Comparison of sedation scores and propofol induction doses in dogs after intramuscular premedication with butorphanol and either dexmedetomidine or medetomidine.
To compare sedation scores and propofol induction doses in dogs receiving either dexmedetomidine or medetomidine, both with butorphanol intramuscularly (IM) prior to general anaesthesia. Prospective, 'blinded', randomized, clinical study. Fifty client-owned dogs scheduled for elective diagnostic imaging procedures. Dogs were allocated to receive butorphanol 0.1 mg kg(-1) with either medetomidine (group M) 0.01 mg kg(-1) or dexmedetomidine (group D) 0.005 mg kg(-1) IM. Sedation was scored before and 20 minutes after pre-anaesthetic medication using a composite simple descriptive sedation score giving a score of 0 to 15 (0 = no sedation; 15 = profound sedation). Forty-five minutes after pre-anaesthetic medication, propofol was administered in increments of 0.5 mg kg(-1) over 15 seconds until tracheal intubation was possible. The time required to check intubation conditions between each propofol aliquot was 15 seconds. Total propofol dose required to perform tracheal intubation and the number of dogs achieving a clinically desired sedation score of ≥9/15 was recorded in each group. Sedation score and propofol dose were compared using the Mann-Whitney U-test. Results are reported as median (range). Statistical significance was set at p < 0.05. The sedation score 20 minutes after pre-anaesthetic medication was significantly higher in group M [11 (2-14)] than in group D [7 (0-14)]. There was no significant difference between propofol dose requirements in group M [1.5 (1-2.5) mg kg(-1)] or D at [1.5 (1-3) mg kg(-1)]. Significantly more dogs in group M achieved a sedation score of ≥9/15 than in group D. Combined IM with butorphanol, medetomidine 0.01 mg kg(-1) produced effective sedation more frequently than dexmedetomidine 0.005 mg kg(-1) in dogs undergoing sedation prior to anaesthesia for elective procedures but this did not affect the propofol dose required for induction of anaesthesia significantly.


Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes.
The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.


Ultrafast Coulomb explosion of a diiodomethane molecule induced by an X-ray free-electron laser pulse.
Coulomb explosion of diiodomethane CH2I2 molecules irradiated by ultrashort and intense X-ray pulses from SACLA, the Japanese X-ray free electron laser facility, was investigated by multi-ion coincidence measurements and self-consistent charge density-functional-based tight-binding (SCC-DFTB) simulations. The diiodomethane molecule, containing two heavy-atom X-ray absorbing sites, exhibits a rather different charge generation and nuclear motion dynamics compared to iodomethane CH3I with only a single heavy atom, as studied earlier. We focus on charge creation and distribution in CH2I2 in comparison to CH3I. The release of kinetic energy into atomic ion fragments is also studied by comparing SCC-DFTB simulations with the experiment. Compared to earlier simulations, several key enhancements are made, such as the introduction of a bond axis recoil model, where vibrational energy generated during charge creation processes induces only bond stretching or shrinking. We also propose an analytical Coulomb energy partition model to extract the essential mechanism of Coulomb explosion of molecules from the computed and the experimentally measured kinetic energies of fragment atomic ions by partitioning each pair Coulomb interaction energy into two ions of the pair under the constraint of momentum conservation. Effective internuclear distances assigned to individual fragment ions at the critical moment of the Coulomb explosion are then estimated from the average kinetic energies of the ions. We demonstrate, with good agreement between the experiment and the SCC-DFTB simulation, how the more heavily charged iodine fragments and their interplay define the characteristic features of the Coulomb explosion of CH2I2. The present study also confirms earlier findings concerning the magnitude of bond elongation in the ultrashort X-ray pulse duration, showing that structural damage to all but C-H bonds does not develop to a noticeable degree in the pulse length of ∼10 fs.


Reactions of 2-indolylphosphines with Ru3(CO)12: cluster capping with mu 3,eta 2-indolylphosphine as an anionic six-electron P,N-donor ligand.
Stepwise bidentate coordination of the novel indolylphosphine ligands HL (1, HL = P(C(6)H(5))(2)(C(9)H(8)N)(diphenyl-2-(3-methylindolyl)phosphine); 2, HL = P(C(6)H(5))(C(9)H(8)N)(2)(phenyldi-2-(3-methylindolyl)phosphine); and 3, HL = P(C(6)H(5))(C(17)H(12)N(2))(di(1H-3-indolyl)methane-(2,12)-phenylphosphine)) to the ruthenium cluster Ru(3)(CO)(12) is demonstrated. Reactions of 1-3 with Ru(3)(CO)(12) led to the formation of Ru(3)(CO)(11)(HL) (4-6), in which HL is mono-coordinated through the phosphorus atom. The X-ray structures of 4-6 show that the phosphorus atom is equatorially coordinated to the triruthenium core. In all cases, gentle heating of Ru(3)(CO)(11)(HL) resulted in the formation of Ru(3)(CO)(9)(mu-H)(mu(3),eta(2)-L)(7-9) in which the NH proton of the indolyl substituent had migrated to the ruthenium core to form a bridging hydride ligand. The X-ray structure of Ru(3)(CO)(9)(mu-H)[mu(3),eta(2)-P(C(6)H(5))(2)(C(9)H(7)N)] (7) shows the deprotonated nitrogen atom of the indolyl moiety bridging over the face of the triruthenium core, bonding to the two ruthenium metal centers to which the phosphorus atom is not bound. The phosphorus atom is forced to adopt an axial bonding mode due to the geometry of the indolylphosphine ligand. Cluster electron counting and X-ray data suggest that the indolylphosphine behaves as a six-electron ligand in this mode of coordination. Compounds 4-9 have been characterized by IR, (1)H, (13)C and (31)P NMR spectroscopy.


A Study of Visual and Musculoskeletal Health Disorders among Computer Professionals in NCR Delhi.
To study the prevalence of health disorders among computer professionals and its association with working environment conditions. Cross sectional. A sample size of 200 computer professionals, from Delhi and NCR which included software developers, call centre workers, and data entry workers. The prevalence of visual problems in the study group was 76% (152/200), and musculoskeletal problems were reported by 76.5% (153/200). It was found that there was a gradual increase in visual complaints as the number of hours spent for working on computers daily increased and the same relation was found to be true for musculoskeletal problems as well. Visual problems were less in persons using antiglare screen, and those with adequate lighting in the room. Musculoskeletal problems were found to be significantly lesser among those using cushioned chairs and soft keypad. A significant proportion of the computer professionals were found to be having health problems and this denotes that the occupational health of the people working in the computer field needs to be emphasized as a field of concern in occupational health.


Diaphragm muscle thinning in patients who are mechanically ventilated.
Approximately 40% of patients in medical ICUs require mechanical ventilation (MV). Approximately 20% to 25% of these patients will encounter difficulties in discontinuing MV. Multiple studies have suggested that MV has an unloading effect on the respiratory muscles that leads to diaphragmatic atrophy and dysfunction, a process called ventilator-induced diaphragmatic dysfunction (VIDD). VIDD may be an important factor affecting when and if MV can be discontinued. A sensitive and specific diagnostic test for VIDD could provide the physician with valuable information that might influence decisions regarding extubation or tracheostomy. The purpose of this study was to quantify, using daily sonographic assessments, the rate and degree of diaphragm thinning during MV. Seven intubated patients receiving MV during acute care were included. Using sonography, diaphragm muscle thickness was measured daily from the day of intubation until the patient underwent extubation or tracheostomy or died. We analyzed our data using standard descriptive statistics, linear regression, and mixed-model effects. The overall rate of decrease in the diaphragm thickness of all seven patients over time averaged 6% per day of MV, which differed significantly from zero. Similarly, the diaphragm thickness decreased for each patient over time. Sonographic assessment of the diaphragm provides noninvasive measurement of diaphragmatic thickness and the degree of diaphragm thinning in patients receiving MV. Our data show that diaphragm muscle thinning starts within 48 h after initiation of MV. However, it is unclear if diaphragmatic thinning correlates with diaphragmatic atrophy or pulmonary function. The relationship between diaphragm thinning and diaphragm strength remains to be elucidated.


Uncovering the cellular capacity for intensive and specific feedback self-control of the argonautes and MicroRNA targeting activity.
The miRNA pathway has three segments-biogenesis, targeting and downstream regulatory effectors. We aimed to better understand their cellular control by exploring the miRNA-mRNA-targeting relationships. We first used human evolutionarily conserved sites. Strikingly, AGOs 1-3 are all among the top 14 mRNAs with the highest miRNA site counts, along with ANKRD52, the phosphatase regulatory subunit of the recently identified AGO phosphorylation cycle; and the AGO phosphorylation cycle mRNAs share much more than expected miRNA sites. The mRNAs for TNRC6, which acts with AGOs to channel miRNA-mediated regulatory actions onto specific mRNAs, are also heavily miRNA-targeted. In contrast, upstream miRNA biogenesis mRNAs are not, and neither are downstream regulatory effectors. In short, binding site enrichment in miRNA targeting machinery mRNAs, but neither upstream biogenesis nor downstream effector mRNAs, was observed, endowing a cellular capacity for intensive and specific feedback control of the targeting activity. The pattern was confirmed with experimentally determined miRNA-mRNA target relationships. Moreover, genetic experiments demonstrated cellular utilization of this capacity. Thus, we uncovered a capacity for intensive, and specific, feedback-regulation of miRNA targeting activity directly by miRNAs themselves, i.e. segment-specific feedback auto-regulation of miRNA pathway, complementing miRNAs pairing with transcription factors to form hybrid feedback-loop.


Exogenous peptides delivered by ricin require processing by signal peptidase for transporter associated with antigen processing-independent MHC class I-restricted presentation.
In this study we demonstrate that a disarmed version of the cytotoxin ricin can deliver exogenous CD8(+) T cell epitopes into the MHC class I-restricted pathway by a TAP-independent, signal peptidase-dependent pathway. Defined viral peptide epitopes genetically fused to the N terminus of an attenuated ricin A subunit (RTA) that was reassociated with its partner B subunit were able to reach the early secretory pathway of sensitive cells, including TAP-deficient cells. Successful processing and presentation by MHC class I proteins was not dependent on proteasome activity or on recycling of MHC class I proteins, but rather on a functional secretory pathway. Our results demonstrated a role for signal peptidase in the generation of peptide epitopes associated at the amino terminus of RTA. We showed, first, that potential signal peptide cleavage sites located toward the N terminus of RTA can be posttranslationally cleaved by signal peptidase and, second, that mutation of one of these sites led to a loss of peptide presentation. These results identify a novel MHC class I presentation pathway that exploits the ability of toxins to reach the lumen of the endoplasmic reticulum by retrograde transport, and suggest a role for endoplasmic reticulum signal peptidase in the processing and presentation of MHC class I peptides. Because TAP-negative cells can be sensitized for CTL killing following retrograde transport of toxin-linked peptides, application of these results has direct implications for the development of novel vaccination strategies.


[National handbook for the prevention and control of diabetes in primary care (2019)].
National handbook for the prevention and control of diabetes in primary care (2019) is made for the use in combination with the national guidelines for the prevention and control of diabetes in primary care (2018). It provides detailed information and supplementary for the contents involved in the guidelines.


Study protocol of a multicenter randomized controlled trial of mindfulness-based cognitive therapy and treatment as usual in bipolar disorder.
Despite multiple pharmacological interventions, many people with bipolar disorder (BD) experience substantial residual mood symptoms, even in the absence of severe mood episodes, which have a negative impact on the course of illness and quality of life. Limited data are available on how to optimize treatment for BD, especially for those who suffer from persistent and residual depressive symptoms. Preliminary evidence suggests Mindfulness-Based Cognitive Therapy (MBCT) as a psychological treatment option for BD. This study aims to investigate whether adding MBCT to treatment as usual (TAU) will result in symptomatic and functional improvements in adults with BD compared to TAU alone. This study is a prospective, evaluator blinded, multicenter, randomized controlled trial of MBCT + TAU and TAU alone in 160 adults with bipolar type I and type II. Assessments will be conducted at baseline (T0), mid-treatment (Tmid), and at 3 (T1), 6 (T2), 9 (T3), 12 (T4), and 15 (T5) months follow-up. Primary outcome is post-treatment severity of depressive symptoms (Inventory of Depressive Symptomatology- Clinician administered). Secondary outcomes are severity of (hypo) manic symptoms, anxiety, relapse rates, overall functioning, positive mental health, and cost-effectiveness. As possible mediators will be assessed rumination of negative affect, dampening and rumination of positive affect, mindfulness skills, and self-compassion. This study will provide valuable insight into the (cost-)effectiveness of MBCT on clinician- and self-rated symptoms of BD, relapse rates, positive mental health, and overall functioning. NCT03507647 . Registered 25th of April 2018.


A method for Porphyromonas gingivalis based on recombinase polymerase amplification and lateral flow strip technology.
A practical visual detection method was established to detect Porphyromonas gingivalis (P. gingivalis) by employing a combination of recombinase polymerase amplification and lateral flow strips (RPA-LF) assay, designed for conducting point-of-care testing in clinical settings. Primers and probes targeting the P. gingivalis pepO gene were designed. The RPA-LF assay was established by optimising reaction temperature and time, determining the limit of detection (LOD). The specificity of the method was determined by assessing its cross-reactivity with deoxyribonucleic acid from 23 pathogenic bacteria. Finally, the clinical samples from healthy controls (n = 30) and individuals with periodontitis (n = 31) were analysed. The results were compared with those obtained using real-time polymerase chain reaction (PCR). The optimal reaction temperature and time were 39 °C and 12 min. The method exhibited a LOD at 6.40 × 10-4 μg/mL and demonstrated high specificity and sensitivity during cross-reactivity assessment. The RPA-LF assay achieved a P. gingivalis detection rate of 84 % in individuals with periodontitis and 3 % in healthy controls. The results were consistent with those obtained through real-time PCR. An RPA-LF assay was developed for detecting P. gingivalis, characterised by its high sensitivity, high specificity, simple operational procedure, and rapid reaction time.


The Significance of Serum S100A9 and TNC Levels as Biomarkers in Colorectal Cancer.
Purpose: The aim of this study was to evaluate the diagnostic value of S100A9 and tenascin-c (TNC) levels as colorectal cancer (CRC) biomarkers in several ways, including through screening tests, differentiation tests, combination with existing biomarkers (CEA and CA19-9), and serum level measurements before and after surgery. Materials and Methods: In this case-control study, S100A9 and TNC serum levels were measured in 460 participants: 258 CRC patients, 99 patients with benign colonic disease (BCD) and 103 healthy donors (HD). Results: The serum levels of S100A9 were 22.32 (14.88-29.55) ng/ml, 10.02 (5.83-14.15) ng/ml and 10.05 (7.68-15.34) ng/ml in the CRC, BCD and HD groups, respectively. The serum levels of TNC were 4.30 (2.12-6.04) ng/ml, 1.60 (1.06-2.30) ng/ml and 2.00 (1.37-3.00) ng/ml in the CRC, BCD and HD groups, respectively. Significantly higher levels of both biomarkers (S100A9 and TNC) were found in CRC patients (both p<0.001). Both S100A9 and TNC levels were superior to CEA and CA19-9 levels as CRC diagnostic biomarkers; the combination of S100A9, TNC and CEA levels was an excellent biomarker with 79.8% sensitivity and 89.6% specificity. The serum levels of S100A9 and TNC in CRC patients were significantly lower after surgery than before surgery (p<0.01). Conclusion: S100A9 and TNC levels could serve as diagnostic biomarkers of colorectal cancer.


Extraction of pectins from renewable grapefruit (Citrus paradisi) peels using deep eutectic solvents and analysis of their structural and physicochemical properties.
This study presents an innovative attempt to extract high-quality pectins from grapefruit (Citrus paradisi) peels by using deep eutectic solvents (DESs) as extraction agents. The maximum yield of betaine-citric acid (BC)-extracted pectin (BC-P) reached 36.47 % under the optimum process conditions: an L/S ratio of 25 mL/g, a pH of 2.0, and a temperature of 85 °C for 120 min. The yield of BC-P was significantly higher than HCl-extracted pectin (HCl-P, 8.76 %) under a pH of 2.0. In addition, the structural, physicochemical, and emulsifying properties of the purified pectins (BC-P and HCl-P) and commercial pectin (CP) were comparatively analyzed. Results showed that BC-P exhibited higher RG-I value, more arabinan side-chains, bigger Mw and Mn value than HCl-P. Moreover, the viscosity, G' and G'' of BC-P were significantly higher than those of HCl-P and CP. More importantly, BC-P demonstrated better emulsifying activity and stability compared to HCl-P and CP. When the concentration of BC-P was increased to 1.50 %, a stable emulsion containing a 50 % soybean oil fraction could be obtained. Our results confirmed that DESs can be considered as high-effective agents for pectin extraction. Pectins extracted from grapefruit peels can be as a promising natural emulsifiers that can be used in the food industry.


Effects of instability of samples during liquid scintillation counting on the results of ligand-binding studies by equilibrium dialysis.
In binding studies using equilibrium dialysis, mixing of the aqueous samples with scintillation cocktails designed to accommodate aqueous samples produced grossly erroneous binding data. The amount of [1,5-14C]citrate apparently bound to rabbit muscle phosphofructokinase was a linear function of the citrate concentration, with no tendency to approach saturation, and highly variable. This problem was caused by very slow precipitation of citrate in the scintillation cocktail. Addition of a solubilizer stabilized the count rate during scintillation counting and resulted in acceptable binding curves.


A theoretical model of financial burden after cancer diagnosis.
Current models of financial burden after cancer do not adequately define types of financial burden, moderators or causes. We propose a new theoretical model to address these gaps. This model delineates the components of financial burden as material and psychological as well as healthcare-specific (affording treatment) versus general (affording necessities). Psychological financial burden is further divided into worry about future costs and rumination about past and current financial burden. The model hypothesizes costs and employment changes as causes, and moderators include precancer socioeconomic status and post-diagnosis factors. The model outlines outcomes affected by financial burden, including depression and mortality. Theoretically derived measures of financial burden, interventions and policy changes to address the causes of financial burden in cancer are needed.


Novel antibiotics in development to treat Clostridium difficile infection.
Clostridium difficile infections (CDI) remain a challenge to treat clinically due primarily to limited number of antibiotics available and unacceptably high recurrence rates. Because of this, there has been significant demand for creating innovative therapeutics, which has resulted in the development of several novel antibiotics. This review updates seven different antibiotics that are currently in development to treat CDI including fidaxomicin, surotomycin, ridinilazole, ramoplanin, cadazolid, LFF571, and CRS3123. Available preclinical and clinical data are compared between these antibiotics. Many of these new antibiotics display almost ideal properties for antibiotics directed against CDI. Despite these properties, not all clinical development of these compounds has been successful. These studies have provided key insights into the pathogenesis of CDI and will continue to inform future drug development. Successful phase III clinical trials should result in several new and novel antibiotics to treat CDI.


Surface Roughness Effects on Self-Interacting and Mutually Interacting Rayleigh Waves.
Rayleigh waves are very useful for ultrasonic nondestructive evaluation of structural and mechanical components. Nonlinear Rayleigh waves have unique sensitivity to the early stages of material degradation because material nonlinearity causes distortion of the waveforms. The self-interaction of a sinusoidal waveform causes second harmonic generation, while the mutual interaction of waves creates disturbances at the sum and difference frequencies that can potentially be detected with minimal interaction with the nonlinearities in the sensing system. While the effect of surface roughness on attenuation and dispersion is well documented, its effects on the nonlinear aspects of Rayleigh wave propagation have not been investigated. Therefore, Rayleigh waves are sent along aluminum surfaces having small, but different, surface roughness values. The relative nonlinearity parameter increased significantly with surface roughness (average asperity heights 0.027-3.992 μm and Rayleigh wavelengths 0.29-1.9 mm). The relative nonlinearity parameter should be decreased by the presence of attenuation, but here it actually increased with roughness (which increases the attenuation). Thus, an attenuation-based correction was unsuccessful. Since the distortion from material nonlinearity and surface roughness occur over the same surface, it is necessary to make material nonlinearity measurements over surfaces having the same roughness or in the future develop a quantitative understanding of the roughness effect on wave distortion.


Psychological predictors of the antihypertensive effects of music-guided slow breathing.
The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure (ABP), and predictors of efficacy were explored in a randomized, placebo-controlled trial with parallel design. Age-matched and sex-matched hypertensive patients were randomized to music-guided slow breathing exercises (4-6 breaths/min; 1: 2 ratio of inspiration: expiration duration) (Intervention; n = 29) or to control groups who were thought to relax while either listening to slow music (Control-M; n = 26) or reading a book (Control-R; n = 31). At baseline and at follow-up visits (1 week and 1, 3 and 6 months), ABP monitoring was performed. At mixed model analysis, intervention was associated with a significant reduction of 24-h (P = 0.001) and night-time (0100-0600 h) (P < 0.0001) systolic ABP. The average reduction of systolic 24-h ABP at 6 months was 4.6 mmHg [confidence limits at 95% 1.93-7.35] and 4.1 mmHg (95% confidence limits 1.59-6.67) vs. Control-M and Control-R groups, respectively, (P < 0.001 for both). Antihypertensive treatment was selected as negative predictor of BP reduction at multivariate stepwise analysis. When antihypertensive treatment was inserted as covariate in a generalized linear model, psychological subscales assessed at baseline by the Mental Health Inventory questionnaire were found to affect systolic blood pressure reduction at 6-month follow-up (general positive affect P < 0.001; emotional ties, P < 0.001; loss of behavioral control, P = 0.035). In particular, a level of general positive affect higher than the 75th percentiles was found to be significantly associated with low treatment efficacy (odds ratio 0.09; 95% confidence limits 0.01-0.93). Daily sessions of voluntary music-guided slow breathing significantly reduce 24-h systolic ABP, and psychological predictors of efficacy can be identified.


Cancer recurrences and secondary primary cancers after use of antihistamines or antidepressants.
Reports in the scientific literature have described accelerated tumor growth in association with antidepressant and antihistamine exposure in experimental rodent cancer models. This study was designed to determine whether exposure to prescription antidepressants or antihistamines is associated with tumor growth in humans. Two nested case-control studies were conducted with a cohort of 1467 patients with breast cancer, colon cancer, or melanoma diagnosed between 1988 and 1994. Eligible patients included 95 with a cancer recurrence and 78 with a second primary lesion diagnosed during the follow-up period. Five control subjects were matched to each case patient according to cancer site, stage, and follow-up time. Conditional logistic regression was used to compare risk for tumor recurrence or occurrence of a second primary tumor among patients using antidepressants or antihistamines with risk among unexposed patients. For a cohort of patients who were predominantly female (78%), with breast cancer (57%) and with a tumor in situ or with localized disease (79%), the average age was 62 years at cancer diagnosis and average duration of follow-up period was 2.2 years. Use of antidepressants or antihistamines was unrelated to risk for tumor recurrence (odds ratio, 0.97; 95% confidence interval, 0.52 to 1.78) or second primary tumors (odds ratio, 0.94; 95% confidence interval, 0.50 to 1.77). Typical use of antidepressant or antihistamine drugs did not increase risk for recurrent or second primary tumors among patients with cancer.


An In-Vitro Evaluation of Microleakage in Resin-Based Restorative Materials at Different Time Intervals.
A vital feature of conservative dentistry is the adhesion of the restorative material to the tooth structure for restoration of the tooth substance lost due to dental decay, trauma, or dental imperfections. In a perfect world, a restorative material should generate a lasting adhesion by bonding the restoration with tooth tissues. The ingress of micro-organisms, oral fluids, molecules, and ions through microscopic spaces due to faulty adhesion between restoration and tooth structure is known as microleakage. This study is focuses on the evaluation of adhesive failures between the restorative materials. In the past, studies have focused more on the bonding potential of a restorative material with the tooth surface. Therefore, there is need to carry out a study that compares the microleakage between resin-based restorative materials in a sandwich manner with and without the intermediate bonding layer after immersion in 2% methylene blue dye at different time intervals. The restorative materials used were composite Ceram X Mono plus (DENTSPLY) and Z350 (3M ESPE), Vitremer resin modified glass ionomer cement (RMGIC) (3M ESPE), smart dentine replacement SDR (3M ESPE), Bond NT (DENTSPLY), and Universal Bond (3M ESPE). A light emitting diode (LED) was used to cure the specimens. Artificial saliva was used as a storage medium for the specimens. Thermocycling of specimens was carried out at 500 cycles/30 s and 1000 cycles/30 s. The world health organization (WHO) grading tool for microleakage was used to analyze fluid ingress in the specimens through disclosing by 2% methylene blue dye. The statistical analysis was carried out with one-way analysis of variance (ANOVA) and Tukey post hoc test, keeping the level of significance at p ≤ 0.05. In Grade 0 = 85 samples, Grade 1 = 10 samples, Grade 2 = 7 samples, Grade 3 = 16 samples, and in Grade 4 = 2 samples were identified. This study describes that no microleakage was observed in SDR and resin composite groups as compared to Vitremer and resin composite groups.


Collagen Anchoring Protein-Nucleic Acid Chimeric Probe for In Situ In Vivo Mapping of a Tumor-Specific Protease.
In situ analysis of biomarkers in the tumor microenvironment (TME) is important to reveal their potential roles in tumor progression and early diagnosis of tumors but remains a challenge. In this work, a bottom-up modular assembly strategy was proposed for a multifunctional protein-nucleic chimeric probe (PNCP) for in situ mapping of cancer-specific proteases. PNCP, containing a collagen anchoring module and a target proteolysis-responsive isothermal amplification sensor module, can be anchored in the collagen-rich TME and respond to the target protease in situ and generate amplified signals through rolling cycle amplification of tandem fluorescent RNAs. Taking matrix metalloproteinase 2 (MMP-2), a tumor-associated protease, as the model, the feasibility of PNCP was demonstrated for the in situ detection of MMP-2 activity in 3D tumor spheroids. Moreover, in situ in vivo mapping of MMP-2 activity was also achieved in a metastatic solid tumor model with high sensitivity, providing a useful tool for evaluating tumor metastasis and distinguishing highly aggressive forms of tumors.


A cost-effective statistical method to correct for differential genotype misclassification when performing case-control genetic association.
There is a growing interest regarding the effect of differential misclassification on power and type I error rate in genome-wide association studies. We present an extension of a previously published test statistic: the likelihood ratio test allowing for errors (LRTAE). This test uses double-sample information on a subset of individuals to increase power for genetic association in the presence of nondifferential misclassification. We extend the original LRTAE by allowing for differential genotype misclassification between case and control populations. We label this new statistic as LRT(D)A(M)E . We test the performance of this statistic with data simulated under differential misclassification specifications and two different types of genetic models: null and power. For simulations using the null model, we specify that there is no difference between case and control genotype frequencies before the introduction of errors. For simulations under power, we consider three modes of inheritance: dominant, multiplicative, and recessive. We show that the LRT(D)A(M)E , with p values computed using permutation, maintains a correct type I error rate under the null model after the introduction of differential genotyping errors. Also, we find that as little as 10 to 15% of double-sampled genotype data is needed to achieve this effect. Aside from a few situations (particularly recessive mode of inheritance simulations) the LRT(D)A(M)E version that calculates p values through permutation requires 15 to 20% double sampling to maintain an 80% power for a 0.05 significance level and approximately 20% double sampling for a 0.01 significance level.


Nonsurgical management of acute jejunal diverticulitis: a review.
Diverticular disease of the colon and its complications are well known and readily considered when patients present with the proper clinical scenario. Conversely, complications of small bowel diverticula are very uncommon entities and are not often thought of as a cause of bleeding, obstruction, or an acute abdomen. To report two patients presenting with an acute abdomen caused by acute jejunal diverticulitis who were treated nonsurgically as opposed to surgically as the literature dictates. Two patients presented with sudden onset of acute periumbilical pain that had increased progressively over 1-2 days before admission. An emergent CT scan performed in each patient with localized peritonitis revealed "collections" consistent with abscess cavities. One patient was treated with antibiotics alone and the other with a combination of antibiotics and percutaneous CT-guided aspiration. CT-guided needle aspiration was performed and the injection of contrast clearly revealed communication with a jejunal diverticulum. Both patients did well and were subsequently discharged without incident or surgical intervention. Acute jejunal diverticulitis must be considered in the differential diagnosis of an acute abdominal process and may be successfully treated nonsurgically despite the recommendations of previous reports.


Combination of Backbone Rigidity and Richness in Aryl Structures Enables Direct Membrane Translocation of Polymer Scaffolds for Efficient Gene Delivery.
The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.


Preparation and characterization of methotrexate-loaded microcapsules.
Methotrexate (MTX) has toxic effect to healthy tissues. Microencapsulation coats particles with a functional coat to optimize storage stability and to modulate release. In the present study, a new MTX encapsulated microcapsules were synthesized for controlling MTX release. Controlled drug release provides releasing of efficient dose and prevent drug side effect to tissues and also protects MTX from oxygen, pH and other interactions. MTX was encapsulated through biocompatible hyaluronic acid (HA) and sodium alginate (SA) with an encapsulation system to reduce its toxicity and for controlled release. The microcapsules prepared by vibrating nozzle were cross-linked with SA, HA and calcium chloride. Nozzle diameter and MTX concentration were changed according to loaded MTX and encapsulation efficiency were determined using HPLC. For the reliability of the data, validation studies of the HPLC method were performed. The precision of the method was demonstrated using intra- and inter-day assay relative standard deviation (RSD) values which are less than 2% in all instances. For the characterization of microcapsules, particle size, drug loading and in vitro drug release studies were performed. Diameters of MTX-loaded microcapsules were acquired approximately 160, 400 and 800 µm. Surface morphology of encapsulated microcapsules were displayed with light microscope. Eighty-nine percent MTX encapsulation efficiencies were achieved. Encapsulated MTX microcapsules showed controlled release when compared to pure MTX. While powder MTX dissolved completely in 10 min in the dissolution medium, MTX release from encapsulated MTX microcapsules became 40 h in 0.1 M PBS pH 7.4, including NaCl. MTX release from MTX-loaded microcapsules was reached to 79%. Moreover, drug efficiency was examined in vitro cell culture tests. Viability of 5RP7 cells were decreased to 88.5% for 96 h. When MTX was given directly to 5RP7 cells, viability of 5RP7 cells was decreased to 49.7% for 96 h. Flow cytometry studies also showed that, MTX microcapsules induced apoptosis. The goal of this study is to provide controlled release of MTX and to reduce the toxic effect of MTX.


Transience in polarization of cytolytic effectors is required for efficient killing and controlled by Cdc42.
Cytolytic effectors polarize toward target cells for effective killing and IFN-gamma secretion. The spatiotemporal features of this polarization and their importance for cytolysis have not been resolved. In cytotoxic T cells and natural killer (NK) cells, transient polarization was consistently associated with effective killing. Polarization was regulated by Cdc42, a small Rho family GTPase universally critical for cytoskeletal dynamics. Transient accumulation of active Cdc42 at the cytolytic effector/target cell interface and focus of such accumulation on the interface center were closely related to cytolysis. Surprisingly, however, the intensity of Cdc42 activation was not. We interfered with Cdc42 activation in NK cells such that sustained polarization in long lasting nonkilling cell couples was selectively blocked. Thus the proportion of the NK cell population displaying transient polarization was increased. As a consequence, cytolytic responder frequency and IFN-gamma production were enhanced upon such interference with Cdc42 activation. These data support the notion that transience in polarization is critical for cytolytic effector function, likely by preventing cytolytic effectors from becoming trapped in nonproductive target cell interactions.


Encapsulation of antihypertensive drugs in cellulose-based matrix microspheres: characterization and release kinetics of microspheres and tableted microspheres.
This study is an attempt to prepare microspheres loaded with two antihypertensive drugs viz., nifedipine (NFD) and verapamil hydrochloride (VRP) using cellulose-based polymers viz., ethyl cellulose (EC) and cellulose acetate (CA). Emulsification and solvent evaporation methods were optimized using ethyl acetate as a dispersing solvent. The particles are spherical in shape and have smooth surfaces, as evidenced by the scanning electron microscopy. The microspheres were characterized for their particle size and distribution, tapped density and encapsulation efficiency. Smaller sized particles with a narrow size distribution were produced with EC when compared to CA matrices. Molecular level drug distribution in the microspheres was confirmed by differential scanning calorimetry. The microspheres were directly compressed into tablets using different excipients. The drug release from CA was faster than EC microspheres and, also, the VRP release was faster than NFD. The excipients used in tableting showed an effect on the release as well as the physical properties of the tablets.


Geometric morphometrics of face profile across horse breeds and within Arabian horses: Horse face geometric morphometrics.
Horse traits under selection are largely quantitative and affected by multiple genes. Horse face shape is an example of a continuous trait, which due to the reliance on observational assessments, is classified into; "dished", "straight", and "roman-nosed". This categorization is often inadequate to convey the full spectrum of the face shape variation especially for genetic studies. The first objective of the current study was to use geometric morphometric methods to quantitatively phenotype face shapes and examine its variation across horse breeds. The second objective was to analyze the face shape variation within Arabian horses since face shape is (1) favored, valued, and genetically selected in certain lineages (e.g. Egyptian), (2) is evaluated by registries and scored in shows, and (3) in its extreme forms pose health concerns. We digitized landmarks on lateral profile photos, particularly on the dorsal curvature of the rostrum, and subjected these landmarks to Generalized Procrustes Analysis to generate independent shape and size variables which were statistically compared across breeds and within Arabians. Horse breeds varied in nasal curvature, ranging from extremely concave to extremely convex, with over 70% of horse breeds exhibiting intermediate concavity (i.e., straight profile). Interestingly, Arabian horses possessed the highest diversity in face profile and individuals clustered into three distinct shape sub-groups (one dished and two straight profile clusters). Our quantitative phenotyping method can be the basis of future genetic studies of facial profile within Arabian lineages as a favored traits and potentially manage its extreme forms as a likely genetic disease.


Contributions of exercise, body composition, and age to bone mineral density in premenopausal women.
The purpose of this cross-sectional study were to determine whether exercisers have greater bone mineral density (BMD) than nonexercisers, whether aerobic dancers have greater BMD than walkers, and to determine the contributions of energy expenditure, body composition, and dietary factors to spine and femur BMD. Measurements were obtained on 93 eumenorrheic women (walkers N = 28; aerobic dancers, N = 34; nonexercisers, N = 31) ages 25-41 yr; lumbar spine and proximal femur BMD, body composition, physical activity, and nutrient intakes. Mean height, weight, and body mass index and median age and calcium intakes were similar for the three groups. Mean (+/- SD) values of the spine, total femur, and femoral neck BMD, respectively, were: walkers (1.092 (+/- 0.098), 0.947 g.cm-2), dancers (1.070 (+/- 0.124), 0.990 (+/- 0.104), 0.908 (+/- 0.106) g.cm-2), and nonexercisers (1.020 (+/- 0.112), 0.887 (+/- 0.073), 0.792 (+/- 0.089) g.cm-2) multiple regression analyses indicated that exercise contributed to spine (P = 0.018), total femur (P =0.012), and femoral neck (P < 0.0001) BMD, whereas type of exercise (aerobic dance vs walking) did not (P > 0.05). Total femoral BMD was influenced by exercise (P = 0.012) and energy expenditure (P = 0.023), while vertebral BMD was influenced by age (P = 0.0067), body weight (P = 0.017), and exercise (P = 0.018). These findings suggest that walking and aerobic dance exercise may provide physically active premenopausal women with greater lumbar and femoral BMD than sedentary females.


The interaction of purified rabbit bone collagenase with purified rabbit bone metalloproteinase inhibitor.
1. Pure rabbit bone metalloproteinase inhibitor (TIMP) bound tightly to pure rabbit bone collagenase with an apparent Kd of 1.4 X 10(-10) M. 2. The molecular weight of the enzyme-inhibitor complex was found to be 54 000, but no enzyme activity could be recovered from the complex after treatment with either mercurials or proteinases. The complex thus differed from latent collagenase in terms of size, susceptibility to mercurials and behaviour on concanavalin A-Sepharose. 3. The interaction of the purified components was compared with that of crude collagenase and crude inhibitor in culture medium. Mercurial treatment partially reversed the inhibition in the crude system, but not when the purified components were used. 4. The significance of the results is discussed in relation to the extracellular control of the activity of collagenase.


Requirement for RAR-mediated gene repression in skeletal progenitor differentiation.
Chondrogenesis is a multistep process culminating in the establishment of a precisely patterned template for bone formation. Previously, we identified a loss in retinoid receptor-mediated signaling as being necessary and sufficient for expression of the chondroblast phenotype (Weston et al., 2000. J. Cell Biol. 148:679-690). Here we demonstrate a close association between retinoic acid receptor (RAR) activity and the transcriptional activity of Sox9, a transcription factor required for cartilage formation. Specifically, inhibition of RAR-mediated signaling in primary cultures of mouse limb mesenchyme results in increased Sox9 expression and activity. This induction is attenuated by the histone deacetylase inhibitor, trichostatin A, and by coexpression of a dominant negative nuclear receptor corepressor-1, indicating an unexpected requirement for RAR-mediated repression in skeletal progenitor differentiation. Inhibition of RAR activity results in activation of the p38 mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) pathways, indicating their potential role in the regulation of chondrogenesis by RAR repression. Accordingly, activation of RAR signaling, which attenuates differentiation, can be rescued by activation of p38 MAPK or PKA. In summary, these findings demonstrate a novel role for active RAR-mediated gene repression in chondrogenesis and establish a hierarchical network whereby RAR-mediated signaling functions upstream of the p38 MAPK and PKA signaling pathways to regulate emergence of the chondroblast phenotype.


Divergent immune responses in behaviorally-inhibited vs. non-inhibited male rats.
Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific health outcomes, however, we have limited information on whether immune function varies by personality. In the present study, we examined the relationship between a basic behavioral trait (behavioral-inhibition vs. non-inhibition) and two immune responses (innate inflammation and delayed-type hypersensitivity, DTH) in a rodent model. In humans, behavioral inhibition (fearful temperament) is associated with altered stress physiology and allergies. In laboratory rats, the trait is associated with elevated glucocorticoid production. We hypothesized that behavioral inhibition is associated with glucocorticoid resistance and dampened T-helper 1 cell responses often associated with chronic stress and allergies. Further, this immune profile would predict poorly-regulated innate inflammation and dampened DTH. In male Sprague-Dawley rats, we quantified consistent behavioral phenotypes by measuring latency to contact two kinds of novelty (object vs. social), then measured lipopolysaccharide(LPS)-induced innate inflammation or keyhole limpet hemocyanin(KLH)-induced DTH. Behaviorally-inhibited rats had heightened glucocorticoid and interleukin-6 responses to a low/moderate dose of LPS and reduced DTH swelling to KLH re-exposure compared to non-inhibited rats. These results suggest that behavioral inhibition is associated with a glucocorticoid resistant state with poorly regulated innate inflammation and dampened cell-mediated immune responses. This immune profile may be associated with exaggerated T-helper 2 responses, which could set the stage for an allergic/asthmatic/atopic predisposition in inhibited individuals. Human and animal models of temperament-specific immune responses represent an area for further exploration of mechanisms involved in individual differences in health.


Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes.
Hyperglycemia plays an important role in the pathogenesis of type 2 diabetes mellitus, i.e., glucotoxicity, and it also is the major risk factor for microvascular complications. Thus, effective glycemic control will not only reduce the incidence of microvascular complications but also correct some of the metabolic abnormalities that contribute to the progression of the disease. Achieving durable tight glycemic control is challenging because of progressive β-cell failure and is hampered by increased frequency of side effects, e.g., hypoglycemia and weight gain. Most recently, inhibitors of the renal sodium-glucose cotransporter have been developed to produce glucosuria and reduce the plasma glucose concentration. These oral antidiabetic agents have the potential to improve glycemic control while avoiding hypoglycemia, to correct the glucotoxicity, and to promote weight loss. In this review, we will summarize the available data concerning the mechanism of action, efficacy, and safety of this novel antidiabetic therapeutic approach.


Interaction of human and mouse Abeta peptides.
Transgenic mice over-expressing mutant human amyloid precursor protein have become an important tool for research on Alzheimer's disease (AD) and, in particular, for therapeutic screening. Many models have reported formation of amyloid plaques with age as is detected in AD. However, the plaques generated in transgenic mice are more soluble than human plaques. Differences in solubility may occur for a number of reasons; one proposal is the presence of murine Abeta peptides within the CNS milieu. Here, we report the interaction of human and murine Abeta peptides, Abeta40 and Abeta42, utilizing a fluorescence assay to monitor formation of mixed pre-fibrillar aggregates, electron microscopy to examine morphological characteristics and detergent solubility to monitor stability. Our results demonstrate that interspecies Abeta aggregates and fibres are readily formed and are more stable than homogenous human fibres. Furthermore, these results suggest that the presence of endogenous murine Abeta in human APP transgenic mice does not account for the increased solubility of plaques.


Predictors of abdominal aortic aneurysm sac enlargement after endovascular repair.
The majority of infrarenal abdominal aortic aneurysm (AAA) repairs in the United States are performed with endovascular methods. Baseline aortoiliac arterial anatomic characteristics are fundamental criteria for appropriate patient selection for endovascular aortic repair (EVAR) and key determinants of long-term success. We evaluated compliance with anatomic guidelines for EVAR and the relationship between baseline aortoiliac arterial anatomy and post-EVAR AAA sac enlargement. Patients with pre-EVAR and at least 1 post-EVAR computed tomography scan were identified from the M2S, Inc. imaging database (1999 to 2008). Preoperative baseline aortoiliac anatomic characteristics were reviewed for each patient. Data relating to the specific AAA endovascular device implanted were not available. Therefore, morphological measurements were compared with the most liberal and the most conservative published anatomic guidelines as stated in each manufacturer's instructions for use. The primary study outcome was post-EVAR AAA sac enlargement (>5-mm diameter increase). In 10 228 patients undergoing EVAR, 59% had a maximum AAA diameter below the 55-mm threshold at which intervention is recommended over surveillance. Only 42% of patients had anatomy that met the most conservative definition of device instructions for use; 69% met the most liberal definition of device instructions for use. The 5-year post-EVAR rate of AAA sac enlargement was 41%. Independent predictors of AAA sac enlargement included endoleak, age ≥ 80 years, aortic neck diameter ≥ 28 mm, aortic neck angle >60°, and common iliac artery diameter >20 mm. In this multicenter observational study, compliance with EVAR device guidelines was low and post-EVAR aneurysm sac enlargement was high, raising concern for long-term risk of aneurysm rupture.


Emotional competence and nursing education: a New Zealand study.
Effective nursing practice requires the ability to recognise emotions and handle responses in relationships with clients and their families. This emotional competence includes nurses managing their own emotional life along with the skill to relate effectively to the multiple colleagues and agencies that nurses work alongside. The research was designed to explore the views of nurse educators about the challenges they encounter when seeking to assess a student's development of emotional competence during the three year bachelor of nursing degree. Focus groups were used to obtain from educators evidence of feeling and opinion as to how theory and practice environments influence student nurses' development of emotional competence. The process of thematic analysis was utilised and three key themes arose as areas of importance to the participants. These were personal and social competence collectively comprises emotional competence in nursing; emotional competence is a key component of fitness to practise; and transforming caring into practice. The findings of the study indicate a need for definition of what emotional competence is in nursing. It is argued that educators and practicing nurses, who work alongside students, must uphold the expectation that emotional competence is a requisite ability and should themselves be able to role model emotionally competent communication.


[Eludication of pathomechanism of and development of therapy for autophagic vacuolar myopathies].
Autophagic vacuolar myopathy (AVM) is an entity defined by the presence of autophagic vacuoles on muscle pathology. There are two emerging categories in AVM in addition to the best characterized Pompe disease. One is Danon disease and its related disorders, which are characterized by autophagic vacuoles with unique sarcolemmal features (AVSF). AVSF express virtually all sarcolemmal proteins, in addition to acetylcholinesterase, on their vacuolar membranes. Danon disease is caused by primary deficiency of a lysosomal membrane protein, LAMP-2. Interestingly, in this disease, the number of AVSF increases as the patients age. Other AVSF myopathies include X-linked myopathy with excessive autophagy which is now known to be caused by VMA21 mutations. The other AVM is typified by the presence of rimmed vacuoles, which are actually clusters of autophagic vacuoles on electron microscopy. One of the well known diseases in this group is distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion body myopathy (HIBM). DMRV is caused by mutations in GNE gene that encode a rate-limiting enzyme in the sialic acid biosynthetic pathway. Interestingly, in DMRV model mice, sialic acid supplementation almost completely precluded the disease phenotype, indicating that decreased sialic acid is the cause of myopathic phenotype and sialic acid supplementation can prevent the disease process. Interestingly, both genetically diagnosable AVSF myopathies are primarily due to lysosomal dysfunctions. In contrast, rimmed vacuoles are secondarily caused by extra-lysosomal defects, such as hyposialylation in DMRV/HIBM, and are formed at later stages of the disease.


Successful implementation of modern critical care in the low-resources country Bosnia and Herzegovina : Single-center experience.
Critical care medicine is a relatively young discipline, developed in the mid-1950s in response to the outbreak of poliomyelitis. The mass application of mechanical ventilation and its subsequent technical advancement helped manage large numbers of patients with respiratory failure. This branch of medicine evolved much faster in high-income (HIC) than low- and middle-income countries (LMIC). Seventy years later, mankind's encounter with coronavirus disease 2019 (COVID-19) represents another major challenge for critical care medicine especially in LMIC countries where over two thirds of the world population live. Systematic analysis of written documents related to the establishment of the first multidisciplinary medical intensive care unit (MICU) in Bosnia and Herzegovina and its development to the present day. We describe the experience of setting up a modern critical care program under LMIC constraints as a promising way forward to meet the increased worldwide demand for critical care. Successful development is contingent on formal education and continued mentorship from HIC, establishment of a multidisciplinary team, the support from local health care authorities, development of a formal subspecialty training, academic faculty development, and research. Novel technologies including tele-education provide additional opportunities for rapid development and dissemination of critical care medicine programs in LMIC. Critical care medicine is a critical public health need in HIC and LMIC alike. The challenges associated with the coronavirus pandemic should serve as a wakeup call for rapid development of critical care programs around the world.


Dietary egg white protein inhibits lymphatic lipid transport in thoracic lymph duct-cannulated rats.
Dietary egg white protein (EWP) decreases serum cholesterol levels. We previously showed that EWP decreased cholesterol absorption in the intestine. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of dietary EWP on lipid transport. They were fed diets with 20% EWP and casein, and their lymph was collected to quantify lymphatic lipid levels. Dietary EWP decreased lymphatic cholesterol transport compared with casein. It was previously shown that EWP excluded cholesterol from bile acid micelles. Therefore, pepsin-hydrolyzed EWP and casein were prepared. EWP was not completely digested. Ovalbumin, which is the most abundant protein in EWP, showed resistance to digestion by pepsin. This study investigated the effects of EWP pepsin hydrolysate (EWP-ph) on cholesterol micellar solubility, cholesterol transfer from the micellar to the oil phase, water-holding capacity (WHC), settling volume in water (SV), and relative viscosity and compared them with the effects of casein pepsin hydrolysate (C-ph). EWP-ph significantly decreased the micellar solubility and transfer rate and increased the WHC, SV, and relative viscosity compared with C-ph. Moreover, the pepsin hydrolysate of ovalbumin, a major protein in EWP, played a role in decreasing cholesterol micellar solubility, leading to the inhibition of cholesterol absorption. In conclusion, dietary EWP decreased cholesterol intestinal absorption by exerting combined effects of these physicochemical properties in the gut.


The Canadian Heart Health Strategy and Action Plan: Cardiac rehabilitation as an exemplar of chronic disease management.
In October 2006, federal funding was announced for the development of a national strategy to fight cardiovascular disease (CVD) in Canada. The comprehensive, independent, stakeholder-driven Canadian Heart Health Strategy and Action Plan (CHHS-AP) was delivered to the Minister of Health on February 24, 2009. The mandate of CHHS-AP Theme Working Group (TWG) 6 was to identify the optimal chronic disease management model that incorporated timely access to rehabilitation services and end-of-life planning and care. The purpose of the present paper was to provide an overview of worldwide approaches to CVD and cardiac rehabilitation (CR) strategies and recommendations for CR care in Canada, within the context of the well-known Chronic Care Model (CCM). A separate paper will address end-of-life issues in CVD. TWG 6 was composed of content representatives, primary care representatives and patients. Input in the area of Aboriginal and indigenous cardiovascular health was obtained through individual expert consultation. Information germane to the present paper was gathered from international literature and best practice guidelines. The CCM principles were discussed and agreed on by all. Prioritization of recommendations and overall messaging was discussed and decided on within the entire TWG. The full TWG report was presented to the CHHS-AP Steering Committee and was used to inform the recommendations of the CHHS-AP. Specific actionable recommendations for CR are made in accordance with the key principles of the CCM. The present CR blueprint, as part of the CHHS-AP, will be a first step toward reducing the health care burden of CVD in Canada.


Understanding and harnessing the health effects of rapid urbanization in China.
China is undergoing a rapid transition from a rural to an urban society. This societal change is a consequence of a national drive toward economic prosperity. Rapid urbanization impacts on infrastructure, environmental health and human wellbeing. Unlike many cases of urban expansion, Chinese urbanization has led to containment, rather than to increase, in the spread of infectious diseases. Conversely, the incidence of chronic conditions such as cardiovascular and metabolic diseases has risen, with higher rates occurring in urban regions. This rural-urban gradient in disease incidence seems not to be a reflection simply of more aggressive diagnosis or healthcare access. Other diseases exhibit little rural versus urban differences (e.g., liver cancer or respiratory disease), or even occur at a higher rate in the rural population (e.g., esophageal cancer). This article examines the impact of this changing demographic on environmental health and human wellbeing in China. Lessons learned from epidemiological studies mostly carried out in Europe and the U.S. may not be directly transferable to China. We advocate that there is now a need to establish robust systems of accurate data collection, a Chinese biobank network to facilitate the profiling of human health effects, and relevant randomized controlled trials to identify effective interventions in the Chinese urbanized setting. Such studies could allow for the future implementation of disease-preventive strategies.


[Properties of cathepsin D from unfertilized eggs, embryos and skeletal muscles of the loach].
The action and some properties of cathepsin D, partly purified from unfertilized loach eggs, embryos and skeletal muscles were determined. The enzyme from embryo cells displays the activity maximum at pH 3.0 and pH 4.8 while enzyme from skeletal muscles--only at pH 3.0. Cathepsin D purified from all three sources splits actively hemoglobin, albumin, alpha-glycerophosphate dehydrogenase, pyruvate kinase and practically does not influence casein, hexokinase, glucose-6-phosphate dehydrogenase. The enzyme is comparatively thermolabile and its activity decreases in the presence of thiol compounds. The main part of cathepsin D in skeletal muscle cells and in embryo cells is precipitated after differential centrifugation of homogenates (25000 g; 60 min).


Correlation of applied kinesiology muscle testing findings with serum immunoglobulin levels for food allergies.
The pilot study attempted to determine whether subjective muscle testing employed by Applied Kinesiology practitioners, prospectively determine those individuals with specific hyperallergenic responses. Seventeen subjects were found positive on Applied Kinesiology (A.K.) muscle testing screening procedures indicating food hypersensitivity (allergy) reactions. Each subject showed muscle weakening (inhibition) reactions to oral provocative testing of one or two foods for a total of 21 positive food reactions. Tests for a hypersensitivity reaction of the serum were performed using both a radio-allergosorbent test (RAST) and immune complex test for IgE and IgG against all 21 of the foods that tested positive with A.K. muscle screening procedures. These serum tests confirmed 19 of the 21 food allergies (90.5%) suspected based on the applied kinesiology screening procedures. This pilot study offers a basis to examine further a means by which to predict the clinical utility of a given substance for a given patient, based on the patterns of neuromuscular response elicited from the patient, representing a conceptual expansion of the standard neurological examination process.


The effect of live music on decreasing anxiety in patients undergoing chemotherapy treatment.
The purpose of this study was to investigate the effects of familiar live music on the anxiety levels of patients undergoing chemotherapy treatment. Randomly selected patients were assigned to experimental (n = 25) and control (n = 25) conditions. Pre and posttests consisted of questionnaires and the recording of the patient's heart rate and blood pressures. Subjects in the experimental group received 20 minutes of familiar live music during their chemotherapy treatment. Subjects in the control group received standard chemotherapy. It was assumed that those patients receiving music intervention would: (a) lower their anxiety levels; (b) experience a decrease in heart rate and blood pressure; (c) improve their levels of negative reactions including fatigue, worry, and fear; and (d) improve their levels of positive reactions including comfort and relaxation. Results of the study showed statistically significant improvement for the experimental group on the measures of anxiety, fear, fatigue, relaxation, and diastolic blood pressure. No significant differences between groups were found for heart rate and systolic blood pressure. Descriptive values indicated that, on average, the experimental group was influenced positively by the music intervention, and participants improved their quality of life while undergoing chemotherapy treatment.


Orientational disorder in solvent-free solid c70.
The high-temperature structure of solvent-free C(70) has been determined with high-resolution x-ray powder difraction and electron microscopy. Samples crystallized from solution form hexagonal close-packed crystals that retain an appreciable amount of residual toluene, even after prolonged heating. Samples prepared by sublimation, which contain no detectable solvent, are primarily face-centered cubic with some admixture of a hexagonal phase. The relative volume of the hexagonal phase can be further reduced by annealing. The structures of both phases are described by a model of complete orientational disorder. The cubic phase contains an appreciable density of stacking faults along the [111] direction.


The providers' profile of the disability support workforce in New Zealand.
To understand one of the predominant groups supporting people with disabilities and illness, this study examined the profile of New Zealand paid caregivers, including their training needs. Paid caregivers, also known as healthcare assistants, caregivers and home health aides, work across several long-term care settings, such as residential homes, continuing-care hospitals and also private homes. Their roles include assisting with personal care and household management. New Zealand, similar to other countries, is facing a health workforce shortage. A three-phased design was used: phase I, a survey of all home-based and residential care providers (N = 942, response rate = 45%); phase II, a targeted survey of training needs (n = 107, response = 100%); phase III, four focus groups and 14 interviews with 36 providers, exploring themes arising from phases I and II. Findings on 17,910 paid caregivers revealed a workforce predominantly female (94%), aged between 40 and 50, with 6% over the age of 60. Mean hourly pay NZ$10.90 (minimum wage NZ$10.00 approx. UK3.00 at time of study) and 24 hours per week. The national paid caregiver turnover was 29% residential care and 39% community. Most providers recognised the importance of training, but felt their paid caregivers were not adequately trained. Training was poorly attended; reasons cited were funding, family, secondary employment, staff turnover, low pay and few incentives. The paid caregiver profile described reflects trends also observed in other countries. There is a clear policy direction in New Zealand and other countries to support people with a disability at home, and yet the workforce which is facilitating this vision is itself highly vulnerable. Paid caregivers have minimum pay, are female, work part-time and although it is recognised that training is important for them, they do not attend, so consequently remain untrained.


Relative Deprivation, Poverty, and Mortality in Japanese Older Adults: A Six-Year Follow-Up of the JAGES Cohort Survey.
Most studies have evaluated poverty in terms of income status, but this approach cannot capture the diverse and complex aspects of poverty. To develop commodity-based relative deprivation indicators and evaluate their associations with mortality, we conducted a 6-year follow-up of participants in the Japan Gerontological Evaluation Study (JAGES), a population-based cohort of Japanese adults aged 65 and older. We analyzed mortality for 7614 respondents from 2010 to 2016. Cox regression models with multiple imputation were used to estimate hazard ratios (HRs) for mortality. Seven indicators were significantly associated with mortality: no refrigerator, no air conditioner, cut-off of essential services in the past year for economic reasons, and so on. Among participants, 12.0% met one item, and 3.3% met two items or more. The HRs after adjusting for relative poverty and some confounders were 1.71 (95%CI: 1.18⁻2.48) for relative deprivation, and 1.87 (95%CI: 1.14⁻3.09) for a combination of relative poverty and deprivation. Relative deprivation was attributable to around 27,000 premature deaths (2.3%) annually for the older Japanese. Measurement of relative deprivation among older adults might be worthwhile in public health as an important factor to address for healthy aging.


Effect of Diuretic or Calcium-Channel Blocker Plus Angiotensin-Receptor Blocker on Diastolic Function in Hypertensive Patients.
Hypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction. Hypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e', cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E' velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was -0.02 (-0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e' velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group. The combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients.


A Rare Simultaneous Occurrence of Odontogenic Keratocyst and Unicystic Ameloblastoma in Mandible: A Case Report.
Odontogenic Keratocyst (OKC) and Ameloblastomas are slow growing benign odontogenic lesions that primarily occur in the molar region of the mandible. Clinically and radiographically both ameloblastoma, especially the Unicystic ameloblastoma and OKC are indistinguishable due to the similar location of occurrence and the age of patients. It is very rare for these lesions to arise simultaneously in a patient's jaw. The co-occurrence of Ameloblastomas with odontogenic cysts or other odontogenic lesions (histologically in a single lesion)have already been described as combined or hybrid lesions. There are very few reported cases in the English literature for simultaneous occurrence of Unicystic Ameloblastoma and OKC as completely distinct lesions. Here we present such a rare case of the simultaneous occurrence of OKC and ameloblastoma in the posterior region of the mandible of a 22-year-old male in close relation.


New portable tool to screen vestibular and visual function--National Institutes of Health Toolbox initiative.
As part of the National Institutes of Health Toolbox initiative, we developed a low-cost, easy-to-administer, and time-efficient test of vestibular and visual function. A computerized test of dynamic visual acuity (cDVA) was used to measure the difference in visual acuity between head still and moving in yaw. Participants included 318 individuals, aged 3 to 85 years (301 without and 17 with vestibular pathology). Adults used Early Treatment of Diabetic Retinopathy Study (ETDRS) optotypes; children used ETDRS, Lea, and HOTV optotypes. Bithermal calorics, rotational chair, and light box testing were used to validate the cDVA. Analysis revealed that the cDVA test is reliable for static (intraclass correlation coefficient [ICC] >/= 0.64) and dynamic (ICC >/= 0.43-0.75) visual acuity. Children younger than 6 years old were more likely to complete cDVA with Lea optotypes, but reliability and correlation with ETDRS was better using HOTV optotypes. The high correlation between static acuity and light box test scores (r = 0.795), significant difference of cDVA scores between those with and without pathology (p </= 0.04), and the good to excellent sensitivity (73%) and specificity (69%) establish that the cDVA is a valid and reliable measure of visual acuity when the head is still and moving, as well as a good proxy of vestibular function to yaw rotation.


Disentangling the Relationships Between the Clinical Symptoms of Schizophrenia Spectrum Disorders and Theory of Mind: A Meta-analysis.
Previous studies have suggested links between clinical symptoms and theory of mind (ToM) impairments in schizophrenia spectrum disorders (SSD), but it remains unclear whether some symptoms are more strongly linked to ToM than others. A meta-analysis (Prospero; CRD42021259723) was conducted to quantify and compare the strength of the associations between ToM and the clinical symptoms of SSD (Positive, Negative, Cognitive/Disorganization, Depression/Anxiety, Excitability/Hostility). Studies (N = 130, 137 samples) including people with SSD and reporting a correlation between clinical symptoms and ToM were retrieved from Pubmed, PsycNet, Embase, Cochrane Library, Science Direct, Proquest, WorldCat, and Open Gray. Correlations for each dimension and each symptom were entered into a random-effect model using a Fisher's r-to-z transformation and were compared using focused-tests. Publication bias was assessed with the Rosenthal failsafe and by inspecting the funnel plot and the standardized residual histogram. The Cognitive/Disorganization (Zr = 0.28) and Negative (Zr = 0.24) dimensions revealed a small to moderate association with ToM, which was significantly stronger than the other dimensions. Within the Cognitive/Disorganization dimension, Difficulty in abstract thinking (Zr = 0.36) and Conceptual disorganization (Zr = 0.39) showed the strongest associations with ToM. The association with the Positive dimension (Zr = 0.16) was small and significantly stronger than the relationship with Depression/Anxiety (Zr = 0.09). Stronger associations were observed between ToM and clinical symptoms in younger patients, those with an earlier age at onset of illness and for tasks assessing a combination of different mental states. The relationships between Cognitive/Disorganization, Negative symptoms, and ToM should be considered in treating individuals with SSD.


Carotid artery wall motion analysis from B-mode ultrasound using adaptive block matching: in silico evaluation and in vivo application.
Valid risk stratification for carotid atherosclerotic plaques represents a crucial public health issue toward preventing fatal cerebrovascular events. Although motion analysis (MA) provides useful information about arterial wall dynamics, the identification of motion-based risk markers remains a significant challenge. Considering that the ability of a motion estimator (ME) to handle changes in the appearance of motion targets has a major effect on accuracy in MA, we investigated the potential of adaptive block matching (ABM) MEs, which consider changes in image intensities over time. To assure the validity in MA, we optimized and evaluated the ABM MEs in the context of a specially designed in silico framework. ABM(FIRF2), which takes advantage of the periodicity characterizing the arterial wall motion, was the most effective ABM algorithm, yielding a 47% accuracy increase with respect to the conventional block matching. The in vivo application of ABM(FIRF2) revealed five potential risk markers: low movement amplitude of the normal part of the wall adjacent to the plaques in the radial (RMA(PWL)) and longitudinal (LMA(PWL)) directions, high radial motion amplitude of the plaque top surface (RMA(PTS)), and high relative movement, expressed in terms of radial strain (RSI(PL)) and longitudinal shear strain (LSSI(PL)), between plaque top and bottom surfaces. The in vivo results were reproduced by OF(LK(WLS)) and ABM(KF-K2), MEs previously proposed by the authors and with remarkable in silico performances, thereby reinforcing the clinical values of the markers and the potential of those MEs. Future in vivo studies will elucidate with confidence the full potential of the markers.


Metabolic profile analysis of zebrafish embryos.
A growing goal in the field of metabolism is to determine the impact of genetics on different aspects of mitochondrial function. Understanding these relationships will help to understand the underlying etiology for a range of diseases linked with mitochondrial dysfunction, such as diabetes and obesity. Recent advances in instrumentation, has enabled the monitoring of distinct parameters of mitochondrial function in cell lines or tissue explants. Here we present a method for a rapid and sensitive analysis of mitochondrial function parameters in vivo during zebrafish embryonic development using the Seahorse bioscience XF 24 extracellular flux analyser. This protocol utilizes the Islet Capture microplates where a single embryo is placed in each well, allowing measurement of bioenergetics, including: (i) basal respiration; (ii) basal mitochondrial respiration (iii) mitochondrial respiration due to ATP turnover; (iv) mitochondrial uncoupled respiration or proton leak and (iv) maximum respiration. Using this approach embryonic zebrafish respiration parameters can be compared between wild type and genetically altered embryos (mutant, gene over-expression or gene knockdown) or those manipulated pharmacologically. It is anticipated that dissemination of this protocol will provide researchers with new tools to analyse the genetic basis of metabolic disorders in vivo in this relevant vertebrate animal model.


Determination of taxol in Taxus chinensis by HPLC method.
A method for the determination of taxol in Taxus chinensis by HPLC method using betamethasone as internal standard is described. The column employed was packed with 10 microns silica gel YWG 80 (250 x 4 mm), the eluting solvent consisted of CH2Cl2--MeOH (95:5) and the effluent was monitored at 228 nm. The coefficients of variation are less than 2%.


Perceived Stress among Caregivers of Children with Autism Spectrum Disorder: A State-Wide Study.
Caregivers of children with autism spectrum disorder (ASD) experience increased stress and more significant negative caregiving consequences than those with typically developing children. There is a lack of studies specifically focusing on stress among caregivers with ASD children in Asian countries. The current study examines levels of perceived stress and factors associated with it among caregivers in Kelantan, Malaysia. In a cross-sectional study, the Malay version of the Perceived Stress Scale (PSS) was administered to 227 caregivers of children with ASD. The caregivers were recruited from ASD databases in four tertiary hospitals in Kelantan and a meeting was set up during the child's follow-up in the clinic. Multiple linear regression analyses were applied to determine the predictors of perceived stress. The mean total perceived stress score was 20.84 (4.72). This was considered higher than average. Higher perceived stress was significantly predicted among caregivers who live far from the health institution, caregivers who do not own transportation to bring the child to the treatment center, and caregivers who have an ASD child with a learning disability. Caregivers of an ASD child perceived significant stress while taking care of their children. Institutions should alleviate the factors that were predicted to increase the caregivers' perceived stress to improve the quality of the lives of children and ASD families as a whole.


Isolation and chemical characterization of plasma membranes from the yeast and mycelial forms of Candida albicans.
It has been possible to induce the yeast-mycelium transformation in Candida albicans by growth of the organism under completely defined conditions in batch culture. Protoplasts have been obtained from the two forms by using a lytic enzyme preparation from Streptomyces violaceus. A plasma membrane fraction was prepared by osmotic lysis of these protoplasts and fractionated by using a combination of differential and discontinuous sucrose density-gradient flotation centrifugation. The purity of this fraction was determined by radioactive dansylation and iodination of plasma membranes of intact protoplasts followed by localization of the radioactivity upon fractionation. This procedure demonstrated less than 4% contamination of the plasma membrane fraction with other cell membranes. Chemical analysis of this fraction revealed that the major components were protein and lipid. Membranes from the yeast form contained (w/w): 50% protein, 45% lipid, 9% carbohydrate and 0.3% nucleic acid. Plasma membranes from the mycelial form contained significantly more carbohydrate and were found to be composed of (w/w): 43% protein, 31% lipid, 25% carbohydrate and 0.5% nucleic acid. Marked differences were also observed between the phospholipid, free and esterified sterols, and total fatty acids of membranes from the two forms of the organism.


Several deep-sea mussels and their associated symbionts are able to live both on wood and on whale falls.
Bathymodiolin mussels occur at hydrothermal vents and cold seeps, where they thrive thanks to symbiotic associations with chemotrophic bacteria. Closely related genera Idas and Adipicola are associated with organic falls, ecosystems that have been suggested as potential evolutionary 'stepping stones' in the colonization of deeper and more sulphide-rich environments. Such a scenario should result from specializations to given environments from species with larger ecological niches. This study provides molecular-based evidence for the existence of two mussel species found both on sunken wood and bones. Each species specifically harbours one bacterial phylotype corresponding to thioautotrophic bacteria related to other bathymodiolin symbionts. Phylogenetic patterns between hosts and symbionts are partially congruent. However, active endocytosis and occurrences of minor symbiont lineages within species which are not their usual host suggest an environmental or horizontal rather than strictly vertical transmission of symbionts. Although the bacteria are close relatives, their localization is intracellular in one mussel species and extracellular in the other, suggesting that habitat choice is independent of the symbiont localization. The variation of bacterial densities in host tissues is related to the substrate on which specimens were sampled and could explain the abilities of host species to adapt to various substrates.


Ancestral genetic variation in phenotypic plasticity underlies rapid evolutionary changes in resurrected populations of waterfleas.
The role of phenotypic plasticity in adaptive evolution has been debated for decades. This is because the strength of natural selection is dependent on the direction and magnitude of phenotypic responses to environmental signals. Therefore, the connection between plasticity and adaptation will depend on the patterns of plasticity harbored by ancestral populations before a change in the environment. Yet few studies have directly assessed ancestral variation in plasticity and tracked phenotypic changes over time. Here we resurrected historic propagules of Daphnia spanning multiple species and lakes in Wisconsin following the invasion and proliferation of a novel predator (spiny waterflea, Bythotrephes longimanus). This approach revealed extensive genetic variation in predator-induced plasticity in ancestral populations of Daphnia It is unlikely that the standing patterns of plasticity shielded Daphnia from selection to permit long-term coexistence with a novel predator. Instead, this variation in plasticity provided the raw materials for Bythotrephes-mediated selection to drive rapid shifts in Daphnia behavior and life history. Surprisingly, there was little evidence for the evolution of trait plasticity as genetic variation in plasticity was maintained in the face of a novel predator. Such results provide insight into the link between plasticity and adaptation and highlight the importance of quantifying genetic variation in plasticity when evaluating the drivers of evolutionary change in the wild.


Implications of attachment theory and research for developmental-behavioral pediatrics.
This article presents a basic overview of attachment theory, concepts, and research. The review includes a discussion of the nature of the attachment relationship, its origins in human evolutionary history, and common misconceptions about attachment. We describe phases in the development of attachment relationships and review research on factors that influence attachment variations. We discuss the implications of variations in early attachment relationships for later development (adaptation and maladaptation). And finally, we review briefly the implications of attachment theory and research for pediatric practice. Some key points are that (1) virtually all infants become attached to caregivers regardless of quality of care; (2) attachment relationships evolve in phases over time; (3) children with disabilities form attachment relationships in ways comparable to nondisabled children but manifest attachment somewhat differently; (4) the consequences for attachment of out-of-home care, separations, and significant disruptions (e.g., adoption) depend on timing and circumstances; (5) many infant regulatory difficulties, as well as child behavior problems, originate in the caregiving relationship; and finally, (6) change in parent-child relationship disturbances is complex and requires time and effort.


The thyroid and pregnancy: a novel risk factor for very preterm delivery.
The major cause of neonatal mortality and morbidity is preterm delivery in general (< 37 completed weeks), and especially very preterm delivery (< 32 completed weeks). The objective of this study is to determine if either thyroid hormonal dysfunction and/or the presence of thyroid autoantibodies in the mother are associated with an increased risk of preterm and/or very preterm delivery. Data were collected prospectively and analyzed as a nested-case control study. There were 953 delivered gravidas enrolled between 1996 and 2002. Samples were collected at entry to care and stored at -70 degrees C. Cases included all women with preterm delivery (n = 124). Controls (n = 124) were randomly selected from among the 829 women who delivered at term (> 37 completed weeks). All samples were assessed for thyroid stimulating hormone, thyroperoxidase antibody, and thyroglobulin antibody. Gravidas with high thyrotropin (TSH) levels had a greater than threefold increase in risk of very preterm delivery. In some analyses, gravidas who tested positive for thyroglobulin antibody at entry to prenatal care also had a better than twofold increased risk of very preterm delivery. There were no significant associations between TSH level or thyroglobulin antibody positivity and the risk of moderately preterm delivery.


Concentrations of reactive Mn(III)-L and MnO2 in estuarine and marine waters determined using spectrophotometry and the leuco base, leucoberbelin blue.
In terms of its oxidative strength, the MnO2/Mn2+ couple is one of the strongest in the aquatic environment. The intermediate oxidation state, manganese(III), is stabilized by a range of organic ligands (Mn(III)-L) and some of these complexes are also strong oxidants or reductants. Here, we present improved methods for quantifying soluble reactive oxidized manganese(III) and particulate reactive oxidized manganese at ultra-low concentrations; the respective detection limits are 6.7 nM and 7 pM (100-cm spectrophotometric path length) and 260 nM and 2.6 nM (1-cm path length). The methods involve a simple, specific, spectrophotometric technique using a water-soluble leuco base (leucoberbelin blue; LBB). LBB is oxidized by manganese through a hydrogen atom transfer reaction forming a colored complex that is stoichiometrically related to the oxidation state of the manganese, either Mn(III)-L or manganese(III,IV) oxides (MnOx). At the concentration of LBB used in this study, nitrite may be a minor interference, so we provide concentration ranges over which it interferes and suggest potential strategies to mitigate the interference. Unlike previous methods devised to quantify Mn(III)-L, which use ligand exchange reactions, the LBB oxidation requires an electron and therefore needs to physically contact manganese(III) for inner-sphere electron transfer to occur. The method for measuring soluble Mn(III)-L was evaluated in the laboratory, and LBB was found to be oxidized by an extensive suite of weak Mn(III)-L complexes, as it is by MnOx, but could not react with or reacted very slowly with strong Mn(III)-L complexes. According to the molecular structures of the Mn(III)-L complexes tested, LBB can also be used to qualitatively assess the binding strength of Mn(III)-L complexes based on metal-chelate structural considerations. The assays for soluble Mn(III)-L (membrane filtered) and particulate manganese oxides (trapped by membrane filters) were applied to the well-oxygenated estuarine waters of the Saguenay Fjord, a major tributary of the Lower St. Lawrence Estuary, and to Western North Atlantic oceanic waters, off the continental shelf, where there is an oxygen minimum zone (< 67% O2 saturation). The methods applied can be used in the field or onboard ships and provide important new insights into oxidized manganese speciation.


Catalytic ozonation of aqueous phenol over metal-loaded HZSM-5.
The performances of HZSM-5 and transition metal-loaded HZSM-5 (Mn, Cu, Fe, Ti) catalysts during catalytic ozonation of phenol have been investigated. It was observed the performance order for removal of phenol and COD was Mn/HZSM-5 > Fe/HZSM-5 > Cu/HZSM-5 > Ti/HZSM-5 > HZSM-5. The presence of metals on HZSM-5 enhanced the phenol removal capability of HZSM-5. Mn loading on HZSM-5 was optimized due to its high phenol removal capability amongst metal-loaded HZSM-5 catalysts. Experimental results suggested that low amount of Mn loading on HZSM-5 was sufficient for HZSM-5 to act as catalyst and adsorbent. A maximum of 95.8 wt% phenols and 70.2 wt% COD were removed over 2 wt% Mn/HZSM-5 in 120 min. It was supposed that transition metals mainly acted as ozone decomposers due to their multiple oxidation states that enhanced the ozonation of phenol.


Expression of acrB, acrF, acrD, marA, and soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance.
Comparative reverse transcription-PCR in combination with denaturing high-pressure liquid chromatography analysis was used to determine the levels of expression of soxS, marA, acrF, acrB, and acrD in multiple-antibiotic-resistant (MAR) Salmonella enterica serovar Typhimurium isolates and mutants of S. enterica serovar Typhimurium SL1344 with defined deletions. Posttherapy MAR clinical isolates had increased levels of expression of all genes except soxS. S. enterica serovar Typhimurium SL1344 Delta acrB expressed 7.9-fold more acrF than the parent strain. A strain with an acrF deletion expressed 4.6-fold more acrB. Deletion of acrB and/or acrF resulted in 2.7- to 4.3-fold more marA mRNA and 3.6- to 4.9-fold increases in the levels of expression of acrD but had a variable effect on the expression of soxS. All mutants were hypersusceptible to antibiotics, dyes, and detergents; but the MIC changes were more noticeable for SL1344 with the acrB deletion than for the mutant with the acrF disruption. These mutants had different but overlapping phenotypes, and the concentrations of ciprofloxacin accumulated by the mutants were different. These data suggest that acrB, acrF, and acrD are coordinately regulated and that their expression influences the expression of the transcriptional activators marA and soxS.


Psychosocial interventions for non-professional carers of people with Parkinson's disease: a systematic scoping review.
This paper is a report of a scoping review to systematically identify and collate the evidence on psychosocial interventions for non-professional carers of people with Parkinson's disease. Carers are critical to people with Parkinson's disease maintaining independent living and quality of life. Parkinson's disease imposes a challenging constellation of symptoms and no summary of effective interventions for carers and their unique support needs exists. Thirty electronic databases were searched from their inception to July 2006, and bibliographies and specific internet sites were scanned. Eligible studies were categorized according to design, type of economic evaluation where applicable, number of participants, country of evaluation, intervention, orientation, provider, setting, method of delivery, carer population, patient population, carer outcomes, patient outcomes and authors' conclusions. Data were extracted by one reviewer and checked by another reviewer; discrepancies were resolved through discussion or arbitration by a third reviewer. Thirty studies met the inclusion criteria. Most investigated relatively unique interventions involving multiple elements; the majority were not aimed primarily at carers but were embedded in patient treatment programmes. Many were pilot studies, employing weak research designs and involving very small numbers of participants and most were not designed to assess the clinical or cost effectiveness of the intervention for the carers. Several interventions merit further investigation but there is currently little evidence to show which approaches are effective and cost effective in supporting carers. Future studies need to employ appropriate and rigorous research designs with adequate samples and outcome measures, and with more focus on the carer.


Is staurosporine a specific inhibitor of protein kinase C in intact porcine coronary arteries?
We assessed the specificity of staurosporine, a putative protein kinase C inhibitor, for the enzyme in intact porcine coronary arteries by examining its effects on changes in intracellular free calcium level ([Ca++]i) and force induced by a phorbol ester, high KCl and caffeine. [Ca++]i was measured simultaneously with force by the fura-2 microfluorimetric method. Phorbol 12,13-dibutyrate (PDBu, 10(-6) M) produced a slowly developing and sustained contraction; however, [Ca++]i only increased slightly and transiently in the initial phase and then decreased gradually. On the other hand, 90 mM KCl elicited a contraction with a sustained increase in [Ca++]i. Staurosporine (10(-10) to 10(-7) M) applied 20 min before the addition of PDBu inhibited the PDBu-induced changes in [Ca++]i and force in a concentration-dependent manner. In contrast, staurosporine only at 10(-7) M reduced an increase in [Ca++]i and contractile force produced by 90 mM KCl. The inhibitory effects of staurosporine on PDBu- and KCl-induced contractions depended on exposure time. The [Ca++]i-force relationship obtained with variable concentrations of KCl was shifted slightly to the right by staurosporine at 10(-7) M. Furthermore, staurosporine even at 10(-7) M did not affect an increase in [Ca++]i by caffeine (25 mM), although it slightly attenuated a caffeine-induced contraction. These results suggest that staurosporine is a relatively specific inhibitor of protein kinase C in intact arteries at lower concentrations. At higher concentrations it may have actions unrelated to its inhibitory effect of protein kinase C, which include the inhibition of calcium influx into smooth muscle cells through the voltage-dependent Ca++ channel.


Evidence of brain target engagement in Parkinson's disease and multiple sclerosis by the investigational nanomedicine, CNM-Au8, in the REPAIR phase 2 clinical trials.
Impaired brain energy metabolism has been observed in many neurodegenerative diseases, including Parkinson's disease (PD) and multiple sclerosis (MS). In both diseases, mitochondrial dysfunction and energetic impairment can lead to neuronal dysfunction and death. CNM-Au8® is a suspension of faceted, clean-surfaced gold nanocrystals that catalytically improves energetic metabolism in CNS cells, supporting neuroprotection and remyelination as demonstrated in multiple independent preclinical models. The objective of the Phase 2 REPAIR-MS and REPAIR-PD clinical trials was to investigate the effects of CNM-Au8, administered orally once daily for twelve or more weeks, on brain phosphorous-containing energy metabolite levels in participants with diagnoses of relapsing MS or idiopathic PD, respectively. Brain metabolites were measured using 7-Tesla 31P-MRS in two disease cohorts, 11 participants with stable relapsing MS and 13 participants with PD (n = 24 evaluable post-baseline scans). Compared to pre-treatment baseline, the mean NAD+/NADH ratio in the brain, a measure of energetic capacity, was significantly increased by 10.4% after 12 + weeks of treatment with CNM-Au8 (0.584 units, SD: 1.3; p = 0.037, paired t-test) in prespecified analyses of the combined treatment cohorts. Each disease cohort concordantly demonstrated increases in the NAD+/NADH ratio but did not reach significance individually (p = 0.11 and p = 0.14, PD and MS cohorts, respectively). Significant treatment effects were also observed for secondary and exploratory imaging outcomes, including β-ATP and phosphorylation potential across both cohorts. Our results demonstrate brain target engagement of CNM-Au8 as a direct modulator of brain energy metabolism, and support the further investigation of CNM-Au8 as a potential disease modifying drug for PD and MS.