Esophageal ulceration in human immunodeficiency virus infection. Causes, response to therapy, and long-term outcome.
To determine the causes of esophageal ulceration, the response rate to currently available therapies, and the long-term outcome in patients with human immunodeficiency virus (HIV) infection. Prospective cohort study. An urban county hospital. Consecutive patients with HIV infection and endoscopically detected esophageal ulceration during a 4-year period. Causes of ulcers were determined from clinical, endoscopic, and pathologic findings. Standard medical therapies for the identified causes were instituted, and ulcer healing was endoscopically confirmed when possible. Symptomatic and endoscopic response to therapy and long-term outcome, including survival. 100 patients with esophageal ulcer were identified. Ulcers caused by cytomegalovirus alone were the most common (n = 45); idiopathic ulcers were almost as frequent (n = 40). Herpes simplex virus esophagitis alone was identified as a cause in only 5 patients. Several potential causes of ulcer were found in 5 patients, including Candida esophagitis in 27 patients. Ten patients developed more than one cause of ulceration during long-term follow-up. Eighty-five patients had specific medical therapy for their identified disorders and had an overall response rate of 98%. Median survival from time of diagnosis was 8.9 months (range, 2 days to > 42 months). A difference in median survival was found between patients with cytomegalovirus esophagitis and those with idiopathic esophageal ulcer (7.6 months compared with 13.1 months; P = 0.03). Given 1) the broad spectrum of causes of esophageal ulceration, 2) that each of these causes requires specific therapy, and 3) the apparent high response rate, it is important to do endoscopic evaluation with mucosal biopsy in patients with HIV infection so that a diagnosis can be established and appropriate therapy instituted. Despite effective therapy, long-term survival is poor; however, long-term remission and survival may occur in some patients.


Structure and function of Rnt1p: An alternative to RNAi for targeted RNA degradation.
The double-stranded RNA-binding protein (dsRBP) family controls RNA editing, stability, and function in all eukaryotes. The central feature of this family is the recognition of a generic RNA duplex using highly conserved double-stranded RNA-binding domain (dsRBD) that recognizes the characteristic distance between the minor grooves created by the RNA helix. Variations on this theme that confer species and functional specificities have been reported but most dsRBPs retain their capacity to bind generic dsRNA. The ribonuclease III (RNase III) family members fall into four classes, represented by bacterial RNase III, yeast Rnt1p, human Drosha, and human Dicer, respectively. Like all dsRBPs and most members of the RNase III family, Rnt1p has a dsRBD, but unlike most of its kin, it poorly binds to generic RNA helices. Instead, Rnt1p, the only known RNase III expressed in Saccharomyces cerevisiae that lacks the RNAi (RNA interference) machinery, recognizes a specific class of stem-loop structures. To recognize the specific substrates, the dsRBD of Rnt1p is specialized, featuring a αβββααα topology and a sequence-specific RNA-binding motif at the C-terminus. Since the discovery of Rnt1p in 1996, significant progress has been made in studies of its genetics, function, structure, and mechanism of action, explaining the reasons and mechanisms for the increased specificity of this enzyme and its impact on the mechanism of RNA degradation. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Processing > Processing of Small RNAs RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.


Toward High-Performance Hematite Nanotube Photoanodes: Charge-Transfer Engineering at Heterointerfaces.
Vertically ordered hematite nanotubes are considered to be promising photoactive materials for high-performance water-splitting photoanodes. However, the synthesis of hematite nanotubes directly on conducting substrates such as fluorine-doped tin oxide (FTO)/glass is difficult to be achieved because of the poor adhesion between hematite nanotubes and FTO/glass. Here, we report the synthesis of hematite nanotubes directly on FTO/glass substrate and high-performance photoelectrochemical properties of the nanotubes with NiFe cocatalysts. The hematite nanotubes are synthesized by a simple electrochemical anodization method. The adhesion of the hematite nanotubes to the FTO/glass substrate is drastically improved by dipping them in nonpolar cyclohexane prior to postannealing. Bare hematite nanotubes show a photocurrent density of 1.3 mA/cm(2) at 1.23 V vs a reversible hydrogen electrode, while hematite nanotubes with electrodeposited NiFe cocatalysts exhibit 2.1 mA/cm(2) at 1.23 V which is the highest photocurrent density reported for hematite nanotubes-based photoanodes for solar water splitting. Our work provides an efficient platform to obtain high-performance water-splitting photoanodes utilizing earth-abundant hematite and noble-metal-free cocatalysts.


Clinical efficacy and safety of the factor VIII/von Willebrand factor concentrate BIOSTATE in patients with von Willebrand's disease: a prospective multi-centre study.
von Willebrand's disease (VWD) is an inherited bleeding disorder characterized by deficient levels of or dysfunctional von Willebrand factor (VWF). This phase II/III open-label, multicentre study evaluated the efficacy and safety of BIOSTATE, a high purity plasma-derived double-virus inactivated FVIII/VWF concentrate, when used in non-surgical bleeds, surgical procedures and prophylactic therapy in VWD patients for whom desmopressin treatment was deemed ineffective, inadequate or contraindicated. Twenty three patients (7 type 1, 9 type 2 and 7 type 3; 12 male, 11 female), who received FVIII/VWF concentrate as part of their VWD management, were recruited prospectively between December 2004 and May 2007 from eight centres in Australia and New Zealand. BIOSTATE dosing was based on pre-treatment FVIII:C and/or VWF:RCo plasma levels and a predetermined dosing guide. Haemostatic efficacy of BIOSTATE was rated as excellent or good for all major and minor surgery events, long-term prophylaxis, and for four of the six assessable non-surgical bleeding events. Blood transfusions were required by two major surgery patients as well as one patient with a non-surgical bleed. The median overall exposure to BIOSTATE across all groups was 8 days, greater in the prophylactic group (range 53-197) compared with major surgery (3-24), minor surgery (1-8) and non-surgical bleeds (1-10). BIOSTATE was shown to be efficacious and well tolerated when treating patients with VWD. This study also provides important insights into dosing regimens with BIOSTATE and the role of monitoring therapy with FVIII:C and VWF:RCo.


Diagnostic labeling of COPD in five Latin American cities.
COPD is a major worldwide problem with a rising prevalence. Despite its importance, there is a lack of information regarding underdiagnosis and misdiagnosis of COPD in different countries. As part of the Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar study, we examined the relationship between prior diagnostic label and airway obstruction in the metropolitan areas of five Latin American cities (São Paulo, Santiago, Mexico City, Montevideo, and Caracas). A two-stage sampling strategy was used in each of the five areas to obtain probability samples of adults aged >or= 40 years. Participants completed a questionnaire that included questions on prior diagnoses, and prebronchodilator and postbronchodilator spirometry. A study diagnosis of COPD was based on airway obstruction, defined as a postbronchodilator FEV(1)/FVC < 0.70. Valid spirometry and prior diagnosis information was obtained for 5,303 participants; 758 subjects had a study diagnosis of COPD, of which 672 cases (88.7%) had not been previously diagnosed. The prevalence of undiagnosed COPD was 12.7%, ranging from 6.9% in Mexico City to 18.2% in Montevideo. Among 237 subjects with a prior COPD diagnosis, only 86 subjects (36.3%) had postbronchodilator FEV(1)/FVC < 0.7, while 151 subjects (63.7%) had normal spirometric values. In the same group of 237 subjects, only 34% reported ever undergoing spirometry prior to our study. Inaccurate diagnostic labeling of COPD represents an important health problem in Latin America. One possible explanation is the low rate of spirometry for COPD diagnosis.


Optimisation of rocker sole footwear for prevention of first plantar ulcer: comparison of group-optimised and individually-selected footwear designs.
Appropriate footwear for individuals with diabetes but no ulceration history could reduce the risk of first ulceration. However, individuals who deem themselves at low risk are unlikely to seek out bespoke footwear which is personalised. Therefore, our primary aim was to investigate whether group-optimised footwear designs, which could be prefabricated and delivered in a retail setting, could achieve appropriate pressure reduction, or whether footwear selection must be on a patient-by-patient basis. A second aim was to compare responses to footwear design between healthy participants and people with diabetes in order to understand the transferability of previous footwear research, performed in healthy populations. Plantar pressures were recorded from 102 individuals with diabetes, considered at low risk of ulceration. This cohort included 17 individuals with peripheral neuropathy. We also collected data from 66 healthy controls. Each participant walked in 8 rocker shoe designs (4 apex positions × 2 rocker angles). ANOVA analysis was then used to understand the effect of two design features and descriptive statistics used to identify the group-optimised design. Using 200 kPa as a target, this group-optimised design was then compared to the design identified as the best for each participant (using plantar pressure data). Peak plantar pressure increased significantly as apex position was moved distally and rocker angle reduced (p < 0.001). The group-optimised design incorporated an apex at 52% of shoe length, a 20° rocker angle and an apex angle of 95°. With this design 71-81% of peak pressures were below the 200 kPa threshold, both in the full cohort of individuals with diabetes and also in the neuropathic subgroup. Importantly, only small increases (<5%) in this proportion were observed when participants wore footwear which was individually selected. In terms of optimised footwear designs, healthy participants demonstrated the same response as participants with diabetes, despite having lower plantar pressures. This is the first study demonstrating that a group-optimised, generic rocker shoe might perform almost as well as footwear selected on a patient by patient basis in a low risk patient group. This work provides a starting point for clinical evaluation of generic versus personalised pressure reducing footwear.


[Entrapment neuropathies: a contemporary approach to pathophysiology, clinical assessment, and management : German version].
Entrapment neuropathies such as carpal tunnel syndrome, radiculopathies, or radicular pain are the most common peripheral neuropathies and also the most common cause for neuropathic pain. Despite their high prevalence, they often remain challenging to diagnose and manage in a clinical setting. Summarising the evidence from both preclinical and clinical studies, this review provides an update on the aetiology and pathophysiology of entrapment neuropathies. Potenzial mechanisms are put in perspective with clinical findings. The contemporary assessment is discussed and diagnostic pitfalls highlighted. The evidence for the noninvasive and surgical management of common entrapment neuropathies is summarised and future areas of research are identified.


A reinvestigation of somatic hypermethylation at the PTEN CpG island in cancer cell lines.
PTEN is an important tumour suppressor gene that is mutated in Cowden syndrome as well as various sporadic cancers. CpG island hypermethylation is another route to tumour suppressor gene inactivation, however, the literature regarding PTEN hypermethylation in cancer is controversial. Furthermore, investigation of the methylation status of the PTEN CpG island is challenging due to sequence homology with the PTEN pseudogene, PTENP1. PTEN shares a CpG island promoter with another gene known as KLLN. Here we present a thorough reinvestigation of the methylation status of the PTEN CpG island in DNA from colorectal, breast, ovarian, glioma, lung and haematological cancer cell lines. Using a range of bisulphite-based PCR assays we investigated 6 regions across the PTEN CpG island. We found that regions 1-4 were not methylated in cancer cell lines (0/36). By allelic bisulphite sequencing and pyrosequencing methylation was detected in regions 5 and 6 in colorectal, breast and haematological cancer cell lines. However, methylation detected in this region was associated with the PTENP1 promoter and not the PTEN CpG island. We show that methylation of the PTEN CpG island is a rare event in cancer cell lines and that apparent methylation most likely originates from homologous regions of the PTENP1 pseudogene promoter. Future studies should utilize assays that reliably discriminate between PTEN and PTENP1 to avoid data misinterpretation.


Endocrine changes in patients with acute organophosphate poisoning.
In critical illness, several drugs and various stressful conditions modify the functions of neurotransmitters which consequently affect the secretion of pituitary hormones. Although the role of neurotransmitters in the regulation of endocrine system is well known, cholinergic actions have been less investigated. In animals, cholinesterase inhibitors were shown to modify the pituitary-thyroid and pituitary-adrenal axes, and to affect prolactin levels. The aim of the present study was to determine the effect of the organophosphate compounds on endocrine system, particularly pituitary hormones. This prospective study was performed in Medical Intensive Care Unit of Erciyes University Medical School Hospital. Twenty-two consecutive patients (ten males and 12 females aged 28+/-8 years) with organophosphate poisoning were included in the study. ACTH (P<0.002), cortisol (P<0.0005) and PRL (P<0.005) levels were significantly higher during poisoning than after resolution of poisoning. FSH levels were significantly lower during poisoning (P<0. 05). Sick euthyroid syndrome was determined in seven patients (31. 8%). Two of them had low fT3 (with normal fT4 and TSH), two had low fT4 (with normal fT3 and TSH) and three had low TSH (with normal fT3 and fT4) levels. Serum levels of these hormones returned to normal values after resolution of poisoning. The present study demonstrated that organophosphate compounds affected PRL, ACTH and cortisol levels, but did not change LH levels. Organophosphate compounds may result in sick euthyroid syndrome. These conditions may be related to the effects of acetylcholine and direct effect of organophosphate compounds.


Composition, antioxidant and antimicrobial activities of methanol extracts of some Acinos Miller species.
GC and GC/MS analyses of the methanol extracts obtained from the aerial parts of six Acinos Miller species from Serbia and Montenegro were performed. Seventy-four constituents, accounting for 84.9-99.0% of the total composition of the extracts, were identified. The common feature of the A. suaveolens, A. majoranifolius and A. alpinus methanol extracts was the high content of monoterpenes, while the common feature of the A. graveolens, A. arvensis and A. hungaricus methanol extracts was the prevalence of sesquiterpenes. The total flavonoids, polyphenols and tannins content, as well as antioxidant activity (FRAP and DPPH assay) of the methanolic extracts were investigated. The highest antioxidant activity was observed in the extract of A. alpinus which had high levels of all polyphenol classes examined. A disk diffusion method was used for the evaluation of the antimicrobial activities of the extracts against a panel of microorganisms (bacteria: Bacillus subtilis, Clostridium pyogenes, Enterococcus sp., Micrococcus flavus, Sarcina lutea, Staphylococcus aureus, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enteritidis and Escherichia coli; fungi: Aspergillus niger, Candida albicans and Saccharomyces cerevisiae). The preliminary bioassay results indicated that the methanol extract of A. alpinus could be a possible source of antioxidant and antimicrobial compounds.


Influence of effective communication by surgery students on their oral examination scores.
This study investigated the influences of specific elements of surgery students' verbal and nonverbal communication on evaluators' "objective" ratings of several categories of the students' performances on oral examinations. Three actors and two actresses, dressed as surgery students in a wide range of attire, were videotaped as they reenacted five transcripts of actual students' responses in their oral examinations. For each examination, the actors portrayed the students' responses to the same examining surgeon in two formats, one using direct eye contact with a moderate response rate (Style A) and the other using indirect eye contact with a slower response rate (Style B). All transcripts were taped at least twice. The resulting 255 videotaped "examinations" were randomly distributed in 1988 to 78 clinical surgery faculty representing 46 institutions throughout the United States and Canada. These faculty viewed the reenactments (under the impression they were actual examinations) and rated the "students" performances overall and in ten categories concerning different aspects of the students' knowledge, clinical decision-making skills, and personal characteristics. The performances done in Style A were rated significantly higher than those done in Style B (1) in every performance category except decision making and (2) when the scores were classified by the content of the responses and how professionally dressed the students were. There were also a significant relationship between scores on communication skills and the overall all scores on examinations. These findings suggest that regardless of the content of a student's responses on an oral examination, evaluators are strongly influenced by how well the student communicates.


Comparative study of lectin reactivity in the vomeronasal organ of human and nonhuman primates.
The main and accessory olfactory systems of certain mammals (e.g., rodents, ungulates, and carnivores) have been investigated using lectin histochemistry to probe for sugar residues that may reflect physiological aspects of signal transduction or development. Morphologically, the vomeronasal organs (VNOs) of strepsirrhine primates (lemurs and lorises) are typical of functional VNOs in other mammals, whereas in humans and chimpanzees the VNOs appear vestigial. However, the human VNO is considered functional by some authors. To elucidate the cellular nature of the VNO in human and chimpanzees, a panel of six lectins (Con-A, ECL, PNA, RCA, s-WGA, and UEA-1) was applied to the VNO in eight species of primates, including humans and chimpanzees. The results indicated that there were few, if any, lectin-reactive cells in the human or chimpanzee VNO that resembled those seen in the vomeronasal neuroepithelium in other primates. The overall pattern of lectin reactivity in the human and chimpanzee VNO is unlike that seen in mammals with chemosensory VNOs, suggesting that the VNO of these hominoids does not function similarly to that of other primates.


Cannabis, tobacco, and caffeine use modify the blood pressure reactivity protection of ascorbic acid.
Cannabis, caffeine, and tobacco use are associated with increased mesolimbic dopamine activity. Ascorbic acid (AA) modulates some dopaminergic agent effects, and was recently found to decrease systolic blood pressure (SBP) stress reactivity. To examine how AA SBP stress reactivity protection varies by use of these substances, data from an AA trial (Cetebe, 3000 mg/day for 14 days; N=108) were compared by substance use level regarding SBP reactivity to the anticipation and actual experience phases of a standardized psychological stressor (10 min of public speaking and arithmetic). Self-reported never users of cannabis, persons not currently smoking tobacco, and persons consuming three or more caffeine beverages daily all exhibited AA SBP stress reactivity protection to the actual stressor, but not during the anticipation phase. Conversely, self-reported ever cannabis users, current tobacco smokers, and persons consuming less than three caffeine beverages daily exhibited the AA SBP protection during the anticipation phase, but only the lower caffeine consumption group exhibited AA protection during both phases. Covariates (neuroticism, extraversion, and depression scores, age, sex, body mass index) were all nonsignificant. Results are discussed in terms of dopaminergic effects of these substances, modulation of catecholaminergic and endothelial activity, and AA support of coping styles.


Uterine transplantation--a real possibility? The Indianapolis consensus.
A group of experts gathered in Indianapolis in December 2011 to address lingering concerns related to uterus transplantation (UTn). They represent a multi-national group of four research teams who have worked for over 15 years on bringing UTn to reality for patients. Presented here are a set of parameters that must be considered in order for UTn to become an acceptable procedure in the human setting. UTn has been proposed as a potential solution to absolute uterine factor infertility (AUFI). Causes of AUFI include congenital uterine factors (i.e. absence or malformation) or acquired uterine factors (e.g. hysterectomy for uncontrollable hemorrhage) rendering a woman 'unconditionally infertile'. Current estimates are that in the USA, up to 7 million women with AUFI may be appropriate candidates for UTn. As a result of a first human attempt in 2000, investigators have responded with a plethora of publications demonstrating successful UTn attempts, including pregnancies, in various autogeneic, syngeneic and allogeneic animal models. Before UTn can become an accepted procedure, it must satisfy defined criteria for any surgical innovation, i.e. research background, field strength and institutional stability. Equally important, UTn must satisfy accepted bioethical principles (respect for autonomy, beneficence, non-maleficence and justice) and their application (informed consent, appropriate assessment of risk and benefit and fair selection of individuals). Furthermore, we believe that a defined number of transplants should not be exceeded worldwide without a successful term delivery, to minimize proceeding in futility using current techniques. Even if UTns were to become relatively common, the following research objectives should be continuously pursued: (i) additional pregnancies in a variety of large animal/primate models (to search for unanticipated consequences), (ii) continuous assessment of women diagnosed with AUFI regarding UTn, (iii) continuous assessment using 'borrowed' psychological tools from transplant centers, adoption agencies and assisted reproductive technology centers with potential recipients and (iv) continuous careful ethical reflection, assessment and approval.


Freshwater availability status across countries for human and ecosystem needs.
Water demand is expected to continue rising to support growing population, particularly in water-stressed countries and regions. Amid competitive water needs for agricultural, domestic, and industrial sectors, water allocations for environmental requirements are critical to ensure the sustainability of the ecosystems. This study takes stock of water availability trends per capita across countries and proposes a water scarcity indicator to quantify the amount of water available for agricultural, domestic, and industrial activities after the needs of freshwater ecosystems (environmental flow requirements, EFR) are ideally fulfilled. The study reveals that by 2050, 87 out of 180 countries will have annual renewable water resources (ARWR) per capita below 1700 m3/year. The number of countries with absolute water scarcity - ARWR per capita below 500 m3/year is projected to increase from 25 in 2015 to 45 by 2050. Population growth is projected to cause a sharp decline in water availability in many low-income and lower-middle-income countries, while economic development will push water use upwards, making the water supply gap more complicated and challenging to address. After the Middle East and North Africa region, Sub-Saharan Africa is expected to become the next hotspot of water scarcity along with several countries from Asia. In response, water-scarce countries need to promote water conservation, water recycling, and reuse; ensure sustainable water resources augmentation via harnessing the potential of unconventional water resources; support productivity enhancement of underperforming land and water resources; and address challenges beyond technical solutions. Pertinent political agenda and associated public policies, supportive institutions, institutional collaborations, and skilled professionals would be the key to ensure sufficient water supply for human use and ecosystems.


The physiologic effects of pneumoperitoneum in the morbidly obese.
To review the physiologic effects of carbon dioxide (CO2) pneumoperitoneum in the morbidly obese. The number of laparoscopic bariatric operations performed in the United States has increased dramatically over the past several years. Laparoscopic bariatric surgery requires abdominal insufflation with CO2 and an increase in the intraabdominal pressure up to 15 mm Hg. Many studies have demonstrated the adverse consequences of pneumoperitoneum; however, few studies have examined the physiologic effects of pneumoperitoneum in the morbidly obese. A MEDLINE search from 1994 to 2003 was performed using the key words morbid obesity, laparoscopy, bariatric surgery, pneumoperitoneum, and gastric bypass. The authors reviewed papers evaluating the physiologic effects of pneumoperitoneum in morbidly obese subjects undergoing laparoscopy. The topics examined included alteration in acid-base balance, hemodynamics, femoral venous flow, and hepatic, renal, and cardiorespiratory function. Physiologically, morbidly obese patients have a higher intraabdominal pressure at 2 to 3 times that of nonobese patients. The adverse consequences of pneumoperitoneum in morbidly obese patients are similar to those observed in nonobese patients. Laparoscopy in the obese can lead to systemic absorption of CO2 and increased requirements for CO2 elimination. The increased intraabdominal pressure enhances venous stasis, reduces intraoperative portal venous blood flow, decreases intraoperative urinary output, lowers respiratory compliance, increases airway pressure, and impairs cardiac function. Intraoperative management to minimize the adverse changes include appropriate ventilatory adjustments to avoid hypercapnia and acidosis, the use of sequential compression devices to minimizes venous stasis, and optimize intravascular volume to minimize the effects of increased intraabdominal pressure on renal and cardiac function. Morbidly obese patients undergoing laparoscopic bariatric surgery are at risk for intraoperative complications relating to the use of CO2 pneumoperitoneum. Surgeons performing laparoscopic bariatric surgery should understand the physiologic effects of CO2 pneumoperitoneum in the morbidly obese and make appropriate intraoperative adjustments to minimize the adverse changes.


Retinal and post-retinal contributions to the quantum efficiency of the human eye revealed by electrical neuroimaging.
The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed) but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12). Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities.


Genetic Aspects of Dental Erosive Wear and Dental Caries.
The present review aims to give an overview of the literature focusing on novel genetic aspects of dental erosion and dental caries. Once the tooth erupts into the oral cavity, the regenerative capability of enamel is fundamentally limited due to the loss of dental epithelium during eruption. The susceptibility or resistance to dental erosion and caries is presumably a result of environmental, phenotypic, and/or genetic influence. Even though it is evident that individuals frequently exposing their teeth to acid and sugar are at high risk of developing dental erosion and caries, the findings exclusively based on these factors are elusive. Data resources and study selection. The present review was based on data collected from the National Library of Medicine database with different combinations of the following terms: "tooth," "dental," "dentin," "enamel," "erosion," "erosive wear," "caries," "decay," "gene," and "genetic." A total of forty-six studies met the inclusion criteria. Data were extracted by one reviewer and verified by another. The high prevalence of erosion and caries among certain groups, and observations that not all individuals appearing to be at risk develop these lesions, has sparked research on identifying genetic effects to these conditions. A connection of genome-wide and candidate gene studies has increased considerably in the literature. This review reveals largely varying success among studies, demonstrating the difficulties of developing the study with adequate sample sizes and durable phenotype definitions that permit enough statistical power to identify genetic contributors.


Independent and Joint Associations of Physical Activity and Dietary Behavior with Older Adults' Lower Limb Strength.
Studies have indicated that sufficient physical activity levels and balanced dietary behavior are independently related to physical function in older populations; however, their joint association with physical function remain unclear. This study examined the independent and combined associations of sufficient physical activity and balanced selection of foods with lower limb strength among 122 older Taiwanese adults living in community (mean age: 69.9 ± 5.0 years). The assessments included accelerometer-measured moderate-to-vigorous physical activity (MVPA) and self-reported selection of foods. Lower limb strength performance was measured using the five times sit-to-stand test. Binary logistic regression analyses were performed to estimate the associations in question before and after adjusting for potential confounders. The results showed that in the adjusted model, lower limb strength had no significant independent association with either meeting the recommended level of MVPA or balanced selection of foods. Compared to older adults who neither met the recommended MVPA level nor reported a balanced selection of foods, those who conformed to both these criteria were more likely to have better lower limb strength (odds ratio = 6.28, 95% confidence interval = 1.36-29.01) after adjusting for covariates. Health promotion initiatives addressing disability prevention for older adults need to consider promoting both MVPA and food selection.


Ethnic differences in the use of prescription drugs: a cross-sectional analysis of linked survey and administrative data.
Evidence from the United States and Europe suggests that the use of prescription drugs may vary by ethnicity. In Canada, ethnic disparities in prescription drug use have not been as well documented as disparities in the use of medical and hospital care. We conducted a cross-sectional analysis of survey and administrative data to examine needs-adjusted rates of prescription drug use by people of different ethnic groups. For 19 370 non-Aboriginal people living in urban areas of British Columbia, we linked data on self-identified ethnicity from the Canadian Community Health Survey with administrative data describing all filled prescriptions and use of medical services in 2005. We used sex-stratified multivariable logistic regression analysis to measure differences in the likelihood of filling prescriptions by drug class (antihypertensives, oral antibiotics, antidepressants, statins, respiratory drugs and nonsteroidal anti-inflammatory drugs [NSAIDs]). Models were adjusted for age, general health status, treatment-specific health status, socio-economic factors and recent immigration (within 10 years). We found evidence of significant needs-adjusted variation in prescription drug use by ethnicity. Compared with women and men who identified themselves as white, those who were South Asian or of mixed ethnicity were almost as likely to fill prescriptions for most types of medicines studied; moreover, South Asian men were more likely than white men to fill prescriptions for antibiotics and NSAIDs. The clearest pattern of use emerged among Chinese participants: Chinese women were significantly less likely to fill prescriptions for antihypertensives, antibiotics, antidepressants and respiratory drugs, and Chinese men for antidepressant drugs and statins. We found some disparities in prescription drug use in the study population according to ethnic group. The nature of some of these variations suggest that ethnic differences in beliefs about pharmaceuticals may generate differences in prescription drug use; other variations suggest that there may be clinically important disparities in treatment use.


IL-33-mediated IL-13 secretion by ST2+ Tregs controls inflammation after lung injury.
Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events is poorly understood. Herein we reveal that IL-33, an alarmin sequestered in the lung epithelium, is required to limit inflammation after injury due to an unappreciated capacity to mediate Foxp3+ Treg control of local cytokines and myeloid populations. Specifically, Il33-/- mice are more susceptible to lung damage-associated morbidity and mortality that is typified by augmented levels of the proinflammatory cytokines and Ly6Chi monocytes in the bronchoalveolar lavage fluid. Local delivery of IL-33 at the time of injury is protective but requires the presence of Treg cells. IL-33 stimulates both mouse and human Tregs to secrete IL-13. Using Foxp3Cre × Il4/Il13fl/fl mice, we show that Treg expression of IL-13 is required to prevent mortality after acute lung injury by controlling local levels of G-CSF, IL-6, and MCP-1 and inhibiting accumulation of Ly6Chi monocytes. Our study identifies a regulatory mechanism involving IL-33 and Treg secretion of IL-13 in response to tissue damage that is instrumental in limiting local inflammatory responses and may shape the myeloid compartment after lung injury.


Effect of peer education on stroke prevention: the prevent recurrence of all inner-city strokes through education randomized controlled trial.
Efforts to reduce disparities in recurrent stroke among Black and Latino stroke survivors have met with limited success. We aimed to determine the effect of peer education on secondary stroke prevention among predominantly minority stroke survivors. Between 2009 and 2012, we enrolled 600 stroke or transient ischemic attack survivors from diverse, low-income communities in New York City into a 2-arm randomized clinical trial that compared a 6 week (1 session/week), peer-led, community-based, stroke prevention self-management group workshop (N=301) to a wait-list control group (N=299). The primary outcome was the proportion with a composite of controlled blood pressure (<140/90 mm Hg), low-density lipoprotein cholesterol <100 mg/dL, and use of antithrombotic medications at 6 months. Secondary outcomes included control of the individual stroke risk factors. All analyses were by intent-to-treat. There was no difference in the proportion of intervention and control group participants achieving the composite outcome (34% versus 34%; P=0.98). The proportion with controlled blood pressure at 6 months was greater in the intervention group than in the control group (76% versus 67%; P=0.02). This corresponded to a greater change in systolic blood pressure in the intervention versus control group (-3.63 SD, 19.81 mm Hg versus +0.34 SD, 23.76 mm Hg; P=0.04). There were no group differences in the control of cholesterol or use of antithrombotics. A low-cost peer education self-management workshop modestly improved blood pressure, but not low-density lipoprotein cholesterol or antithrombotic use, among stroke and transient ischemic attack survivors from vulnerable, predominantly minority urban communities. http://www.clinicaltrials.gov/show/NCT0102727. Unique identifier: NCT01027273.


Type of attending physician influenced feeding tube insertions for hospitalized elderly people with severe dementia.
Striking variation has been documented in the rates of feeding tube insertion for hospitalized patients with advanced dementia. This occurs despite the harms of the procedure, which may outweigh its benefits, and the procedure's inconsistency with care focused on the patient's comfort. Among nursing home residents with advanced dementia who were hospitalized in 2001-10 with an infection or dehydration, we found that rates of insertion of a percutaneous endoscopic gastrostomy feeding tube varied by type of attending physician. Insertion rates were markedly lower when all of a patient's attending physicians were hospitalists (1.6 percent) or nonhospitalist generalists (2.2 percent), compared to all subspecialists (11.0 percent) or a mixture of physicians by type, which typically included a subspecialist (15.6 percent). The portion of patients seen by a mixture of attending physicians increased from 28.9 percent in 2001 to 38.3 percent in 2010. Efforts to improve decision making in the care of patients with advanced dementia should include interventions to improve communication among physicians and the education of subspecialists about the merits of using feeding tubes with this population.


SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D.
Natural killer (NK) cells are cytotoxic effector cells that target and lyse virally infected cells; many viruses therefore encode mechanisms to escape such NK cell killing. Here, we interrogate the ability of SARS-CoV-2 to modulate NK cell recognition and lysis of infected cells. We find that NK cells exhibit poor cytotoxic responses against SARS-CoV-2-infected targets, preferentially killing uninfected bystander cells. We demonstrate that this escape is driven by downregulation of ligands for the activating receptor NKG2D (NKG2D-L). Indeed, early in viral infection, prior to NKG2D-L downregulation, NK cells are able to target and kill infected cells; however, this ability is lost as viral proteins are expressed. Finally, we find that SARS-CoV-2 non-structural protein 1 (Nsp1) mediates downregulation of NKG2D-L and that Nsp1 alone is sufficient to confer resistance to NK cell killing. Collectively, our work demonstrates that SARS-CoV-2 evades direct NK cell cytotoxicity and describes a mechanism by which this occurs.


Changes in estrogenicity and micropollutant concentrations across unit processes in a biological wastewater treatment system.
The behavior of 10 micropollutants, i.e. four estrogens (estrone, 17β-estradiol, estriol, 17α-ethynylestradiol), carbamazepine (CBZ), sulfamethoxazole (SMX), triclosan, oxybenzone, 4-nonylphenol, and bisphenol A, was investigated in a typical domestic wastewater treatment plant. LC-MS and yeast estrogen screen bioassay were used to study the changes in micropollutants and estrogenicity across unit processes in the treatment system. Primary treatment via sedimentation showed that only 4-nonylphenol was removed, but led to no significant change in estrogenicity. Secondary treatment by the biological nitrification-dentrification process showed complete removal of oxybenzone and partial removal of the estrogens, which led to a decrease in estrogenic activity from 80 to 48 ng/L as estradiol equivalent (EEq). Ultraviolet treatment completely degraded the estrogens and triclosan, but failed to lower the concentrations of bisphenol A, SMX, and CBZ; a decrease in estrogenic activity from 48 to 5 ng/L EEq across the unit, a value that was only slightly larger than the observed EEq of 1 ng/L for the deionized control. Similarly, the anaerobic digestion of sludge completely degraded estrogens, oxybenzone, and SMX, but had no impact on bisphenol A, triclosan, and CBZ. The study emphasises the need to complement chemical analyses with estrogenic bioassays to evaluate the efficacy of waste water treatment plants.


Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios.
As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = -4.709, d = 0.69, p = 2.41 × 10-5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.


Comparison of patients with early-, typical-, and late-onset affective psychosis.
The authors compared the clinical characteristics and family history of patients with early-onset (before age 18), typical-onset (at 20-25 years), and late-onset (after age 35) affective psychosis at the time of first hospitalization. Diagnostic, symptom, and family history information was obtained from 88 consecutively hospitalized patients. Major depression was more common in the late-onset group, and a family history of affective and substance abuse disorders was more common among the early-onset patients. Affective symptoms differed significantly among groups; specifically, early-onset patients had more energy, minimal sleep disruption, and greater suicidality, while typical-onset patients had more severe abnormal thought content. Among patients with affective psychosis, there may be heterogeneity of symptoms and family history associated with age at first hospitalization.


Serine-305 phosphorylation modulates estrogen receptor alpha binding to a coregulator peptide array, with potential application in predicting responses to tamoxifen.
With current techniques, it remains a challenge to assess coregulator binding of nuclear receptors, for example, the estrogen receptor alpha (ERα). ERα is critical in many breast tumors and is inhibited by antiestrogens such as tamoxifen in cancer therapy. ERα is also modified by acetylation and phosphorylation that affect responses to the antiestrogens as well as interactions with coregulators. Phosphorylation of ERα at Ser305 is one of the mechanisms causing tamoxifen resistance. Detection of resistance in patient samples would greatly facilitate clinical decisions on treatment, in which such patients would receive other treatments such as aromatase inhibitors or fulvestrant. Here we describe a coregulator peptide array that can be used for high-throughput analysis of full-length estrogen receptor binding. The peptide chip can detect ERα binding in cell and tumor lysates. We show that ERα phosphorylated at Ser305 associates stronger to various coregulator peptides on the chip. This implies that ERαSer305 phosphorylation increases estrogen receptor function. As this is also detected in a breast tumor sample of a tamoxifen-insensitive patient, the peptide array, as described here, may be applicable to detect tamoxifen resistance in breast tumor samples at an early stage of disease and contribute to personalized medicine.


Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolation.
In adapting to the challenge to make more informed selection of compounds for development, the pharmaceutical industry is increasingly embracing the application of mechanism-based models and prediction tools for prediction of pharmacokinetic parameters. This review first outlines the concepts and application of the major physiologically based prediction tools to extrapolate clearance, tissue distribution, and rate and extent of absorption from minimal in vitro or animal in vivo input data. Finally, the ability of these prediction tools, when placed within a generic whole body physiologically based model of pharmacokinetics, to predict plasma concentration-time profiles is briefly discussed.


Ethanol-ethylene conversion mechanism on hydrogen boride sheets probed by in situ infrared absorption spectroscopy.
Two-dimensional hydrogen boride (HB) sheets were recently demonstrated to act as a solid acid catalyst in their hydrogen-deficient state. However, both the active sites and the mechanism of the catalytic process require further elucidation. In this study, we analyzed the conversion of ethanol adsorbed on HB sheets under vacuum during heating using in situ Fourier transform infrared (FT-IR) absorption spectroscopy with isotope labelling. Up to 450 K, the FT-IR peak associated with the OH group of the adsorbed ethanol molecule disappeared from the spectrum, which was attributed to a dehydration reaction with a hydrogen atom from the HB sheet, resulting in the formation of an ethyl species. At temperatures above 440 K, the number of BD bonds markedly increased in CD3CH2OH, compared to CH3CD2OH; the temperature dependence of the formation rate of BD bonds was similar to that of the dehydration reaction rate of ethanol on HB sheets under steady-state conditions. The rate-determining step of the dehydration of ethanol on HB was thus ascribed to the dehydrogenation of the methyl group of the ethyl species on the HB sheets, followed by the immediate desorption of ethylene. These results show that the catalytic ethanol dehydration process on HB involves the hydrogen atoms of the HB sheets. The obtained mechanistic insights are expected to promote the practical application of HB sheets as catalysts.


Pharmacokinetics of drugs in patients with the nephrotic syndrome.
Since the binding of drugs to plasma proteins can significantly after the intensity of pharmacological and toxicological effects of drugs, we studied the pharmacokinetics of three drugs in patients with hypoalbuminemia secondary to the nephrotic syndrome, but with relatively normal renal function. No significant differences were seen in the pharmacokinetic parameters observed for antipyrine, a drug which is less than 10% bound to plasms proteins. The percentage of unbound diphenylhydantoin, a highly plasms protein-bound drug, was found in patients with the nephrotic syndrome to be twice that of healthy individuals (19,2 vs. 10.1%, P smaller than 0.001). However, there was also a lower steady-state plasma concentration of diphenylhydantoin (2.9 plus or minus 0.6 vs. 6.8 plus or minus 0.6 mug/ml, P smaller than 0.001) secondary to an increase in the plasms clearance (0.048 plus or minus 0.019 vs. 0.022 plus or minus 0.006 liter/kg.h, P smaller than 0.001) in the nephrotic patients. The net effect is no difference in the absolute concentration of unbound diphenylhydantoin in healthy individuals (0.69 plus or minus 0.05 mug/ml) and patients with the nephrotic syndrome (0.59 plus or minus 0.06 mug/ml). Qualitatively, similar differences were observed with clofibrate. The dose of these drugs need not be routinely reduced in patients with the nephrotic syndrome as long as they have reasonably normal renal function (creatinine clearance greater than 50 ml/min). With all highly bound acidic drugs, knowledge of the concentration of unbound drug is essential to the proper interpretation of total blood levels and subsequent treatment of the patient.


The value of value congruence.
Research on value congruence has attempted to explain why value congruence leads to positive outcomes, but few of these explanations have been tested empirically. In this article, the authors develop and test a theoretical model that integrates 4 key explanations of value congruence effects, which are framed in terms of communication, predictability, interpersonal attraction, and trust. These constructs are used to explain the process by which value congruence relates to job satisfaction, organizational identification, and intent to stay in the organization, after taking psychological need fulfillment into account. Data from a heterogeneous sample of employees from 4 organizations indicate that the relationships that link individual and organizational values to outcomes are explained primarily by the trust that employees place in the organization and its members, followed by communication, and, to a lesser extent, interpersonal attraction. Polynomial regression analyses reveal that the relationships emanating from individual and organizational values often deviated from the idealized value congruence relationship that underlies previous theory and research. The authors' results also show that individual and organizational values exhibited small but significant relationships with job satisfaction and organizational identification that bypassed the mediators in their model, indicating that additional explanations of value congruence effects should be pursued in future research.


Techniques to investigate neuronal mitochondrial function and its pharmacological modulation.
Mitochondria are central regulators of neuronal homeostasis and survival, and increasingly viewed as a drug target in several acute and chronic neurological disorders, e.g. stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Frequent working hypotheses aim to establish whether and how chemical or genetic lesions affect mitochondrial function in neurons, and whether this can be rescued by pharmacological treatments. However, the generic designation 'mitochondrial function' actually encompasses a wide spectrum of individual activities, too numerous to be fully quantified by any single available technique. This review aims to provide a broad perspective on the roles played by neuronal mitochondria, and addresses multiple techniques that can be used to derive instructive functional indicators. These include measurements of mitochondrial respiration, ATP production, membrane potential, calcium handling, biogenesis, dynamic movement as well as fusion and fission. Technique descriptions are preceded by a summary of mitochondrial physiology and pharmacological tools required for functional modulation and parameter determination. Hopefully, these will assist researchers interested in testing mitochondria as a drug target in neurological disease models.


Evolutionary dynamics of the mitochondrial genome in the evaniomorpha (hymenoptera)—a group with an intermediate rate of gene rearrangement.
We determined the complete mitochondrial (mt) genomes of three evaniomorph species, Ceraphron sp. (Ceraphronoidea), Gasteruption sp. (Evanioidea), and Orthogonalys pulchella (Trigonalyoidea) as well as the nearly complete mt genome from another evaniomorph species, Megalyra sp. (Megalyroidea). Each of them possesses dramatic gene rearrangements, including protein-coding or rRNA genes. Gene inversions were identified in all of these mt genomes; for example, the two rRNA genes have inverted and moved into the nad2-cox1 junction in the Megalyra sp. mt genome. In addition, we found two copies of a 10-bp complementary repeat at the beginning of rrnS and at the end of trnL(2) in the Gasteruption sp. mt genome, consistent with recombination as the possible mechanism for gene inversion and long-range movement. Although each of the genomes contains a number of repeats of varying size, there was no consistent association of the size or number of repeats with the extent or type of gene rearrangement. The breakpoint distance analysis showed the Evaniomorpha has an intermediate rate of gene rearrangement. Sequence-based phylogenetic analyses of 13 protein-coding and 2 rRNA genes in 22 hymenopteran taxa recovered a paraphyletic Evaniomorpha with the Aculeata nested within it. Within the Evaniomorpha, our analyses confirmed the Trigonalyoidea + Megalyroidea as the sister group to the Aculeata and recovered a novel clade, Ceraphronoidea + Evanioidea. In contrast to previous hymenopteran phylogenetic studies, the internal relationships of the Evaniomorpha were highly supported and robust to the variation of alignment approach and phylogenetic inference approach.


Pulmonary artery to aorta ratio and risk of all-cause mortality in the general population: the Rotterdam Study.
A pulmonary artery to aorta ratio (PA:A) >1 is a proxy of pulmonary hypertension. It is not known whether this measure carries prognostic information in the general population and in individuals with chronic obstructive pulmonary disease (COPD).Between 2003 and 2006, 2197 participants from the population-based Rotterdam Study (mean±sd age 69.7±6.7 years; 51.3% female), underwent cardiac computed tomography (CT) scanning with PA:A quantification, defined as the ratio between the diameters of the pulmonary artery and the aorta. COPD was diagnosed based on spirometry or clinical presentation and obstructive lung function measured by a treating physician. Cox regression was used to investigate the risk of mortality.We observed no association between 1-sd increase of PA:A and mortality in the general population. Larger PA:A was associated with an increased risk of mortality in individuals with COPD, particularly in moderate-to-severe COPD (hazard ratio 1.36, 95% CI 1.03-1.79). We demonstrated that the risk of mortality in COPD was driven by severe COPD, and that this risk increased with decreasing diffusing capacity.Larger PA:A is not associated with mortality in an older general population, but is an independent determinant of mortality in moderate-to-severe COPD. Measuring PA:A in CT scans obtained for other indications may yield important prognostic information in individuals with COPD.


Acute flaccid paralysis surveillance in southeastern Turkey, 1999-2010.
The aim of the study was to report the results of acute flaccid paralysis (AFP) surveillance and to evaluate the performance of surveillance in the southeastern region of Turkey in the 12 years from 1999 to 2010. We investigated cases in seven provinces of the southeastern region of Turkey. In the evaluation, AFP Case Report Form, Laboratory Investigation Form and 60-Day Case Investigation Form were used; individuals' demographic characteristics, clinical findings, status of vaccination, sample results, and 60-day follow-up were evaluated. Incidence ranged from 0.60/100,000 in 2008 to 1.60/100,000 in 1999. Dysstasia and loss of strength were the most frequently reported prodromal symptoms. Coxsackievirus and echoviruses were the most frequent viruses detected. One-quarter of the AFP cases could not be followed up in the present surveillance system.


Mindfulness Training in UK Secondary Schools: a Multiple Case Study Approach to Identification of Cornerstones of Implementation.
This paper examined the facilitators and barriers to implementation of mindfulness training (MT) across seven secondary/high schools using a qualitative case study design. Schools varied in level of implementation. Within schools, head teachers, members of school senior leadership teams, and staff members involved in the implementation of MT were interviewed individually. In addition, focus groups were conducted with other members of school staff to capture a broad range of views and perspectives. Across the case studies, several key themes emerged, which suggested four corner stones to successful implementation of MT in schools. These were: people, specifically the need for committed individuals to champion the approach within their schools, with the support of members of the senior leadership teams; resources, both time and financial resources required for training and delivery of MT; journey, reflecting the fact that implementation takes time, and may be a non-linear process with stops and starts; and finally perceptions, highlighting the importance of members of the school community sharing an understanding what MT is and why it is being introduced in each school context. Similarities and differences between the current findings and those of research on implementation of other forms of school mental health promotion programs, and implementation of MT in healthcare settings, are discussed.


Physical activity types and life expectancy with and without cardiovascular disease: the Rotterdam Study.
We aimed to determine the contribution of specific physical activity (PA) types (i.e. walking, cycling, domestic work, sports and gardening) on total life expectancy (LE) and LE with and without cardiovascular disease (CVD). We constructed multistate life tables to calculate the effects of total PA and PA types on LE, among individuals older than 55 years from the Rotterdam Study. For the life table calculations, we used sex-specific prevalences, incident rates and hazard ratios for three transitions (healthy-to-CVD, healthy-to-death and CVD-to-death) by levels of PA and adjusted for confounders. High total PA was associated with gains in total and CVD-free LE. High cycling contributed to higher total LE in men (3.7 years) and women (2.1 years) and higher LE without CVD in men (3.1 years) and women (2.4 years). Total and CVD-free LE were increased by high domestic work in women (2.6 and 2.4 years, respectively) and high gardening in men (2.7 and 2.0 years, respectively). Higher PA levels are associated with increased LE and more years lived without CVD. Of the different PA types, cycling provided high effects in both men and women. Cycling could be more strongly encouraged in activity guidelines to maximize the population benefits of PA.


Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans.
For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters--not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals--e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death.


Orthovoltage intraoperative radiation therapy for pancreatic adenocarcinoma.
To analyze the outcomes of patients from a single institution treated with surgery and orthovoltage intraoperative radiotherapy (IORT) for pancreatic adenocarcinoma. We retrospectively reviewed 23 consecutive patients from 1990-2001 treated with IORT to 23 discrete sites with median and mean follow up of 6.5 and 21 months, respectively. Most tumors were located in the head of the pancreas (83%) and sites irradiated included: tumor bed (57%), vessels (26%), both the tumor bed/vessels (13%) and other (4%). The majority of patients (83%) had IORT at the time of their definitive surgery. Three patients had preoperative chemoradiation (13%). Orthovoltage X-rays (200-250 kVp) were employed via individually sized and beveled cone applicators. Additional mean clinical characteristics include: age 64 (range 41-81); tumor size 4 cm (range 1.4-11); and IORT dose 1106 cGy (range 600-1500). Post-operative external beam radiation (EBRT) or chemotherapy was given to 65% and 76% of the assessable patients, respectively. Outcomes measured were infield control (IFC), loco-regional control (LRC), distant metastasis free survival (DMFS), overall survival (OS) and treatment-related complications. Kaplan-Meier (KM) 2-year IFC, LRC, DMFS and OS probabilities for the whole group were 83%, 61%, 26%, and 27%, respectively. Our cohort had three grade 3-5 complications associated with treatment (surgery and IORT). Orthovoltage IORT following tumor reductive surgery is reasonably well tolerated and seems to confer in-field control in carefully selected patients. However, distant metastases remain the major problem for patients with pancreatic adenocarcinoma.


Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain.
The Douleur Neuropathique 4 questionnaire (DN4) is a simple and objective tool developed by the French Neuropathic Pain Group to screen for neuropathic pain. This prospective observational study was undertaken in three hospitals to assess the validity of a Japanese translation of the DN4. We first translated the DN4 into Japanese using a forward-backward method. Pain specialists then examined patients independently and diagnosed them with neuropathic or non-neuropathic pain, according to the International Association for the Study of Pain definitions. The Japanese version of the DN4 questionnaire was then given to each patient. Of 187 patients that met our inclusion criteria, 100 and 87 were diagnosed with neuropathic and non-neuropathic pain, respectively. The test-retest intra-class correlation coefficient (95% confidence interval) was 0.827 (0.769-0.870). Among patients with identical diagnoses of neuropathic or non-neuropathic pain, receiver-operating characteristic curve analysis revealed an area under the curve of 0.89. A cut-off point of equal or greater than 4 resulted in a sensitivity of 71% and specificity of 92%. The Japanese version of the DN4 was found to be a helpful tool for discriminating between neuropathic and non-neuropathic pain.


Ecological approaches to rural development projects.
Most rural development projects include ecological considerations, and most conservation projects include some reference to sustainable development. However, conservation projects frequently fail because they do not incorporate local communities' perceptions and needs. Many development projects are also unsuccessful because they are not based on adequate ecological assessment. We focus here on the most important ecological issues to be addressed in order to place development projects in an ecosystem context. Such projects should incorporate updated and precise ecological concepts and methods. Some key ecological issues in development projects are the relationships between ecosystem functions, services, and sustainability, the concept of loose connectivity, the distinct and complementary concepts of ecosystem resistance and resilience, and the links between biodiversity and ecosystem functioning. We claim that an ecologically sound development project maximizes the preservation and improvement of ecosystem services, especially for local communities. We pose a series of questions aimed at placing rural development projects in an ecosystem context and suggest ways of organizing this information.


International development and psychometric properties of the Child and Adolescent Trauma Screen (CATS).
Systematic screening is a powerful means by which children and adolescents with posttraumatic stress symptoms (PTSS) can be detected. Reliable and valid measures based on current diagnostic criteria are needed. To investigate the internal consistency and construct validity of the Child and Adolescent Trauma Screen (CATS) in three samples of trauma-exposed children in the US (self-reports: n=249; caregiver reports: n=267; pre-school n=190), in Germany (self-reports: n=117; caregiver reports: n=95) and in Norway (self-reports: n=109; caregiver reports: n=62). Internal consistency was calculated using Cronbach's α. Convergent-discriminant validity was investigated using bivariate correlation coefficients with measures of depression, anxiety and externalizing symptoms. CFA was used to investigate the DSM-5 factor structure. In all three language samples the 20 item symptom score of the self-report and the caregiver report proved good to excellent reliability with α ranging between .88 and .94. The convergent-discriminant validity pattern showed medium to strong correlations with measures of depression (r =.62-.82) and anxiety (r =.40-.77) and low to medium correlations with externalizing symptoms (r =-.15-.43) within informants in all language versions. Using CFA the underlying DSM-5 factor structure with four symptom clusters (re-experiencing, avoidance, negative alterations in mood and cognitions, hyperarousal) was supported (n =475 for self-report; n =424 for caregiver reports). The external validation of the CATS with a DSM-5 based semi-structured clinical interview and corresponding determination of cut-points is pending. The CATS has satisfactory psychometric properties. Clinicians may consider the CATS as a screening tool and for symptom monitoring.


The distinct genetic pattern of ALS in Turkey and novel mutations.
The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.


The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis.
Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.


Water in Earth's Mantle: The Role of Nominally Anhydrous Minerals.
Most minerals of Earth's upper mantle contain small amounts of hydrogen, structurally bound as hydroxyl (OH). The OH concentration in each mineral species is variable, in some cases reflecting the geological environment of mineral formation. Of the major mantle minerals, pyroxenes are the most hydrous, typically containing approximately 200 to 500 parts per million H(2)O by weight, and probably dominate the water budget and hydrogen geochemistry of mantle rocks that do not contain a hydrous phase. Garnets and olivines commonly contain approximately 1 to 50 parts per million. Nominally anhydrous minerals constitute a significant reservoir for mantle hydrogen, possibly accommodating all water in the depleted mantle and providing a possible mechanism to recycle water from Earth's surface into the deep mantle.


[Comparison of prognostic scoring systems in the prediction of mortality and complications from sepsis].
To compare the Mortality in Emergency Department Sepsis (MEDS), Sepsis-related Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), and Confusion, Urea, Respiratory rate, Blood pressure, 65 years of age and older (CURB-65) scoring systems for predicting mortality and complications in septic patients. A prospective study of diagnostic test assessment was carried out. Scores were compared by analysis of receiver operating characteristic (ROC) curves corresponding to each score, with the development of death or complications as the dependent variable. There were 265 patients included in the analysis; 155 (58.4%) patients died and/or presented complications. The multivariate analysis revealed variables associated with mortality and complications were age, oliguria, mental health impairment, acute lung injury, and the use of inotropes. Analysis of ROC curves showed the area below the ROC curve was 0.74 (95% CI: 0.68-0.80) for SOFA, 0.73 (95% CI: 0.67-0.79) for MEDS, 0.73 (95% CI: 0.66-0.79) for APACHE II, and 0.67 (95% CI: 0.60-0.73) for CURB-65, the latter being significantly lower than the first three. The MEDS, SOFA, and APACHE II are adequate scoring systems for predicting mortality and complications in septic patients. It is essential to utilize these scoring systems in emergency medical assistance in hospitals in Peru.


Cognitive effects of acute tryptophan depletion in the healthy elderly.
Studies investigating the cognitive effects of serotonin depletion, using the technique of acute tryptophan depletion (ATD) by dietary means, have generally suggested that ATD impairs delayed verbal recall and recognition. In two previous studies in the elderly, this result has not been replicated and ATD impaired working memory. These results may be susceptible to type II error but a similar testing schedule in the individual studies allows data to be pooled in a larger analysis. Data from two separate double-blind placebo-controlled studies of the effects of ATD on cognitive function in the elderly were combined. In one study, a low dose and in the other a high dose of amino acids was used. In a repeated measures analysis of variance, the effects of ATD and the interaction of this with the other factors (age, gender and dose) on cognitive measures was examined. Data from 31 healthy subjects aged between 60 and 81 years were analysed. There were no main effects of ATD or consistent interactions between ATD and age, gender or dose. There were significant interactions between ATD, gender and dose. When tryptophan depleted, females having the higher dose drink had reduced scores on Digit span and immediate recall on the Rey Auditory Verbal Learning Test. The enlarged data set did not confirm an overall effect of ATD on working memory or on delayed word recall but does suggest an effect of ATD on encoding or registration in the subgroup of females receiving a higher strength drink.


Role of C3d and C4d complement fragments in the diagnostics of acute allograft rejection after transplantations.
Transplantation is a widely recognized method of treatment at the terminal stages of many renal, cardiac, hepatic and pulmonary diseases. Despite considerable advances in that field, graft rejection is still an important clinical problem. The reaction of the graft recipient to an organ presenting foreign antigens is dependent on complex immune mechanisms, involving both acquired and congenital immune responses. In most general terms, cellular and humoral immunity can be distinguished. The kidneys and the heart are the organs whose acute humoral rejection has been thoroughly investigated and defined, and the role of C4d and C3d fragments of the complement system has been confirmed by numerous studies. The studies concerning C4d and C3d expression in patients with acute humoral lung and liver rejection conducted to date have given contradictory results. Some of them confirm, while others fail to confirm, the correlation between their increased expression and AHR. From the practical point of view, C4d and C3d could be used in liver transplantology for differential diagnostics of acute graft rejection and recurrence of HCV infection. A few preliminary studies suggest the usefulness of these markers in the diagnostics of AMR and differentiation between both liver pathologies. There are only single reports concerning the role of C4d complement fragment in the diagnostics of acute rejection with a humoral component in case of small intestine grafts, as well as complex ones such as the hands and face, and their results suggests that these complement fragments are not important markers of acute rejection of these organs.


Visual mismatch negativity (vMMN): A review and meta-analysis of studies in psychiatric and neurological disorders.
The visual mismatch negativity (vMMN) response is an event-related potential (ERP) component, which is automatically elicited by events that violate predictions based on prior events. VMMN experiments use visual stimulus repetition to induce predictions, and vMMN is obtained by subtracting the response to rare unpredicted stimuli from those to frequent stimuli. One increasingly popular interpretation of the mismatch response postulates that vMMN, similar to its auditory counterpart (aMMN), represents a prediction error response generated by cortical mechanisms forming probabilistic representations of sensory signals. Here we discuss the physiological and theoretical basis of vMMN and review thirty-three studies from the emerging field of its clinical applications, presenting a meta-analysis of findings in schizophrenia, mood disorders, substance abuse, neurodegenerative disorders, developmental disorders, deafness, panic disorder and hypertension. Furthermore, we include reports on aging and maturation as they bear upon many clinically relevant conditions. Surveying the literature we found that vMMN is altered in several clinical populations which is in line with aMMN findings. An important potential advantage of vMMN however is that it allows the investigation of deficits in predictive processing in cognitive domains which rely primarily on visual information; a principal sensory modality and thus of vital importance in environmental information processing and response, and a modality which arguably may be more sensitive to some pathological changes. However, due to the relative infancy of research in vMMN compared to aMMN in clinical populations its potential for clinical application is not yet fully appreciated. The aim of this review and meta-analysis therefore is to present, in a detailed systematic manner, the findings from clinically-based vMMN studies, to discuss their potential impact and application, to raise awareness of this measure and to improve our understanding of disease upon fundamental aspects of visual information processing.


Water salination: a source of energy.
The thermodynamically reversible mixing of freshwater and seawater at constant temperature releases free energy. Salination power as a resource is comparable with hydroelectric power in magnitude; U.S. freshwater runoff could yield over 10(10) watts. The energy flux available for natural salination is equivalent to each river in the world ending at its mouth in a waterfall 225 meters high. An osmotic salination converter could possibly operate at 25 percent efficiency. This energy source is renewable and nonpolluting. Although its full utilization would destroy estuarine environments, it might be practical for specialized purposes.


Learning the compositional nature of visual object categories for recognition.
Real-world scene understanding requires recognizing object categories in novel visual scenes. This paper describes a composition system that automatically learns structured, hierarchical object representations in an unsupervised manner without requiring manual segmentation or manual object localization. A central concept for learning object models in the challenging, general case of unconstrained scenes, large intraclass variations, large numbers of categories, and lacking supervision information is to exploit the compositional nature of our (visual) world. The compositional nature of visual objects significantly limits their representation complexity and renders learning of structured object models statistically and computationally tractable. We propose a robust descriptor for local image parts and show how characteristic compositions of parts can be learned that are based on an unspecific part vocabulary shared between all categories. Moreover, a Bayesian network is presented that comprises all the compositional constituents together with scene context and object shape. Object recognition is then formulated as a statistical inference problem in this probabilistic model.


Analysis of the Complete Genome Sequence of a Novel, Pseudorabies Virus Strain Isolated in Southeast Europe.
Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease giving rise to significant economic losses worldwide. Many countries have implemented national programs for the eradication of this virus. In this study, long-read sequencing was used to determine the nucleotide sequence of the genome of a novel PRV strain (PRV-MdBio) isolated in Serbia. In this study, a novel PRV strain was isolated and characterized. PRV-MdBio was found to exhibit similar growth properties to those of another wild-type PRV, the strain Kaplan. Single-molecule real-time (SMRT) sequencing has revealed that the new strain differs significantly in base composition even from strain Kaplan, to which it otherwise exhibits the highest similarity. We compared the genetic composition of PRV-MdBio to strain Kaplan and the China reference strain Ea and obtained that radical base replacements were the most common point mutations preceding conservative and silent mutations. We also found that the adaptation of PRV to cell culture does not lead to any tendentious genetic alteration in the viral genome. PRV-MdBio is a wild-type virus, which differs in base composition from other PRV strains to a relatively large extent.


BRAF V600E is a determinant of sensitivity to proteasome inhibitors.
A critical step toward defining tailored therapy in patients with cancer is the identification of genetic interactions that may impair-or boost-the efficacy of selected therapeutic approaches. Cell models able to recapitulate combinations of genetic aberrations are important to find drug-genotype interactions poorly affected by the heterogeneous genetics of human tumors. In order to identify novel pharmacogenomic relationships, we employed an isogenic cell panel that reconstructs cancer genetic scenarios. We screened a library of 43 compounds in human hTERT-HME1 epithelial cells in which PTEN or RB1 were silenced in combination with the targeted knockin of cancer-associated mutations in EGFR, KRAS, BRAF, or PIK3CA oncogenes. Statistical analysis and clustering algorithms were applied to display similar drug response profiles and mutation-specific patterns of activity. From the screen, we discovered that proteasome inhibitors show selectivity toward BRAF V600E-mutant cells, irrespective of PTEN or RB1 expression. Preferential targeting of BRAF-mutant cells by proteasome inhibitors was corroborated in a second BRAF V600E isogenic model, as well as in a panel of colorectal cancer cell lines by the use of the proteasome inhibitor carfilzomib. Notably, carfilzomib also showed striking in vivo activity in a BRAF-mutant human colorectal cancer xenograft model. Vulnerability to proteasome inhibitors is dependent on persistent BRAF signaling, because BRAF V600E blockade by PLX4720 reversed sensitivity to carfilzomib in BRAF-mutant colorectal cancer cells. Our findings indicated that proteasome inhibition might represent a valuable targeting strategy in BRAF V600E-mutant colorectal tumors.


The role of arginine vasopressin in alcohol tolerance.
Administration of the neuropeptide, arginine vasopressin, to animals that have acquired functional tolerance to ethanol will maintain such tolerance, even in the absence of further ethanol ingestion by the animals. In mice, this action of the peptide is mediated by central nervous system V1 receptors and requires intact brain noradrenergic systems. Autoradiographic studies have shown that some V1 receptors are localized presynaptically on catecholaminergic neuronal terminals in the mouse lateral septum, suggesting that vasopressin may act via modulation of catecholamine release. In addition, vasopressin has been found to increase mRNA levels for the proto-oncogene, c-fos, in septum and hippocampus, possibly by an action at postsynaptic receptors. Expression of c-fos, which has been hypothesized to play a role in central nervous system neuroadaptation, could transform short-term actions of vasopressin into long-term effects on ethanol tolerance. Studies with vasopressin antagonists indicate that the endogenous peptide influences tolerance, and therefore the effect of chronic ethanol ingestion on vasopressin synthesis and release was studied. In mice and rats, hypothalamic vasopressin mRNA is decreased by chronic ethanol exposure, although effects on plasma vasopressin levels differ in the two species. The effect of ethanol on extrahypothalamic vasopressin synthesis in brain is under investigation. The results suggest mechanisms by which vasopressin can produce long-term changes in central nervous system function, and provide evidence for a disturbance of vasopressin regulation during chronic ethanol ingestion.


Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination.
Three distinct DNA ligases, I to III, have been found previously in mammalian cells, but a cloned cDNA has been identified only for DNA ligase I, an essential enzyme active in DNA replication. A short peptide sequence conserved close to the C terminus of all known eukaryotic DNA ligases was used to search for additional homologous sequences in human cDNA libraries. Two different incomplete cDNA clones that showed partial homology to the conserved peptide were identified. Full-length cDNAs were obtained and expressed by in vitro transcription and translation. The 103-kDa product of one cDNA clone formed a characteristic complex with the XRCC1 DNA repair protein and was identical with the previously described DNA ligase III. DNA ligase III appears closely related to the smaller DNA ligase II. The 96-kDa in vitro translation product of the second cDNA clone was also shown to be an ATP-dependent DNA ligase. A fourth DNA ligase (DNA ligase IV) has been purified from human cells and shown to be identical to the 96-kDa DNA ligase by unique agreement between mass spectrometry data on tryptic peptides from the purified enzyme and the predicted open reading frame of the cloned cDNA. The amino acid sequences of DNA ligases III and IV share a related active-site motif and several short regions of homology with DNA ligase I, other DNA ligases, and RNA capping enzymes. DNA ligases III and IV are encoded by distinct genes located on human chromosomes 17q11.2-12 and 13q33-34, respectively.


Anthropogenic effects on population genetics of phytophagous insects associated with domesticated plants.
The hypothesis of isolation by distance (IBD) predicts that genetic differentiation between populations increases with geographic distance. However, gene flow is governed by numerous factors and the correlation between genetic differentiation and geographic distance is never simply linear. In this study, we analyze the interaction between the effects of geographic distance and of wild or domesticated status of the host plant on genetic differentiation in the bean beetle Acanthoscelides obvelatus. Geographic distance explained most of the among-population genetic differentiation. However, IBD varied depending on the kind of population pairs for which the correlation between genetic differentiation and geographic distance was examined. Whereas pairs of beetle populations associated with wild beans showed significant IBD (P < 10(-4)), no IBD was found when pairs of beetle populations on domesticated beans were examined (P= 0.2992). This latter result can be explained by long-distance migrations of beetles on domesticated plants resulting from human exchanges of bean seeds. Beetle populations associated with wild beans were also significantly more likely than those on domesticated plants to contain rare alleles. However, at the population level, beetles on cultivated beans were similar in allelic richness to those on wild beans. This similarity in allelic richness combined with differences in other aspects of the genetic diversity (i.e., IBD, allelic diversity) is compatible with strongly contrasting effects of migration and drift. This novel indirect effect of human actions on gene flow of a serious pest of a domesticated plant has important implications for the spread of new adaptations such as resistance to pesticides.


Long-term Outcomes of Laparoscopic Surgery for Colorectal Cancer.
The long-term results of a laparoscopic resection for colorectal cancer have been reported in several studies, but reports on the results of laparoscopic surgery for rectal cancer are limited. We investigated the long-term outcomes, including the five-year overall survival, disease-free survival and recurrence rate, after a laparoscopic resection for colorectal cancer. Using prospectively collected data on 303 patients with colorectal cancer who underwent a laparoscopic resection between January 2001, and December 2003, we analyzed sex, age, stage, complications, hospital stay, mean operation time and blood loss. The overall survival rate, disease-free survival rate and recurrence rate were investigated for 271 patients who could be followed for more than three years. Tumor-node-metastasis (TNM) stage I cancer was present in 55 patients (18.1%), stage II in 116 patients (38.3%), stage III in 110 patients (36.3%), and stage IV in 22 patients (7.3%). The mean operative time was 200 minutes (range, 100 to 535 minutes), and the mean blood loss was 97 mL (range, 20 to 1,200 mL). The mean hospital stay was 11 days and the mean follow-up period was 54 months. The mean numbers of resected lymph nodes were 26 and 21 in the colon and the rectum, respectively, and the mean distal margins were 10 and 3 cm. The overall morbidity rate was 26.1%. The local recurrence rates were 2.2% and 4.4% in the colon and the rectum, respectively, and the distant recurrence rates were 7.8% and 22.5%. The five-year overall survival rates were 86.1% in the colon (stage I, 100%; stage II, 97.6%; stage III, 77.5%; stage IV, 16.7%) and 68.8% in the rectum (stage I, 90.2%; stage II, 84.0%; stage III, 57.6; stage IV, 13.3%). The five-year disease-free survival rates were 89.8% in the colon (stage I, 100%; stage II, 97.7%; stage III, 74.2%) and 74.5% in the rectum (stage I, 90.0%; stage II, 83.9%; stage III, 59.2%). Laparoscopic surgery for colorectal cancer is a good alternative method to open surgery with tolerable oncologic long-term results.


Adélie penguin survival: age structure, temporal variability and environmental influences.
The driving factors of survival, a key demographic process, have been particularly challenging to study, especially for winter migratory species such as the Adélie penguin (Pygoscelis adeliae). While winter environmental conditions clearly influence Antarctic seabird survival, it has been unclear to which environmental features they are most likely to respond. Here, we examine the influence of environmental fluctuations, broad climatic conditions and the success of the breeding season prior to winter on annual survival of an Adélie penguin population using mark-recapture models based on penguin tag and resight data over a 16-year period. This analysis required an extension to the basic Cormack-Jolly-Seber model by incorporating age structure in recapture and survival sub-models. By including model covariates, we show that survival of older penguins is primarily related to the amount and concentration of ice present in their winter foraging grounds. In contrast, fledgling and yearling survival depended on other factors in addition to the physical marine environment and outcomes of the previous breeding season, but we were unable to determine what these were. The relationship between sea-ice and survival differed with penguin age: extensive ice during the return journey to breeding colonies was detrimental to survival for the younger penguins, whereas either too little or too much ice (between 15 and 80% cover) in the winter foraging grounds was detrimental for adults. Our results demonstrate that predictions of Adélie penguin survival can be improved by taking into account penguin age, prior breeding conditions and environmental features.


Positive affect regulation in anxiety disorders.
Although individual differences exist in how people respond to positive affect (PA), little research addresses PA regulation in people with anxiety disorders. The goal of this study was to provide information about responses to PA in people with symptoms of social phobia, generalized anxiety disorder, panic disorder, agoraphobia, and obsessive-compulsive disorder. The tendency to dampen PA and the ability to savor PA were examined in an undergraduate sample. Analyses examined the unique links between these reactions and symptoms of anxiety disorders, controlling for a history of depression. Given the high comorbidity of depression and anxiety, exploratory analyses further controlled for generalized anxiety disorder. Results demonstrated that one or both measures of affect regulation made a unique and substantial contribution to predicting each anxiety disorder except agoraphobia, above and beyond prediction afforded by symptoms of depression and generalized anxiety disorder. Clinical implications and areas for future research are discussed.


The allele encoding the mycobacterial Erp protein affects lung disease in mice.
Erp (exported repetitive protein), also known as P36, Pirg and Rv3810, is a member of a mycobacteria-specific family of extracellular proteins. These proteins consist of three domains, the N- and C-terminal domains are similar in all mycobacterial species, however, the central domain contains a repeated PGLTS module and differs considerably between species. The erp knockout mutant of Mycobacterium tuberculosis displays very low levels of multiplication both in macrophage cell lines and in vivo in a mouse model of infection. The high interspecies variability of the central repeated region of the Erp protein led us to investigate whether these orthologous proteins were functionally equivalent in a mouse model of tuberculosis. We expressed a gene fusion with the erp gene of Mycobacterium smegmatis, Mycobacterium leprae or M. tuberculosis in trans in an erp-M. tuberculosis mutant and found that these three alleles restored multiplication to similar levels in the spleen of infected mice. However, these alleles gave different levels of colonization in the lung, for the early time-points. Quantitative histological analyses of the lungs of infected animals showed that the nature of the erp allele strongly affected the number and the size of lung lesions, demonstrating the importance of surface determinants for virulence and tissue damage.


Alterations in bone mineral density and lower extremity lean mass after hip arthroscopy in a professional female Ironman triathlete: a case study.
Femoroacetabular impingement is a pathomechanical condition of the hip, which is often treated through arthroscopic techniques. The ensuing immobilization period is associated with decreases in muscle mass and bone mass. To date, minimal knowledge is present about the development of tissue mass during the considerably short rehabilitation period before returning to competition in elite endurance athletes. Before and after surgery, a professional female Ironman triathlete underwent dual-energy X-ray absorptiometry and peripheral quantitative computed tomography measurements. Areal bone mineral density (aBMD) of the proximal femur and lower extremity lean mass decreased in the surgically treated lower extremity during the two-month period of immobilization after the hip arthroscopy. These losses were compensated for after only six weeks of rehabilitation. A similar progression of aBMD values was observed in the lumbar spine. The adaptational pattern in volumetric BMD (vBMD) and volumetric bone mineral content (vBMC) of the tibiae were more complex, but attained pre-immobilization values for most variables also after six weeks of rehabilitation. All other variables attained pre-immobilization values no later than nine months after the surgical intervention. The athlete showed a high plasticity of bone and lean tissue with an optimal short- and midterm outcome. Following a two months immobilization period after a hip arthroscopy, aBMD, vBMD and vBMC achieved pre-surgical levels after four months of rehabilitation in a female Ironman triathlete. A nine-month follow-up measurement confirmed the safety of the fast return to sport.