Profiling several key milk miRNAs and analysing their signalling pathways in dairy sheep breeds during peak and late lactation.

BACKGROUND: The comprehensive understanding of microRNAs (miRNAs) in sheep milk during various lactation periods and their impact on milk yield and composition remains limited. OBJECTIVES: This study aimed to investigate the expression patterns of four highly expressed miRNAs in sheep milk and their association with milk composition and yield parameters during peak and late lactation stages. METHODS: A total of 40 healthy 4-year-old Akkaraman (n = 20) and Awassi (n = 20) ewes registered with the Ministry of Agriculture and Forestry of the Republic of Türkiye were used in the present study. For miRNA isolation from milk, the Qiagen miRNeasy Serum/Plasma Advanced Kit was utilised following the manufacturer's instructions. The expression levels of miRNAs were assessed using Qiagen miRNA PCR Assays. RESULTS: The significant fold changes in the expression levels of oar-miR-30a-5p, oar-miR-148a and oar-miR-181a were observed between peak and late lactation periods in the Awassi sheep breed. Conversely, only oar-miR-30a-5p and oar-miR-148a exhibited statistically significant changes in the Akkaraman sheep breed during the same lactation periods. Furthermore, oar-miR-21-5p demonstrated a significant fold change exclusively in peak lactation compared to Akkaraman and Awassi ewes. CONCLUSIONS: The findings suggest that the expression of the analysed miRNAs is influenced by both the lactation stage and different sheep breeds. This study offers valuable insights into the relationship between key miRNA expressions in sheep milk and milk composition and yield parameters during peak and late lactation, contributing to the existing knowledge in this field.

Genetic analysis of PALB2 gene WD40 domain in canine mammary tumour patients.

BACKGROUND: DNA repair mechanisms are essential for tumorigenesis and disruption of HR mechanism is an important predisposing factor of human breast cancers (BC). PALB2 is an important part of the HR. There are similarities between canine mammary tumours (CMT) and BCs. As its human counterpart, PALB2 mutations could be a predisposing factor of CMT. OBJECTIVES: In this study, we aimed to investigate the impacts of PALB2 variants on tumorigenesis and canine mammary tumor (CMT) malignancy. METHODS: We performed Sanger sequencing to detect germline mutations in the WD40 domain of the canine PALB2 gene in CMT patients. We conducted in silico analysis to investigate the variants, and compared the germline PALB2 mutations in humans that cause breast cancer (BC) with the variants detected in dogs with CMT. RESULTS: We identified an intronic (c.3096+8C>G) variant, two exonic (p.A1050V and p.R1354R) variants, and a 3' UTR variant (c.4071T>C). Of these, p.R1354R and c.4071T>C novel variants were identified for the first time in this study. We found that the p.A1050V mutation had a significant effect. However, we could not determine sufficient similarity due to the differences in nucleotide/amino acid sequences between two species. Nonetheless, possible variants of human sequences in the exact location as their dog counterparts are associated with several cancer types, implying that the variants could be crucial for tumorigenesis in dogs. Our results did not show any effect of the variants on tumor malignancy. CONCLUSIONS: The current project is the first study investigating the relationship between the PALB2 gene WD40 domain and CMTs. Our findings will contribute to a better understanding of the pathogenic mechanism of the PALB2 gene in CMTs. In humans, variant positions in canines have been linked to cancer-related phenotypes such as familial BC, endometrial tumor, and hereditary cancer predisposition syndrome. The results of bioinformatics analyses should be investigated through functional tests or case-control studies.

Clinical outcomes of the Myval transcatheter heart valve system in patients with severe aortic valve stenosis: a two-year follow-up observational study.

Introduction: Limited data exist on long-term follow-up of severe aortic stenosis (SAS) patients who have undergone transcatheter aortic valve implantation (TAVI) with a new generation, balloon expandable Myval transcatheter heart valve (THV). Thus, we sought to investigate the performance and 2-year clinical outcome of the Myval THV system based on Valve Academic Research Consortium-3 (VARC-3) criteria. Material and methods: A multi-centre, registry-based, observational study was conducted, which included 207 consecutive degenerative SAS patients, from Turkey (n = 128), Italy (n = 58), and Greece (n = 21) (mean [standard deviation] 81 (7) years, 94 [45%] men; 73% NYHA III or IV; EuroSCORE II 5.2% [2.4%]); all patients underwent TAVI with Myval. Patients were followed up at 1 year and 2 years after implantation. Clinical and procedural outcomes were defined according to VARC-3 criteria. Results: Technical success was observed in 204 (99%), device success was observed in 189 (91%), early safety was observed in 161 (78%), and clinical efficacy was observed in 163 (79%) patients. The 30-day death rate was 7.7%; of these, 3.4% were due to cardiovascular reasons. All-cause and cardiovascular mortality rates were 9.7% and 4.3% at 1-year follow-up, and 17.4% and 9.7% at 2-year follow-up, respectively. Incidence of ≥ moderate paravalvular leak (PVL) at 30 days, 1 year and 2 years of follow-up were 3.4%, 4.3% and 4.8%. A total of 11.1% of patients required a permanent pacemaker implantation (PPI) at 30 days after implantation, while the cumulative rate of PPI at 2 years was 12.1%. Conclusions: In this cohort of patients with SAS, the Myval was found to be safe and effective in up to 2 years of follow-up.

A Variação Anormal da Pressão Arterial Circadiana está Associada aos Escores SYNTAX em Pacientes Hospitalizados com Síndrome Coronariana Aguda / Abnormal Circadian Blood Pressure Variation is Associated with SYNTAX Scores in Hospitalized Patients with Acute Coronary Syndrome

Resumo Fundamento Menor redução da pressão arterial (PA) noturna, conhecida como hipertensão não-dipper, é um forte preditor de morbimortalidade cardiovascular. Objetivos Este estudo visou investigar a relação entre a hipertensão não-dipper e a gravidade e complexidade da doença arterial coronariana usando o escore SYNTAX em pacientes hospitalizados com síndrome coronariana aguda. Métodos Foram selecionados 306 pacientes consecutivos com síndrome coronariana aguda. Pacientes clinicamente estáveis internados na unidade de terapia intensiva intermediária pelo menos 24 horas após a angiografia e/ou revascularização bem sucedida. Após os critérios de exclusão, foram incluídos 141 pacientes (34 mulheres e 107 homens; idade média 61 ± 11 anos). A hipertensão não-dipper foi definida como uma queda de 0% a 10% na PA sistólica média durante a noite em comparação com o dia, medida em intervalos de 1 hora, usando o mesmo dispositivo automático de medição de PA em monitores de beira de leito (Vismo PVM-2701; Nihon Kohden Corp., Tóquio, Japão). O escore SYNTAX foi calculado com uma calculadora online. Os preditores independentes do escore SYNTAX foram avaliados por meio de análise de regressão logística multivariada. P < 0,05 foi considerado estatisticamente significativo. Resultados Os pacientes com hipertensão não-dipper apresentaram escore SYNTAX maior do que os pacientes com hipertensão dipper (11,12 ± 6,41 versus 6,74 ± 6,45, p < 0,0001). Em um modelo de regressão logística multivariável, o status de hipertensão não dipper (odds ratio: 5,159; intervalo de confiança de 95%: 2,246 a 11,852, p < 0,001), sexo (p = 0,012) e colesterol de lipoproteína de baixa densidade (p = 0,008) emergiram como preditores independentes de alto escore SYNTAX. Conclusões Os resultados do nosso estudo fornecem um possível mecanismo adicional ligando o perfil anormal da PA circadiana à gravidade e à complexidade da doença arterial coronariana em pacientes com síndrome coronariana aguda.

Abstract Background Blunted nocturnal blood pressure (BP) reduction, referred to as non-dipper hypertension, is a strong predictor of cardiovascular morbidity and mortality. Objectives This study aimed to investigate the relationship between non-dipper hypertension and the severity and complexity of coronary artery disease using SYNTAX score in hospitalized patients with acute coronary syndrome. Methods A total of 306 consecutive patients with acute coronary syndrome were screened. Patients who were clinically stable and admitted to the intermediate intensive care unit at least 24 hours after angiography and/or successful revascularization. After the exclusion criteria, 141 patients (34 female and 107 male; mean age 61 ± 11 years) were included. Non-dipper hypertension has been defined as a 0% to 10% decrease in average systolic BP at nighttime compared to daytime, measured at hourly intervals using the same automatic BP measuring device on bedside monitors (Vismo PVM-2701; Nihon Kohden Corp., Tokyo, Japan). SYNTAX score was calculated with an online calculator. The independent predictors of SYNTAX score were assessed using multivariable logistic regression analysis. P < 0.05 was considered statistically significant. Results The patients with non-dipper hypertension had higher SYNTAX score than the patients with dipper hypertension (11.12 ± 6.41 versus 6.74 ± 6.45, p < 0.0001). In a multivariable logistic regression model, non-dipper hypertension status (odds ratio: 5.159; 95% confidence interval: 2.246 to 11.852, p < 0.001), sex (p = 0.012) and low-density lipoprotein cholesterol (p = 0.008) emerged as independent predictors of high SYNTAX score. Conclusions The results of our study provide a possible additional mechanism linking abnormal circadian BP profile with coronary artery disease severity and complexity in patients with acute coronary syndrome.

Bilateral subconjunctival hemorrhage secondary to abciximab use: case report

ABSTRACT CONTEXT: There are no reports on cases of subconjunctival hemorrhage due to use of glycoprotein IIb/IIIa inhibitors. In this report, we present the case of a patient with bilateral subconjunctival hemorrhage after receiving abciximab. CASE REPORT: A 40-year-old male patient underwent coronary angiography after acute anterior myocardial infarction and a coronary stent was placed. Abciximab was added to the therapy because of stent thrombosis. Bilateral subconjunctival hemorrhage was observed after the administration of the abciximab treatment. We treated our patient by stopping abciximab and administering artificial tears. CONCLUSİON: For the first time in the literature, we presented the case of a patient with bilateral subconjunctival hemorrhage after receiving abciximab, which was managed conservatively.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus / Onda Pressistólica Associada à Disfunção Ventricular Esquerda Subclínica e Avaliada com Base no Índice de Performance Miocárdica em Pacientes com Diabetes Mellitus Tipo 2

Abstract Background: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. Objective: To investigate the relationship between PSW and MPI in type 2 diabetic patients. Method: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. Results: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). Conclusion: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Resumo Fundamento: O índice de performance miocárdica (IPM) avalia as funções sistólica e diastólica do ventrículo esquerdo. A onda pressistólica (OPS) é geralmente detectada no exame Doppler da via de saída do ventrículo esquerdo e seus possíveis mecanismos são complacência prejudicada e rigidez do ventrículo esquerdo. Objetivo: Investigar a relação entre OPS e IPM em pacientes com diabetes tipo 2. Método: 129 pacientes com diabetes tipo 2 foram incluídos no estudo. Os sujeitos foram alocados em dois grupos, com base na presença de OPS no exame ecocardiográfico com Doppler. Foram incluídos 90 pacientes (38 homens, idade média 57,77 ± 10,91 anos) no grupo OPS-positiva e 39 pacientes (13 homens; idade média 55,31 ± 11,29 anos) no grupo OPS-negativa. Valor de p < 0,05 foi considerado para significância estatística. Resultados: O IPM foi mais alto no grupo OPS-positiva (0,63 ± 0,17 vs 0,52 ± 0,13, p < 0,001). Além disso, a disfunção ventricular esquerda subclínica (DVE) foi maior no grupo OPS-positiva (p = 0,029). Análise univariada mostrou associação de OPS com IPM anormal (p = 0,031), assim como o coeficiente de correlação de Pearson mostrou correlação entre velocidade de OPS e IPM (r: 0,286, p = 0,006). Conclusão: Presença de OPS na ecocardiografia com Doppler foi associada à DVE subclínica em pacientes com diabetes tipo 2. Esse exame ecocardiográfico de fácil execução pode ser relacionado à DVE subclínica entre pacientes com diabetes tipo 2.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus / Onda Pressistólica Associada à Disfunção Ventricular Esquerda Subclínica e Avaliada com Base no Índice de Performance Miocárdica em Pacientes com Diabetes Mellitus Tipo 2

Abstract Background: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. Objective: To investigate the relationship between PSW and MPI in type 2 diabetic patients. Method: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. Results: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). Conclusion: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Resumo Fundamento: O índice de performance miocárdica (IPM) avalia as funções sistólica e diastólica do ventrículo esquerdo. A onda pressistólica (OPS) é geralmente detectada no exame Doppler da via de saída do ventrículo esquerdo e seus possíveis mecanismos são complacência prejudicada e rigidez do ventrículo esquerdo. Objetivo: Investigar a relação entre OPS e IPM em pacientes com diabetes tipo 2. Método: 129 pacientes com diabetes tipo 2 foram incluídos no estudo. Os sujeitos foram alocados em dois grupos, com base na presença de OPS no exame ecocardiográfico com Doppler. Foram incluídos 90 pacientes (38 homens, idade média 57,77 ± 10,91 anos) no grupo OPS-positiva e 39 pacientes (13 homens; idade média 55,31 ± 11,29 anos) no grupo OPS-negativa. Valor de p < 0,05 foi considerado para significância estatística. Resultados: O IPM foi mais alto no grupo OPS-positiva (0,63 ± 0,17 vs 0,52 ± 0,13, p < 0,001). Além disso, a disfunção ventricular esquerda subclínica (DVE) foi maior no grupo OPS-positiva (p = 0,029). Análise univariada mostrou associação de OPS com IPM anormal (p = 0,031), assim como o coeficiente de correlação de Pearson mostrou correlação entre velocidade de OPS e IPM (r: 0,286, p = 0,006). Conclusão: Presença de OPS na ecocardiografia com Doppler foi associada à DVE subclínica em pacientes com diabetes tipo 2. Esse exame ecocardiográfico de fácil execução pode ser relacionado à DVE subclínica entre pacientes com diabetes tipo 2.