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1.
Psychother Psychosom ; 93(2): 94-99, 2024.
Article En | MEDLINE | ID: mdl-38382481

Clinical interviewing is the basic method to understand how a person feels and what are the presenting complaints, obtain medical history, evaluate personal attitudes and behavior related to health and disease, give the patient information about diagnosis, prognosis, and treatment, and establish a bond between patient and physician that is crucial for shared decision making and self-management. However, the value of this basic skill is threatened by time pressures and emphasis on technology. Current health care trends privilege expensive tests and procedures and tag the time devoted to interaction with the patient as lacking cost-effectiveness. Instead, the time spent to inquire about problems and life setting may actually help to avoid further testing, procedures, and referrals. Moreover, the dialogue between patient and physician is an essential instrument to increase patient's motivation to engage in healthy behavior. The aim of this paper was to provide an overview of clinical interviewing and its optimal use in relation to style, flow and hypothesis testing, clinical domains, modifications according to settings and goals, and teaching. This review points to the primacy of interviewing in the clinical process. The quality of interviewing determines the quality of data that are collected and, eventually, of assessment and treatment. Thus, interviewing deserves more attention in educational training and more space in clinical encounters than it is currently receiving.


Motivation , Motivational Interviewing , Humans
2.
Crit Pathw Cardiol ; 22(4): 141-145, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-37535848

BACKGROUND: There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5-2% of the general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF. MATERIALS AND METHODS: This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months. RESULTS: Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an [area under the curve, 0.69; 95% confidence intervals (CI), 0.59-0.79] and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF. CONCLUSIONS: The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.


Atrial Fibrillation , Hypertension , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Longitudinal Studies , Pandemics , Risk Factors , Electrocardiography , Predictive Value of Tests , Hypertension/diagnosis , Hypertension/epidemiology
3.
Eur J Med Chem ; 251: 115245, 2023 May 05.
Article En | MEDLINE | ID: mdl-36905916

Protein phosphatase 2A (PP2A) is an important Ser/Thr phosphatase that participates in the regulation of multiple cellular processes. This implies that any deficient activity of PP2A is the responsible of severe pathologies. For instance, one of the main histopathological features of Alzheimer's disease is neurofibrillary tangles, which are mainly comprised by hyperphosphorylated forms of tau protein. This altered rate of tau phosphorylation has been correlated with PP2A depression AD patients. With the goal of preventing PP2A inactivation in neurodegeneration scenarios, we have aimed to design, synthesize and evaluate new ligands of PP2A capable of preventing its inhibition. To achieve this goal, the new PP2A ligands present structural similarities with the central fragment C19-C27 of the well-established PP2A inhibitor okadaic acid (OA). Indeed, this central moiety of OA does not exert inhibitory actions. Hence, these compounds lack PP2A-inhibiting structural motifs but, in contrast, compete with PP2A inhibitors, thus recovering phosphatase activity. Proving this hypothesis, most compounds showed a good neuroprotective profile in neurodegeneration models related to PP2A impairment, highlighting derivative 10, named ITH12711, as the most promising one. This compound (1) restored in vitro and cellular PP2A catalytic activity, measured on a phospho-peptide substrate and by western-blot analyses, (2) proved good brain penetration measured by PAMPA, and (3) prevented LPS-induced memory impairment of mice in the object recognition test. Thus, the promising outcomes of the compound 10 validate our rational approach to design new PP2A-activating drugs based on OA central fragment.


Alzheimer Disease , Tauopathies , Mice , Animals , Alzheimer Disease/metabolism , Okadaic Acid/pharmacology , Okadaic Acid/metabolism , Neuroprotection , Tauopathies/drug therapy , Tauopathies/metabolism , tau Proteins/metabolism , Protein Phosphatase 2/metabolism , Phosphorylation
4.
Clin Neuropsychiatry ; 20(6): 495-504, 2023 Dec.
Article En | MEDLINE | ID: mdl-38344466

Objective: A significant body of research has suggested that the contraction of SARS-CoV-2 may cause memory impairment, even in the months following recovery. In this regard, studies suggest that COVID-19 predominantly targets structures and cortices within the temporal lobe, and the hippocampus, a critical brain structure for memory and spatial navigation.The purpose of this study was to investigate the potential impact of the COVID-19 pandemic on subjective memory complaints, which represent an individual's perception of subtle changes in memory in the absence of an objective memory impairment. Method: to explore how the COVID-19 pandemic may affect subjective memory complaints, we incorporated ad hoc self-reported measures of subjective memory complaints, the "Subjective Memory Complaints Questionnaire" (SMCQ) and the "Prospective and Retrospective Memory Questionnaire" (PRMQ), in our cross-sectional study. Both measures referred to two periods: the pre-pandemic period (T0) and the moment of survey administration (T1) (December 28th, 2021, to February 6th, 2022). Results: 207 Italian participants accessed the survey, out of which 189 participants were included in the final sample. The majority of the participants were females, and their age ranged from 55 to 65 years. The study revealed a significant increase in the total PRMQ score at T1 compared to T0 (p = 0.02). However, no significant differences were found between PRMQ and SMCQ scores of COVID-19-negative individuals and those who tested positive for COVID-19 in the last 12 months from the date of completing the survey. McNemar's test showed a statistically significant increase in the score of item 1 ("Do you think that you have a memory problem?" (p = 0.016) and item 10 ("Do you lose objects more often than you did previously") (0.019) of the SMCQ, while for the PRMQ, significant increases were found in several individual items. Conclusions: our study suggests that subjective memory complaints increased during the pandemic, potentially due to the compound effects of stress and social isolation, rather than solely due to COVID-19 infection. Although a marginal association between COVID-19 and reported prospective memory issues was detected, further investigation is warranted to understand its persistent effects.

5.
Article Es | LILACS-Express | LILACS | ID: biblio-1410063

RESUMEN Introducción: las enfermedades cardiovasculares están entre las primeras causas de muerte en todo el mundo. Esta prevalencia podría explicarse por múltiples factores de riesgo. Objetivo: determinar la frecuencia de factores de riesgo cardiovascular en médicos jóvenes del Hospital de Clínicas, San Lorenzo, Paraguay. Material y método: se aplicó un diseño observacional, descriptivo, retrospectivo, de corte transversal, con muestreo no probabilístico. Se incluyó a 175 médicos jóvenes entre 22 y 45 años de edad, de ambos sexos, del Hospital de Clínicas en el año 2020. Se midieron las variables demográficas (edad, sexo, estado civil, especialidad), medidas antropométricas (peso y talla), factores de riesgo cardiovascular (hipertensión arterial, diabetes mellitus tipo 2, antecedente patológico familiar de enfermedad cardiovascular), hábitos tóxicos (alcohol y/o tabaco), comportamiento sedentario, dislipidemia, horario laboral (diurno, nocturno o ambos y horas laborales de trabajo). Se calculó el índice de masa corporal. Resultados: el promedio de edad fue 30 ± 3 años. Fue constatada predominancia del sexo masculino con más de la mitad de participantes (50,8%). El factor de riesgo cardiovascular más frecuente fue el antecedente de enfermedad cardiovascular (89,1%), la prevalencia de los demás factores de riesgo cardiovascular fueron el comportamiento etilista (56,5%), comportamiento sedentario (54,5%), pre obesidad y obesidad (49,5%), dislipidemia (17,1%), tabaquismo (10,2%), hipertensión arterial (5,1%), diabetes mellitus tipo 2 (0,5%) y la enfermedad renal crónica (0,5%). Conclusión: la frecuencia de factores de riesgo cardiovascular en médicos jóvenes del Hospital de Clínicas fue alta, predominando el antecedente familiar de enfermedad cardiovascular, el comportamiento etilista, el comportamiento sedentario y a pre obesidad y obesidad.


ABSTRACT Introduction: Cardiovascular diseases are among the leading causes of death worldwide. This prevalence could be explained by multiple risk factors. Objective: To determine the frequency of cardiovascular risk factors in young physicians of the Hospital de Clínicas, San Lorenzo, Paraguay. Material and method: An observational, descriptive, retrospective, cross-sectional design was applied, with non-probabilistic sampling. One hundred seventy-five young male and female physicians between 22 and 45 years of age, from the Hospital de Clínicas were included in 2020. Demographic variables (age, sex, marital status, specialty), anthropometric measurements (weight and height), cardiovascular risk factors (hypertension, type 2 diabetes mellitus, family pathological history of cardiovascular disease), toxic habits (alcohol and/or tobacco), sedentary behavior, dyslipidemia, working hours (daytime, nighttime or both, and working hours). Body mass index was calculated. Results: The average age was 30±3 years. A predominance of male sex was verified with more than half of the participants (50.8%). The most frequent cardiovascular risk factor was a history of cardiovascular disease (89.1%), the prevalence of the other cardiovascular risk factors was drinking behavior (56.5%), sedentary behavior (54.5%), pre-obesity and obesity (49.5%), dyslipidemia (17.1%), smoking (10.2%), arterial hypertension (5.1%), type 2 diabetes mellitus (0.5%) and chronic kidney disease (0.5%). Conclusion: The frequency of cardiovascular risk factors in young physicians of the Hospital de Clínicas was high, with a predominance of family history of cardiovascular disease, drinking behavior, sedentary behavior, and pre-obesity and obesity.

6.
Front Pain Res (Lausanne) ; 3: 928985, 2022.
Article En | MEDLINE | ID: mdl-35910263

Psychological acceptance has emerged as an important construct to explain low psychological distress in different clinical samples. However, the incremental validity of psychological acceptance to explain adjustment to medical conditions over other related and well-established constructs, such as coping, is relatively unclear. This study explored whether psychological acceptance significantly contributes to explain adjustment above and beyond coping in females with endometriosis. A total of 169 females (M age = 34.95 years; SD age = 6.07 years) with endometriosis and pain symptoms completed the Acceptance and Action Questionnaire-II, the Brief-COPE, the Hospital Anxiety and Depression Scale, the Psychological Wellbeing Scale, and the Endometriosis Health Profile-5. We conducted Hierarchical Regression Analyses to determine the contribution of psychological acceptance to explaining adjustment. The results showed that the contribution of psychological acceptance ranged from 11 to 20% when controlling for coping, while coping explained from 1 to 8% when the model was reversed. The findings suggest that psychological acceptance is a more useful construct than coping for predicting PD and other psychological outcomes in females with endometriosis.

7.
J Affect Disord ; 311: 276-283, 2022 08 15.
Article En | MEDLINE | ID: mdl-35609763

BACKGROUND: The assessment of psychological well-being and euthymia represents an emerging issue in clinical psychology and psychiatry. Rating scales and indices such as the 5-item version of the World Health Organization Well-Being Index (WHO-5) and the Euthymia Scale (ES) were developed but insufficient attention has been devoted to the evaluation of their cross-cultural validity. This is the first study using Clinimetric Patient-Reported Outcome Measures (CLIPROM) criteria to assess cross-cultural validity and sensitivity of five different versions of the WHO-5 and ES. METHODS: A multicenter cross-sectional study involving a total of 3762 adult participants from different European (i.e., Italy, Poland, Denmark) and non-European (i.e., China, Japan) countries was conducted. Item Response Theory models (Mokken and Rasch analyses) were applied. RESULTS: Mokken coefficients of scalability were found to range from 0.42 to 0.84. The majority of the versions of the WHO-5 fitted the Rasch model expectations. Paired t-tests revealed that the Italian and Danish WHO-5 versions were unidimensional. Person Separation Reliability indices showed that the Polish, Danish, and Japanese ES versions could reliably discriminate between subjects with different levels of euthymia. LIMITATIONS: A convenience sampling was used, thus limiting the generalizability of study findings. In addition, no measures of negative mental health were administered. CONCLUSIONS: WHO-5 can be used in international studies for cross-cultural comparisons since it covers transcultural components of subjective well-being. Findings also suggest that the ES can be used as a cross-cultural screening tool since it entailed the clinimetric property of sensitivity.


Cross-Cultural Comparison , Adult , Cross-Sectional Studies , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , World Health Organization
8.
Psychother Psychosom ; 90(4): 222-232, 2021.
Article En | MEDLINE | ID: mdl-34038901

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients' subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini-metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.


Patient Reported Outcome Measures , Humans , Psychometrics , Reproducibility of Results
9.
Article Es | LILACS-Express | LILACS | ID: biblio-1390256

RESUMEN Introducción: las infecciones transmisibles por transfusión constituyen una complicación, ocasionando morbilidad y mortalidad en los receptores de sangre y derivados. Objetivo: determinar la prevalencia de serologías reactivas y la asociación con las características sociodemográficas de los donantes del Banco Sangre del Hospital de Clínicas de San Lorenzo, en el año 2018. Material y método: diseño observacional, descriptivo, retrospectivo, de corte transversal, con muestreo no probabilístico de casos consecutivos. Se incluyó a donantes del Banco de Sangre del Hospital de Clínicas del periodo de enero a diciembre del 2018. Se midieron las variables demográficas (edad y sexo), la presencia o ausencia de serologías reactivas para hepatitis B y C, VIH, enfermedad de Chagas, HTLV I-II y Treponema pallidum. Resultados: la prevalencia global de las serologías reactivas en donantes fue 2,78%. De los 278 donantes incluidos en el estudio, 66,91% fueron masculinos, la media de edad fue 40,89 ± 11 años. Las serologías positivas más frecuentes fueron: hepatitis B 53,96%, enfermedad de Chagas 34,89% y sífilis 20,14%. Existe asociación entre sexo femenino y hepatitis C (p 0,001), procedencia del donante y serología positiva para enfermedad de Chagas, (p 0,005), para hepatitis C (p 0,001) y para Treponema pallidum (p 0,04). Conclusión: las serologías reactivas en donantes del Banco de Sangre del Hospital de Clínicas fue 2,78%. Las más prevalentes fueron para hepatitis B, enfermedad de Chagas y Treponema pallidum. Éstas están asociadas a variables sociodemográficas.


ABSTRACT Introduction: Transfusion-transmissible infections are a complication, causing morbidity and mortality in blood and blood derivatives recipients. Objective: To determine the prevalence of reactive serologies and the association with the sociodemographic characteristics of the donors of the Blood Bank of the Hospital de Clínicas from San Lorenzo, in 2018. Material and method: Observational, descriptive, retrospective, cross-sectional design, with non-probabilistic sampling of consecutive cases. Donors from the Blood Bank of the Hospital de Clínicas were included from January to December 2018. Demographic variables (age and sex), the presence or absence of reactive serologies for hepatitis B and C, HIV, Chagas disease, HTLV I-II and Treponema pallidum were measured. Results: The global prevalence of reactive serologies in donors was 2.78%. Of the 278 donors included in the study, 66.91% were male, the mean age was 40.89±11 years. The most frequent positive serologies were: hepatitis B 53.96%, Chagas disease 34.89% and syphilis 20.14%. There was an association between female sex and hepatitis C (p 0.001), donor origin and positive serology for Chagas disease (p 0.005), hepatitis C (p 0.001) and Treponema pallidum (p 0.04). Conclusion: Reactive serologies in donors from the Hospital de Clínicas Blood Bank was 2.78%. The most prevalent ones were hepatitis B, Chagas disease and Treponema pallidum and were associated with sociodemographic variables.

10.
J Biol Chem ; 296: 100341, 2021.
Article En | MEDLINE | ID: mdl-33515545

Gene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evolution although they have very few known functions. Here we examine the brain function of one of these genes (CHRFAM7A) and its product (dupα7 subunit). This gene results from a partial duplication of the ancestral CHRNA7 gene encoding the α7 subunit that forms the homopentameric α7 nicotinic acetylcholine receptor (α7-nAChR). The functions of α7-nAChR in the brain are well defined, including the modulation of synaptic transmission and plasticity underlying normal attention, cognition, learning, and memory processes. However, the role of the dupα7 subunit remains unexplored at the neuronal level. Here, we characterize that role by combining immunoblotting, quantitative RT-PCR and FRET techniques with functional assays of α7-nAChR activity using human neuroblastoma SH-SY5Y cell variants with different dupα7 expression levels. Our findings reveal a physical interaction between dupα7 and α7 subunits in fluorescent protein-tagged dupα7/α7 transfected cells that negatively affects normal α7-nAChR activity. Specifically, in both single cells and cell populations, the [Ca2+]i signal and the exocytotic response induced by selective stimulation of α7-nAChR were either significantly inhibited by stable dupα7 overexpression or augmented after silencing dupα7 gene expression with specific siRNAs. These findings identify a new role for the dupα7 subunit as a negative regulator of α7-nAChR-mediated control of exocytotic neurotransmitter release. If this effect is excessive, it would result in an impaired synaptic transmission that could underlie the neurocognitive and neuropsychiatric disorders associated with α7-nAChR dysfunction.


Neurons/metabolism , Neurotransmitter Agents/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Calcium Signaling , Cell Line, Tumor , Exocytosis , Humans , Receptors, Nicotinic/genetics , Receptors, Nicotinic/metabolism , Up-Regulation , alpha7 Nicotinic Acetylcholine Receptor/genetics
11.
Bioorg Chem ; 100: 103874, 2020 07.
Article En | MEDLINE | ID: mdl-32361056

We herein report the design, synthesis, and functional impact of an okadaic acid (OA) small analogue, ITH12680, which restores the activity of phosphoprotein phosphatase 2A (PP2A), whose deficient activity has been implicated in nicotine-mediated tumor progression and chemoresistance in non-small cell lung cancer (NSCLC). For its design, we paid attention to the structure of the PP2A-OA complex, where the C16-C38 OA fragment confers PP2A affinity and selectivity, but it is not involved in the inhibitory effect. Confirming this hypothesis, PP2A activity was not inhibited by ITH12680. By contrast, the compound partially restored OA-exerted PP2A inhibition in vitro. Moreover, flow cytometry and immunoblotting experiments revealed that ITH12680 reversed nicotine-induced cisplatin resistance in NSCLC cells, as it prevented nicotine-induced reduction of Bax expression and inhibited nicotine-mediated activation of cell survival and proliferation kinases, Akt and ERK1/2. Our findings suggest that the rescue of nicotine-inhibited PP2A activity could diminish the resistance to cisplatin treatment observed in NSCLC patients who continue smoking.


Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Lung Neoplasms/drug therapy , Okadaic Acid/pharmacology , Protein Phosphatase 2/metabolism , A549 Cells , Carcinoma, Non-Small-Cell Lung/metabolism , Enzyme Activation/drug effects , Humans , Lung Neoplasms/metabolism , Models, Molecular , Molecular Docking Simulation , Nicotine/adverse effects , Okadaic Acid/analogs & derivatives
13.
Lung Cancer ; 128: 134-144, 2019 02.
Article En | MEDLINE | ID: mdl-30642446

OBJECTIVES: Tobacco smoking is strongly correlated with the onset and progression of non-small cell lung cancer (NSCLC). By activating α7 nicotinic acetylcholine receptors (α7-nAChRs) in these tumors nicotine and its tobacco-derived nitrosamine, NNK, contribute to these oncogenic processes. Here, we investigated whether the human-specific duplicated form of the α7-nAChR subunit (dupα7) behaves as an endogenous negative regulator of α7-nAChR-mediated tumorigenic activity induced by tobacco in NSCLC cells, similarly to its influence on other α7-nAChR-controlled functions in non-tumor cells. METHODS: Two human NSCLC cell lines, lung adenocarcinoma (A549) and squamous cell carcinoma of the lung (SK-MES-1), both wild-type or with stable overexpression of dupα7 (A549dupα7 or SK-MES-1dupα7), were used to investigate in vitro anti-tumor activity of dupα7 on nicotine- or NNK-induced tumor progression. For this purpose, migration, proliferation or epithelial-mesenchymal transition (EMT) were examined. The anti-tumor effect of dupα7 on nicotine-promoted tumor growth, proliferation or angiogenesis was also assessed in vivo in an athymic mouse model implanted with A549dupα7 or A549 xenografts. RESULTS: Overexpression of dupα7 in both cell lines almost completely suppresses the in vitro tumor-promoting effects induced by nicotine (1 µM) or NNK (100 nM) in wild-type cells. Furthermore, in mice receiving nicotine, A549dupα7 xenografts show: (i) a significant reduction of tumor growth, and (ii) decreased expression of cell markers for proliferation (Ki67) or angiogenesis (VEGF) compared to A549 xenografts. CONCLUSION: Our study demonstrates, for the first time, the in vitro and in vivo anti-tumor capacity of dupα7 to block the α7-nAChR-mediated tumorigenic effects of tobacco in NSCLC, suggesting that up-regulation of dupα7 expression in these tumors could offer a potential new therapeutic target in smoking-related cancers.


Gene Duplication , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Smoking/adverse effects , alpha7 Nicotinic Acetylcholine Receptor/genetics , Animals , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Disease Models, Animal , Disease Progression , Disease Susceptibility , Epithelial-Mesenchymal Transition/genetics , Gene Expression , Heterografts , Humans , Mice , alpha7 Nicotinic Acetylcholine Receptor/metabolism
14.
J Biol Chem ; 293(36): 13874-13888, 2018 09 07.
Article En | MEDLINE | ID: mdl-30006348

The α7 nicotinic receptor subunit and its partially duplicated human-specific dupα7 isoform are coexpressed in neuronal and non-neuronal cells. In these cells, α7 subunits form homopentameric α7 nicotinic acetylcholine receptors (α7-nAChRs) implicated in numerous pathologies. In immune cells, α7-nAChRs are essential for vagal control of inflammatory response in sepsis. Recent studies show that the dupα7 subunit is a dominant-negative regulator of α7-nAChR activity in Xenopus oocytes. However, its biological significance in mammalian cells, particularly immune cells, remains unexplored, as the duplicated form is indistinguishable from the original subunit in standard tests. Here, using immunocytochemistry, confocal microscopy, coimmunoprecipitation, FRET, flow cytometry, and ELISA, we addressed this challenge in GH4C1 rat pituitary cells and RAW264.7 murine macrophages transfected with epitope- and fluorescent protein-tagged α7 or dupα7. We used quantitative RT-PCR of dupα7 gene expression levels in peripheral blood mononuclear cells (PBMCs) from patients with sepsis to analyze its relationship with PBMC α7 mRNA levels and with serum concentrations of inflammatory markers. We found that a physical interaction between dupα7 and α7 subunits in both cell lines generates heteromeric nAChRs that remain mainly trapped in the endoplasmic reticulum. The dupα7 sequestration of α7 subunits reduced membrane expression of functional α7-nAChRs, attenuating their anti-inflammatory capacity in lipopolysaccharide-stimulated macrophages. Moreover, the PBMC's dupα7 levels correlated inversely with their α7 levels and directly with the magnitude of the patients' inflammatory state. These results indicate that dupα7 probably reduces human vagal anti-inflammatory responses and suggest its involvement in other α7-nAChR-mediated pathophysiological processes.


Inflammation/physiopathology , Protein Isoforms/metabolism , Sepsis/pathology , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Animals , Cell Line , Endoplasmic Reticulum/metabolism , Humans , Macrophages , Mice , Pituitary Gland/cytology , Protein Isoforms/analysis , Protein Isoforms/genetics , RNA, Messenger/analysis , Rats , Sepsis/metabolism , Transfection , alpha7 Nicotinic Acetylcholine Receptor/analysis , alpha7 Nicotinic Acetylcholine Receptor/genetics
15.
Oncotarget ; 8(40): 67878-67890, 2017 Sep 15.
Article En | MEDLINE | ID: mdl-28978081

Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, ß4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and under-representation of cancer-inhibiting α4ß2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type.

16.
Article Es | LILACS-Express | LILACS | ID: biblio-1390112

Se presentan dos casos de actinomicosis abdominal relacionada a dispositivo intrauterino de 12 y 13 años de uso, sin seguimiento ginecológico, que se presentaron como abdomen agudo quirúrgico no sospechándose el origen bacteriológico en primera instancia.


These are two cases of abdominal actinomycosis associated to intrauterine devices that were used for 12 and 13 years respectively, without gynecological follow-up. The two cases presented as surgical acute abdomen without suspicion of the bacteriological origin at the beginning.

17.
Psicothema (Oviedo) ; 28(3): 266-271, ago. 2016. tab
Article En | IBECS | ID: ibc-154621

BACKGROUND: This study explored the contribution of Psychological Flexibility (PF) to predict adjustment to breast cancer. METHOD: Sixty-four females with breast cancer completed self-report measures of PF and adjustment (anxiety, depression, negative and positive affect) at baseline, and forty-two patients returned for assessment six months later. RESULTS: Higher flexibility at baseline significantly contributed to predict lower anxiety, depression and negative affect at follow-up. The effect sizes ranged from moderate to large. CONCLUSIONS: Results provide evidence for targeting PF to prevent enhanced psychological distress in patients with breast cancer, and add to a growing body of research supporting PF as a common protective factor across different contexts and populations


ANTECEDENTES: este estudio explora el grado de contribución de la Flexibilidad Psicológica (FP) en el pronóstico de diversos indicadores de adaptación al cáncer de mama. MÉTODO: 64 mujeres con cáncer de mama completaron medidas de FP, ansiedad, depresión, afecto negativo y positivo en un primer momento (T1), y 42 de ellas repitieron la evaluación seis meses después (T2). RESULTADOS: los resultados indican que la FP en T1 contribuye significativamente en la predicción de ansiedad, depresión y afecto negativo en T2, con tamaños del efecto que oscilan entre moderado y grande. Elevados niveles de FP se asocian significativamente con niveles más bajos de distrés psicológico. CONCLUSIONES: los resultados apoyan que la FP es un factor protector de niveles excesivos de distrés en pacientes con cáncer de mama. Estos resultados se suman al creciente cuerpo de evidencias que sugiere que la FP es un factor general de protección de la salud mental, transversal a diferentes contextos y poblaciones


Humans , Female , Breast Neoplasms/psychology , Adaptation, Psychological , Emotional Adjustment , Stress, Psychological/psychology , Anxiety/psychology , Depression/psychology
18.
Psicothema ; 28(3): 266-71, 2016 Aug.
Article En | MEDLINE | ID: mdl-27448259

BACKGROUND: This study explored the contribution of Psychological Flexibility (PF) to predict adjustment to breast cancer. METHOD: Sixty-four females with breast cancer completed self-report measures of PF and adjustment (anxiety, depression, negative and positive affect) at baseline, and forty-two patients returned for assessment six months later. RESULTS: Higher flexibility at baseline significantly contributed to predict lower anxiety, depression and negative affect at follow-up. The effect sizes ranged from moderate to large. CONCLUSIONS: Results provide evidence for targeting PF to prevent enhanced psychological distress in patients with breast cancer, and add to a growing body of research supporting PF as a common protective factor across different contexts and populations.


Adaptation, Psychological , Breast Neoplasms/psychology , Adult , Aged , Female , Forecasting , Humans , Middle Aged , Prospective Studies , Young Adult
19.
J Infect Dis ; 211(1): 146-55, 2015 Jan 01.
Article En | MEDLINE | ID: mdl-25092899

BACKGROUND: Stimulation of the vagus nerve in the so-called cholinergic antiinflammatory pathway (CAP) attenuates systemic inflammation, improving survival in animal sepsis models via α7 nicotinic acetylcholine receptors on immunocompetent cells. Because the relevance of this regulatory pathway is unknown in human sepsis, this pilot study assessed whether the α7 gene expression level in septic patients' peripheral blood mononuclear cells (PBMC) might be used to assess CAP activity and clinical outcome. METHODS: The PBMCs α7 messenger RNA levels were determined by real-time quantitative reverse-transcription polymerase chain reaction in 33 controls and 33 patients at enrollment and after their hospital discharge. Data were analyzed to find significant associations between α7 level, vagally mediated heart rate variability as an indirect reflection of CAP activity, serum concentrations of different inflammation markers, and clinical course. RESULTS: Septic patients' α7 levels were significantly increased and returned to control values after recovery. These α7 levels correlated directly with the vagal heart input and inversely with the magnitude of the patient's inflammatory state, disease severity, and clinical outcome. CONCLUSIONS: This study reveals that the PBMC α7 gene expression level is a clinically relevant marker for CAP activity in sepsis: the higher the α7 expression, the better the inflammation control and the prognosis.


Leukocytes, Mononuclear/metabolism , RNA, Messenger/blood , Sepsis/genetics , alpha7 Nicotinic Acetylcholine Receptor/genetics , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Biomarkers/metabolism , Case-Control Studies , Cell Line , Cholinergic Agents/therapeutic use , Female , Gene Expression/drug effects , Heart Rate/drug effects , Humans , Inflammation/drug therapy , Inflammation/genetics , Inflammation/microbiology , Male , Middle Aged , Pilot Projects , Prospective Studies , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Sepsis/blood , Sepsis/drug therapy , Sepsis/metabolism , Vagus Nerve/physiology , alpha7 Nicotinic Acetylcholine Receptor/metabolism
20.
PLoS One ; 9(9): e108397, 2014.
Article En | MEDLINE | ID: mdl-25259522

Nicotine stimulation of α7 nicotinic acetylcholine receptor (α7 nAChR) powerfully inhibits pro-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated macrophages and in experimental models of endotoxemia. A signaling pathway downstream from the α7 nAChRs, which involves the collaboration of JAK2/STAT3 and NF-κB to interfere with signaling by Toll-like receptors (TLRs), has been implicated in this anti-inflammatory effect of nicotine. Here, we identifiy an alternative mechanism involving interleukin-1 receptor-associated kinase M (IRAK-M), a negative regulator of innate TLR-mediated immune responses. Our data show that nicotine up-regulates IRAK-M expression at the mRNA and protein level in human macrophages, and that this effect is secondary to α7 nAChR activation. By using selective inhibitors of different signaling molecules downstream from the receptor, we provide evidence that activation of STAT3, via either JAK2 and/or PI3K, through a single (JAK2/PI3K/STAT3) or two convergent cascades (JAK2/STAT3 and PI3K/STAT3), is necessary for nicotine-induced IRAK-M expression. Moreover, down-regulation of this expression by small interfering RNAs specific to the IRAK-M gene significantly reverses the anti-inflammatory effect of nicotine on LPS-induced TNF-α production. Interestingly, macrophages pre-exposed to nicotine exhibit higher IRAK-M levels and reduced TNF-α response to an additional LPS challenge, a behavior reminiscent of the 'endotoxin tolerant' phenotype identified in monocytes either pre-exposed to LPS or from immunocompromised septic patients. Since nicotine is a major component of tobacco smoke and increased IRAK-M expression has been considered one of the molecular determinants for the induction of the tolerant phenotype, our findings showing IRAK-M overexpression could partially explain the known influence of smoking on the onset and progression of inflammatory and infectious diseases.


Anti-Inflammatory Agents/pharmacology , Interleukin-1 Receptor-Associated Kinases/metabolism , Macrophages/metabolism , Nicotine/pharmacology , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Cells, Cultured , Down-Regulation/drug effects , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Phosphatidylinositol 3-Kinases/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Up-Regulation/drug effects
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