Marcadores de funcionamiento renal en pacientes infectados por SARS-CoV-2. Revisión rápida de la literatura.

 Objetivo. Resumir la evidencia científica sobre las altera-ciones renales asociadas con la infección por SARS-CoV-2. Material y métodos. Se realizó una revisión rápida con la metodología Cochrane. Resultados. La enfermedad renal crónica (ERC) preexistente en pacientes con SARS-CoV-2 varió de 1 a 38% y la lesión renal aguda (LRA), de 2.9 a 86.4%. El pronóstico de la infección fue peor en pacientes con ERC y en aquellos con reserva renal remanente (RRR) intacta que desarrollaron LRA. El riesgo de muerte fue mayor (riesgo relativo combinado = 1.49; IC95%: 1.09-2.04) en pacientes infectados por SARS-CoV-2 con ERC preexistente. Los mar-cadores de RRR mostraron alteraciones en pacientes con SARS-CoV-2 graves y fatales; el marcador más utilizado fue la creatinina sérica. Conclusiones. La evidencia científica muestra la relevancia de la evaluación y monitoreo perma-nente de la RRR en pacientes hospitalizados por SARS-CoV-2 para mejorar el pronóstico de aquellos con ERC preexistente, así como de aquellos sin ERC que desarrollan LRA.

Marcadores de funcionamiento renal en pacientes infectados por SARS-CoV-2. Revisión rápida de la literatura / Markers of kidney function among SARS-CoV-2 infected patients. A rapid review of the literature

Resumen Objetivo: Resumir la evidencia científica sobre las alteraciones renales asociadas con la infección por SARS-CoV-2. Material y métodos: Se realizó una revisión rápida con la metodología Cochrane. Resultados: La enfermedad renal crónica (ERC) preexistente en pacientes con SARS-CoV-2 varió de 1 a 38% y la lesión renal aguda (LRA), de 2.9 a 86.4%. El pronóstico de la infección fue peor en pacientes con ERC y en aquellos con reserva renal remanente (RRR) intacta que desarrollaron LRA. El riesgo de muerte fue mayor (riesgo relativo combinado = 1.49; IC95%: 1.09-2.04) en pacientes infectados por SARS-CoV-2 con ERC preexistente. Los marcadores de RRR mostraron alteraciones en pacientes con SARS-CoV-2 graves y fatales; el marcador más utilizado fue la creatinina sérica. Conclusiones: La evidencia científica muestra la relevancia de la evaluación y monitoreo permanente de la RRR en pacientes hospitalizados por SARS-CoV-2 para mejorar el pronóstico de aquellos con ERC preexistente, así como de aquellos sin ERC que desarrollan LRA.

Abstract: Objective: To summarize the scientific literature on kidney abnormalities associated with SARS-CoV-2 infection. Materials and methods: It was conducted a rapid review using the Cochrane methodology. Results: Pre-existing chronic kidney disease (CKD) in SARS-CoV-2 infected patients ranged from 1-38% and acute kidney injury (AKI) ranged from 2.9-86.4%. The prognosis of patients with SARS-CoV-2 infection was worse among those with CKD and those with normal remnant kidney function (RKF) that developed AKI. The risk of death was higher (pooled risk ratio =1.49; 95%CI: 1.09-2.04) among SARS-CoV-2 infected patients with pre-existing CKD. The RKF markers showed alterations among severe and non-surviving SARS-CoV-2 patients; the most common marker was serum creatinine. Conclusions: The scientific evidence shows the relevance of the evaluation and permanent monitoring of the RKF in SARS-CoV-2 hospitalized patients to improve the prognosis of those with pre-existing CKD as well as the prognosis of those without CKD who develop AKI.

Maternal antenatal stress has little impact on child sleep: results from a prebirth cohort in Mexico City.

STUDY OBJECTIVES: Maternal antenatal stress may influence offspring development and behavior, but any association with child sleep is unknown. METHODS: From 2007 to 2011, we recruited pregnant women in Mexico City to the Programming Research in Obesity, Growth, Environment, and Social Stressors prebirth cohort. Mothers completed the Perceived Stress Scale (PSS, a 4-item questionnaire assessing past-month stress) and the Crisis in Family Systems measure assessing negative life events (NLEs; how many domains among the 11 assessed in which the mother experienced a stressful event in the prior 6 months)-with higher scores reflecting higher stress-and provided 5 timed salivary samples per day on 2 consecutive days, from which we derived cortisol area under the curve, slope, and awakening response. At age 4-6 years, children's sleep was estimated using accelerometry over a 7-day period. We performed secondary analysis of associations of antenatal maternal stress with child sleep duration and efficiency (time asleep/time in bed) using linear regression adjusted for maternal and child characteristics. RESULTS: Among 594 mother-child dyads, mean antenatal PSS score was 5.2 (SD = 3.2) out of 16, and mean NLE was 3.2 (SD = 2) out of 11; child sleep duration was 7.7 hours (SD = 0.7), and sleep efficiency was 79% (SD = 6). There was no association between any of the stress measures-PSS, NLE, or salivary cortisol-and sleep duration or sleep efficiency in adjusted or unadjusted models. CONCLUSIONS: Among mother-child dyads in a Mexico City cohort, antenatal stress was not associated with important changes in child sleep at 4-6 years.

Systemic Implications of Hyperuricemia.

Systemic implications of hyperuricemia need to be reconsidered in the context of the energy and protein wasting being an early indicator of organ deterioration in patients affected by the cardiometabolic syndrome and other frequent pathology states like pre-eclampsia, hyperparathyroidism, and chronic renal failure. This chapter points out physiological alterations that are to be made related to hyperuricemia, new diagnostic strategies, and early therapeutic interventions in the context of the old enemy: asymptomatic hyperuricemia. This chapter also concludes with a proposal to undertake research in this emerging, primary care, cost-efficient scenario.

Prenatal co-exposure to manganese and depression and 24-months neurodevelopment.

BACKGROUND: Normal prenatal neurodevelopment follows stages that are potentially influenced by both chemical and psychosocial environments. Exposure to elevated manganese during this critically vulnerable period has been found to be neurotoxic. Independently, maternal prenatal depression has been associated with subsequent neurodevelopmental decrements in children. The association between child neurodevelopment and prenatal co-exposure to manganese and maternal depression has not been sufficiently studied. METHODS: During pregnancy and at birth, we measured maternal blood and cord blood manganese levels respectively. Maternal depression was assessed in the 3rd trimester of pregnancy using the Edinburgh Depression Scale. Neurodevelopment was evaluated at 24 months of age with the Bayley Scales of Infant Development. A multivariate multiple regression model was used to analyze cognitive, language and motor scores simultaneously for 473 children from the PROGRESS birth cohort in Mexico City. RESULTS: Over 25% of our study participants reported having depressive symptoms. 3rd trimester blood manganese as well as depressive symptoms were independently negatively associated with all neurodevelopment scores in adjusted models. In stratified analyses, the negative association between manganese (maternal as well as cord blood) and 24-month language scores was stronger among women with depressive symptoms. Receptive language was mostly affected. Inverted U-shaped curves were seen for the association between with cord blood manganese and neurodevelopment scores. CONCLUSIONS: Our findings are in line with previous studies of manganese and depression neurotoxicity. The prenatal period may be particularly sensitive to manganese and depression co-exposures and should be of interest for public health interventions to promote healthy emotional and nutritional pregnancies.

Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment.

BACKGROUND: Lead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies. OBJECTIVE: To evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity. METHODS: We used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24month-old children (n=360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire. RESULTS: 3rd trimester lead (mean 3.9±3.0 SDµg/dL) and stress (median=3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10µg/dL) and observed a dose-response for the developmental scores when lead levels were below 2µg/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association. CONCLUSIONS: Our work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life.

Longitudinal associations of age and prenatal lead exposure on cortisol secretion of 12-24 month-old infants from Mexico City.

BACKGROUND: Cortisol has functions on homeostasis, growth, neurodevelopment, immune function and the stress response. Secretion follows a diurnal rhythm that mediates these processes. Our objective was to examine the association between prenatal lead exposure and infant diurnal cortisol rhythms. METHODS: We measured infant cortisol rhythms in saliva collected repeatedly over 2 days at either 12 (n = 255) or 18-24 (n = 150) months of age. Prenatal lead exposure was assessed by measuring maternal pregnancy blood lead levels and early postnatal maternal bone lead content. We analyzed age-specific basal secretion and the association between trimester-specific and cumulative lead exposure with a) change in total diurnal cortisol and b) the shape of the cortisol curve across the length of the day. RESULTS: Our results showed age related differences in salivary cortisol secretion and an age dependent association with maternal lead exposure. In age-stratified models we saw an inverse association between lead and cortisol levels in 12-month-old infants and a positive association for 18-24-month-old infants. For the 12-month-old infants 2nd-trimester-lead ≥10 µg/dL was associated with 40 % lower cortisol levels (95 % CI (-57, -16)) and a significant change in the shape of the cortisol curve (p = 0.01), compared to infants with low blood lead levels (<5 µg/dL). CONCLUSIONS: Basal cortisol secretion changes with age. Increased early gestation lead exposure alters diurnal cortisol rhythms and the association is modified by infant age, perhaps representing an early maturation of cortisol homeostasis.

Lead in candy consumed and blood lead levels of children living in Mexico City.

BACKGROUND: Recent studies have shown that lead exposure continues to pose a health risk in Mexico. Children are a vulnerable population for lead effects and Mexican candy has been found to be a source of exposure in children. There are no previous studies that estimates lead concentrations in candy that children living in Mexico City consume and its association with their blood lead level. OBJECTIVES: To evaluate whether there is an association between reported recent consumption of candies identified to have lead, and blood lead levels among children in Mexico City. METHODS: A subsample of 171 children ages 2-6 years old, from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort study was assessed between June 2006 and July 2007. The candy reported most frequently were analyzed for lead using ICP-MS. The total weekly intake of lead through the consumption of candy in the previous week was calculated. Capillary blood lead levels (BLL) were measured using LeadCare (anodic stripping voltammetry). RESULTS: Lead concentrations ≥0.1ppm, the FDA permitted level (range: 0.13-0.7ppm) were found in 6 samples out of 138 samples from 44 different brands of candy. Median BLL in children was 4.5µg/dl. After adjusting for child's sex, age, BMI, maternal education & occupation, milk consumption, sucking the candy wrapper, use of lead-glazed pottery, child exposure behavior, living near a lead exposure site and use of folk remedies, an increase of 1µg of lead ingested through candy per week was associated with 3% change (95% CI: 0.1%, 5.2%) in BLL. CONCLUSIONS: Although lead concentrations in candy were mostly below the FDA permitted level, high lead concentrations were detected in 4% of the candy samples and 12% of brands analyzed. Although candy intake was modestly associated with children's BLL, lead should not be found in consumer products, especially in candy that children can consume due to the well documented long-lasting effect of lead exposure.

Prenatal and postnatal stress and wheeze in Mexican children: Sex-specific differences.

BACKGROUND: Increasing evidence links early-life exposure to psychosocial stress with adverse childhood respiratory outcomes. The influence of exposure timing has not been completely elucidated. OBJECTIVE: To examine the association between prenatal and postnatal maternal stress and wheeze in 417 children enrolled in a prospective birth cohort in Mexico City. METHODS: Maternal negative life event (NLE) scores were ascertained in the second or third trimester of pregnancy and at the 48-month postnatal visit. Children's respiratory outcomes, caregiver report of ever wheeze, and wheeze in the past 12 months were obtained from the International Study of Asthma and Allergies in Childhood survey administered at 48 months. Associations between prenatal and postnatal NLE scores and wheeze were analyzed using a modified Poisson regression approach adjusting for covariates. RESULTS: In separate models, higher maternal psychosocial stress during pregnancy (relative risk [RR], 1.12; 95% CI, 1.00-1.26) and postnatally (RR, 1.21; 95% CI, 1.08-1.35) were associated with increased risk of wheeze in the past 12 months with an evident exposure-response relationship. There was a significant interaction between postnatal stress and sex in relation to current wheeze. In a sex-stratified model, the association between postnatal stress and risk of wheeze in the past 12 months was stronger in girls (RR, 1.35; 95% CI, 1.13-1.61) than in boys (RR, 1.11; 95% CI, 0.97-1.27) (P for interaction = .04). CONCLUSION: Prenatal and postnatal stress in mothers was associated with wheeze in preschool-aged children, and the effect of postnatal stress was stronger in girls. Understanding the temporal- and sex-specific effects of stress may better inform prevention strategies.

Relating Phthalate and BPA Exposure to Metabolism in Peripubescence: The Role of Exposure Timing, Sex, and Puberty.

CONTEXT: Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis. OBJECTIVE: To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis. DESIGN: Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring. SETTING: Public maternity hospitals in Mexico City. PATIENTS OR OTHER PARTICIPANTS: Women recruited during pregnancy; offspring recruited for follow-up at age 8-14 years (n = 250). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance. RESULTS: Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8-14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P = .02) and higher leptin among girls (P = .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P = .01). CONCLUSIONS: Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.

Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight.

Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns. We enrolled pregnant women in the PROGRESS birth cohort in Mexico City. Using pyrosequencing, we analyzed DNA methylation of 3 CpG sites within the AHRR gene promoter from the umbilical cord blood of 531 infants. We used generalized estimating equations to account for the correlation of DNA methylation between CpG sites. Multivariable models were used to adjust for maternal age, BMI, education, parity, smoke-exposure, infant sex, gestational age, and birth weight-for-gestational age. AHRR DNA methylation was positively associated with maternal BMI (P = 0.0009) and negatively associated with the length of gestation (P < 0.0001) and birth weight-for-gestational age (P < 0.0001). AHRR DNA methylation was 2.1% higher in offspring of obese vs. normal weight mothers and 3.1% higher in preterm vs. term infants, representing a third and a half standard deviation differences in methylation, respectively. In conclusion, offspring AHRR DNA methylation was associated with maternal obesity during pregnancy as well as infant gestational age and birth weight-for-gestational age. Further work to discover the health impacts of altered AHRR DNA methylation is warranted.

Mercury and psychosocial stress exposure interact to predict maternal diurnal cortisol during pregnancy.

BACKGROUND: Disrupted maternal prenatal cortisol production influences offspring development. Factors influencing the hypothalamic-pituitary-adrenal axis include social (e.g., stressful life events) and physical/chemical (e.g., toxic metals) pollutants. Mercury (Hg) is a common contaminant of fish and exposure is widespread in the US. No prior study has examined the joint associations of stress and mercury with maternal cortisol profiles in pregnancy. OBJECTIVES: To investigate potential synergistic influences of prenatal stress and Hg exposures on diurnal cortisol in pregnant women. METHODS: Analyses included 732 women (aged 27.4 ± 5.6 years) from a Mexico City pregnancy cohort. Participants collected saliva samples on two consecutive days (mean 19.52 ± 3.00 weeks gestation) and reported life stressors over the past 6 months. Hg was assessed in toe nail clippings collected during pregnancy. RESULTS: There were no main effects of Hg or psychosocial stress exposure on diurnal cortisol (ps > .20) but strong evidence of interaction effects on cortisol slope (interaction B = .006, SE = .003, p = .034) and cortisol at times 1 and 2 (interaction B = -.071, SE = .028, p = .013; B = -.078, SE = .032, p = .014). Women above the median for Hg and psychosocial stress exposure experienced a blunted morning cortisol response compared to women exposed to higher stress but lower Hg levels. CONCLUSIONS: Social and physical environmental factors interact to alter aspects of maternal diurnal cortisol during pregnancy. Research focusing solely on either domain may miss synergistic influences with potentially important consequences to the offspring.

Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study.

BACKGROUND: Lead (Pb) exposure during pregnancy may increase the risk of adverse maternal, infant, or childhood health outcomes by interfering with hypothalamic-pituitary-adrenal-axis function. We examined relationships between maternal blood or bone Pb concentrations and features of diurnal cortisol profiles in 936 pregnant women from Mexico City. METHODS: From 2007-11 we recruited women from hospitals/clinics affiliated with the Mexican Social Security System. Pb was measured in blood (BPb) during the second trimester and in mothers' tibia and patella 1-month postpartum. We characterized maternal HPA-axis function using 10 timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14-35 weeks gestation). We used linear mixed models to examine the relationship between Pb biomarkers and cortisol area under the curve (AUC), awakening response (CAR), and diurnal slope. RESULTS: After adjustment for confounders, women in the highest quintile of BPb concentrations had a reduced CAR (Ratio: -13%; Confidence Interval [CI]: -24, 1, p-value for trend < 0.05) compared to women in the lowest quintile. Tibia/patella Pb concentrations were not associated with CAR, but diurnal cortisol slopes were suggestively flatter among women in the highest patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: -2, 33). BPb and bone Pb concentrations were not associated with cortisol AUC. CONCLUSIONS: Concurrent blood Pb levels were associated with cortisol awakening response in these pregnant women and this might explain adverse health outcomes associated with Pb. Further research is needed to confirm these results and determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal-axis function during pregnancy.

Intake of dehydrated nopal (Opuntia ficus indica) improves bone mineral density and calciuria in adult Mexican women.

BACKGROUND: The intake of dehydrated nopal (DN) at a high stage of maturity along with high calcium content could improve bone mineral density (BMD) and calciuria and thus prevent osteoporosis. OBJECTIVE: To evaluate the effect of calcium intake from a vegetable source (DN) on BMD and calciuria covering a 2-year period in menopausal and non-menopausal women with low bone mass (LBM). METHODS: The study was quasi-experimental, blinded, and randomized, and included 131 Mexican women aged 35-55. Urinary calcium/creatinine index (CCI) was determined; BMD was analyzed on lumbar spine and total hip regions. Four groups were studied: Control group (CG), women with normocalciuria and a minimum dose of DN; experimental group 1 (EG1), women with hypercalciuria and a minimum dose of DN; experimental group 2 (EG2), women with hypercalciuria, and a maximum dose of DN; and normal group (NG) for reference in BMD. RESULTS: After the first semester of treatment, calciuria levels in women from both experimental groups returned to normal, remaining constant for the rest of the treatment. The percentage difference in BMD increased in the total hip region in the CG (pre 4.5% and post 2.1%) and EG2 (pre 1.8% and post 2.5%) groups significantly in comparison to NG and EG1, which exhibited a significant decrease in their BMD. BMD increased only for the lumbar region in the EG2 group (premenopausal). CONCLUSION: The use of a vegetable calcium source such as nopal improves BMD in women with LBM in the total hip and lumbar spine regions principally in the premenopausal women, maintaining constant and normal calciuria levels.

Utilidad de los bifosfonatos en el síndrome de distrofia simpática refleja / Bisphosphonates utility in sympathetic dystrophy syndrome

En distrofia simpática refleja suele ocurrir un dolor tan intenso que no guarda relación con la causa del padecimiento, además de una pérdida de la función clara y evidencia de trastorno autónomo. Los hallazgos radiológicos son importantes en su diagnóstico y en el diagnóstico diferencial; las radiografías convencionales típicamente, aunque no en forma invariable, revelan osteopenia difusa "en parches". La medida preventiva más efectiva es lograr el control del dolor y efectuar una movilización temprana; muchos tratamientos han sido intentados aunque con respuesta no consistente. Los medicamentos incluyen analgésicos, antiinflamatorios no esteroideos, antidepresivos y esteroides. El objetivo del presente estudio fue revisar la bibliografía internacional para evaluar la eficacia y la seguridad de diferentes bifosfatos como tratamiento de nueva elección en el control del dolor y la osteopenia propios de la distrofía simpática refleja

Utilidad diagnóstica de la exploración de las manos en el pacientes reumático / Diagnostic usefulness of the exploration of the hands in the reumatic patient

La identificación precisa y oportuna de diferentes enfermedades que afectan las manos es posible si se pone en práctica una exploración física sencilla y correcta. Esto permite en forma adecuada la sospecha y la confirmación de padecimientos de índole reumática y puede ser accesible al médico no especialista en padecimientos musculoesqueléticos. Ello posibilita, a la vez, prescribir un tratamiento apropiado que evite una mayor pérdida funcional, deformidad e incapacidad en este tipo de pacientes. En este artículo se analiza y ejemplifica cómo explorar adecuadamente las manos, cuáles son las enfermedades reumáticas que con mayor frecuencia repercuten en la anatomía y función de las mismas, además de las características de aparación clínica de cada una de las diferentes artropatías

Origen de la osteoporosis en el paciente con artritis reumatoide / Origin of osteoporosis in the patient with rheumatoid arthritis

La artritis reumatoide se asocia a osteoporosis tanto localizada como generalizada. Se considera que la osteoporosis localizada está causda por mecanismos locales de la enfermedad; la causa de la osteoporosis generalizada ha resultado defícit de presisar; aún es incierto si ésta es consecuencia de la actividad de la enfermedad, la inmovilidad o el tratamiento mismo. La introducción de la densitometría ósea ha permitido evaluar con mayor precisión la densidad mineral. El tratamiento con corticoesteroides favorece el desarrollo de la osteoporosis en este tipo de pacientes; se discute el empleo de nuevos corticoesteroides. Se evalúa la densidad mineral ósea en diferentes grupos internacionales de pacientes con artritis reumatoide y osteoporosis

Metodología formal de la investigación científica / Formal Metodology of the scientific investigation

Presenta técnicas existentes para llevar a cabo una metodología de investigación científica