All-cause mortality among people with HIV released from an integrated system of jails and prisons in Connecticut, USA, 2007-14: a retrospective observational cohort study.
People transitioning from prisons or jails have high mortality, but data are scarce for people with HIV and no studies have integrated data from both criminal justice and community settings. We aimed to assess all-cause mortality in people with HIV released from an integrated system of prisons and jails in Connecticut, USA. We linked pharmacy, custodial, death, case management, and HIV surveillance data from Connecticut Departments of Correction and Public Health to create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut between 2007 and 2014. We compared the mortality rate of adults with HIV released from incarceration with the general US and Connecticut populations, and modelled time-to-death from any cause after prison release with Cox proportional hazard models. We identified 1350 people with HIV who were released after 24 h or more of incarceration between 2007 and 2014, of whom 184 (14%) died after index release; median age was 45 years (IQR 39-50) and median follow-up was 5·2 years (IQR 3·0-6·7) after index release. The crude mortality rate for people with HIV released from incarceration was 2868 deaths per 100 000 person-years, and the standardised mortality ratio showed that mortality was higher for this cohort than the general US population (6·97, 95% CI 5·96-7·97) and population of Connecticut (8·47, 7·25-9·69). Primary cause of death was reported for 170 individuals; the most common causes were HIV/AIDS (78 [46%]), drug overdose (26 [15%]), liver disease (17 [10%]), cardiovascular disease (16 [9%]), and accidental injury or suicide (13 [8%]). Black race (adjusted hazard ratio [HR] 0·52, 95% CI 0·34-0·80), having health insurance (0·09, 0·05-0·17), being re-incarcerated at least once for 365 days or longer (0·41, 0·22-0·76), and having a high percentage of re-incarcerations in which antiretroviral therapy was prescribed (0·08, 0·03-0·21) were protective against mortality. Positive predictors of time-to-death were age (≥50 years; adjusted HR 3·65, 95% CI 1·21-11·08), lower CD4 count (200-499 cells per μL, 2·54, 1·50-4·31; <200 cells per μL, 3·44, 1·90-6·20), a high number of comorbidities (1·86, 95% CI 1·23-2·82), virological failure (2·76, 1·94-3·92), and unmonitored viral load (2·13, 1·09-4·18). To reduce mortality after release from incarceration in people with HIV, resources are needed to identify and treat HIV, in addition to medical comorbidities, psychiatric disorders, and substance use disorders, during and following incarceration. Policies that reduce incarceration and support integrated systems of care between prisons and communities could have a substantial effect on the survival of people with HIV. US National Institutes of Health.


Accuracy of non-invasive techniques for diagnosis of coronary artery disease and prediction of cardiac events in patients with left bundle branch block: a meta-analysis.
Non-invasive evaluation of coronary artery disease (CAD) in patients with left bundle branch block (LBBB) has limitations inherent to different tests, and the relative merits of these tests are unclear. This meta-analysis assessed the accuracy of the frequently used non-invasive techniques, including exercise electrocardiography (ECG), myocardial perfusion imaging (MPI) and stress echocardiography (SE), for detection of CAD and prediction of cardiac events in patients with LBBB. A review was conducted of all reports on detection of CAD and prediction of cardiac events in patients with LBBB (published between January 1970 and December 2004), and revealed 55 diagnostic and nine prognostic reports with sufficient details to calculate test accuracy. Weighted (by sample size) sensitivity and specificity were calculated. Summary relative risk ratios (95% confidence intervals) were calculated. Overall sensitivity was higher for exercise ECG and (quantitatively analysed) MPI than for SE (83.4% and 88.5% versus 74.6% respectively, p<0.0001). SE had a higher specificity (88.7%) than MPI (41.2%) and exercise ECG (60.1%) (p<0.0001). Based on analysis of eight reports, the relative risk of cardiac death or myocardial infarction in patients with an abnormal SE and MPI was elevated more than sevenfold, but it did not differ by imaging modality (p=0.9). Meta-analysis of non-invasive CAD assessment in LBBB patients revealed that exercise ECG and MPI had the highest sensitivity, while SE had the highest specificity. The prognostic accuracy of MPI and SE appeared similar.


Haemopexin behaviour in an acute hyperhaemolytic crisis secondary to favism (erythrocyte glucose-6-phosphate dehydrogenase deficiency).
The behaviour of serum haemopexin was studied in patients with hyperhaemolysis after ingestion of fava beans. The linear increase in this substance after a crisis is particularly emphasized. This finding is of special importance for G-6-PD subjects with various haematological disorders.


Effects of platelet-derived growth factor and fibroblast growth factor on free intracellular calcium and mitogenesis.
Although increased free intracellular calcium (Cai) may be one of the main regulators of cell growth and differentiation, studies in cell populations have implied that not all growth factors produce Cai increases. In order to examine in more detail whether Cai increases were related to mitogenesis, we used digital image analysis of intracellular Fura-2 fluorescence to measure Cai in individual BALB/c 3T3 cells stimulated with either platelet-derived growth factor (PDGF) or fibroblast growth factor (FGF). We found that PDGF induced larger and more prolonged Cai increases than FGF did, but that both growth factors induced an initial rapid increase in Cai (less than 2 min) followed by a later sustained increase (greater than 20 min). Only the prolonged Cai increase required extracellular calcium. Following PDGF treatment (1-8 units/ml), the percentage of cells with a large peak Cai increase (greater than twofold) correlated with the percentage of cells made competent (subsequent growth in 1% platelet-poor-plasma). In contrast, purified bovine basic FGF (200-800 pg/ml) and recombinant human acidic FGF (10-300 ng/ml) produced peak Cai increases that were not directly correlated with mitogenesis. In addition, concentrations of intracellular Quin 2 that inhibited Cai transients also inhibited PDGF stimulation but not FGF stimulation of mitogenesis. Thus, Cai increases are necessary for mitogenesis in BALB/c 3T3 cells stimulated by PDGF, but not that stimulated by FGF.


Development of a measure quantifying adverse psychotherapeutic ingredients: the Experiences of Therapy Questionnaire (ETQ).
While psychotherapies are of established value, they may, as active treatments, risk adverse outcomes. As there is no validated measure of potentially negative psychotherapeutic ingredients, we sought to develop such a measure for use in psychotherapy evaluation studies. Based on a review of the literature, a 103-item experiential measure was derived. Psychometric properties and scale score correlates were examined in a sample of more than 700 respondents. Principal component analyses revealed a five-factor solution, explaining 53.4% of the variance; namely 'Negative Therapist', 'Pre-occupying Therapy', 'Beneficial Therapy', 'Idealization of Therapist' and 'Passive Therapist' constructs. Derived factors had high internal consistency, and scale scores were correlated with a number of clinically relevant demographic and treatment characteristics. An independent study established high test-retest reliability for the measure. Assessment of any adverse effects of psychotherapy is of clinical and research significance. We report the development of a measure that should allow the impact of such effects to be quantified in treatment studies, and especially in apportioning the contribution of such non-specific therapeutic effects.


Subclavian artery approach for insertion of intra-aortic balloon.
Subperiosteal clavicular resection for access to the subclavian artery is described. In those patients requiring intra-aortic balloon placement in the nonsurgical setting, such an approach provides a reasonably benign alternative when aortoiliac atherosclerosis prevents the usual retrograde femoral placement. Little morbidity or functional compromise is associated with clavicular wedge resections, and the anatomic availability of a large artery without the need for major surgical maneuvers in these gravely ill patients is a distinct advantage.


Assessment by general practitioners of suitability of thrombolysis in patients with suspected acute myocardial infarction.
To assess the clinical ability of general practitioners to decide to give thrombolytic therapy to patients with suspected myocardial infarction and to assess the contribution of the electrocardiograph (ECG) to this decision-making process. 7 practices on the North side of Glasgow and the coronary care unit of Stobhill General Hospital. 137 patients presenting with chest pain who required direct admission to the coronary care unit. Agreement between the general practitioner's clinical decision to give thrombolytic therapy with or without reference to the ECG and the prescription of thrombolytic therapy in the coronary care unit. The predictive accuracy of the general practitioner's assessment of the necessity for thrombolytic therapy was 71.5%. The ECG had no impact on the accuracy of this decision and there were problems with the recording and interpretation of the ECG. Clinical decision making was altered in six cases by the ECG: wrongly in four. The diagnostic accuracy among general practitioners would result in some patients who did not have acute myocardial infarction being given thrombolytic therapy. In this study the ECG did not contribute towards diagnostic accuracy. Substantial improvement in both the recording and interpretation of ECGs is needed before thrombolytic agents can be routinely prescribed at home.


An avifaunal survey of mesic manmade ecosystems "Oases" in algerian hot-hyperarid lands.
Man made ecosystems of dry lands are key habitats due to their ecological characteristics to survey biodiversity. This study investigated bird diversity in three oases of the Northern Algerian Sahara (i.e., Biskra in 2006, Oued Souf in 2008 and Ouargla in 2009), by using the spot-mapping method. Bird density "D" (pairs/10 ha), species richness "S" (number species), diversity (Shannon index) "H'" (in bits), and evenness "E" varied from one oasis to another (Biskra: D = 98.5, S = 47, H' = 4.49, E = 0.81; Oued Souf: D = 96, S = 33, H' = 3.9, E = 0.77; Ouargla: D = 91.5, S = 44, H' = 4.39, E = 0.80). Differences in bird diversity between the monitored palm groves are due to the ecological characteristics of each environment. Documented literature outlined close taxonomic similarities between bird assemblages of the study area with many Northern Saharan oases. The Hybrid Sparrow Passer domesticus x Passer. hispaniolensis and some Columbidae species including Columba livia, Streptopelia turtur, Streptopelia senegalensis, and Streptopelia decaocto were the abundant species throughout surveyed oases in which they represented more than half (55.6%) of the sum of species densities (D = 286 pairs/10 ha). These synthropic species have known a huge expansion of their distribution range throughout Algerian oases. The correspondence analysis allowed the aggregation of both families and species into oasis they belong to. One-way ANOVA was tested to analyse variations of both family and species densities between studied oases. The ANOVA revealed there was no significant variation either in family densities (p = 0.937) or in bird densities (p = 0.622) between the surveyed oases because of the small size of bird populations.


Impact of environmental discourses on public health policy arrangements: a comparative study in the UK and Flanders, (Belgium).
Theoretically inspired by discursive institutionalism and multi-level governance, this paper assesses the extent to which 'environmental health' has emerged as a new discourse at European level, the effects it has had on national public health governance in two European countries, and what mechanisms have triggered or hindered these effects. Comparison of the dynamics in public health policy arrangements in Flanders (Belgium) and the UK, nations influenced by both international and European environmental health discourses. The Policy Arrangement Approach was the analytical framework used to structure the results of this textual analysis. Despite their shared focus on environmental health, Belgium and the UK display quite different approaches to environmental health governance. While Belgium works on environmental health in a predominantly top-down approach, the UK has developed a more inward-facing approach to environmental health policies. The cases of the UK and Belgium show that, although these countries respond similarly to internationally agreed charters and both are members of the European Union, national differences in environmental health policies persist, mainly due to pre-existing national policy arrangements and the activities of national institutions. This leads to a divergent interplay between national and international institutions.


NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.
Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood-brain barrier, conventional CD11b(+)CD27(+) NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation.


Right-sided diaphragmatic hernia in infants after liver transplantation.
Liver transplantation is just as successful in infants as in older children, but more challenging. This relates to the low weight of the recipients and to their rapidly deteriorating clinical condition (malnutrition and end-stage liver disease) ( J Pediatr 1990;117:205-210; BMJ 1993;307:825-828; Ann Surg 1996;223:658-664; Transplantation 1997;64:242-248; J Pediatr Surg 1998;33:20-23). In addition, higher rates of diaphragmatic complications have been shown to significantly correlate with a younger age ( Transplantation 2002;73:228-232; Transpl Int 1998;11:281-283; Pediatr Transplant 2000;4:39-44), but diaphragmatic hernia has never been reported as a complication of liver transplantation. In this report, 2 patients who developed diaphragmatic hernia after liver transplantation are presented. The possible role of several contributing factors resulting in diaphragmatic hernia is discussed. These factors include (1) diaphragm thinness related to low weight and malnutrition, (2) direct trauma at operation (dissection and diathermy), (3) increased abdominal pressure after transplantation caused by the use of a slightly oversized liver graft, and (4) the medial positioning of the partial liver graft in the abdomen.


Objective evaluation of laparoscopic surgical skills in wet lab training based on motion analysis and machine learning.
Our aim was to build a skill assessment system, providing objective feedback to trainees based on the motion metrics of laparoscopic surgical instruments. Participants performed tissue dissection around the aorta (tissue dissection task) and renal parenchymal closure (parenchymal-suturing task), using swine organs in a box trainer under a motion capture (Mocap) system. Two experts assessed the recorded movies, according to the formula of global operative assessment of laparoscopic skills (GOALS: score range, 5-25), and the mean scores were utilized as objective variables in the regression analyses. The correlations between mean GOALS scores and Mocap metrics were evaluated, and potential Mocap metrics with a Spearman's rank correlation coefficient value exceeding 0.4 were selected for each GOALS item estimation. Four regression algorithms, support vector regression (SVR), principal component analysis (PCA)-SVR, ridge regression, and partial least squares regression, were utilized for automatic GOALS estimation. Model validation was conducted by nested and repeated k-fold cross validation, and the mean absolute error (MAE) was calculated to evaluate the accuracy of each regression model. Forty-five urologic, 9 gastroenterological, and 3 gynecologic surgeons, 4 junior residents, and 9 medical students participated in the training. In both tasks, a positive correlation was observed between the speed-related parameters (e.g., velocity, velocity range, acceleration, jerk) and mean GOALS scores, with a negative correlation between the efficiency-related parameters (e.g., task time, path length, number of opening/closing operations) and mean GOALS scores. Among the 4 algorithms, SVR showed the highest accuracy in the tissue dissection task ([Formula: see text]), and PCA-SVR in the parenchymal-suturing task ([Formula: see text]), based on 100 iterations of the validation process of automatic GOALS estimation. We developed a machine learning-based GOALS scoring system in wet lab training, with an error of approximately 1-2 points for the total score, and motion metrics that were explainable to trainees. Our future challenges are the further improvement of onsite GOALS feedback, exploring the educational benefit of our model and building an efficient training program.


Relationship between absolute mean cerebral transit time and absolute mean flow velocity on transcranial Doppler ultrasound after ischemic stroke.
Previous studies of transcranial Doppler (TCD) sonography in acute stroke have used the relative difference between the symptomatic and asymptomatic arteries to assess arterial occlusion. However, a simple measure of absolute mean flow velocity might provide a direct assessment of "perfusion reserve" in acute ischemic stroke. In a prospective study, 62 patients with ischemic stroke had TCD and a mean cerebral transit time examination within 48 hours of stroke. Absolute intracranial arterial mean flow velocities were correlated with the corresponding absolute mean transit times. The authors found a significant correlation between middle cerebral artery (MCA) mean flow velocity and transit time in the symptomatic (Spearman rank correlation coefficient [rho] = -0.65, P < .01) but not in the asymptomatic (rho = -0.04, P = ns) MCA territory. Equations relating absolute mean flow velocity to absolute transit time were derived. The findings suggest that in the normal hemisphere (with intact autoregulation on the horizontal portion of the autoregulation curve), flow velocity and transit time are not closely related to each other, but in the symptomatic hemisphere (on the downward slope of the autoregulation curve), flow velocity is directly proportional to the transit time and, therefore, to its inverse, perfusion reserve. The use of absolute mean flow velocity values on TCD should be further explored as a simple way of assessing "perfusion" in acute ischemic stroke.


Modeling the impact of genetically modified male mosquitoes in the spatial population dynamics of Aedes aegypti.
The mosquito Aedes aegypti is the primary vector of diseases such as dengue, Zika, chikungunya, and yellow fever. Improving control techniques requires a better understanding of the mosquito's life cycle, including spatial population dynamics in endemic regions. One of the most promising techniques consists of introducing genetically modified male mosquitoes. Several models proposed to describe this technique present mathematical issues or rely on numerous parameters, making their application challenging to real-world situations. We propose a model describing the spatial population dynamics of the Aedes aegypti in the presence of genetically modified males. This model presents some mathematical improvements compared to the literature allowing deeper mathematical analysis. Moreover, this model relies on few parameters, which we show how to obtain or estimate from the literature. Through numerical simulations, we investigate the impacts of environmental heterogeneity, the periodicity of genetically modified male releases, and released genetically modified males quantity on the population dynamics of Aedes aegypti. The main results point to that the successful application of this vector control technique relies on releasing more than a critical amount of modified males with a frequency exceeding a specific critical value.


Development of professional identity during early training in oral and maxillofacial surgery: a qualitative study.
Development of professional identity is becoming increasingly important in medical education, and has been found to be beneficial in a surgeon's training. However, despite the complex, demanding nature of early training in oral and maxillofacial surgery (OMFS), we know of little research on how it develops during this time. We therefore used qualitative research methodology based on a grounded theory approach to investigate how trainees gain a sense of identity as they progress through their 2 undergraduate degrees. Data from in-depth, semi-structured interviews with OMFS specialist trainees were transcribed and coded to allow for thematic analysis and subsequent theory construction. We propose a model of how professional identity develops in early OMFS training. Of note, professional experience gained during the second degree was found to be of great importance in the development of a strong professional identity. We look at reasons for this in terms of "cognitive space" and use the concept to discuss potential improvements to the training pathway.


CD14 positive cells accelerate hematopoietic stem cell engraftment.
The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34+ and lentivirus-transfected CD34+ cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14+CD16- classical subset, in co-culture systems increase survival and stemness of CB-CD34+ cells. Both soluble factors and direct-cell contact interactions, such as JAG/NOTCH and COX-2/PGE2 pathways, are critically involved in the HSC-monocyte crosstalk. Our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.


Long-term results of percutaneous treatment of hydatid liver cysts: a single center 17 years experience.
Liver cystic echinococcosis is considered a relatively benign disease, nevertheless, treatment is mandatory in symptomatic cysts and recommended in active cysts because of the risk of severe complications. Surgery is still considered the gold standard treatment. In the last two decades percutaneous injection of scolicidal agents has been developed with excellent results in terms of disappearance of the cyst, very low side effects and low mortality rate. One hundred sixty eight patients with 225 liver cysts were studied. A total of 108 patients with 151 viable hydatid liver cysts underwent Double Percutaneous Aspiration and Injection of alcohol of the cyst without re-aspiration of the ethanol, which remained in situ. The mortality rate was 0.9% (1 patient), the overall morbidity was 8.6% with only 2.5% of major side effects. The mean hospital stay was very short (2.9 days). Follow-up ranged from 14 to 204 months (median 48 months). Ultrasonography showed complete disappearance of the cyst with reconstitution of liver parenchyma in 109 out of 225 (48.4%) cysts; in the remaining cysts a solid or a liquid findings were observed in 104 (46.2%) and 12 (5.3%), respectively, with a decreased volume of 50-80%. These data show that Double Percutaneous Aspiration and Injection of alcohol for hydatid liver cysts can achieve comparable results to open surgery. The low incidence of side effects shows that this technique is safe and cost effective, compared to radical or conservative surgery.


Shifting roles: physiotherapists' perception of person-centered care during a pre-implementation phase in the acute hospital setting - A phenomenographic study.
Person-centered care (PCC) is an acknowledged health care practice involving increased patient influence regarding decisions and deliberation. Research indicates that physiotherapists (PTs) embrace patient participation, but that PCC is difficult to grasp and fully implement. To contribute to knowledge about how PCC influences physiotherapy by eliciting PTs' experiences from the acute care setting, this study aims to describe and illuminate variations in perceptions of PCC during a pre-implementation phase, among PTs in acute hospital care. Phenomenological approach: individual interviews with PTs in acute care (n = 7) combined with focus group interviews (n = 3). The analysis yielded two main categories: 1) Physiotherapists perceived a transformed patient role involved in the transition from patient to person; and 2) Physiotherapists perceived a challenged professional role when departing from the expert role, and entailed restrictions to prescribing the best treatment and, instead, meant aiming for a collaborative and equal relationship with the patient. Although the interviewed PTs embraced PCC in principle, PCC does seem to challenge the professional roles of patient and PT. The findings indicate that theories of power relations need to be considered, and further reflection may facilitate implementation. More research is needed to deepen the knowledge of how PTs perceive PCC during all implementation phases.


Acute-onset surgically induced necrotizing scleritis after strabismus surgery.
Surgically induced necrotizing scleritis (SINS) is an uncommon but devastating complication that may occur days to years after ocular surgery. We report the case of a 32-year-old man who underwent uncomplicated strabismus surgery for large-angle exotropia and developed SINS characterized by painless scleral inflammation, choroidal exposure, and globe ectasia within days of surgery. Work-up revealed no associated infectious process or underlying systemic inflammatory condition. Clinical resolution occurred with oral immunosuppression alone, without need for graft.


Design and Implementation of Multi-protein Expression Constructs and Combinatorial Libraries using Start-Stop Assembly.
Start-Stop Assembly is a multi-part, modular, Golden Gate-based DNA assembly system with two key features which distinguish it from previous DNA assembly methods. Firstly, coding sequences are assembled with upstream and downstream sequences via overhangs corresponding to start and stop codons, avoiding unwanted 'scars' in assembled constructs at coding sequence boundaries. Scars at these crucial, sensitive locations can affect mRNA structure, activity of the ribosome binding site, and potentially other functional RNA features. Start-Stop Assembly is therefore both functionally scarless (an advantage usually only achieved using bespoke, overlap-based assembly methods) and suitable for efficient, unbiased and combinatorial assembly (a general advantage of Golden Gate-based methods). Secondly, Start-Stop Assembly has a new, streamlined assembly hierarchy, meaning that typically only one new vector is required in order to assemble constructs for any new destination context, such as a new organism or genomic location. This should facilitate more rapid and convenient development of engineered metabolic pathways for diverse nonmodel organisms in order to exploit their applied potential. This chapter explains both design considerations and practical procedures to implement multi-part, hierarchical assembly of multi-protein expression constructs, either individually or as combinatorial libraries, using Start-Stop Assembly.


Dysregulated expression of dicer and drosha in breast cancer.
Large-scale profiling approaches have revealed global down-regulation of microRNAs (miRNAs) in several human cancer types including breast cancer. Altered expression of Dicer and Drosha, two key enzymes in the miRNA maturation, is believed to be one of the most important mechanisms. By using quantitative real-time RT-PCR (QT-PCR), we examined the expression of Dicer and Drosha in 49 pairs of matched human breast cancer tissues. Decreased expression was observed in 53.1% (Dicer), 51.9% (Drosha) and 75.5% (Dicer plus Drosha) breast cancer tissues. In conclusion, the decreased expression of Dicer and Drosha may play a role in down-regulation of miRNAs in breast cancer.


Oxidized tea polyphenols prevent lipid accumulation in liver and visceral white adipose tissue in rats.
Tea polyphenols are the prominent component in tea. After the fermentation process, tea polyphenols are oxidized by polyphenol oxidase to form oxidized tea polyphenols (OTPs). OTPs contain a significant amount of hydrophobic phenyl groups that can bind with non-aqueous materials. Here, we determined whether OTPs can bind with lipids and reduce fat uptake and assessed the effect of OTPs on decreasing obesity and alleviating hyperlipidaemia and other metabolic syndromes. Rats were divided into three groups: control, high-fat diet (HFD) and OTP groups. The control and HFD groups were fed a chow diet and a high-fat diet, respectively, for 12 weeks; the OTP group was fed a high-fat diet for 6 weeks and then a high-fat diet containing 2 % OTP for 6 weeks. The serum and excrement triglyceride (TAG) and total cholesterol (CHOL) concentrations were determined, and liver tissue and white adipose tissue were collected to detect the expression levels of genes involved in lipid metabolism. Our results revealed that OTPs failed to decrease the serum concentrations of TAG and CHOL. OTPs alleviated the accumulation of lipids in the liver tissue and changed the expression levels of the regulators of lipid metabolism, i.e., peroxisome proliferation-activated receptors (ppars), compared with the rats fed a high-fat diet alone. We also observed a significantly decreased reduction of weight in the visceral white adipose, enhanced regulation of fatty acid β-oxidation by PPARα and enhanced biosynthesis of mitochondria in the visceral white adipose of the OTP rats compared with the HFD rats. Additionally, OTPs promoted the excretion of lipids. Our results suggest that OTPs alleviate the accumulation of lipids in liver and visceral white adipose tissue and promote lipid excretion in rats in vivo.


Human group behavior: the ideal free distribution in a three-patch situation.
A group of 15 college students was exposed to repeated trials of a task in which money was available for choosing among three colors (blue, red, and green). The amount of winning tokens for each color was varied across phases to test whether group distribution would track the ratio of winning tokens between patches. Confirming previous reports on ideal free performance in humans, group choice proved sensitive to the available resources but tended to undermatch the ratio of winning tokens. The difference-equalization rule of Sokolowski, Tonneau, and Freixa i Baqué [Psychonom. Bull. Rev. 6 (1999) 157] gave a satisfactory fit to the data.


Practical Challenges-Use of Paracetamol in Children and Youth Who are Overweight or Obese: A Narrative Review.
Worldwide, > 380 million children and adolescents are overweight or obese, including 41 million children aged < 5 years. Obesity can change the pharmacokinetic properties of drugs by altering their distribution, metabolism, and elimination. Thus, children who are overweight or obese are at increased risk for receiving inappropriate doses of commonly used drugs, which can result in treatment failure, adverse events, and/or drug toxicity. This review analyzes available data on paracetamol dosing for pain and fever in children and adolescents who are overweight or obese to identify gaps and challenges in optimal dosing strategies. Literature searches using Medline, Embase, and ClinicalTrials.gov were conducted to identify English-language articles reporting paracetamol pharmacokinetics, dosing practices, and guidelines in children and adolescents who are overweight or obese. Of 24 relevant studies identified, 20 were specific to overweight/obese individuals and 15 were specific to children and/or adolescents. Data on paracetamol pharmacokinetics in children and adolescents who are overweight or obese are lacking, and there is no high-quality evidence to guide paracetamol prescribing practices in these patients. Adult data have been extrapolated to pediatric populations; however, extrapolation does not address differences in paracetamol metabolism in adults versus children; the efficacy and safety effects of such differences are unknown. Given the growing worldwide prevalence of obesity in children and adolescents and the likelihood that paracetamol use in this population will increase accordingly, obesity-specific pediatric dosing guidelines for paracetamol are urgently needed. High-quality research is necessary to inform such guidelines.


Insulin-like growth factor 1 gene polymorphism in women with breast cancer.
Breast cancer is a disease of unknown etiology; however, the major risk factors are genetic alterations. Studies have demonstrated an association between insulin-like growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two polymorphic variants of the IGF-1 gene are highlighted in association with breast cancer, rs6220 and rs7136446, although controversy exists as to this relationship. The current study included 137 women (68 breast cancer cases and 69 controls without breast cancer) who had 3 ml of peripheral blood drawn for the study of genomic DNA extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction. The CC genotype (rs7136446) was present in 4 women (5.9%) from the case group and in 2 (3.0%) women from the control group (p = 0.67), while the GG genotype (rs6220) occurred in 8 (11.5%) women from the case group and in 5 (7.2%) women from the control group (p = 0.75). No statistically significant difference was observed between the CC genotype of variant rs7136446 in premenopausal case and control women (p = 0.31), thus as there was also no significant difference between case and control postmenopausal women (p = 1.00). Concerning the GG genotype of rs6220, it occurred in 6 (14.2%) premenopausal case and 4 (8%) control women (p = 0.71) and no difference was found in postmenopausal women (p = 1.00). In the current study, IGF-1 gene polymorphism of SNP variants rs6220 and rs7136446 had no statistically significant association with breast cancer, both in premenopausal and postmenopausal women.


Ginsenoside Rb1 protected PC12 cells from Aβ25-35-induced cytotoxicity via PPARγ activation and cholesterol reduction.
Accumulating evidences suggest that amyloid β (Aβ)-peptide plays a key role in pathogenesis of Alzheimer's disease (AD) through aggregation and deposition into plaques in neuronal cells. Membrane components such as cholesterol and gangliosides not only enhance the production of amyloidogenic Aβ fragments, but also appear to strengthen Aβ-membrane interaction. Ginsenoside Rb1 (GRb1) is a major active component of Panax, which is widely used to improve learning and memory. In the present study, whether ginsenoside Rb1 could protect pheochromocytoma cells (PC12 cells) from Aβ25-35-induced cytotoxicity including inhibiting cell growth, inducing apoptosis, producing reactive oxygen species (ROS), destroying the cytoskeleton and bringing about membrane toxicity was investigated. Our results indicated that ginsenoside Rb1 could serve as an agonist of peroxisom proliferator-activated receptor-γ (PPARγ) and reduce the level of cholesterol in AD model cells. Reduction of the Aβ25-35-induced cytotoxicity by lowering cholesterol was evidenced by reduction of ROS production, lipid peroxidation, and protection of cytoskeleton and membrane surface rigidity. Most importantly, the viability of PC12 cells increased from 50.42 ± 5.51% for the AD group to 102.72 ± 4.34% for the 50 μM ginsenoside Rb1 group with cholesterol reduction. Our results suggested that ginsenoside Rb1 might function as an effective candidate to promote reverse cholesterol transport and lower ROS production, therefore providing a new insight into prevention and treatment of AD.


Harnessing regulatory T cells for therapeutic purposes.
Lai and colleagues demonstrate that pretreatment with N,N-dimethylsphingosine (DMS), a naturally occurring sphingosine derivative, provides renoprotection in ischemia/reperfusion injury. This DMS-induced renoprotection was abolished by the administration of agents that suppress regulatory T cells (Tregs) or by anti-CTLA-4 or anti-CD45 monoclonal antibodies, suggesting that Tregs played a critical role. The finding that Tregs are recruited to the kidney via DMS points to the exciting potential of new approaches to harnessing Tregs for therapeutic purposes.


Neuroendocrinology: Electromagnetogenetic Control over Feeding and Glucose Metabolism.
Cutting-edge experiments show a new means to control the activity of specifically genetically targeted neurons in the hypothalamus using electromagnetic force. At the flip of a switch, the system bidirectionally regulates feeding behavior and glucose homeostasis, demonstrating wireless control over deep brain regions and their strong influence over energy balance.


Clinical utility of new quinolones in treatment of osteomyelitis and lower respiratory tract infections.
In the eight major clinical studies published on use of oral quinolones in therapy of contiguous osteomyelitis, clinical and microbiologic cure/improvement rates were 75% and 73%, respectively, when drug therapy was combined with appropriate surgical debridement. This included many cases of polymicrobial osteomyelitis, as well as infection caused by recalcitrant pathogens such as Pseudomonas aeruginosa. In contrast, the response of staphylococcal osteomyelitis to oral quinolones, especially in cases caused by methicillin-resistant strains, appeared suboptimal. Quinolones appear to have a limited role in the treatment of community-acquired pneumonia, since other established antibiotic regimens have been proven effective in such situations. Quinolones may play an important role in the treatment of nosocomially acquired aerobic gram-negative bacillary pneumonia, either as primary parenteral therapy or as transitional oral therapy when affected patients become outpatients. In cystic fibrosis-associated acute exacerbations of chronic pseudomonal pneumonitis, the outcome of oral ciprofloxacin therapy was very satisfactory in the six major studies reported (approximately 85% improvement rates). In three comparative studies oral quinolone treatment of such pulmonary exacerbations resulted in clinical response rates equivalent to those for aminoglycoside plus beta-lactam therapy given intravenously. Quinolone-resistant Pseudomonas aeruginosa strains were commonly isolated from sputum during treatment; however, such patients continued to respond clinically to quinolone treatment, and sputum became rapidly repopulated with quinolone-susceptible Pseudomonas aeruginosa strains after discontinuation of therapy.


Repression of eEF2 kinase improves deficits in novel object recognition memory in aged mice.
The normal aging process is commonly associated with mild cognitive deficits including memory decline. Previous studies indicate a role of dysregulated messenger ribonucleic acid translation capacity in cognitive defects associated with aging and aging-related diseases, including hyperphosphorylation of eukaryotic elongation factor 2 (eEF2). Phosphorylation of eEF2 by the kinase eEF2K inhibits its activity, hindering general protein synthesis. Here, we sought to determine whether cognitive deficits in aged mice can be improved by genetically deleting eEF2K (eEF2K KO) and consequently reduction of eEF2 phosphorylation. We found that suppression of eEF2K prevented aging-related deficits in novel object recognition memory. Interestingly, deletion of eEF2K did not alter overall protein synthesis in the hippocampus. Ultrastructural analysis revealed increase size and larger active zone lengths of postsynaptic densities in the hippocampus of aged eEF2K KO mice. Biochemical assays showed hippocampal eIF2α hyperphosphorylation in aged eEF2K KO mice, indicating inhibition of translation initiation. Our findings may provide insight into mechanistic understanding and thus development of novel therapeutic strategies for aging-related cognitive decline.


Anthropogenic impact on the reproductive health of two wild Patagonian fish species with differing reproductive strategies.
A particularly concerning outcome of environmental pollution is the disturbance of reproductive processes. However, studies on the impacts of pollution on the reproductive health of fish inhabiting South American environments are limited. We studied the impact of anthropogenic pollution on the reproductive health of two sympatric Patagonian marine fish species with different reproductive strategies: the live-bearing rockfish Sebastes oculatus and the egg-laying Brazilian sandperch Pinguipes brasilianus. Our findings reveal that both species presented some degree of reproductive disturbance when inhabiting an affected site, but the specific alterations differed depending on the species, sex, and season. During the reproductive season, 17β-estradiol levels were elevated in females of both species living in polluted areas, while no differences in androgen levels were observed in either species or season. The gonadosomatic index (GSI) was affected in both sexes of S. oculatus during the non-reproductive season, while the gonadal stages were mainly affected in both sexes of P. brasilianus. No signs of intersex condition were observed. Our results highlight the importance of including diverse reproductive parameters to better understand anthropogenic effects on wild animals. Long-term studies including other fish species and including offspring (to evaluate possible transgenerational effects) will be necessary to determine the consequences of the documented reproductive alterations, particularly whether fish species inhabiting Patagonian marine reef areas will be able to reproductively adapt to increasing marine anthropogenic disturbances.


Impact of computerized pre-authorization of broad spectrum antibiotics in Pseudomonas aeruginosa at a children's hospital in Japan.
The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post-intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa.


Influence of radiation damage on the structure and chemical durability of titanites.
Previous studies on chemical durability of radioactive waste forms mainly focused on samples containing no radionuclides. We performed a hydrothermal experiment with several variably self-irradiated natural titanites and the leaching results indicate that radiation damage has some influence over chemical durability through its ability to change the microstructures of materials, including cracks, holes, interconnected amorphous clusters, and nano-sized defects. However, chemical durability is not influenced if the variation in local microstructures induced by radiation damage is insignificant.


Blumgart anastomosis with polyglycolic acid felt reduces the incidence of pancreatic fistula after pancreaticoduodenectomy: A propensity score analysis.
Polyglycolic acid (PGA) felt has been used to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). However, there has been no related research on Blumgart anastomosis. Therefore, this study aimed to investigate the practical significance of Blumgart anastomosis with our new method involving PGA felt to prevent CR-POPF following PD. Data from 133 consecutive patients who underwent Blumgart anastomosis during PD between June 2015 and November 2021 were reviewed. We applied PGA felt to 35 of these patients starting from July 2020. Surgical outcomes were analyzed by propensity score matching. Thirty-five (35.7%) of the 98 patients in the without-PGA group were matched with an equal number from the with-PGA group after adjusting for covariates. CR-POPF was found in 17 patients (49%) in the without-PGA group and two patients (6%) in the with-PGA group (P < .001). The multivariate analysis results indicated that male sex, pancreatic duct size <3 mm, soft pancreatic texture, and nonuse of PGA were independently associated with CR-POPF after PD. In conclusion, Blumgart anastomosis with our new penetrating method for PGA felt reduces the incidence of CR-POPF after PD.


Breast cancers as ecosystems: a metabolic perspective.
Breast cancer (BC) is the most frequently diagnosed cancer and one of the major causes of cancer death. Despite enormous progress in its management, both from the therapeutic and early diagnosis viewpoints, still around 700,000 patients succumb to the disease each year, worldwide. Late recurrency is the major problem in BC, with many patients developing distant metastases several years after the successful eradication of the primary tumor. This is linked to the phenomenon of metastatic dormancy, a still mysterious trait of the natural history of BC, and of several other types of cancer, by which metastatic cells remain dormant for long periods of time before becoming reactivated to initiate the clinical metastatic disease. In recent years, it has become clear that cancers are best understood if studied as ecosystems in which the impact of non-cancer-cell-autonomous events-dependent on complex interaction between the cancer and its environment, both local and systemic-plays a paramount role, probably as significant as the cell-autonomous alterations occurring in the cancer cell. In adopting this perspective, a metabolic vision of the cancer ecosystem is bound to improve our understanding of the natural history of cancer, across space and time. In BC, many metabolic pathways are coopted into the cancer ecosystem, to serve the anabolic and energy demands of the cancer. Their study is shedding new light on the most critical aspect of BC management, of metastatic dissemination, and that of the related phenomenon of dormancy and fostering the application of the knowledge to the development of metabolic therapies.


Ultraviolet enhanced reactivation of a human virus: effect of delayed infection.
The ability of UV-irradiated herpes simplex virus to form plaques was examined in monolayers of CV-1 monkey kidney cells preexposed to UV radiation at different intervals before virus assay. From analysis of UV reactivation (Weigle reactivation) curves it was found that as the interval between cell UV irradiation (0-20 J/m2) and initiation of the virus assay was increased over a period of five days, (1) the capacity of the cells to support unirradiated virus plaque formation, which was decreased immediately following UV exposure to the monolayers, increased and returned to approximately normal levels within five days, and (2) at five days an exponential increase was observed in the relative plaque formation of irradiated virus as a function of UV fluence to the monolayers. For high UV fluence (20 J/m2) to the cells, the relative plaque formation by the UV-irradiated virus at five days was about 10-fold higher than that obtained from assay on unirradiated cells. This enhancement in plaque formation is interpreted as a delayed expression of Weigle reactivation. The amount of enhancement resulting from this delayed reactivation was several fold greater than that produced by the Weigle reactivation which occurred when irradiated herpes virus was assayed immediately following cell irradiation.


Hepatic tumor ablation with clustered microwave antennae: the US Phase II trial.
Thermal ablation techniques have become important treatment options for patients with unresectable hepatic malignancies. Microwave ablation (MWA) is a new thermal ablative technique that uses electromagnetic energy to produce coagulation necrosis. We report outcomes from the first clinical trial in the United States using MWA and a 915 MHz generator. Patients with unresectable primary or metastatic liver cancer were enrolled in a multi-institutional trial from March 2004 through May 2006. Demographic information, diagnosis, treatment, and outcomes were documented. Eighty-seven patients underwent 94 ablation procedures for 224 hepatic tumors. Forty-two ablations (45%) were performed open, 7 (7%) laparoscopically, and 45 (48%) percutaneously. The average tumor size was 3.6 cm (range 0.5-9.0 cm). Single antenna ablation volumes were 10.0 ml (range 7.8-14.0 ml), and clustered antennae ablation volumes were 50.5 ml (range 21.1-146.5 ml). Outcome variables were measured with a mean follow-up of 19 months. Local recurrence at the ablation site occurred in 6 (2.7%) tumors, and regional recurrence occurred in 37 (43%) patients. With a mean follow-up of 19 months, 41 (47%) patients were alive with no evidence of disease. There were no procedure-related deaths. The overall mortality rate was 2.3%. Microwave ablation is a safe and effective technology for hepatic tumor ablation. In our study, clustered antennae resulted in larger ablation volumes. Further studies with histological confirmation are needed to verify clinical results.


Transition of phenolics and cyanogenic glycosides from apricot and cherry fruit kernels into liqueur.
Popular liqueurs made from apricot/cherry pits were evaluated in terms of their phenolic composition and occurrence of cyanogenic glycosides (CGG). Analyses consisted of detailed phenolic and cyanogenic profiles of cherry and apricot seeds as well as beverages prepared from crushed kernels. Phenolic groups and cyanogenic glycosides were analyzed with the aid of high-performance liquid chromatography (HPLC) and mass spectrophotometry (MS). Lower levels of cyanogenic glycosides and phenolics have been quantified in liqueurs compared to fruit kernels. During fruit pits steeping in the alcohol, the phenolics/cyanogenic glycosides ratio increased and at the end of beverage manufacturing process higher levels of total analyzed phenolics were detected compared to cyanogenic glycosides (apricot liqueur: 38.79 μg CGG per ml and 50.57 μg phenolics per ml; cherry liqueur 16.08 μg CGG per ml and 27.73 μg phenolics per ml). Although higher levels of phenolics are characteristic for liqueurs made from apricot and cherry pits these beverages nevertheless contain considerable amounts of cyanogenic glycosides.


An innovative strategy for direct electrochemical detection of microRNA biomarkers.
We report an electrochemical method for direct, reagentless, and label-free detection of microRNA, based on a conjugated copolymer, poly(5-hydroxy-1,4-naphthoquinone-co-5-hydroxy-2-carboxyethyl-1,4-naphthoquinone), acting as hybridization transducer. Hybridization between the oligonucleotide capture probe and a microRNA target of 22 base pairs generates an increase in the redox current ("signal-on"), which is evidenced by square wave voltammetry. Selectivity is good, with little hybridization for non-complementary targets, and the limit of detection reaches 650 fM. It is also evidenced that this sensitivity benefits from the high affinity of DNA for RNA.


A digital approach to fabricating an abutment replica to control cement volume in a cement-retained implant prosthesis.
If a cement-retained implant prosthesis is placed on an abutment, excess cement should be minimized or removed to prevent periimplant inflammation. Various methods for fabricating an abutment replica have been introduced to maintain tissue health and reduce clean-up time. The purpose of this article is to present an alternative technique for fabricating an abutment replica with computer-aided design/computer-aided manufacturing (CAD/CAM) technology.


Computer analysis of vestibular responses to putative neurotransmitters.
An inexpensive microcomputer (Commodore 64K) based system was developed for the analysis of neural spike trains. The trains were recorded from single ampullary units in response to mechanical stimulation of the isolated semicircular canal of the bullfrog (Rana catesbeiana). A BASIC program provided a number of options while machine language subroutines generated interstimulus interval (ISI) and peristimulus time (PST) histograms. Up to thirty 5-s spike trains could be combined for analysis (0.1 ms resolution ISI, 100 ms bin width PST). Histograms and summary statistics were saved on floppy disks. The cost of adding this computer system to an existing neurophysiology laboratory is less than US $600 (printed, tape, and disk versions of these programs are available). The system was used to measure vestibular responses to putative vestibular neurotransmitters such as carbachol (an acetylcholine mimic) (Rossi et al., 1980) and gamma-aminobutyric acid (GABA) (Flock and Lam, 1974).


Precision medicine: Ray of hope in overcoming cancer multidrug resistance.
Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.


Reaction of guanosine with glucose under oxidative conditions.
Incubation of glucose with guanosine under oxidative conditions at 37 degrees C or 70 degrees C leads to the formation of a main product, which can be detected by HPLC/DAD. The compound was isolated and identified as N2-carboxymethyl-guanosine (CMG). To confirm the structure, CMG was also synthesized from glyoxal and guanosine.


Relation of client variables to continuance in five types of alcohol treatment settings.
Multiple regression analyses were used to assess the relationship of 29 client variables to continuance in five types of alcohol treatment settings (outpatient, inpatient, social detoxification, halfway houses with highly structured treatment regimens, and halfway houses with minimal structured treatment; N = 3,240). Socioeconomic variables were most often related to continuance; however, the pattern of the relationship between predictor variables and continuance varied greatly from setting to setting. The strongest multiple regression coefficients were found for outpatient and inpatient settings and the weakest were found for the two types of halfway house settings. It was concluded that archive-derived variables had significant, but limited, power to predict continuance and that other approaches to investigating continuance are needed.


The polypeptide structure and assembly of Ly-2/3 heterodimers.
Mild reduction of mature, thymic Ly-2/3 heterodimers of Mr 67 000 resulted in dissociation into three individual polypeptide chains, alpha, alpha', and beta, of respective Mr values 38 000, 35 000, and 30 000. The alpha and alpha' chains were both immunoprecipitated by a monoclonal antibody directed to the Ly-2.1 epitope whereas the Ly-3.1 antibody bound only the beta chain. The possibility that the alpha and beta chains of each heterodimer established their interchain links within a labile precursor protein in which alpha and beta segments were fused was considered but discounted by the finding that in mice heterozygous for both Ly-2 and Ly-3 loci, the Ly-2 product of one chromosome was not exclusively joined to Ly-3 structures coded by the same chromosome. By utilizing ionic detergents which selectively alter the charge of intrinsic membrane proteins, both Ly-2 and Ly-3 polypeptides were shown to have membrane insertion sites. It is suggested that as a consequence of their likely synthesis on membrane-bound polysomes, newly synthesized Ly-2 and Ly-3 structures accumulate within the same subcellular compartment - the membranes of the rough endoplasmic reticulum. Their elevated concentration within this space may facilitate a low affinity binding interaction between Ly-2 and Ly-3 which is later stabilized by interchain disulfide bond formation.


Symposium on infections in the compromised host. The competent internal immune system.
As has been shown, each part of the body's immune system is an effectively functioning entity. Since the whole is so much greater than the sum of its parts, a deficit in any one system can seriously affect the function of the others leaving the host without protection against the multiplicity of external and internal challenges. Without appropriate intervention or preventive measures, serious infection and even death can result.


A personalised diet approach study: Interaction between PPAR-γ Pro12Ala and dietary insulin indices on metabolic markers in diabetic patients.
The present study aimed to investigate the effect of the interaction between peroxisome proliferator-activated receptor gamma (PPAR-γ) Pro12Ala polymorphisms and dietary insulin load and insulin index (DIL and DII) on cardio-metabolic markers among diabetic patients. This cross-sectional study was conducted on 393 diabetic patients. A food-frequency questionnaire was used for DIL and DII calculation. PPAR-γ Pro12Ala was genotyped by a polymerase chain reaction-restriction fragment length polymorphism method. Biochemical markers, including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, superoxide dismutase, C-reactive protein, total antioxidant capacity, pentraxin-3, isoprostaneF2α, interleukin-18, leptin and ghrelin, were measured by a standard protocol. Risk-allele carriers (CG, GG) had higher obesity indices [body mass index (pinteraction = 0.006) and WC (pinteraction = 0.04)] compared to individuals with the CC genotype when they consumed a diet with higher DIL and DII respectively. Besides, carriers of the G-allele who were in the highest tertile of DIL had lower high-density lipoprotein (pinteraction = 0.04) and higher isoprostaneF2α (pinteraction = 0.03) and pentraxin-3 (pinteraction = 0.03). Moreover, the highest tertile of the DII, showed an increase in interleukin-18 (pinteraction = 0.01) and lower superoxide dismutase (pinteraction = 0.03) for risk-allele carriers compared to those with CC homozygotes. We revealed that the PPAR-γ Pro12Ala polymorphism was able to intensify the effect of DIL and DII on cardiovascular disease risk factors; risk-allele carriers who consumed a diet with high DIL and DII score were more likely to be obese and have higher inflammatory markers. Also, protective factors against cardiovascular disease risk factors were reduced significantly in this group compared to CC homozygotes.


No association of G72 and D-amino acid oxidase genes with schizophrenia.
The genes of D-amino acid oxidase (DAAO) activator (DAOA or G72; 13q34) and DAAO (12q24) have been suggested as candidate genes and involved in the N-methyl-D-aspartate receptor regulation pathway for schizophrenia. In order to evaluate the potential association of these two genes with schizophrenia in a Taiwanese sample, three single nucleotide polymorphisms (SNPs) for DAAO (rs2111902, rs3918346, rs3741775) and eleven SNPs for G72 (rs3916965, rs3916966, rs3916967, rs2391191, rs3916968, rs947267, rs778294, rs3916970, rs3916971, rs778293, rs3918342) were genotyped by the MALDI-TOF mass spectrometry method in 218 families (864 individuals) containing at least two siblings affected with schizophrenia. In SNP-based single locus association analyses, neither G72 nor DAAO showed significant association with schizophrenia. Additionally, a three-SNP haplotype in DAAO, and a four-SNP as well as a two-SNP haplotype in G72, showed no significant associations with schizophrenia. These results suggest that the DAAO and G72 genes are not susceptibility genes for schizophrenia in a Taiwanese sample.


L p Regularization for Bioluminescence Tomography Based on the Split Bregman Method.
Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L p regularization with the Split Bregman method. The diffusion equation was used as the forward model. Then, we defined the objective function of L p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method. The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions. The Split Bregman iteration method is able to minimize the L p regularization problem and achieve fast and accurate reconstruction in BLT.


Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study.
Thyroid function has been associated with metabolic syndrome (MetS) in a number of observational studies but the direction of effects and the exact causal mechanism of this relationship is still unknown. To examine genetically predicted effects of thyroid function on MetS risk and its components, and vice versa, using large-scale summary genetic association data. We performed a two-sample bidirectional Mendelian randomization (MR) study using summary statistics from the most comprehensive genome-wide association studies (GWAS) of thyroid-stimulating hormone (TSH, n = 119 715), free thyroxine (fT4, n = 49 269), MetS (n = 291 107), and components of MetS: waist circumference (n = 462 166), fasting blood glucose (n = 281 416), hypertension (n = 463 010), triglycerides (TG, n = 441 016) and high-density lipoprotein cholesterol (HDL-C, n = 403 943). We chose the multiplicative random effects inverse variance weighted (IVW) method as the main analysis. Sensitivity analysis included weighted median and mode analysis, as well as MR-Egger and Causal Analysis Using Summary Effect estimates (CAUSE). Our results suggest that higher fT4 levels lower the risk of developing MetS (OR = 0.96, P = .037). Genetically predicted fT4 was also positively associated with HDL-C (β = 0.02, P = .008), while genetically predicted TSH was positively associated with TG (β = 0.01, P = .044). These effects were consistent across different MR analyses and confirmed with the CAUSE analysis. In the reverse direction MR analysis, genetically predicted HDL-C was negatively associated with TSH (β = -0.03, P = .046) in the main IVW analysis. Our study suggests that variations in normal-range thyroid function are causally associated with the diagnosis of MetS and with lipid profile, while in the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.


mTOR and autophagy pathways are dysregulated in murine and human models of Schaaf-Yang syndrome.
MAGEL2 is a maternally imprinted, paternally expressed gene, located in the Prader-Willi region of human chromosome 15. Pathogenic variants in the paternal copy of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG), a neurodevelopmental disorder related to Prader-Willi syndrome (PWS). Patients with SHFYNG, like PWS, manifest neonatal hypotonia, feeding difficulties, hypogonadism, intellectual disability and sleep apnea. However, individuals with SHFYNG have joint contractures, greater cognitive impairment, and higher prevalence of autism than seen in PWS. Additionally, SHFYNG is associated with a lower prevalence of hyperphagia and obesity than PWS. Previous studies have shown that truncating variants in MAGEL2 lead to SHFYNG. However, the molecular pathways involved in manifestation of the SHFYNG disease phenotype are still unknown. Here we show that a Magel2 null mouse model and fibroblast cell lines from individuals with SHFYNG exhibit increased expression of mammalian target of rapamycin (mTOR) and decreased autophagy. Additionally, we show that SHFYNG induced pluripotent stem cell (iPSC)-derived neurons exhibit impaired dendrite formation. Alterations in SHFYNG patient fibroblast lines and iPSC-derived neurons are rescued by treatment with the mTOR inhibitor rapamycin. Collectively, our findings identify mTOR as a potential target for the development of pharmacological treatments for SHFYNG.


Preoperative patient counseling for diagnostic renal biopsy and complications with renal radiofrequency ablation.
To identify preoperative factors associated with surgical complications and successful diagnostic renal biopsy in both laparoscopic and percutaneous radiofrequency ablation (RFA) of renal masses in order to help aid in preoperative patient counseling for renal RFA. We reviewed our Institutional Review Board approved database from November 2001 to January 2011, containing 335 tumors treated with either laparoscopic (LRFA) or percutaneous RFA (CTRFA). Preoperative patient demographics, tumor characteristics, and intraoperative surgical data were collected along with biopsy results and clinicopathologic outcomes. RFA was performed on 335 renal tumors (124 LRFA, 211 CTRFA). Non-diagnostic biopsy occurred in 18 (5.5%) tumors. Of the 317 procedures performed, 121 complications occurred in 103 (30.7%) procedures. Multivariate analysis only showed CTRFA (vs LRFA) to increase the likelihood of non-diagnostic biopsy (OR 5.1, 95% CI 1.2-22, p = 0.032). Increased tumor size (p = 0.007) and synchronous ablations (p = 0.019) increased the risk for major complications, while decreased surgeon experience (p = 0.003) and tumors close to the collecting system (p = 0.005) increased the risk of any complication. Preoperative recommendations can be made to patients in the future. We suggest counseling patients that when undergoing RFA, percutaneous approach increases the risk of non-diagnostic biopsy, increased tumor size increases the risk of major complications, having more than 1 tumor ablated increases the risk of a major complication, and tumors close to the collecting system may increase the risk of complications.


Neuropsychological dysfunction after minimally invasive direct coronary artery bypass grafting.
We compared postoperative neuropsychological dysfunction after minimally invasive direct coronary artery bypass grafting (MIDCAB) operation with coronary artery bypass graft operations using cardiopulmonary bypass. Neuropsychological assessment was performed preoperatively and before discharge on 7 patients undergoing MIDCAB procedures, 9 patients undergoing single-graft cardiopulmonary bypass operation, and 27 patients undergoing multiple-graft cardiopulmonary bypass operation. From a matched control group of 40 normal subjects reliable change indices were derived for each measure and used to determine the incidence of postoperative decline. There was little difference between the MIDCAB and single-graft cardiopulmonary bypass groups on the incidence of neuropsychologic decline. However, the multiple-graft cardiopulmonary bypass group had a significantly higher incidence of decline than the MIDCAB and single-graft cardiopulmonary bypass groups on specific neuropsychologic measures, coupled with a significantly greater number of postoperative deteriorations per patient. The elimination of cardiopulmonary bypass does not prevent neuropsychological dysfunction after cardiac operation as patients undergoing MIDCAB and single-graft cardiopulmonary bypass experience similar deteriorations in performance. However, the deterioration is markedly worsened when the number of surgical grafts is increased.


Developing specialty-wide standards of practice: the experience of ophthalmology.
In 1986, the American Academy of Ophthalmology (AAO) developed national guidelines for the diagnosis and treatment of major eye disease. A core committee of 10 AAO members detailed the framework and goals for the guidelines and wrote a series of broad criteria outlining the ophthalmologist's moral and ethical responsibilities. Several panels of AAO-physician experts were formed to develop guidelines for specific conditions. The panels were formed according to subspecialty and were assigned well-defined issues, such as the diagnosis and management of chronic, adult-onset open-angle glaucoma. Process and structure standards were developed first; outcome standards are scheduled for future development. The first five sets of practice guidelines have been approved by the AAO's Governing Council. These include standards for the comprehensive eye exam, as well as four disease-specific guidelines--open-angle glaucoma, glaucoma suspect, diabetic eye disease, and cataract.


Brain sites involved in the antinociceptive effect of bradykinin in rats.
The localization of brain sites where bradykinin (BK) induces its antinociceptive effect in rats, was studied using as index the threshold for the jaw-opening reflex elicited by the dental pulp electrical stimulation test (DPEST). The microinjection of BK into the lateral or fourth cerebral ventricles induced an antinociceptive effect, with Index of Antinociception (IA) of 0.51+/-0.03 and 0.68+/-0.05, respectively. However, microinjections of the peptide into the third ventricle induced a less marked antinociception (IA = 0.28+/-0.08). The brain sites where the microinjection of BK caused an antinociceptive effect were: locus coeruleus, principal nucleus, oral part of the spinal sensorial trigeminal nucleus, and the sensory root of the trigeminal nerve. The antinociceptive effect was more intense when BK (4-16 nmol) was injected into the locus coeruleus. Microinjection of BK (4 nmol) into the fourth ventricle, but not into the locus coeruleus, induced an increase in blood pressure. The microinjection of the peptide into the nucleus tractus solitarius, a site that is also involved in the pressor effect of BK, did not induce an antinociceptive effect. These results indicate that the antinociceptive effect of BK is not related to blood pressure changes. The microinjection of BK into some of the sites involved in the mechanisms of analgaesia, including the periaqueductal gray matter (dorsal, lateral and ventrolateral) and the dorsal raphe nucleus did not induce an antinociceptive effect. The results suggest that the most likely brain sites involved in the antinociceptive effect of BK are the locus coeruleus and the principal sensory trigeminal nucleus. The present results did not exclude the involvement of other brain sites surrounding the lateral and the third ventricles.


Mild traumatic brain injury in the mouse induces axotomy primarily within the axon initial segment.
Traumatic axonal injury (TAI) is a consistent component of traumatic brain injury (TBI), and is associated with much of its morbidity. Increasingly, it has also been recognized as a major pathology of mild TBI (mTBI). In terms of its pathogenesis, numerous studies have investigated the susceptibility of the nodes of Ranvier, the paranode and internodal regions to TAI. The nodes of Ranvier, with their unique composition and concentration of ion channels, have been suggested as the primary site of injury, initiating a cascade of abnormalities in the related paranodal and internodal domains that lead to local axonal swellings and detachment. No investigation, however, has determined the effect of TAI upon the axon initial segment (AIS), a segment critical to regulating polarity and excitability. The current study sought to identify the susceptibility of these different axon domains to TAI within the neocortex, where each axonal domain could be simultaneously assessed. Utilizing a mouse model of mTBI, a temporal and spatial heterogeneity of axonal injury was found within the neocortical gray matter. Although axonal swellings were found in all domains along myelinated neocortical axons, the majority of TAI occurred within the AIS, which progressed without overt structural disruption of the AIS itself. The finding of primary AIS involvement has important implications regarding neuronal polarity and the fate of axotomized processes, while also raising therapeutic implications, as the mechanisms underlying such axonal injury in the AIS may be distinct from those described for nodal/paranodal injury.


Actions on gamma-motoneurones elicited by electrical stimulation of group II muscle afferent fibres in the hind limb of the cat.
The reflex effects elicited by electrical stimulation of group II muscle afferent fibres were recorded with micro-electrodes in ninety-eight hind-limb gamma-motoneurones of cats anaesthetized with chloralose. Eighty-one of the gamma-cells were classified as either static or dynamic by means of stimulation in the mesencephalic area for dynamic control known to influence dynamic gamma-motoneurones selectively. A high responsiveness to activity in group II muscle fibres was found for the whole sample of gamma-cells. Group II muscle action on dynamic gamma-motoneurones was found to be more frequent than that on static ones. Excitation from group II fibres outweighed inhibition. This was clear cut for flexor gamma-motoneurones. In extensor gamma-cells, excitation prevailed by a small margin only. However, for both static and dynamic extensor gamma-cells, excitation prevailed from both posterior biceps--semitendinosus and the gastrocnemius--soleus nerves, whereas inhibition was more frequent from the deep peroneal and quadriceps nerves. All the reflex effects studied were likely to be mediated via oligosynaptic pathways. The shortest latencies of excitatory effects were compatible with a disynaptic coupling. The fastest inhibitions were presumably trisynaptic. The present findings, supported by a parallel study of reflexes evoked by group III muscle afferents, strongly suggest that the reflexes on gamma-motoneurones are not organized in accordance with the concept of flexion reflex afferents as conceived for alpha-motoneurones. The interpretation of the results suggests a particularly independent position for dynamic gamma-cells in relation to alpha- and static gamma-motoneurones. Hence, the results also furnish an argument against the concept of alpha-gamma linkage.


Human cancer risk from the inhalation of formaldehyde in different indoor environments in Guiyang City, China.
This study was conducted to estimate the risk of human cancer from the inhalation of formaldehyde in different indoor environments in Guiyang City in China. Offices had the highest mean formaldehyde concentration (0.11 mg/m(3)) and classrooms had the lowest mean formaldehyde concentration (0.04 mg/m(3)). The cancer risk levels in different indoor environments ranged from 6.96 x 10(-6 )to 2.48 x 10(-4) and were greater than the acceptable cancer risk 1 x 10(-6). High human formaldehyde risks imply a critical influence on human health in Guiyang City. The highest cancer risk values occurred in bedrooms (ranging from 1.87 in 10,000 to 2.48 in 10,000). For office workers, offices were the highest risk environment after bedrooms where formaldehyde concentration levels were identified. Students were the most sensitive population, and the highest priority should be given to protecting their health in indoor environments. Regulations and standards for low emission materials and public education in relation to indoor pollution are highly recommended in China to protect human health.


Useful technique for long-term urinary drainage by inlying ureteral stent. Six-year experience.
Endoscopically placed inlying ureteral stents have proved useful in the conservative management of patients with ureteral obstruction, urinary fistula, and malignancy and have obviated the need for operative intervention. In high-risk symptomatic patients with widespread malignancy, internal urinary diversion offers the opportunity for an improved quality of life without the surgical risk or potential morbidity of supravesical diversion. Potential candidates for this simple, safe, and effective technique include: those with postsurgical obstruction and/or fistula, retroperitoneal fibrosis, metastatic carcinoma, congenital ureteropelvic junction obstruction, as well as those with reversible obstruction from lymphoma and carcinoma of the prostate who are undergoing radiotherapy and/or chemotherapy. The focus of this report is on the technique we have found successful in providing us with stents that fit our individual patients. Readily available fabricated graduated ureteral catheter can be cut and shaped to particular measurements unlike prefabricated catheters. Minimal preparation time is demanded, and there is no need for extensive stocking of various catheter sizes.


Nitric oxide and nitric oxide-generating agents induce a reversible inactivation of protein kinase C activity and phorbol ester binding.
Since S-nitrosylation of protein thiols is one of the cellular regulatory mechanisms induced by nitric oxide (NO), and since protein kinase C (PKC) has critical thiol residues which influence its kinase activity, we have determined whether NO could regulate this enzyme. Initial studies were carried out with purified PKC and the NO-generating agent S-nitrosocysteine. This agent decreased phosphotransferase activity of PKC in a Ca(2+)- and oxygen-dependent manner with an IC50 of 75 microM. Phorbol ester binding was affected partially only at higher concentrations (> 100 microM) of S-nitrosocysteine. This inactivation of PKC was blocked by the NO scavenger oxyhemoglobin or reversed by dithiothreitol. It is likely that NO initially induced an S-nitrosylation of vicinal thiols, which were then oxidized to form an intramolecular disulfide. Other NO-generating agents such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside, as well as authentic NO gas, induced similar types of PKC modifications. In intact B16 melanoma cells treated with S-nitrosocysteine a rapid decrease in PKC activity in both cytosol and membrane was observed. Unlike in experiments with purified PKC, in intact cells treated with S-nitrosocysteine the phorbol ester binding also decreased to a rate equal to that of PKC activity. These modifications were readily reversed by treating the homogenates with dithiothreitol in test tubes or by removing the NO-generating source from intact cells. To determine whether the limited amounts of NO generated within the intact cells could induce this type of PKC modification, the macrophage cell line IC-21 was treated with lipopolysacharide and Ca2+ ionophore A23187 to induce the NO production. With an increase in generation of NO (3-12-h period) in these cells, a parallel and irreversible decrease in PKC activity and phorbol ester binding was observed. A specific inhibitor for NO synthase, NG-monomethyl-L-arginine, inhibited both the production of NO and PKC inactivation. In experiments using purified enzyme or intact cells there was no decrease in cAMP-dependent protein kinase activity. Conceivably, NO production for limited time induces a reversible inactivation of PKC due to the formation of a disulfide bridge(s), whereas the chronic production of NO could induce irreversible inactivation of PKC. The reversible or irreversible inactivations of PKC may in part influence NO-mediated cytoprotective or cytotoxic actions, respectively.


Effects of chlorpromazine and some of its metabolites on the EEG and on dopamine metabolism of the isolated perfused rat brain.
The study concerned the effects of chlorpromazine (CPZ), monodesmethyl-chlorpromazine (NOR1-CPZ), didesmethyl-chlorpromazine (NOR2-CPZ), and chlorpromazine-N-oxide (CPZ-NO) on the EEG and on dopamine metabolism of the isolated perfused rat brain. Isolated brains were perfused with 100 ml of a perfusion medium containing 30% bovine red cells (v/v), 2 g bovine serum albumin, 14 mM glucose as well as one of the agents in a concentration of 10 micrometers. The main dopamine metabolite homovanillic acid (HVA) was measured fluorimetrically in the striatum of the isolated brain. The EEG was recorded by two symmetrical bipolar leads from the parietal regions at various times during the 30 min perfusion period and was stored on magnetic tape. The recordings were evaluated visually and quantitatively by automatic analysis. CPZ-NO was found to be the most active agent both in changing the EEG and in elevating the HVA level in the striatum. The mean EEG amplitude and the slow wave activity increased significantly. The increase of the HVA level in the striatum was correlated with the increase of delta waves as well as excess of kurtosis and skewness calculated from the amplitude histography data. The desmethylated metabolites caused only moderate central effects.


Non-Hodgkin's lymphoma revealed by a cerebral vascular stroke: A case report.
Hemorrhagic lesions in CNS lymphoma are extremely rare. We report the case of a 75-year-old patient admitted to the emergency room following a classic hemorrhagic stroke. The CT scan showed a hyperdense tumor-like process with perilesional edema, the diagnosis reinforced by (MRI). The patient underwent macroscopically total surgical excision and the anatomo pathological examination concluded a diffuse non-Hodgkin's B large cell lymphoma. The follow up was marked by a clear clinical improvement. Primary cerebral lymphomas can be polymorphic, so this diagnosis should always be kept in mind during stroke manifestations. This case illustrates the diagnostic difficulty of this rare and poor prognosis condition.


Knowledge of Flemish paediatricians about children's oral health--results of a survey.
To examine the knowledge paediatricians have about oral health in children. A questionnaire on oral health knowledge was mailed to all members of the Flemish Paediatric Association representing 350 out of 676 Flemish paediatricians. Questions concerned timing of the first dental visit, effects of thumb sucking, fluoride supplements, trauma, fluorosis, mutans streptococci and caries, prevention of dental caries, nursing bottle caries and use of sealants. Two hundred seventy-six questionnaires (79%) were returned. Of the respondents, 71% said they have had some training on dental topics, and most rely on information brochures to be informed on dental subjects. Parents frequently questioned paediatricians about dental eruption. Paediatricians stated that the first dental visit should be scheduled at the age of 3. Eighty-three percent of the paediatricians stated that thumb sucking was harmful to dentition; 7% regularly prescribed fluoride supplements. Knowledge about fluorosis was moderate. Paediatricians judged community water fluoridation and tooth brushing after consuming erosive drinks as effective. The efficacy of dairy products was underrated. Seventy-three percent of the paediatricians were aware of nursing bottle caries, whereas only 39% were familiar with fissure sealing. Initiatives are needed to improve knowledge about oral health of physicians involved in preventive health care of children.


Novel sulfonamides having dual dopamine D2 and D3 receptor affinity show in vivo antipsychotic efficacy with beneficial cognitive and EPS profile.
A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile.


Thermodynamically-robust Pitzer equations for volumetric properties of electrolyte solutions.
Pitzer equations are widely employed to correlate and predict the volumetric properties of aqueous electrolyte solutions over broad ranges of pressure and temperature. However, the currently-used pressure and temperature terms are empirical and tend to violate known thermodynamic behaviour. Three functional constraints have been identified that overcome this problem.


Angiographic and clinical outcomes of a pharmacokinetic study of sirolimus-eluting stents: lesson from restenosis cases.
A pharmacokinetic (PK) study was conducted to evaluate sirolimus-eluting stents (SES) in Japanese people, representing the first clinical trial of the use of drug-eluting stents in Japan. The PK study was conducted in 20 patients with 30 lesions treated with sirolimus-coated BX Velocity stents. All lesions were treated with a single SES (3 x 18 mm). Angiographic follow-up was performed at 8 months after SES implantation, and the clinical outcomes were evaluated at 1 year in all cases. All procedures were successful, and all patients were discharged without any adverse cardiac events. The total restenosis rate was 10% (3 lesions) and target vessel revascularization was performed in those 3 cases (15%). Restenoses occurred at the proximal and distal stent margins. Intravascular ultrasound examination of restenosis cases revealed abundant plaque burden at the stent edges even though the luminal area was preserved. The sirolimus-eluting BX Velocity stent is safe and useful for Japanese patients with coronary artery disease. However, restenosis at proximal stent edge seems to be a problem.


Effect of Selenium on Ion Profiles and Antioxidant Defense in Mice Livers.
Se entering the mammalian body from diverse sources shows different liver accumulation patterns. However, the effects of Se from diverse sources on the body's I on spectrum and the relationship between the changes in the ion spectrum and antioxidant function are not clear. In this study, 80 3-week-old female mice were randomly divided into four groups: a control group, sodium selenite group, yeast Se group, and seaweed Se group. The estimated Se contents were 0.03, 0.23, 0.23, and 0.23 mg/kg, respectively. The liver was collected from mice on day 60. The results showed that, compared with the control group, sodium selenite significantly reduced Na and Li contents and significantly increased Cr, Ni, Se, and Sb contents (P < 0.05); yeast Se significantly increased Mg, Ca, Si, Cr, Fe, Co, Cu, Se, Sb, and Al contents, and significantly reduced Tl, As, and Hg contents (P < 0.05); seaweed Se significantly increased B, Si, Cr, Fe, Se, As, and Hg contents, and significantly reduced Zn and Tl contents (P < 0.05). The results of antioxidant parameter analysis showed that Se from three sources increased total superoxide dismutase content and significantly reduced malondialdehyde content (P < 0.05), whereas no clear effect was observed on total antioxidant capacity (P > 0.05). Combined with the ion spectrum and antioxidant test results, yeast Se was found to most effectively promote the accumulation of beneficial elements, enhance antioxidant capacity, and reduce the concentration of toxic elements. The variety of ion spectrum antioxidants followed a similar trend, which indicated that the ion spectrum might be related to antioxidant activity.


Mindfulness, anxiety, and high-stakes mathematics performance in the laboratory and classroom.
Mindfulness enhances emotion regulation and cognitive performance. A mindful approach may be especially beneficial in high-stakes academic testing environments, in which anxious thoughts disrupt cognitive control. The current studies examined whether mindfulness improves the emotional response to anxiety-producing testing situations, freeing working memory resources, and improving performance. In Study 1, we examined performance in a high-pressure laboratory setting. Mindfulness indirectly benefited math performance by reducing the experience of state anxiety. This benefit occurred selectively for problems that required greater working memory resources. Study 2 extended these findings to a calculus course taken by undergraduate engineering majors. Mindfulness indirectly benefited students' performance on high-stakes quizzes and exams by reducing their cognitive test anxiety. Mindfulness did not impact performance on lower-stakes homework assignments. These findings reveal an important mechanism by which mindfulness benefits academic performance, and suggest that mindfulness may help attenuate the negative effects of test anxiety.


Deciphering the underlying wound healing mechanisms of Streptocaulon juventas (Lour.) Merr. by integrating network pharmacology, transcriptomics, and experimental validation.
Streptocaulon juventas (Lour.) Merr. (SJ), a traditional Chinese folk medicine, has been widely used for the treatment of dysentery and traumatic injuries since ancient times. However, the mechanisms underlying its wound healing activity remain unclear. The aim of this study was to evaluate the wound healing activity of SJ and clarify the underlying molecular mechanisms. The wound healing activity of an ethanol extract of SJ (ESJ) was confirmed in rat full-thickness wound models. UPLC-Q-TOF-MS/MS was used to analyze the composition of ESJ. Potential molecular targets and signaling pathways involved in the wound healing activity of ESJ were predicted using network pharmacology and transcriptomic analyses. In addition, the L929 cells were used to evaluate the in vitro wound healing activity of ESJ and to verify the predicted pathways. In rat wound models, ESJ significantly accelerated wound healing and promoted hydroxyproline production in wounds. Network pharmacology and transcriptomic analyses results revealed that ESJ might promote wound healing by activating the AKT and MAPK pathways. In L929 cells, ESJ significantly promoted cell proliferation, migration, and expression of collagen I and α-SMA. Additionally, ESJ treatment increased the phosphorylation of AKT, mTOR, ERK, and p38 in a time- and dose-dependent manner. ESJ significantly promoted wound healing in vivo and in vitro. AKT-mTOR and ERK-p38 signaling pathways were involved in the wound healing activity of ESJ.


A multidisciplinary approach for the treatment of GIST liver metastasis.
Advanced gastrointestinal stromal tumors (GISTs) can metastasize and recur after a long remission period, resulting in serious morbidity, mortality, and complex management issues. A 67-year-old woman presented with epigastric fullness, mild jaundice and weight loss with a history of a bowel resection 7 years prior for a primary GIST of the small bowel. The finding of a heterogeneous mass 15.5 cm in diameter replacing most of the left lobe of the liver by ultrasonography and CT, followed by positive cytological studies revealed a metastatic GIST. Perioperative optimization of the patient's nutritional status along with biliary drainage, and portal vein embolization were performed. Imatinib was successful in reducing the tumor size and facilitating surgical resection. A well-planned multidisciplinary approach should be part of the standard management of advanced or metastatic GIST.


Retracted: Application Effect Analysis of Clinical Nursing Pathway in the Care of Neonatal Hypoxic-Ischemic Encephalopathy.
[This retracts the article DOI: 10.1155/2022/9379361.].


"It's Always About Sharing, and Caring, and Loving, and Giving": Decolonized and Transcendent Indigenist Foodways Fostering Health and Resilience.
Centuries of historical oppression have targeted and undermined Indigenous foodways, which fundamentally disrupts the culture and wellness, yet decolonized, resilient, and transcendent Indigenist practices persist. The purpose of this research was to use the framework of historical oppression, resilience, and transcendence (FHORT) to understand foodway practices among Indigenous Peoples. Given a limited understanding of how foodways may promote health and wellness the focal research questions for this critical ethnographic inquiry were: (a) How do participants describe Indigenist foodways? (b) How do Indigenist foodways reflect decolonized values and practices? and (c) How may Indigenist foodways be promotive for health and wellness? Data were drawn from 31 participants across a rural, reservation-based Southeast (SE) region and an urban Northwest (NW) region. Reconstructive data analysis revealed the following emergent themes: (a) Indigenous Values of Generosity Expressed Through Foodways: "It's Always About Sharing, and Caring, and Loving, and Giving"; (b) Gardening, Subsistence, and Food Sharing: "You Bring Enough for Everybody to Share"; (c) Decolonized Feasts and Foodways: "Everybody Pitch in and Help as Much as They Can." Despite centuries of historical oppression, participants reported decolonized values, worldviews, and foodways that reflected unity, cooperation, sharing, and social cohesion and caring, which were promotive factors for family resilience, health, and cultural identification. This research provides promising pathways about how Indigenist foodways remain salient in daily and cultural life, reflect decolonized values and practices, and may be promotive for health and wellness within the natural world.


Morphologic analysis of bipolar radiofrequency lesions: implications for treatment of the sacroiliac joint.
Sacroiliac (SI) joint dysfunction is an important cause of mechanical low-back pain. Bipolar radiofrequency ablation has been proposed as a long-lasting treatment for pain in patients with SI dysfunction who report temporary pain relief with local-anesthetic injection into the joint. No data are available to guide the technical aspects of bipolar radiofrequency lesion creation. This study documents the optimal spacing of cannulae and time required to produce bipolar lesions by use of radiofrequency technology. Two radiofrequency cannulae were secured in a parallel position 2, 4, 6, 8, and 10 mm apart and submerged in egg white for lesion production in a medium that would allow visualization of the size and shape of the lesions as they were created. Temperatures of the probes were raised from 40 degrees C to 90 degrees C at a constant rate and were held at 90 degrees C for 190 seconds. The progress of lesion formation was photographed every 10 seconds, and the resultant surface area of the lesions was measured from the digital images. Contiguous strip lesions were produced when the cannulae were spaced 6 mm or less apart; unipolar lesions around each cannula resulted if they were spaced more than 6 mm apart. Ninety percent of the final lesion area was reached by 120 seconds, and the final lesion size was reached by 150 seconds, regardless of spacing. Bipolar radiofrequency treatment creates continuous "strip" lesions proportional in size to the distance between the probes when the distance between cannulae is 6 mm or less. Spacing the cannulae 4 to 6 mm apart and treating at 90 degrees C for 120 to 150 seconds maximizes the surface area of the lesion.