Odorant and gustatory receptors in the tsetse fly Glossina morsitans morsitans.
Tsetse flies use olfactory and gustatory responses, through odorant and gustatory receptors (ORs and GRs), to interact with their environment. Glossina morsitans morsitans genome ORs and GRs were annotated using homologs of these genes in Drosophila melanogaster and an ab initio approach based on OR and GR specific motifs in G. m. morsitans gene models coupled to gene ontology (GO). Phylogenetic relationships among the ORs or GRs and the homologs were determined using Maximum Likelihood estimates. Relative expression levels among the G. m. morsitans ORs or GRs were established using RNA-seq data derived from adult female fly. Overall, 46 and 14 putative G. m. morsitans ORs and GRs respectively were recovered. These were reduced by 12 and 59 ORs and GRs respectively compared to D. melanogaster. Six of the ORs were homologous to a single D. melanogaster OR (DmOr67d) associated with mating deterrence in females. Sweet taste GRs, present in all the other Diptera, were not recovered in G. m. morsitans. The GRs associated with detection of CO2 were conserved in G. m. morsitans relative to D. melanogaster. RNA-sequence data analysis revealed expression of GmmOR15 locus represented over 90% of expression profiles for the ORs. The G. m. morsitans ORs or GRs were phylogenetically closer to those in D. melanogaster than to other insects assessed. We found the chemoreceptor repertoire in G. m. morsitans smaller than other Diptera, and we postulate that this may be related to the restricted diet of blood-meal for both sexes of tsetse flies. However, the clade of some specific receptors has been expanded, indicative of their potential importance in chemoreception in the tsetse.


The role of hydrogen peroxide produced by polychlorinated biphenyls in PMR1-deficient yeast cells.
Polychlorinated biphenyls (PCBs) are well-known recalcitrant environmental pollutants. Although the metabolism of the PCBs has been intensively studied, very little is known about their mechanism of toxicity in living organisms or how they are degraded. We have examined the effects of PCBs on two different yeast strains to determine their mechanism of action. One yeast strain (K601, wild type) is resistant to the growth-inhibitory effect of PCBs, whereas the other strain (AA542, PMR1 mutant) is susceptible. PCBs increased the level of intracellular hydrogen peroxide in AA542 cells but not in K601 cells. In the presence of alpha-tocopherol or ursolic acid the growth of AA542 cells was not inhibited by treatment with PCBs. These results suggest that PCBs block cell growth through production of hydrogen peroxide in the PMR1 mutant strain, AA542. We compared superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities in both strains. The catalase activity in K601 cells was 10 times higher than that in AA542 cells. In contrast, there was no difference in activities of SOD and GPx between the two strains. Collectively, these observations indicate that oxidative stress causes the inhibition of cell growth observed in catalase-deficient yeast cells exposed to PCBs.


Simulated viewpoint jitter shakes sensory conflict accounts of vection.
Sensory conflict has been used to explain the way we perceive and control our self-motion, as well as the aetiology of motion sickness. However, recent research on simulated viewpoint jitter provides a strong challenge to one core prediction of these theories -- that increasing sensory conflict should always impair visually induced illusions of self-motion (known as vection). These studies show that jittering self-motion displays (thought to generate significant and sustained visual-vestibular conflict) actually induce superior vection to comparable non-jittering displays (thought to generate only minimal/transient sensory conflict). Here we review viewpoint jitter effects on vection, postural sway, eye-movements and motion sickness, and relate them to recent behavioural and neurophysiological findings. It is shown that jitter research provides important insights into the role that sensory interaction plays in self-motion perception.


Expression of red-shifted green fluorescent protein by Escherichia coli O157:H7 as a marker for the detection of cells on fresh produce.
Escherichia coli O157:H7 was transformed with a plasmid vector red-shifted green fluorescence protein (pEGFP) to express red-shifted green fluorescence protein (EGFP) from Aequorea victoria. The EGFP expression among total cells and nonviable cells was determined at the cellular level by microscopic observation of immunostained and membrane-impermeable, dye-stained cultures, respectively. E. coli O157:H7 retained pEGFP during frozen storage at -80 degrees C. The percentage of EGFP expression was improved by repeated subculturing, reaching 83.4 +/- 0.1%, although the fluorescence intensity varied among cells. A low percentage of EGFP-expressing cells was nonviable. The percentage of EGFP decreased when the culture plate was kept at 4 degrees C, suggesting that some cells lost pEGFP during refrigeration. The storage of the culture suspension in sterile deionized water at 4 degrees C for 24 h reduced the percentage of EGFP expression, indicating that some EGFP was denatured. The application of EGFP as a marker for E. coli O157:H7 on green leaf lettuce, cauliflower, and tomato was evaluated using confocal scanning laser microscopy. EGFP-transformed cells were readily visible under confocal scanning laser microscopy on all produce types. The numbers of E. coli O157:H7 cells detected with EGFP were equivalent to those detected with immunostaining for green leaf lettuce and cauliflower but less for tomato. E. coli O157:H7 attached preferentially to damaged tissues of green leaf lettuce and tomato over intact tissue surfaces and to flowerets of cauliflower than to stem surfaces. EGFP can serve as a marker to characterize E. coli O157:H7 attachment on green leaf lettuce and cauliflower but may not be suitable on tomato.


Predictive Factors of Regular Physical Activity among Middle-Aged Women in the West of Iran, Hamadan: Application of PRECEDE Model.
Regular physical activity is important for midlife women. Models and theories help better understanding this behavior among middle-aged women and better planning for change behavior in target group. This study aimed to investigate predictive factors of regular physical activity among middle-aged women based on PRECEDE model as a theoretical framework. This descriptive-analytical study was performed on 866 middle-aged women of Hamadan City western Iran, recruited with a proportional stratified sampling method in 2015. The participants completed a self-administered questionnaire including questions on demographic characteristics and PRECEDE model constructs and IPAQ questionnaire. Data were then analyzed by SPSS-16 and AMOS-16 using the Pearson correlation test and the pathway analysis method. Overall, 57% of middle-aged women were inactive (light level) or not sufficiently active. With SEM (Structural Equation Modeling) analysis, knowledge b=0.84, P<0.001, attitude b=0.799, P<0.001, self-efficacy b=0.633, P<0.001 as predisposing factor and social support as reinforcing factor b=0.2, P<0.001 were the most important predictors for physical activity among middle-aged women in Hamadan. The framework of the PRECEDE model is useful in understanding regular physical activity among middle-aged women. Furthermore, results showed the importance of predisposing and reinforcing factors when planning educational interventions.


C3a receptor antagonist attenuates brain injury after intracerebral hemorrhage.
Neuroprotective therapy targeting the complement cascade may reduce injury associated with intracerebral hemorrhage (ICH). We investigated the role of C3a-receptor antagonist (C3aRA) after ICH in mice. Autologous whole blood was infused into the right striatum of mice that were treated with C3aRA or vehicle, using both a pre- and postinjury dosing regimen. Hematoma volume, brain water content, and inflammatory cell profile were assessed at 72 h post-ICH. Neurologic dysfunction was assessed by evaluating both spatial memory and sensorimotor capacity. Animals pretreated with C3aRA showed significantly improved neurologic function, brain water content, and granulocyte infiltration relative to vehicle-treated animals when assessed at 72 h. There was no significant difference in hemorrhagic/nonhemorrhagic ratio of microglial activation among all groups. Hematoma volumes were also not significantly different between C3aRA-treated and vehicle-treated animals. Administration of C3aRA beginning 6 h postinjury afforded significant amelioration of neurologic dysfunction as well as a reduction in brain water content. Treatment with C3aRA improved neurologic outcome while reducing inflammatory cell infiltration and brain edema formation after experimental ICH in mice. Results of this study suggest that the C3a receptor may be a promising target for therapeutic intervention in hemorrhagic stroke.


A Behavioral Index for Assessing Bison Stress Level during Handling and Demographic Predictors of Stress Response.
There are an estimated half-a-million Plains Bison (Bison bison) present in North America in commercial and conservation herds. Most bison are rounded up and "worked" annually for parasite control, veterinarian attention, and processing, making it important to understand the impacts of these operations. Research indicates bison generally experience higher levels of stress than cattle during similar handling processes. However, most methods for assessing stress-level during working are invasive, increase handling time, and paradoxically increase stress levels. We designed a behavioral index to assess bison stress level during handling and used it to evaluate various predictors of stress response in a semi-wild bison herd. We examined how sex, age, herd of origin, previous experience, calf rearing, and body condition influenced bison stress response during working operations from 2015 to 2017. Our results indicate that stress level decreased with age and previous experience being worked through a particular facility. Additionally, herd of origin influenced stress level, indicating that stress response may have a genetic or epigenetic component. Our study provides an easily applicable tool for monitoring bison stress levels.


Mapping Light-Dressed Floquet Bands by Highly Nonlinear Optical Excitations and Valley Polarization.
Ultrafast nonlinear optical phenomena in solids have been attracting a great deal of interest as novel methodologies for the femtosecond spectroscopy of electron dynamics and control of the properties of materials. Here, we theoretically investigate strong-field nonlinear optical transitions in a prototypical two-dimensional material, hBN, and show that the k-resolved conduction band charge occupation patterns induced by an elliptically polarized laser can be understood in a multiphoton resonant picture, but, remarkably, only if using the Floquet light-dressed states instead of the undressed matter states. Our work demonstrates that Floquet dressing affects ultrafast charge dynamics and photoexcitation even from a single pump pulse and establishes a direct measurable signature for band dressing in nonlinear optical processes in solids, opening new paths for ultrafast spectroscopy and valley manipulation.


Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients.
Asymptomatic bacteriuria is a very common complication after kidney transplantation and the need for antibiotic therapy is controversial. The aim of this study was to evaluate the effect of antibiotic therapy on the clinical course of asymptomatic bacteriuria in renal transplant recipients. In the present study, 88 kidney transplant recipients with asymptomatic bacteriuria were divided into two groups of cases and controls. The patients had been selected from among those with at least 1 year follow-up. In the case group, asymptomatic bacteriuric episodes were treated with antibiotics, and in control group, they were followed without antibiotic therapy. The follow-up period was 9 to 12 months. Bacteriuric episodes, symptomatic urinary tract infection (UTI) episodes, and changes in plasma creatinine level were recorded and compared between the two groups. The rate of bacteriuric episodes and symptomatic UTIs were not significantly different between the two groups (P >0.05). In addition, level of plasma creatinine did not increase significantly in neither of the groups during the study (P >0.05). It seems that treatment of asymptomatic bacteriuria in kidney recipients does not decrease the rate of UTI episodes afterwards. Asymptomatic bacteriuria does not affect renal function in short term. Thus, we can abandon antibiotic therapy, subject to careful follow-up.


Knowledge to action: a challenge for neck pain treatment.
For clinicians, systematic reviews can enhance incorporation into practice of the large volumes of information emerging from research on effectiveness and risks. But we believe that these reviews are most useful with simplified tools to facilitate translation of this knowledge into practice. We provide a "Neck Care Tool Kit" that gives a diagrammatic approach to prioritizing intervention. The evidence from a series of 11 systematic reviews by the Cervical Overview Group is depicted in decision flow-charts and tables to enhance clinical interpretation of the overview findings. On simple visual inspection of symbols in a table, the reader can establish where there is evidence of benefit or no benefit, the strength of the recommendation, and if these data represent short- or long-term findings. Where possible, we guide clinicians to dosage of specific treatment methods. There is no consensus as to which outcome measures to prioritize among the large number in use. This clinical commentary guides clinicians to view the evidence in enough detail to integrate it into their clinical practice environment. We conclude by delineating research gaps and proposing future research directions. Therapy, level 5.


National Mental Health Programme-Optimism and Caution: A Narrative Review.
India was one of the major World Health Organization (WHO) member countries to launch its National Mental Health Programme (NMHP) in 1982 in accordance with WHO's recommendations to deliver mental health services to the people under the framework of general health care system in the community. NMHP underwent major strategic revisions over its course, starting from setting a district as the unit for program planning and implementation under the District Mental Health Program (DMHP) to incorporating it with the National Rural Health Mission (NRHM) for effectively scaling up the program. The program also underwent evaluations by government bodies and independent agencies and was reviewed by many researchers. The program has been partly successful in terms of enhancing its reach to community, improving service delivery, and getting increased budgetary allocation, but at the same time, its impact was limited by financial and human resource constraints, lack of community participation, ineffective training, poor NGO/private partnership, and lack of a robust monitoring and evaluation (M and E) system. The latest National Mental Health Policy and the incorporation of its objectives have given a new impetus to the ongoing NMHP, however, its implementation needs to be monitored and the impact is yet to be evaluated. We attempted to review the available literature pertaining to NMHP and DMHP to highlight the determinants of its outcome, with special emphasis on on-going programs and to provide some important future directions.


Dietary Energy Density and Postmenopausal Breast Cancer Incidence in the Cancer Prevention Study II Nutrition Cohort.
Dietary energy density (ED) is a measure of diet quality that estimates the amount of energy per unit of food (kilocalories per gram) consumed. Low-ED diets are generally high in fiber and fruits and vegetables and low in fat. Dietary ED has been positively associated with body mass index (BMI) and other risk factors for postmenopausal breast cancer. We evaluated the associations of total dietary ED and energy-dense (high-ED) foods with postmenopausal breast cancer incidence. Analyses included 56,795 postmenopausal women from the Cancer Prevention Study II Nutrition Cohort with no previous history of breast or other cancers and who provided information on diet, lifestyle, and medical history in 1999. Multivariable-adjusted breast cancer incidence rate ratios (RRs and 95% CIs) were estimated for quintiles of total dietary ED and for the consumption of high-ED foods in Cox proportional hazards regression models. During a median follow-up of 11.7 y, 2509 invasive breast cancer cases were identified, including 1857 estrogen receptor-positive and 277 estrogen receptor-negative tumors. Median dietary ED was 1.5 kcal/g (IQR: 1.3-1.7 kcal/g). After adjusting for age, race, education, reproductive characteristics, and family history, high compared with low dietary ED was associated with a statistically significantly higher risk of breast cancer (RR for fifth quintile compared with first quintile: 1.20; 95% CI: 1.05, 1.36; P-trend = 0.03). The association between the amount of high-ED foods consumed and breast cancer risk was not statistically significant. We observed no differences by estrogen receptor status or effect modification by BMI, age, or physical activity. These results suggest a modest positive association between total dietary ED and risk of postmenopausal breast cancer.


Does community-based point of care HIV testing reduce late HIV diagnosis? A retrospective study in England and Wales.
The objective of this study was to investigate if patients diagnosed in community clinics have higher baseline CD4 cell counts than those diagnosed in Genitourinary medicine (GUM)/HIV clinics. We undertook a retrospective review of baseline CD4 cell counts for patients receiving a reactive HIV test in community-testing clinics. Eleven local HIV clinics were contacted to determine the baseline CD4 cell counts of these patients. Baseline CD4 cell counts of those diagnosed in the community were compared with mean local GUM/HIV clinic and median national baseline CD4 cell count for their year of diagnosis. Clients diagnosed in community settings had a mean baseline CD4 cell count of 481 cells/mm3 (SD 236 cells/mm3) and median baseline of 483 cells/mm3 (interquartile range 311-657 cells/mm3). This was significantly higher than those diagnosed in the GUM/HIV clinic local to the community-testing site (mean baseline CD4 397 cells/mm3, p = 0.014) and the national median for that year (336 cells/mm3, p < 0.001). HIV testing in community settings identifies patients at an earlier stage of infection than testing in clinical settings.


Production of oligosaccharides in yogurt containing bifidobacteria and yogurt cultures.
Yogurts were prepared by using yogurt cultures combined to mixed cultures of bifidobacteria (Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium longum) and by adding a preincubation step (1.5 h at 50 degrees C) with bifidobacteria to the conventional method of manufacture in order to produce oligosaccharides. The survival of bifidobacteria was drastically affected during storage of yogurts, except for products containing B. animalis, in which viable counts remained at >10(6) cfu/g after 28 d of storage at 4 degrees C. Oligosaccharides with a degree of polymerization of 3 were produced during the preincubation step (0.31 to 0.68%), and the amount in the final products varied according to the species of bifidobacteria inoculated during the preincubation step or the concentration of bifidobacteria used as second inoculum during the fermentation process. In fact, the higher concentration of oligosaccharides measured at the end of the fermentation process (0.72%) and the 28 d-storage period (0.67%) was obtained for yogurts containing B. infantis. However, yogurts containing B. breve showed higher beta-galactosidase activities and had lower lactose concentrations after the fermentation process and the storage period than the other yogurts. The use of a mixed cultures of bifidobacteria (B. animalis, B. infantis, or B. breve) thus allows the production of yogurts in which bifidobacteria can survive in relatively high cell numbers and contain appreciable amount of oligosaccharides.


Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors.
Limited oxygen delivery to tissues (hypoxia) is common in a variety of disease states. A number of parallels exist between hypoxia and acute inflammation, including the observation that both influence vascular permeability. As such, we compared the functional influence of activated polymorphonuclear leukocytes (PMN) on normoxic and posthypoxic endothelial cells. Initial studies indicated that activated PMN preferentially promote endothelial barrier function in posthypoxic endothelial cells (>60% increase over normoxia). Extension of these findings identified at least one soluble mediator as extracellular adenosine triphosphate (ATP). Subsequent studies revealed that ATP is coordinately hydrolyzed to adenosine at the endothelial cell surface by hypoxia-induced CD39 and CD73 (>20-and >12-fold increase in mRNA, respectively). Studies in vitro and in cd39-null mice identified these surface ecto-enzymes as critical control points for posthypoxia-associated protection of vascular permeability. Furthermore, insight gained through microarray analysis revealed that the adenosine A2B receptor (AdoRA2B) is selectively up-regulated by hypoxia (>5-fold increase in mRNA), and that AdoRA2B antagonists effectively neutralize ATP-mediated changes in posthypoxic endothelial permeability. Taken together, these results demonstrate transcription coordination of adenine nucleotide and nucleoside signaling at the vascular interface during hypoxia.


Reverse shoulder arthroplasty for the management of proximal humerus fractures.
The use of reverse shoulder arthroplasty is becoming increasingly popular for the treatment of complex three- and four-part proximal humerus fractures in the elderly compared with the often unpredictable and poor outcomes provided by open reduction and internal fixation and by hemiarthroplasty. Inferior results with plate osteosynthesis are often a result of complications of humeral head osteonecrosis, loss of fixation, and screw penetration through the humeral head, whereas major concerns with hemiarthroplasty are tuberosity resorption, malunion, and nonunion resulting in pseudoparalysis. Comparative studies support the use of reverse shoulder arthroplasty in elderly patients with complex proximal humerus fractures because the functional outcomes and relief of pain are reliably improved. Repair and union of the greater tuberosity fragment during reverse shoulder arthroplasty demonstrates improved external rotation, clinical outcomes, and patient satisfaction compared with outcomes after tuberosity resection, nonunion, or resorption. Satisfactory results can be obtained with careful preoperative planning and attention to technical details.


Automatic Lung Cancer Subtypes Classification on CT Images with Self-generated Multi-modality Hybrid Features.
Lung cancer is a malignant tumor with rapid progression and high fatality rate. According to histological morphology and cell behaviours of cancerous tissues, lung cancer can be classified into a variety of subtypes. Since different cancer subtype corresponds to distinct therapies, the early and accurate diagnosis is critical for following treatments and prognostic managements. In clinical practice, the pathological examination is regarded as the gold standard for cancer subtypes diagnosis, while the disadvantage of invasiveness limits its extensive use, leading the non-invasive and fast-imaging computed tomography (CT) test a more commonly used modality in early cancer diagnosis. However, the diagnostic results of CT test are less accurate due to the relatively low image resolution and the atypical manifestations of cancer subtypes. In this work, we propose a novel automatic classification model to offer the assistance in accurately diagnosing the lung cancer subtypes on CT images. Inspired by the findings of cross-modality associations between CT images and their corresponding pathological images, our proposed model is developed to incorporate general histopathological information into CT imagery-based lung cancer subtypes diagnostic by omitting the invasive tissue sample collection or biopsy, and thereby augmenting the diagnostic accuracy. Experimental results on both internal evaluation datasets and external evaluation datasets demonstrate that our proposed model outputs more accurate lung cancer subtypes diagnostic predictions compared to existing CT-based state-of-the-art (SOTA) classification models, by achieving significant improvements in both accuracy (ACC) and area under the receiver operating characteristic curve (AUC).Clinical Relevance- This work provides a method for automatically classifying the lung cancer subtypes on CT images.


A case report of a patient with Ribbing disease underlines the connections between the skeletal and cardiovascular complications.
A 69-year-old woman suffered from Ribbing disease, a hereditary X autosomal dominant disease with multiple sclerosing dysplasias. However, it is less known that the genetic mutation can often induce cardiovascular complications. The patient had a hypertensive cardiopathy and had been treated with percutaneous coronary angioplasty and stenting because of a myocardial infarction. She was seen because of dyspnea and we detected an aneurysm of the ascending thoracic aorta. The patient underwent surgical repair. In Ribbing disease an up-regulation of genes interferes with the production, processing, or formation of collagen type II and XI. These genetic effects are thought to be specific for osteoblasts and are responsible for the skeletal pathology. However, the defective synthesis of collagen can also induce cardiovascular complications which may be similar to those described in patients with type III Ehlers-Danlos syndrome, with type IV Marfan syndrome, and with osteogenesis imperfecta. Rheumatologists who treat patients with Ribbing disease should seek the advice of cardiologists for the occurrence of cardiovascular complications.


Heterodyne interferometer for absolute amplitude vibration measurements with femtometer sensitivity.
A heterodyne interferometer for highly sensitive vibration measurements in the range 100 kHz - 1.3GHz is presented. The interferometer measures absolute amplitude and phase. The signal processing of the setup is analyzed and described in detail to optimize noise suppression. A noise floor of 7.1 fm/Hz(1/2) at 21 MHz was achieved experimentally where the bandwidth is the inverse of all time needed for filter settling and signal sampling. To demonstrate the interferometer, measurements up to 220 MHz were performed on arrays of capacitive micromachined ultrasonic transducers (CMUTs). The measurements provided detailed information e.g. about the frequency response, vibration patterns and array uniformity. Such measurements are highly valuable in the design process of ultrasonic transducers.


Status and trends in poisonings in Denmark 2007-2009.
The Danish Poison Information Centre (DPIC) provides information to the public and health care professionals on acute poisonings. The DPIC received 41,000 enquiries during the first three years of its existence as an open 24h telephone service. The aim of this data register study was to classify all substance exposures, to gain knowledge of the status and trends in poisonings (toxico-surveillance) and to evaluate the development in the number of contacts. Information and inquiries were continuously entered into a poison-centre database. A new classification system was established during the study to ensure that all agents were properly classified. A total of 41,139 calls were divided into 18 substance categories, each consisting of 3-11 subgroups. The number of contacts per year increased by 70% from 2007 to 2009. Three contacts per thousand individuals in the Danish population were registered in 2009. For all groups, except drugs of abuse, the data showed an increase in the actual number of exposures from 2008 to 2009. Pharmaceuticals represent one third of substance exposures, and analgesics constitute a third of these poisonings. A relative increase in contacts concerning household substances, plants and vitamins was observed. The classification gave detailed knowledge of the current poisoning status. Evaluation of subgroups showed a need for a larger number of subgroups to ensure a sufficient level of toxico-surveillance. Compared to other national poison centres, we predict a doubling in enquiries during the next ten years, mainly from the public.


Navβ subunits modulate the inhibition of Nav1.8 by the analgesic gating modifier μO-conotoxin MrVIB.
Voltage-gated sodium channels (VGSCs) consist of a pore-forming α-subunit and regulatory β-subunits. Several families of neuroactive peptides of Conus snails target VGSCs, including μO-conotoxins and μ-conotoxins. Unlike μ-conotoxins and the guanidinium alkaloid saxitoxin (STX), which are pore blockers, μO-conotoxins MrVIA and MrVIB inhibit VGSCs by modifying channel gating. μO-MrVIA/B can block Na(v)1.8 (a tetrodotoxin-resistant isoform of VGSCs) and have analgesic properties. The effect of Na(v)β-subunit coexpression on susceptibility to block by μO-MrVIA/B and STX has, until now, not been reported. Here, we show that β1-, β2-, β3-, and β4-subunits, when individually coexpressed with Na(v)1.8 in Xenopus laevis oocytes, increased the k(on) of the block produced by μO-MrVIB (by 3-, 32-, 2-, and 7-fold, respectively) and modestly decreased the apparent k(off). Strong depolarizing prepulses markedly accelerated MrVIB washout with rates dependent on β-subunit coexpression. Thus, coexpression of β-subunits with Na(v)1.8 can strongly influence the affinity of the conopeptide for the channel. This observation is of particular interest because β-subunit expression can be dynamic, e.g., β2-expression is up-regulated after nerve injury (J Neurosci, 25:10970-10980, 2005); therefore, the effectiveness of a μO-conotoxin as a channel blocker could be enhanced by the conditions that may call for its use therapeutically. In contrast to MrVIB's action, the STX-induced block of Na(v)1.8 was only marginally, if at all, affected by coexpression of any of the β-subunits. Our results raise the possibility that μO-conotoxins and perhaps other gating modifiers may provide a means to functionally assess the β-subunit composition of VGSC complexes in neurons.


Determinant factors of life expectancy at birth in the European union countries.
The main aim of this article is to explore determinants of life expectancy at birth among 28 European Union countries. Selected variables namely, gross domestic product (GDP) growth rate, population growth rate, level of education attained, education enrolment, GDP per capita and life expectancy have been considered for abovementioned countries in the period from 2001 to 2011 on a yearly basis by applying panel data analyses approach. Obtained results reveal that GDP per capita and attained education level together explain between 72.6% and 82.6% of differences in life expectancy at birth (depending on year of observation).


Noninvasive assessment of coronary plaque using multidetector row computed tomography: does MDCT accurately estimate plaque vulnerability? (Con).
As a result of the advent and advances of multidetector row computed tomography (MDCT), coronary computed tomography (CT) has become popular and is performed at many institutions. Coronary CT is useful for diagnosing cases of moderate risk of coronary artery disease. On the other hand, it has been shown that most cardiac infarctions (≍ 70%) occur from mild to moderate stenoses (ie, ≤ 50%). Thus, conventional cardiac angiographic findings alone cannot predict developing cardiac infarction. The mechanism by which ruptured plaque and subsequent thrombus leads to developing cardiac infarction has been shown, so determining which plaque tended to rupture, the so-called "vulnerable plaque", and treatment of it are in the spotlight. Coronary CT can visualize and evaluate non-invasively not only the lumen but also the arterial wall. The findings that are suspicious for vulnerable plaque on coronary CT are low-density plaque, positive remodeling, and spotty calcification. However, CT is restricted in its resolution (temporal, spatial and contrast resolution). The diagnosis of vulnerable plaque by CT is still challenging. This report demonstrates the present conditions and problems for the characterization of the plaque using coronary CT.


Avoiding sexually transmitted diseases.
As the spectrum of sexually transmitted diseases (STDs) has broadened to include many infections that are not readily cured, prevention of STDs has become more important than ever. Primary prevention methods include abstinence, careful selection of sexual partners, condoms, vaginal spermicides, and a vaccine for hepatitis B. Condoms will protect against STDs only if they are used consistently and correctly; vaginal spermicides may also reduce risk of certain STDs. Health care providers should routinely counsel women on methods to reduce risk of STDs.


Etorphine binds to multiple opiate receptors of the caudate nucleus with equal affinity but with different kinetics.
The binding of [3H]etorphine, a potent opiate agonist of the oripavine series, to membranes derived from sheep brain caudate nucleus is analyzed. Although the receptors are saturated by [3H]etorphine in a homogeneous fashion with an apparent dissociation constant of 1.16 +/- 0.3 nM, kinetic displacement studies reveal that at least two classes of sites are involved. All of the specific sites for [3H]etorphine are blocked by morphine or naloxone if these ligands are added prior to, or simultaneously with [3H]etorphine. Otherwise, when [3H]etorphine is added prior to morphine or naloxone, only one-third of the specific binding can be effectively displaced. The difference in the displacement patterns between the two classes of sites can be accounted for by the kinetics of the interaction between [3H]etorphine and the receptors. At 37 degrees [3H]etorphine dissociates from one-third of the sites with a half-life of 2.3 min and from the remaining sites with a half-life of 70 min. The sites which release [3H]etorphine slowly have a 10-fold higher apparent affinity for morphine and for naloxone as compared with the more rapidly reversible sites. The binding data are only partially compatible with a model which involves two independent classes of sites. The possibility of identifying the site from which [3H]etorphine dissociates slowly with millimicron, delta, or kappa opiate receptors is explored in light of the fact that [3H]etorphine is a mixture of D- and L-stereoisomers.


The changing epidemiology of hepatitis B in Greece.
The epidemiology of hepatitis B virus (HBV) infection has changed in recent years as a result of various factors. Our aim was to assess the epidemiological characteristics and the evolution of the HBV infection in a well-defined area of Greece. Prospectively collected data from 1910 consecutive patients (60.8% male, age: 50.1 years) with chronic hepatitis B (CHB) followed from 1999-2016 were analyzed. Of the patients evaluated, 90.6% were of Greek and 8% of Albanian origin. Vertical/intrafamilial transmission during early childhood (56.8%) and traditional practices (17.2%) were the most common infection sources. Several areas with higher rates of CHB were identified. At first evaluation, 68.8% had chronic infection, 21.7% chronic hepatitis, 6.1% cirrhosis and 3.4% hepatocellular carcinoma (HCC). Comparison between 2 periods (1999-2010 and 2011-2016) revealed older age and longer disease duration at first presentation (P<0.001 for both) to be more common during 2011-2016, while patients of foreign nationality doubled during this period. There was a trend towards more advanced disease stage at first assessment during 2011-2016. Patients after 2011 had lower rates of virological and biochemical breakthrough (P<0.001 for both) during treatment with new antivirals. In addition, fewer patients progressed to cirrhosis (P=0.02) and HCC (P=0.04). CHB continues to be a major health problem in Central Greece, as highlighted by the preservation of high prevalence areas and a tendency towards an increase of chronic liver disease burden longitudinally. Our data highlight the need for scaling-up prevention and treatment strategies, especially in at-risk populations.


Histone acetyltransferase CBP is critical for conventional effector and memory T-cell differentiation in mice.
Compared with naïve T cells, memory CD8+ T cells have a transcriptional landscape and proteome that are optimized to generate a more rapid and robust response to secondary infection. Additionally, rewired kinase signal transduction pathways likely contribute to the superior recall response of memory CD8+ T cells, but this idea has not been experimentally confirmed. Herein, we utilized an MS approach to identify proteins that are phosphorylated on tyrosine residues in response to Listeria-induced T-cell receptor (TCR) stimulation in both naïve and memory CD8+ T cells from mice and separated by fluorescence- and flow cytometry-based cell sorting. This analysis identified substantial differences in tyrosine kinase signaling networks between naïve and memory CD8+ T cells. We also observed that an important axis in memory CD8+ T cells couples Janus kinase 2 (JAK2) hyperactivation to the phosphorylation of CREB-binding protein (CBP). Functionally, JAK2-catalyzed phosphorylation enabled CBP to bind with higher affinity to acetylated histone peptides, indicating a potential epigenetic mechanism that could contribute to rapid initiation of transcriptional programs in memory CD8+ T cells. Moreover, we found that CBP itself is essential for conventional effector and memory CD8+ T-cell formation. These results indicate how signaling pathways are altered to promote CD8+ memory cell formation and rapid responses to and protection from repeat infections.


Rare Extracardiac Anomalies Presented with Right Heterotaxy Syndrome in a Newborn Baby: A Case Report.
BACKGROUND Heterotaxy is a syndrome of abnormal arrangement of the internal thoracic-abdominal structures across the left-right axis of the body. It is a primary disorder with 2 main settings - bilateral left sidedness (polysplenia syndrome) or right sidedness (asplenia syndrome) - although some overlapping or uncertainties may occur. Patients with right heterotaxy typically present with asplenia, complex heart disease, and other thoracoabdominal organ situs abnormalities. CASE REPORT We present a unique case of congenital asplenia syndrome with complex heart disease, annular pancreas, and other extra-heterotaxic anomalies (e.g., musculoskeletal) in the form of a radius aplasia and partial syndactyly of the thumb and index finger of the left hand. These associated anomalies have not been reported before. CONCLUSIONS This case shows the need for paying increased attention to the implications of other extracardiac anomalies that can be associated with heterotaxy syndrome.


Testicular Cancer, Version 2.2015.
Germ cell tumors (GCTs) account for 95% of testicular cancers. Testicular GCTs constitute the most common solid tumor in men between the ages of 20 and 34 years, and the incidence of testicular GCTs has been increasing in the past 2 decades. Testicular GCTs are classified into 2 broad groups--pure seminoma and nonseminoma--which are treated differently. Pure seminomas, unlike nonseminomas, are more likely to be localized to the testis at presentation. Nonseminoma is the more clinically aggressive tumor associated with elevated serum concentrations of alphafetoprotein (AFP). The diagnosis of a seminoma is restricted to pure seminoma histology and a normal serum concentration of AFP. When both seminoma and elements of a nonseminoma are present, management follows that for a nonseminoma. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Testicular Cancer outline the diagnosis, workup, risk assessment, treatment, and follow-up schedules for patients with both pure seminoma and nonseminoma.


Tissue factor regulates plasminogen binding and activation.
Tissue factor (TF) has been implicated in several important biologic processes, including fibrin formation, atherogenesis, angiogenesis, and tumor cell migration. In that plasminogen activators have been implicated in the same processes, the potential for interactions between TF and the plasminogen activator system was examined. Plasminogen was found to bind directly to the extracellular domain of TF apoprotein (amino acids 1-219) as determined by optical biosensor interaction analysis. A fragment of plasminogen containing kringles 1 through 3 also bound to TF apoprotein, whereas isolated kringle 4 and miniplasminogen did not. Expression of TF on the surface of a stably transfected Chinese hamster ovary (CHO) cell line stimulated plasminogen binding to the cells by 70% more than to control cells. Plasminogen bound to a site on the TF apoprotein that appears to be distinct from the binding site for factors VII and VIIa as judged by a combination of biosensor and cell assays. TF enhanced two-chain urokinase (tcuPA) activation of Glu-plasminogen, but not of miniplasminogen, in a dose-dependent, saturable manner (half maximal stimulation at 59 pmol/L). TF apoprotein induced an effect similar to that of relipidated TF, but a relatively higher concentration of the apoprotein was required (half maximal stimulation at 3.8 nmol/L). The stimulatory effect of TF on plasminogen activation was confirmed when plasmin formation was examined directly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In accord with this, TF inhibited fibrinolysis by approximately 74% at a concentration of 14 nmol/L and almost totally inhibited the binding of equimolar concentrations of plasminogen to human umbilical vein endothelial cells and human trophoblasts. Further, CHO cells expressing TF inhibited uPA-mediated fibrinolysis relative to a wild-type control. TF apoprotein and plasminogen were found to colocalize in atherosclerotic plaque. These data suggest that plasminogen localization and activation may be modulated at extravascular sites through a high-affinity interaction between kringles 1 through 3 of plasminogen and the extracellular domain of TF.


[Challenges and advances in the care of injuries in the Republic of Serbia].
There are many problems that trauma care system in Serbia is facing today. Few of them are: 1) Lack of categorization of trauma centers; 2) Diversity in managing of trauma patients among institutions; 3) There is no trauma management training, 4) Inappropriate cooperation between pre hospital trauma care and hospital trauma care; 5) There is no standard in managing of trauma patients as well as procedures. To improve trauma care quality throughout the country we must learn from the experiences of other countries. The aim of this paper was to report representative data about organization, management, stuff and equipment of ambulance and emergency services in Serbia. We analyzed 12 out of 138 parameters we obtained from the relevant institutions.


Cardiac involvement in adult polymyositis or dermatomyositis: a systematic review.
To investigate the clinical features of cardiac involvement in polymyositis (PM) or dermatomyositis (DM). More attention will be focused on the heart in PM/DM as we would have wished, which contribute to improve the prognosis. All articles published in English were retrieved by searching MEDLINE via PubMed (1975-2011). After selecting eligible articles according to the predefined inclusion and exclusion criteria, a systemic review was carried out. A total of 26 articles were included in this study, which included 1530 patients. The incidence of cardiac involvement was 9% to 72%. Heart failure was the most frequent (32% to 77%) clinical symptom. Among the abnormal electrocardiogram and ultrasonic cardiogram, the incidence of conduction abnormalities, left ventricular diastolic dysfunction, and hyperkinetic left ventricular contraction were 25% to 38.5%, 42%, and 6% to 12%, respectively. The pathologic findings revealed myocardial inflammation, degenerative changes and necrosis similar to that in skeletal muscles. Cardiac manifestations of some patients improved after glucocorticoid and immunosuppressant treatment. Thirty-seven patients (46.3%) died as a direct result of heart disease. Heart abnormalities are frequent in patients with PM/DM, most of which were subclinical. The efficacy of glucocorticoids and immunosuppressants is uncertain. Cardiac involvement is a common cause of death.


Buccal fat pad versus sandwich graft for treatment of oroantral defects: A comparison.
To compare the efficacy of buccal fat pad (BFP) graft with sandwich graft (hydroxyapatite crystals embedded within collagen sheath) in closure of oroantral defects. A 2-year prospective study was conducted; 20 patients were included in the study were divided into two groups having 10 patients in each. Group I patients underwent surgical closure of oroantral fistula with sandwich graft and Group II patients with buccal pad of fat. In Group I, the mean pain scores were 7.60 ± 0.84, 3.90 ± 1.10, 2.30 ± 1.16, 1.10 ± 0.99 and 0.40 ± 0.70 at immediate post-op., 1, 3, 6 and 12 week time intervals, respectively, whereas in Group II these were 7.30 ± 0.67, 3.50 ± 0.53, 1.70 ± 0.48, 1.00 ± 0.47 and 0.30 ± 0.48, respectively, at the corresponding time intervals. In Group I, swelling was seen to be present in 10 (100%), 7 (70%), 2 (20%) and nil (0%) patients at 1, 3, 6 and 12 weeks, respectively, whereas in Group II, it was seen to be present in 10 (100%), 10 (100%), 2 (20%) and nil (0%) patients at the corresponding time intervals. At 1 week, infection was seen to be present in 1 (10%) patient of Group I and 2 (20%) patients of Group II. At 3 and 6 weeks, infection was seen to be present in 1 (10%) patient of Group I and none of the patients of group II. No radiologic evidence of bone formation was seen in either group up to 1 week. At 3 week interval, there were 6 (60%) patients in Group I and nil (0%) in Group II showing bone formation, thus showing a statistically significant difference between the two groups. By 6 week time interval, radiologic evidence of bone formation was seen in 9 (90%) patients of Group I but in no patients of Group II, thereby showing a statistically very highly significant (P < 0.001) difference between the two groups. In Group I, in 1 (10%) patient, graft was rejected by first week; however, no further graft rejection took place. In Group II, no case of graft rejection was reported. The sandwich graft technique yielded a more promising closure of oroantral communication by provision of a more biologically apt base in terms of regeneration of lost bone structure at the floor of the maxillary sinus.


Electrophysiological study of the rectosigmoid canal: evidence of a rectosigmoid sphincter.
Previous studies strongly suggest the presence of a sphincter at the rectosigmoid junction, an area with a mean length of 2.8 cm in adults, called the rectosigmoid canal (RSC). To find supporting evidence of a sphincteric function for the RSC, two recording electrodes were applied to each of the sigmoid colon (SC), RSC and rectum (R) in 11 subjects during operative repair of huge incisional hernias. The RSC, SC and R were individually stimulated by a further electrode and their pressures monitored by a three-channel microtip catheter. The variables of the slow waves or pacesetter potentials, recorded at rest from the RSC and R, were significantly higher than those of the SC. While the frequency and conduction velocity of pacesetter potentials of the RSC and R were similar, the potential pacesetter amplitude of the RSC was significantly higher. The increase of the electrical activity and pressure upon electrostimulation was significantly greater in the RSC than that of the SC or R. Electrostimulation led to an increase in pressure of all three areas, the RSC increase being significantly the greatest. The greater increase of the electrical activity and pressure of the rectosigmoid canal upon electrostimulation, compared to that of the SC or R, strongly supports the presence of a rectosigmoid sphincter.


Guillain-Barré Syndrome and multiple lacunar infarcts in a COVID-19 patient.
Hyperactivity immune responses to coronavirus disease 2019 (COVID-19) can lead to several manifestations in the human organ. One of the most affected organs is the respiratory system. Not only does it affect the respiratory system, but hyperactivity can also affect the neuromuscular and cerebrovascular systems, though it is scarce for both systems to be affected simultaneously. We presented a mild COVID-19 patient with a history of progressive general weakness and dysphagia on day seventh day after patient was first diagnosed with COVID-19, which continued with diplopia and shortness of breath. The patient experienced respiratory failure type 1 and was admitted to an intensive care unit. A head CT scan showed multiple lacunar infarcts in the nucleus lentiform, while the electromyography (EMG) showed Guillain-Barré syndrome (GBS) with the subtype acute inflammatory demyelinating polyneuropathy (AIDP). The patient was reported to have successful therapy with intravenous immunoglobulin (IVIG) for five days and physical rehabilitation for three months. General weakness disappeared after the therapy, and the patient could do regular daily activities. Various neurological symptoms can manifest in COVID-19 patients. Acute progressive muscle weakness should be considered as an autoimmune and cerebrovascular disease induced by COVID-19. Early diagnosis and treatment can provide a better outcome for the patient.


Factors Associated With the Increasing Rates of Discharges Directly Home From Intensive Care Units-A Direct From ICU Sent Home Study.
To evaluate the relationship between rates of discharge directly to home (DDH) from the intensive care unit (ICU) and bed availability (ward and ICU). Also to identify patient characteristics that make them candidates for safe DDH and describe transfer delay impact on length of stay (LOS). Retrospective cohort study of all adult patients who survived their stay in our medical-surgical-trauma ICU between April 2003 and March 2015. Median age was 49 years (interquartile range [IQR]: 33.5-60.4), and the majority of the patients were males (54.8%). Median number of preexisting comorbidities was 5 (IQR: 2-7) diagnoses. Discharge directly to home increased from 28 (3.1% of all survivors) patients in 2003 to 120 (12.5%) patients in 2014. The mean annual rate of DDH was between 11% and 12% over the last 6 years. Approximately 62% (n = 397) of patients waited longer than 4 hours for a ward bed, with a median delay of 2.0 days (IQR: 0.5-4.7) before being DDH. There was an inverse correlation between ICU occupancy and DDH rates ( rP = -.55, P < .0001, 95% confidence interval [CI] = -0.36 to -0.69, R2 = .29). There was no correlation with ward occupancy and DDH rates ( rs = -.055, P = .64, 95% CI = -0.25 to 0.21). The DDH rates have been increasing over time at our institution and were inversely correlated with ICU bed occupancy but were not associated with ward occupancy. The DDH patients are young, have few comorbidities on admission, and few discharge diagnoses, which are usually reversible single system problems with low disease burden. Transfers to the ward are delayed in a majority of cases, leading to increased ICU LOS and likely increased overall hospital LOS as well.


Is there an association between the use of heeled footwear and schizophrenia?
Existing etiological and pathogenetical theories of schizophrenia have only been able to find support in some epidemiological, clinical, and pathophysiological facts. A selective literature review and synthesis is used to present a hypothesis that finds support in all facts and is contradicted by none. Heeled footwear began to be used more than a 1000 years ago, and led to the occurrence of the first cases of schizophrenia. Industrialization of shoe production increased schizophrenia prevalence. Mechanization of the production started in Massachusetts, spread from there to England and Germany, and then to the rest of Western Europe. A remarkable increase in schizophrenia prevalence followed the same pattern. In Baden in Germany the increasing stream of young patients more or less hastily progrediating to a severe state of cognitive impairment made it possible for Kraepelin to delineate dementia praecox as a nosological entity. The patients continued to use heeled shoes after they were admitted to the hospitals and the disease progrediated. High rates of schizophrenia are found among first-generation immigrants from regions with a warmer climate to regions with a colder climate, where the use of shoes is more common. Still higher rates among second-generation immigrants are caused by the use of shoes during the onset of walking at an age of about 11-12 months. Other findings point to the importance of this in the later development of schizophrenia. A child born in January-March begins to walk in December-March, when it's cold outside and the chances of going barefoot are smaller. They are also smaller in urban settings. During walking synchronised stimuli from mechanoreceptors in the lower extremities increase activity in cerebello-thalamo-cortico-cerebellar loops through their action on NMDA-receptors. Using heeled shoes leads to weaker stimulation of the loops. Reduced cortical activity changes dopaminergic function which involves the basal ganglia-thalamo-cortical-nigro-basal ganglia loops. Bicycle riding reduces depression in schizophrenia due to stronger stimulation by improved lengthening contractions of the triceps surae muscles. Electrode stimulation of cerebellar loops normally stimulated by mechanoreceptors in the lower extremities could improve functioning in schizophrenia. Cross-sectional prevalence studies of the association between the use of heeled footwear and schizophrenia should be made in immigrants from regions with a warmer climate or in groups of people who began to wear shoes at different ages.


Programmed cell death in rat intestine: effect of feeding and fasting.
The regulation of intestinal cell death by luminal factors is poorly understood. The objectives of this study were to determine whether a diurnal rhythm of intestinal apoptosis exists, and to determine the role that feeding and fasting play in this process. Mucosal apoptotic death was measured in fed and 24-h fasted rats and at various times after feeding by DNA fragmentation and in situ immunohistochemical staining (TUNEL). In 24-h fasted rats, 32% of total mucosal DNA was fragmented as compared to 9% in fed animals. In both jejunal and ileal segments, the fragmented DNA exhibited characteristic apoptotic DNA ladders on agarose gels. Immunohistochemical staining revealed significant location of apoptotic cells at the upper third of the intestinal villus. In the duodenum, DNA fragmentation at 6-12 h post feeding was 20% and decreased to 4% at 24 h. In comparison, DNA fragmentation in the jejunum and ileum was low from 0 to 6 h post feeding (2%-9%) and significantly increased at 12 h (18% versus 12%) and 24 h (30% versus 32%), respectively. These results are consistent with a temporal relationship between percent fragmented DNA and time after feeding with greater cell death at longer fasting period. A postprandial rhythm of DNA fragmentation was evident in the jejunum and ileum, in which fragmentation was at a peak between 0900 h and 1200 h. Collectively, the data show that initiation of apoptosis in apical enterocytes is coincident with cessation of feeding and commencement of fasting, and is consistent with a rhythm of programmed cell death in these cells that parallels the cyclical pattern of feeding and fasting.


Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally streptozotocin-diabetic rats.
The effects of nutrient and neurotransmitter stimuli on insulin release, loss of phosphoinositides (PI), and production of inositol phosphates (InsP) were investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished. Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP accumulation were both reduced. D-Glucose was unable to increase the levels of both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3. Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed. Thus a disturbed coupling between nutrient recognition and activation of phospholipase C, possibly together with a shortage of available polyphosphoinositides, could be responsible for the altered islet PI turnover in the nSTZ rats. It is proposed that such defects may contribute to the impairment of glucose-stimulated insulin secretion in this model of non-insulin-dependent diabetes mellitus.


Arteriosclerosis in normal and von Willebrand pigs: long-term prospective study and aortic transplantation study.
In a long-term prospective study, five normal control pigs and five pigs with homozygous von Willebrand's disease received a nonfatty diet from age 3 months to 4 years; then the aortas were analyzed. The fibrous arteriosclerotic plaques in the distal abdominal aortic region involved an average of 28% of the surface area in control pigs and only 7% of the surface area in pigs with von Willebrand's disease (P less than 0.01). In a subsequent study of 3-month-old pigs, the distal abdominal aortic segments from nine normal pigs were cross-transplanted with segments from nine other normal pigs (control study), and aortic segments from four normal pigs were transplanted into four host pigs with von Willebrand's disease (exchange study). All pigs received a 2% cholesterol diet for up to 6 months; then the transplanted aortic segments were analyzed. The donor normal aortic segments in the host normal pigs developed arteriosclerosis that involved an average of 20% of the surface; the endothelial fluorescent pattern of von Willebrand factor was identified. In contrast, the donor normal aortic segments in the host pigs with von Willebrand's disease had arteriosclerosis that involved an average of only 4% of the surface (P less than 0.01); the endothelial cell von Willebrand factor was not identified. The long-term prospective study indicates that pigs with von Willebrand's disease are resistant to the development of spontaneous arteriosclerosis. The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis.


Anticoagulants in cerebrovascular disease. A critical review of studies.
Anticoagulant therapy in the treatment of cerebral thromboembolism remains controversial despite 20 years of statistical studies. Among the unresolved questions are (1) the relative value of aspirin vs coumarin derivatives for long-term therapy; (2) the relative benefits of long-term therapy vs short-term therapy; (3) the complications of anticoagulant therapy vs their therapeutic benefits; and (4) the optimal therapy of the various types of cerebral thromboembolic events, eg, transient ischemic attacks, strokes in evolution, and completed strokes. Much of this controversy derives from the same problems that have plagued the question of anticoagulation for acute myocardial infarction, namely that "the existing statistics were obtained without adequate attention to fundamental principles of clinical science". We have examined the available clinical studies bearing on this issue and are reporting our analysis of these studies.


Survival of methicillin-resistant Staphylococcus aureus during thermal processing of frankfurters, summer sausage, and ham.
Infections from antibiotic-resistant bacteria are a major concern for human health professionals around the world. Methicillin-resistant Staphylococcus aureus (MRSA) is just one of the resistant organisms of concern. MRSA prevalence has also been recently reported in retail meat products at rates higher than originally thought. Although the risk of contracting an infection from handling contaminated meat products is thought to be low, very little is known about this organism from a food safety perspective. The objective of this study was to determine the survival of MRSA during thermal processing of frankfurters, summer sausage, and boneless ham. Frankfurters, summer sausage, and boneless ham were manufactured using formulations and processing procedures developed at the Iowa State University meat laboratory. Thermal processing resulted in a significant log reduction (p<0.05) for boneless ham, summer sausage, and frankfurters when compared to uncooked, positive controls for each of the three processed meat products. All products were thermally processed to an internal temperature of 70°C and promptly cooled to 7.2°C. Boneless ham showed the highest log reduction (7.28 logs) from cooking, followed by summer sausage (6.75 logs) and frankfurters (5.53 logs). The results of this study indicate that thermal processing of ham, summer sausage, and frankfurters to 70°C is sufficient to reduce the risk of MRSA as a potential food safety hazard.


Testing for drugs of abuse in children and adolescents: addendum--testing in schools and at home.
The American Academy of Pediatrics continues to believe that adolescents should not be drug tested without their knowledge and consent. Recent US Supreme Court decisions and market forces have resulted in recommendations for drug testing of adolescents at school and products for parents to use to test adolescents at home. The American Academy of Pediatrics has strong reservations about testing adolescents at school or at home and believes that more research is needed on both safety and efficacy before school-based testing programs are implemented. The American Academy of Pediatrics also believes that more adolescent-specific substance abuse treatment resources are needed to ensure that testing leads to early rehabilitation rather than to punitive measures only.


Ultrasonic assisted liposuction.
Ultrasonic assisted liposuction is a new and highly advanced technology that uses sound waves to emulsify body fat thereby allowing an efficient removal compared with the mechanical disruption of fat used in traditional liposuction. Safe application requires an exceptionally sophisticated plastic surgical, anesthetic, and operating room team. The media bombards patients with "magic wand" medical technology but seems less inclined to portray limitations, complications, and deaths. As with any emerging technology, ultrasonic assisted liposuction is producing its share of problems. This article provides an overview of this procedure and guidelines for patient selection. A conservative approach is emphasized for safety.


Activation of transcription factor circuity in 2i-induced ground state pluripotency is independent of repressive global epigenetic landscapes.
Mouse embryonic stem cells (mESCs) cultured with MEK/ERK and GSK3β (2i) inhibitors transition to ground state pluripotency. Gene expression changes, redistribution of histone H3K27me3 profiles and global DNA hypomethylation are hallmarks of 2i exposure, but it is unclear whether epigenetic alterations are required to achieve and maintain ground state or occur as an outcome of 2i signal induced changes. Here we show that ESCs with three epitypes, WT, constitutively methylated, or hypomethylated, all undergo comparable morphological, protein expression and transcriptome changes independently of global alterations of DNA methylation levels or changes in H3K27me3 profiles. Dazl and Fkbp6 expression are induced by 2i in all three epitypes, despite exhibiting hypermethylated promoters in constitutively methylated ESCs. We identify a number of activated gene promoters that undergo 2i dependent loss of H3K27me3 in all three epitypes, however genetic and pharmaceutical inhibition experiments show that H3K27me3 is not required for their silencing in non-2i conditions. By separating and defining their contributions, our data suggest that repressive epigenetic systems play minor roles in mESC self-renewal and naïve ground state establishment by core sets of dominant pluripotency associated transcription factor networks, which operate independently from these epigenetic processes.


[Detection of HTLV-I viral antibodies in donor blood samples].
Sera from 867 donors were tested for antibodies to the virus of T-lymphocyte leukemia of adults (HTLV-I) in parallel by indirect immunofluorescence on acetone-fixed cells of HUT-102 culture producing HTLV-I and by agglutination test using a commercial set ("Serodia-ATLA", Japan). Twelve (1.38%) out of 867 sera were positive in the agglutination test and only 7 of them in immunofluorescence test. The specificity of the results was verified by absorption experiments. The activity of the sera in the agglutination test disappeared completely after their absorption with HUT-102 culture cells but did not change after absorption with LLU cells producing no HTLV-I despite a low percent of virus infection, donor blood control for HTLV-I infection becomes mandatory.


Multidisciplinary education ensures successful formulary conversion.
Anticipating and preparing for objections to formulary changes is essential to the success of policies set by Pharmacy & Therapeutics Committees. At the University of Kentucky Medical Center, a 461-bed teaching hospital, an intensive educational plan was under way well before the hospital converted from ranitidine to cimetidine as the preferred formulary H2-receptor antagonist.


Simple laser transmitter pair as polarization-independent coherent homodyne detector.
Coherent optical reception promises performance gains for a wide range of telecom applications and photonic sensing. However, the practical implementation and the particular realization of homodyne detection is by no means straight-forward. Local oscillator requirements and polarization management need to be cost-effectively supported for accurate signal detection at high sensitivity, preferably without relying on digital processing resources. Towards this direction we propose a conceptually simple, laser-based homodyne receiver. We exploit the injection locking of a pair of externally modulated lasers that simultaneously serve as optically synchronized local oscillators and photodetectors in a polarization-diversity analogue coherent receiver arrangement. We demonstrate signal detection at 2.5 Gb/s over an optical budget of 35 dB and a dynamic range of >20 dB. Long-term measurements over field-installed fiber confirm the correct operation independent of the polarization state of light. Stability considerations for the injection locking process are drawn in view of even higher loss budgets.


Attenuation of acute lung injury in transgenic mice expressing human transforming growth factor-alpha.
Transforming growth factor-alpha (TGF-alpha) is produced in the lung in experimental and human lung diseases; however, its physiological actions after lung injury are not understood. To determine the influence of TGF-alpha on acute lung injury, transgenic mouse lines expressing differing levels of human TGF-alpha in distal pulmonary epithelial cells under control of the surfactant protein C gene promoter were generated. TGF-alpha transgenic and nontransgenic control mice were exposed to polytetrafluoroethylene (PTFE; Teflon) fumes to induce acute lung injury. Length of survival of four separate TGF-alpha transgenic mouse lines was significantly longer than that of nontransgenic control mice, and survival correlated with the levels of TGF-alpha expression in the lung. The transgenic line expressing the highest level of TGF-alpha (line 28) and nontransgenic control mice were then compared at time intervals of 2, 4, and 6 h of PTFE exposure for differences in pulmonary function, lung histology, bronchoalveolar lavage fluid protein and cell differential, and lung homogenate proinflammatory cytokines. Line 28 TGF-alpha transgenic mice demonstrated reduced histological changes, decreased bronchoalveolar lavage fluid total protein and neutrophils, and delayed alterations in pulmonary function measures of airway obstruction compared with those in nontransgenic control mice. Both line 28 and nontransgenic control mice had similar increases in interleukin-1beta protein levels in lung homogenates. In contrast, interleukin-6 and macrophage inflammatory protein-2 levels were significantly reduced in line 28 transgenic mice compared with those in nontransgenic control mice. In the transgenic mouse model, TGF-alpha protects against PTFE-induced acute lung injury, at least in part, by attenuating the inflammatory response.


Motor-free mitochondrial presequence translocase drives membrane integration of preproteins.
The mitochondrial inner membrane is the central energy-converting membrane of eukaryotic cells. The electrochemical proton gradient generated by the respiratory chain drives the ATP synthase. To maintain this proton-motive force, the inner membrane forms a tight barrier and strictly controls the translocation of ions. However, the major preprotein transport machinery of the inner membrane, termed the presequence translocase, translocates polypeptide chains into or across the membrane. Different views exist of the molecular mechanism of the translocase, in particular of the coupling with the import motor of the matrix. We have reconstituted preprotein transport into the mitochondrial inner membrane by incorporating the purified presequence translocase into cardiolipin-containing liposomes. We show that the motor-free form of the presequence translocase integrates preproteins into the membrane. The reconstituted presequence translocase responds to targeting peptides and mediates voltage-driven preprotein translocation, lateral release and insertion into the lipid phase. Thus, the minimal system for preprotein integration into the mitochondrial inner membrane is the presequence translocase, a cardiolipin-rich membrane and a membrane potential.


Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.
Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 μg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 μg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.


Low-frequency modes of peptides and globular proteins in solution observed by ultrafast OHD-RIKES spectroscopy.
The low-frequency (1-200 cm(-1)) vibrational spectra of peptides and proteins in solution have been investigated with ultrafast optical heterodyne-detected Raman-induced Kerr-effect spectroscopy (OHD-RIKES). Spectra have been obtained for di-L-alanine (ALA(2)) and the alpha-helical peptide poly-L-alanine (PLA) in dichloroacetic acid solution. The poly-L-alanine spectrum shows extra amplitude compared to the di-L-alanine spectrum, which can be explained by the secondary structure of the former. The globular proteins lysozyme, alpha-lactalbumin, pepsin, and beta-lactoglobulin in aqueous solution have been studied to determine the possible influence of secondary or tertiary structure on the low-frequency spectra. The spectra of the globular proteins have been analyzed in terms of three nondiffusive Brownian oscillators. The lowest frequency oscillator corresponds to the so-called Boson peak observed in inelastic neutron scattering (INS). The remaining two oscillators are not observed in inelastic neutron scattering, do therefore not involve significant motion of hydrogen atoms, and may be associated with delocalized backbone torsions.


Echinoderm phylogeny including Xyloplax, a progenetic asteroid.
Reconstruction of the phylogeny of the five extant classes of the phylum Echinodermata has proven difficult. Results concerning higher-level taxonomic relationships among echinoderms are sensitive to the choice of analytical parameters and methods. Moreover, the proposal of a putative sixth class based on a small enigmatic disc-shaped echinoderm, Xyloplax, from the deep seas of the Bahamas and New Zealand in the 1980s further complicated the problem. Although clearly an echinoderm, Xyloplax did not have clear affinity among known groups. Using molecular sequence and developmental data from recently collected Xyloplax adults and embryos, we show that rather than representing an ancient distinct lineage as implied by its status as a class, Xyloplax is simply a starfish that is closely related to the asteroid family Pterasteridae. Many members of the Pterasteridae and all Xyloplax inhabit deep or polar seas and brood young. Brooding pterasterids and Xyloplax hold their young in specialized adult chambers until the young reach an advanced juvenile stage after which they are released as free-living individuals. We hypothesize that the unique morphology of Xyloplax evolved via progenesis--the truncation of somatic growth at a juvenile body plan but with gonadal growth to maturity. Although the overall phylogeny of extant echinoderms remains sensitive to the choice of analytical methods, the placement of Xyloplax as sister to pterasterid asteroids is unequivocal. Based on this, we argue that the proposed class and infraclass status of Xyloplax should be suppressed.


Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs.
Multidrug resistance MDR proteins (MRPs) are members of the C family of a group of proteins named ATP binding cassette (ABC) transporters. MRPs can transport drugs including anticancer drugs, nucleoside analogs, antimetabolites and tyrosine kinase inhibitors. Drugs used in HCC therapy, such as tyrosine kinase inhibitor sorafenib, are substrates of uptake and/or efflux transporters. Variable expression of MRPs at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. Recently, we reported that the hepatocyte SLAMF3 expression (Signaling Lymphocytic Activation Molecule Family member 3) was reduced in tumor cells from hepatocellular carcinoma (HCC) compared to its high expression in adjacent tissues. In the present study, we make a strong correlation between induced SLAMF3 overexpression and the specific loss of MRP-1 expression and its functionalities as a drugs resistance transporter. No changes were observed on expression of ABCG2 and MDR. More importantly, we highlight a strong inverse correlation between MRP-1 and SLAMF3 expression in patients with HCC. We propose that the SLAMF3 overexpression in cancerous cells could represent a potential therapeutic strategy to improve the drugs sensibility of resistant cells and thus control the therapeutic failure in HCC patients.


Deletion of naive CD8 T cells requires persistent antigen and is not programmed by an initial signal from the tolerogenic APC.
Activation of naive CD8 T cells in vivo requires the recognition of cognate peptide-MHC complexes on APCs. Depending upon the activation status of the APC, such recognition will promote either a vigorous immune response or T cell tolerance and deletion. Recent studies suggest that the initial signals provided by APCs are sufficient to program the proliferation of naive CD8 T cells and their differentiation into effector cells. In this study, we sought to determine whether an initial encounter with tolerogenic APCs was sufficient to program deletion of naive CD8 T cells. Surprisingly, we find that regardless of whether naive CD8 T cells were stimulated by activated or quiescent APCs, transfer of the activated T cells into an Ag-free host was sufficient to ensure survival. Thus, although the extent of clonal expansion and development of effector function is determined by the activation status of the stimulatory APC, peripheral clonal deletion requires persistent Ag and is not determined by the initial stimulatory event.


HIV prevention is not all about HIV - using a discrete choice experiment among women to model how the uptake and effectiveness of HIV prevention products may also rely on pregnancy and STI protection.
In sub-Saharan Africa, considerable HIV-burden exists among women. Anti-retroviral (ARV) based prevention products could decrease this burden, and their uptake could be increased if they also protect against pregnancy and sexually transmitted infections (STI). A discrete choice experiment (DCE) was undertaken in South Africa (2015) through a household survey of adult females (n = 158) and adolescent girls (n = 204) who self-reported HIV-negative status. The DCE was used to project the uptake (percentage using product) of oral pre-exposure prophylaxis (PrEP), vaginal rings, and injectable long-lasting ARV agents among these women, and how uptake could depend on whether these products protect against pregnancy or STI acquisition. Uptake estimates were used to model how each product could decrease a women's HIV acquisition risk. In adolescent women, there will be limited uptake (< 6% for any product) and impact (< 4% decrease in HIV acquisition risk) of new products unless they provide pregnancy protection, which could quadruple use and impact. Adult women have weaker preference for pregnancy protection, with moderate use (< 17% for each) and impact (< 14 percentage point decrease) if they only provide HIV protection. All women had highest preference for injectable ARVs, with oral PrEP having high preference if injectable ARVs are not available. Adult women will use the ring, but adolescent women will not. Importantly, even with three additional prevention products, all providing pregnancy and STI protection, > 14% of women will remain unprotected and > 31% of the baseline acquisition risk will remain. Incorporating multiple prevention components into new ARV-based prevention products may increase their uptake and impact among women.


Violently reactive women and their relationship with an abusive mother.
This article sheds light on the abuse of mothers toward their daughters and its potential influence on the violent behavior of the latter as adults. It contributes to the scarce knowledge on the effects of abuse of each parent on their children by gender. The article is part of a larger study describing the experience of 30 women in Israel who were abusive or violent toward their male partners. It presents the stories of 14 women from the sample who, when sharing their memories of childhood and family-of-origin, spoke of an abusive relationship with their mothers. The various types of these relationships are presented along a continuum based on the severity of violence and emotional detachment of the mothers toward the interviewees, ranging from physical and emotional distancing, through chronic expressions of bitterness and criticism, and ending with severe physical violence. The findings are analyzed through the prism of social construction, relating to the interviewees' use of the psychodynamic discourse when accounting for their past and present abusive relationships. Some limitations and clinical implementations of the study, and needs for further research, are addressed.


Engagement Strategies to Advance Community-Centered Primary Care.
The Louisiana Public Health Institute designed and implemented the Primary Care Capacity Project (PCCP) with the purpose of expanding access to high-quality, integrated, and sustainable community-based primary care, including linkages to behavioral health services, as well as environmental and occupational health services. With a primary focus to invest in community health centers across 17 Gulf Coast counties and parishes, PCCP engaged stakeholders, including 4 primary care organizations, over 20 federally qualified health centers, public health institutes, health information exchanges, national experts, academic organizations, and health departments along with their relevant community partners. This article examines the strategies PCCP used to engage stakeholders and partners throughout the project in order to strengthen sustainable primary care systems. The PCCP team fostered trusted partnerships with a wide range of stakeholders to not only understand the need of the communities but to also identify ways to complement and not duplicate already existing efforts. Specifically, community prioritization convenings, peer-to-peer learning through the Regional Care Collaborative, and dyadic interviews were instrumental in linking stakeholders and maximizing capacity-building efforts. Health partners across the 4 states are now better positioned to collaborate on future regional opportunities including continued knowledge transfer through special interest groups, ongoing engagement with an annual regional convening, continued efforts to advance emergency management and resiliency, and potential development of group purchasing and other shared services. The PCCP experience suggests that in disaster-prone areas the sustainability of integrated primary care and behavioral health services is enhanced when cross-jurisdiction collaborations are established.


Chapter 3. A multidimensional model for narrative analysis of substance use-related dependency.
This chapter examines the possibilities and limitations of using a narrative method as a framework within a multidimensional model for exploring and analyzing the use and misuse of alcohol and drugs. It is posited that a multidimensional model, based on narrative reasoning, can give a more detailed and specific understanding of substance users, who represent a heterogeneous population of people, and of substance use-related dependency problems. Such a model describes and analyses the drug-use related problems in a manner that provides holistic and important information and knowledge about the person by contextual and situation interaction processes which are involved in the use/misuse of alcohol and drugs. Tentative conclusions and unresolved critical issues are considered.


Studies on the Turtle Tumor Susceptibility Gene TSG101: Full-Length cDNA Sequence, Genomic Structural Analysis, and Role in Green Turtle Fibropapilloma.
The tumor susceptibility gene TSG101 is a recently discovered gene whose functional knockout in mouse fibroblasts leads to transformation and tumor formation in nude mice. Human and mouse TSG101 cDNAs are 86% and 94% similar at the nucleotide and deduced amino acid levels, respectively. The highly conserved protein sequences suggest that the mouse and human TSG101 are true gene homologs that share fundamental biological functions. Here, we report that the turtle TSG101 full-length cDNA sequence contained a 1,176-base-pair open translational reading frame predicted to encode a 392-amino-acid protein. Alignment of TSG101 sequences showed that the turtle cDNA sequence was 82.3% and 84.4% similar to mouse and human TSG101, respectively, at the nucleotide level and 89.3% and 91.9% similar to mouse and human TSG101 proteins, respectively. A coiled-coil domain and a proline-rich region typical of the activation domain of transcription factors were highly conserved among the turtle, mouse, and human TSG101. The leucine zipper motifs in the coiled-coil domains of turtle, mouse, and human TSG101 proteins were identical. Expression of TSG101 was observed in all turtle organs examined. The role of TSG101 in green turtle fibropapilloma (GTFP) was investigated by performing reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA derived from various turtle tumor tissues and tumor cell lines. No transcript abnormalities of turtle TSG101 were found in all examined GTFP samples (10 GTFP tumor tissues and 2 GTFP tumor cell lines) from RT-PCR products. Future study will analyze the difference in turtle TSG101 expressions between GTFP and the corresponding normal tissue. In mammalian systems, TSG101 productions outside of a narrow range, either overexpression or deficiency, can lead to abnormal cell growth. It needs to be clarified whether turtle TSG101 in GTFP is up or down regulated.


ALADDIN: Docking Approach Augmented by Machine Learning for Protein Structure Selection Yields Superior Virtual Screening Performance.
Protein flexibility and solvation pose major challenges to docking algorithms and scoring functions. One established strategy for addressing these challenges is to use multiple protein conformations for docking (all-against-all ensemble docking). Recent studies have shown that the performance of ensemble docking can be improved by selecting the most relevant protein structures for docking. In search for a robust approach to protein structure selection, we have come up with an integrated mAchine Learning AnD DockINg approach (ALADDIN). ALADDIN employs a battery of random forest classifiers to select, individually for each compound of interest, from an ensemble of protein structures, the single most suitable protein structure for docking. ALADDIN outperformed the best single-structure docking runs, ensemble docking and a similarity-based docking approach on three out of four investigated targets, with up to 0.15, 0.11 and 0.16 higher area under the receiver operating characteristic curve (AUC) values, respectively. Only in the case of cytochrome P450 3A4, ALADDIN, like any of the other tested approaches, failed to obtain decent performance. ALADDIN can be particularly useful for structure-based virtual screening of malleable proteins, including kinases, some viral enzymes and anti-targets.


Deep sepsis following total knee arthroplasty. Ten-year experience at the University of California at Los Angeles Medical Center.
Between September 1971 and May 1982, at the University of California at Los Angeles Medical Center, 821 total knee arthroplasties were performed in 604 patients, all of whom received perioperative antibiotics. Deep sepsis, proved by a positive culture of a specimen obtained by postoperative arthrocentesis, developed fourteen times in thirteen knees of twelve patients, an incidence of 1.71 per cent. In one of these patients, who had systemic lupus erythematosus and bilateral knee replacement, the right knee became infected with two distinct organisms on two different occasions (separated by ten months). The first infection was probably hematogenous while the second, developing after a dental procedure, definitely was. Over-all, five infections were hematogenous with an identified source and one other was suspected of having a hematogenous origin. The time from operation to the diagnosis of sepsis averaged 8.3 months over-all, but five of the fourteen infections were recognized less than two months after arthroplasty. For the six infections that were assumed to be hematogenous, the time from operation to the diagnosis of sepsis averaged 16.4 months. The major presenting symptom was pain in thirteen of the fourteen infections. The initial treatments of the fourteen infections consisted of intravenous antibiotics in all of them, primary removal of the prosthesis and so-called exchange arthroplasty after five days in one, removal of the prosthesis and fusion in one, arthrotomy and débridement in six, arthroscopic irrigation in three, and antibiotics alone in three (of which one was treated with an exchange arthroplasty after three weeks). At last follow-up, only four of the thirteen prostheses had been salvaged.(ABSTRACT TRUNCATED AT 250 WORDS)


The active platelet: translation and protein synthesis in an anucleate cell.
Platelets are the major cellular component of the hemostatic system that controls vessel and wound repair. However, platelets also have a variety of additional functions in inflammatory responses and host defense. The function and structure of the platelet was assumed to be very simple for a long period of time. With more modern tools of investigation such as cDNA arrays and proteomics, we have discovered a cell that is becoming a more sophisticated libero that functions in the classic mechanisms of white blood cells--inflammation and immunity.


Flow Diversion for the Treatment of Intracranial Aneurysms in a Peruvian Cohort: Experiences from a Limited-Resource Setting and Barriers to Implementation.
Stenting with flow diverter devices (FDDs) has increasingly emerged as a treatment for intracranial aneurysms. The use of FDDs in the developing world has not been described. A retrospective review was performed of a cohort of patients who underwent flow diversion at 4 tertiary-care centers in Lima, Peru between January 2017 and June 2021. Demographics, clinical features, and aneurysm morphology were evaluated. Clinical outcomes were observed 3 months after discharge and occlusion rates were assessed 12 months after treatment. Sixty-nine patients (mean age, 46 ±14.5 years; 17% female) were treated with FDDs; 4% (n = 3) of the treated aneurysms were ruptured. Most aneurysms were saccular (n = 65; 94%), <10 mm in maximum size (n = 60; 87%), and located in the anterior circulation (n = 67; 97%). Minor complications, such as groin hematoma, occurred in 7 cases. No serious complications or deaths occurred. Patients' functional status was excellent (modified Rankin Scale score 0-1) in 99% (n = 66) at discharge and 100% (n = 67) at 3 months. Although some patients were lost to follow-up, complete occlusion was seen in 76% (n = 31) of 41 treated patients at 12 months. We report the largest multicenter experience of FDDs for cerebral aneurysm treatment in Peru, with reasonable outcomes that are comparable to other settings despite various challenges, suboptimal circumstances, and lack of resources.


Cryopreservation of human pulmonary alveolar macrophages.
Human pulmonary alveolar macrophages (PAM) from 30 patients with a variety of pulmonary diseases were tested for their ability to undergo cryopreservation. The cells were cryopreserved and stored under liquid nitrogen for intervals of 2, 4, 6, 8, or 12 wk, then assayed for viability (using the trypan dye exclusion method as well as the NADH-dependent cytochrome c reductase (cytochrome c) assay) and cellular function (as documented by the measurement of in vitro aryl hydrocarbon hydroxylase (AHH) induction by benzanthracene (BA) and by quantitation of PAM particulate phagocytosis). These results demonstrated no decrease in PAM viability after 2 wk of cryopreservation compared with that of the control cells (p greater than 0.30, paired, 2-tailed t test). However, PAM viability decreased slightly compared with the 0-time (p less than 0.003 in all instances) when cells were stored for intervals of 4, 6, 8, or 12 wk. In addition, cells demonstrated no further decrease in viability after being cryopreserved for as long as 12 wk, thawed, and cultured for as long as 48 h compared with the 0-time control cells (p greater than 0.10 in all instances). Similarly, when AHH induction was fluorometrically quantitated in PAM cultured for 24 h, there was no decrease in BA-induced AHH levels after a 2-wk cryopreservation period. However, AHH levels decreased slightly compared with those in the 0-time control cells (p less than 0.004), when PAM were stored for longer intervals of 4, 6, or 8 wk. The phagocytic activity of cryopreserved PAM was also quantitated using amorphous silica as a substrate.(ABSTRACT TRUNCATED AT 250 WORDS)


Chelation therapy. Unproved modality in the treatment of Alzheimer-type dementia.
Despite a dramatic increase in the understanding of the neuropathologic and neurochemical alterations accompanying Alzheimer's disease, by far the largest cause of progressive and incapacitating cognitive dysfunction in the elderly, physicians have as yet no pharmacologic agent that can be prescribed safely either to arrest or reverse this decline. This lack of effective therapeutic agents is contributing to the use by an increasing number of health professionals, including physicians and concerned families, of unproved, costly, and potentially dangerous modalities, such as chelation therapy. The purpose of this paper is to describe some individuals with Alzheimer-type dementia who have undergone chelation therapy.


Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six i(7)(q10)-positive HSTL cases, including HSTL-derived cell line (DERL-2), and three cases with ring 7 [r(7)], the recently identified rare variant aberration. Using high resolution array CGH, we profiled all cases and mapped the common deleted region (CDR) at 7p22.1p14.1 (34.88 Mb; 3506316-38406226 bp) and the common gained region (CGR) at 7q22.11q31.1 (38.77 Mb; 86259620-124892276 bp). Interestingly, CDR spans a smaller region of 13 Mb (86259620-99271246 bp) constantly amplified in cases with r(7). In addition, we found that TCRG (7p14.1) and TCRB (7q32) are involved in formation of r(7), which seems to be a byproduct of illegitimate somatic rearrangement of both loci. Further transcriptomic analysis has not identified any CDR-related candidate tumor suppressor gene. Instead, loss of 7p22.1p14.1 correlated with an enhanced expression of CHN2 (7p14.1) and the encoded β2-chimerin. Gain and amplification of 7q22.11q31.1 are associated with an increased expression of several genes postulated to be implicated in cancer, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any disease-defining mutation or gene fusion. Thus, chromosome 7 imbalances remain the only driver events detected in this tumor. We hypothesize that the Δ7p22.1p14.1-associated enhanced expression of CHN2/β2-chimerin leads to downmodulation of the NFAT pathway and a proliferative response, while upregulation of the CGR-related genes provides growth advantage for neoplastic δγT-cells and underlies their intrinsic chemoresistance. Finally, our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies.


Levels of sexual activity among adolescent males in the United States.
Although three-fifths of adolescent males aged 15-19 say they have had sexual intercourse, analyses of data from the 1988 National Survey of Adolescent Males indicate that their level of sexual activity is relatively moderate. The data show that among sexually experienced young men the mean number of partners in the last 12 months is 1.9, and the mean frequency of intercourse in the last four weeks is 2.7 times. Black males have had more partners than white or Hispanic males; however, after the number of years since first intercourse are controlled for, these differences disappear. On average, sexually experienced youth spent six out of the last 12 months with no sexual partner, and only 21 percent of sexually active males had more than one partner in any month in the last year. Comparisons with 1979 data suggest that proportionately more adolescents were sexually experienced in 1988, but fewer non-black males had first intercourse before their 15th birthday. The number of partners since first intercourse and in the past four weeks appears to have decreased, as has the frequency of intercourse in the last four weeks.


Social problem-solving abilities and personality disorder characteristics among dual-diagnosed persons in substance abuse treatment.
We examined the relation of self-appraised social problem-solving abilities and personality-disorder characteristics to the adjustment and compliance of persons with dual diagnoses in substance-abuse treatment. It was hypothesized that elements of the problem-orientation component would remain predictive of depressive behavior and distress after considering personality-disorder characteristics among 117 persons receiving inpatient-substance-abuse treatment. Furthermore, self-appraised problem-solving abilities were expected to predict the occurrence of "dirty" drug and alcohol screens during treatment and compliance with the first scheduled community follow-up visit. Results supported predictions concerning the relation of problem-solving confidence to depressive behavior, distress, and substance-use screens; however, a paradoxical relation was observed between the problem-orientation variables and compliance with the first outpatient visit. The results are interpreted within the context of contemporary models of social problem solving and the implications for cognitive-behavioral assessment and intervention are considered.