The Google Health Digital Well-Being Study: Protocol for a Digital Device Use and Well-Being Study.

BACKGROUND: The impact of digital device use on health and well-being is a pressing question. However, the scientific literature on this topic, to date, is marred by small and unrepresentative samples, poor measurement of core constructs, and a limited ability to address the psychological and behavioral mechanisms that may underlie the relationships between device use and well-being. Recent authoritative reviews have made urgent calls for future research projects to address these limitations. The critical role of research is to identify which patterns of use are associated with benefits versus risks and who is more vulnerable to harmful versus beneficial outcomes, so that we can pursue evidence-based product design, education, and regulation aimed at maximizing benefits and minimizing the risks of smartphones and other digital devices. OBJECTIVE: The objective of this study is to provide normative data on objective patterns of smartphone use. We aim to (1) identify how patterns of smartphone use impact well-being and identify groups of individuals who show similar patterns of covariation between smartphone use and well-being measures across time; (2) examine sociodemographic and personality or mental health predictors and which patterns of smartphone use and well-being are associated with pre-post changes in mental health and functioning; (3) discover which nondevice behavior patterns mediate the association between device use and well-being; (4) identify and explore recruitment strategies to increase and improve the representation of traditionally underrepresented populations; and (5) provide a real-world baseline of observed stress, mood, insomnia, physical activity, and sleep across a representative population. METHODS: This is a prospective, nonrandomized study to investigate the patterns and relationships among digital device use, sensor-based measures (including both behavioral and physiological signals), and self-reported measures of mental health and well-being. The study duration is 4 weeks per participant and includes passive sensing based on smartphone sensors, and optionally a wearable (Fitbit), for the complete study period. The smartphone device will provide activity, location, phone unlocks and app usage, and battery status information. RESULTS: At the time of submission, the study infrastructure and app have been designed and built, the institutional review board of the University of Oregon has approved the study protocol, and data collection is underway. Data from 4182 enrolled and consented participants have been collected as of March 27, 2023. We have made many efforts to sample a study population that matches the general population, and the demographic breakdown we have been able to achieve, to date, is not a perfect match. CONCLUSIONS: The impact of digital devices on mental health and well-being raises important questions. The Digital Well-Being Study is designed to help answer questions about the association between patterns of smartphone use and well-being. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49189.

A recognition test in monkeys to differentiate recollection from familiarity memory.

Episodic memory is memory for experiences within a specific temporal and spatial context. Episodic memories decline early in Alzheimer's Disease (AD). Recollection of episodic memories can fail with both AD and aging, but familiarity and recollection memory uniquely fail in AD. Finding a means to differentiate specific memory failures in animal models is critical for translational research. Four cotton top tamarins participated in an object recognition test. They were exposed to two unique objects placed in a consistent context for 5 daily sessions. Next a delay of 1 day or 1 week was imposed. Subjects' memory of the objects was tested by replacing one of the familiarized objects with a novel one. The tamarins looked longer at the novel object after both delays, an indication of remembering the familiar object. In other tests, the test pair was relocated to a new location or presented at a different time of day. With context changes, tamarins showed greater interest in the novel object after a 1-week delay but not after a 1-day delay. It seems that context changes disrupted their recollection of recent events. But the monkeys showed accurate familiarity memory across context changes with longer delays.

Cost-Utility Analysis of Deep Learning and Trained Human Graders for Diabetic Retinopathy Screening in a Nationwide Program.

INTRODUCTION: Deep learning (DL) for screening diabetic retinopathy (DR) has the potential to address limited healthcare resources by enabling expanded access to healthcare. However, there is still limited health economic evaluation, particularly in low- and middle-income countries, on this subject to aid decision-making for DL adoption. METHODS: In the context of a middle-income country (MIC), using Thailand as a model, we constructed a decision tree-Markov hybrid model to estimate lifetime costs and outcomes of Thailand's national DR screening program via DL and trained human graders (HG). We calculated the incremental cost-effectiveness ratio (ICER) between the two strategies. Sensitivity analyses were performed to probe the influence of modeling parameters. RESULTS: From a societal perspective, screening with DL was associated with a reduction in costs of ~ US$ 2.70, similar quality-adjusted life-years (QALY) of + 0.0043, and an incremental net monetary benefit of ~ US$ 24.10 in the base case. In sensitivity analysis, DL remained cost-effective even with a price increase from US$ 1.00 to US$ 4.00 per patient at a Thai willingness-to-pay threshold of ~ US$ 4.997 per QALY gained. When further incorporating recent findings suggesting improved compliance to treatment referral with DL, our analysis models effectiveness benefits of ~ US$ 20 to US$ 50 depending on compliance. CONCLUSION: DR screening using DL in an MIC using Thailand as a model may result in societal cost-savings and similar health outcomes compared with HG. This study may provide an economic rationale to expand DL-based DR screening in MICs as an alternative solution for limited availability of skilled human resources for primary screening, particularly in MICs with similar prevalence of diabetes and low compliance to referrals for treatment.

Desprendimiento bilateral de retina en una embarazada con síndrome de HELLP. Reporte de caso y revisión de la bibliografía / Bilateral retinal detachment in a pregnant woman with HELLP syndrome. Case report and literature review

Resumen ANTECEDENTES: El síndrome de HELLP es una complicación del embarazo que pone en riesgo la vida de la madre y el feto y es una variante del espectro de la preeclampsia, casi siempre relacionada con cambios visuales; las complicaciones, como el desprendimiento de retina, son excepcionales. CASO CLÍNICO: Paciente de 26 años, primigesta, con 36 semanas de embarazo y trastorno hipertensivo, tipo síndrome de HELLP, que se complicó con desprendimiento bilateral seroso de la retina que se resolvió espontáneamente. CONCLUSIONES: Las manifestaciones oculares relacionadas con la preeclampsia y el síndrome de HELLP suelen ser transitorias y se relacionan más con un síntoma de alarma que con un trastorno orgánico ocular. Es importante que las pacientes con este tipo de afecciones obstétricas reciban atención multidisciplinaria.

Abstract BACKGROUND: HELLP syndrome is a life-threatening complication of pregnancy in both mother and fetus. It manifests as a variant of the preeclampsia spectrum, almost always related to visual changes, complications, such as retinal detachment, are exceptional. CLINICAL CASE: A 26-year-old primigravida patient, 36 weeks pregnant, with hypertensive disorder, HELLP syndrome type, complicated by bilateral serous retinal detachment that resolved spontaneously. CONCLUSIONS: Ocular manifestations related to preeclampsia and HELLP syndrome are usually transient and are related more to an alarm symptom than to an organic ocular disorder. It is important that patients with these types of obstetric conditions receive multidisciplinary care.

Molecular Characterization Reveals Subclasses of 1q Gain in Intermediate Risk Wilms Tumors.

Chromosomal alterations have recurrently been identified in Wilms tumors (WTs) and some are associated with poor prognosis. Gain of 1q (1q+) is of special interest given its high prevalence and is currently actively studied for its prognostic value. However, the underlying mutational mechanisms and functional effects remain unknown. In a national unbiased cohort of 30 primary WTs, we integrated somatic SNVs, CNs and SVs with expression data and distinguished four clusters characterized by affected biological processes: muscle differentiation, immune system, kidney development and proliferation. Combined genome-wide CN and SV profiles showed that tumors profoundly differ in both their types of 1q+ and genomic stability and can be grouped into WTs with co-occurring 1p-/1q+, multiple chromosomal gains or CN neutral tumors. We identified 1q+ in eight tumors that differ in mutational mechanisms, subsequent rearrangements and genomic contexts. Moreover, 1q+ tumors were present in all four expression clusters reflecting activation of various biological processes, and individual tumors overexpress different genes on 1q. In conclusion, by integrating CNs, SVs and gene expression, we identified subgroups of 1q+ tumors reflecting differences in the functional effect of 1q gain, indicating that expression data is likely needed for further risk stratification of 1q+ WTs.

Fetal alcohol spectrum disorders and access to regional center services in San Diego County.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2-5% of elementary school children and that negatively impact a child's ability to function without support. Timely diagnosis-informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown. METHODS: An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5- to 7-year-old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria. RESULTS: Among 216 eligible caregiver-child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol-related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services. CONCLUSIONS: The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5- to 7-year-old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD.

Privacy-first health research with federated learning.

Privacy protection is paramount in conducting health research. However, studies often rely on data stored in a centralized repository, where analysis is done with full access to the sensitive underlying content. Recent advances in federated learning enable building complex machine-learned models that are trained in a distributed fashion. These techniques facilitate the calculation of research study endpoints such that private data never leaves a given device or healthcare system. We show-on a diverse set of single and multi-site health studies-that federated models can achieve similar accuracy, precision, and generalizability, and lead to the same interpretation as standard centralized statistical models while achieving considerably stronger privacy protections and without significantly raising computational costs. This work is the first to apply modern and general federated learning methods that explicitly incorporate differential privacy to clinical and epidemiological research-across a spectrum of units of federation, model architectures, complexity of learning tasks and diseases. As a result, it enables health research participants to remain in control of their data and still contribute to advancing science-aspects that used to be at odds with each other.

Orbitofrontal Cortex Encodes Preference for Alcohol.

Orbitofrontal cortex (OFC) plays a key role in representation and regulation of reward value, preference, and seeking. OFC function is disrupted in drug use and dependence, but its specific role in alcohol use disorders has not been thoroughly studied. In alcohol-dependent humans OFC activity is increased by alcohol cue presentation. Ethanol (EtOH) also alters OFC neuron excitability in vitro, and OFC manipulation influences EtOH seeking and drinking in rodents. To understand the relationship between OFC function and individual alcohol use, we recorded OFC neuron activity in rats during EtOH self-administration, characterizing the neural correlates of individual preference for alcohol. After one month of intermittent access to 20% EtOH, male Long-Evans rats were trained to self-administer 20% EtOH, 10% EtOH, and 15% sucrose. OFC neuronal activity was recorded and associated with task performance and EtOH preference. Rats segregated into high and low EtOH drinkers based on homecage consumption and operant seeking of 20% EtOH. Motivation for 10% EtOH and sucrose was equally high in both groups. OFC neuronal activity was robustly increased or decreased during sucrose and EtOH seeking and consumption, and strength of changes in OFC activity was directly associated with individual preference for 20% EtOH. EtOH-associated OFC activity was more similar to sucrose-associated activity in high versus low EtOH drinkers. The results show that OFC neurons are activated during alcohol seeking based on individual preference, supporting this brain region as a potential substrate for alcohol motivation that may be dysregulated in alcohol misuse.

Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats.

BACKGROUND: The orbitofrontal cortex (OFC) encodes internal representations of outcomes and subjective value to facilitate flexible reward seeking. OFC activation is associated with drug seeking in both human subjects and animal models. OFC plays a role in alcohol use, but studies in animal models have produced conflicting results with some showing decreased seeking after OFC inactivation but others showing increased seeking or no changes. In part, this may be due to the different measures of alcohol seeking used (e.g., homecage drinking vs. operant seeking). METHODS: We characterized the impact of transient inactivation of OFC (primarily lateral and, to a lesser extent, ventral subregions) using inhibitory hM4Di designer receptors exclusively activated by designer drugs (DREADDs). OFC neurons were transiently inhibited during 10% and 20% alcohol (ethanol, EtOH) and sucrose homecage consumption, fixed ratio (FR1) operant self-administration, and cue-induced reinstatement of either 10% EtOH or sucrose in male and female rats. RESULTS: OFC inactivation did not affect sucrose or EtOH consumption in the homecage, nor did it influence seeking or consumption under FR1 operant conditions. In contrast, OFC inactivation suppressed cued-induced reinstatement for both EtOH and sucrose in both male and female rats. CONCLUSIONS: Our results are aligned with previous work indicating a selective suppressive effect of OFC inactivation on reinstatement for alcohol and other drugs of abuse. They extend these findings to demonstrate no effect on homecage consumption or FR1 seeking as well as showing an impact of sucrose reinstatement. These data indicate that OFC plays a uniquely important role when reward seeking is driven by associations between external stimuli and internal representations of reward value, both for natural and drug rewards. They further implicate the OFC as a key structure driving relapse-associated seeking and potentially contributing to alcohol use disorder and other diseases of compulsive reward seeking.

The Project Baseline Health Study: a step towards a broader mission to map human health.

The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.

Enfoque del paciente con adenopatías generalizadas. Importancia de la estrategia didáctica del estudio de casos clínicos: a propósito de un paciente con linfoma de Hodgkin asociado a una infección por el virus de Epstein-Barr

Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.

SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.

Automated Subdaily Sampling of Cyanobacterial Toxins on a Buoy Reveals New Temporal Patterns in Toxin Dynamics.

Temporal variability of toxins produced by cyanobacteria in lakes is relatively unknown at time scales relevant to public health (i.e., hourly). In this study, a water quality monitoring buoy was outfitted with an automated water sampler taking preserved samples every 6 h for 68.75 days over a drinking water intake. A total of 251 samples were analyzed by tandem mass spectrometry for 21 cyanotoxin congeners in 5 classes producing 5020 data points. Microcystins (MCs) were the most abundant toxins measured (mean ± sd = 3.9 ± 3.3 µg/L) followed by cyanopeptolins (CPs) (1.1 ± 1.5 µg/L), anabaenopeptins (APs) (1.0 ± 0.6 µg/L), anatoxin-a (AT-A) (0.03 ± 0.06 µg/L), and microginin-690 (MG-690) (0.002 ± 0.01 µg/L). Advanced time series analyses uncovered patterns in cyanotoxin production. The velocity of cyanotoxin concentration varied from -0.7 to 0.9 µg/L/h with a maximum positive velocity just prior to peak toxin concentration during nonbloom periods. A backward-looking moving window of variance analysis detected major increases in cyanotoxin concentration and predicted the two greatest increases in MC. A wavelet analysis identified a significant ( p < 0.01) 2.8-4.2 day periodicity in toxin concentration over a ∼25 day period during peak toxin production, which is partially explained by easterly wind velocity ( R = -0.2, p < 0.05). Diversity in congener profiles was explored with principle component analysis showing that cyanotoxin dynamics followed a seasonal trajectory where toxin profiles were significantly clustered (ANOSIM R = 0.7, p < 0.05) on a daily basis. Variability in toxin profiles was strongly correlated with time ( R = -0.8, p < 0.001) as well as the C:N ratio of the toxin pool ( R = 0.17, p < 0.05). The methods employed here should be useful for uncovering patterns in cyanotoxin dynamics in other systems.

Measuring The Lifetime Costs Of Serious Mental Illness And The Mitigating Effects Of Educational Attainment.

Serious mental illness (SMI) is a disabling condition that develops early in life and imposes substantial economic burden. There is a growing belief that early intervention for SMI has lifelong benefits for patients. However, assessing the cost-effectiveness of early intervention efforts is hampered by a lack of evidence on the long-term benefits. We addressed this by using a dynamic microsimulation model to estimate the lifetime burden of SMI for those diagnosed by age twenty-five. We estimated that the per patient lifetime burden of SMI is $1.85 million. We also found that a policy intervention focused on improving the educational attainment of people with SMI reduces the average per person burden of SMI by $73,600 (4.0 percent)-a change driven primarily by higher lifetime earnings-or over $8.9 billion in reduced burden per cohort of SMI patients. These findings provide a benchmark for the potential value of improving educational attainment for people with SMI.

A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

[Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort].

INTRODUCTION: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. OBJECTIVE: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. MATERIALS AND METHODS: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. RESULTS: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. CONCLUSIONS: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Long-term sensitization training in Aplysia decreases the excitability of a decision-making neuron through a sodium-dependent mechanism.

In Aplysia, long-term sensitization (LTS) occurs concurrently with a suppression of feeding. At the cellular level, the suppression of feeding is accompanied by decreased excitability of decision-making neuron B51. We examined the contribution of voltage-gated Na+ and K+ channels to B51 decreased excitability. In a pharmacologically isolated Na+ channels environment, LTS training significantly increased B51 firing threshold, compared with untrained controls. Conversely, in a pharmacologically isolated K+ channels environment, no differences were observed between trained and untrained animals in either amplitude or area of B51 K+-dependent depolarizations. These findings suggest that Na+ channels contribute to the decrease in B51 excitability induced by LTS training.

Efecto del tratamiento prenatal con espiramicina en la frecuencia de retinocoroiditis por toxoplasmosis congénita en una cohorte colombiana / Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort

Resumen Introducción. La toxoplasmosis de la gestación es frecuente y grave. Hasta ahora no hay consenso sobre la utilidad del tratamiento para prevenir complicaciones oculares en el neonato. En la actualidad, uno de los medicamentos utilizados en las madres diagnosticadas es la espiramicina oral. Infortunadamente, en algunas mujeres gestantes no se hace el diagnóstico prenatal y, por esta u otras razones, no reciben el tratamiento. Objetivo. Describir la relación entre el tratamiento con espiramicina durante el embarazo en madres con toxoplasmosis de la gestación y la presentación de toxoplasmosis ocular en los recién nacidos. Materiales y métodos. Se llevó a cabo un estudio observacional descriptivo de serie de casos. Se evaluó una serie prospectiva de pacientes con toxoplasmosis de la gestación durante tres años de seguimiento en el Servicio de Retinología de la Clínica Universitaria Bolivariana de Medellín. Resultados. Se registraron 23 madres con diagnóstico de toxoplasmosis de la gestación. Quince de ellas (65 %) recibieron durante la gestación tratamiento con espiramicina en dosis de 3 g al día; uno de los neonatos (6,6 %) presentó toxoplasmosis ocular. De las ocho (35 %) pacientes que no recibieron tratamiento, cinco (62,5 %) tuvieron hijos con compromiso ocular por toxoplasma. La razón de momios (odds ratio, OR) del efecto protector contra dicho compromiso en los pacientes cuyas madres recibieron tratamiento fue de 0,04 (IC95% 0,00-0,67), con valor de p menor de 0,01 en la prueba exacta de Fisher. Solo se evidenció compromiso del sistema nervioso central por toxoplasmosis mediante las imágenes de tomografía o ecografía cerebral en dos (14 %) pacientes de las 14 en quienes se hicieron estos estudios. Los dos pacientes presentaron, además, compromiso ocular; ambos fueron diagnosticados en el momento del nacimiento y sus madres no habían recibido tratamiento prenatal. Conclusiones. Estos resultados evidencian que el tratamiento con espiramicina durante el embarazo en la toxoplasmosis de la gestación redujo en 96 % (IC95% 33-100 %) el riesgo relativo de presentar la enfermedad en el recién nacido.

Abstrat Introduction: Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. Objective: To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. Materials and methods: We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Results: Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. Conclusions: A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials.

BACKGROUND: Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). OBJECTIVE: To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. METHODS: A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n = 4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. RESULTS: The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS. CONCLUSIONS: Using data from a recent patient level meta-analysis and contemporary cost data, this analysis found that PCI with Co-Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Standardized Extract from Caesalpinia spinosa is Cytotoxic Over Cancer Stem Cells and Enhance Anticancer Activity of Doxorubicin.

Cancer stem cells (CSC) are the primary cell type responsible for metastasis and relapse. ABC-transporters are integral membrane proteins involved in the translocation of substrates across membranes protecting CSC from chemotherapeutic agents. A plant extract derived from C. spinosa (P2Et) previously investigated for its antitumor activity has been shown to reduce lung and spleen metastasis in mice that have been transplanted with breast cancer cells, suggesting that P2Et has a significant activity against cancer stem cells (CSC). P2Et extract was thoroughly characterized by HPLC/MS. The cytotoxicity of P2Et extract was evaluated using a MTT assay in human and murine cell lines with different profiles of resistance, by Pgp overexpression or by enrichment in cancer stem cells. The synergistic effect of P2Et with doxorubicin was evaluated in vitro in several cell lines and in vivo in mice transplanted with TS/A cells, a highly resistant cell line and enriched in CD44[Formula: see text]CD24[Formula: see text]CSC. The chromatographic fingerprint of P2Et extract revealed 13 gallotannins. We also found that P2Et extract was cytotoxic to cells regardless of their resistant phenotype. Similarly, complementary activities were observed as drug efflux reversion and antioxidant activity. Short-treatment with P2Et extract, revealed a synergistic effect with doxorubicin in resistant cell lines. In vivo the P2Et increases mice survival in a TS/A breast cancer model associated with augmentation of calreticulin expression. Our results suggest that P2Et treatment could be used as adjuvant along with conventional chemotherapy to treat tumors with a MDR phenotype or with high frequency of CSC.