Factors associated with antiretroviral treatment interruption in human immunodeficiency virus (HIV)-1-infected children attending the Jos University Teaching Hospital, Jos, Nigeria.
Interrupting anti-retroviral therapy (ART) for any number of reasons is an indication of a compromised adherence to ART. Several factors, including the pill burden from other drugs used in treating co-infections in children with human immunodeficiency virus (HIV), may influence ART adherence. The aim of this study was to identify the factors associated with ART interruption in HIV-1-infected children. A retrospective cohort study analysing data on 580 children consecutively enrolled on ART between February 2006 and December 2010 at the paediatric HIV clinic of Jos University Teaching Hospital (JUTH), Jos. Subjects were children aged 2 months - 15 years diagnosed with HIV-1 infection and on first-line ART. Cotrimoxazole prophylaxis was usually commenced at diagnosis while awaiting ART commencement. Children diagnosed with tuberculosis (TB) were also placed on multiple individual anti-TB drugs. A comparison of the data on children with and without ART interruption was made. Variables associated with ART interruption in a univariate analysis were fit in a multivariate logistic model to determine the factors that were associated with ART interruption. Children on anti-TB drugs were twice more likely to interrupt ART compared to those who were not, (adjusted odds ratio, AOR = 1.84 (1.03-3.28); P = 0.04). But children on cotrimoxazole prophylaxis had a 57% reduction in the odds of interrupting ART compared to those who were not, (AOR = 0.43 (0.20-0.93); P = 0.03). Children on ART and also taking multiple individual anti-TB drugs should be monitored closely for ART adherence. Cotrimoxazole prophylaxis should be encouraged in children diagnosed with HIV while awaiting ART commencement as this may prime them for a better ART adherence.


On the potential roles of ticks and migrating birds in the ecology of West Nile virus.
Mosquitoes are the primary vectors of West Nile virus (WNV). Ticks have, however, been suggested to be potential reservoirs of WNV. In order to investigate their role in the spread of the virus, ticks, which had been collected from birds migrating northwards from Africa to Europe, were analyzed for the potential presence of WNV-RNA. On the Mediterranean islands Capri and Antikythira a total of 14,824 birds were captured and investigated from which 747 ticks were collected. Most of the identified ticks (93%) were nymphs and larvae of Hyalomma marginatum sensu lato, most of which were or appear to be Hyalomma rufipes. Of these ticks 729 were individually screened for WNV-RNA. None of the ticks was found to be WNV positive. Thus, there was no evidence that Hyalomma marginatum s.l. ticks play a role in the spread of WNV from Africa to Europe.


We Know the Yin-But Where Is the Yang? Toward a Balanced Approach on Common Source Bias in Public Administration Scholarship.
Surveys have long been a dominant instrument for data collection in public administration. However, it has become widely accepted in the last decade that the usage of a self-reported instrument to measure both the independent and dependent variables results in common source bias (CSB). In turn, CSB is argued to inflate correlations between variables, resulting in biased findings. Subsequently, a narrow blinkered approach on the usage of surveys as single data source has emerged. In this article, we argue that this approach has resulted in an unbalanced perspective on CSB. We argue that claims on CSB are exaggerated, draw upon selective evidence, and project what should be tentative inferences as certainty over large domains of inquiry. We also discuss the perceptual nature of some variables and measurement validity concerns in using archival data. In conclusion, we present a flowchart that public administration scholars can use to analyze CSB concerns.


Validity and Inter-observer Reliability of the TURN 180 Test to Identify Older Adults Who Reported Falls.
Falls while turning are associated with increased risk of hip fracture in older adults. Reliable and clinically valid methods for turn ability assessments are needed. To explore the inter-observer reliability and known group validity of the TURN 180 test. We divided 78 independent older adults (mean age 76.6 ± 6.5 years) into three groups: non-fallers, infrequent fallers (1-2 falls per year), and recurrent fallers (> 2 falls per year). Participants underwent performance-based tests: Timed Up and Go (TUG), Performance Oriented Mobility Assessment (POMA), and Berg Balance Scale (BBS). TUG was videotaped for later analysis of the TURN 180 test by two blinded observers. A significant difference was found in the TURN 180 test parameters among the groups (P < 0.04). TURN 180 was highly correlated with TUG (r = 0.81-0.89, P < 0.001) and BBS (r = -0.704-0.754, P < 0.0001) and moderately with POMA (r = -0.641-0.698, P < 0.0001). The number of steps was found to be the strongest parameter to determine fallers among older adults (specificity 96.3%, sensitivity 40%). Inter-rater reliability (intraclass correlation coefficient 0.91-0.96, P < 0.0001) was found to be excellent for the number of steps, time taken to accomplish a turn, and total test score categories. The TURN 180 test is highly reliable and can identify the older adults who fall. Our results show that the TURN 180 test can serve as a good performance-based examination for research or clinical setting.


The advanced dementia prognostic tool: a risk score to estimate survival in nursing home residents with advanced dementia.
Estimating life expectancy is challenging in advanced dementia. To create a risk score to estimate survival in nursing home (NH) residents with advanced dementia. This was a retrospective cohort study performed in the setting of all licensed U.S. NHs. Residents with advanced dementia living in U.S. NHs in 2002 were identified using Minimum Data Set (MDS) assessments. Mortality data from Medicare files were used to determine 12-month survival. Independent variables were selected from the MDS. Cox proportional hazards regression was used to model survival. The accuracy of the final model was assessed using the area under the receiver operating characteristic curve (AUROC). To develop a risk score, points were assigned to variables in the final model based on parameter estimates. Residents meeting hospice eligibility guidelines for dementia, based on MDS data, were identified. The AUROC assessed the accuracy of hospice guidelines to predict six-month survival. Over 12 months, 40.6% of residents with advanced dementia (n=22,405) died. Twelve variables best predicted survival: length of stay, age, male, dyspnea, pressure ulcers, total functional dependence, bedfast, insufficient intake, bowel incontinence, body mass index, weight loss, and congestive heart failure. The AUROC for the final model was 0.68. The risk score ranged from 1 to 32.5 points (higher scores indicate worse survival). Only 15.9% of residents met hospice eligibility guidelines for which the AUROC predicting six-month survival was 0.53. A mortality risk score derived from MDS data predicted six-month survival in advanced dementia with moderate accuracy. The predictive ability of hospice guidelines, simulated with MDS data, was poor.


Capturing Alzheimer's disease genomes with induced pluripotent stem cells: prospects and challenges.
A crucial limitation to our understanding of Alzheimer's disease (AD) is the inability to test hypotheses on live, patient-specific neurons. Patient autopsies are limited in supply and only reveal endpoints of disease. Rodent models harboring familial AD mutations lack important pathologies, and animal models have not been useful in modeling the sporadic form of AD because of complex genetics. The recent development of induced pluripotent stem cells (iPSCs) provides a method to create live, patient-specific models of disease and to investigate disease phenotypes in vitro. In this review, we discuss the genetics of AD patients and the potential for iPSCs to capture the genomes of these individuals and generate relevant cell types. Specifically, we examine recent insights into the genetic fidelity of iPSCs, advances in the area of neuronal differentiation, and the ability of iPSCs to model neurodegenerative diseases.


Management of abnormal uterine bleeding - focus on ambulatory hysteroscopy.
The rapid evolution in ambulatory hysteroscopy (AH) has transformed the approach to diagnose and manage abnormal uterine bleeding (AUB). The medical management in primary care remains the mainstay for initial treatment of this common presentation; however, many women are referred to secondary care for further evaluation. To confirm the diagnosis of suspected intrauterine pathology, the traditional diagnostic tool of day case hysteroscopy and dilatation and curettage in a hospital setting under general anesthesia is now no longer required. The combination of ultrasound diagnostics and modern AH now allows thorough evaluation of uterine cavity in an outpatient setting. Advent of miniature hysteroscopic operative systems has revolutionized the ways in which clinicians can not only diagnose but also treat menstrual disorders such as heavy menstrual bleeding, intermenstrual bleeding and postmenopausal bleeding in most women predominantly in a one-stop clinic. This review discussed the approach to manage women presenting with AUB with a focus on the role of AH in the diagnosis and treatment of this common condition in an outpatient setting.


Using viromes to predict novel immune proteins in non-model organisms.
Immunity is mostly studied in a few model organisms, leaving the majority of immune systems on the planet unexplored. To characterize the immune systems of non-model organisms alternative approaches are required. Viruses manipulate host cell biology through the expression of proteins that modulate the immune response. We hypothesized that metagenomic sequencing of viral communities would be useful to identify both known and unknown host immune proteins. To test this hypothesis, a mock human virome was generated and compared to the human proteome using tBLASTn, resulting in 36 proteins known to be involved in immunity. This same pipeline was then applied to reef-building coral, a non-model organism that currently lacks traditional molecular tools like transgenic animals, gene-editing capabilities, and in vitro cell cultures. Viromes isolated from corals and compared with the predicted coral proteome resulted in 2503 coral proteins, including many proteins involved with pathogen sensing and apoptosis. There were also 159 coral proteins predicted to be involved with coral immunity but currently lacking any functional annotation. The pipeline described here provides a novel method to rapidly predict host immune components that can be applied to virtually any system with the potential to discover novel immune proteins.


Trials, settlements, and arbitration. The plaintiff's perspective.
From a plaintiff's perspective, a jury trial and verdict are prepared for in every case. Experienced trial lawyers know, however, that it is preferable for both sides to reach an equitable compromise as to the value of a case, rather than risk the unknowns involved in a jury determination of a verdict. There are legal elements that require an independent analysis to determine whether a trial, settlement, or some form of arbitration is the appropriate strategy for a plaintiff to pursue.


ALTITUDE-ASSOCIATED INTRAOCULAR PRESSURE CHANGES IN A GAS-FILLED EYE.
Intraocular gases are commonly used in vitreoretinal surgery. Patients are routinely advised against air travel before the complete absorption of intraocular gas. Consequently, reports on air travel in patients with large intraocular gas bubbles are highly unusual. Here, we report the intraocular pressure changes of a patient ascending to an altitude of 2,600 feet in a helicopter with a 50% fill perfluoropropane (C3F8) gas bubble in his left eye. Case report and literature review. A 61-year-old male patient underwent pars plana vitrectomy for a rhegmatogenous retinal detachment, with fluid-gas exchange using 16% C3F8. With a 50% fill bubble in the left eye, the patient took a short helicopter trip ascending to a maximum altitude of 2,600 feet. Before take-off, intraocular pressure in the operated eye was 14 mmHg. The average increase in intraocular pressure was 10.8 mmHg per 1,000 feet of ascent, with a maximum recorded intraocular pressure of 42 mmHg. The patient denied both ocular pain and loss of vision but did report changes in the appearance of the gas bubble meniscus at 2,100 feet. Short-term low-altitude air travel may be tolerated by some patients with intraocular gas in situ. Further studies are required to define the conditions by which patients with gas bubbles may fly safely.


Multi-observation PET image analysis for patient follow-up quantitation and therapy assessment.
In positron emission tomography (PET) imaging, an early therapeutic response is usually characterized by variations of semi-quantitative parameters restricted to maximum SUV measured in PET scans during the treatment. Such measurements do not reflect overall tumor volume and radiotracer uptake variations. The proposed approach is based on multi-observation image analysis for merging several PET acquisitions to assess tumor metabolic volume and uptake variations. The fusion algorithm is based on iterative estimation using a stochastic expectation maximization (SEM) algorithm. The proposed method was applied to simulated and clinical follow-up PET images. We compared the multi-observation fusion performance to threshold-based methods, proposed for the assessment of the therapeutic response based on functional volumes. On simulated datasets the adaptive threshold applied independently on both images led to higher errors than the ASEM fusion and on clinical datasets it failed to provide coherent measurements for four patients out of seven due to aberrant delineations. The ASEM method demonstrated improved and more robust estimation of the evaluation leading to more pertinent measurements. Future work will consist in extending the methodology and applying it to clinical multi-tracer datasets in order to evaluate its potential impact on the biological tumor volume definition for radiotherapy applications.


Diagnosis and management of acute pancreatitis.
Acute pancreatitis usually occurs as a result of alcohol abuse or bile duct obstruction. A careful review of the patient's history and appropriate laboratory studies can help the physician identify the etiology of the condition and guide management. Serum amylase and lipase levels are still used to confirm the diagnosis of acute pancreatitis. Although not routinely available, the serum trypsin level is the most accurate laboratory indicator for pancreatitis. Ultrasonography, computed tomography and endoscopic retrograde cholangiopancreatography are additional modalities that can help the family physician choose the best treatment approach. Prompt identification of patients who need intensive care referral or subspecialty consultation is crucial. The APACHE II and the multiple organ system failure scales provide prognostic information at the time of admission and may be repeated daily to monitor disease progression. Therapies such as nasogastric suctioning, anticholinergics and histamine H2-receptor blockers have not been shown to decrease symptoms or hospital stays in patients with acute pancreatitis. Systemic antibiotics have been found to improve outcome in patients with severe disease. With supportive care, most patients have a good clinical outcome.


Drug discovery for inflammatory diseases.
Drug Discovery for Inflammatory Diseases was a 3-day conference organised by the IBC Life Sciences as part of their Drug Discovery Series. The meeting featured a keynote presentation by Edward Keystone (University of Toronto) on the new strategies in managing rheumatoid arthritis, followed by five themed sessions: protein kinase inhibition, cytokines, chemokines, Toll-like receptors/innate immunity and transcription factors. The programme included a good mix of speakers from academia and biotechnology, and covered a wide spectrum of topics, ranging from developing strategies to suppress immune responses in autoimmune and inflammatory diseases, to novel means of stimulating the immune system for vaccine development and cancer therapy. Fundamental basic science questions were addressed along with the new approaches to drug design and clinical studies. Overall, the meeting included over 25 presentations, and there was ample time to exchange ideas in an informal setting. This review will focus on five talks representing three different areas of research: the role of an unusual cytokine, leptin, in autoimmunity; targeting of Toll-like receptors in vaccine development and in cancer therapy; and the molecular dissection of glucocorticoid-mediated repression and of selective glucocorticoids with anti-inflammatory activities.


The analgesic effect of pamidronate is not caused by the elevation of beta endorphin level in Paget's disease--a controlled pilot study.
Although an analgesic effect is an essential component of the mode of action of bisphosphonates, its physiological mechanisms are still unclear. Beta-endorphin release plays an important role in the analgesic effect of both calcitonin and raloxifene. As patients with Paget's disease receive large doses of bisphosphonates within relatively short time periods, we examined whether repeated pamidronate infusion therapy would cause measurable change in beta-endorphin levels Visual analog scale (VAS) scores of pain intensity, beta-endorphin levels, and alkaline phosphatase activity of 11 patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) were determined at baseline, as well as after 3 and 6 infusions (on Days 6 and 12 of treatment, respectively). Eleven untreated patients with Paget's disease (7 with the mono- and 4 with the polyostotic form) served as controls. It was established that in the course of pamidronate infusion therapy BE levels remained constant, whereas the values in serum alkaline phosphatase and pain intensity scores were significantly reduced. Although high-dose pamidronate therapy does mitigate pain substantially (as demonstrated by the reduction of VAS scores), its analgesic action is probably unrelated to the enhancement of beta-endorphin release.


Tolerance and effects of FK506 (tacrolimus) on nerve regeneration: a pilot study.
In adults, the outcome of nerve suture and nerve autograft remains generally unsatisfactory. FK506 (tacrolimus), an immunosuppressant drug used in transplantation, has been reported in animal studies to enhance nerve regeneration. In hand transplantation patients, nerve regeneration was unexpectedly good and rapid, and this observation has been attributed to FK506. The present Phase II experiment investigated the tolerance to FK506 after nerve suture or autograft, and the potential effects of the drug on axonal regeneration. Following strict criteria, five patients were included in this study. Within 7 days of nerve repair (median, ulnar and sciatic transections), patients received FK506 (aiming for blood concentrations between 5 and 8 ng/ml) for a total duration of 60 days. The patients were carefully followed with clinical and biological monitoring in order to detect side-effects. A clinical and electrophysiological assessment of the effect of FK506 on nerve regeneration was conducted. No undesirable side-effect was observed during or after FK506 treatment, but one non-compliant patient discontinued treatment. There was no evident improvement of sensory, motor or functional recovery at the end of the follow-up period (average duration 39.8 months), as compared to the expected clinical result without treatment. Although statistically non-significant, FK506 seemed to accelerate the progression of the Hoffmann-Tinel sign, but without impact on the final result.


Mitochondrial DNA ligase III function is independent of Xrcc1.
Hamster EM9 cells, which lack Xrcc1 protein, have reduced levels of DNA ligase III and are defective in nuclear base excision repair. The Xrcc1 protein stabilizes DNA ligase III and may even play a direct role in catalyzing base excision repair. Since DNA ligase III is also thought to function in mitochondrial base excision repair, it seemed likely that mitochondrial DNA ligase III function would also be dependent upon Xrcc1. However, several lines of evidence indicate that this is not the case. First, western blot analysis failed to detect Xrcc1 protein in mitochondrial extracts. Second, DNA ligase III levels present in mitochondrial protein extracts from EM9 cells were indistinguishable from those seen in similar extracts from wild-type (AA8) cells. Third, the mitochondrial DNA content of both cell lines was identical. Fourth, EM9 cells displayed no defect in their ability to repair spontaneous mitochondrial DNA damage. Fifth, while EM9 cells were far more sensitive to the cytotoxic effects of ionizing radiation due to a defect in nuclear DNA repair, there was no apparent difference in the ability of EM9 and AA8 cells to restore their mitochondrial DNA to pre-irradiation levels. Thus, mitochondrial DNA ligase III function is independent of the Xrcc1 protein.


Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction.
As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role. Patients in the Swedish Heart Failure Registry were divided into three groups based on EF (≥50%, 40-49% and <40%). CKD was defined as an estimated glomerular filtration rate ≤60 mL/min.1.73 m2 . Associations between covariates and CKD and between CKD and mortality were assessed with multivariable regressions. Of 40 230 patients, 8875 (22%) had HFpEF, 8374 (21%) had HFmrEF, and 22 981 (57%) had HFrEF, with a CKD prevalence of 56%, 48%, and 45%, respectively. Associations between covariates and CKD were similar in all EF groups. One-year mortality with vs. without CKD was 23% vs. 13% in HFpEF, 22% vs. 8% in HFmrEF, and 23% vs. 8% in HFrEF (P < 0.001 for all). After adjustment, CKD was more strongly associated with death in HFrEF and HFmrEF than in HFpEF [hazard ratio (HR) and 95% confidence interval (CI); 1.49 (1.42-1.56) and 1.51 (1.40-1.63) vs. 1.32 (1.24-1.42); P for interaction <0.001]. In receiver operating characteristic (ROC) analyses, CKD was also a stronger predictor of death in HFrEF and HFmrEF than in HFpEF [area under the curve (AUC) 0.699 (0.689-0.709) and 0.700 (0.683-0.716) vs. 0.629 (0.613-0.645)]. CKD was associated with similar covariates regardless of EF. Although CKD was more common in HFpEF than in HFmrEF and HFrEF, it may have more of a 'bystander' role in HFpEF, being less associated with mortality and with lower prognostic discrimination.


Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.
While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8)), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29)) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.


[Comparative importance of different transmission factors in the spread of acute intestinal infections].
The authors generalized literature data on a comparative epidemiological significance of individual ways of transmission in the spread of escherichiasis, shigelloses, salmonelloses and cholera. Resistance of the corresponding causative agents to the factors of external environment and the action of gastric juice were considered. Data on concentrations of different enteropathogenic agents in the feces of patients, convalescents and healthy carriers were compared with the observations on doses causing the disease in man. On the basis of analysis a conclusion was drawn on a different significance of water, food and domestic ways of infection in the spread of various etiological forms of acute intestinal infections.


Glutamine synthetase gene expression in the lungs of endotoxin-treated and adrenalectomized rats.
During sepsis, the lung responds by exporting increased amounts of the amino acid glutamine. This response is accompanied by increased enzymatic activity of glutamine synthetase (GS), which catalyzes the synthesis of glutamine from glutamate and ammonia. It is also known that GS expression in the rat lung can be induced by glucocorticoid hormones. To determine whether the septic response and the response to glucocorticoids are related, we have characterized the induction of GS expression during lipopolysaccharide (LPS)-induced endotoxemia in normal, neutropenic, and adrenalectomized rats. Normal rats exhibited a time- and dose-dependent induction of GS mRNA levels after a single intraperitoneal dose of LPS. Responses to LPS were maximal at doses of 0.1 mg/kg body wt and above. A single 10 mg/kg body wt dose of LPS led to a rapid, transient sevenfold increase in GS mRNA (P < or = 0.1) and a twofold increase in GS protein level 8 h postinjection. Induction of lung GS mRNA 4 h after LPS injection was approximately fivefold in neutropenic (P < or = 0.1) and fourfold in nonneutropenic control rats (P < or = 0.1), suggesting that infiltrating neutrophils or neutrophil-derived factors are not required for GS induction. In response to high-dose, short-term endotoxemia, adrenalectomized rat lung GS mRNA increased twofold (P < or = 0.02) compared with sixfold in sham-operated control rats (P < or = 0.02). However, in response to low-dose, long-term endotoxemia, adrenalectomized rat lung GS mRNA increased threefold (P < or = 0.02) compared with fourfold in sham-operated control rats (P < or = 0.02). Adrenalectomy did not affect the elevation of lung GS mRNA levels in response to dexamethasone. In addition, GS mRNA was induced four- and sixfold in rat microvascular pulmonary endothelial cells exposed to plasma from control and septic rats, respectively. The addition of a glucocorticoid antagonist, RU-38486, completely blocked GS gene induction in the presence of control plasma but only attenuated the response to plasma from septic animals by 30%. These results suggest that GS gene induction during sepsis is only partially mediated by adrenal-derived glucocorticoid hormones.


Low-Level Laser Effect on Peripheral Sciatic Regeneration Under the Systemic Inflammatory Condition of Periodontal Disease.
Introduction: Periodontal disease (PD) is an inflammatory condition, which leads to tooth loss and promotes a systemic inflammatory state that can aggravate the nerve degeneration. As laser therapy may stimulate regeneration, this study aimed to evaluate the effect of the low-level laser (LLL) on peripheral nerve regeneration under the systemic inflammatory condition of PD. Methods: Thirry-two male rats were used, distributed in 4 groups: nerve injury (NIG); periodontal disease with nerve injury (PDNI); nerve injury and treatment (TNIG); periodontal disease with nerve injury and treatment (PDNIT). On the 7th day of the experiment, the animals had ligatures placed around the lower first molars. On the 22nd day, they underwent peripheral nerve damage, and on the 25th day, the LLL treatment was initiated, performed for two weeks. The sciatic functional index (SFI) was evaluated with subsequent euthanasia of all the animals on the 37th day of the experiment. The sciatic nerve was collected for morphological and oxidative stress analysis and the hemi jaws for radiographic analysis. Results: Regarding the SFI, there was no difference among the groups in the first evaluation (EV) pre-injury; as for theEV2, after injury, all the groups presented a decrease in these values, which remained in post-treatment. For the morphology of the PDNI, nerve tissue presented larger diameter fibers, whereas, for NIT and PDNIT, fibers had smaller diameters with endoneurial organization. When it comes to the antioxidant system, there was an increase in protein concentration, higher superoxide activity, and decreased glutathione transferase activity in the treated groups. Catalase and cholinesterase did not differ between the groups, and lipoperoxidation (LPO) increased in the PD groups. For the mandible radiographic analysis, it was possible to verify the induction of PD. Conclusion: As for the used parameters, the low-level laser was not effective in increasing the nociceptive threshold, but it contributed to the regeneration of nerve fibers, although the inflammation was still present in the site. However, the treatment was effective in protecting cells against oxidative damage due to increased SOD and increased protein, although the decrease in GST demonstrates the inhibition of this stage of the antioxidant system.


[Surgery and radiotherapy of early glottic carcinoma].
167 patients with early glottic carcinoma treated by surgery or radiotherapy in the past 25 years are analysed. Of these patients, 74 with T1 N0 M0 glottic carcinoma treated by surgery gave a 5-year survival rate of 93.2%. In these 74 patients, 5 who received total laryngectomy and 69, partial laryngectomy gave 5-year survival rates of 80% and 94.2%. In this series, 93 patients treated by radiotherapy gave a 5-year survival rate of 87.4%. There was no significant difference between the two groups (X2 test P greater than 0.05). The above results showed that the results of surgery and radiotherapy are similar. The authors suggest that radiotherapy be considered as the first choice for this type of cancer for its advantages over surgery.


Palladium-Catalyzed Synthesis of 3-Trifluoromethyl-Substituted 1,3-Butadienes by Means of Directed C-H Bond Functionalization.
A palladium-catalyzed C-H bond functionalization of acrylamides was developed to build up stereoselectively trifluoromethylated 1,3-butadienes. Using a tertiary amide as a directing group, olefins were selectively functionalized with 2-bromo-3,3,3-trifluoropropene to access these important fluorinated compounds. The methodology was extended to the construction of pentafluoroethyl-substituted 1,3-dienes. Mechanistic studies supported by density functional theory calculations suggested a redox neutral mechanism for this transformation.


[The morphological study of the Perfoost demineralized bone alloimplant applied for the plastic reconstruction of the posterior wall of the external auditory canal].
The objective of the present study was to enhance the effectiveness of the surgical treatment of chronic suppurative otitis media (CSOM) by means of the application of the Perfoost demineralized bone alloimplant for the plastic reconstruction of the posterior wall of the external auditory canal. This aim was attained by the elucidation of morphological features the Perfoost alloimpalnt at the site of surgical intervention one year after the operation. The study included 12 patients presenting with CSOM (epi- and epimesotympanitis) who had underwent "closed-type" sanation surgery of the middle ear. A Perfoost demineralized bone implant (DBI) plate was used for plastic reconstruction of the posterior wall of the external auditory canal. The secondary intervention within one year after the implantation was used to obtain 5×5 mm biopsy specimens containing a fragment of Perfoost DBI together with the adjacent cicatrical tissue bordering the "living" bone. The biopsies were subjected to standard histological treatment. It was shown that the fragment of the transplanted bone tissue underwent resorption accompanied by neo-osteogenesis. The source of formation of the new bone was fibroblastic elements of connective tissue of the recipient undergoing transformation into osteoblasts under the influence of resorbable components of the alloimplant. The presence of pre-existing bone canals and perforation holes in the implant provides the favourable conditions for its invasion by connective tissue that ensures its strong immobilization and gradual replacement by the newly formed bone tissue which corresponds by "carcass" regeneration. The results of the present study give evidence of the high clinical effectiveness of reconstructive surgery for the treatment of CSOM with the application of the Perfoost demineralized bone alloimplant used for the plastic correction of the posterior wall of the external auditory canal.


The BCG controversy. A methodological and statistical reappraisal.
Because of the conflicting results of eight major controlled trials, BCG vaccination against tuberculosis remains controversial despite more than 50 years of use. Suspecting a methodological source for the controversy, we reviewed the scientific and statistical quality of each trial. The analysis showed that (1) although biased allocation of the vaccine appeared an unlikely explanation for the disparate results, adequate demonstration of unbiased detection of tuberculosis was available only for the three trials reporting 75% or greater protective efficacy; and (2) in most trials reporting low efficacy, the results had wide confidence intervals that could not exclude high efficacy, but the trials reporting high efficacy all had narrow confidence intervals that excluded low efficacy. Because the trials with the best methodological quality and greatest statistical precision reported high efficacy, the evidence suggests that BCG can confer a high degree of protection against tuberculosis and that bias or inadequate statistical power may have contributed to the conflicting data.


Continuous tamoxifen and dose-dense temozolomide in recurrent glioblastoma.
The current standard-of-care for glioblastoma (GBM) is represented by concomitant radiotherapy (RT) and temozolomide (TMZ), according to Stupp's protocol. Second-line treatments for GBM have not been yet defined. Tamoxifen is an anti-estrogen molecule with anti-neoplastic effects whose role is under investigation. tamoxifen is generally well tolerated but thromboembolic complications have been reported. In this study, we report our experience on the administration of tamoxifen plus dose-dense TMZ in patients with recurrent GBM. All patients underwent surgical resection of GBM and completed concomitant RT and TMZ. Eligibility criteria also included evidence of GBM recurrence and good general conditions [Karnofsky Performance Score (KPS) >70] at recurrence. Patients with rapidly progressive disease, clearly unfavorable prognosis, or history of deep-venous thrombosis were excluded. The second-line treatment consisted of dose-dense TMZ (75-150 mg/m(2) one week on/ one week off) plus daily tamoxifen (80 mg/m(2)). Follow-up was performed with contrast-enhanced brain Magnetic Resonance Imaging (MRI) every three months. Thirty-two patients (18 males, 14 females; median age 57 years) with GBM relapse were included. Median overall survival time (OS) and time to tumor progression after recurrence (TTP-2) were 17.5 and 7 months, respectively. Interestingly, no differences in OS and TTP-2 were noted in GBM between those with methylated and unmethylated MGMT. None of the patients had complications related to TMZ plus tamoxifen administration. The combinatorial administration of tamoxifen and TMZ appeared to be well-tolerated, and potentially effective in increasing the efficacy of dose-dense TMZ schedule as a second-line therapeutic strategy.


Evaluation of the mydriatic effect of intracameral lidocaine hydrochloride injection in eyes of clinically normal dogs.
OBJECTIVE-To evaluate the mydriatic effect of intracameral injection of preservative-free 1% and 2% lidocaine hydrochloride solutions and determine the onset and duration of mydriasis according to the concentration and volume of lidocaine administered in healthy dogs. ANIMALS-5 healthy adult Beagles weighing 7 to 10 kg, with no apparent ocular disease. PROCEDURES-A double-blind randomized 9-session crossover trial was designed. Both eyes were assigned to 9 treatments with a minimum 7-day washout period between treatments: 0.1, 0.2, and 0.3 mL of 2% lidocaine solution; 0.1, 0.2, and 0.3 mL of 1% lidocaine solution; and 0.1, 0.2, and 0.3 mL of balanced salt solution. Dogs were anesthetized, and the allocated treatment was injected intracamerally after aspiration of the same volume of aqueous humor from the anterior chamber of each eye. Two perpendicular pupil diameters were measured. Intraocular pressure, heart rate, respiratory rate, ECG readings, and end-tidal partial pressure of CO(2) were monitored. RESULTS-Intracameral injection of 1% or 2% lidocaine solutions in volumes of 0.1 to 0.3 mL induced a significant degree of mydriasis, and the effect was maintained for 74 to 142 minutes. Lidocaine injection had no significant effect on intraocular pressure, heart rate, respiratory rate, ECG readings, or end-tidal partial pressure of CO(2). CONCLUSIONS AND CLINICAL RELEVANCE-Intracameral lidocaine injection in healthy dogs induced mydriasis, the timing of which was affected by concentration and volume of lidocaine. This technique could serve as an alternative to topically administered mydriatics for intraocular surgery in dogs.


Assisting Australian indigenous resource management and sustainable utilization of species through the use of GIS and environmental modeling techniques.
Information on distribution and relative abundance of species is integral to sustainable management, especially if they are to be harvested for subsistence or commerce. In northern Australia, natural landscapes are vast, centers of population few, access is difficult, and Aboriginal resource centers and communities have limited funds and infrastructure. Consequently defining distribution and relative abundance by comprehensive ground survey is difficult and expensive. This highlights the need for simple, cheap, automated methodologies to predict the distribution of species in use, or having potential for use, in commercial enterprise. The technique applied here uses a Geographic Information System (GIS) to make predictions of probability of occurrence using an inductive modeling technique based on Bayes' theorem. The study area is in the Maningrida region, central Arnhem Land, in the Northern Territory, Australia. The species examined, Cycas arnhemica and Brachychiton diversifolius, are currently being 'wild harvested' in commercial trials, involving sale of decorative plants and use as carving wood, respectively. This study involved limited and relatively simple ground surveys requiring approximately 7 days of effort for each species. The overall model performance was evaluated using Cohen's kappa statistics. The predictive ability of the model for C. arnhemica was classified as moderate and for B. diversifolius as fair. The difference in model performance can be attributed to the pattern of distribution of these species. C. arnhemica tends to occur in a clumped distribution due to relatively short distance dispersal of its large seeds and vegetative growth from long-lived rhizomes, while B. diversifolius seeds are smaller and more widely dispersed across the landscape. The output from analysis predicts trends in species distribution that are consistent with independent on-site sampling for each species and therefore should prove useful in gauging the extent of resource availability. However, some caution needs to be applied as the models tend to over predict presence which is a function of distribution patterns and of other variables operating in the landscape such as fire histories which were not included in the model due to limited availability of data.


Micronutrient intakes among children and adults in Greece: the role of age, sex and socio-economic status.
The aim of the present study was to report the usual nutrient intakes of sixteen micronutrients by schoolchildren, adults and the elderly in Greece and to further explore the role of age, sex and socio-economic status (SES) on meeting the recommended nutrient intakes. Dietary intake, demographic and SES data from three existing studies conducted in Greece (in 9-13-year-old children; 40-60-year-old adults; and 50-75-year-old women) were collected. The prevalence of study participants with inadequate micronutrient intakes were assessed using the estimated average requirement (EAR) cut-point method. Regarding sex and age differences, the highest prevalences of inadequate nutrient intakes occurred in post-menopausal women. In both sexes and all age groups, the prevalence of vitamin D intake below EAR reached 100%. Furthermore, nutrient intakes of 75% or more below EAR were found for vitamin E in all age groups, folate in women and for calcium and magnesium in post-menopausal women (p < 0.05). Regarding SES differences, the prevalences of inadequate calcium and vitamin C intakes were higher for children and postmenopausal women of lower SES compared to their higher SES counterparts (p < 0.05). The current study reported the highest prevalences of inadequate intakes for both sexes and all age and SES groups for calcium, folate and vitamins D and E. These findings could provide guidance to public health policy makers in terms of updating current dietary guidelines and fortifying foods to meet the needs of all population subgroups.


NAD-specific isocitrate dehydrogenase from bovine heart. Interaction with Ca2+ chelators.
The activity of NAD-specific isocitrate dehydrogenase was inhibited by EDTA, EGTA and other nitrogen-containing polycarboxylate Ca2+ chelators in the absence and in the presence of ADP by a mechanism that could not be attributed solely to the removal of free Ca2+. Carboxymethyltartronate (2-oxapropane-1,1,3-tricarboxylate), an oxygen ether polycarboxylate chelator, did not inhibit when ADP was absent. The activation by ADP, a positive effector of the enzyme, decreased with increasing concentration of carboxymethyltartronate, paralleling the removal of free Ca2+ by this chelator. The following were found when free Ca2+ was decreased to negligible concentrations (5-50 nM) with carboxymethyltartronate. (1) Free Ca2+ enhanced, but was not absolutely required for, activation by ADP. (2) Activation of enzyme activity by magnesium citrate neither required nor was increased by Ca2+ when ADP was absent. However, the potentiation of citrate activation by ADP was facilitated by free Ca2+. (3) The reversal of NADPH inhibition of enzyme activity by ADP did not absolutely require Ca2+, but it was enhanced by free Ca2+. (4) The inhibition of enzyme activity by NADH was not reversed by ADP either with or without Ca2+.


[Tuberculosis of the palatine tonsil mimicking a malignant lesion and associating pulmonary tuberculous miliaria: about a case in Ouagadougou, Burkina Faso].
Tonsillar tuberculosis is the infectious localization of Koch's bacillus in the palatine tonsils. It is rare. Tonsillar tuberculosis associated with miliary tuberculosis is even more exceptional. The aim of our work is to report a rare case of tuberculous tonsillitis associated with miliary tuberculosis. This was a case of tonsillar tuberculosis associated with miliary tuberculosis. The main complaint was chronic odynophagia, which had been present for 7 months and was associated with weight loss. Questioning also revealed alcohol, tobacco and marijuana consumption. Oropharyngoscopy revealed an enlarged, ulcerated and hemorrhagic right tonsil, suggesting a malignant lesion. Diagnostic tonsillectomy with anatomopathological examination of the surgical specimen led to the diagnosis of tonsillar tuberculosis. A postoperative chest X-ray revealed tuberculous miliaria. No other tuberculosis site was identified. No other confirmatory biological tests were carried out. The patient was treated with 4 anti-tuberculosis drugs (rifampicin, isoniazid, pyrazinamide, ethambutol) during 2 months and 2 anti-tuberculosis drugs (Rifampicin, Isoniazid) during 4 months. The evolution was favorable and the patient was declared cured at the end of treatment. There was no recurrence after 5 years. Tonsillar tuberculosis is rare. Tonsillar tuberculosis associated with pulmonary miliaria is even more exceptional. Tonsil biopsy for anatomopathological examination is sufficient for diagnosis. A chest X-ray should be requested as part of the preoperative workup prior to any tonsillar biopsy or tonsillectomy. GeneXpert (MTB/RIF) should be carried out if possible, not only for its value in the biological confirmation of tuberculosis but also to identify rifampicin resistance. Antibacillary treatment often leads to a favorable outcome.


Factors that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration.
1. 2,4-Dinitrophenol (0.1mm) increases by 100-160% the rate of ethanol metabolism by rat liver slices incubated in a medium saturated with a gas mixture containing O(2)+CO(2)+N(2) (18:5:77). Similar effects are produced by relatively low concentrations of arsenate (10mm). At higher concentrations (37.5 and 50mm) arsenate inhibits the rate of ethanol metabolism. 2. When liver slices are incubated under an atmosphere containing O(2)+CO(2) (95:5) the metabolism of ethanol increases by about 100% over that obtained with O(2)+CO(2)+N(2) (18:5:77). However, under these conditions the activating effect of dinitrophenol is no longer observed. 3. Chronic administration of ethanol to rats for 3-4 weeks, in doses from 3 to 8g/kg per day, increases by 70-90% the ability of the liver to metabolize ethanol. In the liver slices of these rats, although an O(2)+CO(2)+N(2) (18:5:77) mixture was used, dinitrophenol does not further increase the metabolism of ethanol. If the chronic administration of ethanol is discontinued for two weeks, the rate of ethanol metabolism is lowered to control values and the activating effect of dinitrophenol is recovered. 4. No change in alcohol dehydrogenase activity was found in the liver of the rats in which the metabolism of ethanol had been increased as a result of the chronic ethanol treatment; a 40% increase in the activity of succinate dehydrogenase was observed.


Designing and evaluating culturally specific smoking cessation interventions for American Indian communities.
American Indians have the highest smoking rates in the United States, yet few randomized controlled trials of culturally specific interventions exist. This study assessed American Indians' opinions about evidence-based treatment and attitudes toward participating in clinical trials. Six focus groups were conducted based on smoking status (current/former smoker), sex, and elder status (55 years and older or younger). Meetings were held at local American Indian community organizations. This project was accomplished in partnership with the American Indian Community Tobacco Projects, a community-academic research partnership at the University of Minnesota. Thematic qualitative data analyses were conducted. Participants desired the following: (a) programs led by trained American Indian community members, (b) the opportunity to connect with other American Indian smokers interested in quitting, and (c) programs promoting healthy lifestyles. Strategies desired for treatment included (a) free pharmacotherapy, including nicotine replacement therapy (NRT); (b) nominal incentives, e.g., gift cards for groceries; and (c) culturally specific program components such as American Indian images, education on traditional tobacco use, and quit-smoking messages that target the value of family and include narratives or story telling in recruitment and program materials. Biochemical verification of smoking abstinence, such as salivary cotinine or carbon monoxide breathalyzers, is likely acceptable. Standard treatment or delayed treatment control groups were viewed as potentially acceptable for randomized study designs. Rigorously conducted randomized controlled trials of culturally specific smoking cessation interventions are sorely needed but will only be accomplished with the commitment of funders, researchers, and collaborative trusting relationships with the community.


Persimmon leaf extract protects mice from atopic dermatitis by inhibiting T cell activation via regulation of the JNK pathway.
Persimmon leaf extracts (PLE) have been widely used as a traditional medicine in East Asian countries. The effects of persimmon leaves, including antioxidant, antiinflammatory, hypotensive, and anti-allergy effects, have been investigated; however, there is little evidence on the inhibition of T cell activation in vitro and effects on T cell-related diseases, such as atopic dermatitis (AD), in vivo by persimmon leaves. PLE (50 μg/mL) effectively attenuated the mRNA levels of IL-2 in Jurkat T cells stimulated with PMA/A23187 and Staphylococcus enterotoxin E-loaded Raji B cells without causing cytotoxicity. In Jurkat T cells stimulated with PMA/A23187, treatment with 50 μg/mL PLE blocked the translocation of p65 and IκBα degradation. Moreover, the JNK signaling pathway in Jurkat T cells stimulated with PMA/A23187 was affected by treatment with PLE. The oral administration of PLE markedly attenuated AD manifestations in mice, including ear thickness, IgE levels, and lymph node sizes. These results indicate PLE significantly blocked T cell activation via NF-κB signaling and the JNK pathway. This suggests underlying mechanisms of PLE involving the control of effector cytokines produced by activated T cells in ear tissue and lymph nodes, as well as the infiltration of mast cells and the therapeutic potential of AD.


Colorectal Cancer Survival Gains and Novel Treatment Regimens: A Systematic Review and Analysis.
The past 2 decades have witnessed progress in the management of metastatic colorectal cancer (mCRC) with more effective agents and better surgical, medical, and supportive care. While substantial progress has been made, much more must be achieved to prolong the lives of patients. To conduct a systematic review to ascertain what percentage of the life expectancy gain in locally advanced and mCRC over the past 2 decades is due to novel therapies vs improvements in supportive care or secular trends and to thus inform treatment development strategies. We searched Cochrane Controlled Trials Register, Medline, Embase, CancerLit, and Healthstar electronic databases for trials covering the period 1993 to 2015, scanned reference lists of articles, and searched recent conference abstracts. Ninety-six phase 3 trials and large (>50 patients) phase 2 trials in mCRC were examined. Outcomes evaluated in the experimental arms (EAs) and control arms (CAs) included overall response rate, stable disease, progression-free survival (PFS), and overall survival (OS). Over the period covered by the studies, the OS in EAs increased at a mean (95% CI) rate of 0.80 (0.67-0.93) mo/y. Importantly, OS in the CAs improved 0.63 (0.51-0.75) mo/y, reflecting in part the use of experimental regimens in subsequent studies. Chemotherapy contributed only partly to the gains in OS, given that (1) mean (95% CI) improvements in PFS were only 0.31 (0.22-0.39) mo/y in the EAs and 0.23 (0.15-0.31) mo/y in CAs; (2) gains in survival not directly attributable to the protocol were greater than gains in PFS (0.46 [0.36-0.57] mo/y in EAs and 0.39 [0.29-0.49] mo/y in CAs; and (3) effects on OS were much lower in second-line trials (median [interquartile range] response rates, 8.6% [0%-11.0%] in EAs and 7.5% [3.8%-12.8%] in CAs) compared with first-line trials (39.5% [24.0%-50.2%] for EAs and 29.4% [16.4%-39.4%] for CAs). The OS of patients with mCRC has improved gradually over the past 2 decades, with gains from chemotherapy occurring alongside gains from lead-time bias and improved locoregional approaches and supportive care. Gains from first-line therapies have been modest but consistent; however, gains from second-line therapies have been disappointing. We believe that future progress will be greater if emphasis is placed on enrolling patients in experimental trials to explore and develop alternative first-line regimens and better second-line therapies.


A systematic review finds methodological improvements necessary for prognostic models in determining traumatic brain injury outcomes.
To describe the modeling techniques used for early prediction of outcome in traumatic brain injury (TBI) and to identify aspects for potential improvements. We reviewed key methodological aspects of studies published between 1970 and 2005 that proposed a prognostic model for the Glasgow Outcome Scale of TBI based on admission data. We included 31 papers. Twenty-four were single-center studies, and 22 reported on fewer than 500 patients. The median of the number of initially considered predictors was eight, and on average five of these were selected for the prognostic model, generally including age, Glasgow Coma Score (or only motor score), and pupillary reactivity. The most common statistical technique was logistic regression with stepwise selection of predictors. Model performance was often quantified by accuracy rate rather than by more appropriate measures such as the area under the receiver-operating characteristic curve. Model validity was addressed in 15 studies, but mostly used a simple split-sample approach, and external validation was performed in only four studies. Although most models agree on the three most important predictors, many were developed on small sample sizes within single centers and hence lack generalizability. Modeling strategies have to be improved, and include external validation.


Sequence variation of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene in chronic lymphocytic leukemia and healthy volunteer subjects.
Epstein-Barr virus-related malignancies have been linked to variations in the sequences of EBV genes, notably EBNA1. Therefore, the purpose of this study was to examine the DBD/DD domain and USP7 binding domain sequences at the C-terminus of the EBNA1 gene in patients with chronic lymphocytic leukemia (CLL). This study included 40 CLL patients and 21 healthy volunteers. Using commercial kits, total DNA was extracted from buffy coat samples, and each sample was tested for the presence of the EBV genome. The C-terminus of EBNA1 was then amplified from positive samples, using nested PCR. Sanger sequencing was used to identify mutations in the PCR products, and the results were analyzed using MEGA11 software. The mean ages of CLL patients and healthy individuals were 61.07 ± 10.2 and 59.08 ± 10.3, respectively. In the EBNA-1 amplicons from CLL patients and healthy individuals, 38.5% and 16.7%, respectively, harbored mutations in the DBD/DD domain of the C-terminal region of the EBNA1 gene (P = 0.378). The mutation frequency at locus 97,320 was significantly higher in CLL patients than in healthy individuals (P = 0.039). Three EBV subtypes based on residue 487 were detected. The frequency of alanine, threonine, and valine in both groups was 88, 8, and 4 percent, respectively (P = 0.207). Moreover, all of the isolates from healthy donors had alanine at this position. The findings indicated that the presence of threonine or valine at residue 487 as well as a synonymous substitution at residue 553 in the C-terminal region of EBNA1 might be involved in the pathogenesis of EBV in CLL patients.


Coupling of DNA replication to growth rate in Escherichia coli: a possible role for guanosine tetraphosphate.
Two promoters for the Escherichia coli operon that contains the four genes dnaA, dnaN, recF, and gyrB were found to be growth rate regulated and under stringent control. Transcript abundance relative to total RNA increased with the growth rate. Changes in transcription from the dnaAp1 and dnaAp2 promoters that were induced by amino acid starvation and chloramphenicol and were relA dependent were correlated with the stringent response. The abundance of these transcripts per total RNA also decreased in spoT mutants as the severity of the mutation increased (guanosine 5'-diphosphate 3'-diphosphate [ppGpp] basal levels increased). Because expression of these promoters appears to be inhibited by ppGpp, it is proposed that one mechanism for coupling DNA replication to the growth rate of bacteria is through ppGpp synthesis at the ribosome.


Impact of piped water supply on the incidence of typhoid fever and diarrhoeal diseases in Lusaka.
The effect of piped water supply on the incidence of typhoid fever and diarrhoeal diseases in the City of Lusaka is reported. The incidence of typhoid fever and diarrhoeal diseases reduced in the City as the piped drinking water was extended to the Urban and peri Urban self-help settlements.


Temperature manipulation during layer chick embryogenesis.
The current study investigated the effects of temperature manipulation (TM) during late embryogenesis on temperature preference, response to high environmental temperature, behavior, and performance in young layer chicks. Control (CC) embryos (n = 96) were incubated at 37.8 degrees C eggshell temperature throughout incubation. Thermally manipulated embryos (n = 96) were incubated at 37.8 degrees C eggshell temperature throughout incubation and were exposed to 40 degrees C for 4 h/d from embryonic d 14 to 18 (TM chicks). After hatch, chicks from each treatment were divided into 3 subgroups (n = 32 per group) and were subjected to a temperature preference test at d 1, 7, or 33. One day after the temperature preference test, each subgroup was exposed to 1 thermal challenge for 4 h (d 2, 40 degrees C; d 8, 40 degrees C; or d 34, 35 degrees C). Effects of TM on (fearfulness) behavior of chicks were investigated in a tonic immobility test and during home pen observations. Temperature manipulation decreased incubation time with 7 h (P < 0.0001) and body temperature at hatch with 0.2 degrees C (P = 0.002). The TM chicks preferred a lower ambient temperature in the temperature preference test (P < 0.05) and showed a higher body temperature response than CC chicks to the thermal challenge at d 2 and 8 (P < 0.05). No effects of TM on behavior and performance were observed. Because most TM studies are conducted in broilers, this study is the first attempt to unravel the effects of TM during late embryogenesis on posthatch environmental adaptation in layer chicks. The results demonstrated that effects of our TM on postnatal temperature preference and response to high environmental temperatures are only found until d 8 of age. This may suggest 1 of 3 options: a) the timing or the level, or both, of TM and duration were not at the sensitive period of embryogenesis or not sufficient, or both, respectively; b) the level of the postnatal thermal challenge was not strong enough to induce a hyperthermic response; and c) the postnatal effects of TM in layers are limited in time.


Anesthesia for ERCP: Impact of Anesthesiologist's Experience on Outcome and Cost.
The present study evaluates the effect of anesthesiologist's experience in providing deep sedation for endoscopic retrograde cholangiopancreatography (ERCP) on cost and safety. Methodology. Perioperative records of 1167 patients who underwent ERCP were divided on the basis of anesthesiologist assisting these procedures either on regular basis (Group R) or on ad hoc basis (Group N). Comparisons were made for anesthesia times, complication rates, and airway interventions. Results. Across all American Society of Anesthesiologists (ASA) Classes, regular anesthesiologists were more efficient (overall mean anesthesia time in Group R was 24.82 ± 12.96 versus 48.63 ± 21.53 minutes in Group N). Within Group R, anesthesia times across all ASA classes were comparable. In Group N, anesthesia times for higher ASA status patients were significantly longer (ASA IV, 64.62 ± 35.78 versus ASA I, 45.88 ± 11.19 minutes). Intubation rates (0.76% versus 12.8%) and median minimal oxygen saturation (100% versus 97.01%) were significantly higher in Group R. Had Group R anesthesiologists performed all procedures, the hospital could have saved US $ 758536 (based upon operating room time costs). Conclusion. Experience in providing deep sedation improved patient safety and decreased the operating room turnaround time, thereby lowering operating room costs associated with these procedures.


[Gas chromatographic study of odor and flavor components of dry wine].
6, 12 and 18 months after bottling, 1 sample of the primary wine, 2 samples of tank-fermented sparkling wines (taken at different production phases, i.e., during and after the second fermentation) and 3 samples of bottle-fermented raw champagne were analysed for aroma and flavour components. The samples were extracted with ether-pentane (2:1) and analysed by gas chromatography. 21 components were detected, 9 of which were identified (isopropanol, n-propanol, isobutanol, n-butanol, isopentanol, heptanal, n-hexanal, n-heptanol, isooctanol). There were marked qualitative and quantitative differences in composition between the aroma and flavour components of the primary wine sample and the sparkling wines sample taken during the main phase of the tank-fermenting process. This is essentially attributable to the fermenting activities of the yeasts. On the contrary, the aroma and flavour components of the primary wine sample agreed in quality with those of the sparkling wines sample taken at the end of tank-fermentation. It is concluded from these findings that greater amounts of new components do not form during the second fermentation. On the other hand, aroma and flavour components already present in the primary wine came to the fore by the quantitative increase of certain bouquet components. The comparison of the samples of bottle-fermented sparkling wines revealed, irrespective of slight changes, a clear-cut developmental trend. During the aging process, the contents of isopentanol and of a still unidentified component decreased, whereas those of isobutanol, isopropanol, heptanol and a still unidentified component increased markedly. It is stated that differences in the fermenting process manifest themselves mainly by the ratios of the components. The bouquet components were almost similar for both fermenting processes.


A genome-wide SNP scan reveals novel loci for egg production and quality traits in white leghorn and brown-egg dwarf layers.
Availability of the complete genome sequence as well as high-density SNP genotyping platforms allows genome-wide association studies (GWAS) in chickens. A high-density SNP array containing 57,636 markers was employed herein to identify associated variants underlying egg production and quality traits within two lines of chickens, i.e., White Leghorn and brown-egg dwarf layers. For each individual, age at first egg (AFE), first egg weight (FEW), and number of eggs (EN) from 21 to 56 weeks of age were recorded, and egg quality traits including egg weight (EW), eggshell weight (ESW), yolk weight (YW), eggshell thickness (EST), eggshell strength (ESS), albumen height(AH) and Haugh unit(HU) were measured at 40 and 60 weeks of age. A total of 385 White Leghorn females and 361 brown-egg dwarf dams were selected to be genotyped. The genome-wide scan revealed 8 SNPs showing genome-wise significant (P<1.51E-06, Bonferroni correction) association with egg production and quality traits under the Fisher's combined probability method. Some significant SNPs are located in known genes including GRB14 and GALNT1 that can impact development and function of ovary, but more are located in genes with unclear functions in layers, and need to be studied further. Many chromosome-wise significant SNPs were also detected in this study and some of them are located in previously reported QTL regions. Most of loci detected in this study are novel and the follow-up replication studies may be needed to further confirm the functional significance for these newly identified SNPs.


Pliocene-Pleistocene Boundary in Deep-Sea Sediments: Extinctions and evolutionary changes in microfossils clearly define the abrupt onset of the Pleistocene.
For a hundred years students of the Pleistocene have looked for evidence of the climatic change which initiated the Pleistocene epoch. Glacial deposits on the continents have been of little help because of their discontinuity and because of the destructive effect of later glaciations. Hence, Pleistocene geologists have turned to the uplifted Pliocene-Pleistocene marine sediments of the Mediterranean region. In the absence of evidence of a single, clearly defined climatic change in this sedimentary section, they have agreed to define the beginning of the Pleistocene by the first appearance of Anomalina baltica, a species of benthic Foraminifera tolerant of cool water. This definition leaves much to be desired: It rests on a single benthic species whose areal distribution must have been partly determined by local conditions on the sea floor; it is useless outside of the Mediterranean region; and there is no convincing evidence that the first appearance of Anomalina baltica in the Mediterranean coincided with the onset of the first glaciation.


Methods to obtain more clinical and pathologic information from needle core biopsy of the prostate gland.
Prostate needle biopsy can disclose important clinical information on tumor extension and grading, useful prognostic parameters for therapeutic choices and prognostic definition. To obtain more histopathologic information on specimens and clinical prognostic parameters, we used a new method to handle and embed tissue fragments of prostate biopsy as well as a new trans-rectal probe (TRUS) with an end-fire convex ultrasound transducer to guide ultrasonically precise needle placement in the prostate gland. In our experience these methods combined can be useful in obtaining reliable clinical and prognostic information in the management of patients with prostate cancer.


RNaseI from Escherichia coli cannot substitute for S-RNase in rejection of Nicotiana plumbaginifolia pollen.
Unilateral incompatibility often occurs between self-incompatible (SI) species and their self-compatible (SC) relatives. For example, SI Nicotiana alata rejects pollen from SC N. plumbaginifolia, but the reciprocal pollination is compatible. This interspecific pollen rejection system closely resembles intraspecific S-allele-specific pollen rejection. However, the two systems differ in degree of specificity. In SI, rejection is S-allele-specific, meaning that only a single S-RNase causes rejection of pollen with a specific S genotype. Rejection of N. plumbaginifolia pollen is less specific, occurring in response to almost any S-RNase. Here, we have tested whether a non-S-RNase can cause rejection of N. plumbaginifolia pollen. The Escherichia coli rna gene encoding RNAseI was engineered for expression in transgenic (N. plumbaginifolia x SC N. alata) hybrids. Expression levels and pollination behavior of hybrids expressing E. coli RNaseI were compared to controls expressing SA2-RNase from N. alata. Immunoblot analysis and RNase activity assays showed that RNaseI and SA2-RNase were expressed at comparable levels. However, expression of SA2-RNase caused rejection of N. plumbaginifolia pollen, whereas expression of RNaseI did not. Thus, in this system, RNase activity alone is not sufficient for rejection of N. plumbaginifolia pollen. The results suggest that S-RNases may be specially adapted to function in pollen rejection.


A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response.
Calcitonin gene-related peptide-targeted monoclonal antibodies (CGRP mAbs) are increasingly being used as preventive treatments for migraine. Their effectiveness and safety were established through numerous randomized placebo-controlled trials and real-world studies, yet a significant proportion of patients do not respond to this treatment, and currently, there is a lack of accepted predictors of response to guide expectations, as data from studies so far are lacking and inconsistent. We searched Embase and MEDLINE databases for studies reporting on predictors of response to CGRP and/or CGRP-receptor (CGRP-R) mAbs, defined as a 30% or 50% reduction in monthly headache or migraine days at varying durations of follow-up. Quantitative synthesis was performed where applicable. We found 38 real-world studies that investigated the association between various predictors and response rates. Based on these studies, good response to triptans and unilateral pain with or without unilateral autonomic symptoms are predictors of a good response to CGRP(-R) mAbs. Conversely, obesity, interictal allodynia, the presence of daily headaches, a higher number of non-successful previous prophylactic medications, and psychiatric comorbidities including depression are predictive of a poor response to CGRP(-R) mAbs. Future studies should confirm these results and help to generate more tailored treatment strategies in patients with migraine.


Word deafness and auditory cortical function. A case history and hypothesis.
A patient who already had Wernicke's aphasia due to a left temporal lobe lesion suffered a severe deterioration specifically of auditory language comprehension, subsequent to right temporal lobe infarction. A detailed comparison of his new condition with his language status before the second stroke revealed that the newly acquired deficit was limited to tasks related to auditory input. Further investigations demonstrated a speech perceptual disorder, which we analysed as due to deficits both at the level of general auditory processes and at the level of phonetic analysis. We discuss some arguments related to hemisphere specialization of phonetic processing and to the disconnection explanation of word deafness that support the hypothesis of word deafness being generally caused by mixed deficits.


Evaluation of ultrasonographic predictors of alpha-blocker mono-therapy failure in symptomatic benign prostatic enlargement.
Many sonographic parameters for predicting treatment failure for benign prostate enlargement have been described. Patients may take alpha-blockers for a long time at high cost before conversion to surgery. Evaluation of the sonographic parameters that predict alpha 1 adrenoreceptor blocker monotherapy outcomes in symptomatic patients with benign prostate enlargement. Between June 2016 and July 2019, we prospectively enrolled 750 symptomatic patients with benign prostate enlargement. Trans-rectal ultrasonography was performed, and patients were given Tamsulosin (0.4 mg) oral tablets once daily for 6 months. Treatment outcomes were determined using quality of life, the International Prostatic Symptom Score, and maximum urine flow rate measures. The values of the measured baseline sonographic parameters on treatment outcomes were statistically analyzed. Seven-hundred and fifty patients completed the study, and treatment was ineffective in 225 of them (30%). From the measured prostate and bladder sonographic parameters, intra-vesical prostate growth was only significant. Using a cutoff value of 8.2 mm, the area under the receiver operator characteristic curve for intra-vesical prostatic protrusion was 0.866. Using this cutoff value (with 95% confidence interval), both positive and negative predictive values were 73.3% and 98.18%, respectively. Based on sonographic parameters, only the intravesical prostate protrusion was valid for predicting alpha-blocker monotherapy failure in symptomatic benign prostate enlargement patients. This information helps determine a medical therapeutic plan and the need for surgical intervention.


High mobility group AT-hook 1 (HMGA1) is an independent prognostic factor and novel therapeutic target in pancreatic adenocarcinoma.
High mobility group AT-hook 1 (HMGA1) proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. The authors hypothesized that tumor HMGA1 status represents a novel prognostic marker in pancreatic adenocarcinoma. They also tested the hypothesis that HMGA1 promotes anchorage-independent cellular proliferation and in vivo tumorigenicity. Tumor HMGA1 expression was examined by immunohistochemical analysis of tissues from 89 consecutive patients who underwent resection for pancreatic adenocarcinoma. Short-hairpin RNA (shRNA)-mediated RNA interference was used to silence HMGA1 expression in MiaPaCa2 and PANC1 pancreatic cancer cells. Anchorage-independent proliferation was assessed by using soft agar assays. The roles of phosphatidylinositol 3-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK) signaling were investigated by using specific inhibitors and adenoviral dominant-negative/active Akt constructs. In vivo tumorigenicity was assessed by using a nude mouse xenograft model. Tumor HMGA1 expression was detected in 93% of patients with pancreatic adenocarcinoma. Patients with HMGA1-negative tumors had a significantly longer median survival than patients with HMGA1-expressing cancers in univariate analysis (P = .0028) and in multivariate analysis (P<.05). shRNA-mediated HMGA1 silencing resulted in significant reductions in anchorage-independent proliferation in soft agar. Forced HMGA1 overexpression promoted proliferation in soft agar through a process that was dependent on PI3-K/Akt-activited signaling, but not on mitogen-activated protein kinase (MEK)/ERK signaling. Targeted silencing of HMGA1 reduced tumor growth in vivo through reduced proliferation (Ki-67 index) and increased apoptosis (terminal deoxynucleotidyl transferase nick-end labeling). The current findings suggested that HMGA1 is an independent predictor of poor postoperative survival in patients with pancreatic adenocarcinoma. Furthermore, HMGA1 promotes tumorigenicity through a PI3-K/Akt-dependent mechanism. HMGA1 warrants further evaluation as a prognostic marker and therapeutic target in pancreatic cancer.


Outcomes of peripherally inserted double lumen central catheter in very low birth weight infants.
In order to evaluate safety and usefulness of peripherally inserted double lumen central catheter (PIDLCC) in very low birth weight (VLBW) infants, outcomes of VLBW infants who had PIDLCC was studied. Thirty-nine VLBW infants who were admitted to our NICU in 2013 were retrospectively analyzed. Mean birth weight and gestational age was 1042.7 gram and 28.5 weeks, respectively. Total duration of indwelling PIDLCC was 1121 days (mean 28.5+18.2 days) with 85 PIDLCCs used. Dressing at the insertion site was done twice weekly with 10% povidone iodine. Four (10.3% with mean of 48 days) infants had catheter-related blood stream infection (CRBSI), with a 3.57 infection per 1000 catheter-day. The mean for days of PIDLCC in 35 infants without CRBSI was 26.5 days. Organisms isolated were Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus capitis ureolytic. Our study showed significant difference in the duration of indwelling catheter (p = 0.023) and intraventricular hemorrhage (p = 0.043) between the CRBSI group and non-CRBSI group. Five (12.8%) infants had abnormal thyroid function test, in which two infants required thyroxine supplementation upon discharge. However, duration of PIDLCC and abnormal thyroid function test was not statistically significant (p = 0.218). One (2.5%) infant died (death was not related to CRBSI). There was no serious adverse effects secondary to PIDLCC. It is concluded that the use and maintenance of PIDLCC is safe for VLBW infants, but close monitoring should be observed to detect early signs of infection.


Loss of vascular endothelial growth factor A (VEGFA) isoforms in granulosa cells using pDmrt-1-Cre or Amhr2-Cre reduces fertility by arresting follicular development and by reducing litter size in female mice.
Because VEGFA has been implicated in follicle development, the objective of this study was to determine the effects of granulosa- and germ cell-specific VEGFA loss on ovarian morphogenesis, function, and female fertility. pDmrt1-Cre mice were mated to floxed VEGFA mice to develop granulosa-/germ cell-specific knockouts (pDmrt1-Cre;Vegfa-/-). The time from mating to first parturition was increased when pDmrt1-Cre;Vegfa-/- females were mated to control males (P = 0.0008) and tended to be longer for heterozygous females (P < 0.07). Litter size was reduced for pDmrt1-Cre;Vegfa-/- females (P < 0.007). The time between the first and second parturitions was also increased for heterozygous females (P < 0.04) and tended to be increased for pDmrt1-Cre;Vegfa-/- females (P < 0.07). pDmrt1-Cre;Vegfa-/- females had smaller ovaries (P < 0.04), reduced plasma estradiol (P < 0.007), fewer developing follicles (P < 0.008) and tended to have fewer corpora lutea (P < 0.08). Expression of Igf1r was reduced (P < 0.05); expression of Foxo3a tended to be increased (P < 0.06); and both Fshr (P < 0.1) and Sirt6 tended to be reduced (P < 0.06) in pDmrt1-Cre;Vegfa-/- ovaries. To compare VEGFA knockouts, we generated Amhr2-Cre;Vegfa-/- mice that required more time from mating to first parturition (P < 0.003) with variable ovarian size. Both lines had more apoptotic granulosa cells, and vascular staining did not appear different. Taken together these data indicate that the loss of all VEGFA isoforms in granulosa/germ cells (proangiogenic and antiangiogenic) causes subfertility by arresting follicular development, resulting in reduced ovulation rate and fewer pups per litter.


Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake.
Numerous intracellular bacterial pathogens modulate the nature of the membrane-bound compartment in which they reside, although little is known about the molecular basis for this control. Legionella pneumophila is a bacterial pathogen able to grow within human alveolar macrophages and residing in a phagosome that does not fuse with lysosomes. This study demonstrates that the dotA product is required to regulate trafficking of the L. pneumophila phagosome. Phagosomes containing L. pneumophila dotA+ bacteria exhibited differential trafficking profiles when compared with isogenic dotA mutants. Phagosomes containing dotA mutants showed rapid accumulation of the lysosomal glycoprotein LAMP-1 as early as 5 min after uptake, whereas the majority of wild-type L. pneumophila phagosomes did not acquire LAMP-1. The association of LAMP-1 with phagosomes containing dotA mutant bacteria was concomitant with the appearance of the small GTP-binding protein Rab7 on the vacuolar membrane. These data demonstrate that phagosomes containing replication-competent L. pneumophila evade early endocytic fusion events. In contrast, the kinetics of LAMP-1 and Rab7 association indicate that the dotA mutants are routed along a well-characterized endocytic pathway leading to fusion with lysosomes. Genetic studies show that L. pneumophila requires DotA expression before macrophage uptake in order to establish an intracellular site for replication. However, the bacteria do not appear to require continuous expression of the DotA protein to maintain a replicative phagosome. These data indicate that DotA is one factor that plays a fundamental role in regulating initial phagosome trafficking decisions either upon or immediately after macrophage uptake.


Shunt freedom and clinical resolution of idiopathic intracranial hypertension after bariatric surgery in the pediatric population: report of 3 cases.
Idiopathic intracranial hypertension (IIH), formerly known as pseudotumor cerebri, is a disease of elevated intracranial pressure that is thought to develop due to impaired CSF absorption related to elevated venous sinus pressure in the setting of increased intraabdominal and thoracic pressures. Symptoms can be disabling and, if left untreated, can lead to permanent visual loss. Previous treatments directed toward vision preservation include CSF diversion through shunting and optic nerve sheath fenestration. Recently, attention has been turned toward surgical weight loss strategies as an alternative to shunt treatment. The authors present a report of 3 patients with adolescent-onset IIH that was treated at the authors' institution (Duke University) in whom bariatric surgery was pursued successfully. The patients had previously undergone CSF shunting at ages 12, 15, and 23 years. They were shunt dependent for a collective average of 3.3 years prior to bariatriwc surgery. All patients reported "low-pressure" or postural headaches after bariatric surgery that correlated with dramatic reduction in their weight. Two of the 3 patients had their shunts removed and continued to be shunt free 1.5 years later at last follow-up; the third patient remained shunt dependent with the pressure set at 200 mm H2O. Given the significant complications inherent to multiple shunt revisions, earlier intervention for weight loss, including bariatric surgery, in these patients might have prevented complications and the associated health care burden. The authors recommend a multidisciplinary approach for IIH treatment with early consideration for weight loss interventions in select patients.


Failure of the overgown to prevent nosocomial infection in a pediatric intensive care unit.
In a pediatric intensive care unit we conducted a 1-year prospective study of 454 patients to determine whether wearing a gown decreased the overall nosocomial infection rate, incidence of intravascular catheter colonization, breaks in handwashing technique, and traffic. The overall infection rate was 26 (13%) of 198 admissions during the gown-wearing periods v 23 (9%) of 256 admissions for the periods when gowns were not worn (P less than .25). Of 348 intravascular catheter tips cultured 16 (4.6%) were colonized during gown-wearing periods compared with 21 (6.3%) of 330 when no gowns were worn (P less than .25). Of 78 patient contacts 54 (69%) were followed by no handwashing during gown-wearing periods and 59 (70%) of 84 contacts were followed by no handwashing during periods when no gowns were worn. The mean occurrence of visits per patient per hour and total visits per hour differed between gown-wearing and no-gown-wearing periods by analysis of variance, P less than .01 and P less than .005, respectively. Although traffic was decreased during periods of gown use, overgowns are an expensive, ineffective method of decreasing nosocomial infection rates, vascular catheter colonization rates, and breaks in handwashing technique.


Shamanism and complementary therapy.
Shamanism is an ancient tradition which may offer profound insights into the healing process and to our whole understanding of health. It has an extensive historical and geographical distribution, and may contain elements essential to our understanding of humanity. This paper outlines the origin and nature of shamanic practice, and considers its implications for a number of current healing issues. Several areas of potential relevance to complementary practitioners are explored. These include the shamanic concepts of illness, change and growth; illness and healing as rites of passage; death and dying; and the use of imagery in healing. This paper suggests that complementary practitioners may find some shamanic principles highly congruent with their own practice.


Segmental expression of the bradykinin type 2 receptor in rat efferent ducts and epididymis and its role in the regulation of aquaporin 9.
Water and solute transport in the efferent ducts and epididymis are important for the establishment of the appropriate luminal environment for sperm maturation and storage. Aquaporin 9 (AQP9) is the main water channel in the epididymis, but its regulation is still poorly understood. Components of the kinin-kallikrein system (KKS), leading to the production of bradykinin (BK), are highly expressed in the lumen of the male reproductive tract. We report here that the epididymal luminal fluid contains a significant amount of BK (2 nM). RT-PCR performed on epididymal epithelial cells isolated by laser capture microdissection (LCM) showed abundant BK type 2 receptor (Bdkrb2) mRNA expression but no type 1 receptor (Bdkrb1). Double-immunofluorescence staining for BDKRB2 and the anion exchanger AE2 (a marker of efferent duct ciliated cells) or the V-ATPase E subunit, official symbol ATP6V1E1 (a marker of epididymal clear cells), showed that BDKRB2 is expressed in the apical pole of nonciliated cells (efferent ducts) and principal cells (epididymis). Triple labeling for BDKRB2, AQP9, and ATP6V1E1 showed that BDKRB2 and AQP9 colocalize in the apical stereocilia of principal cells in the cauda epididymidis. While uniform Bdkrb2 mRNA expression was detected in the efferent ducts and along the epididymal tubule, marked variations were detected at the protein level. BDKRB2 was highest in the efferent ducts and cauda epididymidis, intermediate in the distal initial segment, moderate in the corpus, and undetectable in the proximal initial segment and the caput. Functional assays on tubules isolated from the distal initial segments showed that BK significantly increased AQP9-dependent glycerol apical membrane permeability. This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9.


Pulmonary Embolism in Autosomal Dominant Polycystic Kidney Patient Induced by Inferior Vena Cava Mechanical Compression.
Autosomal dominant polycystic kidney disease is a common syndrome. Renal and hepatic cysts can cause discomfort, bleeding, rupture, infection, hypertension and a mass effect with compression of adjacent organs. A 48-year-old man with polycystic kidney disease and hypertension presented to the emergency department for bilateral flank pain. An abdominal computed tomography scan with contrast showed a 7 cm heterogeneous process posteriorly and laterally to the right kidney. It appeared to be a renal cyst associated with bleeding and bilateral pulmonary artery filling defects, apparently due to pulmonary embolism. Cavography following inferior vena cava filter insertion did not show any deep vein thrombosis. The pulmonary embolism was probably caused by extrinsic inferior vena cava compression by a liver cyst. Virchow's triad of stasis, vessel damage and hypercoagulability probably resulted in a thrombus which moved on the right side to the pulmonary artery. Autosomal dominant polycystic kidney disease is a common syndrome.Renal and hepatic cysts can compress adjacent organs.The mass effect of a large cyst on the right side compressed the inferior vena cava, resulting in Virchow's triad of stasis, vessel damage and hypercoagulability, which can cause pulmonary embolism.


Adipocyte lactate production remains elevated during refeeding after fasting.
The metabolic state occurring with refeeding after fasting is characterized by the rapid restoration of hepatic glycogen. Recent evidence suggests that a main substrate for glycogenesis is lactate. Because adipose tissue is an active site of lactate production that increases with fasting, we examined the magnitude and duration of lactate production by isolated adipocytes from three adipose depots of rats fasted for 48 h and then refed for up to 96 h. The data show that 48 h of fasting results in a markedly elevated rate of adipocyte lactate production, which increased from 3-9% of total glucose metabolized in the fed state to 49-60% in the fasted state. During the refeeding period, lactate production remained elevated for 12-24 h and then declined. Mesenteric adipocytes had a higher rate and more prolonged elevation in lactate production than cells from the other two depots. We conclude that, with refeeding after a fast, adipocyte glucose conversion to lactate remains elevated during the time of hepatic glycogen restoration. This suggests that adipose tissue may actively produce lactate for glycogenesis during refeeding.


The effect of nicotine on the recovery of rats receiving anesthesia.
To determine the effect of intraperitoneal (ip) nicotine on the recovery of rats receiving general anesthesia compared with placebo. The placebo controlled experimental study was conducted in the Faculty of Medicine, Gazi University, Turkey, between April and May 2005. Twenty-one male and 21 female rats were randomly divided into 3 groups. Group C (n=14), comprising a female group CF (n=7), and male group CM (n=7) received ip 0.9% sodium chloride (NaCl), group P (n=14), comprising a female group PF (n=7), and male group PM (n=7) received ip propofol 150 mg/kg, and group NP (n=14), comprising a female group NPF (n=7), and male group NPM (n=7) received 0.4 mg/kg ip nicotine followed by 150 mg/kg propofol after 15 minutes. For the evaluation of recovery period, tail pinch test was used, and for cognitive performance, the radial arm maze test was used. The number of entrances and exits decreased in group P significantly compared to group C (p<0.05), and the decrease in group PF was higher than it was in group PM. Entrance and exit in group NP increased significantly compared to group P (p<0.05). The increase in entrance and exit in group NPF was much higher compared to group NPM. The recovery period in group NP was significantly shorter than in group P (p<0.05). The ip administration of nicotine in rats shortens the recovery from propofol anesthesia and improves cognitive performance.


Preparation and characterization of textile-based carrier systems for anal fissure treatment.
Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8 µm. Encapsulation efficiency were 96.142 ± 5.931 and 85.571 ± 3.301; drug loading were 65.261 ± 3.914% and 37.844 ± 4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.


Comparative assessment of segmentation algorithms for tumor delineation on a test-retest [(11)C]choline dataset.
Many methods have been proposed for tumor segmentation from positron emission tomography images. Because of the increasingly important role that [(11)C]choline is playing in oncology and because no study has compared segmentation methods on this tracer, the authors assessed several segmentation algorithms on a [(11)C]choline test-retest dataset. Fixed and adaptive threshold-based methods, fuzzy C-means (FCM), Canny's edge detection method, the watershed transform, and the fuzzy locally adaptive Bayesian algorithm (FLAB) were used. Test-retest [(11)C]choline scans of nine patients with breast cancer were considered and the percent test-retest variability %VAR(TEST-RETEST) of tumor volume (TV) was employed to assess the results. The same methods were then applied to two denoised datasets generated by applying either a Gaussian filter or the wavelet transform. The (semi)automated methods FCM, FLAB, and Canny emerged as the best ones in terms of TV reproducibility. For these methods, the %root mean square error %RMSE of %VAR(TEST-RETEST), defined as %RMSE= variance+mean(2), was in the range 10%-21.2%, depending on the dataset and algorithm. Threshold-based methods gave TV estimates which were extremely variable, particularly on the unsmoothed data; their performance improved on the denoised datasets, whereas smoothing did not have a remarkable impact on the (semi)automated methods. TV variability was comparable to that of SUV(MAX) and SUV(MEAN) (range 14.7%-21.9% for %RMSE of %VAR(TEST-RETEST), after the exclusion of one outlier, 40%-43% when the outlier was included). The TV variability obtained with the best methods was similar to the one reported for TV in previous [(18)F]FDG and [(18)F]FLT studies and to the one of SUV(MAX)∕SUV(MEAN) on the authors' [(11)C]choline dataset. The good reproducibility of [(11)C]choline TV warrants further studies to test whether TV could predict early response to treatment and survival, as for [(18)F]FDG, to complement∕substitute the use of SUV(MAX) and SUV(MEAN).


Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis.
Hashimoto thyroiditis (HT), a prevalent autoimmune disorder, is not yet thoroughly understood, especially when it comes to the influence of epigenetics in its pathogenesis. The primary goal of this research was to probe the DNAm profile across the genome in the whole blood derived from patients suffering from HT. Using the Illumina 850K BeadChip, we conducted a genome-wide DNAm assessment on 10 matched pairs of HT sufferers and healthy individuals. Genes with differential methylation (DMGs) were identified and underwent functional annotation via the databases of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The transcriptional significance of potential epigenetic biomarker genes was corroborated through qRT-PCR. The DNAm profiling across the genome indicated an overall reduction in methylation in HT subjects in comparison with their healthy counterparts. We detected 283 DMPs (adjusted P < 0.05 and |Δβ| > 0.1), among which 152 exhibited hypomethylation and 131 demonstrated hypermethylation. Further analysis exposed a noteworthy concentration of hypermethylated DMPs in the 3´UTR, North Shore, and CpG islands, while there was a significant decrease in the Open Sea (all P < 0.001). The 283 DMPs were broadly distributed from chromosome 1 to 22, with chromosome 6 harboring the most DMPs (n = 51) and chromosome 12 carrying the most DMGs (n = 15). The SLFN12 gene, which presented with extreme hypomethylation in its promoter DMPs among HT patients, was identified as the epigenetic marker gene. Consequently, the SLFN12 mRNA expression was markedly upregulated in HT, displaying a negative relationship with its methylation levels. The area under curve (AUC) value for the SLFN12 gene among HT patients was 0.85 (sensitivity: 0.7, specificity: 0.7), a significant difference compared with healthy controls. The methylation levels of all DMPs in SLFN12 gene were negatively correlated with TSH and one CpG site (cg24470734) was positively assocciated with FT4. This investigation presents an initial comprehensive DNAm blueprint for individuals with HT, which permits clear differentiation between HT subjects and normal controls through an epigenetic lens. The SLFN12 gene plays a pivotal role in the onset of HT, suggesting that the methylation status of this gene could serve as a potential epigenetic indicator for HT.


Antecedents of drinking for early- and late-onset elderly alcohol abusers.
The present study compared antecedents to recent drinking for two groups of elderly alcohol abusers admitted for treatment. Twenty-three early-onset alcohol abusers were matched with 23 late-onset alcohol abusers according to age and sex. Depression, loneliness and lack of social support were the most frequently reported antecedents to preadmission drinking behavior for both groups. However, early-onset subjects were more likely to have changed residence, were intoxicated more often and experienced more severe levels of depression and anxiety. Late-onset subjects had greater life satisfaction and motivation for treatment, but were rated by collaterals as having more severe alcohol problems. Early-onset subjects were more likely to drop out of treatment. Treatment implications for age-related commonalities are discussed.


All about being old and shooting hairs: Clade age and urticating hair explain the patterns of diversification in tarantulas.
The extreme asymmetry of species richness distribution across the tree of life has always intrigued evolutionary biologists. Two competing explanations have been proposed to explain this pattern-the clade age hypothesis and diversification rate variation. While these two scenarios may not be mutually exclusive, to what extent time and diversification rates interact to explain species richness patterns remains understudied. Here, we investigate the relative influence of these two scenarios using tarantulas (Family: Theraphosidae) as a model. Tarantulas represent a speciose group of spiders found worldwide but exceptionally diverse in South America. These spiders show two distinct patterns of microhabitat use (ground-dwelling or arboreal) and defence strategies (presence or absence of urticating hairs). Using various trait-independent and dependent diversification models, we test the clade age hypothesis, the role of microhabitat, antipredator defence strategy and geography in influencing diversification rates. Our results suggest that clade age is the primary predictor of species richness distribution across the tarantula subfamilies. However, the presence of urticating hair probably disrupted this pattern in some clades by increasing the net diversification rates, not by increasing the speciation rate but by reducing the extinction rate.