[Mucosal viral vaccines: progress and problems].
Data obtained in the recent years on developing the viral inactivated mucosal vaccines by applying the mucosal-adhesive adjuvants are presented in the survey. Progress achieved in designing the mucosal influenza vaccines and mucosal vaccines against a variety of other viral infections is pointed out. Cross-protection against variations of a virus within its subtype limits as well as overcoming of a negative influence of parent antibodies produced on the immunogenicity of live-vaccines', which were used at young age, were observed in the intranasal administration of viral mucosal vaccines. A number of shortcomings of bacterial toxins used as mucosal-adhesive adjuvants as well as problems, which may arise when the viral mucosal vaccines are used on a large-scale basis due to a need in their two- and-threefold intranasal administration, are in the focus of attention.


Incidental high-grade dysplasia of the cystic duct margin: case report and literature review.
High-grade dysplasia (HGD) of the gallbladder has been proven to be an intermediate step in the pathogenesis from normal mucosa to invasive carcinoma. There is paucity of definitive data concerning the associated risk and optimal management of isolated HGD of the gallbladder involving the cystic duct margin following cholecystectomy. A previously healthy 44-year-old man underwent laparoscopic cholecystectomy for suspected symptomatic gallstones. The gross examination of the gallbladder did not show any discrete masses or lesions, and histopathologic evaluation revealed several proximal foci of HGD with involvement of the cystic duct margin. Subsequent magnetic resonance cholangiopancreatography (MRCP) showed central intra-hepatic ductal dilation, likely post-operative, with no evidence of malignancy. Patient underwent additional surgical exploration with laparoscopic excision of the cystic duct stump and intra-operative cholangiogram. The additionally resected stump showed mild chronic inflammation and reparative fibrosis without dysplasia. A follow-up MRCP two years later showed regression of the previously described dilation and no new lesions were detected. The patient remains disease-free until the present date. Isolated HGD of the gallbladder is an uncommon occurrence but can rarely involve the cystic duct margin. These patients are to be thoroughly investigated for associated carcinoma in other parts of the gallbladder. Additional studies are needed to better understand the long-term risk associated with premalignant lesions of the gallbladder to achieve optimal care and outcome for these patients.


Cognitive, sensory, and emotional changes associated with the menstrual cycle: a review.
The hormones progesterone and estrogen and, more precisely, their sophisticated interdependent fluctuations over the course of the female human lifespan, have long been known to play a dominant role in the physiological development and homeostasis of the human female. What is only recently coming to light, however, is that the fluctuation of these two hormones also plays a crucial role in neurological and psychological development and function which impacts brain function, cognition, emotional status, sensory processing, appetite, and more. The ability of reproductive hormones to impact psychoneurological processes involves the interplay of several body systems, lending credibility to the view of premenstrual syndrome (PMS) as a disorder founded in real biochemical disturbances. The effects of the menstrual cycle on cognitive, emotional, and sensory function in the female of childbearing age are reviewed. In addition, recent evidence is discussed which confirms the biological basis of PMS as a real disorder of primarily autoimmune origin.


Transport of giardia and manure suspensions in saturated porous media.
Experiments were conducted to elucidate the transport behavior of cysts of Giardia and manure suspensions through several aquifer sands. Decreasing the median grain size of the sand resulted in lower peak effluent concentrations and increased deposition of the Giardia and manure particles in the sand near the column inlet. The effluent concentration curves for the manure suspensions also exhibited asymmetric shapes that tended to include larger particle sizes as the manure suspension was continuously added. Simulations of the transport of Giardia and manure particles using a simple and flexible power law model for the solid-water mass exchange term provided a satisfactory description of the effluent and spatial distribution data. The cumulative size distribution (CSD) of manure particles in the suspension initially and after passage through the packed columns was used to identify the mechanisms that were controlling the deposition of manure particles and Giardia. The CSD data indicated that manure particles were completely removed at early times by mechanical filtration and/or straining when the ratio of the particle to the median grain diameter was greater than 0.003 to 0.017. However, the CSD changed with increasing time due to deposition-induced filling of straining sites. The Giardia transport was controlled by straining. For a given sand, higher effluent concentrations of Giardia were observed in the presence than in the absence of manure suspension. The relative increase of Giardia in the effluent concentrations varied from 75 to 172%. Hence, pathogen transport studies conducted in the absence of manure suspension may underestimate transport potential in manure-contaminated environments.


End-of-life decision making: a qualitative study of elderly individuals.
To identify the desired features of end-of-life medical decision making from the perspective of elderly individuals. Qualitative study using in-depth interviews and analysis from a phenomenologic perspective. A senior center and a multilevel retirement community in Los Angeles. Twenty-one elderly informants (mean age 83 years) representing a spectrum of functional status and prior experiences with end-of-life decision making. Informants were concerned primarily with the outcomes of serious illness rather than the medical interventions that might be used, and defined treatments as desirable to the extent they could return the patient to his or her valued life activities. Advanced age was a relevant consideration in decision making, guided by concerns about personal losses and the meaning of having lived a "full life." Decision-making authority was granted both to physicians (for their technical expertise) and family members (for their concern for the patient's interests), and shifted from physician to family as the patient's prognosis for functional recovery became grim. Expressions of care, both by patients and family members, were often important contributors to end-of-life treatment decisions. These findings suggest that advance directives and physician-patient discussions that focus on acceptable health states and valued life activities may be better suited to patients' end-of-life care goals than those that focus on specific medical interventions, such as cardiopulmonary resuscitation. We propose a model of collaborative surrogate decision making by families and physicians that encourages physicians to assume responsibility for recommending treatment plans, including the provision or withholding of specific life-sustaining treatments, when such recommendations are consistent with patients' and families' goals for care.


Hyperlactatemia, Lactate Kinetics and Prediction of Citrate Accumulation in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy With Regional Citrate Anticoagulation.
Citrate accumulation is a major complication of regional citrate anticoagulation during continuous renal replacement therapy. We studied the prediction of citrate accumulation during continuous veno-venous hemodialysis with regional citrate anticoagulation by initial lactate concentrations and lactate kinetics. A retrospective follow-up analysis from a cohort of critically ill patients. Mixed medical-surgical ICUs at a university hospital. All adult patients with acute kidney injury and treated with regional citrate anticoagulation-continuous veno-venous hemodialysis during a 3-year period (n = 1,070) were included in this retrospective study and screened for metabolic signs of citrate accumulation. None. The frequency of citrate accumulation during the first 48 hours of therapy was 2.26%. In patients with initial normal lactate (< 2.2 mmol/L), elevated lactate (≥ 2.2 to < 4 mmol/L), or severe hyperlactatemia (≥ 4 mmol/L), the frequency of citrate accumulation was 0.77%, 2.70%, and 6.33%, respectively. Receiver operating characteristics-area under the curve of initial lactate concentration was 0.789 for the prediction of citrate accumulation. Optimal cutoff from receiver operating characteristics (2.39 mmol/L) showed strong negative prediction (99.28%), but weak positive prediction (5.21%). The slope intercept of lactate kinetics over 48 hours was positive and significantly higher in patients with citrate accumulation compared to those without (+0.2 vs -0.006 mmol/L/hr; p < 0.001). In patients with initial severe hyperlactatemia (≥ 4 mmol/L), the median calculated lactate clearance at 6, 12, and 18 hours was 24.0%, 48.1%, and 59.4% in the nonaccumulation group. These clearance rates were significantly higher at each time-point compared to patients with citrate accumulation (-9.8%, -20.5%, and 2.3%, respectively; p < 0.001 for each time-point). The highest receiver operating characteristics-area under the curve for citrate accumulation was observed for 12-hour values of lactate clearance (area under the curve = 0.839; 95% CI, 0.751-0.927) with an optimal cut-off value of 24.3%. Risk of citrate accumulation during regional citrate anticoagulation in a well-selected cohort of patients is low even in case of initial severe hyperlactatemia. Lactate kinetics rather than initially elevated lactate concentration should be considered in assessing the risk of citrate accumulation.


Radiation-induced Non-targeted Effect and Carcinogenesis; Implications in Clinical Radiotherapy.
Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon.


Susceptibility of Alphitobius diaperinus (Coleoptera: Tenebrionidae) from broiler facilities in Texas to four insecticides.
Lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), adults were collected from six eastern Texas broiler facilities and examined for susceptibility to four formulated insecticides. Data indicate that A. diaperinus adults exposed to filter papers treated with the label rates of the insecticides exhibit some level of recovery. Approximately 20% or less A. diaperinus adults treated with Tempo SC Ultra (8 ml/92.9 m2, 11.8% beta-cyfluthrin) or Talstar WP Insecticide/Miticide (23.3 ml/92.9 m2, 10% bifenthrin) and recorded as moribund at the 4-h observation period recovered by the 24-h observation period. A. diaperinus adults treated with Tempo SC Ultra and Talstar WP also had the greatest percentage of mortality for both observation periods. A. diaperinus adults treated with Dragnet SFR (49.7 ml/92.9 m2, 36.8% permethrin) had the greatest level of recovery at approximately 50-60% overall, which was similar to that recorded for the water-only control. Additionally, five of the six A. diaperinus populations treated with Dragnet SFR resulted in < 10% mortality for both observation periods. Unlike the other insecticides examined, Talstar Professional Insecticide (10 ml/92.9 m2, "Talstar Pro," 7.9% bifenthrin) resulted in approximately 50% more A. diaperinus mortality at the 24-h than the 4-h observation period due primarily to increased mortality recorded for Farm F. A. diaperinus adults from farm D had > or = 87% knockdown 4 h after treatment to all compounds examined, indicating a high degree of sensitivity to these compounds. However, approximately 90% of the A. diaperinus adults from this population treated with Dragnet SFR and recorded as moribund recovered by the 24-h observation. A. diaperinus adults from this population treated with the other insecticides exhibited limited recovery. Susceptible adult A. diaperinus populations are still present in Texas, based on the populations examined. But, identifying these populations is difficult and time-consuming. Consequently, screening populations before treatment might not be feasible. However, newer generation pyrethroids examined in this study seem to be suitable for suppressing A. diaperinus populations in broiler facilities.


Metal Oxide Laser Ionization Mass Spectrometry Imaging (MOLI MSI) Using Cerium(IV) Oxide.
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a powerful technique for spatially resolved metabolomics. A variation on MALDI, termed metal oxide laser ionization (MOLI), capitalizes on the unique property of cerium(IV) oxide (CeO2) to induce laser-catalyzed fatty acyl cleavage from lipids and has been utilized for bacterial identification. In this study, we present the development and utilization of CeO2 as an MSI catalyst. The method was developed using a MALDI TOF instrument in negative ion mode, equipped with a high frequency laser. Instrument parameters for MOLI MS fatty acid catalysis with CeO2 were optimized with phospholipid standards and fatty acid catalysis was confirmed using lipid extracts from reference bacterial strains, and sample preparation was optimized using mouse brain tissue. MOLI MSI was applied to the imaging of normal mouse brain revealing differentiable fatty acyl pools in myelinated and nonmyelinated regions. Similarly, MOLI MSI showed distinct fatty acyl composition in tumor regions of a patient derived xenograft mouse model of glioblastoma. To assess the potential of MOLI MSI to detect pathogens directly from tissue, a pseudoinfection model was prepared by spotting Escherichia coli lipid extracts on mouse brain tissue sections and imaged by MOLI MSI. The spotted regions were molecularly resolved from the supporting mouse brain tissue by the diagnostic odd-chained fatty acids and reflected control bacterial MOLI MS signatures. We describe MOLI MSI for the first time and highlight its potential for spatially resolved fatty acyl analysis, characterization of fatty acyl composition in tumors, and its potential for pathogen detection directly from tissue.


On the potential for extinction by Muller's ratchet in Caenorhabditis elegans.
The self-fertile hermaphrodite worm C. elegans is an important model organism for biology, yet little is known about the origin and persistence of the self-fertilizing mode of reproduction in this lineage. Recent work has demonstrated an extraordinary degree of selfing combined with a high deleterious mutation rate in contemporary populations. These observations raise the question as to whether the mutation load might rise to such a degree as to eventually threaten the species with extinction. The potential for such a process to occur would inform our understanding of the time since the origin of self-fertilization in C. elegans history. To address this issue, here we quantify the rate of fitness decline expected to occur via Muller's ratchet for a purely selfing population, using both analytical approximations and globally distributed individual-based simulations from the evolution@home system to compute the rate of deleterious mutation accumulation. Using the best available estimates for parameters of how C. elegans evolves, we conclude that pure selfing can persist for only short evolutionary intervals, and is expected to lead to extinction within thousands of years for a plausible portion of parameter space. Credible lower-bound estimates of nuclear mutation rates do not extend the expected time to extinction much beyond a million years. Thus we conclude that either the extreme self-fertilization implied by current patterns of genetic variation in C. elegans arose relatively recently or that low levels of outcrossing and other factors are key to the persistence of C. elegans into the present day. We also discuss results for the mitochondrial genome and the implications for C. briggsae, a close relative that made the transition to selfing independently of C. elegans.


Simplified trimming and finishing of glass-polyalkenoate (ionomer) cement restorations.
Shaping and fine working of restorations necessitated by cervical lesions, abrasions at the necks of teeth, or root surface caries can often be arduous to complete. As an example of a facilitated trimming and simplified finishing technique for cervical restorations, the use of "tissue-protective" finishing diamonds to adapt a Class V Type II glass-polyalkenoate (ionomer) cement restoration is demonstrated. Because of their noncutting guiding tips, these "safe-ended" diamond instruments can help prevent discontinuous and nonanatomic contouring of restorations. In addition, these special instruments allow a less traumatic working procedure in areas of marginal gingiva.


Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid β levels in humans.
Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.


Mitochondrial clustering at the vertebrate neuromuscular junction during presynaptic differentiation.
During vertebrate neuromuscular junction (NMJ) development, presynaptic motor axons differentiate into nerve termini enriched in synaptic vesicles (SVs). At the nerve terminal, mitochondria are also concentrated, but how mitochondria become localized at these specialized domains is poorly understood. This process was studied in cultured Xenopus spinal neurons with mitochondrion-specific probe MitoTracker and SV markers. In nerve-muscle cocultures, mitochondria were concentrated stably at sites where neurites and muscle cells formed NMJs, and mitochondria coclustered with SVs where neurites were focally stimulated by beads coated with growth factors. Labeling with a mitochondrial membrane potential-dependent probe JC-1 revealed that these synaptic mitochondria were with higher membrane potential than the extrasynaptic ones. At early stages of bead-stimulation, actin-based protrusions and microtubule fragmentation were observed in neurites at bead contact sites, suggesting the involvement of cytoskeletal dynamics and rearrangement during presynaptic differentiation. Treating the cultures with an actin polymerization blocker, latrunculin A (Ltn A), almost completely abolished the formation of actin-based protrusions and partially inhibited bead-induced mitochondrial and SV clustering, whereas the microtubule disrupting agent nocodazole was ineffective in inhibiting the clustering of mitochondria and SVs. Lastly, in contrast to Ltn A, which blocked bead-induced clustering of both mitochondria and SVs, the ser/thr phosphatase inhibitor okadaic acid inhibited SV clustering but not mitochondrial clustering. These results suggest that at developing NMJs, synaptogenic stimuli induce the clustering of mitochondria together with SVs at presynaptic terminals in an actin cytoskeleton-dependent manner and involving different intracellular signaling molecules.


Vesicle traffic to the immunological synapse: a multifunctional process targeted by lymphotropic viruses.
The site of contact between T lymphocytes and antigen-presenting cells becomes, upon antigen recognition, an organized junction named the immunological synapse. Various T cell organelles polarize, together with microtubules, toward the antigen-presenting cell. Among them, intracellular vesicular compartments, such as the Golgi apparatus, the recycling endosomal compartment, or cytotoxic granules help to build the immunological synapse and ensure effector functions, such as polarized secretion of cytokines by helper T cells, or exocytosis of lytic granules by cytotoxic T cells. Lymphotropic retroviruses, such as the human immunodeficiency virus type 1, the human T cell leukemia virus type 1, or the Herpesvirus saimiri, can subvert some of the vesicle traffic mechanisms impeding the generation and function of the immunological synapses. This review focuses on the polarization of vesicle traffic, its regulation, and its role in maintaining the structure and function of the immunological synapse. We discuss how some lymphotropic viruses target the vesicle traffic in T lymphocytes, inhibiting the formation of immunological synapses and modulating the response of infected T cells.


Treatment strategies for myeloid growth factors and intravenous iron: when, what, and how?
Myeloid growth factors can reduce the risk of chemotherapy-induced neutropenia (CIN) and thus impact the survival of patients with cancer. Patients should be assessed for risk, taking into consideration patient-related risk factors and chemotherapy regimens. Patients stratified as having at least a 20% risk for CIN should be considered for prophylactic growth factors. The NCCN Guidelines for Myeloid Growth Factors provide category 1 recommendations for the daily use of filgrastim, tbo-filgrastim, and pegfilgrastim. Cancer-related anemia can be treated with erythropoiesis-stimulating agents, red blood cell transfusion, or intravenous iron.


SIOP pediatric oncology services Global Mapping Program: Latin American data collection.
The International Society of Paediatric Oncology (SIOP) launched a program to map all pediatric cancer facilities around the world. After the results in Africa were completed, the strategy for data collection for Latin America was revised to improve the accuracy and avoid duplications. In partnership with SIOP, the Sociedad Latino Americana de Oncología Pediátrica (SLAOP) approached their delegates who provided the contacts for a 10-question survey about their institutional capacities. Data were collected by email, online meetings, or telephone calls, and stored in a secure platform. All but one country participated and a high number of centers were recorded.


Sex differences of inflammatory and immune response in pups of Wistar rats with SIRS.
It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-β) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.


Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.
The spatial relation between mitochondria and endoplasmic reticulum (ER) in living HeLa cells was analyzed at high resolution in three dimensions with two differently colored, specifically targeted green fluorescent proteins. Numerous close contacts were observed between these organelles, and mitochondria in situ formed a largely interconnected, dynamic network. A Ca2+-sensitive photoprotein targeted to the outer face of the inner mitochondrial membrane showed that, upon opening of the inositol 1,4,5-triphosphate (IP3)-gated channels of the ER, the mitochondrial surface was exposed to a higher concentration of Ca2+ than was the bulk cytosol. These results emphasize the importance of cell architecture and the distribution of organelles in regulation of Ca2+ signaling.


Heparins and mechanical methods for thromboprophylaxis in colorectal surgery.
Colorectal surgery implies higher risk of postoperative thromboembolic complications as deep venous thrombosis (DVT) and pulmonary embolism (PE) than general surgery. The best prophylaxis in general surgery is heparin and graded compression stockings. No systematic review on combination prophylaxis or on thrombosis prophylaxis in colorectal surgery has been published. To compare the incidence of postoperative thromboembolism after colorectal surgery using prophylactic methods focussing on heparins and mechanical methods alone and in combinations. Electronic searches was performed in PUBMED, EMBASE, LILACS and the Cochrane Library. Abstract books from major congresses were handsearched as were reference lists from previously performed reviews. RCT or CCT comparing prophylactic interventions and/or placebo. Outcomes were ascending venography, 125 I-fibrinogen uptake test, ultrasound methods, pulmonary scintigraphy. Studies, using thermographic methods, other isotopic methods, plethysmographic methods, and purely clinical methods as the only diagnostic measure were excluded. 558 studies were identified - 477 were excluded. Only 3 of the identified studies focused exclusively on colorectal surgery. Studies of general surgery contain considerable numbers of colorectal patients. The authors of 66 studies in general and/or abdominal surgery were contacted for retrieving the results from the colorectal patients. Answers were received from very few. 19 studies entered this review. All studies and all data extraction were performed by at least two of the authors. Outcome was deep venous thrombosis and/or pulmonary embolism. Analysis of bleeding complications were unfeasible. 12 meaningful outcomes were analysed by means of the fixed effects model with Peto Odds Ratios. Heparins versus no treatment: Any kind of heparincompared to no treatment or placebo (comparison 07.03, 11 studies). Heparin is better in preventing DVT and/or PE with a Peto Odds ratio at 0.32 (95% Confidence Interval 0.20-0.53) Unfractionated heparin versus low molecular weight heparin (comparison 08.03, 4 studies). The two treatments were found equally effective in preventing DVT and/or PE with a Peto Odds ratio 1.01 (95% Confidence Interval 0.67-1.52). Mechanical methods (comparison 10.3, 2 studies). The combination of graded compression stockings and LDH is better than LDH alone in preventing DVT and/or PE with a Peto Odds ratio at 4.17 (95% Confidence Interval 1.37-12.70). The optimal prophylaxis in colorectal surgery is the combination of graduated compression stockings and low-dose unfractionated heparin. The unfractionated heparin can be replaced with low molecular weight heparin.


Correlation of near-infrared spectroscopy and direct pressure monitoring in an acute porcine compartmental syndrome model.
To correlate near-infrared spectroscopy (NIRS) and the tibial intracompartmental perfusion pressure (TIPP) in an acute limb compartmental syndrome. Landrace swine were subdivided into 2 groups: plasma infusion (n = 16) and blunt trauma plus plasma infusion (n = 15). NIRS sensors were placed over the craniolateral muscle compartment of proximal both tibiae. Albumin infusion elevated tibial intracompartmental pressures (TICP). Time-synchronized measures of systolic, diastolic, and mean arterial pressures, TICP, and percent oxygenation from each leg were collected. For the blunt trauma group, trauma was induced by dropping a 2-kg weight 30 times from 100 cm directly on the muscle compartment. For each group, a repeated-measures analysis of variance model was used to test differences in the TICP, TIPP, and oxygenation values. Pearson correlations were calculated between TICP and oxygenation and between TIPP and oxygenation. Both models created reproducible increases in TICP and decreases in TIPP. Trauma did not alter TICP, TIPP, or percent oxygenation in the model. NIRS was able to detect significant changes in tissue oxygenation at all the same time points. NIRS was able to detect decreased oxygenation at every TIPP decrease and subsequent increase after fasciotomies. An increase in percent oxygenation was seen in all cases once fasciotomy was performed and TICP was reduced. NIRS provided a sensitive measure correlating to both an increase and decrease in TICP and TIPP, respectively, in this infusion model. The addition of blunt trauma to the model did not alter the correlations of NIRS values with TICP and TIPP. Fasciotomy produced a rebound in oxygenation values.


Racial/ethnic differences in predictors of PSA screening in a tri-ethnic population.
This study was carried out to identify racial/ethnic differences in predictors of prostate-specific antigen (PSA) screening in a group of prostate cancer patients. In this cross-sectional study, a total of 935 prostate cancer patients were recruited from the Texas Medical Center, Houston, between 1996 and 2004. It included 372 Caucasians, 346 African Americans and 217 Hispanics. A structured questionnaire was used to collect data on socio-demographic and life-style related variables, and self-reported PSA screening history through personal interview. African American (54.4%) and Hispanic patients (42.3%) were significantly less likely (p = 0.004 and p < 0.001, respectively) to report having had PSA screening than Caucasian patients (63.2%). Only annual check-up was found to be a significant predictor of PSA screening in Hispanics. Among Caucasians, education and annual check-up were significant predictors of PSA screening; whereas in African Americans, education, annual check-up, marital status and BMI were significant predictors of PSA screening. The rates of PSAscreening and its predictors varied by race/ethnicity in this tri-ethnic population. Health-education programs and culturally appropriate educational outreach efforts, especially targeted for high-risk groups, are needed to reduce these disparities.


Controlled analysis of factors associated with insufficient sample on outpatient endometrial biopsy.
We examined the relative significance of hysteroscopic and ultrasonographic evidence of endometrial atrophy in relation to insufficient sample on outpatient endometrial biopsy in women with abnormal uterine bleeding. Multivariate logistic regression modelling was used to evaluate the independent effects of age, menopausal status, hysteroscopic findings and sonographic endometrial thickness on outpatient endometrial sampling (sufficient or insufficient) used as the binary dependent variable. Insufficient sample on endometrial biopsy was associated with hysteroscopic finding of endometrial atrophy (OR 4.79, 95% CI 1.05-21.91, P = 0.04) and sonographic endometrial thickness below 5 mm (OR 0- 19. 95% CI 0.07-0.53, P = 0.001). There was no association with patient's age and menopausal status. In conclusion, when reassuring women with insufficient sample on outpatient endometrial biopsy, one can be confident about absence of pathology provided the hysteroscopic and sonographic endometrial assessment is consistent with endometrial atrophy.


Sexual decision-making in HIV-positive men who have sex with men: how moral concerns and sexual motives guide intended condom use with steady and casual sex partners.
Determinants of intended condom use with steady and casual sex partners were examined among Dutch HIV-positive men who have sex with men (MSM) (N = 296). Given the proposition that safer sex behavior among HIV-positive people is a form of prosocial behavior, the present study extended the general framework of the Theory of Planned Behavior with Schwartz's norm-activation theory and tested the assumption that personal norms would mediate the effects of other psychosocial factors on intended condom use for anal sex. In addition, it was hypothesized that, depending on the context in which sex occurs, specific motives for unprotected anal sex may have a negative influence on intended condom use and, as such, undermine a prosocial tendency to practice safer sex. Therefore, we also investigated the influence of sexual motives for unprotected anal sex on intended condom use with steady and casual sex partners. Results indicated that the Theory of Planned Behavior adequately predicted condom use intentions (for casual sex partners and steady sex partners, the explained variance was 52% and 53%, respectively). However, our proposed model of sexual decision-making significantly improved the prediction of behavioral intentions. For steady and casual sex partners, the assumption of the mediating role of personal norms on condom use intention was confirmed empirically. Additionally, sexual motives for unprotected anal sex exerted, as expected, a direct, negative effect on condom use intention with casual sex partners. The implications of the findings for future research and the development of HIV-prevention programs for HIV-positive MSM are discussed.


Semiflexible polymer brushes and the brush-mushroom crossover.
Semiflexible polymers end-grafted to a repulsive planar substrate under good solvent conditions are studied by scaling arguments, computer simulations, and self-consistent field theory. Varying the chain length N, persistence length lp, and grafting density σg, the chain linear dimensions and distribution functions of all monomers and of the free chain ends are studied. Particular attention is paid to the limit of very small σg, where the grafted chains behave as "mushrooms" no longer interacting with each other. Unlike a flexible mushroom, which has a self-similar structure from the size (a) of an effective monomer up to the mushroom height (h/a ∝ N(v), ν ≈ 3/5), a semiflexible mushroom (like a free semiflexible chain) exhibits three different scaling regimes, h/a ∝ N for contour length L = Na < lp, a Gaussian regime, h/a ∝ (Llp)(1/2)/a for lp ≪ L ≪ R* ∝ (lp(2)/a), and a regime controlled by excluded volume, h/a ∝ (lp/a)(1/5)N(ν). The semiflexible brush is predicted to scale as h/a ∝ (lpaσg)(1/3)N in the excluded volume regime, and h/a ∝ (lpa(3)σ(2))(1/4)N in the Gaussian regime. Since in the volume taken by a semiflexible mushroom excluded-volume interactions are much weaker in comparison to a flexible mushroom, there occurs an additional regime where semiflexible mushrooms overlap without significant chain stretching. Moreover, since the size of a semiflexible mushroom is much larger than the size of a flexible mushroom with the same N, the crossover from mushroom to brush behavior is predicted to take place at much smaller densities than for fully flexible chains. The numerical results, however, confirm the scaling predictions only qualitatively; for chain lengths that are relevant for experiments, often intermediate effective exponents are observed due to extended crossovers.


Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation.
Silybin is one of the main flavonoids produced by milk thistle, which has been used in the treatment of liver diseases. In this study, we examined the protective effects and possible mechanisms of action of silybin in lipopolysaccharide (LPS)‑induced lung injury and inflammation. Pre-treatment of mice with silybin significantly inhibited LPS-induced airway inflammatory cell recruitment, including macrophages, T cells and neutrophils. The production of cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchoalveolar fluid and serum was also decreased following treatment with silybin. Elevated cytokine mRNA levels induced by LPS in lung tissue were all suppressed by silybin and lung histological alterations were also improved. In addition, experiments using cells indicated that silybin significantly decreased the mRNA levels and secretion of IL-1β and TNF-α in THP-1 cells. Moreover, the mechanisms responsible for these effects were attributed to the inhibitory effect of silybin on nuclear factor-κB (NF-κB) signaling and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. The data form our study thus support the utility of silybin as a potential medicine for the treatment of acute lung injury‑associated inflammation and pathological changes. Silybin exerts protective effects against lung injury by regulating NF-κB signaling and the NLRP3 inflammasome activation.


Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01.
Adjuvant postoperative treatment with fluorouracil (5-FU) and levamisole in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival. Biochemical modulation of 5-FU with leucovorin has resulted in increased remission rates in metastatic colorectal cancer, thus reflecting an increased tumor-cell kill. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in comparison with the effects of 5-FU plus levamisole in the prospective multicentric trial adjCCA-01. Patients with a curatively resected International Union Against Cancer stage III colon cancer were stratified according to T, N, and G category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m(2) body-surface area intravenously in the first chemotherapy course, then 450 mg/m(2) x 5 days; 12 cycles, plus leucovorin 100 mg/m(2) (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). Six hundred eighty (96.9%) of 702 patients enrolled onto this study were eligible. After a median follow-up time of 46.5 months, the 5-FU plus leucovorin combination significantly improved disease-free survival (P =.037) and significantly decreased overall mortality (P =.0089) in comparison with 5-FU plus levamisole. In a multivariate proportional hazards model, adjuvant chemotherapy emerged as a significant prognostic factor for survival (P =.0059) and disease-free survival (P =.03). Adjuvant treatment with 5-FU plus levamisole as well as with 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. After a curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated and significantly more effective than 5-FU plus levamisole in reducing tumor relapse and improving survival.


Skill-based differences in option generation in a complex task: a verbal protocol analysis.
In recent models of decision-making, cognitive scientists have examined the relationship between option generation and successful performance. These models suggest that those who are successful at decision-making generate few courses of action and typically choose the first, often best, option. Scientists working in the area of expert performance, on the other hand, have demonstrated that the ability to generate and prioritize task-relevant options during situation assessment is associated with successful performance. In the current study, we measured law enforcement officers' performance and thinking in a simulated task environment to examine the option generation strategies used during decision-making in a complex domain. The number of options generated during assessment (i.e., making decisions about events in the environment) and intervention (i.e., making decisions about personal courses of action) phases of decision-making interact to produce a successful outcome. The data are explained with respect to the development of a situational representation and long-term working memory skills capable of supporting both option generation processes.


Losses of both products of the Cdkn2a/Arf locus contribute to asbestos-induced mesothelioma development and cooperate to accelerate tumorigenesis.
The CDKN2A/ARF locus encompasses overlapping tumor suppressor genes p16(INK4A) and p14(ARF), which are frequently co-deleted in human malignant mesothelioma (MM). The importance of p16(INK4A) loss in human cancer is well established, but the relative significance of p14(ARF) loss has been debated. The tumor predisposition of mice singly deficient for either Ink4a or Arf, due to targeting of exons 1α or 1β, respectively, supports the idea that both play significant and nonredundant roles in suppressing spontaneous tumors. To further test this notion, we exposed Ink4a(+/-) and Arf(+/-) mice to asbestos, the major cause of MM. Asbestos-treated Ink4a(+/-) and Arf(+/-) mice showed increased incidence and shorter latency of MM relative to wild-type littermates. MMs from Ink4a(+/-) mice exhibited biallelic inactivation of Ink4a, loss of Arf or p53 expression and frequent loss of p15(Ink4b). In contrast, MMs from Arf(+/-) mice exhibited loss of Arf expression, but did not require loss of Ink4a or Ink4b. Mice doubly deficient for Ink4a and Arf, due to deletion of Cdkn2a/Arf exon 2, showed accelerated asbestos-induced MM formation relative to mice deficient for Ink4a or Arf alone, and MMs exhibited biallelic loss of both tumor suppressor genes. The tumor suppressor function of Arf in MM was p53-independent, since MMs with loss of Arf retained functional p53. Collectively, these in vivo data indicate that both CDKN2A/ARF gene products suppress asbestos carcinogenicity. Furthermore, while inactivation of Arf appears to be crucial for MM pathogenesis, the inactivation of both p16(Ink4a) and p19(Arf) cooperate to accelerate asbestos-induced tumorigenesis.


Genome-wide DNA Methylation Analysis of Mantle Edge and Mantle Central from Pearl Oyster Pinctada fucata martensii.
DNA methylation is a type of epigenetic modification that alters gene expression without changing the DNA sequence and mediates some cases of phenotypic plasticity. In this study, we identified six DNA methyltransferase (DNMT) genes and two methyl-CpG binding domain protein2 (MBD2) gene from Pinctada fucata martensii. We also analyzed the genome-wide DNA methylation levels of mantle edge (ME) and mantle central (MC) from P. f. martensii via methylated immunoprecipitation sequencing (MeDIP-Seq). Results revealed that both ME and MC had 122 million reads, and had 58,702 and 55,721 peaks, respectively. The obtained methylation patterns of gene elements and repeats showed that the methylation of the protein-coding genes, particularly intron and coding exons (CDSs), was more frequent than that of other genomic elements in the pearl oyster genome. We combined the methylation data with the RNA-seq data of the ME and MC of P. f. martensii and found that promoter, CDS, and intron methylation levels were positively correlated with gene expression levels except the highest gene expression level. We also identified 313 differential methylation genes (DMGs) and annotated 212 of them. These DMGs were significantly enriched in 30 pathways, such as amino acid and protein metabolism, energy metabolism, terpenoid synthesis, and immune-related pathways. This study comprehensively analyzed the methylomes of biomineralization-related tissues and helped enhance our understanding of the regulatory mechanism underlying shell formation.


Eighteen-month follow-up of HIV-1-infected mothers and their children enrolled in the Kesho Bora study observational cohorts.
To assess the effectiveness and safety of antiretrovirals (ARVs) used for treatment or prophylaxis in a breastfeeding population of HIV-1-infected women (Burkina-Faso, Kenya, South Africa). HIV-1-infected pregnant women with <200 CD4 cells per cubic millimeter or with World Health Organization stage 4 disease (cohort A) and asymptomatic women with >500 CD4 cells per cubic millimeter (cohort B) were enrolled into 2 prospective cohorts. Women with 200-500 CD4 cells per cubic millimeter were enrolled in a parallel randomized trial. Women in cohort A initiated antiretroviral therapy. Women in cohort B received zidovudine from 34 to 36 weeks gestation until delivery, with single-dose nevirapine in labor (cohort B). All children received single-dose nevirapine. Of 248 women enrolled, 111 (cohort A) and 125 (cohort B) infants alive at 24 hours after birth were analyzed. Sixty-nine percent and 42% of women had undetectable viral load at delivery, respectively. Ten children in each cohort died. The 18-month cumulative incidences of HIV-1 infection were 7.5% (95% confidence interval: 3.8% to 14.5%) (cohort A) and 5.8% (2.8% to 11.8%) (cohort B). Sixty-one percent (cohort A) and 78% (cohort B) were breastfed for a median duration of 20 weeks. Four children in cohort A and only 1 in cohort B became HIV-1 infected after 6 weeks of age. Antiretroviral therapy initiated a median of 7 weeks before delivery in women with advanced HIV-1 disease was associated with a significant residual risk of HIV-1 transmission due to insufficient decrease in viral load by the time of delivery. Among women with >500 CD4 cells per cubic millimeter, the risk of breast-milk transmission was very low despite lack of postnatal prophylaxis.


Spatiotemporal Gait Analysis and Lower Limb Functioning in Foot Dystonia Treated with Botulinum Toxin.
Foot dystonia (FD) is a disabling condition causing pain, spasm and difficulty in walking. We treated fourteen (14) adult patients experiencing FD with onabotulinum toxin A injection into the dystonic foot muscles. We analyzed the spatiotemporal gait utilizing the GaitRite system pre- and 3 weeks post-botulinum toxin injection along with measuring dystonia by the Fahn⁻Marsden Dystonia Scale (FMDS), pain by the Visual Analog Scale (VAS) and other lower limb functional outcomes such as gait velocity, the Berg Balance Scale (BBS), the Unified Parkinson's Disease Rating Scale⁻Lower Limb Score (UPDRS⁻LL), the Timed Up and Go (TUG) test and the Goal Attainment Scale (GAS). We found that stride length increased significantly in both the affected (p = 0.02) and unaffected leg (p = 0.01) after treatment, and the improvement in stride length was roughly the same in each leg. Similar results were found for step length (p = 0.02) with improvement in the step length differential (p = 0.01). The improvements in the lower limb functional outcomes were also significant-FMDS, VAS, TUG, and UPDRS⁻LL decreased significantly after treatment (all p < 0.001), and BBS (p = 0.001), GAS (p < 0.001) except cadence (p = 0.37). BT injection improved walking in foot dystonia as evidenced through gait analysis, pain and lower limb functional outcomes. Main study limitations were small sample size and lack of control.


The mechanism of supraventricular tachycardia.
In six successive patients, none of whom had the Wolf-Parkinson-White syndrome, recurrent episodes of paroxysmal supraventricular tachycardia (SVT) were analyzed to determine the mechanism by which this arrhythmia is initiated and sustained. In each patient, simultaneous intracavitary atrial electrograms and surface electrocardiograms were recorded during the onset of numerous spontaneous episodes of SVT. Atrial premature depolarizations (APD) produced by programmed stimulation sequences were used to measure atrioventricular refractory periods and to produce atrial echoes and episodes of SVT. Stimulated APDs introduced during sustained episodes of SVT either altered its behavior or terminated it. The electrophysiologic behavior of SVT in these patients strongly suggests that the mechanism responsible for paroxysmal supraventricular tachycardia is atrial reentry utilizing the A-V conducting system.


Papillary thyroid carcinoma presenting as a lateral neck cyst.
Solitary lateral cervical cystic mass is an uncommon presentation of papillary thyroid carcinoma. To report our recent experience in the diagnosis and management of papillary thyroid carcinoma presenting as a lateral neck cyst. Patients who had papillary thyroid carcinoma and presented as a painless lateral neck cyst at the Department of Surgery, Al-Ain Hospital, from April 2005 to June 2009 were retrospectively studied. Their clinical presentation, diagnosis and management were reviewed. Five patients were studied. No thyroid nodules were clinically palpable in all patients. Fine needle aspiration cytology from the cyst was positive for papillary thyroid carcinoma in three patients (60 percent). Two patients were diagnosed after excisional biopsy. Three patients had total thyroidectomy with modified radical neck dissection and postoperative radioactive iodine ablation. Two patients preferred to travel overseas for treatment. Thyroid histopathological examination has shown papillary thyroid carcinoma in all operated patients with multiple microscopic foci in two of them. This was associated with multiple bilateral cervical lymph node involvement. Metastatic papillary thyroid carcinoma presenting as a neck cyst is a diagnostic challenge. Excisional biopsy is indicated if fine needle aspiration cytology was inconclusive so as to rule out malignancy.


Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach.
Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up-regulation of the executive network and a corresponding deficit in the down-regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may cast new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of relevance for diagnostics and new treatments.


Mulberry leaves extract ameliorates alcohol-induced liver damages through reduction of acetaldehyde toxicity and inhibition of apoptosis caused by oxidative stress signals.
Mulberry leaves (Morus alba L.), which are traditional Chinese herbs, exert several biological functions, such as antioxidant, anti-inflammation, antidiabetic, and antitumor. Alcohol intake increases inflammation and oxidative stress, and this increase causes liver injury and leads to liver steatosis, cirrhosis, and hepatocellular carcinoma, which are major health problems worldwide. Previous report indicated that mulberry leaf extract (MLE) exited hepatoprotection effects against chronic alcohol-induced liver damages. In this present study, we investigated the effects of MLE on acute alcohol and liver injury induced by its metabolized compound called acetaldehyde (ACE) by using in vivo and in vitro models. Administration of MLE reversed acute alcohol-induced liver damages, increased acetaldehyde (ACE) level, and decreased aldehyde dehydrogenase activity in a dose-dependent manner. Acute alcohol exposure-induced leukocyte infiltration and pro-inflammation factors, including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were blocked by MLE in proportion to MLE concentration. MLE prevented alcohol-induced liver apoptosis via enhanced caveolin-1 expression and attenuated EGFR/STAT3/iNOS pathway using immunohistochemical analysis. ACE induced proteins, such as iNOS, COX-2, TNF-α, and IL-6, and inhibited superoxide dismutase expression, whereas co-treated with MLE reversed these proteins expression. MLE also recovered alcohol-induced apoptosis in cultured Hep G2 cells. Overall, our findings indicated that MLE ameliorated acute alcohol-induced liver damages by reducing ACE toxicity and inhibiting apoptosis caused by oxidative stress signals. Our results implied that MLE might be a potential agent for treating alcohol liver disease.


Age-Related Trajectories of Memory Function in Middle-Aged and Older Adults with and without Hearing Impairment.
To examine age-related trajectories of memory function associated with hearing status and to explore potential confounding by sociodemographic, physiological, and behavioral factors in that link. A national representative sample of Taiwanese adults ≥50 years with and without hearing impairment in 1996 (n = 4,707) were interviewed every 3-4 years until 2007. Cross-sectional and prospective associations between hearing impairment and memory function were determined using multilevel modeling. In bivariate analyses, hearing impairment was associated not only with poor memory function but also with sociodemographic, behavioral and self-rated health status and chronic conditions. These factors, however, did not confound the relationship of hearing impairment with the level or rate of change in the modified Rey Auditory Verbal Learning Test (m-RAVLT) score - hearing impairment increased the age-related differences in the intercept of the memory function by 25.6%, and that the association was significantly greater in older people than in younger people, but hearing impairment was not associated with the slope of the cognitive trajectory over time. Hearing impairment and the m-RAVLT score at any point in time may have partially combined pathologic mechanisms with age. The vascular risk covariates we considered might also share the etiological pathways and be part of important prevention strategies for guarding against age-related memory decline in the future.


Algorithms for pharmacological treatment of personality dimensions: symptom-specific treatments for cognitive-perceptual, affective, and impulsive-behavioral dysregulation.
A pharmacological approach to treating patients with personality disorders (PD) is based on evidence that some dimensions of personality are mediated by variations in neurotransmitter physiology and are responsive to medication effects. Target symptoms for pharmacotherapy in the PD patient are derived from expressions of cognitive-perceptual, affective, and impulsive-behavioral dysregulation of central neurotransmitter functions. Pharmacotherapy is directed at state symptoms during periods of acute decompensation and at trait vulnerabilities, which represent the diathesis to future episodes. A basic assumption of this approach is that neurotransmitter biology transcends Axis I and Axis II definitions and that closely related symptoms may share a common pathophysiology, independent of categorical definition. A common pathophysiology implies the possibility of shared responsiveness to medication. Using a dimensional definition of symptom domains, the author has developed treatment algorithms for cognitive-perceptual symptoms, affective dysregulation, and impulsive-behavioral dyscontrol in personality disorder patients.


Effect of selected yogic practices on the management of hypertension.
On the basis of medical officers diagnosis, thirty three (N = 33) hypertensives, aged 35-65 years, from Govt. General Hospital, Pondicherry, were examined with four variables viz, systolic and diastolic blood pressure, pulse rate and body weight. The subjects were randomly assigned into three groups. The exp. group-I underwent selected yoga practices, exp. group-II received medical treatment by the physician of the said hospital and the control group did not participate in any of the treatment stimuli. Yoga imparted in the morning and in the evening with 1 hr/session. day-1 for a total period of 11-weeks. Medical treatment comprised drug intake every day for the whole experimental period. The result of pre-post test with ANCOVA revealed that both the treatment stimuli (i.e., yoga and drug) were effective in controlling the variables of hypertension.


Characterization of a class of cationic peptides able to facilitate efficient protein transduction in vitro and in vivo.
Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues. To determine whether cationic peptides are able to function as protein transduction domains, 12-mer peptide sequences from an M13 phage library were selected for synthesis on the basis of their varying cationic charge content. In addition, polylysine and polyarginine peptides were synthesized in order to assess the effect of charge contribution in protein transduction. Coupling of the biotinylated peptides to avidin-beta-galactosidase facilitated transduction in a wide variety of cell lines and primary cells, including islet beta-cells, synovial cells, polarized airway epithelial cells, dendritic cells, myoblasts, and tumor cells. Two of the peptides, PTD-4 and PTD-5, mediated transduction nearly 600-fold more efficiently than a random control peptide, but with an efficiency similar to the TAT PTD and the 12 mers of polylysine and polyarginine. Furthermore, confocal analysis of biotinylated peptide-streptavidin-Cy3 conjugates demonstrated that the internalized PTDs are found in both the nuclei and the cytoplasm of treated cells. When tested in vivo, the PTDs were able to facilitate efficient and rapid protein delivery into rabbit synovium and mouse solid tumors following intraarticular and intratumoral administration, respectively. These novel PTDs can be used to transfer therapeutic proteins and DNA for the treatment of a wide variety of diseases, including arthritis and cancer.


[Imported malaria in a general hospital in Madrid].
To study the clinical and epidemiological characteristics of malaria and the diagnosis of this condition in a general hospital that does not have a specialized tropical medicine unit. Retrospective study of all malaria cases diagnosed by thick film and/or PCR-positive status for any Plasmodium spp. from 1999 to 2003 in Hospital Príncipe de Asturias in Alcalá de Henares (Madrid, Spain). Over the period studied, 89 cases of malaria were diagnosed. Most patients were African immigrants who had recently left their countries of origin (52%), or immigrants residing in Spain who had traveled to Africa for a short visit (35%) and did not take prophylaxis. The distribution of cases by species was Plasmodium falciparum 89%, P. ovale 7% and P. malariae 4%. Clinical data were non-specific and the percentage of severe complications was low (6.7%). A second-generation test for rapid detection of P. falciparum antigen (PfHRP2) was studied in a group of 46 patients with suspected malaria; the results obtained were similar to thick film as compared to PCR for diagnosing P. falciparum infection. Access to information on prevention and chemoprophylaxis should be available to all travelers, particularly immigrants visiting their countries of origin. Most semi-immune patients with uncomplicated malaria can be treated on an outpatient basis. PfHRP2 antigen detection, a fast, reliable method for diagnosing malaria due to P. falciparum, can be used in addition to the thick film method in our setting.


The pseudotemporal bootstrap for predicting glaucoma from cross-sectional visual field data.
Progressive loss of the field of vision is characteristic of a number of eye diseases such as glaucoma, a leading cause of irreversible blindness in the world. Recently, there has been an explosion in the amount of data being stored on patients who suffer from visual deterioration, including visual field (VF) test, retinal image, and frequent intraocular pressure measurements. Like the progression of many biological and medical processes, VF progression is inherently temporal in nature. However, many datasets associated with the study of such processes are often cross sectional and the time dimension is not measured due to the expensive nature of such studies. In this paper, we address this issue by developing a method to build artificial time series, which we call pseudo time series from cross-sectional data. This involves building trajectories through all of the data that can then, in turn, be used to build temporal models for forecasting (which would otherwise be impossible without longitudinal data). Glaucoma, like many diseases, is a family of conditions and it is, therefore, likely that there will be a number of key trajectories that are important in understanding the disease. In order to deal with such situations, we extend the idea of pseudo time series by using resampling techniques to build multiple sequences prior to model building. This approach naturally handles outliers and multiple possible disease trajectories. We demonstrate some key properties of our approach on synthetic data and present very promising results on VF data for predicting glaucoma.


A substantial number of patients with rest pain, ulceration or gangrene are unable to undergo current non-invasive perfusion testing - could another modality be utilised?
Rest pain, ulceration, and gangrene are hallmark features of chronic limb-threatening ischaemia (CLTI). Wound healing can be challenging, and this is compounded by an inability to measure lower limb perfusion via non-invasive tools such as toe pressure (TP). Novel perfusion tests, such as pedal acceleration time (PAT), may overcome some limitations. This study aimed to quantify the proportion of patients with CLTI that were unable to undergo TP measurement. Over a three-year duration, 344 consecutive patients with CLTI underwent PAT assessment (403 limbs). Overall, 32% of limbs were unable to undergo first toe TP, and 12.9% were unable to undergo first and second toe TP due to forefoot/digit amputation or tissue loss. Inability to measure first toe TP disproportionately impacted CLTI patients with diabetes compared to patients without diabetes (39.6% limbs (106/268); vs 17% limbs (23/135); p<.001). Novel modalities may provide a useful tool for assessing perfusion in CLTI.


Attitudes and perceptions of internal medicine residents regarding pulmonary and critical care subspecialty training.
To evaluate the attitudes and perceptions of internal medicine residents regarding pulmonary and critical care medicine (PCCM) training. Prospective study. Three university hospitals. An eight-page survey was distributed and collected between March 1, 2002, and June 30, 2002. All internal medicine or internal medicine/pediatric residents training at the three institutions were eligible for the study. One hundred seventy-eight residents in internal medicine from an eligible pool of 297 residents returned the survey (61% response rate). PCCM accounted for only 3.4% of the career choices. Forty-one percent of the residents seriously considered a pulmonary and/or critical care fellowship during their residency. Of these residents, 23.5% found the combination of programs the more attractive option, while 2.8% found pulmonary alone and 14.5% found critical care alone more attractive. Key factors associated with a higher resident interest in PCCM subspecialty training included more weeks in the ICU (p = 0.008), more role models in PCCM (3.02 +/- 0.78 vs 3.45 +/- 0.78, p = 0.0004), and resident observations of a greater sense of satisfaction among PCCM faculty (3.07 +/- 0.82 vs 3.33 +/- 0.82, p = 0.04) and fellows (3.05 +/- 0.69 vs 3.31 +/- 0.86, p = 0.03) [mean +/- SD]. The five most commonly cited attributes of PCCM fellowship that would attract residents to the field included intellectual stimulation (69%), opportunities to manage critically ill patients (51%), application of complex physiologic principles (45%), number of procedures performed (31%), and academically challenging rounds (29%). The five most commonly cited attributes of PCCM that would dissuade residents from the field included overly demanding responsibilities with lack of leisure time (54%), stress among faculty and fellows (45%), management responsibilities for chronically ill patients (30%), poor match of career with resident personality (24%), and treatment of pulmonary diseases (16%). Internal medicine residents have serious reservations about PCCM as a career choice. Our survey demonstrated that a minority of US medical graduates actually would choose PCCM as a career, which suggests that efforts to expand PCCM training capacity might result in vacant fellowship slots. To promote greater interest in PCCM training, efforts are needed to improve the attractiveness of PCCM and address the negative lifestyle perceptions of residents.


Epidemiological aspects of Pediculosis capitis and treatment evaluation in primary-school children in Iran.
This study was undertaken to assess the prevalence of and epidemiological factors associated with, head lice infections in Iranian primary schools in 2006 and evaluate data on the therapeutic efficacy of lindane shampoo. A total of 40586 children (19774 boys (48.72%) and 20812 girls (51.28%)] from 198 Governmentprimary schools in Kerman, were screened for head lice between March and June 2006. The diagnosis of head lice infestation was confirmed by clinical inspection of scalp and hair for the presence of adult lice nymphal stage, or eggs (nit) by line-toothed head lice comb. All children infested with lice were treated with lindane shampoo (1% gamma benzene hexachloride). The overall prevalence of head lice infestation was 1.8%. The prevalence of infestation was significantly higher in girls (2.9%) than in boys (0.6%) (p = 0.000). The infestation rate was greater among pupils who were living in rural areas (4.6%) than in urban areas (1.5%). Of the 721 children with a positive examination result, 424 pupils (58.8%) were reported as having been infested with head lice in the previous 6 months. Mother's education level was a significant risk factor in this model (p < 0.05). At 2 weeks after the primary treatment, the success rates of treatment were 49%. Comprehensive survey in our work showed the better future of the disease and related factors. Education campaigns by health care officials, physicians and teachers are expected to be helpful for head lice control. It is essential that governments should be supported form cooperation between the school authorities and public health centers to successful control head lice infestation in primary school. Also there is an urgent need to identify safe, novel insecticides for proved efficacy.


[Effect of remifentanil on intraoperative ECoG--a comparison with sevoflurane].
In surgeries for epilepsy, electrocorticography (ECoG) enables tailored resection of the epileptogenic brain and pharmacological stimulation should be employed in surgeries under general anesthesia. To identify the efficacy of continuous remifentanil in surgeries for epilepsy, ECoG findings with remifentanil and those with sevoflurane were compared. Sixteen patients with intractable epilepsy were included with institutional ethics committee approval and informed consent. General anesthesia was induced and maintained with sevoflurane, remifentanil and rocuronium. After dural opening, ECoG recordings were obtained before stimulation, with sevoflurane-stimulation (ET-sevoflurane 2.5%) and with remifentanil-stimulation (0.7 microg x kg(-1) x min(-1) for 2 min followed by 0.35 microg x kg(-1) x min(-1)). In 11 of the 16 cases, activation was confirmed with remifentanil and numbers of spikes with remifentanil- and sevoflurane-stimulation were larger than those before stimulation. There have been some reports on bolus remifentanil on ECoG but not on its continuous infusion. This is the first report of the effect of remifentanil on ECoG as compared to sevoflurane. In this study, continuous infusion of remifentanil showed a stimulating effect on ECoG with the same potency as sevoflurane. Remifentanil may be used as an alternative to sevoflurane.


N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.
Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol contributes to endothelium-derived relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of the effects of nitroglycerin by N-acetylcysteine can be attributed to its enhanced biotransformation to an endothelium-derived relaxing factor equivalent, such as nitrosothiol. These observations support the notion of an equilibrium between nitric oxide and nitrosothiol in biological systems that may be influenced by redox state.


Innate immunity underlies symbiotic relationships.
Here, the modern data regarding interactions between normal microbiota and barrier tissues in plants, humans and animals are reviewed. The main homeostatic mechanisms responsible for interactions between epithelium and innate immune cells with symbiotic bacteria are described. A key step in this process is recognition of soluble microbial products by ligation to pattern-recognition receptors expressed on the host cells. As a result, epithelial cells secrete mucus, antibacterial peptides and immunoregulatory molecules. The main outcomes from immunological reactions towards symbiotic bacteria involve development of conditions for formation and maintenance of microbial biocenosis as well as providing safety for the host. Also, it is considered important to preserve and transfer beneficial bacteria to progeny.


Implicit auditory perception of local and global irregularities in passive listening condition.
The auditory system detects differences in sounds at an implicit level, but data on this difference might not be sufficient to make explicit discrimination. The biomarkers of implicit auditory memory of ambiguous stimuli could shed light on unconscious auditory processing and implicit auditory learning. Mismatch negativity (MMN) and P3a, components of event-related potentials (ERPs) reflecting stimuli discrimination without direct attention, were previously detected in response to the local (short-term) irregularity in the auditory sequence even in an unconscious state. At the same time, P3b was elicited only in case of direct attention in response to the global (long-term) irregularity. In this study, we applied the local-global auditory paradigm to obtain possible electrophysiological signatures of implicit detection of hardly distinguishable auditory stimuli. ERPs were recorded from 20 healthy volunteers during active discrimination of deviant sounds in the old-ball sequence and passive listening of the same sounds in the sequence with local-global irregularity. The discrimination task consisted of two blocks with different deviant sounds targeted to respond. The sound discrimination accuracy was at an average of 40%, implying the difficulty of explicit sound recognition. Comparing ERPs to standard and deviant sounds, we found posterior negativity in ERP around 450-600 ms in response to targeted deviant sounds. MMN was significant only in response to non-target deviants. In the passive local-global paradigm, we observed an anterior positivity (284-412 ms), compatible with P3a, in response to a violation of local regularity. Violation of global regularity elicited an anterior negative response (228-586 ms), resembling the N400 component of ERPs. Importantly, the other indexes of auditory discrimination, such as MMN and P3b, were insignificant in ERPs to both regularity violations. The observed P3a and N400 components of ERPs may reflect prediction error signals in the implicit perception of sound patterns even if behavioral recognition was poor.


Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo.
Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains. A new ELP nanoparticle (ISR) was synthesized that includes the canonical integrin-targeting ligand (Arg-Gly-Asp, RGD). FSI and ISR mixed in a 1:1 molar ratio coassemble into bifunctional nanoparticles containing both the FKBP domain for Rapa loading and the RGD ligand for integrin binding. Coassembled nanoparticles were evaluated for bifunctionality by performing in vitro cell-binding and drug-retention assays and in vivo MDA-MB-468 breast tumor regression and tumor-accumulation studies. The bifunctional nanoparticle demonstrated superior cell target binding and similar drug retention to FSI; however, it enhanced the formulation potency, such that tumor growth was suppressed at a 3-fold lower dose compared to an untargeted FSI-Rapa control. This data suggests that ELP-mediated scaffolds are useful tools for generating multifunctional nanomedicines with potential activity in cancer.


An Examination of Whether Diabetes Control and Treatments Are Associated With Change in Frailty Index Across 8 Years: An Ancillary Exploratory Study From the Action for Health in Diabetes (Look AHEAD) Trial.
The aim of this study was to describe cross-sectional and longitudinal associations between glycated hemoglobin (HbA1c) levels and strategies to control type 2 diabetes with baseline levels and 8-year changes in a deficit accumulation frailty index (FI), a commonly used marker of biological aging. We conducted exploratory analyses from 4,169 participants, aged 45-76 years, who were followed in the Action for Health in Diabetes (Look AHEAD) randomized controlled clinical trial, pooling data across intervention groups. We related baseline and 8-year levels of HbA1c with FI scores using analyses of variance and covariance. Associations between 8-year changes in FI and the use of diabetes medication classes and weight changes were assessed with control for HbA1c levels. Inverse probability weighting was used to assess bias associated with differential follow-up. Baseline and average HbA1c levels over time of <7%, as compared with ≥8%, were associated with less increase in FI scores over 8 years (both P ≤ 0.002). After adjustment for HbA1c, use of metformin and weight loss >5% were independently associated with slower increases in frailty. Lower HbA1c levels among individuals with diabetes are associated with slower biological aging as captured by a deficit accumulation FI. Strategies to control diabetes through weight loss or metformin use may also slow aging.


Pharmacokinetics of recombinant human leukemia inhibitory factor in sheep.
The pharmacokinetics of recombinant human leukemia inhibitory factor (rhLIF) were investigated following i.v. and s.c. administration of a wide range of dose levels. Parallel studies were conducted where single i.v. bolus doses of 12.5, 25, 100, 250, 500, or 750 microg/kg rhLIF (n = 2) or s.c. doses of 10, 20, or 50 microg/kg rhLIF (n = 4) were administered to sheep. Blood samples were collected for up to 24 h postdosing, and the plasma concentrations of rhLIF were analyzed by enzyme-linked immunosorbent assay. Noncompartmental analysis demonstrated an increase in the terminal elimination half-life (from 0.27 to 2.29 h) and a decrease in systemic clearance (from 5.18 to 1.09 ml/min/kg) with increasing i.v. doses of rhLIF, suggesting nonlinear pharmacokinetic behavior. A greater than proportional increase in the area under the plasma concentration-time curve with dose also indicated significantly nonlinear pharmacokinetics after s.c. administration. A mechanistic compartmental model was developed to characterize the pharmacokinetics of rhLIF. The key feature of the model accounting for the nonlinear pharmacokinetic behavior of rhLIF was high-affinity, saturable receptor binding and subsequent cellular internalization and degradation. The apparent total density of LIF cell surface receptors and receptor turnover dynamics were included in the model, along with nonspecific binding and linear elimination from the systemic circulation. The absorption of rhLIF from the s.c. injection site into the systemic circulation was characterized by a first-order absorption process via a delay compartment. The proposed model satisfactorily captured the complex pharmacokinetic profiles of rhLIF following both i.v. and s.c. administration.


Measuring Effects of Spatial Visualization and Domain on Visualization Task Performance: A Comparative Study.
Understanding one's audience is foundational to creating high impact visualization designs. However, individual differences and cognitive abilities influence interactions with information visualization. Different user needs and abilities suggest that an individual's background could influence cognitive performance and interactions with visuals in a systematic way. This study builds on current research in domain-specific visualization and cognition to address if domain and spatial visualization ability combine to affect performance on information visualization tasks. We measure spatial visualization and visual task performance between those with tertiary education and professional profile in business, law & political science, and math & computer science. We conducted an online study with 90 participants using an established psychometric test to assess spatial visualization ability, and bar chart layouts rotated along Cartesian and polar coordinates to assess performance on spatially rotated data. Accuracy and response times varied with domain across chart types and task difficulty. We found that accuracy and time correlate with spatial visualization level, and education in math & computer science can indicate higher spatial visualization. Additionally, we found that motivational differences between domains could contribute to increased levels of accuracy. Our findings indicate discipline not only affects user needs and interactions with data visualization, but also cognitive traits. Our results can advance inclusive practices in visualization design and add to knowledge in domain-specific visual research that can empower designers across disciplines to create effective visualizations.


MicroRNAs in the Vitreous Humor of Patients with Retinal Detachment and a Different Grading of Proliferative Vitreoretinopathy: A Pilot Study.
Although the expression of microRNAs (miRNAs) in retinal pigment epithelial (RPE) cells undergoing epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of proliferative vitreoretinopathy (PVR), its expression in the vitreous of patients with primary retinal detachment (RD) and different PVR grading has not yet been investigated. We assessed the expression of miRNAs in the vitreous humor (VH) of patients diagnosed with RD and different grading of PVR. The VH was extracted from the core of the vitreous chamber in patients who had undergone standard vitrectomy for primary RD. RNA was extracted and TaqMan Low-Density Arrays (TLDAs) were used for miRNA profiling that was performed by single TaqMan assays. A gene ontology (GO) analysis was performed on the differentially expressed miRNAs. A total of 15 eyes with RD, 3 eyes for each grade of PVR (A, B, C, and D) and 3 from unaffected individuals, were enrolled in this prospective comparative study. Twenty miRNAs were altered in the comparison among pathological groups. Interestingly, the expression of miR-143-3p, miR-224-5p, miR-361-5p, miR-452-5p, miR-486-3p, and miR-891a-5p increased with the worsening of PVR grading. We also identified 34 miRNAs showing differential expression in PVR compared to control vitreous samples. GO analysis showed that the deregulated miRNAs participate in processes previously associated with PVR pathogenesis. The present pilot study suggested that dysregulated vitreal miRNAs may be considered as a biomarker of PVR and associated with the PVR-related complications in patients with RD. The correlation between vitreal miRNAs and the pathological phenotypes are essential to identify the novel miRNA-based mechanisms underlying the PVR disease that would improve the diagnosis and treatment of the condition.


Expression of calsenilin in neurons and astrocytes in the Alzheimer's disease brain.
Calsenilin, a multifunctional Ca2+-binding protein, has been identified as an Alzheimer's disease-associated presenilin interactor. Here, we investigated the histochemical localization of calsenilin and its expression levels in the brains of sporadic Alzheimer's disease. Both messenger RNA and protein expression of calsenilin were observed in neurons of the cerebral cortex and hippocampus of control brains, and more intense staining was in Alzheimer's disease brains. Although calsenilin is primarily expressed in neurons, its immunoreactivity was also detected in reactive astrocytes of the Alzheimer's disease brains. In Alzheimer's disease brains, the caspase-derived fragment of calsenilin was only detected in cytosolic fraction. Our findings suggest that calsenilin overexpression in both neurons and reactive astrocytes may play an important role in apoptosis and in Alzheimer's disease pathology.


Role of albumin-induced volume expansion therapy for cerebral vasospasm in aneurysmal subarachnoid hemorrhage: A systematic review.
This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). Computer searches carried out from the Scopus, Medline, Embase, Web of Science, the Cochrane Library, and Internet documents; hand searching of medical journals; and review of reference lists. Randomized controlled trials (RCT) and observational studies (OSs) comparing albumin therapy in combination or alone with crystalloid therapy for the treatment of cerebral vasospasm in aSAH were included in the study. Risk-of-bias assessment was conducted using ROB2.0 and ROBINS-I tools for RCTs and Oss, respectively. Out of a total of 1078 searches, one RCT (published in two articles) and one observational (retrospective) study were included for final analysis. In RCT, albumin was used for volume expansion therapy with a baseline crystalloid regime and comparison made between hypervolemic and normovolemic groups and it showed no beneficial effects on symptomatic vasospasm and clinical outcomes based on the Glasgow outcome scale. Furthermore, the use of albumin showed a tendency for sodium retention with lowering of glomerular filtration rate, limiting the amount of total fluid required for targeted central venous pressure values, and thereby avoiding fluid overload manifestations. The retrospective study results between albumin versus non-albumin groups (crystalloids only) supported improved outcomes in the former group with lower in-hospital mortality. Cardiorespiratory complications were equivocal in RCT and increased in non-albumin group in the retrospective study. Risk-of-bias assessment analyses revealed "some concerns" in RCT and "serious" limitation in OS due to its retrospective design. Albumin-induced volume expansion therapy for cerebral vasospasm does not have substantiative evidence to improve cerebral vasospasm and clinical outcomes in aSAH. Studies with well-designed RCTs are required to compare the use of albumin for volume expansion therapy versus standard fluid management using crystalloids to mitigate the scarcity of published data.


Reproduction of postweaning multisystemic wasting syndrome in pigs experimentally inoculated with a Swedish porcine circovirus 2 isolate.
In recent years, porcine circovirus type 2 (PCV2)-associated postweaning multisystemic wasting syndrome (PMWS) has been reported worldwide. However, to date, PMWS has not been reported in Sweden despite the demonstration of serum antibodies to a PCV2-like virus in Swedish pigs. This communication reports the experimental reproduction of clinical PMWS after inoculation of colostrum-deprived (CD) pigs, derived from a Northern Ireland herd, with an isolate of PCV2 virus recovered from a clinically normal Swedish pig that was necropsied in 1993. The clinical disease and histological lesions observed in CD pigs inoculated with this virus were indistinguishable from those observed in previous studies on CD pigs inoculated with a PCV2 virus isolate recovered from pigs with PMWS. These results highlight the disease potential of PCV2 isolated from regions apparently free of PMWS and suggest that the status of the host and its environment is an important factor in the development of clinical PMWS.


Construction and Cloning of Plastic-degrading Recombinant Enzymes (MHETase).
Polyethylene terephthalate (PET) is the most widely produced polyester plastic in the world. PET is very difficult to catalyze or biological depolymerization due to the limited access to ester bonds. Consequently, plastic will be stockpiled or flowed into the environment which is projected until hundreds of years. The most effective and environmental friendly plastic degradation method is biodegradation with microorganisms. Two specific enzyme for PET hydrolase, PETase and MHETase have been identified from Ideonella sakaiensis 201-F6. Recombinant genes are made to increase the effectiveness of enzymes in degrading PET. Previous studies of the PETase gene have been carried out, but to produce the final degradation PET product, the enzyme MHETase is needed. Thus, in this study the MHETase gene construction was carried out. The goal of this study is to construct MHETase gene in pUCIDT plasmid with native signal peptide from I. sakaensis 201-F6 and constitutive promoter J23106 was expressed in Escherichia coli BL21 (DE3) by heats shock. Expression analysis using SDS-PAGE and activity of enzyme is analyzed by spectrophotometry method and SEM. MHETase gene protein was successfully constructed in pUCIDT +Amp plasmid with native signal peptide from Ideonella sakaensis 201-F6, T7 terminator and constitutive promoter J23106. PCR analysis showed that the gene successfully contained in the cells by band size (1813 bp) in electrophoresis gel. Analysis using Snap Gene, pairwise alignment using MEGA X, and NCBI was demonstrated that MHETase sequence the gene was in-frame in pUCIDT plasmid. MHETase gene was successfully constructed in plasmids by in silico method. Synthetic plasmids transformed in E. coli BL21 (DE3) contain MHETase gene sequences which were in frame. Hence, the E. coli BL21 (DE3) cells have the potential to produce MHETase proteins for the plastic degradation testing process. We will patent the construct of MHETase gene using constitutive promoter and signal peptide from native which expressed in E. coli BL21 (DE3). This patent refers to a more applicable plastic degradation system with a whole cell without the need for purification and environmental conditioning of pure enzymes.


Properties of avian retrovirus particles defective in viral protease.
The structural and enzymatic components of retroviral cores are formed by proteolytic cleavage of precursor polypeptides, mediated by the viral protease (PR). We constructed an active-site mutation, D37I, in the PR of avian leukosis virus. The D37I mutation was introduced into an infectious DNA clone, and quail cell lines expressing the mutant virus were established. These cell lines produce normal amounts of virus particles, the major internal protein components of which are the uncleaved gag and gag-pol precursors. As in other retroviral systems, the protease-defective virions are noninfectious and retain the "immature" type A morphology as determined by thin-section transmission electron microscopy. The virion cores are stable at nonionic detergent concentrations that completely disrupt wild-type cores. Digestion of mutant virions with exogenous PR in the presence of detergent leads to complete and correct cleavage of the gag precursor but incomplete cleavage of the gag-pol precursor. The protease-defective virions encapsidate normal amounts of genomic RNA and tRNA(Trp) that is properly annealed to the primer-binding site, but some of the genomic RNA remains monomeric. Results from UV cross-linking experiments show that the gag polyprotein of mutant virions interacts with viral RNA and that this interaction occurs through the nucleocapsid (NC) domain. However, within mutant virions the interaction of the NC domain with RNA differs from that of mature NC with RNA in wild-type virions. Reverse transcriptase (RT) activity associated with mutant virions is diminished but still detectable. Digestion of the virions with PR leads to a fivefold increase in activity, but this PR-mediated activation of RT is incomplete. Since in vitro cleavage of the gag-pol precursor is also incomplete, we hypothesize that amino acid sequences N terminal to the reverse transcriptase domain inhibit RT activity.


Larval tick infestation: a case report and review of tick-borne disease.
Tick-borne disease in the United States continues to be a threat as people interact with their natural surroundings. We present a case of an 8-year-old boy with a larval tick infestation. Ticks within the United States can carry Lyme disease, Rocky Mountain spotted fever (RMSF), ehrlichiosis, babesiosis, tularemia, tick-borne relapsing fever, and tick paralysis. These preventable diseases are treatable when accurately recognized and diagnosed; however, if left untreated, they can cause substantial morbidity and mortality. This article highlights the knowledge necessary to recognize, treat, and prevent tickborne disease.


Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy.
Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding a specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin, and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ∼70-nm-resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, a process that previously required electron microscopy, and we demonstrate high-fidelity computational discrimination between early breast neoplastic lesions for which pathologists often disagree in classification. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.