Doxycycline Prevents Preclinical Atherosclerosis, Pancreatic Islet Loss and Improves Insulin Secretion after Glycemic Stimulation: Preclinical Study in Individuals with a High-Fat Diet.

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of ß cells per mm2, in addition to losing large islets. The index of ß cell function (∆Insulin0-30/∆Glucose0-30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.

Protective Effect of Neutral Electrolyzed Saline on Gentamicin-Induced Nephrotoxicity: Evaluation of Histopathologic Parameters in a Murine Model.

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Using Artificial Intelligence to Develop a Multivariate Model with a Machine Learning Model to Predict Complications in Mexican Diabetic Patients without Arterial Hypertension (National Nested Case-Control Study): Metformin and Elevated Normal Blood Pressure Are Risk Factors, and Obesity Is Protective.

Diabetes mellitus is a disease with no cure that can cause complications and even death. Moreover, over time, it will lead to chronic complications. Predictive models have been used to identify people with a tendency to develop diabetes mellitus. At the same time, there is limited information regarding the chronic complications of patients with diabetes. Our study is aimed at creating a machine-learning model that will be able to identify the risk factors of a diabetic patient developing chronic complications such as amputations, myocardial infarction, stroke, nephropathy, and retinopathy. The design is a national nested case-control study with 63,776 patients and 215 predictors with four years of data. Using an XGBoost model, the prediction of chronic complications has an AUC of 84%, and the model has identified the risk factors for chronic complications in patients with diabetes. According to the analysis, the most crucial risk factors based on SHAP values (Shapley additive explanations) are continued management, metformin treatment, age between 68 and 104 years, nutrition consultation, and treatment adherence. But we highlight two exciting findings. The first is a reaffirmation that high blood pressure figures across patients with diabetes without hypertension become a significant risk factor at diastolic > 70 mmHg (OR: 1.095, 95% CI: 1.078-1.113) or systolic > 120 mmHg (OR: 1.147, 95% CI: 1.124-1.171). Furthermore, people with diabetes with a BMI > 32 (overall obesity) (OR: 0.816, 95% CI: 0.8-0.833) have a statistically significant protective factor, which the paradox of obesity may explain. In conclusion, the results we have obtained show that artificial intelligence is a powerful and feasible tool to use for this type of study. However, we suggest that more studies be conducted to verify and elaborate upon our findings.

Evaluation of Medical Care for Diabetic and Hypertensive Patients in Primary Care in Mexico: Observational Retrospective Study.

INTRODUCTION: The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. METHODS: 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. RESULTS: Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. CONCLUSION: Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.

Factors associated with increased odds of sensorineural hearing loss in infants exposed to the Zika virus during pregnancy.

INTRODUCTION: The Zika virus (ZIKV) infection in pregnant women has been associated with an increased risk of birth defects. We aimed to estimate the prevalence of sensorineural hearing loss (SNHL) in infants exposed to the ZIKV during their gestation and evaluate the factors associated with its increased odds. METHODOLOGY: A cross-sectional study was performed from July 2016 to June 2019 in a Western state of Mexico and data from 61 infants that presented with laboratory-positive (RT-qPCR) evidence of in utero exposure to ZIKV were analyzed. Brain stem auditory evoked potentials were used. RESULTS: Hearing loss was documented in 6 (9.8%) of infants. The prevalence of SNHL in children with microcephaly was 75.0%, as compared to 5.3% in those without anomalies (odds ratio, OR = 14.31, 95% CI = 2.54 - 19.12). Half of children with SNHL had no physical manifestations of gestational ZIKV exposure. CONCLUSIONS: Hearing loss was a frequent event in ZIKV-exposed children, particularly among those with microcephaly. Our results highlight the relevance of systematic hearing screening.

A novel cell-free formulation for the treatment of knee osteoarthritis generates better patient-reported health outcomes in more severe cases.

BACKGROUND: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a major therapeutic response in severe knee osteoarthritis. However, its effect on patients with mild or moderate stages of the disease has not been studied. OBJECTIVE: To evaluate the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, minimal clinically important improvement (MCII) and sleep disturbances in mild, moderate, and severe stages of knee osteoarthritis (OA) with the novel cell-free formulation treatment (BIOF2). METHODS: An open-label, nonrandomized, baseline-controlled, parallel group study on patients with mild, moderate, and severe knee OA was conducted to evaluate the effect of intra-articular administration of BIOF2. Clinical improvement was determined through the WOMAC score and MCII, whereas sleep disturbances were measured through a Likert scale questionnaire. RESULTS: At 6 months post-treatment, the mean decrease in the total WOMAC score was 16.4 +/- 4.7%, 49.9 +/- 6.4%, and 62.7 +/- 4.5% in the patients with mild, moderate, and severe disease, respectively (p < 0.001, analysis of variance test). MCII at 6 months was 18%, 78%, and 100% for mild, moderate, and severe disease, respectively (p < 0.001, likelihood-ratio χ2 test). Concerning sleep disturbances, 60% of the patients with severe OA had important sleep problems before beginning treatment, and those difficulties were overcome 6 months after treatment. Only 18% of the patients with mild disease and 16% with moderate disease had serious sleep disturbances at the beginning of the study, and there was slight improvement after treatment. No adverse events were recorded during follow-up. CONCLUSION: BIOF2 generates better patient-reported health outcomes (on pain, stiffness, function, and sleep) in the more severe cases of knee OA.

Death related to Cedecea lapagei in a soft tissue bullae infection: a case report.

BACKGROUND: Cedecea lapagei bacterium was discovered in 1977 but was not known to be pathogenic to humans until 2006. In the medical literature there are very few clinical case reports of Cedecea lapagei; none have reported a catastrophic death secondary to a soft tissue hemorrhagic bullae infection. As well as soft tissue infection, rare cases of pneumonia, urinary tract infections, peritonitis, osteomyelitis, bacteremia, and sepsis have been documented with the majority having good outcomes. Here, we present the first case of a fatal outcome in a Cedecea lapagei soft tissue infection with multiple hemorrhagic bullae. CASE PRESENTATION: A 52-year-old Mexican man with antecedents of liver cirrhosis and treated hypertension was brought to our institution with clinical signs of sepsis and 16 to 18 hours of history of pain and edema in his right lower limb. During the course of the first day hospitalized in our institution, he developed several large serohematogenous bullae with ascending progression on his entire right lower limb. He subsequently developed multiple organ failure and septic shock with rapid deterioration, dying on the second day. Bullae fluid samples taken the first day undoubtedly isolated Cedecea lapagei within the second day using MicroScan WalkAway® 96 plus System as well Gram-negative bacteria in MacConkey and blood agar. CONCLUSIONS: The isolation of Cedecea lapagei was an unexpected etiological finding that will enable physicians in the future to consider this bacterium as a probable cause of serohematogenous bullae infections. We do not exclude contamination although it has never been isolated in bullae fluid in the medical literature. Future encounters with this bacterium should not be taken lightly as it may have the potential to have fatal outcomes.

Association Between Nonalcoholic Fatty Liver Disease and Severe Male Reproductive Organ Impairment (Germinal Epithelial Loss): Study on a Mouse Model and on Human Patients.

Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the thoracic aorta, liver tissue, and testicular tissue from the deceased subjects were collected. The degree of germinal epithelial loss (DGEL) was evaluated and the clinical and histologic data were compared between individuals with and without NAFLD. The only metabolic or morphologic variable that caused a significant difference in the DGEL, in both the animal model and humans, was the presence of liver steatosis. The percentage of steatosis was also correlated with the percentage of the DGEL. In humans, steatosis (greater than 20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95% CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD was a strongly associated factor implicated in severe DGEL, as well as the testis was identified as a probable target organ for damage caused by the disease. This finding could result in the search for new approach strategies in the management of men with fertility problems. Further studies are required to confirm these results.

Smoking and female sex as key risk factors associated with severe arthralgia in acute and chronic phases of Chikungunya virus infection.

Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute episodes of Chikungunya fever caused by infection with the Chikungunya virus (CHIKV). To the best of our knowledge, there are no reports on risk factors associated with the intensity of arthralgias in typical acute episodes of the disease. Although a number of studies have reported on risk factors associated with the development of the chronic stage of the disease, smoking habits have not been analyzed. Smoking is an interesting factor to consider since it is the main environmental risk factor for the development of rheumatoid arthritis (RA), a similar disease to CHIKV in many aspects. In the present study, 140 patients infected with CHIKV were assessed for risk factors associated with severe arthralgia intensity in the acute phase (pain of 9/10 on the visual analog scale of 0-10) and moderate to severe intensity (according to the Routine Assessment of Patient Index Data 3) 3.5 months after infection in patients that experienced the chronic phase of the disease. Women and smokers were 2- to 3-times more likely to experience severe pain in the acute and chronic stages. Likewise, the presence of severe arthralgia during the acute disease phase resulted in a 4-fold increased risk for entering the chronic phase. Smoking was a more important risk factor in males compared with females. Smoking resulted in a 20-fold increased risk for severe arthralgia during the acute phase in men, as well as a 10-fold increased risk for developing chronic disease with moderate-to-severe pain 3.5 months after the acute stage. The presence of rash, headache, muscular weakness or conjunctivitis in the acute phase, the presence of diabetes and age >40 years were considered significant risk factors due to their influence on illness progression. In conclusion, smoking and female sex were the main risk factors associated with development of severe joint pain in the acute and chronic phases of Chikungunya fever. These risk factors are similar to those associated with the development and severity of RA, possibly because the two diseases share pathophysiological mechanisms, including elevated interleukin-6 levels.

Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers.

Potassium permanganate has been reported to be an effective treatment for certain types of wounds. The aim of the present study was to evaluate the use of potassium permanganate in the treatment of diabetic foot ulcers. A single-blind, randomized, controlled clinical trial was conducted on patients with type 2 diabetes mellitus that presented with a foot ulcer persisting for >3 months. The control group (n=10) was treated with the current standard treatment, which comprises of measures for reducing pressure in the ulcerated area, daily cleansing of the ulcer with potable water and antiseptic wash solution, and the application of a disinfectant solution on the entire surface area of the ulcer; while the intervention group (n=15) received the standard treatment plus 5% topical potassium permanganate solution applied once a day for 21 days. In the intervention group, 1 patient did not tolerate the treatment and was eliminated from the study on the first day. The remaining patients tolerated the interventions well. At the end of the treatment period, ulcers in the control group had decreased by 38% whereas those in the intervention group decreased by 73% (P<0.009). The degree of decrease was also investigated; the ulcer size was ≥50% decreased in 40% of patients in the control group and in 86% of patients in the intervention group (P=0.02). In conclusion, the results of the present study indicate that topical potassium permanganate is well tolerated and significantly accelerates the healing process of diabetic foot ulcers.

The D9N, N291S, and T495G Polymorphisms of the Lipoprotein Lipase Gene Are Not Associated with Cerebral Infarction.

BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD. METHODS: A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD. RESULTS: The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P = .27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P = .89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P = .48). CONCLUSIONS: In the present study, the D9N, N291S, and T495G polymorphisms of the LPL gene were not risk factors for the development of CVD.

Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia.

Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) and histologic changes in the aorta and liver were analyzed for the study. Aspirin significantly reduced the hepaticsteatosis. All the drugs significantly reduced the hepatic inflammatory infiltrate. In relation to atherosclerosis, there were significant reductions in all the study variables with the use of aspirin and flufenamate. The four medications were able to stop steatosis from progressing into steatohepatitis by reducing inflammation. However, aspirin was the most beneficial, simultaneously reducing steatosis, atherosclerosis, and serum cholesterol levels.

Clinical diagnosis delays and epidemiology of dengue fever during the 2002 outbreak in Colima, Mexico.

Dengue fever is a re-emergent and challenging public health problem in the world. Here, we assess retrospectively the epidemiological and clinical characteristics of the 2002 dengue epidemic in the state of Colima, Mexico. This study is carried out by analysing a database containing demographic, epidemiological and clinical information. Of the 4040 clinical dengue cases diagnosed in the hospitals of the Mexican Institute of Public Health in the state of Colima, 548 cases were confirmed by laboratory tests, and 495 cases presented at least one haemorrhagic manifestation. Of the total clinically diagnosed cases, the most common symptoms observed were: fever (99.6%), headache (92.4%), myalgia (89.4%) and arthralgia (88.6%). The most common haemorrhagic manifestations were: petechiae (7.1%), gingivitis (3.4%) and epistaxis (3.6%). The median time between the onset of illness and visit to the health care clinic (diagnostic delay) was 1 day (interquartile range [IQR]: 0-3). For cases presenting haemorrhagic manifestations, the diagnostic delay was higher (median: 2 days, IQR: 0-4) than for non-haemorrhagic cases (median: 1 day, IQR: 0-3). The proportion of males presenting haemorrhagic manifestations was higher than females (Fisher Exact test; p

Análisis de los factores de riesgo de la hipertensión arterial en Colima, México / Analysis of risk factors for hypertension in Colima, Mexico

OBJETIVO: Evaluar la posible asociación de la edad, el sexo, el sobrepeso, los antecedentes familiares de hipertensión arterial (HTA), el alcoholismo y el sedentarismo con la HTA en la población adulta de la ciudad de Colima, México. MÉTODOS: Estudio transversal analítico de base poblacional. Se aplicó una encuesta estructurada a 280 adultos mayores de 30 años que residían en la ciudad mexicana de Colima en 2001 y 2002. Las variables estudiadas fueron el sexo, la edad, el peso, la talla, los antecedentes familiares de HTA, la práctica de ejercicio físico, el tabaquismo y el consumo de alcohol. La presión arterial (PA) se midió por el método auscultatorio. Las mediciones limítrofes o dudosas se repitieron cuatro o cinco días después. Se consideró que había HTA cuando la PA sistólica era >140 mm Hg y la presión arterial diastólica era > 90 mm Hg, o la persona estaba bajo tratamiento antihipertensivo. Se calcularon las razones de posibilidades (odds ratios, RP) de las variables estudiadas y sus intervalos de confianza de 95 por ciento (IC95 por ciento). La asociación entre las variables y la HTA se estimó mediante regresión logística y la interacción mediante el coeficiente de productos de interacción. RESULTADOS: La prevalencia bruta de HTA fue de 28,6 por ciento. La prevalencia fue mayor en hombres que en mujeres (42,1 por ciento frente a 19,2 por ciento, respectivamente; RP = 3,04; IC95 por ciento: 1,8 a 5,2) y en personas mayores de 49 años que en personas de 30 a 49 años (36,8 por ciento frente a 21,9 por ciento, respectivamente; RP = 2,07; IC95 por ciento: 1,22 a 3,50). Los antecedentes familiares de HTA y el sobrepeso mostraron asociación con la HTA, mientras que la práctica de ejercicio físico tuvo un efecto protector (RP = 0,45; 0,23 a 0,86). Se encontró interacción entre la HTA y la edad (> 50 años), los antecedentes familiares de HTA, el sobrepeso y la práctica de ejercicio físico, particularmente en mujeres. CONCLUSIONES: La prevalencia de HTA en Colima es muy semejante a la encontrada a nivel nacional en México. Su fuerte asociación con el sexo masculino, independientemente de las otras variables, resalta la necesidad de promover campañas preventivas más enfocadas en los hombres.

[Analysis of risk factors for hypertension in Colima, Mexico]. / Análisis de los factores de riesgo de la hipertensión arterial en Colima, México.

OBJECTIVE: To evaluate the possible association that age, sex, excess weight, family history of hypertension, alcoholism, and sedentary lifestyle have with hypertension in the adult population of the city of Colima, Mexico. METHODS: This was a population-based analytic cross-sectional study. A structured survey was used with 280 adults older than 30 years of age who were living in the city of Colima in 2001 and 2002. The variables studied were sex, age, weight, height, family history of hypertension, engaging in physical exercise, smoking, and consuming alcohol. Blood pressure (BP) was measured with the auscultatory method. Borderline or doubtful measurements were checked again four or five days later. Hypertension was defined as systolic BP > or = 140 mm Hg and diastolic blood pressure > or = 90 mm Hg, or as the person being under antihypertensive treatment. The odds ratios (ORs) of the variables studied were calculated, along with their 95% confidence intervals (95% CIs). The association between the variables and hypertension was estimated through logistic regression, and their interaction through the coefficient of the interaction products. RESULTS: The overall prevalence of hypertension was 28.6%. The prevalence was higher in men than in women (42.1% vs. 19.2%; OR = 3.04, 95% CI: 1.8 to 5.2) and in people older than 49 years than in people 30 to 49 years old (36.8% vs. 21.9%; OR = 2.07, 95% CI: 1.22 to 3.50). A family history of hypertension and excess weight were associated with hypertension, while physical exercise had a protective effect (OR = 0.45; 95% CI: 0.23 to 0.86). There was interaction between hypertension and age > or = 50 years, a family history of hypertension, overweight, and physical exercise, especially among women. CONCLUSIONS: The prevalence of hypertension in Colima is very similar to that for Mexico as a whole. The strong association that hypertension had with male gender, regardless of the other variables, emphasizes the need for promoting prevention campaigns that focus more on men.