The Impact of Liquid Biopsy in Advanced Ovarian Cancer Care.

INTRODUCTION: Ovarian cancer is the third most common gynaecological cancer and has a very high mortality rate. The cornerstone of treatment is complete debulking surgery plus chemotherapy. Even with treatment, 80% of patients have a recurrence. Circulating tumour DNA (ctDNA) has been shown to be useful in the control and follow-up of some tumours. It could be an option to define complete cytoreduction and for the early diagnosis of recurrence. OBJECTIVE: We aimed to demonstrate the usefulness of ctDNA and cell-free DNA (cfDNA) as a marker of complete cytoreduction and during follow-up in patients with advanced ovarian cancer. MATERIAL AND METHODS: We selected 22 women diagnosed with advanced high-grade serous ovarian cancer, of which only 4 had complete records. We detected cfDNA by polymerase chain reaction (PCR), presented as ng/mL, and detected ctDNA with droplet digital PCR (ddPCR). We calculated Pearson correlation coefficients to evaluate correlations among cfDNA, ctDNA, and cancer antigen 125 (CA125), a biomarker. RESULTS: The results obtained in the evaluation of cfDNA and ctDNA and their correlation with tumour markers and the radiology of patients with complete follow-up show disease progression during the disease, stable disease, or signs of recurrence. cfDNA and ctDNA correlated significantly with CA125. Following cfDNA and ctDNA over time indicated a recurrence several months earlier than computed tomography and CA125 changes. CONCLUSION: An analysis of cfDNA and ctDNA offers a non-invasive clinical tool for monitoring the primary tumour to establish a complete cytoreduction and to diagnose recurrence early.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Relationship of DRD5 and MAO-B VNTR polymorphisms with paranoid and antisocial personality disorders in polydrug users.

Although multiple studies have shown the role genetics plays in personality disorders and in addictions, few have studied the genetic aspects of their comorbidity. Here, we carried out a cross-sectional study in a sample comprising 303 Caucasian polydrug-consuming patients. The presence of personality disorders was evaluated using the International Personality Disorder Examination, and genes related to dopamine, serotonin and monoamine oxidase (MAO) were genotyped. A significant relationship was observed between the bp 279 DRD5 variable number of tandem repeat (VNTR) polymorphism and paranoid personality disorder OR 95 % CI = 2.186 1.074 ; 4.449 ; p = 0.006 . The bp 182 OR 95 % CI = 0.407 0.178 ; 0.931 ; p = 0.033 and bp 184 OR 95 % CI = 0.391 0.188 ; 0.813 ; p = 0.012 alleles of the MAOB VNTR were also associated with antisocial personality disorder. Among patients with addictions, paranoid personality disorder should also be considered in addition to the importance of antisocial and borderline personality disorders. The higher frequency of the bp 279 DRD5 VNTR allele found in patients with paranoid personality disorder, as well as the associations between alleles of the MAOB VNTR and antisocial personality disorder, support the monoaminergic bases of these personality disorders, especially when dealing with patients with addictions.

Lithium as a Neuroprotective Agent for Bipolar Disorder: An Overview.

Lithium (Li+) is a first option treatment for adult acute episodes of Bipolar Disorder (BD) and for the prophylaxis of new depressed or manic episodes. It is also the preferred choice as maintenance treatment. Numerous studies have shown morphological abnormalities in the brains of BD patients, suggesting that this highly heritable disorder may exhibit progressive and deleterious changes in brain structure. Since treatment with Li+ ameliorates these abnormalities, it has been postulated that Li+ is a neuroprotective agent in the same way atypical antipsychotics are neuroprotective in patients diagnosed with schizophrenia spectrum disorders. Li+'s neuroprotective properties are related to its modulation of nerve growth factors, inflammation, mitochondrial function, oxidative stress, and programmed cell death mechanisms such as autophagy and apoptosis. Notwithstanding, it is not known whether Li+-induced neuroprotection is related to the inhibition of its putative molecular targets in a BD episode: the enzymes inositol-monophosphatase, (IMPase), glycogen-synthase-kinase 3ß (GSK3), and Protein kinase C (PKC). Furthermore, it is uncertain whether these neuroprotective mechanisms are correlated with Li+'s clinical efficacy in maintaining mood stability. It is expected that in a nearby future, precision medicine approaches will improve diagnosis and expand treatment options. This will certainly contribute to ameliorating the medical and economic burden created by this devastating mood disorder.

Prepulse Inhibition in Cocaine Addiction and Dual Pathologies.

Cocaine addiction is frequently associated with different psychiatric disorders, especially schizophrenia and antisocial personality disorder. A small number of studies have used prepulse inhibition (PPI) as a discriminating factor between these disorders. This work evaluated PPI and the phenotype of patients with cocaine-related disorder (CRD) who presented a dual diagnosis of schizophrenia or antisocial personality disorder. A total of 74 men aged 18-60 years were recruited for this research. The sample was divided into four groups: CRD (n = 14), CRD and schizophrenia (n = 21), CRD and antisocial personality disorder (n = 16), and a control group (n = 23). We evaluated the PPI and other possible vulnerability factors in these patients by using different assessment scales. PPI was higher in the CRD group at 30 ms (F(3, 64) = 2.972, p = 0.038). Three discriminant functions were obtained which allowed us to use the overall Hare Psychopathy Checklist Revised score, reward sensitivity, and PPI at 30 ms to predict inclusion of these patients in the different groups with a success rate of 79.7% (42.9% for CRD, 76.2% for CRD and schizophrenia, 100% for CRD and antisocial personality disorder, and 91.3% in the control group). Despite the differences we observed in PPI, this factor is of little use for discriminating between the different diagnostic groups and it acts more as a non-specific endophenotype in certain mental disorders, such as in patients with a dual diagnosis.

The role of nicotinic cholinergic neurotransmission in delusional thinking.

Delusions are a difficult-to-treat and intellectually fascinating aspect of many psychiatric illnesses. Although scientific progress on this complex topic has been challenging, some recent advances focus on dysfunction in neural circuits, specifically in those involving dopaminergic and glutamatergic neurotransmission. Here we review the role of cholinergic neurotransmission in delusions, with a focus on nicotinic receptors, which are known to play a part in some illnesses where these symptoms appear, including delirium, schizophrenia spectrum disorders, bipolar disorder, Parkinson, Huntington, and Alzheimer diseases. Beginning with what we know about the emergence of delusions in these illnesses, we advance a hypothesis of cholinergic disturbance in the dorsal striatum where nicotinic receptors are operative. Striosomes are proposed to play a central role in the formation of delusions. This hypothesis is consistent with our current knowledge about the mechanism of action of cholinergic drugs and with our abstract models of basic cognitive mechanisms at the molecular and circuit levels. We conclude by pointing out the need for further research both at the clinical and translational levels.

Comportamiento de la mortalidad por cáncer cervicouterino en el municipio de Rafael Freyre: 1997-2014 / Behavior of Mortality from Cervical Cancer in the Municipality of Rafael Freyre: 1997-2014

Introducción: el cáncer cervicouterino persiste como un problema de salud no resuelto a nivel mundial; después del cáncer de mama, es el más frecuente en el sexo femenino y ocupa el séptimo lugar entre todas las neoplasias malignas que afectan a ambos sexos. Objetivo: describir el comportamiento de la mortalidad por cáncer cervicouterino en el municipio de Rafael Freyre entre 1997 y 2014. Método: se realizó un estudio de mortalidad con las 56 fallecidas reportadas por esa causa en el municipio y períodos referidos. Como fuente de datos se utilizó el reporte mensual computarizado que envía el Departamento de Estadísticas provincial de los fallecidos a cada municipio. Resultados: la tasa media anual de mortalidad en el municipio fue de 12,3 x 100 000 mujeres; los grupos de edades más afectados son los de 70-74 y 80 y más, con tasas de 62,5 y 60,0, respectivamente. Las áreas geográficas de mayor riesgo epidemiológico de fallecer las mujeres por esta causa fueron el Área de Salud de Santa Lucía y los consejos populares de "Carlos Noris", Dagame y Santa Lucía, con tasas de mortalidad de 23,5; 21,5 y 19,5, respectivamente. Conclusiones: este problema de salud tiene una tendencia descendente en el municipio, pero la tasa de mortalidad media anual supera la tasa provincial y la nacional.

Introduction: cervical cancer persists as an unresolved health problem worldwide; after breast cancer, it is the most frequent in females and ranks seventh among all malignant neoplasms affecting both sexes. Objective: to describe the behavior of cervical cancer mortality in the municipality of Rafael Freyre among the years 1997-2014. Methods: a mortality study was carried out, as universe was chosen the 56 deceaseds reported by that cause in the municipality at referred periods, as a source of data was used the monthly report of death on-line that sends the provincial department of health in Holguin. Results: the annual half rate of mortality in the Municipality was 12.3 x 100 000 women, the groups of ages more affected were 70-74 years and 80 and but, with rates of 62.5 and 60.0 respectively. The geographical areas of more epidemic risk of dying the women for this cause were, the Area of Health of "Santa Lucía" and popular Council of "Carlos Noris", "Dagame" and "Santa Lucía" with rates of mortality of 23.5, 21.5 and 19.5 respectively. Conclusions: this problem of health has a descending tendency in the municipality, but the rate half annual of mortality overcomes the provincial and national rate.

Lack of cytomegalovirus detection in human glioma.

Gliomas are the most common brain tumors and include a variety of histologic types and grades of malignancy. They arise from glial cells and represent approximately 70% of the primary brain tumors. According to the criteria of the World Health Organization (WHO), the majority of gliomas can be classified into four grades of malignancy (I-IV). Virus infection, especially by DNA viruses and retroviruses, which may cause insertion of viral DNA sequences into the host genome, often triggers the host defense mechanisms. Particularly, the DNA methylation machinery can be activated to cause the methylation of foreign movable viral sequences and, therefore, silence viral gene expression. Several studies have shown the presence of Human Cytomegalovirus (HCMV) in glioblastoma, suggesting that the virus may participate in tumor pathogenesis. But this relationship is controversial because many other studies did not detect HCMV in these tumors. This study aims to detect the presence of HCMV in several samples of human glioma (94 formalin-fixed, paraffin-embedded samples and 28 snap-frozen samples) by different sensitive techniques. We have been unable to detect HCMV DNA and proteins in glioma samples. Therefore, arguments used so far to conclude that HCMV is an oncomodulator virus in gliomas must be, in our view, seriously reconsidered.

Comportamiento de la mortalidad por cáncer cervicouterino en el municipio de Rafael Freyre: 1997-2014 / Behavior of Mortality from Cervical Cancer in the Municipality of Rafael Freyre: 1997-2014

Introducción: el cáncer cervicouterino persiste como un problema de salud no resuelto a nivel mundial; después del cáncer de mama, es el más frecuente en el sexo femenino y ocupa el séptimo lugar entre todas las neoplasias malignas que afectan a ambos sexos.Objetivo: describir el comportamiento de la mortalidad por cáncer cervicouterino en el municipio de Rafael Freyre entre 1997 y 2014. Método: se realizó un estudio de mortalidad con las 56 fallecidas reportadas por esa causa en el municipio y períodos referidos. Como fuente de datos se utilizó el reporte mensual computarizado que envía el Departamento de Estadísticas provincial de los fallecidos a cada municipio. Resultados: la tasa media anual de mortalidad en el municipio fue de 12,3 x 100 000 mujeres; los grupos de edades más afectados son los de 70-74 y 80 y más, con tasas de 62,5 y 60,0, respectivamente. Las áreas geográficas de mayor riesgo epidemiológico de fallecer las mujeres por esta causa fueron el Área de Salud de Santa Lucía y los consejos populares de “Carlos Noris”, Dagame y Santa Lucía, con tasas de mortalidad de 23,5; 21,5 y 19,5, respectivamente. Conclusiones: este problema de salud tiene una tendencia descendente en el municipio, pero la tasa de mortalidad media anual supera la tasa provincial y la nacional.(AU)

Introduction: cervical cancer persists as an unresolved health problem worldwide; after breast cancer, it is the most frequent in females and ranks seventh among all malignant neoplasms affecting both sexes.Objective: to describe the behavior of cervical cancer mortality in the municipality of Rafael Freyre among the years 1997-2014. Methods: a mortality study was carried out, as universe was chosen the 56 deceaseds reported by that cause in the municipality at referred periods, as a source of data was used the monthly report of death on-line that sends the provincial department of health in Holguin.Results: the annual half rate of mortality in the Municipality was 12.3 x 100 000 women, the groups of ages more affected were 70-74 years and 80 and but, with rates of 62.5 and 60.0 respectively. The geographical areas of more epidemic risk of dying the women for this cause were, the Area of Health of “Santa Lucía” and popular Council of “Carlos Noris", "Dagame" and “Santa Lucía” with rates of mortality of 23.5, 21.5 and 19.5 respectively.Conclusions: this problem of health has a descending tendency in the municipality, but the rate half annual of mortality overcomes the provincial and national rate.(AU)

Streptococcus gallolyticus infection in colorectal cancer and association with biological and clinical factors.

There is an unambiguous association of Streptococcus gallolyticus infection with colorectal cancer, although there is limited information about epidemiology or interaction between molecular and environmental factors. We performed an original quantitative analysis of S. gallolyticus in unselected colorectal cancer patients (n = 190) and their association with clinical, pathological tumor molecular profiles (microsatellite instability, hypermethylator phenotype and chromosomal instability pathways), and other biological factors in colorectal tumor and normal tissues (cytomegalovirus and Epstein-Barr virus infection). We developed a new quantitative method to assess bacterial load. Analytical validation was reached with a very high sensitivity and specificity. Our results showed a 3.2% prevalence of S. gallolyticus infection in our unselected cohort of colorectal cancer cases (6/190). The average S. gallolyticus copy number was 7,018 (range 44-34,585). No previous reports relating to S. gallolyticus infection have been published for unselected cohorts of patients. Finally, and despite a low prevalence of S. gallolyticus in this study, we were able to define a specific association with tumor tissue (p = 0.03) and with coinfection with Epstein-Barr virus (p = 0.042; OR: 9.49; 95% IC: 1.1-82.9). The prevalence data provided will be very useful in the design of future studies, and will make it possible to estimate the sample size needed to assess precise objectives. In conclusion, our results show a low prevalence of S. gallolyticus infection in unselected colorectal cancer patients and an association of positive S. gallolyticus infection with tumor tissue and Epstein-Barr virus coinfection. Further studies will be needed to definitively assess the prevalence of S. gallolyticus in colorectal cancer and the associated clinicopathological and molecular profiles.