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Ontologies have been successfully used to assign semantics in the Semantic Web context, to support integration of data from different systems or different sources, and to enable reasoning. However, building ontologies is not a trivial task. Ontology reuse can help in this matter. The search and selection of ontologies to be reused should consider the alignment between their scope and the scope of the ontology being developed. In this paper, we discuss how goal modeling can be helpful in this context and we present GO-FOR, a framework in which goals are the central elements to promote ontology reuse. GO-FOR comprises a conceptual architecture, a goal-oriented ontology development process and a supporting tool. In GO-FOR we introduce Goal-Oriented Ontology Patterns (GOOPs) as a new type of pattern to be applied to develop ontologies in a goal-oriented approach. Results of the use of GO-FOR to build an ontology used to integrate patient examination data are also shown in this paper.

BackgroundResearch demonstrates that SARS-CoV-2 infection (COVID-19) among adults disproportionately impacts racial and ethnic minorities and those living in lower-income communities. Similar research in children is limited due, in part, to the relatively low COVID-19 incidence in children compared to adults. This analysis, conducted as part of the RECOVER Initiative, explores this question.MethodsElectronic health record (EHR) data from PEDSnet, a multi-institutional research network of pediatric healthcare organizations, were geocoded and linked to two indices of contextual social deprivation: the Area Deprivation Index and the Child Opportunity Index. Univariate statistics were employed to test the association between each index and COVID19 positivity among children ages 0-20 tested at one of six Children’s hospitals. Multivariate logistic regression was used to explore the relationship between these social context indices and racial disparities in positivity, controlling co-variates.ResultsBoth ADI and COI were significantly associated with COVID-19 positivity in univariate and adjusted models, particularly in the pre-delta and delta variant waves. ADI showed a stronger association. Higher rates of positivity were found for non-Hispanic Black, Hispanic, and multi-racial children compared to non-Hispanic White children. These racial disparities remained significant after control for either index and for other variables.ConclusionADI and COI are significantly associated with COVID-19 test positivity in a population of children and adolescents tested in children’s hospital settings. These social contextual variables do not fully explain racial disparities, arguing that racial disparities are not solely a reflection of socioeconomic status. Future disparities research should consider both race and social context.

Objective Headaches are common among youth and are associated with significant negative outcomes. Despite advances in interdisciplinary treatments for youth with chronic pain, research suggests disparities in access to these services. Methods A total of 186 youth (M = 14.19 years old, 70.8% female) presenting to a neurology appointment at a children’s hospital system were screened using the Pediatric Pain Screening Tool (PPST), a brief, validated measure to identify youth that may benefit from additional pain management services. Results Two-thirds of participants (n = 124, 66.7%) screened as medium or high risk on the PPST. Risk categorization did not vary by patient age or sex. A greater proportion of Hispanic/Latino patients were categorized as low-risk relative to non-Hispanic/Latino patients (55.6% vs. 30.1%), and a somewhat lower proportion of patients of color were categorized as medium-risk relative to White patients (14.0% vs. 30.5%). Three-quarters (n = 94, 75.8%) of patients who were screened as medium or high risk were not referred for any additional pain management services. Referrals did not vary by patient age or ethnicity. While not statistically significant, a lower proportion of males received referrals at both medium (8.3% vs. 17.6%) and high levels of risk (15.8% vs. 34.5%), and a greater proportion of youth of color who screened as medium risk received referrals relative to White youth categorized as medium risk (37.5% vs. 10.3%). Conclusion Future research should continue to explore factors influencing decision-making regarding referral to specialized pain management services for youth with headache.

Intensive interdisciplinary chronic pain treatment programs have demonstrated that pain acceptance predicts positive treatment outcomes, but limited research has focused on less-intensive programs. This study aimed to examine associations between changes in pain acceptance and pain interference among youth participating in an outpatient interdisciplinary chronic pain treatment program.Youth presenting to an evaluation within an interdisciplinary outpatient pediatric chronic pain program completed questionnaires at initial program evaluation (T1) and three months later (T2).Youth (Pain acceptance increased significantly from T1 to T2 (Pain acceptance and interference improved after three months in an outpatient chronic pain treatment program. Improvements in acceptance were strongly related to reductions in interference. Future research should examine these relationships over longer periods, in larger samples.

Limited attention has been devoted in school psychology training programs to students with chronic health conditions. School psychologists are situated to provide behavioral and mental health servi...

Recurrent pain is a common experience in childhood and adolescence and can result in significant disability in youth, including poor quality of life, school absences, and reduced social activities. Evidence has linked adolescent risk and resilience factors with treatment outcomes. However, less research has focused on examining risk and resilience factors that may influence or predict adolescents&rsquo, compliance to treatment within an interdisciplinary pediatric chronic pain management program. Participants included 64 adolescents (M = 15.00 &plusmn, 1.69 years), 85.9% female, 84.4% Caucasian who presented to an initial evaluation in an interdisciplinary pediatric pain management program with their caregiver. Youth completed a series of questionnaires at the initial evaluation targeting pain acceptance, self-efficacy, pain catastrophizing, parental responses, pain intensity, and functional disability. Treatment compliance was measured at 3 and 6 months post-intake. Findings indicated that higher levels of adolescent-reported self-efficacy predict decreased treatment session attendance, whereas lower levels of acceptance and parental encouragement/monitoring of symptoms predict increased treatment compliance overall. Several adolescent-reported risk factors were associated with increased functional impairment among this sample. Results highlight the unique importance of risk and resilience factors within the developmental context of adolescence, while also emphasizing the need for further investigation of other relevant influences towards treatment compliance and functional impairment.

Iron oxide nanoparticles (IONs) are being actively researched and experimented with as contrast agents for Magnetic Resonance Imaging (MRI), as well as image-directed delivery of therapeutics. The efficiency of an MRI contrast agent can be described by its longitudinal and transverse relaxivities, r

Ovotesticular or testicular disorder of sexual development in dogs with female karyotype and lack of SRY (XX DSD) is a common sexual anomaly diagnosed in numerous breeds. The molecular background, however, remains unclear, and epigenetic mechanisms, including DNA methylation, have not been studied. The aim of our study was comparative methylation analysis of CpG islands in promoters of candidate genes for XX DSD: SOX9, SOX3, and WNT4. Methylation studies were performed on DNA extracted from formalin-fixed/paraffin-embedded or frozen gonads from 2 dogs with ovotesticular and 2 dogs with testicular XX DSD as well as control females (n = 4) and males (n = 2). Bisulfite-converted DNA was used for CpG methylation analysis using quantitative pyrosequencing. Promoter regions of SOX9 and WNT4 showed similar CpG methylation in each group, ranging from 0 to 5.5% and from 39 to 74%, respectively. The SOX3 promoter showed significantly higher methylation in the ovotesticular XX DSD cases and the testicular XX DSD and control males, suggesting that SOX3 methylation may play a role in canine XX DSD pathogenesis.

Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1-/- MEF cells, and not in wild-type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436-446, 2017. © 2016 Wiley Periodicals, Inc.

The miR-30 gene family includes potential regulators of adipogenesis. We searched for polymorphism in this gene family in 4 pig breeds: Duroc, Pietrain, Polish Landrace (PL), Polish Large White (PLW) and a synthetic line (L990). Altogether 5 single nucleotide polymorphisms (SNPs) in 3 genes were found, including one already known SNP rs340704946 within the pre-miR-30d genomic sequence. An association of the rs340704946 with intramuscular fat (IMF) content, abdominal fat accumulation and daily body mass gain in L990 was found. Moreover, the AG genotype was associated with an increased content of monounsaturated fatty acids (MUFA) in subcutaneous (P=0.027) and visceral fat (P=0.007) tissues when compared to the GG genotype. Analysis of PLW pigs revealed an association of the rs340704946 with transcript level of the ME1 gene in longissimus dorsi (LD) muscle (P=0.002), as well as the ME1 protein product in the LD muscle (P

Iron oxide nanoparticles (IONs) are being actively researched and experimented with as contrast agents for Magnetic Resonance Imaging (MRI), as well as image-directed delivery of therapeutics. The efficiency of an MRI contrast agent can be described by its longitudinal and transverse relaxivities, r1 and r2. gamma-Fe2O3 nanoparticles - doped with fluoride in a controlled manner and functionalised with citric acid - showed a 3-fold increase in r1 and a 17-fold increase in r2 in a magnetic field of 3 T and almost 6-fold increase in r1 and a 14-fold increase in r2 at 11 T. Following fluorination, PXRD shows that the crystal structure of gamma-Fe2O3 is maintained, Mössbauer spectroscopy shows that the oxidation state of the Fe cation is unchanged and HREM shows that the particle size does not vary. However, magnetisation curves show a large increase in the coercive field, pointing towards a large increase in the magnetic anisotropy for the fluorinated nanoparticles compared to the un-doped gamma-Fe2O3 nanoparticles. Therefore, a chemically induced increase in magnetic anisotropy appears to be the most relevant parameter responsible for the large increase in relaxivity for gamma-Fe2O3 nanoparticles.

Breast cancer is the leading cause of cancer-related deaths among women. Approximately 75% of breast cancers are estrogen receptor α (ERα) positive, underscoring the dependence of cancer cells on estrogen for growth and survival. Patients treated with endocrine therapy often develop resistance, either de novo or acquired, which in some cases is caused by aberrations within the growth factor signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) has emerged as a critical node in estrogenic signaling. We have previously shown that mTORC1 can phosphorylate and activate ERα on S167 via its effector the 40S ribosomal S6 kinase 1 (S6K1). Presently, we have uncovered a direct link between mTORC1 and ERα. We found that ERα binds to regulatory-associated protein of mTOR (Raptor) and causes it to translocate to the nucleus upon estrogen stimulation. Additionally, we identified mTOR as the kinase that phosphorylates ERα on S104/106 and activates transcription of ER target genes. Our findings show a direct link between mTORC1 and ERα, which further implicates mTORC1 signaling in the pathogenesis of ER-positive breast cancer and provides rationale for FDA-approved use of mTORC1 inhibitors in combination with endocrine agents for treatment of this disease.

78,XX testicular or ovotesticular disorder of sex development (DSD) is the most common sex anomaly in dogs, but its molecular background remains unknown. It was hypothesized that the causative mutation may reside in canine chromosome 23 (CFA23), where two genes playing a pivotal role in ovarian development (CTNNB1 and FOXL2) are located. The aim of our study was to search for polymorphism in both candidate genes in 15 DSD dogs (78,XX and a lack of the SRYgene) and 29 normal females. Altogether, 7 novel polymorphic variants were identified: 5 SNPs in CTNNB1 and 2 indels in the FOXL2 gene. The distribution of the identified variants was similar in the DSD and control dogs. Therefore, we concluded that the conducted research did not prove an association between these polymorphisms and canine testicular or ovotesticular XX DSD.

Background Interest and participation in complementary and alternative medicine (CAM) has steadily increased over the last decade. Research is needed to empirically explore beliefs about the characteristics of individuals who participate in CAM to determine the pervasiveness and generalisability of these opinions. Objective To explore the stereotype of the typical CAM user and how this construct may impact recruitment and retention in paediatric CAM research. Methods Parents and emerging adults were recruited using community sampling. Subjects responded to an electronic survey by judging likeliness to participate based on a series of demographic factors. From a total of 570 individuals who completed the survey, 209 responded to a vignette on acupuncture and 361 to a vignette on yoga. Results Taking the results together, it appears that the individual characteristics associated with a higher likelihood of engaging in CAM, or being stereotypical of a CAM user, were being white or Asian, female or homosexual male, highly educated, identifying as socially liberal and having a religious affiliation of Buddhist or Hindu. Conclusions It is important to understand how these factors may affect people's decisions to participate in CAM interventions and the potential implication for future research on the effectiveness of CAM therapies.

The primary aim of the current study was to provide preliminary data on the feasibility, acceptability, and safety of alignment-based yoga for youths with chronic headaches. A secondary aim was to provide preliminary estimates of yoga's ability to improve headache pain, daily functioning, quality of life, and anxiety level in this population. The yoga intervention consisted of 8 weekly, 75-minute classes. Participant flow data revealed challenges to feasibility primarily due to recruitment and retention. Scores on most outcome measures changed in the predicted direction with medium effect sizes found for the functional outcomes. Pain measures did not change significantly. This pilot suggests that yoga for pediatric headaches may be acceptable, as indicated by positive parent and participant ratings of the yoga experience. These preliminary findings suggest that yoga trials for pediatric headaches include both challenges and promise. Recommendations for overcoming challenges include designs that optimize family convenience.

A disorder of sexual development (DSD) of dogs with a female karyotype, missing SRY gene, and presence of testicles or ovotestes is quite commonly diagnosed. It is suggested that this disorder is caused by an autosomal recessive mutation; however, other models of inheritance have not been definitely ruled out. In an earlier study it was hypothesized that the mutation may reside in a pericentromeric region of canine chromosome 23 (CFA23). Three positional candidate genes (CLASP2, UBP1, and FBXL2) were selected in silico in the search for polymorphisms in 7 testicular or ovotesticular XX DSD dogs, 8 XX DSD dogs of unknown cause (SRY-negative, with enlarged clitoris and unknown histology of gonads), and 29 normal female dogs as a control group. Among the 15 molecularly studied dogs with enlarged clitoris there were 3 new cases of testicular or ovotesticular XX DSD and 4 new cases of XX DSD with unknown cause (histology of the gonads unknown). Altogether, 11 (including 10 novel) polymorphisms in 5′- and 3′-flanking regions of the studied genes were found. The distribution analysis of these polymorphisms showed no association with the DSD phenotypes. Thus, it was concluded that the presence of the causative mutation for testicular or ovotesticular XX DSD in the pericentromeric region of CFA23 is unlikely.

Class I PI 3-kinases signal by producing the signaling lipid phosphatidylinositol(3,4,5) trisphosphate, which in turn acts by recruiting downstream effectors that contain specific lipid-binding domains. The class I PI 3-kinases comprise four distinct catalytic subunits linked to one of seven different regulatory subunits. All the class I PI 3-kinases produce the same signaling lipid, PIP3, and the different isoforms have overlapping expression patterns and are coupled to overlapping sets of upstream activators. Nonetheless, studies in cultured cells and in animals have demonstrated that the different isoforms are coupled to distinct ranges of downstream responses. This review focuses on the mechanisms by which the production of a common product, PIP3, can produce isoform-specific signaling by PI 3-kinases.

Fatty acid composition in porcine intramuscular fat affects the dietetic value and technological properties of meat. The stearoyl-CoA desaturase (SCD) gene is a strong positional and functional candidate for fatty acid composition. Our sequence analysis in 4 breeds (Duroc, Pietrain, Polish Landrace, and Polish Large White) revealed a novel SNP in the 5'-flanking sequence and 9 novel SNP and 2 novel indels in the 3' untranslated region (UTR). Transcript level of the SCD in subcutaneous fat was significantly greater than in muscle tissue (n=83; P0.001) and the interbreed comparison revealed a greater transcript level in the fat tissue of Polish Landrace (P0.01). We found no association between the abundance of the SCD transcript and fatty acid composition in any of the tissues. We performed an association analysis between 4 SNP (c.-353CT, c.-233TC, c.*164AG, and c.*928GC), 1 indel (c.*2574_2576delGTC), and production traits in Polish Large White (n=185) and synthetic line 990 (n=243). The most pronounced associations were observed for the c.*928GC polymorphism, which occurs within a predicted target site for 2 microRNA (ssc-miR-185 and ssc-miR-491). In line 990, this polymorphism was significantly associated with daily BW gain (P0.04 under the general model) and feed conversion ratio (P0.0004) but not with fatness traits. The same tendency, but not significant, was observed in the Polish Large White breed. When both breeds were analyzed together, these associations were again highly significant (daily BW gain P0.003; feed conversion ratio P0.0001). We conclude that c.*928GC is a promising marker for both porcine traits.

In humans the fat mass and obesity-associated (FTO) gene represents a low-penetrance susceptibility gene for obesity risk. The pig (Sus scrofa) is an important model organism for human obesity. The purpose of this study was to search for polymorphisms in the 5′ flanking region of the pig FTO gene and to analyze its association with fatness and other production traits in three modern pig breeds. We detected a SNP g−167 T>G (GQ179639). An association study between this SNP and fatness and performance traits in Polish Large White (PLW, n=187), Polish Landrace (PL, n=237), and a synthetic line 990 (L990, n=238) revealed multiple significant associations with back fat thickness (P=0.009), abdominal fat weight (P=0.029) and lean meat content in PL (P=0.047). Our data indicate that FTO variants can be associated with fatness traits in purebred pigs selected for low fatness and also can be useful in model studies on human obesity. An updated survey of the pig FTO gene polymorphism is also presented.

Homologous recombination (HR) is a conserved process that maintains genome stability and cell survival by repairing DNA double-strand breaks (DSBs). The RAD51-related family of proteins is involved in repair of DSBs; consequently, deregulation of RAD51 causes chromosomal rearrangements and stimulates tumorigenesis. RAD51C has been identified as a potential tumor suppressor and a breast and ovarian cancer susceptibility gene. Recent studies have also implicated estrogen as a DNA-damaging agent that causes DSBs. We found that in ERα-positive breast cancer cells, estrogen transcriptionally regulates RAD51C expression in ERα-dependent mechanism. Moreover, estrogen induces RAD51C assembly into nuclear foci at DSBs, which is a precursor to RAD51 complex recruitment to the nucleus. Additionally, disruption of ERα signaling by either anti-estrogens or siRNA prevented estrogen induced upregulation of RAD51C. We have also found an association of a worse clinical outcome between RAD51C expression and ERα status of tumors. These findings provide insight into the mechanism of genomic instability in ERα-positive breast cancer and suggest that individuals with mutations in RAD51C that are exposed to estrogen would be more susceptible to accumulation of DNA damage, leading to cancer progression.

Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1

Promoting resilience for children and adolescents with chronic health conditions has been a guiding framework for the field of pediatric psychology. Much of the literature is now focused on the specific risk and resource factors that contribute to psychosocial outcomes, specifically, how to improve health-related quality of life (HRQL) with targeted and effective interventions. Pediatric cancer and sickle cell disease (SCD) serve as excellent examples to highlight risk and resource factors associated with resilience as similarities and differences in sociodemographics, disease characteristics, and treatments allow for unique comparisons and generalizations to other chronic health conditions. This chapter includes a description of risk and resource factors and associated interventions within a social ecological framework for both pediatric cancer and pediatric SCD taking into consideration the individual, family systems, social, and health care systems level. Future directions to address risk and resource factors within each level are provided.

Research on how adolescents with type 2 diabetes mellitus (T2DM) understand and use social support is limited. Therefore, we explored how adolescents with T2DM experience and perceive social support.Adolescents with T2DM were interviewed, and data were qualitatively analyzed using Consensual Qualitative Research methodology.Four themes emerged: support for nondiabetes and diabetes-specific behaviors, feelings of belonging, and disclosure. All participants expressed emotional and self-care-specific support. For some, disclosure and a sense of belonging with others who had diabetes often led to support elicitation. Participants also expressed a fear of disclosing their diabetes to others.Adolescents with T2DM value tangible and emotional support for behaviors both related and not related to diabetes. Fear of disclosure was a typical experience with disclosure often limited to close friends and family. Recommendations for health professionals to assist adolescents in promoting appropriate disclosure and means of requesting support are discussed.

The K + channel KCa3.1 is required for Ca 2+ influx and the subsequent activation of CD4 T cells. The class II phosphatidylinositol 3 kinase C2β (PI3KC2β) is activated by the T-cell receptor (TCR) and is critical for KCa3.1 channel activation. Tripartite motif containing protein 27 (TRIM27) is a member of a large family of proteins that function as Really Interesting New Gene (RING) E3 ubiquitin ligases. We now show that TRIM27 functions as an E3 ligase and mediates lysine 48 polyubiquitination of PI3KC2β, leading to a decrease in PI3K enzyme activity. By inhibiting PI3KC2β, TRIM27 also functions to negatively regulate CD4 T cells by inhibiting KCa3.1 channel activity and TCR-stimulated Ca 2+ influx and cytokine production in Jurkat, primary human CD4 T cells, and Th0, Th1, and Th2 CD4 T cells generated from TRIM27 −/− mice. These findings provide a unique mechanism for regulating class II PI3Ks, and identify TRIM27 as a previously undescribed negative regulator of CD4 T cells.

The study had two aims--to determine the efficacy of a family-based cognitive-behavioral pain management intervention for adolescents with sickle cell disease (SCD) in (1) reducing pain and improving health-related variables and (2) improving psychosocial outcomes. Each adolescent and a family support person were randomly assigned to receive a brief pain intervention (PAIN) (n = 27) or a disease education attention control intervention (DISEASE ED) (n = 26) delivered at home. Assessment of primary pain and health-related variables (health service use, pain coping, pain-related hindrance of goals) and secondary psychosocial outcomes (disease knowledge, disease self-efficacy, and family communication) occurred at baseline (prior to randomization), post-intervention, and one-year follow-up. Change on outcomes did not differ significantly by group at either time point. When groups were combined in exploratory analyses, there was evidence of small to medium effects of intervention on health-related and psychosocial variables. Efforts to address barriers to participation and improve feasibility of psychosocial interventions for pediatric SCD are critical to advancing development of effective treatments for pain. Sample size was insufficient to adequately test efficacy, and analyses did not support this focused cognitive-behavioral pain management intervention in this sample of adolescents with SCD. Exploratory analyses suggest that comprehensive interventions, that address a broad range of skills related to disease management and adolescent health concerns, may be more effective in supporting teens during healthcare transition.

Aims Management of type 1 diabetes mellitus (T1DM) involves adherence to complex daily behaviors. Some adolescents have difficulty maintaining these regimens within social contexts due to peer pressure and apprehension about being singled out (Wysocki et al., 2003 [1] ). Previous research suggests that negative social attributions have a role in adherence difficulties (Hains et al., 2006 [6] ). This pilot study examined a cognitive-behavioral intervention geared towards challenging and restructuring negative thinking patterns. Methods Ten adolescents with T1DM and HbA1c readings greater then 7.0% were recruited from a large, Midwestern Children's Hospital. The intervention consisted of a 1-h session followed by three weekly phone calls, which focused on cognitive restructuring and problem-solving training. Measures of diabetes-related stress and concerns surrounding self-care in social situations were completed by the adolescents pre- and post-intervention and at one-month follow-up. Results A series of repeated measure ANOVAS did not reveal significant differences between pre-intervention and follow-up scores across measures. Conclusions While there were no significant differences between pre-intervention and follow-up scores, the results highlight some important trends. Specifically, preliminary results suggest that the trends in individual scores indicate that problem-solving may be helpful for improving adherence in social situations.

Objective Confirmatory factor analysis was used to evaluate the factor structure of the Social Consequences of Pain (SCP) questionnaire in youth referred for specialty pain treatment. The existing four-factor structure (i.e., Positive Attention, Negative Attention, Activity Restriction, Privileges) was compared to an alternate threefactor structure merging Positive Attention and Privileges into a single scale (Favorable Consequences). Methods Participants were 373 youth (aged 8–18 years) with chronic pain referred to a tertiary pain clinic. Most participants presented with pain in the head, abdomen, legs, or back. Participants completed the SCP questionnaire at or before an intake appointment. Results Both three-factor and four-factor solutions were acceptable. The three-factor solution emerged as preferable due to stronger internal consistencies. Conclusions Findings support the validity of the SCP for the assessment of social consequences in diverse presentations of pediatric chronic pain.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic metastatic disease affecting women of childbearing age. LAM is caused by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis complex (TSC) 1/2 inactivation. Clinically, LAM results in cystic lung destruction. mTORC1 inhibition using rapamycin analogs (rapalogs) is partially effective in reducing disease progression and improving lung function. However, cessation of treatment results in continued progression of the disease. In the present study, we investigated the effectiveness of the combination of rapamycin treatment with resveratrol, an autophagy inhibitor, in the TSC2-null xenograft tumor model. We determined that this combination inhibits phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/Akt/mTORC1 signaling and activates apoptosis. Therefore, the combination of rapamycin and resveratrol may be an effective clinical strategy for treatment of LAM and other diseases with mTORC1 hyperactivation.

Isoform-specific signaling by Class IA PI 3-kinases depends in part on the interactions between distinct catalytic subunits and upstream regulatory proteins. From among the class IA catalytic subunits (p110α, p110β, and p110δ), p110β has unique properties. Unlike the other family members, p110β directly binds to Gβγ subunits, downstream from activated G-protein coupled receptors, and to activated Rab5. Furthermore, the Ras-binding domain (RBD) of p110β binds to Rac and Cdc42 but not to Ras. Defining mutations that specifically disrupt these regulatory interactions is critical for defining their role in p110β signaling. This chapter describes the approach that was used to identify the Rab5 binding site in p110β, and discusses methods for the analysis of p110β-Rab5 interactions.

Chez les races caprines saisonnées, les méthodes d’amélioration de production et de conservation de semence doivent prendre en considération l’influence de l’environnement et en particulier de la photopériode. Par la fonction qu’elle exerce sur la régulation du développement gonadique, celle-ci contribue indirectement au contrôle du comportement sexuel et de la production de sperme, tant du point de vue quantitatif que qualitatif. L’utilisation de traitements photopériodiques constitue donc un outil efficace pour augmenter la production des doses de sperme destinées à l’insémination artificielle durant la carrière de reproducteur du bouc. Afin d’optimiser la production et la qualité de la semence, une sélection préalable des mâles est cependant nécessaire. Un problème spécifique dans la conservation de la semence de bouc est l’effet délétère du plasma séminal sur la viabilité des spermatozoïdes après congélation / décongélation, principalement lorsqu’ils sont dilués dans des milieux à base de lait ou de jaune d’œuf. La protéine responsable de cet effet est une enzyme sécrétée par les glandes bulbo-uréthrales appartenant à la famille des lipases pancréatiques et qui possède une double activité lipasique et phospholipasique. La conservation de la semence à l’état liquide, peu coûteuse, est un complément à la cryconservation pour développer l’insémination artificielle à grande échelle. Mais la diminution de la fécondance après 12 heures de conservation est un frein à l’utilisation de cette technique. Les méthodes de congélation disponibles actuellement diffèrent sur plusieurs aspects. Les plus efficaces incluent le lavage de la semence pour éliminer le plasma séminal dès la collecte.

The leptin gene (LEP) is considered as a functional candidate for production traits in livestock due to its crucial role in energy homeostasis. Because polymorphisms in regulatory sequences may affect gene expression, we searched for them in the 3'UTR of LEP and analyzed their association with production traits. Four breeds and a composite line were studied. In the Polish Landrace and Polish Large White breeds, 8 SNPs and 1 indel were observed; whereas, in the Duroc breed, 9 specific SNPs were found. Pietrain and Line 990 were monomorphic. One SNP (g.+168C>T), observed in the Duroc breed only, was located within a target site for microRNA (miR-9). Association studies showed a weak association between one SNP (c.+846C>T) and abdominal fat weight in the Polish Landrace only. Thus, we concluded that contribution of polymorphisms in the 3'UTR to phenotypic variability of pig production traits is marginal. Moreover, we presented an overview of known polymorphisms (128) in the pig leptin gene.

The molecular background of disorders of sex development (DSD) in cats is poorly recognized. In this study we present cytogenetic, molecular and histological analyses of four cats subjected for the analysis due to ambiguous external genitalia. Three cases, with rudimentary penises and an abnormal position of the urethral orifice, represented different types of hypospadias. The fourth case had a normal penis, a blind vulva and spermatogenetically active testes. Histological studies showed structures typical of testes, but spermatogenic activity was observed in two cats only. All the cats had a normal male chromosome complement (38,XY) and the Y-chromosome linked genes ( SRY and ZFY ) were also detected. Fluorescent in situ hybridization (FISH), with the use of the feline BAC probe harboring the SRY gene, excluded the possibility of chromosome translocation of the Y chromosome fragment carrying the SRY gene onto another chromosome. Sequencing of four candidate genes ( SRY —sex determining region Y; AR— androgen receptor; SRD5A2— steroid-5-alfa reductase 2 and MAMLD1— mastermind-like domain containing (1) revealed one SNP in the SRY gene, one common polymorphism in exon 1 of the AR gene (tandem repeat of a tri-nucleotide motif—CAG), six polymorphisms (5 SNPs and 1 indel) in the SRD5A2 gene and one SNP in the MAMLD1 gene. Molecular studies of the candidate genes showed no association with the identified polymorphisms, thus molecular background of the studied DSD phenotypes remains unknown.