Search

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]

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. (Contains 5 tables.)

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]

Nonmedical prescription stimulant use (NPS) is increasing, particularly among college students. College students typically engage in NPS for cognitive enhancement, recreational, and appetite/weight-related purposes; however, little research has used these motives to identify specific risk for, or consequences of, NPS. Moreover, there may be unique risk factors for motive-specific NPS that have yet to be explored, such as relevant personality traits (i.e., distress tolerance, impulsivity, and perfectionism) that are associated with NPS in general. Therefore, this study aimed to examine whether NPS users and nonusers could be differentiated via facets of impulsivity, perfectionism, and distress tolerance, and whether users could be further differentiated by reported motive for use based on these traits. Midwestern university undergraduate students (N = 668) who were enrolled in a psychology research pool completed an online survey assessing demographics, NPS and motives, and measures of distress tolerance, impulsivity, and perfectionism. Participants were primarily female (78%) and aged 18-54 (M = 20.10, SD = 3.19) years. Univariate and multivariate analysis of variance tests revealed associations between lifetime NPS and higher impulsivity, higher perfectionism, and lower distress tolerance. Further tests revealed NPS for appetite/weight-related purposes was associated with lower distress tolerance, while NPS for recreational purposes was associated with higher impulsivity. These findings contribute novel information regarding NPS motives and personality constructs. This information may aid in comprehensive identification of high-risk individuals for NPS and inform the development of specialized prevention and intervention efforts. [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]

Gestation and lactation have high energetic requirements. Up to three-fourths of the gestation period in moose (Alces alces) overlaps with the food-scarce period in winter. During this period, moose deal with the limited forage resources available through hypometabolism with decreased heart rate and body temperature (T b). Body temperature is also an indicator of oestrus, pregnancy and parturition, which is well documented in several domestic species. In this study, we sought to determine if moose displayed a similar T b pattern during pregnancy and parturition to domesticated ruminants, and if we could detect parturition by combining T b and activity data. We studied the T b pattern of 30 free-ranging adult female moose (≥1.5 years old), equipped with ruminal temperature loggers and GPS collars. We documented a 0.13–0.19°C higher T b in pregnant compared to non-pregnant moose, depending on the study area with the T b difference increasing along a south-north gradient, and a drop in T b and in activity when parturition was imminent. Detection of parturition was highly successful when combining T b and activity data with an accuracy of 91.5%. Our findings demonstrate that T b responses to pregnancy and parturition in a wild capital-breeding ruminant are similar to those of domesticated ruminants. • Body temperature in female moose varies between reproductive states. • Pregnant moose have a higher body temperature than non-pregnant females. • The body temperature of female moose drops when parturition is imminent. • Combined use of body temperature and activity data allows successful detection of parturition. [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 poor prognosis in gastric cancer patients, and its inhibition suppresses gastric tumorigenesis in experimental animal models. The mechanism that leads to COX-2 overexpression in this tumor type is unknown. We have now shown that inhibition of phosphatidylinositol 3-kinase by LY294002 suppresses both basal and phorbol myristate acetate-induced COX-2 expression in TMK-1 and MKN-28 gastric cancer cells. Furthermore, inhibition of glycogen synthase kinase-3β (GSK-3β) by SB415286 induced expression of COX-2 mRNA and protein as well as the enzyme activity in the gastric cancer cells. The effect of SB415286 was confirmed by the use of two additional GSK-3β inhibitors, lithium chloride and SB216763. SB415286 had a modest 1.6-fold stimulatory effect on a 2-kb COX-2 promoter reporter construct, but more importantly, it was shown to block the decay of COX-2 mRNA. In contrast to modulation of phosphatidylinositol 3-kinase/Akt/GSK-3β pathway, inhibitors of mitogen-activated protein kinases (MEK 1/2, p38, INK) or the mammalian target of rapamycin did not alter COX-2 expression in gastric cancer cells. Our data show that inhibition of GSK-3β stimulates COX-2 expression in gastric cancer cells, which seems to be primarily facilitated via an increase in mRNA stability and to a lesser extent through enhanced transcription. [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]

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., Competing Interests: TL is an employee by Medtronic Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thiel, Giroud, Hertel, Friebe, Devineau, Fuchs, Blanc, Støen, Laske, Arnemo and Evans.)

Lead (Pb) exposure is associated with adverse health effects in both humans and wildlife. Blood lead levels (BLL) of sentinel wildlife species can be used to monitor environmental lead exposure and ecosystem health. BLL analyzers, such as the LeadCare®, are validated for use in humans, assessed for use in some avian species and cattle, and are increasingly being used on wildlife to monitor lead exposure. The LeadCare® analyzers use a technique called anodic stripping voltammetry (ASV). Species-specific conversion equations have been proposed to approximate the levels found with gold standard measuring methods such as inductively coupled plasma mass spectrometry (ICP-MS) because the ASV method has been shown to underestimate BLL in some species. In this study we assessed the LeadCare® Plus (LCP) for use on Scandinavian brown bears ( Ursus arctos ). LCP measurements were correlated with ICP-MS with a Bland-Altman analyzed bias of 16.3-22.5%, showing a consistent overestimation of BLL analyzed with LCP. Based on this analysis we provide conversion equations for calculating ICP-MS BLL based on the LCP results in Scandinavian brown bears. Our study shows that the LeadCare® Plus can be used for monitoring of lead exposure by approximating gold standard levels using conversion equations. This enables comparison with other gold standard measured BLL within the observed range of this study (38.20-174.00 μg/L). Our study also found that Scandinavian brown bears are highly exposed to environmental lead.

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites. KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent. As altered glycosylation can promote carcinogenesis, we compared N -linked glycan profiles of PMP tissues to those of normal appendix. Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry. Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation. We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls. Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry. We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2 , which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene. Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP. Glycomic data are available via ProteomeXchange with identifier PXD010086., (© 2018 Saarinen et al.)

Purpose: We have investigated the expression and regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer., Experimental Design: Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines., Results: In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E(2) production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues (n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210)., Conclusions: 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.

Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E2 (PGE2) production. Human small intestine epithelial cell line FHsInt74 and EGF-R-deficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.

Purpose: Cyclooxygenase-2 (COX-2) promotes carcinogenesis and its expression associates with clinicopathologic characteristics in gastric cancer. HuR is an mRNA binding protein that controls the stability of certain transcripts including COX-2. We evaluated the prognostic significance of COX-2 and HuR expressions in gastric cancer and whether there exists a link between HuR and COX-2 expressions., Experimental Design: The study included 342 consecutive patients with histologically confirmed gastric adenocarcinoma, of whom 321 patients had tissue specimens available for COX-2 and 316 for HuR immunohistochemistry. Specimens were stained by COX-2- and HuR-specific monoclonal antibodies and scored by two independent observers. Correlation to clinical data and survival was assessed. TMK-1 gastric adenocarcinoma cells were treated with small interfering RNA against HuR and expressions of HuR and COX-2 were detected by immunofluorescence and Western blot analysis., Results: Patients with low COX-2 expression had a cumulative 5-year survival of 53% and those with high COX-2 expression had 16% (P < 0.0001). In multivariate analysis, COX-2 was an independent prognostic factor (P = 0.003). Cytoplasmic HuR expression was associated with high COX-2 expression (P < 0.0001) and with reduced survival (P = 0.004) whereas nuclear positivity for HuR was not. When TMK-1 cells were treated with HuR small interfering RNA, expressions of HuR and COX-2 were reduced., Conclusions: High COX-2 is an independent prognostic factor in gastric cancer. Cytoplasmic expression of HuR associates with high COX-2 expression and with reduced survival, and tissue culture experiments show that HuR can regulate expression of COX-2 in gastric cancer cells.