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Probiotics and prebiotics have gained attention for their potential health benefits. However, their efficacy hinges on probiotic survival through the harsh gastrointestinal environment. Microencapsulation techniques provide a solution, with resistant starch (RS)-based techniques showing promise in maintaining probiotic viability. Specifically, RS-encapsulated probiotics significantly improved probiotic survival in gastric acid, bile salts, and simulated intestinal conditions. This study investigated the effects of a resistant-starch-encapsulated probiotic cocktail (RS-Pro) in the context of 5-fluorouracil (5-FU) chemotherapy, which frequently induces microbiota dysbiosis and intestinal mucositis. Female BALB/c mice were divided into three groups: a 5-FU group, a 5-FU+Pro group receiving free probiotics, and a 5-FU+RS-Pro group receiving RS-encapsulated probiotics. After 28 days of treatment, analyses were conducted on fecal microbiota, intestinal histology, peripheral blood cell counts, and body and organ weights. It was revealed by 16S rRNA MiSeq sequencing that 5-FU treatment disrupted gut microbiota composition, reduced microbial diversity, and caused dysbiosis. RS-Pro treatment restored microbial diversity and increased the population of beneficial bacteria, such as Muribaculaceae, which play roles in carbohydrate and polyphenol metabolism. Furthermore, 5-FU administration induced moderate intestinal mucositis, characterized by reduced cellularity and shortened villi. However, RS-Pro treatment attenuated 5-FU-induced intestinal damage, preserving villus length. Mild leukopenia observed in the 5-FU-treated mice was partially alleviated in 5-FU+Pro and 5-FU+RS-Pro groups. These findings suggest that RS-Pro may serve as an adjunct to chemotherapy, potentially reducing adverse effects and improving therapeutic outcomes in future clinical applications.
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5-Fluorouracil (5-FU) is commonly used as the primary chemotherapy for colorectal cancer (CRC). However, it can lead to unwanted chemoresistance. Resistant starch (RS), which functions similarly to fermentable dietary fiber, has the potential to reduce the risk of CRC. The effects of RS on improving CRC-associated cachectic symptoms and 5-FU chemotherapy-induced microbial dysbiosis remain unknown. Female BALB/cByJNarl mice were randomly divided into four groups: one tumor group (with CT26 colonic carcinoma but no treatment) and three CT26 colonic carcinoma-bearing groups that were administered 20 mg/kg 5-FU (T+5-FU group), a probiotic cocktail (4 × 108 CFUs) plus chemotherapy (T+5-FU+Pro), or resistant-starch-encapsulated probiotics plus chemotherapy (T+5-FU+RS-Pro). T+5-FU and T+5-FU+RS-Pro administration significantly suppressed tumor growth and activated apoptotic cell death in CT26-bearing mice. 5-FU-induced increases in inflammatory cytokines and NF-κB signaling were mitigated by the Pro or RS-Pro supplementation. A gut microbial composition comparison indicated that the abundance of intestinal bacteria in the T and T+5-FU groups decreased significantly, while the groups receiving Pro or RS-Pro maintained a greater abundance and healthy gut microbiota composition, suggesting that RS can reduce the microbial dysbiosis that occurs during 5-FU chemotherapy. The use of RS-Pro before chemotherapy should be considered for the regulation of chemotherapy-associated cachectic symptoms, inflammation, and chemotherapy-induced microbial dysbiosis.
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The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.
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Disbiose , Microbioma Gastrointestinal , Infecções por Mycobacterium não Tuberculosas , Receptor 2 Toll-Like , Disbiose/microbiologia , Animais , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Humanos , Camundongos , Masculino , Feminino , Infecções por Mycobacterium não Tuberculosas/microbiologia , Pessoa de Meia-Idade , Fezes/microbiologia , Idoso , Prevotella , Pneumopatias/microbiologia , Micobactérias não Tuberculosas , Suscetibilidade a Doenças , Camundongos Endogâmicos C57BL , Pulmão/microbiologiaRESUMO
Aim: The association between cytochrome P450 (CYP) gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity (ATDH) was investigated in patients with or without pre-existing liver diseases (PLD). Materials & methods: We followed 164 tuberculosis subjects, 58 with PLD and 106 without PLD. Polymorphisms in CYP2D6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 were analyzed using the TaqMan® SNP genotyping assay.Results: The CYP3A4*18 heterozygous genotype was associated with ATDH (OR: 3.24, 95% CI: 1.06-9.86) regardless of PLD presence. Among subjects without PLD, CYP3A4*18 heterozygotes had significantly higher ATDH risk (OR: 9.10, 95% CI: 1.56-53.16). Conversely, in the PLD group, CYP3A4*18 heterozygotes had lower ATDH risk (OR: 0.21, 95% CI: 0.05-0.98).Conclusion: CYP3A4*18 genotype is linked to ATDH in tuberculosis patients, with differential effects based on PLD presence.
[Box: see text].
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Antituberculosos , Doença Hepática Induzida por Substâncias e Drogas , Citocromo P-450 CYP3A , Polimorfismo de Nucleotídeo Único , Tuberculose , Humanos , Doença Hepática Induzida por Substâncias e Drogas/genética , Masculino , Citocromo P-450 CYP3A/genética , Feminino , Antituberculosos/efeitos adversos , Pessoa de Meia-Idade , Adulto , Polimorfismo de Nucleotídeo Único/genética , Tuberculose/genética , Tuberculose/tratamento farmacológico , Genótipo , IdosoRESUMO
The immune checkpoint proteins were reported to involve to host resistance to Mycobacteria tuberculosis (Mtb). Here, we evaluated 11 single nucleotide polymorphisms (SNPs) in PDCD1, CTLA4, and HAVCR2 genes between participants with and without TB infection. Genomic DNA isolated from 285 patients with TB and 270 controls without TB infection were used to perform the genotyping assay. Odds ratios were used to characterize the association of 11 SNPs with TB risk. In this study, the various genotypes of the 11 SNPs did not differ significantly in frequency between the non-TB and TB groups. When patients were stratified by sex, however, men differed significantly from women in genotype frequencies at HAVCR2 rs13170556. Odds ratios indicated that rs2227982, rs13170556, rs231775, and rs231779 were sex-specifically associated with TB risk. In addition, the combinations of rs2227982/rs13170556 GA/TC in men and the A-C-C haplotype of rs231775-rs231777-rs231779 in women were significantly associated with TB risk. Our results indicate that rs2227982 in PDCD1 and rs13170556 in HAVCR2 are associated with increased TB susceptibility in men and that the CTLA4 haplotype appears protective against TB in women.
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Antígeno CTLA-4 , Predisposição Genética para Doença , Receptor Celular 2 do Vírus da Hepatite A , Receptor de Morte Celular Programada 1 , Tuberculose , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Antígeno CTLA-4/genética , Genótipo , Haplótipos , Receptor Celular 2 do Vírus da Hepatite A/genética , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1/genética , Tuberculose/genéticaRESUMO
BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.
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BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.
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Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.
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Melanoma , Receptor de Morte Celular Programada 1 , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteína do Gene 3 de Ativação de Linfócitos , Progressão da Doença , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Nivolumabe/uso terapêutico , Nivolumabe/farmacologia , Antígenos CD/metabolismoRESUMO
Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.
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Asma , Receptores de Calcitriol , Humanos , Receptores de Calcitriol/genética , Predisposição Genética para Doença , Genótipo , Vitamina D/genética , Polimorfismo de Nucleotídeo Único , Asma/genética , Estudos de Casos e ControlesRESUMO
BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) preferentially occurs in postmenopausal women and may have immune exhaustion involving the programmed cell death 1 (PD-1) pathway. It is still unknown whether sex-specific associations between susceptibility to MAC-LD and programmed cell death 1 gene (PDCD1) polymorphisms exist. METHODS: Adult patients with MAC-LD (n = 152) and controls (n = 167) were included at 2 medical centers in Taiwan. Five single-nucleotide polymorphisms in PDCD1 genes were genotyped, and their associations with MAC-LD and soluble PD-1 protein were analyzed, especially in sex subgroups. RESULTS: PDCD1 rs2227982 polymorphism was associated with increased risk of MAC-LD in women (adjusted odds ratio for AA vs AG vs GG, 2.205 [95% confidence interval, 1.108-4.389]; P = .02), and the rs10204525 TT genotype was associated with low risk in men (TT vs TC and CC, 0.396 [.176-.890]; P = .02). Compared with men with rs10204525 TT, women with rs2227982 AG and with AA had 2.7- and 5.0-fold increased risks, respectively. Soluble PD-1 levels were lower in the female subgroup with rs2227982 AG and AA than in the remainder (median level [interquartile range], 46.7 [33.7-71.5] pg/mL vs 66.2 [48.6-101.5] pg/mL; P < .001). CONCLUSIONS: PDCD1 genetic polymorphisms were associated with the risk of MAC-LD in a sex-specific pattern, possibly through regulation of PD-1 expression.
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Pneumopatias , Infecção por Mycobacterium avium-intracellulare , Masculino , Adulto , Humanos , Feminino , Complexo Mycobacterium avium/genética , Predisposição Genética para Doença , Receptor de Morte Celular Programada 1/genética , Infecção por Mycobacterium avium-intracellulare/genética , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Pneumopatias/microbiologia , ApoptoseRESUMO
Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.
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Ozônio , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Pulmão/metabolismo , Proteína D Associada a Surfactante Pulmonar/genética , Proteína D Associada a Surfactante Pulmonar/metabolismo , Macrófagos/metabolismo , Líquido da Lavagem Broncoalveolar , Inflamação/metabolismo , Ozônio/farmacologia , Ozônio/metabolismo , Lipídeos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The extra-intestinal effects of probiotics for preventing allergic diseases are well known. However, the probiotic components that interact with host target molecules and have a beneficial effect on allergic asthma remain unknown. Lactobacillus gasseri attenuates allergic airway inflammation through the activation of peroxisome proliferator- activated receptor γ (PPARγ) in dendritic cells. Therefore, we aimed to isolate and investigate the immunomodulatory effect of the PPARγ activation component from L. gasseri. METHODS: Culture supernatants of L. gasseri were fractionated and screened for the active component for allergic asthma. The isolated component was subjected to in vitro functional assays and then cloned. The crystal structure of this component protein was determined using X-ray crystallography. Intrarectal inoculation of the active component-overexpressing Clear coli (lipopolysaccharide-free Escherichia coli) and intraperitoneal injection of recombinant component protein were used in a house dust mite (HDM)-induced allergic asthma mouse model to investigate the protective effect. Recombinant mutant component proteins were assayed, and their structures were superimposed to identify the detailed mechanism of alleviating allergic inflammation. RESULTS: A moonlighting protein, glycolytic glyceraldehyde 3-phosphate dehydrogenase (GAPDH), LGp40, that has multifunctional effects was purified from cultured L. gasseri, and the crystal structure was determined. Both intrarectal inoculation of LGp40-overexpressing Clear coli and intraperitoneal administration of recombinant LGp40 protein attenuated allergic inflammation in a mouse model of allergic asthma. However, CDp40, GAPDH isolated from Clostridium difficile did not possess this anti-asthma effect. LGp40 redirected allergic M2 macrophages toward the M1 phenotype and impeded M2-prompted Th2 cell activation through glycolytic activity that induced immunometabolic changes. Recombinant mutant LGp40, without enzyme activity, showed no protective effect against HDM-induced airway inflammation. CONCLUSIONS: We found a novel mechanism of moonlighting LGp40 in the reversal of M2-prompted Th2 cell activation through glycolytic activity, which has an important immunoregulatory role in preventing allergic asthma. Our results provide a new strategy for probiotics application in alleviating allergic asthma.
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Asma , Lactobacillus gasseri , Animais , Asma/terapia , Modelos Animais de Doenças , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/farmacologia , Inflamação , Pulmão , Macrófagos/metabolismo , Camundongos , PPAR gama/metabolismo , Proliferadores de Peroxissomos/metabolismo , Proliferadores de Peroxissomos/farmacologia , PyroglyphidaeRESUMO
This study examines the properties of the linear probability difference-in-differences estimator when the data are in fact generated by a single-decrement, continuous-time hazard process. We focus on the textbook case of two groups and two periods in which the control and treatment groups are observed before and after treatment. We provide formal derivations and illustrate matters concretely by reexamining economic studies that have relied on the linear probability difference-in-differences estimator when attempting to obtain estimates of the causal effect of unilateral and no-fault divorce. In particular, we show that the increasing then decreasing pattern of effects found by Wolfers (2006) can be generated by a time-invariant effect of treatment in a proportional hazard setting. We conclude that often implicit assumptions about how the data are generated are an important and necessary component of causal identification.
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Modelos Estatísticos , Simulação por Computador , Demografia , Humanos , ProbabilidadeRESUMO
OBJECTIVES: Because health care personnel (HCP) are potentially at increased risk of contracting COVID-19, high vaccination rates in this population are essential. The objective of this study was to assess vaccination status, barriers to vaccination, reasons for vaccine acceptance, and concerns about COVID-19 vaccination among HCP. METHODS: We conducted an anonymous online survey at a large US health care system from April 9 through May 4, 2021, to assess COVID-19 vaccination status and endorsement of reasons for acceptance and concerns related to vaccination (based on selections from a provided list). RESULTS: A total of 4603 HCP (12.2% response rate) completed the survey, 3947 (85.7%) had received at least 1 dose of a COVID-19 vaccine at the time of the survey, and 550 (11.9%) reported no plans to receive the vaccine. Unvaccinated HCP were 30 times more likely than vaccinated HCP to endorse religious or personal beliefs as a vaccine concern (odds ratio = 30.95; 95% CI, 21.06-45.48) and 15 times more likely to believe that personal vaccination is not needed if enough others are vaccinated (odds ratio = 14.99; 95% CI, 10.84-20.72). The more reasons endorsed for vaccination (ß = 0.60; P < .001), the higher the likelihood of having received the vaccine. However, the number of concerns about COVID-19 vaccine was not related to vaccination status (ß = 1.01; P = .64). CONCLUSIONS: Our findings suggest that reasons for vaccination acceptance and concerns about vaccination need to be considered to better understand behavioral choices related to COVID-19 vaccination among HCP, because these beliefs may affect vaccination advocacy, responses to vaccine mandates, and promotion of COVID-19 vaccine boosters.
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COVID-19 , Vacinas contra Influenza , Influenza Humana , Atitude do Pessoal de Saúde , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Pessoal de Saúde , Humanos , Influenza Humana/prevenção & controle , VacinaçãoRESUMO
Affective switch is an important clinical issue when treating bipolar disorder. Though commonly seen in clinical practice, the benefits of prescribing antidepressants for bipolar depression are still controversial. To date, there have been few genetic studies and no genome-wide association study (GWAS), focusing on manic switch following bipolar depression. This study aims to investigate the effects of individual genomics and antidepressant medication on the risk of manic switch in bipolar I disorder (BPI). A total of 1004 patients with BPI who had at least one depressive episode with complete data on antidepressant treatment and outcome were included. Clinical assessment of mania and depression was performed by trained psychiatric nurses and psychiatrists using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), and the diagnosis of BPI was made according to DSM-IV criteria. Manic switch was defined as a manic episode occurring within eight weeks of remission from an acute depressive episode. The age at first depressive episode of the study patients was 30.7 years (SD 12.5) and 56% of all patients were female. GWAS was carried out in a discovery group of 746 patients, followed by replication in an independent group of 255 patients. The top SNP rs10262219 on chromosome 7 showed the strongest allelic association with manic switch (p = 2.21 × 10−7) in GWAS, which was however not significantly replicated. Antidepressant treatment significantly (odds ratio 1.7; 95% CI 1.3−2.2; p < 0.001) increased the risk of manic switch. In logistic regression analysis, the CC genotype of rs10262219 (odds ratio 3.0; 95% CI 1.7−5.2) and antidepressant treatment (odds ratio 2.3; 95% CI 1.4−3.7) significantly increased the risk of manic switch with a joint effect (odds ratio 5.9; 95% CI 3.7−9.4). In conclusion, antidepressant medication and rs10262219 variants jointly increased the risk of manic switch after bipolar depression.
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To identify psychological antecedents of COVID-19 vaccine hesitancy among healthcare personnel (HCP). We surveyed 4603 HCP to assess psychological antecedents of their vaccination decisions (the '5 Cs') for vaccines in general and for COVID-19 vaccines. Most HCP accept vaccines, but many expressed hesitancy about COVID-19 vaccines for the psychological antecedents of vaccination: confidence (vaccines are effective), complacency (vaccines are unnecessary), constraints (difficult to access), calculation (risks/benefits), collective responsibility (need for vaccination when others vaccinate). HCP who were hesitant only about COVID-19 vaccines differed from HCP who were consistently hesitant: those with lower confidence were more likely to be younger and women, higher constraints were more likely to have clinical positions, higher complacency were more likely to have recently cared for COVID-19 patients, and lesser collective responsibility were more likely to be non-white. These results can inform interventions to encourage uptake of COVID-19 vaccines in HCP.
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COVID-19 , Vacinas , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos Transversais , Feminino , Humanos , Vacinação/psicologia , Hesitação VacinalRESUMO
Women in the United States are much more likely to become mothers as teens than those in other rich countries. Teen births are particularly likely to be reported as unintended, leading to debate over whether better information on sex and contraception might lead to reductions in teen births. We contribute to this debate by providing causal evidence at the population level. Our causal identification strategy exploits county-level variation in the timing and receipt of federal funding for more comprehensive sex education and data on age-specific teen birth rates at the county level constructed from birth certificate natality data covering all births in the United States. Our results show that federal funding for more comprehensive sex education reduced county-level teen birth rates by more than 3%. Our findings thus complement the mixed evidence to date from randomized control trials on teen pregnancies and births by providing population-level causal evidence that federal funding for more comprehensive sex education led to reductions in teen births.
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Gravidez na Adolescência/prevenção & controle , Gravidez na Adolescência/psicologia , Educação Sexual/tendências , Adolescente , Coeficiente de Natalidade/tendências , Anticoncepção/tendências , Feminino , Humanos , Modelos Teóricos , Gravidez , Educação Sexual/estatística & dados numéricos , Comportamento Sexual/psicologia , Estados Unidos , Adulto JovemRESUMO
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by a persistent limitation in airflow. Gut microbiota is closely correlated with lung inflammation. However, gut microbiota has not been studied in patients with declining lung function, due to chronic lung disease progression. SUBJECTS AND METHODS: Stool samples were obtained from 55 patients with COPD that were in stable condition at enrolment (stage 1) and at a 1-year follow-up (stage 2). After extracting stool DNA, we performed next generation sequencing to analyse the distribution of gut microbiota. RESULTS: Patients were divided to control and declining lung function groups, based on whether the rate of forced expiratory volume in 1 s (FEV1) had declined over time. An alpha diversity analysis of initial and follow-up stool samples showed a significant difference in the community richness of microbiota in the declining function group, but not in the control group. At the phylum level, Bacteroidetes was more abundant in the control group and Firmicutes was more abundant in the declining function group. The Alloprevotella genus was more abundant in the control group than in the declining function group. At 1-year follow-up, the mean proportions of Acinetobacter and Stenotrophomonas significantly increased in the control and declining function groups, respectively. CONCLUSION: Some community shifts in gut microbiota were associated with lung function decline in COPD patients under regular treatment. Future studies should investigate the mechanism underlying alterations in lung function, due to changes in gut bacterial communities, in COPD.