Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.
Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse.


In vivo Skin Penetration, Radical Protection, and Structural Changes after Topical Application of a Herbal Oil Cream Compared to Topical Calcipotriol in Mild to Moderate Psoriasis.
The chronicity of psoriasis often requires continuous topical treatment. Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis.


Lymphoplasmacyte rich meningioma. A case report and review of the literature.
A peculiar type of meningioma with conspicious plasma-cell components is described. In accordance with the World Health Organization's Histological Typing of Tumours of the Central Nervous System, this rare clinical entity is recently designed as lymphoplasmacyte rich (LPR) meningioma. This type of meningioma is usually accompanied by prominent peripheral blood abnormalities, anemia and/or policlonal gammophaty, that disappear after surgical removal of the tumor. Actually, the origin (neoplastic or inflammatory) of this tumor is unclear; its biological behavior and clinical course are anomalous so it is considered closer to intracranial inflammatory masses rather than typical meningioma. In this paper, a new case of intracranial LPR meningioma occurring in a woman, is reported and a review the literature is made.


Use of copper shavings to remove mercury from contaminated groundwater or wastewater by amalgamation.
The efficacy of copper shavings (Cu(0)) for the removal of Hg2+ from aqueous solution by amalgamation is demonstrated. Two kinds of copper shavings were investigated: (a) chemically processed shavings (Fluka) and (b) recycled shavings from scrap metal. Batch sorption experiments yielded very high retardation coefficients of 28 850-82 830 for the concentration range studied (1-10 000 microg/L Hg2+ dissolved in distilled water or in a 0.01 M CaCl2 matrix solution). Sorption data were well-described bythe Freundlich isotherm equation. Kinetic batch sorption experiments showed that 96-98% of Hg2+ was removed within 2 h. Column experiments were performed with a mercury solution containing 1000 microg/L Hg in a 0.01 M CaCl2 matrix with a flow rate of 0.5 m/d. No mercury breakthrough (c/c(0) = 0.5) could be detected after more than 2300 percolated pore volumes, and the high retardation coefficients determined in the batch studies could be confirmed. Copper was released from the shavings due to the amalgamation process and to copper corrosion by oxygen, resulting in concentrations of mobilized copper of 0.2-0.6 mg/L. Due to their high efficiency in removing Hg2+ from aqueous solution, the use of copper shavings for the removal of mercury from contaminated water is suggested, employing a sequential system of mercury amalgamation followed by the removal of mobilized copper by an ion exchanger such as zeolites. Possible applications could be in environmental technologies such as wastewater treatment or permeable reactive barriers for in situ groundwater remediation.


Assessment of Knowledge, Attitude, and Practice of Skilled Assistance Seeking Maternal Healthcare Services and Associated Factors among Women in West Shoa Zone, Oromia Region, Ethiopia.
This study aimed to assess women's knowledge, attitude, and practice towards skilled assistance seeking maternal healthcare services in West Shoa Zone, Oromia Region, Ethiopia. Cross-sectional survey design was conducted from 1 February to 23 March 2018 in West Shoa Zone, Oromia, Ethiopia. A simple random sampling technique was used to select the participants. The data were collected using a pretested and structured questionnaire. Data were entered using EpiData version 3.1, and descriptive analysis and bivariate and multivariate logistic regression analyses were carried out using SPSS version 20 statistical software package. The study revealed that the knowledge, attitude, and practice towards skilled maternal health services were found such that 473.3 (72.4%) of the study participants had good knowledge, 180.7 (27.6%) had poor knowledge, and 400 (61.3%) had positive attitude, 254 (38.84%) had negative attitude, 460.3 (70.4%) had good practice, and 193.7 (29.6%) had poor practice towards skilled maternal health services. Factors that had a significant association with antenatal care utilization were planned pregnancy (AOR = 8.2, 95% CI = 3.39-19.78-0.87) and access to transport (AOR = 3.1, 95% CI = 1.46-6.61). Attending ANC at least once (AOR = 3.1, 95% CI = 1.13-8.41), women's education (AOR = 3.0, 95% CI = 1.18-7.84), and unplanned pregnancy (AOR = 0.3, 95% CI = 0.21-0.75) were factors associated with skilled delivery service utilization. Attending ANC at least once (AOR = 2.1, 95% CI = 1.1-4.2), birth complications (AOR = 2.2, 95% CI = 1.35-3.66), unplanned pregnancies (AOR = 0.3, 95% CI = 0.22-0.68), and awareness about skilled obstetric care (AOR = 3.7, 95% CI = 1.68-12.79) were factors associated with postnatal care utilization. This study found that the knowledge, attitude, and practice of skilled maternal health services among the study participants are low, showing less than three-quarters of the total sample size. Therefore, this study implied that interventions are required to improve women's knowledge, attitude, and practice of skilled maternal health services in the study area. Furthermore, women's education is significantly associated with skilled delivery service utilization. Accordingly, this study recommends that improving equity among the marginalized population is needed to increase maternal health service coverage.


Combating stigma in autism research through centering autistic voices: a co-interview guide for qualitative research.
As autism has gained increased attention in the past few decades, autistic advocates have adopted the phrase "Nothing about us without us," illustrating the idea that autistic people should be centered in all conversations regarding autism. However, in a large portion of autism research, autistic people are still not meaningfully engaged throughout the research process, leading to continued stigma in research through biased methods. Thus, stigma about autism influences not only the content of autism research, but the ways in which neurotypical people conduct research alongside (or without) autistic people, ultimately resulting in less valid conclusions or research that actively harms the autistic community. One way to address this stigma is through involving autistic individuals as equal partners in the research process, such as by including autistic co-interviewers in qualitative studies of autistic people. In this perspectives piece, we will highlight the benefits of participatory research practices within qualitative research. Furthermore, we will outline methods for conducting co-interviews with autistic research partners and share insights from our experiences implementing this practice. We hope this piece provides researchers the practical resources and inspiration to continue working toward decreasing the stigma surrounding autism in research spaces.


BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.
BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.


Tics and Tourette's: a continuum of symptoms?
Analysis of the families of 39 unselected children with Tourette syndrome revealed other members with tic disorders in twenty kindreds. In eight families there were 13 individuals with chronic multiple tics, usually motor, not vocal. Twelve different families contained 18 subjects with Tourette syndrome other than the index patient. In three of these families there were 6 additional individuals with chronic motor tics, forming a bridge to the first group. An autosomal dominant mode of inheritance was suggested in all cases. Tourette syndrome and chronic motor tics appear to represent conditions along a continuum and have, in many instances, a hereditary basis.


Enhanced cell killing through the use of cell kinetics-directed treatment schedules for two-drug combinations in vitro.
Kinetics-directed drug treatment schedules were tested in Chinese hamster ovary cells. Ten hr after treatment with 1,2:5,6-dianhydrogalactitol (DAG) (at a dose lethal to less than 5% of the cells), a 150% enrichment of cells into the S phase of the cell cycle was observed. This blockade in S phase was reversible and was followed at 18 hr after an exposure to DAG by a 200% increase in the fraction of cells in the G2-M phases of the cell cycle. Bleomycin, known to be most effective against G2 + M cells, had the greatest effect on cell killing when administered at that time. Rapid analysis by flow microfluorometry techniques was used to determine the DAG-induced kinetics changes, thus allowing treatment with the second drugs at the most opportune time. The DAG-induced kinetics changes were also demonstrated in a line of human adenocarcinoma of the stomach in vitro and in Ehrlich ascites tumor cells in vivo. In all cases, the enrichment of cells into S phase was reversible at the doses used and was followed by a reversible blockade in G2-M.


Kuwait acute coronary syndromes registry: baseline characteristics, management practices and in-hospital outcomes of patients hospitalized with acute coronary syndromes in Kuwait.
To identify the characteristics of patients with acute coronary syndromes (ACS), their hospital management and in-hospital outcomes, through a prospective registry system in Kuwait. A registry involving all 7 general hospitals in Kuwait was set up. Consecutive patients diagnosed as having ACS over a period of 6 months were enrolled. Of 2,129 patients enrolled, 718 (34%) had ST segment elevation myocardial infarction (STEMI), 576 (27%) non-ST segment elevation myocardial infarction (NSTEMI) and 835 (39%) unstable angina (UA). Thrombolytic therapy was used in 556 (77%) patients with STEMI. The median time from diagnostic electrocardiogram to administration of thrombolytic therapy was 38 min. Almost all patients with ACS (2,050, 96%) received aspirin during hospitalization. Only a minority received clopidogrel, 18 (3%) STEMI, 36 (6%) NSTEMI and 96 (12%) UA patients. The use of glycoprotein IIb/IIIa antagonists was minimal (38 patients, 2%). beta-Blockers were used in 1,473 (69%) patients, while 982 (46%) received angiotensin-converting enzyme inhibitors. Coronary angiography during hospitalization was performed in 119 (17%), 120 (21%) and 126 (15%) patients with STEMI, NSTEMI and UA, respectively. In-hospital mortality occurred in 31 (4%) myocardial infarction patients and 4 (0.5%) UA patients (p < 0.0001). This registry has enabled us to determine the incidence and characteristics of ACS patients in Kuwait. It has also enabled us to identify some barriers that we need to overcome for the full implementation of published guidelines for the management of patients with ACS.


Evaluation of the molecular polarizability using the IPPP-CLOPPA-INDO/S method. Application to molecules of biological interest.
The IPPP-CLOPPA-INDO/S method is introduced to investigate the static molecular polarizability in macromolecules. As an example of application, the polarizability of phospholipidic compounds, with and without the presence of water molecules has been estimated. The IPPP technique was employed to calculate the polarizability of the polar head and the hydrocarbon chains separately to analyze the feasibility of evaluating the total polarizability of the molecule by addition of these two projected results. INDO/S dipole moments of different fragments of the complex molecule were obtained by means of localized molecular orbitals in order to evaluate the charge transfer in the system.


[Value and limitations of sport in cardiac patients].
Regular physical exercise increases effort capacity, the quality of life, and improves symptoms in all cardiac patients. In addition, and much more importantly, all studies show a close correlation between exercise and the reduction of mortality and morbidity with a beneficial effect on the progression of atherosclerosis. This relationship is particularly well documented in patients with coronary artery disease. Exercise has a beneficial effect due to its action on all the principal coronary risk factors, an endothelial dysfunction, coagulability and prevention of thrombosis and an autonomic nervous system tone. All forms of physical activity and some sports may therefore be considered by these patients. In some cases, competitive sport may be permitted, in accordance with popular social custom. In order to obtain these cardiocirculatory protection, physical exercise and sporting activities should be the object of a personalised therapeutic prescription which takes into account the intensity, the type of effort, its duration and frequency. Indeed, if the intensity of the exercise is too low, these patients may not obtain the desired benefits. On the other hand, excessively intensive exercise could trigger serious adverse effects such as severe arrhythmias, sudden death or an acute coronary syndrome. It is, therefore, essential before "prescribing" exercise to perform a preliminary evaluation to stratify the patient's risk and in order to recommend appropriate and well adapted exercise programs.


High-speed imaging system to visualize particle removal/collection via wipe sampling and aerodynamic sampling.
This work describes a high-speed imaging system that enables the microscopic visualization of the removal and collection of micrometer-sized particles from surfaces during wipe sampling and aerodynamic sampling events. The system features a high-speed digital camera, microlens, custom sample mount and sampling sled, and an illumination source. This imaging system enables direct visualization of wipe-particle and particle-particle interactions during sampling and provides insights relevant to the dynamics of particle removal and collection. Examples of common and adhesive-modified wipe materials sampling polymer microspheres and an explosive-laden fingerprint are given, along with visualization of particle removal via air jet impingement.


High-quality remission: potential benefits of the melatonergic approach for patients with major depressive disorder.
Full remission of symptoms is the goal for the acute treatment of depression, because incomplete remission is associated with poor outcomes including higher risk of relapse and chronicity. The current definitions for remission (e.g. a score of </=7 on the Hamilton Depression Rating Scale), however, allow for the presence of residual symptoms of depression even if remission is attained. The focus now is on the quality of remission, that is, ensuring a minimum of such residual symptoms, because the consequences of low-quality remission also include impairment in psychosocial functioning. The most common residual symptoms are sleep disturbances, fatigue, and disinterest. Sleep-associated residual symptoms are particularly common, and are a major concern because most current treatments fail to adequately address sleep disturbances and may even aggravate them. Other side effects of current treatments, such as weight gain and sexual dysfunction, may also reduce the quality of remission. A novel approach to the treatment of depression with agomelatine, a melatonergic MT1 and MT2 receptor agonist and 5-HT2C receptor antagonist, may be an effective treatment that improves the quality of remission, as it combines good efficacy with positive effects on sleep, neutral effects on sexual function, and a favorable side effect profile.


Adenylyl cyclase type VI corrects cardiac sarcoplasmic reticulum calcium uptake defects in cardiomyopathy.
Calcium malfunction plays a central role in heart failure. Here, we provide evidence that adenylyl cyclase type VI restores sarco(endo)plasmic reticulum 2a (SERCA2a) affinity for calcium and maximum velocity of cardiac calcium uptake by sarcoplasmic reticulum in murine dilated cardiomyopathy. Restoration of normal SERCA2a affinity for calcium is associated not only with decreased phospholamban protein expression but also with increased phospholamban phosphorylation by PKA activation. The ratio of phosphorylated ryanodine receptor 2 (RyR2) to RyR2 protein was increased, but the amount of phosphorylated RyR2 was unaffected. These data provide a possible mechanism by which adenylyl cyclase type VI (in contrast to other signaling elements associated with increased cAMP generation) has a salutary effect in the failing heart.


Practice characteristics associated with patient-specific receipt of dental diagnostic radiographs.
To quantify the role of practice characteristics in patient-specific receipt of dental diagnostic radiographic services. Florida Dental Care Study (FDCS). Study Design. The FDCS was a 48-month prospective observational cohort study of community-dwelling adults. Participants' dentists were asked to complete a questionnaire about their practice characteristics. In-person interviews and clinical examinations were conducted at baseline, 24, and 48 months, with 6-monthly telephone interviews in between. A single multivariate (four radiographic service outcomes) multivariable (multiple explanatory covariates) logistic regression was used to model service receipts. These practice characteristics were significantly associated with patient-specific receipt of radiographic services: number of different practices attended during follow-up; dentist's rating of how busy the practice was; typical waiting time for a new patient examination; practice size; percentage of patients that the dentist reported as interested in details about the condition of their mouths; percentage of African American patients in the practice; percentage of patients in the practice who do not have dental insurance; and dentist's agreement with a statement regarding whether patients should be dismissed from the practice. Effects had differential magnitudes and directions of effect, depending upon radiograph type. Practice characteristics were significantly associated with patient-specific receipt of services. These effects were independent of patient-specific disease level and patient-specific sociodemographic characteristics, suggesting that practitioners do influence receipt of these diagnostic services. These findings are consistent with the conclusion that practitioners act in response to a mix of patients' interests, economic self-interests, and their own treatment preferences.


Pulmonary endothelial thiazine uptake: separation of cell surface reduction from intracellular reoxidation.
The objective of this study was to further evaluate the hypothesis that the accumulation of thiazine dyes, such as methylene blue, by cultured bovine pulmonary arterial endothelial cells involves reduction on the cell surface, followed by diffusion of the lipophilic reduced form of the dye into the cells and intracellular reoxidation to the relatively membrane-impermeant hydrophilic form. The specific question addressed was whether inhibition of methylene blue uptake by cyanide and azide is via inhibition of extracellular reduction or inhibition of intracellular reoxidation. We used the cell membrane-impermeant ferricyanide ion as a secondary electron acceptor to measure the extracellular reduction of methylene blue independently from its uptake by the cells. In addition, toluidine blue O, incorporated into an acrylamide polymer so that it could not permeate the cells in either its reduced or oxidized forms, was used to examine the effects of cyanide and azide on the extracellular reduction. Microscopic observations of the effect of the inhibitors on the intracellular accumulation of methylene blue were also made. The results indicate that the reduction and intracellular sequestration are separate processes and that, in doses that inhibited intracellular reoxidation, and therefore uptake and sequestration, neither cyanide nor azide had an inhibitory effect on extracellular reduction. The intracellular distribution of the observable oxidized form of the dye was consistent with oxidation of the reduced dye within subcellular organelles. The demonstration that extracellular reduction and intracellular sequestration are separate events is consistent with the hypothesized sequence of events.


Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends.
The role of Pseudomonas aeruginosa in nosocomial infections occurring since 1975 is reviewed. Data from the National Nosocomial Infections Study conducted by the Centers for Disease Control, from individual medical centers, and from the literature were used to compare the relative frequency of occurrence of nosocomial infection caused by P. aeruginosa with that of infection caused by other gram-negative bacilli. The relative frequency of P. aeruginosa as a nosocomial pathogen has increased, although wide variations are seen among individual medical centers. P. aeruginosa continues to be a major pathogen among patients with immunosuppression, cystic fibrosis, malignancy, and trauma. While Staphylococcus aureus has become the predominant pathogen in some large burn centers, P. aeruginosa is the most important gram-negative pathogen. Periodic review of the epidemiology of P. aeruginosa infection is warranted in view of the changing incidence of infection caused by this organism.


Effects of anxiety and depression on anagram performance, ratings of cognitive interference, and the negative subjective evaluation of performance.
Studied whether any differential effects of anxiety and depression could be discerned in the anagram performance, ratings of cognitive interference, and subjective evaluation of anagram performance displayed by college students. Seventy-two undergraduates (36 male, 36 female) were selected to participate in the present experiment on the basis of their scores on the State-Trait Anxiety Inventory (A-Trait) and/or the Beck Depression Inventory. Results showed that depressed-anxious and anxious Ss displayed a tendency toward reduced efficiency in anagram solution, rated themselves as having experienced significantly more cognitive interference during the anagram task, and displayed a significantly more negative subjective evaluation of their anagram performance than did control Ss. Quasi-F analyses revealed that these results were related significantly to the anxiety factor common to both depressed-anxious and anxious Ss. Implications of these results for future research on anxiety and depression were discussed.


Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy.
Gene therapy has been recently shown as a promising tool for cancer treatment as nanotechnology-based safe and effective delivery methods are developed. Generally, genes are wrapped up in extremely tiny nanoparticles which could be taken up easily by cancer cells, not to their healthy neighboring cells. Several nanoparticle systems have been investigated primarily to address the problems involved in other methods of gene delivery and observed improved anticancer efficacy suggesting that nanomedicine provides novel opportunities to safely deliver genes, thus treat cancer. In this review, various nanoparticle types and related strategies, used in gene delivery for cancer treatment, have been discussed.


The insect excretory system as a target for novel pest control strategies.
The insect excretory system plays essential roles in osmoregulation, ionoregulation and toxin elimination. Understanding the mechanisms of fluid and ion transport by the epithelial cells of the excretory system provides a foundation for development of novel pest management strategies. In the present review, we focus on two such strategies: first, impairment of osmoregulation by manipulation of diuretic or antidiuretic signaling pathways and second, interference with toxin elimination by inhibition of toxin transport systems.


Shoulder and elbow evaluation of pitchers in National High School Baseball Invitational Tournaments and National High School Baseball Championships from 1993 to 2016 in Japan.
Shoulder and elbow examinations for pitchers have been performed in Japan's National High School Baseball Invitational Tournaments (NHSBITs) and National High School Baseball Championships (NHSBCs) since 1993. However, for years the results have not been analyzed. The purpose of this study was to evaluate changes in the condition of shoulders and/or elbows of pitchers from 1993 to 2016. Pitchers in NHSBITs and NHSBCs, 1994-2016, were examined together with those who received a trial examination (Trial) in the NHSBC 1993. Shoulder and elbow symptoms were comprehensively graded into five categories; none, mild, moderate, severe and dysfunction. Standard plain radiographs of the shoulder and elbow were obtained. Average Annual Percent Changes (AAPCs) in the percentages of pitchers with symptoms and positive radiographic findings were analyzed. The percentages of pitchers with moderate or worse symptoms in the shoulder or elbow were 14.6% and 13.8%, respectively, in the Trial, 1.1% and 1.1% in NHSBITs and 1.3% and 2.0% in NHSBCs. The AAPC of pitchers with a symptomatic shoulder in NHSBITs was reduced over the study period, at -3.36% (P < 0.05), but that in NHSBCs was unchanged at -1.01%. The AAPCs of pitchers with a symptomatic elbow in NHSBITs and in NHSBCs decreased, at -3.13% and -3.33%, respectively (P < 0.05), while that of pitchers with residual apophyseal fragmentation at the ulnar collateral ligament insertion increased at +2.79% (P < 0.05). The decreased percentages of symptomatic pitchers suggest that joint condition is well controlled in high school days; however, the increased frequency of radiographic findings suggests the necessity of protection against overuse in younger players. The percentages of pitchers with symptomatic shoulders and elbows in NHSBITs and those with symptomatic elbows in NHSBCs have decreased over the 23 years. However, the increased frequency of residual medial humeral epicondyle apophyseopathy should be noted.


Assessment of exposure to alcohol vapor from alcohol-based hand rubs.
This study assessed the inhaled dose of alcohol during hand disinfection. Experiments were conducted with two types of hand rub using two hand disinfection procedures. Air samples were collected every 10 s from the breathing zone, by bubbling through a mixture of K(2)Cr(2)O(7) and H(2)SO(4). The reduction of dichromate ions in the presence of alcohols was followed by UV-vis spectrophotometry. The difference in intensity of the dichromate absorption peak was used to quantify the alcohol concentration expressed in ethanol equivalent. During hygienic hand disinfection, the mean ethanol equivalent concentrations peaked at around 20-30 s for both hand rubs (14.3 ± 1.4 mg/L for hand rub 1 and 13.2 ± 0.7 mg/L for hand rub 2). During surgical hand disinfection, two peaks were found at the same time (40 and 80 s) for both hand rubs. The highest mean concentrations were 20.2 ± 0.9 mg/L for hand rub 1 and 18.1 ± 0.9 mg/L for hand rub 2. For hand rub 1, the total absorbed doses, calculated from ethanol with an inhalation flow of 24 L/min and an absorption rate of 62%, were 46.5 mg after one hygienic hand disinfection and 203.9 mg after one surgical hand disinfection. Although the use of ABHRs leads to the absorption of very low doses, sudden, repeated inhalation of high alcohol concentrations raises the question of possible adverse health effects.


Design, synthesis and expression of a human interleukin-2 gene incorporating the codon usage bias found in highly expressed Escherichia coli genes.
A synthetic gene encoding human interleukin-2 (IL-2) was designed such that the codon usage bias resembled that found in highly expressed Escherichia coli genes. The percentage of preferred codons was increased from 43% in the native cDNA sequence to 85% in the synthetic sequence. The cDNA and synthetic IL-2 genes were placed under the control of the trc promoter and expressed in E. coli JM101. While Northern blot analysis of IL-2 mRNA from each genetic construct demonstrated equivalent message half-lives, immunoblot and bioactivity analyses showed the synthetic gene to direct the synthesis of up to 16 times more IL-2 than the native cDNA sequence.


Epidemiology of sarcopenia among the elderly in New Mexico.
Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.


Microsatellite-based genetic diversity patterns in disjunct populations of a rare orchid.
We investigated the patterns of genetic diversity and structure in seven disjunct populations of a rare North American orchid, Cypripedium kentuckiense by including populations that represented the periphery and the center of the its range. Eight nuclear and two chloroplast microsatellites were used. Genetic diversity was low across the sampled populations of C. kentuckiense based on both nuclear (average An = 4.0, Ho = 0.436, He = 0.448) and cpDNA microsatellites (average An = 1.57, Nh = 1.57 and H = 0.133). The number of private alleles ranged from one to four per population with a total of 17 private alleles detected at five nuclear microsatellites. One private allele at one cpDNA microsatellite was also observed. Although the absolute values for nuclear microsatellite based population differentiation were low (Fst = 0.075; ϕPT = 0.24), they were statistically significant. Pairwise Fst values ranged from 0.038 to 0.123 and each comparison was significant. We also detected isolation by distance with nDNA microsatellites based on the Mantel test (r(2) = 0.209, P = 0.05). STRUCTURE analysis and the neighbor joining trees grouped the populations similarly whereby the geographically proximal populations were genetically similar. Our data indicate that the species is genetically depauperate but the diversity is distributed more or less equally across its range. Population differentiation and isolation by distance were detectable, which indicates that genetic isolation is beginning to manifest itself across the range in this rare species.


Educational environment in intensive care medicine--use of Postgraduate Hospital Educational Environment Measure (PHEEM).
The educational climate is an important measure within medical education. This is because there are still accounts of poor teaching, humiliation, bullying and harassment of doctors in training. Deaneries and schools must be able to demonstrate to the Postgraduate Medical Education and Training Board that trainees are working and learning in a good environment. This study used the Postgraduate Hospital Educational Environment Measure (PHEEM) to measure the educational climate in nine intensive care training schemes within hospitals in England and Scotland. 134 trainees replied out of 190 (71% response). Neither the identities of the nine units nor the trainees were known to the researchers. The results showed that there was a good overall educational climate in the intensive care units studied, with no racism or sexism, and trainees were happy with their teaching, their support and the work they did. The junior trainees (house officers and senior house officers) perceived a significantly better climate than did the senior trainees (specialist registrars). There were also significant differences in scores for the nine different intensive care units. PHEEM has proved to be a reliable and consistent tool to assess educational climate with an overall Cronbach's alpha of 0.921.


Understanding the Role of Patient Portals in Fostering Interprofessional Collaboration Within Mental Health Care Settings: Mixed Methods Study.
Patient portals are web-based systems through which patients can access their personal health information and communicate with their clinicians. The integration of patient portals into mental health care settings has been evolving over the past decade, as cumulated research to date has highlighted the potential role of portals in facilitating positive health outcomes. However, it is currently unknown whether portal use can foster interprofessional collaboration between clinicians and patients or whether the portal is a tool to support an already established collaborative relationship. This mixed methods study aimed to understand how the use of a patient portal within mental health settings can impact the level of interprofessional collaboration between clinicians and patients. This study was conducted in a large mental health care organization in Ontario, Canada. A convergent mixed methods design was used, where the primary data collection methods included questionnaires and semistructured interviews with patients who had experience using a portal for their mental health care. For the quantitative strand, participants completed the Health Care Communication Questionnaire and the Self-Empowerment subscale of the Mental Health Recovery Measure at 3 time points (baseline, 3 months of use, and 6 months of use) to measure changes in scores over time. For the qualitative strand, semistructured interviews were conducted at the 3-month time point to assess the elements of interprofessional collaboration associated with the portal. For the quantitative strand, 113 participants completed the questionnaire. For the Health Care Communication Questionnaire scores, the raw means of the total scores at the 3 time points were as follows: baseline, 43.01 (SD 7.28); three months, 43.19 (SD 6.65); and 6 months, 42.74 (SD 6.84). In the univariate model with time as the only independent variable, the scores did not differ significantly across the 3 time points (P=.70). For the Mental Health Recovery Measure scores, the raw mean total scores at the 3 time points were as follows: baseline, 10.77 (SD 3.63); three months, 11.09 (SD 3.81); and 6 months, 11.10 (SD 3.33). In the univariate model with time as the only independent variable, the scores did not differ significantly across the 3 time points (P=.34). For the qualitative strand, 10 participants were interviewed and identified various elements of how interprofessional collaboration can be supplemented through the use of a patient portal, including improved team functioning, communication, and conflict resolution. Although the quantitative data produced nonsignificant findings in interprofessional collaboration scores over time, the patients' narrative accounts described how the portal can support various interprofessional collaboration concepts, such as communication, leadership, and conflict resolution. This provides useful information for clinicians to support the interprofessional relationship when using a portal within a mental health setting. RR2-10.1136/bmjopen-2018-025508.


Integrated multi-omic analyses provide insight into colon adenoma susceptibility modulation by the gut microbiota.
Colon cancer onset is strongly associated with the differences in microbial taxa in the gastrointestinal tract. Although recent studies highlight the role of individual taxa, the effect of a complex gut microbiome (GM) on the metabolome and host transcriptome is still unknown. We used a multi-omics approach to determine how differences in the GM affect the susceptibility to adenoma development in a rat model of human colon cancer. Ultra-high performance liquid chromatography mass spectrometry of feces collected prior to observable disease onset identified putative metabolite profiles that likely predict future disease severity. Transcriptome analyses performed after disease onset from normal colonic epithelium and tumor tissues show a correlation between GM and host gene expression. Integrated pathway analyses of the metabolome and transcriptome based on putatively identified metabolic features indicate that bile acid biosynthesis is enriched in rats with high tumors along with increased fatty acid metabolism and mucin biosynthesis. Targeted pyrosequencing of the Pirc allele indicates that the GM alters the mechanism of adenoma development and may drive an epigenetic pathway of tumor suppressor silencing. This study reveals how untargeted metabolomics identifies signatures of susceptibility and integrated analyses uncover pathways of differential mechanisms of loss of tumor suppressor gene function and for potential prevention and therapeutic intervention. IMPORTANCE The association between the gut microbiome and colon cancer is significant but difficult to test in model systems. This study highlights the association of differences in the pathogen-free gut microbiome to changes in the host transcriptome and metabolome that correlate with colon adenoma initiation and development in a rat genetic model of early colon cancer. The utilization of a multi-omics approach integrating metabolomics and transcriptomics reveals differences in pathways including bile acid biosynthesis and fatty acid metabolism. The study also shows that differences in gut microbiomes significantly alter the mechanism of adenoma formation, shifting from genetic changes to epigenetic changes that initiate the early loss of tumor suppressor function. These findings enhance our understanding of the gut microbiome's role in colon cancer susceptibility, offer insights into potential biomarkers and therapeutic targets, and may pave the way for future prevention and intervention strategies.


MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin.
Preclinical and clinical studies suggest that peroxisome proliferator-activated receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone. The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin. This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites. This study evaluated 181 overweight men and women with mixed dyslipidemia. Subjects were administered once daily placebo, atorvastatin 20 mg, or MBX-8025 at 50 or 100 mg alone or combined with atorvastatin for 8 wk. The main efficacy measures included change from baseline in apolipoprotein B-100, lipid levels, high-sensitivity C-reactive protein, and additional metabolic parameters, as well as the effect on the metabolic syndrome and LDL particle size. Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P < 0.05) reduced apolipoprotein B-100 20-38%, LDL 18-43%, triglycerides 26-30%, non-high-density lipoprotein cholesterol 18-41%, free fatty acids 16-28%, and high-sensitivity C-reactive protein 43-72%; it raised high-density lipoprotein cholesterol 1-12% and also reduced the number of patients with the metabolic syndrome and a preponderance of small LDL particles. MBX-8025 was safe and generally well-tolerated. MBX-8025 also reduced liver enzyme levels. MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.


Percutaneous Image-guided Thermal Ablation for Renal Cell Carcinoma.
Nephrectomy is the gold standard for the treatment of renal cell carcinoma (RCC). However, some patients are not suitable candidates for nephrectomy because of high surgical risk, reduced renal function, or the presence of multiple renal tumors. Percutaneous image-guided thermal ablation, including cryoablation and radiofrequency ablation, is a minimally invasive and highly effective treatment and can be used to treat RCC in patients who are not good candidates for surgery. This article will review percutaneous image-guided thermal ablation for RCC, covering treatment indications, ablation modalities and techniques, oncologic outcomes, and possible complications. In addition, the characteristics of each ablation modality and its comparison with nephrectomy are also presented.


Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening.
Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many molecules and could deliver small molecules and proteins, which are susceptible to degradation and show poor absorption by oral application. The low rate of biotransformation and proteolytic degradation increases bioavailability of drugs but accumulation of not absorbed material may impair normal lung function. This limitation is more relevant for compounds that should be systematically active because higher doses have to be applied to the lung. The review describes processes that determine absorption of orally inhaled formulations, namely dissolution in the lung lining fluid and uptake and degradation by alveolar epithelial cells and macrophages. Dissolution testing in simulated lung fluid, screening for cytotoxicity and pro-inflammatory action in respiratory cells and study of macrophage morphology, and phagocytosis can help to identify adverse effects of pulmonary formulations.


Hemimegalencephaly, a paradigm for somatic postzygotic neurodevelopmental disorders.
Combining human genomics and molecular biology, recent studies have made pivotal progress toward understanding the cause of hemimegalencephaly (HME) and other cerebral megalencephaly syndromes. The present article highlights recent advances of the genetic cause of these conditions, and considers the role of somatic postzygotic genetic lesions in brain maldevelopment. Studies over the past 12 months have identified de-novo somatic mutations as one possible cause in HME. The gene mutations involve components of the phosphatidylinositol 3-kinase (PI3K)-AKT (also known as protein kinase B)-mammalian target of rapamycin (mTOR) pathway and include PIK3CA, PIK3R2, AKT3, and MTOR. These mutations were identified by comparing genomic data obtained from surgically resected brain tissue with nondiseased tissue, and by single-neuron sequencing in combination with molecular biology techniques. The association between the somatic mutations and downstream activation of the PI3K-mTOR pathway suggests that HME is a neurodevelopmental disease caused by gain-of-function activation of the PI3K-AKT-mTOR pathway. The studies reviewed suggest that somatic mutations of the PI3K-AKT-mTOR pathway limited to the brain may represent one cause of HME. Dysregulation of this pathway has possible therapeutic potential in the identification of HME. Somatic mutations may be an important yet underappreciated disease mechanism in developmental neurological diseases.


Spin-current Seebeck effect in quantum dot systems.
We first bring up the concept of the spin-current Seebeck effect based on a recent experiment (Vera-Marun et al 2012 Nature Phys. 8 313), and investigate the spin-current Seebeck effect in quantum dot (QD) systems. Our results show that the spin-current Seebeck coefficient S is sensitive to different polarization states of the QD, and therefore can be used to detect the polarization state of the QD and monitor the transitions between different polarization states of the QD. The intradot Coulomb interaction can greatly enhance S due to the stronger polarization of the QD. By using the parameters for a typical QD whose intradot Coulomb interaction U is one order of magnitude larger than the linewidth Γ, we demonstrate that the maximum value of S can be enhanced by a factor of 80. On the other hand, for a QD whose Coulomb interaction is negligible, we show that one can still obtain a large S by applying an external magnetic field.


A novel method for evaluation of capillarity in human skeletal muscles from confocal 3D images.
A well developed capillary bed is essential for proper function of skeletal muscles. We present for the first time a triple immunofluorescent method suitable for staining capillaries and muscle fibre outlines in thick sections of human skeletal muscle, applying antibodies against collagen IV (in red) and F8 (in green) as well as Ulex europaeus lectin, visualized in green fluorescence. Further, we present possibilities for quantitative evaluation of the capillary network which implies the length of capillaries per unit volume of muscle tissue (Lcap/Vmuscle) and the length of capillaries supplying individual muscle fibres per unit fibre length (Lcap/Lfib), per surface area (Lcap/Sfib) and per volume (Lcap/Vfib) as well as the course of capillaries in the muscle. The latter can be described by the tortuosity, orientation and mean capillary length. To get reasonable results we met the following requirements: i) high quality thick tissue sections, from which 3D image data were acquired; ii) immunofluorescent methods suitable for confocal microscopy; iii) penetration of the fluorescent dyes throughout the tissue section; iv) proper 3D image analysis methods for performing reliable measurements and v) control over relevant tissue deformations. The developed methodology is illustrated by results obtained from autopsy or biopsy samples of three human muscles, i.e. vastus lateralis, multifidus and masseter muscle that exhibit differences in genetic background, innervation, tasks and functional activity.


Monotropein: A comprehensive review of biosynthesis, physicochemical properties, pharmacokinetics, and pharmacology.
Monotropein, a principal natural compound in iridoid glycosides extracted from Morindae officinalis radix, has potent pharmacological activities. To understand and utilize monotropein, we systematically summarized the studies on monotropein, including its biosynthetic pathway, physicochemical properties, pharmacokinetics, and pharmacology. Interestingly, we found that the multiple bioactivities of monotropein, such as anti-osteoporosis, anti-inflammation, anti-oxidation, anti-nociception, and hepatic or renal protection, are closely associated with its capability of downregulating the nuclear factor-κB signaling pathway, inhibiting the mitogen-activated protein kinase signaling pathway, attenuating the activation of nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway, and regulating the mammalian target of rapamycin/autophagy signaling pathway. However, the clinically therapeutic effects and the potential problems need to be addressed. This review highlights the current research progress on monotropein, which provides a reference for further investigation of monotropein.


New aporphine alkaloids from the aerial parts of Piper semiimmersum §.
Two new aporphine alkaloids, semiimmersumines A (1) and B (2), along with 20 known compounds, were isolated from the aerial parts of Piper semiimmersum (Piperaceae). The structures of the new compounds were elucidated based on the analysis of 1D and 2D NMR, MS, and CD data. The absolute configuration of semiimmersumine A (1) was determined by single crystal X-ray diffraction analysis using anomalous dispersion with copper radiation. The effects of all compounds from the plant on rabbit platelet aggregation induced by thrombin (IIa) or PAF were also evaluated.


Advancements in pharmacotherapy for angina.
Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19th century, there has been considerable advancement in the pharmacologic management of angina. Areas covered: Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness. Expert opinion: Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.


Simultaneous discrimination of diameter, handedness, and metallicity of single-walled carbon nanotubes with chiral diporphyrin nanocalipers.
We have been developing the methodology to discriminate the handedness and diameter of single-walled carbon nanotubes (SWNTs) through molecular recognition using chiral diporphyrin nanotweezers. Although relatively small diameters of SWNTs (<1.0 nm) were recognized well, nanotweezers were not able to form stable complexes with the SWNTs having the diameters >1.0 nm. In this context, we designed chiral diporphyrin with a much larger cavity, namely, "nanocalipers". The feature of the newly designed host molecule is: (1) long spacer with more than 1.4 nm consisting of three aromatic moieties; (2) nearly parallel orientation of the two porphyrins; (3) restricted conformation by biaryl linkages of the porphyrin-carbazole and carbazole-anthracene; (4) strong interaction of two porphyrins and anthracene with the surface of a SWNT through π-π stacking; and (5) stereogenic centers at the periphery of porphyrins discriminating helicity of SWNTs. As expected, we obtained optically active SWNTs with >1.0 nm in diameter and, unexpectedly, enriched metallic SWNTs over semiconducting ones. The optically active metallic SWNTs are identified for the first time, in addition to the optically active semiconducting SWNTs with such large diameters. The nanocalipers are found to recognize the diameter, handedness, and metallicity of SWNTs simultaneously.


[Dynamics of ascitic fluid in decompensated cirrhosis].
The ascitic fluid in decompensated liver cirrhosis constitutes a continuously circulating pool which carries on sustained water exchanges with plasma and extracellular fluids through the whole peritoneal membrane. The actual ascites volume results therefore from the steady-state between the formation and reabsorption transperitoneal water flows. The ascitic reabsorption concerns both the "iso-osmotic" (i.e. the portion bound to the ascitic proteins and solutes) and the "free-water" (i.e. the amount exceeding the osmotic bounding ability of the peritoneal solutes) fractions of total ascitic water. By means of a simple dilution test, it is possible an in vivo estimation of both the ascites volume and the rate of transperitoneal free-water reabsorption, which is the actual free-water peritoneal clearance (CPAL) and an evaluation of the total intra-abdominal pressure (PIA). PIA results from the sum of the ascitic hydrostatic pressure, and the tension of the abdominal wall. Diuretic administration is able to significantly reduce CPAL, inducing a negative sodium balance and thus leading to a readjustment of ascites steady-state. This fact may cause reductions of ascites volume and PIA only after several days of diuretic treatment. An acute diuretic treatment by itself, even if intensive and resulting in a rapid diuresis and a significant modification of CPAL, does not appear able to determine rapid and detectable modifications of PIA. CPAL has an intrinsic prognostic value in patients with decompensated cirrhosis, since the cumulative mortality was reported to be significantly higher in the patients with lower CPAL levels. The peritoneal clearance ability may be regarded as a compensatory mechanisms of portal hypertension, and its estimate may be a reliable index of patient's aptitude to a lower hydro-retentive trend, which is in turn correlated to a greater cirrhosis severity and a worse prognosis.


Iterative Rupture of the Patellar Tendon: A Case Report of an Original Technique for Revision Reconstruction Using an Adjustable Loop and an Artificial Ligament.
Chronic rupture of the patellar tendon is a severe injury that leads to dramatic functional consequences including lack of extension and walking difficulty. Surgery is the gold standard to treat this type of injury, but revision reconstructions are problematic because an ipsilateral graft was often harvested for the initial surgery. Because fibrotic tissues on the patellar tendon need to be debrided, another graft must be added to reinforce the tendon. We reported the case of a former semiprofessional handball player, a 29-year-old man who presented an iterative rupture with the fracture of the transverse patellar tunnel 6 months after reconstruction using a semitendinosus graft and suture repair. We performed revision reconstruction surgery using an artificial ligament placed between the extensor mechanism and the tibia for extra-articular reinforcement to maintain extensor mechanism continuity. Two adjustable loops were also used to repair the patellar tendon tear. At 2-year follow-up, the patient was able to resume the practice of handball at a competitive level with good clinical and functional results. This technique can therefore be used as a salvage procedure for chronic iterative rupture of the patellar tendon.


Plasma norepinephrine and epinephrine in acromegaly.
Plasma norepinephrine and epinephrine concentrations were measured, in the supine resting position and in response to standing, in 10 unselected patients with active acromegaly, in 2 effectively treated acromegalic patients with normal serum growth hormone concentrations and in 15 nonacromegalic normal subjects. Plasma catecholamine concentrations were not significantly related to serum growth hormone levels or to the diastolic blood pressure in the acromegalic patients. Mean (+/- SE) plasma norepinephrine concentrations rose from 211 +/- 28 pg/ml supine to 501 +/- 65 pg/ml after 10 minutes standing in the active acromegalic patients and from 210 +/- 20 pg/ml supine to 502 +/- 54 pg/ml after 10 min standing in the normal subjects. Corresponding plasma epinephrine concentrations were 33 +/- 6 and 60 +/- 14 pg/ml in the acromegalics and 57 +/- 7 pg/ml in the normals. Thus, no abnormality in basal or stimulated plasma catecholamine concentrations was found in acromegalic patients.


Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin.
Fluoroquinolones (FQs) have been infrequently used in children, largely because of concern that these agents can cause lesions of the cartilage in juvenile animals. However, the relevance of this laboratory observation to children treated with FQs is unknown. A retrospective, observational study was conducted to assess the incidence and relative risk of tendon or joint disorders (TJDs) that occur after use of selected FQs compared with azithromycin (AZ), a drug with no known effect on cartilage or tendons in humans or animals. An automated database was searched to identify patients younger than 19 years who had been prescribed ofloxacin (OFX), levofloxacin, ciprofloxacin (CPX), or AZ. Potential cases of TJD occurring within 60 days of a prescription of one of the study drugs were identified based on assignment of a claims diagnosis consistent with a TJD within this period. Verified cases were identified by a blinded review of abstracts of medical records from subjects identified as potential cases. The incidence of verified TJD was 0.82% for OFX (13 of 1593) and CPX (37 of 4531) and was 0.78% for AZ (118 of 15,073). The relative risk of TJD for OFX and CPX compared with AZ was 1.04 (95% confidence interval, 0.55 to 1.84) and 1.04 (95% confidence interval, 0.72 to 1.51), respectively. The distributions of claims diagnoses and time to onset of TJD were comparable for all groups. The most frequently reported category of TJD involved the joint followed by tendon, cartilage and gait disorder. In this observational study involving more than 6000 FQ-treated children, the incidence of TJD associated with selected FQ use in children was <1% and was comparable with that of the reference group, children treated with AZ.


Esophageal Motility Disorders Associated With Death or Allograft Dysfunction After Lung Transplantation? Results of a Retrospective Monocentric Study.
Pathological gastroesophageal reflux (GER) is a known risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation. This study aimed at determining whether functional esophageal evaluation might predict BOS occurrence and survival in this setting. Ninety-three patients who underwent esophageal high-resolution manometry and 24-hour pH-impedance monitoring within the first year after lung transplantation were retrospectively included. A univariable analysis was performed to evaluate the parameters associated with GER disease and BOS occurrence. The Cox regression model was used to identify the prognostic factors of death or retransplantation. Thirteen percent of patients exhibited major esophageal motility disorders and 20% pathological GER. GER occurrence was associated with younger age, cystic fibrosis, and hypotensive esophagogastric junction. Within a median follow-up of 62 months, 10 patients (11%) developed BOS, and no predictive factors were identified. At the end of the follow-up, 10 patients died and 1 underwent retransplantation. The 5-year cumulative survival rate without retransplantation was lower in patients with major esophageal motility disorders compared with that in those without (75% vs 90%, P = 0.01) and in patients who developed BOS compared with that in those without (66% vs 91%; P = 0.005). However, in multivariable analysis, major esophageal motility disorders and BOS were no longer significant predictors of survival without retransplantation. Major esophageal motility disorders and BOS were associated with allograft survival in lung transplantation in the univariable analysis. Although the causes of this association remain to be determined, this observation confirms that esophageal motor dysfunction should be evaluated in the context of lung transplantation.


Team-based care.
Health care is a team sport, but too often practitioners act as individual players. This foldout section considers barriers to collaboration and how to overcome them. Case studies describe how three hospital organizations are tackling the issue.


Carotid endarterectomy significantly improves postoperative laryngeal sensitivity.
Iatrogenic injury of the vagus nerve or its branches during carotid endarterectomy (CEA) can result in globus sensation, dysphagia, and even vocal fold immobility. Knowledge of morphologic and functional laryngopharyngeal outcomes after CEA is poor. The present study was performed to determine potential iatrogenic damage to the laryngeal innervation after CEA. An area of particular interest was the supraglottic sensory threshold, which was examined by Fiberoptic Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST; Pentax Medical Company, Montvale, NJ), a validated and safe method for the determination of the motor and sensory components of swallowing. FEESST was used preoperatively in 32 patients scheduled to undergo CEA and twice postoperatively to examine the motor and sensory components of swallowing. In this endolaryngeal examination, laryngopharyngeal sensory thresholds (in mm Hg) were defined as normal at <4.0 mm Hg air pulse pressure (APP), moderate deficit at 4.0 to 6.0 mm Hg APP, or severe deficit at >6.0 mm Hg APP, with a value >10.0 mm Hg APP indicating abolished laryngeal adductor reflex. Acoustic voice parameters were also analyzed for further functional changes of the larynx. The mean ± standard deviation preoperative FEESST measures showed no significant differences (P = .065) between the operated-on side (6.73 ± 1.73 mm Hg) and the opposite side (5.83 ± 1.68 mm Hg). At 2 days postoperatively, the threshold increased (P = .001) to 7.62 ± 1.98 mm Hg on the operated-on side. A laryngopharyngeal mucosal hematoma on the operated side was endoscopically detectable in eight patients (30.8%); in these patients, we found a markedly elevated (P = .021) measure of 9.50 ± 0.93 mm Hg. On the opposite (nonoperated-on) side of the laryngopharynx, the thresholds remained at the same level as preoperatively over all assessments (P >.05), whereas the differences between the operated and nonoperated-on sides and the hematoma and nonhematoma groups were highly significant (P = .004 and P = .001, respectively). Surprisingly, the sensory threshold on the operated-on side (6.08 ± 2.02 mm Hg) decreased significantly at the 6-week follow-up, even in relation to the preoperative measure (P = .022). With the exception of one patient with permanent unilateral vocal fold immobility, no signs of nerve injury were detected. In accordance with previous reports, injuries to the recurrent laryngeal nerve during CEA seem to be rare. In most patients, postoperative symptoms (globus, dysphagia, dysphonia) and signs fade within a few weeks without any specific therapeutic intervention. This study shows an improved long-term postoperative superior laryngeal nerve function with regard to laryngopharyngeal sensitivity.


Esthetic rehabilitation with laminated ceramic veneers reinforced by lithium disilicate.
Because of their predictable results and conservation of tooth structure, ceramic veneers are indicated for the esthetic treatment of anterior teeth with anomalous positions or appearance. The objective of this case report is to highlight the steps in dental rehabilitation using ceramic veneers reinforced by lithium disilicate. In this case the patient had diastemas between the mandibular incisors. After preliminary procedures, diagnostic models, waxing, and mock-up were completed, an impression was made with addition silicone, and the veneers were fabricated and cemented with light-cure cement. As a result, the esthetics and function expected by the patient were achieved. The use of ceramic veneers enabled a conservative and esthetically successful rehabilitation treatment.


Acorn consumption improves the immune response of the dung beetle Thorectes lusitanicus.
Thorectes lusitanicus, a typically coprophagous species is also actively attracted to oak acorns, consuming, burying them, and conferring ecophysiological and reproductive advantages to both the beetle and the tree. In this study, we explored the possible relation between diet shift and the health status of T. lusitanicus using a generalist entomopathogenic fungus (Metarhizium anisopliae) as a natural pathogen. To measure the health condition and immune response of beetles, we analysed the protein content in the haemolymph, prophenoloxidase (proPO) content, phenoloxidase (PO) activity and mortality of beetles with diets based on either acorns or cow dung. Protein content, proPO levels and PO levels in the haemolymph of T. lusitanicus were found to be dependent on the type of diet. Furthermore, the beetles fed with acorns developed a more effective proPO-PO system than the beetles fed with cow dung. Furthermore, a significant decrease in mortality was observed when infected individuals were submitted to an acorn-based diet. In addition to enhancing an understanding of the relevance of dietary change to the evolutionary biology of dung beetles, these results provide a more general understanding of the ecophysiological implications of differential dietary selection in the context of fitness.


Prenatal diagnosis of glutathione synthase deficiency.
Prenatal diagnosis for glutathione synthase (EC 184.108.40.206) deficiency in two pregnancies of an at-risk couple was performed on amniotic fluid taken at 16 weeks' gestation. 5-Oxoproline (pyroglutamic acid) levels were 970 and 790 mumol/l compared with the normal mean value of 29 mumol/l (range 13-51 mumol/l). The pregnancies were terminated and the diagnosis in one case was subsequently confirmed by assay of glutathione synthase in cultured fetal fibroblasts. In the other, post-mortem tissue samples failed to grow.


[Management of pectus excavatum].
Management of pectus excavatum Congenital chest wall deformities are considered to be anomalies in chest wall growth related to excessive or insufficient growth (aplasia or dysplasia) of the osseous or cartilaginous structures or the rib cage. These deformities are associated in 95% to overgrowth leading into depression (pectus excavatum) or protuberance of the sternum (pectus carinatum). Pectus excavatum may lead to cardiopulmonary disorder or impact on patient's self-esteem. The management of pectus excavatum has evolved this last decade with minimal invasive repair.


Activated K-Ras and H-Ras display different interactions with saturable nonraft sites at the surface of live cells.
Ras-membrane interactions play important roles in signaling and oncogenesis. H-Ras and K-Ras have nonidentical membrane anchoring moieties that can direct them to different membrane compartments. Ras-lipid raft interactions were reported, but recent studies suggest that activated K-Ras and H-Ras are not raft resident. However, specific interactions of activated Ras proteins with nonraft sites, which may underlie functional differences and phenotypic variation between different Ras isoforms, are unexplored. Here we used lateral mobility studies by FRAP to investigate the membrane interactions of green fluorescent protein-tagged H- and K-Ras in live cells. All Ras isoforms displayed stable membrane association, moving by lateral diffusion and not by exchange with a cytoplasmic pool. The lateral diffusion rates of constitutively active K- and H-Ras increased with their expression levels in a saturable manner, suggesting dynamic association with saturable sites or domains. These sites are distinct from lipid rafts, as the activated Ras mutants are not raft resident. Moreover, they appear to be different for H- and K-Ras. However, wild-type H-Ras, the only isoform preferentially localized in rafts, displayed cholesterol-sensitive interactions with rafts that were independent of its expression level. Our findings provide a mechanism for selective signaling by different Ras isoforms.


Multimodal Lentiviral Vectors for Pharmacologically Controlled Switching Between Constitutive Single Gene Expression and Tetracycline-Regulated Multiple Gene Collaboration.
Multimodal lentiviral vectors (LVs) allow switching between constitutive and tetracycline-regulated gene co-expressions in genetically modified cells. Transduction of murine primary hematopoietic progenitor cells (HPCs) with multimodal LVs in the absence of doxycycline ensures the constitutive expression of gene of interest 1 (GOI1) only. In the presence of doxycycline, induced tetracycline-regulated expression of a second GOI (GOI2) allows evaluation of the collaboration between two genes. Drug removal retains constitutive expression, which allows the contribution of an individual gene into created networks to be studied. Doxycycline-dependent switching can be tracked via fluorescent markers coupled to constitutive and tetracycline-regulated GOIs. This article describes transduction of murine primary HPCs with different doses of multimodal LVs, distinct cytokine conditions, and their influence on the number and viability of cells co-expressing both collaborating GOIs upon doxycycline induction. A 2-week protocol is provided for multimodal LV production, titer determination, and evaluation of tetracycline responsive promoter background activity in a murine fibroblast cell line. The power of this model to assess the dose/time/order-controlled contribution of single and multiple genes into hematopoietic networks opens new routes in reprogramming, stem cell, and leukemia biology.


Ginger (zingiber officinale) might improve female fertility: A rat model.
Ginger (Zingiber officinale) is a well known and extensively used antioxidant in traditional remedies. In this study, we aimed to investigate the effects of ginger powder on ovarian folliculogenesis and implantation in rats. There were two study groups. In the 5-day treatment group (one estrous cycle), 100 mg ginger powder, 200 mg ginger powder or distilled water was given for 5 days to the three subgroups each containing seven rats. In the 10-day treatment group, same doses were given for 10 days (two estrous cycle) to the three subgroups each containing seven rats. At the end of the 5th and 10th days, ovarian volumes, ovarian weights, primordial follicles, antral follicles, atretic follicles, and corpus luteum counts were assessed. To evaluate the angiogenic effects of ginger, vascular endothelial growth factor (VEGF) and for the antioxidant effects of ginger endothelial nitric oxide synthase (eNOS) were examined in the ovaries and in the endometrium immunohistochemically. In the 5-day treatment group, antral follicle count and ovarian stromal VEGF were significantly high in the 100 mg ginger subgroup in comparison to the control group (p < 0.05). In the 10-day treatment group, endometrial VEGF and ovarian stromal eNOS were significantly high in the 100 mg ginger subgroup in comparison to the control group (p < 0.05). There was no statistically significant difference at 200 mg ginger dose both in 5-day and 10-day treatment groups. The increases in the antral follicle count and ovarian stromal VEGF in the 100 mg/5-day treatment subgroup indicate that ginger have positive effects on folliculogenesis in short term with low dose. Additionally, ginger may enhance implantation in rats in long term with low dose.


A new retainer using magnetic attachment.
A 58-year-old man with a complaint of masticatory disturbance presented. His mandibular left premolars and molars were missing, and the mandibular left canine, which was neighboring to the missing part, showed marked labial tipping. A cobalt-chromium removable partial denture was fabricated using a new magnetic attachment retainer because it seemed difficult to apply a conventional clasp for this case. This retainer is constructed from the buccal hook arm sliding bucco-lingually and the magnetic attachment which works to lock the movable part when it was closed. Six years after the delivery of this denture, both the abutment tooth and the periodontal tissue are healthy, and the denture is functioning well. As this retainer does not use the elasticity of clasp arms, block out area can be minimized, and the maximum area of the contacting surface of the hook arm brings about very positive retention and bracing. The function of attractive force is to resist the splitting force and not to become directly involved in the retention of the denture. Therefore, the attractive force for this system does not need to be very strong. This system also provides the advantages of a sectional denture, allowing protection of the abutment tooth and the use of the abutment tooth in its original form. The retainer described in this report has many advantages including, no hazardous lateral force, adequate retentive force, and application to natural teeth or tipped teeth.


Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidenced by autoradiography.
In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with 125I-labeled sCT. Autoradiograms demonstrated a heterogenous distribution of 125I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert its physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.


Detecting and characterizing high-frequency oscillations in epilepsy: a case study of big data analysis.
We develop a framework to uncover and analyse dynamical anomalies from massive, nonlinear and non-stationary time series data. The framework consists of three steps: preprocessing of massive datasets to eliminate erroneous data segments, application of the empirical mode decomposition and Hilbert transform paradigm to obtain the fundamental components embedded in the time series at distinct time scales, and statistical/scaling analysis of the components. As a case study, we apply our framework to detecting and characterizing high-frequency oscillations (HFOs) from a big database of rat electroencephalogram recordings. We find a striking phenomenon: HFOs exhibit on-off intermittency that can be quantified by algebraic scaling laws. Our framework can be generalized to big data-related problems in other fields such as large-scale sensor data and seismic data analysis.


CMS-NET: deep learning algorithm to segment and quantify the ciliary muscle in swept-source optical coherence tomography images.
The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo. However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality. This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images. A perspective cross-sectional study. In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared. For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.


Cytokines derived from alveolar macrophages induce fever after bronchoscopy and bronchoalveolar lavage.
As much as one-third of patients develop fever and flu-like symptoms after fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown reasons. The aim of the present study was to investigate factors mediating these side effects. Fifty consecutive patients with various pulmonary diseases who underwent FOB without further interventions (n = 30) or combined with BAL (n = 20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6 h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at t2. At to and t1, generally only low cytokine concentrations could be detected. At t2, however, significant increases of cytokine levels were found. IL-6 and TNF-alpha were significantly higher in patients after BAL than in patients after FOB. Comparing patients who developed fever (n = 12) with those who did not (n = 38), irrespective of the endoscopic procedures performed, dramatic increases of all three cytokines were detected in febrile patients that were significantly higher than in patients without fever. In the FOB group only patients who received local anesthesia by prilocaine bolus injection into the airways via the working channel of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile and had slight IL-6 increases only. There was a highly significant correlation between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98). All blood cultures remained sterile. These results indicate that fever after FOB and BAL is induced by proinflammatory cytokines derived from alveolar macrophages activated by instillation of fluid into the airways.


Epigenetic Changes Associated With Interleukin-10.
IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an important role in autoimmune diseases, inflammatory diseases and cancer. IL-10 is closely related to epigenetic modification, in which changes in DNA methylation of IL-10 gene can affect mRNA and protein levels of IL-10. In addition, changes in histone modifications, especially histone acetylation, can also lead to abnormal expression of IL-10 mRNA. At the same time, a handful of IL-10 related microRNAs (miRNAs) are found to be aberrantly expressed in multiple diseases. Besides, long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) also inhibits IL-10 expression. Here, we reviewed the epigenetic changes related to IL-10 in various diseases, as well as the regulation of IL-10 gene expression in various diseases by epigenetic modifications such as DNA methylation, histone modification, miRNA, and lncRNA.


A Novel Nanoprobe Based on Core-Shell Au@Pt@Mesoporous SiO2 Nanozyme With Enhanced Activity and Stability for Mumps Virus Diagnosis.
Nanoporous materials with core-shell structure have received lots of attention owing to the great versatility of the functional cores and shells and their potential application in catalysis and biological applications. In this work, a facile method has been developed to synthesize uniform Au@Pt@mesoporous SiO2 nanostructures with high peroxidase-like activity, which had a well-defined core-shell structure with Au nanorods@Pt nanodots as a core and mesoporous SiO2 as a shell. The mesoporous SiO2 shell can not only provide convenient transmission channels but offer a substantial location for accommodation of large biomolecules, such as antibodies and antigens. Here a novel nanoprobe based on Au@Pt@mesoporous SiO2 nanozyme modified with mumps antigens was reported. Notably, the encapsulation of Au@Pt nanorod in mesoporous SiO2 shell was able to hinder the interaction between catalytical nanoparticles and recognition antigens, retaining the catalytic activity of the inner active nanoparticle core. Furthermore, this nanoprobe exhibited an extraordinarily stability and showed excellent activity. As a result, we presented an enzyme linked immunosorbant assay (ELISA) for the diagnosis of mumps virus; this proposed method exhibited good sensitivity to mumps-specific IgM antibodies. The limit of detection can be as low as 10 ng/mL, which was more sensitive compared to the conventional immunoassay. Our results indicated that this nanoprobe hold great promise with opportunities for applications of biosensors, catalysis and biotechnology.


Chikungunya Masquerading as Acute Rheumatism in an Omani Traveler.
Chikungunya is a mosquito-borne viral disease. It typically presents as an acute febrile illness associated with a varying degree of arthralgia and musculoskeletal sequelae. Cases of chikungunya have been reported from more than 40 countries in several continents. Chikungunya is often reported in travelers returning to non-endemic/epidemic countries. With increasing international travel, it is vital that clinicians in non-endemic areas are made aware of this rapidly spreading infection. Increasing international travel (for social, leisure, and business) between Oman and several chikungunya endemic countries including Pakistan may facilitate the introduction of chikungunya to Oman. We report the first imported case of chikungunya in an Omani traveler with a link to the current outbreak in Pakistan.


Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients.
Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients.


Effect of plasma arc curing on polymerization shrinkage of orthodontic adhesive resins.
The purpose of this study was to evaluate the polymerization shrinkage of three orthodontic adhesive resins when polymerized with a high-energy plasma arc light (1340 mW cm(-2)) and a conventional halogen light (500 mW cm(-2)), and to correlate the polymerization shrinkage with the degree of conversion. To equalize the total light energy delivered to the adhesive resin, irradiation time was varied between 3 or 6 s for a plasma arc-curing unit, and 8 or 16 s for a halogen light-curing unit. The polymerization shrinkage of adhesive resins during the light-curing process was measured using a computer-controlled mercury dilatometer and the degree of conversion was measured using Fourier transform infrared spectroscopy. A plasma arccuring unit produced significantly lower polymerization shrinkage than a halogen light-curing unit when the equivalent total light energy was irradiated to the orthodontic adhesive resins (P < 0.05). The magnitude of polymerization shrinkage was significantly different depending on the kind of adhesive resins (P < 0.05), but there was no significant correlation between the filler fraction and the polymerization shrinkage (r2 = 0.039). There was strong correlation (r2 = 0.787) between the polymerization shrinkage and the degree of conversion with a halogen light-curing unit, but poor correlation (r2 = 0.377) was observed with a plasma arc-curing unit.


Atypical squamous cells and low squamous intraepithelial lesions in postmenopausal women: implications for management.
To determine whether the use of local Estrogen Replacement Therapy (ERT) affects the adequacy of colposcopic examination; to distinguish abnormal cervical smears secondary to hypoestrogenism from abnormal cervical smears due to true preneoplastic changes; and to suggest an effective management of atypical squamous cells of undeterminated significance (ASCUS) and low grade squamous intraepithelial lesion (L-SIL) in menopausal women. Two-hundred fifty-four postmenopausal women with abnormal pap smears (L-SIL or ASCUS) underwent colposcopy and HPV DNA testing. All patients with positive colposcopy underwent punch biopsy, and all patients with positive histological findings underwent surgical treatment. Patients with negative colposcopy, both satisfactory [visible Squamo-Columnar Junction (SCJ)] and unsatisfactory, were treated with local estrogenic replacement therapy (ERT) for 3 months, and repeated colposcopy and pap smears. Patients with negative colposcopy and negative pap smears after ERT were included in a 6 months cytological and colposcopic follow-up. Patients with positive colposcopy underwent punch biopsy, if colposcopy was negative and cytology was positive, patients underwent endocervical curettage. One-hundred ninety-five had a diagnosis of ASCUS and 59 a diagnosis of L-SIL. At the first colposcopy, 39 patients showed a lesion and had an appropriate treatment. One-hundred eighty-eight in the ASCUS group and 27 in the L-SIL group had a negative colposcopy and were treated with local ERT. At first colposcopic examination, 37 of the 215 negative colposcopies resulted satisfactory and 178 of the 215 resulted unsatisfactory. After local ERT, 130 of the 178 patients had a satisfactory follow-up colposcopy. After ERT, 25 patients of 215 with initial abnormal CVS and negative colposcopy, required appropriate treatment. After ERT, 190 patients of 215 showed negative colposcopy and at cytologic follow-up showed 23 ASCUS and 167 normal CVS. A correct diagnosis and an efficient treatment seem to be obtained with a short-time ERT followed by a short-time cytological and colposcopic follow-up. With a single course of local ERT it may be possible to distinguish between benign CVS mimicking atrophy and true preneoplastic changes. Estrogen therapy will often cause enough ectropion of the endocervical cells so that the entire SCJ can be visualized. Moreover, it may reduce the number of endocervical curettage or loop excision or cone procedure for women with inadequate colposcopic examination.


A Putative Association of Interleukin-1β Promoter Polymorphisms and IL-1β Levels in Saudi Diabetic Patients.
Type 2 diabetes mellitus (T2DM) is a well-known endocrine disorder affecting a significant number of individuals across the globe. Risk factors such as inflammation, obesity, high blood glucose level, cardiovascular disease, and genetic alteration are believed to be the reason for T2DM onset. The current study was intended to envisage the possible association between polymorphisms in the interleukin-1β (IL-1β) promoter and IL-1β serum levels in Saudi T2DM patients. Biochemical parameters such as fasting blood glucose (FBS), percentage glycosylated hemoglobin (HbAic), and lipid profile were measured spectrophotometrically. Serum insulin levels were measured using an immunochemistry analyzer. The commercial enzyme-linked immune assay (ELISA) kit was used to estimate the level of IL-1β in the serum samples. The Sanger sequencing method was adopted to determine single-nucleotide polymorphisms (SNPs) in the IL-1β promoter. We observed a significant (P < 0.001) elevation in FBS, Hb1Ac, insulin, and low-density lipoprotein cholesterol in T2DM patients compared with control individuals. Similarly, IL-1β level were found to be increased by 221% in T2DM patients compared with controls. A nonsignificant genotypic association was observed in the IL-1β gene at the -511C/T and -31C/T positions in T2DM patients compared with control individuals. However, a significant association (P < 0.05) was observed at the allelic level. Further studies on larger sample sizes are recommended to establish the exact role of IL-1β polymorphism in the pathogenesis of T2DM and its genetic risk.


Evaluation of cardiovascular effects of caffeine using telemetric monitoring in the conscious rat.
Caffeine (1,3,7 trimethylxanthine) affects the cardiovascular system, with potential toxic effects ranging from a moderate increase in heart rate to more severe cardiac arrhythmias. Telemetry transmitters were implanted in Wistar rats in the peritoneal cavity with a pressure catheter in the aorta and electrodes for electrocardiogram (ECG) recording subcutaneously. After a single oral administration of saline, each rat was administered single oral doses of 5, 15 and 45 mg/kg b.w. of caffeine. Caffeine was found to induce, to various degrees, a dose-dependent early increase in spontaneous physical activity, heart rate, dp/dt and systolic-diastolic blood pressure. No arrhythmias or visual changes were observed in the ECG complex. High doses induced more strong responses and of longer duration. The increase in systolic blood pressure at the median dose remained in the rats until 20 h after administration. However, the highest dose of caffeine (45 mg/kg b.w.) induced a biphasic response, with an early and pronounced increase in body temperature, spontaneous physical activity, systolic and diastolic blood pressure that later decreased, except for the systolic blood pressure. The results show that the dose level for long-lasting signs of intoxication to develop in the rat, in terms of effects on spontaneous physical activity, body temperature and cardiovascular function, was reached after a single oral dose of caffeine at 45 mg/kg b.w.


Association of H-2 types with genetic control of immune reponsiveness to IgG (gamma2a) allotypes in the mouse.
Immune responsiveness to IgG allotypes in the mouse was found to be controlled by an immune response gene Ir-IgG linked to the H-2 locus. This was demonstrated by the analysis of the immune response to BALB/c IgG (gamma2a) myeloma proteins in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains. Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to BALB/c IgG myeloma proteins was found in mice with the same heavy-chain immunoglobulin linkage group as BALB/c but of different H-2 types. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgG myeloma proteins was found in H-2 types b, bc, p, r, s, and v; a low response in a, d, k, and q. The Ir-IgG gene is controlled by a dominant autosomal gene.