Pituitary-gonadal function during sleep in men with erectile impotence and normal controls.
Studies of pituitary-gonadal function in men with erectile disorders have provided conflicting findings. This study compares blood LH and testosterone during sleep in 17 physically healthy men with erectile impotence and 12 matched normal controls, and relates hormonal variations to stages of sleep and penile tumescence. Subjects, aged 23-36 were studied in a sleep laboratory for 3-6 nights with the last two nights devoted to sequential blood sampling every 20 minutes. Five men had never been able to achieve intercourse (primary impotent group) and 12 suffered from a life-long history of intermittent erectile failures (secondary-impotent group). There were no significant differences in sleep duration and REM time among the impotent groups and normal controls. Primary-impotent men showed half as many full tumescent episodes as secondary-impotent men and controls, and spent significantly less time above 80% of full tumescence. The secondary-impotent group did not differ in nocturnal penile tumescent measures from controls. There was a pattern of irregularly occurring fluctuations in plasma LH and testosterone with no differences among groups in frequency and amount of peak hormonal increases. Normal subjects had significantly higher mean testosterone concentrations during REM sleep than during other sleep stages, and during full tumescence than during partial and nontumescent periods. A direct causal relation between REM-related activity and circulating testosterone was not supported by the observation that the hormonal levels during REM sleep and during full tumescence did not differ statistically from the levels measured during adjacent time periods. As with normal subjects, the secondary-impotent group exhibited higher testosterone levels during REM sleep and full tumescence; by contrast, the primary-impotent group did not show significant hormonal differences across stages of sleep and tumescent/ nontumescent periods. These data are discussed with respect to the possible existence of subgroups of impotent men without known organic pathology than may be characterized by psychophysiologic and endocrine differences during sleep.


[Opportunistic infections in HIV-positive patients hospitalized in the Clinic of Infectious Diseases AMG].
Opportunistic infections are one of the major problem among HIV infected patients still connected with high mortality. The aim of the investigation is to evaluate the incidence and mortality from opportunistic infections in HIV infected population in Pomeranian region of Poland. The paper presents analysis of incidence of opportunistic infections among 141 AIDS patients hospitalised in Clinic for Infectious Diseases in Gdańsk from 1988 to 2001/June/. In examined group 179 opportunistic infections were diagnosed. Most frequent was oesophageal candidiasis 58%, tuberculosis 29%, pneumocystis carinii pneumonia 21% and central nervous system toxoplasmosis 13%. The occurrence of opportunistic infections depends on CD4 count and rises with CD4 decline. Opportunistic infections were the reason of death in 33 from 74 cases/45%/. In examined group 28% of patients did not know about HIV infection when first opportunistic infection was diagnosed. Most frequent opportunistic infections in AIDS patients were oesophageal candidiasis, tuberculosis, pneumocystis carinii pneumonia and toxoplasmosis. In 98% of cases opportunistic infection developed when no HAART nor infection prophylaxis was administered. Opportunistic infection was the reason of death in 45% of cases, the most frequent were PCP and CNS toxoplasmosis.


Implications of Antibiotic Resistance for Patients' Recovery From Common Infections in the Community: A Systematic Review and Meta-analysis.
Antibiotic use is the main driver for carriage of antibiotic-resistant bacteria. The perception exists that failure of antibiotic treatment due to antibiotic resistance has little clinical impact in the community. We searched MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science from inception to 15 April 2016 without language restriction. We included studies conducted in community settings that reported patient-level data on laboratory-confirmed infections (respiratory tract, urinary tract, skin or soft tissue), antibiotic resistance, and clinical outcomes. Our primary outcome was clinical response failure. Secondary outcomes were reconsultation, further antibiotic prescriptions, symptom duration, and symptom severity. Where possible, we calculated odds ratios with 95% confidence intervals by performing meta-analysis using random effects models. We included 26 studies (5659 participants). Clinical response failure was significantly more likely in participants with antibiotic-resistant Escherichia coli urinary tract infections (odds ratio [OR] = 4.19; 95% confidence interval [CI] = 3.27-5.37; n = 2432 participants), Streptococcus pneumoniae otitis media (OR = 2.51; 95% CI = 1.29-4.88; n = 921 participants), and S. pneumoniae community-acquired pneumonia (OR = 2.15; 95% CI = 1.32-3.51; n = 916 participants). Clinical heterogeneity precluded primary outcome meta-analysis for Staphylococcus aureus skin or soft-tissue infections. Antibiotic resistance significantly impacts on patients' illness burden in the community. Patients with laboratory-confirmed antibiotic-resistant urinary and respiratory-tract infections are more likely to experience delays in clinical recovery after treatment with antibiotics. A better grasp of the risk of antibiotic resistance on outcomes that matter to patients should inform more meaningful discussions between healthcare professionals and patients about antibiotic treatment for common infections.


The scope and consequences of metaphoric thinking: Using individual differences in metaphor usage to understand how metaphor functions.
People often think, feel, and behave metaphorically according to conceptual metaphor theory. There are normative sources of support for this theory, but individual differences have received scant attention. This is surprising because people are likely to differ in the frequency with which they use metaphors and, therefore, the frequency with which they experience the costs and benefits of metaphoric thinking. To investigate these ideas, a 5-study program of research (total N = 532) was conducted. Study 1 developed and validated a Metaphor Usage Measure (MUM), finding that people were fairly consistent in their tendencies toward literal thought and language on the one hand versus metaphoric thought and language on the other. These differences were, in turn, consequential. Although metaphor usage predicted susceptibility to metaphor transfer effects (Studies 2 and 3), it was also linked to higher levels of emotional understanding (Studies 4 and 5). The findings provide support for several key premises of conceptual metaphor theory in the context of a new measure that can be used to track the consequences of metaphoric thinking. (PsycINFO Database Record


Symptomatic cervical perineural (Tarlov) cyst: a case report.
Perineural (Tarlov) cysts are benign, usually asymptomatic, cerebrospinal fluid filled cysts of the spine, most often found in the sacral region. We report a Tarlov cyst, located in the cervical spine, in a 44-year-old woman who presented with a 3-week history of radicular symptoms of the right C6 root. The perineural cyst was identified at the C5-C6 level following magnetic resonance imaging of the cervical spine. A conservative approach was chosen, with the use of a soft cervical collar for two weeks, a 15-day-course of oral non-steroidal anti-inflammatory medication and instructions concerning limitation of her activities. The outcome of this approach was 90% improvement of her symptoms 24 months after her diagnosis. This is the first report of a cervical Tarlov cyst treated conservatively without the use of oral or injected steroids. The perineural cyst should be included in the differential diagnosis of patients presenting with radicular symptoms. Hippokratia 2015, 19 (1): 76-77.


Determination of blood everolimus concentrations in kidney and liver transplant recipients using the sirolimus antibody conjugated magnetic immunoassay (ACMIA).
The aim of our study was to evaluate the possible determination of everolimus concentrations using the newly-introduced sirolimus antibody conjugated magnetic immunoassay (ACMIA). Everolimus concentrations were determined in 100 blood samples from kidney (n = 47) and liver (n = 53) transplant recipients using the IMx sirolimus microparticle enzyme immunoassay (MEIA) from Abbott as previously described (Clin Biochem 2007;40:132-36) and sirolimus ACMIA from Siemens Healthcare Diagnostics Ltd. The ACMIA everolimus values were significantly higher than those of MEIA (p < 0.001). Analogous slope and intercept values were obtained in the linear regression between the ACMIA and MEIA results when compared to the Seradyn Certican everolimus controls or the blood samples from transplant recipients. Correction of the ACMIA values using the regression equation obtained for the control material (ACMIAcorrected = 0.55 ACMIA + 1.14) led to a satisfactory relationship with the results provided by the MEIA for the patients' samples (MEIA = 1.00 ACMIAcorrected + 0.30, r = 0.905, p < 0.001). The sirolimus ACMIA on the Dimension platform, which does not require manual pre-treatment of the blood samples, may be an acceptable option for therapeutic everolimus monitoring, significantly reducing technician time in comparison to other widely-used immunoassays.


Patient classification systems and staffing. Part 2, Practice and process.
How can nurse executives ensure flexible staffing to meet rapidly changing patient care requirements? Part 1 of this two-part series offered a new way to conceptualize and evaluate current methods of staffing with patient classification systems (PCS). Advantages and disadvantages of each PCS-driven staffing method are explored and implications for nurse executives are examined. A promising new method of PCS-related staffing is described further in Part 2, and implementation strategies are discussed.


Exploration of Underlying Mechanism of Anti-adipogenic Activity of Sulfuretin.
Sulfuretin is a natural flavonoid found in the plant Rhus verniciflua STOKES. The plant has been traditionally used as medicinal agent for antiviral, cathartic, diaphoretic, anti-rheumatic and sedative activities in East Asia. In this study we isolated and identified sulfuretin from R. verniciflua and investigated its anti-adipogenic activity against 3T3-L1 preadipocytes cells. We evaluated the effects of sulfuretin on the adipogenic transcription factors like peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), Fabp4, adiponectin and zinc fingerprint protein (Zfp) 521 by gene expression (real-time QPCR) and Western blot analysis. Sulfuretin treatment at Day 0 and 2 showed significant reduction of lipid production in 3T3-L1 cells in concentration dependent manner. Gene expression analysis (real-time PCR) revealed that sulfuretin inhibited the both major adipogenic factors (C/EBPα, C/EBPβ and PPARγ) and minor adipogenic factors (sterol regulatory element-binding protein (SREBP1c), adiponectin, FAS, Fabp4, Zfp423, and Ebf1). Western blot analysis showed the increased expression of β-catenin and suppression of PPARγ after sulfuretin treatment. Overall, sulfuretin is a natural flavonoid having potent anti-adipogenic activity through the suppression of major adipogenic factors C/EBPα, C/EBPβ and PPARγ, which initiate adipogenesis.


A role for Ras signaling in coreceptor regulation during differentiation of a double-positive thymocyte cell line.
Evidence suggests that the Ras/mitogen-activated protein kinase signaling pathway is required for positive selection of thymocytes. We have asked whether Ras activation is also sufficient to mediate changes in gene expression that are associated with positive selection. To accomplish this, we expressed a constitutively active form of Ras in the immature CD4+ 8+ DPK thymocyte cell line. DPK cells that express active Ras have reduced levels of CD8alpha and CD8beta at the level of cell surface protein and mRNA. These data provide evidence of a direct link between Ras signaling pathways and coreceptor regulation during positive selection. They also suggest that a sustained or potent Ras signal may play a critical role in directing thymocytes into the CD4 lineage. DPK cells that express active Ras, however, were not fully differentiated, indicating that Ras signaling provides only a partial signal for double-positive thymocyte differentiation.


Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy.
We have previously shown that myofibers formed by fusion of muscle satellite cells from spinal muscular atrophy (SMA) I or II undergo degeneration 1 to 3 weeks after innervation by rat embryonic spinal cord explants, whereas normal myofibers survive for several months. In the "muscle component" of the coculture, the only cells responsible for the degeneration are the SMA muscle satellite cells. Moreover, SMA muscle satellite cells do not fuse as rapidly as do normal muscle satellite cells. To determine whether death of muscle cells precedes that of motor neurons, we studied the origin and kinetics of release of apoptotic microparticles. In SMA cocultures, motor neuron apoptosis occurred before myofiber degeneration becomes visible, indicating that SMA myofibers were unable to sustain survival of motor neurons. In normal cocultures, motor neuron apoptosis occurred 4 days after innervation. However, it did not continue beyond 2 days. These results strengthen the hypothesis that SMA is due to a defect in neurotrophic muscle cell function.


Malnutrition negatively impacts the quality of life of patients with cirrhosis: An observational study.
To verify how malnutrition is related to health-related quality of life (HRQL) impairment in patients with cirrhosis. Data was retrospectively abstracted from medical records and obtained by direct interview. We included patients with cirrhosis from any etiology, evaluated at the Liver Clinic from Gastroenterology Department in a tertiary healthcare center, from June 2014 to June 2016. Child-Pugh score, data about complications, and demographic, clinical and anthropometric characteristics of patients were obtained. Nutritional status was evaluated by the Subjective Global Assessment (SGA). HRQL was evaluated through the Chronic Liver Disease Questionnaire. Patients were requested to assess their global HRQL with the following code: 0 = impairment of HRQL, when it was compared with other healthy subjects; 1 = good HRQL, if it was similar to the quality of life of other healthy subjects. To compare the primary outcome between malnourished and well-nourished groups, the χ2 test, Fisher's exact test or Student's t-test were used, based on the variable type. Associations between predictor variables and deterioration of HRQL were determined by calculating the hazard ratio and 95% confidence interval using Cox proportional hazards regression. A total of 127 patients with cirrhosis were included, and the mean age was 54.1 ± 12.3 years-old. According to Child-Pugh scoring, 25 (19.7%) were classified as A (compensated), 76 (59.8%) as B, and 26 (20.5%) as C (B/C = decompensated). According to SGA, 58 (45.7%) patients were classified as well-nourished. Sixty-nine patients identified HRQL as good, and 76 patients (59.8%) perceived impairment of their HRQL. Multivariate analysis to determine associations between predictor variables and self-perception of an impairment of HRQL found strong association with malnutrition (P < 0.0001). The most important impaired characteristics in malnourished patients were: Presence of body pain, dyspnea on exertion with daily activities, decreased appetite, generalized weakness, trouble lifting or carrying heavy objects, and decreased level of energy (P < 0.0001). Malnutrition is a key factor related to impairment of HRQL in patients with cirrhosis.


[Introduction of reduced rank regression and development of a user-written Stata package].
Reduced rank regression is an extended multivariate linear regression model with the function of dimension reduction. It has been more and more widely used in nutritional epidemiology research to understand people's dietary patterns in recent years. However, there has been no existing Stata package or command to implement reduced rank regression independently. Therefore, we developed a new user-written package named "rrr" for its implementation in Stata. This paper summarizes the methodology of reduced rank regression, the development and functions of the Stata rrr package and its application in the China Kadoorie Biobank dataset, with the aim of facilitating the future wide use of this statistical method in epidemiology and public health research.


Eu(III)-functionalized MIL-124 as fluorescent probe for highly selectively sensing ions and organic small molecules especially for Fe(III) and Fe(II).
A layerlike MOF (MIL-124, orGa2(OH)4(C9O6H4)) has been prepared and chosen as a parent compound to encapsulate Eu(3+) cations by one uncoordinated carbonyl group in its pores. The Eu(3+)-incorporated sample (Eu(3+)@MIL-124) is fully characterized, which shows excellent luminescence and good fluorescence stability in water or other organic solvents. Subsequently, we choose Eu(3+)@MIL-124 as sensitive probe for sensing metal ions, anions, and organic small molecules because of its robust framework. Studying of the luminescence properties reveals that the complex Eu(3+)@MIL-124 was developed as a highly selective and sensitive probe for detection of Fe(3+) (detection limit, 0.28 μM) and Fe(2+) ions through fluorescence quenching of Eu(3+) and MOF over other metal ions. In connection to this, a probable sensing mechanism was also discussed in this paper. In addition, when Eu(3+)@MIL-124 was immersed in the different anions solutions and organic solvents, it also shows highly selective for Cr2O7(2-)(detection limit, 0.15 μM)and acetone. Remarkably, it is the first Eu-doped MOF to exhibit an excellent ability for the detection of Fe(3+) and Fe(2+) in an aqueous environment without any structural disintegration of the framework.


Mapping polycyclic aromatic hydrocarbon and aromatic amine-induced DNA damage in cancer-related genes at the sequence level.
Genomic injury induced by environmental carcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines, is the initial step that can trigger mutagenesis and carcinogenesis. In addition to the physico-chemical property of DNA damaging agents, several important factors such as primary sequence, chromatin structure, methylation, protein association, and transcriptional activity can affect not only the initial level and distribution of DNA damage but also the efficiency of repair. Therefore, mapping the DNA damage induced by environmental agents in cancer-related genes such as p53 and ras at the sequence level provides essential information for assessing their carcinogenic potential. Recently, using the E. coli nucleotide excision enzyme complex, UvrABC nucleases in combination with ligation-mediated polymerase chain reaction, we developed a method to map DNA damage in the p53 and ras genes. These studies led us to conclude that targeted DNA damage, in combination with growth selection, contributes greatly in shaping the mutation spectrum in these genes in human cancer. Here we present the rationale and details of this approach, typical experimental results and necessary precautions.


[The spa-health resort and touristic-recreational facilities of the region: the methodological aspects of their development].
The correction and optimization of the motor activity of the patients are currently the main priorities of all rehabilitative and recreational activities based at the spa and health resort facilities. The forms of such activities include walking tours and excursion trips. In other words, the excursion potential is one of the very important attributes of the recreational recourses. Under the current conditions characterized by the rapid socio-economic changes, the studies concerning the structural and functional transformation of spa and health resorts, recreational and tourist facilities acquire special importance, both from the humanitarian and economic points of view. The results of these studies may greatly contribute to the organization and the further development of rehabilitative and recreational activities based at the spa and health resort facilities, recreational and tourist centers taking into consideration their evolution. The objective of the present article is to analyze the structure and functions of the recreation and tourist centres as well as the modes of their cooperation with the spa and health resort facilities. In other words, these structures and their functions are both the object and the subject of the present study. The methodology of the study is based on the logical analysis of the development of the recreational and tourist systems in the framework of the evolutionary approach. (1) the notions of «tourist destination» and «recreation» have been substantiated; (2) the results of the studies carried out at the Institute of Physical Culture, Sports and Tourism and the Petrozavodsk State University have been used to elaborate the affiliate international Master Degree program «Project management in the tourism industry». The main emphasis in this program is placed on the necessity and methods of the improvement of recreational activities and more efficacious utilization of the climatic factors and the health resort infrastructure as well as personnel training for the sake of improvement of services to the visitors. The analysis of various aspects of recreation and tourism development has demonstrated that the services provided by the recreational and tourist systems in cooperation with the health resort infrastructure open up new employment opportunities and thus reduce the risk of social tension. The prospects for the continuation of investigations along these lines are associated with the extension of the recreational and touristic activities over the rural and countryside localities with special reference to the trans-border interactions as well as specific features of the tourist and recreational resources of the given regions and territories.


Lisofylline, a novel antiinflammatory agent, protects pancreatic beta-cells from proinflammatory cytokine damage by promoting mitochondrial metabolism.
Proinflammatory cytokine-mediated pancreatic beta-cell dysfunction is a key pathological event in type I diabetes mellitus. Lisofylline (LSF), an anti-inflammatory agent, has been shown to protect pancreatic islets from IL-1 beta-induced inhibitory effects on insulin release. However, the mechanism of LSF action is not known. Increasing evidence suggests that the mitochondria play an important role in regulating the beta-cell insulin release capacity and the control of cellular viability. To examine the direct effects of LSF on beta-cells, insulin-secreting INS-1 cells were exposed to a combination of recombinant IL-1 beta, TNF alpha, and IFN gamma with or without LSF for 18 h. Basal and glucose-stimulated static insulin release were measured using RIA. INS-1 cell viability was determined using in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and LIVE/DEAD dual fluorescence labeling. To evaluate INS-1 mitochondrial function, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism, change in mitochondrial membrane potential, and intracellular ATP levels were assessed. Cytokine addition reduced basal (7.8 +/- 0.30 vs. 10.0 +/- 0.46 ng/ml.h; P < 0.005), glucose-stimulated insulin secretion (11.6 +/- 0.86 vs. 17.4 +/- 1.86 ng/ml.h; P < 0.005), and MTT metabolism in INS-1 cells. Over 40% of the cytokine-treated beta-cells exhibited nuclear DNA breakage, whereas the control cell death rate remained at 1-2%. Simultaneous application of LSF and cytokines to INS-1 cells restored insulin secretion, MTT metabolism, mitochondrial membrane potential, and cell viability to control levels. LSF increased beta-cell MTT metabolism as well as insulin release and glucose responsiveness. In summary, proinflammatory cytokines lead to a reduction of glucose-induced insulin secretion, mitochondrial activity, and viability in INS-1 cells. LSF at concentrations achievable in vivo protected beta-cells from the cytokine effects. The mechanism of LSF-induced protection may be by promoting mitochondrial metabolism.


Human and simian T-cell leukemia viruses type 2 (HTLV-2 and STLV-2(pan-p)) transform T cells independently of Jak/STAT activation.
Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 differ in pathogenicity in vivo. HTLV-1 causes leukemia and neurologic and inflammatory diseases, whereas HTLV-2 is less clearly associated with human disease. Both retroviruses transform human T cells in vitro, and transformation by HTLV-1 was found to be associated with the constitutive activation of the Jak/STAT pathway. To assess whether HTLV-2 transformation may also result in constitutive activation of the Jak/STAT pathway, six interleukin-2-independent, HTLV-2-transformed T-cell lines were analyzed for the presence of activated Jak and STAT proteins by electrophoretic mobility shift assay. In addition, the phosphorylation status of Jak and STAT proteins was assessed directly by immunoprecipitation and immunoblotting with an antiphosphotyrosine antibody. Jak/STAT proteins were not found to be constitutively activated in any of the T-cell lines infected by the type 2 human and nonhuman primate viruses, suggesting that HTLV-2 and the cognate virus simian T-lymphotropic virus type 2 from Pan paniscus transform T cells in vitro by mechanisms at least partially different from those used by HTLV-1.


Gene Therapy for Autoimmune Disease.
Advances in understanding the immunological and molecular basis of autoimmune diseases have made gene therapy a promising approach to treat the affected patients. Gene therapy for autoimmune diseases aims to regulate the levels of proinflammatory cytokines or molecules and the infiltration of lymphocytes to the effected sites through successful delivery and expression of therapeutic genes in appropriate cells. The ultimate goal of gene therapy is to restore and maintain the immune tolerance to the relevant autoantigens and improve clinical outcomes for patients. Here, we summarize the recent progress in identifying genes responsible for autoimmune diseases and present examples where gene therapy has been applied as treatments or prevention in autoimmune diseases both in animal models and the clinical trials. Discussion on the advantages and pitfalls of gene therapy strategies employed is provided. The intent of this review is to inspire further studies toward the development of new strategies for successful treatment of autoimmune diseases.


A randomized pilot trial of a videoconference couples communication intervention for advanced GI cancer.
This study aims to test the feasibility and preliminary efficacy of a couple-based communication intervention for advanced GI cancer delivered via videoconference. Thirty-two couples were randomly assigned to either couples communication skills training (CCST) or an education comparison intervention, both delivered via videoconference. Participation was limited to couples who reported communication difficulties at screening. Patients and partners completed measures of relationship functioning and individual functioning at baseline and post-intervention. Eighty-eight percent of randomized dyads completed all six sessions and reported high levels of satisfaction with the intervention. Between-group effect sizes suggested that the CCST intervention led to improvements in relationship satisfaction for patients and partners and to improvements in intimacy and communication for patients. A couples-based communication intervention delivered via videoconference is feasible and acceptable in the context of advanced cancer. Preliminary findings suggest that the intervention shows promise in contributing to enhanced relationship functioning. Copyright © 2016 John Wiley & Sons, Ltd.


Adaptation of endothelial cells to physiologically-modeled, variable shear stress.
Endothelial cell (EC) function is mediated by variable hemodynamic shear stress patterns at the vascular wall, where complex shear stress profiles directly correlate with blood flow conditions that vary temporally based on metabolic demand. The interactions of these more complex and variable shear fields with EC have not been represented in hemodynamic flow models. We hypothesized that EC exposed to pulsatile shear stress that changes in magnitude and duration, modeled directly from real-time physiological variations in heart rate, would elicit phenotypic changes as relevant to their critical roles in thrombosis, hemostasis, and inflammation. Here we designed a physiological flow (PF) model based on short-term temporal changes in blood flow observed in vivo and compared it to static culture and steady flow (SF) at a fixed pulse frequency of 1.3 Hz. Results show significant changes in gene regulation as a function of temporally variable flow, indicating a reduced wound phenotype more representative of quiescence. EC cultured under PF exhibited significantly higher endothelial nitric oxide synthase (eNOS) activity (PF: 176.0±11.9 nmol/10(5) EC; SF: 115.0±12.5 nmol/10(5) EC, p = 0.002) and lower TNF-a-induced HL-60 leukocyte adhesion (PF: 37±6 HL-60 cells/mm(2); SF: 111±18 HL-60/mm(2), p = 0.003) than cells cultured under SF which is consistent with a more quiescent anti-inflammatory and anti-thrombotic phenotype. In vitro models have become increasingly adept at mimicking natural physiology and in doing so have clarified the importance of both chemical and physical cues that drive cell function. These data illustrate that the variability in metabolic demand and subsequent changes in perfusion resulting in constantly variable shear stress plays a key role in EC function that has not previously been described.


The mucocele - floor of the mouth.
Three cases are reported to illustrate certain features related to swellings of the salivary glands. With a mucocele of the floor of the mouth difficulites may arise in the correct identification of the gland of origin, in elucidating the aetiological factors, and in obtaining adequate radiographic or sialographic views of the area. Surgical treatment follows the surgical removal of the involved gland.


Prevalence of Osteosclerosis Among Patients Visiting Dental Institute in Rural Area of Western India.
Idiopathic osteosclerosis (IO) is a benign lesion of unknown aetiology and is not attributed to any dysplastic, inflammatory, neoplasia, or systemic disorder. To assess the prevalence and distribution of IO according to its location and to patients' age and gender, among rural population of western India. Seven hundred and fifty patients were examined for the presence of IO in the jaw bone. After a thorough clinical examination, radiographic examination was done using OPG. Age specified by WHO were used 5, 12, 15, 35-44 and 65-74. The data collected was than tabulated and subjected to descriptive statistics and chi square test. Among the total study population 89 (11.8%) were found to be suffering from IO out of which 27 (7.2%) were males and 62 (16.53%) were females. The maximum number of IO cases cases was seen among the age group of 35-44 y, 33 (22.0%) and minimum in 5 y 9 (6%). IO is higher among the females as compared to males and mostly seen among the 3(rd) and 4(th) decade individuals.


Comparison Between Signature Cytokines of Nasal Tissues in Subtypes of Chronic Rhinosinusitis.
Endotype in chronic rhinosinusitis (CRS) has been established in the last decade. However, the exact immunologic profile of CRS still has controversy because it has a considerable immunologic heterogeneity. Therefore, we investigated various inflammatory mediators according to different nasal tissues in chronic rhinosinusitis and compared them within the same subject. We collected uncinate process mucosa (UP) and nasal polyp (NP) tissues from controls, CRS without NP (CRSsNP) and CRS with NP (CRSwNP). Expression levels of 28 inflammatory mediators including T helper (Th) 1, Th2, Th17, proinflammatory cytokines and remodeling markers were determined by multiplex immunoassay and were analyzed using paired tests as well as principal component analysis (PCA) to investigate endotype in each subtype of CRS. Signature inflammatory mediators are interleukin (IL)-5, C-C motif chemokine ligand (CCL)-24, monocyte chemoattractant protein (MCP)-4, and vascular cell adhesion molecule (VCAM)-1 in eosinophilic NP, whereas IL-17A, IL-1β, and matrix metallopeptidase (MMP)-9 were detected as signature inflammatory markers in non-eosinophilic NP. Despite differences in inflammatory cytokine profile between eosinophilic and non-eosinophilic NP, the common upregulation of IL-5, CCL-11, IL-23, IL-2Rα, VCAM-1, MMP-3 and MMP-9 were shown in NP compared to UP within the same subject. In the PCA, we observed that Th2 immune response was helpful in discriminating between nasal tissues in subtypes of CRS and that there was a partial overlap between non-eosinophilic NP and eosinophilic NP in terms of Th2 mediators. Commonly upregulated mediators in NP were Th2-associated, compared with UP regardless of CRS subtypes, whereas signature markers were distinct in each NP subtype. These findings imply that Th2 inflammatory responses may play a role in the development of NP regardless of CRSwNP subtypes.


Hypothalamic hamartoma in an unusual case with delayed puberty.
Hypothalamic hamartoma (HH) is a rare intracranial lesion that usually presents with classic triad of central precocious puberty, gelastic epilepsy, and developmental delay. Herein, a 14-year old boy is presented in whom the diagnosis of HH was made by magnetic resonance imaging. While he did not have any complain of precocious puberty, he surprisingly suffered from delay in puberty. The definite diagnosis of HH can only be made by appropriate imaging, in a case with atypical feature of delay in puberty and in the absence of gelastic epilepsy. To our best knowledge, this is the first case of HH who is presented with delay in puberty as of first manifestation.


[4-aminopyridine induced rage reaction in mice].
Rage reaction was induced in mice by sc 4-aminopyridine (4-AP) 6 mg . kg-1. Mice appeared hyperreactive after 8-12 min and then squeaked and fought each other. These manifestations were most distinct in 10-30 min and subsided after 40-60 min. The occurrence of rage reaction on this dose level was around 90%. At higher doses 4-AP caused convulsions and death after evocation of rage reaction. The ED50 of 4-AP for eliciting rage reaction was 4.7 +/- 0.7 mg . kg-1 sc. No significant difference in induction of rage reaction was seen between male and female mice of different body weights. Both neuroleptic drugs (chlorpromazine, haloperidol, tarden and clozapine) and anxiolytic drugs (diazepam, chlordiazepoxide, and meprobamate) inhibited 4-AP-induced rage reaction in mice. Barbiturates, Chloral hydrate, methaqualone, morphine hydrochloride, aspirin, phenytoin sodium, diphenhydramine hydrochloride, atropine sulfate, and procaine hydrochloride did not affect rage reaction. The 4-AP-induced aggressive behavior, similar to that induced by electric footshock or isolation, has the merits of convenience to deal with and time saving. Hence we recommended it as a screening method for drugs with neuroleptic and anxiolytic activities.


Skin lesion classification using HG-PSO and YOLOv7 based convolutional network in real time.
Skin cancer is a chronic illness seen visually and further diagnosed with a dermoscopic examination. It is crucial to precisely localize and classify lesions from dermoscopic images to diagnose and treat skin cancers as soon as possible. This work presents melanoma identification, and the classification method significantly improves accuracy and precision. This work proposes a method Hybrid of Genetic and Particle swarm optimization (HG-PSO), and You only look once version 7 (YOLOv7) based convolutional network for skin cancer classification. The infected region is first located using optimized YOLOv7 object detection. Then color thresholding is applied to segment it, which is passed to the proposed convolutional network for classification. This work is tested on the Human Against Machine with 10,000 training images (HAM10000), International Skin Imaging Collaboration (ISIC)-2019, and Hospital Pedro Hispano (PH2) datasets, and the findings are compared to the state-of-the-art methods for classifying skin cancer. The proposed method achieves 98.86% accuracy, 99.00% average precision, 98.85% average recall, and 98.85% average F1-score on the HAM10000 dataset. It achieves 97.10% accuracy on ISIC-2019 datasets. The average precision obtained is 97.37%, the average recall is 97.13%, and the average F1-score is 97.13% on the ISIC-2019 dataset. It achieves a 97.7% accuracy on the PH2 dataset. The average precision obtained is 99.00%, the average recall is 96.00%, and the average F1-score is 97.00% on the PH2 dataset. The test time taken by this method on datasets HAM10000, ISIC-2019, and PH2 dataset is 2, 3, and 2 s, respectively, which may help give faster responses in telemedicine.


Linear frequency modulation reverberation suppression using difference of singular values.
This letter proposes a reverberation suppression method to improve the target detection probability in reverberation environment induced by a linear frequency modulation signal. Using the singular value decomposition and an assumption of local spatial stationarity, the proposed algorithm suppresses reverberation utilizing the difference of singular values between the reference beam and the current beam of interest. Several experiments using real oceanic reverberation data justify the validity of the proposed algorithm.


[The roles of cytokine in organ-specific tumor metastasis].
The production of cytokines by tumor cells has been suggested as the molecular perturbation responsible for the development of malignant tumors. The behavior of tumor cells in animals is presumed to be affected by these factors, which include such hematopoietic cytokines as GM-CSF, IL-1, and IL-6. Here, we report findings demonstrating that GM-CSF is produced by many murine transplantable tumors with metastatic ability in the lungs, and IL-6 and/or IL-1 are produced by the tumors metastatic in the liver. We discuss the notion that the particular organ or organs in which tumor cells metastasize may be associated with the type of cytokines produced by the tumors. Metastatic spread requires interactions of tumor cells with components of the extracellular matrix of host tissues or with other cells, almost all of which depend on cell surface determinants such as cell adhesion molecules. We also discuss the possibility that the expression and adhesive potentials of adhesive protein (CD44) may be regulated by the cytokine (GM-CSF) excreted from the tumor cells. We then emphasize the possibility that both gene expression of cytokines and adhesive proteins play a critical role in tumor metastasis and in determining organ specificity in metastasis.


Inoculation With Ectomycorrhizal Fungi and Dark Septate Endophytes Contributes to the Resistance of Pinus spp. to Pine Wilt Disease.
Pine wilt disease (PWD) is a deadly disease to pines (Pinus spp.) worldwide. The occurrence of PWD can reduce the relative abundance of root ectomycorrhizal fungi (ECMF) and dark septate endophytes (DSE). However, the effects of exogenous ECMF/DSE inoculation on the rhizosphere microbial community structure of Pinus tabulaeformis infected by pine wood nematode (PWN) is little known. Here, we tested how ECMF/DSE may improve resistance to PWD by quantifying microbial carbon biomass and soil enzymatic activity among different treatments at 6 and 9 months after PWN infection. Denaturing gradient gel electrophoresis (DGGE) was used to study the microbial community structure at 3, 6, and 9 months after PWN infection in the rhizosphere of P. tabulaeformis seedlings inoculated with ECMF/DSE. The results showed that exogenous ECMF/DSE inoculation reduced the disease severity caused by PWN infection. After PWN infection, the rhizosphere microbial carbon of seedlings inoculated with Amanita vaginata, Suillus bovinus, Gaeumannomyces cylindrosporus, and Paraphoma chrysanthemicola was 38.16, 49.67, 42.11, and 96.05% higher than that of the control group, respectively. Inoculation of ECMF/DSE inhibited the decrease of rhizosphere microbial biomass caused by PWN infection. The richness and diversity of P. tabulaeformis rhizosphere fungi at 9 months were reduced by PWN infection but partially recovered by the exogenous fungi (ECMF/DSE) inoculation except for P. chrysanthemicola, which indicates a role of ECMF/DSE in maintaining stability of the microbial community. Inoculation with ECMF/DSE increased the beneficial bacterial (Thauera sp., Mesorhizobium sp., etc.) and fungal groups (Tomentella ellisii, Wilcoxina mikolae, etc.) of in the rhizosphere. In summary, exogenous ECMF/DSE inoculation could increase P. tabulaeformis resistance to PWD probably by improving the rhizosphere microenvironment.


Lessons learned from cross-validating alignments between large anatomical ontologies.
To compare the alignments of two large anatomical ontologies (the Foundational Model of Anatomy and GALEN) produced by three ontology alignment systems (AOAS, FALCON and PRIOR) in the framework of the Ontology Alignment Evaluation Initiative during its 2006 campaign. Number of mappings identified by AOAS: 3,132, FALCON: 2,518 and PRIOR: 2,589. Three approaches to analyzing and comparing the results were utilized: computing the overlap among result files, manual review of some 2,000 mappings and structural validation. The generic systems FALCON and PRIOR identify many false positives and false negatives. With a stricter and domain-specific lexical similarity model, AOAS has a better precision, but is more sensitive to missing synonyms and misspellings.


[Junzo Kodama, a pioneer of Dutch learning in the Bizen feudal clan, and Hosetsu Nanba, an eclectic of Chinese and Dutch medicines].
J. Kodama (1806-1861) and H. Nanba (1791-1859) were the physicians to the chief retainers of the Bizen feudal clan; Mr. Iki and Mr. Hiki. They lived in the same age, but Kodama lived in obscurity all his life, while Nanba spent his life in famous circumstances. Kodama absconded from the Bizen feudal clan and studied Dutch learning at the private school in Nagasaki which had been founded by Dr. Ph. F. von siebold. But on returning to his native shores his superior officers had no regard for his Dutch learning, resulting in his moving to Osaka, where he died. Nanba learned Chinese medicine from Nangai Yoshimasu, obstetrics from Ransai Kagawa, and surgery from Rokujyō Hanaoka and Seishū Hanaoka. On returning to his native shores, Kanagawa, he founded a private school for the study of medicine, Shiseido, and cultivated many physicians by writing medical books extensively. The author described their activity on the basis of new materials.


Characterization of the cell wall and outer membrane of Rhodopseudomonas capsulata.
Sucrose density gradient centrifugation of cell envelopes of chemotrophically grown cells of Rhodopseudomonas capsulata St. Louis (= ATCC 23782) resulted in the separation of a cytoplasmic membrane from a cell wall fraction (buoyant densities, 1.139 and 1.215 g/cm3, respectively). The cell wall fractions (untreated or Triton extracted) contained peptidoglycan- and lipopolysaccharide-specific components. Their neutral sugar content, mainly rhamnose and galactose, was high (250 and 100 micrograms/mg [dry weight] of material) due to a non-lipopolysaccharide polymer. The fatty acid content was low (less than or equal to 60 micrograms/mg [dry weight] of material), and half of it was contributed by lipopolysaccharide (3-OH-C10:0, C12:1, and 3-oxo-C14:0). The predominant other fatty acid was C18:1. An outer membrane fraction, obtained by lysozyme treatment of the Triton-extracted cell wall, showed essentially the same chemical composition except for almost complete removal of peptidoglycan. Saline extraction (0.9% NaCl, 37 degrees C, 2 h) removed a lipopolysaccharide-protein(-phospholipid?) complex from whole cells of R. capsulata St. Louis. The polypeptide patterns of the cell wall and outer membrane as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis comprised 20 to 25 different polypeptides (most of them very faint) and were dominated by a single, heat-modifiable major protein (Mr 69,000 after solubilization below 60 degrees C; Mr 33,000 at temperatures above 70 degrees C).


Genetic diversity and profiles of genes associated with virulence and stress resistance among isolates from the 2010-2013 interagency Listeria monocytogenes market basket survey.
Whole genome sequencing (WGS) was performed on 201 Listeria monocytogenes isolates recovered from 102 of 27,389 refrigerated ready-to-eat (RTE) food samples purchased at retail in U.S. FoodNet sites as part of the 2010-2013 interagency L. monocytogenes Market Basket Survey (Lm MBS). Core genome multi-locus sequence typing (cgMLST) and in-silico analyses were conducted, and these data were analyzed with metadata for isolates from five food groups: produce, seafood, dairy, meat, and combination foods. Six of 201 isolates, from 3 samples, were subsequently confirmed as L. welshimeri. Three samples contained one isolate per sample; mmong the 96 samples that contained two isolates per sample, 3 samples each contained two different strains and 93 samples each contained duplicate isolates. After 93 duplicate isolates were removed, the remaining 102 isolates were delineated into 29 clonal complexes (CCs) or singletons based on their sequence type. The five most prevalent CCs were CC155, CC1, CC5, CC87, and CC321. The Shannon's diversity index for clones per food group ranged from 1.49 for dairy to 2.32 for produce isolates, which were not significantly different in pairwise comparisons. The most common molecular serogroup as determined by in-silico analysis was IIa (45.6%), followed by IIb (27.2%), IVb (20.4%), and IIc (4.9%). The proportions of isolates within lineages I, II, and III were 48.0%, 50.0% and 2.0%, respectively. Full-length inlA was present in 89.3% of isolates. Listeria pathogenicity island 3 (LIPI-3) and LIPI-4 were found in 51% and 30.6% of lineage I isolates, respectively. Stress survival islet 1 (SSI-1) was present in 34.7% of lineage I isolates, 80.4% of lineage II isolates and the 2 lineage III isolates; SSI-2 was present only in the CC121 isolate. Plasmids were found in 48% of isolates, including 24.5% of lineage I isolates and 72.5% of lineage II isolates. Among the plasmid-carrying isolates, 100% contained at least one cadmium resistance cassette and 89.8% contained bcrABC, involved in quaternary ammonium compound tolerance. Multiple clusters of isolates from different food samples were identified by cgMLST which, along with available metadata, could aid in the investigation of possible cross-contamination and persistence events.


Enhancing public confidence in vaccines through independent oversight of postlicensure vaccine safety.
The National Immunization Program of the Centers for Disease Control and Prevention is responsible for controlling infectious diseases through vaccination, but the program also plays a key role in postlicensure vaccine safety assessment. The time has come to separate postlicensure vaccine safety assessment from vaccine risk management as recommended by the National Research Council of the National Academy of Sciences.The National Transportation Safety Board offers a useful model for developing an independent National Vaccine Safety Board that would have the authority to leverage resources and expertise of various government agencies, academia, and industry to oversee postlicensure vaccine safety investigations. Such a board would have been useful in recent vaccine safety concerns, and its independence from government programs would ensure optimal vaccine safety and enhance public confidence in vaccines.


Knowledge, Attitudes and Practices of Postnatal Mothers on Ophthalmia Neonatorum in the Central Region, Ghana.
Health education is key in the prevention of Ophthalmia Neonatorum (ON). However, health education in relation to eye care in Ghana is very low. To determine the knowledge, attitudes and practices (KAPs) of mothers on Ophthalmia Neonatorum (eye infection in newborns), a descriptive cross-sectional design was adopted, using a standardised interviewer-administered questionnaire to collect data. Using a consecutive sampling technique, we enrolled 407 mothers to participate in the study. The overall KAPs of the study participants were assessed using the sum score of each outcome based on Bloom's cut-off point. Completed data was then analysed using descriptive statistics with SPSS version 22.0 at the level of P < .05. Out of the 407 participants, 321 (78.9%) had not heard about Ophthalmia Neonatorum with nearly 93% having low levels of knowledge on the neonatal infection. We found a significant association between formal education (P = .001), skilled occupation (P = .008) and a high level of knowledge on Ophthalmia Neonatorum. The study highlights the need to find improved and alternative methods of educating mothers on Ophthalmia Neonatorum in the bid to reduce blindness attributed to the condition.


Visual search in infantile nystagmus syndrome.
Research on infantile nystagmus syndrome (INS) and visual search is limited. Conducting this research could assist practitioners in understanding how INS affects the real-life visual activities of patients and aid in developing new clinical visual function assessments for INS. The aim of this work is to investigate how subjects with INS perform visual search tasks, and, particularly, to assess how INS subjects perform when targets are located at their null position or away from it, and when under additional cognitive demands. INS subjects (N = 15) and controls (N = 20) performed conjunction and feature search tasks, both with and without mental arithmetic. Search performance was assessed using log-transformed total search time, gaze-dependent search time, and accuracy. Cognitive demand was quantified by pupil size and the NASA task-load index score. INS subjects showed longer search times compared to controls in conjunction search (P < 0.01), but not in feature search. Within INS and control subjects, the total search times were significantly increased by the addition of mental arithmetic (P < 0.0001). There was no difference in gaze-dependent search times between null target position and 15° away from null target position of subjects in conjunction search (P > 0.05). Accuracies were 100% for both control and INS subjects in both conjunction and feature search. Conjunction visual search was impaired in adult INS subjects, and further worsened under increased cognitive demand. The null position did not affect the visual search performance in INS.


Interaction Between Cyclosporine and Palbociclib in a Renal Transplant Patient: Case Report and Pharmacokinetic Perspective.
Solid organ transplant recipients have increased cancer risk due in part to chronic immunosuppression and opportunistic oncogenic viral infections. The management of drug interactions in transplant recipients being treated for cancer is important both to minimize the likelihood of drug-related toxicities and to optimize therapeutic outcomes. We present a case of a 41-year-old woman with a stable living-related kidney transplant maintained on an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and prednisone, who was subsequently diagnosed with a metastatic lobular breast carcinoma and papillary thyroid cancer and started palbociclib, a time-dependent CYP3A inhibitor. After initiation of palbociclib, cyclosporine trough and peak concentrations were increased by 159% and 81%, respectively, relative to the average cyclosporine concentrations pre-palbociclib. Using the Drug Interaction Probability Scale (DIPS), the interaction between palbociclib and cyclosporine was rated as "probable." Dose reductions of immunosuppressive agents that are CYP3A substrates are warranted if palbociclib is initiated, followed by close monitoring of blood concentrations. This report also highlights the challenges of coadministering a time-dependent inhibitor with a narrow therapeutic index drug that is metabolized by the same enzyme, particularly when the inhibitor is given in cycles with off-treatment periods.


Modulation of cell surface antigens induced by 12-O-tetradecanoyl-phorbol 13-acetate in two myeloblastic cell lines, a promyelocytic cell line, and a monoblastic cell line: detection with five monoclonal antibodies.
The modulation of cell surface antigens in 2 myeloblastic cell lines (ML-1 and KG-1), a promyelocytic cell line (HL-60), and a monoblastic cell line (THP-1-0) by the presence of 12-O-tetradecanoyl-phorbol 13-acetate [(TPA) CAS: 16561-29-8] was investigated by indirect membrane immunofluorescence with the use of three monoclonal antibodies (MoAb) (OKM-1, 63D3, and MCS-2) reacting with myeloid-monocyte antigens (expressed by cells of both granulocyte and monocyte lineages) and two MoAb (1/12/13 and MCS-1) reacting with myeloid antigens (expressed by cells of the granulocyte lineage). Functionally mature macrophage properties, such as adherence, morphologic character, and phagocytosis, were induced by the presence of TPA in each of the cell lines except for adherence in the HL-60 cells. After 3 days in culture, the expression of the OKM-1-defined antigen was markedly augmented in all 4 cell lines. The expression of the 63D3-defined antigen was also markedly augmented in the ML-1, KG-1, and THP-1-0 cells, but it was not significantly altered in the HL-60 cells. The MCS-2-defined antigen was amplified in expression in the ML-1 and HL-60 cells, but it showed minimum decrease in the KG-1 and THP-1-0 cells. The MCS-1-defined antigen expression was suppressed in ML-1, HL-60, and THP-1-0 but was enhanced in KG-1. The suppressed expression of My-1 antigen (detected by the MoAb 1/12/13) was noted in all 4 cell lines. Thus in the ML-1 cells, expression of the myeloid-monocyte antigens was augmented, whereas myeloid antigen expression was inhibited in the presence of TPA, a result that parallels antigenic expression in terminal macrophage differentiation. The trend was true, except for the 4 cell line-antigen combinations (MCS-2-defined antigen and MCS-1-defined antigen in KG-1, 63D3-defined antigen in HL-60, and MCS-2-defined antigen in THP-1-0). The heterogeneous attitude of some antigens to TPA found in these cell lines may result from the fact that they represent different points in the myeloid-monocyte differentiation scheme.


The effect of ischemic cholinergic damage on cognition in patients with subcortical vascular cognitive impairment.
Prior research has shown that the total amount of white matter ischemia had no significant correlation with cognitive deficits. We compared the association of white matter hyperintensities (WMHs) of total as well as cholinergic pathways with clinical dementia severity and investigated whether cholinergic ischemic burden had an independent predictive value with respect to cognitive decline in subcortical vascular cognitive impairment (SVCI). Forty-eight patients underwent detailed neuropsychological tests and brain magnetic resonance imaging. Quantification of WMH in the total white matter and in cholinergic pathways was achieved using the visual Scheltens scale and Cholinergic Pathway HyperIntensity Scale (CHIPS), respectively. We explored the association between WMH scores and clinical dementia rating scale (CDR). To assess the relation between WMH and cognitive scores, multiple linear regression analysis was used. The CHIPS score was higher in subcortical vascular dementia compared to subcortical vascular MCI, while this difference was not found with the total TMHs (TWMH) score. The TWMH score had a positive correlation with CHIPS, however only CHIPS scores positively correlated with sum of box scores of CDR scale (CDR SB; ρ = .474, P = .001). Higher CHIPS scores were associated with lower performance on the semantic word fluency test (β = -.447, P = .036), whereas the TWMH scores had no independent predictive value with respect to cognitive impairment, after controlling for CHIPS score. Our data confirmed the association of ischemic damage within cholinergic pathways with dementia severity, independent of TWMH in SVCI. In addition, this cholinergic deficit is clinically relevant to cognitive deterioration, especially with frontal dysfunction.


Symptomatic cervical vertebral hemangioma treated by percutaneous vertebroplasty.
Vertebral hemangioma (VH) is considered to be a benign lesion of bone with a rich vasculature. Most incidentally discovered hemangiomas are asymptomatic. Percutaneous vertebroplasty (PVP) has demonstrated efficacy in the treatment of symptomatic thoracic and lumbar VHs. To our knowledge, the reports concerning PVP on symptomatic cervical VHs are quite rare. Our intent was to assess PVP as treatment for symptomatic cervical hemangiomas. Prospective evaluation. An inteventional pain management practice, single medical center. Eight patients with symptomatic cervical VHs were enrolled between December 2008 and February 2012, all of whom underwent magnetic resonance imaging (MRI) of the cervical spine. The patients with 8 vertebral bodies of VHs were treated by using PVP. The clinical and radiological data were collected and analyzed. Postoperative outcomes were determined using a visual analog scale. Surgical levels include C3 (2 patients), C4 (3 patients), C5 (2 patients), and C6 (one patient). The average follow-up period was 27.4 months, with a minimum of 12 months. Mean operative time and x-ray exposure time were respectively 35 ± 7.1 minutes and 25 ± 7.7 seconds. The visual analogue scale for neck pain decreased significantly from 6.9 ± 0.6 preoperatively to 1.3 ± 0.5 (P < 0.01) on the second day after surgery, with a final score of 1.2 ± 0.5 (P < 0.01). Cement distribution was always diffuse and homogeneous. No cement leakage was observed in all cases except for 2 patients. There were no other major complications at the time of last follow-up evaluation. An observational clinical trial with a relatively small sample size. Short-term results indicate that PVP appears to be an effective and safe treatment for symptomatic cervical VHs.


MiR-223-3p attenuates the migration and invasion of NSCLC cells by regulating NLRP3.
Lung cancer is the malignant tumor with high invasion and metastasis, which seriously threatens public health. Previous study showed that NLRP3 could promote the occurrence of lung tumors in B(a)P-induced mice. MicroRNAs are closely related to the progression and metastasis of lung cancer by regulating target genes. However, which miRNAs affect the migration and invasion of lung cancer cells through regulating NLRP3 remains poorly defined. In this study, the miRNAs targeting NLRP3 were selected from TargetScan and miRDB database and finally miR-223-3p was chosen due to the consistent expression in both A549 and H520 cells. Then, the migration and invasion of lung cancer cells were detected with miR-223-3p mimic and inhibitor using Transwell assay, at the same time the expression of NLRP3, cleaved caspase-1, IL-1β and IL-18 was determined using Western Blot and immunohistochemistry assay. Our data demonstrated that miR-223-3p was upregulated in both A549 and H520 cells. Furthermore, the migration and invasion of A549 and H520 cells were promoted after inhibiting miR-223-3p. Besides, the levels of NLRP3, cleaved caspase-1, IL-1β and IL-18 were increased in the two lung cancer cells. And the corresponding results were contrary in miR-223-3p mimic group. Taken together, miR-223-3p attenuates the migration and invasion of NSCLC cells by regulating NLRP3, which provides evidence for the prevention and targeted treatment of NSCLC.


Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.
Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit.


Nitric oxide-donating aspirin inhibits beta-catenin/T cell factor (TCF) signaling in SW480 colon cancer cells by disrupting the nuclear beta-catenin-TCF association.
Dysregulation of the Wnt pathway and altered Beta-catenin expression are central early events in colorectal carcinogenesis. We studied the ortho, meta, and para (o-, m-, and p-) positional isomers of NO-donating aspirin (NO-ASA), a chemopreventive agent against colon cancer, for their effect on Beta-catenin/T cell factor (TCF) signaling. In human SW480 colon carcinoma cells, cell-growth inhibition by NO-ASA [IC50 values for p-, o-, and m- were 48.1 +/- 4.3 (mean +/-SEM), 60.4 +/- 2.1, and 900 +/-50 microM, respectively] was accompanied by significant inhibition of Beta-catenin signaling. We determined Beta-catenin-dependent TCF-4 transcriptional activity by measuring the activity of the luciferase gene placed under the control of TCF-4 regulatory sequences. The IC50 values for Beta-catenin/TCF-4-signaling inhibition by NO-ASA were: o-, 2.6 +/- 0.4; m-, 15 +/- 5; p-, 1.1 +/- 0.1 microM; and for ASA, >5,000 microM. Total or nuclear levels of Beta-catenin and its distribution in the cell were not altered by NO-ASA, as judged by protein expression levels and semiquantitative immunofluorescence analysis. NO-ASA disrupted the association of Beta-catenin and TCF-4 in the nucleus, whereas ASA did not affect it. NO-ASA reduced the expression of cyclin D1, a downstream target gene that plays an important role in colon carcinogenesis. In contrast, a structural analog of NO-ASA lacking the -NO2 moiety did not affect TCF-4 transcriptional activity. Thus, NO-ASA inhibits Beta-catenin-mediated TCF activity by preventing the formation of the Beta-catenin/TCF-4 complex. This effect, occurring at NO-ASA concentrations far below those required to inhibit cell growth, may be a critical early event in the chemopreventive activity of NO-ASA against colon cancer.


Objective and Subjective Assessments of Sleep in Children: Comparison of Actigraphy, Sleep Diary Completed by Children and Parents' Estimation.
In research and clinical contexts, parents' report and sleep diary filled in by parents are often used to characterize sleep-wake rhythms in children. The current study aimed to investigate children self-perception of their sleep, by comparing sleep diaries filled in by themselves, actigraphic sleep recordings, and parental subjective estimation. Eighty children aged 8-9 years wore actigraph wristwatches and completed sleep diaries for 7 days, while their parents completed a sleep-schedule questionnaire about their child' sleep. The level of agreement and correlation between sleep parameters derived from these three methods were measured. Sleep parameters were considered for the whole week and school days and weekends separately and a comparison between children with high and low sleep efficiency was carried out. Compared to actigraphy, children overestimated their sleep duration by 92 min and demonstrated significant difficulty to assess the amount of time they spent awake during the night. The estimations were better in children with high sleep efficiency compared to those with low sleep efficiency. Parents estimated that their children went to bed 36 min earlier and obtained 36.5 min more sleep than objective estimations with actigraphy. Children and parents' accuracy to estimate sleep parameters was different during school days and weekends, supporting the importance of analyzing separately school days and weekends when measuring sleep in children. Actigraphy and sleep diaries showed good agreement for bedtime and wake-up time, but not for SOL and WASO. A satisfactory agreement for TST was observed during school days only, but not during weekends. Even if parents provided more accurate sleep estimation than children, parents' report, and actigraphic data were weakly correlated and levels of agreement were insufficient. These results suggested that sleep diary completed by children provides interesting measures of self-perception, while actigraphy may provide additional information about nocturnal wake times. Sleep diary associated with actigraphy could be an interesting tool to evaluate parameters that could contribute to adjust subjective perception to objective sleep values.


'Revolutions, philosophical as well as civil': French chemistry and American science in Samuel Latham Mitchill's Medical Repository.
From 1797 to 1801 a controversy played out on the pages of the Medical Repository, the first scientific journal published in the United States. At its centre was the well-known feud between the followers of Antoine Lavoisier and Joseph Priestley, the lone supporter of the phlogiston model. The American debate, however, had more than two sides. The Americans chemists, Samuel Latham Mitchill and Benjamin Woodhouse, who rushed to support Priestley did not defend his scientific views. Rather, as citizens of a republic, they defended his right to have them. They also castigated the assertions of the "French chemists," whose claims that the new chemistry obviated debate seemed unsettlingly similar to the dictatorial ambitions of the French state. Using the Medical Repository, Mitchill and Woodhouse sought a compromise that validated the new chemistry, but united it with a more egalitarian form of discourse. The desired balance eluded them. Priestley proved too stubborn, and as the French Revolution descended into dictatorship and war, Mitchill and Woodhouse came more to realize that truly prising French chemistry from the culture of the revolutionary era. The episode left Mitchill and Woodhouse disillusioned with chemistry and hoping to redirect scientific enthusiasm to more pious ends.


[Real-time Quaking-induced Conversion Analysis of Prion-like Seeding Activity of Pathological α-Synuclein].
Pathological α-synuclein (αSyn) has been shown to retain the ability to propagate as prions in humans and animals. However, the molecular basis underlying the prion-like properties of αSyn remains poorly understood. We examined whether brain tissues from cases of dementia with Lewy bodies (DLB), which contain serine 129 (Ser129)-phosphorylated insoluble aggregates of αSyn, exhibit prion-like seeding activity in vitro using the real-time quaking-induced conversion (RT-QuIC) seeding assay. Brain tissues from cases of diffuse neocortical DLB yielded a 50% seeding dose of 107.3-109.8/g brain. The RT-QuIC assay could discriminate between DLB and other neurological and neurodegenerative disorders, suggesting its potential applicability for differential diagnosis. Insoluble aggregates of αSyn>250 kDa detected only in DLB brain tissues by Western blotting analysis were specifically phosphorylated at Ser129. Therefore, we postulated that Ser129-phosphorylated insoluble aggregates of αSyn have prion-like seeding activity. However, insoluble aggregates of recombinant human αSyn (rSyn) with increased β-sheet structures showed little seeding activity in either the phosphorylated or nonphosphorylated state. In contrast, prefibrillar oligomers of rSyn showed seeding activity both with and without phosphorylation. The findings of the present study suggested that soluble oligomeric αSyn, but not the fully fibrillary form, is a seeding species in vitro.


Gender stereotypes and superior conformity of the self in a sample of cyclists.
In the field of driving, people tend to think they are more competent and more cautious than others. This is the superior conformity of the self (SCS). Our main hypothesis was that, among cyclists, women would show a higher SCS on cautiousness, though men would show a higher SCS concerning competence. 1799 cyclists provided a self-assessment of their own cautiousness and of other people's cautiousness. The same procedure was used for competence. Consistent with the hypothesis, the SCS was gender-specific: it was more prominent for women concerning cautiousness and more prominent for men concerning competence. These results could explain why people tend to ignore the safety campaigns. They also indicate the importance of adapting messages concerning safety measures to gender.


Sequences and techniques in spinal MR imaging.
The optimal protocol in spinal MR imaging is not evident. Sagittal T2 weighted FSE, sagittal T1 weighted SE and axial T2 weighted FSE sequences are widely accepted for imaging patients with sciatica and/or lumbar pain. Because of the limited amount of CSF compared to the lumbar spine, the choice of sequences is much more complex in the study of the cervical spine. Sagittal T2 FSE, sagittal T1 SE and axial 2D GE images are suggested in routine cervical spine imaging. To assess the bone marrow, a STIR sequence can be added to this protocol on both lumbar and cervical spine examinations. The 2D GE produces an acceptable image quality to differentiate between the disc and bony protrusions. The use of FLAIR for imaging spinal cord lesions remains controversial in the literature.


Flight Test Techniques for Quantifying Pitch Rate and Angle of Attack Rate Dependencies.
Three different types of maneuvers were designed to separately quantify pitch rate and angle of attack rate contributions to the nondimensional aerodynamic pitching moment coefficient. These maneuvers combined pilot inputs and automatic multisine excitations, and were demonstrated with the subscale T-2 and Bat-4 airplanes using the NASA AirSTAR flight test facility. Stability and control derivatives, in particular C m q and C m α ˙ , were accurately estimated from the flight test data. These maneuvers can be performed with many types of aircraft, and the results can be used to improve physical insight into the flight dynamics, facilitate more accurate comparisons with wind tunnel experiments or numerical investigations, and increase simulation prediction fidelity.


Finding the right words: A focus group investigation of nurses' experiences of writing diaries for intensive care patients with a poor prognosis.
The overall purpose of diaries written during an intensive care stay is to help patients fill in memory gaps from the illness trajectory, which might promote long-term psychological recovery. Diaries have also been shown to benefit nurses in maintaining a view of the patient as a person in the highly technical environment and to promote reflection. There is a lack of research on how nurses might be affected by writing a diary for critically ill patients with a poor prognosis. The aim of this study was to investigate nurses' experience of writing diaries for intensive care patients with a poor prognosis. This study has a qualitative descriptive design and was inspired by the methodology of interpretive description. Twenty-three nurses from three Norwegian hospitals with a well-established practice of writing diaries participated in four focus groups. Reflexive thematic analysis was used. The study was reported according to the Consolidated Criteria for Reporting Qualitative Research checklist. The overarching theme resulting from our analysis was "Finding the right words". This theme represents the challenge of writing in view of the uncertainty of the patient's survival and of who would read the diary. It was important to strike the right tone with these uncertainties in mind. When the patient's life could not be saved, the purpose of the diary expanded to comforting the family. To put an extra effort into making the diary something special when the patient was dying was also a meaningful activity for the nurses. Diaries may serve other purposes than helping patients to understand their critical illness trajectory. In cases of a poor prognosis, nurses adapted their writing to comfort the family rather than informing the patient. Diary writing was meaningful for the nurses in managing care of the dying patient.


Feral ferrets (Mustela furo) as hosts and sentinels of tuberculosis in New Zealand.
The control and eventual eradication of bovine tuberculosis (TB) poses major challenges in New Zealand, given the variety of wildlife species susceptible to TB, many of which are capable of onwards transmission of Mycobacterium bovis infection. Here we discuss the role of feral ferrets (Mustela furo), focussing on potential transmission or risk pathways that have implications for management of TB. Firstly inter-specific transmission to ferrets. Ferrets scavenge potentially infected wildlife, including other ferrets, thus prevalence of TB can be amplified through ferrets feeding on tuberculous carcasses, particularly brushtail possums (Trichosurus vulpecula). Secondly intra-specific transmission between ferrets. The rate of ferret-ferret transmission depends on population density, and in some places ferret densities exceed the estimated threshold for disease persistence. TB can therefore potentially be maintained independently of other sources of infection. Thirdly transmission from ferrets to other wildlife. These include the main wildlife maintenance host, brushtail possums, that will occasionally scavenge potentially tuberculous ferret carcasses. Fourthly transmission from ferrets to livestock. This is considered to occur occasionally, but the actual rate of transmission has never been measured. Fifthly geographical spread. M. bovis-infected ferrets can travel large distances and cause new outbreaks of TB at locations previously free of TB, which may have caused an expansion of TB-endemic areas. Ferrets play a complex role in the TB cycle in New Zealand; they are capable of contracting, amplifying and transmitting M. bovis infection, sometimes resulting in ferret populations with a high prevalence of TB. However, ferret population densities are usually too low to sustain infection independently, and transmission to other wildlife or livestock appears a rarer event than with possums. Nevertheless, management of ferrets remains a key part of the National Pest Management Strategy for TB. Control is prudent where M. bovis-infected ferret populations exist in high numbers, to reduce the onward transmission risk of any self-sustained infection to livestock. When ferret numbers are well below the theoretical disease maintenance threshold, ferret control is still sometimes warranted because of the animals' ability to acquire infection when young and, through dispersal, transport it outside TB-endemic areas. Ferrets can also be used as disease sentinels for TB, especially in areas where alternative sentinel species are rare or expensive to survey, and when sampling of possums is not cost-effective.


Primary cutaneous mucormycosis of the lower extremity in a male patient with diabetes.
Mucormycosis is a rare but serious angioinvasive fungal infection that can affect the cutaneous system. Primary cutaneous mucormycosis is caused by direct inoculation and is most prevalent in immunocompromised hosts, particularly those with diabetes. A high index of suspicion is necessary for this condition in patients with rapid and deep extension of necrosis despite aggressive surgical intervention. Deep tissue specimens should be sent for fungal culture and histologic analysis for confirmation of the diagnosis. Early and aggressive debridement to prevent spread to deeper tissues and organs, concurrent antifungal therapy, and medical management of comorbidities are paramount to the treatment of primary cutaneous mucormycosis. This case report highlights the presentation and recommended treatment of primary cutaneous mucormycosis in 1 patient for reduced morbidity and mortality associated with this type of infection.


Robotic devices for movement therapy after stroke: current status and challenges to clinical acceptance.
Robotic devices for movement therapy are moving closer to becoming commercially available tools for aiding in stroke rehabilitation. Robotic technology offers a range of functions that will augment current clinical practice by leveraging therapists' time, cost effectively extending therapy programs, providing new measures of impairment, and offering new therapy protocols. In this article, we review work from several research laboratories that supports the clinical value of stroke therapy systems. A commercialization effort based on these results is described. We also discuss challenges to achieving clinical acceptance and practical implementation of these devices.


[A trend analysis of the incidence of occupational diseases in Chongqing, China, from 2006 to 2014].
Objective: To investigate the incidence of occupational diseases in Chongqing, China, from 2006 to 2014, and to analyze the harm, features, and trend of occupational diseases in Chongqing. Methods: The data of new cases of occupational diseases from 2006 to 2014 were collected, and the patients with a confirmed diagnosis of occupational diseases were selected as study subjects to analyze the incidence of occupational diseases in Chongqing. Results: There were 17499 cases of occupational diseases in total in Chongqing from 2006 to 2014. Among these patients, 17124 (97.86%) were male, most of whom (95.40%) had occupational pneumoconiosis, and 375 (2.14%) were female, most of whom (72.80%) had occupational chemical poisoning. There were 16400 cases (93.72%) of occupational pneumoconiosis in total, mainly coal workers' pneumoconiosis (55.87%) and silicosis (43.02%) , and the main industries involved were coal mining and washing, railway transport equipment manufacturing, and mining and washing of bituminous coal and anthracite. There were 724 cases of occupational poisoning in total; there were 281 cases of acute occupational poisoning, mainly gas poisoning (39.86%) and carbon monoxide poisoning (33.10%) ; there were 443 cases of chronic occupational poisoning, mainly poisoning caused by benzene (47.63%) , mercury and its inorganic compounds (32.74%) , and lead and its inorganic compounds (9.03%) . Conclusion: Occupational diseases in Chongqing are mainly occupational pneumoconiosis, and occupational health supervision should be enhanced in the industries of coal mining and washing and railway transport equipment manufacturing to protect workers' health.


[A role of platelet activating factor in experimental hemorrhagic enteritis induced by Clostridium difficile toxin].
Clostridium difficile is thought to be an important causative agent of antibiotics associated colitis. However its mechanisms are not fully understood. The present study was designed to elucidate the effect of PAF and free radicals on experimental hemorrhagic enteritis induced by Clostridium difficile toxin. PAF concentration in the portal blood and accumulated fluid, disturbance of the vascular endothelial cells in the ligated jejunal loops and chemiluminescence activity of WBC in the control group's rats increased from 4 hrs over 10 hrs after the administration of Clostridium difficile toxin. On the other hand, the amount of fluid accumulation, protein concentrations in the accumulated fluids, histological changes in the ligated jejunal loops of toxin administered rats and chemiluminescence activity of WBC were significantly suppressed by PAF antagonist (CV6209:TAKEDA). These results suggest that PAF and free radicals may have some role in microcirculatory disturbance and hyperpermeability of the blood vessels in the intestine of hemorrhagic enteritis induced by Clostridium difficile toxin.


Clinical Implication of Genetic Testing in Dilated Cardiomyopathy.
Dilated cardiomyopathy (DCM) is one of the important causes of heart failure (HF). With the rapidly evolving technologies for gene analysis and tremendous advances in knowledge of HF genetics, the importance of genetic testing in DCM is currently highlighted. Several genetic variants causing DCM have been identified and this information is used for diagnosis, risk stratification and family screening of DCM patients. However, there are still several challenges in applying genetic testing to real clinical practice. In this review, we will summarize recent understandings in DCM genetics and provide an evidence-based practical guide to the use of genetic testing for DCM patients.


Leaching of copper, chromium, and boron from treated timber during aboveground exposure.
Field studies were conducted to evaluate leaching of Cu, Cr, and B from timber treated with a Cr, Cu, and B wood preservative and exposed aboveground in Spanish weathering conditions during one year with a total rainfall of approximately 500 mm. The effect of timber orientation (horizontal for decks and vertical for fences) on metal leaching was assessed. Leaching of metals after one year was higher for decks than for fences, with total amounts of metals leached being 226.6 and 87.8 mg/m2 for Cu, 199.5 and 42.4 mg/m2 for Cr, and 110.1 and 32.6 mg/m2 for B from decks and fences, respectively. Leaching rates did not drop constantly with time, because an increase in metal leaching, except for B, was observed at the end of the year after a long dry period. The order of metal emission varied with cumulative rainfall: Leaching of B was higher than Cr initially, but the opposite occurred at the end of the assay. Total emissions of Cu and Cr obtained in a laboratory assay were lower than those for decks and fences under field conditions when expressed per unit surface area (mg/m2), but they were similar to the values obtained for fences when expressed as a percentage of the initial amount. However, the percentage of B leached from wood was higher in laboratory than in field assays for both orientations, with the amount of B leached per unit surface area under laboratory conditions being higher than that leached from fences but lower than that leached from decks. Emission rates extrapolated to one year from laboratory data underestimated metal leaching from decks and overestimated emissions from fences.


Effects of antenatal betamethasone on maternal and fetoplacental matrix metalloproteinases 2 and 9 activities in human singleton pregnancies.
A single course of antenatal betamethasone is administered to women at risk of preterm labor to advance fetal lung maturation. Matrix metalloproteinases (MMPs) are collagen-degrading enzymes that remodel extracellular matrix components during lung development. We tested the hypothesis that the effects of betamethasone on fetal lung maturation involve changes in MMP activity. We conducted a prospective, observational pilot study of three groups of singleton pregnancies. Group 1 (n = 21) was composed of women who were antenatally treated with a single course of betamethasone and who delivered < 37 weeks of gestation, group 2 (n = 7) was composed of matched untreated women who delivered < 37 weeks of gestation, and group 3 (n = 15) was composed of untreated women who delivered > 37 weeks of gestation. Maternal blood, mixed cord blood, and placental samples were collected at the time of delivery for MMP-2 and MMP-9 activity and tissue inhibitor of metalloproteinases (TIMP)-1 and -2 levels. MMP-2 activity was significantly higher in the maternal, placental, and fetal compartments in group 1 compared with group 2 (p < .05). TIMP-2 levels were lower in groups 1 and 2 compared with group 3. Maternal TIMP-2 levels were higher (p < 0.003), whereas fetal TIMP-1 (p < .01) and MMP-9 to TIMP-1 ratios (p < .05) were lower when delivery was delayed more than 2 weeks following betamethasone treatment. We conclude that elevated MMP-2 activity in the maternal and fetoplacental compartments may suggest a mechanism, in part, for betamethasone-induced fetal lung maturation.


Novel members of the AGAMOUS LIKE 6 subfamily of MIKCC-type MADS-box genes in soybean.
The classical (C) MIKC-type MADS-box transcription factors comprise one gene family that plays diverse roles in the flowering process ranging from floral initiation to the development of floral organs. Despite their importance in regulating developmental processes that impact crop yield, they remain largely unexplored in the major legume oilseed crop, soybean. We identified 57 MIKC(c)-type transcription factors from soybean and determined the in silico gene expression profiles of the soybean MIKC(c)-type genes across different tissues. Our study implicates three MIKC(c)-type transcription factors as novel members of the AGAMOUS LIKE 6 (AGL6) subfamily of the MIKC(C)-type MADS-box genes, and we named this sister clade PsMADS3. While similar genes were identified in other legume species, poplar and grape, no such gene is represented in Arabidopsis thaliana or rice. RT-PCR analysis on these three soybean PsMADS3 genes during early floral initiation processes revealed their temporal expression similar to that of APETALA1, a gene known to function as a floral meristem identity gene. However, RNA in situ hybridisation showed that their spatial expression patterns are markedly different from those of APETALA1. Legume flower development system differs from that in the model plant, Arabidopsis. There is an overlap in the initiation of different floral whorls in soybean, and inflorescent meristems can revert to leaf production depending on the environmental conditions. MIKC(C)-type MADS-box genes have been shown to play key regulatory roles in different stages of flower development. We identified members of the PsMADS3 sub-clade in legumes that show differential spatial expression during floral initiation, indicating their potential novel roles in the floral initiation process. The results from this study will contribute to a better understanding of legume-specific floral developmental processes.


Bioequivalence studies with metformin: comparability of reference tablets from different origins.
The choice of an appropriate reference product is still a problem within the European Union. When no direct comparisons between originator products in different countries are available, registration authorities are sometimes only prepared to grant registration for a generic product on the basis of a comparison with the originator product in the respective country. The aim of the investigation was therefore to evaluate the bioequivalence of reference products from different origins in two different bioequivalence trials with the same test drug. Two separate bioequivalence trials were performed involving the oral administration of one test and two reference products containing 500 mg metformin. Both studies had a randomized, open, single-dose, three-period crossover design and were carried out in 24 healthy volunteers. The reference products in the first trial were Glucophage mite (Germany) and Diabex (Australia). In the second trial the reference drugs were Glucophage mite (France) and Glucophage mite (Switzerland). The results of each trial were analyzed regarding the bioequivalence of the respective reference drugs. The reference drugs in each of both trials were bioequivalent: the 90% confidence intervals for both AUC(0-tlast) and C(max) were entirely within the acceptance range for bio-equivalence trials (0.80 - 1.25 for both parameters). In the case of metformin, the reference products available in the countries examined were very similar. This retrospective analysis involving two studies, therefore, confirmed bioequivalence between these reference products.


Relationship between admission criteria and academic performance: A correlational study in nursing students.
An admission criterion is one of the key indicators of academic success. The purpose of admission process is to select best candidates for the particular program who will complete the program successfully. Thus rigorous admission criteria can predict academic performance, decrease failure rate and successful completion of degree. The objective of this study was to determine the relationship between various variables in the existing admission criteria and academic performance. A cross sectional study design was chosen. Data (2009-2017) was gathered from the records of Institute of Nursing Science, Khyber Medical University. Variables in the admission criteria included age, gender, previous academic performance, entry test score and experience. The dependent variable was academic performance measured in CGPA. The data was analyzed using correlation and regression analysis through SPSS and STATA. The results reported a significant relationship between admission criteria and the academic performance of nursing students. Various variables in the admission criteria i.e. SSC marks (r=0.32, p=>0.001), previous academic score at diploma level (r=0.48, p=>0.001) and entry test scores (r=0.26, p=>0.001) have significant relationship between academic performance. However, previous academic scores at diploma level were better predictors of the academic performance. The study concludes to use integrated admission criteria for the selection of students and bring changes in the traditional admission process.


Electrophilic warhead-based design of compounds preventing NLRP3 inflammasome-dependent pyroptosis.
Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we describe the synthesis and chemical tuning of α,β-unsaturated electrophilic warheads toward the development of antipyroptotic compounds. Their pharmacological evaluation and structure-activity relationships are also described. Compound 9 was selected as a model of this series, and it proved to be a reactive Michael acceptor, irreversibly trapping thiol nucleophiles, which prevented both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner. Moreover, 9 and other structurally related compounds, inhibited caspase-1 and NLRP3 ATPase activities. Our findings can contribute to the development of covalent, multitarget antipyroptotic compounds targeting molecular components of the NLRP3 inflammasome regulatory pathway.


Helsinki Heart Study. New perspectives in the prevention of coronary heart disease.
The Helsinki Heart Study tested the effect of modifying plasma low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol on the primary prevention of coronary heart disease in middle-aged men with non-HDL-cholesterol greater than or equal to 5.2 mmol/L (200 mg/dl). One group (2046 men) received 600mg of gemfibrozil twice daily, and the other (2035 men) received placebo. Averaged over the 5-year trial period, gemfibrozil induced mean decreases of 11% in LDL-cholesterol and 35% in triglycerides and a mean increase of 11% in HDL-cholesterol compared with placebo. These changes were accompanied by a 34% reduction (number of end-points; 56 vs 84) in the incidence of coronary heart disease. The reduction was largest in subjects with type IIB hyperlipoproteinaemia and smallest in subjects with type IIA hyperlipoproteinaemia. The changes in serum HDL- and LDL-cholesterol during the trial were associated (p less than 0.02 and p less than 0.05, respectively) with the risk of coronary heart disease in the gemfibrozil group, but not in the placebo group.


Sustainable Fuel Production from Ambient Moisture via Ferroelectrically Driven MoS2 Nanosheets.
Unlike traditional water splitting in an aqueous medium, direct decomposition of atmospheric water is a promising way to simultaneously dehumidify the living space and generate power. Here, a tailored superhygroscopic hydrogel, a catalyst, and a solar cell are integrated into a humidity digester that can break down ambient moisture into hydrogen and oxygen, creating an efficient electrochemical cell. The function of the hydrogel is to harvest moisture from ambient humidity and transfer the collected water to the catalyst. Barium titanate and vertical 2D MoS2 nanosheets are integrated as the catalyst: the negatively polarized cathode can enhance the electron transport and attract H+ to the MoS2 surface for water reduction, while water oxidation takes place at the positively polarized anode. By employing this mechanism, it is possible to maintain the relative humidity in a medium-sized room at <60% without any additional energy input, and a stable current of 12.5 mA cm-2 is generated by the humidity digester when exposed to ambient light.


Predictors of Clinical Success After Transcatheter Paravalvular Leak Closure: An International Prospective Multicenter Registry.
Transcatheter closure of a symptomatic prosthetic paravalvular leak (PVL) is feasible, but there is presently no conclusive evidence to show consistent efficacy. We aimed to identify predictors of clinical success after transcatheter PVL closure. Consecutive patients referred to 24 European centers for transcatheter PVL closure in 2017 to 2019 were included in a prospective registry (Fermeture de Fuite ParaProthétique, FFPP). Clinical success was absence of any of the following within 1 month: re-admission for heart failure, blood transfusion, open-heart valvular surgery, and death. We included 216 symptomatic patients, who underwent 238 percutaneous PVL closure procedures on the mitral (64.3%), aortic (34.0%), or tricuspid (1.7%) valve. Symptoms were heart failure, hemolytic anemia, or both in 48.9%, 7.8%, and 43.3% of patients, respectively. One, 2, and 3 leaks were treated during the same procedure in 69.6%, 26.6%, and 3.8% of patients, respectively. The PVL was pinpoint or involved 1/8 or 1/4 of the valve circumference in 18.6%, 52.4%, and 28.1% of cases, respectively. The most frequently used devices were the Vascular Plug 3, Ventricular Septal Defect Occluder, Vascular Plug 2, and Paravalvular Leak Device (45.0%, 16.6%, 14.2%, and 13.6% of cases, respectively). Successful device(s) implantation with leak reduction to ≤grade 2 was obtained in 85.0% of mitral and 91.4% of aortic procedures, respectively (P=0.164); with major periprocedural adverse event rates of 3.3% and 1.2%, respectively (P=0.371); and clinical success rates of 70.3% and 88.0%, respectively (P=0.004). By multivariate analysis, technical failure, mechanical valve, and hemolytic anemia were independently associated with absence of clinical success (odds ratios [95% CIs], 7.7 [2.0-25.0]; P=0.002; 3.6 [1.1-11.1]; P=0.036; and 3.7 [1.2-11.9]; P=0.025; respectively). Transcatheter PVL closure is efficient and safe in symptomatic patients but is associated with a lower clinical success rate in patients with hemolysis and/or a mechanical valve. URL: https://www. gov; Unique identifiers: NCT05089136.


Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy.
Chemotherapy-induced nausea and vomiting includes both Acute (0-24 h) and Delayed (24-120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3-4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy. Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication. Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen. A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.