[Rocky Mountain spotted fever in Mexican children: Clinical and mortality factors]. / Fiebre maculosa de las Montañas Rocosas en niños y adolescentes mexicanos: cuadro clínico y factores de mortalidad.

OBJECTIVE: Characterize clinical manifestations and predictors of mortality in children hospitalized for spotted fever. MATERIALS AND METHODS: Cross-sectional study in 210 subjects with a diagnosis of Rocky Mountain spotted fever (RMSF) in a pediatric hospital in Sonora, from January 1st, 2004 to June 30th, 2015. Data were analyzed using descriptive statistics and multivariate logistic regression. RESULTS: An upward trend was observed in RMSF morbidity and mortality. Fatality rate was 30%.Three predictors were associated with risk of death: delay ≥ 5 days at the start of doxycycline (ORa= 2.95, 95% CI 1.10-7.95), acute renal failure ((ORa= 8.79, 95% CI 3.46-22.33) and severe sepsis (ORa= 3.71, 95% CI 1.44-9.58). CONCLUSIONS: RMSF causes high mortality in children, which can be avoided with timely initiation of doxycycline. Acute renal failure and severe sepsis are two independent predictors of death in children with RMSF.

[Proposal of a five MIRU-VNTR panel to screen clinical isolates of Mycobacterium tuberculosis in Mexico]. / Propuesta de un panel MIRU-VNTR 5 para el tamizaje de aislamientos clínicos de Mycobacterium tuberculosis en México.

INTRODUCTION: Tuberculosis is a public health problem across Mexico. This paper aims to select a panel, with a minimum number of repetitive elements (MIRU-VNTR) for genotypic characterization of Mycobacterium tuberculosis (M. tuberculosis) clinical isolates. METHOD: In this study, a full panel of 24 MIRU-VNTR loci was used to discriminate 65 clinical isolates of M. tuberculosis from three different geographical regions of Mexico. Those loci with the highest discriminatory power were subsequently selected. RESULTS: The panel, including five loci, was obtained by selecting the highest values of allelic diversity among the genotypes obtained. The dendrogram, generated by the panel MIRU-VNTR 5, showed a high discriminatory power with 65 unique genotype profiles and formed clusters according to the geographical region of origin. CONCLUSIONS: The panel MIRU-VNTR 5 can be useful for characterizing clinical isolates of M. tuberculosis in Mexico.

Systematic review and bioinformatics analysis of plasma and serum extracellular vesicles proteome in type 2 diabetes.

Background: Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications. Methods: In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464). Results: Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels. Conclusion: These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.

Evaluation of Systemic Inflammation Before and After Standard Anti-tuberculosis Treatment in Patients With Active Pulmonary Tuberculosis and Diabetes Mellitus.

Background Diabetes mellitus (DM) is a common comorbidity of active pulmonary tuberculosis (APTB) that increases the risk of treatment failure during anti-tuberculosis chemotherapy. Evaluating systemic inflammatory response could help determine differences in response to treatment between APTB patients and those with APTB and DM. Methodology To explore changes in systemic inflammation, measured by a set of inflammatory mediators in subjects with APTB and TBDM before and after six months of anti-tuberculosis chemotherapy, 30 APTB and nine TBDM subjects underwent cytokine testing, including interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta 1 (TGF-ß1) by enzyme-linked immunosorbent assay, C-reactive protein by nephelometry, and sialic acid by colorimetric assay at baseline and following six months of standard anti-tuberculosis treatment. Sputum smear microscopy or molecular biology (Xpert MTB/RIF) was used for diagnosis, and sputum smear microscopy was performed monthly during the treatment of the patient with pulmonary tuberculosis to evaluate his evolution. Principal component analysis examined changes in the inflammatory status. Results Both groups showed negative sputum smear microscopy in the sixth month after starting anti-tuberculosis chemotherapy. TGF-ß1 was found to be significantly higher in subjects with TBDM before treatment compared to APTB patients (p<0.001), and systemic inflammation continued only in TBDM subjects after treatment (accumulation and persistence of inflammatory mediators like IL-6, IL-8, IL-10, IFN-γ, TNF-α, TGF-ß1, C-reactive protein, and sialic acid in blood). On the other hand, the mediators IFN-γ, C-reactive protein, and total sialic acid were found to be most influential in distinguishing pre- and post-treatment inflammatory response in subjects with APTB without DM. Conclusions Inflammatory mediators analyzed in combination, including IFN-γ, CRP, and total sialic acid, may be useful in evaluating the systemic inflammatory response in subjects with APTB and TBDM before and after anti-tuberculosis treatment. Determining these mediators revealed persistent systemic inflammation in TBDM subjects after six months of standard tuberculosis treatment, despite negative sputum smear microscopy results and good glycemic control. This suggests a need for inflammation-modulating therapies during tuberculosis control. Finally, monitoring sputum smear microscopy results alongside the determination of proposed inflammatory mediators (IFN-γ, CRP, and total sialic acid) are effective in evaluating the response to anti-tuberculosis treatment in APTB subjects without DM, warranting further investigation.

N-(2-ozoazepan-3-yl)-pyrrolidine-2-carboxamide, a novel Octopus vulgaris ink-derived metabolite, exhibits a pro-apoptotic effect on A549 cancer cell line and inhibits pro-inflammatory markers.

This research aimed to chemically synthesize and evaluate the antiproliferative and anti-inflammatory potential of ozopromide (OPC), a novel compound recently isolated from O. vulgaris ink. After chemical synthesis, OPC structural characterization was confirmed by COSY2D, FTIR, and C-/H-NMR. OPC inhibited the growth of human breast (MDA-MB-231), prostate (22Rv1), cervix (HeLa), and lung (A549) cancerous cells, being the highest effect on the latter (IC50: 53.70 µM). As confirmed by flow cytometry, OPC induced typical apoptosis-derived morphological features on A549 cells, mostly at early and late apoptosis stages. OPC generated a dose-dependent effect inhibiting IL-6 and IL-8 on LPS-stimulated peripheral mononuclear cells (PBMCs). A major affinity of OPC to Akt-1 and Bcl-2 proteins in silico agreed with the observed pro-apoptotic mechanisms. Results suggested that OPC has the potential to alleviate inflammation and be further studied for anticancer activity. Marine-derived food products such as ink contains bioactive metabolites exhibiting potential health benefits.

Factors influencing adults to drop out of intensive lifestyle interventions for weight loss.

Reducing ≥5% of body weight can decrease the risk of developing chronic diseases in adults with excess weight. Although Intensive Lifestyle Interventions (ILIs) that include cognitive-behavioral techniques to improve physical activity and eating habits are the best approach for losing weight, the failure to retain participants is a barrier to their successful implementation. We aimed to investigate the factors influencing adults to drop out of ILIs for weight loss at six months. We conducted retrospective multiple logistic regression analysis of 268 participants with excess weight (body mass index ≥ 25 kg/m2) from a multicenter study (n = 237, in-person ILI in five clinics, delivered by nutrition interns), and a randomized controlled trial (n = 31, one online ILI, delivered by a master's degree student). The same research team conducted both studies in Northern Mexico, using the same intervention components, and identical instruments and techniques to collect the data. We found that older participants (≥50 years) were less likely to drop out of the ILI for weight loss compared to participants <35 years old (OR = 0.34, 95% CI = 0.16-0.70). For each unit increase in the bodily pain scale of the SF-36 (less perceived pain), the risk of dropping out decreased by 2% (OR = 0.98, 95% CI = 0.97, 0.996), while a change in the interventionist during the 6-month intervention more than doubled the risk of dropping out (OR 2.25, 95% CI = 1.23-4.14). Retention in ILIs may be improved by ensuring that the same interventionist remains during the six-month intervention. In addition, ILIs may need further tailoring for younger ages and for participants with higher perceived pain.

Weight loss is hard. The best way to do it is to enroll in an intervention that includes frequent sessions with a health coach who uses cognitive-behavioral techniques to help participants improve their eating and physical activity habits. Retaining participants in these types of intervention is a challenge for health practitioners and researchers. Our objective was to identify the factors that increase the participants' risk of dropping out of the intervention. We analyzed the data of 268 Mexican adults who participated in studies that evaluated intensive lifestyle interventions for weight loss. We found that participants who are younger, experience more pain, and whose health coaches are replaced before the intervention is completed have a higher risk of dropping out of the intervention. By accounting for these factors when designing the intervention, we could increase the chances that participants stay in the intervention until the end. This way they are more likely to be successful in losing weight.

[DNA mutations associated to rifampicin or isoniazid resistance in M. tuberculosis clinical isolates from Sonora, Mexico]. / Mutaciones asociadas con resistencia a rifampicina o isoniazida en aislamientos clínicos de M. tuberculosis de Sonora, México.

OBJECTIVE: To perform the analysis of specific regions of the major genes associated with resistance to isoniazid or rifampin. MATERIALS AND METHODS: Twenty two M. tuberculosis strains, isolated from human samples obtained in Sonora, Mexico. Specific primers for hotspots of the rpoB, katG, inhA genes and the ahpC-oxyR intergenic region were used. The purified PCR products were sequenced. RESULTS: Mutations in the promoter of inhA, the ahpC-oxyR region, and codon 315 of katG and in 451 or 456 codons of rpoB, were identified. CONCLUSIONS: Detection of mutations not previously reported requires further genotypic analysis of Mycobacterium tuberculosis isolates in Sonora.

ESBL-producing Escherichia coli and Klebsiella pneumoniae from health-care institutions in Mexico.

We investigated the phenotypic and molecular characteristics of Extended-Spectrum-ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates from four health-care institutions in Hermosillo, Sonora, Mexico. ESBL-producing isolates were collected from February to August 2016. The prevalence of ESBL-producing E. coli and K. pneumoniae was 11.9 and 8.7%, respectively. High dissemination of resistance to ciprofloxacin (88%), trimethoprim/sulfamethoxazole (72%) and aminoglycosides (59%) were detected, as well as susceptibility to meropenem, amikacin and tigecycline. The ESBL found variants were CTX-M-1 (88%) and CTX-M-9 (5%). The plasmid-mediated quinolone resistance (PMQR) gene aac(6´)-Ib-cr was identified in 62% of a representative sample, whereas the qnrB and qnrS genes were detected in 49% of the isolates. PFGE analyses detected many unrelated clones among the hospital or community isolates. A constant programme of epidemiological surveillance is recommended to understand the dynamics of bacterial resistance to both cephalosporin as well as the fluoroquinolone family of antibiotics.

Increased serum ferritin is associated with oxidized low-density lipoprotein in prediabetes patients: A pilot study.

AIMS: This pilot study aimed to determine if increased serum ferritin (SF) is associated with cardiovascular risk factors in patients with prediabetes. METHODS: Eighteen patients with prediabetes and 36 subjects without prediabetes (control), non-white Hispanic, non-indigenous origin, Mexican mestizo descent were included. Participants had no inflammation, or vascular complications. SF and metabolic markers were evaluated in both groups. RESULTS: SF and oxidized low-density lipoprotein (oxLDL) were increased in prediabetes subjects. Moreover, in prediabetes and control groups as a whole, natural logarithm (ln)-SF correlated with oxLDL and ln-oxLDL/LDL after adjustment for sex, ln-age, ln-fasting plasma glucose (FPG), ln-body mass index, ln-triglyceride (TG), total cholesterol (TC), and high-density lipoproteins. Finally, ln-SF was an independent contributor to ln-oxLDL/LDL ratio in control and prediabetes subjects (ß = 0.2915) after the introduction of potential confounders such as FPG, TC, TG, and hypertension. CONCLUSIONS: The results of this study indicate that hyperferritinemia is associated with oxLDL, considered one of the main cardiovascular risk factors, which allows us to suggest that an increase in SF could contribute to the progression of prediabetes, prior to the appearance of diabetes. Further research is required to establish a causal relationship of iron disruption metabolism in oxLDL generation under prediabetes conditions.

Metabolic syndrome screening using visceral adipose tissue (VAT) from opportunistic MRI locations in a multi-ethnic population.

OBJECTIVE: To determine if visceral adipose tissue (VAT) area measured through MRI can be used opportunistically to assess the presence of cardiometabolic risk factors and compare its performance to simpler adiposity measures. METHODS: A cross-sectional analysis was carried out on a subset of 1683 participants (856 women) from the Adiposity Phenotype Study (mean age=69.2y; range 59.9-77.4). The association of total VAT area (sum of four cross sections, L1-L2, L2-L3, L3-L4, L4-L5) and each location, as well as BMI and body fat % (per SD) with the metabolic syndrome (MetSx) or its components was evaluated through logistic regression analysis. RESULTS: Total VAT can be accurately predicted using all sites evaluated (R2 range=0.82-0.96). In men, VAT did not show a superior association to MetSx compared to BMI in men. However, in women, VAT was consistently superior to BMI and body fat % in its association to MetSx, independent of ethnicity [odds ratio for BMI, body fat %and total VAT area=2.25 (95% CI: 1.93-2.62); 1.66 (95% CI: 1.36-2.03); 6.20 (95% CI: 4.69-8.21) respectively in all women]. Ethnic-specific odds ratios to MetSx in women ranged from 5.38 to 8.63 for total VAT area and 2.12-4.08 for BMI. CONCLUSION: Total VAT area can be accurately predicted from individual VAT regions in men and women and offers superior association to BMI for MetSx in women but not in men for five ethnicities. Therefore, opportunistic screening for elevated VAT area in women may be warranted across multiple ethnic groups.

Hydrogel with silver nanoparticles synthesized by Mimosa tenuiflora for second-degree burns treatment.

In this work we use Mimosa tenuiflora (MtE) extracts as reducing agents to synthesize silver nanoparticles (AgMt NPs) which were characterized by DPPH and Total Polyphenols Assays, UV-visible, X-ray diffractometer (XRD), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and Thermogravimetric analysis (TGA). AgMt NPs possess average sizes of 21 nm and fcc crystalline structure, it was also confirmed that the MtE is present in the AgMt NPs even after the cleaning protocol applied. Subsequently, carbopol hydrogels were made and the MtE and the synthesized AgMt NPs were dispersed in different gels (MtE-G and AgMt NPs-G, respectively) at 100 µg/g concentration. The gels were characterized by UV-Vis, IR, and rheology. Antimicrobial tests were performed using Staphylococcus aureus and Escherichia coli. Burn wound healing was evaluated in a second-degree burn injury on a Wistar rats model for 14 days and additional skin biopsies were examined with histopathological analysis. Gel with commercial silver nanoparticles (Ag NPs) was prepared and employed as a control on the biological assays. Hydrogel system containing silver nanoparticles synthesized with Mimosa tenuiflora (AgMt NPs-G) is a promising therapeutic strategy for burn wound healing, this due to bactericidal and anti-inflammatory effects, which promotes a more effective recovery (in percentage terms) by damaged area.

[Geometric coding and cluster analysis to assess metabolic control of patients with type 2 diabetes mellitus]. / Codificación geométrica y análisis de conglomerados para evaluar el control metabólico de pacientes con diabetes mellitus tipo 2.

OBJECTIVE: Determine the frequency of combinations of higher-than-normal metabolic control parameters, using geometric coding and hierarchical cluster analysis, in patients with type 2 diabetes (DM2) METHODOLOGY: A descriptive cross-sectional study was conducted in Mexico to assess a group of 1 051 patients with DM2. The inclusion criteria were to have one or more of the following values: fasting glucose of 130 mg/dL, total cholesterol of 240 mg/dL, total triglycerides of 200 mg/dL, Body Mass Index of 27 kg/m(2), and systolic blood pressure higher than 130 mmHg or diastolic blood pressure higher than 85 mmHg. Through geometric coding, the frequencies of all combinations were obtained. Cluster analysis was used to determine similarities among the combinations. RESULTS: Using the proposed instrument, it was observed that the paired combinations with the highest number of subjects were hyperglycemia-hypertriglyceridemia (7.3%) and hyperglycemia-hypercholesterolemia (3.6%). The most frequent polycombinations were hyperglycemia-hypercholesterolemia-hypertriglyceridemia (13.2%) and hyperglycemia-hypertriglyceridemia-hypercholesterolemia-hypertension (10.5%). CONCLUSIONS: Geometric coding and cluster analysis could become a suitable instrument for assessing the metabolic control of patients with DM2, as well as for identifying parameters that will help improve their monitoring and treatment.

Lifestyle intervention for obesity: a call to transform the clinical care delivery system in Mexico.

Obesity and its comorbidities have become the most important public health problems for Latin America. In Mexico obesity has increased dramatically to the point where the government has declared it an epidemiological emergency. The most recent national data showed overweight and obesity affects 72.5% of adults, or around 56 million Mexicans. Most Mexican adults with obesity are undiagnosed. According to data derived from a national representative survey, only 20% of adults with BMI >30 kg/m2 were diagnosed with obesity by a health provider. Likewise, only 8% of individuals with obesity had received treatment for obesity. Interventions offered in the Mexican health care delivery system generally consist of traditional consultations with recommendations on diet and exercise, visits are monthly to quarterly, and validated behavior change protocols are not used. Evidence from clinical trials has shown that weight loss with this type of treatment is generally less than 1 kg per year. In contrast, intensive lifestyle interventions - protocols focusing on achieving changes in diet, physical activity, and moderate weight loss using behavioral strategies with weekly or bi-weekly sessions for the first 3 to 6 months, and a maintenance phase with trained interventionists - as implemented in the Diabetes Prevention Program and the Look AHEAD studies achieved weight loss of 7-9% at one year. Additionally, translation studies of these interventions to the community and to real-world clinical practice have achieved weight loss of around 4%. Adaptations of intensive lifestyle interventions have been implemented in the United States, both in clinical practice and in the community, and this type of intervention represents a potential model to combat obesity in Mexico and other Latin American countries. It is essential that primary care providers in Mexico implement clinical practice guidelines based on the best evidence available as discussed here to effectively treat obesity. The authors make recommendations to improve the treatment of obesity in the clinical care delivery system in Mexico using intensive lifestyle interventions.

Medical knowledge related to Rocky Mountain spotted fever in Sonora, Mexico.

Background: Rocky Mountain spotted fever (RMSF) is a tick-borne disease with a high case-fatality rate unless diagnosed promptly and treated timely with doxycycline. Physician knowledge about presentation and treatment can improve outcomes of RMSF in endemic regions, such as Sonora in northern Mexico, where RMSF has caused 1348 non-fatal cases and 247 deaths from 2003 to 2016. Methods: A cross-sectional study was conducted with 343 physicians working in medical facilities in Sonora, Mexico. A 25-item questionnaire explored physician knowledge of clinical, epidemiological and preventive aspects of RMSF. Results: Only 62% of physicians agreed that doxycycline should be used as the first choice treatment for children under 8 years with suspected RMSF. Additionally, 40% of primary care physicians correctly identified the time to initiate doxycycline, and 32% correctly identified the case-fatality rate of untreated RMSF in all patients. Conclusions: Inadequate medical knowledge may adversely affect how patients infected with Rickettsia rickettsii are diagnosed and treated. Educational programs that improve the risk perception and medical knowledge about RMSF should be targeted at physicians most likely to have initial contact with diseased patients.

Rocky Mountain Spotted Fever and Pregnancy: Four Cases from Sonora, Mexico.

We present a series of four pregnant women with Rocky Mountain spotted fever (RMSF) that occurred in Sonora, Mexico, during 2015-2016. Confirmatory diagnoses were made by polymerase chain reaction or serological reactivity to antigens of Rickettsia rickettsii by using an indirect immunofluorescence antibody assay. Each patient presented with fever and petechial rash and was treated successfully with doxycycline. Each of the women and one full-term infant delivered at 36 weeks gestation survived the infection. Three of the patients in their first trimester of pregnancy suffered spontaneous abortions. RMSF should be suspected in any pregnant woman presenting with fever, malaise and rash in regions where R. rickettsii is endemic.

Clinical profile and predictors of fatal Rocky Mountain spotted fever in children from Sonora, Mexico.

BACKGROUND: Rocky Mountain spotted fever (RMSF) is an increasingly important cause of preventable mortality in children in Sonora, Mexico. Although early treatment with tetracycline has shown to prevent fatal outcome, the disease remains a life-threatening condition, particularly for children. This study describes the clinical factors associated with pediatric mortality due to RMSF in Sonora, in order to guide healthcare practices. METHODS: This is a retrospective analysis of 104 children consecutively hospitalized at the major pediatric hospital of Sonora, diagnosed with RMSF between January 2004 and December 2013. Descriptive statistics and multiple logistic regression were used to identify risk factors for fatal outcome. RESULTS: The case fatality ratio in this cohort was 20.2%. Children were hospitalized after a median of 6 days from onset of symptoms including fever (100%), rash involving palms and soles (88.5%) and headache (79.8%); 90.4% of fatal cases had low platelet counts (<50,000/µL) and 33.3% showed serum creatinine concentrations above the normal value. Acute kidney injury increased mortality, odds ratio (OR(adj)) = 4.84, 95% confidence interval (CI): 1.2-16.2, as well as delay in treatment (≥ 5th day from onset) with doxycycline, OR(adj) = 2.62, 95% CI: 1.24-5.52 and hemorrhage, OR(adj) = 6.11, 95% CI: 1.89-19.69. CONCLUSIONS: RMSF is a public health problem in Sonora. Clinically, fatal cases differ from non-fatal cases in renal function and hemorrhagic manifestations, although these findings may occur too late for a timely intervention. First-line providers must be educated to harbor a timely suspicion of RMSF, and should provide empiric treatment with doxycycline when febrile patients first present for care.

Proposal of a Screening MIRU-VNTR Panel for the Preliminary Genotyping of Mycobacterium bovis in Mexico.

Mycobacterium bovis is the major causative agent of bovine tuberculosis, one of the most relevant zoonoses in the world, and affects a wide range of wild and domesticated animals. Development of screening panels in mycobacterial genotyping, according to specific geographical regions, is strongly needed. The aim of this study is to select a panel, constituted by highly polymorphic MIRU-VNTR loci, to discriminate clinical isolates of M. bovis in Mexico. In this study, 65 isolates of M. bovis obtained from clinical bovine samples proceeding from different geographic regions of Mexico were identified by phenotypic and genotypic tests and subsequently genotyped by a 24-locus MIRU-VNTR panel. The most polymorphic loci were selected to build a panel with a high discriminatory power similar to the 24-locus panel results. A panel of seven elements (QUB 11a, MIRU 26, ETR-A, QUB 26, MIRU 16, MIRU 27, and MIRU 39) with the highest allelic diversity showed an appropriate differentiation. The selected MIRU-VNTR elements, according to the regional allelic variability, may be used in the preliminary genotyping of Mycobacterium bovis isolates in Mexico.