Publications by authors named "Pablo Martinez"

133 Publications

[Clinical-epidemiological characterization of patients with tuberculosis in the Department of Caaguazú, Paraguay. 2014-2017].

Rev Chilena Infectol 2020 Dec;37(6):750-755

Ministerio de Salud Pública y Bienestar Social, Asunción, Paraguay.

Background: Tuberculosis (TB) is one of the ten leading causes of death worldwide.

Aim: To characterize the clinical and epidemiological point of view of TB cases reported in the Department of Caaguazú-Paraguay, from 2014 to 2017.

Methods: Observational, descriptive, retrospective study; Population: 659 cases of TB registered in the National Tuberculosis Control Program (NTCP); variables: age, sex, population group, type of TB, TB/HIV coinfection. We procesed database in Excel 2016 © using Stata 14.0®.

Results: 63.3% were of male gender, average age: 35.8 years, 39.6% were indigenous and 85.4% were liberty deprived persons known as inmates (LDP), 89.6% had pulmonary TB and 2,4% had TB/HIV coinfection. Incidence rate exceed 21.6/100,000 inhabitants in 2014. Indigenous incidence was 76.5/100,000 inhabitants in 2017, LDP incidence was 2,272.1/ 100,000 inhabitants in 2017.

Conclusion: The incidence of TB in the Department of Caaguazú is low, mainly affecting men, while TB incidence in indigenous people and LDP was high.
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http://dx.doi.org/10.4067/S0716-10182020000600750DOI Listing
December 2020

[Validation of patient health Questionnaire-2 to detect depressive symptoms in diabetic or hypertensive patients].

Rev Med Chil 2020 Nov;148(11):1614-1618

Departamento de Psiquiatría y Salud Mental, Hospital Clínico, Universidad de Chile, Santiago, Chile.

Background: Patient Health Questionnaire (PHQ-9) has nine questions and is used in diabetic or hypertensive patients to detect depressive symptoms. The PHQ-2 uses the first two questions of the PHQ-9 to rapidly detect those patients that should answer the whole questionnaire.

Aim: To validate the PHQ-2 to detect depressive symptoms in diabetic or hypertensive patients consulting at Primary Health Care (PHC).

Material And Methods: Secondary analysis of data obtained during the baseline assessment of a clinical trial. Diabetic and hypertensive patients aged 18 years or more, attending a public health care clinic of Metropolitan Santiago, were invited to participate. Those accepting, answered the Patient Health Questionnaire (PHQ-9), consisting in nine questions about depressive symptoms. Demographics and health data were also collected. The PHQ-2 capacity to discriminate PHQ-9 scores equal or higher than 10 and 15 and the correlation between both versions, were assessed.

Results: Ninety-four participants aged 64 ± years (73% women) answered the questionnaire. A cut-off score of 3 or more points in the PHQ-2 achieved the best tradeoff between sensitivity and specificity for discriminating PHQ-9 scores equal or higher than 10 (area under the receiver operating characteristic curve (ROC) = 0.92, 95% confidence interval [95% CI] = 0.87 to 0.97) and 15 points (area under the ROC curve = 0.95, 95% CI = 0.92 to 0.99). Both versions had a high positive correlation (r = 0.87).

Conclusions: The PHQ-2 allows a stepped, simple and accurate screening for depressive symptoms. Diabetic or hypertensive patients with 3 or more points should be immediately assessed with the remaining questions of the PHQ-9.
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http://dx.doi.org/10.4067/S0034-98872020001101614DOI Listing
November 2020

Phase I trial of MEDI3726, a prostate-specific membrane antigen-targeted antibody-drug conjugate, in patients with mCRPC after failure of abiraterone or enzalutamide.

Clin Cancer Res 2021 Apr 1. Epub 2021 Apr 1.

Prostate and Urologic Cancers Program, Yale Cancer Center.

Purpose: MEDI3726 is an antibody-drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This Phase 1 study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.

Experimental Design: MEDI3726 was administered at 0.015-0.3 mg/kg IV Q3W until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD)/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of {greater than or equal to}50% after {greater than or equal to}12 weeks, and/or decrease from {greater than or equal to}5 to <5 circulating tumor cells/7.5 mL blood.

Results: Between 1 February 2017 and 13 November 2019, 33 patients received MEDI3726. By the data cutoff (17 January 2020), treatment-related AEs (TRAEs) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued due to TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3-1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%) and the incidence was 13/32 (40.6%).

Conclusions: Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4528DOI Listing
April 2021

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2020 Dec 17. Epub 2020 Dec 17.

Division of Hematology & Oncology, MUSC Health Hollings Cancer Center, Charleston, SC.

Background: Despite recent advances, outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) remain poor. Immune checkpoint inhibitors have shown limited efficacy in this setting, but combinations with novel agents may enhance benefit. Combination therapy with durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, and danvatirsen (AZD9150; an antisense oligonucleotide inhibiting signal transducer and activator of transcription 3 [STAT3]) or tremelimumab (an anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] antibody) may augment endogenous antitumor activity.

Patients And Methods: In this phase 1b dose escalation and dose expansion study, we evaluated durvalumab 20 mg/kg every 4 weeks plus either tremelimumab 1 mg/kg every 4 weeks or danvatirsen 2 or 3 mg/kg (administered on days 1, 3, 5, 8, 15, and 22, then every week). Treatment continued until disease progression. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.

Results: As of April 4, 2019, 32 patients were enrolled and treated, receiving a median of 2 prior lines of systemic therapy. Treatment-related adverse events occurred in 21 patients (65.6%), most commonly alanine aminotransferase/aspartate aminotransferase increased (grade 1-3), anemia (grade 1-3), and fatigue (grade 1). The overall objective response rate was 6.3%, with 2 partial responses. Median time to response was 11.0 weeks (range, 7.7-14.3 weeks). Median progression-free survival was 7.4 weeks (range, 0.1-31.4 weeks), and median overall survival was 28.0 weeks (range, 1.9-115.4 weeks).

Conclusion: The primary endpoint was met, with durvalumab plus tremelimumab/danvatirsen generally well tolerated in patients with relapsed/refractory DLBCL; however, antitumor activity was limited.
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http://dx.doi.org/10.1016/j.clml.2020.12.012DOI Listing
December 2020

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2020 Dec 17. Epub 2020 Dec 17.

Division of Hematology & Oncology, MUSC Health Hollings Cancer Center, Charleston, SC.

Background: Despite recent advances, outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) remain poor. Immune checkpoint inhibitors have shown limited efficacy in this setting, but combinations with novel agents may enhance benefit. Combination therapy with durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, and danvatirsen (AZD9150; an antisense oligonucleotide inhibiting signal transducer and activator of transcription 3 [STAT3]) or tremelimumab (an anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] antibody) may augment endogenous antitumor activity.

Patients And Methods: In this phase 1b dose escalation and dose expansion study, we evaluated durvalumab 20 mg/kg every 4 weeks plus either tremelimumab 1 mg/kg every 4 weeks or danvatirsen 2 or 3 mg/kg (administered on days 1, 3, 5, 8, 15, and 22, then every week). Treatment continued until disease progression. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics, and immunogenicity.

Results: As of April 4, 2019, 32 patients were enrolled and treated, receiving a median of 2 prior lines of systemic therapy. Treatment-related adverse events occurred in 21 patients (65.6%), most commonly alanine aminotransferase/aspartate aminotransferase increased (grade 1-3), anemia (grade 1-3), and fatigue (grade 1). The overall objective response rate was 6.3%, with 2 partial responses. Median time to response was 11.0 weeks (range, 7.7-14.3 weeks). Median progression-free survival was 7.4 weeks (range, 0.1-31.4 weeks), and median overall survival was 28.0 weeks (range, 1.9-115.4 weeks).

Conclusion: The primary endpoint was met, with durvalumab plus tremelimumab/danvatirsen generally well tolerated in patients with relapsed/refractory DLBCL; however, antitumor activity was limited.
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http://dx.doi.org/10.1016/j.clml.2020.12.012DOI Listing
December 2020

2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling.

PLoS Negl Trop Dis 2021 Feb 22;15(2):e0009196. Epub 2021 Feb 22.

Institute of Chemistry, University of Campinas (UNICAMP), Campinas-SP, Brazil.

Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro properties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.
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http://dx.doi.org/10.1371/journal.pntd.0009196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932521PMC
February 2021

Vulnerable areas to accidents with scorpions in Brazil.

Trop Med Int Health 2021 Feb 9. Epub 2021 Feb 9.

Laboratório de Pesquisas Integrativas em Biodiversidade, Universidade Federal de Sergipe, São Cristóvão, Brazil.

Objective: To identify areas that present a higher risk of exposure to accidents with scorpions in Brazil.

Methods: We used techniques of spatial prioritisation to determine the most vulnerable localities to envenomation by four scorpion species. Our prioritisation integrated ecological niche models with health investment, antivenin availability, access to health care facilities and metrics of human impact data.

Results: The ecological niche models indicated that three scorpion species (Tityus bahiensis, Tityus serrulatus, and Tityus stigmurus) are more associated with human population density, while T. obscurus demonstrated a strong association with temperature variations during the year. Spatial prioritisation indicated that the areas with higher risk exposure to accidents with scorpions are in northern and northeastern Brazil. Alternatively, more isolated but densely populated areas in the southeastern and central regions also emerged as a priority.

Conclusion: Mapping areas where humans are more likely to interact with scorpions can assist in the design of efficient public health policies.
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http://dx.doi.org/10.1111/tmi.13561DOI Listing
February 2021

Water constraints drive allometric patterns in the body shape of tree frogs.

Sci Rep 2021 Jan 13;11(1):1218. Epub 2021 Jan 13.

Departamento de Biologia, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil.

The origin of morphological diversity is a critical question in evolutionary biology. Interactions between the environment and developmental processes have determining roles in morphological diversity, creating patterns through space and over time. Also, the shape of organisms tends to vary with increasing size as a result of those developmental processes, known as allometry. Several studies have demonstrated that the body sizes of anurans are associated with hydric conditions in their environments and that localities with high water stress tend to select for larger individuals. However, how environmental conditions alter those patterns of covariance between size and shape is still elusive. We used 3D geometric morphometric analyses, associated with phylogenetic comparative methods, to determine if the morphological variations and allometric patterns found in Arboranae (Anura) is linked to water conservation mechanisms. We found effects of the hydric stress on the shape of Arboranae species, favouring globular shapes. Also, the allometric patterns varied in intensity according to the water stress gradient, being particularly relevant for smaller frogs, and more intense in environments with higher water deficits. Our study provides empirical evidence that more spherical body shapes, especially among smaller species, reflect an important adaptation of anurans to water conservation in water-constrained environments.
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http://dx.doi.org/10.1038/s41598-020-80456-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806824PMC
January 2021

Historical climatic instability predicts the inverse latitudinal pattern in speciation rate of modern mammalian biota.

J Evol Biol 2021 Feb 28;34(2):339-351. Epub 2020 Nov 28.

PIBiLab (Laboratorio de Pesquisas Integrativas em Biodiversidade), Federal University of Sergipe, São Cristóvão, Brazil.

Evolutionary rate explanations for latitudinal diversity gradients predict faster speciation and diversification rates in richer, older and more stable tropical regions (climatic stability hypothesis). Numerous modern lineages have emerged in high latitudes, however, suggesting that climatic oscillations can drive population divergence, at least among extratropical species (glacial refugia hypothesis). This conflicting evidence suggests that geographical patterns of evolutionary rates are more complicated than previously thought. Here, we reconstructed the complex evolutionary dynamics of a comprehensive data set of modern mammals, both terrestrial and marine. We performed global and regional regression analyses to investigate how climatic instability could have indirectly influenced contemporary diversity gradients through its effects on evolutionary rates. In particular, we explored global and regional patterns of the relationships between species richness and assemblage-level evolutionary rates and between evolutionary rates and climatic instability. We found an inverse relationship between evolutionary rates and species richness, especially in the terrestrial domain. Additionally, climatic instability was strongly associated with the highest evolutionary rates at high terrestrial latitudes, supporting the glacial refugia hypothesis there. At low latitudes, evolutionary rates were unrelated to climatic stability. The inverse relationship between evolutionary rates and the modern latitudinal diversity gradient casts doubt on the idea that higher evolutionary rates in the tropics underlie the current diversity patterns of modern mammals. Alternatively, the longer time spans for diversity to accumulate in the older and more stable tropics (and not high diversification rates) may explain the latitudinal diversity gradient.
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http://dx.doi.org/10.1111/jeb.13737DOI Listing
February 2021

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group.

Rev Invest Clin 2020 05 7;72(5). Epub 2020 May 7.

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies.

Objective: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥ 75 years of age.

Methods: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (less than 75 vs. ≥75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications.

Results: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p less than 0.01) and higher ASA score (ASA > 2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications.

Conclusions: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities.
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http://dx.doi.org/10.24875/RIC.20000018DOI Listing
May 2020

[Argentine Consensus in effective management of anticoagulation clinics for the use of vitamin k antagonists].

Medicina (B Aires) 2020 ;80 Suppl 4:1-26

Laboratorio LAHT SRL, Rosario, Santa Fe, Argentina.

Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.
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September 2020

Durvalumab activity in previously treated patients who stopped durvalumab without disease progression.

J Immunother Cancer 2020 08;8(2)

Oncology Research and Development, AstraZeneca, Gaithersburg, Maryland, USA.

Background: Limited data exist on potential clinical benefit with anti-programmed cell death ligand-1 (PD-L1) retreatment in patients who stop initial therapy for reasons other than disease progression or toxicity and develop disease progression while off treatment.

Patients And Methods: NCT01693562 was a phase I/II study evaluating durvalumab monotherapy in advanced solid tumors. Patients benefiting from treatment were taken off durvalumab at 1 year per protocol and prospectively followed. At disease progression, they were eligible for durvalumab retreatment. Outcomes evaluated during retreatment included best overall response (BOR2), duration of response (DoR2), disease control rate (DCR2), and progression-free survival (PFS2).

Results: Of 980 patients enrolled and treated with durvalumab 10 mg/kg every 2 weeks (Q2W) in the dose-expansion cohorts, 168 completed 1 year of initial durvalumab treatment with confirmed BOR1 of complete response in 20 (11.9%), partial response (PR) in 84 (50%), stable disease (SD) in 52 (31%), and disease progression in 12 (7.1%). All 168 patients stopped treatment and were eligible for retreatment at progression; 70 patients (41.7%) representing 14 primary tumor types were retreated and response evaluable. Confirmed BOR2 was PR in 8 patients (11.4%), SD in 42 (60.0%), disease progression in 16 (22.9%), and unevaluable in 4 (5.7%). Median DoR2 was 16.5 months. DCR2 ≥24 weeks (DCR2 24) was 47.1%. PFS2 rate at 12 months was 34.2%, and median PFS2 was 5.9 months. Median overall survival (OS2) was 23.8 months. Response rates, DCR2 24, and median DoR2 were generally greater in patients with high PD-L1 expression than those with low/negative expression. No new safety signals were observed during retreatment.

Conclusion: Retreatment restored antitumor activity, resulting in high rates of durable disease control with an acceptable safety profile. This evidence supports retreatment of patients who stop anti-PD-L1 therapy for reasons other than progression or toxicity, and supports further investigation.
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http://dx.doi.org/10.1136/jitc-2020-000650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451272PMC
August 2020

Development and validation of a three-item version of the Edinburgh Postnatal Depression Scale.

J Clin Psychol 2020 12 18;76(12):2198-2211. Epub 2020 Aug 18.

Millennium Institute for Research in Depression and Personality, Santiago, Chile.

Objective: To develop and validate a brief screening instrument for postpartum depression in resource-constrained primary care settings.

Method: Secondary data analysis of a cohort of 305 mothers (Mdn  = 26) attending well-child check-ups in six primary care centers in Santiago, Chile, answered the Edinburgh Postnatal Depression Scale (EPDS), the 36-Item Short Form Health Survey, and the Mini International Neuropsychiatric Interview depression module. A predictive model for postpartum depression was built using logistic and least absolute shrinkage and selection operator regressions, with bootstrap validation.

Results: A three-item version of the EPDS exhibited excellent discriminative capacity (c statistic = 0.95) and showed no significant differences versus the full version of the EPDS (χ (1) = 1.75, p = .187). The best trade-off between sensitivity (92.86%) and specificity (86.70%) was achieved at a cut-off score of 8/9.

Conclusions: The three-item version of the EPDS can save clinicians valuable time, which might potentially improve communication of results to patients.
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http://dx.doi.org/10.1002/jclp.23041DOI Listing
December 2020

Health outcomes of unpaid caregivers in low- and middle-income countries: A systematic review and meta-analysis.

J Clin Nurs 2020 Nov 4;29(21-22):3950-3965. Epub 2020 Sep 4.

Escuela de Psicología, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, Chile.

Aims And Objectives: To explore differences in health outcomes between unpaid caregivers and noncaregivers living in low- and middle-income countries (LMICs).

Background: Previous meta-analyses found worse health outcomes for unpaid caregivers in high-income nations. However, no meta-analysis has considered unpaid caregivers from LMICs. A systematic integration of this topic may contribute to nursing care for unpaid caregivers in LMICs.

Design: Systematic review and meta-analysis of observational studies.

Methods: Following PRISMA statement, studies were searched for using the CINAHL, PubMed and SciELO databases, limited to publications until 31 December 2019. Random- and fixed-effects meta-analyses were used for data synthesis.

Results: Fourteen studies from Africa, Asia and South America were included. Unpaid caregivers of people with ill-health were more anxious and depressed than noncaregivers. Studies conducted in Asia and South America reported poorer health outcomes for unpaid caregivers than noncaregivers, whereas the trend for African studies was the opposite. Unpaid caregivers of healthy individuals may have better health status than noncaregivers, particularly those caring between 1-14 hr per week. Of the six studies which examined gender differences, two studies informed worse health outcomes for women, one presented the opposite effect, and three found no differences.

Conclusions: Individual, social, cultural and systemic factors play an important role in the health outcomes of unpaid caregivers in LMICs. More evidence is needed from LMICs. As unpaid caregivers are predominantly female, urgent attention to the health outcomes of female unpaid caregivers is required.

Relevance To Clinical Practice: The management of mental health problems, particularly anxiety and depression, should be an integral part of nursing care for unpaid caregivers living in LMICs. To further promote the health of unpaid caregivers in developing countries, stakeholders should consider launching educational campaigns that assist caregivers in finding ways to meet their cultural obligations while also reinforcing caregiver self-care.
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http://dx.doi.org/10.1111/jocn.15450DOI Listing
November 2020

[Validation of the Childhood Trauma Questionnaire-Short Form in Chile].

Rev Med Chil 2020 Mar;148(3):336-343

Instituto Milenio para la Investigación en Depresión y Personalidad, Santiago, Chile.

Background: Childhood Trauma Questionnaire-Short Form (CTQ-SF) is an instrument to assess child abuse and neglect Aim: to adapt and confirm the psychometric properties of the Spanish version of the CTQ-SF in Chile.

Material And Methods: The CTQ-SF was applied to 89 clinically depressed subjects (77.5% women) who consulted at an outpatient mental health clinic. Confirmatory factor analysis (CFA), reliability (Cronbach's α) tests, and convergent validity analyses with clinical markers of complex depression were carried out.

Results: The Chilean version of the CTQ-SF demonstrated an acceptable fit to a five-factor model, with adequate psychometric properties. The CFA revealed that a better fit to a five-factor model would be achieved after elimination of two items from the physical neglect scale, the less reliable scale of the questionnaire. The physical abuse scale discriminated between patients with a complex depression versus non-complex depression, and all the CTQ-SF's scales discriminated between patients with high suicide risk and/or history of psychiatric admissions versus those patients without this background.

Conclusions: the Chilean version of the CTQ-SF shows evidence of structural and discriminant validity, and reliability, in a clinical sample. Better alternatives to specifically assess the physical neglect construct should be developed.
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http://dx.doi.org/10.4067/S0034-98872020000300336DOI Listing
March 2020

TANGLED1 mediates microtubule interactions that may promote division plane positioning in maize.

J Cell Biol 2020 08;219(8)

Biochemistry and Molecular Biology Graduate Program, University of California, Riverside, CA.

The microtubule cytoskeleton serves as a dynamic structural framework for mitosis in eukaryotic cells. TANGLED1 (TAN1) is a microtubule-binding protein that localizes to the division site and mitotic microtubules and plays a critical role in division plane orientation in plants. Here, in vitro experiments demonstrate that TAN1 directly binds microtubules, mediating microtubule zippering or end-on microtubule interactions, depending on their contact angle. Maize tan1 mutant cells improperly position the preprophase band (PPB), which predicts the future division site. However, cell shape-based modeling indicates that PPB positioning defects are likely a consequence of abnormal cell shapes and not due to TAN1 absence. In telophase, colocalization of growing microtubules ends from the phragmoplast with TAN1 at the division site suggests that TAN1 interacts with microtubule tips end-on. Together, our results suggest that TAN1 contributes to microtubule organization to ensure proper division plane orientation.
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http://dx.doi.org/10.1083/jcb.201907184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401798PMC
August 2020

Widespread loss of the silencing epigenetic mark H3K9me3 in astrocytes and neurons along with hippocampal-dependent cognitive impairment in C9orf72 BAC transgenic mice.

Clin Epigenetics 2020 02 18;12(1):32. Epub 2020 Feb 18.

Institute of Biomedical Sciences (ICB), Faculty of Medicine & Faculty of Life Sciences, Universidad Andres Bello, Santiago, Chile.

Background: Hexanucleotide repeat expansions of the GC motif in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Tissues from C9ALS/FTD patients and from mouse models of ALS show RNA foci, dipeptide-repeat proteins, and notably, widespread alterations in the transcriptome. Epigenetic processes regulate gene expression without changing DNA sequences and therefore could account for the altered transcriptome profiles in C9ALS/FTD; here, we explore whether the critical repressive marks H3K9me2 and H3K9me3 are altered in a recently developed C9ALS/FTD BAC mouse model (C9BAC).

Results: Chromocenters that constitute pericentric constitutive heterochromatin were visualized as DAPI- or Nucblue-dense foci in nuclei. Cultured C9BAC astrocytes exhibited a reduced staining signal for H3K9me3 (but not for H3K9me2) at chromocenters that was accompanied by a marked decline in the global nuclear level of this mark. Similar depletion of H3K9me3 at chromocenters was detected in astrocytes and neurons of the spinal cord, motor cortex, and hippocampus of C9BAC mice. The alterations of H3K9me3 in the hippocampus of C9BAC mice led us to identify previously undetected neuronal loss in CA1, CA3, and dentate gyrus, as well as hippocampal-dependent cognitive deficits.

Conclusions: Our data indicate that a loss of the repressive mark H3K9me3 in astrocytes and neurons in the central nervous system of C9BAC mice represents a signature during neurodegeneration and memory deficit of C9ALS/FTD.
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http://dx.doi.org/10.1186/s13148-020-0816-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029485PMC
February 2020

Open-Circuit Voltage of Organic Photovoltaics: A Time-Dependent and Unrestricted DFT Study in a P3HT/PCBM Complex.

J Phys Chem A 2020 Feb 6;124(7):1300-1305. Epub 2020 Feb 6.

Institut de Quı́mica Computacional i Catàlisi and Departament de Quı́mica , Universitat de Girona , C/Maria Aurèlia Capmany, 69 , 17003 Girona , Catalonia , Spain.

Solar cells based on blends of poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid methyl ester, P3HT/PCMB, constitute one of the most efficient polymer photovoltaic cell types. One of the main factors that determine the efficiency of the solar cells is the open-circuit voltage, . In this work, we provide an analysis of the parameters affecting the in a P3HT/PCBM complex. Electronic transitions, excited states, and electron transfer parameters are evaluated under the classical Marcus formalism via the time-dependent and unrestricted CAM-B3LYP/6-31G* methods. The charge-recombination driving force is found to mainly affect the charge-recombination rate constant and, in turn, . Even though other parameters also determine the value of like density of states, dimensions of the cell, and microstructure of the donor/acceptor interface, the current work highlights the understanding attained by modeling charge-transfer parameters. The analysis reported here encourage further quantum-chemical investigations in organic photovoltaics with the aim of estimating and improving , such that more efficient organic solar cells may be predicted.
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http://dx.doi.org/10.1021/acs.jpca.9b10097DOI Listing
February 2020

Improving Mental Health Care in Developing Countries Through Digital Technologies: A Mini Narrative Review of the Chilean Case.

Front Public Health 2019 20;7:391. Epub 2019 Dec 20.

Millennium Nucleus to Improve the Mental Health of Adolescents and Youths (Imhay), Santiago, Chile.

The uneven distribution of mental health resources contributes to the burden of mental disorders in vulnerable groups, especially in developing countries. Internet-based interventions and digital technologies can contribute to reducing the gap between high prevalence of mental disorders, demand for treatment, and access to mental health care, thereby reducing inequities in mental health. This mini review summarizes the current state of the field of e-mental health research in Chile, showing its progress, limitations, and challenges. Internet-based interventions are at an early stage of development in Chile. The interventions included are heterogeneous in terms of participants (e.g., secondary students, patients, healthcare professionals) and contexts (e.g., rural, urban, schools, primary health care), aims, and modalities (e.g., website, online games). While these studies confirmed the feasibility of Internet-based interventions, the shortage of studies on effectiveness and cost-effectiveness makes it difficult to disseminate and scale up these Internet-based programs. However, the growing amount of knowledge accumulated in the Chilean context could guide practices in other developing countries for supporting the mental health of underserved populations.
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http://dx.doi.org/10.3389/fpubh.2019.00391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933524PMC
December 2019

Safe mobility, socioeconomic inequalities, and aging: A 12-year multilevel interrupted time-series analysis of road traffic death rates in a Latin American country.

PLoS One 2020 7;15(1):e0224545. Epub 2020 Jan 7.

CITIAPS, Universidad de Santiago de Chile, Santiago, Chile.

As the resources for road safety in developing countries are scarce and unevenly distributed, vulnerable road users -such as the elderly- may be particularly at risk of road traffic deaths. To date, the impact of road safety measures over the rate of road traffic deaths in older adults (60 years or older), considering the within-country socioeconomic inequalities, has not been explored in developing nations. This study takes the Chilean case as an example -with its 2005 traffic law reform as one of the road safety measures investigated-, in which open data available from official national sources for all its 13 regions over the 2002-2013 period were used for a multilevel interrupted time-series analysis. A statistically significant secular reduction of the rates of road traffic deaths in the elderly population was found (incidence rate ratio [IRR] 0.95, 95% confidence interval [CI] 0.91 to 0.99), but no evidence for a significant intercept or slope change after the traffic law reform was observed. Regions with the highest number of traffic offenses prosecuted in local police courts had lower rates of road traffic deaths in older adults (IRR 0.95, 95% CI 0.90 to 1.00), and those regions in the third (IRR 1.61, 95% CI 1.16 to 2.25) and the fifth (IRR 1.66, 95% CI 1.08 to 2.54) quintiles of socioeconomic deprivation had higher rates of road traffic deaths in the elderly. Such findings strongly support the conceptualization of the road safety of seniors in developing countries as a social equity issue, with implications for the design of traffic regulations and road environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224545PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946134PMC
March 2020

The effects of Chile's 2005 traffic law reform and in-country socioeconomic differences on road traffic deaths among children aged 0-14 years: A 12-year interrupted time series analysis.

Accid Anal Prev 2020 Mar 28;136:105335. Epub 2019 Dec 28.

CITIAPS, Universidad de Santiago de Chile, Santiago, Chile; Escuela de Psicología, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, Chile.

Objectives: This study assessed the effect of Chile's 2005 traffic law reform (TLR) on the rates of road traffic deaths (RTD) in children aged 0-14 years, adjusting for socioeconomic differences among the regions of the country.

Methods: Free-access sources of official and national information provided the data for every year of the study period (2002-2013) and for each of the country's 13 upper administrative divisions with respect to RTD in child pedestrians and RTD in child passengers (dependent variables), and the following control variables: the number of road traffic tickets processed, investment in road infrastructure, poverty, income inequality, insufficient education, unemployment, population aged 0-14 years, and prevalence of alcohol consumption in the general population. Interrupted time series analyses (level and slope change impact model), using generalized estimating equation methods, were conducted to assess the impact of the TLR (independent variable) on the dependents variables.

Results: There was a significant interaction between time and Chile's 2005 TLR for a reduction in child pedestrians (incidence rate ratio [IRR] 0.87, 95% confidence interval [CI] 0.79-0.96) and passengers RTD (IRR for interaction 0.80, 95% CI 0.67-0.96) trends. In addition, in child pedestrians, RTD rates were affected by poverty (IRR 1.04, 95% CI 1.02-1.05), income inequality (IRR 1.02, 95% CI 1.00-1.04), and unemployment (IRR 0.94, 95% CI 0.90-0.98), whereas in the case of child passengers, poverty (IRR 1.05, 95% CI 1.01-1.08) and income inequality (IRR 0.93, 95% CI 0.91-0.95) were significant.

Conclusions: Large-scale legislative actions can be effective road safety measures if they are aimed at promoting behavioral change in developing countries, improving the safety of children on the road. Additionally, regional socioeconomic differences are associated with higher RTD rates in this population, making this an argument in favor of road safety policies that consider these inequalities. The number of road traffic tickets processed and the investment in road infrastructure were not significant.
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http://dx.doi.org/10.1016/j.aap.2019.105335DOI Listing
March 2020

[Idiopathic hypercalciuria: can the diuretics be avoided?]

Medicina (B Aires) 2019 ;79(6):477-482

Instituto de Investigaciones Metabólicas (IDIM), Universidad del Salvador (USAL), Buenos Aires, Argentina.

Idiopathic hypercalciuria is defined as calcium excretion greater than 220 and 300 mg/day in women and men respectively, or greater than 4 mg/kg body weight. In women with osteoporosis it is observed in 19% of cases, while in kidney stones cases varies between 50 and 70%. We selected 206 hypercalciuric patients from our database, with and without renal lithiasis, to whom a restricted diet had been indicated. We divided them, according to the response, into a dependent diet and an independent diet. We considered 122 patients with diagnosis of hypercalciuria diet dependent (105 women and 17 men), which were followed with dietary control (800 mg of calcium, around 1 g of animal proteins and < 100 mEq sodium a day). The appearance of stones, or the recurrence of stones, was not considered, nor was bone involvement. After an average of 17 months, everyone had their calciuria controlled and there were even 16 (13%) who, after 42 months of follow-up, continued to be normocalciuric only on a diet. We conclude that the division of the hypercalciurias is fundamental, according to their response to a restricted diet, in order to avoid or postpone the use of diuretics and its adverse effects, with an adequate management of the diet.
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February 2020

Oribatid mites (Acari: Oribatida) from the Patagonian steppe, Argentina.

Zootaxa 2019 Oct 15;4686(2):zootaxa.4686.2.4. Epub 2019 Oct 15.

Laboratorio de Investigaciones en Evolución y Biodiversidad (LIEB-UNPSJB), Ruta N° 259, km 16,5. CP 9200 Esquel, Chubut, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET),.

Knowledge of the oribatid mite community from Patagonian steppe is scarce compared with other environments, such as the Andean-Patagonian forest. In the present research we identified oribatid mites under different environmental conditions: two Patagonian steppe types (grass and shrub), two soil characteristics (bare and covered soil) and two different seasons (autumn and spring). A total of 42 species/morphospecies were found, 13 were new records for Chubut and one was a new record for Argentina. In view of its ecological role in soil formation, it is fundamental that knowledge about this fauna is enhanced in order to provide baselines for study and to aid further understanding about its ecology.
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http://dx.doi.org/10.11646/zootaxa.4686.2.4DOI Listing
October 2019

The impact of polar fraction of the fine particulate matter on redox responses in different rat tissues.

Environ Sci Pollut Res Int 2019 Nov 15;26(31):32476-32487. Epub 2019 Oct 15.

Instituto de Ciências Biológicas, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil.

Particulate matter (PM) contains different chemical substances that have been associated with health effects and an increased risk of mortality due to their toxicity. In this study, fine particulate matter (PM) samples were collected in a region with rural characteristics (Seropédica (Se)) and another with some industries (Duque de Caxias (DC)) (Brazil, RJ). Rats were exposed to PM extracts daily for 25 days at different dilutions: 10×, 5×, and a concentrated solution (CS). Biochemical analyses were investigated for total antioxidant capacity (ACAP), lipid peroxidation (LPO) levels, reduced glutathione (GSH) concentration, activity of glutamate cysteine ligase (GCL), and activity of glutathione S-transferase (GST). The liver showed a significant increase in GCL (DC-5×, DC-CS and Se-CS) and GST activities (DC-CS and Se-CS) in both regions when compared to the control group. In the renal cortex, GCL activity decreased in most of the tested groups while GST activity increased only in the 5× groups of both regions (DC and Se). In the renal medulla, GCL activity decreased for Se-10× and DC-CS but increased for Se-5×, and GST activity increased in the Se-10×, DC-5×, and DC-CS groups. Lung GCL increased in all groups for both regions. Moreover, this organ also showed an increase in GST activity when higher metal concentrations were present (5× and CS). TBARS levels were increased for all tissues in most tested concentrations. These data indicate that soluble compounds (e.g., metals) from PM sampled in areas with different pollution indexes can change the redox status and cause damage to different tissues.
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http://dx.doi.org/10.1007/s11356-019-06452-9DOI Listing
November 2019

Assessment of ventricular repolarization instability in terms of T-wave alternans induced by head-down bed-rest immobilization.

Physiol Meas 2019 10 30;40(10):104001. Epub 2019 Oct 30.

Department of Biomedical Engineering, Lund University, Lund, Sweden. BSICoS Group, Instituto de Investigación en Ingeniería de Aragón (I3A), IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain.

Objective: To assess the effects of different durations of simulated microgravity exposure on ventricular repolarization (VR) in terms of T-wave alternans (TWA) as well as to test whether an increase in VR heterogeneity could be detected once normal gravity was restored.

Approach: A total of 63 healthy volunteers were recruited in several head-down bed-rest (HDBR) experiments in the context of the European Space Agency bed-rest strategy. TWA is evaluated during the night period using ambulatory ECG recordings, before, during and after long- (60 d), mid- (21 d) and short- (5 d) duration HDBR by the long-term averaging technique.

Main Results: 5-21 d of exposure to simulated microgravity by means of the HDBR model do not lead to a significant increase of cardiac electrical instability in healthy myocardial substrates up to the point of eliciting TWA on the surface ECG. However, TWA indices increased after long-term HDBR exposure, once normal gravity was re-established, indicative of incipient electrical instability on VR at the conclusion of 60 d of HDBR.

Significance: The results of this work underline the importance of focusing future research on immediate effects after long-term microgravity exposure, both simulated by HDBR or from space mission scenarios, once partial gravity conditions are re-established. A deeper insight in the understanding of human body reactions in these scenarios results crucial in the design of future long-duration spaceflight missions, to mitigate any potential risk that can limit astronaut's performance.
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http://dx.doi.org/10.1088/1361-6579/ab4c18DOI Listing
October 2019

Internet-Based Interventions for the Prevention and Treatment of Mental Disorders in Latin America: A Scoping Review.

Front Psychiatry 2019 13;10:664. Epub 2019 Sep 13.

Millennium Nucleus to Improve the Mental Health of Adolescents and Youths (Imhay), Santiago, Chile.

There is a huge gap in the treatment of mental disorders in Latin America, especially among socioeconomically disadvantaged groups. Given the sharp increase in Internet access and the rapid penetration of smartphones in the region, the use of Internet-based technologies might potentially contribute to overcoming this gap and to provide more widely distributed and low-cost mental health care in a variety of contexts. We conducted a scoping review of the literature in order to systematically map the existing evidence on use of Internet-based interventions for prevention, treatment, and management of mental disorders across Latin American countries, as well as to identify existing gaps in knowledge. Six electronic databases were searched for published papers (PubMed, Embase, CINAHL, Web of Science, SciELO, and CENTRAL). After the eligibility assessment, we identified 22 Internet-based studies carried out in Latin America for prevention, treatment, education, or facilitating self-management of mental disorders. Included studies mainly targeted depression ( = 11), substance misuse ( = 6), anxiety ( = 3), and mental health literacy for education and health professionals ( = 2). Most studies were undertaken in Brazil ( = 6), Mexico ( = 5), and Chile ( = 4). Only 3 studies were randomized controlled trials (RCTs), 4 were pilot RCTs, and 15 were naturalistic, acceptability, or feasibility studies. The three RCTs identified showed disparate results, but overall, there are challenges to face. Better results are seen in the short-term (postintervention or after 3 months), but most studies do not explore outcomes for long enough (follow-up after 6 or 12 months). Most of the feasibility and pilot studies showed reasonably good acceptability for a wide range of strategies but difficulties to engage and retain participants for long enough or adhering to established protocols. This study shows that Internet-based interventions for the prevention and treatment of mental disorders are growing rapidly in Latin America, but there are few studies on effectiveness and cost effectiveness, making it difficult to provide the evidence needed to justify scaling up these interventions.
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http://dx.doi.org/10.3389/fpsyt.2019.00664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753742PMC
September 2019

Measuring Primary Health Care Clinicians' Skills for Depression Management.

Front Psychiatry 2019 14;10:570. Epub 2019 Aug 14.

Departamento de Psiquiatría y Salud Mental, Hospital Clínico Universidad de Chile, Santiago, Chile.

Primary health care clinicians play an important role in the management of depression. Thus, it is very important to have a valid and reliable assessment of the competences needed to manage depression in primary health care, with the use of clinical simulation providing such an opportunity. The present study describes the assessment of primary health care clinicians' depression-related skills through a series of objective structured clinical examination stations. Clinicians from multi-professional teams for the management of depression at two primary health care clinics in Santiago, Chile, went through seven objective structured clinical examination stations, lasting 10 to 20 min each, to assess their depression-related skills. The clinical and communicative skills measured were in accordance with clinical guidelines. Standardized patients portrayed cases usually encountered in clinical practice, while expert raters evaluated clinicians' performance with standardized checklists. Psychosocial clinicians performed better than biomedical clinicians in the assessed skills. The most notable results were as follows: a high level of accomplishment in the relationship with patient, medical anamnesis, health checkup, and lab test requests; heterogeneous performance in patient management according to screening results, feedback to the patient, and registration in clinical records; and major deficiencies in the differential diagnosis of bipolar disorder. The objective structured clinical examinations administered provided an opportunity to perform an in-depth examination of the depression-related skills of primary health care clinicians, where flaws in the screening and diagnosis procedures used by biomedical clinicians were detected. Given the significant involvement of these types of clinicians in depression management, undergraduate-level and continuing health education opportunities are needed.
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http://dx.doi.org/10.3389/fpsyt.2019.00570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703131PMC
August 2019

Oncotherapy: A Decision Support System to Validate Oncological Treatments.

Stud Health Technol Inform 2019 Aug;264:1799-1800

Medical Oncology, National Cancer Institute, Uruguay.

Making therapy decisions in oncology is a challenging task in the medical precision era. Oncotherapy is a decision support system that provides oncologists with suitable therapies for the patient within the national guidelines. The system is capable, on the one hand, to help the oncologist to maximize fitting therapy to the patient and, on the other hand, to provide control tools for the country's sanitary authorities.
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http://dx.doi.org/10.3233/SHTI190654DOI Listing
August 2019