Allergic inflammation of the anterior surface of the eye.
Background: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis and includes tear film dysfunction. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs, lubricants and methods of administration, there is a need to update new treatments to optimize the care of ocular allergy patients. Methods: An overview of mediators, clinical characteristics and management is provided in a summary format. Results: Lubricants (best when refrigerated provide immediate relief that is short lived (several minutes) due to its dilutional effect on mediators and pollen in the tear film. Immediate and longer-term benefit occurs from different topical and oral medications - primarily histamine receptor agonists. Conclusion: The newest prescription topical ophthalmic histamine H1 receptor antagonist (an inverse agonist) to be approved by the U.S. Food and Drug Administration in the past 10 years (U.S. NDA approved May 30, 2017) is cetirizine ophthalmic solution for the treatment of ocular itching with allergic conjunctivitis in adults and in children more than 2 years old.


A fundamental bimodal role for neuropeptide Y1 receptor in the immune system.
Psychological conditions, including stress, compromise immune defenses. Although this concept is not novel, the molecular mechanism behind it remains unclear. Neuropeptide Y (NPY) in the central nervous system is a major regulator of numerous physiological functions, including stress. Postganglionic sympathetic nerves innervating lymphoid organs release NPY, which together with other peptides activate five Y receptors (Y1, Y2, Y4, Y5, and y(6)). Using Y1-deficient (Y1(-/-)) mice, we showed that Y1(-/-) T cells are hyperresponsive to activation and trigger severe colitis after transfer into lymphopenic mice. Thus, signaling through Y1 receptor on T cells inhibits T cell activation and controls the magnitude of T cell responses. Paradoxically, Y1(-/-) mice were resistant to T helper type 1 (Th1) cell-mediated inflammatory responses and showed reduced levels of the Th1 cell-promoting cytokine interleukin 12 and reduced interferon gamma production. This defect was due to functionally impaired antigen-presenting cells (APCs), and consequently, Y1(-/-) mice had reduced numbers of effector T cells. These results demonstrate a fundamental bimodal role for the Y1 receptor in the immune system, serving as a strong negative regulator on T cells as well as a key activator of APC function. Our findings uncover a sophisticated molecular mechanism regulating immune cell functions that can lead to stress-induced immunosuppression.


Communication: Predictive partial linearized path integral simulation of condensed phase electron transfer dynamics.
A partial linearized path integral approach is used to calculate the condensed phase electron transfer (ET) rate by directly evaluating the flux-flux/flux-side quantum time correlation functions. We demonstrate for a simple ET model that this approach can reliably capture the transition between non-adiabatic and adiabatic regimes as the electronic coupling is varied, while other commonly used semi-classical methods are less accurate over the broad range of electronic couplings considered. Further, we show that the approach reliably recovers the Marcus turnover as a function of thermodynamic driving force, giving highly accurate rates over four orders of magnitude from the normal to the inverted regimes. We also demonstrate that the approach yields accurate rate estimates over five orders of magnitude of inverse temperature. Finally, the approach outlined here accurately captures the electronic coherence in the flux-flux correlation function that is responsible for the decreased rate in the inverted regime.


Health care costs associated with acute asthma: a prospective economic analysis.
To determine the direct and indirect costs associated with the care of acute asthma in an adult teaching hospital. A prospective, cost identification study. Patients aged 15 to 55 years presenting with acute asthma. Consecutive emergency department visits for asthma at Vancouver Hospital and Health Sciences Centre over six months were prospectively monitored. The duration of hospital stay, physician's care, laboratory procedures and medication given were recorded. Time lost from work or school was determined by follow-up telephone calls. The costs were calculated in 1997 Canadian dollars. One hundred and forty-nine patients made 195 emergency department visits over the six-month study. Twenty-eight (14%) of these visits led to hospital admissions. The total cost associated with the care of these patients was $250,570. The median (standard deviation in brackets) direct medical costs associated with each emergency department visit and hospital day were $324.00 (+/-52.00) per visit, and $677.00 (+/-76.00) per day, respectively. The present study provides a more accurate estimation of the operational cost of managing asthma in a teaching hospital setting than previous studies. The data presented in this study can be used in future cost effectiveness and cost-benefit studies in acute asthma, particularly where these studies involve specific intervention such as asthma education. More studies, which include children with asthma and patients treated outside of the hospital setting, are needed.


Effects of the Pythagorean Self Awareness Intervention on Childhood Emotional Eating and Psychological Wellbeing: a Pragmatic Trial.
Emotional eating is the tendency to regulate negative emotions (such as stress, depression and anxiety) through increased or unhealthy food intake. Emotion management, such as stress management could be an appropriate approach to prevent or control maladaptive eating behavior among children. This is a controlled pragmatic trial, testing the effects of Pythagorean Self Awareness Intervention (PSAI), a cognitive stress management program in a primary school setting. The eligibility criterion was being a 4th grade active pupil. Participants were randomly assigned to either the intervention group (n = 23) or the control group (n = 22). Self-report measures were used for the evaluation of various variables at the beginning and the end of the 8-week monitoring period. Descriptive and inferential statistic methods were used for the statistical analysis. At the end of the 8-week period pupils in the intervention group experienced statistically significant reduction in stress (SIC, p < 0.001), anxiety (STAIC-trait anxiety, p = 0.019, STAIC-state anxiety, p = 0.006), guilt (p < 0.001) and emotional eating (EES-C, p < 0.001) and an increase in Mediterranean diet quality (KIDMED, p = 0.001) and pride (p < 0.001). No statistically significant differences between the two groups were recorded regarding depression symptoms (CDI, p = 0.551) and shame (p = 0.120). PSAI had positive effects on a sample of primary school attendants' emotional eating and psychological state.


CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin.
In vivo, CCN2 (connective tissue growth factor) promotes angiogenesis, osteogenesis, tissue repair, and fibrosis, through largely unknown mechanisms. In vitro, CCN2 promotes cell adhesion in a variety of systems via integrins and heparin sulfate proteoglycans (HSPGs). However, the physiological relevance of CCN2-mediated cell adhesion is unknown. Here, we find that HSPGs and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade are required for adult human dermal fibroblasts to adhere to CCN2. Endogenous CCN2 directly binds fibronectin and the fibronectin receptors integrins alpha4 beta1 and alpha5 and syndecan 4. Using Ccn2-/- mouse embryonic fibroblasts, we show that loss of endogenous CCN2 results in impaired spreading on fibronectin, delayed alpha-smooth muscle actin stress fiber formation, and reduced ERK and focal adhesion kinase phosphorylation. These results suggest that a physiological role of CCN2 is to potentiate the ability of fibroblasts to spread on fibronectin, which may be important in modulating fibroblast adhesion to the provisional matrix during tissue development and wound healing. These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo.


Bevacizumab therapy for macular edema in central retinal vein occlusion: Long-term results.
There is no proven effective treatment for vision loss in central retinal vein occlusion (CRVO). Bevacizumab has been reported in small series with limited follow-up, to have a positive effect in reducing cystoid macular edema (CME) and improving vision in CRVO. To report long-term results with the use of bevacizumab in CRVO. Prospective interventional case series included 15 patients, serially evaluated with best corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography, and tonometry. Results were statistically analyzed. Mean follow-up was 12 +/- 3.6 months (range, 6-18 months); mean number of injections was 2.2 (range, 1-4) per patient. Statistically significant reduction of macular thickness (P < 0.001) was seen at six weeks (mean, 346 mu); three months (mean, 353 mu); six months (mean, 348 mu); and final follow-up (mean, 342 mu). Significant BCVA improvement was seen at six weeks (mean, 0.27 logMAR), three months (mean, 0.3 logMAR), three months (0.15 logMAR), and final follow-up (mean, 0.21 logMAR) (P = 0.009). Also, 73.3% patients had BCVA improvement at the last follow-up. Intravitreal bevacizumab is an effective treatment option for CME in CRVO patients. Reinjections at appropriate timing, based on the OCT findings, are important for better visual outcome.


The Transition From Ambrisentan to Macitentan in Patients With Pulmonary Arterial Hypertension: A Real-word Prospective Study.
Background: In a long-term event-driven trial, macitentan has demonstrated beneficial time to clinical worsening in patients with pulmonary arterial hypertension (PAH) and reduced PAH-related hospitalization rates compared with placebo. Macitentan is the most recently approved endothelin receptor antagonist (ERA) and is the first ERA that has shown efficacy for morbidity and mortality in PAH patients; therefore, patients and physicians may consider converting treatment from ambrisentan to macitentan. Our study evaluated the safety, efficacy, and quality of life in PAH patients transitioning from ambrisentan to macitentan. Methods: This was a real-world, prospective study with a 12-month follow-up. PAH patients who had received stable doses of ambrisentan for over 3 months, were within the World Health Organization Functional Class II/III, and 6-min walk distance ≥ of 250 m were enrolled. The study included a screening period, followed by a transition phase, after which patients entered the long-term follow-up. Clinical data and treatment satisfaction outcomes were collected to assess and monitor the safety and efficacy of the transition. The trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn; No. ChiCTR2000034898). Results: One hundred and fifty-seven enrolled PAH patients completed the transition. All criteria for continuous treatment transition were met by 145 patients (92.4%). Results showed improvements in exercise capacity, cardiac function, and hemodynamics compared with baseline. During the process, 4 patients discontinued macitentan due to adverse events. There was no statistical difference in the overall incidence of adverse events before and after the transition. Conclusion: Transition to macitentan from ambrisentan was successful and well-tolerated by PAH patients, and was associated with greater efficacy and satisfaction.


Heterotopic Ossification After Arthroscopic Procedures: A Scoping Review of the Literature.
Heterotopic ossification (HO) is the formation of bone in soft tissue resultant from inflammatory processes. Lesion formation after arthroscopic procedures is an uncommon but challenging complication. Optimal prophylaxis and management strategies have not been clearly defined. To present a scoping review of the pathophysiology, risk factors, diagnostic modalities, prophylaxis recommendations, and current treatment practices concerning HO after arthroscopic management of orthopaedic injuries. Scoping review; Level of evidence, 4. A scoping review via a PubMed search was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The search strategy was based on the terms "heterotopic ossification" AND "arthroscopy." The clinical outcomes review included studies on the arthroscopic management of orthopaedic injuries in which the primary subject matter or a secondary outcome was the development of HO. An analysis of the pathophysiology, diagnostic modalities, and management options was reported. A total of 43 studies (33,065 patients) reported on HO after hip arthroscopy, while 21 (83 patients) collectively reported on HO after arthroscopic procedures to the shoulder, elbow, knee, or ankle; however, management techniques were not standardized. Identified risk factors for HO included male sex and mixed impingement pathology, while intraoperative capsular management was not suggested as a contributing factor. Diagnosis of ossification foci was performed using radiography and computed tomography. The rate of HO after hip arthroscopy procedures approached 46% without prophylaxis, and administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreased occurrence rates to 4% but carries associated risks. External beam radiation has not been exclusively studied for use after arthroscopic procedures. HO is a known complication after arthroscopic management of orthopaedic injuries. NSAID prophylaxis has been demonstrated to be effective after hip arthroscopy procedures. Patients with persistent symptoms and mature lesions may be indicated for surgical excision, although variability is present in patient-reported outcome scores postoperatively.


A phase II study of gemcitabine plus cisplatin in previously untreated advanced ovarian cancer.
The primary objective was the evaluation of the effects of gemcitabine plus cisplatin on the overall response rate (ORR) of patients with advanced ovarian cancer; the secondary assessments included toxicity, time to progressive disease (TtPD) and the duration of response. Chemonaive patients with stage III/IV ovarian cancer received gemcitabine 1250 mg/m2 (d 1,8) and cisplatin 75 mg/m2 (d 1), every 21 days for a maximum of six cycles. Between March 1999 and June 2003, 28 patients (median age 52 years, range 23-72) had received chemotherapy. Of 26 assessable patients, the ORR was 57.7% (95% CI, 42.7%-83.6%) based on four complete responses and eleven partial responses, six patients experienced stable disease, while five had progressive disease. The median survival was 28.1 months (95% CI, 11.4-33.4 months), the median TtPD was 10.5 months (95% CI, 1.4-44.2 months) and the median duration of response was 24.3 months (95% CI, 12.3-33.4 months). The most common grade 3/4 toxicities were nausea/vomiting (15.2%) and neutropenia (10.7%). There was no grade 3 or 4 thrombocytopenia. Gemcitabine plus cisplatin exhibited activity in advanced ovarian cancer with an acceptable toxicity profile.


Cabozantinib Is Effective in Melanoma Brain Metastasis Cell Lines and Affects Key Signaling Pathways.
Melanomas have a high potential to metastasize to the brain. Recent advances in targeted therapies and immunotherapies have changed the therapeutical landscape of extracranial melanomas. However, few patients with melanoma brain metastasis (MBM) respond effectively to these treatments and new therapeutic strategies are needed. Cabozantinib is a receptor tyrosine kinase (RTK) inhibitor, already approved for the treatment of non-skin-related cancers. The drug targets several of the proteins that are known to be dysregulated in melanomas. The anti-tumor activity of cabozantinib was investigated using three human MBM cell lines. Cabozantinib treatment decreased the viability of all cell lines both when grown in monolayer cultures and as tumor spheroids. The in vitro cell migration was also inhibited and apoptosis was induced by cabozantinib. The phosphorylated RTKs p-PDGF-Rα, p-IGF-1R, p-MERTK and p-DDR1 were found to be downregulated in the p-RTK array of the MBM cells after cabozantinib treatment. Western blot validated these results and showed that cabozantinib treatment inhibited p-Akt and p-MEK 1/2. Further investigations are warranted to elucidate the therapeutic potential of cabozantinib for patients with MBM.


Serum trace metal levels in Alzheimer's disease and normal control groups.
To determine whether serum trace metals are related to abnormal cognition in Alzheimer's disease (AD). We studied serum lead (Pb), cadmium (Cd), mercury (Hg), and arsenic(As) in 89 patients with AD and in 118 cognitively normal individuals. We analyzed the results of the blood tests and the food intake. Serum Pb levels correlated with word list recall (P = .039) and word list recognition (P = .037). Without age adjustment, serum Cd levels (P = .044) were significantly higher in the AD group. After stratified age adjustment, the levels of selected trace metals did not differ significantly between AD and normal individuals. Food intakes regarding selected trace metals were not significantly different between the 2 groups. In this study, serum Pb, Cd, Hg, and As levels were not directly related to abnormal cognition in AD. Serum Pb levels were significantly negatively correlated with verbal memory scores.


Two different forms of homozygous sickle cell disease occur in Saudi Arabia.
Haematological, clinical and some molecular genetic features of homozygous sickle cell (SS) disease in Saudi Arabia have been compared in 33 patients from the Eastern Province (Eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian beta globin haplotype whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had more deletional alpha thalassaemia, higher total haemoglobin and fetal haemoglobin levels, and lower HbA2, mean cell volume, reticulocytes, and platelet counts. Clinically, Eastern patients had a greater persistence of splenomegaly, a more normal body build and greater subscapular skin fold thickness, and Western patients had more dactylitis and acute chest syndrome. Painful crises and avascular necrosis of the femoral head were common and occurred equally in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe consistent with the Benin haplotype suggesting an African origin.


[Resistance of Aujeszky disease viruses, present in the blood of pigs, to potassium thiosulphate and hydrogen chloride].
A trial was conducted to study the sensitivity of the Aujeszky disease virus, present in the blood of pigs, to the effect of two preservatives: potassium thiosulphate ( K2S2O5 ) and hydrogen chloride (HCl). The sensitivity of the virus was determined on rabbits infected with pig blood containing Aujeszky disease virus with different additions of the two preservatives. As found, 0.5% of K2S2O5 and 3% of HCl are concentrations fully sufficient for the inactivation of all the viruses present in the blood. Blood preserved in this way can be used for feeding purposes in pig stocks without the hazard of introducing Aujeszky disease in healthy stocks via the blood included in feed rations.


Organophosphate increases the sensitivity of human exocrine pancreas to acetylcholine.
Human pancreas contains two cholinesterase isoenzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In the present study, binding potency of two organophosphates for human cholinesterases were compared by the Ellman method. Echothiophate was found to have much greater potency than iso-OMPA for both cholinesterases. Using Karnovsky histochemical stains on human pancreatic tissue, the same results were confirmed. Dose-response studies with acetylcholine were done on viable pancreas fragments from nine human donors, without pancreatic disease (group I). Cold-preservation time was less than 30 h. Pancreas was minced into fragments, after the technique of Scheele and Palade, placed in Eagle's medium, and gassed with O2. Amylase release was measured by the Phadebas Method and corrected for basal release. There was a dose-dependent response to acetylcholine at 1 and 2 h, with a shift in peak amylase release to the left, when fragments were preincubated in 10(-4) M echothiophate. This indicated a 100-fold increase in sensitivity to acetylcholine. In three patients with chronic pancreatitis (Group II), there were variable patterns of response of amylase release to acetylcholine, and higher basal outputs. In Group III, prolonged storage conditions of over 40 h were tested for 4 pancreas donor tissues. There was no response to acetylcholine. These studies show that for up to 30 h cold storage, fragments of pancreas from human organ donors respond to acetylcholine in dose-dependent manner. An organophosphate, echothiophate (10(-4) M) which inhibits both cholinesterases, increases pancreatic sensitivity to acetylcholine, and these results are similar to findings from canine pancreas fragments, which also showed increased sensitivity.


Disparate effects of serum on basal and evoked NFAT activity in primary astrocyte cultures.
In astrocytes, the Ca(2+)-dependent protein phosphatase calcineurin (CN) strongly regulates neuro-immune/inflammatory cascades through activation of the transcription factor, nuclear factor of activated T cells (NFAT). While primary cell cultures provide a useful model system for investigating astrocytic CN/NFAT signaling, variable results may arise both within and across labs because of differences in culture conditions. Here, we determined the extent to which serum and cell confluency affect basal and evoked astrocytic NFAT activity in primary cortical astrocyte cultures. Cells were grown to either approximately 50% or >90% confluency, pre-loaded with an NFAT-luciferase reporter construct, and maintained for 16 h in medium with or without 10% fetal bovine serum (FBS). NFAT-dependent luciferase expression was then measured 5h after treatment with vehicle alone to assess basal NFAT activity, or with Ca(2+) mobilizers and IL-1 beta to assess evoked activity. The results revealed significantly higher levels of basal NFAT activity in FBS-containing medium, regardless of cell confluency. Conversely, evoked NFAT activation was significantly lower in serum-containing medium, with an even greater inhibition observed in confluent cultures. Application of 10% FBS to serum-free astrocyte cultures quickly evoked a roughly seven-fold increase in NFAT activity that was significantly reduced by co-delivery of neutralizing agents for IL-1 beta, TNFalpha, and/or IFN gamma, suggesting that serum occludes evoked NFAT activation through a cytokine-based mechanism. Together, the results demonstrate that the presence of serum and cell confluency have a major impact on CN/NFAT signaling in primary astrocyte cultures and therefore must be taken into consideration when using this model system.


Fasting blood glucose to HDL-C ratio as a novel predictor of clinical outcomes in non-diabetic patients after PCI.
Background The present study was to assess the prognostic value of fasting blood glucose to high-density lipoprotein cholesterol ratio (GHR) in non-diabetic patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods and results A total of 6645 non-diabetic patients from two independent cohorts, the CORFCHD-PCI study (n=4282) and the CORFCHD-ZZ (n=2363) study, were enrolled in Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI. Patients were divided into two groups according to the GHR value. The primary outcome included all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 36.51 ± 22.50 months. We found that there were significant differences between the two groups in the incidences of ACM (P=0.013) and CM (P=0.038). Multivariate Cox regression analysis revealed GHR as an independent prognostic factor for ACM. The incidence of ACM increased 1.284-times in patients in the higher GHR group (hazard ratio [HR]: 1.284 [95% confidence interval [CI]: 1.010-1.631], P<0.05). Kaplan-Meier survival analysis suggested that patients with high GHR value tended to have an increased accumulated risk of ACM. However, we did not find significant differences in the incidence of major adverse cardiac events, main/major adverse cardiovascular and cerebrovascular events (MACCE), stroke, recurrent myocardial infarction (MI) and bleeding events. Conclusions The present study indicates that GHR index is an independent and novel predictor of ACM in non-diabetic CAD patients who underwent PCI.


Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy.
We report on the ability to use polarized light to measure the particle size distribution of thin layers of polystyrene microspheres on top of a solid Intralipid phantom. The optical properties of each layer were adjusted to match the absorption and scattering properties of the epidermis (polystyrene layer) and dermis (Intralipid layer). Polarized light was used to discriminate between light scattered from the top layer of polystyrene and the lower layer of Intralipid. In this paper we also study the effect of the thickness of the top layer on the ability to reconstruct the polystyrene size distribution.


[Laparoscopic cystectomy of the ovary; results of a new technique].
The results of a prospective study of laparoscopic management of ovarian cysts are discussed. This technique of minimally invasive surgery was introduced at the department of Gynaecology of the Leiden University Medical Centre in 1991. Only premenopausal women with unilocular ovarian cysts smaller than 10 cm in diameter and with sonographically benign characteristics were included in this study. In a period of one year, 25 cystectomies and one ovariectomy were performed. 88% of the cysts were initially treated with hormone therapy. Mean age of the patients was 30 years (range: 21-54), average size of the cysts was 6 cm (range: 4-10) and mean operating time was 80 minutes (range: 35-120), there were no complications during operation or in the postoperative period. No laparotomies had to be performed. Three times (11.5%) pathological specimen examination revealed a corpus luteum cyst. The other 23 were non-functional cysts. No carcinoma was detected. The results of this minimally invasive surgery for removal of ovarian cysts are encouraging. Morbidity compared with the conventional cystectomy by laparotomy is low as appears from a shorter hospital stay and quicker recovery. Cystectomy of the ovary, compared with laparoscopic aspiration and fenestration, has a better therapeutic effect and the histological evaluation is more reliable. Persistent, unilocular ovarian cysts, which fulfill the criteria used in our study, are best treated by laparoscopic removal instead of laparotomy.


Physicochemical Characterization and Cytotoxicity Screening of a Novel Colloidal Nanogold-Based Phenytoin Conjugate.
A novel, colloidal nanogold-based drug delivery system for phenytoin, a well-known anti-epileptic drug with an enhanced efflux via P-glycoprotein, has been proposed in this study. The vital physical properties that would aid in predicting the biological interaction of this system were profiled using various techniques such as UV-Vis, DLS, and TEM in corroboration with theoretical calculations. It was significant to note that the binding of phenytoin to colloidal nanogold was strongly pH-dependent with the optimum at pH 5.5 and a consistently reproducible spectral shift. Analysis of the conjugate by FTIR revealed that the imide functional group of phenytoin mediated a dative coordinate bond to colloidal nanogold at the optimum pH. The amount of the drug bound to the gold was quantified to be 85.8±2.5% (w/v) by HPLC. Hypothetically, the surface charge of the conjugate could possibly imply charge-mediated uptake across the cell membrane. Further, the novel conjugate was screened for its cytotoxicity in two cell lines and the dosage range was identified. Subsequent development, thorough evaluations in suitable model systems, and the potential for bioimaging to track the payload would validate our hypothesis on the conjugate for better intracellular retention at the site of action, and thereby achieve the targeted delivery.


Isolation of the Bacillus subtilis cdd downstream region and analysis of genetic structure around the cdd vicinity.
A 310 bp EcoRI/HindIII fragment downstream of the Bacillus subtilis cdd gene was isolated from pSO52 which harbours the cdd gene and its vicinity, and was inserted into the pDIA5304. The hybrid vector pSO701 was integrated into the targeted locus of the B. subtilis chromosome and the cdd downstream region was rescued by furthermost BamHI walking toward the sigA locus. By sequencing and analyzing the intergenic region between the cdd and p23-dnaG-sigA operon from the selected clone pSO702, the era genes encoding glycyl tRNA synthetase alpha and beta chains with two unknown distal genes at both terminals were identified and mapped. The cdd was separated by 6,964 bp from the p23-dnaG-sigA operon. Combined data with an additional analysis of the cdd upstream from the sequenced 280 kb stretch in GenBank database (accession No. D84432) indicates that the revised gene order like hrcA-grpE-dnaK-dnaJ-phoH-dgk-cdd-era-tRNA( gly) synthetase alpha and beta-p23-dnaG-sigA-cccA with unidentified distal genes was established genetically on a counter clockwise orientation at 225 degrees of the linkage map.


Does Helicobacter pylori eradication therapy trigger or protect against Crohn's disease?
Helicobacter pylori (H. pylori) infection is involved in multiple gastrointestinal and extra-gastrointestinal disorders. This review focuses on possible link between H. pylori eradication and Crohn's disease (CD) which is a chronic inflammatory bowel disease (IBD). Fecal calprotectin and; to lesser extent; fecal lactoferrin are sensitive and specific markers for monitoring CD activity. Data about link between H. pylori eradication and CD are limited and inconclusive. The infection likely shifts equilibrium between T helper 1 (Th1) and Th2 immune responses to the Th2 pattern. In subjects genetically predisposed to CD (a Th1-related disease), H. pylori eradication increases Th1 proinflammatory cytokines causing development of CD. In contrast, clarithromycin and/or proton pump inhibitors that are used to eradicate H. pylori can suppress Th1 factors, and theoretically can protect against CD, but there are no data to support this supposition. This Th1/Th2 approach seems very simplistic. Another theory is that alterations in gut microbiota form "continuous antigenic stimulation" predisposing to IBD. H. pylori infection can inhibit such stimulation through activation of regulatory T cells, and thus eradication may predispose to CD. Probiotics weren't found useful in treatment of CD. The reported data about link between H. pylori eradication and CD are currently limited. Case reports, suggesting a positive association between both conditions, provide a very little evidence. On eradicating H. pylori in CD patients and/or patients with high risk for CD, patient counseling and follow-up in addition to measuring fecal calprotectin may help monitor CD activity. (Acta gastro-enterol. belg., 2016, 79, 349-354).


Depressive Symptoms, Disclosure, HIV-Related Stigma, and Coping Following HIV Testing Among Outpatients in Uganda: A Daily Process Analysis.
As efforts to end the HIV epidemic accelerate there is emphasis on reaching those living with undiagnosed HIV infection. Newly diagnosed individuals face a number of psychosocial challenges, yet we know little about depressive symptoms in the weeks immediately following diagnosis and how disclosure, coping, and other factors may affect short and longer-term depressive symptoms. Purposively sampled Ugandan outpatients completed structured interviews immediately prior to testing for HIV, daily for 28 days after receiving their test results, and at 3 and 6 months post-test. The sample included a total of 244 participants: 20 who tested HIV positive at baseline and who provided 342 daily data points, and 224 who tested HIV negative at baseline and who provided 4388 daily data points. We used linear mixed effects modeling to examine changes in depressive symptom scores over the 28 day daily interview period and predictors of depressive symptom scores and changes over time. Results from the mixed modeling revealed that while those diagnosed with HIV showed initially high depressive symptoms following diagnosis, their symptoms decreased significantly and on average fell below the cutoff for possible depression approximately 15 days after diagnosis. Among those who tested HIV-negative, on average their depressive symptoms were below the cutoff for possible depression and did not change over time. Among those diagnosed with HIV, disclosure, especially to a partner, on a particular day was associated with higher depressive symptoms that day. However, those who disclosed to their partner during the 28 days after diagnosis had significantly lower depression scores by the end of the 28 days as well as lower depression scores 3 and 6 months after diagnosis than did those who did not disclose to their partner during the 28 days after diagnosis. Scoring higher on HIV-related stigma on a particular day was associated with higher depressive symptoms that day and engaging in positive coping on a particular day was associated with lower depressive symptoms that day. Positive coping also accelerated the decrease in depressive symptoms over time. These data underscore the importance of timely disclosure to partners and suggest that regular depression screening after diagnosis and provision of mental health services could improve HIV care engagement and treatment outcomes.


Time reversal of flexural waves in a beam at audible frequency.
There has been very limited work on the application of time reversal to the propagation of audible frequency waves in mechanical structures. The present work concentrates on the application of time reversal to the focusing of audible range, flexural waves in an infinite beam, and to the detection of local heterogeneity in such a beam. Practical applications of time reversal of flexural waves in structures include vibration energy focusing, detection of vibratory or acoustic sources, and detection of defects in mechanical structures. An analytical model of flexural wave propagation in the beam as well as sensing and emission using piezoelectric transducers is presented. Time reversal experiments are conducted and compared to the model results in either a homogeneous beam or a beam with point mass heterogeneities. In the various situations tested, it is shown that time reversal effectively compensates the spreading in time of the impulse due to the dispersive propagation of flexural waves. One interesting aspect of this property is the generation of large amplitude impulsive responses in the beam using remote actuators. Finally, the "Decomposition de l'Operateur de Retournement Temporel" approach is examined to detect and localize point mass scatterers in the beam.


pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene.
Transcription of the ipnA gene encoding isopenicillin N synthetase, an enzyme of secondary metabolism, is under the control of the pH regulatory system in the fungus Aspergillus nidulans. External alkaline pH or mutations in pacC, the wide domain regulatory gene which mediates pH regulation, override carbon regulation of ipnA transcript levels, resulting in elevation of the levels of this message in sucrose broth. Strains carrying these mutations, which mimic growth at alkaline pH, produce higher levels of penicillins when grown in sucrose broth compared with the wild type strain grown under carbon derepressing conditions. ipnA transcription is regulated by carbon (C) source, but extreme mutations in creA (the regulatory gene mediating carbon catabolite repression) only slightly increase repressed transcript levels. Precise deletion of the only in vitro CreA binding site present in a region of the ipnA promoter involved in carbon regulation has no effect on ipnA expression. The levels of ipnA transcript in broths with acetate or glycerol as principal C sources are inconsistent with direct or indirect creA-mediated transcriptional control of the gene. We conclude that a second, creA-independent mechanism of carbon repression controls expression of this gene. All derepressing C sources tested result in alkalinization of the growth media. In contrast, all repressing C sources result in external acidification. Neither acidic external pH nor pal mutations, mimicking the effects of growth at acid pH, prevent carbon derepression, providing strong support for independent regulatory mechanisms, one mediating carbon regulation (via thus far unidentified genes) and another mediating pH regulation (through the pacC-encoded transcriptional regulator). External pH measurements suggest that these two independent forms of regulation normally act in concert. We propose that external alkalinity represents a physiological signal which triggers penicillin biosynthesis.


Evaluation of a brief parenting discussion group for parents of young children.
Although behavioral parenting programs are effective at treating child behavioral problems, a significant number of parents experiencing these problems do not receive help, and briefer, more cost-effective parenting interventions are lacking. This study aimed to evaluate the efficacy of a brief parenting discussion group. Sixty-seven parents were randomly assigned to either an intervention or waitlist control condition. Parents in the intervention condition took part in a 2-hour discussion group in which they were taught positive parenting strategies to prevent and manage their child's disobedience, and they received 2 follow-up telephone calls after the discussion group. Results showed that after intervention, there were reductions in child behavior problems and use of dysfunctional parenting and improvements in parental self-efficacy and the parenting experience for parents. These effects were maintained at 6-month follow-up. The results are promising because they show that a brief intervention can be minimally sufficient to improve child and parent outcomes for parents experiencing high levels of child behavior problems.


Formation and decay of the S3 EPR signal species in acetate-inhibited photosystem II.
A 230-G-wide EPR signal is induced in acetate-treated photosystem II by 30 s of illumination at 277 K followed by freezing under illumination to 77 K [MacLachlan, D. J., & Nugent, J. H. A. (1993) Biochemistry 32, 9772-9780]. This signal, referred to as the S3 EPR signal, has been interpreted to arise from an S2X+ species where X+ is an amino acid radical. Investigation of the factors responsible for the formation and decay of the S3 EPR signal reveals that the yield of the S3 EPR signal is strongly temperature-dependent and depends on the rate of oxidation of QA-. Quantitation of the number of centers contributing to the S3 EPR signal produced by the optimal continuous illumination times of 3 min at 250 K, 30 s at 273 K, and 5 s at 294 K gave values of 13, 38, and 49 +/- 3%, respectively. By using 5 s of illumination at 294 K to induce the S3 EPR signal, and then illumination at 200 K to reduce QA, both the S3 and QA(-)Fe EPR signals were induced in high yield. This result indicates that the S3 EPR signal does not arise from an acceptor-side species. When saturating laser flashes were used to induce the S3 EPR signal in a dark-prepared, dark-adapted, acetate-treated sample, the yield was small after one flash and close to maximal after two flashes. An EPR signal at g = 4.1 was observed to be formed at intermediate times during the decay of the S3 EPR signal in the dark; the rates of decay of the S3 EPR signal at 273 and 294 K corresponded to the rates of formation of the g = 4.1 EPR signal. These results, together with the flash results, indicate that two steps are involved in both the generation and decay of the S3 EPR signal. The rates of formation and decay of both the S3 and QA(-)Fe EPR signals were measured at 250, 273, and 294 K. A kinetic model is presented that accounts for these kinetic data and the yield of the S3 EPR signal.


Degenerative Lumbar Disc Disease: A Questionnaire Survey of Management Practice in India and Review of Literature.
Objective To identify the current management modalities practiced by neurosurgeons in India for degenerative lumbar disc disease. Materials and Methods Survey questionnaires were prepared in Google forms. It covered the following aspects of managing the lumbar disc pathology: (1) Demographic, institutional details, experience of surgeons, (2)choice of surgical procedures, (3) use of endoscopy and minimally invasive techniques, and (4) pre- and postoperative care. Responses obtained were entered in SPSS datasheet and analyzed. Results Of the 300 surveys sent, 80 were returned and response rate was 26.6%. But four surveys were highly incomplete and were discarded from the analysis. So, the study content is from the analysis of practices of 76 spinal surgeons working in different parts of the country. Majority of the spine surgeons ( n = 70) were neurosurgeons, while 6 were orthopaedic surgeons. Fifty-four were from urban area, 12 from semiurban area, and 10 from rural area. Forty-seven spine surgeons practiced in a teaching hospital. Total 73.6% of spine surgeons opted initial medical management. Sixty-three percent preferred microlumbar discectomy (MLD) and only eight neurosurgeons preferred minimally invasive techniques. None of the respondents used in situ fusion. Fifty-three percent of spine surgeons preferred early mobilization (first postoperative day). Fifty-nine percent preferred to follow-up patients clinically and opted for magnetic resonance imaging only when recurrence or infection was suspected. The institutional nature (government teaching, government nonteaching, private teaching, and private nonteaching) and location of the hospital (urban/semiurban/rural) were found to be influencing the preferred surgical technique, trial of medical management, or postoperative care and complications. Considerable practice variations exist for medical and perioperative management. Conclusion The preferred treatment of choice of majority was MLD, although laminectomy and discectomy were still used by many. Consensus lacks in the operative, perioperative, and postoperative management of degenerative disc disease. Present survey points toward the importance of making management guidelines for this common spinal surgical entity.


Thoracoscopic diagnosis of pleurolithiasis after laparoscopic cholecystectomy.
We describe a patient with right pleuritic chest pain and an enlarging exudative pleural effusion four months after laparoscopic cholecystectomy. Several radiographic imaging procedures and thoracenteses were nondiagnostic. Thoracoscopy, however, revealed bilious concretions in the parietal pleura. Thoracoscopic drainage, lysis of adhesions, and antibiotic treatment of a Klebsiella pneumoniae pleuritis resulted in relief of symptoms.


Position of crown margin in relation to the tooth preparation line.
It is of paramount importance to have the crown margin precisely adjusted to the preparation lines of the teeth in order to reduce the bacterial plaque which is known to cause inflammations of the periodontal tissues. The aim of the present study was to determine the position of the crown margin in relation to the preparation line in axial and transversal directions for various types of crowns. The study included 89 extracted teeth with the attached restorative construction (crown or crown bridge) divided into groups by types of tooth and construction. Each tooth was cleaved into two halves along its axial plane obtaining thus two crown surfaces (a total of 178). Each half of the cleft tooth was embedded in fast-polymerising resin, then sections were made which were studied using a standard ocular measure scale at a magnification of 20x. The position of the crown margin in relation to the preparation border in axial direction was defined as either a precise fit, or longer, or shorter, and in transversal direction--as a precise fit, reverse shoulder or wider. The results were analysed statistically by analysis of variance and alternative analysis. Longer crown margins were seen more frequently in the axial direction (57 to 72% of all cases) but were prevalent in the cast veneer crowns. Wider crowns were found to be more frequent transversally (86 to 97% of all cases), but were prevalent in swaged crowns. Precise fit of the crown margin with the preparation line is very rare. The crowns that are most often fabricated in our country are wider crowns followed by crowns with longer crown margin. The discrepancies in axial and transversal directions are a significant plaque retention factor of iatrogenic nature that is conducive to the development of periodontal diseases.


Control of A-system amino acid transport by a second regulatory gene R2 in Chinese hamster ovary cells CHO-K1 and the possible connection of this gene with insulin activity.
Evidence based on a study of alanine-resistant (Alar), constitutive mutants of CHO-K1 cells and the conditions that favor stimulation of the A system of amino acid activity supports the model that the A system of amino acid transport in these cells is repressible and under negative control of regulatory gene R1. In this study, we show that mutant Alar6, when grown under conditions of repression, has an A system of amino acid transport activity similar to that of the derepressed parental cell line, CHO-K1 (wild type) and of the fully constitutive mutant in gene R1, Alar4. However, the A system of Alar6 is further derepressible. The Vmax for proline transport through this system in mutant Alar6 is four times that of the parental culture, with no significant change in Km. Analysis of hybrids produced by crossing mutant Alar6 with the parental culture and with Alar4 shows that mutant Alar6 is recessive to wild type and complements mutant Alar4. Although the amino acid transport A system of CHO-K1 is stimulated by insulin, mutant alar6 is not stimulated by insulin. These results support the hypothesis that mutant alar6 results from mutation in another regulatory gene, R2, that, in conjunction with gene R1, negatively controls the expression of a structural gene for the A-system transport. Evidence also indicates that R2 gene product is not responsive to amino acids and that insulin stimulation of the A system may result from insulin inactivation of this repressor.


Cord factor detection and macroscopic evaluation of mycobacterial colonies: an efficient combined screening test for the presumptive identification of Mycobacterium tuberculosis complex on solid media.
The rapid differentiation between Mycobacterium tuberculosis and nontuberculous mycobacteria is fundamental for patients co-infected with tuberculosis and HIV. To that end, we use two methods in our laboratory: detection of cord factor and PCR-restriction enzyme analysis (PRA). The objective of this study was to evaluate the accuracy of a screening test on solid medium as a rapid method for the presumptive identification of M. tuberculosis complex, considering costs and turnover time. A total of 152 strains were submitted to a combined screening test, consisting of the detection of cord factor under microscopy (Ziehl-Neelsen staining) and evaluation of the macroscopic aspect of colonies, as well as to PRA, which was used as the gold standard. Costs were estimated by calculating the price of all of the materials needed for each test. The overall accuracy of cord factor detection alone was 95.4% (95% CI: 90.7-98.1%), and that of the combined screening test was 99.3% (95% CI: 96.4-100%). Cord factor detection costs US$ 0.25, whereas the PRA costs US$ 7.00. Results from cord factor detection are ready in 2 days, whereas PRA requires 4 days to yield results. The presumptive identification of M. tuberculosis using the macroscopic evaluation of colonies combined with cord factor detection under microscopy is a simple, rapid and inexpensive test. We recommend the combined screening test to rapidly identify M. tuberculosis in resource-poor settings and in less well-equipped laboratories while awaiting a definite identification by molecular or biochemical methods.


Fabrication and Characterization of Diclofenac Sodium Loaded Hydrogels of Sodium Alginate as Sustained Release Carrier.
The aim of the current study was to fabricate naturally derived polymer based hydrogels for controlled release of diclofenac sodium (DS) for a long duration of time. In this research work, sodium alginate-co-poly(2-acrylamido-2-methyl propane sulphonic acid) (SA-co-poly(AMPS)) hydrogels were prepared by the free radical polymerization technique, where sodium alginate (SA) and 2-acrylamido-2-methyl propane sulphonic acid (AMPS) were used as the polymer and monomer while ammonium peroxodisulfate (APS) and N,N'-Methylene bisacrylamide (MBA) were used as the initiator and cross-linker, respectively. A swelling study was performed to determine the swelling index of developed hydrogels in both acidic (pH 1.2) and basic (pH 7.4) media and pH-independent swelling was observed due to the presence of AMPS. An in vitro release study was conducted to evaluate the percentage of drug released, and a high release of the drug was found at the higher pH of 7.4. Sol-gel analysis was performed to analyze the crosslinked and uncrosslinked part of the hydrogels, and results showed a rise in gel fraction as the composition of SA, AMPS and MBA increased while the sol fraction decreased and vice versa. This work demonstrated a potential for sustained delivery of diclofenac sodium by employing various concentration of SA, AMPS and MBA.


Dyslipoproteinaemia in children with or without family history of premature myocardial infarction.
In order to examine the relationship between certain risk factors for atherosclerosis and family history of myocardial infarction, we compared a group of children (n = 51) whose parents had survived myocardial infarction (n = 34) with a control group of children (n = 90) with a negative family history of atherosclerosis (62 parents). The study revealed a surprising fact that 26.7% of control children had hypercholesterolaemia compared to 15.7% incidence in "risk" children. "Risk" children differed from the controls most in the apo-A-I levels and a higher risk index expressed by the proportion of apo-B:apo-A-I (1.22, 1.34 g/l, p = 0.001, 0.58, 0.46, p = 0.05, respectively). Since the most frequent primary hyperlipoproteinaemia in myocardial infarction families was familial combined hyperlipoproteinaemia, we assume that this condition may be presented in affected children by an unfavourable proportion of apolipoproteins of the lipoprotein classes.


Reduction of obliterative bronchiolitis (OB) by prolyl-hydroxylase-inhibitors activating hypoxia-inducible transcription factors in an experimental mouse model.
Obliterative bronchiolitis (OB) is the major limiting factor for long-term survival after lung transplantation. As previously shown, donor treatment with a PHD-inhibitor activating hypoxia-inducible transcription factors (HIFs) prevents graft injury both in an allogenic kidney and aortic allograft transplant model. The aim of this study was to investigate the effect of HIF activation with a PHD-inhibitor on the development of OB. Fully MHC-mismatched C57BL/6 (H-2b) donor tracheas were orthotopically transplanted into CBA/J (H-2k) recipients. Donor animals received a single dose of PHD-inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) (40mg/kg i.p.) or vehicle control 4h before transplantation. Transplanted tracheas were harvested 14 or 30days after transplantation and were analyzed by histology, by immunofluorescence and by rtPCR for mRNA expression. Donor pre-conditioning with ICA resulted in HIF accumulation and induction of HIF target genes: HO-1, VEGF, MIF, TGFβ, and EpoR, which persisted during different times of ischemia. Grafts of vehicle treated controls showed substantially more luminal obliteration on postoperative day 30 in contrast to groups pre-treated with ICA [luminal obliteration 29.2±5% (ICA) vs. 36.7±8% (control), p<0.01]. We found significantly lower expression of TNFα, PDGFß, MCP-1, E-selectin, and ICAM-1 14days after ICA premedication. In addition ICA pre-treated groups revealed decreased T-cell and macrophage infiltration in tracheal grafts on days 30 after transplantation (p<0.05). Pre-treatment with ICA effectively reduced obliterative bronchiolitis. Our data suggest that activation of hypoxia-inducible transcription factors (HIFs) and thereby adaptation to low oxygen prevents the development of OB and allograft injury. Pharmaceutical inhibition of PHDs appears to be an attractive strategy for organ preservation that deserves further clinical evaluation.


Expansion of Human Limbal Epithelial Stem/Progenitor Cells Using Different Human Sera: A Multivariate Statistical Analysis.
Transplantation of human cultured limbal epithelial stem/progenitor cells (LESCs) has demonstrated to restore the integrity and functionality of the corneal surface in about 76% of patients with limbal stem cell deficiency. However, there are different protocols for the expansion of LESCs, and many of them use xenogeneic products, being a risk for the patients' health. We compared the culture of limbal explants on the denuded amniotic membrane in the culture medium-supplemental hormone epithelial medium (SHEM)-supplemented with FBS or two differently produced human sera. Cell morphology, cell size, cell growth rate, and the expression level of differentiation and putative stem cell markers were examined. Several bioactive molecules were quantified in the human sera. In a novel approach, we performed a multivariate statistical analysis of data to investigate the culture factors, such as differently expressed molecules of human sera that specifically influence the cell phenotype. Our results showed that limbal cells cultured with human sera grew faster and contained similar amounts of small-sized cells, higher expression of the protein p63α, and lower of cytokeratin K12 than FBS cultures, thus, maintaining the stem/progenitor phenotype of LESCs. Furthermore, the multivariate analysis provided much data to better understand the obtaining of different cell phenotypes as a consequence of the use of different culture methodologies or different culture components.


The politics of school-based clinics: a community-level analysis.
School-based primary health care, supported as an effective means for addressing the health needs of youth, also tends to be perceived as controversial partly due to opposition by national and state level organizations. This investigation used case studies of four selected school-based clinic (SBC) sites, and of one community in which an SBC was disputed, to investigate the existence of organized opposition, how proponents contended with opposition, and effects of organized opposition on SBC approval and implementation. Four sites experienced opposition affiliated with larger conservative organizations. Opponents' strategies and proponents counterstrategies were identified. Effects ranged from limiting SBC services to preventing an SBC's establishment. Proponents, consisting largely of medical and school administrative professionals, overcame opposition through strategies to increase public awareness about youth health issues and to demonstrate public support in the face of expressed opposition. Implications for planning and implementing potentially controversial programs are offered.


Gain and dispersion focusing in a high gain laser.
The transverse modes of a laser resonator containing a medium with a strong radial gain profile differ greatly from the modes of a similar resonator containing a low gain medium. Focusing and defocusing effects result from the gain profile and from the associated dispersion profile. The dispersion focusing causes an asymmetry in the power output as the laser is tuned across the gain line. The theory has been verified using a high gain 3.51-micro xenon laser.


Possibilities to Use Physical Simulations When Studying the Distribution of Residual Stresses in the HAZ of Duplex Steels Welds.
Dual phase steels combine very good corrosion resistance with relatively high values of mechanical properties. In addition, they can maintain good plastic properties and toughness at both room temperature and lower temperatures as well. Despite all the advantages mentioned above, their utility properties can be reduced by technological processing, especially by the application of the temperature cycles. As a result, in the material remain residual stresses with local stress peaks, which are quite problematic especially during cyclic loading. Moreover, determining the level and especially the distribution of such residual stresses is very difficult for duplex steels both due to the structure duality and in light of the very small width of the heat-affected zone (HAZ). This is why the paper presents the possibilities of using physical simulations to study the effect of temperature cycles in residual stresses' magnitude and distribution, where it is possible to study the HAZ in more detail as well as on a much larger sample width due to the utilization of special samples. In the thermal-mechanical simulator Gleeble 3500, temperature-stress cycles were applied to testing samples, generating stress fields with local peaks in the testing samples. In addition, the supplied steel X2CrMnNiN21-5-1 had different phase rations in the individual directions. Therefore, as the residual stresses were measured in several directions and at the same time, it was possible to safely confirm the suitability of the used measurement method. Moreover, the effect of the stress and strain on the change of partial phases' ratios was observed. It has been experimentally confirmed that annealing temperatures of at least 700 °C are required to eliminate local stress peaks after welding. However, an annealing temperature of 550 °C seems to be optimal to maintain sufficient mechanical properties.


Cochlear Implant in Patients with Intralabyrinthine Schwannoma without Tumor Removal.
(1) Background: Schwannomas of the vestibulocochlear nerve are benign, slow-growing tumors, arising from the Schwann cells. When they originate from neural elements within the vestibule or cochlea, they are defined as intralabyrinthine schwannomas (ILSs). Cochlear implant (CI) has been reported as a feasible solution for hearing restoration in these patients. (2) Methods: Two patients with single-sided deafness (SSD) due to sudden sensorineural hearing loss and ipsilateral tinnitus were the cases. MRI detected an ILS. CI was positioned using a standard round window approach without tumor removal. (3) Results: The hearing threshold was 35 dB in one case and 30 dB in the other 6 mo after activation. Speech audiometry with bisillables in quiet was 21% and 27% at 65 dB, and the tinnitus was completely resolved or reduced. In the localization test, a 25.9° error azimuth was obtained with CI on, compared to 43.2° without CI. The data log reported a daily use of 11 h and 14 h. In order to not decrease the CI's performance, we decided not to perform tumor exeresis, but only CI surgery to restore functional binaural hearing. (4) Conclusions: These are the sixth and seventh cases in the literature of CI in patients with ILS without any tumor treatment and the first with SSD. Cochlear implant without tumor removal can be a feasible option for restoring binaural hearing without worsening the CI's performance.


Carbonic anhydrase inhibitors: Schiff's bases of aromatic and heterocyclic sulfonamides and their metal complexes.
Schiff's bases were obtained from aromatic/heterocyclic sulfonamides and amino-sulfonamide derivatives, such as sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide and 5-amino-1,3,4-thiadiazole-2-sulfonamide. Metal complexes of some of these Schiff's bases, incorporating Zn(II), Co(lI), Ni(II) and Cu(II) ions, were also prepared and tested as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more specifically the red blood cell isozymes I and II. The Schiff's bases behaved as medium potency CA I and CA II inhibitors, whereas their metal complexes showed a highly enhanced potency, with several low nanomolar CA II inhibitors detected.


Sizing up ethanol-induced plasticity: the role of small and large conductance calcium-activated potassium channels.
Small (SK) and large conductance (BK) Ca(2+)-activated K(+) channels contribute to action potential repolarization, shape dendritic Ca(2+)spikes and postsynaptic responses, modulate the release of hormones and neurotransmitters, and contribute to hippocampal-dependent synaptic plasticity. Over the last decade, SK and BK channels have emerged as important targets for the development of acute ethanol tolerance and for altering neuronal excitability following chronic ethanol consumption. In this mini-review, we discuss new evidence implicating SK and BK channels in ethanol tolerance and ethanol-associated homeostatic plasticity. Findings from recent reports demonstrate that chronic ethanol produces a reduction in the function of SK channels in VTA dopaminergic and CA1 pyramidal neurons. It is hypothesized that the reduction in SK channel function increases the propensity for burst firing in VTA neurons and increases the likelihood for aberrant hyperexcitability during ethanol withdrawal in hippocampus. There is also increasing evidence supporting the idea that ethanol sensitivity of native BK channel results from differences in BK subunit composition, the proteolipid microenvironment, and molecular determinants of the channel-forming subunit itself. Moreover, these molecular entities play a substantial role in controlling the temporal component of ethanol-associated neuroadaptations in BK channels. Taken together, these studies suggest that SK and BK channels contribute to ethanol tolerance and adaptive plasticity.


[Tobacco use among paramedical students in Tunis].
To assess smoking habits among Tunisian paramedical students, and their attitudes and knowledge about smoking. During the first quarter of the school year 2002-2003 we investigate 1288 paramedical students of the College of Sciences and Techniques of the Health in Tunis. The smoker was the student who declare to smoke daily or by occasionally at the time of the survey. About three quarters of the students (77,2 %) were female and half of them was less than 20 years old. Smokers were those who smoked daily or occasionally. The prevalence of smoking was weak but it was 10 fold higher in male than in female (35,5% vs 3,5%) The rate of the ex-smokers was 4,1 %. Progress in studies does not affect smoking behaviour. The knowledge of tobacco induced diseases was generally good. However, there was substantial underestimation of tobacco contribution to causing bladder cancer, coronary artery disease and peripheral vascular disease. The study evidences insufficient awareness of medical students about their responsibilities for heath education and prevention. It is recommended to improve tobacco control educational programs at the paramedical students with elaboration of practical smoking cessation trainings.


[Mechanism of inhibitory action of sodium ferulate on liver lipid peroxidation in mice].
The study has shown that sodium ferulate (SF) significantly inhibits the rise of liver lipid peroxides MDA content, alleviates the depletion of hepatic GSH pond, and reverses the decline of GST, GSH-Px levels in ethanol treated mice. The results indicate this inhibitory action of SF is related to diminishing the generation of oxygen free radicals by stabilizing GSH and related enzyme levels.


The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium.
Interactions of metastatic cancer cells with vasculatory endothelium are critical during early stages of cancer metastasis. Understanding the molecular underpinnings of these interactions is essential for the development of new efficacious cancer therapies. Here we demonstrate that cancer-associated carbohydrate T antigen plays a leading role in docking breast and prostate cancer cells onto endothelium by specifically interacting with endothelium-expressed beta-galactoside-binding protein, galectin-3. Importantly, T antigen-bearing glycoproteins are also capable of mobilizing galectin-3 to the surface of endothelial cells, thus priming them for harboring metastatic cancer cells. The T antigen-mediated, tumor-endothelial cell interactions could be efficiently disrupted using synthetic compounds either mimicking or masking this carbohydrate structure. High efficiency of T antigen-mimicking and T antigen-masking inhibitors of tumor cell adhesion warrants their further development into antiadhesive cancer therapeutics.


Physical activity in the therapy of overweight and obesity in children and adolescents. Needs and recommendations for intervention programs.
Overweight and obesity may lead to serious health problems, and negatively affect everyday functioning in physical, psychological and social spheres. The high prevalence of overweight and obesity in children and adolescents constitutes a huge public health burden. One way of designing and implementing behavioral interventions aimed at the reduction of adipose tissue is to promote physical activity. In this review we present recommendations regarding the planning, monitoring and implementation of intervention programs involving controlled physical activity. Considering specific individual determinants and needs in terms of improving children's health, physical condition and physical performance, we have separately discussed recommendations for interventions involving aerobic and anaerobic exercises with moderate and high intensity, including high-intensity interval training (HIIT). We have also focused on the role of resistance training. Finally, we have emphasized that children and adolescents with overweight or obesity should also be motivated to undertake activities referred to as non-exercise activity thermogenesis (NEAT).


Connectivity Measures Differentiate Cortical and Subcortical Sub-Acute Ischemic Stroke Patients.
Brain lesions caused by cerebral ischemia lead to network disturbances in both hemispheres, causing a subsequent reorganization of functional connectivity both locally and remotely with respect to the injury. Quantitative electroencephalography (qEEG) methods have long been used for exploring brain electrical activity and functional connectivity modifications after stroke. However, results obtained so far are not univocal. Here, we used basic and advanced EEG methods to characterize how brain activity and functional connectivity change after stroke. Thirty-three unilateral post stroke patients in the sub-acute phase and ten neurologically intact age-matched right-handed subjects were enrolled. Patients were subdivided into two groups based on lesion location: cortico-subcortical (CS, n = 18) and subcortical (S, n = 15), respectively. Stroke patients were evaluated in the period ranging from 45 days since the acute event (T0) up to 3 months after stroke (T1) with both neurophysiological (resting state EEG) and clinical assessment (Barthel Index, BI) measures, while healthy subjects were evaluated once. Brain power at T0 was similar between the two groups of patients in all frequency bands considered (δ, θ, α, and β). However, evolution of θ-band power over time was different, with a normalization only in the CS group. Instead, average connectivity and specific network measures (Integration, Segregation, and Small-worldness) in the β-band at T0 were significantly different between the two groups. The connectivity and network measures at T0 also appear to have a predictive role in functional recovery (BI T1-T0), again group-dependent. The results obtained in this study showed that connectivity measures and correlations between EEG features and recovery depend on lesion location. These data, if confirmed in further studies, on the one hand could explain the heterogeneity of results so far observed in previous studies, on the other hand they could be used by researchers as biomarkers predicting spontaneous recovery, to select homogenous groups of patients for the inclusion in clinical trials.


Prevalence of dental caries in 4- to 5-year-old children partly explained by presence of salivary mutans streptococci.
The correlation between dental caries and the number of oral mutans group streptococci (ms) present has been shown to be weak. The aim of this investigation was to study associations between caries experience (decayed, missing, and filled surfaces [dmfs]) and the number of ms in stimulated saliva, with emphasis on the level of disease and the confounding effect of regular intake of sweets, the presence of salivary lactobacilli, and oral hygiene. In some 2,700 4- to 5-year-old South African children of different ethnic origins, caries was diagnosed on the basis of World Health Organization criteria and saliva samples were analyzed for ms after cultivation on mitis salivarius-bacitracin agar and for lactobacilli by using the Dentocult kit. Oral hygiene was scored on the basis of the Greene and Vermillion simplified debris index, while data on intake of sweets were derived from extensive interviews. Pearson's coefficient of correlation was computed, and multiple regression analysis was performed to correct for confounding factors. The distribution of the children in the eight caries classes was strongly associated with the ms class (P < 0.001), with those in the lower ms classes generally having low dmfs scores and those in the higher ms classes having dmfs scores distributed over the whole range. The r value for the two variables was 0.25 for the total material; this was reduced to 0.18 by correction for confounding factors. The corresponding values for children with caries were 0.21 and 0.17, for those in the 1 to 6 dmfs interval they were 0.07 and 0.03, and for those in the 7 to 81 dmfs interval they were 0.16 and 0.14. The data imply that the explanatory values for ms, those for the lower caries interval not counted, ranged from 6 to 2%. The unexpected results for children with caries might be due to their distribution pattern. It is concluded that there is a need for reevaluation of ms as a risk factor in dental caries.


Brain metabolic DNA: recent evidence for a mitochondrial connection.
This review highlights recent data concerning the synthesis of brain metabolic DNA (BMD) by cytoplasmic reverse transcription and the prompt acquisition of the double-stranded configuration that allows its partial transfer to nuclei. BMD prevails in the mitochondrial fraction and is present in presynaptic regions and astroglial processes where it undergoes a turnover lasting a few weeks. Additional data demonstrate that BMD sequences are modified by learning, thus indicating that the modified synaptic activity allowing proper brain responses is encoded in learning BMD. In addition, several converging observations regarding the origin of BMD strongly suggest that BMD is reverse transcribed by mitochondrial telomerase.


Review article: Safety profile of propofol for paediatric procedural sedation in the emergency department.
The use of propofol for paediatric procedural sedation (PPS) is increasing because of its favourable pharmacodynamic profile. Its paediatric use has been limited in some ED (emergency departments) because of the perceived high rate of serious adverse events in comparison with other sedation agents. A systematic literature review of propofol use for PPS outside the operating theatre environment from 1966 to 2008 was carried out to profile the adverse event rate in comparison with other procedural sedation agents. Sixty studies with a total of 17,066 paediatric propofol sedations in a variety of hospital settings were identified. The incidence of complications were: desaturation 9.3%, apnoea 1.9%, assisted ventilation 1.4%, hypotension 15.4%, unplanned intubation 0.02%, emesis post procedure 0.14%, laryngospasm 0.1% and bradycardia 0.1%. There were no reported incidents of aspiration or emesis during sedation and there were no deaths associated with procedural propofol sedation. The use of propofol for PPS is associated with a low rate of minor adverse events that are all reversible with minimal intervention and do not produce long-term sequelae and occur at similar rates to minor adverse events experienced with other sedation agents. Major adverse events with propofol sedation are extremely rare and appropriate patient and procedure selection would decrease these risks further. The increasing use of propofol for ED PPS is supported by the current evidence because of its comparable adverse event rate to other agents.


Validation and comparison of five preference-based measures among age-related macular degeneration patients: evidence from mainland China.
To compare the psychometric properties of five preference-based measures (PBMs) among patients with age-related macular degeneration (AMD) in mainland China, including three health-related quality of life (HRQoL) measures [the 15D, the Assessment of Quality of Life (AQoL)-7D, and EQ-5D-5L] and two capability wellbeing measures [the ICEpop CAPability measure for Adults (ICECAP-A) and ICECAP measure for Older people (ICECAP-O)]. A convenience sampling framework was used to successively recruit inpatients with AMD who attended a large ophthalmic hospital in Jinan, China. Psychometric properties (known-group validity, concurrent validity, and sensitivity) were assessed. The agreements between PBMs were reported. A valid sample of 210 AMD inpatients (median duration: 12 months) was analyzed. Overall, the AQoL-7D had the best performance based on the psychometric tests been conducted. Sufficient evidence was found on psychometric properties for other 2 preference-based HRQoL measures. The ICECAP-A outperformed ICECAP-O on known-group validity and concurrent validity whereas opposite results were found on sensitivity. The Bland-Altman plots indicate that there was no pair of PBMs that could be used interchangeably. The AQoL-7D had shown better psychometric properties than other four PBMs based on Chinese AMD inpatients. The EQ-5D-5L demonstrated sufficient psychometric properties and given the availability of a Chinese-specific tariff and the recommendations of China guidelines for pharmacoeconomic evaluations, it may be prioritized to be used in China. Capability wellbeing instruments could also be considered given they provide information that goes beyond health. Further evidence on responsiveness and reliability for all five PBMs among AMD patients is required.


18,19-Dihydroxydeoxycorticosterone, a new metabolite produced from 18-hydroxydeoxycorticosterone by cytochrome P-450(11) beta. Chemical synthesis and structural analysis by 1H NMR.
A new metabolite was produced from 18-hydroxydeoxycorticosterone by the cytochrome P-450(11) beta linked hydroxylase system purified from bovine adrenocortical mitochondria. It was identified as 18,19-dihydroxydeoxycorticosterone by chemical synthesis on the basis of high-performance liquid chromatography, gas chromatography-mass spectrometry, and proton nuclear magnetic resonance (1H NMR) spectroscopy, and detailed structural analysis of it was performed by 1H NMR spectroscopy. The methylene protons at the C-19 position of the steroid were nonequivalent and coupled with each other, having a coupling constant of 10.6 Hz. These protons had different coupling constants, 6.7 and 3.4 Hz, for the hydroxy proton at the C-19 position. Due to these couplings, the signals of the methylene protons were observed around 3.9 ppm as two double doublets. The methylene protons at the C-21 position were also nonequivalent, having a coupling constant of 11.1 Hz. Coupling constants between these methylene protons and the hydroxy proton at the C-21 position were 8.2 and 4.2 Hz, respectively. These results indicate that both hydroxymethyl groups at the C-19 and C-21 positions do not freely rotate in chloroform solution. The signals of hydroxy protons at the C-19 and C-21 positions were found at 1.25 and 1.87 ppm, respectively, by means of decoupling of the corresponding methylene protons. The hydroxy proton at the C-18 position was found to scarcely couple with any proton. This fact suggests that this hydroxy group is linked to the C-20 position, making a hemiketal bridge between the C-18 and the C-20.


Use of eye care and associated charges among the Medicare population: 1991-1998.
To examine trends in the utilization and cost of eye care in the Medicare population. Data were obtained from fee-for-service physician claims (Part B) from a 5% sample of Medicare beneficiaries 65 years and older. Use of eye care services and procedures, frequency of ocular diagnoses, and allowed charges were compared for each year from 1991 through 1998. The proportion of beneficiaries receiving eye care increased from 41.4% to 48.1% during the 8-year period. Part B charges attributable to eye care decreased from 12.5% to 10.4%, with annual inflation-adjusted charges per beneficiary decreasing from 235 dollars to 176 dollars (1998 dollars). The proportion of beneficiaries with cataract-related claims increased from 23.4% to 27.3%, accounting for approximately 60% of eye care charges each year; beneficiaries with retinal disease claims increased from 7.8% to 11.4%, capturing 15.4% of eye care charges in 1998, up from 10.7% in 1991; and beneficiaries with glaucoma claims increased from 6.8% to 9.5%, accounting for nearly 10% of eye care charges each year. The proportion of the Medicare population receiving eye care increased between 1991 and 1998. Nevertheless, eye care costs did not increase, primarily because of constraints in charges associated with the management of cataract.


Triboelectric Energy Harvesting of the Superhydrophobic Coating from Dropping Water.
In this paper, the superhydrophobic coating was prepared by spraying the composites of fluorocarbon emulsion and nanosized silica on the conductive glass sheet for the triboelectric energy harvesting from water droplets. The low surface energy of fluorine in the fluorocarbon emulsion and nanosilica renders the coating with the static contact angle and sliding angle of 156.2° and 6.74°, respectively. The conductive aluminum tape was attached on the surface of the superhydrophobic coating to complete the circuit constituted with the aluminum electrode, charged superhydrophobic coating, and the conductive glass sheet. During the contact electrification with the bouncing water droplet, the superhydrophobic coating with the aluminum electrode can obtain the electric energy with an open-circuit voltage of 20 V and short-circuit current of 4.5 μA, respectively. While the control device only produced an open-circuit voltage of 0.2 V. The generated power by one drop was enough to light up 16 commercial LEDs. Results demonstrate that the fluorocarbon/silica composite superhydrophobic coating is potentially a strong candidate for scavenging energy in sliding mode from raindrops.


[Characteristics and expression of Mip5, a novel gene associated with myocardial ischemia/reperfusion in rats].
To determine the characteristics of a novel gene Mip5 (GenBank accession number AY553870) and its expression under physiological and pathological conditions. The characteristics of Mip5 were analyzed by bioinformatic programs including BLAST, spidey, psort, ClustalW and so on. RT-PCR was performed to detect Mip5 expression. Bioinformatic analysis showed that Mip5 gene lied in the 13th chromosome and contained 8 exons and 7 introns, its open reading frame contained 909 bp and its protein production was 302 amino acid residues including 6 kelth domains. Under normal conditions, MIP5 expressed abundantly in the heart, brain and kidney, but its expression could not be detected in the liver and muscle. Expression of Mip5 gene was increased significantly after ischemia-reperfusion compared with the sham groups, and reached its peak at 3 h and recovered at 12 h after the reperfusion. Conclusion Mip5 gene is a novel gene containing a putative open reading frame of 302 amino acids residues and may play an important role in rat cardiomyocytes suffering ischemia processing.


Minimum Free Energy Pathways of Reactive Processes with Nudged Elastic Bands.
The determination of minimum free energy pathways (MFEP) is one of the most widely used strategies to study reactive processes. For chemical reactions in complex environments, the combination of quantum mechanics (QM) with a molecular mechanics (MM) representation is usually necessary in a hybrid QM/MM framework. However, even within the QM/MM approximation, the affordable sampling of the phase space is, in general, quite restricted. To reduce drastically the computational cost of the simulations, several methods such as umbrella sampling require performing a priori a selection of a reaction coordinate. The quality of the computed results, in an affordable computational time, is intimately related to the reaction coordinate election which is, in general, a nontrivial task. In this work, we provide an approach to model reactive processes in complex environments that does not require the a priori selection of a reaction coordinate. The proposed methodology combines QM/MM simulations with an extrapolation of the nudged elastic bands (NEB) method to the free energy surface (FENEB). We present and apply our own FENEB scheme to optimize MFEP in different reactive processes, using QM/MM frameworks at semiempirical and density functional theory levels. Our implementation is based on performing the FENEB optimization by uncoupling the optimization of the band in a perpendicular and tangential direction. In each step, a full optimization with the spring force is performed, which guarantees that the images remain evenly distributed. The robustness of the method and the influence of sampling on the quality of the optimized MFEP and its associated free energy barrier are studied. We show that the FENEB method provides a good estimation of the reaction barrier even with relatively short simulation times, supporting that its combination with QM/MM frameworks provides an adequate tool to study chemical processes in complex environments.


Cardiovascular health and risk of hospitalization with COVID-19: A Mendelian Randomization study.
Susceptibility to and severity of COVID-19 is associated with risk factors for and presence of cardiovascular disease. We performed a 2-sample Mendelian randomization to determine whether blood pressure (BP), body mass index (BMI), presence of type 2 diabetes (T2DM) and coronary artery disease (CAD) are causally related to presentation with severe COVID-19. Variant-exposure instrumental variable associations were determined from most recently published genome-wide association and meta-analysis studies (GWAS) with publicly available summary-level GWAS data. Variant-outcome associations were obtained from a recent GWAS meta-analysis of laboratory confirmed diagnosis of COVID-19 with severity determined according to need for hospitalization/death. We also examined reverse causality using exposure as diagnosis of severe COVID-19 causing cardiovascular disease. We found no evidence for a causal association of cardiovascular risk factors/disease with severe COVID-19 (compared to population controls), nor evidence of reverse causality. Causal odds ratios (OR, by inverse variance weighted regression) for BP (OR for COVID-19 diagnosis 1.00 [95% confidence interval (CI): 0.99-1.01, P = 0.604] per genetically predicted increase in BP) and T2DM (OR for COVID-19 diagnosis to that of genetically predicted T2DM 1.02 [95% CI: 0.9-1.05, P = 0.927], in particular, were close to unity with relatively narrow confidence intervals. The association between cardiovascular risk factors/disease with that of hospitalization with COVID-19 reported in observational studies could be due to residual confounding by socioeconomic factors and /or those that influence the indication for hospital admission.


Development and Validation of SafeHIT: An Instrument to Assess the Self-Reported Safe Use of Health Information Technology.
Implementing health information technology (HIT) may cause unintended consequences and safety risks when incorrectly designed and used. Yet, the tools to assess self-reported safe use of HIT are not well established. This study aims to develop and validate SafeHIT, an instrument to assess self-reported safe use of HIT among health care practitioners. Systematic literature review and a semistructured interview with 31 experts were adopted to generate SafeHIT instrument items. In total, 450 physicians from various departments at three Malaysian public hospitals participated in the questionnaire survey to validate SafeHIT. Exploratory factor analysis and confirmatory factor analysis (CFA) were undertaken to explore the items that best represent a specific construct and to confirm the reliability and validity of the SafeHIT, respectively. The final SafeHIT consisted of 14 constructs and 58 items in total. The result of the CFA confirmed that all constructs demonstrated adequate convergent and discriminant validity. A reliable and valid theoretically underpinned measure of determinants of safe HIT use behavior has been developed. Understanding external factors that influence safe HIT use is useful for developing targeted interventions that favor the quality and safety of health care.


Pancreatic abscesses.
This paper presents the clinical features and problems in the management of 34 patients with pancreatic abscesses. In the majority of patients the abscesses developed following an attack of pancreatitis due to alcohol or gallstones. The abscesses were usually multilocular, and often had spread widely in the retroperitoneal space. Invasion into surrounding viscera or the peritoneal cavity occurred in 12 instances, and eight patients developed major bleeding into the abscess cavity. Obstructive complications (affecting bowel, common bile duct and large veins) occurred in eight patients. Twelve of the 34 patients (35 per cent) died, most deaths being due to failure to control sepsis (seven patients) or to massive bleeding from the abscess cavity (three patients). The mortality of this condition is likely to remain high, but may be reduced by better drainage techniques at the initial exploration. The importance of the infra-mesocolic approach for drainage is emphasized.


Surviving sepsis campaign in Brazil.
Severe sepsis and septic shock have long been a challenge in intensive care because of their common occurrence, high associated costs of care, and significant mortality. The Surviving Sepsis Campaign (SSC) was developed in an attempt to address clinical inertia in the adoption of evidence-based strategies. The campaign relies on worldwide support from professional societies and has gained consensus on the management of patients with severe sepsis. The guidelines have subsequently been deployed into two bundles, with each bundle component sharing a common relationship in time. The widespread adoption of such evidence-based practice in clinical care has been disappointingly slow despite the quantifiable benefits regarding mortality. In Brazil, a country of continental dimensions with a heterogeneous population and unequal access to health services, this reality is no different. From 2004 to 2007, four prospective studies were published describing the country's reality. In the multicenter Promoting Global Research Excellence in Severe Sepsis (PROGRESS) Study, the in-hospital mortality rate was higher in Brazil when compared with other countries: 56% against 30% in developed countries and 45% in other developing countries. During these 2.5 years of the campaign in Brazil, 43 hospitals have been receiving the necessary training to put in practice the recommended measures in all Brazilian regions, except for the North. The idea of the campaign is based on a 25% reduction in the relative risk of death from severe sepsis and septic shock within 5 years in the SSC-participating Brazilian hospitals. Ideally, the mortality rate should come to a 41.2% level subject to the 2009 deadline. This article aims to describe the actual scenario of the SSC implementation in Brazilian institutions and to report on some initiatives that have been used to overcome barriers.


Peptide conformational imprints enhanced the catalytic activity of papain for esterification.
Peptide conformational imprints (PCIs) offer a promising perspective to directly generate binding sites for preserving enzymes with high catalytic activity and stability. In this study, we synthesized a new chiral cross-linker cost-effectively for controlling the matrix morphology of PCIs on magnetic particles (PCIMPs) to stabilize their recognition capability. Meanwhile, based on the flank part of the sequences on papain (PAP), three epitope peptides were selected and synthesized. Molecularly imprinted polymers (MIPs) were then fabricated in the presence of the epitope peptide using our new cross-linker on magnetic particles (MPs) to generate PCIMPs. PCIMPs were formed with helical cavities that complement the PAP structure to adsorb specifically at the targeted position of PAP. PCIMPs65-79 were found to have the best binding parameters to the PAP with K d = 0.087 μM and B max = 4.56 μM. Upon esterification of N-Boc-His-OH, proton nuclear magnetic resonance (1H-NMR) was used to monitor the yield of the reaction and evaluate the activity of PAP/PCIMPs. The kinetic parameters of PAP/PCIMPs65-79 were calculated as V max = 3.0 μM s-1, K m = 5 × 10-2 M, k cat = 1.1 × 10-1 s-1, and k cat/K m = 2.2 M-1 s-1. In addition, PAP is bound tightly to PCIMPs to sustain its activity after four consecutive cycles.


A developmental investigation of inattentiveness and hyperactivity.
The development of inattentiveness and hyperactivity in middle childhood was investigated using a prospective longitudinal approach. Endogenous and exogenous predictors measured in infancy and in early and middle childhood were examined independently and in combination. In early childhood, quality of caregiving more powerfully predicted distractibility, an early precursor of hyperactivity, than did early biological or temperament factors. Caregiving and contextual factors together with early distractibility significantly predicted hyperactivity in middle childhood. While environmental variables also predicted hyperactivity in later elementary years, these factors did not improve the prediction beyond the influence of hyperactivity in early elementary years. The findings support a developmental view of the origins and course of hyperactivity in childhood, that is, that the emergence and persistence of AD/HD symptoms depend on developmental history along with current circumstances.


Effects of leptin and leptin fragments on corticosterone secretion and growth of cultured rat adrenocortical cells.
Compelling evidence indicates that leptin, acting via specific receptors (Ob-Ra and Ob-Rb) modulates adrenocortical-cell secretion. However, the results are controversial, inasmuch as either secretagogue or antisecretagogue effects have been reported. Hence, we decided to study the effects of a 96-h incubation with leptin and leptin fragments 116-130, 150-167, 138-167, 93-105, 22-56 and 26-39 (10(-8) and 10(-6) M) on the secretion and growth of cultured rat adrenocortical cells. Reverse transcription-polymerase chain reaction showed that control cultures expressed both Ob-Ra and Ob-Rb isoforms. As expected, ACTH (10(-8) M) raised corticosterone secretion and lowered proliferation rate of cultured cells. Native leptin elicited ACTH-like effects, while fragment 116-130 was ineffective. Leptin fragments 150-167 and 26-39 stimulated corticosterone production, and fragments 138-167 and 22-56 inhibited it. Fragment 93-105 exerted a dose-dependent biphasic effect on corticosterone secretion (i.e. stimulation and inhibition at the concentration of 10(-8) and 10(-6) M, respectively). Leptin fragment 26-39 enhanced proliferation of cultured cells, while fragments 138-167 and 22-56 were ineffective. Fragments 150-167 and 93-105 displayed proliferogenic and antiproliferogenic effects at the concentration of 10(-8) and 10(-6) M, respectively. Taken together, these findings allows us to conclude that native leptin and its fragments interact differently with Ob-Rs or interact with different Ob-R isoforms, thereby variously modulating secretion and growth of cultured rat adrenocortical cells.


A hydrophilic magnetic MOF for the consecutive enrichment of exosomes and exosomal phosphopeptides.
Hydrophilic Fe3O4@PDA@UIO-66-NH2 is employed to consecutively enrich urinary exosomes and exosomal phosphopeptides through the strong bond between Zr and phosphate groups. The recovery of exosomes reached 95% and 707 phosphopeptides were identified from 255 phosphoproteins via LC-MS/MS. This work will make a great contribution to further functional analysis of exosomes.


In flight negative pion assessments using time-of-flight technique.
Time-of-flight measurement was applied to obtain the energy spectra of the neutron emitted from tissue-equivalent plastic (TEP) exposed by pi- mesons. The separation of electrons and muons in beams was attempted. Neutrons from TEP exposed by pi- mesons at P pi = 500 MeV/c were separated from gamma-rays by the NE 213 liquid scintillator and the pulse-height analyzer. The double differential cross sections for neutron energy are obtained. The cross sections of the neutron energy distributions show a preponderance of low energy neutrons and a high energy tail extending to approximately 100 MeV.


A randomized clinical trial of guided self-help intervention based on mindfulness for patients with hepatocellular carcinoma: effects and mechanisms.
Compared with face-to-face mindfulness-based interventions (MBIs), online mindfulness interventions may be more convenient for patients with limited resources and can provide self-help mindfulness methods to improve the quality of life of cancer patients. This study investigated the effects of guided self-help mindfulness-based interventions (GSH-MBIs) on psychological distress, quality of life and sleep quality in patients with hepatocellular carcinoma and explored the underlying mechanisms. A total of 122 patients with hepatocellular carcinoma were randomly divided into the intervention group or the conventional treatment group. Psychological distress, quality of life, sleep quality, psychological flexibility and perceived stress were evaluated in the groups before the intervention at baseline, after the intervention, at 1-month follow-up and 3-month follow-up. The intervention's effects over time and the potential mediating effects were analysed using generalized estimating equations (GEE). GEE results indicated significant time-group interaction effects on psychological distress (P < 0.001) and sleep quality (P < 0.001). The intervention significantly improved psychological flexibility (β, -2.066; 95% CI, -3.631, -0.500) and reduced perceived stress (β, -2.639; 95% CI, -4.110, -1.169). Psychological flexibility and perceived stress played a mediating role in the observed results. GSH-MBIs can improve psychological distress and sleep quality via changing the psychological flexibility and perceived stress in hepatocellular carcinoma patients.


Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.
Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification.


Intrafamily relations, migration and remittances.
"This paper attempts to develop a formal model of interdependent decision making within the context of the family with regard to migration and remittances. The migration process is viewed as a deliberate strategy designed by the family for maximizing its total welfare. The interrelationships between the migrant and the rest of the family are modelled as a self-enforcing co-operative game and the remittances are an a priori requirement for the distribution of gains in an implicit co-insurance system. The migration decision and the remittances are determined by the bargaining strength of the migrant and the rest of the family, who act to promote their own self-interest." The focus is on developing countries.