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1.
Horm Behav ; 164: 105577, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38878493

ABSTRACT

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.

2.
J Healthc Qual Res ; 39(4): 258-265, 2024.
Article in English | MEDLINE | ID: mdl-38616433

ABSTRACT

BACKGROUND: Improper compliance with antibiotic prophylaxis (AP) in surgery is associated with an increased risk of surgical site infection (SSI), and impacts the efficiency of healthcare. OBJECTIVE: Evaluate the impact of an intervention in compliance with AP in selected surgical procedures and its effect on antibiotic consumption and cost. METHODS: A prospective interventional study was performed in a community hospital from January to December 2022. The baseline period was considered January-April 2022 and the intervention period May-December 2022. All patients who underwent cesarean section, appendectomies, hernia surgery, open reduction and internal fixation (ORIF), abdominoplasty, and cholecystectomy during the study period were selected. The intervention includes staff education, pharmacy interventions, monitoring the quality of prescriptions and feedback, and improved role of anesthesia staff, and department champions. RESULTS: The study involved 192 and 617 surgical procedures in the baseline and intervention periods respectively. The compliance with timing, selection, dose, and discontinuation achieved 100%, 99.2%, and 97.6% from baseline figures of 92.7%, 95.8%, and 81.3%, respectively. The antibiotic consumption was reduced by 55.1% during the intervention with a higher contribution of other antibiotics (94.1% reduction) in comparison with antibiotics as per policy (31.2% reduction). The cost was reduced by 47.2% (antibiotic as per policy 31.9%, other antibiotics 94.2%). CONCLUSION: The implemented strategy was effective in improving the quality of antibiotic prophylaxis with a significant impact in reducing antibiotic consumption and cost.


Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Quality Improvement , Surgical Wound Infection , Humans , Antibiotic Prophylaxis/economics , Prospective Studies , Surgical Wound Infection/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/economics , Anti-Bacterial Agents/therapeutic use , Female , Male , Guideline Adherence , Hospitals, Community , Surgical Procedures, Operative , Adult , Middle Aged
3.
Article in English, Spanish | MEDLINE | ID: mdl-38657788

ABSTRACT

OBJECTIVE: To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs. MATERIAL AND METHODS: Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II to V, the infiltration of the corresponding compound was carried out spaced one week apart. Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis. RESULTS: We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed. The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III). CONCLUSIONS: The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

4.
Arch Pediatr ; 30(2): 77-82, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36526499

ABSTRACT

BACKGROUND: Congenital adrenal hyperplasia (CAH) is a disease that is part of neonatal screening. There are many causes of false-positive results on neonatal screening, and maternal opioid consumption during pregnancy is suspected to increase 17-hydroxyprogesterone (17-OHP) levels at birth. The aim of this study was to determine the effect of maternal drug consumption on 17-OHP values on neonatal screening. MATERIAL AND METHODS: We studied 17-OHP levels of term newborns with reported maternal drug consumption born at the Maternity Hospital of Nancy between 2002 and 2018. These infants were matched with newborns of mothers without drug addiction. The 17-OHP levels, withdrawal syndromes, birth parameters, and maternal characteristics were compared between the two groups. RESULTS: The study included 241 patients (121 in the drug-exposed group, 120 in the control group). The mean 17-OHP levels in newborns of mothers with substance addiction were 9.83 nmol/L compared to 4.90 nmol/L (p=0.0001) in the control group. Newborns exposed to drugs were smaller (p=0.0001), lighter (p=0.0001), had smaller head circumference (p=0.0001), and had lower Apgar scores (p=0.004 at 1 min and p=0.0001 at 5 min). The 17-OHP level did not differ in cases of withdrawal syndrome in drug-exposed newborn (p=0.911). CONCLUSION: A significant increase in 17-OHP levels was observed in newborns exposed to drugs, with no influence of withdrawal syndrome on 17-OHP levels. Maternal substance addiction may be associated with moderately increased 17-OHP levels during neonatal screening.


Subject(s)
Adrenal Hyperplasia, Congenital , Opioid-Related Disorders , Substance Withdrawal Syndrome , Humans , Infant, Newborn , Female , Pregnancy , Progesterone , Neonatal Screening/methods , Adrenal Hyperplasia, Congenital/diagnosis , 17-alpha-Hydroxyprogesterone , Mothers , Opioid-Related Disorders/diagnosis
5.
Br J Surg ; 108(11): 1315-1322, 2021 11 11.
Article in English | MEDLINE | ID: mdl-34467970

ABSTRACT

BACKGROUND: There is a lack of information regarding the provision of parental leave for surgical careers. This survey study aims to evaluate the experience of maternity/paternity leave and views on work-life balance globally. METHODS: A 55-item online survey in 24 languages was distributed via social media as per CHERRIES guideline from February to March 2020. It explored parental leave entitlements, attitude towards leave taking, financial impact, time spent with children and compatibility of parenthood with surgical career. RESULTS: Of the 1393 (male : female, 514 : 829) respondents from 65 countries, there were 479 medical students, 349 surgical trainees and 513 consultants. Consultants had less than the recommended duration of maternity leave (43.8 versus 29.1 per cent), no paid maternity (8.3 versus 3.2 per cent) or paternity leave (19.3 versus 11.0 per cent) compared with trainees. Females were less likely to have children than males (36.8 versus 45.6 per cent, P = 0.010) and were more often told surgery is incompatible with parenthood (80.2 versus 59.5 per cent, P < 0.001). Males spent less than 20 per cent of their salary on childcare and fewer than 30 hours/week with their children. More than half (59.2 per cent) of medical students did not believe a surgical career allowed work-life balance. CONCLUSION: Surgeons across the globe had inadequate parental leave. Significant gender disparity was seen in multiple aspects.


Subject(s)
Career Choice , Internship and Residency/statistics & numerical data , Parental Leave/statistics & numerical data , Students, Medical/statistics & numerical data , Surgeons/statistics & numerical data , Surveys and Questionnaires , Adult , Attitude of Health Personnel , Female , Humans , Male , Sex Factors , Young Adult
6.
Enferm. univ ; 17(4): 379-389, oct.-dic. 2020. tab, graf
Article in Spanish | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1345991

ABSTRACT

Resumen Introducción: El panorama de la salud y nutrición de la población mexicana se enmarca en la conjunción de desnutrición crónica infantil, sobre todo en el medio rural e indígena, y el incremento significativo del sobrepeso y obesidad. Esta información proveniente de encuestas arroja resultados generalizados, sin considerar las particularidades del contexto biosociocultural en que viven comunidades indígenas, codeterminante de la condición nutricional de éstas. Objetivo: Estudiar el estatus nutricional de un grupo de escolares de cultura otomí residentes en una comunidad de México en situación de marginación, considerando el contexto biosociocultural en el que viven. Métodos: Estudio prospectivo transversal realizado en una localidad del Estado de México. Muestra por conveniencia constituida por 214 menores, entre 6 y 12 años de edad. Se emplearon técnicas antropométricas internacionalmente aceptadas para recabar la estatura y el peso, y se calculó el IMC. El estatus de nutrición se estimó con base en el peso, la estatura y el IMC para la edad y se compararon con los referentes de la OMS. Resultados: La prevalencia de estatura baja para la edad y la desnutrición es menor, no así el sobrepeso/obesidad que afecta a un tercio de los menores. Solo para el IMC por edad y sexo hubo diferencias en ciertos grupos de edad. Las puntuaciones z de los tres indicadores son semejantes entre niños y niñas. Discusión y Conclusiones: En comparación con los parámetros nacional y estatal, los menores estudiados muestran prevalencia menor de sobrepeso y obesidad asociado a su contexto sociocultural.


Abstract Introduction: The health and nutrition outlook of the Mexican population may be framed in terms of chronic infant malnutrition, largely in the rural and indigenous sectors, and a significant increase in overweight and obesity. This general information is obtained from surveys without taking into account the biosociocultural context that is a codeterminant of the nutritional condition of many small indigenous communities. Objective: To study the nutritional status of Otomí school children living in a marginalized Mexican community from the perspective of the biosociocultural context in which they live. Methods: This is a prospective and transversal study carried out in a location of the state of México, México. The convenience sample was constituted by 214 children between 6 and 12 years old. Internationally accepted anthropometric techniques were used to collect data on the height and weight of these children. BMIs were calculated. The status of nutrition was estimated based on the expected weight, height, and BMI for each age. These data were compared with the corresponding WHO references. Results: The prevalence of low height and malnutrition related to the ages of these children was found to be low, but one in three of these children was found to be overweight or obese. There were some age groups differences regarding the BMI. The z scores of the three indicators are similar between boys and girls. Discussion and Conclusions: In comparison to the national and state parameters, the children studied showed a low prevalence of overweight and obesity associated with their sociocultural context.


Resumo Introdução: O panorama da saúde e nutrição da população mexicana se enquadra na conjunção de desnutrição infantil crónica, sobretudo no médio rural e indígena, e o incremento significativo do sobrepeso e obesidade. Esta informação vinda de enquetes gera resultados generalizados, sem considerar as particularidades do contexto biosociocultural em que vivem comunidades indígenas, co-determinante da condição nutricional destas. Objetivo: Estudar o estado nutricional de um grupo de escolares de cultura Otomí residentes em uma comunidade do México em situação de marginação, considerando o contexto biosociocultural em que vivem. Métodos: Estudo prospectivo transversal realizado em uma localidade do Estado do México. Amostra de conveniência constituída por 214 menores entre 6 e 12 anos de idade. Empregaram-se técnicas antropométricas internacionalmente aceitas para coletar a altura e o peso, e foi calculado o IMC. O estado de nutrição foi estimado com base no peso, a altura e o IMC para a idade e foram comparados com os referentes da OMS. Resultados: A prevalência da baixa altura para a idade e a desnutrição é menor, no entanto o sobrepeso/obesidade afeta a um terço dos meninos. Apenas para o IMC por grupos de idade e sexo houve diferenças em determinadas faixas etárias. As pontuações z dos três indicadores são semelhantes entre meninos e meninas. Discussão e Conclusões: Em comparação com os parâmetros nacionais e estaduais, os meninos estudados mostram menor prevalência de sobrepeso e obesidade associado ao seu contexto sociocultural.

7.
J Gastrointest Surg ; 24(12): 2814-2821, 2020 12.
Article in English | MEDLINE | ID: mdl-31823319

ABSTRACT

AIM: To assess clinical healing in patients with perianal Crohn's disease with local intrafistular injection of autologous platelet-rich plasma. METHOD: The pilot study was conducted at a single centre between January 2013 and December 2015. Autologous platelet-rich plasma was prepared in platelet-rich and platelet-poor fractions for local intrafistular injection in patients with proven, established perianal Crohn's disease. Patients were permitted biological therapies, and the Perianal Crohn's Disease Activity Index was recorded. Patients were followed for 48 weeks for clinical signs of healing (complete, partial or non-healing), monitoring fistula drainage, closure and epithelialization. RESULTS: The study included 29 patients (19 males; mean age 38 ± 12.8 years) with four exclusions in the operating room because surgery was not indicated and four lost to follow-up. Five adverse events were recorded, with two requiring the drainage of abscess collections. Of the 21 patients assessable at 24 weeks, there was complete healing, partial healing and non-healing in 7 (33.3%), 8 (38.1%) and 6 (28.6%) patients, respectively. By 48 weeks, there was complete healing, partial healing and non-healing in 6 (40%), 6 (40%) and 3 (20%) patients, respectively, with a reduction in the number of visible external fistula openings at both time points (P = 0.021). By the end of the study, there was a higher trend of healing if biological therapies were continued (85.7% with biologics vs. 75% without, P = 0.527), but there were no statistically significant differences and no differences in the Perianal Crohn's Disease Activity Index. CONCLUSION: Autologous platelet-rich plasma is safe in patients with perianal Crohn's disease, with an acceptable healing rate over a medium-term follow-up, particularly if biological therapies are used concomitantly.


Subject(s)
Crohn Disease , Platelet-Rich Plasma , Rectal Fistula , Adult , Crohn Disease/complications , Crohn Disease/therapy , Humans , Male , Middle Aged , Pilot Projects , Rectal Fistula/etiology , Rectal Fistula/therapy , Treatment Outcome
8.
J Healthc Qual Res ; 34(1): 3-11, 2019.
Article in Spanish | MEDLINE | ID: mdl-30713137

ABSTRACT

OBJECTIVE: Examine the effects of an educational intervention to improve patients' level of activation and promote their participation improving their safety during health system pathway. MATERIAL AND METHODS: Selection and study of the care process on which to apply the research. Design and edition the audiovisual educational material. Intentional sampling of patients on the waiting list for scheduled operation by the Traumatology Service. Telephone collection through study's explanatory script. Realization of two focus groups, with heterogeneous distribution by gender, age and level of studies. Visualization of the educational video and exploration of aspects of interest through semi-structured questions script, based on the research objectives. Recording and transcription of generated speeches. Qualitative analysis of resulting information. RESULTS: Patients are aware that failures and errors occur, and recognize the weaknesses of the system and professionals. The educational activity brings more value to people with less previous experience or less knowledge about the dynamics of the health system. The interaction between people with different experiences entails an exchange of knowledge, enhancing the educational effect of the intervention. The level of knowledge and the degree of activation increases in all participants, regardless of their starting situation. CONCLUSIONS: Strengthening the role of the patient as a safety barrier through an educational intervention of an audiovisual nature is feasible in real conditions and useful for the objective pursued.


Subject(s)
Patient Education as Topic , Patient Safety , Adult , Aged , Audiovisual Aids , Comprehension , Educational Status , Female , Focus Groups , Humans , Male , Middle Aged , Patient Participation , Qualitative Research , Young Adult
9.
Trends Immunol ; 40(1): 66-80, 2019 01.
Article in English | MEDLINE | ID: mdl-30595189

ABSTRACT

Infiltrating and tissue-resident myeloid cells are essential regulators of innate and adaptive immunity. During inflammation, and in response to microbial products, these cells can adapt to microenvironmental conditions and acquire specialized functions, including phagocytosis and the production of proinflammatory cytokines. Such myeloid plasticity is driven, in part, by epigenetic dynamics that can sustain stable phenotypes after activation, and which may lead to maladaptive cell polarization states associated with inflammation and autoimmunity. Here, we review recent reports describing epigenetic mechanisms linked to such polarization states and innate immune memory (tolerance and training) in monocyte and macrophage lineages. We discuss how these mechanisms might be targeted to develop putative immunomodulatory tools that might be used to treat a variety of immune-mediated diseases.


Subject(s)
Epigenesis, Genetic/drug effects , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Immunologic Memory/drug effects , Myeloid Cells/drug effects , Animals , Epigenesis, Genetic/genetics , Epigenesis, Genetic/immunology , Humans , Immunity, Innate/immunology , Immunologic Factors/immunology , Immunologic Memory/immunology , Myeloid Cells/immunology
11.
Talanta ; 179: 131-138, 2018 Mar 01.
Article in English | MEDLINE | ID: mdl-29310212

ABSTRACT

A sensitive amperometric immunosensor has been prepared by immobilization of capture antibodies onto gold nanoparticles (AuNPs) grafted on a screen-printed carbon electrode (SPCE) through aryl diazonium salt chemistry using 4-aminothiophenol (AuNPs-S-Phe-SPCE). The immunosensor was designed for the accurate determination of clinically relevant levels of B-type natriuretic peptide (BNP) in human serum samples. The nanostructured electrochemical platform resulted in an ordered layer of AuNPs onto SPCEs which combined the advantages of high conductivity and improved stability of immobilized biomolecules. The resulting disposable immunosensor used a sandwich type immunoassay involving a peroxidase-labeled detector antibody. The amperometric transduction was carried out at -0.20V (vs the Ag pseudo-reference electrode) upon the addition of hydroquinone (HQ) as electron transfer mediator and H2O2 as the enzyme substrate. The nanostructured immunosensors show a storage stability of at least 25 days, a linear range between 0.014 and 15ngmL-1, and a LOD of 4pgmL-1, which is 100 times lower than the established cut-off value for heart failure (HF) diagnosis. The performance of the immunosensor is advantageously compared with that provided with immunosensors prepared by grafting SPCE with p-phenylendiamine (H2N-Phe-SPCE) and attaching AuNPs by immersion into an AuNPs suspension or by electrochemical deposition, as well as with immunosensors constructed using commercial AuNPs-modified SPCEs. The developed immunosensor was applied to the successful analysis of human serum from heart failure (HF) patients upon just a 10-times dilution as sample treatment.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Heart Failure/diagnosis , Immunoassay , Metal Nanoparticles/chemistry , Natriuretic Peptide, Brain/blood , Aniline Compounds/chemistry , Antibodies/chemistry , Biomarkers/blood , Carbon/chemistry , Diazonium Compounds/chemistry , Electrodes , Gold/chemistry , Heart Failure/blood , Humans , Hydrogen Peroxide/chemistry , Hydroquinones/chemistry , Immunoconjugates/chemistry , Metal Nanoparticles/ultrastructure , Nanostructures/chemistry , Nanostructures/ultrastructure , Peroxidase/chemistry , Sulfhydryl Compounds/chemistry
13.
Clin Genet ; 93(1): 191-193, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28742214

ABSTRACT

Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.


Subject(s)
Fucosyltransferases/genetics , Genetic Predisposition to Disease/genetics , Intrinsic Factor/genetics , Mutation , Neural Tube Defects/genetics , Polymorphism, Single Nucleotide , Cohort Studies , Fetus/metabolism , Gene Frequency , Genotype , Heterozygote , Humans , Infant, Newborn , Sequence Analysis, DNA/methods , Galactoside 2-alpha-L-fucosyltransferase
15.
Int J Colorectal Dis ; 32(11): 1545-1550, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28755243

ABSTRACT

PURPOSE: The aim of this paper is to evaluate to the safety, feasibility and efficacy of a novel treatment for transsphincteric cryptoglandular fistula: injection of autologous plasma rich in growth factors (PRGF) into the fistula tract accompanied by sealing using a fibrin plug created from the activated platelet-poor fraction of the same plasma. METHOD: This article is a prospective, phase II clinical trial. The procedure was externally audited. Thirty-six patients diagnosed with transsphincteric fistula-in-ano were included. All patients underwent follow-up examinations at 1 week and again at 3, 6 and 12 months after discharge. Main outcome measures safety (number of adverse events), feasibility and effectiveness of the treatment. RESULTS: A total of 36 patients received the study treatment, with the procedure found to be feasible in all patients. A total of seven adverse events (AE) related to the injected product or surgical procedure were identified in 4 of 36 patients. At the end of the follow-up period (12 months), 33.3% of patients (12/36) had achieved complete fistula healing and 11.1% of patients (4/36) had achieved partial healing. In total, this amounted to 44.4% of patients (16/36) being asymptomatic at final follow-up. In successfully healed patients, a gradual reduction in pain was observed, as measured using a Visual Analog Scale (VAS) (p = 0.0278). Compared to baseline, a significant improvement in Wexner score was seen in patients achieving total or partial healing of the fistula (p = 0.0195). CONCLUSIONS: The study treatment was safe and feasible, with apparently modest efficacy rates. Continence and pain improvement following treatment may be considered predictive factors for healing.


Subject(s)
Intercellular Signaling Peptides and Proteins/pharmacology , Pain , Platelet-Rich Plasma , Rectal Fistula , Wound Healing/drug effects , Adult , Feasibility Studies , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/methods , Pain/diagnosis , Pain/etiology , Pain Management/methods , Pain Measurement , Rectal Fistula/complications , Rectal Fistula/diagnosis , Rectal Fistula/therapy , Treatment Outcome
17.
Am J Transplant ; 17(9): 2254-2262, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28173625

ABSTRACT

In order to develop new efficient therapies for organ transplantation, it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation, and fibrosis, which lead to rejection and long-term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4, and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes. These proteins recognize acetylated lysines in histones and master transcription factors to recruit regulatory complex and, finally, modify the transcriptional program. Recent studies indicate that BET proteins are essential in the NF-kB-mediated inflammatory response, during the activation and differentiation of Th17-immune cells, and in profibrotic processes. Here, we review this new body of data and highlight the efficiency of BET inhibitors in several models of diseases. The promising results obtained from these preclinical models indicate that it may be time to translate these outcomes to the transplantation field, where epigenetics will be of increasing value in the coming years.


Subject(s)
Epigenesis, Genetic , Graft Rejection/prevention & control , Organ Transplantation/adverse effects , Transcription Factors/antagonists & inhibitors , Animals , Chromatin/genetics , Graft Rejection/etiology , Graft Rejection/metabolism , Humans , Multigene Family , Signal Transduction , Transcription Factors/metabolism
18.
Int J Colorectal Dis ; 32(3): 437-440, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28054134

ABSTRACT

BACKGROUND: Faecal incontinence (FI) is both a medical and social problem, with an underestimated incidence. For patients with internal anal sphincter damage, implantation of biomaterial in the anal canal is a recognised treatment option. One such material, Gatekeeper™, has previously shown promising short- and medium-term results without any major complications, including displacement. The main aim of the present study is to assess the degree to which displacement of Gatekeeper prostheses may occur and to determine whether this is associated with patient outcomes. METHODS: Seven patients (six females) with a mean age of 55.6 years [50.5-57.2] and a mean FI duration of 6 ± 2 years were prospectively enrolled in the study. Each subject was anaesthetised and underwent implantation of six prostheses in the intersphincteric region, guided by endoanal 3D ultrasound (3D-EAU). Follow-up was performed at post-interventional months 1, 3, and 12 (median 12 ± 4 months), during which data were obtained from a defaecation diary, Wexner scale assessment, anorectal manometry (ARM), 3D-EAU, and a health status and quality of life questionnaire (FIQL). RESULTS: At 3-month follow-up, 3D-EAU revealed displacement of 24/42 prostheses in 5/7 patients. Of these, 15 had migrated to the lower portion and 9 to the upper portion of the anal canal and rectum. Despite this migration, treatment was considered successful in 3/7 patients. In one patient, it was necessary to remove a prosthesis due to spontaneous extrusion. CONCLUSIONS: We have shown that displacement of the Gatekeeper™ prosthesis occurs, but is not associated with poorer clinical outcomes.


Subject(s)
Fecal Incontinence/diagnostic imaging , Fecal Incontinence/surgery , Prostheses and Implants , Prosthesis Failure , Female , Humans , Male , Manometry , Middle Aged , Quality of Life , Treatment Outcome , Ultrasonography
19.
Colorectal Dis ; 19(5): 485-490, 2017 May.
Article in English | MEDLINE | ID: mdl-27634544

ABSTRACT

AIM: Low anterior resection syndrome (LARS) comprises a collection of symptoms affecting patients after restorative surgery for rectal cancer. The aim of the present study was to analyse the incidence of LARS in patients undergoing rectal cancer surgery with and without subsequent ileostomy and to determine whether the interval to ileostomy closure is a factor associated with its occurrence. METHOD: All patients undergoing curative anterior resection for rectal cancer from 2008 to 2012 in our institution were included in the study. They were divided into two groups according to whether or not a defunctioning ileostomy had been performed. Patients were assessed for LARS at a median interval of 23.60 ± 16.73 (12-48) months from anterior resection in those who did not have an ileostomy and at an interval of 11.31 ± 14.24 (12-60) months from closure of the ileostomy in those who did. They underwent a structured telephone interview based on a validated LARS score questionnaire. Univariate and multivariate analysis was carried out to assess possible associations between LARS and the variables studied. RESULTS: There were 150 patients (93 men) of whom 54.7% had no evidence of LARS, 17.3% had minor symptoms and 28% major symptoms of LARS. Univariate analysis showed that male gender, the presence of a temporary ileostomy and neoadjuvant therapy were predisposing factors for LARS. The interval from construction of the ileostomy to its closure did not appear to be a factor associated with LARS. In multivariate analysis, male gender and preoperative neoadjuvant therapy were significant predisposing factors for LARS. CONCLUSION: Male gender and preoperative neoadjuvant therapy are risk factors for LARS. The presence of ileostomy or time to ileostomy closure is not associated with the development of this syndrome.


Subject(s)
Digestive System Surgical Procedures/adverse effects , Ileostomy/adverse effects , Postoperative Complications/etiology , Rectal Neoplasms/surgery , Rectum/surgery , Aged , Anastomosis, Surgical/adverse effects , Colon/surgery , Digestive System Surgical Procedures/methods , Female , Humans , Ileostomy/methods , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Syndrome , Time Factors
20.
Br J Dermatol ; 177(3): 688-695, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27861727

ABSTRACT

Wet wrap therapy (WWT) consists of topical steroids administered under a layer of wet cotton bandages or garments. Several trials with WWT have reported promising results in atopic dermatitis (AD). However, no systematic review and meta-analysis on its efficacy and safety has been published. Our objective was to conduct a systematic review of the literature on WWT in AD to assess its efficacy and safety. We included randomized controlled trials among patients of all ages with a diagnosis of AD based on predefined criteria or made by a dermatologist. Electronic searches were performed from 1970 to 30 March 2016 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase and the World Health Organization International Clinical Trials Registry. Selection of studies and data extraction were performed independently by two researchers, and discrepancies were resolved by consensus. Six trials comparing WWT with topical steroids in children or adults with AD were included. Sample sizes ranged from 19 to 51 patients. Results on clinical severity and quality of life were reported incompletely and proved heterogeneous across studies. A nonsignificant tendency to increased risk of mild skin infections was observed in those treated with WWT (pooled relative risk 6·35, 95% confidence interval 0·83-48·55). The overall grade of quality of evidence for the efficacy and safety outcomes was low. In conclusion, the evidence that WWT is more effective than conventional treatment with topical steroids in AD is of low quality. Further clinical trials should establish the efficacy of WWT in AD.


Subject(s)
Dermatitis, Atopic/drug therapy , Steroids/administration & dosage , Administration, Cutaneous , Bandages/adverse effects , Humans , Quality of Life , Randomized Controlled Trials as Topic , Risk Factors , Skin Diseases, Infectious/etiology , Steroids/adverse effects , Treatment Outcome
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