Depression in Parkinson's disease: health risks, etiology, and treatment options.
Depression is found in about 30%-40% of all patients with Parkinson's disease (PD), but only a small percentage (about 20%) receive treatment. As a consequence, many PD patients suffer with reduced health-related quality of life. To address quality of life in depressed PD patients, we reviewed the literature on the health correlates of depression in PD (eg, cognitive function), etiology of depression in PD, and treatment options (ie, antidepressants, electroconvulsive therapy, and psychotherapy). The current review is unique in its focus on psychosocial aspects, as well as neuropathological factors, of depression in PD. Overall, we conclude that neurochemical (eg, serotonin) and psychosocial factors (eg, coping style, self-esteem, and social support) contribute to the affective disturbances found in this neuropsychiatric population. Therefore, we recommend that a multidisciplinary (eg, pharmacotherapeutic, psychoeducational, and/or psychotherapeutic) approach to treatment be taken with depressed PD patients.


Proliferation and number of Clara cell 10-kDa protein (CC10)-reactive epithelial cells and basal cells in normal, hyperplastic and metaplastic bronchial mucosa.
Clara cell 10-kDa protein (CC10) is an inhibitor of phospholipase A2 and binds to phosphatidylinositol. It may therefore interfere with intracellular signal transduction. Bronchial CC10-reactive cells have been described by several authors. In contrast to the bronchiolar CC10-containing Clara cell, which is a progenitor cell of terminally differentiated airway epithelium, the role of bronchial CC10-reactive cells remains to be elucidated. We assessed the number of bronchial CC10-reactive cells in relation to cytokeratin (CK) expression and proliferative activity in normal, hyperplastic and squamous metaplastic epithelium. Sixty-five human bronchial mucosal specimens were investigated immunohistochemically for CK expression (CK7, CK13 and CK5/6), proliferative activity (MIB-1) and number of CC10-reactive epithelia. The proliferation fraction of CC10-reactive cells was assessed with double staining for MIB-1 and CC10. The proliferation index of the epithelium differed significantly between normal, hyperplastic and metaplastic epithelium. The number of CC10-reactive cells was inversely related to the epithelial proliferation. Bronchial CC10-reactive cells showed no proliferative activity as assessed using immunohistochemical double staining for CC10 and MIB-1. In contrast to normal and hyperplastic epithelium, squamous metaplasia disclosed CK5/6 in all epithelial layers, a loss of CK7 and a gain of CK13. We conclude that CC10-reactive cells have no progenitor role in the bronchial mucosa. However, because the proliferative activity is inversely related to the number of CC10-reactive cells, the CC10 protein may play a role in the regulation of epithelial repair. Squamous metaplasia most likely originates from basal cells.


The effects of 7-OH-DPAT, quinpirole and raclopride on licking for sucrose solutions in the non-deprived rat.
Pharmacological manipulations that alter dopamine (DA) at DA receptor subtypes produce reductions in feeding behaviour. What remains uncertain is the exact way in which these reductions in feeding are achieved as a consequence of differing drug actions at separate receptor subtypes. In this study our aim was to compare the anorectic effects of the preferential D3/D2 agonists 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT) and quinpirole and the non-selective D2/D3 antagonist raclopride on the microstructure of licking responses in non-deprived rats. In a 20-min test, trained adult, male hooded rats had access to one of three solutions: 1%, 3% or 10% sucrose. 7-OH-DPAT (0.1-1.0 mg/kg, i.p.), quinpirole (0.03-0.3 mg/kg, s.c.), raclopride (0.03-0.3 mg/kg, i.p.) or vehicle were injected 20 min prior to the start of the licking test. A lickometer recorded the timing of each lick, from which the microstructural parameters of bout frequency and bout duration were also computed. All compounds reduced the mean bout duration, while 7-OH-DPAT and raclopride also brought about a compensatory increase in bout number. Analysis of the licking rates over the test session showed that 7-OH-DPAT, quinpirole and raclopride decreased the initial rate, without affecting the rate of decline of licking. Changes in licking microstructure (i.e. initial rate of licking and mean bout duration) after the administration of 7-OH-DPAT, quinpirole and raclopride, are consistent with an action of these dopaminergic compounds to reduce palatability.


NTAGI subcommittee recommendations on Haemophilus influenzae type B (Hib) vaccine introduction in India.
WHO estimates that Haemophilus influenzae type b (Hib) caused over 8 million cases of serious disease and 376,000 deaths globally in the year 2000. The introduction of Hib vaccines has essentially eliminated Hib disease in countries where they are routinely used. Now, almost all Hib disease cases and deaths occur in countries where Hib vaccines is not incorporated in the routine immunization program. The Hib and Pneumococcal subcommittee of National Technical Advisory Group on Immunization (NTAGI) in India met in April 2008. This paper focuses on the discussions regarding Hib vaccine introduction; the pneumococcal vaccine discussion is being published separately. The subcommittee reviewed the available published and unpublished literature as well as consulted prominent Hib experts to make an informed decision regarding the introduction of Hib vaccine into the routine Universal Immunization Program (UIP) in India. The meeting was conducted with the objectives of reviewing the existing Indian, regional and global data on Hib disease (meningitis and pneumonia), the data on safety and immunogenecity of Hib vaccines manufactured in India, as well as the programmatic and operational requirements for the introduction of Hib vaccine in India, with the goal of making a recommendation on the introduction of Hib vaccine into the UIP. The committee noted that Hib diseases burden is suffiently high in India to warrant prevention by vaccination. Hib vaccines have been demonstrated to be safe, both globally and in India, and extremely efficacious in all settings where they have been used. Hib vaccine fits into the UIP immunization schedule. Several Indian manufacturers are currently producing Hib vaccines, and a detailed analysis showed that supplier capacity would be sufficient to meet the present and future demand for India if given sufficient lead time to increase production. Recognizing that it is the poorest children that are most at risk, the Indian Academy of Pediatrics has already recommended this vaccine for routine use in India. This subcommittee strongly recommended that Hib vaccine should immediately be introduced in India's UIP.


Effects of ivabradine therapy on heart failure biomarkers.
Heart rate (HR) reduction is associated with improved outcomes in patients with heart failure (HF) and biomarkers can be a valuable diagnostic tool in HF management. The primary aim of our study was to evaluate the short-term (6 months) effect of ivabradine on N-terminal pro B-type natriuretic peptide (NT-proBNP), CA-125, and cystatin-C values in systolic HF outpatients, and secondary aim was to determine the relationship between baseline HR and the NT-proBNP, CA-125, cystatin-C, and clinical status variation with ivabradine therapy. Ninety-eight patients (mean age: 65.81 ± 10.20 years; 33 men), left ventricular ejection fraction < 35% with Simpson method, New York Heart Association (NYHA) class II-III, sinus rhythm and resting HR > 70/min, optimally treated before the study were included. Among them, two matched groups were formed: the ivabradine group and the control group. Patients received ivabradine with an average (range of 10-15) mg/day during 6 months of follow-up. Blood samples for NT-proBNP, CA-125, and cystatin-C were taken at baseline and at the end of a 6-month follow-up in both groups. There was a significant decrease in NYHA class in the ivabradine group (2.67 ± ± 0.47 vs. 1.85 ± 0.61, p < 0.001). When ivabradine and control groups were compared, a significant difference was also found in NHYA class 6 months later (p = 0.013). A significant decrease was found in HR in the ivabradine and control groups (84.10 ± 8.76 vs. 68.36 ± ± 8.32 bpm, p = 0.001; 84.51 ± 10 vs. 80.40 ± 8.3 bpm, p = 0.001). When both groups were compared, a significant difference was also found in HR after 6 months (p = 0.001). A significant decrease was found in cystatin-C (2.10 ± 0.73 vs. 1.50 ± 0.44 mg/L, p < 0.001), CA-125 (30.09 ± 21.08 vs. 13.22 ± 8.51 U/mL, p < 0.001), and NT-proBNP (1,353.02 ± 1,453.77 vs. 717.81 ± 834.76 pg/mL, p < 0.001) in the ivabradine group. When ivabradine and control groups were compared after 6 months, a significant decrease was found in all HF parameters (respectively; cystatin-C: p = 0.001, CA-125: p = 0.001, NT-proBNP: p = 0.001). Creatinine level was significantly decreased and glomerular filtration rate (GFR) was significantly increased in the ivabradine group (1.02 ± 0.26 vs. 0.86 ± 0.17, creatinine: p = 0.001; 79.26 ± 18.58 vs. 92.48 ± 19.88, GFR: p = 0.001). There was no significant correlation between NYHA classes (before and after ivabradine therapy) and biochemical markers, or HR. In the outpatients with systolic HF, persistent resting HF > 70/min with optimal medical therapy, the NT-proBNP, CA-125, and cystatin-C reductions were obtained with ivabradine treatment. Measurement of NT-proBNP, CA-125, and cystatin-C may prove to be useful in biomarker panels evaluating ivabradine therapy response in HF patients.


Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis.
Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4). 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. Agency for Healthcare Research and Quality.


Determinants of the autopsy decision: a statistical analysis.
Our goal was to use cross-sectional national mortality data to provide a multivariable statistical analysis of the factors that contribute to the decision of whether an autopsy will be performed. The identification of determinants of the autopsy is an important prerequisite for finding cost-effective alternatives for arresting or reversing the decline of autopsy rates in the circumstances in which the autopsy can continue to make a crucial contribution to clinical medicine and public health. The source of the data was 1986 National Center for Health Statistics (Washington, DC) mortality data tapes for Kentucky, Maryland, Minnesota, and Washington for the 1986 calendar year. Separate multiple logistic regressions were conducted on these data on a state-by-state basis, with a total of 139,063 individual mortality records as the unit of analysis. The dependent variable in all models was autopsy (yes/no). Odds ratios for selected explanatory variables were estimated for all four states, and the relative contribution of each explanatory variable was studied in a detailed analysis of one state. In general, the following independent variables had a statistically significant positive relationship with whether an autopsy will be performed: male sex; nonwhite ethnicity; death due to ill-defined or unknown cause; death due to accident, suicide, or homicide; presence of a nationally recognized medical center in the county of death; and death occurring in a standard metropolitan statistical area. In general, the following independent variables had a statistically significant negative relationship with whether an autopsy will be performed: older age at death; higher income level of the decedent; death in a nursing home; death at home; and residency in the county of death. The two most important variables influencing the autopsy decision were age at death (especially old age) and death due to accident, homicide, or suicide.


A Multi-Scale Approach to Membrane Remodeling Processes.
We present a multi-scale simulation procedure to describe membrane-related biological processes that span over a wide range of length scales. At macroscopic length-scale, a membrane is described as a flexible thin film modeled by a dynamic triangulated surface with its spatial conformations governed by an elastic energy containing only a few model parameters. An implicit protein model allows us to include complex effects of membrane-protein interactions in the macroscopic description. The gist of this multi-scale approach is a scheme to calibrate the implicit protein model using finer scale simulation techniques e.g., all atom and coarse grain molecular dynamics. We previously used this approach and properly described the formation of membrane tubular invaginations upon binding of B-subunit of Shiga toxin. Here, we provide a perspective of our multi-scale approach, summarizing its main features and sketching possible routes for future development.


Substance Use and Misuse: A Pilot Study to Improve Screening and Interventions at a Comprehensive Cancer Hospital.
Mounting evidence suggests patients diagnosed with cancer may be at increased risk for opioid misuse and diversion. Substance use disorders (SUDs), involving prescription medications and/or illegal substances, may significantly compromise the ability of healthcare professionals to deliver high-quality cancer care. A substance use screening pilot was conducted in ambulatory oncology clinics at a large cancer hospital in the midwestern United States. In this article, the authors present results from this quality improvement project. Future directions involve innovative methods to deliver addiction-specific knowledge to oncology healthcare providers and should focus on discussing screening results, as well as providing tailored recommendations using shared decision-making with patients and caregivers.


Percutaneous endoscopic gastrostomies: attitudes of general practitioners and how management may be improved.
Percutaneous endoscopic gastrostomy (PEG) has replaced surgical gastrostomy in patients requiring long-term enteral nutrition. Increasing numbers of patients are being referred for PEG placement. Concern has been raised about patient selection and subsequent follow-up of these patients in the community. We report the views of Northern Ireland GPs to PEGs and how management may be improved.


Resveratrol, a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias.
A natural product, resveratrol (3,4,40-trihydroxy-trans-stilbene), a phytoalexin found in grapes and other food products, is known as a cancer chemopreventive agent. We studied the in vitro biological activity of this compound by examining its effect on proliferation and differentiation in myeloid leukemia cell lines (HL-60, NB4, U937,THP-1, ML-1, Kasumi-1) and fresh samples from 17 patients with acute myeloid leukemia. Resveratrol (20 microM, 4 days) alone inhibited the growth in liquid culture of each of the 6 cell lines. Resveratrol (10 microM) enhanced the expression of adhesion molecules (CD11a, CD11b, CD18, CD54) in each of the cell lines except for Kasumi-1. Moreover, resveratrol (25 microM, 4 days) induced 37% of U937 cells to produce superoxide as measured by the ability to reduce nitroblue tetrazolium (NBT). The combination of resveratrol (10 microM) and all-trans-retinoic acid (ATRA) (50 nM, 4 days) induced 95% of the NB4 cells to become NBT-positive, whereas <1% and 12% of the cells became positive for NBT after a similar exposure to either resveratrol or ATRA alone, respectively. In U937 cells exposed to resveratrol (25 microM, 3 days), the binding activity of nuclear factor-kappaB (NFkappaB) protein was suppressed. Eight of 19 samples of fresh acute leukemia cells reduced NBT after exposure to resveratrol (20 microM, 4 days). Taken together, these findings show that resveratrol inhibits proliferation and induces differentiation of myeloid leukemia cells.


Cervical spine injury: a ten-year multicenter analysis of evolution of care and risk factors for poor outcome in southeast Nigeria.
Retrospective study. To describe the evolution of care and risk factors for poor outcome in patients with cervical spine injury (CSI) treated at three centers in southeast Nigeria. Nigeria, southeast. A 10-year retrospective multicenter analysis of patients with CSI, managed at three centers in southeast Nigeria, from January 2003 to December 2012. Two hundred and seven patients (55%) had CSI out of 377 spinal injury cases in the three study centers, but 195 cases had complete records and were studied. There were 148 males and 47 females. The age range was 3-74 years with a mean of 32.6 (± 1.9) years 95% CI. Most injuries (149 cases) resulted from motor vehicular accidents (MVA). The C5 spinal level was involved in 75 (38%) cases One hundred and seventeen patients (60%) presented with American Spinal Injury Association A (ASIA A) injury. CSI care evolved from the application of a Minerva jacket or cervical traction only to cervical traction and spinal fusion resulting in a reduction in hospital stay (F = 52.5, DF (2, 3) P < 0.05). When compared to 51 patients with incomplete injuries, who improved in neurologic al status at discharge, only three patients with ASIA grade A experienced some improvement. The mortality rate from our series is 16% (32 patients). Those who died were more likely to have a complete injury (25 patients) or a high cervical injury (X² = 61.2, P < 0.05) among other factors. The cervical spine is the most commonly injured spinal segment in southeast Nigeria. Although treatment evolution has resulted in reduction of hospital stay, the associated mortality risk still remains high.


Epidemiology of diarrhea among expatriate residents living in a highly endemic environment.
To determine the etiology of diarrhea among expatriate residents living in a developing country and identify risk factors for travelers' diarrhea that are difficult to evaluate in tourist populations. Clinic based case-control study. Primary care travel medicine clinic in Kathmandu, Nepal. A total of 69 expatriate residents with diarrhea, compared with 120 tourists with diarrhea, and 112 asymptomatic resident and tourist controls, selected systematically during a 1-year period. Risk factors for diarrhea assessed by questionnaire and pathogen prevalence assessed by microbiologic analysis of stool specimens. The dominant risk factors for diarrhea among expatriate residents included younger age (P = .003), shorter duration of stay in Nepal (P < .001), and eating out in restaurants (P = .01). Eating raw vegetables, salads, fresh fruit, or ice served in restaurants was not significantly associated with diarrhea. Longer duration of residence was linearly correlated with protection. Enteric pathogens were identified in 44 (64%) of 69 residents with diarrhea compared with 100 (83%) of 120 tourists with diarrhea, with enterotoxigenic Escherichia coli, Campylobacter, and Shigella predominant for both groups. Pathogens were also found in stools from 32 (37%) of 87 asymptomatic resident controls and 13 (52%) of 25 tourist controls. The attack rate of diarrhea among expatriates was estimated to be 49% (95% confidence interval, 37% to 61%) per month during the first 2 years of residence. The highest-risk months were April through July. Diarrhea among expatriates in a highly endemic environment is a persistent risk. The extremely high prevalence of enteric pathogens among asymptomatic persons reflects widespread exposure. The most important risk factors for travellers' diarrhea are difficult to modify, including younger age, duration of stay, eating in restaurants, and seasonality. Preventive dietary recommendations may not be fully protective, suggesting that pretravel advice should emphasize empiric treatment in addition to strategies to avoid exposure.


Transgene expression in rat fetal brain grafts is maintained for 7 months after ex vivo adenoviral vector-mediated gene transfer.
Fetal brain tissue fragments containing the suprachiasmatic nucleus were infected with an adenoviral vector containing the marker gene LacZ encoding for beta-galactosidase, and subsequently cultured or transplanted in the third ventricle of SCN-lesioned adult Wistar rats. In previous studies we optimized the infection procedure and characterized the immunological response directed against the viral vector in this model. The present study reports on beta-gal expression for at least 7 months in neuronal and glial cells. Maturation of the transplanted fetal SCN with respect to immunoreactivity for vasoactive intestinal polypeptide and C-terminal propressophysin was not hampered by the viral infection.


[Differential diagnostic strategy in obstructive jaundice].
An analysis of effectiveness of diagnostic noninvasive and invasive measures for obstructive jaundice was made using clinical findings of 383 patients. The efficacy of these measures was assessed and limits were determined in relation to etiology of obstructive jaundice and the condition of extrahepatic bile ducts. The criteria of selection of diagnostic methods were detected on preoperative and intraoperative stages. The rational report of diagnostic strategy was formulated.


Role of cytochrome P-450 from the human CYP3A gene family in the potentiation of morpholino doxorubicin by human liver microsomes.
The cytotoxicity of the morpholino derivative of doxorubicin (MRA) can be potentiated 50- to 100-fold by human liver microsomes and NADPH (J. Natl. Cancer Inst., 81: 1034, 1989). This metabolic potentiation is inhibited by carbon monoxide or hypoxia, indicating that it is cytochrome P-450-dependent. The potentiation is also inhibited by the cytochrome P-450 inhibitors, SKF-525A and cimetidine. The metabolism by the microsomes is substrate-specific, varying markedly with alterations of either the morpholino or anthracycline ring substituents. No potentiation occurred with doxorubicin itself, or the cyanomorpholinyl, methoxypiperidinyl, N-hydroxyethyl or the O-bridged cyanomorpholinyl analogues of doxorubicin. We utilized a panel of human liver microsomes and cytochrome P-450 type-specific antibodies to further identify the isoform(s) of cytochrome P-450 that potentiated the cytotoxicity of MRA. The potentiation correlates well with the benzyloxyresorufin assay (r2 = 0.98) and aflatoxin B1 metabolism (r2 = 0.98), both assays that are relatively specific for CYP3A proteins. Correlations were also observed for the expression of protein(s) cross-reacting with an antibody against rat cytochrome P-450 CYP3A1 (r2 = 0.97) and MRA metabolism. This antibody against the rat cytochrome P-450 CYP3A isoform(s) inhibited more than 90% of the potentiation of the cytotoxicity by human liver microsomes. Antibodies against the CYP1A2, CYP2C6, and CYP2B2 isoforms produced no inhibition, nor did their expression by Western blotting correlate with MRA potentiation. Complete inhibition of the potentiation of MRA by human liver microsomes was found when the CYP3A substrates cyclosporin A and erythromycin were used in the reaction system. These data indicate that the CYP3A isoform(s) of cytochrome P-450 play a major role in the metabolism of MRA in vitro to a more active species.


Personal and social variables as co-determinants of noise annoyance.
This paper starts with the fact that noise annoyance is partly due to acoustic factors, partly due to so-called moderating variables, i.e. personal and social aspects of the residents. Noise annoyance is considered to be the (long-term) negative evaluation of living conditions with respect to noise. This evaluation is not simply dependent on past disturbances, but on attitudes and expectations, too. The personal factors influencing the evaluation and described here are: Sensitivity to noise, fear of harm connected with the source, personal evaluation of the source, and coping capacity with respect to noise. The social factors described here are: General (social) evaluation of the source, trust or misfeasance with source authorities, history of noise exposure, and expectations of residents. For most of these variables, data from different community studies are used in order to illustrate the respective moderating effect on annoyance. In addition, some of the moderators are presented as possible tools in order to reduce noise annoyance. It is expected that a significant decrease in a negatively moderating variable is as effective in reducing noise annoyance, as is a significant decrease in noise level.


Isolation of encysted Toxoplasma gondii from musculature of moose and pronghorn in Montana.
Pieces of skeletal muscle from 43 mule deer, 34 elk, 4 white-tailed deer, 21 pronghorn, 7 moose, and 2 bison were examined for Toxoplasma infection, by the acid-pepsin digestion technique. Toxoplasma gondii was isolated from 1 moose and 1 pronghorn. The isolated strains of T gondii were of low virulence to mice.


HIV-1 incidence among opiate users in northern Thailand.
The incidence of human immunodeficiency virus type 1 (HIV-1) infection among opiate users was determined in a retrospective cohort of 436 patients with multiple admissions to the only inpatient drug treatment program in northern Thailand between October 1993 and September 1995. During 323.4 person-years of follow-up, 60 patients presenting for detoxification acquired HIV-1 infection, for a crude incidence rate of 18.6 per 100 person-years (95% confidence interval 14.4-23.9). All seroconverters were male. HIV-1 incidence varied by the current route of drug administration: 31.3 per 100 person-years for injectors and 2.8 per 100 person-years for noninjectors (smoking and ingestion). Significant differences were found by ethnicity: HIV-1 incidence was 29.3 per 100 person-years for Thai lowlanders and 8.5 per 100 person-years for hill tribes. Multivariate relative risk estimates showed that injecting opiates (vs. use by other routes), being unmarried, being under age 40 years, being a Thai lowlander, having a primary and secondary education, and being employed in the business sector were each independently associated with human immunodeficiency virus seroconversion. This HIV-1 incidence rate is double that reported for Bangkok and suggests that prevention and control programs for drug users need to be expanded throughout Thailand. Improved availability of more-effective treatment regimens and increased access to sterile injection equipment are needed to confront the HIV-1 epidemic among opiate users in northern Thailand.


Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats.
D1-Like agonists are self-administered by drug-naive animals, whereas D2-like agonists reinstate cocaine-seeking behavior, but the rewarding and reinstating effects of D1- and D2-like agonists in pavlovian-based conditioned place preference are equivocal. To compare the ability of D1 and D2 agonists to produce conditioned place preference with their modulation of expression and reinstatement of an established cocaine place preference. Using an unbiased procedure, we measured the place preference induced by the D1 receptor agonist SKF 81297 and the D2/D3 receptor agonist quinpirole in drug-naive or cocaine-exposed rats. The rewarding effects of the D1 agonists SKF 82958, ABT-431, A-77636, and the D2/D3 receptor agonist 7-OH-DPAT were also tested. Additionally, we tested the ability of SKF 81297 and quinpirole to modulate expression and reinstatement of an established cocaine place preference. The D1 receptor agonists SKF 81297, SKF 82958, and ABT-431 produced dose-dependent conditioned place preferences, whereas A-77636 produced only place aversion, and the D2/D3 agonists quinpirole and 7-OH-DPAT were without effect in drug naive rats. In cocaine-treated rats, SKF-81297-induced place preference was reduced, whereas quinpirole-induced place preference was revealed. Pretreatment using either D1 or D2/D3 agonists blocked expression of an established cocaine place preference, but only the D1 agonist SKF 81297 and cocaine dose-dependently reinstated an extinguished cocaine place preference, whereas the D2/D3 agonist quinpirole induced place aversion but failed to alter cocaine-induced reinstatement. D1, but not D2/D3, agonists mediate rewarding effects and reinstatement of cocaine place preference, but the reinstating effects differ markedly from self-administration paradigms.


A biocomputing platform with electrochemical and fluorescent signal outputs based on multi-sensitive copolymer film electrodes with entrapped Au nanoclusters and tetraphenylethene and electrocatalysis of NADH.
In this work, poly(N,N'-dimethylaminoethylmethacrylate-co-N-isopropylacrylamide) copolymer films were polymerized on the surface of Au electrodes with a facile one-step method, and Au nanoclusters (AuNCs) and tetraphenylethene (TPE) were synchronously embedded in the films, designated as P(DMA-co-NIPA)/AuNCs/TPE. Ferrocene dicarboxylic acid (FDA), an electroactive probe in solution displayed inverse pH- and SO42--sensitive on-off cyclic voltammetric (CV) behaviors at the film electrodes. The electrocatalytic oxidation of nicotinamide adenine dinucleotide (NADH) mediated by FDA in solution could substantially amplify the CV response difference between the on and off states. Moreover, the two fluorescence emission (FL) signals from the TPE constituent at 450 nm and AuNCs component at 660 nm in the films also demonstrated SO42-- and pH-sensitive behaviors. Based on the aforementioned results, a 4-input/9-output biomolecular logic circuit was constructed with pH, Na2SO4, FDA and NADH as the inputs, and the CV signals and the FL responses at 450 and 660 nm at different levels as the outputs. Additionally, some functional non-Boolean devices were elaborately designed on an identical platform, including a 1-to-2 decoder, a 2-to-1 encoder, a 1-to-2 demultiplexer and different types of keypad locks. This work combines copolymer films, bioelectrocatalysis, and fluorescence together so that more complicated biocomputing systems could be established. This work may pave a new way to develop advanced and sophisticated biocomputing logic circuits and functional devices in the future.


The nerve growth factor-inducible large external (NILE) glycoprotein and neural cell adhesion molecule (N-CAM) have distinct patterns of expression in the developing rat central nervous system.
The nerve growth factor-inducible large external (NILE) glycoprotein and the neural cell adhesion molecule (N-CAM) have both been implicated in the process of nerve fiber fasciculation. To evaluate the respective roles of the 2 molecules in fiber tract formation, we used immunohistochemical means to compare their distributions in the developing rat central nervous system. In the spinal cord, hindbrain, forebrain, retina, and cerebellum, N-CAM was present on undifferentiated cells in germinal zones as well as on differentiating cells and in nerve fiber tracts. In contrast, NILE was restricted to the developing fiber tracts in all these areas. No fiber tracts were found that were obviously lacking one or the other of the 2 molecules during the period of tract development. However, in all cases except that of the cerebellar molecular layer, nerve fiber tracts appeared to lose NILE and retain N-CAM after the major phases of tract development were completed. The fact that NILE is restricted to nerve fiber tracts during relatively short but crucial phases of tract development suggests that NILE plays a very specific role in the formation of fiber bundles. The more ubiquitous N-CAM molecule may have a more general role in neural histogenesis.


[Meningitis-retention syndrome. Report of one case].
The Meningitis-Retention Syndrome associates aseptic meningitis and neurogenic bladder, with a vesical dysfunction that outlasts meningitis widely. Urodynamic assessment shows a detrusor palsy with normal function of the external sphincter. We report a 24-year-old male admitted for headache, fever, myalgias and acute urinary retention, which was diagnosed as a urinary tract infection. Worsening of symptoms and slight meningeal signs prompted for a lumbar puncture that yielded a cerebrospinal fluid with 94 lymphocytes, in which etiological evaluation was inconclusive. Meningeal syndrome and myalgia subsided by the fifth day, while urinary retention persisted. A magnetic resonance imaging of the brain and spinal cord done at the fifth day, showed high intensity signals in basal ganglia and central spinal cord, not altered by contrast. These images disappeared in the imaging control performed two months later. Bladder dysfunction lasted at least until the second month of follow up.


A review on the effect of COX-2-mediated mechanisms on development and progression of gastric cancer induced by nicotine.
Smoking is a documented risk factor for cancer, e.g., gastric cancer. Nicotine, the principal tobacco alkaloid, would exert its role of contribution to gastric cancer development and progression through nicotinic acetylcholine receptors (nAChRs) and β-adrenergic receptors (β-ARs), which then promote cancer cell proliferation, migration and invasion. As a key isoenzyme in conversion of arachidonic acid to prostaglandins, cyclooxygenase-2 (COX-2) has been demonstrated to have a wide range of effects in carcinogenesis and tumor development. At present, many studies have reported the effect of nicotine on gastric cancer by binding to nAChR, as well as indirectly stimulating β-AR to mediate COX-2-related pathways. This review summarizes these studies, and also proposes more potential COX-2-mediated mechanisms. These events might contribute to the growth and progression of gastric cancer exposed to nicotine through tobacco smoke or cigarette substitutes. Also, this review article has therefore the potential not only to make a significant contribution to the treatment and prognosis of gastric cancer for smokers but also to the clinical application of COX-2 antagonists. In addition, this work also discusses the considerable challenges of this field with special reference to the future perspective of COX-2-mediated mechanisms in development and progression of gastric cancer induced by nicotine.


Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone.
The IRIS trial (Insulin Resistance Intervention After Stroke) demonstrated that pioglitazone reduced the risk for both cardiovascular events and diabetes mellitus in insulin-resistant patients. However, concern remains that pioglitazone may increase the risk for heart failure (HF) in susceptible individuals. In IRIS, patients with insulin resistance but without diabetes mellitus were randomized to pioglitazone or placebo (1:1) within 180 days of an ischemic stroke or transient ischemic attack and followed for ≤5 years. To identify patients at higher HF risk with pioglitazone, we performed a secondary analysis of IRIS participants without HF history at entry. HF episodes were adjudicated by an external review, and treatment effects were analyzed using time-to-event methods. A baseline HF risk score was constructed from a Cox model estimated using stepwise selection. Baseline patient features (individually and summarized in risk score) and postrandomization events were examined as possible modifiers of the effect of pioglitazone. Net cardiovascular benefit was estimated for the composite of stroke, myocardial infarction, and hospitalized HF. Among 3851 patients, the mean age was 63 years, and 65% were male. The 5-year HF risk did not differ by treatment (4.1% pioglitazone, 4.2% placebo). Risk for hospitalized HF was low and not significantly greater in pioglitazone compared with placebo groups (2.9% versus 2.3%, P=0.36). Older age, atrial fibrillation, hypertension, obesity, edema, high C-reactive protein, and smoking were risk factors for HF. However, the effect of pioglitazone did not differ across levels of baseline HF risk (hazard ratio [95% CI] for pioglitazone versus placebo for patients at low, moderate, and high risk: 1.03 [0.61-1.73], 1.10 [0.56-2.15], and 1.08 [0.58-2.01]; interaction P value=0.98). HF risk was increased in patients with versus those without incident myocardial infarction in both groups (pioglitazone: 31.4% versus 2.7%; placebo: 25.7% versus 2.4%; P<0.0001). Edema, dyspnea, and weight gain in the trial did not predict HF hospitalization but led to more study drug dose reduction with a lower mean dose of pioglitazone versus placebo (29±17 mg versus 33±15 mg, P<0.0001). Pioglitazone reduced the composite outcome of stroke, myocardial infarction, or hospitalized HF (hazard ratio, 0.78; P=0.007). In IRIS, with surveillance and dose adjustments, pioglitazone did not increase the risk of HF and conferred net cardiovascular benefit in patients with insulin resistance and cerebrovascular disease. The risk of HF with pioglitazone was not modified by baseline HF risk. The IRIS experience may be instructive for maximizing the net benefit of this therapy. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00091949.


Management of Incidental Finding of Triorchidism Diagnosed During Routine Hernia Repair.
Polyorchidism is a rare congenital anomaly which refers to the presence of more than two intra- or extrascrotal testicles. Triorchidism, the presence of one extra testicle is the most common type. This report describes the case of a 29-year-old male who was found to have a right supernumerary undescended testis encountered incidentally during hernia repair. With this in mind, the current knowledge of management of supernumerary testis was analysed, including potential scenarios, to delineate what a urologist should do when a supernumerary testis is found during routine surgical procedures such as orchidopexy or hernia repair.


Effect of cyproheptadine on bar-pressing for food reward in rats.
Lever pressing rate under a continuous reinforcement schedule for food reward in rats was reduced significantly by cyproheptadine in the dose of 5 and 10 mg/kg body weight. Under fixed ratio schedule of reinforcement, the responding was also suppressed significantly by 5 and 10 mg/kg body weight doses of cyproheptadine. However, high dose (20 mg/kg) of cyproheptadine administered subsequent to the low doses, failed to inhibit the bar pressing rate under either continuous or fixed ratio schedules.


Chitosan membranes in a rat model of full-thickness cutaneous wounds: healing and IL-4 levels.
The aim of this study was to examine the effect of chitosan membrane on wound healing. The effect of chitosan membranes was evaluated in an experimental rat model. On day 0, circular full-thickness skin sections were excised from the scalps of rats. The wounds were then measured and the surrounding area tattooed. Rats were sacrificed either immediately after excision, or randomised into control and chitosan groups and followed up on day 3, 7, 14 or 21. Control group wounds were covered with Aquacel (wound dressing). Chitosan group wounds were covered with chitosan membranes and the wound dressing. Wounds and the distances between the tattooed marks were measured on follow-up, the wound sites were harvested and histologically examined, and serum interleukin (IL-4) levels were analysed. A total of 54 rats were examined and all time points included 6 control and 6 chitosan treated animals, except for day 0 which consisted of control animals only. On day 3, wounds in the chitosan group were significantly (p<0.05) smaller (60±6% versus 78±19% of the original wound area) than in the control group. Chitosan membranes were found to degrade at the wound sites between days 7 and 14. Leukocyte counts were lower in the chitosan group than in the control group on day seven (p<0.05). IL-4 levels were significantly higher on day 7 (p<0.001) and 14 (p<0.001) in the chitosan group. According to our results chitosan membrane may promote early wound healing, reduce inflammation and affect the IL-4 pathway, however, the membrane degrades at the wound site after day 7.


Keys to the species of Athesmia Loss, 1899 (Digenea: Dicrocoeliidae: Dicrocoeliinae), with the description of a new species from the clapper rail, Rallus longirostris Boddaert (Gruiformes: Rallidae), from Galveston, Texas, U.S.A.
Eleven specimens of a previously undescribed species of Athesmia Looss, 1899 were recovered from six clapper rails, Rallus longirostris Boddaert (Rallidae), collected from November, 1984 through October, 1995 from the Galveston, Texas area of the Gulf of Mexico. Species of Athesmia can be divided into two body types based on the posterior extent of the ceca relative to the vitelline field (vitellarium): the attilae type where the ceca may be uneven, but they both extend at least to near the level of the posterior margin of the vitelline field, or more commonly surpass the vitelline field posteriorly and the heterolechithodes type where the cecum on the side of the vitelline field terminates well above the posterior margin of the vitelline field, usually near its anterior extremity, while the cecum opposite the vitelline field extends at least to the level of the posterior margin of the vitelline field, or more commonly surpasses the vitelline field posteriorly. Athesmia ralli n. sp. is assigned to the attilae type. The new species is most similar to Athesmia butensis Petri, 1942, but differs from this species by having a longer space from posterior testis to ovary (600-790 compared to less than 200), which represent a larger percentage of the total body length (7-8% compared to 2%) and a larger maximum egg size (47 by 29 compared to 42 by 25). The new species further differs from A. butensis by having a somewhat larger body, a longer forebody and the vitelline field reaches posteriorly to the posterior third of the body in the new species but is confined to the middle third of the body in A. butensis. A key to species also is provided.


A blind test of the serological response of dogs to infection with Taenia ovis.
Fifty six dogs of mixed age and sex were acquired from farms in the Otago/Southland region, and maintained at the Hydatid Research Unit, Taieri, where 43 were each fed two Tueniu ovis cysts. All were bled fortnightly for six or 12 weeks. Coded sera were sent to Wallaceville Animal Research Centre for testing using ELISA, with antigen from T. ovis scoleces. Dog treatments were identified after all tests were complete. A discriminant level was derived from the mean absorbance value plus three standard deviations of 56 sera taken at time zero and 78 sera from serially bled uninfected dogs. None of these 134 sera registered as a false positive using this discriminant level. The data showed no significant deviation from normality, and the expected frequency of the occurrence of false positives is therefore less than 0.14%. Four weeks after infection 63% of dogs proved to be infected were serologically positive, rising to 78% after 6 weeks. When worms were removed by anthelmintic treatment, ELISA absorbance levels decreased. Four weeks after removal 70% of previously infected dogs remained positive, decreasing to 30% after 6 weeks. Six weeks after infection the sensitivity of the test was 78%, and the specificity 63%. However, if dogs with positive ELISA absorbance levels, but which did not purge worms, were regarded as having had worms, the respective figures would be 82% and 100%. The latter figures are similar to our previously published laboratory results. The test is of comparable efficiency to arecoline purgation for surveillance, and has the additional advantage of detecting infection in the majority of those dogs that have been infected for three weeks or more but fail to pass worms on purgation, and a substantial proportion of those infected dogs that were treated by their owners prior to presenting them for purgation in order to avoid detection of infection.


Tumour biomarkers in heart failure: is there a role for CA-125?
Tumour markers are used for the screening, diagnosis, and stratification of cancer disease. Recently, the potential role of some tumour markers has also been explored in the context of heart failure. These include CA-125, CA 15-3, CA 19-9, carcinoembryonic antigen, alpha-feto protein, tissue polypeptide antigen, tissue polypeptide specific antigen, cytokeratin 19 fragment, and chromogranins. Of these markers, CA-125, a tumour antigen that is expressed on the surface of ovarian cancer cells and which is a well-established biomarker for monitoring ovarian cancer growth, has been investigated most extensively. Trials have consistently indicated that CA-125 could serve as both a diagnostic and prognostic biomarker of heart failure, although the pathophysiology remains to be established. In this review paper we discuss the potential role of tumour markers in heart failure with a special focus on CA-125 within the context of recent trials.


[Factors associated with patient satisfaction with hospital care].
To identify the influence of sociodemographic, care and communication factors on patient satisfaction. Cross-sectional study by means of a telephonic survey of patients discharged during September, 2006. Instrument for measuring satisfaction: SERQVHOS questionnaire. we used odds ratio (OR) and its 95% confidence interval (CI); adjustment for confusion factors was performed using multiple logistic regression. Response rate was 80.9%. On evaluating the influence of sociodemographic characteristics, we observed that patients whose nationality did not correspond to the European Union were more satisfied than Spanish patients (OR=3.01; 95% CI: 1.40-3.51); subjects who had only completed primary studies were more satisfied than those with university studies (OR = 2.85, 95% CI: 1.88-4.35). With respect to care factors, patients readmitted because of the same major diagnostic category had lower satisfaction (OR=0.67, bordering statistical significance). Finally, with regard to communication factors, the three aspects most associated with patient satisfaction were: correct health-care personnel identification (OR: 6.22 95% CI: 3.52-10.97), receiving enough information about his/her state of health (OR: 3.83 95% CI: 1.94-7.57), and being informed about the place and schedule for medical information (OR: 2.60, 95% CI: 1.60-4.22). Communication favourably affects the final perception of care, which justifies the continuity of its improvement in the health centres of our region.


Modulation of macromolecular permeability by immune-complexes and a beta-adrenoceptor stimulant.
The suffused, noneverted cheek pouch of ovalbumin (OA)-immunized hamsters was employed to study changes in vascular permeability utilizing intravital light microscopy and direct measurements of plasma to suffusate tracer efflux. Suffusion of the cheek pouches of immunized animals with OA for 10 min stimulated the formation of focal venular fluorescein isothiocyanate dextran (FITC-D, 70,000 Da) leakage sites and produced increases in the plasma to suffusate FITC-D efflux resulting in marked increases in concentration of FITC-D in suffusate ([FITC-D]s). The intravenous injection of the FITC-D 15 to 60 min after the start of the OA suffusion failed to reveal the formation of vascular FITC-D leakage sites or increases in [FITC-D]s. In contrast, the intravenous injection of the tracer at the start or 10 min after the start of the OA suffusion revealed the formation of venular FITC-D leakage sites and marked increases in [FITC-D]s. Treatment with diphenhydramine or isoproterenol completely inhibited the antigen-stimulated formation of venular FITC-D leakage sites and increases in [FITC-D]s. It is concluded that antigen-antibody reactions resulting in the production of immune complexes trigger immediate increases in the plasma to suffusate FITC-D clearance via the formation of venular FITC-D leakage sites subsequent to the release of endogenous histamine. The increase in venular permeability is marked but transient, lasting approximately 10 min, and is subject to inhibition by either diphenhydramine or isoproterenol.


Metabonomics study of urine and plasma in depression and excess fatigue rats by ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry.
A novel metabonomic method based on fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was applied to study the metabolic changes of plasma and urine in depression and excess fatigue rats. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied for classifying the depression, excess fatigue and the control rats. Metabolites which were important for the classification in the three groups of rats were selected as potential biomarkers and identified by MS(n) information achieved from UFLC/MS-IT-TOF analysis. Spermine, propionylcarnitine, butyrylcarnitine, phenylalanine, lysophosphatidylcholine (LPC) C14:0 and LPC C18:2 were down-regulated, methyl-hippuric acid and chenodeoxycholic acid (CDCA) were up-regulated significantly in plasma of the excess fatigue rats. Spermine, leucine, propionylcarnitine, and butyrylcarnitine decreased, hippuric acid, methyl-hippuric acid, cholic acid, CDCA and LPC C16:0 increased markedly in plasma of the depression rats. Ethyl N2-acetyl-L-argininate and N-methyl-2-pyridone-5-carboxamide (2-PY) (or N-methyl-4-pyridone-3-carboxamide (4-PY)) were down-regulated, leucylproline and pantothenic acid were up-regulated remarkably both in urine of depression and excess fatigue rats. The concentration of kynurenic acid and N2-succinyl-L-ornithine was low in urine of depression rats compared with control rats. Based on the data, correlation networks for depression and excess fatigue rats revealed the abnormality of nicotinate and nicotinamide metabolism, arginine metabolism, cholesterol metabolism, tryptophan metabolism and kynurenine metabolism in depression rats, and in excess fatigue rat alterations of energy metabolism, nicotinate and nicotinamide metabolism and lecithin metabolism. Our results provide novel insights in the complex metabolic mechanisms occurring in depression and excess fatigue rats.


A Fe/Fe3O4/N-carbon composite with hierarchical porous structure and in situ formed N-doped graphene-like layers for high-performance lithium ion batteries.
A Fe/Fe3O4/N-carbon composite consisting of a porous carbon matrix containing a highly conductive N-doped graphene-like network and Fe/Fe3O4 nanoparticles was prepared. The porous carbon has a hierarchical structure which is inherited from rice husk and the N-doped graphene-like network formed in situ. When used as an anode material for lithium batteries, the composite delivered a reversible capacity of approximately 610 mA h g(-1) at a current density of 200 mA g(-1) even after 100 cycles, due to the synergism between the unique hierarchical porous structures, highly electrically conductive N-doped graphene-like networks and nanosized particles of Fe/Fe3O4. This work provides a simple approach to prepare N-doped porous carbon activated nanoparticle composites which could be used to improve the electrochemical performance of lithium ion batteries.


Microdentistry: a new standard of care.
Micro-dentistry offers a new standard of care to address and solve the current challenges facing the dental profession. Patients will be grateful for accurate diagnosis of the pit and fissure system with caries detection dye and magnification, followed with comfortable air abrasion debridement and preparation for restoration with an adhesive composite material.


Mesenchymal stem cells transplantation for neuroprotection in preterm infants with severe intraventricular hemorrhage.
Severe intraventricular hemorrhaging (IVH) in premature infants and subsequent posthemorrhagic hydrocephalus (PHH) causes significant mortality and life-long neurological complications, including seizures, cerebral palsy, and developmental retardation. However, there are currently no effective therapies for neonatal IVH. The pathogenesis of PHH has been mainly explained by inflammation within the subarachnoid spaces due to the hemolysis of extravasated blood after IVH. Obliterative arachnoiditis, induced by inflammatory responses, impairs cerebrospinal fluid (CSF) resorption and subsequently leads to the development of PHH with ensuing brain damage. Increasing evidence has demonstrated potent immunomodulating abilities of mesenchymal stem cells (MSCs) in various brain injury models. Recent reports of MSC transplantation in an IVH model of newborn rats demonstrated that intraventricular transplantation of MSCs downregulated the inflammatory cytokines in CSF and attenuated progressive PHH. In addition, MSC transplantation mitigated the brain damages that ensue after IVH and PHH, including reactive gliosis, cell death, delayed myelination, and impaired behavioral functions. These findings suggest that MSCs are promising therapeutic agents for neuroprotection in preterm infants with severe IVH.


Improved glucose tolerance in insulin-resistant rats after pea hull feeding is associated with changes in lipid metabolism-targeted transcriptome.
Understanding of the mechanisms by which pulse grain fractions elicit beneficial effects on glucose tolerance is incomplete. An untargeted metabolomic analysis of serum from insulin-resistant rats was carried out to identify potential metabolic pathways affected by feeding rats the hull fraction of dried peas for 4 weeks. From this, we hypothesized that transcription of hepatic genes involved in lipid metabolism would be altered. cDNA was prepared from total RNA extracted from livers of rats fed a high-fat diet (HFD) or HFD + pea hulls (PH) diet. The liver lipid transcriptome of each cDNA sample was characterized using a PCR-based array of 84 genes. The activity of peroxisome-proliferator-activated receptor alpha (PPAR-α) was measured in hepatocyte nuclei. The predominant findings of the metabolomic analysis revealed a significant increase in the intermediaries of β-oxidation: C16-OH and C16:1 acylcarnitines (>50%, p < 0.05) and 3-hydroxybutyrate (100%, p < 0.05) in the PH group compared with the HFD group. mRNA of hadha, a gene involved in β-oxidation, was significantly reduced by 53% (p < 0.005) in the PH group compared with the HFD group, but no differences in PPAR-α activity were detected. 3-Hydroxybutyrate concentrations were associated with insulin sensitivity and reduced demand for insulin. The results indicate that feeding PH alters lipid metabolism in liver, which may contribute to improved glucose tolerance in insulin-resistant rats.


Electrophysiological correlates of cognitive control and the regulation of shyness in children.
Shyness is associated with social-emotional maladjustment in some, but not all, children. The ability to flexibly regulate attention under conditions of potential conflict may protect shy children from developing internalizing problems. In the current study, the associations between shyness, the N2 event related potential (ERP) response, and social-emotional adjustment were examined in a sample of 36 typically developing 9- to 13-year-old children. It was hypothesized that the N2 amplitude, an ERP measure associated with aspects of cognitive and attention control, would moderate the associations between shyness and social-emotional functioning (negative attribution style, social self-perceptions, social anxiety). Shyness was unrelated to behavioral or ERP measures collected during a modified Flanker task; however, shyness and N2 amplitude were alone and in combination associated with all three measures of social adjustment. In general, shyness was associated with poor outcomes primarily among children with relatively large amplitude, or enhanced, N2 responses. The results are discussed in terms of the role of conflict sensitivity in the regulation of attention and emotions associated with shyness and the importance of studying the combined influences of reactive and self-regulatory aspects of temperament in relation to adjustment in childhood.


Daily Sperm Output, Spermatogenic Efficiency, and Sexual Behavior of Dezhou Donkey Jacks Mounting Jennies in Estrus.
This study aimed to assess the sexual behavior of jacks mounting jennies in estrus and determine the daily sperm output (DSO) and spermatogenic efficiency using two equations to calculate testicular volume (TV). Eight sexually rested mature jacks, aging 5 to 10 years old, had semen collected once a day for 10 consecutive days using jennies in good standing estrus for mounting. Sexual behavior and semen parameters were assessed during each collection. Testicular measurements of height, width, and length were taken immediately before the first semen collection, and these measurements were used to calculate TV. After that, the TV was used to predict the DSO. The average total sperm number (TSN) obtained on days 8 to 10 was deemed the actual DSO. Differences in the predicted vs. the actual DSO were used to calculate the spermatogenic efficiency. In addition, the actual DSO was also used to calculate the number of inseminating doses a jack could produce for both on- and off-site breeding. Jack's sexual behavior and sperm motility did not vary across collection days. Sperm concentration and TSN reduced over time (P < .05). The actual DSO was 9.1 ± 4.1 billion, and the predicted DSO varied from 4.7 to 18 billion. Spermatogenic efficiency varied from 50 to 150% based on jack and the equation used to calculate TV. The number of inseminating doses ranged from 15 to 47 at 300-500 million progressively motile sperm (pms)/dose for on-site breeding. In contrast, the number of breeding doses with cooled-shipped semen (1 billion pms/dose) varied from 4 to 14 doses across donkeys. In conclusion, sexual behavior was not affected by daily semen collections. Sexual rest did not affect sperm motility. The predicted DSO varied with the equation used to determine TV. Clinically normal donkeys have high spermatogenic efficiency, which confirms previous histology reports.


Chronic abdominal wall pain: a frequently overlooked problem. Practical approach to diagnosis and management.
Chronic abdominal wall pain is frequently misdiagnosed as arising from a visceral source, often resulting in inappropriate diagnostic testing, unsatisfactory treatment, and considerable cost. Its prevalence in general medical practice is unknown, although it may account for about 10% of patients with chronic idiopathic abdominal pain seen in gastroenterological practices. The most common cause appears to be entrapment of an anterior cutaneous branch of one or more thoracic intercostal nerves; myofascial pain and radiculopathy are less frequent. Sharply localized pain and superficial tenderness are suggestive of abdominal wall origin. Carnett's test (accentuated localized tenderness with abdominal wall tensing) is a helpful diagnostic sign, especially when incorporated with other findings. Early exclusion of a parietal source should increase diagnostic accuracy when evaluating patients with chronic abdominal pain. Reassurance of patients by the correct diagnosis and avoidance of precipitating causes is often sufficient treatment. However, accurately placed anesthetic/corticosteroid injections give substantial pain relief to more than 75% of patients, often for prolonged periods, and may be confirmatory for the source of the complaint. The probability of missing visceral disease is small (probably less than 7%) with strict adherence to diagnostic criteria and diligent observation of patients.


[Urinary incontinence in degenerative spinal disease].
The aim of the study was to evaluate the presence of urinary incontinence in patients with chronic degenerative spinal disease and to identify factors affecting the occurrence and changes in urinary incontinence after surgery. The group evaluated comprised 214 patients undergoing surgery for degenerative spinal disease at our department between January 1 and December 31, 2008. The patients were categorised according to the type of their degenerative disease (cervical disc herniation, lumbar disc herniation, spinal stenosis, spinal instability or olisthesis) and the spine level involved (cervical or lumbar spine). The symptoms of urinary incontinence included leakage of urine and non-obstructive chronic urinary retention developing in association with the manifestation of vertebrogenic disorder. Patients with diseases known to increase the risk of incontinence were not included in the study. Based on a retrospective analysis of the patients' clinical notes, the occurrence of urinary incontinence in each type of degenerative spinal disease was assessed. The effect of gender, age, body mass index (BMI), neurological status and spinal disease type on the development of incontinence was statistically evaluated. The efficacy of surgical treatment was assessed on the basis of the patients' subjective complaints at the first follow-up one month after surgery. The data were evaluated by the statistical programme InSTAT (analysis of variance ANOVA, t-test). All tests were two-sided; a 0.05 level of statistical significance was used. Of the 214 patients with degenerative spinal disease, 27 (12.6%) had urinary incontinence. A higher risk of developing incontinence was found in women (p = 0.008) and in patients with radicular weakness (p = 0.023). The patients with urinary incontinence had their BMI significantly lower than patients without this disorder (p = 0.019). Age had no effect. The differences in the occurrence of urinary incontinence amongst the different types of degenerative disease were regarded as approaching statistical significance (p = 0.09). The surgical treatment resulted in incontinence control in 15 (55.5 %) affected patients. A comparison of the factors leading to the development of urinary incontinence in degenerative spinal disease and those associated with the development of incontinence in the general population suggests that the aetiology in each case is different. The relationship between low back pain and urinary incontinence remains unknown. Degenerative spinal disease can result in acute or chronic urinary incontinence. Factors associated with its development include gender, BMI, radicular weakness and the type of degenerative disease. Surgical treatment improved or eliminated the symptoms of urinary incontinence in more than half of the patients affected.


The use of technology in creating individualized, meaningful activities for people living with dementia: A systematic review.
There is a growing interest in using technology to provide meaningful activities for people living with dementia. The aim of this systematic review was to identify and explore the different types of digital technologies used in creating individualized, meaningful activities for people living with dementia. From 1414 articles identified from searches in four databases, 29 articles were included in the review. The inclusion criteria were the study used digital technology to deliver an individually tailored activity to participants with dementia, the process of individualization was described, and findings relating to the mental, physical, social, and/or emotional well-being of the participant were reported. Data extracted from the included studies included participant demographics, aims, methods, and outcomes. The following information on the technology was also extracted: purpose, type, training, facilitation, and the individualization process. A narrative synthesis of the results grouped the various technologies into four main purposes: reminiscence/memory support, behavior management, stimulating engagement, and conversation/communication support. A broad range of technologies were studied, with varying methods of evaluation implemented to assess their effect. Overall, the use of technology in creating individualized, meaningful activities seems to be promising in terms of improving behavior and promoting relationships with others. Furthermore, most studies in this review involved the person with dementia in the individualization process of the technology, indicating that research in this area is adopting a more co-creative and inclusive approach. However, sample sizes of the included studies were small, and there was a lack of standardized outcome measures. Future studies should aim to build a more concrete evidence base by improving the methodological quality of research in this area. Findings from the review indicate that there is also a need for more evidence concerning the feasibility of implementing these technologies into care environments.


Multiple scattering of arbitrarily incident Bessel beams by random discrete particles.
In this paper, we introduce an efficient numerical method to characterize the multiple scattering by random discrete particles illuminated by Bessel beams with arbitrary incidence. Specifically, the vector expressions of Bessel beams that perfectly satisfy Maxwell's equations in combination with rotation Euler angles are used to represent the arbitrarily incident Bessel beams. A hybrid vector finite element-boundary integral-characteristic-basis function method is utilized to formulate the scattering problems involving multiple discrete particles with a random distribution. Due to the flexibility of the finite element method, the adopted method can conveniently deal with the problems of multiple scattering by randomly distributed homogeneous particles, inhomogeneous particles, and anisotropic particles. Some numerical results are included to illustrate the validity and capability of the proposed method and to show the scattering behaviors of random discrete particles when they are illuminated by Bessel beams.


Prevalence of junctional ST-depression with tall symmetrical T-waves in a pre-hospital field triage system for STEMI patients.
The prevalence of the junctional ST-depression with tall symmetrical T-waves in a field triage system for ST-Elevation Myocardial Infarction (STEMI) is unknown. We prospectively collected all transmitted 12-lead electrocardiograms (ECGs) from the STEMI field triage system in Amsterdam from 2011 to 2013. Electrocardiograms with junctional ST-depression with tall symmetrical T-waves were recognized and angiographic documentation and clinical follow up were collected. A total of 5588 patients with at least 1 transmitted field ECG were identified from the database. ST-elevation infarction was present on the field ECG in 1864 patients (33%) and 701 ECGs (12,5%) showed anterior infarction. In 11 patients, junctional ST-depression with tall symmetrical T-waves was identified (0,2% of total transmitted ECGs and 1,6% of anterior infarctions). The 11 angiograms invariably showed involvement of the proximal Left Anterior Descending (LAD) artery (segment 5,6 and 7). Mortality was 27% within the first week. An ECG with junctional ST-depression with tall symmetrical T-waves is an infrequent finding. Because this pattern of STEMI equivalent is associated with LAD occlusions, it is important to recognize this pattern, so patients can be transported to the catheterization laboratory without delay.


Parasitic nematodes, proteinases and transgenic plants.
Parasite proteinases have important functions in host-parasite interactions. Consequently, they have been investigated as targets for the control of both plant and animal parasites. Plant parasitic nematodes cause estimated annual losses to world agriculture of US$100 billion and, currently, their control often relies on highly toxic nematicides, with associated environmental risks. The potential of disrupting digestive proteinases for plant parasitic nematode control, via expression of proteinase inhibitors in transgenic plants, is summarized here by Catherine Lilley, Pauline Devlin, Peter Urwin and Howard Atkinson. They then consider whether the approach of expressing antinematode proteins in plants can be adapted for control of certain animal parasitic nematodes.


The Battle of the Pneumonia Predictors: A Comprehensive Meta-Analysis Comparing the Pneumonia Severity Index (PSI) and the CURB-65 Score in Predicting Mortality and the Need for ICU Support.
The CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥ 65 years) score and the pneumonia severity index (PSI) are widely used and recommended in predicting 30-day mortality and the need for intensive care support in community-acquired pneumonia. This study aims to compare the performance of these two severity scores in both mortality prediction and the need for intensive care support. A systematic review and meta-analysis was carried out, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 2020 guidelines, and PubMed, Scopus, ScienceDirect, and Google Scholar were searched for articles published from 2012 to 2022. The reference lists of the included studies were also searched to retrieve possible additional studies. Twenty-five studies reporting prognostic information for CURB 65 and PSI were identified. ReviewManager (RevMan) 5.4.1 was used to produce risk ratios, and a random effects model was used to pool them. Both PSI and CURB-65 showed a high strength in identifying high-risk patients. However, CURB-65 was slightly better in early mortality prediction and had more sensitivity (96.7%) and specificity (89.3%) in predicting admission to intensive care support. Thus, CURB-65 seems to be the preferred tool in predicting mortality and the need for admission into intensive care support.


Effects of (+)-HA-966 and 7-chlorokynurenic acid on the kinetics of N-methyl-D-aspartate receptor agonist responses in rat cultured cortical neurons.
It has been suggested that one of the effects of glycine at the N-methyl-D-aspartate (NMDA) receptor complex is to reduce the amount of apparent receptor desensitization. Thus, blockade with a glycine site antagonist results in NMDA responses that show an increased amount of fade. In agreement with this, we found that antagonism of NMDA-evoked whole-cell currents by 7-chlorokynurenic acid (7-Cl-KYNA) indeed resulted in NMDA responses that displayed an increased amount of fade. However, those responses that were antagonized by (+)-HA-966 showed the opposite, i.e., less tendency to fade. On examination of these responses, it appeared that those produced in the presence of (+)-HA-966 were slower in onset and faster in offset than control responses recorded in the presence of glycine alone. Kinetic analysis of the on- and off-rates of NMDA- and glutamate-evoked NMDA receptor-mediated responses revealed that these were markedly affected by (+)-HA-966 but only slightly by 7-Cl-KYNA. The decrease of the glutamate response decay time constant and the increase of the response rise time constant produced by (+)-HA-966 indicated that it reduced the affinity of glutamate for its recognition site on the NMDA receptor by 5-fold. These results suggest that binding of (+)-HA-966 to the glycine site on the NMDA receptor complex produces an allosteric reduction in the affinity of agonists for the glutamate recognition site, whereas 7-Cl-KYNA has relatively little effect and, thus, acts more as a pure antagonist at the glycine site.


Influence of CD80, interleukin-2, and interleukin-7 expression in human renal cell carcinoma on the expansion, function, and survival of tumor-specific CTLs.
A renal cell carcinoma (RCC) line, RCC-26, has been identified as a suitable candidate for development of an allogeneic tumor cell vaccine based on its expression of a variety of tumor-associated antigens (TAA). To improve immunogenicity, RCC-26 cells were genetically engineered to express CD80 alone or in combination with interleukin (IL)-2 or IL-7. The effect of these modifications on proliferation, function, and survival of autologous and allogeneic tumor-specific CTLs was assessed. RCC-26 sublines expressing different transgenes were tested for their capacity to reactivate cytokine secretion and cytotoxicity in autologous tumor-infiltrating lymphocytes, to improve proliferation and survival of tumor-associated T cells present in autologous peripheral blood, and to induce tumor-associated responses in naive allogeneic lymphocytes. The expression of several common TAA was quantitated in the RCC-26 sublines using reverse transcription-PCR to identify surrogate markers for immune monitoring in clinical trials. Gene-modified RCC-26 cells showed enhanced immunogenicity. CD80 expression was necessary to induce RCC-associated CTL in blood of healthy allogeneic donors. It also improved proliferation of autologous effector-memory T cells. Further enhancement was achieved with IL-2 through induction of the antiapoptosis protein Bcl-x(L). The candidate vaccine lines overexpressed several common TAA that are suitable markers for immune monitoring. RCC-26 cells coexpressing CD80 and cytokine transgenes display improved immunogenic characteristics, supporting their use as allogeneic tumor cell vaccines for HLA-A2-matched patients with metastatic RCC.


Maintenance of the anterior chamber during penetrating keratoplasty.
A description of the author's (S.G.K.) technique for penetrating keratoplasty is provided. The salient features include corneal removal, storage, and corneal graft cutting procedures of Kaufman and his co-workers. In addition, a specially designed suturing contact lens is described which allows maintenance of the anterior chamber during penetrating keratoplasty. It is suggested that trauma to the all-important cornea endothelium can be minimized by application of this technique, because it significantly reduces the likelihood of endothelial trauma induced by mechanical contact of the endothelium with intraocular recipient structures during suturing.


Enhancing the quality and safety of the perioperative patient.
Many possible hazards bedevil the perioperative patient. This review focuses on a number of aspects of perioperative management where the patient's quality and safety can be enhanced. Our understanding of the relationship between preoperative preparation and postoperative outcomes has improved. There have also been recent developments in our understanding of how to construct useful cognitive aids and make the best use of checklists by understanding the cultural environment supporting their use. Postoperatively, the concept of 'failure to rescue' in the surgical patients has been explored. A clear vision of what postoperative recovery should mean for practitioner and patients; careful risk stratification and prophylactic measures to avoid postoperative complications; the judicious use of checklists and other cognitive aids to complement clinical expertise in promoting safety within each local context; and the prompt recognition and rescue of postoperative problems when they occur are all important aspects of a safe perioperative care.


[Current aspects of hepatotoxicity in occupational medicine].
A large number of chemical agents encountered occupationally are known as potential hepatotoxins. The practical relevance of these results should be considered critically for the individual case and under usual work layout. In this paper the current state of knowledge for hepatotoxicity in occupational medicine is described. Different diagnostical methods and criteria for suspected chemical-induced liver injury are shown. The paper focuses on the potential hepatotoxic effects of chronic exposures to solvents, since these substances are used in a large variety of modern places of work. On the basis of field studies in occupationally exposed workers the potential hepatotoxical effects of mixtures of solvents are discussed. Recommendations for medical surveillance places of work are proposed.


Working memory performance in typically developing children and adolescents: behavioral evidence of protracted frontal lobe development.
Post-mortem histological and in vivo neuroimaging findings both reveal frontal lobe development that extends beyond the adolescent years. Few studies have examined whether this protracted neurodevelopment coincides with improvements in adolescent performance on putative frontal lobe tasks. An instrumental function supported by the frontal lobes is working memory, the ability to maintain and manipulate information online. This study investigated the performance of typically developing children and adolescents on a battery of working memory tasks. Findings revealed an improvement in performance on most working memory tasks across the adolescent years. In contrast, no improvement was observed on tasks largely supported by more posterior neural substrates. Current findings indicate a similar unfolding of the executive aspects of verbal working memory as previously demonstrated with spatial working memory. Factor analysis revealed a grouping of working memory tasks based largely on task demands, irrespective of working memory domain, adding support for process-specific models of prefrontal organization. Important implications for typical and atypical frontal lobe development are discussed.


Realizing tissue integration with supramolecular hydrogels.
Biomaterial matrices must permit tissue growth and maturation for the success of tissue regeneration strategies. Naturally, this accommodation is achieved via the dynamic remodeling of a cell's extracellular matrix (ECM). Synthetically, hydrolytic or enzymatic degradation are often engineered into materials for this purpose. More recently, supramolecular interactions have been used to provide a biomimetic and tunable mechanism to facilitate tissue formation via their dynamic and reversible non-covalent interactions. By engineering the mechanical and bioactive properties of a material, supramolecular chemists are able to design permissivity into the construct and facilitate tissue integration in-vivo. Furthermore, via the reversibility of non-covalent interactions, injectability and responsiveness can be designed for enhanced delivery and spatio-temporal control. In this review, we delineate the basic considerations needed when designing permissive supramolecular hydrogels for tissue engineering with an eye toward tissue growth and integration. We highlight three archetypal hydrogel systems that have shown well-documented tissue integration in vivo, and provide avenues to assess tissue in-growth. Careful design and assessment of the biomedical potential of a supramolecular hydrogels can inspire the creation of robust and dynamic implants for new tissue engineering applications.


Comparison of methods for coccidioidomycosis complement fixation.
A Laboratory Branch Task Force of the National Communicable Disease Center has proposed a standardized complement fixation procedure (LBCF) and an adaptation of this to microtitration techniques (MT) as uniform methods for performing complement fixation (CF) tests. A common procedure should make CF results from one laboratory more comparable to another. In addition, it would be preferable if the common procedure reproduced the titer levels of a testing procedure which is to be replaced, particularly when valid clinical interpretations have been derived from the latter. Replicated sets of sera were tested by the LBCF, MT, and the standard Smith CF procedure for coccidioidomycosis. Results with all three procedures were highly reproducible within an acceptable one-tube variation of a twofold dilution series, but the frequency of one-tube variations was greater with the MT method than with the other two. There was no statistical difference in the titers obtained with the Smith and LBCF procedures, but there was a significant difference when the MT results were compared to those with the Smith method. The LBCF method should be acceptable as a standardized and uniform CF procedure for coccidioidomycosis, subject to comparative testing between different laboratories.


Decreased Weight-for-Age Associated with Mass Deworming among Young Ethiopian Schoolchildren in Jimma Town, Southwest Ethiopia: A School-Based Cross-Sectional Study.
School-based mass deworming programs are implemented to reduce soil-transmitted helminth (STH) infection prevalence and intensity among school-aged children. However, previous studies debate the impact of deworming beyond the removal of worms. Hence, this study aimed to examine the effect of mass deworming on nutritional indicators in young Ethiopian schoolchildren. A school-based cross-sectional study was conducted among 1,036 participants from April to May 2020 in Jimma Town, Ethiopia. An interviewer-based questionnaire was administered to the children to gather data on sociodemographic, lifestyle variables, and deworming status. Anthropometric measurements were taken for the height and weight of the children. Stool samples were collected and analyzed for STH infection using direct wet mount microscopy and the Kato-Katz technique. In multivariate logistic regression analysis, deworming within the past 6 months or 1 year was not significantly associated with underweight, stunting, and thinning. However, deworming within the past year was significantly associated with decreased weight-for-age z-score (adjusted mean difference = -0.245; 95% CI: -0.413 to -0.076; P = 0.004). Deworming in the past 6 months demonstrated a nonsignificant trend toward increased stunting (adjusted odds ratio = 1.258; 95% CI: 0.923-1.714; P = 0.145). This study provides evidence that deworming in the past 6 months or 1 year was not significantly associated with underweight, stunting, and thinning. However, deworming within the past year was associated with a significantly decreased weight-for-age z-score in young Ethiopian schoolchildren of Jimma Town after adjustment for confounding variables.


Rotator cuff muscles perform different functional roles during shoulder external rotation exercises.
The aim of this study was to compare activity in shoulder muscles during an external rotation task under conditions of increasing arm support to investigate whether changing support requirements would influence muscle recruitment levels, particularly in the rotator cuff (RC) muscles. Electromyographic recordings were collected from seven shoulder muscles using surface and indwelling electrodes. The dominant shoulder of 14 healthy participants were examined during dynamic shoulder external rotation performed at 90° abduction with the arm fully supported, partially supported, and unsupported. Linear regressions between arm support load and the averaged muscle activity across participants for each muscle showed infraspinatus predominantly contributing to rotating the shoulder whilst supraspinatus, deltoid, upper trapezius, and serratus anterior were predominantly functioning in support/stabilization roles. During dynamic shoulder external rotation in mid-range abduction, the RC muscles perform different functional roles. Infraspinatus is responsible for producing external rotation torque, supraspinatus is playing a larger joint stabilizer role, and subscapularis is contributing minimally to joint stability. The results also indicate that increasing support load requirements during an external rotation task may be a functionally specific way to retrain the stabilization function of axioscapular muscles. Manipulating joint stabilization requirements while maintaining constant rotational load is a novel method of investigating the differential contribution of muscles to joint movement and stabilization during a given task.


Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway.
Honokiol is one of the main active components of Magnolia officinalis, and has been demonstrated to have multiple pharmacological activities against a variety of diseases. Recently, this phenolic compound is known to have antioxidant activity, but its mechanism of action remains unclear. The purpose of the current study was to evaluate the preventive effects of honokiol against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. The present study found that honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation. The inhibitory effect of honokiol on H2O2-induced apoptosis was associated with the up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, these results demonstrate that honokiol defends C2C12 myoblasts against H2O2-induced DNA damage and apoptosis, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS.


Pre-operative clonal hematopoiesis is related to adverse outcome in lung cancer after adjuvant therapy.
Clonal hematopoiesis (CH) frequently progresses after chemotherapy or radiotherapy. We evaluated the clinical impact of preoperative CH on the survival outcomes of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection followed by adjuvant therapy. A total of 415 consecutive patients with NSCLC who underwent surgery followed by adjuvant therapy from 2011 to 2017 were analyzed. CH status was evaluated using targeted deep sequencing of blood samples collected before surgery. To minimize the possible selection bias between the two groups according to CH status, a propensity score matching (PSM) was adopted. Early-stage patients were further analyzed with additional matched cohort of patients who did not receive adjuvant therapy. CH was detected in 21% (86/415) of patients with NSCLC before adjuvant therapy. Patients with CH mutations had worse overall survival (OS) than those without (hazard ratio [95% confidence interval] = 1.56 [1.07-2.28], p = 0.020), which remained significant after the multivariable analysis (1.58 [1.08-2.32], p = 0.019). Of note, the presence of CH was associated with non-cancer mortality (p = 0.042) and mortality of unknown origin (p = 0.018). In patients with stage IIB NSCLC, there was a significant interaction on OS between CH and adjuvant therapy after the adjustment with several cofactors through the multivariable analysis (HR 1.19, 95% CI 1.00-1.1.41, p = 0.041). In resected NSCLC, existence of preoperative CH might amplify CH-related adverse outcomes through adjuvant treatments, resulting in poor survival results.


Changes in health-related quality of life before and after a 12-month enhanced primary care model among chronically ill primary care patients in Australia.
Evidence suggests that Patient-centred Medical Home (PCMH) model facilitates person-centred care and improves health-related quality of life for patients with chronic illness. This study aims to evaluate changes in health-related quality of life (HRQoL), before and after enrolment into a 12-month integrated care program called 'WellNet'. This study includes 616 eligible consented patients aged 40 years and above with one or more chronic conditions from six general practices across Sydney, Australia. The WellNet program included a team of general practitioners (GPs) and clinical coordinators (CCs) providing patient-tailored care plans configured to individual risk and complexity. HRQoL was recorded using the validated EuroQol five dimensions five levels (EQ-5D-5L) instrument at baseline and 12 months. Additionally, patients diagnosed with osteoarthritis also reported HRQoL using short versions of Knee and/or Hip disability and osteoarthritis outcome scores (KOOSjr and HOOSjr). A case-series study design with repeated measures analysis of covariance (ANCOVA) was used to assess changes in mean differences of EQ-5D index scores after controlling for baseline covariates. Additionally, backward stepwise multivariable linear regression models were conducted to determine significant predictors of EQ-5D index scores at follow-up. Out of 616 patients, 417 (68%) reported EQ-5D scores at follow-up. Almost half (48%) of the WellNet patients reported improved EQ-5D index scores at follow-up. After controlling for baseline covariates, the adjusted mean difference was statistically significant whilst also meeting the bare minimal clinically important difference (MCID) with a change of 0.03 (95% CI 0.01, 0.05). The multivariable regression models determined that baseline EQ-5D scores and positive diagnosis of a respiratory illness were significant predictors of HRQoL at follow-up. There were significant improvements across both KOOS and HOOS assessments, specifically, the pain and symptom scores in both scales met statistical significance in addition to meeting the MCID. Patient-tailored chronic disease management (CDM) plans designed by team of GPs and CDM clinical coordinators could lead to better HRQoL among primary care patients.


Identification of the catalytic triad of the lipase/acyltransferase from Aeromonas hydrophila.
Aeromonas hydrophila secretes a lipolytic enzyme that has several properties in common with the mammalian enzyme lecithin-cholesterol acyltransferase. We have recently shown that it is a member of a newly described group of proteins that contain five similar blocks of sequence arranged in the same order in their primary structures (C. Upton and J. T. Buckley, Trends Biochem. Sci. 233:178-179, 1995). Assuming that, like other lipases, these enzymes have a Ser-Asp-His catalytic triad, we used these blocks to predict which aspartic acid and histidine would be at the active site of the Aeromonas enzyme. Targeted residues were replaced with other amino acids by site-directed mutagenesis, and the effects on secretion and activity were assessed. Changing His-291 to asparagine completely abolished enzyme activity, although secretion by the bacteria was not affected. Only very small amounts of the D116N mutant appeared in the culture supernatant, likely because it is sensitive to periplasmic proteases it encounters en route. Assays of crude preparations containing this variant showed no detectable enzyme activity. We conclude that, together with Ser-16, which we have identified previously, Asp-116 and His-291 compose the catalytic triad of the enzyme.


Bilateral versus posterior injection of botulinum toxin in the internal anal sphincter for the treatment of acute anal fissure.
Comparison of bilateral versus posterior injection of botulinum toxin into the internal anal sphincter for treatment of acute anal fissure. Forty patients with acute anal fissure were randomly divided into two equal groups. Group 1 was treated by injecting 20 units of botulinum toxin into each side of the internal anal sphincter, and group 2 by injecting 25 units of botulinum toxin into the midline posteriorly. The mean time to pain relief was 8.45 (standard deviation (SD) 7.41) days in group 1 and 7.20 (SD 7.19) days in group 2. Healing took place in a mean of 5.20 (SD 1.85) weeks in group 1 and 5.40 (SD 2.01) weeks in group 2. Fissures failed to heal in 2 patients in group 1 and 3 in group 2, and recurred in 4 patients in group 1 and 3 in group 2. Botulinum toxin injection is effective in treating acute anal fissure. A single posterior injection is easier and less painful than bilateral injection, and is as effective in pain relief.


Migration or residency? The evolution of movement behavior and information usage in seasonal environments.
Migration, the seasonal movement of individuals among different locations, is a behavior found throughout the animal kingdom. Although migration is widely studied at taxonomically restricted levels, cross-taxonomic syntheses of migration are less common. As a result, we lack answers to broad questions such as what ultimate factors generally drive animal migration. Here we present such a synthesis by using a spatially explicit, individual-based model in which we evolve behavior rules via simulations under a wide range of ecological conditions to answer two questions. First, under what types of ecological conditions can an individual maximize its fitness by migrating (vs. being a resident)? Second, what types of information do individuals use to guide their movement? We show that migration is selected for when resource distributions are dominated more by seasonality than by local patchiness, and residency (nonmigratory behavior) is selected for when the reverse is true. When selected for, migration evolves as both a movement behavior and an information usage strategy. We also find that different types of migration can evolve, depending on the ecological conditions and availability of information. Finally, we present empirical support for our main results, drawn from migration patterns exhibited by a variety of taxonomic groups.


Long-acting risperidone vs. placebo in the treatment of hospital inpatients with schizophrenia.
Maintenance treatment regimens for patients with schizophrenia are often suboptimal. Partial adherence and outright noncompliance are associated with symptom recurrence and increased likelihood of rehospitalization. Long-acting conventional neuroleptics have limited efficacy and are associated with treatment-limiting adverse events, while oral atypical antipsychotics have not improved adherence substantially. A long-acting formulation of risperidone, an atypical antipsychotic with proven efficacy, has been developed. Introduction of long-acting injectable treatment may be appropriate during inpatient hospitalization, when consequences of relapse are most evident. To support this intervention, a subanalysis of patients who were inpatients at study initiation was conducted from a 12-week, double-blind, placebo-controlled long-acting risperidone study (N = 214). Long-acting risperidone was associated with a significant reduction in total Positive and Negative Syndrome Scale (PANSS) score (mean change +/- standard error [S.E.] at endpoint: long-acting risperidone, -9.27 +/- 1.44, n = 133; placebo, 0.72 +/- 2.59, n = 41; P < 0.001), and a significantly higher rate of treatment response, defined as > or = 20% reduction in total PANSS score (50% vs. 27%, P < 0.05). Significantly more long-acting risperidone patients had endpoint Clinical Global Impressions (CGI) assessments of not ill, very mild or mild (32% vs. 5%; P < 0.01). Long-acting risperidone was well tolerated. Long-acting risperidone initiated during inpatient treatment may be an important strategy in improving long-term outcomes among patients with schizophrenia.


DQB1*0602 allele shows a strong association with multiple sclerosis in patients in Malaga, Spain.
The human leukocyte antigen (HLA) class II DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) has been associated with multiple sclerosis (MS) in all ethnic groups and very strongly in Caucasians. To investigate the possible HLA class II (DRB1, DQA1 and DQB1) associations with MS in Malaga, southern Spain. We analysed the HLA class II sub-regions DRB1, DQA1 and DQB1 by polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (PCR/SSO) for DRB1 and DQB1 and with sequence-specific primers (PCR/SSP) for DRB1 subtypes and DQA1. Possible HLA class II associations with clinical MS characteristics were investigated in 149 subjects with and 160 without MS. Associations were detected between MS and the HLA class II alleles DRB1*1501 (45.6 % vs. 21.3%, p=0.001), DQA1*0102 (44% vs. 29.4%, p=0.001) and DQB1*0602 (45% vs. 20.6%, p=0.001). The DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) was associated with MS (43.6 % vs. 20%, p=0.002). DQB1*0602 was the only allele that maintained an association with MS in a logistic regression model. No HLA class II alleles or genotypes were significantly associated with any clinical characteristics of MS. Our results confirm the positive association of the DR2 haplotype with MS, particularly the allele DQB1*0602, in the population studied. DR4 was not associated with the disease in Malaga. HLA class II alleles or haplotypes were not associated with clinical or demographic characteristics, or clinical form or severity of MS.


Age of pension eligibility, gains in life expectancy, and social policy.
Canadians are living longer and retiring younger. When combined with the aging of the baby-boom generation, that means that the "inactive" portion of the population is increasing and there are concerns about possibly large increases in the burden of support on those who are younger. We model the impact of continued future gains in life expectancy on the size of the population that receives public pension benefits. We pay special attention to possible increases in the age of eligibility and the pension contribution rate that would maintain the publicly financed component of the retirement income security system.