Interventions for idiopathic intracranial hypertension.
Idiopathic intracranial hypertension (IIH) has an estimated incidence of one to three people per 100,000 people per year, and occurs most commonly in obese, young women. IIH is associated with severe morbidity, notably due to a significant threat to sight and severe headache. Several different management options have been proposed. Conservative measures centre on weight loss. Pharmacological therapy includes use of diuretics. Refractory and sight-threatening cases demand surgical intervention, most often in the form of cerebrospinal fluid (CSF) diversion or optic nerve sheath fenestration. Other treatments include venous sinus stenting and bariatric surgery. To assess the effects of any intervention for IIH in any patient group. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2015), EMBASE (January 1980 to July 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 July 2015. We included only randomised controlled trials (RCTs) in which any intervention was compared to placebo, or to another form of treatment, for people with a clinical diagnosis of IIH. Two review authors independently assessed the search results for trials to be included in the review. We resolved any discrepancies by third party decision. We identified two completed RCTs (enrolling a total of 211 participants and conducted in the UK and US) and two ongoing trials that met the inclusion criteria. Both completed trials compared acetazolamide to placebo, in conjunction with a weight loss intervention in both groups. Attrition bias was a problem in both trials with high loss to follow-up, in one study this loss to follow-up occurred particularly in the acetazolamide arm. One trial was unmasked and we judged it to be at risk of performance and detection bias.In these studies, change in visual acuity was similar in the treatment and control groups as measured by logMAR acuity. In one study people in the acetalomazide group had a similar change in logMAR acuity compared to the placebo group between baseline and 12 months in the right eye (MD 0.04 logMAR, 95% CI -0.08 to 0.16) and left eye (MD 0.03 logMAR, 95% CI -0.09 to 0.15). In the other study people in the acetalomazide group had a similar change in vision over six months compared with people in the placebo group (mean difference in change in letters read was 0.01 (95% CI -1.45 to 1.46). One study reported no cases of visual loss in 21 people treated with acetalomazide compared to 2/20 cases in the placebo group (odds ratio 0.17, 95% CI 0.01, 3.82).The prespecified outcome for this review was reduction in CSF pressure to normal levels which was not reported by the two trials. One trial reported that, in a subsample of 85 participants who agreed to lumbar puncture at 6 months, people in the acetalomazide group on average had a greater reduction in CSF pressure (MD -59.9 mmH(2)O, 95% CI -96.4, -23.4).In one study, people in the acetalozamide group on average experienced a greater reduction in papilloedema as assessed by fundus photographs MD -0.70 (95% CI -1.00 to -0.40) and by clinical grading MD -0.91 (95% CI -1.27 to -0.54) between baseline and six months in the study eye.Headache was recorded as present/absent in one study at 12 months (OR 0.42, 95% CI 0.12,1.41, 41 participants). Both studies reported headache on visual analogue scales (different ones) but results were inconclusive (MD for change in headache score measured on 10-point visual analogue scale at 12 months was 1.0 (-1.80, 3.70, 41 participants) and MD for change in headache score on a 6 point scale measured at 6 months was -0.45 (-3.5,2.6, number of participants unclear).In one study, a similar proportion of people in the acetalomazide group were in remission (however, the trial authors did not state their definition of this term) at 12 months compared to the placebo group. However, the 95% CIs were wide and there is considerable uncertainty as to the effect (OR 1.13 (95% CI 0.32 to 3.90, 41 participants).In one study of 185 participants, people in the acetalomazide group had an increased risk of decreased CO2, diarrhoea, dysgeusia, fatigue, nausea, paresthesia, tinnitus and vomiting compared to people in the placebo group. In general, the estimates of effect were uncertain with wide 95% CIs. Adverse effects were not reported in the other study.One study reported that quality of life was better in acetazolamide-treated patients based on the visual quality of life (VFQ-25) (MD 6.35, 95% CI 2.22 to 10.47) and the physical (MD 3.02, 95% CI 0.34 to 5.70) and mental (MD 3.45, 95% CI 0.35 to 6.55) components of the 36-Item Short Form Health Survey tool at six months. Costs were not reported in either study.We judged the evidence to be low certainty (GRADE) downgrading for imprecision and risk of bias. Although the two included RCTs showed modest benefits for acetazolamide for some outcomes, there is insufficient evidence to recommend or reject the efficacy of this intervention, or any other treatments currently available, for treating people with IIH. Further high-quality RCTs are required in order to adequately assess the effect of acetazolamide therapy in people with IIH.


Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA.
Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides.


Clinical course of thyroid function and thyroid associated-ophthalmopathy in patients with euthyroid Graves' disease.
Euthyroid Graves' disease (EGD) is a rare condition defined as the presence of thyroid-associated ophthalmopathy (TAO) in patients with normal thyroid function. Due to the rarity of this disease, only a limited number of studies and case reports are available for further evaluation of the characteristics of the disease. The aim of this study was to examine the changes in the thyroid function, thyrotropin receptor antibodies (TRAb) and eye symptoms, and then determine whether TRAb is related to TAO in EGD patients. TRAb in this study was defined as including both thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSAb). Medical records of patients diagnosed with EGD were reviewed. Ophthalmologists specializing in TAO examined the eyes of all subjects. Of the 58 patients diagnosed with EGD, 24.1% developed hyperthyroidism, while 3.4% developed hypothyroidism. A total of 72.4% of the 58 patients remained euthyroid throughout the entire follow-up period. At the initial presentation, TBII and TSAb were positive in 74.5% and 70.5%, respectively. Ophthalmic treatments were administered to 30 (51.7%) out of the 58 patients. A significant spontaneous improvement of the eye symptoms was found in 28 of the EGD patients who did not require eye treatments. EGD patients exhibited positive rates for both TBII and TSAb, with the number of the TRAb-positive patients gradually decreasing while the eye symptoms spontaneously improved over time. There were no correlations found between TRAb at initial presentation and the eye symptoms. TBII and TSAb were positive in about 70% of EGD patients at their initial visit. Thyroid functions of EGD patients who have been euthyroid for more than 6.7 years may continue to remain euthyroid in the future.


The application of materials balancing to the characterization of sequential secondary metabolite formation in Streptomyces cattleya NRRL 8057.
The high substrate yield factor (0.73 g biomass g glucose-1) and low R.Q. (respiratory quotient, i.e. mol CO2 evolved per mol O2 consumed) value (0.8) measured during growth-phase batch cultures of Streptomyces cattleya could be rationalized in terms of the fermentation mass balance when the oxidized elemental composition of biomass was considered. R.Q. was also indicative of the sequence of secondary metabolite formation, the value rising in steps as each new product was formed. The period of maximum respiratory activity and phosphate uptake preceded maximum growth and glucose uptake. At the end of the lytic phase, a cyclopentenedione cobalt chelator was produced. The termination of lysis coincided with melanin production. Sequential cephamycin C and thienamycin production then took place. Specific hyphal protein content (per unit RNA) peaked before the production of each new metabolite. Melanin, cephamycin C and thienamycin production were initiated when glucose, ammonia and phosphate, respectively, became growth-limiting.


Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses.
With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to compare identical numbers of antigen-specific naive T cells from young and aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts, there was significantly reduced expansion and germinal center (GC) differentiation of the antigen-specific B cell population after immunization. This reduced cognate helper function was seen at all time points and over a wide range of donor cell numbers. In hosts receiving aged CD4 cells, there were also dramatically lower levels of antigen-specific IgG. These age-related defects were not due to defects in migration of the aged CD4 T cells, but may be attributable to reduced CD154 (CD40L) expression. Furthermore, we found that there was no difference in B cell expansion and differentiation or in IgG production when young CD4 T cells were transferred to young or aged hosts. Our results show that, in this model, age-related reductions in the cognate helper function of CD4 T cells contribute significantly to defects in humoral responses observed in aged individuals.


[Medical informatics in research, teaching and patient management].
The field of medical informatics in its current understanding is defined and criteria distinguishing this field from similar areas are provided. Special consideration is given to its position at a School of Medicine - in particular to the University of Vienna Medical School with the Vienna General Hospital as its teaching hospital. Demands for medical informatics and electronic data processing (EDP) in this extended field of activity come from four different sources: (1) research in medical informatics, (2) teaching of medical informatics as well as EDP training, (3) EDP service for research and teaching, and (4) EDP hospital operations to assist patient care. (Purely administrative EDP demands are not considered here.) It is shown that the different demands can be fulfilled by the usually available institutions involved in medical informatics and EDP at a School of Medicine. At many places these institutions are as follows: (1) a department or division of medical informatics with a possibly attached computer center dedicated to provide assistance in the area of research and teaching, (2) the computer center of the respective university the School of Medicine belongs to, (3) the computer center of the hospital-owned institution responsible for all EDP activities connected to patient care, and (4) external software companies and EDP training centers. To succeed in the development of an exhaustive, school-wide system of medical informatics and EDP that considers the different demands in research, teaching, and EDP hospital operations equally, close and well-suited coordination between the institutions involved is necessary.


Multiplex DNA detection of food allergens on a digital versatile disk.
The development of a DNA microarray method on a digital versatile disk (DVD) is described for the simultaneous detection of traces of hazelnut ( Corylus avellana L.), peanut ( Arachis hypogaea ), and soybean ( Glycine max ) in foods. After DNA extraction, multiplex PCR was set up using 5'-labeled specific primers for Cor a 1, Ar h 2, and Le genes, respectively. Digoxin-labeled PCR products were detected by hybridization with 5'-biotinylated probes immobilized on a streptavidin-modified DVD surface. The reaction product attenuates the signal intensity of the laser that reached the DVD drive used as detector, correlating well with the amount of amplified sequence. Analytical performances showed a detection limit of 1 μg/g and good assay reproducibility (RSD 8%), suitable for the simultaneous detection of the three targeted allergens. The developed methodology was tested with several commercially available foodstuffs, demonstrating its applicability. The results were in good agreement, in terms of sensitivity and reproducibility, with those obtained with ELISA, PCR-gel agarose electrophoresis, and RT-PCR.


Follicular Helper T Cells in Pulmonary Tuberculosis: A Retrospective Study.
Follicular helper T lymphocyte (Tfh) promotes antibody production by B lymphocytes in various diseases, including Pulmonary Tuberculosis (PTB). To explore the potential role of Tfh cells and assess the expression level of PD-1, and IL-21 in PTB. 54 newly diagnosed smear-positive PTB, 27 people with latent tuberculosis (LTB) and 27 healthy controls (HC) were enrolled. The PTB group was further divided based on the range of lung field involved (focus number>=3, PTB-X3; <3, PTB-X2). After 6-month therapy, sputum smear (positive, PTB-SP; negative, PTB-SN) or imaging examinations (lesion reduction significant, PTB-os; insignificant, PTB-s) were used to evaluate the conditions of PTB patients. Blood samples were collected from PTB group at month six. CD4+CXCR5+Tfh, and its subsets, CD4+CXCR5+PD-1+Tfh and CD4+CXCR5+ICOS+Tfh in peripheral blood mononuclear cells (PBMCs) were detected. Serum IL-21 concentrations were measured. The frequencies of CD4+CXCR5+Tfh, CD4+CXCR5+ICOS+Tfh and CD4+CXCR5+PD-1+Tfh were higher in PTB group than in HC. IL-21, IL-4 and IFNγ concentrations were significantly higher in PTB group than in HC. The proportion of CD4+CXCR5+Tfh in PTB-X2 was lower than in PTB-X3 group. CD4+CXCR5+PD-1+Tfh proportion in PTB-X2 was lower than that in the PTB-X3. After treatment, CD4+CXCR5+Tfh proportion was significantly lower in the PTB-SN group. CD4+CXCR5+Tfh was lower in the PTB-os group than in the PTB-s group. However, the CD4+CXCR5+PD-1+Tfh and cytokine concentrations of IL-21 were not different. CD4+CXCR5+Tfh level might predict the sputum results, and lesion decrease rate while CD4+CXCR5+PD-1+Tfh subset and IL-21 were not associated with sputum results or lesion decrease after treatment.


[Principles of cytogenetic examination for detecting occupational hazards].
The main principles are stated of carrying out a cytogenetic examination of human populations on the basis of critical analysis of data from literature and the authors' own experience in this field. The method for estimation of sister chromatid exchanges is shown expedient to be used together with the chromosome aberration analysis in carrying out cytogenetic examinations. Statistically ascertained approaches are adduced to select the necessary amount of persons examined in groups and the number of cells for analysis when using methods for estimation of sister chromatid exchanges and chromosome aberrations.


Prenatal testosterone excess alters Sertoli and germ cell number and testicular FSH receptor expression in rams.
Exposure to excess testosterone (T) during fetal life has a profound impact on the metabolic and reproductive functions in the female's postnatal life. However, less is known about the effects of excess testosterone in males. The aim of the present study was to evaluate the impact (consequences) of an excess of T during fetal development on mature male testis. The testicular evaluation was by histological analysis and by determination of mRNA expression of the FSH receptor (FSH-R), transforming growth factor-β type I receptor (TβR-I), and two members of the TGF-β superfamily, transforming growth factor-β3 (TGFβ3) and anti-Müllerian hormone (AMH) in males born to mothers receiving an excess of T during pregnancy. At 42 wk of age, postpubertal males born to mothers treated with 30 mg of T propionate twice weekly from day 30 to 90, followed by 40 mg of T propionate from day 90 to 120 of pregnancy (T males), showed higher concentrations of FSH in response to a GnRH analog, a higher number of Sertoli cells/seminiferous tubule cross-section, and a lower number of germ cells/tubules (P < 0.05) than control males (C males) born to mothers treated with the vehicle. The mRNA expression of FSH-R and of TβR-I was higher in T males compared with C males (P < 0.05). Moreover, in T males, AMH expression level correlated negatively with the expression level of TGFβ3. In C males, this latter correlation was not observed. These results suggest that prenatal exposure to an excess of T can negatively modify some histological and molecular characteristics of the mature testis.


Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease.
The purpose of this study was to assess the five-year treatment effects of a short course of intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) due to Alzheimer disease (AD). Fifty subjects 50 to 84 years of age with MCI due to AD were administered 0.4 g/kg 10% IVIG or 0.9% saline every two weeks x five doses in a randomized double-blinded design as part of a two-year study. Twenty-seven subjects completed an additional three-year extension study. MRI brain imaging, cognitive testing, and conversion to dementia were assessed annually. Participants were stratified into early MCI (E-MCI) and late MCI (L-MCI). The primary endpoint was brain atrophy measured as annualized percent change in ventricular volume (APCV) annually for five years. ANOVA was used to compare annualized percent change in ventricular volume from baseline between the groups adjusting for MCI status (E-MCI, L-MCI). Differences in brain atrophy between the groups, which were statistically significant after one year, were no longer significant after five years. IVIG-treated L-MCI subjects did demonstrate a delay in conversion to dementia of 21.4 weeks. An eight-week course of IVIG totaling 2 g/kg in MCI is safe but is not sufficient to sustain an initial reduction in brain atrophy or a temporary delay in conversion to dementia at five years. Other dosing strategies of IVIG in the early stages of AD should be investigated to assess more sustainable disease-modifying effects. Trial registration ClinicalTrials.gov NCT01300728. Registered 23 February 2011.


Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype.
Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants. Overlapping features included developmental delay, intellectual disability, behavioral abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals (n = 26) are missense, including six that recurrently affect two residues. Four unrelated probands were identified with inherited variation affecting Arg441, a site at which variation has been previously seen in NDD-affected siblings, and two individuals have de novo variation resulting in p.Arg1294Cys (c.3880C>T). All variants affect evolutionarily conserved sites, and most are predicted to damage protein structure or function. ZMYM3 is relatively intolerant to variation in the general population, is widely expressed across human tissues, and encodes a component of the KDM1A-RCOR1 chromatin-modifying complex. ChIP-seq experiments on one variant, p.Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. While we are unable to perform statistical evaluations to definitively support a causative role for variation in ZMYM3, the totality of the evidence, including 27 affected individuals, recurrent variation at two codons, overlapping phenotypic features, protein-modeling data, evolutionary constraint, and experimentally confirmed functional effects strongly support ZMYM3 as an NDD-associated gene.


[Changes in the epidemiology of gastroenteritis caused by Salmonella during 2005-2014 in Salamanca, Spain].
In Spain there are not many updated population studies about salmonellosis, despite being one of the most common etiologies of acute gastroenteritis (AGEs) caused by bacteria in the world. The aim of the study was to know the most relevant epidemiological features of AGEs produced by Salmonella spp. between 2005 and 2014 in Salamanca (Spain). Descriptive cross-sectional study carried out through review of the clinical microbiologic records at Complejo Asistencial Universitario de Salamanca. Culture, isolation, identification and serotyping were performed according to standard methodology. Salmonella was isolated in 1,477 patients, representing 47.7% of all positive stool cultures and 53.3% of all income bacterial AGE. The average prevalence was 42.1 cases/100,000 people per year. The mean age was 23 ± 28 years and the median 7 years. 40.2% of all isolates occurred in children under 5 years, with an average prevalence of 45.1 cases/ 10,000 people per year. Overall, the most frequently isolated serotype was S. Typhimurium with 57%, followed by S. Enteritidis with 35.8%. The prevalence of Salmonella decreased over time. The group aged 0-4 years had the highest rate throughout the period. However, Salmonella produced the highest percentage of hospitalizations for bacterial AGE. In recent years, S. Typhimurium serotype has replaced S. Enteritidis serotype and predominates in younger patients. It is observed under-reporting of cases of salmonellosis produced in Salamanca despite being mandatory notification of these since 2007.


Prevalence of depression in maintenance hemodialysis patients and its correlation with adherence to medications.
This study was designed to evaluate the adherence of maintenance hemodialysis patients to medications and its correlation with quality of life and depressive symptoms. A total of 150 maintenance hemodialysis patients with a mean age of 56.4 ± 16.4 years (52.7% women) were included. Medication adherence was evaluated via the Simplified Medication Adherence Questionnaire, based on which nonadherent patients were identified. Specifically, the Drug-Intake Percentage Questionnaire was used for evaluation of adherence to phosphate binders, quality of life was assessed with short Form-36 and depression by the Beck Depression Inventory (BDI). A BDI score of 15 and greater was documented in 40.7%, and nonadherence in 24.7% of the patients. Adherent patients were significantly older than nonadherent ones, had a lower mean parathyroid hormone level, and had lower BDI scores. The quality of life scores were not significantly different between adherent and nonadherent patients. Multivariable analysis demonstrated that BDI score was a significant predictor of nonadherence (odds ratio for each unit increase, 1.11; 95% confidence interval, 1.04 to 1.18; P = .001). Overall, 55.5% of patients were taking more than 66% of their prescribed dose of calcium carbonate, while 10.3% and 53.8% of patients were taking more than 66% of their prescribed dose of aluminum hydroxide and sevelamer, respectively. Adherence to medication was mainly associated with hemodialysis patients' depressive symptom scores. Control of depression may significantly improve adherence to medications and patient management.


Transgenic animals as new approaches in pharmacological studies.
Transgenic animals are becoming useful tools for pharmacological studies. The use of transgenic technology raises two types of questions, "How are transgenic animals made?" and "What types of pharmacological questions can be answered using transgenic technologies?" Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromosomes. The second strategy is to select particular genetic loci for site-specific changes. There are two well-established procedures for simple introduction of DNA into an animal genome, pronuclear DNA injection and transduction using a retrovirus. In contrast, methods for targeting specific DNA sequences to definite sites in the chromosomes are evolving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacological studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology.


[Acupuncture at Baihui(GV 20) and Shenting(GV 24) combined with basic treatment and regular rehabilitation for post-stroke cognitive impairment:a randomized controlled trial].
To observe the clinical effect of acupuncture at Baihui(GV 20) and Shenting(GV 24) combined with rehabilitation for post-stroke cognitive impairment(PSCI). Fifty patients with PSCI were randomly assigned to an observation group and a control group,25 cases in each one. In the control group,basic treatment and regular rehabilitation were applied. In the observation group,acupuncture at Baihui(GV 20) and Shenting(GV 24) and the same therapies as the control group were used for continuous four weeks,once a day and five times a week. Mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA) were observed before and after treatment in the two groups. After treatment,the scores of MMSE and MoCA were improved apparently(both P<0.05),with better results in the observation group(both P<0.05). Acupuncture at Baihui(GV 20) and Shenting(GV 24) combined with basic treatment and regular rehabilitation can obviously improve the cognitive function of PSCI,and the effect is superior to that of basic treatment and regular rehabilitation.


A Review of Switching Strategies for Patients with Schizophrenia Comorbid with Metabolic Syndrome or Metabolic Abnormalities.
Metabolic syndrome (MetS) in patients with schizophrenia occurs 2-3 times more frequently than in the general population. Antipsychotic medication is a primary risk factor for patients with MetS. In particular, the widely used second-generation antipsychotics can affect glucose and lipid metabolism and can induce insulin resistance and other metabolic abnormalities through various receptors. Notably, the metabolic risks of various antipsychotics may differ because of their different pharmacological affinity to MetS-related receptors. Several previous studies have shown that switching from high to low metabolic risk antipsychotics may improve patients' metabolic parameters. The current review aims to discuss the strategies for switching antipsychotic medications and the impact on metabolic abnormalities in patients with schizophrenia.


Impact of surface modifications of Acanthocheilonema viteae microfilariae on cell adhesion.
Exposure of A. viteae microfilariae to various lectins reduced their capacity to react with the peritoneal exudate cells of the host, Mastomys natalensis. Sugars corresponding to these lectins with the exception of N-acetyl glucosamine, did not affect the adhesion per se. They however, protected the parasite against the adverse effect of lectins. Neuraminidase and chitinase also suppressed adhesion capacity of the microfilariae. Except sodium dodecylsulphate which enhanced cell attachment, other surfactants inhibited this reaction considerably. The results indicate that antibody dependent adhesion of the microfilariae with the macrophages involves surface moieties of the parasite, where N-acetylglucosamine acts as the principal sugar residue. Participation of -SH groups also is inferred from the observations that p-chloromercuribenzoate and dithiobis-(2-nitrobenzoic acid) inhibited cell attachment and dithiothreitol provided protection against these agents.


Folic acid prescription and suicide attempt prevention: effect of past suicidal behaviour, psychiatric diagnosis and psychotropic medication.
We previously showed that folic acid prescriptions for any indication were associated with lower rates of suicidal behaviour. Given that future randomised clinical trials are likely to focus on psychiatric disorders carrying elevated risk for suicide, we now report on the moderating effects of prior suicidal behaviour, psychiatric diagnoses and psychotropic medications on potential antisuicidal effects of folic acid. Data were obtained from the MarketScan Commercial Claims and Encounters databases that cover 164 million insured persons from 2005-2017, from which a cohort of 866 586 patients was derived. Analysis revealed no significant moderation effects on the antisuicidal effect of folic acid. These findings indicate that the potential benefit of folic acid for preventing suicidal behaviour is comparable in psychiatric populations at higher risk of suicide and that it may be additive to any benefit from psychotropic medications.


Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes.
The MHC class I-related chain (MIC) A and MICB ligands for the activating receptor NKG2D can be shed from tumor cells, and the presence of these soluble molecules in sera is related with compromised immune response and progression of disease. Recently, thiol disulphide isomerases and members of the ADAM (a disintegrin and metalloproteinase) gene family were identified as key enzymes in mediating MICA/B shedding from cells. Here, we report shedding of the most frequently expressed MICA allele in human populations (MICA*008) into exosomes, small membrane vesicles that are secreted upon fusion with the plasma membrane. Although similar to other MICA/B molecules in the extracellular domain, the predicted transmembrane and cytoplasmic domains of MICA*008 are quite different, and this difference seemed to be critical for the mode of release from tumor cells. Treatment of natural killer (NK) cells with exosomes containing MICA*008 molecules not only triggered downregulation of NKG2D from the cell surface but also provoked a marked reduction in NK cytotoxicity that is independent of NKG2D ligand expression by the target cell. Our findings reveal a mechanism of NK suppression in cancer that may facilitate immune escape and progression.


Comparative patterns of modified nucleotides in individual tRNA species from a mesophilic and two thermophilic archaea.
To improve and complete our knowledge of archaeal tRNA modification patterns, we have identified and compared the modification pattern (type and location) in tRNAs of three very different archaeal species, Methanococcus maripaludis (a mesophilic methanogen), Pyrococcus furiosus (a hyperthermophile thermococcale), and Sulfolobus acidocaldarius (an acidophilic thermophilic sulfolobale). Most abundant isoacceptor tRNAs (79 in total) for each of the 20 amino acids were isolated by two-dimensional gel electrophoresis followed by in-gel RNase digestions. The resulting oligonucleotide fragments were separated by nanoLC and their nucleotide content analyzed by mass spectrometry (MS/MS). Analysis of total modified nucleosides obtained from complete digestion of bulk tRNAs was also performed. Distinct base- and/or ribose-methylations, cytidine acetylations, and thiolated pyrimidines were identified, some at new positions in tRNAs. Novel, some tentatively identified, modifications were also found. The least diversified modification landscape is observed in the mesophilic Methanococcus maripaludis and the most complex one in Sulfolobus acidocaldarius Notable observations are the frequent occurrence of ac4C nucleotides in thermophilic archaeal tRNAs, the presence of m7G at positions 1 and 10 in Pyrococcus furiosus tRNAs, and the use of wyosine derivatives at position 37 of tRNAs, especially those decoding U1- and C1-starting codons. These results complete those already obtained by others with sets of archaeal tRNAs from Methanocaldococcus jannaschii and Haloferax volcanii.


Effect of restriction of the binocular visual field on driving performance.
The importance of the visual field on driving performance was investigated. This was undertaken by simulating binocular visual field defects for a group of young normal subjects and assessing the impact of these defects on performance on a driving course. Constriction of the binocular visual field to 40 or less, significantly increased time taken to complete the course, reduced the ability to detect and correctly identify road signs, avoid obstacles and to manoeuvre through limited spaces. Accuracy of road positioning and reversing were also impaired. Constriction of the binocular visual field did not significantly affect speed estimation, stopping distance, or the time taken for the reversing and manoeuvring tasks. The monocular condition did not significantly affect performance for any of the driving tasks assessed.


Dynamics of detachment of Escherichia coli from plasma-mediated coatings under shear flow.
A series of plasma-mediated coatings, containing silver nanoparticles embedded in an organosilicon or silica-like matrix, were deposited onto stainless steel and chemically characterized. Their anti-adhesive properties were evaluated in vitro towards Escherichia coli by performing shear-flow induced detachment experiments. Increasing the wall shear stress facilitated E. coli cell detachment, irrespective of the coating characteristics. When nanosilver was incorporated, cell detachment was lower, probably due to the affinity of the embedded silver for biological components of the cell wall. The presence of methyl groups in the matrix network could also promote enhanced hydrophobic interactions. Within the population fraction remaining attached to the coating under increasing shear flow, different association phenotypes were observed, viz. progressively lying flat, moving laterally, remaining tethered, or rotating by a single anchoring point, until alignment with the flow direction. This re-orientation phenotype and its relation with detachment were dependent of the coating. The effects of such heterogeneities should be more deeply explored.


Mechanism of Spontaneous Surface Modifications on Polycrystalline Cu Due to Electric Fields.
We present a credible mechanism of spontaneous field emitter formation in high electric field applications, such as Compact Linear Collider in CERN (The European Organization for Nuclear Research). Discovery of such phenomena opens new pathway to tame the highly destructive and performance limiting vacuum breakdown phenomena. Vacuum breakdowns in particle accelerators and other devices operating at high electric fields is a common problem in the operation of these devices. It has been proposed that the onset of vacuum breakdowns is associated with appearance of surface protrusions while the device is in operation under high electric field. Moreover, the breakdown tolerance of an electrode material was correlated with the type of lattice structure of the material. Although biased diffusion under field has been shown to cause growth of significantly field-enhancing tips starting from initial nm-size protrusions, the mechanisms and the dynamics of the growth of the latter have not been studied yet. In the current paper we conduct molecular dynamics simulations of nanocrystalline copper surfaces and show the possibility of protrusion growth under the stress exerted on the surface by an applied electrostatic field. We show the importance of grain boundaries on the protrusion formation and establish a linear relationship between the necessary electrostatic stress for protrusion formation and the temperature of the system. Finally, we show that the time for protrusion formation decreases with the applied electrostatic stress, we give the Arrhenius extrapolation to the case of lower fields, and we present a general discussion of the protrusion formation mechanisms in the case of polycrystalline copper surfaces.


Vascular endothelium in sepsis and endotoxemia.
Since septic or endotoxin shock was high mortality and morbidity, mechanisms for cardiovascular collapse have been intensely investigated. The vascular response to catecholamines and other agonists is greatly attenuated. The mechanisms are considered to be related to changes in endothelium function. The endothelium releases vasoconstrictor and vasodilator compounds. These autocoids normally interact with systemic and other local vascular controls, but during endotoxemia this balance is severely altered. Large artery endothelia are destroyed whereas the microvessels remain intact and functional. The release of nitric oxide, prostacyclin and endothelin is greatly enhanced. The cytokines from endotoxin seem, however, to be the major causal agents of the syndrome and affect the endothelial or receptors on the endothelia differentially, dependent on tissue location.


Timing the "magical number seven": Presentation rate and regularity affect verbal working memory performance.
The informative value of time and temporal structure often remains neglected in cognitive assessments. However, next to information about stimulus identity we can exploit temporal ordering principles, such as regularity, periodicity, or grouping to generate predictions about the timing of future events. Such predictions may improve cognitive performance by optimising adaptation to dynamic stimuli. Here, we investigated the influence of temporal structure on verbal working memory by assessing immediate recall performance for aurally presented digit sequences (forward digit span) as a function of standard (1000 ms stimulus-onset-asynchronies, SOAs), short (700 ms), long (1300 ms) and mixed (700-1300 ms) stimulus timing during the presentation phase. Participant's digit spans were lower for short and mixed SOA presentation relative to standard SOAs. This confirms an impact of temporal structure on the classic "magical number seven," suggesting that working memory performance can in part be regulated through the systematic application of temporal ordering principles.


New class of sensitive and selective fluorogenic substrates for serine proteinases. Amino acid and dipeptide derivatives of rhodamine.
A series of dipeptide derivatives of Rhodamine, each containing an arginine residue in the P1 position and one of ten representative benzyloxycarbonyl (Cbz)-blocked amino acids in the P2 position, has been synthesized, purified and characterized as substrates for serine proteinases. These substrates are easily prepared with high yields. Cleavage of a single amide bond converts the non-fluorescent bisamide substrate into a highly fluorescent monoamide product. Macroscopic kinetic constants for the interaction of these substrates with bovine trypsin, human and dog plasmin, and human thrombin are reported. Certain of these substrates exhibit extremely large specificity constants. For example, the kcat./Km for bovine trypsin with bis-(N-benzyloxycarbonylglycyl-argininamido)-Rhodamine [(Cbz-Gly-Arg-NH)2-Rhodamine] is 1 670 000 M-1 X S-1. Certain of these substrates are also highly selective. For example, the most specific substrate for human plasmin, (Cbz-Phe-Arg-NH2)-Rhodamine, is not hydrolysed by human thrombin, and the most specific substrate for human thrombin, (Cbz-Pro-Arg-NH)2-Rhodamine, is one of the least specific substrates for human plasmin. Comparison of the kinetic constants for hydrolysis of the dipeptide substrates with that of the single amino acid derivative, (Cbz-Arg-NH)2-Rhodamine, indicates that selection of the proper amino acid residue in the P2 position can effect large increases in substrate specificity. This occurs primarily as a result of an increase in kcat. as opposed to a decrease in Km and, in certain cases, is accompanied by a large increase in selectivity. Because of their high degree of sensitivity and selectivity, these Rhodamine-based dipeptide compounds should be extremely useful substrates for studying serine proteinases.


A P3-Type K1/2Mn5/6Mg1/12Ni1/12O2 Cathode Material for Potassium-Ion Batteries with High Structural Reversibility Secured by the Mg-Ni Pinning Effect.
Mn-based layered oxides are very attractive as cathodes for potassium-ion batteries (PIBs) due to their low-cost and environmentally friendly precursors. Their transfer to practical application, however, is inhibited by some issues including consecutive phase transitions, sluggish K+ deintercalation/intercalation, and serious capacity loss. Herein, Mg-Ni co-substituted K1/2Mn5/6Mg1/12Ni1/12O2 is designed as a promising cathode material for PIBs, with suppressed phase transitions that occurred in K1/2MnO2 and improved K+ storage performance. Part of Mg2+ and Ni2+ occupies the K+ layer, playing the role of a "nailed pillar", which restrains metal oxide layer gliding during the K+ (de)intercalation. The "Mg-Ni pinning effect" not only suppresses the phase transitions but also reduces the cell volume variation, leading to the improved cycle performance. Moreover, K1/2Mn5/6Mg1/12Ni1/12O2 has low activation barrier energy for K+ diffusion and high electron conductivity as demonstrated by first-principles calculations, resulting in better rate capability. In addition, K1/2Mn5/6Mg1/12Ni1/12O2 also delivers a higher reversible capacity owing to the participation of the Ni element in electrochemical reactions and the pseudocapacitive contribution. This study provides a basic understanding of structural evolution in layered Mn-based oxides and broadens the strategic design of cathode materials for PIBs.


Sequential measurements of bone lead content by L X-ray fluorescence in CaNa2EDTA-treated lead-toxic children.
With the development of L X-ray fluorescence (LXRF) to measure cortical bone lead directly, safely, rapidly, and noninvasively, the present study was undertaken to a) evaluate LXRF as a possible replacement for the CaNa2EDTA test; b) quantify lead in tibial cortical bones of mildly to moderately lead-toxic children before treatment; and c) quantify lead in tibial cortical bones of lead-toxic children sequentially following one to two courses of chelation therapy. The clinical research design was based upon a longitudinal assessment of 59 untreated lead-toxic children. At enrollment, if the blood lead (PbB) was 25 to 55 micrograms/dL and the erythrocyte protoporphyrin (EP) concentration was greater than or equal to 35 micrograms/dL, LXRF measurement of tibial bone lead was carried out. One day later, each child underwent a CaNa2EDTA provocative test. If this test was positive, lead-toxic children were admitted to the hospital for 5 days of CaNa2EDTA therapy. These tests were repeated 6 weeks and 6 months after enrollment. Abatement of lead paint hazards was achieved in most apartments by the time of initial hospital discharge. The LXRF instrument consists of a low energy X-ray generator with a silver anode, a lithium-doped silicon detector, a polarizer of incident photons, and a multichannel X-ray analyzer. Partially polarized photons are directed at the subcutaneous, medial mid-tibial cortical bone. The LXRF spectrum, measured 90 degrees from the incident beam, reveals a peak in the 10.5 KeV region, which represents the lead L alpha line.(ABSTRACT TRUNCATED AT 250 WORDS)


Geographic cohorting by clinical care team: a narrative review.
Geographic cohorting refers to localization of inpatients to designated hospital areas (typically a unit or a set of beds) based on specified criteria. One such criterion that has been commonly discussed and studied since the early days of the hospitalist movement in the US is a patient's assigned clinical care team. Because implementing cohorting of this type requires substantial operational investment, it is important to understand the benefits and the tradeoffs associated with bringing patients into closer spatial proximity with their full team of providers and allowing clinicians to work within a defined clinical space. We conducted a narrative review of the evidence around geographic cohorting of patients by clinical care team. We performed a comprehensive search of the PubMed, Embase, Cinahl and Scopus databases, identifying relevant English language articles. We used an inductive approach to developing thematic domains for categorization of article content. We reviewed eighteen articles published between 2008 and 2022, and identified four thematic outcomes domains: patient-centered outcomes, communication, efficiency, and satisfaction. The existing literature demonstrates associations with improved communication and staff satisfaction. The data regarding patient outcomes and overall work efficiency, on the other hand, are equivocal and, in general, limited by study methodology. Geographic cohorting of inpatients according to clinical care team offers some promise for improved workplace culture. More rigorously designed studies are needed, however, to understand its impact on patient outcomes, and there should be added attention paid to throughput metrics and tradeoffs that often limit its implementation.


Suspension sutures aid facial reconstruction.
Suspension, pexing or tacking sutures, which have a long history of use in facial cosmetic surgery, have only recently begun use in reconstruction. In this study, the suspension suture was used to fix the closure line at the junction of cosmetic units, to prevent distortion of free margins secondary to wound contraction, eg, ectropion or eclabium, to prevent tenting across concavities, and to prevent scar spreading of wounds closed under tension. The acute complications and long-term effectiveness of this suturing technique in achieving the 4 desired results were evaluated. During a 10-year period, 136 cases of surgical defects of the face created by the removal of nonmelanoma skin cancer by Mohs micrographic surgery were repaired using absorbable suspension sutures. The wounds were evaluated initially for acute complications of hemorrhage, infection, dehiscence, and necrosis; and later over 3 years for chronic sequela of hypertrophic scar, spread scar, contraction deformities such as distortion of free margins, and pigmentary changes. Suspension sutures were used in 60 cases of primary layered closure and 76 flaps of the face. Suspension sutures allowed primary closure of defects that would have required flaps in 72% of the cases and prevented distortion of free margins. There were more acute and long-term complications related to excess tension with primary closure than with flaps. Suspension sutures fixed the closure line at the junction of cosmetic units, prevented tenting across concavities, and both features were maintained over the duration of the study. Suspension sutures aided in obtaining linear closures, prevented distortion of free margins, prevented tenting across concavities, and fixed the closure line at the junction of cosmetic units; however, they did not prevent spread scars.


Synergistic Interaction of Dietary Pattern and Concordance Lifestyle with Abnormal Liver Function among Young Adults in Taiwan: A Population-Based Longitudinal Study.
While diet and lifestyle are independently implicated in the etiology of liver disease, the interaction of diet and lifestyle may be more helpful for determining the risk of liver abnormality. Thus, our study aimed to evaluate the interaction between the dietary pattern associated with liver biomarkers and lifestyle factors among Taiwanese adults with abnormal liver enzymes. A liver-associated dietary pattern, generated using reduced rank regression, was characterized by high intake of soy sauce or other dips, sugar sweetened beverages, and preserved and processed foods, but low intake of seafood, fruits, eggs, and dark-colored vegetables. In the fully adjusted model, liver-associated dietary patterns or unhealthy concordance lifestyle factors were associated with an increased risk of having liver function abnormality (OR = 1.08, 95% CI: 1.04, 1.12 and OR = 1.42, 95% CI: 1.31, 1.53, respectively). Moreover, the interaction between liver-associated dietary pattern and unhealthy concordance lifestyle factors showed more significant correlation, with an elevated risk of abnormal liver function (OR = 2.14, 95% CI: 2.02, 2.26). Therefore, our study suggests that participants who have a strong liver-associated dietary pattern along with unhealthy concordance lifestyles are likely to have increased odds of abnormal liver function.


Killing Bugs at the Bedside: a prospective hospital survey of how frequently personal digital assistants provide expert recommendations in the treatment of infectious diseases.
Personal Digital Assistants (PDAS) are rapidly becoming popular tools in the assistance of managing hospitalized patients, but little is known about how often expert recommendations are available for the treatment of infectious diseases in hospitalized patients. To determine how often PDAs could provide expert recommendations for the management of infectious diseases in patients admitted to a general medicine teaching service. Prospective observational cohort study Internal medicine resident teaching service at an urban hospital in Dayton, Ohio 212 patients (out of 883 patients screened) were identified with possible infectious etiologies as the cause for admission to the hospital. Patients were screened prospectively from July 2002 until October 2002 for infectious conditions as the cause of their admissions. 5 PDA programs were assessed in October 2002 to see if treatment recommendations were available for managing these patients. The programs were then reassessed in January 2004 to evaluate how the latest editions of the software would perform under the same context as the previous year. PDAs provided treatment recommendations in at least one of the programs for 100% of the patients admitted over the 4 month period in the 2004 evaluation. Each of the programs reviewed improved from 2002 to 2004, with five of the six programs offering treatment recommendations for over 90% of patients in the study. Current PDA software provides expert recommendations for a great majority of general internal medicine patients presenting to the hospital with infectious conditions.


Molecular computation of solutions to combinatorial problems.
The tools of molecular biology were used to solve an instance of the directed Hamiltonian path problem. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This experiment demonstrates the feasibility of carrying out computations at the molecular level.


Neurotoxicities of current leukemia therapy.
While major advances have been made in the treatment of acute leukemia, complications of therapy are significant. One of the most worisome complications is the neurotoxicity which is related to both central nervous system prophylaxis (cranial irradiatif neurotoxicity may be acute or delayed, and may range in severity from mild headaches ann of treatment-related neurotoxicity is important since this may permit amelioration of otherwise irreversible neurological sequelae in some patients. We review the clinical, phyh irradiation and chemotherapy, and offer recommendations for monitoring, evaluating and treating patients with potential or proven neurotoxicity.


A phase II trial of image-guided radiofrequency ablation of small invasive breast carcinomas: use of saline-cooled tip electrode.
Local ablative therapy of breast cancer represents the next frontier in the evolution of minimally-invasive breast conservation therapy. We performed this Phase II trial to determine the efficacy and safety of Radiofrequency (RF) ablation of small invasive breast carcinomas. Seventeen patients with biopsy-proven invasive breast cancer, < or = 1.5 cm in diameter were enrolled in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RF electrode followed by surgical resection. Pathologic and immunohistochemical stains were performed to assess tumor viability. We examined whether loss of ER, PR receptor and pancytokeratin expression following RF ablation would correlate with non-viability. Fifteen patients completed the treatment. The mean tumor size was 1.28 cm. The mean ablation time was 21 minutes using a mean power of 35.5 watts. During ablation, the tumors became progressively echogenic that corresponded with the region of severe electrocautery injury at pathological examination. Of the 15 treated patients, NADPH viability staining was available for 14 patients and in 13 (92.8%), there was no evidence of viable malignant cells. ER, PR expression and pancytokeratin immunohistochemistry analysis were unreliable surrogates for determining non-viability. Following RF ablation, 2 patients developed skin puckering. RF ablation is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further research is necessary to optimize this image-guided technique and evaluate its future role as the sole local therapy.


Functional interplay of DnaE polymerase, DnaG primase and DnaC helicase within a ternary complex, and primase to polymerase hand-off during lagging strand DNA replication in Bacillus subtilis.
Bacillus subtilis has two replicative DNA polymerases. PolC is a processive high-fidelity replicative polymerase, while the error-prone DnaEBs extends RNA primers before hand-off to PolC at the lagging strand. We show that DnaEBs interacts with the replicative helicase DnaC and primase DnaG in a ternary complex. We characterize their activities and analyse the functional significance of their interactions using primase, helicase and primer extension assays, and a 'stripped down' reconstituted coupled assay to investigate the coordinated displacement of the parental duplex DNA at a replication fork, synthesis of RNA primers along the lagging strand and hand-off to DnaEBs. The DnaG-DnaEBs hand-off takes place after de novo polymerization of only two ribonucleotides by DnaG, and does not require other replication proteins. Furthermore, the fidelity of DnaEBs is improved by DnaC and DnaG, likely via allosteric effects induced by direct protein-protein interactions that lower the efficiency of nucleotide mis-incorporations and/or the efficiency of extension of mis-aligned primers in the catalytic site of DnaEBs. We conclude that de novo RNA primer synthesis by DnaG and initial primer extension by DnaEBs are carried out by a lagging strand-specific subcomplex comprising DnaG, DnaEBs and DnaC, which stimulates chromosomal replication with enhanced fidelity.


Respiratory failure and mechanical ventilation in severe bronchiolitis.
A retrospective review of children who needed mechanical ventilation for severe bronchiolitis identified 62 cases over a 10 year period. The mean age at initiation of ventilation was 73 days (range: 14-201). Compared with a group of 150 children in hospital for bronchiolitis but not transferred to the intensive care unit, these 62 cases were significantly younger (73.0 compared with 166.3 days), and smaller (4.5 compared with 6.8 kg), and significantly more had been born prematurely (40% compared with 16%). Taken independently, age, weight, and prematurity were significantly associated with the need for artificial ventilation, weight being the most important factor. Using stepwise logistic regression, prematurity in itself added to the quality of the prediction but age did not. The mean duration of mechanical ventilation was 105 hours (range 2-381). Duration of ventilation was significantly longer in children with a low gestational age at birth and a positive familial history of atopy. There were no deaths, and no patient developed pneumothorax or pneumomediastinum. Mechanical ventilation is well tolerated and safe in acute bronchiolitis.


Pattern formation and coarsening dynamics in three-dimensional convective mixing in porous media.
Geological carbon dioxide (CO2) sequestration entails capturing and injecting CO2 into deep saline aquifers for long-term storage. The injected CO2 partially dissolves in groundwater to form a mixture that is denser than the initial groundwater. The local increase in density triggers a gravitational instability at the boundary layer that further develops into columnar plumes of CO2-rich brine, a process that greatly accelerates solubility trapping of the CO2. Here, we investigate the pattern-formation aspects of convective mixing during geological CO2 sequestration by means of high-resolution three-dimensional simulation. We find that the CO2 concentration field self-organizes as a cellular network structure in the diffusive boundary layer at the top boundary. By studying the statistics of the cellular network, we identify various regimes of finger coarsening over time, the existence of a non-equilibrium stationary state, and a universal scaling of three-dimensional convective mixing.


Absorbed Pump Power, Thermal Profile and Stresses in a cw Pumped Nd:YAG Crystal.
A Nd : YAG crystal 7.6 cm long and 6.35 mm in diameter was pumped by two krypton filled arc lamps in a double elliptical pumping cavity. The pump radiation absorbed and the heat dissipated by the Nd : YAG crystal were measured. This was done by a calorimetric measurement of the heat removed from the YAG crystal cooling loop and by monitoring the laser output power. In separate experiments the pump cavity transfer efficiency and the optical losses of the resonator were determined. The results of these measurements show that in the case of a high powered YAG system having an output power of 250 W at 12 kW input, which is six times threshold, 7.5% of the electrical input to the lamp is being absorbed by the crystal, and 40% of the absorbed pump power leaves the crystal as stimulated emission. The experiments revealed that 15% of the electrical input into the krypton arc lamps is emitted into the absorption bands of Nd:YAG crystal. The temperature profile and the associated stress components in the YAG crystal are calculated from the experimental data.


Normal recovery of the stratum corneum barrier function following damage induced by tape stripping in patients with atopic dermatitis.
Patients with atopic dermatitis (AD) constantly inflict mechanical damage to their skin by scratching induced by pruritus. On excoriated lesions of the cheek we found exceedingly high levels of transepidermal water loss (TEWL) as compared to those in the normal skin of healthy subjects. However, it is not clear whether the skin of patients with AD also shows an abnormally slow recovery after mechanical damage. We compared the recovery of the barrier function of the stratum corneum (SC), after its complete removal by tape stripping, in patients with AD and age-matched healthy control subjects. On the normal-looking skin of the flexor forearm, we found no difference in the recovery process of the water barrier function of the SC between the two groups. This suggests that ability to reconstruct SC barrier function after mechanical damage is not impaired in AD patients.


Bioinformatics features and immunogenic epitopes of Echinococcus granulosus Myophilin as a promising target for vaccination against cystic echinococcosis.
Cystic echinococcosis (CE) is a neglected zoonosis especially in underdeveloped countries around the world. Hence, immunization strategies are beneficial to avert the infection. The present investigation was aimed to predict the primary biochemical characteristics of the EgMyophilin and its potential B-cell and human leukocyte antigen (HLA)-binding epitopes as a promising vaccine candidate. Different web servers were used to predict physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, tertiary model refinement and validations. B-cell and HLA-binding epitopes were predicted and screened in terms antigenicity, allergenicity, solubility (B-cell) or hydrophobicity (T-cell). The 89.82 KDa protein was non-allergenic, hydrophilic, stable, with improved thermotolerance and 94 post-translational modification sites. The secondary structure included 42.94% alpha helix, 42.82% random coil and 41.23% extended strand. Based on Ramachandran plot output for refined model, 96.2%, 99.5%, and 0.45% of amino acid residues were incorporated in the favored, allowed, and outlier regions of the refined model, respectively. After epitope screening, four B-cell and five HLA-binding epitopes possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against CE. More empirical studies are required using the EgMyophilin alone or in combination with other antigens/epitopes in the future.


Stimulation of human peripheral blood lymphocytes by periodate, galactose oxidase, soybean agglutinin, and peanut agglutinin: differential effects of adherent cells.
Blastogenic responses of normal human peripheral lymphocytes to three distinct groups of mitogens were studied: Group I--phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM); Group II--soybean agglutinin (SBA) and peanut agglutinin (PNA); and Group III--galactose oxidase (GO) and sodium periodate (IO4-). SBA was mitogenic for human cells, and this effect was enhanced by treating the cells with neuraminidase (NA). PNA was mitogenic only after cells had been treated with NA. GO was effective before and activity was increased after lymphocytes were treated with NA. Responses to Group II and III mitogens were more variable than were those to Group I mitogens. Studies with purified T and B cells indicated that SBA and PNA were T cell mitogens, whereas IO4- and GO failed to stimulate either T or B cells. Adding macrophages back to this system indicated that they were both T cell mitogens with strict macrophage requirements. T cell responses to SBA and PNA were enhanced over responses to unfractionated cells to a degree that could not be explained simply by enrichment of the cultures with T cells. Removal of adherent cells from unfractionated cell suspensions again revealed a marked enhancement of responses to SBA and PNA, a consistent decrease in responses to IO4-, and a variable decrease in responses to GO. Similar results were found with 14C-leucine and 3H-uridine incorporation, as well as 3H-thymidine for the assessment of bastogenic response. Mechanisms responsible for these differential effects of macrophage depletion on lymphocyte responses to different groups of mitogens are yet to be determined. Either different mitogens require different lymphocyte to macrophage ratios for optimal stimulation, or some mitogens (i.e., SBA and PNA) form inhibitory complexees in the lymphocyte-macrophage mixture. In any case, variability in response to mitogenic agents in normal as well as pathologic states may be dependent on adherent cell populations, rather than on the lymphocytes themselves.


Regulation of manganese peroxidase gene transcription by hydrogen peroxide, chemical stress, and molecular oxygen.
The expression of manganese peroxidase (MnP) in nitrogen-limited cultures of the lignin-degrading fungus Phanerochaete chrysosporium is regulated at the level of gene transcription by H2O2 and various chemicals, including ethanol, sodium arsenite, and 2,4-dichlorophenol, as well as by Mn(II) and heat shock. Northern (RNA) blot analysis demonstrates that the addition of 1.0 mM H2O2 to 5-day-old cultures grown in the absence of Mn results in the appearance of mnp mRNA within 15 min. Higher levels of mnp mRNA are obtained with simultaneous induction by Mn and H2O2 than with H2O2 alone. Although neither MnP activity nor associated protein is detectable in H2O2-induced cultures grown in the absence of Mn, simultaneous induction with Mn and H2O2 results in a 1.6-fold increase in MnP activity compared with the MnP activity resulting from Mn induction alone. In the presence of Mn, purging of low-nitrogen cultures with 100% O2, in contrast to incubation under air, results in an increase in the accumulation of mnp mRNA and a 13-fold increase in MnP activity on day 5. However, in contrast to the effects of H2O2 and heat shock, O2 purging of Mn-deficient cultures results in negligible accumulation of mnp mRNA.


Implementation of Calf Endurance Training in a Touring Group of Professional Circus Performers: A Feasibility Study.
Demanding performance schedules in modern professional circus can result in less time for injury rehabilitation and strength and conditioning for injury prevention. Lower limb injuries are a common injury presentation in Cirque du Soleil touring show performers. To examine the feasibility of introducing a calf raise exercise program in an established professional touring circus show over a 9-week period. Twenty-nine professional Cirque du Soleil circus performers were recruited (mean age 31.28 [SD 4.99] yrs). Performers completed the Oslo Sports Trauma Research Centre Overuse (OSTRC) questionnaire each week for 18 weeks. In the second 9-week period, performers completed one set of single-leg calf raises to fatigue on each limb, once per day, every workday. Health problems between each 9-week period were compared. Feasibility was measured via program adherence and an end-of-study survey. Calf endurance was assessed by measuring the number of single leg calf raises to fatigue. Adherence was high throughout the program, with 93.5% of all exercise sessions completed. Endurance increased by a mean of 22.62 (SD 27.99) calf raises. No significant changes in the prevalence of self-reported soreness and injury were found: 51.9 (95%CI 44.4, 57.5) of the population reported lower limb injuries during the pre-intervention period and 52.5 (95%CI 49.2, 55.8) during the intervention. Similarly, no significant changes were found in severity scores: 20.7 (95%CI 17.7, 23.7) pre-intervention and 20.9 (95%CI 19.4, 22.4) during intervention. A single-leg calf raise exercise program can be feasibly introduced into a touring, performing professional circus show without increasing injury numbers or self-reported soreness. Furthermore, gains in calf raise endurance can be obtained during a 9-week intervention period.


Plasma Cell Leukemia: A Review of 3 Cases Managed in Kenya.
Plasma Cell Leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia that can arise either de novo (primary plasma cell leukemia) or evolve from previously diagnosed and treated multiple myeloma (secondary PCL). We highlight three clinical cases with very different presentations as a reminder of this diagnosis. The cases also highlight the diversity and variability that cover a patient's journey that is highly dependent on accessibility based on financial capability and social support. The clinical presentation is more aggressive due to the higher tumour burden and more proliferative tumor cells with cytopenias being profound and more organomegaly. The diagnosis is made based on at least 20% of total white blood cells being circulating plasma cells with a peripheral blood absolute plasma cell count of at least 2 × 109/l. Treatment with novel agents followed by autologous stem cell transplant in those who are transplant eligible leads to better outcomes.


Clinical importance of eosinophil count in nasal fluid in patients with allergic and non-allergic rhinitis.
Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNF's accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNF's median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNF's median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNF's median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNF's median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was < or = 5.0, AUC = 0.94. ECNF's median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was < or = 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNF's performance was moderately accurate in distinguish patients with AR and NAR.


Laryngeal electromyography-guided hyaluronic acid vocal fold injection for unilateral vocal fold paralysis--preliminary results.
The purpose of this study is to investigate the feasibility of using an injectable needle electrode to guide hyaluronic acid (HA) vocal fold injection (VFI) during laryngeal electromyography (LEMG) for unilateral vocal fold paralysis (UVFP). Prospective study. From March to June 2010, 20 UVFP patients received LEMG examination at our clinic. Before completion of LEMG, 1.0 cc of HA (Restylane Perlane(®); Q-Med, Uppsala, Sweden) was injected via a 26-gauge monopolar injectable needle electrode into paralyzed thyroarytenoid muscle. After injection, 20 patients completed 3-months follow-up and 16 patients completed 6-months follow-up. The data before, 1 week, 3 months, and 6 months after injection, including the normalized glottal gap area (NGGA) from videostroboscopy, maximal phonation time (MPT), mean airflow rate (MAFR), phonation quotient (PQ), perceptual evaluation of voice (grade, roughness, breathiness, asthenia, strain [GRBAS] scale), Voice Handicap Index (VHI), and self-grading of choking (grade 1-7), were analyzed by the Wilcoxon signed rank test. All of the patients completed the procedure without complications. After injection, mean NGGA was significantly reduced from 8.28 units to 0.52 units (1 week), 1.79 units (3 months), and 1.36 units (6 months). The mean MPT was prolonged from 5.66 seconds to 11.73, 11.25, and 11.93 seconds, respectively. VHI was reduced from 76.05 to 38.10, 37.40 and 35.00, respectively. Other analyzed data (PQ, MAFR, GRBAS scale, and choking severity) also showed statistically significant improvement. LEMG-guided HA VFI provides UVFP patients with neuromuscular function evaluation and treatment in one step. This clinical technique is feasible, and the short-term results are satisfactory.


Sleep disorders in children with cerebral palsy.
To determine the frequency and predictors of sleep disorders in children with cerebral palsy (CP) we analyzed the responses of 173 parents who had completed the Sleep Disturbance Scale for Children. The study population included 100 males (57.8%) and 73 females (42.2%; mean age 8y 10mo [SD 1y 11mo]; range 6y-11y 11mo). Eighty-three children (48.0%) had spastic diplegia, 59 (34.1%) congenital hemiplegia, 18 (10.4%) spastic quadriplegia, and 13 (7.5%) dystonic/dyskinetic CP. Seventy-three children (42.2%) were in Gross Motor Function Classification System Level I, 33 (19.1%) in Level II, 30 (17.3%) in Level III, 23 (13.3%) in Level IV, and 14 (8.1%) in Level V. Thirty children (17.3%) had epilepsy. A total sleep problem score and six factors indicative of the most common areas of sleep disorder in childhood were obtained. Of the children in our study, 23% had a pathological total sleep score, in comparison with 5% of children in the general population. Difficulty in initiating and maintaining sleep, sleep-wake transition, and sleep breathing disorders were the most frequently identified problems. Active epilepsy was associated with the presence of a sleep disorder (odds ratio [OR]=17.1, 95% confidence interval [CI] 2.5-115.3), as was being the child of a single-parent family (OR=3.9, 95% CI 1.3-11.6). Disorders of initiation and maintenance of sleep were more frequent in children with spastic quadriplegia (OR=12.9, 95% CI 1.9-88.0), those with dyskinetic CP (OR=20.6, 95% CI 3.1-135.0), and those with severe visual impairment (OR=12.5, 95% CI 2.5-63.1). Both medical and environmental factors seem to contribute to the increased frequency of chronic sleep disorders in children with CP.


[The INHES cohort study on the health status of nurses in Italy: research protocol].
Due to the intense emotional involvement and the often problematic working conditions characterizing their profession, Nurses appear to be especially susceptible to the negative effects of a complex set of stressors, with important repercussions to their health. Nevertheless, scientific literature assessing the health status of Nurses in Italy is still scarce. With INHES (Italian Nurses' HEalth Study), we propose to remedy this gap by implementing a cohort study which will start from the analysis of some local healthcare facilities and which may subsequently extend throughout the country. Study participants will be Nurses selected according to the following inclusion criteria: 1) age between 30 and 55 years; 2) having been employed in the current healthfacilityfor the last five years; 3) having performed care duties in wards or in day care services for the last five years. The objectives of this study, which will be carried out through the administration of a validated questionnaire, are the following: to measure the incidence and prevalence rates of a series of diseases in the nursing population, highlighting potential correlations with working activity, job-related stress or environmental and personal risk factors; to assess the quality of life and psychological health of the participants, evaluating the interference of psychophysical disorders with their work and social activities; to investigate the implementation of wellness promotion, prevention, case management and disability management policies by healthcare facilities. The evidence gathered will provide a valid scientific support for the development of more effective policies for protecting Nurses' health, with positive social and economic repercussions for the entire community.


Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow.
The adhesive mechanisms allowing hematopoietic progenitor cells (HPC) homing to the bone marrow (BM) after BM transplantation are poorly understood. We investigated the role of endothelial selectins and vascular cell adhesion molecule-1 (VCAM-1) in this process. Lethally irradiated recipient mice deficient in both P-and E-selectins (P/E-/-), reconstituted with minimal numbers (</=5 x 10(4)) of wild-type BM cells, poorly survived the procedure compared with wild-type recipients. Excess mortality in P/E-/- mice, after a lethal dose of irradiation, was likely caused by a defect of HPC homing. Indeed, we observed that the recruitment of HPC to the BM was reduced in P/E-/- animals, either splenectomized or spleen-intact. Homing into the BM of P/E-/- recipient mice was further compromised when a function-blocking VCAM-1 antibody was administered. Circulating HPC, 14 hr after transplantation, were greatly increased in P/E-/- mice treated with anti-VCAM-1 compared with P/E-/- mice treated with just IgG or wild-type mice treated with either anti-VCAM-1 or IgG. Our results indicate that endothelial selectins play an important role in HPC homing to the BM. Optimal recruitment of HPC after lethal doses of irradiation requires the combined action of both selectins and VCAM-1 expressed on endothelium of the BM.


MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry. To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects. Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE). The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease. There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.


Performance and tissue copper concentrations of control and Ascaris suum-infected pigs fed excess dietary copper.
Ninety-eight crossbred growing-finishing swine were used in 2 experiments to investigate the interaction between naturally occurring Ascaris suum infections and excess copper ingestion. In both experiments, pigs were fed a 14% crude protein basal diet or the basal diet + 250 ppm copper. These 2 dietary groups were subsequently divided into 2 additional treatment groups (A. suum-infected or uninfected) based on worm recovery from the intestine or from fecal egg counts. Excess dietary copper improved pig performance slightly, but it dramatically increased liver, kidney and lung copper levels. The A. suum infection did not affect pig performance, but it tended (not significantly) to reduce tissue copper levels. Serum copper was not affected by dietary copper or by A. suum infection.


Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells.
Deleted in malignant brain tumors 1 (DMBT1) is an innate defence protein expressed in the lungs of preterm infants and adults. Recent studies showed that DMBT1 is important in angiogenesis and can bind to different growth factors including VEGF. We aimed at examining relationships between VEGF and IL-6 levels to DMBT1 expression in the lungs of preterm and term infants and in lung epithelial cells in vitro. We examined by ELISA VEGF levels in 120 tracheal aspirates of 57 preterm and term infants and tested for correlation with different perinatal factors as well as with DMBT1 levels. To examine the effect of DMBT1 on VEGF and IL-6 expression we compared type II lung epithelial A549 cells stably transfected with a DMBT1 expression plasmid (DMBT1+ cells) to A549 cells stably transfected with an empty expression plasmid (DMBT1- cells). The concentrations of VEGF and IL-6 were determined via ELISA in the supernatant of the unstimulated cells and after stimulation with LPS, TNFα and Phorbol-12-myristate-13-acetate (PMA). The VEGF levels in the tracheal aspirates of preterm and term infants were significantly correlated with DMBT1 levels (p = 0.0032), the postnatal age (p = 0.0073) and the presence of neonatal infection/sepsis (p = 0.0002). Unstimulated DMBT1+ A549 cells showed significantly higher VEGF expression (p = 0.0017) than DMBT1- cells. Significantly elevated VEGF levels were also confirmed for DMBT1+ cells after stimulation with TNFα (p = 0.0008), LPS (p = 0.0232) and PMA (p = 0.0025). The IL-6 levels were comparable in DMBT1+ versus DMBT1- cells without stimulation (p = 0.6028), but they were significantly reduced in DMBT1+ cells after stimulation with TNFα (p = 0.0003), LPS (p = 0.0088) and PMA (p = 0.0039). The data indicate that DMBT1 promotes VEGF and suppresses IL-6 production in alveolar tissues, which could point to DMBT1 having a possible role in the transition from inflammation to regeneration and being a potentially useful clinical marker.


Prognostic Value of Preoperative Fibrinogen for Predicting Clinical Outcome in Patients with Nonmetastatic Colorectal Cancer.
The prognostic role of preoperative fibrinogen in colorectal cancer (CRC) patients remains controversial. Therefore, we assessed the predictive value of preoperative fibrinogen and developed a tool for predicting the survival of CRC patients. This retrospective study evaluated 1869 patients who underwent curative resection for CRC. Univariate and multivariate survival analyses were conducted to identify the factors correlated with overall survival (OS) and cancer-specific survival (CSS). Nomograms were developed as a graphical representation of the Cox proportional hazards regression models. The performance of the nomograms was assessed by Harrell's concordance index (c-index) and calibration plots. The preoperative fibrinogen levels were correlated with age, tumor differentiation, tumor location, pT category, and TNM stage. In the multivariate analysis, elevated fibrinogen level was independently correlated with worse OS and CSS (OS: hazard ratio [HR] = 0.777, 95% confidence interval [95% CI] = 0.630-0.958, P = 0.018; CSS: HR = 0.757, 95% CI = 0.605-0.947, P = 0.015). The nomograms could predict outcomes with a c-index for OS and CSS of 0.79 and 0.81, respectively. The nomograms also had a good calibration. Preoperative fibrinogen level was an independent marker of poor prognosis in patients with nonmetastatic CRC, and there was a threshold level for the use of fibrinogen as a prognostic factor. Furthermore, nomograms may help predict the individual risk of OS and CSS in patients treated for CRC.


Purification and characterization of interleukin 1 beta from human plantar stratum corneum. Evidence of interleukin 1 beta processing in vivo not involving interleukin 1 beta convertase.
The major interleukin 1 beta (IL-1 beta) species from human plantar stratum corneum was purified and found to have an N-terminal amino acid sequence homologous to a stretch of the human IL-1 beta precursor, starting with His115. Whereas SDS-polyacrylamide gel electrophoresis followed by immunoblotting revealed only one component in plantar stratum corneum with IL-1 beta-like immunoreactivity, and with an apparent molecular mass around 18 kDa, isoelectric focusing under non-denaturing conditions showed one major component with isoelectric point around 6.1 and two minor components isoelectric at pH 6.3 and 6.9, respectively. Digestion of recombinant human IL-1 beta precursor with chymotrypsin, producing a C-terminal fragment with N-terminal Yal114, yielded a component with IL-1 beta-like immunoreactivity isoelectric at pH 6.3. Recombinant bacterial variants of human IL-1 beta with N-terminal amino acids corresponding to Val114, His115 and Ala117 were isoelectric at pH 6.3, 6.1 and 6.9, respectively. Cloning and subsequent nucleotide sequencing of IL-1 beta precursor cDNA from a human keratinocyte line showed total identify with the sequence previously published for the human monocyte IL-1 beta precursor. The authors conclude that the IL-1 beta species present in plantar stratum corneum have isoelectric points determined by their respective amino acid sequences, and that there is a mechanism for IL-1 beta activation in human epidermis not involving interleukin 1 beta convertase.


Chemical composition and insecticidal properties of essential oils of Piper septuplinervium and P. subtomentosum (Piperaceae).
Essential oils of Piper subtomentosum (leaves and inflorescences) and Piper septuplinervium (aerial parts) were analyzed by GC-MS; sixty-three compounds were determined, representing 92.0%, 86.9 %, and 91.8 % of the total relative oil composition of the leaves, inflorescences, and aerial parts, respectively. The most abundant component in the aerial parts and inflorescence oils was α-pinene (27.3%, 21.0%, respectively), and δ-cadinene was the main component of the leaf oil. Insecticidal activity of the essential oils were determined on the Spodoptera frugiperda second instar larvae; the essential oil from the aerial parts of P. septuplinervium was the most active against insect pests (LC50= 9.4 μL/L of air). Statistical analysis by direct Pearson correlation showed that the insecticidal activity of the essential oils was primarily due to camphene and α- and β-pinene. The effect of the oils on the insect life cycle was also evaluated, and in some cases, a delay in growth and inhibition of the oviposition in the females were observed.


Recurrent herpes in the rabbit and man.
Herpesvirus was present in secretory glands and frequently in tears of rabbits with recurrent herpetic keratitis even in the absence of corneal lesions. In normal people, herpesvirus could be cultured from saliva and tears. Chronic virus multiplication in structures such as the lacrimal and salivary glands, rather than latency, may cause recurrent herpetic disease.


[The role of the oral flora in the pathogenesis of aspiration pneumonia].
The bacterial pneumonia is one of the most frequent complications leading to death among hospitalized patients. The morbidity and mortality of pneumonia is extremely high in the intensive care units and in chronic nursing stations, especially in institutes dealing with old patients. The most common form of lung infection is the aspiration pneumonia. Periodontal diseases play an evident role in the etiology of aspiration pneumonia due to their effect to alter the oral bacterial flora. Authors review the significance of pathogen microorganisms originating from the oral cavity in the development of bacterial pneumonia. The extent of the affected population is discussed and the importance of their oral hygiene and bacterial flora is also specified. The bacterial, enzymatic and molecular pathomechanisms leading to aspiration pneumonia are described, and high risk populations and treatment types are determined. The possibilities of prevention methods for aspiration pneumonia are fully explained and recent directions of actual researches and proposals to minimize the incidence of this disease are summarized.


Patient-Reported Outcomes and Quality of Life with Sunitinib Versus Placebo for Pancreatic Neuroendocrine Tumors: Results From an International Phase III Trial.
The objective of this analysis was to compare patient-reported outcomes and health-related quality of life (HRQoL) in a pivotal phase III trial of sunitinib versus placebo in patients with progressive, well-differentiated pancreatic neuroendocrine tumors (NCT00428597). Patients received sunitinib 37.5 mg (n = 86) or placebo (n = 85) on a continuous daily-dosing schedule until disease progression, unacceptable adverse events (AEs), or death. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 at baseline, Day 1 of every 4-week cycle, and end of treatment or withdrawal. Changes ≥10 points on each scale or item were deemed clinically meaningful. Sunitinib had anti-tumor effects and improved progression-free survival (PFS) compared with placebo. The study was terminated early for this reason and because of more serious AEs and deaths with placebo. Baseline HRQoL scores were well balanced between study arms, and were generally maintained over time in both groups. In the first 10 cycles, there were no significant differences between groups in global HRQoL, cognitive, emotional, physical, role, and social functioning domains, or symptom scales, except for worsening diarrhea with sunitinib (p < 0.0001 vs. placebo). Insomnia also worsened with sunitinib (p = 0.0372 vs. placebo), but the difference was not clinically meaningful. With the exception of diarrhea (a recognized side effect), sunitinib had no impact on global HRQoL, functional domains, or symptom scales during the progression-free period. Hence, in patients with pancreatic neuroendocrine tumors, sunitinib provided a benefit in PFS without adversely affecting HRQoL.


Impact of brief exposure to antifungal agents on the post-antifungal effect and hemolysin activity of oral Candida albicans.
Post-antifungal effect (PAFE) of Candida and its production of hemolysin are determinants of candidal pathogenicity. Candida albicans is the foremost aetiological agent of oral candidosis, which can be treated with polyene, azole, and echinocandin antifungals. However, once administered, the intraoral concentrations of these drugs tend to be subtherapeutic and transient due to the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intra-orally, Candidamay undergo a brief exposure to antifungal drugs.Objective Therefore, the PAFE and hemolysin production of oral C. albicans isolates following brief exposure to sublethal concentrations of the foregoing antifungals were evaluated.Material and Methods A total of 50 C. albicans oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to sublethal concentrations of nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole for 60 min. Thereafter, the drugs were removed and the PAFE and hemolysin production were determined by previously described turbidometric and plate assays, respectively.Results Nystatin, amphotericin B, caspofungin and ketoconazole induced mean PAFE (hours) of 2.2, 2.18, 2.2 and 0.62, respectively. Fluconazole failed to produce a PAFE. Hemolysin production of these isolates was suppressed with a percentage reduction of 12.27, 13.47, 13.33, 8.53 and 4.93 following exposure to nystatin, amphotericin B, caspofungin, ketoconazole and fluconazole, respectively.Conclusions Brief exposure to sublethal concentrations of antifungal drugs appears to exert an antifungal effect by interfering with the growth as well as hemolysin production of C. albicans.


Epizootiologic investigations of selected infectious disease agents in free-ranging Eurasian lynx from Sweden.
Serum samples from 106 Eurasian lynx (Lynx lynx) from across Sweden, found dead or shot by hunters in 1993-99, were investigated for presence of antibodies to feline parvovirus (FPV), feline coronavirus, feline calicivirus, feline herpesvirus, feline immunodeficiency virus, Francisella tularensis, and Anaplasma phagocytophila, and for feline leukemia virus antigen. In addition, tissue samples from 22 lynx submitted in 1999 were analyzed by real-time polymerase chain reaction (PCR) to detect nucleic acids specific for viral agents and A. phagocytophila. Except for FPV antibodies in one lynx and A. phagocytophila in four lynx, all serology was negative. All PCR results also were negative. It was concluded that free-ranging Swedish lynx do not have frequent contact with the infectious agents considered in this study.


Interactions Between Meloidogyne incognita and Pratylenchus brachyurus on Soybean.
Interactions among Meloidogyne incognita, Pratylenchus brachyurus, and soybean genotype on plant growth and nematode reproduction were studied in a greenhouse. Coker 317 (susceptible to both nematodes) and Gordon (resistant to M. incognita, susceptible to P. brachyurus) were inoculated with increasing initial population densities (Pi) of both nematodes individually and combined. M. incognita and P. brachyurus individually usually suppressed shoot growth of both cultivars, but only root growth on Coker 317 was influenced by a M. incognita x P. brachyurus interaction. Reproduction of both nematodes, although dependent on Pi, was mutually suppressed on Coker 317. P. brachyurus reproduced better on Gordon than on Coker 317 but did not affect resistance to M. incognita. Root systems of Coker 317 were split and inoculated with M. incognita or P. brachyurus or both to determine the nature of the interaction. M. incognita suppressed reproduction of P. brachyurus either when coinhabiting a half-root system or infecting opposing half-root systems; however, P. brachyurus affected M. incognita only if both nematodes infected the same half-root system.


Orthodontic considerations in the treatment of bimaxillary protrusion with anterior subapical osteotomy.
Severe bimaxillary dentoalveolar protrusion, a dentofacial deformity prevalent among Asians, can be easily addressed with the use of anterior subapical osteotomies in conjunction with extraction of a tooth in each quadrant. Presurgical orthodontic preparation for anterior subapical osteotomy includes intra-arch (leveling, alignment, and derotations) and interarch (sagittal, vertical, and transverse) objectives. The procedure requires careful attention to the use of segmental orthodontic mechanics and surgical arch wires, in conjunction with surgical splints and rigid osteosynthesis. The controlled use of training box and vertical elastics postsurgically and the proper choice of retainers have greatly facilitated the achievement of a good and stable end result.


Efficient bipedal locomotion on rough terrain via compliant ankle actuation with energy regulation.
Legged locomotion enables robotic platforms to traverse on rough terrain, which is quite challenging for other locomotion types, such as in wheeled and tracked systems. However, this benefit-moving robustly on rough terrain-comes with an inherent drawback due to the higher cost of transport in legged robots. The ultimate need for energy efficiency motivated the utilization of passive dynamics in legged locomotion. Nevertheless, a handicap in passive dynamic walking is the fragile basin of attraction that limits the locomotion capabilities of such systems. There have been various extensions to overcome such limitations by incorporating additional actuators and active control approaches at the expense of compromising the benefits of passivity. Here, we present a novel actuation and control framework, enabling efficient and sustained bipedal locomotion on significantly rough terrain. The proposed approach reinforces the passive dynamics by intermittent active feedback control within a bio-inspired compliant ankle actuation framework. Specifically, we use once-per-step energy regulation to adjust the spring precompression of the compliant ankle based on the liftoff instants-when the toe liftoffs from the ground-of the locomotion. Our results show that the proposed approach achieves highly efficient (with a cost of transport of 0.086) sustained locomotion on rough terrain, withstanding height variations up to 15% of the leg length. We provide theoretical and numerical analysis to demonstrate the performance of our approach, including systematic comparisons with the recent and state-of-the-art techniques in the literature.


Bleomycin-related lung damage: CT evidence.
Computed tomography (CT) examinations of the chest were evaluated in 100 patients treated with bleomycin. The CT findings were compared with those of conventional chest radiographs and lung-function tests. Lung damage due to bleomycin was detected in 38% of patients by CT, while damage was detected in only 15% by radiography. Changes in appearance seen on CT scans due to bleomycin damage were compared with measurements of lung volume and gas transfer per unit lung volume. There was good correlation between severity of damage shown on CT scans and changes in lung volume (P less than 0.01). Gas transfer capabilities were reduced in most patients regardless of changes observed on CT scans. Sequential CT studies showed that complete resolution of bleomycin damage may occur within 9 months in patients with minor or moderate damage. Residual abnormalities were seen in all patients with severe damage. CT can confirm lung damage in a patient with suspected toxicity but a normal chest radiograph and can define the anatomic extent of disease in a patient with an abnormal lung-function test.