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Indexación Scopus Wnt signaling plays a key role in neurodevelopment and neuronal maturation. Specifically, Wnt5a stimulates postsynaptic assemblies, increases glutamatergic neurotransmission and, through calcium signaling, generates nitric oxide (NO). Trying to unveil the molecular pathway triggering these postsynaptic effects, we found that Wnt5a treatment induces a time-dependent increases in the length of the postsynaptic density (PSD), elicits novel synaptic contacts and facilitates F-actin flow both in in vitro and ex vivo models. These effects were partially abolished by the inhibition of the Heme-regulated eukaryotic initiation factor 2α (HRI) kinase, a kinase which phosphorylates the initiation translational factor eIF2α. When phosphorylated, eIF2α normally avoids the translation of proteins not needed during stress conditions, in order to avoid unnecessary energetic expenses. However, phosphorylated eIF2α promotes the translation of some proteins with more than one open reading frame in its 5′ untranslated region. One of these proteins targeted by Wnt-HRI-eIF2α mediated translation is the GluN2B subunit of the NMDA receptor. The identified increase in GluN2B expression correlated with increased NMDA receptor function. Considering that NMDA receptors are crucial for excitatory synaptic transmission, the molecular pathway described here contributes to the understanding of the fast and plastic translational mechanisms activated during learning and memory processes. © 2021, The Author(s). https://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-021-86708-y

Background Cognitive dysfunction (CD) is common among patients with the autoimmune disease systemic lupus erythematosus (SLE). Anti-ribosomal P autoantibodies associate with this dysfunction and have neuropathogenic effects that are mediated by cross-reacting with neuronal surface P antigen (NSPA) protein. Elucidating the function of NSPA can then reveal CD pathogenic mechanisms and treatment opportunities. In the brain, NSPA somehow contributes to glutamatergic NMDA receptor (NMDAR) activity in synaptic plasticity and memory. Here we analyze the consequences of NSPA absence in KO mice considering its structural features shared with E3 ubiquitin ligases and the crucial role of ubiquitination in synaptic plasticity. Results Electrophysiological studies revealed a decreased long-term potentiation in CA3-CA1 and medial perforant pathway-dentate gyrus (MPP-DG) hippocampal circuits, reflecting glutamatergic synaptic plasticity impairment in NSPA-KO mice. The hippocampal dentate gyrus of these mice showed a lower number of Arc-positive cells indicative of decreased synaptic activity and also showed proliferation defects of neural progenitors underlying less adult neurogenesis. All this translates into poor spatial and recognition memory when NSPA is absent. A cell-based assay demonstrated ubiquitination of NSPA as a property of RBR-type E3 ligases, while biochemical analysis of synaptic regions disclosed the tyrosine phosphatase PTPMEG as a potential substrate. Mice lacking NSPA have increased levels of PTPMEG due to its reduced ubiquitination and proteasomal degradation, which correlated with lower levels of GluN2A and GluN2B NMDAR subunits only at postsynaptic densities (PSDs), indicating selective trafficking of these proteins out of PSDs. As both GluN2A and GluN2B interact with PTPMEG, tyrosine (Tyr) dephosphorylation likely drives their endocytic removal from the PSD. Actually, immunoblot analysis showed reduced phosphorylation of the GluN2B endocytic signal Tyr1472 in NSPA-KO mice. Conclusions NSPA contributes to hippocampal plasticity and memory processes ensuring appropriate levels of adult neurogenesis and PSD-located NMDAR. PTPMEG qualifies as NSPA ubiquitination substrate that regulates Tyr phosphorylation-dependent NMDAR stability at PSDs. The NSPA/PTPMEG pathway emerges as a new regulator of glutamatergic transmission and plasticity and may provide mechanistic clues and therapeutic opportunities for anti-P-mediated pathogenicity in SLE, a still unmet need.

OBJECTIVE To compare the prevalence of diabetic retinopathy (DR) between low-income Mexicans from Mexico City and Mexican-Americans from San Antonio, Texas. RESEARCH DESIGN AND METHODS We designed a cross-sectional population-based study in low-income neighborhoods of Mexico City and San Antonio. The men and non-pregnant women included in the study had NIDDM and were between 35 and 64 years of age. Ophthalmologic evaluation was performed in 414 patients, 204 in San Antonio and 210 in Mexico City. Seven field standard stereophotographs of each eye were obtained, adapting the Early Treatment Diabetic Retinopathy Study protocol, and graded at the Fundus Photograph Reading Center of the University of Wisconsin. RESULTS Early nonproliferative DR occurred in 37 (17.6%) and 39 (19.1%) patients in Mexico City and San Antonio, respectively. Moderate-to-severe nonproliferative DR occurred in 55 (26.2%) and 37 (18.1%) patients in Mexico City and San Antonio, respectively, and proliferative DR occurred in 12 (5.7%) and 7 (3.4%) patients in Mexico City and San Antonio, respectively. Using univariate and multivariate logistic regression analysis with DR as the dependent variable, age, duration of disease, and fasting glucose concentration were positively and significantly associated with retinopathy, whereas city, systolic blood pressure, and other selected metabolic variables were not. We defined moderate-to-severe DR to include the categories of moderate-to-severe nonproliferative and proliferative DR. For this combined category, Mexico City patients with diabetes had a significantly higher prevalence (P < 0.01) than those from San Antonio when analyzed by multiple logistic regression analysis (odds ratio for Mexico City/San Antonio, 1.72; 95% CI 1.10–2.70). CONCLUSIONS Overall prevalence of DR is similar in both cities. However, moderate-to-severe DR is significantly higher in Mexico City.

The most frequent cause of preventable blindness in adults, in the developed world, is diabetic retinopathy (DR). The early treatable phase of this complication is clinically silent. In order to institute effective laser photocoagulation and prevention of blindness, timely detection is crucial. Consequently there is a need for periodic funduscopic examinations of all diabetics. Due to the high prevalence of DM in Mexico most of the primary care facilities are limited. We present the results of a DR screening program (DRSP) using a mobile unit equipped with a fundus photography camera, parked outside of a clinic. We report the prevalence of the various stages of DR and clinical characteristics observed in this population as well as our experience working in such an environment. The study period was from September 1 to December 22, 1995. All the diabetics that presented for care to the clinic were identified and all other persons were invited to participate. A total of 231 participants were invited (112 men, 119 women). Non-stereo fundus photos of two retinal fields (macula and optic disk centered) were taken with technique and classification according to international standards. Response rate to the invitation was 95.3%. Mean age was 62.4 +/- 13 years and 63.5 +/- 10 years and duration of diabetes was 12.3 +/- 10.1 years and 11.0 +/- 7.5 years for men and women, respectively. DR was detected in 38% of the cases, of these only 5.6% have received treatment. DR was uncovered in 84.5% of the cases and was associated with duration of diabetes (p0.001 in men and p = 0.04 in women) and hyperglycemia (in men p0.005, only). DR has a high prevalence in this population and can be detected through a screening program which reveals undiagnosed high risk DR in an efficient, and standardized manner.

The authors present the results of a population-based survey of cholelithiasis carried out in a low-income area of Mexico City using high-resolution gallbladder ultrasound. The purpose of the study was to estimate the prevalence and selected associated risk factors of cholelithiasis (CL). The population of the studied area was 15,532 subjects, of whom 3,505 (22.6%) were eligible for the baseline survey (men and non-pregnant women between 35-64 years of age). Of this group, 1,735 (76.03%, 702 men and 1,033 women) were located for a follow-up study. Ultrasonography was performed on all except for 100 subjects who had undergone previous cholecystectomy. Crude prevalence of CL was 14.1% (95% CI 12.5-15.5). The prevalence was 5.8% (95% CI 4.1-7.5) in men and 19.7% (95% CI 17.3-22.1) in women. Presence of gallstones was associated with age, sex (men p0.006, women p0.001), and multiparity (p0.002). Centrality index in men and body mass index in women were positive and significantly associated with CL when compared with subjects without CL. High levels of fasting and post-glucose load insulin in women and men respectively were associated with CL. The authors conclude that the population of this study has a high prevalence of CL and confirm some known risk factors such as age, sex, BMI and multiparity. Proper assessment of the magnitude problem and characterization of potentially modifiable risk factors will play a major role in preventing this pathology.

Proper detection, adequate laser therapy and follow-up of diabetic retinopathy (DR), using guidelines established by landmark studies, are important to prevent blindness. In this report we analyze the agreement between 11 retina specialists and the Preferred Practice Pattern of the American Academy of Ophthalmology in the therapeutic and follow-up criteria for DR. Color fundus stereophotographs of seven standard fields of each eye of 15 diabetics were sent to 11 retina specialists. Their treatment and follow-up criteria were surveyed. For treatment of DR mean percent agreement was 65%. Kappa statistic, which corrects for chance agreement, was between -0.23 and 0.63 with a mean of 0.26. The therapeutic recommendations for macular edema were analyzed separately and the mean kappa was between -0.10 and 0.71 with a mean of 0.32. With respect to recommendations for interval until follow up, following initial visit, mean percent agreement was 73% with a kappa statistic between -0.22 and 0.33 and a mean of 0.07. Based on conventional interpretation of kappa statistic these mean values are in the range of poor agreement. Since there is a significant discrepancy in the concordance level in both therapeutic and follow-up recommendations for the management of DR, there is a need to improve agreement in these criteria, since these are key elements in the decision making process of the specialist caring for diabetic patients.

We present the results of a population-based survey carried out in a low income area of Mexico City. The aim of this study is to characterize the prevalence of clinically significant gallbladder disease (CSGD) using the self-reported history of cholecystectomy (CG) or cholelithiasis (CL) demonstrated by cholecystography and/or ultrasonography. The population of the studied area was 15,532 inhabitants, of whom 3505 (22.6%) were age eligible (35-64 year-old men and non-pregnant women). Home interviews were obtained in 2810 (80.2%). A physical and laboratory examination was performed in 2282 individuals (65.1%; 941 men and 1341 women). The prevalence of CSGD in men was 2.0% (95% confidence intervals 1.1-2.9%) and 9.2% in women (95% confidence intervals 7.7-10.7%). Patients with CSGD were older, men (p0.003) and women (p0.001). Women with CSGD had higher waist to hip circumference ratio (p0.06), higher fasting glucose (p0.03) as well as 2 h post challenge glycemia (p0.04) and insulinemia (p0.03). In the multiple logistic regression model only age (p0.001) and sex (p0.001) remained significantly associated. We conclude that CSGD is quite prevalent in this population. It is associated with age in both genders and in women, higher glucose and insulin levels. The prospective follow-up of this cohort is important since it could generate the information needed to implement a preventive program to diminish the impact of this condition.

Among the most serious complications associated with diabetes mellitus (DM) is nephropathy (DN). In Mexico, there is little information on the frequency and clinical characteristics of DN in the Mexican population. We present results of a population-based survey designed to estimate the prevalence of DN. The low income population consisted of 15,532 inhabitants. All 35- to 64-year-old males and non-pregnant women residing in the survey area were identified as eligible for the study (3505; 22.6%). A home interview was obtained in 2810 (80.2%). A physical exam with oral glucose tolerance test was obtained in 2282 (81.2% of those interviewed). DM was diagnosed in 304 (crude rate 13.3%). Mean age for men and women with DM was 51.6 +/- 8.4 and 52.2 +/- 7.5, respectively. Duration of DM in men was 9.2 +/- 8.1 and in women, 7.3 +/- 6.7 years. Hypertension was diagnosed in 19.8% of men and 18.1% of women. Diabetic retinopathy of any level was found in 55.4% of men and 45.7% of women. Mean glycohemoglobin in men was 9.6 +/- 2.1 and in women 9.5 +/- 2.2% (normal 4-8%). At baseline, proteinuria (1+ or more, by dipstick) was found in 24.7% of men and 9.6% of women, microalbuminuria (MA) in 84.4% of men and 63.8% of women. Quantitative albuminuria was abnormally high in 54.7% of men and 40.3% of women. In the 203 diabetics studied with 24 h urine collection for creatinine clearance, normal renal function was found in 69.1% of men and 47.5% of women, reduced renal function was found in 26% of men and 50% of women, renal insufficiency was diagnosed in 4.9% of men and 1.6% of women. One patient was on dialysis and in a subsequent follow up, we found that 2.3% of the patients had died of renal failure, six men (46-63 years) and a woman of 62 years. We conclude that DN is a very serious threat to this population. The high case fatality rate associated with this condition maintains a low prevalence. It is important to develop a program to diminish the frequency of this condition.

In this report we present the results of a population based survey designed to characterize the prevalence of hypercholesterolemia (HCL: total cholesterolor = 240 mg/dl) in a low income urban area of Mexico City (The Mexico City Diabetes Study). In an area of 15,532 inhabitants, 3505 (22.57%) were found to be study eligible (all 35-64 year-old men and nonpregnant women residing in the area permanently). A home interview was obtained in 2813 (80.26%) subjects. A physical exam and oral glucose tolerance test was performed on 2282 (81.2% of the individuals that gave the interview and 65.1% of all study eligibles, 941 men and 1341 women). The crude prevalence of HCL for men in this group was 12.3% and for women 12.5%. Severe HCL (total cholesterolor = 260 mg/dl) was found in 6.6% of men and 6.5% of women. In the older age group (55-64 years) prevalence in women reached 21.1%. Of the individuals with HCL this abnormality was previously diagnosed in only 15.9% of men and in 7.8% of women. Despite having been diagnosed, the abnormality remained untreated in all cases. HCL was associated with higher mean systolic blood pressure (in women), higher mean diastolic blood pressure (in men) and higher mean fasting and 2 h post-glucose load glycemia as well as post-challenge insulinemia in both sexes. Mean TG was found high in both groups (with and without HCL), but in subjects with HCL the values were significantly higher. We conclude that HCL is very common in this population. The majority of the cases remained undiagnosed and of the small fraction of subjects that have been diagnosed, virtually none is under medical care. It is necessary to design and implement a national program to reduce the impact of this serious health problem.

We present the results of a population based survey designed to estimate the prevalence and clinical characteristics of carotid artery atherosclerosis (CAS) diagnosed using vascular ultrasonography (VUS) in a low income area of Mexico City encompassing six neighborhoods that we previously studied. We attempted to locate all the non-diabetic participants of the first two neighborhoods (n = 834) and all diabetics from the six neighborhoods (n = 304). We located 1078 (94.7%) participants and examined 770 (71.4%). All study subjects were men and non-pregnant women between 35-64 years of age and had standardized VUS protocol. In men, the prevalence of CAS was 16.29%, in women the prevalence was 12.3%. CAS was significantly associated in both sexes to age (p0.001) and systolic blood pressure (p0.001). The ratio of the subscapular to triceps skinfolds was significantly higher in men with CAS (p0.04). In women, fasting glucose was higher in subjects with CAS (p0.04). The lipid profile was similar in men with and without CAS. However, women with CAS had significantly higher total cholesterol (p0.001), LDL cholesterol (p0.002), VLDL cholesterol (p0.092) and mean TG (p0.033). The percent of patients with hypertension, tobacco use, myocardial infarction and diabetic retinopathy of any degree was significantly higher in the subjects with CAS. CAS of any degree was observed in 12.4% of the non-diabetic population and 18.13% of the diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Proper detection and adequate laser therapy of diabetic retinopathy (DR) using guidelines established by landmark studies is important to prevent blindness. We analyzed the agreement between diagnostic classification of DR as determined by certified retina specialists compared with standardized readings of fundus photographs performed by the Fundus Photograph Reading Center (FPRC) of the University of Wisconsin. Color fundus stereophotographs of seven standard fields of each eye of 15 diabetics were sent to FPRC and to 11 retina specialists practicing in Mexico City and representing the major health care institutions. These centers are sites for training programs in ophthalmology. In addition, leading specialists in private practice were invited to participate. Their diagnostic criteria were surveyed. Information was collected using a specially designed form on which the investigator entered his/her diagnostic classification using his/her clinical judgment. Mean overall percent agreement was 74%. Kappa statistic, which corrects for chance agreement, was between 0.29-0.87 with a mean of 0.53. Weighted kappa measuring level of disagreement was between 0.34-0.90, mean 0.57. Data were analyzed separately for macular edema and for this end point the weighted kappa statistic was 0.68. Based on conventional interpretation of the kappa statistic, these mean values are in the range of fair agreement. However, since there is a significant discrepancy in the concordance level observed, there is a need for promoting further applications of internationally accepted diagnostic criteria to assure optimal therapy.

The results of a population based survey, carried on in a low income area of Mexico City, with a total population of 15,532 inhabitants, are presented. From these, 3,505 individuals were considered eligible (35-64 years of age and non pregnant women). A home interview was performed in 2,810 households (80.17%). Physical exam with oral glucose tolerance test was performed in 2,282 (65.10%) participants. A total of 340 patients were identified as type II diabetics (WHO criteria); 140 of them were males and 200 females. Impaired glucose tolerance (IG) was diagnosed in 376 subjects, 120 (12.78%) of whom were males and 256 (19.06%) females. Approximately three years after the first exam, an attempt was made to recontact all the participants. A home or telephone interview was obtained in 2,139 subjects; they were asked if they had been hospitalized in the past three years, their length of stay and the cause. Due to incomplete data 194 subjects were excluded from the analyses presented in this report. A total of 101 participants that had normal glucose tolerance were hospitalized (6.4%). Of the ones diagnosed as IG, 15 (5.45%) were hospitalized. Of the patients diagnosed as diabetics 31 (12.5%) were hospitalized. At least 30 per cent of this excess demand is potentially preventable, since it is related directly to decompensation of DM control. We identified the need to implement a mechanism for guaranteeing entrance of all patients diagnosed with IG to health facilities.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to characterize the prevalence and detection of systemic hypertension in a low income urban area of Mexico City. The population of the studied area was 15,532 inhabitants, of whom 3505 (22.6%) were eligible for study (men aged 35-64 years and non-pregnant women). Home interviews were obtained on 2810 (80.2%) and physical and laboratory examination was performed on 2282 individuals (941 men, 1341 women, 81.2% of those interviewed and 65.1% of all the eligibles). Blood pressure (BP) was measured using a random zero sphygmomanometer (Hawksley, London). Three measurements were made on the right arm after a 5 min rest, with the patient seated. The average of the last two determinations was taken as the patient's BP. High blood pressure (HBP) was defined as systolic BPor = 160 and/or diastolic BPor = 95 mmHg, or if the patient was taking antihypertensive therapy regardless of the blood pressure value. A total of 216 subjects (77 men, 139 women) met criteria for HBP. In the 35-44 age group, prevalence for men was 4.16% and for women 3.06%. In the 44-55 age groups the prevalence for men was 7.81% and for women 12.55%. In the 55-64 year group the prevalence for men was 16.51% and for women 22.2%. Obesity was associated with HBP (body mass index in men with HBP was 28.9 kg/m2 vs. without 26.9 kg/m2, p0.001; women with HBP, 30.8 kg/m2 vs. without 28.5 kg/m2, p0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

We present the results of a population based study designed to estimate the prevalence of diabetic retinopathy in a series of 284 type 2 diabetics residing in low income areas of Mexico City. These patients were identified in a survey performed between February 1990 and October 1992 (The Mexico City Diabetes Study). We located 214 (75.35%) of the original 284 patients and invited them to attend a clinic where they were interviewed and had a complete ophthalmologic examination. All participants had, in addition to the retinal examination by a certified ophthalmologist, seven fields stereo fundus photographs taken with a Topcon 50X retinal camera. Photos were taken using ASA 100 Kodak film and processed in their laboratory. All photographs were read and graded for quality and level of diabetic retinopathy (DR) in the Reading Center of the Department of Ophthalmology of the University of Wisconsin. A total of 37 (43.5%) men and 69 (53.5%) women had no evidence of DR. In 16 (18.8%) men and 21 (16.3%) women there was background DR. In 25 (29.4%) men and 30 (23.3%) women there was preproliferative DR. In 5 (5.9%) men and in 7 (5.4%) women there was proliferative DR. Macular edema was diagnosed in 7 (8.2%) men and 6 (4.7%) women, of these in 3 (3.5%) men and in 5 (3.9%) women the macular edema was central. This complication is associated with duration of diabetes, chronic poor metabolic control and microalbuminuria. A very significant proportion of cases with sight threatening DR remains undiagnosed and untreated. Consequently there is a significant number of cases developing into blindness that could have been prevented.

The importance of good metabolic control in the treatment of diabetes mellitus (DM) is unquestionable. Measurements of the level of control (LC) are available such as glycohemoglobin (GH) and fructosamine (FA). The aims of this study are: to estimate LC in a population based case series of type II DM patients, to assess the effect of clinical, metabolic and sociodemographic variables usually associated with the LC and to estimate the clinical impact of the LC on vascular complications of DM. A low income area of Mexico City was enumerated. All males and non-pregnant females between 35-64 years of age were considered eligible. Home interview was obtained in 2813 and a medical exam including an oral glucose tolerance test was performed in 2282 (65.1%). Three hundred and four subjects met the criteria (WHO) for DM. Three years later, 213 (70.1%) were located for GH and FA measurements. Cases were divided according to the level of GH: Group I, good LC (GHor = 8.6%, n = 66); and group II poor LC (GHor = 8.7%, n = 147). A significant difference was observed in the mean value of FA between groups (Group I 255 +/- 52.3 mumol/dl. Group II 306.4 +/- 51.1; p0.001). In comparison with subjects with good LC, patients with poor LC had higher values of duration of DM (p0.01), waist/hip ratio (p0.04), fasting glucose (p0.001) and lower values of fasting insulin (p0.07), LDL cholesterol (p0.006) and VLDL cholesterol (p0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

The results of a population based study carried out in a low income area of Mexico City are presented in this paper. The study was designed to investigate tobacco consumption as a cardiovascular risk factor in the population ages range of 35-64 years. A home interview was accomplished for 2,155 individuals. Monthly family income, employment status, years of schooling and tobacco consumption were investigated. The majority of the participants reported a monthly family income of 500 to one hundred new pesos and the average of school years was 5.8 +/- 3.2 years. In most cases (93.8%), participants reported to have a paid job and only 2.09 per cent were unemployed. A total of 74.2 of men and 24.5 per cent of women reported that they had smoked at least 50 cigarettes in their lifespan and 52.5 per cent of men and 17.9 of women were current smokers. Most smokers (62.9% men, 74.5% women) consume 10 or less cigarettes per day, but 33.2 per cent of men and 24.2 of women were heavy smokers, that is 10-29 cigarettes per day. Only eleven men and seven women smoked cigars or pipe. This results show a high rate of tobacco consumption in this population, therefore it is imperative to strengthen education programs aimed at promoting healthier habits and to stop tobacco consumption.

BALB/c mice infected with Leishmania mexicana developed a chronic infection usually accompanied by the appearance of metastatic lesions. Throughout the 20 weeks of observation, infected mice ;howed an impairment in both in vivo delayed hypersensitivity response and in vitro lymphocyte reactivity to leishmanial antigen. Four to 8 weeks after inoculation infected mice displayed a transitory enhancement of spleen cell responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide. At the same time, immunization with sheep erythrocytes resulted in a greater number of immunoglobulin P, lipopolysaccharide, and sheep erythrocytes diminished progressively, whereas reactivity to concanavalin A was markedly augmented. When cocultivated with spleen cells from mice infected for 12 to 20 weeks, normal lymphocyte responses to phytohemagglutinin P, concanavalin A, and lipopolysaccharide were drastically reduced. These results suggest a role for suppressor cells in chronic experimental cutaneous leishmaniasis.