Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).
During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers. During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL). Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF.


Modeling of post-stroke stimulation of cortical tissue.
Following a stroke, cortical networks in the penumbra area become fragmented and partly deactivated. We develop a model to study the propagation of waves of electric potential in the cortical tissue with integro-differential equations arising in neural field models. The wave speed is characterized by the tissue excitability and connectivity determined through parameters of the model. Post-stroke tissue damage in the penumbra area creates a hypoconnectivity and decreases the speed of wave propagation. It is proposed that external stimulation could restore the wave speed in the penumbra area under certain conditions of the parameters. Model guided cortical stimulation could be used to improve the functioning of cortical networks.


Genetic variation in prostaglandin E2 synthesis and signaling, prostaglandin dehydrogenase, and the risk of colorectal adenoma.
Prostaglandins are important inflammatory mediators; prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of omega-6 and omega-3 polyunsaturated fatty acids; their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk. We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of omega-3 fatty acids. A 30% adenoma risk reduction was observed for EP2 4950G>A (intron 1; OR(GA/AA vs. GG), 0.71; 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4 Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (P(interaction) = 0.02). An interaction with fish intake was also observed for PGES -664A>T (5' untranslated region; P(interaction) = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR(>2 t/wk vs. <1 t/wk), 0.56; 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C>A (intron 1) and PGDH 343C>A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression; neither method detected significant interactions. These data provide little support for associations between adenoma risk and genetic variability related to PGE(2), yet suggest gene-environment interactions with anti-inflammatory exposures.


Mortality rate increases steeply with nonadherence to statin therapy in patients with acute coronary syndrome.
In a prospective cohort of consecutive acute coronary syndrome (ACS) patients, we compared the adherence rate of statin usage and mortality rate during a median follow-up of 23 months. Adherence to statin therapy after acute coronary syndrome affects mortality rate. We analyzed ACS patients (N = 1969; age, 65.9 ± 11.8 years; female 30.4%) who underwent angiography between March 2006 and March 2008. The postdischarge usage of statins was based on the purchase register of the Social Insurance Institution of Finland. The death rate was verified from Statistics Finland. At discharge, the rate of statin prescription to patients was 95.4% (n = 1878). When comparing adherent patients (n = 1200; 61.7%), who purchased the medication systematically until the end of the median 23-month follow-up, with nonadherent patients (n = 94; 4.8%), who did not use the medication at all, there was a vast difference in absolute death rate between the groups: 4.9% vs 14.9%, respectively (P < 0.001). We conducted Cox proportional hazards model with ACS type, cerebrovascular attack, diabetes, age, 3-artery disease, and cancer as adjusted confounders. Compared with regular statin users, nonusers were associated with a >2× increased hazard ratio of mortality (hazard ratio: 2.70, 95% confidence interval: 1.49-4.90, P = 0.001). Statin medication is essential for discharged ACS patients. They should be strongly encouraged to purchase and use it.


Cerebrospinal fluid volumetric net flow rate and direction in idiopathic normal pressure hydrocephalus.
The aim of the present study was to examine cerebrospinal fluid (CSF) volumetric net flow rate and direction at the cranio-cervical junction (CCJ) and cerebral aqueduct in individuals with idiopathic normal pressure hydrocephalus (iNPH) using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI). An in-depth, pixel-by-pixel analysis of regions of interest from the CCJ and cerebral aqueduct, respectively, was done in 26 iNPH individuals, and in 4 healthy subjects for validation purposes. Results from patients were compared with over-night measurements of static and pulsatile intracranial pressure (ICP). In iNPH, CSF net flow at CCJ was cranially directed in 17/22 as well as in 4/4 healthy subjects. Estimated daily CSF volumetric net flow rate at CCJ was 6.9 ± 9.9 L/24 h in iNPH patients and 4.5 ± 5.0 L/24 h in healthy individuals. Within the cerebral aqueduct, the CSF net flow was antegrade in 7/21 iNPH patients and in 4/4 healthy subjects, while it was retrograde (i.e. towards ventricles) in 14/21 iNPH patients. Estimated daily CSF volumetric net flow rate in cerebral aqueduct was 1.1 ± 2.2 L/24 h in iNPH while 295 ± 53 mL/24 h in healthy individuals. Magnitude of cranially directed CSF net flow in cerebral aqueduct was highest in iNPH individuals with signs of impaired intracranial compliance. The study results indicate CSF flow volumes and direction that are profoundly different from previously assumed. We hypothesize that spinal CSF formation may serve to buffer increased demand for CSF flow through the glymphatic system during sleep and during deep inspiration to compensate for venous outflow.


HPV testing in cervical screening.
High-risk human papillomavirus (hrHPV) bearing cervical intraepithelial neoplasia (CIN) is considered, as the real precursor lesion of cervical cancer and persistence of an hrHPV infection is necessary for the progression to cervical cancer. This knowledge warrants the use of hrHPV testing as an adjunct to cervical cytology in population-based screening programmes and for monitoring therapy efficacy of high-grade CIN lesions. Replacement of cytology by hrHPV testing altogether is considered, but for this to be (cost-) effective, accurate information about the specificity of the hrHPV test is required. Additional test systems that can be used to stratify women with a positive hrHPV test are HPV genotyping, viral load analysis and hrHPV mRNA analysis. The need for HPV genotyping of cervical smears is illustrated by the increased risk for high-grade cervical lesions associated with HPV types 16 and 18. In particular, for women who have normal but persistently (>1 year) HPV18-positive smears, endocervical curettage is suggested (evidently considering the age and possible future pregnancies of the respective woman) because HPV18 is associated with glandular lesions in the cervix, which are difficult to detect by cytology.


Purification and properties of the cytoplasmic hexokinase from rabbit brain.
About 90% of the total hexokinase activity in rabbit brain was found to be associated with mitochondria while the remaining part was found in the cytosolic fraction. The soluble enzyme was purified 4,700-fold to near homogeneity by a combination of ion-exchange chromatography, dye-ligand chromatography and affinity chromatography. The purified enzyme showed a specific activity of 110 units/mg of protein and was obtained in 70% yield. The molecular weight of the purified hexokinase was found to be approximately 98,000 both for the native and the denatured enzyme. The isoelectric point, pI, was 6.2 pH units by isoelectric focusing and the enzyme was found to be able to phosphorylate several hexoses. Mg . ATP2-, among the nucleotide substrates, was the most effective phosphate donor. The properties of the purified cytoplasmatic hexokinase were compared with those of the solubilized mitochondrial enzyme. No significant differences were found in molecular weight, isoelectric point, pH dependence of activity, electrophoretic mobility and affinity for glucose and Mg.ATP2-. However, the temperature dependence of activity, and the specificity for several hexose substrates were markedly different.


Methodological issues in social cognition research in autism spectrum disorder and schizophrenia spectrum disorder: a systematic review.
Recent systematic reviews and meta-analyses conclude that similar social cognitive impairments are found in autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD). While methodological issues have been mentioned as a limitation, no study has yet explored the magnitude of methodological heterogeneity across these studies and its potential impact for their conclusion. The purpose of this study was to systematically review studies comparing social cognitive impairments in ASD and SSD with a focus on methodology. Following the PRISMA guidelines, we searched all publications on PubMed, PsycINFO, and Embase. Of the 765 studies identified in our data base searches, 21 cross-sectional studies were included in the review. We found significant methodological heterogeneity across the studies. In the 21 studies, a total of 37 different measures of social cognition were used, 25 of which were only used in 1 study. Across studies, the same measure was often said to be assessing different constructs of social cognition - a confusion that seems to reflect the ambiguous definitions of what these measures test in the studies that introduced them. Moreover, inadequate differential diagnostic assessment of ASD samples was found in 81% of the studies, and sample characteristics were markedly varied. The ASD and SSD groups were also often unmatched in terms of medication usage and substance use disorder history. Future studies must address these methodological issues before a definite conclusion can be drawn about the potential similarity of social cognitive impairments in ASD and SSD.


Highly diastereoselective 5-hexenyl radical cyclizations with Lewis acids and carbohydrate scaffolds.
[figure: see text] Carbohydrates as removable chiral scaffolds for free radical cyclizations were examined for the first time. This investigation illustrates the utility of two inexpensive carbohydrate derivatives as sources of asymmetry for 5-hexenyl radical cyclizations. Diastereomeric ratios as high as 100:1 were achieved with an ester-appended (+)-isosorbide hexose and 70:1 for a diol-protected D-xylose pentose. Temperature dependence, Lewis acids, and solvents were all examined. By correlation with known compounds, the newly generated chiral centers were of the (S)-configuration.


The challenges of initiating a multi-professional clinical skills project.
Health care professionals are required to work collaboratively to prevent fragmented care and improve the quality of the patient's journey. The drive for multi-professional and inter-professional education is aimed at nurturing collaboration by engaging in joint educational initiatives. Although many United Kingdom (UK) policy documents endorse multi-professional and inter-professional initiatives, few seek to address the significant challenges inherent within these ventures. This paper uses force field analysis to make explicit the challenges experienced by two National Health Service (NHS) organizations on the east coast of Scotland during the initiation phase of a multi-professional clinical skills project. An action research methodology is employed to highlight the strategies adopted by the project team. The authors suggest that gaining insight into the cultural, logistical and educational challenges inherent in such initiatives provides valuable data to plan appropriate strategies to aid project success.


C-O cleavage of aromatic oxygenates over ruthenium catalysts. A computational study of reactions at step sites.
We studied the C-O cleavage of phenolate and catecholate at step sites of a Ru catalyst using periodic DFT methods at the GGA level. Both C-O scission steps are associated with activation barriers of about 75 kJ mol(-1), hence are significantly more facile than the analogous reactions on Ru terraces. With these computational results, we offer an interpretation of recent experiments on the hydrodeoxygenation of guaiacol (2-methoxyphenol) over Ru/C. We hypothesize that the experimentally observed dependency of the product selectivity on the H2 pressure is related to the availability of step sites on a Ru catalyst.


Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo.
Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I-mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases.


Pulmonary hamartoma. A rare case report.
Pulmonary hamartoma is a rare lung neoformation, usually symptomless and by chance discovered, of a probable dysontogenetic origin with prevailing cartilaginous tissue and adult, onset age. The Authors report a rare case of a 25-year-old student, symptomless and fortuitously found by means of a radiograph of the chest. Many interesting features characterize the case report: histological nature of the pulmonary hamartoma, mainly vascular, so much as to feign an angiosarcoma at the macroscopical examination, and with small peripheral calcifications as shown by lung CT scan; the measures (about 7 cm) plentifully above the parameters usually reported in the literature (from 2 cm to 4 cm); the young onset age (about 10 years old). We may consider a case exceptionally reported in the literature. Besides, on the base of a few studies and of our experience, the results of the pulmonary hamartoma growth rate and doubling time are reported.


Cutaneous nasociliary neuralgia.
Nasociliary neuralgia has not to our knowledge been linked with inflammatory cutaneous lesions. We observed the phenomenon and postulate that it may be frequent but overlooked.


Sexual factors and the risk of prostate cancer.
A population-based case-control study of prostate cancer was performed in King County, Washington, in White men and Black men aged 40-64 years, between 1993 and 1996. Incident prostate cancer cases (n = 753) were identified from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Controls (n = 703) were identified through random digit dialing and were frequency matched to cases on age. Sexual behavior, medical history, and other potential prostate cancer risk factors were ascertained through an in-person interview. There was no relation between sexual orientation and prostate cancer, although the number of men who had sex with men was small. Risk estimates increased directly with the lifetime number of female sexual partners (trend p < 0.001) but not with male partners (trend p = 0.62). Risk also increased with decreasing age at first intercourse, but this effect disappeared after adjusting for the number of female partners. Prior infection with gonorrhea was positively associated with risk (odds ratio = 1.50; 95% confidence interval: 1.0, 2.2), but no effect was seen among men with other sexually transmitted diseases. No relation between lifetime frequency of sexual intercourse and risk of prostate cancer was apparent. These findings are consistent with previous studies that support an infectious etiology for prostate cancer.


Healthcare Workers Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak.
Healthcare workers (HCWs) are at high risk of contracting Middle East respiratory syndrome coronavirus (MERS-CoV) during an epidemic. We explored the emotions, perceived stressors, and coping strategies of healthcare workers who worked during a MERS-CoV outbreak in our hospital. A cross-sectional descriptive survey design. A tertiary care hospital. HCWs (150) who worked in high risk areas during the April-May 2014 MERS-CoV outbreak that occurred in Jeddah, Saudi Arabia. We developed and administered a "MERS-CoV staff questionnaire" to study participants. The questionnaire consisted of 5 sections with 72 questions. The sections evaluated hospital staffs emotions, perceived stressors, factors that reduced their stress, coping strategies, and motivators to work during future outbreaks. Responses were scored on a scale from 0-3. The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. Completed questionnaires were returned by 117 (78%) of the participants. The results had many unique elements. HCWs ethical obligation to their profession pushed them to continue with their jobs. The main sentiments centered upon fear of personal safety and well-being of colleagues and family. Positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among HCWs after adopting strict protective measures alleviated their fear and drove them through the epidemic. They appreciated recognition of their efforts by hospital management and expected similar acknowledgment, infection control guidance, and equipment would entice them to work during future epidemics. The MERS-CoV outbreak was a distressing time for our staff. Hospitals can enhance HCWs experiences during any future MERS-CoV outbreak by focusing on the above mentioned aspects.


Liquid-based urine cytology as a tool for detection of human papillomavirus, Mycoplasma spp., and Ureaplasma spp. in men.
Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The β-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis.


Enzyme-Catalytic Self-Triggered Release of Drugs from a Nanosystem for Efficient Delivery to Nuclei of Tumor Cells.
Stimulus-responsive drug delivery nanosystems (DDSs) are of great significance in improving cancer therapy for intelligent control over drug release. However, among them, many DDSs are unable to realize rapid and sufficient drug release because most internal stimulants might be consumed during the release process. To address the plight, an abundant supply of stimulants is highly desirable. Herein, a core crosslinked pullulan-di-(4,1-hydroxybenzylene)diselenide nanosystem, which could generate abundant exogenous-stimulant reactive oxygen species (ROS) via tumor-specific NAD(P)H:quinone oxidoreductase-1 (NQO1) catalysis, was constructed by the encapsulation of β-lapachone. The enzyme-catalytic-generated ROS induced self-triggered cascade amplification release of loaded doxorubicin (DOX) in the tumor cells, thus achieving efficient delivery of DOX to the nuclei of tumor cells by breaking the diselenide bond of the nanosystem. As a result, the antitumor effect of this nanosystem was significantly improved in the HepG2 xenograft model. In general, this study offers a new paradigm for utilizing the interaction between the loaded agent and carrier in the tumor cells to obtain self-triggered drug release in the design of DDSs for enhanced cancer therapy.


"Generalized-to-focal" epilepsy: stereotactic EEG and high-frequency oscillation patterns
We aimed to clarify the pathophysiology of epilepsy involving seizures with apparently generalized onset, progressing to focal ictal rhythm through stereotactic EEG (SEEG) implantation, recording, stimulation and high-frequency oscillation (HFO) analysis. We identified two patients with seizures with bilateral electrographic onset evolving to focal ictal rhythm, who underwent SEEG implantation. Patients had pre-surgical epilepsy work-up, including prolonged video scalp EEG, brain MRI, PET, ictal/interictal SPECT, MEG, and EEG-fMRI prior to SEEG implantation. Both patients had childhood-onset seizures involving behavioural arrest and left versive head and eye deviation, evolving to bilateral tonic-clonic convulsions. Seizures were electrographically preceded by diffuse, bilateral 3-Hz activity resembling absence seizures. Both had suspected focal lesions based on neuroimaging, including 3T MRI and voxel-based post-processing in one patient. Electrode stimulation did not elicit any habitual electroclinical seizures. HFO analysis showed bilateral focal regions with high fast-ripple rates. "Generalized-to-focal" seizures may occur due to a diffuse, bilateral epileptic network, however, both patients showed ictal evolution from a generalized pattern to a single dominant focus which may explain why the focal aspect of their seizures had a consistent clinical semiology. Patients such as these may have a unique form of generalized epilepsy, but focal/multifocal cerebral abnormalities are also a possibility.


Iodonium salts as efficient iodine(iii)-based noncovalent organocatalysts for Knorr-type reactions.
Hypervalent iodine(iii)-derivatives display higher catalytic activity than other aliphatic and aromatic iodine(i)- or bromine(i)-containing substrates for a Knorr-type reaction of N-acetyl hydrazides with acetyl acetone to give N-acyl pyrazoles. The highest activity was observed for dibenziodolium triflate, for which 10 mol% resulted in the generation of N-acyl pyrazole from acyl hydrazide and acetyl acetone typically at 50 °C for 3.5-6 h with up to 99% isolated yields. 1H NMR titration data and DFT calculations indicate that the catalytic activity of the iodine(iii) is caused by the binding with a ketone.


[Cerebral gliomas: imaging diagnosis and follow-up].
The management of gliomas evolves towards more aggressive strategies with a combination of surgery, radiotherapy and chemotherapy. Follow-up imaging based on morphological MRI, with simple and reproducible protocols, may be associated with functional MRI and spectroscopy. Baseline postsurgical MRI must be performed within the first three days. Follow-up examinations should be done 2 months after radiotherapy and during chemotherapy, usually after each cycle of two or three treatments. Continued follow-up after therapy is recommended to assess response and detect recurrences or therapeutic complications.


Explaining drug policy: Towards an historical sociology of policy change.
The goal of seeking to understand the development over time of drug policies is a specific version of the more general intellectual project of finding ways of explaining social change. The latter has been a preoccupation of some of the greatest thinkers within the social sciences of the last 200 years, from Foucault all the way back to the three nineteenth-century pioneers, Marx, Durkheim and Weber. I describe this body of work as 'historical sociology'. In this paper, I outline how a particular approach to historical sociology can be fruitfully drawn upon to understand the development of drug policy, using by way of illustration the example of the analysis of a recent transformation in British drug policy: the rise of the criminal justice agenda. I conclude by arguing that by looking at developments in drug policy in this way, some new insights are opened up.


PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome.
In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, but the mechanisms that drive these heteroplasmy differences are unknown. We find that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. These results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.


Morphometric analysis of human neuromuscular junction in different ages.
Application of morphometric analysis to the study of neuromuscular junction is helpful to the quantitative approach of ultrastructural changes. In this study, twelve autopsied subjects of different ages were examined on the ultrastructure of neuromuscular junctions using morphometric analysis. The postsynaptic area and postsynaptic membrane length were significantly greater in adults than in infants. The results indicate that the number and/or depth of the secondary synaptic clefts of adults are greater than those of infants. In the aged subjects, presynaptic membrane length and postsynaptic membrane density showed a significant decrease. The latter observations were thought to be the results of regressive changes of pre-and postsynaptic structure with aging. The variations of each structural element were also studied. The large variations were found in the postsynaptic area, postsynaptic membrane length, and membrane length ratio of adults and aged group. On the other hand, variations in postsynaptic membrane density were small in all age groups. The importance of the knowledge of these age related changes and variations in the studies of neuromuscular junction was discussed.


Diagnosis and Intervention in Early Psoriatic Arthritis.
Psoriatic arthritis (PsA) is a chronic inflammatory disorder that affects approximately 20-30% of patients with psoriasis. PsA causes deformities and joint damage, impairing quality of life and causing long-term functional disability. Several recent studies demonstrated that early diagnosis and intervention for PsA prevents permanent invalidity. However, the clinical features of PsA vary and are shared with other differential diseases, such as reactive arthritis, osteoarthritis, and ankylosing spondylitis. The common and overlapping features among these diseases complicate the accurate early diagnosis and intervention of PsA. Therefore, this review focuses on the current knowledge of the diagnosis of early PsA and discusses the meaning of early intervention for early PsA.


Sun-Protection Behavior, Pubertal Development and Menarche: Factors Influencing the Melanocytic Nevi Development-The Results of an Observational Study of 1,512 Children.
Observational studies consistently show that melanocytic nevus prevalence increases with age and that phenotypic traits are significantly associated with nevus count in children. An observational study of 1,512 children and adolescents from 2010 to 2013 was conducted. Study dermatologists counted the full body, arm, and facial nevi of each participant. Children and their parents were asked to complete a survey to gather data on personal characteristics, pubertal development, and early-life sun exposure. The main aim of the study was to establish pediatric nevus prevalence and its relationship with age, phenotype, sex, menarche, early-life sun exposure, and sun-protection behaviors. Females had a significantly lower nevus count compared with males, but this sex-related difference was significantly modified by menarche. Sun exposure and sun-protection habits were all significantly associated with nevus count; in particular, children who used sunscreen with a sun-protection factor > 30 had a lower nevus count compared with sun-protection factor ≤ 30 sunscreen users. This study shows that sex, menarche status, and sun-protection practices significantly influence nevus count in this pediatric population.


Studying infant and toddler play.
The play of infants and toddlers is a rich and flexible research modality. Play assessment can be an outcome measure of cognition or social ability, or it can be measured in conjunction with related constructs such as language to give a broad view of early development. Play can also be an effective intervention in studies of cognition, language, motor, or social development. This article offers strategies for the researcher who is interested in infant and toddler play. Emphasis is placed on environmental variables that the researcher manipulates to optimize the child's performance. Play measures are briefly addressed.


Mouse Models for Diseases in the Cholangiocyte Lineage.
Cholangiopathies are an important group of liver diseases affecting the biliary system, and the purpose of this review is to describe how diseases in the biliary system can be studied in mouse models. A particular focus is placed on mouse models for Alagille syndrome, a cholangiopathy with a strong genetic link to dysfunctional Notch signaling. Recently, a number of different genetic mouse models based on various manipulations of the Notch signaling pathway have been generated to study Alagille syndrome, and we discuss the resulting phenotypes, and possible causes for the phenotypic heterogeneity among the various models. In the final section, we provide a more general discussion on how well mouse models can be expected to mimic human liver disease, as well as an outlook toward the need for new technologies that can help us to gain new insights from mouse models for liver disease.


Scraped surface heat exchangers.
Scraped surface heat exchangers (SSHEs) are commonly used in the food, chemical, and pharmaceutical industries for heat transfer, crystallization, and other continuous processes. They are ideally suited for products that are viscous, sticky, that contain particulate matter, or that need some degree of crystallization. Since these characteristics describe a vast majority of processed foods, SSHEs are especially suited for pumpable food products. During operation, the product is brought in contact with a heat transfer surface that is rapidly and continuously scraped, thereby exposing the surface to the passage of untreated product. In addition to maintaining high and uniform heat exchange, the scraper blades also provide simultaneous mixing and agitation. Heat exchange for sticky and viscous foods such as heavy salad dressings, margarine, chocolate, peanut butter, fondant, ice cream, and shortenings is possible only by using SSHEs. High heat transfer coefficients are achieved because the boundary layer is continuously replaced by fresh material. Moreover, the product is in contact with the heating surface for only a few seconds and high temperature gradients can be used without the danger of causing undesirable reactions. SSHEs are versatile in the use of heat transfer medium and the various unit operations that can be carried out simultaneously. This article critically reviews the current understanding of the operations and applications of SSHEs.


Infants of postpartum depressed mothers: temperament and cognitive status.
This study examined the association of postpartum depression with specific infant characteristics. Twenty-five diagnosed depressed and 25 nondepressed mothers and their 2-month-old infants participated in the study. The mothers completed measures of infant temperament and difficulty associated with infant care, and the infants were assessed using the Bayley Scales of Infant Development. Group comparisons indicated that, compared with the infants of the nondepressed mothers, the infants of the depressed women were less competent cognitively and expressed more negative emotions during the testing. The depressed mothers perceived their infants as more difficult to care for and more bothersome than did the nondepressed mothers, but did not attribute these difficulties to the temperament of their infants. These findings suggest that postpartum depression is associated with an identifiable pattern of infant behavior that may exacerbate depressed women's mood.


The nuts and bolts of captive chimpanzee diets and food as enrichment: a survey.
Beyond planning for good nutrition, one of the Cornerstones of a successful captive-chimpanzee wellness program is the opportunity for the nonhuman primates to express normal feeding and foraging behaviors. This study presents the results of a survey of 11 institutions-8 zoological and 3 research facilities-given to ascertain how daily diets and feeding enrichments were accomplished. Information represents 806 captive chimpanzees, and entails a composite of captive chimpanzee daily diets, forage and browse materials, periodic treats, medicating and supplemental foods, alternative feeding techniques, and food devices. Results suggest facilities are moving away from timed feeding schedules, which tend to increase prefeeding levels of agonism, to feeding a wide variety of foods throughout the day and using a wide variety of feeding techniques.


Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women.
To determine whether hydrogenated fat consumption alters triglyceride metabolism and cholesterol esterification rates, 14 women (65-71 years of age) were provided with each of four diets for 5-week periods according to a randomized cross-over design. The experimental diets contained either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines. Triglyceride uptake by adipose tissue was determined by measuring plasma acylation-stimulating protein (ASP), FFA, glucose, and insulin levels, while rates of transfer and esterification rate of newly synthesized cholesterol (ER) were derived by using plasma CETP levels and the deuterium incorporation methodology. Plasma ASP levels were lowest (P < 0.05) in subjects on the SM diet (33.4 +/- 12.7 nM) compared with the SO (48.7 +/- 17.0 nM) and SQM (50.7 +/- 15.7 nM) diets. Conversely, FFA were highest (P < 0.05) on the SM diet (0.86 +/- 0.45 mM) relative to all the other diets. No differences were observed in plasma glucose and insulin levels among diets. A trend toward higher CETP levels after consumption of the SM diet was observed. However, the ER was lowest (P < 0.05) after the SM (0.111 +/- 0.062 g x day(-1)) diet and highest after consumption of the SQM (0.216 +/- 0.123 g x day(-1)) diet. In addition, ASP levels were negatively correlated with FFA (r = -0.63, P < 0.05), LDL cholesterol (r = -0.56, P < 0.05), and TG (r = -0.41, P < 0.05), whereas FFA was positively correlated with apolipoprotein B-containing lipoproteins (r = 0.58 and 0.47, for VLDL and LDL cholesterol, P < 0.05), and negatively correlated with HDL cholesterol (r = -0.51, P < 0.05). The ER was found to positively correlate with HDL cholesterol and HDL2 subfraction (r = 0.53 and 0.45, respectively, P < 0.05). Taken together, these data demonstrate that the alterations in circulating lipid levels, commonly observed with consumption of hydrogenated fat-rich diets, can be explained in part by changes in ASP activity as well as newly synthesized cholesterol ER.


Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-I-associated myelopathy: a possible mechanism to control viral infection in the central nervous system.
Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using the monoclonal antibody TIA-1, a marker of cytotoxic T lymphocytes (CTL). Many TIA-1+, CD8+ cells are distributed in active inflammatory lesions. The number of TIA-1+ cells is related to the amount of HTLV-I proviral DNA in situ. The protein TIA-1 has been associated with the induction of apoptosis in target cells. In active inflammatory lesions, we found cells undergoing apoptosis, most of them identified as helper-inducer CD45RO T lymphocytes, which were consistent with in vivo cellular tropism of HTLV-I in patients with HAM/TSP. These findings suggest that CTL-induced apoptosis of T lymphocytes may be one of the possible mechanisms which eliminate HTLV-I-infected cells from the central nervous system. In addition, many T lymphocytes in the inflammatory lesions expressed bcl-2 oncoprotein, suggesting that infiltrated T lymphocytes may be resistant to apoptosis. Expression of bcl-2 oncoprotein may explain the longstanding inflammatory process in the central nervous system of HAM/TSP.


Non-Invasive Evaluation of Cerebral Microvasculature Using Pre-Clinical MRI: Principles, Advantages and Limitations.
Alterations to the cerebral microcirculation have been recognized to play a crucial role in the development of neurodegenerative disorders. However, the exact role of the microvascular alterations in the pathophysiological mechanisms often remains poorly understood. The early detection of changes in microcirculation and cerebral blood flow (CBF) can be used to get a better understanding of underlying disease mechanisms. This could be an important step towards the development of new treatment approaches. Animal models allow for the study of the disease mechanism at several stages of development, before the onset of clinical symptoms, and the verification with invasive imaging techniques. Specifically, pre-clinical magnetic resonance imaging (MRI) is an important tool for the development and validation of MRI sequences under clinically relevant conditions. This article reviews MRI strategies providing indirect non-invasive measurements of microvascular changes in the rodent brain that can be used for early detection and characterization of neurodegenerative disorders. The perfusion MRI techniques: Dynamic Contrast Enhanced (DCE), Dynamic Susceptibility Contrast Enhanced (DSC) and Arterial Spin Labeling (ASL), will be discussed, followed by less established imaging strategies used to analyze the cerebral microcirculation: Intravoxel Incoherent Motion (IVIM), Vascular Space Occupancy (VASO), Steady-State Susceptibility Contrast (SSC), Vessel size imaging, SAGE-based DSC, Phase Contrast Flow (PC) Quantitative Susceptibility Mapping (QSM) and quantitative Blood-Oxygenation-Level-Dependent (qBOLD). We will emphasize the advantages and limitations of each strategy, in particular on applications for high-field MRI in the rodent's brain.


Dynamic Production of Soluble Extracellular Polysaccharides by Streptococcus mutans.
Caries development in the presence of Streptococcus mutans is associated not only with the production of extracellular water-insoluble polymers but also is based on water-soluble polysaccharides. The aim of this study was the evaluation of a novel glucan-specific Lectin assay for monitoring water-soluble EPS produced by S. mutans during several growth periods in different media. S. mutans cultures were grown for 24 h, 48 h, and 144 h in medium deficient of sucrose (A) and medium supplemented with 5% sucrose (B). Microtiter well plates were coated with cell-free supernatants followed by the addition of labeled Concanavalin-A and enzyme substrate. The substrate reactions were kinetically detected at 405 nm. The validation of the assay was performed using carbohydrates dextran, xanthan, and sucrose as reference. This new Concanavalin-A-based assay showed the highest sensitivity for dextran and revealed that the glucan production of S. mutans reached its maximum at 144 h in medium B according to bacterial maturation.


Reflection and polarization properties of powder materials.
Directional radiance factors and polarization are presented for pure silicon carbide powder with an average albedo of 0.15 over a size range from 8 micro to 86 micro, pure aluminum oxide powder with average albedo about 0.85 over a size range from 0.1 micro to 86 micro, and for a mixture of one part silicon carbide to six parts aluminum oxide with average albedo of about 0.40 over a size range from 5 micro to 86 micro.


Kind enough to care, clever enough to cope.
In my lifetime the human race has reached out to the stars and walked on the surface of the moon. Now I can hold a computer more powerful than the one used to control the moon landing in the palm of my hand. Diseases that once signalled death have been reduced to the status of long-term conditions, the number of people aged 85 and over has more than tripled.


Multifocal myxoid liposarcoma--metastasis or second primary tumor?: a molecular biological analysis.
The classification of multifocal myxoid/round cell liposarcoma, which is defined as tumor presentation in at least two separate sites before manifestation in the lungs, as either metastasis or as a second primary tumor, has essential clinical consequences. Genetically, myxoid/round cell liposarcoma is characterized by t(12;16)(q13;p11) or t(12;22)(q13;q12), and various exon fusion transcripts are described with varying incidences, which permits their use as markers for clonality. Moreover, in solid tumors, analysis of loss of heterozygozity is valuable for clonality analysis. Therefore, fifteen multifocal myxoid/round cell liposarcoma patients with two to five metachronous (n = 12) or synchronous (n = 3) localizations were investigated. Using RT-PCR, the detailed molecular characteristics of the FUS-CHOP and EWS-CHOP breakpoints were determined. Loss of heterozygozity analysis at twelve loci was then used to further analyze clonal relationships. In all patients, tumor sites showed identical FUS-CHOP fusion products. In six patients, identical rare fusion transcripts were found, supporting a clonal relationship. Nine patients had the common exon5-FUS/exon2-CHOP fusion transcript, and two of these were identified as clonally related by loss of heterozygozity analysis. In all other patients, loss of heterozygozity analysis was highly suggestive of a clonal relationship, and no evidence for interpretation of a second primary tumor was found. This study supports the metastatic nature of apparent multifocal myxoid/round cell liposarcoma.


Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38α MAP kinase: a combined computational and experimental study.
A major current challenge for drug design efforts focused on protein kinases is the development of drug resistance caused by spontaneous mutations in the kinase catalytic domain. The ubiquity of this problem means that it would be advantageous to develop fast, effective computational methods that could be used to determine the effects of potential resistance-causing mutations before they arise in a clinical setting. With this long-term goal in mind, we have conducted a combined experimental and computational study of the thermodynamic effects of active-site mutations on a well-characterized and high-affinity interaction between a protein kinase and a small-molecule inhibitor. Specifically, we developed a fluorescence-based assay to measure the binding free energy of the small-molecule inhibitor, SB203580, to the p38α MAP kinase and used it measure the inhibitor's affinity for five different kinase mutants involving two residues (Val38 and Ala51) that contact the inhibitor in the crystal structure of the inhibitor-kinase complex. We then conducted long, explicit-solvent thermodynamic integration (TI) simulations in an attempt to reproduce the experimental relative binding affinities of the inhibitor for the five mutants; in total, a combined simulation time of 18.5 μs was obtained. Two widely used force fields - OPLS-AA/L and Amber ff99SB-ILDN - were tested in the TI simulations. Both force fields produced excellent agreement with experiment for three of the five mutants; simulations performed with the OPLS-AA/L force field, however, produced qualitatively incorrect results for the constructs that contained an A51V mutation. Interestingly, the discrepancies with the OPLS-AA/L force field could be rectified by the imposition of position restraints on the atoms of the protein backbone and the inhibitor without destroying the agreement for other mutations; the ability to reproduce experiment depended, however, upon the strength of the restraints' force constant. Imposition of position restraints in corresponding simulations that used the Amber ff99SB-ILDN force field had little effect on their ability to match experiment. Overall, the study shows that both force fields can work well for predicting the effects of active-site mutations on small molecule binding affinities and demonstrates how a direct combination of experiment and computation can be a powerful strategy for developing an understanding of protein-inhibitor interactions.


A Surface Plasmon Resonance Plastic Optical Fiber Biosensor for the Detection of Pancreatic Amylase in Surgically-Placed Drain Effluent.
Postoperative pancreatic fistula (POPF), the major driver of morbidity and mortality following pancreatectomy, is caused by an abnormal communication between the pancreatic ductal epithelium and another epithelial surface containing pancreas-derived, enzyme-rich fluid. There is a strong correlation between the amylase content in surgically-placed drains early in the postoperative course and the development of POPF. A simple and cheap method to determine the amylase content from the drain effluent has been eagerly advocated. Here, we developed an amylase optical biosensor, based on a surface plasmon resonance (SPR) plastic optical fiber (POF), metallized with a 60 nm layer of gold and interrogated with white light. The sensor was made specific by coupling it with an anti-amylase antibody. Each surface derivatization step was optimized and studied by XPS, contact angle, and fluorescence. The POF-biosensor was tested for its response to amylase in diluted drain effluents. The volume of sample required was 50 µL and the measurement time was 8 min. The POF-biosensor showed selectivity for amylase, a calibration curve log-linear in the range of 0.8-25.8 U/L and a limit of detection (LOD) of ~0.5 U/L. In preliminary tests, the POF-biosensor allowed for the measurement of the amylase content of diluted surgically-placed drain effluents with an accuracy of >92% with respect to the gold standard. The POF-biosensor allows for reliable measurement and could be implemented to allow for a rapid bedside assessment of amylase value in drains following pancreatectomy.


Colorectal hamartomatous polyposis and ganglioneuromatosis in a dog.
A 5-month-old female Great Dane puppy was treated for hematochezia, tenesmus, and rectal prolapse by resection of a 10-cm-long segment of colon and rectum. Grossly, the colorectal segment had diffuse mucosal and submucosal thickening with multiple polypoid nodules. The histologic diagnosis was colorectal hamartomatous polyps with ganglioneuromatosis. Duplication of PTEN was detected by quantitative multiplex polymerase chain reaction testing. The presence of 2 hamartomatous colorectal lesions with PTEN mutation is similar to human Cowden syndrome.


High tech u.
Implementing a certified electronic health record system and then achieving meaningful use are no small tasks for a medical practice. The federal government has made $116 million in grants available nationwide to ramp up training for a robust, qualified workforce to help physicians. Community colleges and universities throughout Texas use the federal money to enhance or create certificate and degree programs that will prepare medical office staff, recent college graduates, and information technology professionals to oversee health information technology at multiple sites, including the physician practice.


UFL1 Alleviates LPS-Induced Apoptosis by Regulating the NF-κB Signaling Pathway in Bovine Ovarian Granulosa Cells.
Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an E3 ligase of ubiquitin fold modifier 1 (UFM1), which can act together with its target protein to inhibit the apoptosis of cells. Lipopolysaccharides (LPS) can affect the ovarian health of female animals by affecting the apoptosis of ovarian granulosa cells. The physiological function of UFL1 on the apoptosis of bovine (ovarian) granulosa cells (bGCs) remains unclear; therefore, we focused on the modulating effect of UFL1 on the regulation of LPS-induced apoptosis in ovarian granulosa cells. Our study found that UFL1 was expressed in both the nucleus and cytoplasm of bGCs. The results here demonstrated that LPS caused a significant increase in the apoptosis level of bGCs in cows, and also dramatically increased the expression of UFL1. Furthermore, we found that UFL1 depletion caused a significant increase in apoptosis (increased the expression of BAX/BCL-2 and the activity of caspase-3). Conversely, the overexpression of UFL1 relieved the LPS-induced apoptosis. In order to assess whether the inhibition of bGCs apoptosis involved in the nuclear factor-κB (NF-κB) signaling pathway resulted from UFL1, we detected the expression of NF-κB p-p65. LPS treatment resulted in a significant upregulation in the protein concentration of NF-κB p-p65, and knockdown of UFL1 further increased the phosphorylation of NF-κB p65, while UFL1 overexpression significantly inhibited the expression of NF-κB p-p65. Collectively, UFL1 could suppress LPS-induced apoptosis in cow ovarian granulosa cells, likely via the NF-κB pathway. These results identify a novel role of UFL1 in the modulation of bGC apoptosis, which may be a potential signaling target to improve the reproductive health of dairy cows.


Factitious neurosurgical emergencies: report of five cases.
Patients with factitious symptoms occasionally present as neurosurgical emergencies. We have had six admissions over an 8-year period. They all presented at night, half of them during a weekend. Although an organic cause had to be excluded, they were all discharged within 24 h of admission without surgical intervention.


Attitudes towards implementation of surveillance-based parasite control on Kentucky Thoroughbred farms - Current strategies, awareness and willingness-to-pay.
Traditionally, equine parasite control has relied heavily on frequent routine anthelmintic treatments applied at regular intervals all year round. However, current recommendations aim to employ a more surveillance-based approach and it remains unknown to what extent these recommendations are being implemented on US horse farms. To describe equine parasite control on Kentucky Thoroughbred farms and evaluate respondents' willingness to pay for various attributes of surveillance-based parasite control strategies. Questionnaire survey performed among the membership of the Kentucky Thoroughbred Farm Managers' Club. The survey collected demographic data and information about current parasite control strategies. Further, respondents were asked to choose between hypothetical parasite control strategies described with a combination of different attributes: costs, time and effort needed, hypothetical disease-risk levels and hypothetical risks of anthelmintic resistance. Data were analysed with multivariable logistic analysis. About 26% responded to the survey (n = 112). Most respondents were concerned about anthelmintic resistance and incorporated veterinary advice in defining their deworming programme. However, almost 70% were following a traditional rotational deworming programme with little or no faecal surveillance. Respondents were willing to pay a premium for a product for which there is no known anthelmintic resistance and provided the highest possible decrease in health risks. The number of young horses on the farm, utilisation of veterinarian advice in developing a deworming programme, expressed concern about drug resistance in parasites and having documented drug resistance on the farm all associated significantly with the type of parasite control programme used. Traditional approaches for equine parasite control are still widely used in the Kentucky Thoroughbred industry. The data suggest that respondents were only willing to make these changes if they could be given assurance that the surveillance-based approach would prevent anthelmintic resistance and decrease health risks significantly for the horses.


Differences in growth promotion, drug response and intracellular protein trafficking of FLT3 mutants.
Mutant forms FMS-like tyrosine kinase-3 (FLT3), are reported in 25% of childhood acute lymphoid leukemia (ALL) and 30% of acute myeloid leukemia (AML) patients. In this study, drug response, growth promoting, and protein trafficking of FLT3 wild-type was compared with two active mutants (Internal Tandem Duplication (ITD)) and D835Y. FLT3 was expressed on factor-dependent cells (FDC-P1) using retroviral transduction. The inhibitory effects of CEP701, imatinib, dasatinib, PKC412 and sunitinib were studied on cell proliferation and FLT3 tyrosine phosphorylation. Total expression and proportion of intracellular and surface FLT3 was also determined. FDC-P1 cells became factor-independent after expression of human FLT3 mutants (ITD and D835Y). FDC-P1 cells expressing FLT3-ITD grow 3 to 4 times faster than those expressing FLT3-D835Y. FD-FLT3-ITD cells were three times more resistant to sunitinib than the FD-FLT3-WT cells. The Geo means for surface FLT3 expression in FD-FLT3-ITD and -D835Y were 65 and 70% less than the FD-FLT3-WT cells. About 40% of expressed FLT3 was detected as intracellular in FD-FLT3-D835Y cell compared to 4 and 4.5% in FD-FLT3-WT and -ITD cells. Retention of D835Y FLT3 mutant protein may cause altered signaling, endoplasmic reticulum stress and activation of apoptotic signaling pathways leading to lower proliferation rate in FD-FLT3-D835Y than the FLT3-WT and ITD mutant., these may also also contribute, along with the preferential affinity, to the increased sensitivity of D835Y of CEP701 and PKC412. Studying these genetic variations can help determining the prognosis and designing a therapeutic plan for the patients with FLT3 mutations.


QuickStats: Percentage* of Adults Aged ≥65 Years Who Reported Ever Receiving a Pneumococcal Vaccination,† by Race/Ethnicity§ and Number of 10 Diagnosed Chronic Conditions¶ - National Health Interview Survey, United States, 2014-2015.
During 2014-2015, the percentage of adults aged ≥65 years who reported ever receiving a pneumococcal vaccination ranged from 42.6% for adults who had none of the 10 selected diagnosed chronic conditions to 78.3% for adults with ≥4 diagnosed chronic conditions. For all racial/ethnic populations the percentage of adults who had ever received a pneumococcal vaccination increased as the number of reported chronic conditions increased. Regardless of the number of selected chronic conditions, non-Hispanic white adults were more likely than Hispanic and non-Hispanic black adults to have received the vaccination.


Au-Pd nanoparticles immobilized on TiO2 nanosheet as an active and durable catalyst for solvent-free selective oxidation of benzyl alcohol.
TiO2nanocrystals with controlled facets have been extensively investigated due to their excellent photocatalytic performance in sustainable and green energy field. However, the applications in thermal catalysis without applying UV irradiation are comparably less and the identification of their intrinsic roles, especially the different catalytic behaviors of each crystal facet, remains not fully recognized. In this study, bimetallic AuPd nanoparticles supported on anatase TiO2 nanosheets exposing {001} facets or TiO2 nanospindles exposing {101} as a catalyst were prepared by sol-immobilization method and used for solvent-free benzyl alcohol oxidation. The experimental results indicated that the exposed facet of the support has a significant effect on the catalytic performance. AuPd/TiO2-001 catalyst exhibited a higher benzyl alcohol conversion than that of the AuPd/TiO2-101. Meanwhile, all the prepared AuPd/TiO2 catalysts were characterized by XRD, ICP-AES, XPS, BET, TEM, and HRTEM. The results revealed that the higher number of oxygen vacancies in TiO2-sheets with the exposed {001} facets of higher surface energy could be responsible for the observed enhancement in the catalytic performance of benzyl alcohol oxidation. The present study displays that it is plausible to enhance the catalytic performance for the benzyl alcohol oxidation by tailoring the exposed facet of the TiO2 as a catalyst support.


Nickel-titanium rotary instruments: current concepts for preparing the root canal system.
The purpose of this paper is to provide useful information that will enable dentists to predictably shape root canals for three-dimensional obturation of the root canal system. The information is intended to help clinicians better understand when and how to safely use Nickel-Titanium (NiTi) rotary shaping instruments. This article is intended to enhance clinical performance for all dentists who perform root canal preparation procedures regardless of which instruments are chosen and the techniques employed during their utilisation. The guidelines for successful access and the concepts and strategies for canal preparation are discussed. Additionally, the advantages of negotiating and then pre-enlarging the coronal two-thirds of the canal before negotiating and finishing the apical one-third are emphasised. Although a set of endodontic instruments can shape a root canal, this article will also review the importance of irrigants and their role in cleaning the root canal system.


Impact of the graphic Canadian warning labels on adult smoking behaviour.
To assess the impact of graphic Canadian cigarette warning labels on current adult smokers. A random-digit-dial telephone survey was conducted with 616 adult smokers in south western Ontario, Canada in October/November 2001, with three month follow up. Smoking behaviour (quitting, quit attempts, and reduced smoking), intentions to quit, and salience of the warning labels. Virtually all smokers (91%) reported having read the warning labels and smokers demonstrated a thorough knowledge of their content. A strong positive relation was observed between a measure of cognitive processing-the extent to which smokers reported reading, thinking about, and discussing the new labels-and smokers' intentions to quit (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.07 to 1.16; p < 0.001). Most important, cognitive processing predicted cessation behaviour at follow up. Smokers who had read, thought about, and discussed the new labels at baseline were more likely to have quit, made a quit attempt, or reduced their smoking three months later, after adjusting for intentions to quit and smoking status at baseline (OR 1.07, 95% CI 1.03 to 1.12; p < 0.001). Graphic cigarette warning labels serve as an effective population based smoking cessation intervention. The findings add to the growing literature on health warnings and provide strong support for the effectiveness of Canada's tobacco labelling policy.


Synthesis of polyhydroxysterols (V): efficient and stereospecific synthesis of 24-methylene-cholest-5-ene-3beta,7alpha-diol and its C-7 epimer.
This paper describes the efficient and stereospecific synthesis of cytotoxic dihydroxylated sterols, 24-methylene-cholest-5-ene-3beta,7alpha-diol 1, and its C-7 epimer, 24-methylene-cholest-5-ene-3beta,7beta-diol 2. The crux of the synthesis is that the selective allylic oxidation of 24-methylene-cholesteryl acetate proceeds to 24-methylene-7-keto-cholesteryl acetate without extensive byproduct formation from reaction at the Delta24(28) double bond. This methodology may be useful for the preparation of other oxysterols with non-standard side chains.


Learning professional touch: an exploration of pre-registration Physiotherapy students' experiences.
Physical touch is considered a core competency in Physiotherapy, central to clinical reasoning and communication. Nevertheless, there is a dearth of research into how the skill is learned and the experiences of students in that process. The aim of this paper is to explore that learning experience among pre-registration physiotherapy students. An approach underpinned by phenomenology and ethnographic methods was undertaken over an 8-month period in one Higher Education Institution in the UK. Data came from a series of observations and focus groups, complemented by personal reflective learning diaries with first- and second-year undergraduate students. Focus group data were analyzed thematically and triangulated with other data sources. Three themes were developed: 1) 'Uncertainty, self-awareness and anxiety' explores the discomfort experienced in the early stages; 2) 'Emerging familiarity and awareness of inter-action' demonstrates developing confidence in bodily capability and communicative capacity; and 3) 'Realities of touch in a clinical environment' focuses on the shift from the pre-clinical to clinical context and highlights the cyclical processes of embodied learning. This study highlights the complexity and immediacy of the embodied learning of touch and its interactions with the development of professional identity. Negotiation of boundaries, both seen and unseen, creates jeopardy in that process through the first two years of the course.


Hot towels: The bedrock of Meibomian gland dysfunction treatment - A review.
Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment. Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included. The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.


[Superior mesentery artery embolization as a complication of the primary angioplasty solved by local thrombolysis].
Acute mesentery artery embolization is a rare complication of invasive catheterizations. The incidence is unknown. In case of late diagnosis the mortality may reach up to 93%. Acute abdominal pain, vomitus, rapid and sudden bowel evacuation with or without blood are the typical symptoms of the disease. Plain X-Rays of abdomen or CT tomography may show no signs of intestinal ischaemia. The diagnostic method to choose is either spiral CT angiography or contrast angiography, respectively. The most common therapeutical approach is surgical revascularization but in selected cases it is feasible to perform local thrombolysis with a microcatheter placed directly into the artery with embolus. We report a case of a man who was admitted with an acute myocardial infarction who underwent primary angioplasty with implantation ofa bare-metal stent. After the procedure he developed severe and progressive abdominal pain as a result of acute superior mesentery artery embolization. In this patient we performed a local thrombolysis with rt-PA (alteplase) with a great technical success and immediate pain relief, with no need of surgical revision. Our approach was concordant to recommendations cited in this article.


Changes in left ventricular performance during chronic pressure or volume overload: importance of physical properties of the arterial system.
The present study was aimed at evaluation of changes in systolic and diastolic left ventricular function during chronic pressure of volume overload, in comparison with normal subjects. Sixty-two patients were included: group 1 was composed of 25 normal subjects, group 2 was composed of 20 subjects with essential hypertension, and group 3 was composed of 17 subjects with aortic regurgitation without congestive heart failure. Cardiac output, aortic and left ventricular pressures (micromanometers), ventricular volume and ascending aortic radius (cineangiography), ejection fraction (EF), mean velocity of fiber shortening (VCF), ventricular mass (m), and the ratio m/EDV (EDV, end diastolic volume) were determined. Also measured were maxima for end systolic pressure (ESP), end systolic stress (ESS), and end systolic volume (ESV) and radius (ESR), as well as the modulus of left ventricular chamber and muscle stiffness (method of Gaash et al.) (1) and characteristic impedance of the ascending aorta (Zc). In hypertensive patients, m and m/EDV were increased, as was the ESP/ESV ratio, whereas EF and VCF were not modified and the ESS/ESR was normal or sometimes decreased. The systolic "pump" function thus appeared to be increased, whereas the muscle function appeared normal or decreased. The moduli of left ventricular chamber stiffness and muscle stiffness were increased. Zc was increased because of a greater pulse wave velocity, although aortic radius was larger. A close relationship was found between Zc and the ratio m/EDV. In patients with aortic regurgitation, the increased left ventricular mass was closely related to the regurgitant fraction (RF). The m/EDV ratio was normal. EF was unmodified and VCF and the ESP/ESV ratio were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


Endoscopic cryosurgery of the thyroid and parathyroid.
In this study we looked at the efficacy of cryosurgery for thyroid and parathyroid tissue ablation in the porcine model. An endoscopic neck approach was successfully used in six 25 kg pigs. T4, free T4 and calcium serum levels were measured pre- and post-operatively. Gross and histologic examination of the glands and surrounding tissue were performed on postoperative Day 40. Postoperative T4, free T4 and calcium levels were not significantly different from preoperative values. Gross examination of the thyroid showed scar tissue in the region that underwent cryosurgery. Parathyroid that was frozen was replaced by scar tissue. Histologic examination of the glands confirmed the gross findings. Trachea, vagus nerve and carotid artery were also resected, and no changes were noted on histological examination. There was no damage to the surrounding tissues after cryosurgery. Directed cryosurgery of the thyroid and parathyroid is safe and feasible in this model.


Plaque reduction technique for demonstrating neutralizing antibodies for Chlamydia.
Some members of the genus Chlamydia (Bedsonia or psittacosis-lymphogranuloma venereum-trachoma-inclusion conjunctivitis group of microorganisms) produce plaques in monolayers of mouse fibroblast (L-929) cells. Hyperimmune chicken antisera may be capable of specifically reducing plaque counts. When the test was applied to chlamydiae isolated from avian species, the results indicated that different isolates with a common source had similar antigenic reactivity. The plaque reduction test is a potentially useful method for serotyping chlamydiae. The difficult aspect of the method appears to be a readily reproducible means of producing neutralizing antiserum.


Type and duration of exogenous hormone use affects breast cancer histology.
It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology. We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined. Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months' use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07-2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users. Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology.


Fast optimal genome tiling with applications to microarray design and homology search.
In this paper, we consider several variations of the following basic tiling problem: given a sequence of real numbers with two size-bound parameters, we want to find a set of tiles of maximum total weight such that each tiles satisfies the size bounds. A solution to this problem is important to a number of computational biology applications such as selecting genomic DNA fragments for PCR-based amplicon microarrays and performing homology searches with long sequence queries. Our goal is to design efficient algorithms with linear or near-linear time and space in the normal range of parameter values for these problems. For this purpose, we first discuss the solution to a basic online interval maximum problem via a sliding-window approach and show how to use this solution in a nontrivial manner for many of the tiling problems introduced. We also discuss NP-hardness results and approximation algorithms for generalizing our basic tiling problem to higher dimensions. Finally, computational results from applying our tiling algorithms to genomic sequences of five model eukaryotes are reported.


Distribution of glutathione S-transferase T1 and M1 genes polymorphisms in North East Indians: a potential report.
Detoxifying glutathione S-transferase (GST) gene polymorphisms show variation in different ethnic populations. GST detoxifies and metabolizes carcinogens, including oxygen free radicals. GST polymorphisms have been associated with susceptibility to different diseases. In the current study, allelic polymorphisms of GSTM1 and GSTT1 were analyzed in three ethnic groups of North East (NE) India where a high prevalence of various cancers and other diseases such as hypertension, tuberculosis, and asthma have been reported. We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 422 voluntary, healthy NE Indians with those of other populations. The data was statistically analyzed. The GSTT1-null genotype was found in 51%, 34.3%, and 15.7% of individuals (from Mizoram, Sikkim, and Assam regions of NE India, respectively), whereas the GSTM1-null genotype was found in 46.9%, 46%, and 35% of individuals from the same areas. The NE Indians differ from the rest of the Indian population with reference to genotypic distribution of GST polymorphisms but the frequency was found to be similar to that which has been reported from China. This may explain the hypothesis of the common ancestral origin of both the NE Indians and the Chinese and a higher frequency of cancers such as gastric, esophageal, and oral cancers, which has been reported from these regions. This study establishes baseline frequency data for GST polymorphisms for future case control studies on the role these polymorphisms play with regard to diseases. The results presented here provide the first report on GST polymorphisms in the NE Indian population.


Circularly Polarised Luminescence in Enantiopure Samarium and Europium Cryptates.
Circularly polarised luminescence (CPL) is a chiroptical phenomenon gaining more and more attention, as the availability of the necessary spectrometers is getting better and first applications in bioimaging or for the preparation of OLEDs (organic light emitting diodes) are coming within range. Until now most examples of distinctly CPL-active compounds were europium and terbium complexes though theoretically the electronic structure of samarium should be as suitable as the one of terbium. This discrepancy can be accounted for by the high susceptibility of samarium to non-radiative deactivation processes. The aim of this study was to strategically circumvent this difficulty by the use of a ligand scaffold which has already proven to efficiently suppress these processes, namely the cryptates. The prepared partly deuterated samarium and europium complexes exhibit distinct circularly polarised luminescence with dissymmetry factors up to glum =+0.13 (SmIII ) or glum =-0.19 (EuIII ).


Trends of transcutaneous bilirubin in neonates who develop significant hyperbilirubinemia.
To provide data on the natural course of transcutaneous bilirubin (TcB) levels in neonates before the development of significant hyperbilirubinemia, and to assess the effect of different demographic and perinatal factors on the rate of TcB increase. We analyzed 2454 TcB measurements from 419 neonates before the development of significant hyperbilirubinemia. Mean TcB values and TcB percentiles for designated times were calculated, and the effect of different risk factors on the rate of TcB increase was assessed. TcB percentile curves were plotted for comparison on a population-based TcB nomogram. Blood incompatibilities and glucose-6-phosphate dehy-drogenase deficiency were associated with higher rates of TcB in-crease during the first 36 to 48 postnatal hours, whereas smaller gestational age, increased weight loss, and exclusive breastfeeding had a similar but later effect. Compared with general population norms, a different pattern of TcB increase was noted in neonates who developed significant hyperbilirubinemia, but with a sub-stantial overlap of TcB values during the first 24 to 48 postnatal hours. We provide data on the natural course of TcB levels before the development of significant hyperbilirubinemia in a white population of term and near-term neonates. Smaller gestational age, blood incompatibilities, glucose-6-phosphate dehydrogenase deficiency, increased weight loss, and exclusive breastfeeding significantly affected the rate of TcB increase in a time-dependent manner. These findings may assist in assessing the risk for significant hyperbilirubinemia and planning appropriate follow-up strategies for neonates with borderline bilirubin levels.


Impact of Education on Knowledge and Practice of Kala Azar Preventive Measures among Seasonal and Migrant Agricultural Workers in Northwest Ethiopia.
Kala azar occurs among seasonal and migrant agricultural workers in northwest Ethiopia and accounts for almost 60% of the disease burden in the country. We conducted a quantitative study on the level of knowledge and practice of this vulnerable group in relation to kala azar transmission and acceptability of its vector control tools. A total of 403 workers were randomly selected from eight farms using a purposive sampling technique. Knowledge and practice scores were calculated based on 12 and 9 core questions, respectively. Binary logistic regression was used to identify factors associated with knowledge and practice. A large gap in knowledge of the disease and the vector was evident with 61.8%, 24.6%, and 13.6% of the workers having poor, moderate, and good levels of knowledge scores, respectively. Similarly, 95% of the seasonal workers reported poor level of use of protective measures against the bite of the sand fly vector. Good level of knowledge about kala azar and its sand fly vector was statistically associated with formal education (adjusted odds ratio [AOR] = 2.11; 95% CI = 1.17, 3.80; P < 0.05) and previous exposure to health education (AOR = 4.72; 95% CI = 1.99, 11.16; P < 0.001). Despite poor current knowledge and practice, a large proportion of the study participants showed interest in using vector control tools if made available, with 78% of the seasonal and migrant workers expressing some willingness to pay for different measures that can protect against sand fly bites. Therefore, we strongly recommend that comprehensive health education and vector control programs should be provided to these workers.


[Effects of emodin on human erythroleukemia cell line HEL].
This study was aimed to investigate the inhibitory effect of emodin on the proliferation of HEL cells, the inducing apoptosis effect of HEL cells and their mechanisms. The proliferation inhibition was detected by MTT method; the change of morphology was observed by AO/EB stains; the cell cycle and apoptosis was analyzed by flow cytometry; the expressions of Akt, P-Akt, P-GSK3β and HSP70 proteins were determined by Western blot. The results indicated that emodin displayed significant anti-proliferative effect on HEL cells in a dose dependent manner(r = 0.99), with IC(50) value of 4.19 µmol/L; AO/EB stains showed that the morphology of HEL cells obviously changed after emodin treatment for 24 hours, and at 24 and 48 hours the apoptosis rates of HEL cells treated by emodin were (27.35 ± 1.68)% and (58.49 ± 1.55)% respectively. Compared with blank control group, the cell ratio in G(0)/G(1) phase increased while that in S phase decreased (p < 0.01); the expression of Akt protein was not changed (p > 0.05), and that of P-Akt, P-GSK3β and HSP70 proteins were down-regulated (p < 0.05). It is concluded that emodin efficiently inhibits the HEL cell proliferation and induces apoptosis of HEL cells, which may be related to the down-regulation of P-Akt, P-GSK3β and HSP70 proteins expression.


Lower rate of genomic variation identified in the trans-membrane domain of monoamine sub-class of Human G-Protein Coupled Receptors: the Human GPCR-DB Database.
We have surveyed, compiled and annotated nucleotide variations in 338 human 7-transmembrane receptors (G-protein coupled receptors). In a sample of 32 chromosomes from a Nordic population, we attempted to determine the allele frequencies of 80 non-synonymous SNPs, and found 20 novel polymorphic markers. GPCR receptors of physiological and clinical importance were prioritized for statistical analysis. Natural variation and rare mutation information were merged and presented online in the Human GPCR-DB database http://cyrix.cgb.ki.se. The average number of SNPs per 1000 bases of exonic sequence was found to be twice the average number of SNPs per Kilobase of intronic regions (2.2 versus 1.0). Of the 338 genes, 111 were single exon genes, that is, were intronless. The average number of exonic-SNPs per single-exon gene was 3.5 (n = 395) while that for multi-exon genes was 0.8 (n = 1176). The average number of variations within the different protein domain (N-terminus, internal- and external-loops, trans-membrane region, C-terminus) indicates a lower rate of variation in the trans-membrane region of Monoamine GPCRs, as compared to Chemokine- and Peptide-receptor sub-classes of GPCRs. Single-exon GPCRs on average have approximately three times the number of SNPs as compared to GPCRs with introns. Among various functional classes of GPCRs, Monoamine GPRCs have lower number of natural variations within the trans-membrane domain indicating evolutionary selection against non-synonymous changes within the membrane-localizing domain of this sub-class of GPCRs.


Maternal Smoking and the Risk of Cancer in Early Life - A Meta-Analysis.
In spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases. The aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations. In a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated. Smoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02-1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05-1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring. According to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies.


Association between depressive symptoms and sarcopenia in older Chinese community-dwelling individuals.
The aim of this study was to assess the prevalence of sarcopenia and depressive symptoms and estimate the association between them in elderly Chinese community-dwelling individuals. A total of 948 elderly Chinese community-dwelling individuals were recruited through leaflets and posters from three communities in Chengdu, and 865 participants were analyzed in this cross-sectional study. Muscle mass was measured using the bioimpedance analysis, handgrip strength was measured with a handheld dynamometer, and physical performance was assessed via usual gait speed on a 6 m course. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia (AWGS). Depressive symptoms were assessed using the Chinese version of 15-item Geriatric Depression Scale (GDS-15) with a score of ≥5 indicative of the presence of depressive symptoms. A total of 865 participants were included in the analysis. The participants had a mean age of 68.68±6.46 years. Sixty-one (7.1%) participants and 71 (8.2%) participants were identified as having sarcopenia and depressive symptoms, respectively. After adjusting for age, sex, and other potential confounders, sarcopenia was found to be significantly associated with depressive symptoms (odds ratio [OR]: 2.23, 95% CI 1.06-4.92). The prevalence rates of sarcopenia and depressive symptoms were 7.1 and 8.2%, respectively, in elderly Chinese community-dwelling individuals, and sarcopenia was significantly associated with depressive symptoms.


The Study of Derivatization Prior MALDI MSI Analysis-Charge Tagging Based on the Cholesterol and Betaine Aldehyde.
Mass spectrometry imaging is a powerful tool for analyzing the different kinds of molecules in tissue sections, but some substances cannot be measured easily, due to their physicochemical properties. In such cases, chemical derivatization could be applied to introduce the charge into the molecule and facilitate its detection. Here, we study cholesterol derivatization with betaine aldehyde from tissue slices and evaluate how different sample preparation methods influence the signal from the derivatization product. In this study, we have tested different solutions for betaine aldehyde, different approaches to betaine aldehyde deposition (number of layers, deposition nozzle height), and different MALDI matrices for its analysis. As a result, we proved that the proposed approach could be used for the analysis of cholesterol in different tissues.


[Deep alkali burns: Evaluation of a two-step surgical strategy].
Chemical burns are rare but often lead to deep cutaneous lesions. Alkali agents have a deep and long lasting penetrating power, causing burns that evolve over several days. The local treatment for these patients is excision of the wound and split thickness skin graft. Early excision and immediate skin grafting of alkali burns are more likely to be complicated by graft failure and delayed wound healing. We propose a two-step method that delays skin grafting until two-three days after burn wound excision. Our population included 25 controls and 16 cases. Men were predominant with a mean age of 41.9 years. In 78% of cases, burns were located on the lower limbs. The mean delay between the burn and excision was 16.5 days. In cases, the skin graft was performed at a mean of 11.3 days after the initial excision. We did not unveil any significant difference between both groups for the total skin surface affected, topography of the burns and the causal agent. Wound healing was significantly shorter in cases vs controls (37.5 days vs 50.3 days; P<0.025). Furthermore, we observed a decreased number of graft failures in cases vs controls (13.3% vs 46.7%; P=0.059). Our study shows the relevance of a two-step surgical strategy in patients with alkali chemical burns. Early excision followed by interval skin grafting is associated with quicker wound healing and decreased rate of graft failure.


[Acute suppurative thyroiditis--laryngologic problem].
Authors present four cases of acute suppurative thyroiditis treated in our department. Initial symptoms are similar to acute pharyngitis or laryngitis but could end in fulminant course that could be life threatening. We present etiology, clinical symptoms and accessory exams as well as new treatment methods. All four patients were cured. In one case pharmacological treatment was sufficient. In second case the patient needed intubation due to stridor. In third one after pharmacological treatment we performed partial thyroidectomy. In last case patient with thyroid abscess needed urgent thyroidectomy due to retropharyngeal and mediastinal multiple abscesses. Acute suppurative thyroiditis needs hospitalisation. Some patients needed surgical intervention due to life threatening course.


[Specific strength measurement of musculus abductor pollicis brevis in order to objectively evaluate muscle regeneration after carpal tunnel release surgery].
47 patients with a carpal tunnel syndrome were preoperatively examined not only by electrophysical studies (nerve velocity and distal motoric latency) and clinical tests (Phalen's sign, Tinel's sign) but also by measuring the strength of the M. abductor pollicis brevis with a specifically designed strength-testing unit. 30 patients agreed to participate in a voluntary postoperative examination. In the 45 degrees -measurement there was a relative strength loss of the injured hand's thumb of about 25 % in comparison with the healthy hand preoperatively. The postoperative strength disadvantage amounted to only 10 %. Measurement of the strength in the neutral zero method showed a relative strength loss of the injured hand's thumb of 8 % while postoperatively there was even a strength advantage of 9 % in comparison with the thumb of the healthy hand. Both methods showed a relevant and significant postoperative strength increase of the injured hand's thumb. We could prove a significant correlation (p = 0.03) of the neutral zero strength measurement and the distal motoric latency of the median nerve. Furthermore, we could show a trend for a correlation between the neutral zero strength measurement and the median motoric velocity. In conclusion, it can be said that the special strength measurement of the M. abductor pollicis brevis is an important parameter to objectively evaluate the motoric symptomatology in carpal tunnel syndrome patients.


Rottlerin plays an antiviral role at early and late steps of Zika virus infection.
Infection of Zika virus (ZIKV) may cause microcephaly and other neurological disorders, while no vaccines and drugs are available. Our study revealed that rottlerin confers a broad antiviral activity against several enveloped viruses, including ZIKV, vesicular stomatitis virus, and herpes simplex virus, but not against two naked viruses (enterovirus 71 and encephalomyocarditis virus). Rottlerin does not have a direct virucidal effect on the virions, and its antiviral effect is independent of its regulation on PKCδ or ATP. Both pretreatment and post-treatment of rottlerin effectively reduce the viral replication of ZIKV. The pretreatment of rottlerin disturbs the endocytosis of enveloped viruses, while the post-treatment of rottlerin acts at a late stage through disturbing the maturation of ZIKV. Importantly, administration of rottlerin in neonatal mice significantly decreased the ZIKV replication in vivo, and alleviated the neurological symptoms caused by ZIKV. Our work suggests that rottlerin exerts an antiviral activity at two distinct steps of viral infection, and can be potentially developed as a prophylactic and therapeutic agent.


Noninvasive evaluation of the patient with a pleural effusion.
Pleural fluid formation is an indicator of a pathologic process that may be of primary pulmonary origin but also may be a reflection of disease in virtually any other organ system or a systemic disease. A thoracentesis should be performed on any patient in whom the cause of the effusion has not been established yet. The possible exception to this is an effusion thought to be secondary to uncomplicated congestive heart failure. The presumptive or definitive diagnosis can be established in 75% of patients by following patient history, physical examination, and pleural fluid analysis.


Crystal structure of pyrimidine-nucleoside phosphorylase from Bacillus subtilis in complex with imidazole and sulfate.
Pyrimidine-nucleoside phosphorylase catalyzes the phosphorolytic cleavage of thymidine and uridine with equal activity. Investigation of this protein is essential for anticancer drug design. Here, the structure of this protein from Bacillus subtilis in complex with imidazole and sulfate is reported at 1.9 Å resolution, which is an improvement on the previously reported structure at 2.6 Å resolution. The localization and position of imidazole in the nucleoside-binding site reflects the possible binding of ligands that possess an imidazole ring.


A patient with liver trauma and incomplete behcet s disease.
Behcet' s Disease (BD ) is a complex multisystemic disease, which is characterized by recurrent oral and genital aphteous ulcers and iritis in which vasculitis can also be one of the possible clinical manifestations. A thirty seven year-old female patient with incomplete BD was admitted to emergency service, with intra-abdominal hemorrhage more severe than that would be expected, with the degree of related trauma. We decided to manage the patient conservatively, observing vital signs, haemogram, computed tomography (CT) and angiography instead. Subcapsular hematomas were detected in the right and left lobes of the liver. No data was encountered in the literature and textbooks referring to liver trauma with BD, except a case of fatal hemobilia. H ere in we present a liver trauma case with hemorrhage and hepatic fragility due to vasculitis in Behcet' s disease and review the literature. Key words: liver trauma, incomplete Behcet' s disease


Pooled-data analysis of three randomized, double-masked, six-month studies comparing intraocular pressure-reducing effects of latanoprost and timolol in patients with ocular hypertension.
To assess retrospectively the intraocular pressure (IOP)-reducing effect of latanoprost compared with timolol in the subset of patients with ocular hypertension (OH). Three randomized, double-masked, multicenter, parallel group, 6-month studies conducted in the United States, United Kingdom, and Scandinavia compared the efficacy and safety of latanoprost and timolol. The present study represents an analysis of the pooled data for the subset of OH patients. Intent-to-treat analyses were based on all randomized OH patients. Of the 441 patients with OH, 247 were treated with latanoprost and 194 were treated with timolol. Baseline mean diurnal IOP levels were 24.4 +/- 0.2 mm Hg (mean +/- standard error of the mean) in the latanoprost group and 24.2 +/- 0.2 mm Hg in the timolol group. Overall, latanoprost lowered mean diurnal IOP by 1.1 +/- 0.2 mm Hg (95% CI: 1.6 to 0.7 mm Hg, P < 0.001) more than timolol. The difference in IOP-lowering ability between the two drugs was not shown to be related to patient sex, age, race, presence or absence of previous treatment of OH, time elapsed since ocular diagnosis, or family history of glaucoma/OH. Percentage reductions from baseline in diurnal IOP levels of at least 20% were achieved by 83% of patients treated with latanoprost versus 62% of those receiving timolol. Latanoprost provides superior IOP reduction compared with timolol in patients with OH.