and correlated with cytodifferentiation and survival. This relationship was less clear for ERMS and ARMS. Five nonbotryoid RMSs without cytodifferentiation had either unchanged or increased proliferative activity, and four of these patients died of RMS. Six nonbotryoid RMSs with both cytodifferentiation and residual foci of undifferentiated cells had variable outcomes, including longer survival. We conclude that BRMS and ERMS exhibit therapy-induced cytodifferentiation more frequently than does ARMS. Cytodifferentiation and decreased proliferative activity are associated with favorable outcome in BRMS; unchanged or increased post-therapeutic proliferative activity suggests aggressive biologic potential in ERMS and ARMS. Combined patterns of cytodifferentiation and residual undifferentiated foci might be associated with increased, decreased, or unchanged proliferative activity and are difficult to interpret, but the presence of cytodifferentiation might presage an improved survival. Immunohistochemical analysis for proliferation markers might be useful for highlighting foci of less differentiated RMS or cytodifferentiated tumor cells in contrast to non-neoplastic, terminally differentiated muscle cells.


Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin.
Loss of argininosuccinate synthetase (ASS) expression in melanoma makes these tumor cells vulnerable to arginine deprivation. Pegylated arginine deiminase (ADI-PEG20) which degrades arginine to citrulline and ammonia has been used clinically and partial responses and stable disease have been noted with minimal toxicity. In order to improve the therapeutic efficacy of ADI-PEG20, we have combined ADI-PEG20 with a DNA damaging agent, cisplatin. We have shown that the combination of the two drugs together significantly improved the therapeutic efficacy when compared to ADI-PEG20 alone or cisplatin alone in 4 melanoma cell lines, regardless of their BRAF mutation. In-vivo study also exhibited the same effect as in-vitro with no added toxicity to either agent alone. The underlying mechanism is complex, but increased DNA damage upon arginine deprivation due to decreased DNA repair proteins, FANCD2, ATM, and CHK1/2 most likely leads to increased apoptosis. This action is further intensified by increased proapoptotic protein, NOXA, and decreased antiapoptotic proteins, SURVIVIN, BCL2 and XIAP. The autophagic process which protects cells from apoptosis upon ADI-PEG20 treatment also dampens upon cisplatin administration. Thus, the combination of arginine deprivation and cisplatin function in concert to kill tumor cells which do not express ASS without added toxicity to normal cells.


Enhancement, integration, expansion: Activating representation of detailed features for occluded person re-identification.
A proposed method, Enhancement, integration, and Expansion, aims to activate the representation of detailed features for occluded person re-identification. Region and context are two important and complementary features, and integrating them in an occluded environment can effectively improve the robustness of the model. Firstly, a self-enhancement module is designed. Based on the constructed multi-stream architecture, rich and meaningful feature interference is introduced in the feature extraction stage to enhance the model's ability to perceive noise. Next, a collaborative integration module similar to cascading cross-attention is proposed. By studying the intrinsic interaction patterns of regional and contextual features, it adaptively fuses features across streams and enhances the diverse and complete representation of internal information. The module is not only robust to complex occlusions, but also mitigates the feature interference problem due to similar appearances or scenes. Finally, a matching expansion module that enhances feature discriminability and completeness is proposed. Providing more stable and accurate features for recognition. Compared with state-of-the-art methods on two occluded and holistic datasets, the proposed method is proved to be advanced and the effectiveness of the module is proved by extensive ablation studies.


Health and welfare of dairy cows in different husbandry systems in Switzerland.
Our objective was to compare health and welfare of dairy cows kept in three types of husbandry systems: (1) tie stalls with regular exercise in summer but minimal outdoor access during winter (the reference level for analyses); (2) tie stalls with regular exercise in an exercise yard or pasture throughout the year; (3) loose-housing with regular access to an outdoor exercise yard or pasture. A total of 134 farms were visited (two to) three times in two years. Cows were examined for lameness, skin alterations at the hock joints, scars or injuries at the teats, and skin injuries at other locations. Lying and standing-up behavior were also evaluated. Farmers were requested to record the incidence of medical treatments for the whole observation period. A multivariable logistic-regression analysis was performed for each indicator of health and welfare with husbandry type, aspects of the housing system, farm characteristics, and management routines as the predictor variables. For welfare indicators recorded on individual animals, regression was performed correcting for clustering of observations within herds by Generalized Estimation Equation. Risk factors for the incidence of medical treatments were analyzed in a negative-binomial regression model. The odds for lameness were reduced for tie stalls with regular exercise throughout the year (OR=0.7). The prevalence of alterations at the hock joints was lower in loose-housing with regular outdoor exercise (OR=0.4). Teat injuries were less frequent in loose-housing with regular outdoor exercise (OR=0.1) and tie stalls with regular exercise (OR=0.4). Farms with loose-housing and regular outdoor exercise had a lower incidence of medical treatments (IR=0.6) than reference level farms.


Disability evaluation of the neck and back. The McBride system.
To properly evaluate residual permanent disability arising from impairment of the spine, it is essential to conduct a careful and complete examination in order to arrive at a diagnosis and a determination that present findings are unlikely to change. A formula for computation of permanent disability as developed by McBride includes functional deficiency and physical disorders, taking into account 12 variables. This formula can be simplified to seven components if the physical disorders are mentally computed into the factors of quickness of action, coordination, strength, security, endurance, safety, and adverse employability, which are given weighted values. This method can provide a valid determination of percentage of disability. Some situations only require a delineation of the impairment present and defer disability determination to an agency or board. Currently, there is a trend toward equating the amount of disability with the loss of earnings, which is quite contrary to the longstanding, traditional view.


Effect of humic acids on electricity generation integrated with xylose degradation in microbial fuel cells.
Pentose and humic acids (HA) are the main components of hydrolysates, the liquid fraction produced during thermohydrolysis of lignocellulosic material. Electricity generation integrated with xylose (typical pentose) degradation as well as the effect of HA on electricity production in microbial fuel cells (MFCs) was examined. Without HA addition the maximum power density increased from 39.5 mW/m(2) to 83 mW/m(2) when initial xylose concentrations increased from 1.5 to 30 mM, while coulombic efficiency ranged from 13.5% to 52.4% for xylose concentrations of 15 and 0.5 mM, respectively. Compared to controls where HAs were not added, addition of commercial HA resulted in increase of power density and coulombic efficiency, which ranged from 7.5% to 67.4% and 24% to 92.6%, respectively. Digested manure wastewater (DMW) was tested as potential mediator for power generation due to its content of natural HA, and although it could produce higher coulombic efficiency namely 32.2% than the control of 18.3%, showed lower power density which was approx. 57 mW/m(2) in comparison to power density of the control which was 69 mW/m(2). Presence of commercial HA or DMW in the anode chamber resulted in faster xylose degradation and formation of more oxidized products (acetate and formate) as well as less reduced products (lactate and ethanol) compared to the controls. The reduced power generation in the presence of DMW was attributed to the presence of bacterial inhibitors such as phenolic compounds. Therefore, new feedstocks for MFCs, containing both mediators and substrates, such as lignocellulose hydrolysates should be considered for their applicability in MFCs.


PPO and HMO performance factors: insurance company evaluation criteria.
A venture into managed care should be done only following the proper amount of due diligence. The goal should be to select the most effective managed care organization with the flexibility to meet long-term needs and the mission to work on an ongoing basis to improve service and managed care performance. Unfortunately, all too often purchasers do not demand critical information from managed care service providers. As a result, poor quality organizations have prospered and delivered less than satisfactory results. In fact, it is not unusual that savings from discounts are more than offset by increased use of health care services because of poor utilization management. It is important to be aware that use of the appropriate selection methods and monitoring performance on an ongoing basis are best done by dedicated professionals. They are also resource intensive and require a sophisticated systems capability. Since resources and systems involve significant investment, the most appropriate course for purchasers is to play the role of educated consumers. Detailed documentation should be demanded from all potential service providers to ensure that due diligence and ongoing management are in fact performed. The health care management staff at ITT Hartford is often told by managed care vendors that few other purchasers perform thorough review. It is imperative that managed care be scrutinized at least as closely as any important business venture.


Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095.
In AIDS Clinical Trials Group A5095, 9% of participants who experienced an adverse event related to efavirenz substituted nevirapine. Most adverse events resolved; 15 participants ultimately discontinued nevirapine therapy. Grade 3/4 hepatotoxicity was observed in 14% of individuals who substituted nevirapine, compared with 6% who continued efavirenz therapy. Substitution of nevirapine because of efavirenz toxicity was generally safe and efficacious. Clinical trials registration. NCT00013520 .


The crucial role that hippocampus Cyclooxygenase-2 plays in memory.
It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signalling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability, cause neuronal structure disorder and influence gamma oscillations. These might be mediated by the inhibition of prostaglandin (PG) E2/cAMP pathway and phosphorylated protein kinase A (p-PKA)-phosphorylated cAMP response element binding protein (p-CREB)-brain derived neurotrophic factor (BDNF) axis. It suggested COX-2 might play a critical role in learning, regulating neuronal structure and gamma oscillations in the hippocampus CA1 by regulating COX-2/BDNF signalling pathway.


Examining models of mental health service delivery in the emergency department.
The purpose of the present paper was to review the current models of mental health service delivery used in the emergency department (ED) setting. A search was conducted of the nursing and medical literature from 1990 to 2007 for relevant articles and reports. Consideration was also given to the global and local context influencing contemporary mental health services. Wider sociopolitical and socioeconomic influences and systemic changes in health-care delivery have dictated a considerable shift in attention for mental health services worldwide. The ED is a topical location that has attracted interest and necessitated a response. The mental health liaison nurse (MHLN) role embedded within the ED structure has demonstrated the most positive outcomes to date. This model aims to raise mental health awareness and address concerns over patient-focused outcomes such as reduced waiting times, therapeutic intervention and more efficient coordination of care and follow up for individuals presenting to the ED in psychological distress. Further research is required into all methods of mental health service delivery to the ED. The MHLN role is a cost-effective approach that has gained widespread approval from ED staff and mental health patients and is consistent with national and international expectations for mental health services to become fully integrated within general health care. The mental health nurse practitioner role situated within the ED represents a potentially promising alternative for enhanced public access to specialized mental health care.


Biochemical and histologic changes in rats after prolonged administration of the crude aqueous extract of the leaves of Vitex grandifolia.
In recent times, many herbal remedies are used to treat variety of ailments. The leaves of Vitex grandifolia is claimed to be effective in the treatment of diabetes mellitus and as a diuretic in the treatment of high blood pressure. However, there are no scientific reports on the therapeutic benefits or toxicity of this plant. This study therefore investigated the effect of prolonged administration of the aqueous extract of the leaves of this plant in Sprague-Dawley rats. The plant leaves (No. FHI 107055) were dried at 40° C, powdered and extracted at room temperature in water (pH 5.72) by percolation. Extract was dried in vacuo to give a yield of 27.32 %w/v. The extract, 0.5-2 g/kg b. wt. was administered by gastric probe to rats for 14 days. The liver and kidney functions, blood chemistry, histopathologic alterations of vital organs and extract effect on rats b. wt. were investigated. V. grandifolia caused significant increase in the serum electrolytes, creatinine, and liver function enzyme dose dependently compared with the control (P≤ 0.001). The extract had no effect on the heart; however, the architecture of the liver, kidney, and lungs were significantly altered in the treated groups compared with the control. The treated rats had significantly reduced body weight compared with the control (P≤ 0.001). Major clinical signs observed in the treated groups were polydipsia, polyuria, puffiness of hair, and calmness, which were consistent with increase in dose of the extract. It could be clearly concluded that prolonged administration of the aqueous leaf extract of V. grandifolia at the dose used in this study tends to be toxic to the rats. Its use in folkloric medicine should be with utmost care.


Antisense expression of the CK2 alpha-subunit gene in Arabidopsis. Effects on light-regulated gene expression and plant growth.
The protein kinase CK2 (formerly casein kinase II) is thought to be involved in light-regulated gene expression in plants because of its ability to phosphorylate transcription factors that bind to the promoter regions of light-regulated genes in vitro. To address this possibility in vivo and to learn more about the potential physiological roles of CK2 in plants, we transformed Arabidopsis with an antisense construct of the CK2 alpha-subunit gene and investigated both morphological and molecular phenotypes. Antisense transformants had a smaller adult leaf size and showed increased expression of chs in darkness and of cab and rbcS after red-light treatment. The latter molecular phenotype implied that CK2 might serve as one of several negative and quantitative effectors in light-regulated gene expression. The possible mechanism of CK2 action and its involvement in the phytochrome signal transduction pathway are discussed.


Anatomical leg length inequality, scoliosis and lordotic curve in unselected clinic patients.
Anatomic leg length inequality (LLI) and various mechanical measures of the lumbar spine, particularly scoliosis, lordosis and Ferguson's angle, were analyzed retrospectively from the X-rays of 106 consecutive patients in a private chiropractic practice. Results showed that 40% of the subjects had LLI greater than 6 mm while 70% had LLI greater than 3 mm. These data compared closely with studies done by other investigators, indicating that our routine diagnostic X-ray procedure is sufficient for accurately determining LLI. Our most noteworthy finding was that patients with LLI greater than 6 mm often (53% of the cases) had scoliosis and/or abnormal lordotic curves. Altered lordotic curves comprised both hypo- and hyperlordosis with about equal frequency. The correlation coefficients between the amount of LLI and any of the parameters taken singly, however, were not significant. The results of this study indicate that while there is no strong correlation between any one of the particular postural adaptations to anatomic leg length deficiency, nevertheless at least one abnormal spinal adaptation (scoliosis or hypo-hyperlordosis) occurs in over half of subjects who have LLI greater than 6 mm.


Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia.
Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.


Humpback whales harbour a combination of specific and variable skin bacteria.
Investigations of marine mammal skin-associated microbiota are limited to cultivation-based studies of lesioned individuals, resulting in a lack of understanding about the composition of 'normal' skin-associated microbial communities, their variation among individuals, and whether or not the microbial communities change with host health or environmental exposures. In this study, bacterial communities associated with the skin of 19 North Pacific humpback whales (Megaptera novaeangliae), including skin from three health-compromised individuals, were examined using small subunit ribosomal RNA gene-based culture-independent techniques. These analyses revealed that the skin-associated bacteria were significantly different from free-living bacterial communities in the surrounding seawater. Two novel groups within the Flavobacteriaceae family of the Bacteroidetes phylum were found to be associated with multiple whales, including a species within the Tenacibaculum genus that associated with 95% of the individuals. Statistical analyses revealed that a group of eight 'healthy' whales harboured similar microbial communities, while the health-compromised and other 'healthy' animals harboured communities that were unique to the specific animal. These results describe two components of the whale skin bacterial community: a specific and potentially co-evolved fraction, and a more variable microbial community fraction that may offer a diagnostic-type tool for investigating the health and life-related events of these endangered animals.


What Factors Influence the Sleep of On-call Workers?
Objective: On-call work is becoming increasingly common in response to service demands. This study had two aims; 1) describe the demographic profile of on-call workers in Australia, and 2) establish the impacts of on-call work on workers' sleep. Methods: A cross-sectional study was conducted using an online questionnaire completed by Australian on-call workers (n = 228) from various professions. The questionnaire included items on i) demographic and work characteristics, ii) rumination about on-call factors, iii) sleep quantity and quality. Analyses were conducted using mixed effects ordinal regression and multivariable logistic regression. Results: Workers slept <7 hours per night when on-call (80%), and reported sleep was impacted on-call even when no-calls were received (56%). On-call workers rated interruptions to family/leisure time (70%), missing a call (69%), preplanning in case of a call (69%), and not able to make plans (67%) as the main factors they ruminated about. Female on-call workers were more likely to think about the likelihood of being called, report frequent thoughts about what they would need to do if called, and think about interruptions to family/leisure time as a result of a call. Younger workers were more likely to think about the likelihood of being called compared to older adults, however middle-aged workers were less likely to plan for a call compared to younger workers. Conclusions: This study is the first to describe Australia's on-call population, including factors that specifically impact sleep. Future studies should implement tailored education and support strategies to address the unique challenges facing on-call workers.


Nutraceuticals and biotics in pediatric gastrointestinal disorders.
In recent years there has been growing interest in the use of nutraceuticals and biotics in both pediatric and adult clinical practice. The overlapping and often ambiguous symptoms of both functional and organic gastrointestinal disorders have led to a search for alternative therapeutic approaches that avoid the use of synthetic or chemical treatments. However, while nutraceuticals and natural supplements are widely used, their health benefits are often not supported by adequate scientific evidence, and an unregulated use of nutraceuticals can be potentially harmful. The correct use of nutraceuticals, prebiotics, and probiotics can optimize the results of drug therapy in some cases and reduce the risk of side effects. This review aims to provide clinicians with guidance on the use of complementary therapies for pediatric gastrointestinal symptoms and disorders, highlighting the scarcity of studies on the kinetics and dynamics of nutraceuticals and biotics. While it is generally difficult to associate their intakes with adverse events due to the often-coexisting pharmacological treatments, it is essential to avoid the abandonment of traditional drugs with proven efficacy in the treatment of single diseases. Overall, the use of nutraceuticals, prebiotics, and probiotics in pediatric gastroenterological practice requires caution and medical supervision. Further research is needed to determine the effects of alternative therapies on pediatric gastrointestinal symptoms and disorders, and to ensure their safe and effective use in the clinical practice.


Beta-endorphin, beta-lipotropin and adrenocorticotropic hormone levels in cerebrospinal fluid, and brain damage in chronic alcoholics.
In 34 chronic alcoholics, subdivided into two groups according to the state of the blood-brain barrier (BBB), beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), ACTH and cortisol levels were determined in basal conditions in the plasma and cerebrospinal fluid (CSF). Hormonal concentrations were correlated with brain damage and mnesic function. The results indicate the reduced CSF beta-EP content in chronic alcoholics and suggest that peripheral beta-EP may penetrate into the CSF compartment when there is BBB damage. They also sustain the different origins of central and peripheral pro-opiocortin-related peptides, and support the concept that beta-EP, beta-LPH and ACTH may be autonomously regulated at the central level. Moreover, both morphological brain damage and mnesic impairment in chronic alcoholics are unrelated to CSF peptide levels. The role of opioid peptides in the nature of alcohol-seeking behavior is supported.


Disparity in outcomes for adult Native American hemodialysis patients? Findings from the ESRD Clinical Performance Measures Project, 1996 to 1999.
There is a paucity of information regarding the quality of care for Native American hemodialysis patients. Outcomes, including 1-year hospitalization and mortality, for adult Native American in-center hemodialysis patients selected for the Centers for Medicare and Medicaid (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project were compared to those for white and black patients to determine if disparity in care existed for this group. Clinical data were abstracted from medical records for the last quarters of 1995 to 1998 and linked to United States Renal Data System (USRDS) data files for data on comorbidities and 1-year hospitalization and mortality. Associations of race were tested by bivariate analyses and multivariate logistic regression and Cox proportional hazard modeling. Two percent (467 of 27876) of patients were Native American, 37% black, and 51% white. Native American, compared to black and white patients, were more likely to have diabetes mellitus as the cause of ESRD (72%, 37%, and 38%, respectively, P < 0.01). In multivariate analyses, Native American patients were more likely to achieve a mean urea reduction ratio (URR) > or = 65% compared to whites (referent) [hazards ratio (HR) (95% CI) 1.7 (1.3, 2.2)] and be dialyzed with an arteriovenous fistula [HR (95% CI) 1.7 (1.2, 2.5)]. They were as likely as Whites to achieve a mean hematocrit > or =33% and a mean serum albumin > or =4.0/3.7 g/dL. In multivariate analyses, Native Americans were no more likely to be hospitalized or die during the follow-up period than whites. These data suggest that adult Native American hemodialysis patients experience equivalent or better dialytic care and are no more likely to experience 1-year hospitalization or mortality compared to whites.


Trauma on Farms in the Republic of Ireland.
Farming is the most dangerous occupation in high-income countries worldwide. However, there is a lack of descriptive literature in this area. Injuries on farms are increasing, at a time when the cohort of trauma patients generally has become older and more medically complex. Farmers continue to work late in life when other industry workers would be retired. This study describes major trauma occurring on farms in the Republic of Ireland, the demographics of patients and treatments they received. Data was gathered from the National Office of Clinical Audit Major Trauma Audit (MTA) 2014 to 2016. Patients were included and excluded based on Trauma Audit and Research Network(TARN) inclusion criteria. There were 430 patients included in this study. The median age was 54.5 years (range 1-93). There were 6.3%(n=27) paediatric patients, and 27%(n=116) over 65-year olds. Patients had predominantly low Charlson Comorbidity Index scores (median 0). Patients >65 years had more comorbidities (p<0.001). The median ISS was 9(IQR 9-17). The most common mechanism of injury was blow from animal (n=126,29%) followed by low fall (n=115,27%). Summer was the most common season of injury (n=128,30%) and most patients presented to a hospital between 8am-12am(n=412,96%). There were 11 patients (2.6%) who died after arrival to hospital - most commonly due to head injury (n=5,45%). The median length of stay was six days; older patients stayed longer than younger patients (6 vs 12 days,p<0.001). The most common body area injured was limbs (n=139,32%), followed by chest (n=89,21%), spine (n=67,16%) and head injuries (n=64,15%). There were 84 patients (19.5%) who underwent operative intervention, and 77(18%) required intensive care unit (ICU) admission. Farm trauma patients were more likely to arrive by helicopter than other MTA patients. A substantial proportion of trauma on Irish farms involves older men who have co-morbidities and complexity of medical need. Farm trauma occurs in rural and remote locations with longer journey times to trauma centres and trauma units-this has implications for trauma care education and mode of EMS transport. Older patients who suffer trauma on farms require longer hospital stays and may not return to independent living.


Methotrexate supports in vivo selection of human embryonic stem cell derived-hematopoietic cells expressing dihydrofolate reductase.
Human embryonic stem cells (hES Cs) are an attractive alternative cell source for hematopoietic gene therapy applications as the cells are easily modified with lentiviral or other vectors and can be subsequently induced to differentiate into hematopoietic progenitor cells. However, demonstration of the full hematopoietic potential of hESC-derived progeny is challenging due to low marrow engraftment and the difficulty of detecting cells in the peripheral blood of human/mouse xenografts. Methotrexate (MTX) chemotherapy coupled with expression of a drug resistant dihydrofolate reductase such as Tyr22 (Tyr22DHFR) has the potential to selectively increase engraftment of gene-modified human hematopoietic cells in mice, which would allow for better phenotypic characterization of hESC-derived cells in vivo. We showed that hES Cs transduced with Tyr22DHFR-GFP encoding lentivirus vectors differentiate into MTX resistant (MTXr) hemato-endothelial cells. MTX treatment of immunodeficient mice infused with Tyr22DHFR hESC-derived hemato-endothelial cells increased the long-term engraftment of human cells in the bone marrow of MTX-treated mice. In contrast to previous studies, these results indicate that MTX administration has the potential to support in vivo selection that is maintained after cessation of treatment. The MTX/Tyr22DHFR system may therefore be useful for enrichment of gene-modified cell populations in human stem cell and gene therapy applications.


Job characteristics and the subjective oral health of Australian workers.
The way in which work is structured and organised is associated with the health and well-being of workers. To examine the associations between hours worked, job security, skill maintenance and work and home interference and subjective oral health; and to compare findings for different occupational groups. Data were collected in 1999 from a random stratified sample of households in all Australian States and Territories using a telephone interview and a questionnaire survey. Subjective oral health was evaluated with the short form Oral Health Impact Profile (OHIP-14), which assesses the adverse impact of oral conditions on quality of life. Data were obtained for 2,347 dentate adults in the workforce. In the 12 months preceding the survey, 51.9% had experienced oral pain and 31.0% reported psychological discomfort from dental problems. Males, young adults, Australian-born workers, and those in upper-white collar occupations reported lower mean OHIP-14 scores (ANOVA p < 0.001). Having controlled for the effects sex, age, country of birth and socioeconomic factors in a linear multiple regression analysis, hours worked, skill maintenance and work and home interference were significantly associated with OHIP-14 scores for all workers. While part-time work was associated with higher OHIP-14 among upper white-collar workers, working >40 hours a week was associated with higher OHIP-14 scores for other workers. Aspects of the work environment are associated with the subjective oral health of workers. Because these contexts are subject to only limited control by individual workers, their influence is a public health issue.


Structural basis for nuclear import selectivity of pioneer transcription factor SOX2.
SOX (SRY-related HMG-box) transcription factors perform critical functions in development and cell differentiation. These roles depend on precise nuclear trafficking, with mutations in the nuclear targeting regions causing developmental diseases and a range of cancers. SOX protein nuclear localization is proposed to be mediated by two nuclear localization signals (NLSs) positioned within the extremities of the DNA-binding HMG-box domain and, although mutations within either cause disease, the mechanistic basis has remained unclear. Unexpectedly, we find here that these two distantly positioned NLSs of SOX2 contribute to a contiguous interface spanning 9 of the 10 ARM domains on the nuclear import adapter IMPα3. We identify key binding determinants and show this interface is critical for neural stem cell maintenance and for Drosophila development. Moreover, we identify a structural basis for the preference of SOX2 binding to IMPα3. In addition to defining the structural basis for SOX protein localization, these results provide a platform for understanding how mutations and post-translational modifications within these regions may modulate nuclear localization and result in clinical disease, and also how other proteins containing multiple NLSs may bind IMPα through an extended recognition interface.


Tactics for vascular protection after acute ischemic stroke.
The vascular events that happen during ischemic stroke worsen outcomes in patients by causing edema, hemorrhagic transformation, and general neurologic tissue compromise. In the past 2 decades, clinical trials in patients after ischemic stroke focused on neuroprotection, but these strategies have failed in providing actual benefit. Vascular protection represents a new field to be explored in acute ischemic stroke in order to develop new approaches to therapeutic intervention. We identified tactics likely to provide vascular protection in patients with ischemic stroke. These tactics are based on knowledge of the molecular processes involved. The pathologic processes due to vascular injury after an occlusion of a cerebral artery can be separated into acute (those occurring within hrs), subacute (hrs to days), and chronic (days to mo). Targets for intervention can be identified for all three stages. In the acute phase, superoxide is the predominant mediator, followed by inflammatory mediators and proteases in the subacute phase. In the chronic phase, proapoptotic gene products have been implicated. Many already-marketed therapeutic agents (statins, angiotensin modulators, erythropoietin, minocycline, and thiazolidinediones), with proven safety in patients, have been shown to have activity against some of the key targets of vascular protection. Currently available pharmacologic agents are poised for clinical trials of vascular protection after acute ischemic stroke.


A new class of stem cells in South Africa: iPS cells.
Created from adult rather than embryonic cells, induced pluripotent stem (iPS) cells represent a breakthrough in stem cell science, and their pioneers have been recognised with the 2012 Nobel Prize in Medicine. These cells offer new hope in the treatment of pathogenetic diseases, but there is still a way to go on the road to effective therapeutic applications.


Apoptotic-like phenotype triggered by hydrogen peroxide and amphotericin B in the fungus Rhizopus arrhizus.
Rhizopus is the most common genus of invasive mucormycosis, whose prognosis and outcome was not improved over the past decades. We studied the apoptotic-like phenotype in Rhizopus arrhizus exposed to hydrogen peroxide (H2 O2 ) and amphotericin B (AMB). The strain provided by Fungal Genetic Stock centre was studied about the apoptotic-like phenotype treated with different concentrations of H2 O2 and AMB, and then analyzed by fluorescent microscopy (observed by Annexin-V/FITC and TUNEL staining), flow cytometry (stained with DHR123/PI), and DNA agarose gel electrophores. When R. arrhizus was treated with H2 O2 and AMB, there was a loss of viability associated with different phenotype of apoptosis makers. Membrane externalization of phosphatidylserine (PS) on the cell surface, DNA fragmentation, chromatin condensation can be induced and observed obviously by Annexin-V/FITC, DAPI and TUNEL staining. DNA smear not DNA ladder was also visible in R. arrhizus. Flowcytometry of R. arrhizus cells revealed not only the increase of apoptosis cell stained with DHR123 under the nonfungicida doses but dead cells stained with PI under the fungicida concentrations.This study indicated that both H2 O2 and AMB could induce the apoptotic-like phenotype in R. arrhizus.


Attitudes toward physical activity and exercise: comparison of memory clinic patients and their caregivers and prediction of activity levels.
Regular physical activity and exercise (PA&E) reduces cognitive aging, may delay dementia onset, and for persons with dementia, may slow progression and improve quality of life. Memory clinic patients and caregivers described their PA&E and completed the Older Persons' Attitudes Toward Physical Activity and Exercise Questionnaire (OPAPAEQ). Caregivers and patients differed in their PA&E attitudes: patients were less likely to believe in the importance of PA&E for health promotion. PA&E attitudes were explored as predictors of self-reported exercise habits. Belief in the importance of high intensity exercise for health maintenance was the only variable that significantly predicted engagement in regular PA&E. Moreover, caregivers' attitudes toward high intensity exercise predicted memory patients' participation in PA&E. These findings may aid in development of exercise interventions for people with memory problems, and suggest that modification of specific attitudes toward exercise is an important component to ensure maximum participation and engagement in PA&E.


Transposon mutagenesis identifies sites upstream of the Neisseria gonorrhoeae pilE gene that modulate pilin antigenic variation.
Gene conversion mediates the variation of virulence-associated surface structures on pathogenic microorganisms, which prevents host humoral immune responses from being effective. One of the best-studied gene conversion systems is antigenic variation (Av) of the pilin subunit of the Neisseria gonorrhoeae type IV pilus. To identify cis-acting DNA sequences that facilitate Av, the 700-bp region upstream of the pilin gene pilE was targeted for transposon mutagenesis. Four classes of transposon-associated mutations were isolated, distinguishable by their pilus-associated phenotypes: (i) insertions that did not alter Av or piliation, (ii) insertions that blocked Av, (iii) insertions that interfered with Av, and (iv) insertions that interfered with pilus expression and Av. Mutagenesis of the pilE promoter did not affect the frequency of Av, directly demonstrating that pilin Av is independent of pilE transcription. Two stretches of sequence upstream of pilE were devoid of transposon insertions, and some deletions in these regions were not recoverable, suggesting that they are essential for gonococcal viability. Insertions that blocked pilin Av were located downstream of the RS1 repeat sequence, and deletion of the region surrounding these insertions completely abrogated pilin Av, confirming that specific sequences 5' to pilE are essential for the recombination events underlying pilin Av.


First Canadian experience with donation after cardiac death simultaneous pancreas and kidney transplants.
Compared with neurologic determination of death (NDD) donor organs, donation after cardiac death (DCD) donor organs have traditionally been considered of inferior quality owing to warm ischemia experienced during procurement. We present, to our knowledge, the first analysis of simultaneous pancreas and kidney (SPK) transplants using DCD donor organs in Canada. We carried out a retrospective cohort study of SPK transplants from 13 DCD and 68 NDD donors performed between October 2008 and July 2016. In all patients immunosuppression was induced with thymoglobulin and continued with tacrolimus, mycophenolate mofetil and prednisone maintenance therapy. Donor and recipient characteristics of DCD and NDD groups were similar with respect to age, sex, body mass index, kidney and pancreas cold ischemia times, and donor terminal creatinine. Mean DCD graft warm ischemia time was 0.5 (range 0.4-0.7) hours. Median follow-up was 2.2 (range 0.1-6.7) years and 2.7 (range 0.3-6.3) years for the DCD and NDD groups, respectively. The DCD and NDD groups were similar with regards to recipient percent panel reactive antibody and presence of human leukocyte antigen antibodies. The groups also received similar total doses of thymoglobulin. In total 38% of patients in the DCD group experienced renal delayed graft function (DGF) compared with 10% in the NDD group (p = 0.027). There were 7 cases of pancreas graft thrombosis requiring relaparotomy in the NDD group compared with none in the DCD group. No patients from either group required insulin at any time after transplant. Although the estimated glomerular filtration rate (eGFR) was lower in the DCD than the NDD group on postoperative days 7 and 14 (p = 0.025), no difference was noted on day 30 or through 4 years after transplant. No differences were seen between the groups with respect to amylase, lipase, or glycosated hemoglobin (HbA1c) up to 4 years after transplant, or in kidney, pancreas, or patient survival at any time after transplant. Our results show that, apart from a higher renal DGF rate, SPK transplants with DCD donor organs have comparable outcomes to standard transplants with NDD donor organs.


Translation and cultural adaptation of Peds QL TM ESRD to Portuguese.
To translate into and adapt to Brazilian Portuguese the Peds QL TM - End Stage Renal Disease version 3.0 questionnaire. The methodology proposed by the creator of the original questionnaire was adopted. It consisted of 4 phases: translation from English into Brazilian Portuguese, back-translation into English, application to a population sample and proof-reading and completion. The translations and review were made by professional experts in Portuguese and English. The questionnaires were composed of versions for children and adolescents' reports and parents' reports, and were divided according to age ranges: 2-4 years (parents' report only), 5-7 years, 8-12 years and 13-18 years. 35 interviews were conducted with 15 children and adolescents and 20 carergivers. The process of translation and cultural adaptation, which consisted of semantic equivalence (equivalence between words), idiomatic equivalence (no equivalent expressions found or items that needed to be replaced) and experimental equivalence (words and situations appropriate to the Brazilian cultural context), resulted in a version that was understandable and easy to apply.


Developmental changes in carbonic anhydrase and adenylate cyclase in quaking mice.
The present investigation focuses on the developmental changes in the activity and levels of carbonic anhydrase, adenylate cyclase and 3',5'-cyclic adenosine monophosphate (cAMP) in the Quaking mouse mutant in different regions of the brain. Carbonic anhydrase activity was found to be lower than normal in the forebrain of the C57/B Quaking mouse. The deficit in forebrain carbonic anhydrase was restricted to subcortical structures and was reflected equally in the membrane and soluble factions, indicating that neither pool was affected selectively. However, no difference in carbonic anhydrase activity was observed in purified myelin from Quaking and control mice. Investigation of the changes in carbonic anhydrase activity as a function of age showed a cessation in enzyme accumulation in Quaking mice at around 20 days postnatally, suggesting an abnormality in cellular development. A tritiated acetazolamide binding assay was used to quantitate the amount of enzyme present. The amount of carbonic anhydrase parallelled enzyme activity, suggesting that the defect in the Quaking animals was at the level of the control of enzyme synthesis. Similar studies on cyclic AMP metabolism showed a higher than normal adenylate cyclase activity in the upper brain stem region of Quaking mice of ages between 19 and 40 days. Adenylate cyclase activity was stimulated by norepinephrine in both control and Quaking animals. The increased adenylate cyclase activity in the Quaking mice was in contrast to a lower cyclic AMP level and could not be accounted for by an alteration in phosphodiesterase activity.


Time-evolving controllability of effective connectivity networks during seizure progression.
Over one third of the estimated 3 million people with epilepsy in the United States are medication resistant. Responsive neurostimulation from chronically implanted electrodes provides a promising treatment alternative to resective surgery. However, determining optimal personalized stimulation parameters, including when and where to intervene to guarantee a positive patient outcome, is a major open challenge. Network neuroscience and control theory offer useful tools that may guide improvements in parameter selection for control of anomalous neural activity. Here we use a method to characterize dynamic controllability across consecutive effective connectivity (EC) networks based on regularized partial correlations between implanted electrodes during the onset, propagation, and termination regimes of 34 seizures. We estimate regularized partial correlation adjacency matrices from 1-s time windows of intracranial electrocorticography recordings using the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO). Average and modal controllability metrics calculated from each resulting EC network track the time-varying controllability of the brain on an evolving landscape of conditionally dependent network interactions. We show that average controllability increases throughout a seizure and is negatively correlated with modal controllability throughout. Our results support the hypothesis that the energy required to drive the brain to a seizure-free state from an ictal state is smallest during seizure onset, yet we find that applying control energy at electrodes in the seizure onset zone may not always be energetically favorable. Our work suggests that a low-complexity model of time-evolving controllability may offer insights for developing and improving control strategies targeting seizure suppression.


Acute endotoxemia increases left ventricular contractility and diastolic stiffness in calves.
We investigated the acute effects of endotoxemia on left ventricular (LV) contractility, relaxation, diastolic properties, and mechanical energetics in closed-chest calves. Twelve male calves (4 to 10 days old) were anesthetized with alpha-chloralose and instrumented to measure the LV pressure-volume relationship. Calves (n = 6) in the control group remained hemodynamically stable for 4 h. Calves (n = 6) administered endotoxin (0.1 microg/kg, O55:B5, i.v., over 0.5 h) had increased heart rate, mean pulmonary artery pressure, LV contractility (end-systolic elastance), chamber stiffness, and mechanical efficiency, no change in LV relaxation, and decreased mean systemic arterial pressure, cardiac output, and LV stroke work and pressure-volume area. Endotoxin-induced changes were maximal at t = 0.5 h, after which time all hemodynamic variables gradually returned towards baseline values. Intravenous administration of isoproterenol (0.02 microg x kg(-1) x min(-1)) alone or combined with phenylephrine (5 microg x kg(-1) x min(-1)) at t = 4 h produced similar increases in heart rate, end-systolic elastance, and cardiac output in control and endotoxin-treated groups. Our findings indicate that circulatory dysfunction, rather than LV dysfunction, predominates during acute endotoxemia (4 h) in chloralose-anesthetized, closed-chest neonatal calves.


Distribution of Helicobacter pylori in north China.
To compare the distribution of virulence-associated genotypes of Helicobacter pylori (H pylori) in two areas of north China with different gastric cancer risk and furthermore probe into the pathogenicity of the bacterium. Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk area of gastric cancer, and 136 subjects from Shenyang, a low risk area of gastric cancer. A total of 149 H pylori strains isolated from these patients were studied by PCR for differences in the genotypes of cagA, vacA, and iceA. In patients with high risk for gastric cancer, higher frequencies of vacA s1 or s1m1b genotypes were found as compared to those from the low risk area. There is significantly different distribution of H pylori genotypes between Zhuanghe and Shenyang areas in north China.


Glycoprotein Ib beta is the only phosphorylated major membrane glycoprotein in human platelets.
Platelets were metabolically labelled with 32P and the phosphoproteins examined by two-dimensional non-reduced/reduced gel electrophoresis and isoelectric-focusing/gel electrophoresis. Comparison with similar separations of surface-labelled platelets showed that the only major glycoprotein which is phosphorylated is the beta-subunit of glycoprotein Ib, indicating that this subunit contains a cytoplasmic segment. The identification was confirmed using immunoblotting with an antibody to the beta-subunit. Phosphoserine was the principal phosphorylation site, with some phosphothreonine, but phosphotyrosine was absent. No quantitative or qualitative differences could be detected in the phosphorylation of glycoprotein Ib beta from resting or activated platelets. These results exclude changes in phosphorylation of the major platelet membrane glycoproteins as a method of signal transmission by these receptors.


Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial.
To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol (E2) gel for relief of menopausal symptoms in a population of postmenopausal women. This study was a randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d (n=136), 1.7 g/d (n=142), or 2.6 g/d (n=69) E2 gel or placebo gel (n=137) topically for 12 weeks. The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined. With increasing E2 doses, mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3-5, E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day (P<.001) and reduced the severity score (P<.01). The numbers needed to treat for benefit for an 80% and 100% decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group. At week 12, vaginal pH was more acidic and vaginal maturation index more mature compared with placebo (P<.001). The lowest dose improved most bothersome vulvovaginal atrophy symptoms (P<.05). Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects. The 0.87 g/d dose produced fewest adverse events. The 0.87 g/d dose of this new transdermal E2 gel, which delivers an estimated 0.0125 mg E2 daily, delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00391417. I.


[Nursing care in the patient with an artificial airway in the intensive care unit].
Complications related to the artificial airway (endotracheal tube and tracheotomy) in intensive care units are a major health problem that depends largely on the management and care applied to these devices. The daily challenge of nursing professionals is to minimize the incidence of these complications (among which highlights the pneumonia associated with mechanical ventilation). We analyzed 21 measures related to management of these devices in order to reflect the recommendations based on scientific evidence and provide quality care applied to the patient that need these devices. Compliance with the standards for care and management of patients with an artificial airways is vital in reducing the incidence of complications associated with these devices. Not all management rules are standardized.


High-power soliton-induced supercontinuum generation and tunable sub-10-fs VUV pulses from kagome-lattice HC-PCFs.
We theoretically study a novel approach for soliton-induced high-power supercontinuum generation by using kagome lattice HC-PCFs filled with a noble gas. Anomalous dispersion and broad-band low loss of these fibers enable the generation of two-octave broad spectra by fs pulses, with high coherence and high spectral peak power densities up to five orders of magnitude larger than in standard PCFs. In addition, up to 20% of the output radiation energy forms a narrow UV/VUV band, which can be tuned by controlling the pressure in the range from 350 nm to 120 nm. In the temporal domain this corresponds to sub-10-fs UV/VUV pulses with pulse energy of few tens of microJ, caused by the formation of a high-order soliton emitting non-solitonic radiation.


The interactive effects of dietary sodium chloride and calcium on cardiovascular stress responses.
Blood pressure increases associated with salt loading in the spontaneously hypertensive rat (SHR) are attenuated with increased dietary calcium. To assess the cardiovascular effects of these nutrients during stress, blood pressure and sympathoadrenal responses to stress were compared in salt-sensitive SHRs fed diets containing normal (0.73%) or high (8.0%) NaCl combined with either low (0.2%) or high (2.0%) calcium. NaCl-loaded rats showed increased blood pressure and exaggerated plasma epinephrine changes during restraint stress. Elevated blood pressure responses to exogenous NE were also observed with high salt intake. Supplementary calcium reduced blood pressure and attenuated the hypertensive effect of NaCl during restraint stress. Animals fed the high calcium diets had lower plasma epinephrine levels while vascular reactivity was not affected. The results indicate that increased sympathoadrenal activity and vascular reactivity contribute to elevated blood pressure and exaggerated pressor responses produced by NaCl loading in the salt-sensitive SHR. However, the hypotensive effects of dietary calcium appear to be related to sympathoadrenal activity but not vascular reactivity.


Altered expression of heat shock proteins in embryonal carcinoma and mouse early embryonic cells.
In a previous paper, we have shown that in the absence of stress, mouse embryonal carcinoma cells, like mouse early embryo multipotent cells, synthesize high levels of 89- and 70-kilodalton heat shock proteins (HSP)(O. Bensaude and M. Morange, EMBO J. 2:173-177, 1983). We report here the pattern of proteins synthesized after a short period of hyperthermia in various mouse embryonal carcinoma cell lines and early mouse embryo cells. Among the various cell lines tested, two of them, PCC4-Aza R1 and PCC7-S-1009, showed an unusual response in that stimulation of HSP synthesis was not observed in these cells after hyperthermia. However, inducibility of 68- and 105-kilodalton HSP can be restored in PCC7-S-1009 cells after in vitro differentiation triggered by retinoic acid. Similarly, in the early mouse embryo, hyperthermia does not induce the synthesis of nonconstitutive HSP at the eight-cell stage, but induction of the 68-kilodalton HSP does occur at the blastocyst stage. Such a transition in the expression of HSP has already been described for Drosophila melanogaster and sea urchin embryos and recently for mouse embryos. It may be a general property of early embryonic cells.


Rehabilitation needs of persons discharged from an African trauma center.
The study prospectively assessed the functional impairments and rehabilitation needs of Africans admitted to a regional trauma center. It also acts as a pilot study to demonstrate the practical use of the Language Independent Functional Evaluation (L.I.F.E.) software in an acute hospital setting. A 5 page questionnaire was used to gather demographic data (age, sex, medical diagnosis, education, housing type, place of residency, occupation), cause of disability/injury, severity of disability or functional impairment, and rehabilitation treatment received (types of rehab, frequency of treatment, duration of therapy, follow up therapy, equipment). Functional status on discharge was evaluated with the L.I.F.E. scale. 84 consecutive consenting subjects were recorded. The predominant disability/injury of respondents involved the lower extremities (70%), followed by upper extremities (23%). The mechanisms of injury were largely related to auto accidents (69%). Falls made up 17% of these injuries and 14% were related to violence. Eleven subjects had disability measured using L.I.F.E and all were classified as having major disabilities. Only 14 patients (17%) received any rehabilitation therapy which consisted of only physical therapy provided at a frequency of once a day for less than one week duration. This study found that most persons admitted to a sophisticated trauma unit in Ghana are discharged without adequate rehabilitation services, and that the level of disability experienced by these people can be measured, even while they are still sick and in the hospital, using L.I.F.E. The implications are clear: African trauma systems must measure the long term outcomes from their treatments and provide the inpatient medical rehabilitation services that are a standard of care for trauma victims elsewhere in the world.


Effect of knock down of spinal cord PSD-93/chapsin-110 on persistent pain induced by complete Freund's adjuvant and peripheral nerve injury.
PSD-93/chapsin-110 is a neuronal PDZ domain-containing protein that binds to and clusters the N-methyl-D-aspartate receptor (NMDAR) at synapses in the central nervous system. It also assembles a specific set of signaling proteins around the NMDAR and mediates downstream signaling by the NMDAR. Thus, PSD-93/chapsin-110 might be involved in many physiological and pathophysiological actions triggered via the activation of the NMDAR. In the current study, we report that abundant PSD-93/chapsin-110 protein was detected in rat spinal cord, particularly in the superficial dorsal horn. The rats injected intrathecally with PSD-93/chapsin-110 antisense oligodeoxynucleotide every 24 h for 4 days displayed not only a remarkable decrease in spinal cord PSD-93/chapsin-110 expression but also a significant reduction in the paw withdrawal responses to thermal and mechanical stimuli during complete Freund's adjuvant-induced inflammatory pain and peripheral nerve injury-induced neuropathic pain. In contrast, the rats injected intrathecally with PSD-93/chapsin-110 missense oligodeoxynucleotide did not exhibit these changes. We also found that pretreatment with PSD-93/chapsin-110 antisense oligodeoxynucleotide did not change the locomotor activity or the responses to acute noxious thermal and mechanical stimuli in intact rats. The present results indicate that the deficiency of spinal cord PSD-93/chapsin-110 protein significantly attenuates thermal and mechanical hyperalgesia in complete Freund's adjuvant- or peripheral nerve injury-induced chronic pain. This suggests that spinal cord PSD-93/chapsin-110 might be involved in the central mechanism of chronic pain. Our work might provide a new target for the therapy of chronic pain.


Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake.
The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) μ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain.


Palliative care in Canada: 1990.
While there has been little change in numbers of programs across the country in the past four years, there does appear to have been an increase in the size of teams and in the variety of professional representation on teams, as well an increased number of programs with volunteers. The information suggests a certain consolidation of earlier efforts. Diversification of programs continues, with an increasing number of programs now in long-term care settings. Heidemann in 1986 raised the questions: What is quality palliative care? How do we know we are delivering quality palliative care? The questions continue to challenge us in 1990, as we continue to lack a set of standards against which to measure our efforts.


Topological data analysis reveals a core gene expression backbone that defines form and function across flowering plants.
Since they emerged approximately 125 million years ago, flowering plants have evolved to dominate the terrestrial landscape and survive in the most inhospitable environments on earth. At their core, these adaptations have been shaped by changes in numerous, interconnected pathways and genes that collectively give rise to emergent biological phenomena. Linking gene expression to morphological outcomes remains a grand challenge in biology, and new approaches are needed to begin to address this gap. Here, we implemented topological data analysis (TDA) to summarize the high dimensionality and noisiness of gene expression data using lens functions that delineate plant tissue and stress responses. Using this framework, we created a topological representation of the shape of gene expression across plant evolution, development, and environment for the phylogenetically diverse flowering plants. The TDA-based Mapper graphs form a well-defined gradient of tissues from leaves to seeds, or from healthy to stressed samples, depending on the lens function. This suggests that there are distinct and conserved expression patterns across angiosperms that delineate different tissue types or responses to biotic and abiotic stresses. Genes that correlate with the tissue lens function are enriched in central processes such as photosynthetic, growth and development, housekeeping, or stress responses. Together, our results highlight the power of TDA for analyzing complex biological data and reveal a core expression backbone that defines plant form and function.


Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage.
On the basis of the free radical and rate of living theories of aging, it has been proposed that decreased metabolism leads to increased longevity through a decreased production of reactive oxygen species (ROS). In this article, we examine the relationship between mitochondrial energy metabolism and life span by using the Clk mutants in Caenorhabditis elegans. Clk mutants are characterized by slow physiologic rates, delayed development, and increased life span. This phenotype suggests that increased life span may be achieved by decreasing energy expenditure. To test this hypothesis, we identified six novel Clk mutants in a screen for worms that have slow defecation and slow development and that can be maternally rescued. Interestingly, all 11 Clk mutants have increased life span despite the fact that slow physiologic rates were used as the only screening criterion. Although mitochondrial function is decreased in the Clk mutants, ATP levels are normal or increased, suggesting decreased energy utilization. To determine whether the longevity of the Clk mutants results from decreased production of ROS, we examined sensitivity to oxidative stress and oxidative damage. We found no evidence for systematically increased resistance to oxidative stress or decreased oxidative damage in the Clk mutants despite normal or elevated levels of superoxide dismutases. Overall, our findings suggest that decreased energy metabolism can lead to increased life span without decreased production of ROS.


Honokiol inhibits bladder cancer cell invasion through repressing SRC-3 expression and epithelial-mesenchymal transition.
Urinary bladder cancer (UBC) is one of the most common urological cancer types. Muscle invasive bladder cancer possesses high propensity for metastasis with poor prognosis. Honokiol is a lignan isolated from Magnolia officinalis with high bioavailability and potent anticancer effects. The results of the present study demonstrated that honokiol significantly inhibited UBC cell migration and invasion in a dose-dependent manner compared with the vehicle-treated control group. In addition, honokiol treatment suppressed epithelial-mesenchymal transition by induction of E-cadherin and repression of N-cadherin. Honokiol was capable of significantly downregulating the expression of cell invasion-associated genes, steroid receptor coactivator-3 (SRC-3), matrix metalloproteinase (MMP)-2 and Twist1. Notably, the inhibition of UBC cell invasion by honokiol was reversed by reintroduction of oncoprotein SRC-3 expression, with the restoration of MMP-2 and Twist1, and reduction of E-cadherin expression. Furthermore, the results of the luciferase assay confirmed that SRC-3 could regulate Twist1 promoter activity. Taken together, the results of the present study suggest that honokiol is a promising agent against UBC cell invasion via downregulation of SRC-3 and its target genes.


C4b-Binding Protein Deposition is Induced in Diseased Aortic Heart Valves, Coinciding with C3d.
It has been found recently that activated complement is more widespread in diseased aortic valves compared to the endogenous complement inhibitors C1-inhibitor and clusterin. Previously, another endogenous inhibitor of complement, C4b-binding protein (C4BP) has been described in atherosclerotic diseased coronary arteries. The study aim was to analyze C4BP levels in diseased aortic valves. Aortic valve tissue was derived from surgical procedures and classified as 'degenerative', 'atherosclerotic' or 'atherosclerotic with bacterial infection'. Valves were stained with specific antibodies against C4BP, C3d and caspase-3. Areas of positivity were then quantified using computer- assisted morphometry. In atherosclerotic valves, the areas of C4BP and C3d positivity (38.8 +/- 0.4% versus 32.7 +/- 1.0%, respectively) were significantly higher compared to the degenerative and control groups. In atherosclerotic valves with bacterial infection, the area of positivity for C4BP was even further increased compared to atherosclerotic valves (65.1 +/- 1.2%; 70.1 +/- 1.9% for C3d). The areas of C4BP and C3d positivity were not significantly different in all groups. Caspase-3 was only present in <10% of endothelial cells in the atherosclerotic valves without bacterial infection and in neutrophilic granulocytes in atherosclerotic valves, with and without bacterial infection. It has been shown for the first time that C4BP is deposited in the diseased aortic valve, coinciding with C3d. The area of C4BP positivity was more extensive compared to the areas of other endogenous complement inhibitors (C1-inhibitor and clusterin).


Acute syphilitic meningitis. Its occurrence after clinical and serologic cure of secondary syphilis with penicillin G.
Acute syphilitic meningitis developed in a 36-year-old man three months after apparently successful treatment of secondary syphilis with doses of penicillin G benzathine recommended by the current Centers for Disease Control guidelines. He was then treated with high-dose intravenous penicillin G sodium, with resolution of symptoms and cerebrospinal fluid abnormalities. Although other instances of neurosyphilis following adequate therapy for early syphilis have been reported, in most cases reinfection cannot be convincingly excluded. We believe this patient represents a particularly well-documented example of progression to neurosyphilis, despite recommended therapy with penicillin. A review of recently reported cases suggests that progression of syphilis, despite "appropriate" therapy, is not an isolated event.


Individual variation of somatic gene mutability in relation to cancer susceptibility: prospective study on erythrocyte glycophorin a gene mutations of atomic bomb survivors.
It has previously been reported that hemizygous mutant fraction (Mf) at the glycophorin A (GPA) locus in erythrocytes increased with radiation dose in heterozygotes among Hiroshima and Nagasaki atomic bomb survivors. In the present study, we analyzed the relationship between GPA Mf and cancer risk using newly developed cancers among previously cancer-free subjects whose GPA Mf had been measured between 1988 and 1996. Among 1,723 survivors (1,117 in Hiroshima and 606 in Nagasaki), we identified 186 subjects who developed a first cancer by the end of 2000. We compared the radiation dose responses of GPA Mf between cancer and cancer-free groups using a linear-quadratic model fit by multiple regression analysis in combination with age, sex, and city. The slope of the GPA Mf dose-response curve was significantly higher in the cancer group than in the cancer-free group among Hiroshima subjects. Moreover, no significant difference of GPA Mf between cancer and cancer-free groups was found in unexposed controls in the two cities. The same conclusions were obtained using a linear dose-response model and by further analysis using Cox regression of cancer incidence. These findings suggest that there might be interindividual variation in mutability of somatic genes and that Hiroshima survivors who have higher mutability in response to radiation exposure would be expected to have a higher probability of suffering radiation-related cancer.


Direct Observation of Vacancy-Cluster-Mediated Hydride Nucleation and the Anomalous Precipitation Memory Effect in Zirconium.
Controlling the heterogeneous nucleation of new phases is of importance in tuning the microstructures and properties of materials. However, the role of vacancy-a popular defect in materials that is hard to be resolved under conventional electron microscopy-in the heterogeneous phase nucleation remains intriguing. Here, this work captures direct in situ experimental evidences that vacancy clusters promote the heterogeneous hydride nucleation and cause the anomalous precipitation memory effect in zirconium. Both interstitial and vacancy dislocation loops form after hydride dissolution. Interestingly, hydride reprecipitation only occurs on those vacancy loop decorated sites during cooling. Atomistic simulations reveal that hydrogen atoms are preferentially segregated at individual vacancy and vacancy clusters, which assist hydride nucleation, and stimulate the unusual memory effect during hydride reprecipitation. The finding breaks the traditional view on the sequence of heterogeneous nucleation sites and sheds light on the solid phase transformation related to vacancy-sensitive alloying elements.


Visna virus exhibits a complex transcriptional pattern: one aspect of gene expression shared with the acquired immunodeficiency syndrome retrovirus.
A complex pattern of gene expression was found for visna virus in a highly permissive cell culture system in vitro. In addition to the genomic RNA (9.4 kilobases [kb]), five other mRNAs were detected. The three large RNA transcripts (5.0 kb and a doublet at 4.3 kb) arise by a single splicing event joining 5' sequences to sequences located at positions 3' to the pol gene. The two smallest transcripts (1.8 and 1.5 kb) are at least doubly spliced mRNAs which contain sequences derived from the 5' end of the genome, the region between the pol and env genes, and 3' terminal sequences. In addition to this complex pattern of transcription, the mRNAs appear to be regulated temporally. The 1.5-kb mRNA appears 6 h later than the other transcripts. The significance of this complex pattern of gene expression in the unique aspects of the lentivirus life cycle and pathogenesis is considered.


Immunoglobulins in the jejunal mucosa in adult coeliac disease and dermatitis herpetiformis after the reintroduction of dietary gluten.
Cells containing immunoglobulin (IgA, IgG, IgM) have been measured and the distribution of extracellular and epithelial cell immunoglobulin assessed in treated patients with adult coeliac disease (ACD) and dermatitis herpetiformis (DH) before and after gluten was reintroduced to the diet. Patients with ACD and DH frequently had IgM and IgG cells above the normal range even before re-exposure to gluten, although the range of IgA cells was normal. In both diseases IgA and IgM cells increased after gluten with a proportionally greater rise in the latter, so that numbers of IgM cells, but not of IgA, exceeded the control range in all but one patient. There were increased quantities of IgA and IgM extracellularly in the lamina propria and in epithelial cells after challenge with gluten. Third component of complement was also found in some biopsies after re-exposure to gluten. These findings support the suggestion that gluten induces a humoral immunological response within the small intestinal mucosa and that both IgA and IgM systems are involved.


The electrophoretic mobility of gram-negative and gram-positive bacteria: an electrokinetic analysis.
The electrophoretic mobility (EPM) of a variety of Gram-negative and Gram-positive bacteria was measured with a Penkem S3000 analyser. Under standard growth conditions and neutral pH all cells displayed a negative EPM. The polysaccharide capsules of Escherichia coli strains K1, K5, K29 and K30 generated the highest EPM; to a lesser and varying degree O-antigens with charged groups and core lipopolysaccharides also contribute to the net EPM. Very little negative EPM was measured in suspension cultures of the gliding bacterium Cytophaga U67. No difference in the EPM was observed between rapidly growing and stationary-phase E. coli B. De-energization of the cell membranes by carbonyl cyanide m-chlorophenylhydrazone (CCCP) did not affect the EPM of wild-type and deep rough mutants of E. coli; and the EPM of Cytophaga U67 and Acholeplasma laidlawii remained unaltered by CCCP when measured in their respective growth media. Extrusion of filamentous bacteriophage f1 from cells of its host, E. coli A95, caused a shift to a higher negative EPM. We also measured a variety of Gram-positive strains, all of which displayed different EPMs. When membrane fractions of E. coli were adsorbed to latex spheres, characteristic differences between the EPM of beads coated with either inner or outer membrane were observed. The results suggest that the rapid EPM analysis is a useful tool to study the net electric charge of microorganisms and to examine changes of surface properties during interaction of cells with viruses, proteins (antibody) and charged antibiotics.


Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation.
The monoterpene perillyl alcohol (POH) has proven efficacious against the formation and progression of a variety of cancers. In this study, we tested the ability of POH to inhibit photocarcinogenesis in a nonmelanoma model of mouse skin carcinogenesis and its ability to inhibit UVB-induced activator protein 1 (AP-1) transactivation in mouse skin and human keratinocytes. POH (10 mM) was applied topically to the ears and shaved dorsal surface of groups of 35 BALB/c mice throughout the experiment, during and after UVB treatment. Topical POH significantly inhibited tumor incidence and multiplicity, average tumor size, and the average tumor burden/mouse without any apparent toxicity. POH inhibited UVB-induced AP-1 transactivation in both cultured human keratinocytes and transgenic mice that stably express a luciferase reporter driven by AP-1 elements. The results suggest that POH might be used for chemoprevention of human skin cancer, and that inhibition of AP-1 activity is functionally related to inhibition of skin carcinogenesis.


PRIMARY SCLEROSING CHOLANGITIS IN CHILDREN AND ADOLESCENTS.
Primary sclerosing cholangitis is a rare disease, but its prevalence has been underestimated in children and adolescents due to broad variation in clinical presentation as well as diagnostic challenges in this life period. To evaluate children and adolescents with primary sclerosing cholangitis and to describe their clinical, laboratorial, histopathological, and cholangiography conditions. This is an observational descriptive research that took place from 2005 to 2016 and included all the patients seen in the Outpatient Unit for Pediatric Hepatology of Hospital das Clinicas of UFMG who had been diagnosed with primary sclerosing cholangitis before the age of 18. Diagnosis was established through clinical, laboratory, radiographic and/or histopathologic criteria. Other chronic liver diseases were excluded, as well as secondary causes of cholangitis. Data analysis used statistic resources in SPSS software. Variables were expressed as averages, standard deviation, absolute frequency, and percentage. Twenty-one patients fulfilled criteria to be included in the research sample. Male patients predominated (3.2:1) and average age at diagnosis was 6.7±3.9 years. Five (23.8%) patients had associated inflammatory bowel disease, four had ulcerative colitis and one indeterminate colitis. Signs and symptoms vary and are usually discrete at presentation. The most frequent symptom was abdominal pain (47.6%) followed less frequently by jaundice (28.6%) and itching (14.3%). The reason for medical investigation was asymptomatic or oligosymptomatic enzyme alterations in 33.3% of patients. All patients presented increased hepatic enzymes: aminotransferases, gamma glutamyl transferase, and alkaline phosphatase. Twenty patients had alterations compatible to primary sclerosing cholangitis in their cholangiography exam; one patient had no alterations at magnetic resonance cholangiography, but presented histopathologic alterations that were compatible to small duct cholangitis. Hepatic fibrosis was present in 60% of 15 patients who were biopsied upon admission; cirrhosis being present in four (26.7%) patients. A total of 28.5% of patients had unfavorable outcomes, including two (9.5%) deaths and four (19%) transplants. Primary sclerosing cholangitis is a rare disease in childhood and adolescence and its initial diagnosis may be delayed or overlooked due to asymptomatic or unspecific clinical manifestations. The association with inflammatory bowel disease is common. Prognosis may be unfavorable as the disease progresses and hepatic transplant is the definitive treatment.


ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) is a new acute-phase protein isolated from cattle during experimental infection.
We have isolated from calf serum a protein with an apparent M(r) of 120,000. The protein was detected by using antibodies against major acute-phase protein in pigs with acute inflammation. The amino acid sequence of an internal fragment revealed that this protein is the bovine counterpart of ITIH4, the heavy chain 4 of the inter-alpha-trypsin inhibitor family. The response of this protein in the sera was determined for animals during experimental bacterial and viral infections. In the bacterial model, animals were inoculated with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum, and Peptostreptococcus indolicus to induce an acute-phase reaction. All animals developed moderate to severe clinical mastitis and exhibited remarkable increases in ITIH4 concentration in serum (from 3 to 12 times the initial values, peaking at 48 to 72 h after infection) that correlated with the severity of the disease. Animals with experimental infections with bovine respiratory syncytial virus (BRSV) also showed increases in ITIH4 concentration (from two- to fivefold), which peaked at around 7 to 8 days after inoculation. Generally, no response was seen after a second infection of the same animals with the virus. Because of the significant induction of the protein in the animals in the mastitis and BRSV infection models, we can conclude that ITIH4 is a new positive acute-phase protein in cattle.


Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression.
Helicobacter pylori is a major cause of the transdifferentiation into intestinal metaplasia that may develop gastric cancer. However, the molecular pathogenesis of this transdifferentiation is poorly understood. A SRY-related HMG box protein Sox2 is an essential transcription factor of organ development in brain, lung, and stomach. Our aim of this study was to investigate the mechanism responsible for regulation of Sox2 in host Th1-dominant response to H. pylori. Sox2 protein was immunohistochemically expressed in both human oxyntic and pyloric glands with H. pylori infection, but not in intestinal metaplasia. Western immunoblotting of gastric epithelial cell lines showed that IL-4, a Th2-related cytokine, dose dependently enhanced Sox2 expression among H. pylori infection-mediated cytokines. Small changes of Sox2 expression were observed after each treatment with IFN-gamma, IL-1beta, or TNF-alpha. IL-4-mediated Sox2 induction was suppressed by the inhibition of STAT6 activation with STAT6 RNA interference, and electrophoretic mobility shift assay indicated that activation of the Sox2 promoter by IL-4 occurred through the action of STAT6. Furthermore, H. pylori and IFN-gamma inhibited the phosphorylation of STAT6, resulting in the suppression of IL-4-mediated Sox2 expression. Immunohistochemical analyses showed significantly the suppressed STAT6 activity in H. pylori-infected human gastric mucosa. Additionally, downregulation of Sox2 by knockdown experiments led to intestinal phenotype with expressions of Cdx2 and MUC2. These results suggest that H. pylori and IFN-gamma interfere with the differentiation into oxyntic and pyloric glands by the downregulation of Sox2 on IL-4/STAT6 signaling, which may contribute to the transdifferentiation into intestinal metaplasia.


Evolutionary relationships among the Schistosomatidae (Platyhelminthes:Digenea) and an Asian origin for Schistosoma.
Schistosome blood flukes parasitize birds, mammals, and crocodilians and are responsible for causing one of the great neglected diseases of humanity, schistosomiasis. A phylogenetic study of 10 schistosome genera using approximately 1,100 bases of the large subunit of the nuclear ribosomal gene complex revealed 2 major clades. One clade is entirely mammalian and includes the genera Schistosoma and Orientobilharzia. A close examination of relationships in this group suggests that the medically important Schistosoma arose in Asia and not in Africa as generally presumed and is paraphyletic. The second clade is primarily avian, consisting of 6 genera of exclusively avian parasites and 2 genera of North American mammal flukes. These results indicate a secondary host capture of mammals on the North American continent. This study provides little evidence concerning the ancestral molluscan or vertebrate schistosome host but does demonstrate that host switching has been an important feature of schistosome evolution. Evidence also indicates that the reduced sexual dimorphism characteristic of some avian schistosomes is derived evolutionarily.


[Small-fibre neuropathy].
Small-fibre neuropathy is a neuropathy that mainly affects the small nerve fibres. Owing to doctors' inadequate knowledge of the condition and limited diagnostic methods, this type of neuropathy is probably under-diagnosed. Small-fibre neuropathy has many causes, but the symptoms are often relatively similar. This review article is intended to give doctors insight into the clinical expressions and diagnosis of the condition. The article is based on literature searches in PubMed and the authors' clinical and scientific experience of the subject. Small-fibre neuropathy generates a characteristic distribution of symptoms, particularly pain, and is associated with a number of common illnesses. Specific tests for small fibre neuropathy, such as skin biopsy and thermal testing, can be used to confirm the diagnosis. The treatment targets the symptoms, but complete pain relief is often difficult to achieve. The clinical neurological examination will not generally be able to detect small-fibre neuropathy, but will contribute primarily to excluding a more general polyneuropathy. Supplementary tests are often necessary to make a final diagnosis.


Propagating Uncertainty Across Cascaded Medical Imaging Tasks for Improved Deep Learning Inference.
Although deep networks have been shown to perform very well on a variety of medical imaging tasks, inference in the presence of pathology presents several challenges to common models. These challenges impede the integration of deep learning models into real clinical workflows, where the customary process of cascading deterministic outputs from a sequence of image-based inference steps (e.g. registration, segmentation) generally leads to an accumulation of errors that impacts the accuracy of downstream inference tasks. In this paper, we propose that by embedding uncertainty estimates across cascaded inference tasks, performance on the downstream inference tasks should be improved. We demonstrate the effectiveness of the proposed approach in three different clinical contexts: (i) We demonstrate that by propagating T2 weighted lesion segmentation results and their associated uncertainties, subsequent T2 lesion detection performance is improved when evaluated on a proprietary large-scale, multi-site, clinical trial dataset acquired from patients with Multiple Sclerosis. (ii) We show an improvement in brain tumour segmentation performance when the uncertainty map associated with a synthesised missing MR volume is provided as an additional input to a follow-up brain tumour segmentation network, when evaluated on the publicly available BraTS-2018 dataset. (iii) We show that by propagating uncertainties from a voxel-level hippocampus segmentation task, the subsequent regression of the Alzheimer's disease clinical score is improved.