The adherence of packaged food products in Hyderabad, India with nutritional labelling guidelines.
India is experiencing a nutrition transition with the consumption of processed foods rapidly increasing. Nutrition labels are essential if consumers are to understand the healthiness of these products. The Food Safety and Standards Authority of India have recently introduced regulation defining national nutrition labelling requirements and Codex Alimentarius recommends a global standard. To quantify the adherence of the declared nutrients on Indian packaged foods with national and global requirements. The presence or absence of data for seven required nutrients was recorded for all food products available for sale. Branches of three major retail chains and three smaller stores in Hyderabad, India between October and November, 2010 were surveyed. Data were collected for 4166 packaged products that fell into 14 different food groups. 52% of products displayed nutrient information on energy, protein, carbohydrate, sugar and total fat, meeting the minimum requirements of the Food Safety and Standards Authority of India. Only 27% met the minimum criteria defined by Codex which also requires the reporting of saturated fat and sodium. There was significant variation in compliance for leading brands, country of manufacture and food group (p<0.01 for all). The majority of Indian packaged foods do not meet national and international nutrient labelling guidelines. With the Indian population likely to consume much more packaged food over coming years full and effective food labelling will be essential. The failure of Indian legislation to require labelling of sodium and saturated fat may warrant review.


Effectively Assessing Treatment Needs in Incarcerated Seriously Mentally Ill Individuals: The Utility of the Personality Assessment Inventory-Level of Care Index.
Early identification of treatment needs in incarcerated individuals with serious mental illness has significant implications. Validated assessment instruments to guide treatment are lacking in correctional settings. Hierarchical linear modeling was used to examine the predictive validity of the Level of Care Index (LOCI) in 35 inmates admitted to a specialized treatment unit. The LOCI score was predictive of levels of depressogenic psychopathology and psychological well-being as well as changes in these constructs over time. These results validate the use of the LOCI in a correctional setting and demonstrate the utility of the LOCI to identify treatment trajectories.


[Practice clinical guideline. Prevention, diagnosis and treatment of overweight and obesity].
Excess body weight (overweight and obesity) is currently recognized as one of the most important challenges of public health in the world, due to its size, speed of growth and the negative effect on health. Currently, Mexico and United States have the highest prevalence of obesity in the adult population (30 %), which is nearly ten times higher than that of Japan or Korea (4 %). In our country, the trends of overweight and obesity in different national surveys show steady increase in prevalence over time. According to the results of the National Survey of Health and Nutrition 2012 (ENSANUT, according to its initials in Spanish), the combined prevalence of overweight or obese (BMI = 25 kg/m(2)) in the population over 20 years is higher in women (73.0 %) than men (69.4 %), while the prevalence of obesity (BMI = 30 kg/m(2)) is almost higher in females than in males. Global experience shows that proper care of obesity and overweight requires formulating and coordinating comprehensive and efficient multilevel strategies for enhancing protective factors to health, particularly to modify individual, family and community behavior. It is unlikely that a single intervention can modify the incidence or natural history of overweight and obesity.


Success of a scabies control program in an Australian aboriginal community.
To adapt, implement and evaluate a model of scabies control in an Australian Aboriginal community. After initially examining the population, we offered all residents treatment with 5% permethrin cream. Visits were made during the ensuing 25 months to rescreen and to treat new-cases of scabies and contacts. The prevalence of scabies was reduced from 28.8% before the program to < 10% during the entire period (from 32.3% to < 10% in children) (P < 0.01 for each visit). The initial prevalence of pyoderma in children was 69.4%, which was reduced and maintained at approximately one-half that rate during the last 16 months (P < 0.004 for the last 4 visits). Residual pyoderma in children was significantly less severe and no longer scabies-related. This simplified model of scabies control had a substantial effect on scabies prevalence and on pyoderma prevalence and severity which was sustained for > 2 years. It could prove useful for other communities with high rates of scabies and pyoderma.


Analytic approach to nonlinear hydrodynamic instabilities driven by time-dependent accelerations.
We extend our earlier model for Rayleigh-Taylor and Richtmyer-Meshkov instabilities to the more general class of hydrodynamic instabilities driven by a time-dependent acceleration g(t). Explicit analytic solutions for linear as well as nonlinear amplitudes are obtained for several g(t)s by solving a Schrödinger-like equation d(2)eta/dt(2)-g(t)kAeta=0, where A is the Atwood number and k is the wave number of the perturbation amplitude eta(t). In our model a simple transformation k-->k(L) and A-->A(L) connects the linear to the nonlinear amplitudes: eta(nonlinear)(k,A) approximately (1/k(L))ln eta(linear)(k(L),A(L)). The model is found to be in very good agreement with direct numerical simulations. Bubble amplitudes for a variety of accelerations are seen to scale with s defined by s=integral(square root of [g(t)]dt), while spike amplitudes prefer scaling with displacement Deltax=integral[integralg(t)dt]dt.


Advances in targeted therapy for pancreatic cancer.
Pancreatic cancer (PC) represents a group of malignant tumours originating from pancreatic duct epithelial cells and acinar cells, and the 5-year survival rate of PC patients is only approximately 12%. Molecular targeted drugs are specific drugs designed to target and block oncogenes, and they have become promising strategies for the treatment of PC. Compared to traditional chemotherapy drugs, molecular targeted drugs have greater targeting precision, and they have significant therapeutic effects and minimal side effects. This article reviews several molecular targeted drugs that are currently in the experimental stage for the treatment of PC; these include antibody-drug conjugates (ADCs), aptamer-drug conjugates (ApDCs) and peptide-drug conjugates (PDCs). ADCs can specifically recognize cell surface antigens and reduce systemic exposure and toxicity of chemotherapy drugs. By delivering nucleic acid drugs to target cells, the targeting RNA of ApDCs can inhibit the expression or translation of mutated genes, thereby inhibiting tumour development. Moreover, PDCs can effectively penetrate tumour cells, and the peptide groups in PDCs preferentially target tumour cells with minimal side effects. In the targeted therapy of PC, molecular targeted drugs have very broad prospects, which provides new hope for the clinical treatment of PC patients and is worth further research.


Millimeter scale electron conduction through exoelectrogenic mixed species biofilms.
The functioning of many natural and engineered environments is dependent on long distance electron transfer mediated through electrical currents. These currents have been observed in exoelectrogenic biofilms and it has been proposed that microbial biofilms can mediate electron transfer via electrical currents on the centimeter scale. However, direct evidence to confirm this hypothesis has not been demonstrated and the longest known electrical transfer distance for single species exoelectrogenic biofilms is limited to 100 μm. In the present study, biofilms were developed on electrodes with electrically non-conductive gaps from 50 μm to 1 mm and the in situ conductance of biofilms was evaluated over time. Results demonstrated that the exoelectrogenic mixed species biofilms in the present study possess the ability to transfer electrons through electrical currents over a distance of up to 1 mm, 10 times further than previously observed. Results indicate the possibility of interspecies interactions playing an important role in the spatial development of exoelectrogenic biofilms, suggesting that these biological networks might remain conductive even at longer distance. These findings have significant implications in regards to future optimization of microbial electrochemical systems.


Effect of protein and(or) carbohydrate fractions of dried whey on performance and nutrient digestibility of early weaned pigs.
One hundred eighty 3-wk-old pigs (initial weight 4.8 kg) were utilized in a 35-d growth trial to determine the effects of the carbohydrate and(or) protein fraction of dried whey on pig performance. In addition, 30, 3-wk-old pigs (initial weight 4.9 kg) were used in two digestion trials to study the effects of the whey fraction on nutrient digestibility. Dietary treatments included a corn-soybean meal diet (control), control + 20% dried whey, control + 14.4% lactose, control + 2.1% lactalbumin, control + 14.4% lactose + 2.1% lactalbumin, and control + 8.4% whey protein concentrate. Pelleted diets containing equal lysine concentrations were fed. Lactose and lactalbumin were added at the same levels as provided by a 20% dried whey diet. Pigs fed diets containing milk products exhibited superior (P less than .05) ADG and efficiency of feed utilization and greater (P less than .05) apparent digestibilities for DM, energy and N compared with pigs fed the control diet. Including either lactose or lactalbumin in the diet for the early weaned pig resulted in similar gain, feed efficiency and nutrient digestibility. These results indicate that both the carbohydrate (lactose) and protein (lactalbumin) fractions of dried whey are important in explaining the beneficial response to dried whey elicited in the weanling pig.


Development of a robust, fast screening method for the potentiometric determination of iodide in urine and salt samples.
In this work, a potentiometric flow injection method is described for the fast bi-parametric determination of iodide and iodate in urine and salt samples. The developed methodology aimed for iodine speciation with a potentially portable system (running on batteries). The iodate reduction to iodide was effectively attained in line within the same manifold. The iodide determination was accomplished in the dynamic range of 2.50×10-6-1.00×10-3M and the total iodine dynamic range, resulted from iodide plus iodate, was 3.50×10-6-2.00×10-3M. The calculated limits of detection were 1.39×10-6M and 1.77×10-6M for iodide and iodate, respectively. A determination rate of 21h-1 for the bi-parametric iodide and iodate determination was obtained for sample injection. The urine samples (RSD <5.8% for iodide and RSD <7.0% for iodate) results were in agreement with those obtained by the classic Sandell-Kolthoff reaction colorimetric reference procedure (RD <7.0%) and standard samples from Centers for Disease Control and Prevention, Atlanta, USA (CDC) international inter-laboratory EQUIP program. The developed flow method was also successfully applied to the iodide and iodate determination in salt samples (RSD <3.1% for iodate and iodide), with comparable results to conventional procedures. No significant interferences were observed interference percentage <9% for both determinations.


Adrenal function in the human immunodeficiency virus-infected patient.
Although clinical manifestations of adrenal dysfunction are uncommon in patients infected with human immunodeficiency virus (HIV), subclinical functional abnormalities of the hypothalamic-pituitary-adrenal axis are frequent. Patients infected with HIV usually have higher basal serum cortisol and lower serum dehydroepiandrosterone concentrations than HIV-seronegative individuals. This imbalance has been related to progression of the infection by inducing a shift from T(H)1 to T(H)2 immunologic responses. Although, adrenal reserve may be marginal in HIV-infected patients, clinically evident adrenal insufficiency is uncommon and, when present, it is observed in advanced stages of the infection. Hypocortisolemia should be treated regardless of the existence of associated symptoms. On the contrary, hypercortisolemia in the absence of features of Cushing syndrome is common and should not promote treatment nor specific studies. The possible influence that alterations of the adrenal function could have on the patients' immune status and the eventual effect of antiretrovirals on these alterations merit further investigation.


Quantitative magnetic resonance imaging differences between Alzheimer disease with and without subcortical lacunes.
Previous reports showed that patients with Alzheimer disease (AD) frequently have coexisting vascular-related pathologies, such as cerebral infarcts and white matter lesions. The aim of this study was to determine the effects of subcortical lacunar infarcts on brain structure in patients with AD. Semi-automated tissue segmentation and volumetry of magnetic resonance imaging data were performed in 38 AD patients without lacunes (AD-L), 24 AD patients with subcortical lacunes (AD+L), and 40 age-matched cognitively healthy subjects without lacunes. The following tissue volumes were quantified, expressed as percentage of total intracranial volume: ventricular cerebrospinal fluid (CSF), sulcal CSF, cortical gray matter (GM), subcortical GM, white matter (WM), white matter signal hyperintensities (WMSH), lacunes, and hippocampus. There was no difference in the Mini-Mental State Examination between the two AD groups. AD+L patients compared with AD-L subjects had significantly greater volumes of WMSH and ventricular CSF spaces (as expected) but smaller sulcal CSF spaces and no significant increase in cortical GM atrophy (both unexpected). In the AD groups, ventricular CSF correlated inversely with cortical GM but not with WM; sulcal CSF correlated inversely with cortical GM and WM. Cognitive impairment was associated with sulcal CSF volume but not with volumes of WMSH or lacunes. In conclusion, the presence of subcortical lacunes in those with AD is associated with more WM lesions and ventriculomegaly but not with cortical atrophy.


Attitude of students of health professions towards a health care workers' mandatory vaccination: a multi-center cross-sectional survey.
Introduction. Seasonal influenza epidemics represent a cost that affects companies in terms of sick leave and lost productivity, therefore vaccination can improve occupational health. The vaccination of Healthcare Workers (HCW) has a dual function because in addition to protecting the workers, it also protects the most fragile patients. The students of medical and nursing degree courses, as well as other health professions, attend the workplace daily and are similar to workers in Legislative Decree 81/08. The purpose of this research is to assess the prevalence of students who are in favor of the introduction of a mandatory vaccination for healthcare workers, and to investigate what factors predispose them to be favorable. Methods. We performed a multi-center cross-sectional study using a validated questionnaire in a sample of students from different university courses from October 10th, 2017 to September 30th, 2018. For qualitative variables, absolute and relative frequencies, and for categorical variables Pearson's Chi-square test (χ2) were calculated. A multivariable logistic regression model was used. Results. A total of 3131 questionnaires were completed by 2132 women and 999 men. The prevalence of students who are favorable to the introduction of a mandatory flu vaccination is 87.3% and that this data is linked to the female gender (aOR 1.52 CI 95% 1.12-2.06), being a medical student compared to nursing (aOR 2.14 CI 95% 1.45-3.17), coming from central Italy (aOR 3.08 CI 95% 2.11-4.51) and northern Italy (aOR 3.09 CI 95% 2.12-4.49) compared to Southern Italy and the Islands, wanting to get vaccinated for the next season (aOR 6.37 CI 95% 3.73-10.88), declaring to have a good/excellent level of knowledge on vaccine-preventable diseases (aOR 1.44 CI 95% 1.04-1.99), planning a recommendation based on ministerial indications (aOR 2.12 CI 95% 1.28-2.30) and having received requests for clarification on vaccinations (aOR 2.02 CI 95% 1.44-2.85). Discussion. The sample of university students showed to be largely in agreement with the introduction of mandatory vaccination for HCW, which is important for the prevention of influenza virus in the workplace. To increase adherence of healthcare workers to vaccination campaigns against seasonal influenza in the workplace, it is necessary that operative strategies are implemented with educational messages.


Infrasonic source altitude localization based on an infrasound ray tracing propagation model.
Based on a three-dimensional Hamiltonian ray tracing program in spherical coordinates, the effective sound speed is confirmed as the determining factor that influences the infrasound propagation path, and a theoretical model for the back-projected infrasound propagation trajectory is established. In this paper, the mass spectrometer incoherent scatter radar model (MSISE00) and horizontal wind model (HWM93) are first used to obtain the effective sound speed at different altitudes in summer and winter in Beijing. Then, the propagation paths generated by an infrasound source in Beijing are simulated with a conventional model. Some of the simulated rays are used to verify the back-projection model, and the verification has a high degree of coincidence with the simulation. Finally, using an experiment to validate the back-projection model, the altitude localization essentially conforms to the true value, proving the feasibility of the ray tracing back-projection algorithm.


Iron oxide nanoparticle enhancement of radiation cytotoxicity.
Iron oxide nanoparticles (IONPs) have been investigated as a promising means for inducing tumor cell-specific hyperthermia. Although the ability to generate and use nanoparticles that are biocompatible, tumor specific, and have the ability to produce adequate cytotoxic heat is very promising, significant preclinical and clinical development will be required for clinical efficacy. At this time it appears using IONP-induced hyperthermia as an adjunct to conventional cancer therapeutics, rather than as an independent treatment, will provide the initial IONP clinical treatment. Due to their high-Z characteristics, another option is to use intracellular IONPs to enhance radiation therapy without excitation with AMF (production of heat). To test this concept IONPs were added to cell culture media at a concentration of 0.2 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for either 48 or 72 hours. Extracellular iron was then removed and all cells were irradiated at 4 Gy. Although samples incubated with IONPs for 48 hrs did not demonstrate enhanced post-irradiation cytotoxicity as compared to the non-IONP-containing cells, cells incubated with IONPs for 72 hours, which contained 40% more Fe than 48 hr incubated cells, showed a 25% decrease in clonogenic survival compared to their non-IONP-containing counterparts. These results suggest that a critical concentration of intracellular IONPs is necessary for enhancing radiation cytotoxicity.


SegAuth: A Segment-based Approach to Behavioral Biometric Authentication.
Many studies have been conducted to apply behavioral biometric authentication on/with mobile devices and they have shown promising results. However, the concern about the verification accuracy of behavioral biometrics is still common given the dynamic nature of behavioral biometrics. In this paper, we address the accuracy concern from a new perspective-behavior segments, that is, segments of a gesture instead of the whole gesture as the basic building block for behavioral biometric authentication. With this unique perspective, we propose a new behavioral biometric authentication method called SegAuth, which can be applied to various gesture or motion based authentication scenarios. SegAuth can achieve high accuracy by focusing on each user's distinctive gesture segments that frequently appear across his or her gestures. In SegAuth, a time series derived from a gesture/motion is first partitioned into segments and then transformed into a set of string tokens in which the tokens representing distinctive, repetitive segments are associated with higher genuine probabilities than those tokens that are common across users. An overall genuine score calculated from all the tokens derived from a gesture is used to determine the user's authenticity. We have assessed the effectiveness of SegAuth using 4 different datasets. Our experimental results demonstrate that SegAuth can achieve higher accuracy consistently than existing popular methods on the evaluation datasets.


Novel monoclonal antibodies identify antigenic determinants unique to cellular senescence.
Normal human diploid fibroblasts exhibit a limited lifespan in vitro and are used as a model to study in vivo aging. Monoclonal antibodies were generated against partially purified surface membranes from human diploid fibroblasts at the end of their lifespan (senescent). Three hybridomas were isolated that secreted antibodies reacting to cellular determinants expressed specifically on senescent human fibroblasts of different origin, including neonatal foreskin, embryonic lung, and adult skin punch biopsy, but not expressed on matched young cells. The antibodies did not bind to immortal human cells and normal young cells made reversibly nondividing, indicating the antigens are not expressed in cells that are not senescent. The antibodies identified senescent cells in a mixed cell population and expression of the senescent cell antigens correlated strongly with the cells inability to synthesize DNA at the onset of senescence. The antigens appeared to be cell surface or extracellular matrix associated, and the epitopes were destroyed by mild trypsin treatment. Western analysis indicated all three antibodies reacted with fibronectin. Though the antigenic determinants on the fibronectin molecule were not accessible in the intact young cell, the epitopes were present in fibronectin extracted from both senescent and young cells, as well as purified human plasma fibronectin. These antibodies and the senescent specific expression of the antigens provide powerful tools to investigate the mechanisms leading to in vitro senescence. This may enable us to investigate directly the relationship between cellular aging and aging of the individual.


Peripharyngeal tissue deformation, stress distributions, and hyoid bone movement in response to mandibular advancement.
Mandibular advancement (MA) increases upper airway (UA) patency and decreases collapsibility. Furthermore, MA displaces the hyoid bone in a cranial-anterior direction, which may contribute to MA-associated UA improvements via redistribution of peripharyngeal tissue stresses (extraluminal tissue pressure, ETP). In the present study, we examined effects of MA on ETP distributions, deformation of the peripharyngeal tissue surface (UA geometry), and hyoid bone position. We studied 13 supine, anesthetized, tracheostomized, spontaneously breathing adult male New Zealand White rabbits. Graded MA was applied from 0 to ∼4.5 mm. ETP was measured at six locations distributed throughout three UA regions: tongue, hyoid, and epiglottis. Axial computed tomography images of the UA (nasal choanae to glottis) were acquired and used to measure lumen geometry (UA length; regional cross-sectional area) and hyoid displacement. MA resulted in nonuniform decreases in ETP (greatest at tongue region), ranging from -0.11 (-0.15 to -0.06) to -0.82 (-1.09 to -0.54) cmH2O/mm MA [linear mixed-effects model slope (95% confidence interval)], across all sites. UA length decreased by -0.5 (-0.8 to -0.2) %/mm accompanied by nonuniform increases in cross-sectional area (greatest at hyoid region) ranging from 7.5 (3.6-11.4) to 18.7 (14.9-22.5) %/mm. The hyoid bone was displaced in a cranial-anterior direction by 0.42 (0.36-0.44) mm/mm MA. In summary, MA results in nonuniform changes in peripharyngeal tissue pressure distributions and lumen geometry. Displacement of the hyoid bone with MA may play a pivotal role in redistributing applied MA loads, thus modifying tissue stress/deformation distributions and determining resultant UA geometry outcomes.


[Trans-sylvian-insular approach endoscopic surgery for basal ganglia hypertensive hemorrhage].
To explore the operative techniques and efficacy of trans-sylvian-insular approach endoscopic surgery for hypertensive basal ganglia hemorrhage. A retrospective analysis was conducted in 54 patients with hypertensive basal ganglia hemorrhage from December 2009 to December 2011. All of them underwent neuroendoscopic surgery via a trans-sylvian-insular approach. The hematoma volume was 30 - 40 ml (n = 8), 40 - 50 ml (n = 42) and > 50 ml (n = 4). And the Glasgow Coma Scale (GCS) was 8 - 12 (n = 48) and 13 - 15 (n = 6). The clearance rate of hematoma was > 90% (n = 44) and 80% - 90% (n = 10). None suffered re-hemorrhage or death. As a mini-invasive and efficacious approach for hypertensive basal ganglia hemorrhage, trans-sylvian-insular approach endoscopic surgery has a high clearance rate of hematoma is high and causes minimal damage to normal brain tissue. It is worth of clinical promotion.


Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.
Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.


Evaluation of maxillary sinus anatomy by cone-beam CT prior to sinus floor elevation.
Surgical complications during sinus floor elevation are frequently caused by septa in the maxillary sinus. In this study, the prevalence of septa was retrospectively determined via three-dimensional imaging to assess the necessity for appropriate imaging prior to sinus floor elevation. The cone-beam computed tomography scans of 1,029 consecutive patients were evaluated to assess the prevalence of septa, taking into account patient age and sex as well as the number and orientation of septa and their locations. If septa were present, the height was measured and the orientation was determined. Septa were found in 47% of patients and 33.2% of sinuses. There was no statistical difference in prevalence with respect to age, sex, or side. Most patients with septa showed one septum in one sinus (24.6%); 13.7% showed one septum in each sinus. Other combinations (up to three septa per sinus) were found in 8.7% of patients. Septa were most commonly located in the first molar region (256 septa), followed by the second molar region (225 septa), the third molar region (144), second premolar region (136), the first premolar region (44), and the canine region (5). The mean septal height was 11.7 +/- 6.08 mm for septa in a sagittal orientation (n = 206, 25.3%; maximum height of 37 mm) and 7.3 +/- 5.08 mm for those oriented transversely (n = 608, 74.7%; maximum height of 36 mm). The variance was larger for the sagittal orientation group (37.03 mm) than for transversely oriented septa (25.9 mm). Septa were found in 47% of the patients in this sample. Appropriate imaging prior to performing sinus surgery seems justified, since complications and the success rate of sinus floor elevation are clearly related to the presence of septa. Int J Oral Maxillofac Implants 2010;25:258-265.


E-selectin inhibition with GMI-1271 decreases venous thrombosis without profoundly affecting tail vein bleeding in a mouse model.
Selectins, such as E-selectin (CD62E), function in venous thrombosis by binding and activating immune cells to initiate the coagulation cascade. GMI-1271 is a small molecule antagonist that inhibits E-selectin activity. Here we determine whether inhibition of E-selectin is sufficient to decrease acute venous thrombosis and associated inflammatory events in both prophylactic and treatment protocols without significantly affecting haemostasis. Male C57BL/6 mice underwent surgery for experimental thrombosis induction and were harvested at peak thrombus formation in our animal model, two days post induction. Groups included non-thrombosed true controls, shams, controls, and prophylactic or treatment groups of GMI-1271 (10 mg/kg intraperitoneal BID (twice a day) and low-molecular-weight heparin (LMWH, Lovenox 6 mg/kg subcutaneously (SC), once a day (SID). Compared with control animals, prophylaxis or treatment with LMWH and GMI-1271 in a dose-dependent manner significantly decreased thrombosis. GMI-1271 significantly lowered tail bleeding times when compared to LMWH. GMI-1271 and LMWH prophylactically administered significantly decreased vein wall neutrophil cell extravasation. However, all treatment and prophylactic therapies significantly decreased vein wall monocyte extravasation versus controls. GMI-1271 prophylactic therapy significantly decreased intra-thrombus cell counts versus control animals and other treatment groups. Immunohistochemistry confirmed that both treatments with GMI-1271 and LMWH significantly decreased activated leukocyte migration. GMI-1271 therapy significantly decreased thrombus weight and resulted in significantly lower bleeding times than LMWH. GMI-1271 treated mice showed decreased local and systemic inflammatory effects while modulating neutrophil activation, suggesting that GMI-1271 is a viable therapeutic candidate for venous thrombosis prophylaxis and treatment.


Low-affinity uptake of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) in BeWo cells.
Understanding the mechanisms of transport processes in the placenta can improve the safety and efficacy of drug delivery during pregnancy. Functional studies of organic cation transporters (OCTs) are usually carried out using radioactivity, and a fluorescent marker would add flexibility to experimental methods. As a published substrate for OCT1 and OCT2, the fluorescent compound 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) was chosen as a candidate for studying placental OCT function in BeWo cells. The expression of OCT1 and OCT2 was also investigated in BeWo cells, an established human choriocarcinoma trophoblastic cell line frequently used as an in vitro model of the rate-limiting barrier for maternal-fetal exchange of drugs and nutrients within the placenta. 4-Di-1-ASP was taken up into BeWo cells by a low-affinity, carrier-mediated process exhibiting a Km of 580+/-110 microM and Vmax of 97+/-9 nmol/mg protein/30 min, and asymmetric transport was observed, with greater permeability in the apical to basolateral (maternal-to-fetal) direction. However, RT-PCR revealed no expression of OCT1 or OCT2 in either BeWo cells or primary cultured human cytotrophoblast cells, and OCT substrates such as TEA and choline did not inhibit the uptake of 4-Di-1-ASP. Although the uptake of this fluorescent compound in BeWo cells is not mediated by an OCT, the colocalization experiments with fluorescence microscopy and inhibition studies confirmed significant mitochondrial uptake of 4-Di-1-ASP. Transport of 4-Di-1-ASP into the nuclear region of BeWo cells was also observed, which is likely mediated by a nucleoside transporter.


Validation of an instrument regarding nursing intervention in patients in vasoactive therapy.
to validate the content of a Standard Operational Procedure, regarding nursing interventions in emergency patients treated with vasoactive drugs. methodological study, carried out from December 2015 to January 2016. Content validity was determined by 16 experts (13 nurses, 2 pharmacists and one biomedical scientist), who judged it through a four-point Likert scale. The items were evaluated in terms of: feasibility, objectivity, simplicity, clearness, pertinence and accuracy. The Content Validity Index was applied, accepting the value ≥ 0.90. two rounds of evaluation were required to achieve the minimum index. The items were reviewed regarding writing, dilution, indication and replacement interval. The instrument was validated with 33 items and with total Content Validity Index of 0.99. the instrument was considered appropriate, fractionally and globally, for nursing care for the patient treated with vasoactive drugs in emergency, in a safe and reliable way.


[Correlation study of physical and biologic parameters to acute radiation pneumonitis].
To study the relationship between the level of plasma transform growth factor-betal (TGF-betal), interleukin-6 (IL-6), thrombomodulin (TM) dose-volume factors and acute radiation pneumonitis (ARP). Three dimensional conformal radiation therapy and chemotherapy were applied to 27 lung cancer patients, 15 esophageal carcinoma, and 1 thymoma patients. 19 patients received adjuvant radiochemotherapy, and 25 patients received concurrent radio-chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum IL-6, TGF-betal and TM levels of patients before radiotherapy (B-RT) and at 30 Gy(M-RT). ARP was graded according to NCI common toxicity criteria (CTCAE v 3.0), Grade 2 or more ARP was taken as the main end point. The relationship between the levels of serum TGF-betal, IL-6, TM, parameters of lung function and dose-volume factors, and the incidence rate of ARP were analyzed. Mean lung dose (MLD) and the Vx were considered as the dose-volume factors. Among 44 patients, 15 of them had ARP. 9 got grade 2 ARP and 6 had grade 3. After received a dose of 30 Gy, TGF-betal value in M-RT was (396 +/- 338) and (866 +/- 270) pg/mL in non-ARP and ARP group (P = 0.000). The ARP incidence rate in <60 and > or =60 age group were 46.15% (12/26) and 16.67% (3/18) (P = 0.042), and 45.45% (15/33), 0% (0/11) (P = 0.017) in had smoking history and nonsmoking history group, respectively. 1 out of 13 patients (7.69%) who had increased M-RT TM value suffered of ARP, while 14 out of 31 patients (45.16%) whose M-RT TM value lower than pr-RT suffered of ARP (P = 0.044). The results of multivariate analysis implied that the MLD and the value of TGF-betal in M-RT were associated with severe ARP. TGF-beta1 and MLD are significant indicators of ARP. FEV1 actual value/predicted value% might have predicting effect for the severity of ARP.


Percutaneous Closure of Ruptured Sinus of Valsalva Aneurysm in a Child Using a Patent Ductus Arteriosus Device.
Ruptured sinus of Valsalva aneurysm is rare, although if left untreated, potentially fatal disease. Surgical approach has been the main treatment in most series; nevertheless, percutaneous closure has been described in selected cases. We report a 5-year-old boy presenting with rapid clinical deterioration who underwent percutaneous closure using a patent ductus arteriosus device, with the resolution of symptoms. Descriptions of this technique being utilized in children are infrequent in the literature.


rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA.
rev (trs/art) is an essential human immunodeficiency virus type 1 (HIV-1) regulatory protein. rev increases the levels of the gag- and env-producing mRNAs via a cis-acting element in the env region of HIV-1, named rev-responsive element. Our results show that rev increases the stability of the unspliced viral mRNA, while it does not affect the stability of the multiply spliced viral mRNAs that do not contain the rev-responsive element. The study of mutated proviral constructs producing mRNA that cannot be spliced revealed that the effect of rev on stability is independent of splicing. Our experiments also indicate that rev promotes the transport of the viral mRNA containing the rev-responsive element from the nucleus to the cytoplasm. The proposed functions of rev are consistent with its nuclear localization as shown by immunofluorescence. The selective effects of rev on the levels of the viral mRNA suggest a model for feedback regulation by rev leading to a steady state of viral expression.


Automated peak detection and cell cycle analysis of flow cytometric DNA histograms.
We describe an algorithm for fully automated flow cytometric DNA histogram classification and analysis that provides rapid, reproducible determination of DNA index and S-phase fraction (SPF). Automated classification agreed with subjective assessment of DNA ploidy in 96-98% of DNA histograms. Automated and conventional analyses of DNA index (r = 0.95) and SPF (r = 0.89) were also highly correlated with one another. In a series of 86 node-negative breast carcinomas, SPF calculated with the fully automated method was a significant predictor of 10 year survival (p = 0.009). Automation greatly increased the speed of DNA histogram analysis, allowing evaluation of the same set of histograms with different methods. In a preliminary study exploring the optimization of DNA histogram analysis, the best association between SPF and prognosis of breast cancer patients was achieved using sliced nuclei debris modeling, reporting only the aneuploid SPF (in aneuploid histograms), while excluding small aneuploid clones (< 15% of total cell count) from evaluation. In conclusion, automated DNA histogram analysis does not replace the need for close human supervision but provides a useful guideline for less experienced users, facilitates interlaboratory comparisons, and makes possible extensive reanalyses of large data sets.


A route to RNA with an alkylating group at the 5'-triphosphate residue.
Reaction of ATP with N,N,N'-tris(2-chloroethyl), N' (p-formyl-phenyl)propylenediamine-1,3 (abbreviation C13R) afforded a gamma-ester of ATP (abbreviation C1RpppA) - the product of alkylation by an aliphatic nitrogen mustard residue of C13R. The alkylating activity of the aromatic nitrogen mustard residue of C1RpppA is suppressed by the electron-acceptor effect of the p-formyl group. C1RpppA is a substrate of RNA-polymerase, and affords RNA with C1RpppA-residues at the 5'-termini.


Associative diazotrophs of pearl millet (Pennisetum glaucum) from semi arid region--isolation and characterization.
Diversity of the native diazotrophs associated with the rhizosphere of pearl millet (P. glaucumn), grown in nutritionally poor soils of semi-arid regions was studied with a view to isolate effective nitrogen fixing and plant growth stimulating bacteria with root associative characteristics. The native population varied from 10(3)-10(4) g(-1) of rhizosphere soil after 40 d growth and belonged to genera Azospirillum, Azotobacter and Klebsiella. Another non-diazotrophic root associative group was Pseudomonas sp., which also produced IAA and enhanced plant growth. Some of these rhizobacteria showed high in vitro acetylene reduction activity along with production of indole acetic acid. Out of 11 selected diazotrophs used as seed inoculants, M10B (Azospirillum sp.), M11E (Azotobacter sp.) and M12D4 (Klebsiella sp.) resulted in significant increase in total root and shoot nitrogen at 45 and 60 days of plant growth under pot culture conditions.


Hepatic infarction following abdominal interventional procedures.
To clarify the incidence, background, and progress of hepatic infarction following interventional procedures, cases of hepatic infarction following interventional procedures at our department during the last decade were identified by reviewing the clinical records of 1982 abdominal angiography and interventional procedures and records of abdominal CT. Nine episodes (0.5%) in 8 patients were identified as hepatic infarction following an interventional procedure. Five episodes were preceded by embolization of the hepatic or celiac artery at emergency angiography for postoperative bleeding with hemorrhagic shock. Three episodes followed the elected interventional procedure for hepatocellular carcinoma, and the remaining episode occurred after 12 months of chemoinfusion through an indwelling catheter in the hepatic artery and portal vein. Hepatic arterial occlusion in all episodes and portal venous flow abnormality in 5 episodes were observed on angiography. Four patients whose liver function was initially impaired died of hepatic infarction, although the extent of the disease on CT did not appear to be related to the mortality. Multiple risk factors, including arterial insufficiency, were observed in each patient. The incidence of hepatic infarction following interventional procedures in this series was low but sometimes fatal, and occurred most frequently in emergency embolization in hemorrhagic shock.


Comparative analysis of how immune sensitization is defined prior to lung transplantation.
Immune sensitization prior to lung transplantation may be associated with worse survival. Using solid phase assays to define sensitization, we assessed the relationship between PRA status, donor specific anti-HLA antibodies (DSA) pre-transplant, cytotoxic cross match results and the clinical outcomes following lung transplantation. Luminex assays determined the presence of antibodies to class I and class II MHC molecules prior to lung transplantation. At the time of transplant, the PRA status, the presence of DSA and prospective cytotoxic cross match result were analysed in 195 patients undergoing lung transplantation between June 2008 and June 2012. Clinical outcomes analysed included acute cellular and antibody-mediated rejection, chronic lung allograft dysfunction (CLAD) and mortality. At the time of transplant, 45% of patients had a positive PRA and 29% had DSA. On univariate analysis, the presence of pre-transplant class I or II anti-HLA donor-specific antibodies was not associated with the development of chronic lung allograft dysfunction (CLAD) despite significant associations with PRA status and B-cell crossmatch. Defining sensitization using solid phase assays provide additional details regarding donor-specific sensitization but did not provide additional prognostic information to that provided by historically available cell-based cross-match assays.


A systematic review of education for the prevention of HIV/AIDS among older adults.
Through a comprehensive literature search, the authors of this systematic review identified 21 articles focused on primary prevention of HIV/AIDS for adults aged 50 and over. Three major challenges to providing HIV/AIDS education for older adults include health professionals' ageism, older adults' reluctance to discuss sexuality, and their misconception of their HIV risk. Clinical guidelines for social workers, nurses, and physicians identified the importance of sharing information and assessing risk, considering cultural diversity, and devising creative delivery strategies. Three models of HIV/AIDS education include group education programs delivered by social workers or other health professionals, peer education models, and one-on-one early intervention models including HIV/AIDS testing. Additional outreach and research on HIV/AIDS prevention among older adults is needed.


Molecular genetics of the most endangered canid: the Ethiopian wolf Canis simensis.
The world's most endangered canid is the Ethiopian wolf Canis simensis, which is found in six isolated areas of the Ethiopian highlands with a total population of no more than 500 individuals. Ethiopian wolf populations are declining due to habitat loss and extermination by humans. Moreover, in at least one population, Ethiopian wolves are sympatric with domestic dogs, which may hybridize with them, compete for food, and act as disease vectors. Using molecular techniques, we address four questions concerning Ethiopian wolves that have conservation implications. First, we determine the relationships of Ethiopian wolves to other wolf-like canids by phylogenetic analysis of 2001 base pairs of mitochondrial DNA (mtDNA) sequence. Our results suggest that the Ethiopian wolf is a distinct species more closely related to gray wolves and coyotes than to any African canid. The mtDNA sequence similarity with gray wolves implies that the Ethiopian wolf may hybridize with domestic dogs, a recent derivative of the gray wolf. We examine this possibility through mtDNA restriction fragment analysis and analysis of nine microsatellite loci in populations of Ethiopian wolves. The results imply that hybridization has occurred between female Ethiopian wolves and male domestic dogs in one population. Finally, we assess levels of variability within and between two Ethiopian wolf populations. Although these closely situated populations are not differentiated, the level of variability in both is low, suggesting long-term effective population sizes of less than a few hundred individuals. We recommend immediate captive breeding of Ethiopian wolves to protect their gene pool from dilution and further loss of genetic variability.


Kawasaki disease--diagnostic difficulties.
The Kawasaki disease is a systemic vasculitis in the childhood, described for the first time in 1967 in Japan. Although it is rare, the disease has worldwide distribution. Most of the patients are between 1 and 5 years of age. The onset is rapid, with high fever up to 40 degrees C, which lasts for more than 5 days. There are changes in the lingual, buccal and pharyngeal mucosa. Diffuse rash--mostly rubella-like, but never vesiculous may be present. Non-purulent, usually cervical lymphadenitis is present. The complications are mainly from the cardiovascular system: myocardial ischemia, aneurysm formation due to thrombosis, etc. The mortality is 1-2%. We present a case of Kawasaki disease in early childhood that kas caused diagnostic difficulties during the management and treatment.


[Is drug resistant partial epilepsy progressive?].
Approximately one third of the patients with epilepsy are drug resistant. For decades it has been speculated whether repetition of the seizures might potentially lead to progression of the disorder. In recent years four levels of evidence (experimental, imaging, epidemiological and neuropsychological) suggest that in at least some types of epilepsy the disorder may progress. In various experimental models of epilepsy it has been shown that the persistence of seizures led to biochemical, structural and cellular changes which are persistent and progressive. However, it is difficult to extrapolate these results to human epilepsy. Studies using magnetic resonance volume measurements and spectroscopy have shown that in temporal lobe epilepsy the lesion seems to progress over the years. However, epidemiological and clinical studies do not consistently show a worsening pattern of seizures over the years of epilepsy duration. In fact, recent evidence has shown that drug resistance may occur from the beginning of the disorder. Neuropsychological studies in patients with drug resistant epilepsy, especially in those with mesial temporal lobe epilepsy, show deterioration of certain cognitive aspects (mainly memory) in relation to the duration and frequency of the partial and secondarily generalized seizures. In case progression of a epilepsy syndrome might be anticipated, this would undoubtedly lead to relevant consequences. If this is so, the therapeutic approach should be more aggressive than at present and might offer early curative treatment, such as epilepsy surgery or neuroprotective drugs, which might halt the progress of the disorder.


Fast axonal transport in auditory neurons of the guinea pig: a rapidly turned-over glycoprotein.
Proteins of the fast component of axonal transport were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis in the guinea pig spiral ganglion, which has its cell bodies in the cochlea and its axons in the eighth cranial nerve projecting to the ipsilateral cochlear nucleus. We found that we could easily identify the proteins of the fast component even though these axons are only about 3 mm long because the cochlea minimized diffusion of labeled precursor into the cochlear nucleus. The composition of the fast component of the spiral ganglion cells was similar, but not identical, to the fast component of guinea pig retinal ganglion cells. One difference was the predominance in the spiral ganglion cell fast component of a rapidly turned-over glycoprotein (RTGP) with a molecular weight of 110,000-140,000 and an isoelectric point of 5.0 RTGP accumulated in the cochlear nucleus for just the first 3 hr after the application of the labeled precursor and then rapidly disappeared, whereas the other major fast component polypeptides continued to accumulate for 12-24 hr. RTGP was also tentatively identified in the fast component of retinal ganglion cells, but was not as prominently labeled relative to the other fast-component proteins in those cells. The rapid disappearance of RTGP from spiral ganglion cell terminals in the cochlear nucleus may be a result of secretion, perhaps as part of a synaptic vesicle, or retrograde transport as a feedback signal. The difference in the relative amounts of RTGP found in spiral ganglion and retinal ganglion cell terminals may reflect differences in the fundamental properties of the two groups of neurons.


Identification of core genes and prediction of miRNAs associated with osteoporosis using a bioinformatics approach.
Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus. Network topological parameters were determined using NetworkAnalyzer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, and ClueGO. Cytoscape with the Search Tool for the Retrieval of Interacting Genes and Molecular Complex Detection plug-in was used to visualize protein-protein interactions (PPIs). Additionally, miRNA-gene regulatory modules were predicted using CyTargetLinker in order to guide future research. In total, 915 DEGs were identified, including 774 upregulated and 141 downregulated genes. Enriched GO terms and pathways were determined, including 'nervous system development', 'regulation of molecular function', 'glutamatergic synapse pathway' and 'pathways in cancer'. The node degrees of DEGs followed power-law distributions. A PPI network with 541 nodes and 1,431 edges was obtained. Overall, 3 important modules were identified from the PPI network. The following 10 genes were identified as core genes based on high degrees of connectivity: Albumin, PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2), DNA topoisomerase 2-α, kininogen 1 (KNG1), interleukin 2 (IL2), leucine-rich repeats and guanylate kinase domain containing, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), leptin, transferrin and RNA polymerase II subunit A (POLR2A). Additionally, 15 miRNA-target interactions were obtained using CyTargetLinker. Overall, 7 miRNAs co-regulated IL2, 3 regulated PHLPP2, 3 regulated KNG1, 1 regulated PIK3CG and 1 modulated POLR2A. These results indicate potential biomarkers in the pathogenesis of OP and therapeutic targets.


Understanding Libraries as Part of the Rural Active Living Environment: Evidence From a Content Analysis of Library Facebook Posts Made in Summer 2022.
As both public health and public libraries continue to evolve, there are opportunities for collaboration focused on building policies, systems, and environments that support communities making healthy choices easy choices. Given the health disparities related to physical inactivity, such as diabetes and heart disease in rural America, public libraries within rural communities are emerging as important settings for health promotion and disease prevention. This study sought to better understand how rural libraries promote physical activity opportunities on Facebook. Based on a content analysis of Facebook posts of a random sample of 118 libraries made during the Summer of 2022, 47 of the 118 had at least one post related to physical activity and 42 had multiple posts. The most frequent offering was events or classes; libraries also supported physical activity by lending equipment and making changes to the built environment. This study provides evidence that some rural libraries are offering physical activity opportunities through community health partnerships, particularly for youth and families. Considering this evidence, public health professionals are encouraged to collaborate with local libraries to promote physical activity and advance rural health equity. Researchers are invited to continue to develop the evidence base around promoting physical activity with rural libraries.


Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics.
The importance of corticosteroids in cardiovascular and other chronic disease is recognised. In addition, plasma steroid precursor-to-product ratios are useful and convenient indirect indicators of efficiency of key steroidogenic enzymes (aldosterone synthase, 11β-hydroxylase and 17α-hydroxylase). The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has enabled measurement of numerous corticosteroid compounds simultaneously. However, normal responses to trophins and variation in salt intake are not well described. This study examined these parameters in a large group of healthy volunteers. Sixty normotensive volunteers were recruited and underwent infusion of angiotensin II (AngII) and ACTH, following low- and high-salt diet. Measurement of plasma steroids at baseline and 30 min after infusion of trophin was carried out by LC-MS. As expected, plasma mineralocorticoid levels increased in response to salt restriction and were suppressed with salt loading; ACTH infusion increased all corticosteroids, while AngII increased mineralocorticoids and suppressed glucocorticoid production. ACTH increased S:F but decreased DOC:B, thus the S:F ratio is a more appropriate index of 11β-hydroxylase efficiency. The B:F ratio increased following ACTH treatment and salt restriction. A larger proportion of plasma B than generally accepted may be derived from the zona glomerulosa and this ratio may be most informative of 17α-hydroxylase activity in salt-replete subjects. Although DOC:aldosterone, B:aldosterone and 18-hydroxyB:aldosterone should provide indices of aldosterone synthase efficiency, responses of individual compounds to trophins suggest that none of them accurately reflect this. Based on these data, aldosterone synthase activity is most accurately reflected by aldosterone concentration alone.


Absence of mutations in the human interferon alpha-2b gene in workers chronically exposed to ionising radiation.
Individuals chronically exposed to low-level ionising radiation (IR) run the risk of harmful and long-term adverse health effects, including gene mutations and cancer development. The search for reliable biomarkers of IR exposure in human population is still of great interest, as they may have a great implementation potential for the surveillance of occupationally exposed individuals. In this context, and considering previous literature, this study aimed to identify mutations in the human interferon alpha-2b (hIFNα-2b) as a potential biomarker of occupational chronic low-dose IR exposure linking low-IR exposure to the effects on haematopoiesis and reduced immunity. The analysis was performed in the genomic DNA of 51 uranium miners and 38 controls from Kazakhstan, and in 21 medical radiology workers and 21 controls from Italy. hIFNα-2b gene mutations were analysed with the real-time polymerase chain reaction (PCR) or Sanger sequencing. However, none of the investigated workers had the hIFNα-2b mutation. This finding highlights the need for further research to identify biomarkers for early detection of health effects associated with chronic low-dose IR exposure.


A Curious Case of Acute Glomerulonephritis - Staphylococcus vs Lupus: Case Report and Literature Review.
Here we report a case of a 65-year-old female, where we encountered acute glomerulonephritis. The patient initially presented with a hemorrhagic blister involving the second through fourth toes with serosanguinous discharge and was on hydralazine for blood pressure control. Differentials included Staphylococcus-associated/lupus nephritis/anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis. Still, detailed history and meticulous clinical approach with supporting labs and imaging helped us to narrow it to Staphylococcus-associated glomerulonephritis, which is rarely encountered in clinical practice and is associated with high mortality. The management of the patient resulted in a positive outcome and she was discharged home.


Tethering of vesicles to the Golgi by GMAP210 controls LAT delivery to the immune synapse.
The T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune synapse by tethering LAT-vesicles to the Golgi. Finally, in a model of ectopic expression of LAT in ciliated cells, we show that GMAP210 tethering activity controls the delivery of LAT to the cilium. Hence, our results reveal a function for the golgin GMAP210 conveying specific vesicles to the immune synapse.


Change in seizure threshold during electroconvulsive therapy.
The seizure threshold (ST) is a measure of the minimum electrical energy necessary to induce a grand mal seizure. Dose titration of the ST has been suggested to optimize stimulus dosing in electroconvulsive therapy (ECT). The change in ST with remission is examined in a large sample of unipolar depressed patients. In a study of continuation treatments after successful ECT, the ST was determined at the first treatment and again 1 week after remission using a conventional ST measurement protocol. Patients were treated with bilateral electrode placement at 150% above the measured ST. In 80 subjects, the ST measured the same in 70%, increased in 21%, and decreased in 9% at remission. In a study of bilateral ECT, the ST did not rise conclusively with remission.


Relationship Between Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio and Obstructive Sleep Apnea Syndrome.
Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) give information about many diseases. An increase in inflammation markers occurs in patients with obstructive sleep apnea syndrome (OSAS). The aim of this study is to determine the relationship between OSAS and NLR and PLR values. Two hundred eighty four patients with complaints of snoring and excessive daytime sleepiness were included in the study. Polysomnography had been performed on all patients and the control group. Fourty eight of these patients with apnea-hypopnea index (AHI) less than 5 (pure snoring) were included in the control group, 67 patients with AHI between 5 and 14.9 in the mild OSAS group, 61 patients with AHI between 15 and 29.9 in the moderate OSAS group and 108 patients with AHI more than 30 in the severe OSAS group. NLR and PLR values were calculated from the complete blood count (CBC) analysis of the patients and control group. The OSAS and control groups were compared by age, gender, body mass index (BMI) and PSG parameters as well as NLR and PLR values. The PLR value in the OSAS group was found to be less than in the control group (p=0.006). As the non-REM AHI increased, the value of PLR decreased. As the nocturnal time spent with arterial oxygen saturation<90% increased, the value of NLR was determined to increase. NLR and PLR values can give valuable information in OSAS.


Two-Dimensional van der Waals Heterostructures Constructed via Perovskite (C4H9NH3)2XBr4 and Black Phosphorus.
Heterogeneous stacking of two-dimensional (2D) perovskites with other 2D materials is a very effective strategy for designing low-cost and high-performance photovoltaic and optoelectronic devices. The structural, electronic, and optical properties of distinctive all-2D M2XBr4-black phosphorus (BP) [M = (C4H9NH3)+; X = Pb2+, Sn2+, Ge2+] van der Waals (vdW) heterostructures have been studied by first-principle calculations. The M2SnBr4-BP and M2GeBr4-BP heterostructures show type-II band arrangement; however, the M2PbBr4-BP heterostructure exhibits type-I band arrangement. The energy level shift is ascribed to the difference of work function between M2XBr4 monolayer and BP monolayer, driving the movement of carriers spontaneously. Furthermore, the BP layers can enhance the light absorption of the total heterostructures, especially the M2GeBr4-BP heterostructure. These results indicate the all-2D perovskite and BP vdW heterostructures are competitive candidates for low-dimensional photovoltaic and optoelectronic applications.


Chronic inflammatory demyelinating polyneuropathy: considerations for diagnosis, management, and population health.
First described almost 50 years ago, chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder characterized by progressive peripheral neuropathy. CIDP is difficult to diagnose, but early diagnosis can be crucial to prevent permanent nerve damage. Initial treatment options include corticosteroids, immunoglobulin given by intravenous administration, and therapeutic plasma exchange. Subcutaneous administration of immunoglobulin provides a new option for patients with CIDP that has the potential to increase independence and improve tolerability. This article reviews the epidemiology, diagnosis, treatment options for first- and second-line therapy, treatment guidelines, and monitoring parameters for CIDP.


Computed tomography findings of tuberculous pleurisy.
Review of the records of 491 patients with tuberculous pleurisy hospitalized between 1993 and 1995 in Izmir, Turkey. Those cases with typical histopathology or demonstrated acid-fast bacilli on pleural needle biopsies and/or positive pleural fluid/tissue cultures and available computed tomography (CT) scans are included. To determine the CT features of tuberculosis of the pleural space. The CT scans of 66 patients with proven tuberculous pleurisy were interpreted retrospectively by three observers. Of 66 patients, 65 (98.5%) had pleural effusions; 38 (57.5%) had pleural lesions; six (9%) had involvement of interlobar fissure; and one patient (1.5%) had involvement only of the mediastinal pleura. All but one of the pleural lesions involved regular thickening of greater than 1 cm. Fibrotic parenchymal changes were seen in 11 of 66 patients (17%), cavitary changes were seen in eight (12%), and heterogeneous nodular shadows were seen in four (6%). Two cases (3%) had parenchymal consolidation and one (1.5%) had a calcified subpleural nodule. In 39% (26/66) of cases, hilar and mediastinal lymphadenopathy was identified. Tuberculous pleurisy in our series was characterized on CT by the presence of pleural effusion, often with smooth pleural thickening; rarely was there involvement of the mediastinal pleura. Underlying lung parenchymal abnormalities were seen in 39% of cases. Although these findings are non-specific, they may help to distinguish tuberculous pleurisy from other causes of pleural effusion, such as malignancy.


Decomposing differences in acute myocardial infarction fatality in Italian regions.
The paper develops a general method for evaluating geographical differences in the outcome of acute myocardial infarction patients, by looking at the process of disease occurrence from infarction to hospitalization and possible death or recovery. The method is applied to regional data in Italy, where the long history of geographical diversities in economical, social and cultural fields is reflected in health care. Specific features of AMI, such as high fatality and fast course of the disease, make it a suitable tracer condition to investigate into the differences of regional health systems during the acute phase of hospitalization. The paper combines administrative and official statistics by region and offers a tool providing suggestions to policy-makers where further eventual investigations are needed around the care pathway and also what possible actions might be undertaken to improve the outcomes.


Some aspects of cutaneous leishmaniasis in Riyadh. Saudi Arabia.
One hundred and sixty nine out of 310 outpatients of Riyadh's hospitals and 104 out of 209 inhabitants from El Kharj showed Leishmania bodies in smears obtained by puncture of indurated edge of sores. Collection of sand flies yielded P. papatasi, Paraphlebotomus caucasicus and S. squamipleuris. The results were discussed.


Left diaphragmatic hernia after pneumonectomy.
Patients undergoing pneumonectomy can suffer by cardiovascular and respiratory postoperative complications that can affect patient's outcome by increasing morbidity and mortality. We describe a diaphragmatic hernia occurring after pneumonectomy. with late presentation and with epidural analgesia confusing the scenario suggesting that anesthesiologists should remain aware on this complication even in the late post operative period.


[Salivary hormones: a new aspect of oral physiology].
Aside from the digestive enzymes the submandibular salivary glands (SSG) synthetize other polypeptides, detected also in saliva, with varied biological activity; NGF and EGF are the knowest. However, over the last decade, steroids hormones have been also found out in the saliva at the same concentrations that the free plasma fraction. The origin of these hormones is largely discussed and certain authors have even proposed a local synthesis for them. This matter, is of clinical interest because gingiva and buccal tissues are knowingly sensitive to steroids. Besides, woman ovulation appears to be monitored through progesterone fluctuations in saliva. Another kind of salivary substances is formed by the neuropeptides of the gut-brain axis, mainly VIP and SRIF. The former likely of nervous origin seems to be involved in the atropine-resistant salivary secretion, whereas the latter-likely of SSG origin--appears as a factor associated with glycemia control.


Characterization of two different toxins of Wickerhamomyces anomalus (Pichia anomala) VKM Y-159.
Wickerhamomyces anomalus VKM Y-159 strain produces two types of toxin designated as WAKT a and WAKT b, encoded by chromosomal genes. The WAKT a toxin is heat-labile, pronase sensitive acting in pH range 3-4 affecting on several yeasts including pathogenic Candida species while the WAKT b toxin is protease- and thermo-resistant, acting in pH range 3-7 on two species, Candida alai and Candida norvegica. The rapid decrease of the number of viable cells after toxin treatment demonstrates that both toxins have cytocidic effect.


Long-lasting synaptic loss after repeated induction of LTD: independence to the means of LTD induction.
Short- and long-lasting synaptic plasticity is assumed to be the cellular basis of short- and long-lasting memory, respectively. However, the cellular consequences leading to the long-lasting synaptic plasticity, assumed to include the processes of synapse formation and elimination, remain unknown. Using hippocampal slices maintained stably in culture, we found previously that the repeated induction of long-term potentiation (LTP) triggered a slowly developing long-lasting enhancement in synaptic transmission strength accompanied by synapse formation, which was separate from LTP itself. We recently reported a phenomenon apparently of a mirror-image effect. The repeated activations of metabotropic glutamate receptor (mGluR), which induces long-term depression (LTD), triggered a long-lasting reduction in synaptic strength accompanied by synapse elimination. To clarify whether the reported long-lasting effect was specific to the drugs used previously and whether the effect was specific to mGluR-mediated LTD, we exposed the cultured slices repeatedly to another Group I metabotropic glutamate receptor (mGluR) agonist, an N-methyl-d-aspartate receptor agonist, and a Na+/K+-pump inhibitor. All these treatments resulted in an equivalent long-lasting synaptic reduction/elimination when repeated three times, indicating that the repeated LTD induction leads to synapse elimination. The independence of synapse elimination to the means of LTD induction suggests that the signals leading to short-term plasticity and long-term plasticity are independent. Detailed inspections in the representative case of mGluR activation revealed that the reduction in synaptic strength developed with a approximately 1-week delay from the decrease in the number of synaptic structures. This synapse elimination should be unique as it is activity-dependent rather than inactivity-dependent.


A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management.
To genotypically and phenotypically characterize a large pediatric myotonic dystrophy type 1 (DM1) cohort to provide a solid frame of data for future evidence-based health management. Among the 2,697 patients with genetically confirmed DM1 included in the French DM-Scope registry, children were enrolled between January 2010 and February 2016 from 24 centers. Comprehensive cross-sectional analysis of most relevant qualitative and quantitative variables was performed. We studied 314 children (52% females, with 55% congenital, 31% infantile, 14% juvenile form). The age at inclusion was inversely correlated with the CTG repeat length. The paternal transmission rate was higher than expected, especially in the congenital form (13%). A continuum of highly prevalent neurodevelopmental alterations was observed, including cognitive slowing (83%), attention deficit (64%), written language (64%), and spoken language (63%) disorders. Five percent exhibited autism spectrum disorders. Overall, musculoskeletal impairment was mild. Despite low prevalence, cardiorespiratory impairment could be life-threatening, and frequently occurred early in the first decade (25.9%). Gastrointestinal symptoms (27%) and cataracts (7%) were more frequent than expected, while endocrine or metabolic disorders were scarce. The pedDM-Scope study details the main genotype and phenotype characteristics of the 3 DM1 pediatric subgroups. It highlights striking profiles that could be useful in health care management (including transition into adulthood) and health policy planning.


Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen-2-one as a new class of microtubule-targeting agents.
A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC(50) = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC(50) = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.


Light-controlled reversible self-assembly of nanorod suprastructures.
Nanorod suprastructures constructed by the coordination of zinc ions with the inclusion complex of 4,4'-dipyridine in β-cyclodextrin can dissociate and rebuild repeatedly via alternate visible light irradiation in the presence of photoacid merocyanine in aqueous solution.


Immune checkpoints in the tumor microenvironment.
Interactions between immune checkpoints (ICs) and their ligands negatively regulate T cell activation pathways involved in physiological immune responses against specific antigens. ICs and their ligands are frequently upregulated in the tumor microenvironment (TME) of various malignancies, and they represent significant barriers for induction of effective anti-tumor immune responses. Several IC inhibitors (ICIs) have been developed, with some currently in clinical trials and others have been approved for the treatment of different cancers. However, tumor cells are able to counteract the activity of ICIs and can commission additional inhibitory pathways via expression of other ICs/ligands within the TME. This review discusses the expression of various ICs/ligands in the TME and their impact on tumor immune evasion. Additionally, we discuss various regulatory mechanisms, including genetic and epigenetic, and other modulatory factors including hypoxia and the presence of immunosuppressive populations in the TME, which result in upregulation of ICs in various cancers. Moreover, we discuss the prognostic significance of ICs and their ligands, and the potential strategies to enhance treatment responses to ICIs. This review aims to advance our current knowledge on the role of ICs in the TME and the clinical benefits of targeting them.


Improving oxygenation at high altitude: acclimatization and O2 enrichment.
When lowlanders go to high altitude, the resulting oxygen deprivation impairs mental and physical performance, quality of sleep, and general well-being. This paper compares the effects of ventilatory acclimatization and oxygen enrichment of room air on the improvement of oxygenation as judged by the increase in the alveolar P(O2) and the reduction in equivalent altitude. The results show that, on the average, complete ventilatory acclimatization at an altitude of 5000 m increases the alveolar P(O2) by nearly 8 torr, which corresponds to a reduction in equivalent altitude of about 1000 m, although there is considerable individual variability. By comparison, oxygen enrichment to 27% at 5000 m can easily reduce the equivalent altitude to 3200 m, which is generally well tolerated. Because full ventilatory acclimatization at altitudes up to about 3600 m reduces the equivalent altitude to about 3000 m, oxygen enrichment is not justified for well-acclimatized persons. At an altitude of 4200 m, where several telescopes are located on the summit of Mauna Kea, full acclimatization reduces the equivalent altitude to about 3400 m, but the pattern of commuting probably would not allow this. Therefore, at this altitude, oxygen enrichment would be beneficial but is not essential. At higher altitudes such as 5050 m, where other telescopes are located or planned, the gain in oxygenation from acclimatization is insufficient to produce an adequate mental or physical performance for most work, and oxygen enrichment is highly desirable. Full ventilatory acclimatization requires at least a week of continuous exposure, although much of the improvement is seen in the first 2 days.


Case Report of Osteopoikilosis: Sparse Cause of Bone Pain and Mimicker of Metastasis on Radiographs.
Osteopoikilosis (OPK) is an extremely rare benign condition with autosomal dominant inheritance characterized by sclerosing bony dysplasia with multiple benign enostoses. It is characterized by symmetrically distributed numerous, small, well-defined, homogenous circular or ovoid radiodensities clustered in epiphysis and metaphysis of long bones in periarticular region, and in some cases diffusely present throughout axial and appendicular skeleton. There is no age and sex predilection; age at the time of diagnosis ranges from 15 to 60 years. It is usually asymptomatic but rarely in 15-20% patients slight juxta-articular pain and joint effusions can be seen. These are incidental radiological findings in most of the cases, also sometimes confused as bony metastasis. There are no specific clinical features; histological features are similar to bony island and it may be associated with connective tissue disorders, synovial osteochondromatosis, and a rare bone condition melorheostosis. We present a case of OPK in a 32-year-old male with bilateral hip and shoulder pain, based on the available literature and focus on clinical significance, due to its mimicking capability of other more severe conditions such as bone metastases and an extremely uncommon cause of bone pain. OPK is an uncommon hereditary condition involving juxta-articular region of long bones with intricate etiopathogenesis, often discovered incidentally on radiographs. It is characterized by multiple, symmetrical ovoid radiodensities, and in most instances confused with osteoblastic metastasis. This concludes that OPK is a condition that should be kept in mind to avoid misdiagnosis, in particular osteoblastic metastasis and undue distress to both the patients and doctors.


Risk of Lymphedema and Death after Lymph Node Dissection with Neoadjuvant and Adjuvant Treatments in Patients with Breast Cancer: An Eight-Year Nationwide Cohort Study.
Knowledge on the impact of neoadjuvant and adjuvant treatments on post-surgery lymphedema (LE) in patients with breast cancer is limited due to methodological limitations and an insufficient sample size. We investigated the risk of LE in patients going through long-term anticancer treatment regimens using a national cohort from the Korean National Health Insurance Service database from 2011-2013. Incidence rate ratio, Kaplan-Meier analysis, and Cox proportional regression analysis were performed. A total of 39,791 patients were included. While minimal lymph node dissection (SLNB) reduced the risk of LE (hazard ratio [HR] 0.51) as expected, neoadjuvant chemotherapy (NAC) followed by SLNB did not reduce the risk. Adjusting for adjuvant chemotherapy (AC) as time-varying exposure decreased the risk of LE in the SLNB group (HR 0.51), but not the mortality risk (HR 0.861). A longer duration of NAC, especially taxane-based, combined with SLNB reversed the effect and increased risk of LE. The findings highlight the importance of not only early surveillance before and after surgery, but also long-term surveillance during adjuvant treatment by surgeons and oncologists in order to reduce the risk of LE.


A microscopic-macroscopic analysis for mixed energy transfer schemes in doped amorphous solids.
In this study we propose a methodology to treat mixed and more complex energy transfer schemes to reach the time-dependent intensities of luminescence in doped amorphous materials. We start outlining the differential equations for the time variation of microscopic probabilities of being in the relevant states and then transforming them into equations for the variation of the relevant macroscopic states populations and solve those equations. By this method, statistical approaches to the initially excited and up-converted states transient populations for up-conversion processes in the presence of cross relaxation in lanthanide-monodoped amorphous solid are calculated. The resultant formulations produce plots that show correct general tendencies and are coherent with what would be expected for systems exhibiting both mechanisms, hence they could be used in the fitting of experimental curves to calculate some important parameters. The new solution method is more convenient that the classical analysis because it permits the introduction of more realistic time dependent functions for the interacting optical centers and allows showing the time dependence of the macroscopic energy transfer rates in the equations for the dynamics of the involved populations. We apply our method to the particular case of mixing of up-conversion and cross relaxation phenomena; however, because of its general characteristics, we suggest it could be applied to other mixings or more complex schemes.


The durability of sitagliptin in elderly patients with type 2 diabetes.
To evaluate the durability of sitagliptin and to assess changes in clinical chronic complications following sitagliptin monotherapy for 48 months in elderly patients with type 2 diabetes mellitus (T2DM). We enrolled 76 drug-naïve patients (40 women and 36 men; mean age: 71.3±11.7 years) with T2DM who received 25-100 mg of sitagliptin therapy from an outpatient clinic. The observational period for each patient was >48 months, beginning at the time sitagliptin therapy was initiated. The following were measured or performed at the beginning of each year: body mass index; serum total cholesterol, low-density lipoprotein, high-density lipoprotein; triglyceride levels; creatinine (Cr) levels; urine albumin and urine Cr; nonmydriatic fundusgraphy; and semiquantified neuropathy. The fasting plasma glucose and glycated hemoglobin (HbA1c) was measured every 3-6 months. The change in HbA1c was significantly reduced after 6 months of therapy (7.1%±0.8% to 6.3%±0.2%). No changes in fasting plasma glucose, Cr, serum total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, body mass index, and microvascular complications were apparent. Using repeated measures to test the sequential changes in HbA1c from month 6 to month 48, the test of within-subjects effect was not significant (P=0.34). Sitagliptin has a durable effect and stabilizes microvascular complication progression in elderly patients. This study can provide useful data for clinicians and health care professionals using sitagliptin monotherapy in the treatment of elderly patients with T2DM.


Efficacy and Safety of Bimekizumab in Moderate to Severe Hidradenitis Suppurativa: A Phase 2, Double-blind, Placebo-Controlled Randomized Clinical Trial.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options. To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS. This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline. Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10). The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores. Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-three participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%). In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS. ClinicalTrials.gov Identifier: NCT03248531.


Rates and predictors of oral medication adherence in pediatric patients with IBD.
Symptoms of inflammatory bowel disease (IBD) include bloody diarrhea, fatigue, abdominal pain, and weight loss. Long-term management of remission for most patients requires adherence to taking 1 or more oral medications daily, in the absence of symptoms. We investigated whether disease characteristics and behavioral characteristics predict adherence to prescribed medical regimens. : Patients aged 8 to 17.5 years, newly diagnosed with IBD, and a matched cohort previously diagnosed were studied over a 6-month period. Adherence was assessed using medication electronic monitoring devices (Medication Event Monitoring Systems); participants and parents completed questionnaires regarding emotional and behavioral functioning, and biological parameters were monitored. : Adherence was monitored for 45 newly and 34 previously diagnosed patients. In total, 16,478 patient-days (including 12,066 discrete days) were electronically monitored. Overall, 70.6% of 5-aminosalicylic acid and 65.4% of 6-mercaptopurine doses were taken. Only 25% and 15% of older adolescents took at least 80% of their 5-aminosalicylic acid and 6-mercaptopurine, respectively, compared with about 83% and 64% of 8-year-olds to 11-year-olds. Only age and behavioral issues were statistically linked to rates of adherence. Adherence to commonly prescribed oral medications for IBD is challenging for patients. Screening for emotional and behavioral problems, especially among older adolescents, would be important in identifying patients at risk of poor adherence, who might benefit from interventions. Biological solutions, although critical, when applied without attention to behavioral issues, are not likely to provide the level of therapeutic benefit that can be provided in a combined biobehavioral approach.


Role of aliesterase in organophosphate poisoning.
Various doses of CBDP (2-(2- methylphenoxy )-4H-1,3,2- benzodioxaphosphorin -2-oxide), a metabolite of tri-o-cresyl phosphate, increased dramatically the acute toxicity of soman ( pinacolyl methylphosphonofluoridate ) in mice. CBDP (5 mg/kg; iv) reduced the soman LD50 value from 136 micrograms/kg in control to 6.95 micrograms/kg. The potentiation of soman toxicity following CBDP pretreatment appeared to be due primarily to inhibition of plasma aliesterase activity. Inhibition of liver aliesterase was not of primary importance in the potentiation of soman toxicity following CBDP pretreatment. In addition pretreatment with ISO-OMPA ( tetraisopropyl pyrophosphoramide ), a selective inhibitor of pseudocholinesterase, had no effect on the acute toxicity of soman. Similarly pretreatment of mice with pyridostigmine, a quaternary carbamate anticholinesterase which does not inhibit aliesterase , resulted in marked inhibition of diaphragm, plasma, and brain acetylcholinesterase had no effect on the acute toxicity of soman. Plasma aliesterase may be a depot for soman poisoning. The acute toxicity of soman by the ip, sc, and iv routes of administration was reduced following pretreatment of mice with phenobarbital (100 mg/kg) for 4 days. The reduced toxicity of soman following phenobarbital pretreatment was due to induction of liver aliesterase activity which subsequently resulted in an increase in plasma aliesterase activity. Thus more soman was probably bound to plasma aliesterase activity resulting in a reduction in acute toxicity of soman. Conversely pretreatment of mice with pentobarbital (70 mg/kg; ip) increased the toxicity of soman. This was probably the result of inhibition of plasma aliesterase by pentobarbital pretreatment combined with the central respiratory depression following pentobarbital administration. Following pentobarbital pretreatment soman inhibition of brain acetylcholinesterase was increased suggesting that plasma aliesterase inhibition alters the distribution of free soman in vivo. In summary, in mice plasma aliesterase appears to be an extremely important detoxification route for soman in vivo.


Comparison of the mechanical hypoalgesic effects of five α2-adrenoceptor agonists in donkeys.
Pharmacological pain management is necessary under many clinical situations, but in donkeys little information on analgesic drugs is available. This controlled, randomised, crossover, Latin-square, operator-blinded study aimed to assess and compare the hypoalgesic effects of intravenously administered saline and five α2-adrenoceptor agonists on mechanical nociceptive thresholds (MNT) in donkeys. Areas under the threshold change versus time curve values for 0-30, 30-60, 60-90 and 90-120 minutes postdrug administration were used to compare the effect of treatment. As compared with saline, which did not increase MNT, the overall degree of mechanical hypoalgesia induced by xylazine (1.1 mg/kg), detomidine (20 μg/kg), medetomidine (5 μg/kg) and dexmedetomidine (3.5 μg/kg) was limited to 0-60 minutes, and that of romifidine (100 μg/kg) to 0-120 minutes. Although there were no significant differences between the five α2-adrenoceptor agonists during the first 30 minutes postadministration, hypoalgesia induced by xylazine and dexmedetomidine was significantly less intense than that achieved by detomidine and/or romifidine from 30 to 60 minutes. Differences in the overall degree of hypoalgesia induced by each of the α2-adrenoceptor agonists may influence veterinary surgeons towards choosing a particular drug over others for a particular donkey patient.


Symptomatic, paradoxical intracranial tuberculomas along non-functional ventricular catheter necessitating its removal.
Symptomatic, paradoxical intracranial tuberculomas is a rare occurrence. A case of tubercular meningitis, developing paradoxical tuberculomas alongside non-functional ventricular catheter is presented. Catheter removal facilitated removal of these paradoxical lesions, with the patient recovering to near-normal state after completing 12 months of anti-tubeculous therapy. Non-functional ventricular catheter may become the site of paradoxical tuberculomas and these lesions, if symptomatic, may require catheter removal.


Inhibition of bacteria in mouse drinking water by chlorination.
Experience with the use of mouse drinking water containing chlorine is discussed. With an initial concentration of 5 p.p.m. bacteria were recovered from the bottles after 7 days and there was considerable growth in untreated bottles. Above this concentration no bacteria survived. It is recommended that 15-20 p.p.m. chlorine are used for practical purposes.


Triboelectric Nanogenerators and Hybridized Systems for Enabling Next-Generation IoT Applications.
In the past few years, triboelectric nanogenerator-based (TENG-based) hybrid generators and systems have experienced a widespread and flourishing development, ranging among almost every aspect of our lives, e.g., from industry to consumer, outdoor to indoor, and wearable to implantable applications. Although TENG technology has been extensively investigated for mechanical energy harvesting, most developed TENGs still have limitations of small output current, unstable power generation, and low energy utilization rate of multisource energies. To harvest the ubiquitous/coexisted energy forms including mechanical, thermal, and solar energy simultaneously, a promising direction is to integrate TENG with other transducing mechanisms, e.g., electromagnetic generator, piezoelectric nanogenerator, pyroelectric nanogenerator, thermoelectric generator, and solar cell, forming the hybrid generator for synergetic single-source and multisource energy harvesting. The resultant TENG-based hybrid generators utilizing integrated transducing mechanisms are able to compensate for the shortcomings of each mechanism and overcome the above limitations, toward achieving a maximum, reliable, and stable output generation. Hence, in this review, we systematically introduce the key technologies of the TENG-based hybrid generators and hybridized systems, in the aspects of operation principles, structure designs, optimization strategies, power management, and system integration. The recent progress of TENG-based hybrid generators and hybridized systems for the outdoor, indoor, wearable, and implantable applications is also provided. Lastly, we discuss our perspectives on the future development trend of hybrid generators and hybridized systems in environmental monitoring, human activity sensation, human-machine interaction, smart home, healthcare, wearables, implants, robotics, Internet of things (IoT), and many other fields.


What risk factors affect hospitalisation for confirmed pertussis cases among infants in the Czech Republic?
We estimated what risk factors affect hospitalisation for confirmed pertussis cases among infants (child up to 1 year) in the Czech Republic based on data from the questionnaire-based enhanced surveillance system (ESS) in years 2015, 2017 and 2019. Retrospective cohort study was conducted in which we assessed demographic, clinical data, vaccination status and risk/protective factors. Vaccination status was extracted from the electronic nationwide notification system (NNS). We performed descriptive, univariable and multivariable analysis using risk ratio (RR) and logistic regression with odds ratio (OR). A total of 104 confirmed cases (27, 13, 64) were reported in the ESS during 2015, 2017 and 2019. Most cases were in age group 1 month (24), more males (57). Fifteen cases were vaccinated and 89 unvaccinated. Of 88 hospitalised cases, 31 cases reported stay in Intensive Care Unit (ICU). The median length of hospitalisation was 8 days. Although the variable vaccinated in infants was statistically significant in a univariable analysis for outcome hospitalisation, RR 0.76 (95% CI 0.53-1.10), it was not in multivariable. Hospitalisation was strongly associated with the younger age group of 0-3 months adjusted by a smoking family member in a household (OR = 9.72; 95% CI: 2.97-31.81). Stay in ICU was strongly correlated with the younger age group of 0-3 months (OR = 5.07; 95% CI: 1.44-17.87) and with a contact with confirmed or probable pertussis (OR = 7.05; 95% CI: 1.36-36.52). Our study demonstrated younger age and contact with other pertussis case as risk factors for hospitalisation of infants with pertussis. It is necessary to consider adolescent and adult boosters, including vaccination during pregnancy. We suggest integrating the variables from the enhanced surveillance system into the nationwide notification system, in order to simplify the data reporting and evaluation. Further studies are needed to evaluate the ESS and to monitor the vaccination of pregnant women against pertussis.


In vitro bonding efficacy of three restorative materials to primary dentin using a one-bottle adhesive system.
The shear bond strength to primary dentin of a new single-bottle adhesive with three restorative materials (composite resin, compomer, and amalgam) was evaluated. Statistical analysis of the data showed significant differences among the means of the groups (ANOVA, p < 0.05). Composite resin and compomer were not significantly different from each other but both were statistically higher than amalgam. The fracture mode was not related to the shear bond strength values. The mean shear bond strengths obtained in this study were statistically comparable to those obtained in a previous study which used the same experimental design but included permanent teeth.