RESUMO
BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.
Assuntos
COVID-19 , Doenças Metabólicas , Síndrome de Linfonodos Mucocutâneos , Neoplasias , Feminino , Gravidez , Humanos , Criança , Estudos Longitudinais , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estudos de Coortes , Fatores de Risco , COVID-19/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologiaRESUMO
Alzheimer's disease (AD) is the most common neurodegenerative disorder, and amyloid beta oligomers (AßO), which are pathological markers of AD, are known to be highly toxic. AßO increase mitochondrial dysfunction, which is accompanied by a decrease in mitochondrial fusion. Although mitofusin (Mfn) 1 and Mfn2 are mitochondrial fusion proteins, Mfn2 is known to regulate endoplasmic reticulum (ER) function, as it is located in the ER. Several studies have shown that AßO exacerbates ER stress, however, the exact mechanism requires further elucidation. In this study, we used mouse neuroblastoma cells stably overexpressing the amyloid precursor protein (APP) with the Swedish mutation (N2a APPswe cells) to investigate the role of Mfn in ER stress. Our results revealed that amyloid beta (Aß) caused cellular toxicity in N2a APPswe cells, upregulated ER stress-related proteins, and promoted ER expansion. The AßO-mediated ER stress was reduced when Mfn1 and Mfn2 were overexpressed. Moreover, Mfn1 and Mfn2 overexpressed resulted in reduced apoptosis of N2a APPswe cells. In conclusion, our results indicate that both Mfn1 and Mfn2 reduce ER stress and apoptosis. Our data provide a foundation for future studies on the roles of Mfn1 and Mfn2 in the molecular mechanisms underlying AßO-mediated ER stress and the pathogenesis of AD.
Assuntos
Peptídeos beta-Amiloides , Apoptose , Estresse do Retículo Endoplasmático , GTP Fosfo-Hidrolases , Animais , Humanos , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/genética , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Mitocôndrias/metabolismoRESUMO
The extracts of Corydalis heterocarpa, a salt-tolerant plant, exhibit diverse physiological properties, including anti-inflammatory, anticancer, and antiadipogenic effects. However, the anti-aging effects of C. heterocarpa extract (CHE) on human skin cells have not yet been investigated. In the present study, we determined that CHE inhibited senescence-associated ß-galactosidase (SA-ß-gal)-stained senescent human dermal fibroblasts (HDFs). Furthermore, CHE markedly suppressed the expression of major regulatory proteins involved in senescence, including p53, p21, and caveolin-1. Interestingly, CHE promoted autophagic flux, as confirmed by the formation of microtubule-associated protein 1 light chain 3B (LC3B) puncta and lysosomal activity. Notably, using RNA sequencing (RNA-seq), we showed that CHE selectively regulated the gene expression of leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1), an important regulator of autophagy. The adenosine-monophosphate activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway, which is essential for autophagy regulation, was also modulated by CHE. LRSAM1 depletion not only inhibited LC3B expression but also decreased the autophagy flux induced by CHE. Moreover, the knockdown of LRSAM1 suppressed the reversal of CHE-induced senescence in old HDFs. Collectively, our study has revealed the rejuvenating effects and molecular mechanisms of CHE, suggesting that CHE may be a promising anti-aging agent.
Assuntos
Corydalis , Humanos , Autofagia , Pele , Envelhecimento , Extratos Vegetais , Ubiquitina-Proteína LigasesRESUMO
AIM: We assessed the association between caesarean birth and age-specific risks of childhood cancer. METHODS: We followed a cohort of 1 034 049 children between 2006 and 2020 in Quebec, Canada, from birth until age 14 years. The exposure was caesarean, operative vaginal, or spontaneous vaginal birth. The outcome included haematopoietic or solid tumours. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between mode of delivery and childhood cancer in age-lagged analyses, adjusted for potential confounders. RESULTS: A total of 249 415 (24.1%) children were born by caesarean and 97 411 (9.4%) by operative vaginal delivery. Compared with spontaneous vaginal birth, caesarean was associated with 1.16 times the risk of any cancer (95% CI 1.04-1.30), 1.12 times the risk of haematopoietic cancer (95% CI 0.92-1.36) and 1.21 times the risk of solid tumours (95% 1.06-1.39). Associations strengthened at 2 years of age and were greatest for lymphoma and sarcoma. Operative vaginal birth was not significantly associated with the risk of cancer. CONCLUSION: Caesarean birth may be associated with selected childhood cancers, including lymphoma and sarcoma early in childhood. The underlying reasons for the associations require further investigation, including whether mucosal dysbiosis or labour hormone exposure explain the excess risk.
Assuntos
Trabalho de Parto , Sarcoma , Gravidez , Feminino , Criança , Humanos , Adolescente , Cesárea/efeitos adversos , Parto Obstétrico , PartoRESUMO
In this study, we provide critical evidence that STAT2 stability regulation plays an essential role in melanoma cell proliferation and colony growth. We found that the interaction of FBXW7 and STAT2 induced STAT2 destabilization via a ubiquitination-mediated proteasomal degradation pathway. Notably, GSK3ß-mediated STAT2 phosphorylation facilitated STAT2-FBXW7 interactions via the DNA binding domain of STAT2 and domains 1, 2, 6, and 7 of FBXW7 WD40. Importantly, the inverse correlation between protein levels of STAT2 and FBXW7 were observed not only in human melanoma cells but also in a human skin cancer tissue array. The relationship between protein levels of STAT2 and FBXW7, cell proliferation, and colony growth were similarly observed in the melanoma cell lines SK-MEL-2, -5, and -28. Moreover, STAT2 knockdown in melanoma cells suppressed melanoma cell proliferation and colony formation. These data demonstrated that FBXW7-mediated STAT2 stability regulation plays an essential role in melanoma cell proliferation and cancer growth.
Assuntos
Proteína 7 com Repetições F-Box-WD/metabolismo , Melanoma/patologia , Fator de Transcrição STAT2/metabolismo , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Estabilidade Proteica , Proteólise , Fator de Transcrição STAT2/química , Fator de Transcrição STAT2/genética , Serina/metabolismo , Transdução de Sinais , Pele/patologia , Treonina/metabolismo , Análise Serial de Tecidos , Ubiquitinação , Repetições WD40RESUMO
A complementary metal-oxide-semiconductor (CMOS) detector array is proposed to improve the sub-terahertz imaging resolution for objects in the conveyor belt system. The image resolution is limited to the implemented configuration, such as the wide spacing in the detector array, the high conveyor belt speed, and the slow response of the signal conditioning block. The proposed array can improve the image resolution in the direction perpendicular to the movement of the belt, which is determined by the size and interval of the detector pixel, by configuring the array into two replaceable columns located at the misaligned horizontal positions. Replaceable detector unit pixels are individually attached to the motherboard after measuring and evaluating the detection performance to construct the proposed array. The intensities of 32 detector pixels placed under the conveyor belt with a width of 160 mm were initially calibrated in every image, including the beam pattern of 0.2 THz signals generated from the gyrotron. The image resolution of the perpendicular direction obtained from the proposed array was measured to be approximately 5 mm at a conveyor belt speed of 16 mm/s, demonstrating a 200% improvement in resolution compared to the conventional linear array under the same conditions.
RESUMO
The nuclear membrane serves a critical role in protecting the contents of the nucleus and facilitating material and signal exchange between the nucleus and cytoplasm. While extensive research has been dedicated to topics such as nuclear membrane assembly and disassembly during cell division, as well as interactions between nuclear transmembrane proteins and both nucleoskeletal and cytoskeletal components, there has been comparatively less emphasis on exploring the regulation of nuclear morphology through nuclear membrane integrity. In particular, the role of type II integral proteins, which also function as transcription factors, within the nuclear membrane remains an area of research that is yet to be fully explored. The integrity of the nuclear membrane is pivotal not only during cell division but also in the regulation of gene expression and the communication between the nucleus and cytoplasm. Importantly, it plays a significant role in the development of various diseases. This review paper seeks to illuminate the biomolecules responsible for maintaining the integrity of the nuclear membrane. It will delve into the mechanisms that influence nuclear membrane integrity and provide insights into the role of type II membrane protein transcription factors in this context. Understanding these aspects is of utmost importance, as it can offer valuable insights into the intricate processes governing nuclear membrane integrity. Such insights have broad-reaching implications for cellular function and our understanding of disease pathogenesis.
Assuntos
Proteínas de Membrana , Membrana Nuclear , Membrana Nuclear/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Nucleares/genética , Citoplasma/metabolismo , Fatores de Transcrição/metabolismo , Núcleo Celular/metabolismoRESUMO
BACKGROUND: Health outcomes of children in families affected by cancer are poorly understood. The authors assessed the risk of hospitalization in children who have a sibling with cancer. METHODS: This was a longitudinal cohort study in which 1600 children who had a sibling with cancer were matched to 32,000 children who had unaffected siblings in Quebec, Canada, from 2006 to 2020. The exposure of interest was having a sibling with cancer. Outcomes included hospitalization for pneumonia, asthma, fracture, and other morbidities any time after the sibling was diagnosed with cancer. The children were followed over time, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the impact of having a sibling with cancer on the risk of hospitalization before age 14 years, adjusted for patient characteristics. RESULTS: Children who had a sibling with cancer had an increased risk of hospitalization compared with unaffected children (HR, 1.15; 95% CI, 1.02-1.29). Conditions associated with a greater risk of hospitalization included pneumonia, hemangioma, other skin conditions, sleep apnea, and inflammatory bowel disease. The risk of hospitalization was greatest for children whose older sibling had cancer (HR, 1.16; 95% CI, 1.01-1.32) and for children whose sibling had hematopoietic cancer (HR, 1.22; 95% CI, 1.01-1.48). CONCLUSIONS: Children who have a sibling with cancer are at risk of hospitalization for conditions such as pneumonia, inflammatory bowel disease, and other morbidities. Families affected by childhood cancer may benefit from additional support to facilitate care for all children in the family. LAY SUMMARY: Little is known about the health of children who have a brother or sister with cancer. The authors studied the types of hospitalization experienced by children who have siblings with cancer. The results indicated that having a sibling with cancer increased the chance of being hospitalized for pneumonia and other conditions that could have been preventable. The results also indicated that children who had an older sibling with cancer or a sibling with blood cancer had a greater chance of being hospitalized. The findings highlight the importance of providing timely care for children in families affected by childhood cancer.
Assuntos
Neoplasias , Irmãos , Adolescente , Criança , Estudos de Coortes , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
BACKGROUND: Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. METHODS: We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. RESULTS: A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. CONCLUSIONS: Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.
Assuntos
Doenças Autoimunes , Hipersensibilidade , Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Doenças Autoimunes/epidemiologia , Criança , Estudos de Coortes , Feminino , Hospitalização , Humanos , Hipersensibilidade/epidemiologia , Neoplasias/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de RiscoRESUMO
A CMOS detector with a concurrent mode for high-quality images in the sub-terahertz region has been proposed. The detector improves output-signal coupling characteristics at the output node. A cross-coupling capacitor is added to isolate the DC bias between the drain and gate. The detector is designed to combine a 180° phase shift based on common source operation and an in-phase output signal based on the drain input. The circuit layout and phase shift occurring in the cross-coupled capacitor during phase coupling are verified using an EM simulation. The detector is fabricated using the TSMC 0.25-µm mixed-signal 1-poly 5-metal layer CMOS process, where the size, including the pad, is 1.13 mm × 0.74 mm. The detector IC comprises a folded dipole antenna, the proposed detector, a preamplifier, and a voltage buffer. Measurement results using a 200-GHz gyrotron source demonstrate that the proposed detector voltage responsivity is 14.13 MV/W with a noise-equivalent power of 34.42 pW/âHz. The high detection performance helps resolve the 2-mm line width. The proposed detector exhibits a signal-to-noise ratio of 49 dB with regard to the THz imaging performance, which is 9 dB higher than that of the previous CMOS detector core circuits with gate-drain capacitors.
RESUMO
OBJECTIVES: To determine the association between cesarean delivery and childhood infections up to 13 years of age. STUDY DESIGN: We conducted a longitudinal cohort study of 731 803 children born between 2006 and 2016 at all hospitals in the province of Quebec, Canada. We followed children born by cesarean, operative vaginal, and nonoperative vaginal delivery up to 13 years of age. Outcomes included hospitalization for otitis media, respiratory, infectious enteritis, and other infections. We estimated hazard ratios with 95% CIs for the association between mode of delivery and childhood infections, adjusted for patient characteristics. RESULTS: At age 3-4 years, cesarean delivery was associated with a 1.07-fold greater risk of otitis media (95% CI, 1.03-1.11), a 1.15-fold greater risk of respiratory infection (95% CI, 1.09-1.22), and a 1.13-fold greater risk of infectious enteritis (95% CI, 1.03-1.25) compared with nonoperative vaginal delivery. However, operative vaginal delivery was associated with these same outcomes. Both cesarean and operative vaginal delivery were more strongly associated with infection hospitalization before age 1 year, but associations disappeared after 5 years. CONCLUSIONS: Cesarean delivery is associated with infection hospitalization before but not after age 5 years. However, associations were also present for operative vaginal delivery, which suggests that mechanisms other than exposure to maternal vaginal flora explain the relationship.
Assuntos
Cesárea/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Infecções/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Parto Obstétrico , Feminino , Seguimentos , Humanos , Lactente , Estudos Longitudinais , Masculino , Gravidez , Estudos RetrospectivosRESUMO
It is supposed that cesarean birth is implicated in the development of autoimmunity. We evaluated the association between cesarean delivery and the risk of hospitalization for autoimmune disease in children up to 14 years of age. We performed a longitudinal cohort study of 934,873 children born between 2006 and 2019 in Quebec, Canada. The main exposure measure was cesarean delivery versus vaginal delivery (spontaneous or induced). Outcomes included hospitalization for type 1 diabetes, celiac disease, or other autoimmune disorders before 14 years of age. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between cesarean delivery and hospitalization for autoimmune disorders, adjusted for patient characteristics. A total of 248,963 children (27%) were delivered by cesarean. Median length of follow-up was 7.4 years. The hospitalization rate for autoimmune disorders was 69.1 per 100,000 person-years for cesarean and 65.9 per 100,000 person-years for vaginal delivery. Cesarean delivery was not associated with autoimmune disorders overall (HR 1.02, 95% CI 0.96-1.10). There was no association with type 1 diabetes (HR 1.00, 95% CI 0.85-1.17), celiac disease (HR 0.86, 95% CI 0.71-1.04), inflammatory bowel disease (HR 1.15, 95% CI 0.88-1.49), or idiopathic thrombocytopenic purpura (HR 1.01, 95% CI 0.82-1.25). Cesarean delivery was not associated with autoimmune disorders at different ages.Conclusion: This study suggests that cesarean delivery is not associated with the risk of hospitalization for autoimmune disorders before 14 years of age. Delivery mode does not seem to mediate the risk of autoimmunity in childhood. What is Known: ⢠Children born by cesarean may be at risk of abnormal immune development. ⢠The association between cesarean delivery and risk of pediatric autoimmune disorders is unclear. What is New: ⢠In this cohort study of over 900,000 children, cesarean delivery was not associated with the risk of hospitalization for a range of autoimmune disorders before 14 years of age. ⢠Cesarean delivery may not be related to the development of autoimmunity.
Assuntos
Cesárea , Diabetes Mellitus Tipo 1 , Cesárea/efeitos adversos , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/etiologia , Feminino , Hospitalização , Humanos , Estudos Longitudinais , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: To assess the association of maternal illicit drug abuse before or during pregnancy with future fractures in offspring. METHODS: We performed a longitudinal cohort study of 792,022 infants born in hospitals of Quebec, Canada, between 2006 and 2016, with 5,457,634 person-years of follow-up. The main exposure was maternal substance abuse before or during pregnancy, including cocaine, opioid, cannabis, and other illicit drugs. The main outcome measure was hospitalization for traumatic fracture in offspring up to 12 years of age. We used adjusted Cox regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal drug abuse with the subsequent risk of fracture in children. RESULTS: The incidence of child fractures was higher for maternal illicit drug abuse than no drug abuse (21.2 vs. 15.4 per 10,000 person-years). Maternal drug abuse before or during pregnancy was associated with 2.35 times the risk of assault-related fractures (95% CI, 1.29 to 4.27) and 2.21 times the risk of transport accident-related fractures (95% CI, 1.34 to 3.66), compared with no drug abuse. Associations were strongest before 6 months of age for assault-related fractures (HR = 2.14; 95% CI, 0.97 to 4.72) and after 6 years for transport-related fractures (HR = 2.86; 95% CI, 1.35 to 6.05). Compared with no drug abuse, associations with assault and transport-related fractures were elevated for all drugs including cocaine, opioids, and cannabis. CONCLUSIONS: Maternal illicit drug abuse is associated with future child fractures due to assault and transport accidents.
Assuntos
Cannabis , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides , Criança , Estudos de Coortes , Humanos , Estudos Longitudinais , Gravidez , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
The etiology of pediatric abdominal disorders is poorly understood, and the relationship with maternal mental health is understudied. We sought to determine the association between maternal psychiatric disorders and abdominal conditions in childhood. We performed a retrospective cohort study of 1,080,518 newborns in Quebec, Canada, between 2006 and 2020. We identified maternal mental disorders before or during pregnancy and computed the incidence of abdominal disorders in offspring before 1 year of age. Outcomes included Hirschsprung disease; hypertrophic pyloric stenosis; and esophageal, intestinal, and biliary atresia. We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the association of maternal mental disorders with these pediatric abdominal disorders. Among 51,371 children exposed to maternal mental disorders, 200 children had an abdominal condition, for a rate of 38.9 cases per 10,000 children (95% CI 33.6-44.3) compared with 27.7 per 10,000 for children who were unexposed to maternal mental disorders (95% CI 26.7-28.7). Compared with no mental disorder, maternal mental disorders were associated with hypertrophic pyloric stenosis (RR 1.39, 95% CI 1.16-1.68). Associations were stronger for severe mental disorders and were more marked for depression and stress and anxiety disorders. Maternal mental disorders are associated with the risk of hypertrophic pyloric stenosis in offspring. The origin of hypertrophic pyloric stenosis may relate to maternal mental disorders that were present during pregnancy.
Assuntos
Transtornos de Ansiedade , Transtornos Mentais , Criança , Feminino , Humanos , Incidência , Recém-Nascido , Transtornos Mentais/epidemiologia , Saúde Mental , Gravidez , Estudos RetrospectivosRESUMO
In the last few decades, there has essentially been an explosion in the use of lasers in medicine, especially in the area of cosmetic dermatology. Potentially harmful substances are liberated when tissues are vaporized with laser. This creates numerous risks, including the spread of infectious disease. Smoke evacuators are devices that capture and filter laser plume, thereby maintaining a safe environment for the surgical team and patient. Our aim was to characterize the microbial community structure within the suction tube and funnel of the smoke evacuator system, identify their origin, and evaluate pathogenicity. Dust particles were collected from the instruments with a cotton swab. DNA was extracted from the swabs and the transport media, and sequencing was performed using the Illumina HiSeq Xplatform. Metagenomic analysis was conducted using the Empowering the Development of Genomics Expertise (EDGE) Bioinformatics pipeline and custom Python scripts. The most abundant bacterial species were Micrococcus luteus and Brevibacterium casei in the suction tube, and Dermacoccus sp. Ellin 185 and Janibacter hoylei in the suction funnel. A total of 15 medium- to high-quality metagenome-assembled genomes (MAGs) were constructed where we found 104 antibiotic-resistant genes (ARGs) and 741 virulence factors. Findings indicate that the suction tube and funnel are likely a reservoir of virulence factor genes and ARGs, which can possibly be passed on to other bacteria via horizontal gene transfer. We would like to emphasize the health risk these microorganisms pose and the need to reevaluate the current hygiene standards with regard to the smoke evacuator system.
Assuntos
Metagenoma , Actinobacteria , Brevibacterium , Poeira , Humanos , Terapia a Laser/instrumentação , Fumaça , Sucção/instrumentaçãoRESUMO
Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G1/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by fargesin treatment in colon cancer cells. We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. Simultaneously, the suppression of CDK2/cyclin E and induction of p21WAF1/Cip1 were correlated with Rb phosphorylation and c-Myc suppression. Taken together, we conclude that fargesin-mediated c-Myc suppression inhibits EGF-induced cell transformation and colon cancer cell colony growth by the suppression of retinoblastoma (Rb)-E2F and CDK/cyclin signaling pathways, which are mainly regulated by MAPK and PKB signaling pathways.
Assuntos
Benzodioxóis/farmacologia , Transformação Celular Neoplásica/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Fator de Crescimento Epidérmico/efeitos adversos , Lignanas/farmacologia , Transdução de Sinais , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
We assessed the association between maternal autoimmune disorders and offspring risk of Kawasaki disease in a longitudinal cohort of 792 108 newborns. We found that maternal autoimmune disorders, especially autoimmune thyroiditis, may be risk factors for Kawasaki disease in children, particularly young children.
Assuntos
Doenças Autoimunes/complicações , Síndrome de Linfonodos Mucocutâneos/etiologia , Medição de Risco/métodos , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The impact of fasting on risk of preterm birth during Ramadan is unclear. OBJECTIVES: We evaluated the association between Ramadan fasting during pregnancy and risk of preterm birth for Arab women in Canada. METHODS: We analyzed birth certificates from 3,123,508 deliveries in Quebec, Canada, from 1981 to 2017. We identified 78,109 births of Arabic-speaking women and determined if Ramadan occurred during any trimester of pregnancy. We calculated rates of extreme (22-27 wk), very (28-31 wk), and late (32-36 wk) preterm birth and estimated RRs and 95% CIs for the association of Ramadan fasting with risk of preterm birth by pregnancy trimester, using log-binomial regression models adjusted for maternal characteristics. RESULTS: Arabic speakers had an overall preterm birth rate of 5.53 per 100 births, but rates varied with timing of Ramadan. Among Arabic speakers, fasting during Ramadan between weeks 15-21 of the second trimester was associated with 1.33 times the risk of very preterm birth relative to no fasting (95% CI: 1.06, 1.68). Between weeks 22 and 27 of the second trimester, fasting during Ramadan was associated with 1.53 times the risk of very preterm birth (95% CI: 1.21, 1.93). Ramadan fasting was not associated with extreme or late preterm birth regardless of the trimester of pregnancy. CONCLUSIONS: In this study of 78,109 births to Arabic-speaking women in Quebec, Ramadan fasting during the second pregnancy trimester was associated with the risk of very preterm birth. Optimal prenatal education about nutritional needs in the second trimester of pregnancy is recommended.
Assuntos
Árabes , Jejum , Islamismo , Nascimento Prematuro , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Trimestres da Gravidez , QuebequeRESUMO
Causes of birth defects are unclear, and the association with electromagnetic fields is inconclusive. We assessed the relationship between residential proximity to extremely low frequency electromagnetic fields from power grids and risk of birth defects. We analyzed a population-based sample of 2,164,246 infants born in Quebec, Canada between 1989 and 2016. We geocoded the maternal residential postal code at delivery and computed the distance to the nearest high voltage electrical transmission line or transformer station. We used log-binomial regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of residential proximity to transmission lines and transformer stations with birth defects, adjusting for maternal and infant characteristics. The prevalence of birth defects within 200 m of a transmission line (579.4 per 10,000 per live births) was only slightly higher compared with distances further away (568.7 per 10,000). A similar trend was seen for transformer stations. Compared with 200 m, a distance of 50 m was not associated with the risk of birth defects for transmission lines (RR 1.00, 95% CI 1.00-1.01) and transformer stations (RR 1.01, 95% CI 1.00-1.03). There was no consistent association when we examined birth defects in different organ systems. We found no compelling evidence that residential proximity to extremely low frequency electromagnetic fields from electrical power grids increases the risk of birth defects. Women residing near electrical grids can be reassured that an effect on the risk of birth defects is unlikely.
Assuntos
Anormalidades Congênitas/etiologia , Fontes de Energia Elétrica/efeitos adversos , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Materna/efeitos adversos , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Canadá/epidemiologia , Feminino , Humanos , Lactente , Gravidez , Prevalência , Características de Residência , Julgamento Moral Retrospectivo , Fatores de Risco , Adulto JovemRESUMO
DD(35)E motif in catalytic core domain (CCD) of integrase (IN) is extremely involved in retroviral integration step. Here, nine single residue mutants of feline foamy virus (FFV) IN were generated to study their effects on IN activities and on viral replication. As expected, mutations in the highly conserved D107, D164, and E200 residues abolished all IN catalytic activities (3'-end processing, strand transfer, and disintegration) as well as viral infectivity by blocking viral DNA integration into cellular DNA. However, Q165, Y191, and S195 mutants, which are located closely to DDE motif were observed to have diverse levels of enzymatic activities, compared to those of the wild type IN. Their mutant viruses produced by one-cycle transfection showed different infectivity on their natural host cells. Therefore, it is likely that effects of single residue mutation at DDE motif is critical on viral replication depending on the position of the residues.