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INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.
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Fibrilação Atrial , Forame Oval Patente , Acidente Vascular Cerebral , Humanos , Projetos Piloto , Fatores de Risco , Cateterismo Cardíaco/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Forame Oval Patente/diagnóstico , Forame Oval Patente/diagnóstico por imagem , Fibrilação Atrial/diagnóstico , Prevenção Secundária , Encéfalo , Resultado do Tratamento , RecidivaRESUMO
BACKGROUND: The issue of sex differences in stroke has gained concern in the past few years. However, multicenter studies are still required in this field. This study explores sex variation in a large number of patients and compares stroke characteristics among women in different age groups and across different countries. METHODS: This multicenter retrospective cross-sectional study aimed to compare sexes regarding risk factors, stroke severity, quality of services, and stroke outcome. Moreover, conventional risk factors in women according to age groups and among different countries were studied. RESULTS: Eighteen thousand six hundred fifty-nine patients from 9 countries spanning 4 continents were studied. The number of women was significantly lower than men, with older age, more prevalence of AF, hypertension, and dyslipidemia. Ischemic stroke was more severe in women, with worse outcomes among women (p: < 0.0001), although the time to treatment was shorter. Bridging that was more frequent in women (p:0.002). Analyzing only women: ischemic stroke was more frequent among the older, while hemorrhage and TIA prevailed in the younger and stroke of undetermined etiology. Comparison between countries showed differences in age, risk factors, type of stroke, and management. CONCLUSION: We observed sex differences in risk factors, stroke severity, and outcome in our population. However, access to revascularization was in favor of women.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Estudos Retrospectivos , Caracteres Sexuais , Estudos Transversais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Fatores de Risco , AVC Isquêmico/complicações , Fatores SexuaisRESUMO
PURPOSE: Up to 50% of patients do not achieve significant left ventricular ejection fraction (LVEF) recovery after primary percutaneous intervention (PPCI) for STEMI. We aimed to identify the echocardiographic predictors for LVEF recovery and assess the value of early follow-up echocardiography (Echo) in risk assessment of post-myocardial infarction (MI) patients. METHODS: One hundred one STEMI patients undergoing PPCI were enrolled provided EF below 50%. Baseline echocardiography assessed LVEF, volumes, wall motion score index (WMSI), global longitudinal strain (GLS), global circumferential strain (GCS), and E/e'. Follow-up echocardiography after 6 weeks reassessed left ventricular volumes, LVEF and GLS.GCS was not assessed at follow up. Patients were classified into recovery and non-recovery groups. Predictors of LVEF recovery and major adverse cardiovascular events (MACE) at 6 months were analysed. RESULTS: The mean change of EF was 8.04 ± 3.32% in group I versus -.39 ± 5.09 % in group II (p < .001). Recovered patients had better baseline GLS, baseline GCS, E/e', and follow-up GLS. Multivariate regression analysis revealed E/e', GCS, and follow-up GLS after 6 weeks to be strong independent predictors for LVEF recovery. Composite MACE was considerably higher in group II (32.7% vs. 4.1%, p < .001) mainly driven by higher heart failure hospitalisation Multivariate regression analysis revealed baseline GLS, E/e', and ejection fraction (EF) percentage recovery as strong independent predictors for MACE. CONCLUSIONS: Multiparametric echocardiographic approach incorporating LVEF, strain parameters, and diastolic function could allow early optimal risk stratification after STEMI treated with PPCI. Follow-up GLS and LVEF percentage change are the strongest predictors for early LV recovery and long term clinical outcome, respectively.
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Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Volume Sistólico , Função Ventricular Esquerda , Seguimentos , Ecocardiografia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/cirurgia , ReperfusãoRESUMO
BACKGROUND: Rapid diagnosis of acute myocardial infarction (AMI) is the subject of many clinical studies as it enables an effective therapy, preventing adverse progression of AMI and increasing survival rates. Recent studies have revealed that specific blood-based long non-coding RNAs (lncRNAs) are deregulated in patients with AMI and serve as promising diagnostic and prognostic tools. The current study aimed to determine the potential role of a hypoxia-responsive lncRNA, hypoxia-inducible factor 1A antisense RNA 2 (HIF1A-AS2), as a biomarker for early diagnosis and predictor of left ventricular dysfunction (LVD). METHODS: This study was carried out on 48 patients with AMI and 50 age-and sex-matched controls. The relative quantification of HIF1A-AS2 expression was done using reverse transcription real-time polymerase chain reaction. RESULTS: Compared to the control group, HIF1A-AS2 were significantly higher in MI patients (P < 0.001). Interestingly, patients presenting within 3 h of chest pain onset had elevated levels of HIF1A-AS2 as compared to patients with late presentation. The ROC curve was constructed to assess HIF1A-AS2 as an early marker. It demonstrated higher sensitivity (94%) and specificity (86%). Moreover, the multivariate regression analysis revealed that HIF1A-AS2 was significantly associated with LVD in the patient group after 6 months follow up (p = 0.018). CONCLUSION: Our study suggests that HIF1A-AS2 may be a potential early diagnostic biomarker of AMI with high sensitivity. In addition, it might have a promising role as a predictor of left ventricular dysfunction.
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Infarto do Miocárdio , RNA Longo não Codificante , Disfunção Ventricular Esquerda , Humanos , RNA Antissenso , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Biomarcadores , Diagnóstico Precoce , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/genética , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genéticaRESUMO
BACKGROUND: Cerebral arterial stenosis (CAS), in the absence of a structural lesion, can result in cognitive impairment that represents an ongoing contention among studies. Accordingly, we investigated cognitive functions in asymptomatic patients with CAS, using P300 which is a neurophysiological tool. We also compared cognition in intracranial stenosis (ICS) and extracranial stenosis (ECS). METHODS: Asymptomatic patients with CAS (≥ 70%) in the absence of structural brain lesions were categorized into ICS and ECS groups of 15 patients each, in addition to 15 normal controls. MRI, MRA, CT angiography, P300 analysis, Mini-Mental State examination (MMSE), Wisconsin Card Sorting Test (WCST), and Wechsler Memory Scale Test-Revised (WMST) were performed to all patients. RESULTS: Impairment on all cognitive scales ranged from 70 up to 100% among CAS group. Prolonged p300 latency and reaction time correlated with worse performance on WMST (p = 0.02), while lower amplitude and decreased accuracy correlated with more errors on WCST (p = 0.01). ICS scores on WCTS were lower than those of ECS group (p = 0.001), while ECS had a longer reaction time (p = 0.02) and lower scores on MMS and WMST than those of ICS group (p = 0.03). CONCLUSION: Patients with asymptomatic CAS had a high prevalence of cognitive dysfunction which places them at risk of higher morbidity. ICS group showed impairment on executive functions, while the ECS group showed predilection to memory and information processing dysfunction.
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Estenose das Carótidas , Disfunção Cognitiva , Humanos , Constrição Patológica/diagnóstico por imagem , Estenose das Carótidas/diagnóstico , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Função Executiva , CogniçãoRESUMO
BACKGROUND: Complications caused by female genital mutilation (FGM), such as clitoral pain, reduced sensation, and diminished sexual function, can be alleviated by clitoral reconstruction, which can also improve the aesthetics and restore the anatomy of the genitalia. OBJECTIVES: The aim of this study was to create sensate labial flaps to cover the neoclitoris and assess the outcome of the procedure. METHODS: Between December 2018 and July 2020, 40 patients with FGM underwent clitoral reconstruction and coverage with sensate labial flaps donated by the remnant of the labia minora and were followed prospectively. Flaps were mapped on the less-mutilated labia minora according to recent descriptions of arterial anatomy and innervation. Before the surgery, the patients' clitoral sensation was assessed on a 6-point scale and they were also given the Female Sexual Functional Index (FSFI) questionnaire to complete. Eight and 24 weeks postoperatively, the same assessment was repeated and the data compared. RESULTS: The mean Female Sexual Functional Index score increased significantly from 11.64 (range, 2.8-25.6) preoperatively to 29.14 (range, 12.8-35.4) postoperatively. Similarly, clitoral sensation increased significantly from 2.35 (range, 1-4) before the surgery to 4.9 (range, 2-6) after the surgery. In total, 95% of patients benefited from the surgery. CONCLUSIONS: Clitoral reconstruction with sensate labial flaps after FGM resulted in significant improvements in sexual function, clitoral sensation, genital aesthetics, and self-esteem.
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Circuncisão Feminina , Procedimentos de Cirurgia Plástica , Circuncisão Feminina/efeitos adversos , Clitóris/cirurgia , Feminino , Humanos , Retalhos Cirúrgicos , Vulva/cirurgiaRESUMO
Hexavelant chromium (Cr (V1)) is a widely distributed environmental pollutant inducing damage in different organs of human and animals. The current study was designed to investigate the mechanistic role of rosmarinic acid (RA) to diminish chromium-induced hepatorenal oxidative damage and preneoplastic lesions in rats. Plant material was collected, identified, and extracted. The isolated RA was elucidated relying on the nuclear magnetic resonance spectroscopic data. Twenty-eight male Wistar rats received the following materials daily via oral gavage for 60 days; (Gp1): normal saline, (Gp2) 25 mg/kg.bwt RA, (Gp3) 10 mg/kg.bwt potassium dichromate (K2 Cr2 O7 ), (Gp4) K2 Cr2 O7 + RA. All rats were euthanized at the end of the experiment by cervical dislocation and the liver and kidney were collected. Prolonged continuous exposure of rats to chromium-induced oxidant/antioxidant imbalance manifested by significant elevation of malondialdehyde with reduction in reduced glutathione levels. Remarkable histopathological alterations in the liver and kidney tissue sections were recorded and confirmed by overexpression of the immunohistochemical staining of caspase-3, placental glutathione-S transferase, proliferating cell nuclear antigen together with a significant downregulation of nuclear factor erythroid-2 related factor 2 (Nrf2) gene and upregulation of nibrin gene. Observable improvements in the entire toxicopathological parameters were recorded in group cotreated with RA. Our findings revealed that Cr-induced preneoplastic lesions on the liver and kidney tissues of rats when exposed daily for long period of time, as well as confirmed the ability of RA to alleviate this toxicity through upregulation of Nrf2 pathway and its powerful antioxidant effects.
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Cromo/toxicidade , Cinamatos/farmacologia , DNA/efeitos dos fármacos , Depsídeos/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Dano ao DNA , Masculino , Ratos , Ratos Wistar , Ácido RosmarínicoRESUMO
Onychomycosis is an important medical disorder affecting both health and quality of life of patients. This study was done to compare the efficacy of CO2 laser in combination with topical tioconazole versus CO2 laser only versus topical tioconazole alone in onychomycosis. A total of 120 patients with onychomycosis were randomly assigned to three groups. Group A patients were treated with fractional CO2 laser followed by topical tioconazole 28% for five sessions with 3 weeks interval. Group B patients were treated with only fractional CO2 laser for five sessions with 3 weeks interval. Group C patients were treated with only topical tioconazole 28% for 16 weeks. The clinical effect, KOH examination, and culture for the affected nails in the three groups were analyzed. One month after the last session, regarding clinical response, 55% showed complete clinical improvement in Group A versus 30% in Group B versus 25% in Group C with a significant difference in between. There was a significant difference between the three studied groups as regard KOH test and culture after treatment. Fractional CO2 laser combined with topical antifungal is a safe and effective treatment for onychomycosis.
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Antifúngicos/administração & dosagem , Imidazóis/administração & dosagem , Lasers de Gás/uso terapêutico , Onicomicose/terapia , Administração Tópica , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
Vitiligo is an autoimmune disease characterized by patches of depigmentation. Zinc is an antiapoptotic molecule that exhibits antioxidant properties. The study aimed to investigate the serum levels of zinc in vitiligo patients compared to healthy controls and to whether exists a correlation between disease severity and serum levels of zinc. Fifty patients with vitilgo (group A) and 50 age and sex matched healthy controls (group B) were recruited and serum zinc level was measured using atomic absorption spectrophotometry and results were compared and correlated to each other and to disease severity and extension. The mean serum zinc levels in group A was 50.93 ± 11.02 in comparison to a mean of 77.09 ± 12.16 in group B (P = .049, T = -1.993). Vitiligo area severity index (VASI) scores in the vitiligo group ranged from 0.5 to 27 with a mean ± SD of (9.19 ± 4.47). A high statistically significant negative correlation was demonstrated between serum zinc levels and the extension of vitiligo (P value = .0001 and R value = - 0.835). A significant association exists between vitiligo and serum zinc levels. Serum zinc levels correlated negatively with vitiligo disease severity and extension. Zinc supplementation and use can be of potential importance in setting vitiligo treatment protocols.
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Vitiligo , Antioxidantes , Humanos , Estudos Prospectivos , Índice de Gravidade de Doença , Vitiligo/diagnóstico , ZincoRESUMO
BACKGROUND: Egypt is a densely populated country with living habits and health care services that differ from urban to rural regions. We aimed to study how characteristics of stroke vary among these regions. METHODS: This is a cross-sectional observational study of ischemic stroke, thus hemorrhagic and venous strokes were excluded. A total of 1475 ischemic stroke patients were recruited for analysis from a tertiary hospital in Cairo representing urban area and from a secondary care hospital in Suhag representing rural region. RESULTS: Analysis was done for 1143 ischemic stroke patients from urban and 332 from rural area. Onset to door was shorter in urban. Urban patients showed an older age and higher prevalence of hypertension and diabetes (65.9%, 48.6% respectively), while rural patients were characterized by female preponderance (51.5%), more dyslipidemia, smoking 44.6%, stroke in young 20.5%, atrial fibrillation 23.8% % and recurrent stroke 44.3%. Rural cases showed a severer deficit at onset and poorer outcome. CONCLUSION: Vascular risk factors, stroke type, and presentation tend to differ in Egypt according to the geographic distribution whether urban or rural. Studying patterns of such difference may aid in planning specific targeted preventive and therapeutic strategies for stroke in urban and rural Egypt.
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Isquemia Encefálica/epidemiologia , Saúde da População Rural , Acidente Vascular Cerebral/epidemiologia , Saúde da População Urbana , Adulto , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Comorbidade , Estudos Transversais , Egito/epidemiologia , Feminino , Nível de Saúde , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Tempo para o TratamentoRESUMO
In forensic medicine, it is vital to verify with the best attainable accuracy once injuries occurred during vital or post-mortem conditions. An immunohistochemical study was carried out to examine the time-dependent expression of macrophage-specific gene CD68 (cluster of differentiation 68), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF) in different skin wound timings (0, 1, 3, 5, 7, and 14 days) in rats. Histopathological studies were performed to assess the wound age and vitality. Eighteen male albino Wister rats (weighing 170-200 g) were used for wound induction. Rats (n = 3) were euthanised at 0, 1, 3, 5, 7, and 14 days from the starting point of wound induction. Histopathological examination showed that the epidermal re-epithelialisation was completed 14 days after skin incision. The inflammatory phase was recorded during the first 3 days of healing and reached the maximum levels at 5 days, then declined after 7 days, and completely removed at 14 days. The beginning of the proliferative phase was dated to day 3 and the peak at days 5 and 7. The initiation of the granulation tissue formation and remodelling phase of the healing process was observed 5 days after wounding. By immunohistochemical staining, negative VEGF gene expressions at early stages (0-3 days) were observed, as well as neither CD68+ macrophages nor α-SMA+ myofibroblast cells were detected. By increasing the wound ages (5-7 days), granulation tissue and angiogenesis were observed, with the migration of macrophages and fibroblast, which expressed VEGF, CD68, and α-SMA positive reaction. Time-dependent expression of the above markers suggested that they would be useful indicators for the determination of wound age. Both VEGF and transforming growth factor-beta 1 (TGFb1) mRNA levels were determined in different skin wound ages. The transcription of TGFb1 and VEGF increased shortly after wounding, until post-wounding day 7. It then declined constantly, reaching minimal values on day 14.
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Cicatrização , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia , Actinas/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Movimento Celular/fisiologia , Fibroblastos/fisiologia , Tecido de Granulação/patologia , Imuno-Histoquímica , Macrófagos/fisiologia , Modelos Animais , Neovascularização Fisiológica , RNA Mensageiro/metabolismo , Ratos Wistar , Reepitelização , Pele/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG) neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage). Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight) of either ginger or propolis (600 mg/kg body weight) once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and ß-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products.
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Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas , Própole/farmacologia , Glutamato de Sódio/efeitos adversos , Zingiber officinale , Administração Oral , Animais , Modelos Animais de Doenças , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Wistar , Glutamato de Sódio/farmacologiaAssuntos
Circuncisão Feminina , Braço , Circuncisão Feminina/efeitos adversos , Clitóris/cirurgia , Estética , Feminino , HumanosRESUMO
BACKGROUND: The prevalence of long diffuse coronary artery disease (CAD) is increasing nowadays due to increase prevalence of multiple risk factors and population ageing. We aimed in our study to show the differences clinically or angiographically (guided by IVUS) between the use of single long stent versus overlapping stents in very long coronary lesions (≥40 mm) in patients presented with chronic coronary syndromes. METHODS: 550 patients presenting with chronic coronary syndromes were included: 320 treated with a single long stent (≥40 mm) and 230 patients with two or more overlapping stents. Angiographic follow-up (guided by IVUS) 6 months after PCI was performed only in 50 patients. We assessed the procedural characteristics and the occurrence of major adverse cardiovascular events (MACE) after a median follow-up of 24 months. RESULTS: Total stent length was 56.16 ± 14.85 mm and mean diameter was 3.05 ± 0.36 mm. At the end of follow-up, MACE rate in the single long stent group was 4.1% vs. 7.8% in the overlapping stents group, with higher incidence in overlapping stents group but non-statistically significant (p value = 0.059). PCI using overlapping stents consumed more contrast volume (248 ± 85.36 vs 164.5 ± 70.43 ml, p < 0.001), and higher fluoroscopy time (23.65 ± 9.19 vs 19.72 ± 9.19 min, p < 0.001). Regarding IVUS subgroup follow-up, there was no significant difference between both groups regarding in-stent restenosis and MACE. CONCLUSIONS: We can conclude that long or overlapping stents are both acceptable therapeutic choices for patients with long CAD. There was no difference between both strategies regarding angiographic follow-up guided by IVUS after 6 months.
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Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Stents Farmacológicos/efeitos adversos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Angiografia Coronária/efeitos adversos , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Stents/efeitos adversos , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: The assessment of the postmortem interval (PMI) represents one of the major challenges in forensic pathology. Because of their stability, microRNAs, or miRNAs, are anticipated to be helpful in forensic research. OBJECTIVE: To see if estimation of PMI is possible using miRNA-21 and Hypoxia-inducible factor-1α (HIF-1α) expression levels in the heart samples from aluminum phosphide toxicity (Alpt). METHODS: This was a cross sectional study on 60 post-mortem samples (heart tissues) collected at different intervals during forensic autopsies. The two groups were allocated equally according to the cause of death into Group I (non-toxicated deaths, n = 30): Deaths caused by other than toxicity, and Group II (toxicated deaths, n = 30): Deaths due to Alpt. MDA (Malondialdehyde) and GSH (Glutathione), were measured in heart tissues using ELIZA. MiRNA- 21and HIF-1α expression levels were measured in heart tissues at different PMI using RT-Q PCR. ROC curve for detection of toxicated deaths using miRNA-21 and HIF was carried out. RESULTS: miRNA-21 and HIF-1α expression levels in Alp deaths were up regulated while GSH was downregulated with statistically significant difference. There was positive correlation between miRNA-21, HIF-1α and MDA with PMI while there was negative correlation between GSH and PMI in Alp deaths. In prediction of post mortem interval in Alp deaths miRNA-21 sensitivity and specificity were (75.9 %, 51.7 %, respectively) while HIF-1α sensitivity and specificity were 100 %. CONCLUSION: PMI can be calculated using the degree to which particular miRNA-21 and HIF-1α are expressed in the heart tissue. The combination of miRNA-21 with HIF-1α in post mortem estimation is precious indicators.
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Background: Soft tissue defects in the lower third of the leg present significant challenges for surgeons. Despite various options available for soft tissue coverage, selecting the most suitable option is limited by potential complications. In response to this challenge, some surgeons have sought to develop algorithms to guide decision-making in the management of lower leg trauma. Methods: This prospective observational cross-sectional study included 53 patients with traumatic injuries to the lower third leg and ankle regions. Each patient underwent a management plan based on our proposed algorithm, which incorporated the utilization of negative pressure wound therapy and dermal substitutes. Outcomes were assessed in terms of the ability to achieve complete coverage, complication rates, duration of hospital stay, and return to normal daily activity. Results: The proposed algorithm proved to be comprehensive and easily applicable, achieving complete coverage in 98.1% of cases. The mean duration for definitive coverage was 21.89â ±â 12.84 days, and the majority of cases (81.1%) returned to normal daily activity within a mean duration of 60.69â ±â 56.7 days. The use of dermal substitutes resulted in achieving coverage in wounds with exposed structures, with favorable outcomes in cases with a mean size of 11.39â ±â 10.05 cm². Conclusions: Our algorithm provides a safe and effective approach to manage traumatic defects of the lower third leg and ankle, considering the patient's general condition and the complexity of the wound. Proper utilization of dermal substitutes and negative pressure wound therapy is emphasized in the algorithm.
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BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.
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Doenças Autoimunes , Síndrome de Down , Doenças Retinianas , Uveíte , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Doenças Autoimunes/complicações , Síndrome de Down/complicações , Estudos Retrospectivos , Autoanticorpos , Uveíte/complicaçõesRESUMO
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks an actionable target with limited treatment options beyond conventional chemotherapy. Therapeutic failure is often encountered due to inherent or acquired resistance to chemotherapy. Previous studies implicated PI3K/Akt/mTOR signaling pathway in cancer stem cells (CSCs) enrichment and hence chemoresistance. The present study aimed at investigating the potential effect of piperine (PIP), an amide alkaloid isolated from Piper nigrum, on enhancing the sensitivity of TNBC cells to doxorubicin (DOX) in vitro on MDA-MB-231 cell line and in vivo in an animal model of Ehrlich ascites carcinoma solid tumor. Results showed a synergistic interaction between DOX and PIP on MDA-MB-231 cells. In addition, the combination elicited enhanced suppression of PI3K/Akt/mTOR signaling that paralleled an upregulation in this pathway's negative regulator, PTEN, along with a curtailment in the levels of the CSCs surrogate marker, aldehyde dehydrogenase-1 (ALDH-1). Meanwhile, in vivo investigations demonstrated the potential of the combination regimen to enhance necrosis while downregulating PTEN and curbing PI3K levels as well as p-Akt, mTOR, and ALDH-1 immunoreactivities. Notably, the combination failed to change cleaved poly-ADP ribose polymerase levels suggesting a pro-necrotic rather than pro-apoptotic mechanism. Overall, these findings suggest a potential role of PIP in decreasing the resistance to DOX in vitro and in vivo, likely by interfering with the PI3K/Akt/mTOR pathway and CSCs.