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OBJECTIVES: Clinical pharmacists rely on different scientific references to ensure appropriate, safe, and cost-effective drug use. Tools based on artificial intelligence (AI) such as ChatGPT (Generative Pre-trained Transformer) could offer valuable support. The objective of this study was to assess ChatGPT's capacity to correctly respond to clinical pharmacy questions asked by healthcare professionals in our university hospital. MATERIAL AND METHODS: ChatGPT's capacity to respond correctly to the last 100 consecutive questions recorded in our clinical pharmacy database was assessed. Questions were copied from our FileMaker Pro database and pasted into ChatGPT March 14 version online platform. The generated answers were then copied verbatim into an Excel file. Two blinded clinical pharmacists reviewed all the questions and the answers given by the software. In case of disagreements, a third blinded pharmacist intervened to decide. RESULTS: Documentation-related issues (n=36) and drug administration mode (n=30) were preponderantly recorded. Among 69 applicable questions, the rate of correct answers varied from 30 to 57.1% depending on questions type with a global rate of 44.9%. Regarding inappropriate answers (n=38), 20 were incorrect, 18 gave no answers and 8 were incomplete with 8 answers belonging to 2 different categories. No better answers than the pharmacists were observed. CONCLUSIONS: ChatGPT demonstrated a mitigated performance in answering clinical pharmacy questions. It should not replace human expertise as a high rate of inappropriate answers was highlighted. Future studies should focus on the optimization of ChatGPT for specific clinical pharmacy questions and explore the potential benefits and limitations of integrating this technology into clinical practice.
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Wind energy is poised to play a major role in the energy transition. Fluctuations in global atmospheric circulation are expected as a result of climate change, and wind projections based on the most up-to-date scenarios of climate change, the Shared Socioeconomic Pathways (SSPs), anticipate significant changes in wind energy potential in many regions; so far, these changes have not been studied in Southeastern Asia and Australasia, a region with notable wind energy potential. This work investigates the evolution of wind power density and its temporal variability considering the latest scenarios of climate change, the SSPs. More specifically, two scenarios are considered, SSP2-4.5 and SSP5-8.5, corresponding to moderate and high emissions, respectively. As many as 18 global climate models are considered and compared against past-present data, and those that perform best are retained to build a large multi-model ensemble. The results show that projected changes in mean wind power density at the end of the 21st century are of little significance (typically below 5 %); nevertheless, this value can be far surpassed locally. In certain areas (e.g., Vietnam, Borneo) and seasons, remarkable changes in wind power density (exceeding 150 %) are anticipated. Typically, mean values and temporal variability changes are greater in the high-emissions scenario, however, seasonal variability is projected to be more pronounced in the moderate-emissions scenario. These effects of climate change on wind energy potential must be taken into account in the development of wind power in the region, for they will affect the energy production and, therefore, the economic viability of wind farms - not least in those areas where drastic changes are projected.
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In advanced stages of Kienböck's disease, the lunate is no longer conservable. One of the surgical options is to resect the lunate and replace it with a prosthesis. The procedure consisted in lunate resection and interposition of a free APSI® or Pi2® pyrocarbon implant through a dorsal approach. Follow-up was clinical and radiological on QuickDASH and PRWE scores. At a median follow-up of 3 years, 12 patients were reviewed, with a median age of 56 years. Flexion significantly decreased from 42° to 28° (p < 0.01). Extension and pronation-supination were conserved. Strength was 94% compared to the opposite side, with no significant difference from the preoperative measurement. Median QuickDASH and PRWE scores were 15.9 and 23.5 respectively and had significantly improved. One patient underwent scaphocapitate fusion because she was still in pain; the other patients were pain-free. No patients had to change jobs because of their wrist. Radiographically, there was no carpal collapse and carpal height was conserved. Radioscaphoid angle and ulnar translation were stable. There was 1 case of asymptomatic implant dislocation. Interposition of a pyrocarbon implant after lunate resection in advanced Kienböck's disease is a motion-conserving procedure that provides pain relief and functional recovery in the short and medium term. LEVEL OF EVIDENCE: IV.
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Miembros Artificiales , Huesos del Carpo , Hueso Semilunar , Osteonecrosis , Femenino , Humanos , Persona de Mediana Edad , Hueso Semilunar/cirugía , Huesos del Carpo/cirugía , Osteonecrosis/cirugíaRESUMEN
Pyogenic flexor tenosynovitis is a frequent and serious condition. However, there is no consensus on the use of antibiotics. The objective of our study was to describe the treatment of this condition and to identify the surgical and medical management parameters to propose an effective and consensual postoperative antibiotic therapy protocol. We retrospectively reviewed pyogenic flexor tenosynovitis of the thumb or fingers treated between 01/01/2013 and 01/01/2018 at a teaching hospital. Inclusion criteria were confirmation of the clinical diagnosis intraoperatively and a minimum post-antibiotic follow-up of 6 months. Comorbidities, type of surgery, antibiotic therapy parameters, and treatment outcome were assessed. One hundred and thirteen patients were included. Fifty-four percent had comorbidities. The most frequent germ was staphylococcus, all patients received postoperative antibiotic therapy. Intravenous or intravenous followed by oral administration did not provide any benefit compared to an exclusively oral treatment (p = 0.46). The duration of postoperative antibiotic therapy (less than 7 days, between 7 and 14 days or more than 14 days) did not lead to any difference in healing rate (p = 0.67). However, treating for less than 7 days versus 7-14 days seemed to be associated with a higher risk of failure, although not statistically significant. Oral postoperative antibiotic therapy with amoxicillin + clavulanic acid for 7-14 days appears to be effective, allowing for outpatient management.
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Tenosinovitis , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Dedos/cirugía , Humanos , Estudios Retrospectivos , Tenosinovitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. METHODS: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. RESULTS: During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.
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Dyslipidaemia is a major risk factor for cardio-vascular disease, as it promotes atherosclerosis. While cross-sectional studies have identified higher serum cholesterol amongst individuals with the A blood group, there is less evidence from prospective studies whether this translates into a higher risk of dyslipidaemia that requires treatment, nor if this genetic factor interacts with smoking status. This study aimed to prospectively determine potential associations between smoking, ABO blood groups, and risk of incident dyslipidaemia requiring treatment, and to assess associations over strata of blood ABO group. We assessed associations between blood ABO group, smoking and dyslipidaemia in 74,206 women participating in the E3N cohort. We included women who did not have cardiovascular disease at baseline. Logistic regression was used to determine associations between ABO group, smoking and prevalent dyslipidaemia at baseline. Cox proportional hazard models were then used to determine if blood ABO group and smoking were associated with the risk of incident dyslipidaemia, amongst women free of dyslipidaemia at baseline. At baseline 28,281 women with prevalent dyslipidaemia were identified. Compared to the O-blood group, the non-O blood group was associated higher odds of with prevalent dyslipidaemia (ORnon-O = 1.09 [1.06: 1.13]). Amongst the women free of dyslipidaemia at baseline, 6041 incident cases of treated dyslipidaemia were identified during 454,951 person-years of follow-up. The non-O blood groups were associated with an increased risk of dyslipidaemia when compared to the O-group (HRnon-O = 1.16 [1.11: 1.22]), specifically the A blood-group (HRA = 1.18 [1.12: 1.25]). Current smokers were associated with an increased risk of incident dyslipidaemia (HR smokers = 1.27 [1.16: 1.37]), compared to never-smokers. No evidence for effect modification between smoking and ABO blood group was observed (p-effect modification = 0.45), although the highest risk was observed among AB blood group women who smoked (HR = 1.76 [1.22: 2.55]). In conclusion, the non-O blood groups, specifically the A group were associated with an increased risk of dyslipidaemia. Current smokers were associated with a 30% increased risk of dyslipidaemia. These results could aid in personalised approaches to the prevention of cardiovascular risk-factors.
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Sistema del Grupo Sanguíneo ABO/efectos adversos , Dislipidemias/etiología , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Estudios de Cohortes , Dislipidemias/epidemiología , Femenino , Francia/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Riesgo , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS: We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. RESULTS: Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. CONCLUSIONS: Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.
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Densidad de la Mama/efectos de los fármacos , Neoplasias de la Mama/etiología , Terapia de Reemplazo de Hormonas/efectos adversos , Menopausia , Anciano , Neoplasias de la Mama/metabolismo , Estudios de Casos y Controles , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Humanos , Análisis de Mediación , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factores de RiesgoRESUMEN
The genital microbiota actively participates in women's reproductive health. Indeed, a genital dysbiosis (microbial imbalance associated with adverse effects on host health) can lead to vaginal infections (such as mycoses or bacterial vaginosis). Recent data reported that genital dysbiosis (e.g. vaginal or endometrial) was associated with fewer chances of live births in assisted reproductive technologies (ART), via decreased pregnancy rates and an increased risk of miscarriages. The presence or diversity of certain bacterial strains (in particular Gardenellavaginalis, Proteobacteria, Lactobacillusjensenii, Lactobacilluscrispatus or Atopobiumvaginae) within the genital microbiota seem to be associated with the outcomes of ART cycles, suggesting new approaches to improve ART results. In this review, we aim at presenting the state of art on the association between the female genital microbiota and ART success. The diagnostic and therapeutic approaches (i.e. probiotics, antibiotic therapy and transplantation of vaginal microbiota) in the management of patients with altered microbiota will also be discussed. The confirmation of these data in the coming years could significantly improve the management of infertile patients in ART with a more personalized approach partially based on the female genital microbiotic profile.
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Infertilidad , Microbiota , Femenino , Humanos , Embarazo , Índice de Embarazo , Técnicas Reproductivas Asistidas , VaginaRESUMEN
AIM: To examine the association between antidepressant medication use and the risk of type 2 diabetes. METHODS: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. RESULTS: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. CONCLUSION: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).
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Antidepresivos/uso terapéutico , Diabetes Mellitus Tipo 2/epidemiología , Anciano , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
The use of chlordecone (CLD), a chlorinated polycyclic pesticide used in the French West Indies banana fields between 1972 and 1993, resulted in a long-term pollution of agricultural areas. It has been observed that this persistent organic pollutant (POP) can transfer from contaminated soils to food chain. Indeed, CLD is considered almost fully absorbed after involuntary ingestion of contaminated soil by outdoor reared animals. The aim of this study was to model toxicokinetics (TKs) of CLD in growing pigs using both non-compartmental and nonlinear mixed-effects approaches (NLME). In this study, CLD dissolved in cremophor was intravenously administrated to 7 Creole growing pigs and 7 Large White growing pigs (1 mg kg-1 body weight). Blood samples were collected from time t = 0 to time t = 84 days. CLD concentrations in serum were measured by GCMS/MS. Data obtained were modeled using Monolix (2019R). Results demonstrated that a bicompartmental model best described CLD kinetics in serum. The influence of covariates (breed, initial weight and average daily gain) was simultaneously evaluated and showed that average daily gain is the main covariate explaining inter-individual TKs parameters variability. Body clearance was of 76.7 mL kg-1 d-1 and steady-state volume of distribution was of 6 L kg-1. This modeling approach constitutes the first application of NLME to study CLD TKs in farm animals and will be further used for rearing management practices in contaminated areas.
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Clordecona/toxicidad , Insecticidas/toxicidad , Animales , Clordecona/análisis , Ingestión de Alimentos , Contaminantes Ambientales , Insecticidas/análisis , Cinética , Modelos Químicos , Musa , Contaminantes del Suelo/análisis , Porcinos , Toxicocinética , Indias OccidentalesRESUMEN
BACKGROUND: Neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by neuronal death involving, among other events, mitochondrial dysfunction and excitotoxicity. Along these lines, several attempts have been made to slow this pathology but none have been yet discovered. Based on its capacity to cross the blood-brain barrier and provide neuronal protection in vitro and in vivo, the pituitary adenylate cyclase-activating polypeptide (PACAP) represents a promising lead molecule. Pharmacological studies showed that PACAP interacts with three different G protein-coupled receptors, i.e. PAC1, VPAC1 and VPAC2. However, only PAC1 is associated with neuronal anti-apoptotic actions, whilst VPAC activation might cause adverse effects. In the context of the development of PAC1-selective agonists, PACAP(1-23) (PACAP23) appears as the shortest known PACAP bioactive fragment. METHODS: Hence, the capacity of this peptide to bind PACAP receptors and protect neuroblastoma cells was evaluated under conditions of mitochondrial dysfunction and glutamate excitotoxicity. In addition, its ability to activate downstream signaling events involving G proteins (Gαs and Gαq), EPAC, and calcium was also assessed. RESULTS: Compared to the endogenous peptide, PACAP23 showed a reduced affinity towards PAC1, although this fragment exerted potent neuroprotection. However, surprisingly, some disparities were observed for PACAP23 signaling compared to full length PACAP, suggesting that downstream signaling related to neuroprotection is distinctly regulated following subtle differences in their PAC1 interactions. CONCLUSIONS: Altogether, this study demonstrates the potent neuroprotective action of amidated PACAP23. GENERAL SIGNIFICANCE: PACAP23 represents an attractive template for development of shorter PACAP-derived neuroprotective molecules.
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Señalización del Calcio/efectos de los fármacos , Fármacos Neuroprotectores , Péptidos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Animales , Células CHO , Cricetulus , Humanos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Péptidos/química , Péptidos/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/química , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Receptores de Tipo II del Péptido Intestinal Vasoactivo/metabolismo , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo/metabolismoRESUMEN
Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. MHT use was assessed through biennial self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990-2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07-1.71). The association was strongest among past users (HR = 1.55, CI = 1.17-2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11-2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (<6 months: HR = 1.55, CI = 1.16-2.07 vs. ≥2 years). Associations between MHT use and melanoma risk were similar after adjustment for UV exposure, although MHT users were more likely to report sunscreen use than nonusers. Our data do not support a strong association between MHT use and melanoma risk. Further investigation is needed to explore potential effect modification by UV exposure on this relationship.
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Terapia de Reemplazo de Hormonas/efectos adversos , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Femenino , Francia/epidemiología , Humanos , Melanoma/inducido químicamente , Persona de Mediana Edad , Posmenopausia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Autoinforme , Neoplasias Cutáneas/inducido químicamente , Factores de Tiempo , Rayos Ultravioleta/efectos adversos , Melanoma Cutáneo MalignoAsunto(s)
Quemaduras , Monitoreo de Drogas , Antibacterianos , Cuidados Críticos , Humanos , Unidades de Cuidados IntensivosRESUMEN
Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. E3N is a prospective cohort of 98,995 French women aged 40-65 years at inclusion in 1990. Exposure to lifetime OC use was assessed in 1992 and through biennial questionnaire updates. To assess the association between OC use and melanoma risk, we used Cox models adjusted for age, pigmentary traits, residential ultraviolet (UV) exposure in county of birth and at inclusion and family history of skin cancer. Over 1992-2008, 539 melanoma cases were ascertained among 79,365 women. In age-adjusted models, we found a modest positive association between ever use of OCs and melanoma risk (hazard ratio (HR) = 1.18, 95% confidence intervals (CIs) = 0.98-1.42), which was reduced after adjustment (HR = 1.14, 95% CI = 0.95-1.38). The association was stronger in long-term users (duration ≥10 years: HR = 1.33, 95% CI = 1.00-1.75) and in women who used high-estrogen OCs (HR = 1.27, 95% CI = 1.04-1.56). Among users, there was an inverse association with age at first use (ptrend < 0.01), but no evidence of an association with age at last use or time since last use. OC use was positively associated with tanning bed use (OR = 1.14, CI = 1.01-1.29), sunburns (ptrend = 0.5) and sunscreen use (OR = 1.13, CI = 1.00-1.28) since age 25. Overall, our findings do not support a strong association between OC use and melanoma risk and suggest intentional UV exposure in OC users, which supports a potential confusion by UV exposure in this relationship.
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Anticonceptivos Orales/administración & dosificación , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores Socioeconómicos , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Negativity is often observed in patients with irritable bowel syndrome (IBS). No study has examined their emotional expressiveness as a marker of emotional reactivity. We investigated IBS patients' vulnerability to an emotional load by associating their expressiveness with psychological and neurophysiological assessments. We hypothesized that IBS would be characterized by a lack of expressiveness coupled with high scores in psychological and neurophysiological parameters. METHODS: We assessed the emotional facial expressions (EMFACS), psychological (anxiety, depression, alexithymia), and neurophysiological (cortisol, heart rate variability (HRV)) parameters of 25 IBS patients and 26 healthy controls (HC) while they watched fear-eliciting movie extracts. KEY RESULTS: Overall, the task elicited an increase in state anxiety and consistent HRV responses. However, IBS patients differed from HC as they displayed more sadness and tended to display more rage. Contrary to HC, IBS patients showed an increase in heart rate and a decrease in parasympathetic regulation, reflecting an enhanced responsiveness corroborated by higher scores in depression and state anxiety. Consistent with their higher difficulty in identifying feelings, a component of alexithymia positively correlated with their expressions of rage, they were not aware of their increase in anxiety during the task, whereas HC were. No linear relationship between patients' expressions and their neurophysiological responses was found. CONCLUSIONS & INFERENCES: Irritable bowel syndrome patients displayed greater emotional expressiveness with negative prevalence. This reflects an emotional vulnerability potentially related to low regulation skills and underscores the importance of considering the central dysregulation hypothesis in IBS as a promising avenue of research.
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Emociones/fisiología , Síndrome del Colon Irritable/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The aim of this study was to update our acknowledgment if there is a link between assisted embryo cryopreservation and epigenetics in human? Animal studies have demonstrated epigenetics consequence and especially imprinting disorders due to in vitro culture. In human, it is important to note that after frozen embryo transfer birth weight is significantly increased by 81 to 250g. But these studies cannot identify the reasons of such difference. This review strongly suggests that embryo cryopreservation is responsible for birth weight variations but mechanisms not yet elucidated. Epigenetics is probably one of these but to date, none study is able to prove it. We have to be attentive on a possible link between assisted reproductive technology (ART) and epigenetics reprogrammation.
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Peso al Nacer , Criopreservación , Transferencia de Embrión/métodos , Epigénesis Genética , Criopreservación/métodos , Criopreservación/estadística & datos numéricos , Femenino , Humanos , Embarazo , Técnicas Reproductivas Asistidas/efectos adversos , Técnicas Reproductivas Asistidas/estadística & datos numéricosRESUMEN
Deficits in hippocampal synaptic plasticity result in cognitive impairment in Huntington's disease (HD). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts neuroprotective actions, mainly through the PAC1 receptor. However, the role of PACAP in cognition is poorly understood, and no data exists in the context of Huntington's disease (HD). Here, we investigated the ability of PACAP receptor stimulation to enhance memory development in HD. First, we observed a hippocampal decline of all three PACAP receptor expressions, i.e., PAC1, VPAC1, and VPAC2, in two different HD mouse models, R6/1 and HdhQ7/Q111, from the onset of cognitive dysfunction. In hippocampal post-mortem human samples, we found a specific decrease of PAC1, without changes in VPAC1 and VPAC2 receptors. To determine whether activation of PACAP receptors could contribute to improve memory performance, we conducted daily intranasal administration of PACAP38 to R6/1 mice at the onset of cognitive impairment for seven days. We found that PACAP treatment rescued PAC1 level in R6/1 mice, promoted expression of the hippocampal brain-derived neurotrophic factor, and reduced the formation of mutant huntingtin aggregates. Furthermore, PACAP administration counteracted R6/1 mice memory deficits as analyzed by the novel object recognition test and the T-maze spontaneous alternation task. Importantly, the effect of PACAP on cognitive performance was associated with an increase of VGlut-1 and PSD95 immunolabeling in hippocampus of R6/1 mice. Taken together, these results suggest that PACAP, acting through stimulation of PAC1 receptor, may have a therapeutic potential to counteract cognitive deficits induced in HD.
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Hipocampo/fisiopatología , Enfermedad de Huntington/fisiopatología , Memoria/fisiología , Plasticidad Neuronal/efectos de los fármacos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Administración Intranasal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastornos del Conocimiento/fisiopatología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/patología , Humanos , Proteína Huntingtina/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/administración & dosificación , Agregado de Proteínas , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
PURPOSE: The aim of this study was to assess if use of the ß LACTA test (BLT) for extended-spectrum beta-lactamase (ESBL) detection and/or early bacterial identification by mass spectrometry (MALDI-TOF MS) improves therapeutic decision-making when combined with advice from the antimicrobial stewardship team (AMST) for the management of Gram-negative bacillary (GNB) bacteraemia. METHODS: Prospective observational theoretical study that included patients with GNB bacteraemia during a 6-month period. We compared, against the antimicrobial choice of the local AMST as informed of the Gram-stain result, a hypothetical choice, i.e. one AMST would have made had it been informed of the MALDI-TOF MS results only (option H) with the actual choice AMST made after being informed of the combined MALDI-TOF MS and BLT results (option A).Results/Key findings. A total of 131 episodes of GNB bacteraemia were included. Options H and A led to virtually the same rate of efficient antimicrobial therapy (in 120/131 and 123/131 episodes, respectively, P=0.63). Compared to the gold standard, options H and A did not lead to a significant reduction of carbapenem prescription (9/131, 6/131 and 12/131, P=0.57 and P=0.65, respectively). CONCLUSIONS: Under our test conditions, BLT, when used in conjunction with MALDI-TOF MS and AMST advice, did not allow a significant optimization of the antimicrobial prescription made on the basis AMST advice only. However, the impact of BLT should be evaluated in a population with high prevalence of ESBL-producing Enterobacteriaceae and/or when treatment choices are not made by infectious disease specialists.