Leukocyte-derived extracellular superoxide dismutase does not contribute to airspace EC-SOD after interstitial pulmonary injury.
The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) is abundant in the lung and is known to limit inflammation and fibrosis following numerous pulmonary insults. Previous studies have reported a loss of full-length EC-SOD from the pulmonary parenchyma with accumulation of proteolyzed EC-SOD in the airspace after an interstitial lung injury. However, following airspace only inflammation, EC-SOD accumulates in the airspace without a loss from the interstitium, suggesting this antioxidant may be released from an extrapulmonary source. Because leukocytes are known to express EC-SOD and are prevalent in the bronchoalveolar lavage fluid (BALF) after injury, it was hypothesized that these cells may transport and release EC-SOD into airspaces. To test this hypothesis, C57BL/6 wild-type and EC-SOD knockout mice were irradiated and transplanted with bone marrow from either wild-type mice or EC-SOD knockout mice. Bone marrow chimeric mice were then intratracheally treated with asbestos and killed 3 and 7 days later. At both 3 and 7 days following asbestos injury, mice without pulmonary EC-SOD expression but with EC-SOD in infiltrating and resident leukocytes did not have detectable levels of EC-SOD in the airspaces. In addition, leukocyte-derived EC-SOD did not significantly lessen inflammation or early stage fibrosis that resulted from asbestos injury in the lungs. Although it is not influential in the asbestos-induced interstitial lung injury model, EC-SOD is still known to be present in leukocytes and may play an influential role in attenuating pneumonias and other inflammatory diseases.


Effects of treatment of whole fat soybeans or soy flour with formaldehyde to protect the polyunsaturated fatty acids from biohydrogenation in the rumen.
Full-fat, ground soy flour (GSF) was treated with 37% formaldehyde (HCHO) and evaluated by in vitro and in vivo criteria to determine the protection afforded linoleic acid against ruminal biohydrogenation when the materials described above were fed as a protein supplement to rations for growing lambs. The supplements compared were soybean meal (SBM), uked for 2 hours. Organoleptic evaluations were conducted to determine if any flavor differences in meat from lambs fed these supplements could be detected. Excellent protection of linoleic acid, the major polyunsaturated fatty acid in soybeans, was noted both in vitro and in vivo. Rump, shoulder, kidney knob and omental fat depots of lambs fed the HCHO treated GSF ration had significantly more linoleic acid than lambs fed untreated GSF while lambs fed untreated GSF had significantly, more linoleic acid in their fat depots than lambs fed SBM. Linoleic acid content of intramuscular (loin) fat from lambs fed HCHO treated GSF was not significantly different from lambs fed untreated GSF, but lambs fed untreated GSF had significantly more loin linoleic acid than lambs fed SBM. No significant differences were noted in daily feed intake, feed efficiency or average daily gain for lambs fed growing-finishing rations containing any of the products tested as the protein supplement. A taste panel could not detect any differences in flavor of ground loin among any of the treatments.


Parenteral versus oral iron therapy for adults and children with chronic kidney disease.
The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. This is an update of a review first published in 2012. To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD, including participants on dialysis, with kidney transplants and CKD not requiring dialysis. We searched the Cochrane Kidney and Transplant Register of Studies up to 7 December 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included randomised controlled trials (RCTs) and quasi-RCTs in which IV and oral routes of iron administration were compared in adults and children with CKD. Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed to investigate between study differences. The certainty of the evidence was assessed using GRADE. We included 39 studies (3852 participants), 11 of which were added in this update. A low risk of bias was attributed to 20 (51%) studies for sequence generation, 14 (36%) studies for allocation concealment, 22 (56%) studies for attrition bias and 20 (51%) for selective outcome reporting. All studies were at a high risk of performance bias. However, all studies were considered at low risk of detection bias because the primary outcome in all studies was laboratory-based and unlikely to be influenced by lack of blinding.There is insufficient evidence to suggest that IV iron compared with oral iron makes any difference to death (all causes) (11 studies, 1952 participants: RR 1.12, 95% CI 0.64, 1.94) (absolute effect: 33 participants per 1000 with IV iron versus 31 per 1000 with oral iron), the number of participants needing to start dialysis (4 studies, 743 participants: RR 0.81, 95% CI 0.41, 1.61) or the number needing blood transfusions (5 studies, 774 participants: RR 0.86, 95% CI 0.55, 1.34) (absolute effect: 87 per 1,000 with IV iron versus 101 per 1,000 with oral iron). These analyses were assessed as having low certainty evidence. It is uncertain whether IV iron compared with oral iron reduces cardiovascular death because the certainty of this evidence was very low (3 studies, 206 participants: RR 1.71, 95% CI 0.41 to 7.18). Quality of life was reported in five studies with four reporting no difference between treatment groups and one reporting improvement in participants treated with IV iron.IV iron compared with oral iron may increase the numbers of participants, who experience allergic reactions or hypotension (15 studies, 2607 participants: RR 3.56, 95% CI 1.88 to 6.74) (absolute harm: 24 per 1000 with IV iron versus 7 per 1000) but may reduce the number of participants with all gastrointestinal adverse effects (14 studies, 1986 participants: RR 0.47, 95% CI 0.33 to 0.66) (absolute benefit: 150 per 1000 with IV iron versus 319 per 1000). These analyses were assessed as having low certainty evidence.IV iron compared with oral iron may increase the number of participants who achieve target haemoglobin (13 studies, 2206 participants: RR 1.71, 95% CI 1.43 to 2.04) (absolute benefit: 542 participants per 1,000 with IV iron versus 317 per 1000 with oral iron), increased haemoglobin (31 studies, 3373 participants: MD 0.72 g/dL, 95% CI 0.39 to 1.05); ferritin (33 studies, 3389 participants: MD 224.84 µg/L, 95% CI 165.85 to 283.83) and transferrin saturation (27 studies, 3089 participants: MD 7.69%, 95% CI 5.10 to 10.28), and may reduce the dose required of erythropoietin-stimulating agents (ESAs) (11 studies, 522 participants: SMD -0.72, 95% CI -1.12 to -0.31) while making little or no difference to glomerular filtration rate (8 studies, 1052 participants: 0.83 mL/min, 95% CI -0.79 to 2.44). All analyses were assessed as having low certainty evidence. There were moderate to high degrees of heterogeneity in these analyses but in meta-regression, definite reasons for this could not be determined. The included studies provide low certainty evidence that IV iron compared with oral iron increases haemoglobin, ferritin and transferrin levels in CKD participants, increases the number of participants who achieve target haemoglobin and reduces ESA requirements. However, there is insufficient evidence to determine whether IV iron compared with oral iron influences death (all causes), cardiovascular death and quality of life though most studies reported only short periods of follow-up. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient-centred outcomes with longer follow-up periods are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects.


Hepatic diseases in the elderly.
The clinical manifestations of liver disease in the geriatric population reflect both the cumulative effects of longevity on the liver and the generalized senescence of the body's ability to adjust to metabolic, infectious, and immunologic insults. Although liver tests are not significantly affected by age, the presentation of liver diseases such as viral hepatitis may be more subtle in the geriatric population than that of younger patients. Alcoholic liver disease and primary biliary cirrhosis usually are advanced in the elderly. Geriatric patients are at risk for untoward drug side effects because of polypharmacy, alterations in the rate of first pass and phase I metabolism, and decreased capacity of carrier proteins such as albumin.


Positive selection and multiple losses of the LINE-1-derived L1TD1 gene in mammals suggest a dual role in genome defense and pluripotency.
Mammalian genomes comprise many active and fossilized retroelements. The obligate requirement for retroelement integration affords host genomes an opportunity to 'domesticate' retroelement genes for their own purpose, leading to important innovations in genome defense and placentation. While many such exaptations involve retroviruses, the L1TD1 gene is the only known domesticated gene whose protein-coding sequence is almost entirely derived from a LINE-1 (L1) retroelement. Human L1TD1 has been shown to play an important role in pluripotency maintenance. To investigate how this role was acquired, we traced the origin and evolution of L1TD1. We find that L1TD1 originated in the common ancestor of eutherian mammals, but was lost or pseudogenized multiple times during mammalian evolution. We also find that L1TD1 has evolved under positive selection during primate and mouse evolution, and that one prosimian L1TD1 has 'replenished' itself with a more recent L1 ORF1 from the prosimian genome. These data suggest that L1TD1 has been recurrently selected for functional novelty, perhaps for a role in genome defense. L1TD1 loss is associated with L1 extinction in several megabat lineages, but not in sigmodontine rodents. We hypothesize that L1TD1 could have originally evolved for genome defense against L1 elements. Later, L1TD1 may have become incorporated into pluripotency maintenance in some lineages. Our study highlights the role of retroelement gene domestication in fundamental aspects of mammalian biology, and that such domesticated genes can adopt different functions in different lineages.


Ambient air pollution exposure and risk of chronic kidney disease: A systematic review of the literature and meta-analysis.
Ambient air pollution has been identified as one of the leading causes of global burden of disease. The relationship between ambient air pollution exposure and risk of chronic kidney disease (CKD) has stimulated increasing scientific interest in the past few years. However, evidence from human epidemiological studies is still limited and inconsistent. We performed an updated systematic review and meta-analysis to clarify the potential association comprehensively. Selected electronic databases were searched for related English language studies until March 1, 2020 with a final follow-up in December 31, 2020. Risk of bias assessment for individual studies were assessed using the OHAT (Office of Health Assessment and Translation) risk-of-bias rating tool. Confidence rating and level-of-evidence conclusions were developed for bodies of evidence for a given ambient air pollutant. Summary effect estimates were calculated using random-effects meta-analyses when three or more studies are identified for the same air pollutant-CKD combination. A total of 13 studies were finally identified in our study. The meta-analytic estimates (ORs) for risk of CKD were 1.15 (95% CI: 1.07, 1.24) for each 10 μg/m3 increase in PM2.5, 1.25 (95% CI: 1.11, 1.40) for each 10 μg/m3 increase in PM10, 1.10 (95% CI: 1.03, 1.17) for each 10 ppb increase in NO2, 1.06 (95% CI: 0.98, 1.15) for each 1 ppb increase in SO2 and 1.04 (95% CI: 1.00, 1.08) for each 0.1 ppm increase in CO, respectively. The level of evidence was appraised as moderate for four of the five tested air pollutant-CKD combinations using an adaptation of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool. In conclusion, this study suggests that certain ambient air pollutant exposure was significantly associated with an increased risk of CKD. Given the limitations, the results of this study should be interpreted with caution, and further well-designed epidemiological studies are needed to draw a definite evidence of a causal relationship.


Temporal trend of mercury in polar bears (Ursus maritimus) from Svalbard using teeth as a biomonitoring tissue.
We examined the use of mercury (Hg) and nitrogen and carbon stable isotopes in teeth of polar bear (Ursus maritimus) from Svalbard as biotracers of temporal changes in Hg pollution exposure between 1964 and 2003. Teeth were regarded as a good matrix of the Hg exposure, and in total 87 teeth of polar bears were analysed. Dental Hg levels ranged from 0.6 to 72.3 ng g(-1) dry weight and increased with age during the first 10 years of life. A decreasing time trend in Hg concentrations was observed over the recent four decades while no temporal changes were found in the stable isotope ratios of nitrogen (δ(15)N) and carbon (δ(13)C). This suggests that the decrease of Hg concentrations over time was more likely due to a lower environmental Hg exposure in this region rather than a shift in the feeding habits of Svalbard polar bears.


Inflammatory myofibroblastic tumour of the duodenum.
Inflammatory myofibroblastic tumours (IMTs) of the duodenum and head of the pancreas are rare. They are of probable immunological aetiology and preoperatively indistinguishable from adenocarcinomas of the pancreatic head. We describe a patient with duodenal IMT and gastric outlet obstruction, and present a review of pancreatic head and duodenal IMTs in the literature. IMTs of the pancreatic head present as obstructive jaundice, while those of the duodenum present as gastric outlet obstruction. Surgery is the primary modality of treatment. Adjuvant chemotherapy and radiotherapy are controversial and reserved for incomplete resections and IMTs of a pathologically aggressive nature. Otherwise, recurrence is uncommon and surgery curative.


Clofibrate-induced increase in coenzyme A concentration in rat tissues.
1. When clofibrate [ethyl 2-(4-chlorophenoxy)-2-methylpropionate] was administered subcutaneously to rats (600mg/kg per day for 5 days), the concentration of CoA and its acyl derivatives increased in several tissues. The increase in total CoA was 3.2-fold in the liver, 1.8-fold in the kidney, 2.7-fold in the heart and 2.4-fold in skeletal muscle. 2. To study the mechanism of this phenomenon, clofibrate-treated rats were injected with [(3)H]pantothenate intracardially and killed after 15min, 30min, 1 and 2h and 1, 3, 5 and 7 days for the determination of the incorporation of radioactivity into CoA and its precursors. Incorporation into CoA after 2h was 6.2-fold in the liver as compared with the control values and 4.6-fold in the kidneys. 3. The disappearance of the label from CoA was very slow compared with the rate of incorporation; it exhibited exponential kinetics, and was slower in the livers of the clofibrate-treated rats (t((1/2)) 18.2 days) than in the controls (t((1/2)) 5.6 days). 4. The rate of CoA degradation, calculated from the calculated rate constants of the apparent first-order kinetics of the disappearance of the label and from the CoA pool sizes, was approximately the same in the clofibrate-treated animals (11.5pmol/min per g), and the controls (11.6pmol/min per g). 5. These rates of CoA degradation indicate that the effect of clofibrate on CoA concentration may be mainly due to inhibition of the enzymes of CoA degradation, although recycling of the label cannot be excluded. The increase in the rate of pantothenate incorporation into CoA suggests that clofibrate also increases the synthesis of CoA.


The Demography of Families: A Review of Patterns and Change.
The authors review demographic trends and research on families in the United States, with a special focus on the past decade. They consider the following several topics: (a) marriage and remarriage, (b) divorce, (c) cohabitation, (d) fertility, (e) same-gender unions, (f) immigrant families, and (g) children's living arrangements. Throughout, the authors review both overall trends and patterns as well as those by social class and race-ethnicity. The authors discuss major strands of recent research, emphasizing emerging themes and promising directions. They close with a summary of central patterns and trends and conclude that recent trends are not as uniform as they tended to be in earlier decades, making the description of family change increasingly complex.


Household Level Drug Utilization and Associated Factors in South Gondar Zone, North Western Ethiopia.
Inappropriate drug utilization may reduce the best possible benefits of drug therapy, and patients may not be cured, they may be exposed to toxicity, and medications may be wasted. The aim of this study is to assess household-level drug utilization practices and their associated factors. A cross-sectional community-based study was conducted from January 15 to March 15, 2020. In total, 847 households selected by stratified multistage sampling were visited. Bivariate and multivariable analyses for association were carried out using a binary logistic regression model. The statistical significance of an association was confirmed at p<0.05. Of the total 847 households, 378 (44.6%) were found to store drugs at home at the time of datacollection. In the 371 households that allowed observation of the drugs stored, a mean of 2.51 (SD=1.68) drugs per household was found; 40.2% of stored medicines were not in use at the time of the study. The prevalences of medication hoarding, sharing, and allopathic self-medication were 20.4%, 26.3%, and 43.8%, respectively. Higher monthly income and the presence of a child aged under 5 years were significantly associated with drug hoarding. The presence of an elderly person aged above 65 years and the presence of a family member with chronic illness were significantly associated with drug hoarding and sharing. Families with higher educational status were less likely to hoard and share medicines. The presence of stored drugs at home was significantly associated with the practice of self-medication. A high prevalence of inappropriate drug utilization was observed. Factors such as the presence of a family member with chronic illness, elderly people, and children under 5, higher income, and the presence of stored drugs were significantly associated with inappropriate drug utilization. Families of higher educational status were less likely to hoard and share medicines.


Intraventricular but not intraparaventricular nucleus metergoline elicits feeding in satiated rats.
Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS)


Family members' needs at intensive care units: comparative analysis between a public and a private hospital.
This cross-sectional study proposed to analyze the needs of adult ICU patients' family members at a public and a private hospital, regarding their level of importance and satisfaction. Ninety-one family members were interviewed, 47 from the public hospital and 44 from the private one, using the Brazilian adaptation of the Critical Care Family Need Inventory (INEFTI). There was no significant difference between the groups in the total score of importance attributed to the needs (p=0.410). The satisfaction score was higher in the private hospital than in the public one (p=0.002). Multiple linear regression analysis allowed us to establish a hierarchy of importance and satisfaction of the family members' needs in each group. The differences observed between the groups suggest that the fulfillment of their needs requires interventions directed at the specificity of each type of hospital.


Bridging the gap of knowledge and skills for diagnosis and treatment of painful neuropathy: Development and evaluation of pain education project for clinicians in primary care settings.
The importance of pain education is widely accepted and recognized. This is a key part of educating the undergraduate and postgraduate healthcare workforce is an essential strategy for promoting effective pain practice. This study aims to evaluate the pain management module training courses for newly graduated doctors to address the knowledge gap between specialist care and primary care physicians. This was an observational study of an evaluation of a pain education project focused on neuropathic pain management core competency was provided. Multimodal teaching approaches such as didactic teaching and vignettes of cases discussion, video teaching, and learning module. A pretest survey was carried out to assess the baseline knowledge of the participants. Completion of the post-test and participant experience questionnaire were collected. Comparison of the pre-and post-test scores for all participants was undertaken using the Wilcoxon signed-ranked test with effect size calculated. The participant's experience questionnaire scores were analyzed descriptively to produce mean and standard deviations from each question. A total of 274 participants completed all of the course sections from the average of 350 eligible participants. Of 274 participants, more than half were female (64.96%), with more than half participants being General Practitioner (54.38%) followed by a neurologist (35.04%). For all sessions, a Wilcoxon signed-rank test outlined that differences between all pre-and post-test scores were significant (P < .001). There was a marked improvement in the post-test as evidenced by statistically significant increases in mean scores differences. We developed an educational training courses for physicians to address the limitation in existing medical undergraduate training of neuropathic pain management. The training led to improvement in participant's knowledge and skills with positive outcomes.


Metabolic Tumor Microenvironment Characterization of Contrast Enhancing Brain Tumors Using Physiologic MRI.
The tumor microenvironment is a critical regulator of cancer development and progression as well as treatment response and resistance in brain neoplasms. The available techniques for investigation, however, are not well suited for noninvasive in vivo characterization in humans. A total of 120 patients (59 females; 61 males) with newly diagnosed contrast-enhancing brain tumors (64 glioblastoma, 20 brain metastases, 15 primary central nervous system (CNS) lymphomas (PCNSLs), and 21 meningiomas) were examined with a previously established physiological MRI protocol including quantitative blood-oxygen-level-dependent imaging and vascular architecture mapping. Six MRI biomarker maps for oxygen metabolism and neovascularization were fused for classification of five different tumor microenvironments: glycolysis, oxidative phosphorylation (OxPhos), hypoxia with/without neovascularization, and necrosis. Glioblastoma showed the highest metabolic heterogeneity followed by brain metastasis with a glycolysis-to-OxPhos ratio of approximately 2:1 in both tumor entities. In addition, glioblastoma revealed a significant higher percentage of hypoxia (24%) compared to all three other brain tumor entities: brain metastasis (7%; p < 0.001), PCNSL (8%; p = 0.001), and meningioma (8%; p = 0.003). A more aggressive biological brain tumor behavior was associated with a higher percentage of hypoxia and necrosis and a lower percentage of remaining vital tumor tissue and aerobic glycolysis. The proportion of oxidative phosphorylation, however, was rather similar (17-26%) for all four brain tumor entities. Tumor microenvironment (TME) mapping provides insights into neurobiological differences of contrast-enhancing brain tumors and deserves further clinical cancer research attention. Although there is a long roadmap ahead, TME mapping may become useful in order to develop new diagnostic and therapeutic approaches.


Superoxide radical generation in peroxisomal membranes: evidence for the participation of the 18 kDa integral membrane polypeptide.
Peroxisomes were isolated from pea (Pisum sativum L.) leaves and the peroxisomal membranes were purified by treatment with Na2CO3. The production of superoxide radicals (O2) induced by NADH was investigated in peroxisomal membranes from intact organelles incubated with proteases (pronase E and proteinase K). Under isoosmotic conditions, in the presence of pronase E, the production of O2-. radicals was inhibited by 80%. SDS-PAGE of peroxisomal membranes after protease treatment demonstrated a decrease in the 18-kDa PMP. This suggests that this polypeptide has a small fragment exposed to the cytosolic side of the peroxisomal membrane which is essential for O2-. production. The 18-kDa PMP was purified by preparative SDS-PAGE and in the reconstituted protein the NADH-driven production of O2-. radicals was investigated. The isolated polypeptide showed a high generation rate of superoxide (about 300 nmol O2-. x mg-1 protein x min-1) which was completely inhibited by 50 mM pyridine. The 18-kDa PMP was recognized by a polyclonal antibody against Cyt b5 from human erythrocytes. The presence of b-type cytochrome in peroxisomal membranes was demonstrated by difference spectroscopy. Results obtained show that in the NADH-dependent O2-. radical generating system of peroxisomal membranes, the 18-kDa integral membrane polypeptide, which appears to be Cyt b5, is clearly involved in superoxide radical production.


Object recognition testing: methodological considerations on exploration and discrimination measures.
The object recognition task (ORT) is a popular one-trial learning test for animals. In the current study, we investigated several methodological issues concerning the task. Data was pooled from 28 ORT studies, containing 731 male Wistar rats. We investigated the relationship between 3 common absolute- and relative discrimination measures, as well as their relation to exploratory activity. In this context, the effects of pre-experimental habituation, object familiarity, trial duration, retention interval and the amnesic drugs MK-801 and scopolamine were investigated. Our analyses showed that the ORT is very sensitive, capable of detecting subtle differences in memory (discrimination) and exploratory performance. As a consequence, it is susceptible to potential biases due to (injection) stress and side effects of drugs. Our data indicated that a minimum amount of exploration is required in the sample and test trial for stable significant discrimination performance. However, there was no relationship between the level of exploration in the sample trial and discrimination performance. In addition, the level of exploration in the test trial was positively related to the absolute discrimination measure, whereas this was not the case for relative discrimination measures, which correct for exploratory differences, making them more resistant to exploration biases. Animals appeared to remember object information over multiple test sessions. Therefore, when animals have encountered both objects in prior test sessions, the object preference observed in the test trial of 1h retention intervals is probably due to a relative difference in familiarity between the objects in the test trial, rather than true novelty per se. Taken together, our findings suggest to take into consideration pre-experimental exposure (familiarization) to objects, habituation to treatment procedures, and the use of relative discrimination measures when using the ORT.


[Long-term follow-up of the Hancock prostheses].
Our purpose was to investigate the long term outcome of Hancock bioprostheses at our Hospital. There were 128 bioprostheses, with histopathological study on 17 of them. The 12.8 years follow-up disclosed dysfunction on 48.18% with an annual dysfunction rate of 3.34 +/- 1.3. One half of the patients with prosthetic dysfunction were re-operated. A comparison of our results is made with those of the literature, either with biological or mechanical prostheses.


Cardiomyopathy as one of the less frequent manifestations of Takayasu's arteritis.
The authors present the case of a young woman with newly diagnosed Takayasu's arteritis. This woman, with arterial hypertension, was investigated for the unspecific symptoms at the beginning. Afterwards, the transthoracic echocardiography showed dysfunction of the left ventricle and the abdominal sonography showed a stenosis of the right renal artery. PET/CT scan showed chronic modification after inflammatory processes on the wall of the thoracic and abdominal aorta. This case report should be instructive to other clinicians and refers to the necessity to remember this rare disease in our country too.


Gendered Conceptions of Preconception Health: A Thematic Analysis of Men's and Women's Beliefs about Responsibility for Preconception Health Behavior.
Preconception health (PCH) focuses on taking steps before a pregnancy to safeguard the health of the woman and future baby. Although recommendations to improve PCH target all people of reproductive age, research shows most interventions and messages focus primarily on women, which may contribute to existing normative beliefs that women are more responsible for protecting children's health. In this study, we explore society's gendered expectations of responsibility for engaging in recommended PCH behaviors (i.e., avoiding smoking, drinking, and environmental toxins). An applied thematic analysis of online survey responses from U.S. men and women (N = 573) identified five main themes and related subthemes: body and health, shared responsibility, choice and moral obligation, gender stereotypes, and doubt and uncertainty. Both men and women frequently referenced biological connections between prospective parents and offspring as justification for PCH behaviors. When challenging PCH recommendations, respondents mentioned excessive control of women and men's secondary role in reproduction. Overall, gender stereotypes were more commonly expressed in relation to men yet reflected both traditional and contemporary male roles (i.e., as supporters, co-parents). When judging personal responsibility, women commonly viewed PCH behaviors as the 'duty of a good mother'. Implications for PCH communication research and practice are discussed.


Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through Activating PPARα in Rats With Diabetes.
The aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats. We established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague-Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal-jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot. Bariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism. Bariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.


T-B collaboration for autoantibody production in lpr mice is cognate and MHC-restricted.
A central question in autoimmunity is the mechanism of T cell help for autoantibody production. For responses to exogenous Ag, T-B collaboration is restricted by MHC class II molecules. To determine whether T cell help that leads to autoantibodies in murine SLE is also MHC-restricted, we have constructed bone marrow chimeras with Ig heavy chain (lgh) allotype- and I-A-congenic donor B6/lpr mice and I-A-congenic recipients. Developing T cells were thus positively selected in the host thymus to interact with B cells bearing I-A of one haplotype or the other. Additional control host mice were heterozygous for I-A expression, allowing T helper cell selection for both I-A haplotypes. Five months after reconstitution, serum total IgG2a, IgM, IgG2a antichromatin, and IgM rheumatoid factor were quantitated by allotype-specific ELISA. Data showed that whereas substantial numbers of B cells were present from both donor strains in all mice, autoantibody production was overwhelmingly from those donor B cells expressing the same I-A haplotype as the host. Sera from the I-A heterozygous control recipient group had roughly equal quantities of autoantibodies of both allotypes, as expected. The finding of MHC class II restriction implies that the T cell help that drives autoantibody production in lpr mice is delivered through cognate (cell-to-cell) interactions and not by soluble factors alone.


Examining HIV-related stigma and discrimination in Ghana: what are the major contributors?
Although AIDS-related stigma and discrimination are considered detrimental to HIV prevention activities, not many studies have attempted to understand stigma and discrimination in sub-Saharan Africa, particularly Ghana. Using the 2008 Ghana Demographic and Health Survey and applying the ordinary least-squares technique, this study examined what influences AIDS-related stigma and discrimination among men and women in Ghana. The results indicate that Ghanaian men and women with relatively high knowledge about HIV/AIDS had low stigmatising and discriminatory attitudes (b=-0.097, P<0.01; b=-0.083, P<0.01), respectively. On the other hand, respondents who endorsed more myths about HIV transmission had high stigma and discriminatory attitudes. Women who had ever tested for their HIV serostatus reported significantly lower levels of stigma and discrimination (b=-0.085, P<0.01) compared with those who had not tested for HIV. Individuals who are highly educated, employed and in wealthy households all reported significantly lower levels of stigma and discrimination compared with those who are uneducated, unemployed and in poorer households. AIDS-related stigma and discrimination can be reduced by encouraging HIV testing, and ensuring that Ghanaians understand and have factual knowledge regarding the transmission of the disease.


Ex situ conservation of plant genetic resources: global development and environmental concerns.
Conservation of plant genetic resources is achieved by protection of populations in nature (in situ) or by preservation of samples in gene banks (ex situ). The latter are essential for users of germplasm who need ready access. Ex situ conservation also acts as a back-up for certain segments of diversity that might otherwise be lost in nature and in human-dominated ecosystems. The two methods are complementary, yet better understanding of this interrelation and the role of ex situ conservation in global environmental considerations is needed. Inclusion of ex situ conservation efforts within current environmental policies conserving global diversity would focus greater international attention on the safeguarding of these efforts.


Combination of pamidronate and thalidomide in the therapy of treatment-resistant multiple myeloma.
Bisphosphonates inhibit the activity of osteoclasts and demonstrate antitumor effect, involving induction of plasmocyte apoptosis, blocking of angiogenesis, stimulation of Tgd lymphocytes and inhibition of metalloproteinases. Bisphosphonates combined with thalidomide, a drug possessing confirmed anti-myeloma activity, seem to have potential favorable effect in patients with treatment-resistant multiple myeloma with advanced osteolytic lesions. 13 patients with treatment-resistant multiple myeloma with advanced osteolytic lesions received combined pamidronate and thalidomide therapy. All the patients underwent detailed clinical and laboratory control once a month. Pamidronate was used at 90 mg i.v. dose administered at 4-week intervals, and thalidomide at doses escalated from 200 mg/d in the first week to 400 mg/d after 3 weeks of the therapy. The mean duration of treatment was 12 weeks with a range of 3 to 36 weeks. 7 patients (53%) receiving pamidronate and thalidomide therapy demonstrated good response involving at least 25% reduction of monoclonal protein levels in comparison with baseline. All these patients reported improvement of osteodynia symptoms, and 3 of them - their complete regression. 70% patients experienced side effects (dizziness, constipation, somnolence, polyneuropathy) due to thalidomide administration Good response to combined pamidronate and thalidomide therapy can be expected in at least 50% of patients with treatment-resistant multiple myeloma with advanced osteolytic lesions.


Managing River Fish Biodiversity Generates Substantial Economic Benefits in Four European Countries.
Ecosystems and biodiversity produce benefits to society, but many of them are hard to quantify. For example, it is unclear whether European societies gain benefits from experiencing rivers that host high native biodiversity. Without such knowledge, monetary investments into ecologically oriented river management plans are difficult to justify. The objective of this study was to reveal how the public in four European countries values ecological characteristics of domestic rivers and the outcomes of hypothetical river basin management plans designed to improve river ecosystems, particularly fish biodiversity. We conducted a choice experiment among the populations in Norway, Sweden, Germany, and France. We found similar preference structures in all countries with high marginal willingness-to-pay for improvements of abiotic river attributes (increased accessiblity of the river banks, improved bathing water quality, decreased river fragmentation). Citizens also benefited from certain fish species occurring in a river with native salmonid species being more valued than nonnatives, particularly in Norway, and from the degree of a river's native biodiversity. Welfare measures calculated for selected river basin management plans (policy scenarios) revealed societal benefits that were primarily derived from ecological river management whereas a scenario focusing on hydroelectricity production generated the lowest utility. We conclude that ecological river management may produce high nonmarket economic benefits in all study countries, particularly through the management of abiotic river attributes and the restoration of declining or extinct fish species. Our results help to inform decisions on restoration efforts by showcasing the benefits that these measures have for the public.


Magnetic fields on British trains.
People on trains can be exposed to static and alternating magnetic fields which are higher than background levels in most homes and many workplaces. Quantification of such exposure may be of interest for epidemiological purposes but it is also important to ensure that exposure guidelines are complied with. This article describes the types of electric trains and trams in use in the UK and the results of measurements of static and alternating magnetic flux density. Many of the data have been supplied by the operators of the systems described. The measurements summarised in this article are indicative of the magnitudes of magnetic field exposures to be encountered on British trains, but without concomitant frequency information, they are not sufficient to allow demonstration of compliance with exposure standards.


High Variability in Lymph Node Counts Among an International Cohort of Pathologists: Questioning the Scientific Validity of Node Counts.
Background: The enumeration of lymph nodes (LNs) from surgical specimens plays a critical role in the staging of patients with cancer. LN count (LNC) can affect prognosis, staging, adequacy of resection, and/or eligibility for clinical trials. However, there is no standard method for counting LNs. Most studies in the literature site the pathology report as the source of LN data, without discussion of the counting criteria. Patients and Methods: Four microscopic slides from separate pelvic LN dissections were digitally scanned and uploaded with their gross descriptions to an online library and an online survey. Respondents were asked how many LNs they would count per slide as part of a staging procedure. The survey was distributed to an international cohort of pathologists. Results: A total of 122 surveys were returned: 79 from practicing pathologists and 43 from residents/fellows. There was no statistical difference between the groups. All slides showed significant individual variability. The LNC range for each slide was as follows: slide 1, 1-3; slide 2, 0-13; slide 3, 1-8; slide 4, 1-11. The intraclass correlation (ICC) for all responders was 0.26 (95% CI, 0.05<ICC<0.74), which demonstrates a very low agreement among individuals. Although there is a small amount of literature assessing causes of variability in counts, nearly all focus on different techniques at the grossing bench. Our study is the largest prospective assessment of LNC by an international cohort of pathologists. We have demonstrated tremendous variation in the number of LNs pathologists report for a given slide, thus significantly altering how many total LNs are counted. This calls into question the clinical utility of node counts, as well as their use as a quality indicator. Conclusions: LNC is subject to tremendous interpathologist variation, which has a significant clinical and research impact. Consensus in pathologic handling and microscopic enumeration of LNs is essential.


[The release of forensic patients (63 StGB) and the problem of predicting dangerousness].
This article presents first results of a prospective prediction study with participation of twenty-three forensic institutions from seven states of FRG. Main objective of this study is the determination of valid criteria for predicting recidivism of mentally disordered offenders. This evaluation (n = 188) investigates which patients are presently released from forensic institutions. In comparison to previous studies the releases per annum have decreased significantly. In the last two years there has been an increase in release of schizophrenic patients and a decrease in release of patients with a personality disorder and sexual offenders. In addition it has been analyzed which criteria therapists use to predict dangerousness from a clinical point of view.


Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells.
Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti‑inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration‑dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose‑dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin‑induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)‑JNK and p‑p38, and cleaved poly‑ADP ribose polymerase, and decreased the levels of Bcl‑2 and p‑ERK1/2 in a concentration‑dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor‑inhibitory effect. Immunohistochemical staining revealed elevated expression of p‑JNK and p‑p38 as well as reduced expression of p‑ERK1/2 associated with silymarin‑treatment. Silymarin was revealed to reduce tumor growth through inhibition of p‑ERK and activation of p‑p38 and p‑JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.


Corporal punishment bans and physical fighting in adolescents: an ecological study of 88 countries.
To examine the association between corporal punishment bans and youth violence at an international level. Ecological study of low-income to high-income 88 countries. School-based health surveys of students. 403 604 adolescents. National corporal punishment bans. Age-standardised prevalence of frequent physical fighting (ie, 4+ episodes in the previous year) for male and female adolescents in each country. Frequent fighting was more common in males (9.9%, 95% CI 9.1% to 10.7%) than females (2.8%, 95% CI 2.5% to 3.1%) and varied widely between countries, from 0.9% (95% CI 0.8% to 0.9%) in Costa Rican females to 34.8% (95% CI 34.7 to 35.0) in Samoan males. Compared with 20 countries with no ban, the group of 30 countries with full bans (in schools and in the home) experienced 69% the rate of fighting in males and 42% in females. Thirty-eight countries with partial bans (in schools but not in the home) experienced less fighting in females only (56% the rate found in countries without bans). Country prohibition of corporal punishment is associated with less youth violence. Whether bans precipitated changes in child discipline or reflected a social milieu that inhibits youth violence remains unclear due to the study design and data limitations. However, these results support the hypothesis that societies that prohibit the use of corporal punishment are less violent for youth to grow up in than societies that have not.


Control of Citrus Post-harvest Green Molds, Blue Molds, and Sour Rot by the Cecropin A-Melittin Hybrid Peptide BP21.
In this study, the activity of the cecropin A-melittin hybrid peptide BP21 (Ac-FKLFKKILKVL-NH2) in controlling of citrus post-harvest green and blue molds and sour rot and its involved mechanism was studied. The minimum inhibitory concentrations of BP21 against Penicillium digitatum, Penicillium italicum, and Geotrichum candidum were 8, 8, and 4 μmol L-1, respectively. BP21 could inhibit the growth of mycelia, the scanning electron microscopy results clearly showed that the mycelia treated with BP21 shrank, formed a rough surface, became distorted and collapsed. Fluorescent staining with SYTOX Green (SG) indicated that BP21 could disintegrate membranes. Membrane permeability parameters, including extracellular conductivity, the leakage of potassium ions, and the release of cellular constituents, visibly increased as the BP21 concentration increased. Gross and irreversible damage to the cytoplasm and membranes was observed. There was a positive correlation between hemolytic activity and the concentration of BP21. These results suggest peptide BP21 could be used to control citrus post-harvest diseases.


Doped Graphene Quantum Dots UV-vis Absorption Spectrum: A High-Throughput TDDFT Study.
We report on time-dependent density functional theory calculations of the excited states of 63 different graphene quantum dots (GQDs) in square shape with side lengths of 1, 1.5, and 2 nm. We investigate the systematics and trends in the UV-vis absorption spectra of these GQDs, which are doped with elements B, N, O, S, and P at dopant percentages of 1.5%, 3%, 5%, and 7%. The results show how the peaks in the UV and visible parts of the spectrum as well as the total absorption evolve in the chemical parameter space along the coordinates of size, dopant type, and dopant percentage. The absorption spectra calculated here can be used to obtain particular GQD mixture proportions that would yield a desired absorption profile such as flat absorption across the whole visible spectrum or one that is locally peaked around a chosen wavelength.


Effect of cadmium and parathion on renal function in rat.
Our results suggest that parathion induces a stimulating effect on PAH uptake. The simultaneous presence of cadmium does not modify this effect. The simultaneous presence of cadmium and parathion produced an hepatotoxic effect in the rat.


Age of onset for binge eating and purging during late adolescence: a 4-year survival analysis.
This prospective study examined age of onset for binge eating and purging among girls during late adolescence and tested whether dieting and negative affectivity predicted these outcomes. Of initially asymptomatic adolescents, 5% reported onset of objective binge eating, 4% reported onset of subjective binge eating, and 4% reported onset of purging. Peak risk for onset of binge eating occurred at age 16, whereas peak risk for onset of purging occurred at age 18. Adolescents more often reported onset of a single symptom rather than multiple symptoms, and symptoms were episodic. Dieting and negative affectivity predicted onset of binge eating and purging. Findings suggest that late adolescence is a high-risk period for onset of bulimic behaviors and identify modifiable risk factors for these outcomes.


The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin's DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.


Direct characterization of linear-optical networks.
We introduce an efficient method for fully characterizing multimode linear-optical networks. Our approach requires only a standard laser source and intensity measurements to directly and uniquely determine all moduli and non-trivial phases of the matrix describing a network. We experimentally demonstrate the characterization of a 6×6 fiber-optic network and independently verify the results via nonclassical two-photon interference.


Evidence of an intestinal phosphate transporter alternative to type IIb sodium-dependent phosphate transporter in rats with chronic kidney disease.
Phosphate is absorbed in the small intestine via passive flow and active transport.NaPi-IIb, a type II sodium-dependent phosphate transporter, is considered to mediate active phosphate transport in rodents. To study the regulation of intestinal phosphate transport in chronic kidney disease (CKD), we analyzed the expression levels of NaPi-IIb, pituitary-specific transcription factor 1 (PiT-1) and PiT-2 and the kinetics of intestinal phosphate transport using two CKD models. CKD was induced in rats via adenine orThy1 antibody injection. Phosphate uptake by intestinal brush border membrane vesicles (BBMV) and the messenger RNA (mRNA) expression of NaPi-IIb, PiT-1 and PiT-2 were analyzed. The protein expression level of NaPi-IIb was measured by mass spectrometry (e.g. liquid chromatography tandem mass spectrometry). In normal rats, phosphate uptake into BBMV consisted of a single saturable component and its Michaelis constant (Km) was comparable to that of NaPi-IIb. The maximum velocity (Vmax) correlated with mRNA and protein levels of NaPi-IIb. In the CKD models, intestinal phosphate uptake consisted of two saturable components. The Vmax of the higher-affinity transport, which is thought to be responsible for NaPi-IIb, significantly decreased and the decrease correlated with reduced NaPi-IIb expression. The Km of the lower-affinity transport was comparable to that of PiT-1 and -2. PiT-1 mRNA expression was much higher than that of PiT-2, suggesting that PiT-1 was mostly responsible for phosphate transport. This study suggests that the contribution of NaPi-IIb to intestinal phosphate absorption dramatically decreases in rats with CKD and that a low-affinity alternative to NaPi-IIb, in particular PiT-1, is upregulated in a compensatory manner in CKD.


Dental infections and cardiovascular diseases: a review.
Accumulating evidence suggests that chronic infections, such as periodontitis, are associated with increased risk for cardiovascular diseases (CVD). The mechanisms behind the association are not known. Like herpes viruses and Chlamydia pneumoniae, periodontal pathogens cause atherosclerosis in experimental animals and have been found in human atherosclerotic lesions. Higher concentrations of total and low density lipoprotein (LDL) cholesterol and triglycerides and lower concentrations of high density lipoprotein (HDL) cholesterol have been observed in individuals with periodontitis before periodontal treatment. Periodontitis also induces a peripheral inflammatory and immune response, reflected in elevated concentrations of C-reactive protein (CRP) and IgA-class antibodies to periodontal pathogens. The prevalence of CVD seems to be highest in those individuals in whom periodontitis coexists with elevated CRP levels. This may indicate that periodontitis is a CVD risk factor in individuals who react to the infection with a systemic inflammatory and immune response. This may be due to genetic reasons and may also apply to other chronic low-grade infections.


Integration of Maps Enables a Cytogenomics Analysis of the Complete Karyotype in Solea senegalensis.
The Pleuronectiformes order, which includes several commercially-important species, has undergone extensive chromosome evolution. One of these species is Solea senegalensis, a flatfish with 2n = 42 chromosomes. In this study, a cytogenomics approach and integration with previous maps was applied to characterize the karyotype of the species. Synteny analysis of S. senegalensis was carried out using two flatfish as a reference: Cynoglossus semilaevis and Scophthalmus maximus. Most S. senegalensis chromosomes (or chromosome arms for metacentrics and submetacentrics) showed a one-to-one macrosyntenic pattern with the other two species. In addition, we studied how repetitive sequences could have played a role in the evolution of S. senegalensis bi-armed (3, and 5-9) and acrocentric (11, 12 and 16) chromosomes, which showed the highest rearrangements compared with the reference species. A higher abundance of TEs (Transposable Elements) and other repeated elements was observed adjacent to telomeric regions on chromosomes 3, 7, 9 and 16. However, on chromosome 11, a greater abundance of DNA transposons was detected in interstitial BACs. This chromosome is syntenic with several chromosomes of the other two flatfish species, suggesting rearrangements during its evolution. A similar situation was also found on chromosome 16 (for microsatellites and low complexity sequences), but not for TEs (retroelements and DNA transposons). These differences in the distribution and abundance of repetitive elements in chromosomes that have undergone remodeling processes during the course of evolution also suggest a possible role for simple repeat sequences in rearranged regions.


Bioluminescent symbionts of the Caribbean flashlight fish (Kryptophanaron alfredi) have a single rRNA operon.
Ribosomal RNA (rRNA) operon copy number and gene order were determined for the luminous bacterial symbiont of Kryptophanaron alfredi, an anomalopid (flashlight) fish, and estimated for the luminous symbionts of 3 other fish families and of 3 luminous seawater isolates. Compared with the seawater isolates and other fish symbionts, the copy number of rRNA genes in the K. alfredi symbiont was radically reduced, although gene order appeared conserved among all the strains. The K. alfredi symbiont possesses only a single rRNA operon, whereas the other strains examined have minimum copy numbers ranging from 8 to 11. No difference in copy number was observed between light organ and seawater isolates of the same species, or between isolates of the same species from the light organs of 2 different host families. Thus, the anomalopid symbiosis appears unique among characterized light organ symbioses.


Creation and Testing of a Deep Learning Algorithm to Automatically Identify and Label Vessels, Nerves, Tendons, and Bones on Cross-sectional Point-of-Care Ultrasound Scans for Peripheral Intravenous Catheter Placement by Novices.
We sought to create a deep learning (DL) algorithm to identify vessels, bones, nerves, and tendons on transverse upper extremity (UE) ultrasound (US) images to enable providers new to US-guided peripheral vascular access to identify anatomy. We used publicly available DL architecture (YOLOv3) and deidentified transverse US videos of the UE for algorithm development. Vessels, bones, tendons, and nerves were labeled with bounding boxes. A total of 203,966 images were generated from videos, with corresponding label box coordinates in a YOLOv3 format. Training accuracy, losses, and learning curves were tracked. As a final real-world test, 50 randomly selected images from unrelated UE US videos were used to test the DL algorithm. Four different versions of the YOLOv3 algorithm were tested with varied amounts of training and sensitivity settings. The same 50 images were labeled by 2 blinded point-of-care ultrasound (POCUS) experts. The area under the curve (AUC) was calculated for the DL algorithm and POCUS expert performance. The algorithm outperformed POCUS experts in detection of all structures in the UE, with an AUC of 0.78 versus 0.69 and 0.71, respectively. When considering vessels, only one of the POCUS experts attained an AUC of 0.85, just ahead of the DL algorithm, with an AUC of 0.83. Our DL algorithm proved accurate at identifying 4 common structures on cross-sectional US imaging of the UE, which would allow novice POCUS providers to more confidently and accurately target vessels for cannulation, avoiding other structures. Overall, the algorithm outperformed 2 blinded POCUS experts.


The effects of methyl palmitate, a putative regulator from perivascular fat, on the contractility of pregnant human myometrium.
Methyl palmitate is thought to cause relaxation in vascular smooth muscle by opening voltage-activated potassium channels. We have tested the hypothesis that methyl palmitate, a putative regulator from perivascular fat, is an inhibitor of the contractility of human pregnant myometrium and that its effects might partially explain the higher incidence of dysfunctional labor in obese women compared to those with normal body mass indices. Strips of myometrium obtained with informed consent from women undergoing elective cesarean section at term were mounted in organ baths. Strips stimulated with oxytocin (1nM) or KCl (30mM) were exposed to cumulatively increasing concentrations of methyl palmitate up to 10μM. Similar strips were exposed to cumulative addition of the potassium channel blockers 4-aminopyridine and tetraethylammonium. The contractility of the strips was monitored and analyzed using conventional methods. Methyl palmitate failed to inhibit oxytocin- or KCl-induced contractions over the concentration range tested. In fact, it exerted a slight excitatory effect in the presence of KCl, though not in the presence of oxytocin. The contractility of naïve strips was unaltered by exposure to 1μM methyl palmitate. Both 4-aminopyridine and tetraethylammonium produced concentration-dependent contractions of human pregnant myometrium providing pharmacological evidence for the presence of voltage-activated potassium channels in this preparation. Our findings do not support the hypothesis that methyl palmitate is an inhibitor of human pregnant myometrial contractility. Alternate hypotheses must be pursued to explain the higher incidence of dysfunctional labor in obese women.


Time-restricted eating effects on performance, immune function, and body composition in elite cyclists: a randomized controlled trial.
Although there is substantial interest in intermittent fasting as a dietary approach in active individuals, information regarding its effects in elite endurance athletes is currently unavailable. The present parallel randomized trial investigated the effects of a particular intermittent fasting approach, called time-restricted eating (TRE), during 4 weeks of high-level endurance training. Sixteen elite under-23 cyclists were randomly assigned either to a TRE group or a control group (ND). The TRE group consumed 100% of its estimated daily energy needs in an 8-h time window (from 10:00 a.m. to 6:00 p.m.) whilst energy intake in the ND group was distributed in 3 meals consumed between 7:00 a.m. and 9:00 p.m. Fat and fat-free mass were estimated by bioelectrical impedance analysis and VO2max and basal metabolism by indirect gas analyzer. In addition, blood counts, anabolic hormones (i.e. free testosterone, IGF-1) and inflammatory markers (i.e. IL-6, TNF-α) were assessed. TRE reduced body weight (- 2%; p = 0.04) and fat mass percentage (- 1.1%; p = 0.01) with no change in fat-free mass. Performance tests showed no significant differences between groups, however the peak power output/body weight ratio (PPO/BW) improved in TRE group due to weight loss (p = 0.02). Free testosterone and IGF-1 decreased significantly (p = 0.01 and p = 0.03 respectively) in TRE group. Leucocyte count decreased in ND group (p = 0.02) whilst the neutrophils-to-lymphocytes ratio (NLR) decreased significantly (p = 0.03) in TRE group. Our results suggest that a TRE program with an 8-h feeding window elicits weight loss, improves body composition and increases PPO/BW in elite cyclists. TRE could also be beneficial for reducing inflammation and may have a protective effect on some components of the immune system. Overall, TRE could be considered as a component of a periodized nutrition plan in endurance athletes. This trial was retrospectively registered at clinicaltrials.gov as NCT04320784 on 25 March 2020.


Label-free CARS microscopy reveals similar triacylglycerol acyl chain length and saturation in myocellular lipid droplets of athletes and individuals with type 2 diabetes.
Intramyocellular lipid (IMCL) content associates with development of insulin resistance, albeit not in insulin-sensitive endurance-trained athletes (trained). Qualitative and spatial differences in muscle lipid composition may underlie this so-called athlete's paradox. Here we studied triacylglycerol (TAG) composition of individual myocellular lipid droplets (LDs) in trained individuals and individuals with type 2 diabetes mellitus. Trained ([Formula: see text] 71.0 ± 1.6 ml O2 [kg lean body mass (LBM)]-1 min-1), normoglycaemic (fasting glucose 5.1 ± 0.1 mmol/l) individuals and untrained ([Formula: see text] 36.8 ± 1.5 ml O2 [kg LBM]-1 min-1) individuals with type 2 diabetes (fasting glucose 7.4 ± 0.5 mmol/l), with similar IMCL content (3.5 ± 0.7% vs 2.5 ± 0.3%, p = 0.241), but at opposite ends of the insulin sensitivity spectrum (glucose infusion rate 93.8 ± 6.6 vs 25.7 ± 5.3 μmol [kg LBM]-1 min-1 for trained individuals and those with type 2 diabetes, respectively) were included from our database in the present study. We applied in situ label-free broadband coherent anti-Stokes Raman scattering (CARS) microscopy to sections from skeletal muscle biopsies to measure TAG acyl chain length and saturation of myocellular LDs. This approach uniquely permits examination of individual LDs in their native environment, in a fibre-type-specific manner, taking into account LD size and subcellular location. Despite a significant difference in insulin sensitivity, we observed remarkably similar acyl chain length and saturation in trained and type 2 diabetic individuals (chain length: 18.12 ± 0.61 vs 18.36 ± 0.43 number of carbons; saturation: 0.37 ± 0.05 vs 0.38 ± 0.06 number of C=C bonds). Longer acyl chains or higher saturation (lower C=C number) could be detected in subpopulations of LDs, i.e. large LDs (chain length: 18.11 ± 0.48 vs 18.63 ± 0.57 carbon number) and subsarcolemmal LDs (saturation: 0.34 ± 0.02 vs 0.36 ± 0.04 C=C number), which are more abundant in individuals with type 2 diabetes. In contrast to reports of profound differences in the lipid composition of lipids extracted from skeletal muscle from trained and type 2 diabetic individuals, our in situ, LD-specific approach detected only modest differences in TAG composition in LD subpopulations, which were dependent on LD size and subcellular location. If, and to what extent, these modest differences can impact insulin sensitivity remains to be elucidated. Graphical abstract.


Therapeutic relationships in aphasia rehabilitation: Using sociological theories to promote critical reflexivity.
Therapeutic relationships are fundamental in aphasia rehabilitation, influencing patient experience and outcomes. While we have good understandings of the components of therapeutic relationships, there has been little exploration of how and why therapists construct and enact relationships as they do. Sociological theories may help develop nuanced understanding of the values, assumptions and structures that influence practice, and may facilitate critical reflexivity on practice. To explore the potential for theoretical approaches from outside speech-language therapy to enable a deeper understanding of the nature and enactment of therapeutic relationships in aphasia rehabilitation. An explanatory single case study of one speech-language therapist-patient dyad in an in-patient stroke rehabilitation setting. Data included observations of five interactions, two interviews with the client and three interviews with the speech-language therapist. Analysis was guided by analytical pluralism that applied aspects of three sociological theories to guide data analysis and make visible the contextual factors that surround, shape and permeate the enactment of therapeutic relationships. The analysis of this dyad made visible individual, interactional and broader structural features that illustrate the dynamic processes that practitioners and patients undertake to enact therapeutic relationships. Clinical practice could be viewed as a performance with each person continually negotiating how they convey different impressions to others, which shapes what work is valued and foregrounded. The patient and therapist took up or were placed in different positions within the interactions, each with associated expectations and rights, which influenced what types of relationships could, or were likely to, develop. Organizational, rehabilitation and individual practitioner structures assigned rules and boundaries that shaped how the therapist developed and enacted the therapeutic relationship. Whilst the therapist had some agency in her work and could resist the different influencing factors, such resistance was constrained because these structures had become highly internalized and routinized and was not always visible to the therapist. While therapists commonly value therapeutic relationships, social and structural factors consciously and unconsciously influence their ability to prioritize relational work. Sociological theories can provide new lenses on our practice that can assist therapists to be critically reflexive about practice, and to enact changes to how they work to enhance therapeutic relationships with clients. What this paper adds What is already known on the subject Therapeutic relationships are critical in aphasia rehabilitation. We have a good understanding of the different components of therapeutic relationships and how relationships are perceived by patients and practitioners. What this paper adds to existing knowledge This study is novel in its use of sociological lenses to explore contexts and complexities inherent in building and maintaining therapeutic relationships. These are often invisible to the practitioner but can have a significant impact on how relational work is enacted and what forms of relationship are possible. What are the potential or actual clinical implications of this work? This study will support clinicians to critically reflect on how they enact therapeutic relationships and may enhance awareness of the often-hidden factors which influence the ways in which they work.


Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images.
Alzheimer's Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1-3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature.


Hallmarks of telomeres in ageing research.
Telomeres are repetitive DNA sequences at the ends of linear chromosomes. Telomerase, a cellular reverse transcriptase, helps maintain telomere length in human stem cells, reproductive cells and cancer cells by adding TTAGGG repeats onto the telomeres. However, most normal human cells do not express telomerase and thus each time a cell divides some telomeric sequences are lost. When telomeres in a subset of cells become short (unprotected), cells enter an irreversible growth arrest state called replicative senescence. Cells in senescence produce a different constellation of proteins compared to normal quiescent cells. This may lead to a change in the homeostatic environment in a tissue-specific manner. In most instances cells become senescent before they can become cancerous; thus, the initial growth arrest induced by short telomeres may be thought of as a potent anti-cancer protection mechanism. When cells can be adequately cultured until they reach telomere-based replicative senescence, introduction of the telomerase catalytic protein component (hTERT) into telomerase-silent cells is sufficient to restore telomerase activity and extend cellular lifespan. Cells with introduced telomerase are not cancer cells, since they have not accumulated the other changes needed to become cancerous. This indicates that telomerase-induced telomere length manipulations may have utility for tissue engineering and for dissecting the molecular mechanisms underlying genetic diseases, including cancer.


Enhanced expression in spleen macrophages of the mouse homolog to the human putative tumor suppressor gene ZFM1.
We have characterized the cDNA of MZFM, the mouse homolog to the novel human putative tumor suppressor gene ZFM1. The total length of the cDNA is 2,637 nucleotides with an open reading frame for a protein of 548 amino acids containing 4.7% methionine and 17.2% proline. The predicted molecular mass of 59 kD fits the 62-kD band experimentally determined by NaDodSO4-PAGE from in vitro translation products of in vitro-transcribed MZFM cDNA. The MZFM cDNA best matches to that ZFM1-isoform without the so-called 0.25-kb E-domain and to the L49345 cDNA recently identified in a human leukemia cell line. Northern analysis reveals expression of MZFM only in spleen macrophages. Reverse transcription polymerase chain reaction (RT-PCR) in combination with Southern analysis also detects a low basal expression in splenic T cells and B cells, as well as in other tissues such as heart, kidney, brain, liver, testis, bone marrow, adrenal gland, lymph nodes, pancreas, and thymus. In splenic macrophages, MZFM mRNA is alternatively spliced yielding a 3.6-kb transcript with E-domain, a 3.0-kb transcript without E-domain, and a 2.7-kb transcript with E-domain. The predicted MZFM protein contains diverse functional domains, i.e., a nuclear localization signal, a metal binding motif, a glutamine/proline stretch, proline-clusters, a CGA-motif, and a QUA1-KH-QUA2 region, thus indicating multiple functions of MZFM. Presumably, MZFM is a new member of those proteins combining features of signal transduction and RNA activation (STAR-proteins). The different MZFM-isoforms may be part of a macrophage-inherent program of transduction of environmental signals into different activational states of macrophages.


MS-TCN++: Multi-Stage Temporal Convolutional Network for Action Segmentation.
With the success of deep learning in classifying short trimmed videos, more attention has been focused on temporally segmenting and classifying activities in long untrimmed videos. State-of-the-art approaches for action segmentation utilize several layers of temporal convolution and temporal pooling. Despite the capabilities of these approaches in capturing temporal dependencies, their predictions suffer from over-segmentation errors. In this paper, we propose a multi-stage architecture for the temporal action segmentation task that overcomes the limitations of the previous approaches. The first stage generates an initial prediction that is refined by the next ones. In each stage we stack several layers of dilated temporal convolutions covering a large receptive field with few parameters. While this architecture already performs well, lower layers still suffer from a small receptive field. To address this limitation, we propose a dual dilated layer that combines both large and small receptive fields. We further decouple the design of the first stage from the refining stages to address the different requirements of these stages. Extensive evaluation shows the effectiveness of the proposed model in capturing long-range dependencies and recognizing action segments. Our models achieve state-of-the-art results on three datasets: 50Salads, Georgia Tech Egocentric Activities (GTEA), and the Breakfast dataset.


Protein kinase C and intracellular free Ca++: relationship to human immunodeficiency virus (HIV)-induced cellular hyporesponsiveness.
Protein Kinase C (PKC) and Ca++ are both involved in the chain of events leading to T-cell activation. An impairment of the immune response is characteristic of T cells obtained from patients with HIV infection. In this report, the involvement of PKC and Ca++ in HIV-mediated cellular hyporesponsiveness was examined. Infection of peripheral blood mononuclear cells (PBMC)s from HIV-seronegative normal donors with HIV strain HTLV IIIB, or two fresh patient isolates produced a 1.4-, 10.7-, and 11.4-fold enhancement in PKC activity at 1 hr postinfection (PI) and a 1.8-, 2.3-, and 3.8-fold enhancement at 12 hr PI, respectively. A marked decrease of PKC content, as determined by Western Blot analysis, was observed in HIV-infected cells by Day 4 and 7 PI compared with mock-infected control cells. Furthermore, PKC synthesis was also inhibited in cells from immunosuppressed AIDS patients. PKC activity of PBMCs from HIV-infected patients did not change in response to 1 microM of phorbal myristate acetate (PMA). In contrast, the same dose enhanced the activity by 50%-100% in PBMCs from normal HIV-seronegative donors. A 40%, 50%, and 125% increase in intracellular free Ca++ in response to HIV infection was observed 12 hr PI in MT4, JURKAT, and PBMCs, respectively. However, the increase in intracellular free Ca++ in HIV-infected PBMCs obtained from normal donors in response to PHA was 56% and 17% compared with an increase of 100% and 120% in mock infected cells at 12 hr and 1 week PI, respectively. Comparing the Ca++ response to PHA in PBMCs from HIV-infected patients showed that patients with < 250 absolute T4 cells/mm3 had an impaired Ca++ response. These data suggest that there is a relationship between intracellular free Ca++ and PKC and HIV-induced T-cell hyporesponsiveness.


Cucurbitacin B inhibits tumor angiogenesis by triggering the mitochondrial signaling pathway in endothelial cells.
Cucurbitacin B (CuB), the active component of a traditional Chinese herbal medicine, Pedicellus Melo, has been shown to exhibit antitumor and anti-inflammation effects, but its role in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism are unknown. Tumor angiogenesis is one of the hallmarks of the development in malignant neoplasias and metastasis. Effective targeting of tumor angiogenesis is a key area of interest for cancer therapy. Here, we demonstrated that CuB significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration, tubulogenesis in vitro, and blocked angiogenesis in chick embryo chorioallantoic membrane (CAM) assay in vivo. Furthermore, CuB induced HUVEC apoptosis and may induce apoptosis by triggering the mitochondrial apoptotic pathway. Finally, we found that CuB inhibiting angiogenesis was associated with inhibition of the activity of vascular endothelial growth factor receptor 2 (VEGFR2). Our investigations suggested that CuB was a potential drug candidate for angiogenesis related diseases.


Self-Control in Aiming Supports Coping With Psychological Pressure in Soccer Penalty Kicks.
This study addressed the question whether coaches better allow athletes to self-control their decisions when under pressure or whether to impose a decision upon them. To this end, an experiment was conducted that manipulated the soccer kickers' degree of control in decision-making. Two groups of elite under-19 soccer players (n = 18) took penalty kicks in a self-controlled (i.e., kickers themselves decided to which side to direct the ball) and an externally controlled condition (i.e., the decision to which side to direct the ball was imposed upon the kickers). One group performed the penalty kick under psychological pressure (i.e., the present coaching staff assessed their performance), while the second group performed without pressure. Just before and after performing the kicks, CSAI-2 was used to measure cognitive and somatic anxiety and self-confidence. Further, the number of goals scored, ball placement and speed, and the duration of preparatory and performatory behaviors were determined. The results verified increased levels of cognitive and somatic anxiety after performing the kicks in the pressured group compared to the no-pressure group. In addition, degree of self-control affected the participants' performance, particularly in the pressured group. They scored more goals and placed the kicks higher in the self-controlled than in the externally-controlled condition. Participants also took more time preparing and performing the run-up in the self-controlled condition. Findings indicate that increased self-control helps coping with the debilitating effects of pressure and can counter performance deteriorations. The findings are discussed within the framework of self-control theories, and recommendations for practitioners and athletes are made.


[The detection and diagnosis of pulmonary tuberculosis in an investigatory isolation ward].
The purpose of the study was to examine the implication of radiation and microbiological methods in the timely detection and diagnosis of pulmonary tuberculosis in untried prisoners in an investigatory isolation ward. Fluorographic films made in 12,298 convicts were analyzed. Abnormal fluorograms were revealed in 14 and 7.7% of the untried prisoners in 2005 and 2006, respectively; the changes were tuberculosis-associated in 70.2% of cases. Fluorescence microscopy and inoculation were used to carry out sputum tests for Mycobacterium tuberculosis in 41.1% of the convicts with abnormal fluorograms and complaints about productive cough. Early diagnosis of pulmonary tuberculosis was made by microscopy in 14.9% of the prisoners; the diagnosis of tuberculosis was verified by the inoculation test in 34.5% of negative microscopy patients. In the remaining patients, the diagnosis of tuberculosis was based on X-ray studies and the results of treatment.


Tertiary mental health services: I. Key concepts.
There are some individuals with severe and persistent mental illnesses who cannot be managed by primary and secondary services and who require tertiary care. Such clients are characterized by aggressiveness, noncompliance with medication, and dangerousness. Tertiary care program elements include psychosocial rehabilitation, sophisticated medication management, and behavioural approaches. Tertiary care may be delivered through assertive community treatment and/or specialized outreach teams, community residential programs, or hospital-based services. Increasingly, organized systems have been developed to ensure that individuals meet criteria for tertiary care and receive the most appropriate level of care. Most importantly, the delivery of tertiary care must not be tied to particular settings or time frames, and level of care must be delinked from model or location of care in order to create flexible, efficient, effective mental health services.


Tobacco-specific nitrosamine adducts: studies in laboratory animals and humans.
This paper describes quantitation of human hemoglobin and DNA adducts of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are believed to be involved in cancers of the lung, esophagus, oral cavity, and pancreas in people who use tobacco products. The adduct dosimetry method employs GC-MS for quantitation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) released by mild base hydrolysis of hemoglobin or acid hydrolysis of DNA as a biochemical marker of the pyridyloxobutylation metabolic activation pathway. Approximately 22% of smokers (n = 101) had elevated levels of HPB released from hemoglobin (range, 200-1600 fmole/g Hb). Adduct levels in snuff dippers ranged from 200-1800 fmole/g Hb. HPB levels in nonsmokers were generally below the detection limit. Acid hydrolysis of lung and tracheal DNA obtained at autopsy and analysis for released HPB revealed levels ranging up to 50 fmole/mg DNA in smokers; the adduct was not detected in nonsmokers. These findings are consistent with data generated in studies of adduct formation by NNK in rats. The biological significance of the HPB-releasing DNA pyridyloxobutylation pathway was compared to that of the DNA methylation pathway in the A/J mouse. These studies demonstrated that the persistence of O6-methylguanine in lung DNA is critical for tumorigenesis by NNK and that pyridyloxobutylation enhances both persistence of O6-methylguanine and tumorigenesis by acetoxymethylmethylnitrosamine. In the rat, the relative roles of methylation and pyridyloxobutylation in lung tumorigenesis by NNK are not as clearly defined.(ABSTRACT TRUNCATED AT 250 WORDS)


Sleep disorders increase the risk of burning mouth syndrome: a retrospective population-based cohort study.
Sleep disorders (SD), including apnea and nonapnea, and burning mouth syndrome (BMS) have been mutually associated with systemic diseases. Based on our research, the association between BMS and SD has not been elucidated. We determined whether SD patients have an increased risk of BMS. We used information from health insurance claims obtained from the Taiwanese National Health Insurance (NHI) program. We identified patients newly diagnosed with sleep apnea syndrome between 1998 and 2001 as the apnea SD cohort, and newly diagnosed patients with nonapnea SD as the nonapnea SD cohort. The non-SD cohort was 1:2 frequency matched the case group according to sex, age, and index year. We analyzed the risks of BMS by using Cox proportional hazards regression models. Compared with the non-SD cohort, both of the apnea SD (adjusted HR = 2.56, 95% CI = 1.30-5.05) and nonapnea SD (adjusted HR = 2.89, 95% CI = 2.51-3.34) were associated with a significantly higher risk of BMS. The hazard ratio (HR) increased with increased age in the apnea SD cohort and in the nonapnea SD cohort compared with patients younger than 40 years of age. Female apnea SD patients (IRR = 4.63, 95% CI = 3.82-5.61) had a higher risk of developing BMS than did male patients (IRR = 1.76, 95% CI = 1.39-2.24). Based on our research, SD might increase the risk of BMS.


Genistein elicits pleiotropic molecular effects on head and neck cancer cells.
Genistein (4,5,7-trihydroxyisoflavone) has been reported to induce cell cycle arrest and apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We have previously reported (S. A. Alhasan et al., Nutr. Cancer, 34:12-19, 1999; S. A. Alhasan et al., Int. J. Oncol., 16: 333-338, 2000) that genistein induces cell cycle arrest and apoptosis by up-regulating p21(WAF1) and Bax, and down-regulating cyclin B1 and Bcl-2 in a head and neck cancer cell line. However, the precise molecular mechanism(s) by which genistein elicits its effects on head and neck cancer cells still remains to be elucidated. In the present study, we report that genistein induces several specific molecular changes in head and neck cancer cells, such as down-regulation of c-erbB-2 expression, down-regulation of MMP-2 and MMP-9 secretion, inhibition of tumor cell invasion and down-regulation of nuclear factor-kappaB DNA binding activity. In addition, genistein inhibited the levels of phosphorylated Akt and the expression of 14-3-3 protein. Moreover, genistein induces telomere shortening in treated cells without affecting telomerase activity in vitro. We also observed that genistein inhibits the translocation of telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] to the nucleus, which may result in telomere shortening, although the activity of telomerase is unaffected, along with the inhibition of metaphase spread of chromosomes. From these results, together with our previously published reports, (S. A. Alhasan et al., Nutr. Cancer, 34: 12-19, 1999; S. A. Alhasan et al., Int. J. Oncol., 16: 333-338, 2000) we conclude that genistein elicits pleiotropic molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of head and neck cancer cells, which suggests that genistein may be useful as a chemotherapeutic and/or chemopreventive agent for head and neck cancer.


[Effect of antiretroviral therapy on carotid intima-media thickness in HIV-infected patients].
The introduction of highly active antiretroviral therapy reduced HIV-associated morbidity and mortality, at the cost of adverse metabolic effects that increase cardiovascular risk. The aim of this study was to evaluate the impact of exposure to protease inhibitors (PI) compared with exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI) on carotid intima-media thickness (IMT) and blood flow velocity and to measure vascular involvement over a 2-year follow-up in HIV-infected patients treated with PI. Thirty-five HIV-infected patients treated with PI (group I) and 15 patients treated with NNRTI (group II) underwent epiaortic vessel ultrasonography. The same evaluation was obtained in a group of 20 healthy subjects. After 20 +/- 2 months, 22 patients of group I were re-evaluated and the follow-up data were compared with those obtained at baseline. The ANOVA test showed a significant difference among the three groups for IMT and flow velocities. Bonferroni analyses showed significant differences in IMT and flow velocities in group I vs group II vs controls: IMT of the right common carotid artery was 0.742 +/- 0.135 mm in group I vs 0.642 +/- 0.131 mm in group II (p < 0.05) and 0.616 +/- 0.069 mm in controls (p = 0.002); IMT of left common carotid artery was 0.720 +/- 0.108 vs 0.659 +/- 0.066 mm (p < 0.05) and 0.640 +/- 0.081 mm (p < 0.01), respectively. There were no differences in group II vs healthy subjects. At follow-up examinations of group I, no significant differences were observed in both IMT and blood flow velocity when compared with baseline values. The HIV-infected patients treated with PI show earlier vascular involvement as compared to those treated with NNRTI and to healthy subjects with similar distribution of cardiovascular risk factors. However, such damage seems to have no significant progression over a 2-year follow-up in HIV-infected patients treated with PI. These data emphasize the need for follow-up studies assessing whether these changes are predictive of adverse cardiac events.


Immune and Inflammatory Pathways Implicated by Whole Blood Transcriptomic Analysis in a Diverse Ancestry Alzheimer's Disease Cohort.
Significant work has identified genetic variants conferring risk and protection for Alzheimer's disease (AD), but functional effects of these variants is lacking, particularly in under-represented ancestral populations. Expression studies performed in easily accessible tissue, such as whole blood, can recapitulate some transcriptional changes occurring in brain and help to identify mechanisms underlying neurodegenerative processes. We aimed to identify transcriptional differences between AD cases and controls in a cohort of diverse ancestry. We analyzed the protein coding transcriptome using RNA sequencing from peripheral blood collected from 234 African American (AA) (115 AD, 119 controls) and 240 non-Hispanic Whites (NHW) (121 AD, 119 controls). To identify case-control differentially expressed genes and pathways, we performed stratified, joint, and interaction analyses using linear regression models within and across ancestral groups followed by pathway and gene set enrichment analyses. Overall, we identified 418 (291 upregulated, 127 downregulated) and 488 genes (352 upregulated, 136 downregulated) differentially expressed in the AA and NHW datasets, respectively, with only 16 genes commonly differentially expressed in both ancestral groups. Joint analyses provided greater power to detect case-control differences and identified 1,102 differentially expressed genes between cases and controls (812 upregulated, 290 downregulated). Interaction analysis identified only 27 genes with different effects in AA compared to NHW. Pathway and gene-set enrichment analyses revealed differences in immune response-related pathways that were enriched across the analyses despite different underlying gene sets. These results support the hypothesis of converging underlying pathophysiological processes in AD across ancestral groups.


Investigation of anterior knee pain after total hip replacement: a pilot study.
There is no previous research to determine if total hip replacement can lead to anterior knee pain. The idea for the present study came from clinical observation of anterior knee pain (AKP) after total hip replacement, and the objective was to investigate anterior knee pain after total hip replacement. The study used a prospective single-system design with a convenience sample. Six men and seven women were assessed before and at six weeks after total hip replacement for the presence and degree of AKP, using a step-down test combined with a visual analogue scale (VAS). Measurements were also taken of leg length, hip and knee motion, thigh circumference and hamstring length using previously validated tests. Eight of thirteen subjects had AKP at six weeks post-operation. Active knee flexion was reduced post-operation (p < 0.0007), and proximal, mid- and distal thigh circumferences were increased (p < 0.0001). Eleven of 13 subjects demonstrated leg lengthening (p < 0.0001), and 10/11 subjects demonstrated a reduction in passive knee flexion (p < 0.002). All biomechanical data were correlated against the VAS. Although none were statistically significant, both decreased active and passive knee flexion, and increased thigh circumference exhibited the greatest trend with the VAS. The results of the present study cannot be compared to other studies, as there are no previous studies on AKP after total hip replacement. Current outcome measures for total hip replacement do not measure for AKP, although it may potentially hinder full functional recovery. Orthopaedic surgeons and physiotherapists need to be aware if this is a possible complication of total hip replacement, and hence further research is required to test external validity.


Parathyroid Hormone Regulates Circulating Levels of Sclerostin and FGF23 in a Primary Hyperparathyroidism Model.
Parathyroid hormone (PTH) increases fibroblast growth factor 23 (FGF23), mediated both by protein kinase A (PKA) and Wnt signaling, and decreases expression of sclerostin, a Wnt antagonist derived from osteocytes. Patients with primary hyperparathyroidism (PHPT) have lower serum sclerostin levels than healthy controls, consistent with the idea of SOST downregulation by PTH. Nevertheless, the relationship between FGF23 and sclerostin in PHPT is still unclear. We examined this issue in a mouse model of PHPT. PHPT mice had increased FGF23 and decreased sclerostin expression in calvaria and in their serum concentrations compared with wild-type (WT) mice. In UMR106 osteoblasts, PTH increased Fgf23 expression and decreased Sost expression, as well as forskolin, a PKA agonist, whereas inhibition of PKA reversed the changes in Fgf23 and Sost expression, stimulated by PTH. Sclerostin treatment had no effect on Fgf23 expression, but when it was added together with PTH, it statistically significantly abrogated the increase in Fgf23 expression. By contrast, there was no statistically significant correlation between serum FGF23 and sclerostin, whereas PTH was positively and negatively correlated with serum FGF23 and sclerostin, respectively. These results indicate that the high level of PTH in PHPT mice leads to increased FGF23 and decreased sclerostin expression in serum and calvaria. A decrease of sclerostin may further augment FGF23 in vitro; however, there was no statistically significant association between circulating FGF23 and sclerostin. It is suggested that the pathogenesis of increased FGF23 expression in PHPT mice may be modified by not only sclerostin, but also other regulatory factors modulated by PTH.