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Alcohol can induce a leaky gut, with translocation of microbial molecules from the gut into the blood circulation. Although the contribution of inflammation to organ-mediated damage in lupus has been previously demonstrated, the mechanistic roles of alcohol consumption in lupus activation are not known. Herein, we tested the effects of 10-week lasting alcohol administration on organ damages and immune responses in 8-week-old lupus-prone Fc gamma receptor IIb-deficient (FcγRIIb-/- ) mice. Our study endpoints were evaluation of systemic inflammation and assessment of fecal dysbiosis along with endotoxemia. In comparison with alcohol-administered wild-type mice, FcγRIIb-/- mice demonstrated more prominent liver damage (enzyme, histological score, apoptosis, malondialdehyde oxidant) and serum interleukin(IL)-6 levels, despite a similarity in leaky gut (fluorescein isothiocyanate-dextran assay, endotoxemia and gut occludin-1 immunofluorescence), fecal dysbiosis (microbiome analysis) and endotoxemia. All alcohol-administered FcγRIIb-/- mice developed lupus-like characteristics (serum anti-dsDNA, proteinuria, serum creatinine and kidney injury score) with spleen apoptosis, whereas control FcγRIIb-/- mice showed only a subtle anti-dsDNA. Both alcohol and lipopolysaccharide (LPS) similarly impaired enterocyte integrity (transepithelial electrical resistance), and only LPS, but not alcohol, upregulated the IL-8 gene in Caco-2 cells. In macrophages, alcohol mildly activated supernatant cytokines (tumor necrosis factor-α and IL-6), but not M1 polarization-associated genes (IL-1ß and iNOS), whereas LPS prominently induced both parameters (more prominent in FcγRIIb-/- macrophages than wild type). There was no synergy in LPS plus alcohol compared with LPS alone in both enterocytes and macrophages. In conclusion, alcohol might exacerbate lupus-like activity partly through a profound inflammation from the leaky gut in FcγRIIb-/- mice.
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Endotoxemia , Receptores de IgG , Animais , Humanos , Camundongos , Células CACO-2 , Disbiose , Etanol , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Receptores de IgG/genéticaRESUMO
Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1â3)-ß-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.
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Microbioma Gastrointestinal , Sepse , Humanos , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Disbiose/microbiologia , Inflamação , BactériasRESUMO
BACKGROUND: Two main strategies to cope with the coronavirus disease 2019 (COVID-19) pandemic-lockdown (social restriction) and non-lockdown (herd immunity plan)-have been implemented in several countries. OBJECTIVE: This study aims to statistically compare the outcomes of the two strategies, represented by data from Thailand and Sweden, respectively. METHODS: Data for COVID-19 pandemic control from Thailand, representing social restriction, versus data from Sweden, representing the herd immunity plan, collected from January 13 to May 31, 2020, were analyzed by using the SIR (susceptible, infectious, recovered) model. RESULTS: The SIR model analysis demonstrated a beneficial effect of each model on the attenuation of the mortality rate, with lower mortality in social restriction and shorter overall pandemic duration in the herd immunity plan. However, the herd immunity plan demonstrated a higher mortality rate than social restriction (46.9% versus 1.9%) despite the later entry of the virus in Sweden. When the SIR model was used for predicting the COVID-19 status, Sweden was shown to likely end its COVID-19 epidemic earlier than Thailand (268 vs. 368 days). With the nonlinear estimation, at least one log difference between total confirmed cases versus active cases could be used as an indicator for relaxation of the lockdown policy in Thailand. CONCLUSIONS: Both the social restriction and herd immunity plans are beneficial for COVID-19 pandemic control in terms of the amelioration of pandemic mortality. The cumulative number of total recovered cases might be a potential parameter that could be used for determining the policy direction for COVID-19 control.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Imunidade Coletiva , Controle de Doenças TransmissíveisRESUMO
BACKGROUND: Together with clinical correlation, nontreponemal titers are used to monitor treatment outcomes. Syphilis patients with HIV and without HIV coinfection were found to have different serological responses after treatment. This study aims to determine time to serological cure for treatment of syphilis and factors associated with it in patients with and without HIV. METHOD: A descriptive study of syphilis patients who visited Bangrak STIs Center between January 1, 2007, and December 31, 2016. Univariate analysis was done to determine factors associated with serological outcomes. Survival curve analysis and multivariate Cox regression analysis were applied to compare time to serological cure between patients with various characteristics. RESULTS: Of 497 syphilis patients, 62.1% had serological cure, 2.2% had nonresponse, 4.6% had treatment failure or reinfection, 9.9% had serofast status, and 21.2% were undetermined because of loss to follow-up. The time to serological cure was 110 days (95% confidence interval [CI], 59-163 days) and 102 days (95% CI, 94-110 days) among patients with HIV and without HIV, respectively (P = 0.162). Time to serological cure was significantly faster in early syphilis and baseline titer ≥1:32. After adjustment with the Cox regression model, patients with early syphilis were associated with serological cure with a hazard ratio of 1.75 (95% CI, 1.32-2.32). Time to serological cure among early syphilis patients was significantly longer in HIV-positive than HIV-negative patients (P = 0.002), whereas no difference was observed in late syphilis (P = 0.104). CONCLUSION: Early syphilis was associated with faster time to serological cure. HIV patients with early syphilis took longer time to reach serological cure than did HIV-negative patients, whereas no such a difference was observed in late syphilis.
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Infecções por HIV/complicações , Sífilis/tratamento farmacológico , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Soronegatividade para HIV , Humanos , Masculino , Sífilis/complicações , Sífilis/epidemiologia , Sorodiagnóstico da Sífilis , Tailândia/epidemiologia , Fatores de Tempo , Tempo para o Tratamento , Falha de TratamentoRESUMO
There is a correlation between DNA methylation and the diseased stage and poor survival. 5-methylcytosine (5-mC) is one of the epigenetic modifications of bases that researchers focus on. Staining with 5-mC immunohistochemistry was used to examine pathological samples taken from individuals diagnosed with cutaneous melanoma. Between Breslow levels 2 and 4, there was a significant difference in the H-score of 5-mC expression (p = 0.046). A significant reduction in 5-mC expression H-scores was seen in patients who were diagnosed with ulcers (p = 0.039). It was shown that patients with low 5-mC had a significantly worse overall survival rate (p = 0.027).
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , 5-Metilcitosina/metabolismo , Imuno-Histoquímica , Prognóstico , Metilação de DNARESUMO
It is unclear how the immune system controls the transition from latent tuberculosis (TB) infection (LTBI) to active pulmonary infection (PTB). Here, we applied mass spectrometry cytometry time-of-flight (CyTOF) analysis of peripheral blood mononuclear cells to compare the immunological landscapes in patients with high tuberculous bacillary load PTB infections and LTBI. A total of 32 subjects (PTB [n = 12], LTBI [n = 17], healthy volunteers [n = 3]) were included. Participants with active PTBs were phlebotomized before administering antituberculosis treatment, whereas participants with LTBI progressed to PTB at the time of household screening. In the present study, CyTOF analysis identified significantly higher percentages of mucosal-associated invariant natural killer T (MAIT NKT) cells in subjects with LTBI than in those with active PTB and healthy controls. Moreover, 6 of 17 (35%) subjects with LTBI progressed to active PTB (LTBI progression) and had higher proportions of MAIT NKT cells and early NKT cells than those without progression (LTBI non-progression). Subjects with LTBI progression also showed a tendency toward low B cell levels relative to other subject groups. In conclusion, MAIT NKT cells were substantially more prevalent in subjects with LTBI, particularly those with progression to active PTB.
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Bacillus , Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Leucócitos MononuclearesRESUMO
Aging fibroblasts, an important factor contributing to skin aging, are affected by numerous mechanisms, including alterations in DNA methylation and age-related diseases. The current study aimed to investigate the role of Alu methylation in aging fibroblasts and hypertension. The Alu methylation levels in dermal fibroblasts obtained from patients of different ages and blood pressure status were analyzed using the combined bisulfite restriction analysis technique. An inverse correlation was observed between Alu methylation in dermal fibroblasts and patient age. Dermal fibroblasts from the high-normal diastolic blood pressure group had higher Alu methylation levels compared with those from the normal group. The findings of the present study suggest that Alu methylation alterations can be observed with chronological aging and hypertension, and are a potential aging marker or therapeutic target.
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P53 is a tumor suppressor gene that is mutated in numerous types of cancer. The aim of the present study was to determine the frequency of this mutation in cutaneous melanomas and to conduct clinicopathological characteristics and clinical outcome association analyses with the P53 mutation. P53 immunohistochemical staining was used as a surrogate marker for P53 mutation analysis to assess P53 status. In the present study, 50 pathological samples of cutaneous melanoma from 2012 to 2018 at Chulalongkorn University (Bangkok, Thailand), were subjected to anti-P53 immunohistochemistry, followed by an examination of the association between P53 statuses and clinical and pathological characteristics, along with clinical outcomes. A positive staining for anti-P53 antibody was detected in 30% of patients (15/50) with cutaneous melanomas. Positivity was significantly associated with female sex, nodular histological subtype and Breslow level 4. Cox regression analysis revealed that an age >65.5 years and Breslow grade 4 disease were associated with mortality. The Kaplan-Meier curve revealed a shorter duration of recurrence time in the P53 mutation than P53 wild type. In the present study, P53 mutations in specific cases of cutaneous melanoma were identified. Notably, patients who were older and/or had a Breslow score of 4 exhibited an increased risk of mortality. These findings suggested the potential involvement of P53 mutations in cutaneous melanoma, highlighting the necessity for further investigations to improve understanding of their roles.
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Our multicenter, medical chart review, cost-of-illness study used a micro-costing approach to evaluate the economic burden associated with varicella in Bangkok, Thailand, from a societal perspective. We reviewed medical charts of adults and children with a primary diagnosis of varicella (2014-2018) from 4 hospitals in Bangkok. Reported healthcare resource utilization and missed school or workdays were extracted from medical charts. Mean direct, indirect, and total costs per patient were estimated for overall, adult, and pediatric patients (2020 USD). Of the 200 children and 60 adults, 99.6%, 5.4%, and 5.4% had a varicella-related outpatient visit, emergency department visit, and hospitalization, respectively. The mean direct medical cost was 33 USD for pediatric and adult patients. The mean cost of outpatient visits (8 vs 13 USD, P<0.001) and medications (7 vs 9 USD, P<0.001) was significantly lower among pediatric patients. Forty-eight children reported a mean of 5.8 school days lost, and 32 adult patients reported a mean of 7.4 workdays lost. The mean total cost per varicella patient was 89 USD, with the mean total cost higher for adult than pediatric patients (145 vs 72 USD, P<0.001). Indirect cost accounted for 63% of the total cost per patient (54% for pediatric patients and 77% for adult patients). There is a substantial economic burden associated with patients seeking varicella-related healthcare in Thailand, including considerable indirect costs.
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BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds. CONCLUSION: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. CLINICAL TRIALS REGISTRATION: NCT05109559.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Ad26COVS1/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Seguimentos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interferon gama/imunologia , Fosfoproteínas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Tailândia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagemRESUMO
BACKGROUND: Most of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host. METHODS: Here, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase). RESULTS: Interestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-α, but not IL-1ß. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa can be discovered from feces of the host. CONCLUSIONS: The phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted.
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Fezes , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Pseudomonas aeruginosa/virologia , Fezes/microbiologia , Fezes/virologia , Camundongos , Infecções por Pseudomonas/terapia , Infecções por Pseudomonas/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , Neutrófilos/imunologia , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Armadilhas Extracelulares , Pneumonia/microbiologia , Pneumonia/terapia , Pneumonia/virologia , Citocinas/metabolismo , Citocinas/sangue , Terapia por Fagos/métodos , Feminino , Pulmão/microbiologia , Pulmão/virologia , Pneumonia Bacteriana/terapia , Pneumonia Bacteriana/microbiologiaRESUMO
The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily Candida gavage with or without probiotics (different times of administration) for 1 week prior to bilateral nephrectomy (Bil Nep) in 8-week-old C57BL6 mice as the possible models more resemble human conditions were performed. Candida-administered Bil Nep mice demonstrated more severe conditions than Bil Nep alone as indicated by mortality (n = 10/group) and other 48 h parameters (n = 6-8/group), including serum cytokines, leaky gut (FITC-dextran assay, endotoxemia, serum beta-glucan, and loss of Zona-occludens-1), and dysbiosis (increased Enterobacteriaceae with decreased diversity in microbiome analysis) (n = 3/group for fecal microbiome) without the difference in uremia (serum creatinine). With nuclear magnetic resonance metabolome analysis (n = 3-5/group), Bil Nep reduced fecal butyric (and propionic) acid and blood 3-hydroxy butyrate compared with sham and Candida-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, Lacticaseibacillus rhamnosus dfa1 (SCFA-producing Lacticaseibacilli) (n = 8/group) attenuated the model severity (mortality, leaky gut, serum cytokines, and increased fecal butyrate) of Bil Nep mice (n = 6/group) (regardless of Candida). In enterocytes (Caco-2 cells), butyrate attenuated injury induced by indoxyl sulfate (a gut-derived uremic toxin) as indicated by transepithelial electrical resistance, supernatant IL-8, NFκB expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by Candida administration; however, the presence of Candida in the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.
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Microbioma Gastrointestinal , Uremia , Humanos , Animais , Camundongos , Candida , Células CACO-2 , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Butiratos , Metaboloma , Nefrectomia , Citocinas/metabolismoRESUMO
International university students are vulnerable travellers due to their unpredictable schedules and lifestyles. As Thailand continues to see an increase in international students, evaluating their pre-travel preparation and preventive behaviours is crucial to identify areas for improvement. For this purpose, an online survey focusing on pre-travel preparation, knowledge and preventive practices related to travel health was distributed to 324 eligible international students from 14 Thai universities, with the majority being from Asia and Oceania (79.0%; n = 256). The results showed that half of the respondents (53.7%; n = 175) received professional pre-travel advice, mainly because of the mandatory health examination and vaccination requirements of the host university. The study also revealed inadequate knowledge about infectious and non-infectious health risks, with only one-third being aware that Japanese encephalitis is transmitted by mosquito bites, and less than half of the students recognising Thailand's emergency services number. Poor preventive practices were also observed, with less than half of those with new sexual partners consistently using condoms and less than half of those riding motorcycles always wearing helmets. These findings highlight the need for a new strategy to improve the standard of travel health preparation among this group of young adult travellers, particularly those from resource-limited countries.
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OBJECTIVE: To describe the clinical characteristics of varicella patients seeking medical consultation and the use of antimicrobials for their management in Thailand in the absence of universal varicella vaccination (UVV). METHODS: A multicenter, retrospective chart review of 260 children and adults with a primary diagnosis of varicella was conducted at one private and three public hospitals in Bangkok, Thailand. Charts of varicella patients (inpatient or outpatient) were randomly selected over a 5-year period. Key outcomes included clinical complications and the use of antibiotics, antivirals, and other medications. RESULTS: Charts of 200 children (mean age 5.7 years, range 0.3-16 years) and 60 adults (mean age 27.9 years, range 18-50 years) were reviewed. Fourteen patients (including 8 children) were hospitalized. Five percent of the children and none of the adults were immunocompromised. At least 1 varicella-related complication was reported by 7.3% (7% of children, 8.3% of adults, p = .778) of all patients, including 57.1% (62.5% of children, 50% of adults) of inpatients (p < .001, compared with outpatients). Skin/soft tissue infection (47.7%) and dehydration (47.4%) were the most common complications. Antivirals (mainly oral acyclovir) were prescribed to 46.5% of patients (31.5% of children, 96.7% of adults, p < .001). Antibiotics were prescribed to 20.8% of patients (19% of children, 26.7% of adults, p = .199). Topical, oral, and intravenous antibiotics were prescribed to 12.3%, 8.5%, and 1.2% of patients, respectively. Antimicrobial prescriptions were higher among adults (p < .001) and immunocompromised patients (p = .025). Apart from antimicrobials, acetaminophen (62.3%) and oral antihistamines (51.5%) were the most prescribed. CONCLUSION: A considerable number of varicella patients, both children and adults, seeking medical consultation in Thai hospitals are prescribed antibiotics and antivirals, with one-fifth of patients being prescribed an antibiotic and almost half prescribed an antiviral. The study may be of interest to policymakers in Thailand and other Asia-Pacific countries considering UVV implementation.
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Varicela , Criança , Humanos , Lactente , Pré-Escolar , Adolescente , Varicela/tratamento farmacológico , Varicela/epidemiologia , Varicela/complicações , Estudos Retrospectivos , Tailândia/epidemiologia , Herpesvirus Humano 3 , Antibacterianos/uso terapêutico , Antivirais/uso terapêuticoRESUMO
BACKGROUND: Prolonged symptoms after corona virus disease 2019 (Long-COVID) in dialysis-dependent patients and kidney transplant (KT) recipients are important as a possible risk factor for organ dysfunctions, especially gastrointestinal (GI) problems, during immunosuppressive therapy. AIM: To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status. METHODS: This observational, prospective study included patients with COVID-19 infection, confirmed by reverse transcription polymerase chain reaction, with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset, either through the out-patient follow-up or by telephone interviews. RESULTS: The 645 eligible participants consisted of 588 cases with hemodialysis (HD), 38 patients with peritoneal dialysis (PD), and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these, 577 (89.5%) cases agreed to the interviews, while 64 (10.9%) patients with HD and 4 (10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups, respectively, and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524 (56%) and 21/34 (62%) in HD and PD, respectively, and 7/19 (37%) KT recipients. Fatigue was the most prevalent (96%) of the non-GI tract symptoms, whereas anorexia (90.9%), loss of taste (64.4%), and abdominal pain (62.5%) were the first three common GI manifestations of Long-COVID. Notably, there were 6 cases of mesenteric panniculitis from 19 patients with GI symptoms in the KT group. CONCLUSION: Different from patients with non-chronic kidney disease, there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.
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COVID-19 , Gastroenteropatias , Falência Renal Crônica , Transplante de Rim , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Diálise Renal/efeitos adversos , Transplante de Rim/efeitos adversos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Estudos Prospectivos , Síndrome de COVID-19 Pós-Aguda , Estudos de Coortes , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologiaRESUMO
Alu elements are retrotransposons related to epigenetic modifications. To date, the role of epigenetics in hypertrophic scars from burn remains unknown. Here, our aim was to examine the pathophysiology of hypertrophic scars from an epigenetic perspective. For that, we performed a cross-sectional analytical study using tissue and blood samples from burned and healthy patients (n = 23 each) to detect Alu methylation levels and patterns. The results of the combined bisulfite restriction analysis technique were categorized into four groups based on the methylation status at the CpG dinucleotides from the 5' to the 3' ends of the Alu sequence: hypermethylated (mCmC), hypomethylated (uCuC), and partially methylated (uCmC and mCuC). Alu methylation levels were significantly lower in hypertrophic scar tissues than in normal skin (29.37 ± 2.49% vs. 35.56 ± 3.18%, p = 0.0002). In contrast, the levels were significantly higher in white blood cells from blood samples of burned patients than in those of control blood samples (26.92 ± 4.04% vs. 24.58 ± 3.34%, p = 0.0278). Alu total methylation (mC) and the uCmC pattern were significantly lower, whereas uCuC was significantly higher, in hypertrophic scar tissues than in normal skin (p < 0.0001). Receiver operating characteristic analysis indicated that the uCmC and uCuC patterns are useful as hypertrophic scar DNA methylation markers after burn, with 91.30% sensitivity and 96.23% specificity and 100% sensitivity and 94.23% specificity, respectively. Our findings suggest that epigenetic modifications play a major role in hypertrophic scar pathogenesis, and may be the starting point for developing a novel technique for burn scar treatment.
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Queimaduras , Cicatriz Hipertrófica , Elementos Alu/genética , Queimaduras/complicações , Queimaduras/genética , Cicatriz Hipertrófica/genética , Estudos Transversais , Metilação de DNA , Marcadores Genéticos , HumanosRESUMO
Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1â3)-ß-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.
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Dengue , Endotoxemia , Dengue Grave , beta-Glucanas , Dengue/complicações , Disbiose/microbiologia , Humanos , LipopolissacarídeosRESUMO
The BRAF V600E mutation in the Thai population has been identified in a considerable percentage of people with cutaneous melanoma. The objectives of this study were to determine the prevalence of this mutation in cutaneous melanomas, conduct a clinicopathological association analysis with the BRAF V600E mutation, and develop a treatment strategy for patients with this mutation that would take advantage of the medications currently available to treat them. Methods: Anti-BRAF V600E (clone VE1) immunohistochemistry was performed on 50 pathological samples of cutaneous melanoma after excluding the samples with a low amount of pathologic tissue, a lack of clinical data' and poor follow-up. BRAF V600E expression DNA sequencing was performed to confirm the results of several cases. Results: Anti-BRAF V600E antibody positivity was noted in 56% (28/50) of cutaneous melanoma cases. DNA sequencing results were consistent with immunohistochemistry results. In cutaneous melanoma, the BRAF V600E mutation was significantly associated with adverse prognosis of patients, including reduced overall survival and disease-free survival. Conclusions: An increased prevalence of the BRAF V600E mutation was determined in a collection of cutaneous melanomas in the Thai population, implying that BRAF-targeted therapy may be a promising strategy for patients with BRAF-mutated cutaneous melanoma. This study revealed an association between the clinicopathological aspects of cutaneous melanoma and overall survival, disease-free survival, and overall mortality. A treatment with anti-BRAF-targeted therapy, which incorporates the already available medications' is being researched and developed.
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OBJECTIVE: This study aimed to determine the real-world effectiveness of bi- or quadrivalent human papillomavirus (HPV) vaccines in Thai adult women ≥5 years post-vaccination in reducing HPV 16/18-associated low-grade squamous intraepithelial lesions or worse (LSIL+), atypical squamous cells of undetermined significance or worse (ASC-US+), and HPV 16/18 positivity. METHODS: A retrospective cohort study was conducted among Thai women aged 20-45 years in Bangkok. The vaccinated and unvaccinated groups were matched according to baseline years. HPV/Pap test results were collected from the medical records and/or obtained by cervical sample collection at the study sites. Adjusted hazard ratios were measured using multivariable Cox regression analyses. RESULTS: A total of 993 participants (493 vaccinated and 500 unvaccinated) were enrolled from 2018 to 2019. The median ages at baseline of the vaccinated and unvaccinated groups were 33 years (interquartile range [IQR] 27-38) and 34 years (IQR 30-38), respectively. The median follow-up periods were 7.3 years (IQR 6.1-8.6) and 7.2 years (IQR 5.8-8.9) for the vaccinated group and the unvaccinated group, respectively. More women in the vaccinated group were single (29.2% vs. 13.2%, P < 0.001) and university graduates (83.2% vs. 75.4%, P = 0.009). The vaccinated and unvaccinated groups had similar personal monthly incomes (>20,000 THB/month, 63.9% vs. 62.4%, respectively, P = 0.685). There were no cases of HPV 16/18-associated LSIL+ in the vaccinated group, whereas there were four cases in the unvaccinated group. HPV vaccine effectiveness was 88.0% (95% CI 2.0-98.5) in the reduction of HPV 16/18-associated ASC-US+, and 84.6% (95% CI 43.5-95.8) in the reduction of HPV 16/18 positivity. CONCLUSIONS: HPV vaccine effectiveness was high in adult women in a real-world scenario in a developing country. Free HPV vaccination in adult women in this age group should be further explored when vaccine supplies are not limited. (HPV: human papillomavirus. LSIL+: low-grade squamous intraepithelial lesion or worse. ASC-US+: atypical squamous cells of undetermined significance or worse).
Assuntos
Alphapapillomavirus , Células Escamosas Atípicas do Colo do Útero , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Estudos Retrospectivos , Tailândia , Displasia do Colo do Útero/prevenção & controleRESUMO
Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).