Closing the quality gap: revisiting the state of the science (vol. 4: medication adherence interventions: comparative effectiveness).
To assess the effectiveness of patient, provider, and systems interventions (Key Question [KQ] 1) or policy interventions (KQ 2) in improving medication adherence for an array of chronic health conditions. For interventions that are effective in improving adherence, we then assessed their effectiveness in improving health, health care utilization, and adverse events. MEDLINE®, the Cochrane Library. Additional studies were identified from reference lists and technical experts. Two people independently selected, extracted data from, and rated the risk of bias of relevant trials and systematic reviews. We synthesized the evidence for effectiveness separately for each clinical condition, and within each condition, by type of intervention. We also evaluated the prevalence of intervention components across clinical conditions and the effectiveness of interventions for a range of vulnerable populations. Two reviewers graded the strength of evidence using established criteria. We found a total of 62 eligible studies (58 trials and 4 observational studies) from our review of 3,979 abstracts. These studies included patients with diabetes, hyperlipidemia, hypertension, heart failure, myocardial infarction, asthma, depression, glaucoma, multiple sclerosis, musculoskeletal diseases, and multiple chronic conditions. Fifty-seven trials of patient, provider, or systems interventions (KQ 1) evaluated 20 different types of interventions; 4 observational studies and one trial of policy interventions (KQ 2) evaluated the effect of reduced out-of-pocket expenses or improved prescription drug coverage. We found the most consistent evidence of improvement in medication adherence for interventions to reduce out-of-pocket expenses or improve prescription drug coverage, case management, and educational interventions across clinical conditions. Within clinical conditions, we found the strongest support for self-management of medications for short-term improvement in adherence for asthma patients; collaborative care or case management programs for short-term improvement of adherence and to improve symptoms for patients taking depression medications; and pharmacist-led approaches for hypertensive patients to improve systolic blood pressure. Diverse interventions offer promising approaches to improving medication adherence for chronic conditions, particularly for the short term. Evidence on whether these approaches have broad applicability for clinical conditions and populations is limited, as is evidence regarding long-term medication adherence or health outcomes.


PRIMEGENS-v2: genome-wide primer design for analyzing DNA methylation patterns of CpG islands.
DNA methylation plays important roles in biological processes and human diseases, especially cancers. High-throughput bisulfite genomic sequencing based on new generation of sequencers, such as the 454-sequencing system provides an efficient method for analyzing DNA methylation patterns. The successful implementation of this approach depends on the use of primer design software capable of performing genome-wide scan for optimal primers from in silico bisulfite-treated genome sequences. We have developed a method, which fulfills this requirement and conduct primer design for sequences including regions of given promoter CpG islands. The developed method has been implemented using the C and JAVA programming languages. The primer design results were tested in the PCR experiments of 96 selected human DNA sequences containing CpG islands in the promoter regions. The results indicate that this method is efficient and reliable for designing sequence-specific primers. The sequence-specific primer design for DNA meth-ylated sequences including CpG islands has been integrated into the second version of PRIMEGENS as one of the primer design features. The software is freely available for academic use at http://digbio.missouri.edu/primegens/.


Characteristics and economic burden of hospitalized patients with herpes zoster in China, before vaccination.
Herpes zoster (HZ) brings a significant economic burden. The HZ vaccine was introduced in China for the first time in 2020, and there is a lack of up-to-date information on the hospitalization costs and characteristics prior to vaccination. This study aimed to describe the characteristics and economic burden of HZ inpatients in Hunan Province, China, and analyze the factors influencing the length of stay (LOS) and costs. This was a retrospective study and we extracted information from the Chinese National Health Statistics Network Reporting System on HZ inpatients in Hunan Province, China from 2017 to 2019. Spatial join tools and Global or Local Moran's Index were used for the geographic analysis of hospitalized HZ incidence. Multivariate linear regression models were used to analyze the factors influencing LOS and costs. There were 44,311 HZ inpatients included in this study, incurring a total of $31,857,734 medical costs. These patients had a median LOS of 8 days and a median expenditure of $573.47. Older age, more comorbidities, and the presence of complications with nervous system involved were all significantly associated with longer LOS and higher costs. HZ infection resulted in a large direct medical cost and heavy disease burden, especially in patients with advanced age or underlying medical conditions. The HZ vaccine has the potential to effectively reduce the disease burden and should be widely popularized especially among high-risk groups.


Unraveling the secrets of γδ T cells with single-cell biology.
Recent technological advancements have enabled us to study the molecular features of cellular states at the single-cell level, providing unprecedented resolution for comprehending the identity and function of a cell. By applying these techniques across multiple time frames, tissues, and diseases, we can delve deeper into the mechanisms governing the development and functions of cell lineages. In this review, I focus on γδ T cells, which are a unique and functionally nonredundant T cell lineage categorized under the umbrella of unconventional T cells. I discuss how single-cell biology is providing unique insights into their development and functions. Furthermore, I explore how single-cell methods can be used to answer several key questions about their biology. These investigations will be essential to fully understand their translational potential, including their role in cytotoxicity and tissue repair in cancer and regeneration.


Coronary flow in heart-lung preparation affected by cardiopulmonary nerves and arterial PCO2.
Studies on coronary vasodilator drugs utilizing heart-lung preparations (HLP) have been disturbed by a spontaneous gradual increase in coronary blood flow. With the purpose of finding out what would cause the gradual increase, the time course of coronary sinus blood flow (CSBF) was investigated in 20 dog HLPs under four experimental conditions, according to whether cardiopulmonary nerves (CPN) were severed or not and whether CO2 content in the inspiratory gas was high (95% O2-5% CO2) or low (50% O2-50% room air). The gradual increase in CSBF was observed, accompanied by a significant increase in 6-ketoprostaglandin F1 alpha in the arterial blood, only when CPN were intact and, simultaneously, inspiratory CO2 was high. Nevertheless, the hemodynamic parameters, except CSBF, were almost similar under four conditions. These results suggested that CSBF in HLP could be affected via a synthesis and/or a release of prostaglandin I2 by the interaction of CPN and arterial PCO2.


[Influence of chronic diseases of reserve military personnel of Ukraine army on their capability to do their duty according military speciality].
The author presents in the article the way of distribution of reserve military personnel of Ukraine army on special groups depending on presence of chronical diseases or pathological conditions. The author analyzed more than 800 personal files of military personnel and other materials related to assessment of functional state of this personnel and efficiency of performing their duty. Data received from Kiev commissariats and other Ukraine military Institutions have been analyzed. The proposed way of military personnel distribution allows optimizing their operating mode by creating a special mode where resource of military personnel's professional health is preserved.


Trajectories of pure and co-occurring internalizing and externalizing problems from early childhood to adolescence: Associations with early childhood individual and contextual antecedents.
As internalizing and externalizing problems often co-occur, the current study utilized a longitudinal dataset of 784 at-risk children (predominantly from low-income families and academically at-risk; 52.6% male) followed yearly from Grade 1 to Grade 12 to: (a) explore the heterogeneity in the codevelopment patterns of internalizing and externalizing problems by using a person-centered approach, and (b) investigate early childhood antecedents that might explain differentiated codevelopmental patterns. The antecedents consisted of individual (i.e., ego-resilient personality, intelligence, language ability, gender, and ethnicity) and contextual factors (i.e., maternal support and responsiveness, family socioeconomic adversity, teacher-child relationship conflict, and peer rejection). We identified 4 distinct codevelopment patterns including a chronic co-occurring group (30.1%), a moderate co-occurring group (28.5%), a pure-externalizing group (18.6%), and a low-risk group (22.8%). While children who belonged to any of the 3 higher risk groups exhibited more adverse early childhood antecedents compared with the low-risk group, the chronic co-occurring group displayed the most severe profiles of early childhood antecedents compared with the moderate co-occurring and the pure-externalizing groups. Common antecedents for the 3 higher risk groups were lower ego-resilient personality, higher teacher-child relationship conflict, being male, and being African American. Low language ability and peer rejection were identified as unique antecedents for the chronic co-occurring group. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Augmented Serum Amyloid A1/2 Mediated by TNF-induced NF-κB in Human Serous Ovarian Epithelial Tumors.
Tumor necrosis factor-α (TNF) is well known to be involved in the immune system and ovarian inflammation. Ovarian cancer is an inflammation-related malignancy that lacks early screening strategies, resulting in late diagnosis followed by high mortality. Based on our previous data, TNF induced abundant serum amyloid A (SAA), an acute phase protein linked to inflammation, in ovarian granulosal cells. To date, the regulation and expression of SAA in ovarian cancer is not fully elucidated. Here, we investigated the relationship between TNF and SAA by comparing human normal ovarian tissues and serous ovarian tumors. We found that SAA1/2 was significantly expressed in tumor tissues, but no or trace expression levels in normal tissues. TNF was also significantly upregulated in ovarian tumor tissues compared to normal tissues. Moreover, TNF significantly increased SAA1/2 levels in human ovarian cancer cell lines, OVCAR-3 and SKOV-3, in a time-dependent manner. Since the SAA1 promoter contains two nuclear factor (NF)-κB sites, we examined whether TNF regulates SAA1 promoter activity. Deletion analysis revealed that the proximal NF-κB site (-95/-85) played a critical role in regulating TNF-induced SAA1 promoter activity. Within 2 h after intraperitoneal injection of lipopolysaccharide, a product known to stimulate release of TNF, SAA preferably localized to ovarian epithelial cells and the thecal-interstitial layers compared to granulosal cell layers. Based on Gene Expression Omnibus (GEO) database, SAA1/2 and TNF were dominantly expressed in advanced grade ovarian cancer. Taken together, the accumulation of SAA1/2 in ovarian cancer could be mediated by TNF-induced NF-κB activation.


Maximal fat oxidation during exercise in trained men.
Fat oxidation increases from low to moderate exercise intensities and decreases from moderate to high exercise intensities. Recently, a protocol has been developed to determine the exercise intensity, which elicits maximal fat oxidation rates (Fat(max)). The main aim of the present study was to establish the reliability of the estimation of Fat(max) using this protocol (n = 10). An additional aim was to determine Fat(max) in a large group of endurance-trained individuals (n = 55). For the assessment of reliability, subjects performed three graded exercise tests to exhaustion on a cycle ergometer. Tests were performed after an overnight fast and diet and exercise regime on the day before all tests were similar. Fifty-five male subjects performed the graded exercise test on one occasion. The typical error (root mean square error and CV) for Fat(max) and Fat(min) was 0.23 and 0.33 l O(2) x min(-1) and 9.6 and 9.4 % respectively. Maximal fat oxidation rates of 0.52 +/- 0.15 g x min(-1) were reached at 62.5 +/- 9.8 % VO(2)max, while Fat(min) was located at 86.1 +/- 6.8 % VO(2)max. When the subjects were divided in two groups according to their VO(2)max, the large spread in Fat(max) and maximal fat oxidation rates remained present. The CV of the estimation of Fat(max) and Fa(min) is 9.0 - 9.5 %. In the present study the average intensity of maximal fat oxidation was located at 63 % VO(2)max. Even within a homogeneous group of subjects, there was a relatively large inter-individual variation in Fat(max) and the rate of maximal fat oxidation.


[Evaluation of the reserve capacity of the heart in acute myocardial infarct by creating a brief volume load].
A combination of non-invasive and invasive procedures was used to assess hemodynamic response to negative pressure applied to the lower parts of the body (NPLB) in 56 patients with acute myocardial infarction and varying degrees of heart failure (HF) and 20 normal subjects. Normal subjects and HF-free patients showed a significant decrease in their stroke and cardiac indices and pulse pressure, and a rise in specific peripheral resistance, while the HF patients demonstrated higher cardiac productivity and lower specific peripheral resistance. Within 3 minutes after the discontinuation of NPLB, part of the depot blood returned to the central channel, creating a volumetric load on the heart. In this situation, the pump function of the heart was activated in normal subjects and HF-free patients, while patients with latent HF showed no such response, and those with obvious HF demonstrated impaired pump function.


Association between inflammatory burden index and all-cause mortality in the general population aged over 45 years: Data from NHANES 2005-2017.
The objective of this study was to investigate the association between inflammatory burden index (IBI) and all-cause mortality in the general population aged over 45 years. The study included 8827 participants from the National Health and Examination Nutrition Survey (NHANES) who were aged over 45 years. The IBI was calculated using three markers: C-reaction protein × neutrophil/lymphocyte, and all the participants were classified into four groups (Quartile 1: IBI ≤0.178, N = 2206; Quartile 2: 0.178 <IBI ≤0.440, N = 2219; Quartile 3: 0.440 <IBI ≤1.099, N = 2195; Quartile 4: IBI >1.099, 2207). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence interval (CI) for the association between IBI and all-cause mortality. During a median follow-up of 129 month, 2431 deaths occurred. The all-cause mortality rate in Quartile 1, Quartile 2, Quartile 3 and Quartile 4 was 14.76 %, 17.67 %, 23.18 % and 29.69 %, respectively (p < 0.001). After adjustment for demographic, and potential clinical factors, higher IBI was significantly associated with an increased risk of all-cause mortality (Quartile 3 vs. Quartile 1: HR = 1.26, 95 % CI: 1.08 to 1.46, p = 0.003; Quartile 4 vs. Quartile 1: HR = 1.59, 95 % CI: 1.40 to 1.80, p < 0.001). Furthermore, the results of the restricted cubic spline analysis suggested that the association between IBI and all-cause mortality was nonlinear and positive, without specific threshold value. This study supports that higher IBI is associated with an increased risk of all-cause mortality in the general population aged over 45 years.


Bioadhesive giant vesicles for monitoring hydroperoxidation in lipid membranes.
Osmotic stresses, protein insertion or lipid oxidation lead to area increase of self-assembled lipid membranes. However, methods to measure membrane expansion are scarce. Challenged by recent progress on the control of phospholipid hydroperoxidation, we introduce a method to quantitatively evaluate membrane area increase based on the bio-adhesion of Giant Unilamellar Vesicles.


The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women's health study).
The purpose of this study was to characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Cases of AF were confirmed by medical record review in 34,309 participants in the Women's Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. During 12.9 +/- 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% confidence interval [CI]: 3.4 to 6.1, p < 0.0001) increase in risk with each kilogram per square meter. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were used to estimate dynamic risk, overweight (hazard ratio [HR]: 1.22; 95% CI: 1.02 to 1.45, p = 0.03), and obesity (HR: 1.65; 95% CI: 1.36 to 2.00; p < 0.0001) were associated with adjusted short-term increases in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of the development of AF (p = 0.02) compared with those maintaining BMI <30 kg/m(2). The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short-term elevations in BMI was substantial (18.3%). In this population of apparently healthy women, BMI was associated with short- and long-term increases in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. (Women's Health Study [WHS]: A Randomized Trial of Low-Dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer; NCT00000479).


Detection of hypermethylated genes as markers for cervical screening in women living with HIV.
To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa. Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects. Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers. Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+ , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings.


Coffee bean polyphenols ameliorate postprandial endothelial dysfunction in healthy male adults.
To reveal the effect of coffee bean polyphenols (CBPs) on blood vessels, this study aimed to investigate the effect of CBPs on acute postprandial endothelial dysfunction. Thirteen healthy non-diabetic men (mean age, 44.9 ± 1.4 years) consumed a test beverage (active: containing CBPs, placebo: no CBPs) before a 554-kcal test meal containing 14 g of protein, 30 g of fat and 58 g of carbohydrates. Then, a crossover analysis was performed to investigate the time-dependent changes in flow-mediated dilation (FMD) in the brachial artery. In the active group, the postprandial impairment of FMD was significantly improved, the two-hour postprandial nitric oxide metabolite levels were significantly increased and the six-hour postprandial urinary 8-epi-prostaglandin F2α levels were significantly reduced compared to the placebo group. The test meal increased the levels of blood glucose, insulin and triglycerides in both groups with no significant intergroup differences. These findings indicate that CBPs intake ameliorates postprandial endothelial dysfunction in healthy men.


Predictors of progression of diabetic nephropathy: implication for timing of kidney transplantation.
Multiple risk factors are important predictors in the development of diabetic nephropathy (DN). Once DN has developed, it progresses steadily to renal failure. To determine the rate of renal function decline and the parameters that influence the rate of decline, we retrospectively reviewed the charts of patients with DN who had undergone dialysis or kidney transplantation at the Mayo Clinic from 1983 to 1993. Forty patients were found to have two or more iothalamate clearance (IothmCl) measurements where a slope of renal function decline over time, expressed as mL/ min/month/1.73 m2, can be calculated. The parameters examined included age of onset and duration of diabetes (DM); age at initial presentation, insulin dosage, glycosylated hemoglobin level, proteinuria, blood pressure (BP), number of antihypertensive medications (HTM), use of ACE inhibitors, creatinine, and initial IothmCl. The mean overall decline of clearance was 1.36 +/- 1.1 mL/min/month, corrected. Univariate regression analysis showed that only systolic and mean BP (p < 0.05), use of HTM (p = 0.02), and the number of HTM used (p = 0.0001) correlated with the rate of clearance decline. No other parameter was significant. The decline of IothmCl was 0.72 +/- 0.41, 1.20 +/- 0.9, and 2.34 +/- 1.38 mL/min/month, for patients taking no HTM, < 3 HTM, and > or = 3HTM, respectively. Of the eight patients on HTM who presented with initial IothmCl of < 30 mL/min/1.73 m2, seven (88%) had clearance of < 10 mL/min/1.73 m2 within 1 yr. We conclude that hypertension is an important marker of DN progression, and that the more HTM required for control of BP, the faster the decline of renal function. We recommend that a suitable transplant candidate with DN who presents with hypertension requiring HTM and a clearance of < 30 mL/min should be placed on the transplant waiting list.


Return to work after specialised burn care: A two-year prospective follow-up study of the prevalence, predictors and related costs.
Burn injuries may cause long-term disability and work absence, and therefore result in high healthcare and productivity costs. Up to now, detailed information on return to work (RTW) and productivity costs after burns is lacking. The aim of this study was to accurately assess RTW after burn injuries, to identify predictors of absenteeism and to calculate healthcare and productivity costs from a societal perspective. A prospective cohort study was conducted in the burn centre of Rotterdam, the Netherlands, including all admitted working-age patients from 1 August 2011 to 31 July 2012. At 3, 12 and 24 months post-burn, patients were sent a questionnaire: including the Work and Medical Consumption questionnaire for the assessment of work absence and medical consumption and the EQ-5D-3L plus a cognitive dimension to assess post-burn and pre-burn quality of life (QOL). Cost analyses were from a societal perspective according the micro-costing method and the friction cost method was applied for the calculation of productivity loss. Univariate logistic regression was used to identify predictors of absenteeism at three months. A total of 104 patients were included in the study with a mean total body surface area (TBSA) burned of 8% (median 4%). 66 respondents were pre-employed, at 3 months 70% was back at work, at 12 months 92% and 8% had not returned to work at time of final follow-up at 24 months. Predictors of absenteeism at 3 months were: TBSA, length of stay, ICU-admission and surgery. Mean costs related to loss in productivity were €11.916 [95% CI 8.930-14.902] and accounted for 30% of total costs in pre-employed respondents in the first two years. This two-year follow-up study demonstrates that burn injuries cause substantial and prolonged productivity loss amongst burn survivors with mixed burn severity. This absenteeism contributes to already high societal costs of burn injuries. Predictors of absenteeism found in this study were primarily fixed patient and treatment related factors, future studies should focus on modifiable factors, in order to improve RTW outcomes. Also, more attention in the rehabilitation trajectory is needed to optimally support RTW in burn survivors.


Iatrogenic catheter-related cardiac tamponade: a case report of fatal hydropericardium following subcutaneous implantation of a chemotherapeutic injection port.
The need to obtain dependable access to the vascular system constitutes a significant component in the treatment and management of critically ill patients. Intravenous chemotherapy administered to cancer patients over an extended period of time often results in loss of peripheral vascular access due to vein sclerosis, "exhaustion" or tissue necrosis. Medical investigators have designed and steadily upgraded a variety of devices constructed to improve venous access for long-term utilization. As with the introduction of any foreign object into the body, each of these devices has complications which may be life threatening and occasionally fatal. We present an unusual case of iatrogenic acute hydropericardium and cardiac tamponade caused by the percutaneous infusion of chemotherapeutic fluid via a right subclavian central venous implant system (Port-a-Cath). Failure to implant and monitor the device with a radiograph following placement according to manufacturer's guidelines and accepted standards of medical practice were causally related to an unusual complication, namely, perforation of the right cardiac ventricle by the catheter tip, resulting in sudden and unexpected cardiac death.


Quality supply of nonprescription medicines in Portuguese community pharmacy: An exploratory case study.
Inappropriate use of non-prescription medicines (NPM) can increase morbidity, mortality and health care associated costs. Pharmacists have a well-established role in self-medication; however, the literature shows that pharmacies performance in the supply of NPM is often suboptimal. To explore the interaction and dependability of pharmacy staff use of oral language, as well as staff's own assessment of reasons underlying their behavior during consultation regarding NPM. In a case-study design, a high street urban community pharmacy was purposively selected as the setting. Covert patient simulation, using trained simulated patients (SPs), was used to ascertain staff's performance in dispensing NPM, via 4 symptom-based scenarios (SbS) and 3 product-based scenarios (PbS). Performance data were converted into 2 composite indexes: the Interpersonal Performance Index (IPI) and Technical Performance Index (TPI). Audiotaped interactions were transcribed verbatim and participants' utterances were identified, time stamped and coded employing the eight higher level categories of a framework inspired by the Roter interaction analysis system (RIAS). The transcripts of the in-depth interviews were analyzed using the Framework Approach. The tripartite model of attitudes was employed to develop the thematic framework. Ten SP visits were considered for analysis. Overall, the mean TPI score was 50% and the mean IPI score was 78%. TPI was higher for SbS (63%) than PbS (31%), whilst there was little difference IPI between SbS (79%) and PbS (76%). The mean number of questions in the evaluation section of technical performance was 4 for SbS and 1 for PbS. There was a clear predominance of closed questions (32%), when compared with open questions (5.5%). Providing advice was more frequent (23.5%) than giving information (12.5%). In line with the SPs data, comparison of information-gathering in SbS and PbS shows that more questions were asked in the former (44% versus 31%), which resulted in more information given by SPs (56% and 49%, respectively). Staff's reaction to their performance showed all the 3 dimensions of attitude: affective, cognitive and behavioral. Divergence between staff's views on what should be done in NPM consultations and performance data surfaced in the interviewees' accounts on direct product requests. While performance data shows that information gathering was scarce, its importance was overtly acknowledged. The supply of NPM appears to be influenced by both cognitive and emotional issues. This suggests that multimodal improvement interventions are needed, targeting not only technical and interpersonal communication skills but also the organizational context. Managerial tools such as the balanced scorecard, may prove valuable in addressing improvement in the quality supply of NPM.


Dietary modulation of the inflammatory cascade.
Dietary supplementation has traditionally consisted of adding vitamins and/or minerals to correct or prevent a nutritional deficiency. When supplementing the diet with other inflammatory mediators, such as essential fatty acids, there is an adjunctive benefit to the standard therapies used in the control of chronic inflammatory diseases such as Crohn's disease or rheumatoid arthritis. This review focuses on the strategies utilized for therapeutic modulation of the inflammatory cascade through dietary supplementation with specific biomolecules. Examples of how these biomolecules affect local and systemic immune responses to chronic inflammation are examined. In particular, an overview of the literature identifying the potential to modify the host response to chronic periodontitis is provided.


Discriminating D-amino acid-containing peptide epimers by radical-directed dissociation mass spectrometry.
The presence of a single D-amino acid in a peptide is very difficult to detect. Mass spectrometry-based approaches rely on differences in fragmentation between all L-amino acid-containing peptides and single D-amino acid-containing peptides (which are epimers) for identification. The success of this approach is dependent on the structural sensitivity of the fragmentation method. Recently, experiments have demonstrated that fragmentation initiated by radical chemistry, or radical-directed dissociation (RDD), is particularly sensitive to the structure of the ion being fragmented. Herein, RDD is used to identify the presence of D-serine, D-alanine, or D-aspartic acid in eight biologically relevant peptides. It is demonstrated that chiral disambiguation by RDD is dependent on both the initial radical site and subsequent radical migration. Fortuitously, RDD can be initiated by a variety of different radical precursors which can be associated with the peptide via covalent or noncovalent means, and RDD can be examined in all observable charge states (both positive and negative). This diversity enables numerous initial radical sites and migration pathways to be explored. For all but one of the peptides that were examined, RDD provides significantly better chiral discrimination than CID. Quantitation of peptide epimers by RDD is also described.


miR-145-5p inhibits the proliferation and migration of bladder cancer cells by targeting TAGLN2.
MicroRNA-145-5p (miR-145-5p) is found to be involved in tumor development and progression. However, there are few studies on the effects of miR-145-5p on bladder cancer (BC). The role of miR-145-5p in BC was predicted by analysis of cell proliferation and migration in this study. The miR-145-5p and transgelin-2 (TAGLN2) expressions were evaluated via reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The MTT and Transwell assay assessed cell proliferation and migration. TAGLN2 targeted to miR-145-5p was determined using luciferase assays. The results showed that the miR-145-5p downregulation was found in BC. miR-145-5p overexpression inhibited cell proliferation and migration in BC. Moreover, miR-145-5p directly targeted TAGLN2, and TAGLN2 expression was increased in BC. In addition, the high expression of TAGLN2 promoted cell proliferation and migration in BC. miR-145-5p appeared to regulate TAGLN2 in BC, and it also inhibited the cell proliferation and migration. The novel miR-145-5p/TAGLN2 axis may provide new therapeutic implications for BC.


Eltrombopag: How secure in triple therapy of HCV?
Triple therapy of hepatitis C usually leads to some hematological and dermatological side effects. Thrombocytopenia is one of the most common side effects that are encountered during triple therapy. Eltrombopag was approved for the treatment of patients with chronic hepatitis C and thrombocytopenia to allow the initiation and maintenance of interferon based therapies. During eltrombopag therapy, some side effects like headache, abdominal pain, and some complications such as portal vein thrombosis, deep vein thrombosis and arterial thrombosis were observed more frequently than placebo. We described here a patient who developing thrombosis secondary to eltrombopag in receiving triple therapy.


The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information.
Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An 'ethic of care' interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent.


The output neurones and the dopaminergic neurones of the substantia nigra receive a GABA-containing input from the globus pallidus in the rat.
One of the major pathways of information flow through the basal ganglia is the pallidonigrofugal system. In order to better understand this system in the rat, experiments have been performed to study the topography, synaptic organization, and neurotransmitter content of the pallidonigral projection and to determine whether the pallidonigral neurones make direct synaptic contacts with nigrofugal cells. This was achieved by combining the anterograde transport of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) with the retrograde transport of lectin-conjugated horseradish peroxidase (WGA-HRP), postembedding immunocytochemistry for gamma-aminobutyric acid (GABA), and pre-embedding immunocytochemistry for tyrosine hydroxylase (TH). Following injections of PHA-L in different regions of the lateral part of the globus pallidus, a substantial number of immunoreactive fibres and terminals occurred in the ipsilateral substantia nigra reticulata (SNr). The immunoreactive elements were distributed according to a rostral to medial and caudal to lateral topography. Injections that were restricted to the medial tip of the globus pallidus led to the anterograde labeling of a small number of fibres that were sparsely distributed in the SNr. The most characteristic feature of the pallidonigral fibres was the presence of large varicosities that were often grouped to form pericellular baskets. Injections of WGA-HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum, including the pedunculopontine nucleus, showed that the perikarya and primary dendrites of the output cells of the SNr were often surrounded by the large pallidonigral varicosities. The number of varicosities surrounding a single cell varied from 2-12. Electron microscopic analysis showed that the varicosities contained round or slightly pleomorphic vesicles and numerous mitochondria and that they established symmetrical synaptic contacts. Quantitative measurements revealed that the varicosities had a maximum diameter varying from 0.5 to 2.5 microns and a mean cross-sectional area of 0.76 +/- 0.25 microns 2 (N = 237, mean +/- S.D.). The postsynaptic structures of the pallidonigral varicosities included perikarya (48%), large dendrites (38%), and small dendrites (14%). A large proportion of these postsynaptic targets were retrogradely labeled after injection of WGA-HRP in the ventromedial thalamic nucleus, superior colliculus, or midbrain tegmentum. Postembedding immunocytochemistry was used to show that the pallidonigral axons and terminals in contact with nigrofugal neurones displayed GABA immunoreactivity. The use of a double immunocytochemical method revealed, that in addition to the nondopaminergic SNr output neurones, the dendrites and perikarya of the substantia nigra pars compacta (SNc) receive an input from the globus pallidus.(ABSTRACT TRUNCATED AT 400 WORDS)


Toward a Holistic Computational Representation for Sleep Quality and its Support for Explainability.
Sleep quality is recognized as one of the main factors that affect human health. Thus, several studies have been encouraged to analyze features, such as stress level and female menopause, which are directly related to sleep quality. While these works rely mostly on reductionism as the philosophical framework, we approach this problem from a holist perspective, using a model with 10 features that could provide more reliable explanations for inductive conclusions. We demonstrate the principles of this hypothesis by analyzing the data regarding the day before a sleep episode of 1736 volunteers. This analysis shows, for example, the performance of each feature when they are jointly used along prediction tasks. Moreover, we evaluate the readability and accuracy of explanations, given as description logic sentences and based on a knowledge representation that considers the 10 features as elements that compose a sleep quality ontological definition.


Variable efficacy of repeated annual influenza vaccination.
Conclusions have differed in studies that have compared vaccine efficacy in groups receiving influenza vaccine for the first time to efficacy in groups vaccinated more than once. For example, the Hoskins study [Hoskins, T. W., Davis, J. R., Smith, A. J., Miller, C. L. & Allchin, A. (1979) Lancet i, 33-35] concluded that repeat vaccination was not protective in the long term, whereas the Keitel study [Keitel, W. A., Cate, T. R., Couch, R. B., Huggins, L. L. & Hess, K. R. (1997) Vaccine 15, 1114-1122] concluded that repeat vaccination provided continual protection. We propose an explanation, the antigenic distance hypothesis, and test it by analyzing seven influenza outbreaks that occurred during the Hoskins and Keitel studies. The hypothesis is that variation in repeat vaccine efficacy is due to differences in antigenic distances among vaccine strains and between the vaccine strains and the epidemic strain in each outbreak. To test the hypothesis, antigenic distances were calculated from historical hemagglutination inhibition assay tables, and a computer model of the immune response was used to predict the vaccine efficacy of individuals given different vaccinations. The model accurately predicted the observed vaccine efficacies in repeat vaccinees relative to the efficacy in first-time vaccinees (correlation 0.87). Thus, the antigenic distance hypothesis offers a parsimonious explanation of the differences between and within the Hoskins and Keitel studies. These results have implications for the selection of influenza vaccine strains, and also for vaccination strategies for other antigenically variable pathogens that might require repeated vaccination.


Psychiatric inpatient expenditures and public health insurance programmes: analysis of a national database covering the entire South Korean population.
Medical spending on psychiatric hospitalization has been reported to impose a tremendous socio-economic burden on many developed countries with public health insurance programmes. However, there has been no in-depth study of the factors affecting psychiatric inpatient medical expenditures and differentiated these factors across different types of public health insurance programmes. In view of this, this study attempted to explore factors affecting medical expenditures for psychiatric inpatients between two public health insurance programmes covering the entire South Korean population: National Health Insurance (NHI) and National Medical Care Aid (AID). This retrospective, cross-sectional study used a nationwide, population-based reimbursement claims dataset consisting of 1,131,346 claims of all 160,465 citizens institutionalized due to psychiatric diagnosis between January 2005 and June 2006 in South Korea. To adjust for possible correlation of patients characteristics within the same medical institution and a non-linearity structure, a Box-Cox transformed, multilevel regression analysis was performed. Compared with inpatients 19 years old or younger, the medical expenditures of inpatients between 50 and 64 years old were 10% higher among NHI beneficiaries but 40% higher among AID beneficiaries. Males showed higher medical expenditures than did females. Expenditures on inpatients with schizophrenia as compared to expenditures on those with neurotic disorders were 120% higher among NHI beneficiaries but 83% higher among AID beneficiaries. Expenditures on inpatients of psychiatric hospitals were greater on average than expenditures on inpatients of general hospitals. Among AID beneficiaries, institutions owned by private groups treated inpatients with 32% higher costs than did government institutions. Among NHI beneficiaries, inpatients medical expenditures were positively associated with the proportion of patients diagnosed into dementia or schizophrenia categories. However, for AID beneficiaries, inpatient medical expenditures were positively associated with the proportion of all patients with a psychiatric diagnosis that were AID beneficiaries in a medical institution. This study provides evidence that patient and institutional factors are associated with psychiatric inpatient medical expenditures, and that they may have different effects for beneficiaries of different public health insurance programmes. Policy efforts to reduce psychiatric inpatient medical expenditures should be made differently across the different types of public health insurance programmes.


Idiosyncratic responses of grizzly bear habitat to climate change based on projected food resource changes.
Climate change vulnerability assessments for species of conservation concern often use species distribution and ecological niche modeling to project changes in habitat. One of many assumptions of these approaches is that food web dependencies are consistent in time and environmental space. Species at higher trophic levels that rely on the availability of species at lower trophic levels as food may be sensitive to extinction cascades initiated by changes in the habitat of key food resources. Here we assess climate change vulnerability for Ursus arctos (grizzly bears) in the southern Canadian Rocky Mountains using projected changes to 17 of the most commonly consumed plant food items. We used presence-absence information from 7088 field plots to estimate ecological niches and to project changes in future distributions of each species. Model projections indicated idiosyncratic responses among food items. Many food items persisted or even increased, although several species were found to be vulnerable based on declines or geographic shifts in suitable habitat. These included Hedysarum alpinum (alpine sweet vetch), a critical spring and autumn root-digging resource when little else is available. Potential habitat loss was also identified for three fruiting species of lower importance to bears: Empetrum nigrum (crowberry), Vaccinium scoparium (grouseberry), and Fragaria virginiana (strawberry). A general trend towards uphill migration of bear foods may result in higher vulnerability to bear populations at low elevations, which are also those that are most likely to have human-bear conflict problems. Regardless, a wide diet breadth of grizzly bears, as well as wide environmental niches of most food items, make climate change a much lower threat to grizzly bears than other bear species such as polar bears and panda bears. We cannot exclude, however, future alterations in human behavior and land use resulting from climate change that may reduce survival rates.


Renal acid excretion in the domestic fowl.
1. In order to assess the role of uricotelism in net renal acid excretion, blood and ureteral urine samples were collected from five hens fed a commercial poultry feed (Diet A) and five hens fed a protein-rich, Na-poor feed (Diet B). All samples were analysed for pH, PCO2, ammonium, phosphate, uric acid and urates (UA + U) and inulin. 2. On Diet A, average pH in venous blood was 7.42, while urinary pH (pHu) ranged from 4.74 to 7.25. At average pHu (6.10), uric acid accounted for 52% of total acid excreted, H2PO4 for 20% and NH4 for 28%. Net acid excretion in ureteral urine was 345 muequiv h-1 kg body weight-1, or 5-10 times that observed in ureotelic vertebrates (amphibians and mammals). 3. The relative contributions of these urinary buffers to net renal acid excretion changed with pHu. Significant negative correlations exist between pHu and both total phosphate and ammonium excretion rates (P less than 0.001). Excretion rates of (UA + U) showed a positive correlation (P less than 0.05) with pHu. 4. Feeding on Diet B revealed the homeostatic power of the avian kidney. Blood pH and PCO2 were not changed relative to values in hens fed the control diet while striking increases in excretion rates of all urinary buffers (except HCO3) were observed. Average pHu fell to 5.12, and the average net renal acid excretion rate doubled.


Extracting the abstraction pyramid from complex networks.
At present, the organization of system modules is typically limited to either a multilevel hierarchy that describes the "vertical" relationships between modules at different levels (e.g., module A at level two is included in module B at level one), or a single-level graph that represents the "horizontal" relationships among modules (e.g., genetic interactions between module A and module B). Both types of organizations fail to provide a broader and deeper view of the complex systems that arise from an integration of vertical and horizontal relationships. We propose a complex network analysis tool, Pyramabs, which was developed to integrate vertical and horizontal relationships and extract information at various granularities to create a pyramid from a complex system of interacting objects. The pyramid depicts the nested structure implied in a complex system, and shows the vertical relationships between abstract networks at different levels. In addition, at each level the abstract network of modules, which are connected by weighted links, represents the modules' horizontal relationships. We first tested Pyramabs on hierarchical random networks to verify its ability to find the module organization pre-embedded in the networks. We later tested it on a protein-protein interaction (PPI) network and a metabolic network. According to Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), the vertical relationships identified from the PPI and metabolic pathways correctly characterized the inclusion (i.e., part-of) relationship, and the horizontal relationships provided a good indication of the functional closeness between modules. Our experiments with Pyramabs demonstrated its ability to perform knowledge mining in complex systems. Networks are a flexible and convenient method of representing interactions in a complex system, and an increasing amount of information in real-world situations is described by complex networks. We considered the analysis of a complex network as an iterative process for extracting meaningful information at multiple granularities from a system of interacting objects. The quality of the interpretation of the networks depends on the completeness and expressiveness of the extracted knowledge representations. Pyramabs was designed to interpret a complex network through a disclosure of a pyramid of abstractions. The abstraction pyramid is a new knowledge representation that combines vertical and horizontal viewpoints at different degrees of abstraction. Interpretations in this form are more accurate and more meaningful than multilevel dendrograms or single-level graphs. Pyramabs can be accessed at http://184.108.40.206/pyramabs.php/.


Choline Is an Intracellular Messenger Linking Extracellular Stimuli to IP3-Evoked Ca2+ Signals through Sigma-1 Receptors.
Sigma-1 receptors (Sig-1Rs) are integral ER membrane proteins. They bind diverse ligands, including psychoactive drugs, and regulate many signaling proteins, including the inositol 1,4,5-trisphosphate receptors (IP3Rs) that release Ca2+ from the ER. The endogenous ligands of Sig-1Rs are unknown. Phospholipase D (PLD) cleaves phosphatidylcholine to choline and phosphatidic acid (PA), with PA assumed to mediate all downstream signaling. We show that choline is also an intracellular messenger. Choline binds to Sig-1Rs, it mimics other Sig-1R agonists by potentiating Ca2+ signals evoked by IP3Rs, and it is deactivated by metabolism. Receptors, by stimulating PLC and PLD, deliver two signals to IP3Rs: IP3 activates IP3Rs, and choline potentiates their activity through Sig-1Rs. Choline is also produced at synapses by degradation of acetylcholine. Choline uptake by transporters activates Sig-1Rs and potentiates Ca2+ signals. We conclude that choline is an endogenous agonist of Sig-1Rs linking extracellular stimuli, and perhaps synaptic activity, to Ca2+ signals.


Urinary Tract Infection in Hemodialysis-Dependent End-Stage Renal Disease Patients.
The aim of this study was to analyze urinalysis findings and urinary bacterial culture in hemodialysis-dependent end-stage renal disease patients. The research goal was to understand the proportion, risk factors, and the causative organisms of urinary tract infection in hemodialysis-dependent end-stage renal disease patients. Between May 2020 and June 2021, this study included 100 hemodialysis-dependent end-stage renal disease patients (50 male patients and 50 female patients). The urine underwent microscopic examination, pyuria was defined as ≥5 white blood cells per high-power field, and urinary bacterial cultures were conducted for patients with pyuria. Bacteriuria was defined as ≥104 colony-forming units/mL in men and ≥105 colony-forming units/mL in women. Daily urine output was investigated by oral listening. Postvoiding residual urine volume was measured. Fifty-six percent of male patients and 30% of female patients had normosthenuria, 24% of male patients and 38% of female patients had pyuria, and 20% of male patients and 32% of female patients had a urinary tract infection. A comparison of normosthenuria and urinary tract infection revealed no statistically significant difference in age, time on dialysis, daily urine output, and postvoiding residual urine volume. The proportion of female patients among those with normosthenuria was 34.8%, whereas the proportion of female patients among those with UTI was 61.5%. Urinary bacterial cultures showed that the major causative organisms were Escherichia coli (45%; 18/40 cultures) and extended spectrum beta-lactamase-producing Escherichia coli (17.5%; 7/40 cultures). The incidence of urinary tract infection was higher in female patients than in male patients. The proportion of resistant bacteria as the causative organisms was high in hemodialysis-dependent end-stage renal disease patients. Urinary bacterial culture should be checked while patients are able to void urine.


The anesthetic eye: an investigation of changes in the anterior ocular segment of the monkey caused by interrupting the trigeminal nerve at various levels along its course.
Operations were performed at four different levels on the fifth nerve of the monkey to determine which procedure offers the best chance of avoiding ocular complications after surgical treatment of trigeminal neuralgia (Figure 18). (1) Section of the ophthalmic branch of N V results in immediate corneal anesthesia. After one week, chromatolysis of the unipolar gasserian ganglion cells subserving the first division occurs and Wallerian degeneration of the corneal nerves of the ipsilateral eye is seen. This is associated with perilimbal round cell invasion of the superficial cornea and subconjunctival area. In addition, iritis develops de novo or becomes worse if it pre-exists. Miosis occurs, but the chemodiagnostic tests of cocaine and adrenalin indicate an intact sympathetic system. The cause for this inflammatory reaction and pupillary change is unexplained by this study. The intraocular pressure is slightly lower on the side of the section than in the normal fellow control eye after surgery, but the difference is not statistically significant. (2) Section of the posterior sensory root of N V in the middle cranial fossa at a point between the gasserian glanglion and the tentorium results in similar ocular changes as is seen after interrupting the ophthalmic division alone. Wallerian degeneration of the corneal nerves, however, is not seen after seven, twelve or twenty-one days. (3) Transtentorial section of the trigeminal posterior sensory root performed in the middle cranial fossa, results in immediate corneal anesthesia. The gasserian ganglion cells, however, remain healthy and there is no perilimbal round cell invasion of the superficial cornea or subconjunctival tissue. Miosis occurs but the chemodiagnostic tests of cocaine and adrenalin indicate an intact sympathetic system. The intraocular pressure is only slightly lower on the side of section than in the control eye, but the difference is not statistically significant. (4) Suboccipital rhizotomy of the posterior sensory root of NV at the pons results in immediate corneal anesthesia. The gasserian ganglion cells remain healthy and there is no perilimbal round cell invasion of the superficial cornea or subconjunctival tissue. Miosis occurs in most animals (2 of 3) and is associated with an intact sympathetic system as indicated by the chemodiagnostic tests of cocaine and adrenalin. Intraocular pressure is very slightly lower on the side of section than in the control eye, but the difference is not statistically significant. (5) Thinning of the corneal epithelium occurs in an anesthetic eye regardless of the location of the section of N V and is not adversely affected by tarsorrhaphy. The corneal stroma, however, remains unchanged. (6) The experimental data demonstrate that to decrease ocular complications, operations on the trigeminal nerve should be performed on the caudal end of the sensory root as far from the gasserian ganglion as is techanically feasible.


An overview of the metabolic differences between Bradyrhizobium japonicum 110 bacteria and differentiated bacteroids from soybean (Glycine max) root nodules: an in vitro 13C- and 31P-nuclear magnetic resonance spectroscopy study.
Bradyrhizobium japonicum is a symbiotic nitrogen-fixing soil bacteria that induce root nodules formation in legume soybean (Glycine max.). Using (13)C- and (31)P-nuclear magnetic resonance (NMR) spectroscopy, we have analysed the metabolite profiles of cultivated B. japonicum cells and bacteroids isolated from soybean nodules. Our results revealed some quantitative and qualitative differences between the metabolite profiles of bacteroids and their vegetative state. This includes in bacteroids a huge accumulation of soluble carbohydrates such as trehalose, glutamate, myo-inositol and homospermidine as well as Pi, nucleotide pools and intermediates of the primary carbon metabolism. Using this novel approach, these data show that most of the compounds detected in bacteroids reflect the metabolic adaptation of rhizobia to the surrounding microenvironment with its host plant cells.


β-glucan, a specific immuno-stimulant, produces rapid antidepressant effects by stimulating ERK1/2-dependent synthesis of BDNF in the hippocampus.
A decline in microglia in the dentate gyrus of the hippocampus has recently been described as an important mechanism for the progression of depression. Reversal of this decline by innate immune system stimulants may represent a novel strategy to ameliorate the depressive phenotype in chronically stressed animals. β-glucan is a polysaccharide from Saccharomyces cerevisiae. It can efficiently stimulate microglia without inducing the production of pro-inflammatory cytokines. Therefore, β-glucan could be an ideal drug to ameliorate depressive phenotypes. In the present study, we found that a single injection of β-glucan reversed depression-like behaviors in mice induced by chronic unpredictable stress (CUS) in a dose-dependent manner, which was accompanied by a reversal of the CUS-induced decrease in brain-derived neurotrophic factor (BDNF) protein levels in the dentate gyrus. The crucial role of BDNF signaling in the antidepressant effect of β-glucan was demonstrated by experiments showing that infusion of an anti-BDNF antibody into dentate gyrus, construction of BDNF-Val68Met allele knock-in mice, or treatment with the BDNF receptor antagonist K252a abolished the antidepressant effect of β-glucan. The increased BDNF signaling induced by β-glucan was mediated by extracellular signal-regulated kinase1/2 (ERK1/2)-mediated BDNF synthesis, and inhibition of ERK1/2 by SL327 was able to abolish the antidepressant effect of β-glucan. Moreover, inhibition or depletion of microglia by minocycline or PLX3397 abolished the reversal effect of β-glucan on CUS-induced depression-like behaviors and CUS-induced impairment of ERK1/2-BDNF signaling. These results suggest that β-glucan exhibits antidepressant effects by stimulating microglia-mediated activation of ERK1/2 and synthesis of BDNF in the hippocampus.


Portland cement versus MTA as a root-end filling material. A pilot study.
To assess periradicular lesions clinically and by computed tomography (CT) after endodontic surgery using either Portland cement or mineral trioxide aggregate (MTA) as a root-end filling material. Three patients diagnosed with periradicular lesions by cone-beam CT underwent endodontic surgery with root-end filling. Patient A was treated with MTA as the root-end filling material, patient B was treated with Portland cement and patient C had two teeth treated, one with MTA and the other with Portland cement. Six months after surgery, the patients were assessed clinically and by CT scan and the obtained results were compared. Periradicular tissue regeneration was observed in all cases, with no significant differences in bone formation when comparing the use of MTA and Portland cement as root-end filling materials. Both mineral trioxide aggregate and Portland cement were successful in the treatment of periradicular lesions.


High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in Postpubertal Boys and Girls: A Comparative Study.
Pal, S, Chaki, B, Chattopadhyay, S, and Bandyopadhyay, A. High-intensity exercise induced oxidative stress and skeletal muscle damage in post-pubertal boys and girls: a comparative study. J Strength Cond Res 32(4): 1045-1052, 2018-The purpose of this study was to examine the sex variation in high-intensity exercise induced oxidative stress and muscle damage among 44 sedentary postpubertal boys and girls through estimation of postexercise release pattern of muscle damage markers like creatine kinase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress markers like extent of lipid peroxidation (thiobarbituric acid-reactive substances) and catalase activity. Muscle damage markers like creatine kinase, LDH, ALT, and AST were measured before, immediately after, and 24 and 48 hours after high-intensity incremental treadmill running. Oxidative stress markers like thiobarbituric acid-reactive substances and catalase activity were estimated before and immediately after the exercise. Lipid peroxidation and serum catalase activity increased significantly in both groups after exercise (p < 0.001) with postexercise values and percentage increase significantly higher in postpubertal boys as compared to girls (p < 0.001). Creatine kinase and LDH activity also increased significantly above pre-exercise level at 24 and 48 hours after exercise in both the sexes, (p < 0.001) with values significantly higher for boys than the girls (p < 0.001). Although ALT and AST increased significantly in both the groups after exercise, the pattern of postexercise release of these markers were found to be similar in both the groups. Accordingly, it has been concluded from the present investigation that high-intensity exercise induces significant oxidative stress and increases indices of skeletal muscle damage in both postpubertal girls and boys. However, postpubertal girls are relatively better protected from oxidative stress and muscle damage as compared to the boys of similar age and physical activity level. It is further evident that sex difference may not be apparent for all the biomarkers of muscle damage in this age group.


US Medical Trainees' Knowledge of Human Papilloma Virus and Head and Neck Cancer.
Given the increasing incidence of human papilloma virus (HPV)-positive head and neck cancers (HNCs), discussion of this oncologic outcome should be incorporated into HPV vaccine counseling practices. Yet, preliminary evidence shows that knowledge of the association between HPV and HNC is lacking among most medical trainees. To better characterize this deficit, we nationally assessed knowledge of HPV's association with HNC among medical students and residents across 4 specialties (pediatrics, obstetrics and gynecology, family medicine, and otolaryngology). A total of 3141 responses from 46 states were obtained (n = 402 pediatric residents, n = 346 obstetrics/gynecology residents, n = 260 family medicine residents, n = 87 otolaryngology residents, and n = 2045 medical students). Only 40.3% of surveyed medical students and 56.1% of surveyed obstetrics/gynecology, pediatrics, and family medicine residents identified associations between persistent HPV infection and HNC. When counseling on the vaccine, nonotolaryngology residents more often discussed cervical cancer (99.8%) as compared with HNC (39.7%), commonly because of less HNC knowledge (61.5%). These results suggest that it is imperative to develop educational interventions targeted at medical students and resident trainees on the front line of HPV vaccine counseling and administration.


Olfactory cortex degeneration in Alzheimer's disease and mild cognitive impairment.
Olfactory deficits are prevalent in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). These symptoms precede clinical onset of cognitive and memory deficits and coincide with AD pathology preferentially in the central olfactory structures, suggesting a potential biomarker for AD early detection and progression. Therefore, we tested the hypothesis that structural degeneration of the primary olfactory cortex (POC) could be detected in AD as well as in MCI patients and would be correlated with olfactory functional magnetic resonance imaging (fMRI) alterations, reflecting loss of olfactory cortex activity. Total structural volumes and fMRI activation volumes of the POC and hippocampus were measured along with olfactory and cognitive behavioral tests in 27 cognitively normal (CN), 21 MCI, and 15 AD subjects. Prominent atrophy in the POC and hippocampus was found in both AD and MCI subjects and correlated with behavioral measurements. While behavioral and volumetric measurements showed a gradual decline from CN to MCI to AD, olfactory activation volume in the POC and hippocampus showed a steeper decline in the MCI group compared to corresponding tissue volume, resembling the AD group. Decline in olfactory activity was correlated with the AD structural degeneration in the POC. A more prominent olfactory activity deficit than that of behavioral and tissue volume measurements was shown in the MCI stage. Olfactory fMRI may thus provide an earlier and more sensitive measure of functional neurodegeneration in AD and MCI patients.


Evolving pandemic diabetic nephropathy.
The expanding impact of chronic kidney disease (CKD) due to pandemic diabetes mellitus is recounted emphasizing its epidemiology that has induced global socioeconomic stress on health care systems in industrialized nations now attempting to proffer optimal therapy for end stage renal disease (ESRD). Strategies to delay and perhaps prevent progression of diabetic nephropathy from minimal proteinuria through nephrotic range proteinuria and azotemia to ESRD appear to have decreased the rate of persons with diabetes who develop ESRD. For those with ESRD attributed to diabetes, kidney transplantation affords better survival and rehabilitation than either hemodialysis or peritoneal dialysis. It is likely that advances in genetics and molecular biology will suggest early interventions that will preempt diabetic complications including renal failure.


Linkage Analysis and Multi-Locus Genome-Wide Association Studies Identify QTNs Controlling Soybean Plant Height.
Plant height is an important target for soybean breeding. It is a typical quantitative trait controlled by multiple genes and is susceptible to environmental influences. Here, we carried out phenotypic analysis of 156 recombinant inbred lines derived from "Dongnong L13" and "Henong 60" in nine environments at four locations over 6 years using interval mapping and inclusive composite interval mapping methods. We performed quantitative trait locus (QTL) analysis by applying pre-built simple-sequence repeat maps. We detected 48 QTLs, including nine significant QTLs detected by multiple methods and in multiple environments. Meanwhile, genotyping of all lines using the SoySNP660k BeadChip produced 54,836 non-redundant single-nucleotide polymorphism (SNP) genotypes. We used five multi-locus genome-wide association analysis methods to locate 10 quantitative trait nucleotides (QTNs), four of which overlap with previously located QTLs. Five candidate genes related to plant height are predicted to lie within 200 kb of these four QTNs. We identified 19 homologous genes in Arabidopsis, two of which may be associated with plant height. These findings further our understanding of the multi-gene regulatory network and genetic determinants of soybean plant height, which will be important for breeding high-yielding soybean.


Daily activities, cognition and community functioning in persons with schizophrenia.
This cross-sectional study explored the relationships between daily activity performance, attention, memory, executive functions and community functioning in people with schizophrenia. More specifically, this study attempted to verify the hypothesis that functional limitations in the performance of daily activities negatively affect community functioning in people with schizophrenia. Eighty-two individuals with schizophrenia living in the community were recruited for the study. The Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis was used to assess participants' functional capacity during a meal preparation task. Visuo-spatial associative memory, spatial working memory, planning, visuo-motor coordination, and selective attention were evaluated as well. Community functioning was assessed with the Independent Living Skills Survey (ILSS) and the Multnomah Community Ability Scale (MCAS). Correlations revealed significant associations between functional capacity and visuo-spatial associative learning, spatial working memory, planning and negative symptoms. Planning skills during meal preparation were found to be associated with MCAS. After regression analyses, only visuo-spatial memory, negative symptoms, education and familiarity with meal preparation explained variation in functional capacity. The findings of the current study suggest that visuo-spatial associative learning, negative symptoms, education and familiarity with task are among the important factors for functional capacity. Planning skills necessary for efficient task performance were also found to be those most determinant for community functioning. Rehabilitation interventions should consider these underlying strength and deficits when developing strategies to help people with schizophrenia build functional skills essential for community living.


Functional characterization of 5-enopyruvylshikimate-3-phosphate synthase from Alkaliphilus metalliredigens in transgenic Arabidopsis.
Although a large number of AroA enzymes (EPSPS: 5-enopyruvylshikimate-3-phosphate synthase) have been identified, cloned, and tested for glyphosate resistance, only two AroA variants, derived from Agrobacterium tumefaciens strain CP4 and Zea mays, have been utilized to produce the commercial glyphosate-resistant crops. Here, we have used a PCR-based twostep DNA synthesis method to synthesize an aroA gene (aroAA. metalliredigens) from Alkaliphilus metalliredigens, encoding a new EPSPS. Furthermore, transgenic Arabidopsis with the new aroAA. metalliredigens gene was obtained to confirm the potential of the novel aroA gene in developing glyphosate-resistant crops.


Non neutralizing antibodies to tissue type plasminogen activator in the serum of acute myocardial infarction patients treated with the recombinant protein.
Recombinant tissue-type plasminogen activator (rt PA) is currently used as a thrombolytic agent in the management of acute myocardial infarction (AMI). Since it is known that other recombinant proteins induce antibody formation when administered to humans, we determined the presence of anti-rt-PA antibodies in serial blood samples from 60 AMI patients (43 treated with and 17 without rt-PA). Blood samples were taken upon hospital admission, 15 days and 1, 3, 6 months thereafter. A blood sample was also collected from 200 healthy subjects. Using an ELISA, anti-rt-PA antibodies were detected as serum immunoglobulins specifically binding immobilized rt-PA, AMI patients before treatment and normal subjects exhibited negligible levels of anti-rt-PA antibodies; both groups had only one outlier value. Fifteen days after rt-PA treatment, 2 AMI patients showed an increase in antibody titer beyond the highest normal value. This titer progressively decreased during the following 6 months. The antibodies from these two patients bound rt-PA both in a solid and fluid phase. They bound melanoma t-PA to a lower degree and did not bind urokinase type plasminogen activator at all, indicating specificity for t-PA. The marked temporal relationship between rt-PA infusion and antibody appearance indicated that antibody formation had been elicited by the infusion of rt-PA. Nevertheless, the lack of anti-rt-PA antibody interference with rt-PA function in vitro, along with the favourable clinical outcome of those patients having such antibodies would indicate that the appearance of anti-rt-PA antibodies does not interfere with the physiological fibrinolytic activity.


The sedimentation of rat skeletal-muscle ribosomes. Effect of hydrocortisone, insulin and diet.
1. The influence of hydrocortisone, insulin and diet on the size distribution of ribosomes in a post-mitochondrial supernatant prepared from rat skeletal muscle was studied by sedimentation analysis with a linear 15-40% (w/v) sucrose gradient. 2. Within 4hr. after the injection of 5mg. of hydrocortisone to well-nourished rats, a decrease in the yield per g. of muscle and proportion of total RNA due to polyribosomes was observed. Similar results were obtained in rats given a protein-free diet for 3 days before administration of the hormone. 3. Insulin injection increased the yield and proportion of polyribosomes within 2hr. and decreased the proportion of the lighter ribosomal aggregates. Similar results were noted in rats given a protein-free diet for 3 days before injection. A protein-free diet given for 3 days decreased the yield and proportion of polyribosomes. Insulin did not increase the yield of polyribosomes if rats were starved for 52hr. before injection, but decreased the yield and proportion of the lighter ribosome species. 4. A 52hr. period of starvation or 2,4-dinitrophenol (15mg./kg. body wt.) given 1hr. before the rats were killed resulted in a decreased yield and proportion of polyribosomes, and, within 6hr. of re-feeding the rats with protein-free diets, an increased concentration of polyribosomes was noted. 5. The effects of a protein-free diet, hydrocortisone and insulin on the sedimentation of muscle ribosomes were found to be in accord with their net effects on muscle protein synthesis.


Fast local search for unrooted Robinson-Foulds supertrees.
A Robinson-Foulds (RF) supertree for a collection of input trees is a tree containing all the species in the input trees that is at minimum total RF distance to the input trees. Thus, an RF supertree is consistent with the maximum number of splits in the input trees. Constructing RF supertrees for rooted and unrooted data is NP-hard. Nevertheless, effective local search heuristics have been developed for the restricted case where the input trees and the supertree are rooted. We describe new heuristics, based on the Edge Contract and Refine (ECR) operation, that remove this restriction, thereby expanding the utility of RF supertrees. Our experimental results on simulated and empirical data sets show that our unrooted local search algorithms yield better supertrees than those obtained from MRP and rooted RF heuristics in terms of total RF distance to the input trees and, for simulated data, in terms of RF distance to the true tree.


Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations.
Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)-induced mutagenesis. In our study, we have identified a rare subset of treatment-naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment-induced hypermutagenesis. We conducted Whole-Exome Sequencing (WES), Whole-Transcriptome Sequencing (WTS), and Single-Cell Sequencing (SCS) of TMZ-naïve and post-TMZ-treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ-naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ-induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ-naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ-naïve and post-TMZ-treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.


Eplerenone, but not steroid withdrawal, reverses cardiac fibrosis in deoxycorticosterone/salt-treated rats.
Aldosterone has been thought to act primarily on epithelia to regulate fluid and electrolyte homeostasis. Mineralocorticoid receptors (MR), however, are also expressed in nonepithelial tissues, such as the heart and vascular smooth muscle. Recently, pathophysiological effects of nonepithelial MR activation by aldosterone have been demonstrated in the context of inappropriate mineralocorticoid levels for salt status, including coronary vascular inflammation and cardiac fibrosis. These effects are mostly prevented by the concomitant administration of MR antagonists, but to date, no equivalent studies have determined whether MR blockade can reverse established inflammation and fibrosis. Uninephrectomized rats maintained on 0.9% NaCl solution to drink were treated as follows: group 1 served as controls; group 2 received deoxycorticosterone (DOC; 20 mg/wk) for 4 wk until death, and group 3 received DOC for 8 wk. Group 4 received DOC for 4 wk and no steroid from wk 5-8; group 5 received DOC for 8 wk and eplerenone in their chow during wk 5-8. DOC progressively raised cardiac collagen accumulation at 4 and 8 wk. Rats given DOC for 4 wk and killed at 8 wk showed levels of fibrosis identical to those in animals killed at 4 wk, i.e. persistently elevated above control values. Rats given DOC for 8 wk and eplerenone for the second half of the period showed cardiac collagen levels indistinguishable from control values. Values for inflammatory marker and NAD(P)H oxidase subunit expression in coronary vessels showed a similar pattern of response, with minor variation. Thus, MR antagonists do not only prevent cardiac fibrosis, but also reverse cardiac fibrosis once it is established. In addition, the continuing vascular inflammatory response and fibrosis after DOC withdrawal (group 4) support a role for activation of vascular MR by endogenous glucocorticoids in the context of tissue damage and generation of reactive oxygen species.


Rectal cancer: Preoperative versus postoperative irradiation as a component of adjuvant treatment.
The search for improved disease control and survival for resectable but high-risk rectal cancers has led to studies that combine all 3 modalities. For surgically resected, high-risk rectal cancers, postoperative chemoradiation has been shown to improve both disease control (local and distant) and survival (disease free and overall) and was recommended as standard adjuvant treatment at the 1990 National Institute of Health Colorectal Cancer Consensus Conference. Three randomized studies showed improved overall survival (OS) and local control for patients treated with postoperative irradiation and chemotherapy when compared with surgery alone or surgery plus irradiation control arms. These include 2 US trials, Gastrointestinal Tumor Study Group and Mayo/North Central Cancer Treatment Group (NCCTG) and a Norway trial. Although most preoperative external beam radiation trials show reductions in local relapse with the addition of preoperative EBRT to resection, only the large Swedish trial of approximately 1,100 patients showed a survival improvement when compared with a surgery alone control arm for resectable primary rectal cancers. In a recent pooled analysis of 3 postoperative adjuvant rectal cancer trials (NCCTG 794751, NCCTG 864751, and GI Intergroup 0114) survival and disease relapse were dependent on both TN and NT stage of disease (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more positive nodes), T substage influenced 5-year OS (T1-2, 69%; T3, 48%; and T4, 38%; P <.001). Ongoing randomized trials are being conducted for patients with high-risk, resectable primary rectal cancers. The intent is to help define optimal combinations of postoperative chemoradiation (US GI Intergroup), to test sequencing issues of preoperative versus postoperative chemoradiation (Germany trial), and to determine if concurrent and maintenance 5-FU and leucovorin add to the benefits found with preoperative irradiation (European Organization for Research and Treatment of Cancer). For subsequent trials, it may be preferable to perform separate studies, or a planned statistical analysis, for different risk groups of patients (low, intermediate, moderately high, and high), as defined in the rectal cancer pooled analysis.


Exergoeconomic and Thermodynamic Analyses of Solar Power Tower Based Novel Combined Helium Brayton Cycle-Transcritical CO2 Cycle for Carbon Free Power Generation.
In the present study, a novel combined power cycle for solar power tower (SPT) system consisting of helium Brayton cycle (HBC) and transcritical CO2 (TCO2) for waste heat recovery is being studied for carbon-free generation. The performance of the proposed SPT based combined cycle (SPT-HBC-TCO2 cycle) is compared with SPT based basic cycle (SPT-HBC) based on exergoeconomic and thermodynamic analyses. It is concluded that the SPT-based combined cycle (SPT-HBC-TCO2 cycle) produces a thermal efficiency of 32.39% and exergy efficiency of 34.68% with an electricity cost of 1.613 UScent kWh-1. The exergy and thermal efficiency of the SPT-based combined cycle are enhanced by 13.18% and 13.21% respectively, while electricity cost is reduced by around 2% as compared to the SPT-based basic cycle (SPT-HBC) configuration at base conditions. A notable finding is that, despite the additional expenditures related to the bottoming cycle, the cost of electricity is lesser for the proposed combined cycle. Additionally, a comparison with the related prior published research exhibits that the performance of the current novel system is superior to that of the systems based on steam rankine cycle and supercritical CO2 cycles.


Applying a contemporary grounded theory methodology.
The aim of this paper is to discuss the application of a contemporary grounded theory methodology to a research project exploring the experiences of students studying for a degree in midwifery. Grounded theory is a qualitative research approach developed by Glaser and Strauss in the 1950s but the methodology for this study was modelled on Clarke's (2005) approach and was underpinned by a symbolic interactionist theoretical perspective, post-structuralist theories of Michel Foucault and a constructionist epistemology. The study participants were 19 midwifery students completing their final placement. Data were collected through individual in-depth interviews and participant observation, and analysed using the grounded theory analysis techniques of coding, constant comparative analysis and theoretical sampling, as well as situational maps. The analysis focused on social action and interaction and the operation of power in the students' environment. The social process in which the students were involved, as well as the actors and discourses that affected the students' competency development, were highlighted. The methodology allowed a thorough exploration of the students' experiences of achieving competency. However, some difficulties were encountered. One of the major issues related to the understanding and application of complex sociological theories that challenged positivist notions of truth and power. Furthermore, the mapping processes were complex. Despite these minor challenges, the authors recommend applying this methodology to other similar research projects.


Preparation and biological evaluation of antibody targeted metal-organic framework drug delivery system (TDDS) in Her2 receptor-positive cells.
In this study, we designed and prepared a trastuzumab-coupled drug delivery system with pH response characteristics using mesoporous zeolitic imidazolate framework-8 (ZIF-8) as the carrier, Trastuzumab@ZIF-8@DOX. As results, the targeted drug delivery system (TDDS) ultimately showed high drug loading and good biocompatibility. The cumulative curve of drug release indicated that the early leakage levels were low under neutral pH conditions. However, under acidic pH conditions, there was an effective enhancement in drug release, indicating the presence of an explicit pH-triggered drug release mechanism. The results indicate that the prepared nanoparticles have the potential to serve as drug delivery systems, as they can release the loaded drug in a controlled manner. The results of cellular uptake tests showed that the uptake of the nanoparticles was greatly enhanced by the internalization mediated by the HER2 antibody. This finding indicates that the prepared nanoparticles can selectively target cancer cells that overexpress HER2. When the doxorubicin dose was 5 μg/ml, the survival rate of SK-BR-3 cells (cancer cells) was 47.75 %, and the survival rate of HaCaT cells (healthy cells) was 75.25 % when co-cultured with both cells. The therapeutic efficacy of Trastuzumab@ZIF-8@DOX was assessed on BALB/c nude mice to validate its potential as an effective drug delivery system for tumor inhibition in vivo. In conclusion, these findings demonstrate the specificity-targeted and pH-responsive nature of this smart drug delivery system, highlighting its promising prospects for efficient and controllable cancer treatment applications.


An outbreak of cutaneous aspergillosis in a tertiary-care hospital.
A cluster of four cases of surgical and burn wound aspergillosis occurred in a 900-bed, adult, tertiary-care hospital. The source was traced to the outside packages of dressing supplies, which had become contaminated during construction in the central Inventory Control area. This resulted in patients with large exposed surface areas being inoculated directly with Aspergillus spores.


The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain--a randomised controlled pilot study.
In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100-mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF-36). In addition, the mechanical-detection thresholds (MDT), vibration-detection thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain-related and control areas. Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001). There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006) and vitality (Δ10.2, p = 0.006). Group differences in PPT were significant at pain-related and control areas (all p < 0.05), but were not significant for MDT or VDT. A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing. The trial was registered at clinicaltrials.gov (NCT01289964).


Social mating system and sex-biased dispersal in mammals and birds: a phylogenetic analysis.
The hypothesis that patterns of sex-biased dispersal are related to social mating system in mammals and birds has gained widespread acceptance over the past 30 years. However, two major complications have obscured the relationship between these two behaviors: 1) dispersal frequency and dispersal distance, which measure different aspects of the dispersal process, have often been confounded, and 2) the relationship between mating system and sex-biased dispersal in these vertebrate groups has not been examined using modern phylogenetic comparative methods. Here, we present a phylogenetic analysis of the relationship between mating system and sex-biased dispersal in mammals and birds. Results indicate that the evolution of female-biased dispersal in mammals may be more likely on monogamous branches of the phylogeny, and that females may disperse farther than males in socially monogamous mammalian species. However, we found no support for a relationship between social mating system and sex-biased dispersal in birds when the effects of phylogeny are taken into consideration. We caution that although there are larger-scale behavioral differences in mating system and sex-biased dispersal between mammals and birds, mating system and sex-biased dispersal are far from perfectly associated within these taxa.


Inclusions on fluid membranes anchored to elastic media.
We model theoretically the effect of localized forces on a fluid membrane anchored to a uniform elastic medium. We use this as a simple model for the plasma membrane of a cell. The atomic force microscope (AFM) has been used to apply such forces, but large membrane perturbations occurring in vivo are also treated within the same framework. Inclusions of this nature may include cell junctions, filipodia, caveolae, and similar membrane invaginations. The breakdown of linear elastic response, as observed by AFM, is predicted to occur for forces as small as 10 pN. We estimate the position of this crossover and the subsequent nonlinear behavior and make encouraging quantitative comparison with experiments. Intrinsic membrane inclusions interact through their overlapping strain fields. For similar, point force-like inclusions at large separations, this yields an attractive potential that scales like the inverse of their separation. For membranes that are intrinsically stiff or under tension, the binding force between inclusions can depend on the properties of the membrane and may be large enough to induce aggregation of inclusions, as observed experimentally. For inclusions that fix the magnitude of the membrane deformation, rather than the applied force, we demonstrate the possibility of metastable states, corresponding to finite separations. Finally, we discuss briefly the case in which inclusions couple to the membrane in more complex ways, such as via a torque (twist). In such cases, the interaction scales like a higher power of the separation, depends on the orientation of the inclusions, and can have either sign.


Determination of stable isotopically substituted histidine in human plasma by gas chromatography-mass spectrometry.
A gas chromatographic-electron-impact mass spectrometric method for the determination of stable isotopically substituted histidine in human plasma has been developed. Histidine was derivatized to alpha N-trifluoroacetyl-imN-carbethoxyhistidine n-butyl ester (TCB derivative) by a three-step reaction: an initial esterification by 3 M n-butanolic hydrochloric acid, followed by trifluoroacetylation with trifluoroacetic anhydride and then ethoxycarbonylation with diethyl pyrocarbonate. Quantitation was carried out by selected-ion monitoring on the molecular ions (m/z 379, 383 and 385) of the respective TCB derivatives of histidine, [1-15N,5,beta,beta-2H3]histidine (histidine-[M + 4]) and [1,3-15N2,5,alpha,beta,beta-2H4]histidine (histidine-[M + 6]). The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for application to a pharmacokinetic study of histidine after administration of a trace amount of stable isotopically substituted histidine (histidine-[M + 4]) in humans.


The dopamine D(3) receptor antagonist YQA14 that inhibits the expression and drug-prime reactivation of morphine-induced conditioned place preference in rats.
Increasing evidence suggests that the mesolimbic dopamine system plays a critical role in opioid addiction. However, there is currently no standard drug treatment for opioid addiction. Growing preclinical evidence indicates that the dopamine D(3) receptor antagonists are the potential anti-addiction pharmacotherapeutic agents based on animal models of multiple drug addiction. In this study, we investigated the inhibitory effects of YQA14, a novel dopamine D(3) receptor antagonist with a high affinity and selectivity for dopamine D(3) receptor, using morphine-induced conditioned place preference (CPP) in rats. The results suggested that YQA14 (6.25-25 mg/kg; intraperitoneal, i.p.) decreased the expression of morphine (10 mg/kg, s.c.)-induced CPP in a dose-related manner but did not influence the acquisition of morphine-induced CPP. At a 25 mg/kg dose of YQA14, it also notably inhibited the reactivation of morphine-priming CPP. These findings suggest that YQA14 is a potential agent for anti-opioid addiction which warrants further study and development.


Evaluation of Locally Isolated Entomopathogenic Fungi against Multiple Life Stages of Bactrocera zonata and Bactrocera dorsalis (Diptera: Tephritidae): Laboratory and Field Study.
Fruit flies including Bactrocera zonata and B. dorsalis (Diptera: Tephritidae) are considered major pests of orchard systems in Pakistan. This study evaluated the laboratory virulence, sub-lethal effects, horizontal transmission, greenhouse, and field-cage efficacy of locally isolated entomopathogenic fungi (EPF) against B. zonata and B. dorsalis. In virulence assays against third instars and adults, all 21 EPF isolates (Beauveria bassiana and Metarhizium anisopliae) tested were pathogenic and caused varying levels of mortality to the fruit flies. Based on the initial screening, four isolates (B. bassiana WG-21 and WG-18 and M. anisopliae WG-07 and WG-02) were selected for further study. The isolate WG-18 was the most virulent against larvae and adults of B. zonata and B. dorsalis followed by WG-21, WG-02, and WG-07. In both species, adults were more susceptible than larvae to all isolates, and pupae were the least susceptible. Isolates WG-18 and WG-21 strongly decreased female fecundity and fertility, the highest adult and larval mortality, and longest developmental time of larvae and pupae. Fungal conidia were disseminated passively from infected to healthy adults and induced significant mortality, particularly from infected males to non-infected females. In greenhouse and field-cage experiments, WG-18 and WG-21 were the most effective isolates in reducing adult emergence when applied to larvae and pupae of both fruit fly species. Our results indicate that B. bassiana isolates WG-18 and WG-21 were the most virulent against multiple life stages of B. zonata and B. dorsalis, and also exerted the strongest sub-lethal effects.


[Myocardial carbohydrate metabolism in limited coronary blood flow].
Dosaged restriction of coronary blood flow (by 30, 50, 70 and 90%) was reproduced for 30 minutes in dogs with a closed chest. In all degrees of coronary blood flow restriction the loss of glycogen, accumulation of lactic acid and cAMP (in reduction of blood flow by 50 and 70%) and activation of glycogenolysis, phosphorylase and phosphofructokinase were recorded in the zone of ischemia. The changes advanced with the deepening of ischemia. Similar, though less pronounced changes were found outside the ischemic zone. Marked metabolic shifts were disclosed in the right ventricle. The mechanisms of anaerobic oxidation activation in ischemia are discussed.