•The responses of dogs to animal-assisted intervention sessions were investigated.•Dogs’ salivary cortisol did not increase during animal-assisted intervention sessions.•Dogs did not have increased ...stress-associated behaviors during AAI sessions.•Dogs who exhibited more stress behaviors also exhibited more affiliative behaviors.•Dogs who exhibited more stress behaviors also had increased salivary cortisol.
Over the past two decades, animal-assisted interventions (AAIs), defined as the purposeful incorporation of specially trained animals in services to improve human health, have become increasingly popular in clinical settings. However, to date, there have been few rigorously-designed studies aimed at examining the impact of AAIs on therapy animals, despite a notable potential for stress. The current study measured physiological and behavioral stress indicators in therapy dogs who participated in AAI sessions in pediatric oncology settings, while also examining the psychosocial effects for patients and their parents. This manuscript describes the study’s canine stress findings. A total of 26 therapy dog-handler teams were paired with newly diagnosed children with cancer at five children’s hospitals in the United States. These teams provided regular AAI visits to the child and his/her parent(s) for a period of four months. The teams completed a demographic form, the Canine Behavioral Assessment & Research Questionnaire (C-BARQ), and a self-report survey to document the types of activities that occurred during each session. Canine saliva was also collected at five baseline time points and 20min after the start of study sessions for cortisol analysis, and all study sessions were video recorded to document the dog’s behavior via an ethogram measure. Data showed no significant differences in salivary cortisol levels between baseline (0.51μg/dL) and AAI sessions (0.44μg/dL; p=0.757). Higher salivary cortisol was significantly associated with a higher number of stress behaviors per session (p=0.039). There was a significant relationship between stress and affiliative session behaviors (p<0.0001), indicating that dogs who exhibited more stress behaviors also exhibited more affiliative behaviors. The dog’s most commonly coded session behaviors were oral behaviors, such as lip licking, and tail wagging. The only C-BARQ factor that was found to have a significant association was stranger-directed fear; higher scores on this factor were significantly associated with the dog exhibiting fewer affiliative behaviors in sessions (b=2.12, p=0.042).
show that therapy dogs did not have significantly increased physiological stress responses, nor did they exhibit significantly more stress-related behaviors than affiliative-related behaviors, while participating in AAIs in pediatric oncology settings. There was a significant relationship between canine cortisol and behavior, thus strengthening the argument for the use of cortisol in canine well-being research. This study discusses the importance of further investigation to confirm these findings, and to enhance therapy dog involvement in hospital settings.
Targeting specific tumor metabolic needs represents an actively investigated therapeutic strategy to bypass tumor resistance mechanisms. In this study, we describe an original approach to impact the ...cancer metabolism by exploiting the redox properties of a ruthenium organometallic compound. This organometallic complex induced p53-independent cytotoxicity and reduced size and vascularization of patients-derived tumor explants that are resistant to platinum drugs. At the molecular level, the ruthenium complex altered redox enzyme activities and the intracellular redox state by increasing the NAD+/NADH ratio and ROS levels. Pathway analysis pointed to HIF-1 as a top deregulated metabolite pathway. Unlike cisplatin, treatment with the ruthenium complex decreased HIF1A protein levels and expression of HIF1A target genes. The rapid downregulation of HIF1A protein levels involved a direct interaction of the ruthenium compound with the redox enzyme PHD2, a HIF1A master regulator. HIF1A inhibition led to decreased angiogenesis in patient-derived xenografted using fragments of primary human colon tumors. Altogether, our results show that a ruthenium compound impacts metabolic pathways acting as anticancer agents in colon cancer via an original mechanism of action that affects redox enzymes differently than platinum-based drugs.
•An anticancer ruthenium complex exerts cytotoxic stress independently of p53 in colon cancer cells.•Transcriptomic analyses show that it alters cancer metabolism, especially by the HIF1 pathway.•The ruthenium complex reduces HIF1A protein level and HIF1A function by inducing the enzymatic activity of PHD2.•The ruthenium complex inhibits tumor angiogenesis in vivo in xenografted human primary tumors.
ObjectiveTesticular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified ...as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18–45 years.MethodsThe TESTIS study is a multicenter case–control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d’Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression.ResultsA positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6–2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4–51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8–5; OR≥2 years 1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings.ConclusionsOur findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development.Trial registration number NCT02109926.
Walker–Warburg syndrome (WWS) is a rare autosomal recessive, congenital muscular dystrophy that is associated with brain and eye anomalies. Several genes encoding proteins involved in α‐dystroglycan ...glycosylation have been implicated in the aetiology of WWS. We describe a patient with nonclassical features of WWS presenting with heart failure related to noncompaction cardiomyopathy resulting in death at 4 months of age. Muscle biopsy revealed absent α‐dystroglycan on immunostaining and genetic testing confirmed the diagnosis with two previously described POMT2 mutations. This is the first reported case of WWS syndrome associated with noncompaction cardiomyopathy.
The etiology of testicular germ cell tumors (TGCT) is suspected to be related to prenatal environmental risk factors. Some solvents have potential endocrine disrupting or carcinogenic properties and ...may disrupt male genital development in utero. The aim of this study was to examine the association between parental occupational exposure to solvents and TGCT risk among their offspring.
A French nationwide case-control study, TESTIS included 454 TGCT cases and 670 controls frequency-matched on region and 5-year age strata. Participants were interviewed via telephone and provided information on parental occupations at birth. Job-exposure matrices (JEM) developed in the French Matgéné program were used to assign exposure to five petroleum-based solvents, five solvents or groups of oxygenated solvents, and five chlorinated solvents. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors.
Occupational exposure to at least one solvent during the year of their son's birth was 41% among fathers and 21% among mothers. Paternal exposure to at least one solvent showed OR 0.89 (95% CI 0.68-1.15). Exposure to perchloroethylene (OR 1.41, 95% CI 0.55-3.61), methylene chloride (OR 1.13, 95% CI 0.54-2.34) and diesel/kerosene/fuel oil (OR 1.17, 95% CI 0.80-1.73) disclosed OR >1 but with low precision. Our results suggest a possible modest increase in non-seminoma risk for sons whose fathers were highly exposed to trichloroethylene (OR 1.44, 95% CI 0.79-2.63). Maternal exposure to at least one solvent showed OR 0.90 (95% CI 0.65-1.24). When stratifying by birth year, men born in the 1970s experienced an increased TGCT risk following maternal exposure to fuels and petroleum-based solvents (OR 2.74, 95% CI 1.11-6.76).
Overall, no solid association was found between parental occupational exposure to solvents and TGCT risk. The association found with maternal occupational exposure to fuels and petroleum solvents among older men needs further investigation.
Chronic low grade inflammation is one of the major metabolic disorders in case of obesity and associated pathologies. By its important secretion function, the role of adipose tissue in this metabolic ...low grade inflammation is well known. Recently, it was demonstrated that the alarmin high mobility group box protein 1 (HMGB1) is involved in obesity-related pathologies by its increased serum levels in obese compared to normal weight individuals, and by its pro-inflammatory effects. However, the role of HMGB1 on adipocytes inflammation is poorly documented and we propose to investigate this point. Primary culture of human subcutaneous adipocytes were performed from human adipose tissue samples. Cells were treated with recombinant HMGB1 with/without anti-TLR4 antibody and inhibitors of NF-κB and P38 MAPK. Supernatants were collected for IL-6 and MCP-1 ELISA. HMGB1 initiates Toll-like receptor 4 (TLR4)-dependent activation of inflammation through the downstream NF-κB and P38 MAPK signaling pathway to upregulate the secretion of the pro-inflammatory cytokine IL-6. HMGB1 has pro-inflammatory effects on adipocytes. This reinforces the role of TLR4 in adipose tissue inflammation and antagonizing the HMGB1 inflammatory pathway could bring on new therapeutic targets to counteract obesity-associated pathologies.
Juvenile hemochromatosis is a rare and severe form of hereditary hemochromatosis. We report the case of a 39-year-old female who presented with heart failure and cirrhosis from previously ...unrecognized juvenile hemochromatosis. This is the latest presentation described in the literature. An important clue to the diagnosis was a history of amenorrhea since the age of 20 that had never been investigated. The patient died of intractable heart failure two months after the initial presentation. Juvenile hemochromatosis should be suspected in a young patient with endocrine or cardiac manifestations. Early diagnosis is crucial since phlebotomy can improve the prognosis and delay or prevent progression to heart failure and cirrhosis.
The purpose of the present multicenter study was to investigate whether an artificial insemination with donor sperm (AID) procedure after intra-couple intracytoplasmic sperm injection (ICSI) failure ...offers a significant chance of pregnancy and to identify prognostic factors for pregnancy after an AID procedure. An eleven-year retrospective multicenter study was conducted among 13 Centre d'Etude et de Conservation des Oeufs et du Sperme (CECOS) centers. A total of 319 couples having undergone an AID procedure after intra-conjugal ICSI failure were included in this study; a total of 1,159 AID and 1,011 intra-conjugal ICSI cycles were performed. Among the prognostics parameters, the parity and the embryo quality could not be adequately addressed, therefore the parity was not included in the statistical analysis and the embryo quality has been presented as preliminary observation
s
. The pregnancy rate per cycle was 12.0% (139/1,159) and the overall AID pregnancy rate per couple was 43.6% (139/319). Normal or oligoasthenoteratozoospermia (OAT) semen and women aged 34 years or above at the time of AID procedure obtained the lowest AID clinical pregnancy rate. Azoospermia or cryptozoospermia semen and women aged below 34 years obtained the highest AID clinical pregnancy rate. In conclusion, the transition to the AID procedure after intra-conjugal ICSI failure allows such couples to obtain a pregnancy, however after each ART failure AID transition should be proposed according to the woman's age and sperm characteristics.
Abbreviations: AID: artificial insemination with donor sperm; ICSI: intracytoplasmic sperm injection; CECOS: Centre d'Etude et de Conservation des Oeufs et du Sperme; OAT: oligoasthenoteratozoospermia; IVF: in vitro fertilization; ART: artificial reproductive technology; β hCG: beta human chorionic gonadotrophin; SD: standard deviation; OR: Odds ratio
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK