SMAC is expressed de novo in a subset of cervical cancer tumors.
Smac/Diablo is a recently identified protein that is released from mitochondria after apoptotic stimuli. It binds IAPs, allowing caspase activation and cell death. In view of its activity it might participate in carcinogenesis. In the present study, we analyzed Smac expression in a panel of cervical cancer patients. We performed semi quantitative RT-PCR on 41 cervical tumor and 6 normal tissue samples. The study included 8 stage I cases; 16 stage II; 17 stage III; and a control group of 6 samples of normal cervical squamous epithelial tissue. Smac mRNA expression was below the detection limit in the normal cervical tissue samples. In contrast, 13 (31.7%) of the 41 cervical cancer biopsies showed detectable levels of this transcript. The samples expressing Smac were distributed equally among the stages (5 in stage I, 4 in stage II and 4 in stage III) with similar expression levels. We found no correlation between the presence of Smac mRNA and histology, menopause, WHO stage or disease status. Smac is expressed de novo in a subset of cervical cancer patients, reflecting a possible heterogeneity in the pathways leading to cervical cancer. There was no correlation with any clinical variable.


Applying Heart Failure Management to Improve Health Outcomes: But WHICH One?
We report on our learning from many years of research testing the value of nurse-led, multidisciplinary, home-based management of heart failure. We discuss and highlight the key challenges we have experienced in testing this model of care relative to alternatives and evolving patient population. Accordingly, we propose a pragmatic approach to adapt current models of care to meet the needs of increasingly complex (and costly) patients with multimorbidity.


Socioeconomic Inequalities in COVID-19 Incidence During Different Epidemic Phases in South Korea.
Area-level socioeconomic status (SES) is associated with coronavirus disease 2019 (COVID-19) incidence. However, the underlying mechanism of the association is context-specific, and the choice of measure is still important. We aimed to evaluate the socioeconomic gradient regarding COVID-19 incidence in Korea based on several area-level SES measures. COVID-19 incidence and area-level SES measures across 229 Korean municipalities were derived from various administrative regional data collected between 2015 and 2020. The Bayesian negative binomial model with a spatial autocorrelation term was used to estimate the incidence rate ratio (IRR) and relative index of inequality (RII) of each SES factor, with adjustment for covariates. The magnitude of association was compared between two epidemic phases: a low phase (<100 daily cases, from May 6 to August 14, 2020) and a rebound phase (>100 daily cases, from August 15 to December 31, 2020). Area-level socioeconomic inequalities in COVID-19 incidence between the most disadvantaged region and the least disadvantaged region were observed for nonemployment rates [RII = 1.40, 95% credible interval (Crl) = 1.01-1.95] and basic livelihood security recipients (RII = 2.66, 95% Crl = 1.12-5.97), but were not observed for other measures in the low phase. However, the magnitude of the inequalities of these SES variables diminished in the rebound phase. A higher area-level mobility showed a higher risk of COVID-19 incidence in both the low (IRR = 1.67, 95% Crl = 1.26-2.17) and rebound phases (IRR = 1.28, 95% Crl = 1.14-1.44). When SES and mobility measures were simultaneously adjusted, the association of SES with COVID-19 incidence remained significant but only in the low phase, indicating they were mutually independent in the low phase. The level of basic livelihood benefit recipients and nonemployment rate showed social stratification of COVID-19 incidence in Korea. Explanation of area-level inequalities in COVID-19 incidence may not be derived only from mobility differences in Korea but, instead, from the country's own context.


A model for successful nursing home-hospice partnerships.
While benefits of hospice care in nursing homes have been documented, interorganizational challenges such as staff conflicts regarding planned care or their respective roles have also been documented. Through case studies, this research aimed to characterize the partnerships of successful nursing home-hospice collaborators. Six nursing homes and hospices with self-identified successful collaborations were studied. Interviews of care providers and chief executive and financial officers collected information on practices relating to seven domains identified as critical to the collaboration. The organizational factors and activities relating to infrastructure development and care collaboration and provision most common across sites were identified. Nursing home-hospice collaborators were philosophically and otherwise aligned; they had similar missions, understood their differing approaches to care, and administrators demonstrated an openness and support for the collaboration. Hospices developed infrastructures to correspond to the uniqueness and complexity of the nursing home environment. For example, they hired nurses with nursing home backgrounds, created teams dedicated to nursing home care, and trained hospice staff in problem solving and conflict resolution. Care collaboration processes focused on the importance of two-way communication by actively soliciting and sharing information with nursing home staff and responding to nursing home staff and administrators' concerns. While successful collaborators were organizational aligned, hospice leaders' acknowledgement that palliative care provision in nursing homes is complex and unique was important to success. Accordingly, the prevalent partnership model was a product of strategic efforts by leaders aimed at matching their staffing to the nursing home environment and promoting good communication and skills needed for problem solving.


Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression.
This study aimed to investigate prospective memory impairment in patients with breast cancer with different expression of hormone receptors, including the estrogen receptor (ER) and the progesterone receptor (PR).A total of 120 patients with breast cancer who underwent chemotherapy following surgery were divided into 2 groups. The A group included 60 patients with ER/PR status, and the B group included 60 patients with ER/PR status. After 6 cycles of postoperative adjuvant chemotherapy, all patients were administered neuropsychological and prospective memory tests, such as the Mini-Mental State Examination (MMSE), verbal fluency test (VFT), and digit span test (DST), as well as examination of event-based prospective memory (EBPM) and time-based prospective memory (TBPM).As the neuropsychological background test results showed, there were no significant differences in MMSE, DST, and TBPM scores (*:P > 0.05) between patients with breast cancer in the ER/PR and ER/PR groups, while the VFT and EBPM scores were significantly greater in patients with breast cancer with ER/PR status than in those with ER/PR status (**: P < 0.01), indicating that patients with ER/PR status have significant impairment in EBPM, although not in TBPM.The results of the present study indicate that different hormone receptor expression in patients with breast cancer may be associated with heterogeneity of chemotherapy-induced prospective memory impairment.


Rationale and design of combination of an immune modulator Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) trial.
Rationale In acute ischemic stroke patients with large vessel occlusion, although reperfusion within 6 h after stroke onset using combined intravenous alteplase and mechanical thrombectomy (bridging therapy) can improve functional outcome, still approximately 50% patients suffer disability which may result from reperfusion injury. Proof-of-concept clinical trials have indicated that the sphingosine-1-phosphate receptor modulator fingolimod may be efficacious in attenuating brain inflammation and improving clinical outcomes in acute ischemic stroke patients as a single therapy beyond 4.5 h of disease onset, or in combination with alteplase within 4.5 h of disease onset. Aim To assess whether the treatment of fingolimod combined with bridging therapy in large vessel occlusion acute ischemic stroke patients is effective and safe. Design and sample size estimates Fingolimod with Alteplase bridging with Mechanical Thrombectomy in Acute Ischemic Stroke (FAMTAIS) study is a randomized, open-label, multiple central trial. This study includes 98 patients with anterior circulation large vessel occlusion acute ischemic stroke who are eligible for bridging therapy, providing 80% power to reject the null hypothesis that, combined with fingolimod, the bridging therapy has an at least 15% higher penumbra tissue salvage index than receiving bridging therapy alone. Study outcomes The primary outcome is the penumbra tissue salvage index. Key secondary outcomes focus on: infarct growth and extent of clinical improvement from day 1 to day 7, frequency of parenchymal hemorrhage at day 1. Discussion If the hypothesis of FAMTAIS is confirmed, combination of fingolimod with bridging therapy is effective in attenuating reperfusion injury in patients with large vessel occlusion treated with 6 h of stroke onset.


[The messenger syndrome].
Since mid 2005 pediatricians of the Groupe hospitalier Sud Reunion de Saint-Pierre have observed a self-imposed requirement to test for mother-to-child transmission of chikungunya. Sanitary authorities refuse to consider such testing as necessary. The risk of mother-to-child transmission was not mentioned in literature of the time.


Tobacco TTG2 regulates vegetative growth and seed production via the predominant role of ARF8 in cooperation with ARF17 and ARF19.
Plant TRANSPARENT TESTA GLABRA (TTG) proteins regulate various developmental activities via the auxin signaling pathway. Recently, we elucidated the developmental role of tobacco (Nicotiana tabacum L.) NtTTG2 in association with 12 genes that putatively encode AUXIN RESPONSIVE FACTOR (ARF) proteins, including NtARF8, NtARF17, and NtARF19. Here we show that NtTTG2 regulates tobacco growth and development by involving the NtARF8, NtARF17, and NtARF19 genes, with the NtARF8 gene playing a predominant contribution. Independent silencing of the NtARF8 gene more strongly repressed tobacco growth than silencing the NtARF17 or NtARF19 gene and more effectively eradicated the growth enhancement effect of NtTTG2 overexpression. In contrast, plant growth was not affected by silencing additional nine NtTTG2-regulated NtARF genes. In double and triple gene silencing combinations, silencing the NtARF8 gene was more effective than silencing the NtARF17 or NtARF19 gene to repress growth as well as nullify growth enhancement. Therefore, the NtARF8 predominantly cooperated with the NtARF17 and NtAFR19 of the NtTTG2 functional pathway. NtARF8 also contributed to NtTTG2-regulated seed production as concurrent NtTTG2 and NtARF8 overexpression played a synergistic role in seed production quantity, whereas concurrent silencing of both genes caused more severe seed abortion than single gene silencing. In plant cells, the NtTTG2 protein facilitated the nuclear import of NtARF8 as well as increased its function as a transcription activator. NtARF8 is an integral component of the NtTTG2 functional pathway, which regulates tobacco growth and development.


Perception of nurses who perform rapid tests in Health Centers.
Learn about the perception of health professionals who perform rapid tests in Health Centers (HCs). This is a descriptive and qualitative study conducted in nine HCs in Recife. Data were collected through individual interviews and evaluated using Bardin's content analysis, in its thematic category. Challenges were observed in rapid tests related to the supply of products, physical structure, training for pre- and post-test counseling, and the need for improvements in permanent education actions. These issues can be resolved with management improvements, systematization of permanent education activities, and definition of care flows that enable early diagnosis. Besides the diagnosis, care lines should be created for people living with HIV and AIDS who use the HCs for early health care process.


Effects of chronic testosterone administration on the degree of preference for a high-fat diet and body weight in gonadal-intact and ovariectomized female rats.
Energy balance and reproductive functions are closely linked in some species. The sex hormones (estrogens and androgens) are involved in the regulation of appetite, metabolism, body weight (BW), and body composition in mammals. Previously, we showed that the effects of testosterone on BW, appetite, and fat weight were markedly affected by alterations to the gonadal hormonal milieu. In this study, we examined whether testosterone administration changes food preferences and whether these effects of testosterone depend on gonadal status in female rats. We also evaluated the underlying mechanisms responsible for these effects, focusing on hypothalamic inflammation and endoplasmic reticulum (ER) stress. In gonadal-intact (sham) female rats, chronic testosterone administration promoted a preference for a high-fat diet (HFD) and increased BW gain, fat weight, and adipocyte size, whereas no such effects were observed in ovariectomized (OVX) rats. Testosterone administration increased hypothalamic interleukin-1 mRNA expression in the sham rats, but not the OVX rats. On the contrary, testosterone administration decreased the hypothalamic mRNA levels of ER stress-response genes in the OVX rats, but not the sham rats. These testosterone-induced alterations in OVX rats might represent a regulatory mechanism for preventing hypothalamic inflammation and the overconsumption of a HFD. In conclusion, testosterone's effects on food preferences and the subsequent changes were affected by gonadal status. Testosterone-induced changes in hypothalamic inflammatory cytokine production and ER stress might be related to these findings.


Permeability of the peroxisomal membrane to cofactors of beta-oxidation. Evidence for the presence of a pore-forming protein.
Peroxisomes were purified from livers of clofibrate-treated rats. Permeability measurements on the isolated organelles revealed that peroxisomes are permeable to small solutes, including sucrose and the cofactors for fatty acid oxidation NAD+, CoA, ATP, and carnitine. The intraperoxisomal distribution volume was equal for all solutes. Peroxisomal solute uptake was rapid, not saturable and not visibly influenced by temperature. NAD+ and carnitine uptake in the solute accessible volume was not diminished by a variety of analogs and inhibitors. Subfractionation of peroxisomes and reconstitution of the subfractions into liposomes preloaded with solutes made the liposomes reconstituted with the integral membrane protein fraction, but not those reconstituted with the other subperoxisomal protein fractions, permeable to the same solutes that entered intact peroxisomes. Solute leakage from the preloaded liposomes was rapid and not visibly influenced by temperature. Leakage activity was destroyed by heat treatment of the integral membrane protein fraction and was not present in lipid extracts of the membrane. Separation of the integral membrane proteins on sucrose density gradients and reconstitution of the gradient fractions into liposomes indicated that the leakage activity was caused by a polypeptide of rather low molecular weight. The gradient distribution of leakage activity corresponded most closely to the presence of a 22- and a 28-kDa polypeptide. Our experiments indicate that the nonspecific permeability of the peroxisomal membrane to small solutes is based on the presence in the membrane of a nonselective pore-forming protein.


Nestling activity levels during begging behaviour predicts activity level and body mass in adulthood.
Across a range of species including humans, personality traits, or differences in behaviour between individuals that are consistent over time, have been demonstrated. However, few studies have measured whether these consistent differences are evident in very young animals, and whether they persist over an individual's entire lifespan. Here we investigated the begging behaviour of very young cross-fostered zebra finch nestlings and the relationship between that and adult activity levels. We found a link between the nestling activity behaviour head movements during begging, measured at just five and seven days after hatching, and adult activity levels, measured when individuals were between three and three and a half years old. Moreover, body mass was found to be negatively correlated with both nestling and adult activity levels, suggesting that individuals which carry less body fat as adults are less active both as adults and during begging as nestlings. Our work suggests that the personality traits identified here in both very young nestlings and adults may be linked to physiological factors such as metabolism or environmental sources of variation. Moreover, our work suggests it may be possible to predict an individual's future adult personality at a very young age, opening up new avenues for future work to explore the relationship between personality and a number of aspects of individual life history and survival.


Quality improvement learning collaboratives.
To identify and synthesize characteristics of successful data-driven Quality improvement learning collaboratives (QILCs) in the United States and Europe, and to extend previously discussed and newly identified guidelines for developing successful data-driven QILCs across health care settings and systems. An interview guide of open-ended questions was developed and posed to 18 key informants of various disciplines involved in the development and implementation of successful QILCs across 10 organizations in 3 countries. Aspects of successful QILCs were analyzed to identify patterns emerging from structure-process interactions between complex health care systems. Shared patterns of successful collaboratives included cultivating trust, attendance to the human dimension, nonlinear development, attendance to organizational culture, integrated philosophy of quality improvement, and a focus on process and outcome measurement to drive change. This study extends the knowledge base through synthesis of findings from previous quality improvement research with the findings from this study to develop guidelines for establishing and developing successful QILCs. The core characteristics identified in this study were critical to successful collaboration when these approaches were used in the contexts identified. The intrinsic complexity of QILCs requires that effectiveness studies employ qualitative as well as quantitative methodologies.


[Hepatobiliary scintigraphy in the diagnosis of common bile duct cysts in children].
A cyst of the common bile duct, the most frequent variant of cystic dilatation of the extrahepatic biliary tract, presents a serious diagnostic problem. Using serial scintigraphy with 99mTc-HIDA 13 children with cysts of the common bile duct confirmed by the results of operative cholangiography, were examined. In 8 of them a radionuclide study was performed at varying times after operation (cyst extirpation with the establishing of hepatoenteroanastomosis--4 patients, and variants of internal drainage operations--4 patients). Typical scintigraphic signs were the following: sacculated or spheroidal dilatation of the common bile duct in combination with dilatation of the left (7), right (1) or both lobular bile ducts, absence of the gall bladder visualization. In the first 15 min of examination in large size cysts zones of the lowered accumulation of the radiopharmaceutical agent were revealed in the area of the portal fissure. Indicators of absorptive-excretory hepatic function changed mainly in children with spheroid-shaped cysts demonstrating alongside with the time of intestinal visualization the degree of disorder of permeability of the choledoch distal parts. The recovery of the anatomic-functional state of the biliferous system occurred earlier (up to 1.5 year) in children after cyst extirpation than after internal drainage operations. It manifested itself in returning the diameter of the bile ducts to normal and in the improvement of absorptive-excretory hepatic function.


Cough in spinal cord injured patients: the relationship between motor level and peak expiratory flow.
Pulmonary complications remain a major cause of morbidity and mortality in patients with higher level spinal cord injury. Neurologically intact individuals can cough in order to clear their air passage of lung secretions and foreign material. Patients with higher level cord injuries, with paralysis of the trunk and abdominal muscles, may not have the ability to generate an effective cough. If coughing is dependent on a caregiver, these patients will cough with reduced frequency. Because the innervation to the muscles involved in cough consists of nerves that arise from varying levels of the spinal cord, some patients with spinal cord injury have partial control over these muscles and thus can cough, though with reduced efficacy. Two hundred patients with varying levels of spinal cord injury were studied to determine if motor level and cough ability are correlated. Cough efficacy was measured using a peak expiratory flowmeter while patients were seated at 90 degrees. We concluded that there is indeed a direct relationship between motor level and peak expiratory flow produced during coughing.


Simulating a memory impairment: can amnesics implicitly outperform simulators?
The purpose of this study was to examine the effectiveness of a variety of tests in differentiating simulating test performances from genuine memory-impaired and normal (control) test performances. A simulation design was implemented, based on an analogue design in which normal participants were given experimental instructions to feign a mental impairment and are compared to (a) other normal participants with instructions to perform honestly, and (b) a comparison group, for example, acquired brain-injured persons, with similar instructions. Forty individuals comprised the simulating and control group and all participants were randomly assigned to the simulating and control groups. Twenty memory-impaired patients, all of whom had been diagnosed as suffering from a memory impairment following acquired brain damage, participated as the memory-impaired control group. The simulation group was directed to imitate a person with a memory impairment. The primary outcome measure involved identifying those tests, if any, where simulators were significantly different from normal and memory-impaired participants. On 5 of the 15 tasks administered, simulators performed significantly differently from normal and memory-impaired participants. Of these 5 tasks, the coin-in-the-hand, when administered in conjunction with the autobiographical interview, identified 95 per cent of the simulators without misclassifying any of the memory-impaired or normal participants. It is suggested that these two tests, when administered jointly, might be of use in clinical settings to assist in the detection of malingerers.


Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis.
Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD.


Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17-dependent manner.
Reperfusion following ischemia leads to neutrophil recruitment into injured tissue. Selectins and β2-integrins regulate neutrophil interaction with the endothelium during neutrophil rolling and firm adhesion. Excessive neutrophil infiltration into tissue is thought to contribute to ischemia-reperfusion injury damage. Hydrogen sulfide mitigates the damage caused by ischemia-reperfusion injury. This study's objective was to determine the effect of hydrogen sulfide on neutrophil adhesion receptor expression. Human neutrophils were either left untreated or incubated in 20 μM hydrogen sulfide and/or 50 μg/ml pharmacologic ADAM-17 inhibitor TAPI-0; activated by interleukin-8, fMLP, or TNF-α; and labeled against P-selectin glycoprotein ligand-1, leukocyte function associated antigen-1, Mac-1 α, L-selectin, and β2-integrin epitopes CBRM1/5 or KIM127 for flow cytometry. Cohorts of three C57BL/6 mice received an intravenous dose of saline vehicle or 20 μM hydrogen sulfide with or without 50 μg/ml TAPI-0 before unilateral tourniquet-induced hind-limb ischemia for 3 hours followed by 3 hours of reperfusion. Bilateral gastrocnemius muscles were processed for histology before neutrophil infiltration quantification. Hydrogen sulfide treatment significantly increased L-selectin shedding from human neutrophils following activation by fMLP and interleukin-8 in an ADAM-17-dependent manner. Mice treated with hydrogen sulfide to raise bloodstream concentration by 20 μM before ischemia or reperfusion showed a significant reduction in neutrophil recruitment into skeletal muscle tissue following tourniquet-induced hind-limb ischemia-reperfusion injury. Hydrogen sulfide administration results in the down-regulation of L-selectin expression in activated human neutrophils. This leads to a reduction in neutrophil extravasation and tissue infiltration and may partially account for the protective effects of hydrogen sulfide seen in the setting of ischemia-reperfusion injury.


Adipose-derived stromal/stem cells and extracellular vesicles for cancer therapy.
Mesenchymal stromal/stem cells (MSCs) hold great perspective for the therapy of a host of diseases due to regenerative and anti-inflammatory properties by differentiation into diverse cell populations, homing to damaged tissue regions, paracrine effects, and release of extracellular vesicles. This review describes the isolation, characterization, and potential use of MSCs and ADSCs for benign and malignant diseases. The MSCs may be administered as whole cells or in form of their secretome that is held responsible for most of their beneficial effects. A special constituent of the paracrine components are the extracellular vesicles (EVs) that carry a biologically potent cargo of proteins, cytokines, and RNA. The applications of MSCs and ADSCs are amply documented and have been investigated in preclinical models and many unregulated and a few controlled trials. Larger numbers of MSCs and ADSCs can be obtained for allogeneic transfer but imply difficulties including perseverance of the cells in vivo and possible differentiation into harmful cell types. MSC-derived cell-free preparations are easier to handle and manufacture for various applications. Especially, with the help of bioreactors, EVs can be obtained in excessive numbers and preloaded or charged with proteins, cytokines, and regulatory RNA specimen to treat inflammatory diseases and cancer.


Understanding Yield Loss and Pathogen Biology to Improve Disease Management: Septoria Nodorum Blotch - A Case Study in Wheat.
The estimated potential yield losses caused by plant pathogens is up to 16% globally and most research in plant pathology aims to reduce yield loss in our crops directly or indirectly. Yield losses caused by a certain disease depend not only on disease severity, but also on the weather factors, the pathogen's aggressiveness, and the ability of the crop to compensate for reduced photosynthetic area. The yield loss-disease relationship in a certain host-pathogen system might therefore change from year to year, making predictions for yield loss very difficult at the regional or even at the farmer's level. However, estimating yield losses is essential to determine disease management thresholds at which acute control measures such as fungicide applications, or strategic measures such as crop rotation or use of resistant cultivars are economically and environmentally sensible. Legislation in many countries enforces implementation of integrated pest management (IPM), based on economic thresholds at which the costs due to a disease justify the costs for its management. Without a better understanding of the relationship between disease epidemiology and yield loss, we remain insufficiently equipped to design adequate IPM strategies that will be widely adapted in agriculture. Crop loss studies are resource demanding and difficult to interpret for one particular disease, as crops are usually not invaded by only one pest or pathogen at a time. Combining our knowledge on disease epidemiology, crop physiology, yield development, damage mechanisms involved, and the effect of management practices can help us to increase our understanding of the disease-crop loss relationship. The main aim of this paper is to review and analyze the literature on a representative host-pathogen relationship in an important staple food crop to identify knowledge gaps and research areas to better assess yield loss and design management strategies based on economic thresholds.


Pertussis vaccination during pregnancy: Antibody persistence in infants.
Maternal pertussis vaccination is associated with higher levels of pertussis antibodies at birth. We assessed the persistence of pertussis antibodies until primary vaccination in infants whose mothers received Tdap (tetanus, diphtheria, acellular pertussis) vaccine during pregnancy. Infants were born at the Hospital Clinic of Barcelona (Spain) in November 2014. Anti-PT IgG was determined by ELISA at delivery, between the first and second month of life, and estimated at 2months of age. The study included 37 infants whose mothers received Tdap between 21 and 38weeks of gestation. Infants presented a decline in GMC of anti-PT IgG between peripartum and follow-up levels, 52.7 (95% CI 34.7-80.2) versus 7.5 (95% CI 4.2-13.3) at 2months of age (p<0.001). The median half-life of maternal antibodies was 47days. More than half (51.4%) the infants presented detectable anti-PT IgG before the start of primary infant vaccination.


Increase of baclofen intoxications: risks involved and management.
Baclofen has been increasingly used in the treatment of alcohol withdrawal syndrome (AWS). We present a patient with AWS and psychiatric comorbidity who ingested 700 mg of baclofen. ICU admission was necessary for ventilatory support and symptomatic treatment. The patient was dismissed without sequelae.


Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation.
Non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation shows good and rapid response to EGFR tyrosine kinase inhibitors (TKIs). We prospectively evaluated the efficacy of EGFR TKI for metastatic brain tumors in NSCLC patients harboring EGFR mutation. This was an open-label, single-institution, phase II study. Patients diagnosed with NSCLC harboring EGFR mutation and measurable metastatic brain tumors were eligible. They received either erlotinib or gefitinib once a day. Out of total 28 patients enrolled, 23 patients (83%) showed a partial response (PR) and 3 patients (11%) did stable disease (SD), giving a disease control rate of 93%. Median progression free survival (PFS) and overall survival (OS) were 6.6 months (95% CI, 3.8-9.3 months) and 15.9 months (95% CI, 7.2-24.6 months), respectively. There was no difference in PFS and OS according to EGFR TKIs used. After discontinuation of the treatment, 14 patients (50%) received local therapy for metastatic brain tumors during their disease course, either whole brain radiotherapy or radiosurgery, giving a local therapy-free interval of 12.6 months (95% CI, 7.6-17.6 months). EGFR TKI therapy might be the treatment of choice for metastatic brain tumors in NSCLC patients harboring an activating EGFR mutation.


Estimation of the amount of β2-glycoprotein I adsorbed at the inner surface of fused silica capillaries after acidic, neutral and alkaline pretreatment.
Sample adsorption to the inner surface of fused silica capillaries is a common problem in CE when analyzing macromolecules and is harmful to the analysis. We previously utilized the pH hysteresis effect of fused silica to facilitate electrophoresis of the strongly adsorbing protein β(2) gpI in plain-fused silica capillaries at neutral pH. In the present paper, the effect of different pretreatments of the capillary on the adsorption of the β(2) -glycoprotein I has been investigated using electroosmosis markers, SDS mobilization, and imaging based on indirect immunofluorescence microscopy for direct visualization. The amount of β(2) gpI adsorbed on the surface was probed using all these independent techniques after electrophoresis at neutral pH on capillaries pretreated with HCl, background electrolyte (BGE), and NaOH. BGE pretreatment was included as a positive control. We found that 80% or more of the starting material was adsorbed to the inner surface of the silica capillaries during electrophoresis after pretreatment with only BGE or with NaOH, but after acidic pretreatment the loss was consistently less than 20%. NaOH most efficiently removes adsorbed protein between runs. A theoretical calculation of the pH change of the BGE showed that electrolysis affects the pH more than the deprotonation of silanols during electrophoresis. We conclude that acidic pretreatment of fused silica capillaries diminishes adsorption of β(2) gpI by decreasing charge-dependent wall adsorption.


Effect of DNA methylation and chromatin structure on ITGAL expression.
LFA-1 (CD11a/CD18, alpha L beta 2) is an integrin expressed in a tissue-specific fashion and is important in inflammatory and immune responses. Promoter analysis has identified transcription factors that may be involved in CD11a expression, but the mechanisms contributing to its tissue-specific expression are incompletely characterized. In this report we have asked if DNA methylation and/or chromatin structure could contribute to tissue-specific CD11a expression. Bisulfite sequencing was used to compare methylation patterns in the promoter and 5' flanking regions of the ITGAL gene, encoding CD11a, in normal human T cells, which express LFA-1, and fibroblasts, which do not. The region was found to be heavily methylated in fibroblasts but not T cells, and methylation correlated with an inactive chromatin configuration as analyzed by deoxyribonuclease 1 sensitivity. Patch methylation of the promoter region revealed that promoter activity was methylation-sensitive but that methylation of the 5' flanking regions more than 500 base pairs 5' to the transcription start site could also suppress promoter function. Treating fibroblasts with a DNA methylation inhibitor decreased ITGAL promoter methylation and increased CD11a messenger RNA. The results thus indicate that methylation and chromatin structure may contribute to the tissue-specific expression of CD11a.


The translation of sports injury prevention and safety promotion knowledge: insights from key intermediary organisations.
A recognised research-to-practice gap exists in the health research field of sports injury prevention and safety promotion. There is a need for improved insight into increasing the relevancy, accessibility and legitimacy of injury prevention and safety promotion research knowledge for sport settings. The role of key organisations as intermediaries in the process of health knowledge translation for sports settings remains under-explored, and this paper aims to determine, and describe, the processes of knowledge translation undertaken by a set of key organisations in developing and distributing injury prevention and safety promotion resources. The National Guidance for Australian Football Partnerships and Safety (NoGAPS) project provided the context for this study. Representatives from five key NoGAPS organisations participated in individual face-to-face interviews about organisational processes of knowledge translation. A qualitative descriptive methodology was used to analyse participants' descriptions of knowledge translation activities undertaken at their respective organisations. Several themes emerged around health knowledge translation processes and considerations, including (1) identifying a need for knowledge translation, (2) developing and disseminating resources, and (3) barriers and enablers to knowledge translation. This study provides insight into the processes that key organisations employ when developing and disseminating injury prevention and safety promotion resources within sport settings. The relevancy, accessibility and legitimacy of health research knowledge is foregrounded, with a view to increasing the influence of research on the development of health-related resources suitable for community sport settings.


MicroRNA regulation of natural killer cell development and function in leukemia.
MicroRNAs (miRNAs) are now recognized as important regulators of all cellular processes, including immune function and cancer survival. These evolutionary preserved, single-stranded, non-coding RNA molecules mediate important functional effects primarily through post-transcriptional regulation of protein expression. MiRNAs are known to mediate multiple oncogenic pathways in tumor cells, both tumor promoting and tumor suppressing. In addition to a direct tumor cell effect, miRNAs have also been shown to play a critical role in immune cell development, function and survival. Here we expand on previous reports to evaluate miRNA regulation in natural killer (NK) cells primarily in humans and focus on their influence on NK cell development and function in the setting of hematologic malignancies. In addition, we highlight the most recent miRNA discoveries in hematologic malignancies and discuss areas of future exploration relevant to the translational field of innate immunology and miRNA-based therapeutic intervention.


Temporal dynamics of the pharmacological MRI response to subanaesthetic ketamine in healthy volunteers: A simultaneous EEG/fMRI study.
Pharmacological magnetic resonance imaging has been used to investigate the neural effects of subanaesthetic ketamine in healthy volunteers. However, the effect of ketamine has been modelled with a single time course and without consideration of physiological noise. This study aimed to investigate ketamine-induced alterations in resting neural activity using conventional pharmacological magnetic resonance imaging analysis techniques with physiological noise correction, and a novel analysis utilising simultaneously recorded electroencephalography data. Simultaneous electroencephalography/functional magnetic resonance imaging and physiological data were collected from 30 healthy male participants before and during a subanaesthetic intravenous ketamine infusion. Consistent with previous literature, we show widespread cortical blood-oxygen-level dependent signal increases and decreased blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex following ketamine. However, the latter effect was attenuated by the inclusion of motion regressors and physiological correction in the model. In a novel analysis, we modelled the pharmacological magnetic resonance imaging response with the power time series of seven electroencephalography frequency bands. This showed evidence for distinct temporal time courses of neural responses to ketamine. No electroencephalography power time series correlated with decreased blood-oxygen-level dependent signal in the subgenual anterior cingulate cortex. We suggest the decrease in blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex typically seen in the literature is the result of physiological noise, in particular cardiac pulsatility. Furthermore, modelling the pharmacological magnetic resonance imaging response with a single temporal model does not completely capture the full spectrum of neuronal dynamics. The use of electroencephalography regressors to model the response can increase confidence that the pharmacological magnetic resonance imaging is directly related to underlying neural activity.


Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases.
The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca2+ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.


Cystic nephroma/mixed epithelial stromal tumor: a benign neoplasm with potential for recurrence.
Cystic nephroma (CN) is a rare, benign, renal neoplasm composed of epithelial and stromal elements. Only about 200 cases have been reported since 1892 and recurrence has rarely been observed. We report a 32-year-old Hispanic woman, with a history of a right, complex cystic, renal mass treated by robotic decortication 2 years ago, who presented with flank pain, hematuria, and recurrent urinary tract infection. A magnetic resonance imaging study showed a 3.4-cm multicystic lesion with thickened septa and enhancement at the right kidney. The partial nephrectomy specimen revealed a well-circumscribed, multicystic tumor abutting the renal pelvis, with thick septa and smooth walls, filled with clear fluid. Microscopic examination showed variably sized cysts lined by cuboidal epithelium with focal hobnailing, without significant cytologic atypia and mitosis. The epithelial lining was positive for CK19, high molecular weight cytokeratin, and α-methylacyl-CoA racemase suggesting a primitive tubular epithelial phenotype. Primitive glomeruli-like structures were also present. The ovarian-like stroma was condensed around the cysts and was variably cellular with areas of muscle differentiation and thick-walled vessels. The stroma was positive for desmin, estrogen receptor, progesterone receptor, and CD10. We suggest that CN represents a variable mixture of epithelial and stromal elements, immature glomerular, tubular, muscle, and vascular elements, which may be present in variable proportions creating a spectrum of lesions previously described as CN and mixed epithelial and stromal tumors (MEST). This case emphasizes that CN/MEST clinically/radiologically mimics other cystic renal neoplasms, especially cystic renal cell carcinoma and tubulocystic carcinoma, necessitating histopathological examination and immunohistochemial studies for definitive diagnosis. Additionally, CN has the tendency to recur when not completely excised initially.


Systems of care: future reform.
Major new ideas and opportunities shape the direction of reform in serving those coming to the end of life. Framing the problems as arising from changing demographics and evaluation of how we envision categories seems better than past ways of framing the issues. Another useful strategy is to build programs around three trajectories of the time course of disability while dying: a confined period of rapidly progressive disability and symptoms; intermittent exacerbations against the background of substantial organ system failure; and extreme multifactorial frailty. Finally, reform requires quality improvement, restructuring, and changes in Medicare payment.


Assessment of the growth of epidural injections in the medicare population from 2000 to 2011.
Among the many diagnostic and therapeutic interventions available for the management of chronic pain, epidural steroid injections are one of the most commonly used modalities. The explosive growth of this technique is relevant in light of the high cost of health care in the United States and abroad, the previous literature assessing the effectiveness of epidural injections has been sparse with highly variable outcomes based on technique, outcome measures, patient selection, and methodology. However, the recent assessment of fluoroscopically directed epidural injections has shown improved evidence with proper inclusion criteria, methodology, and outcome measures. The exponential growth of epidural injections is illustrated in multiple reports. The present report is an update of the analysis of the growth of epidural injections in the Medicare population from 2000 to 2011 in the United States. Analysis of utilization patterns of epidural procedures in the Medicare population in the United States from 2000 to 2011. The primary purpose of this assessment was to evaluate the use of all types of epidural injections (i.e., caudal, interlaminar, and transforaminal in the lumbar, cervical, and thoracic regions) with an assessment of specialty and regional characteristics. This assessment was performed utilizing the Centers for Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS) Master data from 2000 to 2011. Epidural injections in Medicare beneficiaries increased significantly from 2000 to 2011. Overall, epidural injections increased 130% per 100,000 Medicare beneficiaries with an annual increase of 7.5%. The increases per 100,000 Medicare recipients were 123% for cervical/thoracic interlaminar epidural injections; 25% for lumbar/sacral interlaminar, or caudal epidural injections; 142% for cervical/thoracic transforaminal epidural injections; and 665% for lumbar/sacral transforaminal epidural injections. The use of epidurals increased 224% in the radiologic specialties (interventional radiology and diagnostic radiology) and 145% in psychiatric settings, whereas and physical medicine and rehabilitation physicians' use of epidurals increased 520%. Study limitatations include lack of inclusion of Medicare Advantage patients. In addition, the statewide data is based on claims which may include the contiguous or other states. Epidural injections in Medicare recipients increased significantly. The growth was significant for some specialties (radiology, physical medicine and rehabilitation, and psychiatry) and for certain procedures (lumbosacral transforaminal epidural injections).


Placebo-controlled trial of amantadine in multiple-system atrophy.
Multiple-system atrophy (MSA) often presents as atypical parkinsonian syndrome with rapid progression and poor response to levodopa. Reports on the open-label use of amantadine in MSA suggest variable antiparkinsonian efficacy. The authors therefore conducted a double-blind, placebo-controlled crossover trial of amantadine in MSA patients. Eight patients were enrolled in this study. They received either amantadine 200 mg twice daily or placebo for 3 weeks, followed by a 1-week washout and the alternate treatment of 3 weeks. Antiparkinsonian effects were evaluated using the Unified Parkinson's Disease Rating Scale part II (UPDRS-II, activities of daily living) and UPDRS-III (motor examination) before and at the end of each treatment phase. Timed tests were also performed according to the CAPIT protocol. There was a trend toward reduction of UPDRS-III scores during amantadine treatment (P = 0.058). Delta values of the treatment arm were higher than those of the placebo arm. However, this difference (-2.25 pt; 95% CI, -6.7-2.2) failed to reach significance. Reduction of UPDRS-III subscores for akinesia, rigidity, tremor, postural instability, and gait disorder failed to reach significance too. The hand-arm movement test revealed nonsignificant improvement in the amantadine arm. This study suggests that amantadine fails to provide clinically significant antiparkinsonian benefit to patients with MSA. The authors cannot exclude mild effects due to the limited sample size.


A regimen of oral contraceptives restricted to the periovulatory period may permit folliculogenesis but inhibit ovulation.
Increased safety of oral contraceptives (OC) has resulted from a reduction in the estrogen and progestin content per tablet. A reduction in the number of hormonally active pills and their placement at critical points within the cycle may provide a novel regimen for further reducing the hormonal content of OC per cycle and their attendant side effects without compromising efficacy. The objective of this study was to determine the effectiveness of two OC regimens that incorporate a delayed start and limited midcycle use of the combination of ethinyl estradiol and norethindrone, and limited use of norethindrone only during the second half of the cycle. Main outcome measures were defined as ovulation, serum concentrations of estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone (P), follicular diameters, and endometrial thickness. Volunteers were issued blister packs containing 28 pills and randomized to one of two groups. Group 1 used a combination of 50 micrograms ethinyl estradiol and 1 mg norethindrone per tablet day 6-10, and 0.70 mg norethindrone only day 11-19. Placebo tablets were used on days 1-5 and day 20-28. Group 2 used a combination of 50 micrograms ethinyl estradiol and 1 mg norethindrone per tablet on day 8-12, and 0.70 mg norethindrone only on day 13-21. Placebo tablets were used on day 1-7 and day 22-28. A total of 20 cycles were studied using 10 volunteers. To assess any possible carryover effect, two successive cycles were studied for each subject. Serum sampling for E2, FSH, LH, and P, and transvaginal ultrasound imaging to assess endometrial thickness and follicle diameter were carried out at 4 day intervals throughout the cycle. One ovulation occurred in 10 cycles in group 1. Five ovulations occurred in 10 cycles in group 2. All ovulations, regardless of group, occurred in the second cycle. Peak E2 concentrations were not significantly different between groups (152.04 +/- 107.1 pg/mL vs 162.1 +/- 56.1 pg/mL [mean +/- SD] for groups 1 and 2, respectively] but occurred earlier in the cycle in group 1. No differences were noted between the groups in serum concentrations of FSH or LH for any given cycle day. Maximum follicle diameters were not different between groups 1 and 2, regardless of ovulatory status (20.5 +/- 8.1 mm2 vs 20.6 +/- 14.2 mm2, respectively). Ultrasound imaging assessment of midcycle follicle growth revealed diameters ranging from 18.5 mm2 to 34.0 mm2 with gradual resolution through the second half of the cycle in anovulatory cycles, and 16.0 mm2 to 23.5 mm2 with abrupt disappearance in ovulatory cycles. Endometrial thickness did not exceed 10 mm for any anovulatory cycle regardless of group, but ranged from 6 to 9 and 6 to 11 during the luteal phase of ovulatory cycles of groups 1 and 2, respectively. Peak serum P concentrations at midluteal phase in ovulatory cycles ranged from 9.2 ng/ml to 18.2 ng/ml. Data from this preliminary study suggest that ovulation may be prevented with a combination of ethinyl estradiol and norethindrone started as late as cycle day 6 and limited to 5 days' duration using norethindrone only for 9 days during the second half of the cycle. Such a restricted regimen may offer both an effective method of contraception and a means of further reducing both estrogen and progestin content per cycle and the possible short and long term adverse side effects of these hormones.


Structural characterization of apomyoglobin self-associated species in aqueous buffer and urea solution.
The biophysical characterization of nonfunctional protein aggregates at physiologically relevant temperatures is much needed to gain deeper insights into the kinetic and thermodynamic relationships between protein folding and misfolding. Dynamic and static laser light scattering have been employed for the detection and detailed characterization of apomyoglobin (apoMb) soluble aggregates populated at room temperature upon dissolving the purified protein in buffer at pH 6.0, both in the presence and absence of high concentrations of urea. Unlike the beta-sheet self-associated aggregates previously reported for this protein at high temperatures, the soluble aggregates detected here have either alpha-helical or random coil secondary structure, depending on solvent and solution conditions. Hydrodynamic diameters range from 80 to 130 nm, with semiflexible chain-like morphology. The combined use of low pH and high urea concentration leads to structural unfolding and complete elimination of the large aggregates. Even upon starting from this virtually monomeric unfolded state, however, protein refolding leads to the formation of severely self-associated species with native-like secondary structure. Under these conditions, kinetic apoMb refolding proceeds via two parallel routes: one leading to native monomer, and the other leading to a misfolded and heavily self-associated state bearing native-like secondary structure.


Enhancement of apoptotic susceptibility in human endometrial epithelial cell line HHUA by transforming growth factor-beta 1.
Although reports have been published on the generation of transforming growth factor-beta 1 (TGF-beta 1) and expression of TGF-beta receptors in human endometrial tissues, the biological functions of endometrial TGF-beta 1 have remained unclear. In this study, the effects of TGF-beta 1 on endometrial apoptosis were examined by using an endometrial epithelial cell line HHUA which is susceptible to Fas-mediated apoptosis. TGF-beta 1 alone did not affect the cell growth of HHUA, but pretreatment of HHUA with TGF-beta 1 enhanced Fas-mediated growth suppression and DNA fragmentation of the cells. Flow cytometric analyses showed that TGF-beta 1 did not affect Fas expression on the cell surface. These findings lead to the conclusion that TGF-beta 1 enhances susceptibility to Fas-mediated apoptosis in the endometrial epithelial cell. Modulation of Fas-mediated endometrial apoptosis by TGF-beta 1 may thus be a tissue-specific effect which is distinct from other TGF-beta 1 effects on Fas-mediated apoptosis in activated T-cells and rheumatoid synovial cells. The biological functions of endometrial TGF-beta 1 and endometrial apoptosis are also discussed.


Non-criteria manifestations of antiphospholipid syndrome.
Only few studies have addressed the pathogenesis and treatment of the non-criteria manifestations of antiphospholipid antibodies (aPL) such as thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction, skin ulcers, or diffuse pulmonary hemorrhage. There is no consensus on the management of these manifestations; they may occur despite full-dose anticoagulation or may not improve if anticoagulation is initiated after their discovery. This brief review may help physicians in the management of the non-criteria manifestations of aPL.


Spreading of wheat germ agglutinin-induced erythrocyte contact by formation of spatially discrete contacts.
The time dependence of agglutination and cell-cell contact spreading in human erythrocytes exposed to wheat germ agglutinin (WGA) was characterized by light and electron microscopy. Cells (3 x 10(7)/mL) had a threshold lectin concentration in the range of 0.6-2.0 micrograms/mL for initial cell contact. Spreading was essentially completed within 60 and 2 min in undisturbed and gently agitated suspensions, respectively. The cells in large WGA agglutinates retained features of their initial disk form in contrast to the convex outlines of polycation or polyethylene glycol-induced agglutinates. Spreading of contact area was accompanied by development of a pattern of discrete contact regions separated by a distance of the order of 1 micron. Freeze fracture electron microscopy and studies with ferritin-labeled WGA showed no significant aggregation of intramembrane particles or specific lectin receptors under conditions when contact spreading occurred. It is argued that flow stress effects on cells in suspended agglutinates give rise to a situation where opposite membranes, at the leading edge of cell contact, are separated by a thin aqueous layer. When this intercellular water layer exceeds a critical length, it becomes unstable. The layer breaks up by surface wave development to form an array of intracellular water spaces. Formation of the aqueous spaces causes opposite membrane regions to move synchronously toward each other. Lectin molecules crosslink the wave crests to give spatially periodic contact points.


Estimation of ultrasound reference values for the ulnar nerve fascicular number and cross-sectional area in young males: A cross-sectional study.
The objective of this study is to estimate the reference values for the number of fascicles and cross-sectional area (CSA) of the ulnar nerve at a single predetermined site by ultrasound in healthy young adult males.The demographic and physical characteristics of 50 adult male volunteers were evaluated and recorded. The subjects were positioned supine with the elbow flexed at 90° and the palm of the hand placed on a hard surface. The ulnar nerve was scanned bilaterally 1 cm proximal to the medial epicondyle in projection of the cubital tunnel. The number of fascicles and mean CSA of the ulnar nerve were identified. In addition, the side-to-side differences of the estimated reference values and their correlations with the age, weight, height, and body mass index (BMI) were evaluated.The mean fascicular number was 5.66 ± 1.48, the mean ultrasound-estimated CSA of the ulnar nerve was 6.54 ± 1.67 mm and both sides were comparable in the mean CSA and fascicular number (6.43 ± 1.80 mm and 5.88 vs 6.64 ± 1.55 mm and 5.44, for right and left side, respectively). No significant correlations were observed between CSA and fascicles number and age, weight, height, or BMI of study subjects.The reference values for the number of fascicles number and the CSA of the ulnar nerve at a single predetermined site were identified. These values could be used for the sonographic diagnosis and follow-up of the ulnar nerve lesions.


Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats.
It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an α-glucosidase inhibitor (α-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an α-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1β, tumor necrosis factor-α, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.


THE SOURCE OF INFECTION AND THE MOST FREQUENT CAUSES OF REACTIVE ARTHRITIS IN KOSOVO.
Reactive arthritis is an autoimmune condition which emerges as a counteraction towards an infection which has a focus elsewhere in the body. The purpose of this study is isolation of causative agents of reactive arthritis and ascertains the source of infection. The study has been carried out in the Rheumatology Clinic in Prishtina and specialized ambulance O.S. "Vendenisi-AL" in Besiana, whereas isolation of causative agents has been carried out in the National Institute for Public Health (NIPH). The study has prospective, comparative and analytical feature. Out of 100 patients, 66% were males and 34% females. Among males we have noticed domination of post-urethritis and post-streptococcic reactive arthritis, whereas among females dominates reactive arthritis of enteral etiology. The study concludes that: urogenital tract was the source of infection with 66% of cases, nasopharyngeal tract with 19% of cases, and enteral tract with 15% of cases respectively. Predominantly presents bacteria are E. Coli with 21%, Staphylococcus aureus with 20%, Streptococcus B. hem. gr. A with 16% of cases respectively and other species. frequency of arthritis with urogenital etiology was 2:1 in favor of males, with nasopharyngeal etiology 3:1 in favor of males, whereas in arthritis with enteral etiology we have noticed a slight dominance in favor of females.


LIM domain-containing protein Ajuba inhibits chemotherapy-induced apoptosis by negatively regulating p53 stability in colorectal cancer cells.
LIM protein-domain containing protein Ajuba (encoded by AJUBA) functions as a scaffold protein to regulate protein-protein interactions, signalling transduction and genes transcription. AJUBA expression is higher in colorectal cancer (CRC) tissues than normal tissues, but its specific molecular function in CRC progression is still not very clear. Here, we found that, in CRC cancer cell lines, overexpression of AJUBA decreased p53 levels, whereas knock-down of AJUBA significantly increased p53 levels. Although the presence of Ajuba did not influence p53 transcription, it formed a complex with p53 and MDM2 to promote the degradation of p53. AJUBA overexpression reduced the sensitivity of cancer cells to chemotherapeutic drugs and vice versa. In addition, chemotherapeutic drugs significantly induced AJUBA expression, which was largely dependent on the presence of p53. Therefore, Ajuba formed a negative feedback loop to regulate p53 expression and activity. In conclusion, as a novel p53-negative regulator, Ajuba inhibits the apoptosis of CRC cells induced by chemotherapeutic drugs and it may be a new therapeutic target for CRC treatment.


Prolongation of guinea pig-to-rat xenograft survival with BN 52063, a specific antagonist of platelet-activating factor.
Xenotransplantation between different species may possibly solve some of the difficulties associated with human donor organ availability. However, organ xenografts are very rapidly rejected, particularly in discordant donor-recipient combinations, due to the presence of natural cytotoxic antibodies in the recipient. The purpose of this study was to evaluate the efficacy of two potential inhibitors of a xenogeneic antigen-antibody reaction: Iloprost, an analogue of prostacyclin I2, and BN 52063, a PAF-antagonist. Heart (group A) or liver (group B) transplantations were performed in the guinea pig-to-Lewis rat donor-recipient combination. Fifteen minutes prior to revascularization of the graft an intravenous infusion was instituted using saline (0.01 ml/min) (groups A1 and B1), saline and dimethylsulfoxide (DMSO, 0.1 ml/min) (groups A2 and B2), Iloprost (2 ng/Kg/min) (groups A3 and B3) or BN 52063 (6 mg/Kg/min) (groups A4 and B4). Heart graft survival times (min) were 12.3 +/- 1.7 (A1), 13.4 +/- 2.2 (A2), 14.8 +/- 1.0 (A3), 18.3 +/- 1.4 (A4). Liver graft survival times (min) were 158.4 +/- 38.9 (B1), 129.6 +/- 14.4 (B2), 168.1 +/- 18.0 (B3) and 306.2 +/- 36.5 (B4). A significant prolongation (p less than 0.05) was observed in group A4 versus A1, A2, A3 and in group B4 versus B1, B2, B3. These results suggest that prevention of xenograft rejection using PAF-antagonist in association with other methods should be further investigated.


Farm accidents involving power take-off devices.
Primary prevention represents the optimum method of virtually abolishing the factors that lead to this injury scenario. Cooperative effort is required on the part of manufacturers, health education authorities and the user. The present situation is unsatisfactory.


Socio-Cultural Standards Promoted by the Mass Media as Predictors of Restrictive and Bulimic Behavior.
Research lacks in verifying the nature of the relationship between mass media pressure, body image, and the risk of unhealthy eating behaviors. This study aimed to investigate whether the internalization of sociocultural norms, perceived pressure or searching for information about body image promoted by the mass media directly affect restrictive and bulimic behavior toward eating, through the mediating role of body image and physical appearance variables. The research hypotheses were that (1, 2) body image, the pressure and the internalization of sociocultural norms are significant predictors of unhealthy eating behavior among women and men; and (3) the variables related to body image play the role of the mediating variable between the impact of socio-cultural standards of body image promoted by the mass media and unhealthy eating behavior. The sample comprised 514 Polish men and women, aged 16 to 63 old (men M=24.35; SD=13.53; women M=24.77; SD=7.61), with average Body Mass Index (BMI). Assessment comprised the Sociocultural Attitudes Toward Appearance Scale (SATAQ-3), Eating Disorders Inventory (EDI 3), The Multidimensional Body-Self Relations Questionnaire (MBSRQ-AS), and the author's survey questionnaire. The descriptive and comparative statistics, and a path analysis (structural equations modeling) were applied. The statistical analysis showed that the variables related to body image do not play the role of intermediary variables. The pressure of sociocultural standards of body image and physical appearance had the strongest and most direct effect on the development of restrictive eating behavior and appeared to negatively affect body image in women. The search of information on body image in the mass media had the strongest and most direct impact on the development of bulimic eating behavior among women. However, only the global internalization of sociocultural standards of body image and physical appearance had a significant and direct effect on the development of bulimic eating behavior in men. Moreover, the internalization of athletic body shape standards had the strongest and most positive impact on some aspects of body image in this group. No sociocultural variables showed a direct impact on restrictive behavior among studied men. BMI had a positive and direct impact on individual body part satisfaction. These results may help improve prevention of eating disorders and dysfunctional eating behavior.


Comparison of didactic lectures and open-group discussions in surgical teaching.
The teaching of medicine has varied and has continued to develop until today. Most courses rely on the lecture although it may bring less benefit to students. Another teaching technique, the open group discussion, may not be the most effective, but is widely accepted as a teaching development especially for its overall improvement of student skills. Basically, the teaching of surgery has more limitations than other subjects because patients with critical conditions are required. The present study was designed to compare the effectiveness of these two teaching methods, the lecture and the open group discussion, in the Department of Surgery, Rajavithi Hospital. Fifth year medical students enrolled from 2554-2555 BE (AD 2011-2012) were recruited in the study and randomly divided in groups by the Office of Administration, College of Medicine, Rangsit University. A colorectal surgeon taught the subject, common anorectal disease, throughout the study year. The drawing method was used to randomize the members grouped by teaching methods. The assessment comprised multiple choice questions (MCQ) and multiple essay questions (MEQ). Seventy-three students (39 females, 34 males) were recruited. Students' basic characteristic showed no association between groups of teaching methods. Higher mean MEQ scores were found in the open discussion group (55.83%) compared with those taught by lecture (31.23%), exhibiting significant difference (p<0.001). With respect to MCQ1 and MCQ4, students in the open discussion group had higher scores than those in the lecture group), was also with statistical significance (p = 0.02). Teaching medicine differs from other disciplines. To achieve the most effective teaching performance, teaching methods may be limited in some subjects. This study was a partial project for teaching in the Department of Surgery. It was shown that students in the open discussion group had better MCQ and MEQ scores than those in the lecture group. In developing student skills, giving open discussion provided greater interaction between instructors and students. Importantly, the instructor should manage and facilitate questioning techniques to more effectively transfer course content.


Functional versus chemical diversity: is biodiversity important for drug discovery?
Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less. It is likely that many millions of chemically distinct molecules exist in nature but it is inconceivable that the number of different biological functions is near this number. This is corroborated by knowledge obtained from the genome sequences of an increasing number of species. It is unlikely that ligands for specific molecular targets are restricted to one species and even individual compounds are often found in more than one species. Important molecular mechanisms are likely to be ubiquitous and there are no a priori reasons to assume that some are restricted to, for example, tropical rainforests. Thus, there are no obvious advantages of "biodiversity prospecting", which will, possibly, endanger fragile ecosystems in the search for rare species.


Quantitative microscopy of functional HIV post-entry complexes reveals association of replication with the viral capsid.
The steps from HIV-1 cytoplasmic entry until integration of the reverse transcribed genome are currently enigmatic. They occur in ill-defined reverse-transcription- and pre-integration-complexes (RTC, PIC) with various host and viral proteins implicated. In this study, we report quantitative detection of functional RTC/PIC by labeling nascent DNA combined with detection of viral integrase. We show that the viral CA (capsid) protein remains associated with cytoplasmic RTC/PIC but is lost on nuclear PIC in a HeLa-derived cell line. In contrast, nuclear PIC were almost always CA-positive in primary human macrophages, indicating nuclear import of capsids or capsid-like structures. We further show that the CA-targeted inhibitor PF74 exhibits a bimodal mechanism, blocking RTC/PIC association with the host factor CPSF6 and nuclear entry at low, and abrogating reverse transcription at high concentrations. The newly developed system is ideally suited for studying retroviral post-entry events and the roles of host factors including DNA sensors and signaling molecules.


Roles of glutamate receptors in long-term potentiation at hippocampal mossy fiber synapses.
We have investigated the roles of glutamate (Glu) receptors in the mechanism of long-term potentiation observed in rat hippocampal mossy fiber synapses (MF-LTP). The mossy fiber responses were almost completely suppressed by ionotropic Glu receptor (iGluR) antagonists both before and after the induction of LTP. However, tetanic stimulation produced robust LTP even when the synaptic transmission was blocked postsynaptically by iGluR antagonists. In contrast, when the transmission was blocked presynaptically by Ca(2+)-free media, tetanic stimulation produced no LTP. D,L-2-amino-3-phosphono-propionate(D,L-AP3), a metabotropic Glu receptor (mGluR) antagonist, inhibited the induction of MF-LTP. Perfusion with ibotenate, a mGluR agonist, induced long-lasting enhancement of the mossy fiber responses without tetanic stimulation, and this ibotenate-induced potentiation was antagonized by D,L-AP3.


A pilot study on the prevalence of sexually transmitted infections among clients of brothel-based female sex workers in Jessore, Bangladesh.
The prevalence of bacterial sexually transmitted infections among clients of female sex workers (FSWs) was studied. A total of 156 condoms were collected from clients of 13 sex workers during three consecutive days. Condoms used by clients of FSWs were collected and DNA was extracted from the seminal fluid and used for the diagnosis of Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis by polymerase chain reaction. The prevalence of N. gonorrhoeae, C. trachomatis and T. vaginalis among clients of FSWs was 4.5% (7/156), 2.5% (4/156) and 7% (11/156), respectively.


Prevention by nimodipine, a calcium entry blocker, of the effect of alpha 2-adrenoceptor blocking agents on noradrenaline release: differential effects of nimodipine, on [3H]noradrenaline and [14C]acetylcholine release measured concomitantly from the guinea-pig ileum.
The calcium channel blocker, nimodipine (Bay e 9736), inhibited the evoked (1 Hz, 1 msec, 180 pulses) release of [14C]acetylcholine ([14C]ACh) while it enhanced the release of [3H]noradrenaline ([3H]NA) measured concomitantly from the same longitudinal muscle strip of guinea-pig ileum loaded with [14C]choline and [3H]noradrenaline. These effects of nimodipine were concentration-dependent: in 0.1 microM concentration yielding maximal inhibition of [14C]ACh release and in 0.5 microM concentration yielding half maximal stimulation of [3H]NA-release. Enhancement of [3H]NA-release by nimodipine was strongly dependent on stimulation frequency while the inhibitory effect of nimodipine on release of [14C]ACh did not depend on stimulation frequency in the 0.5-10 Hz range. In addition, in the presence of nimodipine when the release of [3H]NA was enhanced, i.e. when a significant negative feedback operation could have been expected, alpha 2-adrenoceptor blocking agents (yohimbine and idazoxane) failed to enhance [3H]NA-release. It is proposed that nimodipine somehow exerts a presynaptic alpha 2-adrenoceptor blocking property at noradrenergic axon terminals through an effect on calcium entry, which may be an essential step in events linking alpha 2-adrenoceptor activation and inhibition of noradrenaline release.


Renal Impairment and Complication After Kidney Transplant at Queen Rania Abdulla Children's Hospital.
Kidney transplant is the treatment of choice for end-stage renal disease, but it is not without complications. We review the medical cause of significant renal impairment and complications that developed after kidney transplant in pediatric patients who required hospital admission and intervention and/or who were followed between 2007 and 2016. A retrospective noninterventional chart review study was conducted in pediatric patients who received a kidney transplant and/or followed at the nephrology clinic at Queen Rania Abdulla Children's Hospital between 2007 and 2016. In this study, 101 pediatric patients received a total of 103 transplants. Forty-eight patients (47%) experienced deterioration of kidney function out of a total of 53 episodes of complications; 37 of these episodes occurred early (0-6 mo after transplant), and 26 episodes occurred late. The causes of kidney function deterioration were surgical complications, acute tubular necrosis, cell- or antibody-mediated rejection, diabetes mellitus, urinary leak, recurrence of original disease, and chronic allograft nephropathy. Thirteen patients experienced graft loss; 50% of these losses were secondary to noncompliance to immunosuppressant medication treatment after transplant. A total of six patients died; 2 (23%) of these deaths occurred in the first week after transplant, whereas the other 4 patients died over a period of 10 years. Pediatric kidney transplant is not without complications; however, most of these complications are treatable and reversible. The most serious complications leading to graft loss and death occur early, in the first week after transplant. Improving immunosuppressant compliance after transplant would prevent 50% of graft losses.


Ten-core versus 16-core transrectal ultrasonography guided prostate biopsy for detection of prostatic carcinoma: a prospective comparative study in Indian population.
To compare the cancer detection rate in patients with raised serum prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE) results between the 10-core and the 16-core biopsy techniques in an Indian population. Between November 2010 and November 2012, 95 men aged >50 years who presented to the Urology Department with lower urinary tract symptoms, elevated serum PSA, and/or abnormal DRE findings underwent transrectal ultrasonography (TRUS)-guided prostate biopsy. A total of 53 patients underwent 10-core biopsy and 42 patients underwent 16-core biopsy. Of the 53 men in the 10-core group, 8 had cancer, whereas in the 16-core biopsy group, 23 of 42 men had cancer. Detection of prostate cancer was significantly higher in patients who underwent 16-core biopsy than in those who underwent 10-core biopsy (P<0.001). Among the 95 men, 44 men had abnormal DRE findings (46.3%), of whom 23 showed cancer (52.27%). Of 51 men with normal DRE findings and elevated PSA, 8 men had malignancy with a cancer detection rate of 15.68%. Among 20 men with PSA between 4.1 and 10 ng/mL, 2 (10%) had cancer. In 31 men with PSA between 10.1 and 20 ng/mL, 3 cancers (9.67%) were detected, and in 44 men with PSA >20 ng/mL, 26 cancers were detected (59.09%). The cancer detection rate with 16-core TRUS-guided biopsy is significantly higher than that with 10-core biopsy (54.76% vs. 15.09%, P<0.001). In patients with both normal and abnormal DRE findings, 16-core biopsy has a better detection rate than the 10-core biopsy protocol. With increasing PSA, there is a high rate of detection of prostate cancer in both 10-core and 16-core biopsy patients.


[Arterial hypertension in the black race].
Hypertension represents a major health problem for black populations living in Western countries. In particular, blacks living in the United States have a three- to fivefold greater mortality from hypertensive disease than do whites. Better knowledge of the pathophysiology of hypertension in blacks can aid in the treatment of recently urbanized black people coming to Italy from African countries. Hypertension occurs more frequently in blacks than in whites, due to increased volemia; this characteristic seems to be related to a genetically determined increase in sodium sensitivity. Environmental factors seem to play a relevant role. Several studies performed on blacks migrating from rural to urban areas both in Africa and the USA, have shown that urbanization is closely related to increased blood pressure. The occurrence of cardiac and cerebrovascular complications of hypertension also seems to be closely related to socioeconomic factors. In fact, recently immigrated black people often lack health care facilities and consequently have poor control of hypertension. The environmental factors could be overcome by implementing systems to improve health care facilities, in particular blood pressure control, for recently urbanized blacks.


Update on management strategies for separation from cardiopulmonary bypass.
To update the reader about clinical management strategies for separation from cardiopulmonary bypass. A number of new drugs are being introduced in clinical practice, with significant utility in operative patient management. Further, there is increased routine use of complex devices to achieve separation from or avoidance of cardiopulmonary bypass. Selected medical and device strategies from the most recent literature will be discussed. First, the rationale for selected innovative agents to achieve myocardial performance is reviewed in four perioperative settings: agents for the management of myocardial dysfunction, vasomotor dysfunction, pulmonary hypertension, and right ventricular failure. Second is an evaluation of less commonly considered aspects of mechanical device use in the context of failure to wean from cardiopulmonary bypass or use to avoid cardiopulmonary bypass. Three devices will be discussed: intra-aortic balloon pump, ventricular assist devices, and extracorporeal membrane oxygenation. As our pharmacological and technological armamentarium improve, our population ages and procedures are attempted on patients with increasing co-morbid conditions, it will be important to both utilize newer pharmacological agents and consider innovative uses for device implementation to achieve optimal perioperative outcomes.


Improving spatial perception in 5-yr.-old Spanish children.
Assimilation of distance perception was studied in 70 Spanish primary school children. This assimilation involves the generation of projective images which are acquired through two mechanisms. One mechanism is spatial perception, wherein perceptual processes develop ensuring successful immersion in space and the acquisition of visual cues which a person may use to interpret images seen in the distance. The other mechanism is movement through space so that these images are produced. The present study evaluated the influence on improvements in spatial perception of using increasingly larger spaces for training sessions within a motor skills program. Visual parameters were measured in relation to the capture and tracking of moving objects or ocular motility and speed of detection or visual reaction time. Analysis showed that for the group trained in increasingly larger spaces, ocular motility and visual reaction time were significantly improved during. different phases of the program.


The introduction of expert systems in animal husbandry.
The intensive nature of modern animal husbandry has changed the environmental conditions, so that protection against diseases, especially those caused by secondary pathogenic organisms, becomes an increasing concern. Production inefficiencies become more and more important. Because of their complex nature, many associated problems cannot be solved by farmers alone. With the introduction of information technology in the form of expert systems, new possibilities emerge for maximal productivity and animal health. Expert systems are a new type of computer programmes which are able to handle problems in limited domains at an expert level, using expert knowledge and reasoning processes, within strictly defined problem limits. Expert systems as they presently exist have the following components: a knowledge base (rule- and data-base), inference engine (deductive mechanism), user-interface (explanatory facilities, etc.). The application of knowledge engineering in animal husbandry may result in improvements in the general health and productivity of the herd and the financial returns of the farm, derived from the improved managerial control. At the same time the use of knowledge engineering may lead to greater understanding of the various epidemiological factors that influence farm results, either positively or negatively.


Investigating the Role of Vanadium-Dependent Haloperoxidase Enzymology in Microbial Secondary Metabolism and Chemical Ecology.
The chemical diversity of natural products is established by an elegant network of biosynthetic machinery and controlled by a suite of intracellular and environmental cues. Advances in genomics, transcriptomics, and metabolomics have provided useful insight to understand how organisms respond to abiotic and biotic factors to adjust their chemical output; this has permitted researchers to begin asking bigger-picture questions regarding the ecological significance of these molecules to the producing organism and its community. Our lab is motivated by understanding how select microbes construct and manipulate bioactive molecules by utilizing vanadium-dependent haloperoxidase (VHPO) enzymology. This commentary will give perspective into our efforts to understand the unique VHPO-catalyzed conversions which modulate the activities within two ecologically relevant natural product families. Through enhancing our knowledge of microbial natural product biosynthesis, we can understand how and why these bioactive molecules are created.


Update on chronic complex patient malnutrition
The Scientific Committee of the Sociedad Española de Nutrición Parenteral y Enteral (SENPE) and the Nutricia Advanced Medical Nutrition company began this Course some years ago, and now, it is a referent course in the multidisciplinary training of Clinical Nutrition. With this issue we review the advances in Clinical Nutrition in different situations and, this year, the topic is the malnutrition in chronic complex patients.


Levels of cytotoxic reactivity to cultured normal skin fibroblasts in sera from normal and sarcoma-bearing patients.
Human sera possess complement-dependent cytotoxic reactivity against autologous and allogeneic cultured normal skin fibroblasts. Previous studies indicated that the natural antibody reactivity is directed against fetal antigens expressed on these cells in tissue culture. The reactivity was further characterized in the present study. Chromatographic analysis of a normal serum indicated that its reactivity belonged to the immunoglobulin M (19S) class of immunoglobulins. Sera from 22 preoperative tumor-bearing osteogenic sarcoma patients, 30 tumor-bearing soft-tissue sarcoma patients, and 52 age- and sex-matched normal individuals were tested against allogeneic skin fibroblasts. The patient and normal groups displayed wide, overlapping ranges of cytotoxicity. The osteogenic sarcoma group showed a small but significant increase in mean cytotoxicity compared to the controls, whereas the soft-tissue sarcoma sera were not significantly different from the controls. Reactivities in the sera of patients whose tumors recurred were not significantly different from those of the patients who remained disease free. Cytotoxic levels in sera from eight osteogenic sarcoma patients followed throughout the clinical course remained constant up to the time of documented recurrence and were not affected by surgical removal of the primary tumor or Bacillus Calmette-Guérin immunotherapy. In three of four patients whose tumors recurred, cytotoxic levels fell, but only after documented recurrence. The natural antibody reactivity against normal fibroblasts does not appear useful as a marker for diagnosis, prognosis, or monitoring tumor presence in sarcoma patients.


[Incidence and mortality of stomach cancer in China, 2013].
Objective: To estimate the incidence and mortality of stomach cancer in China based on the cancer registration data in 2013, collected by the National Central Cancer Registry (NCCR). Methods: There were 347 cancer registries that submitted stomach cancer incidence and deaths occurred in 2013 to NCCR. After evaluating the data quality, 255 registries' data were accepted for analysis and stratified by areas (urban/rural), sex, and age group. Combined with data on national population in 2013, the nationwide incidence and mortality of stomach cancer were estimated. Chinese population census in 2000 and Segi's population were used for age-standardized incidence/mortality rates. Results: Qualified 255 cancer registries covered a total of 226 494 490 populations (111 595 772 in urban and 114 898 718 in rural areas). The percentage of cases morphologically verified and death certificate-only cases were 76.27% and 1.98%, respectively, and the mortality to incidence rate ratio was 0.72. It is estimated that there were 427 000 new cases for stomach cancer nationwide, with a crude incidence rate of 31.38 per 100 000 (42.85 per 100 000 in males, 19.33 per 100 000 in females). The age-standardized incidence rates by Chinese standard population (ASR China) and by world standard population (ASR world) were 21.40 per 100 000 and 21.32 per 100 000, respectively, with a cumulative incidence rate (0-74 age years old) of 2.66%. The crude and ASR China incidence rates of stomach cancer in urban areas were 27.80 per 100 000 and 18.48 per 100 000, respectively, whereas those were 35.54 per 100 000 and 24.93 per 100 000 in rural areas. It is estimated that there were 301 000 deaths for stomach cancer nationwide, with a crude mortality rate of 22.13 per 100 000 (29.85 per 100 000 in males, 14.03 per 100 000 in females). The ASR China and ASR world mortality rates were 14.68 per 100 000 and 14.54 per 100 000, respectively, with a cumulative mortality rate (0-74 years old) of 1.70%. The crude and ASR China mortality rates were 18.94 per 100 000 and 12.20 per 100 000 in urban areas, respectively, whereas those were 25.84 per 100 000 and 17.67 per 100 000 in rural areas. Conclusions: There is still a heavy burden of stomach cancer in China. The burden and patterns of stomach cancer shows different gender and urban-rural differences. Prevention and control strategies should be implemented referring to local status.


Influence of transcutaneous electrical nerve stimulation conditions on disynaptic reciprocal Ia inhibition and presynaptic inhibition in healthy adults.
This study investigated the influence of stimulus conditions of transcutaneous electrical nerve stimulation (TENS) on disynaptic reciprocal Ia inhibition (RI) and presynaptic inhibition (D1 inhibition) in healthy adults. Eight healthy participants received TENS (stimulus frequencies of 50, 100, and 200 Hz) over the deep peroneal nerve and tibialis anterior (TA) muscle in the resting condition for 30 min. At pre- and post-intervention, the RI from the TA to the soleus (SOL) and D1 inhibition of the SOL alpha motor neuron were assessed by evoked electromyography. The results showed that RI was not changed by TENS at any stimulus frequency condition. Conversely, D1 inhibition was significantly changed by TENS regardless of the stimulus frequency. The present results and previous studies pertaining to RI suggest that the resting condition might strongly influence the lack of pre- vs. post-intervention change in the RI. Regarding the D1 inhibition, the present results suggest that the effect of TENS might be caused by post-tetanic potentiation. The knowledge gained from the present study might contribute to a better understanding of fundamental studies of TENS in healthy adults and its clinical application for stroke survivors.


Functionalization of single-walled carbon nanotubes "on water".
Single-walled carbon nanotubes (SWNTs) are exfoliated and functionalized into small bundles and individuals by vigorous stirring "on water" in the presence of a substituted aniline and an oxidizing agent. This is an example of an "on water" reaction that leads to functionalized SWNTs, and it represents a "green", or environmentally friendly, process. A variety of reaction conditions were explored. The products were analyzed with Raman, UV-vis-NIR, and X-ray photoelectron spectroscopies, atomic force and transmission electron microscopies, and thermogravimetric analysis.


Cdk4 promotes adipogenesis through PPARgamma activation.
Cell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis. Here we find that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblasts results in reduced and increased adipogenic potential, respectively, of these cells. We show that the effects of cdk4 are not limited to the control of differentiation; cdk4 also participates in adipocyte function through activation of PPARgamma.


Temporal expression of pro-inflammatory cytokines and inducible nitric oxide synthase in experimental acute Chagasic cardiomyopathy.
To characterize the kinetics of myocardial cytokine and inducible nitric oxide synthase (iNOS) expression in acute Chagasic cardiomyopathy, we studied a rat model of acute Trypanosoma cruzi infection. Rats were euthanized 36 hours and 5, 10, and 15 days after infection, and hearts were collected for histology, mRNA, and protein analyses. Histological analysis of myocardium showed a progressive increase in the number of amastigotes and mononuclear inflammatory cells. Organisms were first detected 5 days after intraperitoneal inoculation as isolated nests and became numerous by day 15. Northern blot analysis of total RNA revealed no signal for interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha and a weak signal for IL-6 in control hearts. High levels of expression for the three genes were detected in the infected animals at 36 hours after infection. Although IL-1beta and IL-6 levels increased steadily up to 10 days, TNF-alpha levels were the highest at 5 days, remained high at 10 days, and declined thereafter. Western blot analysis showed similar results to that of mRNA expression. No signal was detected for iNOS in the controls, but both its mRNA and protein were found in the infected animals, with levels being highest at 15 days after infection. Immunohistochemistry revealed no iNOS immunoreactivity in uninfected animals, but intense iNOS staining was detected in blood vessels of infected animals, which decreased progressively with period of infection. Positive staining for iNOS in cardiomyocytes was first detected at 36 hours after infection (at a time when there was no histological inflammatory reaction), which steadily increased, being the highest at 15 days after infection. These results indicate that, in addition to mechanical damage by T. cruzi, substantial pro-inflammatory cytokine production within the myocardium is likely to participate in the pathophysiology of acute Chagasic cardiomyopathy.


Downstream processing of algal polyunsaturated fatty acids.
Little information exists on recovering polyunsaturated fatty acids from microalgae; however, methods for concentration and purification of PUFAs from fish oil have been extensively reported. This review examines recovery and purification of microalgae derived PUFAs, but techniques developed for use with fish oil are also reviewed as being potentially useful for concentration and purification from microalgae. The two main techniques for concentrating and purifying-urea fractionation and high performance liquid chromatography-are discussed in depth and attention is focused on the process developed by the authors for obtaining highly pure PUFA. Other potentially useful techniques, such as supercritical fluid extraction and lipase-catalyzed processing are detailed.


Polyclonal in vitro proliferative responses from nonimmune donors to Plasmodium falciparum malaria antigens require UCHL1+ (memory) T cells.
The in vitro polyclonal proliferative responses of peripheral blood mononuclear cells to whole blood stage parasites or fractionated antigens from the human malaria parasite Plasmodium falciparum were studied. Cells from healthy laboratory donors who had never been exposed to malaria antigens in vivo consistently proliferated to P. falciparum antigens, as did cord blood mononuclear cells. This response was only observed in sheep rosette-positive cells in the presence of adherent cells and was inhibited by NH4Cl, indicating a requirement for antigen processing. The proliferative response was strongest at day 6 and was dependent on the presence of cells expressing high levels of CD45 180-kD isomer (UCHL1 monoclonal antibody), a marker for activated or memory cells, but not for CD45R (SN130 monoclonal antibody) a marker for naive or unprimed T cells. This suggests a similarity to the recall response to tuberculin antigen. These results suggest that the proliferative response to malaria antigens observed previously and described as a nonspecific mitogenic response may be a cross-reactive response to epitopes shared between P. falciparum and other common immunogens. This would explain the establishment of T cell clones to malaria antigens from such donors, but might suggest that the epitopes to which such clones are specific may be of questionable protective or diagnostic use.