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Introduction: Globally, up to 76.6% of the population may be affected by vitamin D (VD) deficiency, which has been linked to increased morbidity and mortality from COVID-19. This underscores the importance of further research into VD supplementation, particularly for health care workers, who are at higher risk due to indoor work environments and dietary challenges associated with shift schedules. Objective: This study aimed to identify factors associated with VD deficiency in Mexican health care workers exposed to SARS-CoV-2. Materials and methods: We conducted a cross-sectional study from June 2020 to January 2021 among frontline health care workers treating hospitalized COVID-19 patients. Blood samples were collected to measure 25-hydroxy VD levels via radioimmunoassay. We also assessed previous COVID-19 infection and comorbidities that could influence VD levels. Results: The study included 468 health care workers. The median serum VD concentration was 16.6 ng/mL. VD deficiency was found in 69.4% (n = 325) of participants, while only 5.1% (n = 24) had normal levels. Those with type 2 diabetes (13.3 ng/mL vs. 17.1 ng/mL) or obesity (15.7 ng/mL vs. 17.1 ng/mL) had significantly lower VD levels than their counterparts (p < 0.001 and p = 0.049, respectively). No significant differences were found among participants with high blood pressure. Multivariate analysis revealed that type 2 diabetes was independently associated with VD deficiency. Conclusion: There is a high prevalence of VD deficiency among health care workers, which is potentially linked to both personal health factors and occupational conditions.
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INTRODUCTION: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. METHODS: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. RESULTS: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. CONCLUSION: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.
Subject(s)
Escherichia coli Infections , Macrophages , Mice, Knockout , Ribonucleases , Urinary Tract Infections , Uropathogenic Escherichia coli , Animals , Urinary Tract Infections/immunology , Urinary Tract Infections/microbiology , Mice , Uropathogenic Escherichia coli/immunology , Macrophages/immunology , Macrophages/microbiology , Escherichia coli Infections/immunology , Ribonucleases/metabolism , Ribonucleases/genetics , Mice, Inbred C57BL , Humans , Monocytes/immunology , Disease Models, Animal , Female , Cells, CulturedABSTRACT
INTRODUCTION: Healthcare-associated infections (HCAIs) in neonates are frequent and highly lethal, in particular those caused by extended spectrum beta-lactamase (ESBL) producing bacteria. We evaluated the beneficial effects of ultraviolet C (UV-C) disinfection and copper adhesive plating on HCAIs in the Neonatal Intensive Care Unit (NICU) of a third level paediatric hospital in Mexico City, both in combination of hand-hygiene (HH) and prevention bundles. METHODS: All NICU patients were included. There were 4 periods (P): P1: HH monitoring and prevention bundles; P2: P1+UV-C disinfection; P3: P2+Copper adhesive plating on frequent-contact surfaces and P4: Monitoring of P3 actions. RESULTS: 552 neonates were monitored during 15,467 patient days (PD). HCAI rates decreased from 11.03/1000 PD in P1 to 5.35/1000 PD in P4 (p=0.006). HCAIs with bacterial isolates dropped from 5.39/1000 PD in PI to 1.79/1000 PD in P4 (p=0.011). UV-C and copper were associated with significant HCAI prevention (RR 0.49, CI95% 0.30-0.81, p=0.005) and with lesser HCAIs with bacterial isolates (RR 0.33, CI95% 0.14-0.77, p=0.011). CONCLUSIONS: Copper adhesive plating combined with UV-C disinfection were associated with a drop in HCAI rates and with the elimination of ESBL-caused HCAIs. Hence, we propose that these strategies be considered in MDRO proliferation preventions.
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BACKGROUND: During allogeneic Hematopoietic stem cell transplantation (HSCT), frequent pathological scenarios include graft versus host disease (GVHD) and viral infections. We hypothesized if exogenous stimulus as alloantigen and viral antigens might impact on central and effector memory T cells in pediatric recipients. PATIENTS AND METHODS: Subjects included 21 pediatric recipients and 20 healthy children (control group). Peripheral blood samples of patients were collected along the first 712 days post-HSCT. T cell phenotyping of naïve, central, and effector memory T cells (TCMs and TEMs, respectively) was conducted using flow cytometry. Viral nucleic acids were detected using real-time PCR. RESULTS: T cell reconstitution was not reached after 1 year post-HSCT. Chronic GVHD was associated with increased numbers of naïve CD4 T cells (p < 0.05) as well as an increase in TEM and TCM cells of the CD4 (p < 0.0001 and p < 0.05, respectively) and CD8 T cell TEM (p < 0.0001). and TCM (p < 0.001) populations too. Moreover, BK and Epstein-Barr viruses were the main viral pathogens detected (<104 copies), which were associated with a decrease in all T cell compartments. CONCLUSION: During chronic GVHD, alloantigen persistence generates TEM cell enrichment among CD4 and CD8 T cells, and viral infections are associated with deficient recovery of T cells after HSCT.
Subject(s)
Bronchiolitis Obliterans Syndrome , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Virus Diseases , Humans , Child , Memory T Cells , CD8-Positive T-Lymphocytes , IsoantigensABSTRACT
Acute respiratory infections (ARIs) are a major cause of morbidity and mortality among children. The causative pathogens show geographic and seasonal variations. We retrospectively evaluated the frequency and seasonality of respiratory pathogens in children and adolescents (age: 0-19 years) with ARIs treated between January 1, 2021, and March 31, 2022, at a single center in Mexico. Out of 2400 patients, 1,603 were diagnosed with SARS-CoV-2 infection and 797 were diagnosed with other common respiratory pathogens (CRPs). Of the 797 patients, 632 were infected with one CRP and 165 with > 2 CRPs. Deaths occurred only in SARS-CoV-2-infected patients. Rhinovirus/Enterovirus, respiratory syncytial virus B, and parainfluenza virus 3 were the most prevalent in cases with single and multiple infections. CRP showed a high frequency between autumn and winter of 2021, with higher incidence of hospitalization compared to COVID-19. The main comorbidities were immunosuppression, cardiovascular disease (CD), and asthma. The frequency of CRPs showed a downward trend throughout the first half of 2021. CRPs increased in single- and co-infection cases between the fourth and fifth waves of COVID-19, probably due to decreased nonpharmaceutical interventions and changes in diagnostic tests. Age, cyanosis (symptom), and immunosuppression (comorbidity) were found to differentiate between SARS-CoV-2 infection and CRP infection.
Subject(s)
COVID-19 , Respiratory Tract Infections , Humans , Child , Adolescent , Infant , Infant, Newborn , Child, Preschool , Young Adult , Adult , Mexico/epidemiology , Retrospective Studies , Tertiary Care Centers , COVID-19/epidemiology , COVID-19/complicationsABSTRACT
During coral calcification in massive scleractinian corals, a double annual banding of different densities (high- and low-density) is formed in their skeletons, which can provide a retrospective record of growth and the influence of environmental conditions on the coral's lifespan. Evidence indicates that during the last decades, the reduction in coral calcification rate is attributed to the combination of global stress factors such as Sea Surface Temperature (SST) and local anthropic stressors. Yet, coral growth trajectories can vary between regions and coral species, where remote locations of coral reefs can act as natural laboratories, as they are far from the harmful effects of direct anthropogenic stressors. The present study reports historical chronology over a 24-year period (1992-2016) of coral extension rate (cm yr-1), skeletal density (g cm-3), and calcification rate (g cm-2 yr-1) of the reef-building coral Orbicella faveolata at the remote reef Cayo Arenas, Campeche Bank, in the south-eastern Gulf of Mexico. The relationships between the three sclerochronological features show that O. faveolata uses its calcification resources to build denser skeletons. Chronological trends indicate that coral extension increased, skeletal density and calcification rate decreased (33% calcification rate) over time. The results reveal that despite the remoteness of the locality the maximum SST has been increased, and the coral calcification rate decreased over time. If the temperature continues to rise, there is a conceivable risk of experiencing a decline in reef-building coral species. This scenario, in turn, could pose a significant threat, endangering not only the framework of coral reefs but also their ecological functionality, even within remote Atlantic reef ecosystems.
Subject(s)
Anthozoa , Calcinosis , Animals , Coral Reefs , Ecosystem , Gulf of Mexico , Retrospective StudiesABSTRACT
Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.
Subject(s)
Ribonucleases , Urinary Tract Infections , Animals , Humans , Mice , Endoribonucleases/genetics , Kidney , Mice, Transgenic , Ribonucleases/genetics , Urinary Bladder/microbiologyABSTRACT
Introduction: Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%. Materials and methods: A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts. Results: We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years. Conclusion: APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.
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Introduction: Vitamin D (VD) deficiency is common in children with chronic kidney disease (CKD) because of multiple factors. During the coronavirus disease 2019 (COVID-19) pandemic, it increased because of medicine shortage and no enough medical service for patients with non-COVID-19 diseases. Objective: To analyze the effects of the COVID-19 pandemic-related lockdown on the serum levels and status of 25-hydroxyvitamin D3 (25-[OH]D) in children with CKD. Materials and methods: This retrospective study included patients (6-18 years old) who were diagnosed with CKD stage 2-5 and routinely measured for serum VD levels between May 2019 and December 2022. Serum 25-(OH)D levels were measured before, during, and after the pandemic (2019, 2020-2021, and 2022, respectively). The daily dose of cholecalciferol supplementation and the readjustment (if required) were recorded. Results: This study included 171 patients (median age: 12 years). Before the pandemic, the median serum VD level was 25.0 ng/mL (19.3% VD deficiency). Then, VD supplementation was adjusted to 400-1,200 UI daily in 98.8% (n = 169) of patients. During the pandemic, the median VD level decreased to 22.5 ng/mL (43.3% VD deficiency). Hence, the supplementation was readjusted, and after the pandemic, the level was 28.7 ng/mL (18.7% VD deficiency), indicating a statistically significant increase in serum VD levels from the prepandemic period (p = 0.007). Conclusion: Decreased serum VD levels and increased VD deficiency frequency were observed in patients with CKD during the COVID-19 but improved after readjustment of supplementation.
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Coral mortality triggers the loss of carbonates fixed within coral skeletons, compromising the reef matrix. Here, we estimate rates of carbonate loss in newly deceased colonies of four Caribbean reef-building corals. We use samples from living and recently deceased colonies following a stony coral tissue loss disease (SCTLD) outbreak. Optical densitometry and porosity analyses reveal a loss of up to 40% of the calcium carbonate (CaCO3) content in dead colonies. The metabolic activity of the endolithic organisms colonizing the dead skeletons is likely partially responsible for the observed dissolution. To test for the consequences of mass mortality events over larger spatial scales, we integrate our estimates of carbonate loss with field data of the composition and size structure of coral communities. The dissolution rate depends on the relative abundance of coral species and the structural properties of their skeletons, yet we estimate an average reduction of 1.33 kg CaCO3 m-2, nearly 7% of the total amount of CaCO3 sequestered in the entire system. Our findings highlight the importance of including biological and chemical processes of CaCO3 dissolution in reef carbonate budgets, particularly as the impacts of global warming, ocean acidification, and disease likely enhance dissolution processes.
Subject(s)
Anthozoa , Seawater , Animals , Hydrogen-Ion Concentration , Caribbean Region , CarbonatesABSTRACT
Background: More than two years after the pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) there is a great lack of information. The presence of immunoglobulin G (IgG) have been related with disease severity. Patients with comorbidities could develop more severe infection; however, the evaluation of the humoral response in pediatric population are needed especially in patients with comorbidities. Our aim was to describe the behavior of IgG in pediatric patients and to know if there is a difference between patients with comorbidities. Methods: A prospective comparative cohort study was carried out in a single center from June 2020 to January 2021, with a follow-up of 6 months. The study included all the subjects with confirmatory test for SARS-CoV-2 from 1 month to 17 years 11 months, the follow-up of the disease's evolution and measurement of IgG antibodies was collected. We obtained the clinical data, and comorbidities like arterial hypertension, diabetes, obesity, and cancer, the initial symptoms were recorded as well as the evolution regarding the severity of COVID-19 and the need for hospitalization, intensive care unit or mechanical ventilation. The follow up was carried out through medical consultation with an appointment every month that included direct interrogation, examination, and peripheral blood collection for the IgG quantification. The antibodies detection was done through peripheral blood and chemiluminescence microparticle immunoassay. Results: A total of 237 patients with positive polymerase chain reaction (PCR) for SARS-COV-2 were included, of which 147 presented IgG antibodies (62%), 112 (76%) without comorbidity and 35 (24%) with comorbidities, by the sixth month only 2.7% continue with positive antibody measurements. Patients with comorbidities reach higher IgG levels than patients without comorbidities the basal titters were: 5.17 for patients without comorbidities vs. 6.96 for the group with comorbidities (P<0.001). Conclusions: We found an association between the presence of comorbidities and high levels of IgG units in pediatric patients with COVID-19. Additionally, patients with more severe course of the disease have higher levels of IgG and by the third month less than 35% have immunity.
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BACKGROUND: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). CASE REPORT: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. CONCLUSIONS: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.
INTRODUCCIÓN: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. CASO CLÍNICO: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. CONCLUSIONES: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.
Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Female , Humans , Biomarkers , Phenotype , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , RecurrenceABSTRACT
Abstract Background: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). Case report: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. Conclusions: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.
Resumen Introducción: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. Caso clínico: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. Conclusiones: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.
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BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Pandemics , Prospective Studies , Comorbidity , HematopoiesisABSTRACT
Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum-resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.
Subject(s)
COVID-19 , Endoplasmic Reticulum Chaperone BiP , Humans , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Leukocytes, Mononuclear/metabolism , COVID-19/metabolism , Molecular Chaperones/genetics , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum StressABSTRACT
With the emergence of antibiotic-resistant bacteria, innovative approaches are needed for the treatment of urinary tract infections. Boosting antimicrobial peptide expression may provide an alternative to antibiotics. Here, we developed reporter cell lines and performed a high-throughput screen of clinically used drugs to identify compounds that boost ribonuclease 4 and 7 expression (RNase 4 and 7), peptides that have antimicrobial activity against antibiotic-resistant uropathogens. This screen identified histone deacetylase (HDAC) inhibitors as effective RNase 4 and RNase 7 inducers. Validation studies in primary human kidney and bladder cells confirmed pan-HDAC inhibitors as well as the HDAC class I inhibitor, MS-275, induce RNase 4 and RNase 7 to protect human kidney and bladder cells from uropathogenic Escherichia coli. When we administered MS-275 to mice, RNase 4 and 7 expression increased and mice were protected from acute transurethral E. coli challenge. In support of this mechanism, MS-275 treatment increased acetylated histone H3 binding to the RNASE4 and RNASE7 promoters. Overexpression and knockdown of HDAC class I proteins identified HDAC3 as a primary regulator of RNase 4 and 7. These results demonstrate the protective effects of enhancing RNase 4 and RNase 7, opening the door to repurposing medications as antibiotic conserving therapeutics for urinary tract infection.
Subject(s)
Histone Deacetylase Inhibitors , Urinary Tract Infections , Humans , Mice , Animals , Histone Deacetylase Inhibitors/pharmacology , Escherichia coli/metabolism , Drug Repositioning , Ribonucleases/metabolism , Urinary Tract Infections/drug therapy , Urinary Tract Infections/microbiology , Anti-Bacterial AgentsABSTRACT
A severe complication of allogeneic hematopoietic stem cell transplantation (HSCT) is graft failure (GF). Among others, donor-specific anti-HLA antibodies (DSA) are associated with graft rejection after allogeneic or haploidentical transplantation in adults. Knowledge of DSA and pediatric recipients is limited. Hence, we aimed to generate more information about the presence of DSA (pre- and post-HSCT) and the clinical outcomes (graft rejection and poor function) in children. We identified DSA in 27% of the patients. We observed a higher frequency (50%) of DSA-bearing patients with a benign disease diagnosis than those diagnosed with leukemia (16.66%). We observed graft rejection in one patient (with DSA against two alleles of HLA class I molecules) and poor function in three recipients during the first 30 days after HSCT in the absence of DSA. The presence of donor and nondonor HLA-specific antibodies decreased substantially after transplantation. After the transplant, we identified two patients with DSA specific for HLA class I molecules (independent of clinical relevance), and four recipients showed PGF in the absence of DSA. We were unable to establish any association between the presence of DSA and a clinical outcome: graft failure or prevalence of viral infection.
Subject(s)
Hematopoietic Stem Cell Transplantation , Isoantibodies , Child , Humans , Alleles , Histocompatibility Antigens Class I , Histocompatibility Antigens Class IIABSTRACT
One of the most important causes of disease and premature death in the world is environmental pollution. The presence of pollutants in both water and air contributes to the deterioration of the health of human populations. The Mexico City Metropolitan Area is one of the most populous and affected by air pollution worldwide; in addition, in recent years there has been a growing demand for water, so urban reservoirs such as the Madin dam are vital to meet the demand. However, this reservoir is highly polluted due to the urban settlements around it. Therefore, the aim of the present study was to evaluate oxidative stress in clinically healthy subjects by means of the degree of lipoperoxidation, as well as the modification of serum enzyme levels, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase associated with air and drinking water pollutants from three zones of the Mexico City Metropolitan Area, two of them related to Madin Dam. This descriptive cross-sectional study was conducted between March 2019 and September 2021 in 142 healthy participants (age range 18-65 years). Healthy subjects were confirmed by their medical history. The results showed that chronic exposure to air (SO2) and water pollutants (Al and Fe) was significantly associated with elevated levels of lipoperoxidation. There was evidence that contamination from the Madín dam can generate oxidative stress and affect the health status of people who receive water from this reservoir or who consume fish that inhabit it.
Subject(s)
Air Pollutants , Air Pollution , Liver Diseases , Water Pollutants , Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Air Pollutants/analysis , Air Pollution/analysis , Cross-Sectional Studies , Environmental Monitoring , Mexico , Oxidative Stress , Pilot Projects , WaterABSTRACT
Sugary soft drinks modify salivary pH and favor bacterial proliferation and are associated with the development of caries. Information on the effects of consuming carbonated drinks without sucrose is limited. Methods: In this crossover clinical trial, salivary and dental biofilm pH were determined at 0, 5, 10, 15, 30, 45, and 60 min after the participants (n = 18) ingested a soft drink with sucrose, a soft drink with aspartame/acesulfame K, carbonated water, and plain water on different days. Dental biofilm cultures were conducted at 0- and 120-min. Results: Salivary pH decreased significantly after ingestion of the sucrose-containing soft drink when compared with the other types of beverages (median difference, -0.3--0.4, p ≤ 0.05), and the greatest difference was found with mineral water. A greater bacterial proliferation (Colony Forming Units [CFU]) was observed after ingestion of the drink with sucrose (↑310 × 103 CFU, p ≤ 0.01), followed by the drink with aspartame/acesulfame K (↑160 × 103 CFU, p ≤ 0.01) and carbonated water (↑60 × 103 CFU, p ≤ 0.05). No significant changes in bacterial proliferation were observed after the consumption of natural water. Conclusions: Ingestion of sucrose-containing soft drinks favors the acidification of salivary pH and the bacterial proliferation of dental biofilm. Although to a lesser extent, soft drinks containing aspartame/acesulfame K also favor bacterial proliferation.
ABSTRACT
BACKGROUND: We analyzed the demographic, clinical, and diagnostic data of children and adolescents in Mexico, from the first case of coronavirus disease (COVID-19) to 28 February 2022. METHODS: Using the open databases of the Ministry of Health and a tertiary pediatric hospital, we obtained demographic and clinical data from the beginning of the COVID-19 pandemic until 28 February 2022. In addition, quantitative reverse-transcription polymerase chain reaction outputs were used to determine the viral load, and structural protein-based serology was performed to evaluate IgG antibody levels. RESULTS: Of the total 437,832 children and adolescents with COVID-19, 1187 died. Of these patients, 1349 were admitted to the Hospital Infantil de Mexico Federico Gómez, and 11 died. Obesity, asthma, and immunosuppression were the main comorbidities, and fever, cough, and headache were the main symptoms. In this population, many patients have a low viral load and IgG antibody levels. CONCLUSION: During the first 2 years of the COVID-19 pandemic in Mexico, children and adolescents had low incidence and mortality. They are a heterogeneous population, but many patients had comorbidities such as obesity, asthma, and immunosuppression; symptoms such as fever, cough, and headache; and low viral load and IgG antibodies.