Design, synthesis, and exploration of antibacterial activity of 6H-1,2-oxazin-6-ones.

This study reports the in silico design of 30 6H-1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets. Docking compounds 1, 3, 4, 6, and 8 with both enzymes was favorable, outperforming Trimethoprim with DHFR. Therefore, 12 6H-1,2-oxazin-6-ones, including the most promising compounds, were synthesized through an aminolysis reaction of ß-cyanoketones with hydroxylamine hydrochloride, obtaining moderate to high yields (55-88%). Subsequently, antibacterial studies were conducted against five bacteria: four Gram-positive MRSA (ATCC 43300 and three clinical isolates) and one Gram-negative (E. coli ATCC 25922). Compounds 1, 2, 3, 4, 6, and 8 inhibited bacterial growth with MIC values ranging from 3.125 to 200 µg mL-1. Compound 1 showed better activity against Gram-positive bacteria than Linezolid. Toxicity assays indicated no adverse effects of the active oxazinones in silico and in vitro. This study demonstrated the antibacterial potential of the selected 6H-1,2-oxazin-6-ones against resistant human pathogenic bacteria.

Rocky Mountain spotted fever is a neglected tropical disease in Latin America.

Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, has emerged as a widespread public health crisis among predominantly vulnerable populations in several countries of Latin America, particularly evident in northern Mexico. Historically, RMSF has gained less attention than many other tropical infectious diseases, resulting in insufficient allocations of resources and development of capabilities for its prevention and control in endemic regions. We argue that RMSF fulfills accepted criteria for a neglected tropical disease (NTD). The relative neglect of RMSF in most Latin American countries contributes to disparities in morbidity and mortality witnessed in this region. By recognizing RMSF as an NTD, an increased public policy interest, equitable and more appropriate allocation of resources, scientific interest, and social participation can ameliorate the impact of this potentially treatable disease, particularly in vulnerable populations.

trans-Di-chlorido-bis-(secnidazole-κN 3)copper(II).

The use of acetic acid (HOAc) in a reaction between CuCl2·2H2O and secnid-azole, an active pharmaceutical ingredient useful in the treatment against a variety of anaerobic Gram-positive and Gram-negative bacteria, affords the title complex, [CuCl2(C7H11N3O3)2]. This compound was previously synthesized using ethanol as solvent, although its crystal structure was not reported [Betanzos-Lara et al. (2013 ▸). Inorg. Chim. Acta, 397, 94-100]. In the mol-ecular complex, the Cu2+ cation is situated at an inversion centre and displays a square-planar coordination environment. There is a hydrogen-bonded framework based on inter-molecular O-H⋯Cl inter-actions, characterized by H⋯Cl separations of 2.28 (4) Šand O-H⋯Cl angles of 175 (3)°. The resulting supra-molecular network is based on R2 2 (18) ring motifs, forming chains in the [010] direction.

Rocky Mountain Spotted Fever Mimicking Multisystem Inflammatory Syndrome in Hospitalized Children, Sonora, Mexico.

We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.

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.

The emergence of Rocky Mountain spotted fever in the southwestern United States and northern Mexico requires a binational One Health approach.

Rocky Mountain spotted fever (RMSF) is an international and quintessential One Health problem. This paper synthesizes recent knowledge in One Health, binational RMSF concerns, and veterinary and human medical perspectives to this fatal, reemerging problem. RMSF, a life-threatening tick-borne disease caused by the bacterium Rickettsia rickettsii, emerged during the first decade of the 21st century in impoverished communities in the southwestern US and northern Mexico. Lack of an index of suspicion, delay in diagnosis, and delayed initiation of antibiotic treatment contribute to fatality. Campaigns targeting dog neutering, restraint to residents' properties, and on-dog and on-premises treatment with acaricides temporarily reduce prevalence but are often untenable economically. Contemporary Mexican RMSF is hyperendemic in small communities and cities, whereas epidemics occur in the western US primarily in small tribal communities. In in both locations, the epidemics are fueled by free-roaming dogs and massive brown dog tick populations. In the US, RMSF has a case fatality rate of 5% to 7%; among thousands of annual cases in Mexico, case fatality often exceeds 30%.1,2 Numerous case patients in US border states have recent travel histories to northern Mexico. Veterinarians and physicians should alert the public to RMSF risk, methods of prevention, and the importance of urgent treatment with doxycycline if symptomatic. One Health professionals contribute ideas to manage ticks and rickettsial disease and provide broad education for the public and medical professionals. Novel management approaches include vaccine development and deployment, acaricide resistance monitoring, and modeling to guide targeted dog population management and other interventions.

Rickettsia rickettsii and Rickettsia typhi in hospitalized children diagnosed with Pediatric Multisystemic Inflammatory Syndrome in Merida, Yucatan.

Multisystem Inflammatory Syndrome in Children (MIS-C) presents with fever, fatigue, elevated inflammatory markers (acute phase reactants), and a history of exposure to SARS-CoV-2 or positive antibodies to SARS-CoV-2. As the COVID-19 pandemic unfolded, the risk of MIS-C in the pediatric population increased. However, exposure to other viruses and the presence of SARS-CoV-2 positive antibodies in children hospitalized for various pathogen-associated illnesses will also remain common and may complicate differential diagnoses with diseases endemic to the region such as rickettsial diseases. The objective was to highlight the desirability of medical personnel systematically incorporating rickettsiosis as a differential diagnosis for MIS-C when studying a child with fever, non-specific symptoms, and elevated inflammatory markers. In conclusion MIS-C should be considered in children with elevated inflammatory markers when there is a history of COVID-19 and they also meet criteria that have already been established by international agencies, such as CDC and WHO.

Rickettsia rickettsii and Rickettsia typhi in hospitalized children diagnosed with Pediatric Multisystemic Inflammatory Syndrome in Merida, Yucatan

Abstract Multisystem Inflammatory Syndrome in Children (MIS-C) presents with fever, fatigue, elevated inflammatory markers (acute phase reactants), and a history of exposure to SARS-CoV-2 or positive antibodies to SARS-CoV-2. As the COVID-19 pandemic unfolded, the risk of MIS-C in the pediatric population increased. However, exposure to other viruses and the presence of SARS-CoV-2 positive antibodies in children hospitalized for various pathogen-associated illnesses will also remain common and may complicate differential diagnoses with diseases endemic to the region such as rickettsial diseases. The objective was to highlight the desirability of medical personnel systematically incorporating rickettsiosis as a differential diagnosis for MIS-C when studying a child with fever, non-specific symptoms, and elevated inflammatory markers. In conclusion MIS-C should be considered in children with elevated inflammatory markers when there is a history of COVID-19 and they also meet criteria that have already been established by international agencies, such as CDC and WHO

Evidencia molecular de Rickettsia ricketsii y Rickettsia felis en garrapatas colectadas en ganado bovino en la costa de Chiapas.

OBJETIVO: Estimar la diversidad de garrapatas, la prevalencia de infestación y tasa de infección de Rickettsia spp. en ganado bovino en la costa del estado de Chiapas. Material y métodos. Se realizó un estudio transversal de octubre de 2021 a marzo de 2022, que incluyó la extracción de garrapatas de 297 vacas pertenecientes a 5 municipios. Se calcularon los índices de diversidad. El diagnóstico de Rickettsia spp en las garrapatas se realizó mediante PCR anida. RESULTADOS: Se encontró una baja diversidad de especies. Las especies Rhipicephalus microplus, Amblyomma cajennense y Rhipicephalus sanguineus hembra adultas fueron positivas a Rickettsia spp. Los municipios de Pijijiapan y Tonalá presentaron la TMI más alta con 7.5 y 7.2%. Conclusión. Este es primer estudio México que reporta infección de Rickettsia spp, en garrapatas colectadas de ganado bovino, lo cual indica un riesgo de salud pública.

Inhibitory to non-inhibitory evolution of the ζ subunit of the F1FO-ATPase of Paracoccus denitrificans and α-proteobacteria as related to mitochondrial endosymbiosis.

Introduction: The ζ subunit is a potent inhibitor of the F1FO-ATPase of Paracoccus denitrificans (PdF1FO-ATPase) and related α-proteobacteria different from the other two canonical inhibitors of bacterial (ε) and mitochondrial (IF1) F1FO-ATPases. ζ mimics mitochondrial IF1 in its inhibitory N-terminus, blocking the PdF1FO-ATPase activity as a unidirectional pawl-ratchet and allowing the PdF1FO-ATP synthase turnover. ζ is essential for the respiratory growth of P. denitrificans, as we showed by a Δζ knockout. Given the vital role of ζ in the physiology of P. denitrificans, here, we assessed the evolution of ζ across the α-proteobacteria class. Methods: Through bioinformatic, biochemical, molecular biology, functional, and structural analyses of several ζ subunits, we confirmed the conservation of the inhibitory N-terminus of ζ and its divergence toward its C-terminus. We reconstituted homologously or heterologously the recombinant ζ subunits from several α-proteobacteria into the respective F-ATPases, including free-living photosynthetic, facultative symbiont, and intracellular facultative or obligate parasitic α-proteobacteria. Results and discussion: The results show that ζ evolved, preserving its inhibitory function in free-living α-proteobacteria exposed to broad environmental changes that could compromise the cellular ATP pools. However, the ζ inhibitory function was diminished or lost in some symbiotic α-proteobacteria where ζ is non-essential given the possible exchange of nutrients and ATP from hosts. Accordingly, the ζ gene is absent in some strictly parasitic pathogenic Rickettsiales, which may obtain ATP from the parasitized hosts. We also resolved the NMR structure of the ζ subunit of Sinorhizobium meliloti (Sm-ζ) and compared it with its structure modeled in AlphaFold. We found a transition from a compact ordered non-inhibitory conformation into an extended α-helical inhibitory N-terminus conformation, thus explaining why the Sm-ζ cannot exert homologous inhibition. However, it is still able to inhibit the PdF1FO-ATPase heterologously. Together with the loss of the inhibitory function of α-proteobacterial ε, the data confirm that the primary inhibitory function of the α-proteobacterial F1FO-ATPase was transferred from ε to ζ and that ζ, ε, and IF1 evolved by convergent evolution. Some key evolutionary implications on the endosymbiotic origin of mitochondria, as most likely derived from α-proteobacteria, are also discussed.

Detection of Rickettsia amblyommatis and Rickettsia bellii in ticks collected from pet dogs in peri-urban and rural areas in Yucatan, Mexico.

Rickettsia species are bacteria that may cause multiple diseases in animals and humans, via transmission through multiple arthropod vectors. Routine surveillance of Rickettsia spp. within vectors is critical to determine their presence and risk to mammalian hosts within human populations. Therefore, to better characterize the circulating Rickettsia species in an understudied region we targeted pet dogs to survey. Ticks were collected from pet dogs in three populations of the Yucatan where we tested for the presence of Rickettsia spp. by PCR in metagenomic DNA. In these ticks removed from pet dogs we detected Rickettsia amblyommatis and Rickettsia bellii in Amblyomma auriculatum, Amblyomma ovale and Amblyomma mixtum ticks obtained in a rural community in the Mexican state of Yucatan. This is the first report detecting both species for this state in Mexico, underpinning the importance of more routine surveillance.

On the offensive alliance number for the zero divisor graph of Zn.

A nonempty subset $ D $ of vertices in a graph $ \Gamma = (V, E) $ is said is an offensive alliance, if every vertex $ v \in \partial(D) $ satisfies $ \delta_D(v) \geq \delta_{\overline{D}}(v) + 1 $; the cardinality of a minimum offensive alliance of $ \Gamma $ is called the offensive alliance number $ \alpha ^o(\Gamma) $ of $ \Gamma $. An offensive alliance $ D $ is called global, if every $ v \in V - D $ satisfies $ \delta_D(v) \geq \delta_{\overline{D}}(v) + 1 $; the cardinality of a minimum global offensive alliance of $ \Gamma $ is called the global offensive alliance number $ \gamma^o(\Gamma) $ of $ \Gamma $. For a finite commutative ring with identity $ R $, $ \Gamma(R) $ denotes the zero divisor graph of $ R $. In this paper, we compute the offensive alliance (global, independent, and independent global) numbers of $ \Gamma(\mathbb{Z}_n) $, for some cases of $ n $.

Cycle threshold and viral load in SARS-CoV-2-infected patients in Sonora, Mexico.

BACKGROUND: SARS-CoV-2 infection is confirmed with the polymerase chain reaction test. Its positivity is determined by the cycle threshold (Ct), which is inversely proportional to viral load. OBJECTIVE: To describe clinical and epidemiological characteristics of SARS-CoV-2-infected patients according to their viral load estimated by Ct. MATERIAL AND METHODS: Cross-sectional study that included 21,110 confirmed cases, which were stratified according to their viral load: low (Ct > 30), medium (Ct 25-30) and high (Ct < 25). RESULTS: High viral load was identified in 53% of the cases, hospitalization was more common in subjects with medium viral load, and deaths were more prevalent in those with high viral load. Median Ct was lower during the first five days and linearly increased with the days of clinical evolution. There was a higher prevalence of deaths, hospitalizations and ventilatory support in subjects with confirmed SARS-CoV-2 infection who had a medium and high viral load. CONCLUSIONS: The Ct value, correlated with other patient characteristics, can guide the prognosis, as well as the design of interventions that limit the spread of the virus within the population.

ANTECEDENTES: La infección por SARS-CoV-2 se confirma con la prueba de reacción en cadena de la polimerasa. Su positividad se determina mediante el tiempo de ciclado (Ct, cycle threshold), el cual es inversamente proporcional a la carga viral. OBJETIVO: Describir las características clínicas y epidemiológicas de pacientes infectados por SARS-CoV-2 de acuerdo con su carga viral estimada mediante Ct. MATERIAL Y MÉTODOS: Estudio transversal que incluyó 21 110 casos confirmados, los cuales fueron estratificados conforme a su carga viral: baja (Ct > 30), media (Ct 25-30) y alta (Ct < 25). RESULTADO: 53 % de los casos tuvo una carga viral alta, la hospitalización fue más frecuente en sujetos con carga viral media y las defunciones fueron más prevalentes en aquellos con carga viral alta. La mediana del Ct fue más baja durante los primeros cinco días y aumentó linealmente con los días de evolución clínica. Hubo una mayor prevalencia de defunciones, hospitalizaciones y apoyo ventilatorio en sujetos con infección confirmada por SARS-CoV-2 que presentaron carga viral media y alta. CONCLUSIONES: El valor de Ct, correlacionado con otras características del paciente, puede orientar el pronóstico, así como al diseño de intervenciones que limiten la diseminación poblacional del virus.

Tiempo de ciclado y carga viral en pacientes infectados por SARS-CoV-2 en Sonora, México / Cycle threshold and viral load in SARS-CoV-2-infected patients in Sonora, Mexico

Resumen Antecedentes: La infección por SARS-CoV-2 se confirma con la prueba de reacción en cadena de la polimerasa. Su positividad se determina mediante el tiempo de ciclado (Ct, cycle threshold), el cual es inversamente proporcional a la carga viral. Objetivo: Describir las características clínicas y epidemiológicas de pacientes infectados por SARS-CoV-2 de acuerdo con su carga viral estimada mediante Ct. Material y métodos: Estudio transversal que incluyó 21 110 casos confirmados, los cuales fueron estratificados conforme a su carga viral: baja (Ct > 30), media (Ct 25-30) y alta (Ct < 25). Resultado: 53 % de los casos tuvo una carga viral alta, la hospitalización fue más frecuente en sujetos con carga viral media y las defunciones fueron más prevalentes en aquellos con carga viral alta. La mediana del Ct fue más baja durante los primeros cinco días y aumentó linealmente con los días de evolución clínica. Hubo una mayor prevalencia de defunciones, hospitalizaciones y apoyo ventilatorio en sujetos con infección confirmada por SARS-CoV-2 que presentaron carga viral media y alta. Conclusiones: El valor de Ct, correlacionado con otras características del paciente, puede orientar el pronóstico, así como al diseño de intervenciones que limiten la diseminación poblacional del virus.

Abstract Background: SARS-CoV-2 infection is confirmed with the polymerase chain reaction test. Its positivity is determined by the cycle threshold (Ct), which is inversely proportional to viral load. Objective: To describe clinical and epidemiological characteristics of SARS-CoV-2-infected patients according to their viral load estimated by Ct. Material and methods: Cross-sectional study that included 21,110 confirmed cases, which were stratified according to their viral load: low (Ct > 30), medium (Ct 25-30) and high (Ct < 25). Results: High viral load was identified in 53% of the cases, hospitalization was more common in subjects with medium viral load, and deaths were more prevalent in those with high viral load. Median Ct was lower during the first five days and linearly increased with the days of clinical evolution. There was a higher prevalence of deaths, hospitalizations and ventilatory support in subjects with confirmed SARS-CoV-2 infection who had a medium and high viral load. Conclusions: The Ct value, correlated with other patient characteristics, can guide the prognosis, as well as the design of interventions that limit the spread of the virus within the population.

Ordered-domain unfolding of thermophilic isolated ß subunit ATP synthase.

The flexibility of the ATP synthase's ß subunit promotes its role in the ATP synthase rotational mechanism, but its domains stability remains unknown. A reversible thermal unfolding of the isolated ß subunit (Tß) of the ATP synthase from Bacillus thermophilus PS3, tracked through circular dichroism and molecular dynamics, indicated that Tß shape transits from an ellipsoid to a molten globule through an ordered unfolding of its domains, preserving the ß-sheet residual structure at high temperature. We determined that part of the stability origin of Tß is due to a transversal hydrophobic array that crosses the ß-barrel formed at the N-terminal domain and the Rossman fold of the nucleotide-binding domain (NBD), while the helix bundle of the C-terminal domain is the less stable due to the lack of hydrophobic residues, and thus the more flexible to trigger the rotational mechanism of the ATP synthase.

Adaptive changes in redox response and decreased platelet aggregation in lead-exposed workers.

Chronic lead exposure can generate pro-oxidative and pro-inflammatory conditions in the blood, related to high platelet activation and aggregation, altering cell functions. We studied ADP-stimulated aggregation and the oxidant/antioxidant system of platelets from chronically lead-exposed workers and non-exposed workers. Platelet aggregation was low in lead-exposed workers (62 vs. 97%), who had normal platelet counts and showed no clinical manifestations of hemostatic failure. ADP-activated platelets from lead-exposed workers failed to increase superoxide release (3.3 vs. 6.6 µmol/g protein), had low NADPH concentration (60 vs. 92 nmol/mg protein), high concentration of hydrogen peroxide (224 vs. 129 nmol/mg protein) and high plasma PGE2 concentration (287 vs. 79 pg/mL). Altogether, those conditions, on the one hand, could account for the low platelet aggregation and, on the other, indicate an adaptive mechanism for the oxidative status of platelets and anti-aggregating molecules to prevent thrombotic problems in the pro-oxidant and pro-inflammatory environment of chronic lead exposure.

Concomitant use of allopathic medicine and herbal products for weight-loss among people with overweight or obesity from Central Mexico / Uso concomitante de medicina alopática y productos herbales para bajar de peso en personas con sobrepeso u obesidad del centro de México

This study evaluated the prevalence of concomitant use of herbal products for weight loss (HPWL) and allopathic medicine. Factors associated with the prevalence, adverse reactions, and the alteration of medication adherence with the concomitant use of HPWL alone and in combination with allopathic medicine, were assessed. The study was descriptive and cross-sectional using a questionnaire conducted among people with overweight or obesity (n=662) from five cities of Central Mexico. Adherence to medications was measured using the Morisky Medication Adherence Scale. The prevalence of adverse reactions induced by the concomitant use of HPWL, and allopathic medicine was 25.3%. The use of HPWL affected medication adherence by 68%. There is a high prevalence (45.2%) of concomitant use of HPWL and allopathic medicine in people with overweight or obesity in Central Mexico. The concomitant use of HPWL and allopathic medicine induces adverse reactions, mainly gastrointestinal, and thus, medication adherence is affected.

Este estudio evaluó la prevalencia del uso concomitante de productos a base de hierbas para bajar de peso (HPWL) y medicina alopática. Se evaluaron los factores asociados con la prevalencia, las reacciones adversas y la alteración de la adherencia a la medicación con el uso concomitante de HPWL solo y en combinación con medicina alopática. El estudio fue descriptivo y transversal mediante un cuestionario realizado entre personas con sobrepeso u obesidad (n = 662) de cinco ciudades del centro de México. La adherencia a los medicamentos se midió mediante la Escala de adherencia a la medicación de Morisky. La prevalencia de reacciones adversas inducidas por el uso concomitante de HPWL y medicina alopática fue del 25,3%. El uso de HPWL afectó la adherencia a la medicación en un 68%. Existe una alta prevalencia (45.2%) de uso concomitante de HPWL y medicina alopática en personas con sobrepeso u obesidad en el centro de México. El uso concomitante de HPWL y medicina alopática induce reacciones adversas, principalmente gastrointestinales, y por tanto, afecta la adherencia a la medicación.