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Background: Timing of reproductive events can be crucial for a species' population growth and stability. Accurate detection of reproductive phenology presents a challenge to scientists studying wild species, including moose (Alces alces). Currently, there are several established methods for monitoring reproductive activity and events in domestic ruminants, including the use of biologging devices. The main objective of this study was to determine whether female moose display a distinct thermal and activity pattern associated with luteal activity during the estrous cycle, which could be used to determine the onset of their breeding season. We deployed biologging devices and collected fecal samples from 12 captive female moose on the Kenai Peninsula, Alaska, USA to explore variation in vaginal temperature and collar activity and the relationship between these variables and fecal progestagen concentrations. Fecal samples were collected from mid-August to mid-October and analyzed using radioimmunoassay to determine the concentration of fecal progestagens to classify luteal activity. Results: Captive female moose displayed an identifiable thermal pattern during the onset of luteal activity from mid-September to mid-October, associated with the initial estrous cycle of their breeding season. In contrast, we did not observe a distinct pattern in activity during this period. Recurring patterns in both vaginal temperature and activity were identified between mid-October and mid-November, however, which were likely associated with subsequent estrous cycles but not included in our fecal sampling period. Conclusions: This study supports that female moose display an identifiable pattern in vaginal temperature which is associated with luteal activity of the initial estrous cycle of the breeding season. An identifiable pattern was observed for both vaginal temperature and activity registrations at the presumed timing of subsequent estrous cycle of the breeding season. [ABSTRACT FROM AUTHOR]

Background: Despite centuries of research, debate remains on the scaling of metabolic rate to mass especially for intraspecific cases. The high variation of body mass within brown bears presents a unique opportunity to study the intraspecific effects of body mass on physiological variables. The amplitude of metabolic rate reduction in hibernators is dependent on body mass of the species. Small hibernators have high metabolic rates when euthermic but experience a drastic decrease in body temperature during torpor, which is necessary to reach a very low metabolic rate. Conversely, large hibernators, such as the brown bear (Ursus arctos), show a moderate decrease in temperature during hibernation, thought to be related to the bear's large size. We studied body mass, abdominal body temperature, heart rate, and accelerometer-derived activity from 63 free-ranging brown bears (1–15 years old, 15–233 kg). We tested for relationships between body mass and body temperature, heart rate, and hibernation duration. Results: The smallest individuals maintained lower body temperatures during hibernation, hibernated longer, and ended hibernation later than large bears. Unlike body temperature, winter heart rates were not associated with body mass. In summer, the opposite pattern was found, with smaller individuals having higher body temperature and daytime heart rates. Body mass was associated with body temperature in the winter hypometabolic state, even in a large hibernating mammal. Smaller bears, which are known to have higher thermal conductance, reached lower body temperatures during hibernation. During summer, smaller bears had higher body temperatures and daytime heart rates, a phenomenon not previously documented within a single mammalian species. Conclusion: We conclude that the smallest bears hibernated more deeply and longer than large bears, likely from a combined effect of basic thermodynamics, the higher need for energy savings, and a lower cost of warming up a smaller body. [ABSTRACT FROM AUTHOR]

Eating disorders (EDs) are associated with high mortality rates from suicide. Empirical tests of the Interpersonal-Psychological Theory of Suicide (IPTS) have provided preliminary cross-sectional support for its application to individuals with EDs. Because IPTS seeks to predict development and changes in suicidal ideation (SI), longitudinal investigations are ideal. The purpose of this study was to conduct cross-sectional and longitudinal mediational tests of the effect of ED psychopathology on SI as explained by perceived burdensomeness, thwarted belongingness, and hopelessness. Participants were undergraduate students (N = 738) who completed self-report measures of ED symptoms and IPTS variables at up to three time points across 10 weeks. Multiple mediation analyses were conducted on cross-sectional and longitudinal data. Cross-sectional analyses indicate mostly consistent findings with existing literature; however, results from the longitudinal analyses failed to identify any mediational effects of ED psychopathology on SI. These differences emphasize the importance of empirical tests in both cross-sectional and longitudinal data. Given the inconsistent results, the utility of IPTS features in explaining the association between ED psychopathology and SI is unclear. Future studies should seek to replicate these findings using other methods of measurement across time (e.g., ecological momentary assessment) and within clinical ED samples. [ABSTRACT FROM AUTHOR]

Instrumentation and sample collection for wildlife research and management may require chemical immobilisation of animals, which may entail physiological and behavioural effects on them. It is therefore important to evaluate the immobilisation protocols to reduce the risk of mortality and morbidity of the handled animals and their populations. Using a multi-sensor approach, we assessed the short-term (< 10 days) thermal and behavioural responses of 10 adult female moose (Alces alces) equipped with ruminal temperature loggers and GPS collars with accelerometers to helicopter-based chemical immobilisations. We investigated the body temperature (Tb), movement rates, and resting time before, during, and after recapture. Chemical immobilisations on average increased maximum Tb by 0.71 °C during the capture day, and imposed longer travel distances during the capture day and the two following days (3.8 and 1.8 km, respectively), compared to a 10-day reference period before the immobilisation. The probability of resting was 5–6% lower on the capture day and the two following days compared to the reference period, and females with offspring had a higher probability of resting than females without. Maximum Tb, movement rate, and resting time returned to pre-capture levels on an individual level 2 h, 3 days, and 3 days after the immobilisation, respectively. Chemical immobilisation of moose from a helicopter increases the energy expenditure deduced through movement and Tb rise lasting for hours to days. Ecological and physiological studies aimed at inferring general patterns may encounter bias if including sensor and tracking data from tagged animals without accounting for potential post-capture effects. [ABSTRACT FROM AUTHOR]

Biological rhythms, such as rhythms in activity and body temperature, are usually highly synchronized and entrained by environmental conditions, such as photoperiod. However, how the expression of these rhythms changes during hibernation, when the perception of environmental cues is limited, has not yet been fully understood for all hibernators, especially in the wild. The brown bear (Ursus arctos) in Scandinavia lives in a highly seasonal environment and adapts to harsh winter conditions by exhibiting hibernation, characterized by reduced metabolism and activity. In this study, we aimed to explore the expression of biological rhythms in activity, body temperature and heart rate of free-ranging brown bears over the annual cycle, including active, hibernation and the transition states around den entry and exit. We found that rhythms in physiology and activity are mostly synchronized and entrained by the light-dark cycle during the bears' active state with predominantly diel and ultradian rhythms for body temperature, activity and heart rate. However, during hibernation, rhythms in body temperature and heart rate were considerably slowed down to infradian rhythms, influenced by the amount of snow in the denning area, whereas rhythms in activity remained diel. Rhythms in the transition states when bears prepared for entering or coming out of hibernation state displayed a combination of infradian and diel rhythms, indicating the preparation of the body for the change in environmental conditions. These results reveal that brown bears adjust their biological rhythms to the seasonal environment they inhabit. Rhythms in physiology and activity show simultaneity during the active state but are partly disconnected from each other during hibernation, when bears are most sheltered from the environment. [ABSTRACT FROM AUTHOR]

The Morro Bay kangaroo rat Dipodomys heermanni morroensis is a small, nocturnal, burrowing rodent endemic to the vicinity of Morro Bay in San Luis Obispo County, California. It was listed as endangered pursuant to the U.S. Endangered Species Act in 1973. Despite many searches over three decades, the Morro Bay kangaroo rat has not been captured or sighted in the wild since 1986. While recognizing that the Morro Bay kangaroo rat may be extinct, two of us in a previous paper also speculated it may be persisting at extremely low density in isolated colonies and recommended surveying with wildlife scent-detection dogs and baited camera traps. We searched with a wildlife scent-detection dog and baited camera traps in four historically occupied areas and detected no Morro Bay kangaroo rats. Unfortunately, our data combined with all other existing data do not allow us to conclude whether the Morro Bay kangaroo rat is extinct or extant. Essentially, the International Union for the Conservation of Nature international standard has not been met to make a definitive determination of extinction. That is, a species should be considered extinct only when there is no reasonable doubt that the last individual has died. We acknowledge that because of resource limitation we surveyed only a small sample of the numerous patches of habitat in the expansive landscape. Further, we now consider the Morro Bay sand spit (total area 4.35 km2, foredunes 3.75 km2), a peripheral area, as potentially part of the geographic range with suitable habitat, and it has never been searched. Therefore, considering all available information, we conclude that the Morro Bay kangaroo rat must be considered as possibly extant. We recommend that search efforts continue in several specific areas, including the Morro Bay sand spit. If the Morro Bay kangaroo rat still exists, it will be challenging and difficult to rediscover because of its likely low density and patchy distribution in the expansive landscape, combined with its small size, nocturnal nature, and secretive lifestyle. [ABSTRACT FROM AUTHOR]

Optimal management of hunted species requires an understanding of the impacts of hunting on both individual animal and population levels. Recent technological advancements in biologging enable us to obtain increasingly detailed information from free-ranging animals, covering longer periods of time, and providing the data needed to assess such impacts. In Sweden, more than 80 000 moose are harvested annually, mostly hunted with the use of baying dogs. The effects of this hunting method on animal welfare and stress are understudied. Here, we evaluated 6 real and 17 experimental hunting approaches with baying dogs [wearing global positioning system (GPS) collars] on 8 adult female moose equipped with ruminal temperature loggers, subcutaneous heart rate (HR) loggers and GPS collars with accelerometers. The obtained data were used to analyse the behavioural and physiological responses of moose to hunting with dogs. Successful experimental approaches (moose and dog were within 240 m for >10 min) resulted in higher maximum body temperature (Tb, 0.88°C higher) and a mean increase in HR of 24 bpm in moose at the day of the approach compared to the day after. The moose rested on average >90 min longer the day after the approach compared to the day of the approach. The moose travelled on average 4.2 km longer and had a 1.3 m/s higher maximum speed the day of the approach compared to the day after. Our results demonstrate that hunting with dogs increase moose energy expenditure and resting time (and consequently decrease time available for foraging) on an individual level. This could possibly affect body condition and reproduction rates if the hunting disturbances occur frequently. [ABSTRACT FROM AUTHOR]

Background: The Fit fOR The Aged (FORTA) list, a drug classification combining positive and negative labelling of drugs, has been clinically (VALFORTA-trial) validated to improve medication quality and clinical endpoints.Objective: The objective of this study was to determine the association of medication quality with functional abilities tested in cognitive and physical function tests.Patients and Methods: Data from the prospective, randomized controlled VALFORTA trial on 409 geriatric (mean age 81.53 years) in-hospital patients were tested for associations between the FORTA score (sum of over- and under-treatment errors) on admission and cognitive and physical function tests. Univariate and multivariate linear correlations corrected for age, sex, number of medications, number of chronic conditions, and body mass index as well as comparisons between high and low FORTA-score (cut-off 3) patients were performed.Results: The FORTA score was significantly correlated with Instrumental Activities of Daily Living (p < 0.0001), the Tinetti test (p < 0.002), Essen Questionnaire on Age and Sleepiness (p < 0.0001), Mini-Mental State Examination (p < 0.0001), and handgrip strength (p < 0.04) in the univariate analysis, and with Instrumental Activities of Daily Living (p < 0.003), the Tinetti test (p < 0.003), and the Essen Questionnaire on Age and Sleepiness (p < 0.0001) in the multivariate analysis. Effect size was weak for Instrumental Activities of Daily Living (R-squared = 0.12) and the Tinetti test (R-squared = 0.03) and medium for the Essen Questionnaire on Age and Sleepiness (R-squared = 0.22). Significant differences between patients with high and low FORTA scores were found for Instrumental Activities of Daily Living, the Tinetti test, mini-nutritional assessments, Mini-Mental State Examination, Essen Questionnaire on Age and Sleepiness, and the Geriatric Depression Scale. All significant tests revealed that higher FORTA scores (lower medication quality) were associated with less favorable test outcomes.Conclusions: The FORTA score is associated with relevant aspects of comprehensive geriatric assessment, underlining the importance of medication quality for the functional and cognitive well-being of older patients.Trial Registration Number: DRKS00000531. [ABSTRACT FROM AUTHOR]

Purpose: Physicians often face difficulties in choosing appropriate medications for multimorbid older people. The FORTA (Fit for the Aged) classification (A: absolutely, B: beneficial, C: careful, D: don’t) was proposed as a clinical tool for improving the quality of drug treatment in the aged. As an implicit tool, FORTA has been shown to aid medication optimization and improve clinical end points in the VALFORTA trial. In this prospective randomized controlled study, 207 older hospitalized patients received standard geriatric treatment and 202 patients received FORTA-guided treatment.Methods: Here, changes of drug prescriptions at the anatomical-therapeutic-chemical system (ATC) level were evaluated separately for important diagnoses in descriptive analyses; over- and under-treatment rates were compared between groups.Results: At the individual drug/drug class level related to all important diagnoses, the application of FORTA significantly improved under-treatments for 12 drugs/drug classes (e.g., ACE inhibitors to treat arterial hypertension) and over-treatments for 7 drugs/drug classes (e.g., proton pump inhibitors to treat gastroesophageal reflux disease).Conclusions: FORTA representing the first combined positive/negative labeling approach at the individual drug level aids the optimization of drug treatment in older people as detected for drugs/drug classes at the ATC level in important indications. FORTA is effective in addressing over- and under-treatments even if analyzed for smaller subgroups of VALFORTA. [ABSTRACT FROM AUTHOR]

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP. These exome sequencing results were validated with an ultra-deep amplicon sequencing method, leading to 14 validated variants. The validated results contain seven genes that contribute to the protein kinase A (PKA) pathway. PKA pathway, which also contains GNAS, is a major player of overproduction of mucin, which is the characteristic feature of PMP. In addition to PKA pathway, we identified mutations in six genes that belong to the transforming growth factor beta (TGF-β) pathway, which is a key regulator of cell proliferation. Since either GNAS mutation or an alternative mutation in the PKA pathway was identified in 8/9 patients, inhibition of the PKA pathway might reduce mucin production in most of the PMP patients and potentially suppress disease progression. [ABSTRACT FROM AUTHOR]

Trial design: to further validate the FORTA (Fit fOR The Aged) concept, a bicentric randomised, controlled trial was run in two geriatric clinics. Methods: patients (≥65 years, ≥3 drugs or ≥60 years, ≥6 drugs) with three relevant diseases and hospitalisation for ≥5 days were randomised. In the intervention, but not the control group, a FORTA team instructed ward physicians on FORTA. FORTA is the first positive/negative listing approach labelling medications used to treat chronic illnesses in older patients from A (indispensable), B (beneficial), C (questionable) to D (avoid). The primary end point was the FORTA score: sum of medication errors classified as over-, under- and mistreatment. Consecutive patients were randomised to the intervention and control ward; outcome assessment was blinded. Results: four hundred and nine patients (age 81.5 years, 64% female, hospitalisation 17.4 days) were included. The primary end point was significantly (P< 0.0001) more reduced in the intervention versus control groups (2.7 ± 2.25 versus 1 ±1.8, mean ± SD, intergroup comparison of admission/discharge differences). Over- and under-treatment scores and use of A (increase) and D (decrease) drugs were significantly improved (P< 0.01). The total number of adverse drug reactions (ADRs) was significantly reduced by FORTA (P < 0.05, number needed to treat is 5). Activities of daily living and renal failure improved significantly (P < 0.05). Blood pressure remained constant in the intervention, but decreased significantly in the control group. Conclusion: applying FORTA to hospitalised geriatric patients leads to improvement of medication quality and may improve secondary clinical end points (e.g. ADRs). The concept is amenable to successful communication and implementation. Registration (DRKS-ID):DRKS00000531. Funding: DFG-German Research Foundation (WE 1184/15-1). [ABSTRACT FROM AUTHOR]

Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/ HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer. [ABSTRACT FROM AUTHOR]

Pseudomyxoma peritonei (PMP) is a relatively rare clinical syndrome characterized by neoplastic epithelial cells growing in the peritoneal cavity and secreting mucinous ascites. Our aim was to explore the molecular events behind this fatal but under-investigated disease. We extracted DNA from 19 appendix-derived PMP tumors and nine corresponding normal tissues, and analyzed the mutational hotspot areas of 48 cancer-related genes by amplicon-based next-generation sequencing (NGS). Further, we analyzed the protein expression of V600E mutated BRAF, MLH1, MSH2, MSH6 and p53 from a larger set of PMP tumors ( n = 74) using immunohistochemistry. With NGS, we detected activating somatic KRAS mutations in all of the tumors studied. GNAS was mutated in 63% of the tumors with no marked difference between low-grade and high-grade tumors. Only one (5.3%) tumor showed oncogenic PIK3CA mutation, one showed oncogenic AKT1 mutation, three (15.8%) showed SMAD4 mutations and none showed an APC mutation. P53 protein was aberrantly expressed in higher proportion of high-grade tumors as compared with low-grade ones (31.3 vs. 7.1%, respectively; p = 0.012) and aberrant expression was an independent factor for reduced overall survival ( p = 0.002). BRAF V600E mutation was only found in one (1.4%) high-grade tumor by immunohistochemistry ( n = 74). All the studied tumors expressed mismatch repair proteins MLH1, MSH2 and MSH6. Our results indicate that KRAS mutations are evident in all and GNAS mutations in most of the PMPs, but BRAF V600E, PIK3CA and APC mutations are rare. Aberrantly expressed p53 is associated with high-grade histology and reduced survival. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity and polypharmacy represent a major problem for elderly patients; improvement of medication schemes is important and listing approaches (e.g. Beers list) are considered to be potentially useful. Objectives: The aim of this study was to perform expert consensus validation of the FORTA (Fit fOR The Aged) List, a drug classification combining positive and negative labelling of drugs chronically prescribed to elderly patients. Methods: A two-round Delphi procedure was conducted involving 20 experts, 17 geriatric internists and 3 geriatric psychiatrists from Germany and Austria, evaluating the labels assigned to 190 substances or substance groups. These labels ranged from A (indispensable), B (beneficial), C (questionable) to D (avoid), depending on the state of evidence for safety, efficacy and overall age-appropriateness. The experts were also requested to suggest additional substances and indication areas for assessment and possible inclusion in the FORTA List. A weighted (corrected) consensus coefficient was generated for each substance to reflect (1) agreement with the original label, and (2) distribution among raters' labels. Results: The overall consensus for all items and raters was 92 % (corrected). For 54/190 items (28.4 %), a unanimous response was achieved as to the original author-based FORTA label choice. Twenty-four substances (12.6 %) fell short of the consensus cutoff and were re-evaluated in a second round. This yielded confirmation of 171/190, or 90 %, of the original author-based FORTA labels. A total of 35 new substances were also accepted for the FORTA List. Drugs used for dementia and dementia syndromes provoked particular response heterogeneity. Conclusion: The FORTA List now reflects a wider consensus among experts, increasing its validity for clinical use. It represents a tool to improve the quality of drug prescription in older patients by identifying both inappropriate and omitted drugs, and thus overtreatment and undertreatment. The validation of FORTA's impact on clinical endpoints has yielded promising preliminary results, to be corroborated in ongoing larger trials. [ABSTRACT FROM AUTHOR]

The aim of the study was to detect mutations of BRAF oncogene in colorectal cancer and to use this information to identify Lynch syndrome patients. Consecutive cases of primary colorectal cancer ( n = 137) were analyzed for MLH1 protein expression using immunohistochemistry (IHC). BRAF V600E mutation was detected by IHC using a specific monoclonal antibody (VE1) and by qPCR. All MLH1 protein-negative cases were subjected to microsatellite instability analysis and MLH1 promoter methylation assay. MLH1 protein expression deficiency and high microsatellite instability (MSI-H) were detected in 18 of the 137 (13.1 %) consecutive colorectal cancer specimens. Detection of the BRAF V600E mutation by IHC was 100 % sensitive and specific as compared to qPCR, and this mutation was frequently present in the MSI-H group (77.8 %; 14/18) and less frequently in the microsatellite-stable group (7.6 %; 9/118). All BRAF V600E mutated cases of the MSI-H group presented with a MLH1 promoter methylation (14/14) as detected by methylation-specific multiplex ligation-dependent probe amplification. When BRAF was wild type in the MSI-H group, only one MLH1 promoter methylation was detected (1/4), and of the remaining three cases without MLH1 methylation, two were identified to harbor an MLH1 mutation consistent with Lynch syndrome. Finally, 11 previously confirmed Lynch syndrome cases were analyzed for BRAF V600E mutation, and all of them were wild type. In conclusion, detection of BRAF V600E in colorectal cancer specimens by IHC is sensitive and specific and may help to identify Lynch syndrome patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to detect mutations of BRAF oncogene in colorectal cancer and to use this information to identify Lynch syndrome patients. Consecutive cases of primary colorectal cancer (n = 137) were analyzed for MLH1 protein expression using immunohistochemistry (IHC). BRAF V600E mutation was detected by IHC using a specific monoclonal antibody (VE1) and by qPCR. All MLH1 protein-negative cases were subjected to microsatellite instability analysis and MLH1 promoter methylation assay. MLH1 protein expression deficiency and high microsatellite instability (MSI-H) were detected in 18 of the 137 (13.1%) consecutive colorectal cancer specimens. Detection of the BRAF V600E mutation by IHC was 100% sensitive and specific as compared to qPCR, and this mutation was frequently present in the MSI-H group (77.8%; 14/18) and less frequently in the microsatellite-stable group (7.6%; 9/118). All BRAF V600E mutated cases of the MSI-H group presented with a MLH1 promoter methylation (14/14) as detected by methylation-specific multiplex ligation-dependent probe amplification. When BRAF was wild type in the MSI-H group, only one MLH1 promoter methylation was detected (1/4), and of the remaining three cases without MLH1 methylation, two were identified to harbor an MLH1 mutation consistent with Lynch syndrome. Finally, 11 previously confirmed Lynch syndrome cases were analyzed for BRAF V600E mutation, and all of them were wild type. In conclusion, detection of BRAF V600E in colorectal cancer specimens by IHC is sensitive and specific and may help to identify Lynch syndrome patients. [ABSTRACT FROM AUTHOR]

Different genetic aberrations of BRAF have been reported in various malignancies. BRAF is member of the RAS/RAF/MEK/ERK pathway and constitutive activity of this pathway can lead to increased cellular growth, invasion, and metastasis. The most common activating BRAF mutation in colorectal cancer is the V600E mutation, which is present in 5-15% of all tumors, and up to 80% of tumors with high microsatellite instability (MSI) harbor this mutation. BRAF mutation is associated with proximal location, higher age, female gender, MSI-H, high grade, and mucinous histology, and is a marker of poor prognosis in colorectal cancer. The role of BRAF mutation as a predictive marker in respect of EGFR targeted treatments is controversial. BRAF V600 selective inhibitors have been approved for the treatment of V600 mutation positive metastatic melanoma, but the response rates in colorectal cancer are poor. This might be due to innate resistance mechanisms of colorectal cancers against the treatment solely targeting BRAF. To overcome resistance the combination of treatments, simultaneous inhibition of BRAF and MEK or PI3K/mTOR, might emerge as a successful therapeutic concept. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (Cox-2) expression is a marker of reduced survival in gastric cancer patients, and inhibition of Cox-2 suppresses gastrointestinal carcinogenesis in experimental animal models. To investigate the role of Cox-2 in gastric carcinogenesis in vivo, we utilized trefoil factor 1 ( Tff1) deficient mice, which model the neoplastic process of the stomach by developing gastric adenomas with full penetrance. These tumors express Cox-2 protein and mRNA, and we have now investigated the effects of genetic deletion of the mouse Cox-2 gene [also known as prostaglandin-endoperoxide synthase 2 ( Ptgs2)] and a Cox-2 selective drug celecoxib. Our results show that genetic deletion of Cox-2 in the Tff1 deleted background resulted in reduced adenoma size and ulceration with a chronic inflammatory reaction at the site of the adenoma. To characterize the effect of Cox-2 inhibition in more detail, mice that had already developed an adenoma were fed with celecoxib for 8-14 weeks, which resulted in disruption of the adenoma that ranged from superficial erosion to deep ulcerated destruction accompanied with chronic inflammation. Importantly, mice fed with celecoxib for 16 weeks, followed by control food for 9 weeks, redeveloped a complete adenoma with no detectable inflammatory process. Finally, we determined the identity of the Cox-2 expressing cells and found them to be fibroblasts. Our results show that inhibition of Cox-2 is sufficient to reversibly disrupt gastric adenomas in mice. [ABSTRACT FROM AUTHOR]

The worldwide incidence and mortality of gastric cancer ( GC) remain high, and new concepts for diagnosis and treatment are needed. In this review, we summarize recent studies that applied next-generation sequencing approaches and also report the latest development in micro RNA research. Two recently published studies identified somatic mutations in ARID1 A gene in GC using exome sequencing. On the other hand, dysregulation of micro RNA expression can alter processes such as proliferation, apoptosis, invasion, and metastasis. These novel markers may prove to be useful in earlier diagnosis and as prognostic or predictive markers in patients with GC . [ABSTRACT FROM AUTHOR]

Gastric cancer remains a leading cause of cancer-related deaths worldwide, although its incidence has been steadily declining during recent decades. Expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. COX-2 expression associates with reduced survival in gastric cancer patients, and it has also been shown to be an independent factor of poor prognosis. Several molecular mechanisms are involved in the regulation of COX-2 expression in gastric cancer cell lines, including signal transduction pathways activated by Helicobacter pylori. In gastric tumor models in vivo the role of COX-2 seems to be predominantly to facilitate tumor promotion and growth. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. In the last years, molecular oncobiology studies brought to light a number of genes that are implicated in gastric carcinogenesis. This review is intended to focus on the recently described basic aspects that play key roles in the process of gastric carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B, SMAD4, and SERPINE1 have been reported to modify the risk of developing GC. Several genes have been newly associated with gastric carcinogenesis, both through oncogenic activation ( GSK3β, CD133, DSC2, P-Cadherin, CDH17, CD168, CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through tumor suppressor gene inactivation mechanisms ( TFF1, PDX1, BCL2L10, XRCC, psiTPTE-HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and its importance as a potential molecular target for therapy. [ABSTRACT FROM AUTHOR]

The notion of item context effects implies that psychometric properties of an item or scale are altered by the presentation format, for example, blocked versus randomized. In an experimental study with high school students, the experimental group (n = 407) answered a four-dimensional academic self-concept questionnaire, in which the items were presented in a grid with eight identical item stems forming the rows and four academic subjects (math, physics, German, English) forming the columns, thereby maximizing potential blocking effects. The control group (n = 396) answered the identical items presented in a traditional randomized order. Multiple-group confirmatory factor analyses demonstrated similar factorial structures (i.e., factor loadings, factor variances, and factor covariances) of the two versions. Scale means, scale homogeneities, and relations with grades in the corresponding and noncorresponding subjects were very similar. Practical implications of these results for economical measurement of educational and psychological concepts (i.e., using grids) are discussed. [ABSTRACT FROM AUTHOR]

Infectious complications of acute necrotizing pancreatitis (ANP) determine the extent of multiorgan failure and account for 80% of deaths. Prophylactic use of antibiotics can reduce the incidence of these complications. However, the actual indication as well as choice of drug remains a controversial matter. We examined the penetration of moxifloxacin, a new broad-spectrum fluoroquinolone, in healthy and inflamed pancreatic tissue in rats after inducing ANP. The concentration of moxifloxacin in pancreatic tissue and serum was determined 10, 30, 60 and 240 min after the administration of moxifloxacin (5 mg/kg, i.v.). Mean serum concentrations 10 min after administration in rats with ANP were 1,886 ng/ml versus 1,805 ng/ml in healthy controls, and these values decreased to 350 versus 222 ng/ml, respectively, after 240 min. Corresponding concentrations in pancreatic tissue were in the mean 2-3 times higher. [ABSTRACT FROM AUTHOR]

Background: Mammals in the far north are exposed to extreme seasonal changes in environmental conditions, such as temperature and photoperiod, which have notable effects on animal physiology and behaviour. The wolverine (Gulo gulo) is a carnivore with a circumpolar distribution and well-adapted to extreme environmental conditions. Still, ecophysiological studies on free-ranging wolverines are lacking. In this study, we used abdominally implanted body temperature loggers in combination with GPS collars with acceleration sensors on 14 free-ranging wolverines in northern Sweden to study daily and seasonal variation in body temperature and activity patterns. We used generalized additive mixed modelling to investigate body temperature patterns over time and Lomb-Scargle periodogram analysis to analyse circadian rhythms. Results: We found that wolverines have an average core body temperature of 38.5 ± 0.2 °C with a daily variation of up to 6 °C. Body temperature patterns varied between reproductive states. Pregnant females showed a distinct decrease in body temperature during gestation. Wolverines were active both in day and night, but displayed distinct activity peaks during crepuscular hours. However, body temperature and activity patterns changed seasonally, with a gradual change from a unimodal pattern in winter with concentrated activity during the short period of day light to a bimodal pattern in autumn with activity peaks around dusk and dawn. Wolverines were less likely to display 24-h rhythms in winter, when hours of day light are limited. Conclusions: The combination of different biologging techniques gave novel insight into the ecophysiology, activity patterns and reproductive biology of free-ranging wolverines, adding important knowledge to our understanding of animals adapted to cold environments at northern latitudes. [ABSTRACT FROM AUTHOR]