RESUMO
There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD). In 3671 participants aged 46-70 years at baseline, ∆lean mass was a stronger determinant than ∆fat mass of ∆BMD over 6 years. Maintained or increased lean mass may slow down age-related bone loss. PURPOSE: There are limited longitudinal data regarding relationships between changes in body composition and bone mineral density (BMD) with ageing. We examined these in the Busselton Healthy Ageing Study. METHODS: We studied 3671 participants (2019 females) aged 46-70 years at baseline with body composition and BMD assessments by dual-energy x-ray absorptiometry at baseline and after ~6 years. Relationships between changes in total body mass (∆TM), lean mass (∆LM) and fat mass (∆FM) with ∆BMD at total hip, femoral neck and lumbar spine were evaluated using restricted cubic spline modelling (accounting for baseline covariates) and mid-quartile least square means were compared. RESULTS: ∆TM was positively associated with ∆BMD of total hip and femoral neck in both sexes, and spine in females; in females but not males, associations plateaued at ∆TM above ~5kg for all sites. In females, ∆LM was positively associated with ∆BMD of all three sites with plateauing of the relationship at ∆LM above ~1kg. Women in the highest quartile of ∆LM (Q4, mid-quartile value +1.6 kg) had 0.019-0.028 g/cm2 less reduction in BMD than those in the lowest quartile (Q1, -2.1 kg). In males, ∆LM was positively associated with ∆BMD of total hip and femoral neck; men in Q4 (+1.6 kg) had 0.015 and 0.011 g/cm2 less bone loss, respectively, compared with Q1 (-2.7 kg). ∆FM was positively associated with ∆BMD of total hip only in both sexes. CONCLUSION: ∆LM is a stronger determinant than ∆FM of ∆BMD. Maintained or increased LM is associated with less age-related bone loss.
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Densidade Óssea , Osteoporose , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Austrália/epidemiologia , Composição Corporal , Osteoporose/epidemiologia , Absorciometria de Fóton , Vértebras LombaresRESUMO
INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health. MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables. RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (ß: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group. CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.
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Atenção Plena , Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/psicologia , Saúde Mental , Método Simples-Cego , Fumar/psicologiaRESUMO
PURPOSE: To evaluate the outcomes of pre-stented (PS) versus non-pre-stented (NPS) patients who have undergone retrograde intrarenal surgery (RIRS) for renal calculi with subgroup analysis of Asian and non-Asian cohorts. METHODS: Protocol is registered in PROSPERO, CRD42021261123. Eligible studies identified from four electronic databases. Meta-analysis was done to enumerate the outcomes of RIRS in between PS and NPS. Secondary sub-analysis was done to look for differences in outcomes in Asian and non-Asian cohorts. RESULTS: Fourteen studies involving 3831 patients (4 prospective, 10 retrospective studies) were included. PS patients experienced higher success rates of ureteral access sheath (UAS) insertion than NPS (RR 1.09, 95% CI 1.05-1.13, p < 0.00001). PS patients had lower risk of ureteral injuries from UAS placement (RR 0.69, 95% CI 0.50-0.96, p = 0.03). No significant differences in intra- and postoperative complications between two groups were found. Stone-free rate (SFR) outcomes for residual fragment (RF) cut-off of < 1 mm and < 4 mm favoured the PS patients (RR 1.10, 95% CI 1.04-1.17, p = 0.002 for < 4 mm, RR1.10, 95% CI 1.02-1.19, p = 0.02 for < 1 mm). In the subgroup analysis, PS Asian patients had similar SFR as NPS patients for SFR(< 4 mm) but non-Asian population showed better outcomes in the PS patients for SFR(< 4 mm) (RR 1.31, 95% CI 1.13-1.52, p = 0.0005). CONCLUSIONS: This meta-analysis suggests that pre-stenting results in a higher success for UAS placement, minimising intraoperative ureteric injury, with higher overall SFR for any RF cut-off in PS cohorts. In non-Asian cohort, significant differences occurred at SFR < 4 mm but not for SFR < 1 mm. No difference was seen in our Asian cohort for any SFR cut-off in both PS and NPS patients.
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Cálculos Renais , Ureter , Humanos , Cálculos Renais/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Stents , Resultado do Tratamento , Ureter/cirurgiaRESUMO
AIM: To compare peri-operative outcomes of skin closure with octyl cyanoacrylate (OCA) skin adhesive (Dermabond) with or without subcuticular sutures after deep dermal suturing for implantable venous port placement closure. MATERIALS AND METHODS: Seven hundred and ninety-two single-lumen implantable venous port insertions for chemotherapy were reviewed from September 2019 to March 2021 in a retrospective single-centre study. Propensity-score matching by a 1:1 nearest neighbour algorithm was conducted to control for confounding baseline differences. Distances were determined by logistic regression. Propensity-score matching was performed based on the following variables: age at procedure, gender, race, operator's seniority, use of anchoring polypropylene suture (PROLENE), port model, and volume of intra-operative local analgesia. The primary outcome was wound dehiscence at the first follow-up (â¼1 week). RESULTS: The 792 port insertions were conducted in 302 males (38.1%), median age 63 years (IQR: 54-69). Of the 656 wounds closed with subcuticular sutures and skin adhesive, 136 were matched in a 1:1 fashion against procedures closed without a subcuticular suture. No significant differences were demonstrated in pain scores, bleeding, swelling, bruising, fever, wound dehiscence, and discharge at postoperative day 1 (POD1) and at first follow-up between the groups (all p>0.05). Of note, no significant differences in wound dehiscence at first follow-up was found in both unmatched (p=0.133) and matched cohorts (McNemar-Bowker's χ2 = 1.167, p=0.761). CONCLUSION: These findings suggest that the omission of subcuticular sutures during implantable venous port closure may not compromise peri-operative outcomes when OCA skin adhesives were used.
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Neoplasias , Adesivos Teciduais , Adesivos , Cianoacrilatos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Complicações Pós-Operatórias , Estudos Prospectivos , Estudos Retrospectivos , Suturas , Adesivos Teciduais/uso terapêutico , CicatrizaçãoRESUMO
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer-related death worldwide.
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Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/prevenção & controle , Hepacivirus , Hepatite C/complicações , Hepatite C/prevenção & controle , Humanos , Neoplasias Hepáticas/prevenção & controleRESUMO
Patients with haematological malignancy are at increased risk of developing central nervous system (CNS) infections, which are associated with significant morbidity and mortality. Neuroimaging plays a pivotal role in the diagnostic pathway of these patients; however, layers of complexity are added to image interpretation by the heterogeneity in imaging manifestations of haematological malignancies in the CNS, overlapping imaging features of CNS infection, treatment-related parenchymal changes and the presence of intracranial comorbidity. In this article, we review important intracranial findings of CNS infection cases accrued in 1,855 studies over more than a decade at a specialist tertiary centre. We offer schema to identify common and important neuroimaging features, discuss key differential diagnoses and frequent diagnostic pitfalls.
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Infecções do Sistema Nervoso Central/complicações , Infecções do Sistema Nervoso Central/diagnóstico por imagem , Erros de Diagnóstico/prevenção & controle , Diagnóstico por Imagem/métodos , Neoplasias Hematológicas/complicações , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , HumanosRESUMO
Adiposity has a complex relationship with bone health. In 4865 Australian baby boomers (2642 females) aged 45-70 years, we found that higher visceral adipose tissue mass is associated with reduced bone density adjusting for body mass and lifestyle factors, suggesting that excess visceral fat may be deleterious to bone. INTRODUCTION: Increased body mass is associated with higher bone mineral density (BMD), but higher visceral adipose tissue (VAT) may have a negative impact on bone health. In the Busselton Healthy Ageing Study, we examined associations between VAT mass and BMD in 4865 participants (2642 females) aged 45-70 years. METHODS: VAT mass and BMD of whole body, total hip, femoral neck and lumbar spine were measured using DXA. VAT mass was examined as a continuous variable and in quartiles using sex-specific cut-offs. RESULTS: The mean age was 58.0 ± 5.8 years. Males had significantly higher BMI (28.3 ± 3.7 vs 27.5 ± 4.9 kg/m2) and VAT mass (1675 ± 878 vs 882 ± 600 g) than females (both P < 0.001). In males, after adjustment for age, body mass, height and lifestyle factors, VAT mass negatively associated with total body, total hip and femoral neck BMD (ß = - 0.153 to - 0.293, all P < 0.001). Males in the highest quartile of VAT mass (> 2200 g) had significantly lower BMD at all three sites than those in lower quartiles, with estimated BMD differences of 2.3-5.7% (all P < 0.05). In females, VAT mass negatively associated with total body, femoral neck and lumbar spine BMD (ß = - 0.067 to - 0.178, all P < 0.05) and those in the highest quartile (> 1250 g) had significantly lower total body BMD than other quartiles (by 1.7-3.7%, all P < 0.05). CONCLUSION: In middle-aged Australians, after covariate adjustment, higher DXA-derived VAT mass is associated with reduced bone density, suggesting that excess visceral fat may be deleterious to bone, especially in males.
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Densidade Óssea , Gordura Intra-Abdominal , Absorciometria de Fóton , Tecido Adiposo , Adiposidade , Idoso , Austrália/epidemiologia , Feminino , Colo do Fêmur , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. INTRODUCTION: Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). METHODS: Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). RESULTS: After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 µg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 µg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. CONCLUSION: One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.
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Cálcio/farmacologia , Suplementos Nutricionais , Hemoglobinas Glicadas/metabolismo , Osteocalcina/sangue , Tecido Adiposo/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Cálcio/administração & dosagem , Cálcio da Dieta/farmacologia , Método Duplo-Cego , Esquema de Medicação , Feminino , HumanosRESUMO
AIM: To compare the educational outcomes using artificial teeth versus extracted teeth for pre-clinical endodontic training. DATA SOURCES: Literature searches of PubMed, Scopus, Cochrane Library, Trip Database, Web of Science and Open Grey databases were conducted from their inception until November 2018 with no language restriction. Hand searching of most likely relevant journals was performed. The review followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Studies that compared pre-clinical endodontic training using extracted teeth and artificial teeth were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of included studies was appraised by Joanna Briggs Institute Critical Appraisal tools. The findings were tabulated and summarized according to their outcomes with distinct narrative syntheses. RESULTS: Five studies were included. The component studies included 359 operators in total, mainly consisting of undergraduate students (97%, n = 349) and 10 endodontists (3%). Forty-seven per cent (n = 170) operated on artificial teeth only, whilst 19% (n = 67) worked primarily on extracted teeth, with the final treatment outcome being evaluated by independent observers using objective criteria. Operators in two studies (34%, n = 122) used both artificial teeth and ET and compared their experiences in surveys. Regarding technical outcomes, no significant differences between training with artificial teeth and extracted teeth were found, but the performance tended to be better in artificial teeth than extracted teeth. Operators trained solely on artificial teeth appeared to be adequately educated for subsequent root canal treatment (RCT) in the clinical setting. LIMITATIONS: Due to the scarcity of research on the topic overall, and the methodological variation between the studies, it was not possible to perform a quantitative analysis (meta-analysis). CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Based on the available evidence, the use of artificial teeth for pre-clinical endodontic training achieved similar educational outcomes compared to extracted teeth. However, the experiences reported by the operators diverged. Further studies assessing other artificial teeth available in the market testing other RCT procedures are necessary.
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Endodontia , Tratamento do Canal Radicular , Dente Artificial , Endodontia/educação , Humanos , Tratamento do Canal Radicular/métodos , DenteRESUMO
Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert, it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB has an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. We have reviewed the history and anatomy of the nvlDBB and now propose guidelines for distinguishing nvlDBB from other neighbouring cholinergic cell groups for standardizing future clinicopathological work. Thorough review of the literature regarding neurodegenerative conditions reveals inconsistent results in terms of cholinergic neuronal loss within the nvlDBB. This is likely to be due to the use of variable neuronal inclusion criteria and omission of cholinergic immunohistochemical markers. Extrapolating from those studies showing a significant nvlDBB neuronal loss in Lewy body dementia, we propose an anatomical and functional connection between the cholinergic component of the nvlDBB (Ch2) and the CA2 subfield in the hippocampus which may be especially vulnerable in Lewy body disorders.
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Doença de Alzheimer/patologia , Neurônios Colinérgicos/patologia , Feixe Diagonal de Broca/patologia , Doença por Corpos de Lewy/patologia , Doença de Parkinson/patologia , HumanosRESUMO
Cues and experiences of the deprivation of financial/material resources have been associated with increased caloric intake and risk for overweight/obesity. Given that social comparisons may serve as a powerful reference for the adequacy of one's standing and resources, the present research tested whether subjective feelings of personal relative deprivation (PRD) or "losing out" to others stimulates calorie selection and intake. Study 1 demonstrated that self-reported chronic experiences of PRD positively predicted calories selected for a portion and consumed during an ad-libitum meal. Study 2 revealed that experimentally-induced PRD resulted in an increase in the amount of calories selected on a portion selection task and a stronger desire to consume the foods. Consequently, these findings demonstrate that chronic and acute subjective deprivation of non-food resources may contribute to socioeconomic gradients in obesity, and that perceived social inequality may have inherently obesogenic properties that promote excess calorie intake.
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Restrição Calórica/psicologia , Ingestão de Alimentos/psicologia , Tamanho da Porção/psicologia , Autocontrole/psicologia , Fatores Socioeconômicos , Adolescente , Adulto , Índice de Massa Corporal , Dieta , Feminino , Humanos , Masculino , Obesidade/prevenção & controle , Sobrepeso/prevenção & controle , Inquéritos e Questionários , Adulto JovemRESUMO
The obesity-BMD relationship is complex. In 3045 middle-aged adults, we found that in women (but not men) with discordant fat mass index (FMI)/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone. INTRODUCTION: The relationship between obesity and BMD is complex. FMI (fat mass (kg) / height (m)2) is a more accurate measure of fatness than BMI, and depending on body composition, some individuals have discordant BMI/FMI categories. We examined associations between FMI, BMI and BMD in participants in the Busselton Healthy Ageing Study. METHODS: Body composition and BMD of the hip, spine and total body were measured using DXA in 3045 participants (1644 females) aged 45-67 years. Using standard BMI/FMI categories, the participants were classified as underweight/fat deficit, normal, overweight/excess fat, obese I and obese II-III. RESULTS: BMI and FMI categories were concordant in 77.3 % of females and 71.2 % of males. There were 12.9 % females and 13.2 % males in a higher FMI than BMI category (high body fat for BMI), whereas 9.8 % females and 15.6 % males were in a lower category (low body fat for BMI). Females with high body fat for BMI had significantly lower covariate-adjusted BMD at the femoral neck, total hip and total body (differences of 3.8, 5.1 and 2.6 %, respectively, all P < 0.05) than females with low body fat for BMI and lower total body BMD than women with concordant FMI/BMI (by 1.4 %, P = 0.04). In males, BMD did not differ significantly between those who were concordant or discordant for FMI/BMI categories. CONCLUSION: In women (but not men) with discordant FMI/BMI categories, higher body fat for BMI was associated with lower BMD, suggesting that increased fat mass without an accompanying increase in lean mass may be deleterious to bone.
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Tecido Adiposo/anatomia & histologia , Índice de Massa Corporal , Densidade Óssea/fisiologia , Caracteres Sexuais , Absorciometria de Fóton/métodos , Tecido Adiposo/fisiologia , Idoso , Antropometria/métodos , Composição Corporal/fisiologia , Feminino , Envelhecimento Saudável/fisiologia , Articulação do Quadril/fisiologia , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Sobrepeso/fisiopatologiaAssuntos
Tumor Carcinoide , Neoplasias Pulmonares , Neoplasias do Timo , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiologia , Tumor Carcinoide/terapia , Seguimentos , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Prognóstico , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/epidemiologia , Neoplasias do Timo/terapiaRESUMO
Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been associated with both experimental and clinical pain phenotypes. In this prospective study, we investigated the association of three common polymorphisms with experimentally induced pressure pain, postoperative pain and amount of self-administered morphine in 973 patients who underwent scheduled total hysterectomy. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were significantly associated with morphine use, whereas rs4818 was associated with time-averaged pain scores. Statistically significant associations were found between COMT rs4633 and rs4680 genotypes and the amount of morphine self-administered through a patient-controlled analgesia pump. For rs4818, the only statistically significant association was with time-averaged pain scores. Haplotype analysis showed statistically significant association of the low pain sensitivity haplotype with time-averaged pain scores; and average pain sensitivity haplotype with total morphine and weight-adjusted morphine.
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Analgésicos Opioides/administração & dosagem , Catecol O-Metiltransferase/genética , Histerectomia/efeitos adversos , Morfina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Analgesia Controlada pelo Paciente , Povo Asiático , Etnicidade , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Masculino , Estudos Observacionais como Assunto , Dor Pós-Operatória/etnologia , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único , Estudos ProspectivosRESUMO
In recurrent hepatitis C (HCV) post-liver transplantation (OLT), the combination of immunosuppressants and HCV is postulated to increase hepatocyte apoptosis and liver fibrosis. We evaluated hepatocyte apoptosis within the liver tissue of patients with postOLT HCV recurrence compared to HCV-negative individuals and correlated these findings with the effects of immunosuppressants on HCV-induced cell death and its inhibition in primary mouse hepatocytes (PMoH). Liver biopsies from patients with and without HCV were evaluated by immunohistochemistry for markers of apoptosis M30 CytoDEATH (M30) and cleaved PARP (clPARP). PMoH from C57BL/6 mice were infected with recombinant adenoviruses (rAdHCV) that expressed HCV proteins in hepatocytes. Infected cells were treated with cyclosporine, tacrolimus, sirolimus and/or MMF with or without pan-caspase inhibitor Q-VD-Oph. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved caspase-3 (clCas3) and clPARP. Both M30 and clPARP were increased in the liver biopsies of patients with postOLT HCV recurrence compared to HCV-negative individuals. Treatment of rAdHCV-infected PMoH with cyclosporine, tacrolimus or sirolimus reduced cell viability and increased clCas3 and clPARP compared to rAdHCV infection alone. Addition of MMF to cyclosporine, tacrolimus or sirolimus further reduced cell viability and increased clCas3 and clPARP. Q-VD-Oph improved cell viability in HCV-infected PMoH treated with immunosuppressants alone and in combination and reduced clCas3 and clPARP by approximately 90%. Immunosuppressive agents, especially in combination, enhanced apoptosis in HCV-infected hepatocytes. The finding that Q-VD-Oph reversed hepatocyte death suggests that treatments utilizing apoptosis inhibition might reduce liver injury in postOLT HCV recurrence.
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Apoptose , Hepatite C/patologia , Hepatócitos/fisiologia , Hepatócitos/virologia , Imunossupressores/uso terapêutico , Transplante de Fígado , Animais , Biópsia , Sobrevivência Celular , Células Cultivadas , Humanos , Imuno-Histoquímica , Fígado/patologia , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-κB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-κB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-κB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations.
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Proteínas Adaptadoras de Sinalização CARD/genética , Guanilato Ciclase/genética , Proteínas de Membrana/genética , Mutação/genética , Psoríase/genética , População Branca/genética , Adulto , Regulação para Baixo/genética , Feminino , Humanos , Masculino , NF-kappa B/metabolismo , Psoríase/etnologia , Transdução de Sinais , Tunísia , Regulação para Cima/genética , População Branca/etnologia , Adulto JovemRESUMO
OBJECTIVE: Chemoradiotherapy is often considered the 'standard of care' for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery. METHODS: Systematic review and meta-analyses (random and fixed effects) were performed. Searches of Medline and Embase (1980-2013) were conducted. Abstracts from thoracic scientific meetings were searched. Reference lists of all relevant studies were reviewed. All studies of patients with N2 disease who received induction chemotherapy or chemoradiotherapy and randomised to surgery or radiotherapy were included. No language restrictions were imposed. The main outcome was overall survival. RESULTS: 805 publications were identified. 519 and 281 were excluded because they were not primary results from randomised trials (or did not include N2 disease) or did not compare surgery with radiotherapy, respectively. The final six trials consisted of 868 patients. In four trials, patients received induction chemotherapy and in two trials patients received induction chemoradiotherapy. The HR comparing patients randomised to surgery after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients randomised to surgery after chemoradiotherapy was 0.87 (0.75 to 1.01; p=0.068). The overall HR of all pooled trials was 0.92 (0.81 to 1.03; p=0.157). CONCLUSIONS: Surgery should be considered as part of multimodality treatment for patients with resectable lung cancer and ipsilateral mediastinal nodal disease. In trials where patients received surgery as part of trimodality treatment, overall survival was better than chemoradiotherapy alone.
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Neoplasias Pulmonares , Estadiamento de Neoplasias , Pneumonectomia , Quimioterapia Adjuvante , Humanos , Quimioterapia de Indução , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. CONCLUSIONS: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.