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Ageing of the immune system is characterized by decreased lymphopoiesis and adaptive immunity, and increased inflammation and myeloid pathologies1,2. Age-related changes in populations of self-renewing haematopoietic stem cells (HSCs) are thought to underlie these phenomena3. During youth, HSCs with balanced output of lymphoid and myeloid cells (bal-HSCs) predominate over HSCs with myeloid-biased output (my-HSCs), thereby promoting the lymphopoiesis required for initiating adaptive immune responses, while limiting the production of myeloid cells, which can be pro-inflammatory4. Ageing is associated with increased proportions of my-HSCs, resulting in decreased lymphopoiesis and increased myelopoiesis3,5,6. Transfer of bal-HSCs results in abundant lymphoid and myeloid cells, a stable phenotype that is retained after secondary transfer; my-HSCs also retain their patterns of production after secondary transfer5. The origin and potential interconversion of these two subsets is still unclear. If they are separate subsets postnatally, it might be possible to reverse the ageing phenotype by eliminating my-HSCs in aged mice. Here we demonstrate that antibody-mediated depletion of my-HSCs in aged mice restores characteristic features of a more youthful immune system, including increasing common lymphocyte progenitors, naive T cells and B cells, while decreasing age-related markers of immune decline. Depletion of my-HSCs in aged mice improves primary and secondary adaptive immune responses to viral infection. These findings may have relevance to the understanding and intervention of diseases exacerbated or caused by dominance of the haematopoietic system by my-HSCs.
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Imunidade Adaptativa , Envelhecimento , Linhagem da Célula , Células-Tronco Hematopoéticas , Linfócitos , Células Mieloides , Rejuvenescimento , Animais , Feminino , Masculino , Camundongos , Imunidade Adaptativa/imunologia , Envelhecimento/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Inflamação/imunologia , Inflamação/patologia , Linfócitos/citologia , Linfócitos/imunologia , Linfopoese , Células Mieloides/citologia , Células Mieloides/imunologia , Mielopoese , Fenótipo , Linfócitos T/citologia , Linfócitos T/imunologia , Vírus/imunologiaRESUMO
Significant racial disparities exist between Black and White patients with uterine serous carcinoma (USC). While the reasons for these disparities are unclear, several studies have demonstrated significantly different rates of driver mutations between racial groups, including TP53. However, limited research has investigated the transcriptional differences of tumors or the composition of the tumor microenvironment (TME) between these groups. Here, we report the single-nuclei RNA-sequencing profiles of primary USC tumors from diverse racial backgrounds. We find that there are significant differences between the tumors of Black and White patients. Tumors from Black patients exhibited higher expression of specific genes associated with aggressiveness, such as PAX8, and axon guidance and synaptic signaling pathways. We also demonstrated that T cell populations are reduced in the tumor tissue compared to matched benign, while anti-inflammatory macrophage populations are retained within the TME. Furthermore, we investigated the connection between PAX8 overexpression and immunosuppression in USC through regulation of several cytokines and chemokines. Notably, we show that PAX8 activity can influence macrophage gene expression and protein secretion. These studies provide a detailed understanding of the USC transcriptome and TME, and identify differences in tumor biology from patients of different racial backgrounds.
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Fator de Transcrição PAX8 , Transdução de Sinais , Microambiente Tumoral , Neoplasias Uterinas , Humanos , Feminino , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Fator de Transcrição PAX8/genética , Fator de Transcrição PAX8/metabolismo , Transdução de Sinais/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/imunologia , Regulação Neoplásica da Expressão Gênica , População Branca/genética , Análise de Célula Única , Pessoa de Meia-IdadeRESUMO
Calcium ions serve as key intracellular signals. Local, transient increases in calcium concentrations can activate calcium sensor proteins that in turn trigger downstream effectors. In neurons, calcium transients play a central role in regulating neurotransmitter release and synaptic plasticity. However, it is challenging to capture the molecular events associated with these localized and ephemeral calcium signals. Here we present an engineered biotin ligase that generates permanent molecular traces in a calcium-dependent manner. The enzyme, calcium-dependent BioID (Cal-ID), biotinylates nearby proteins within minutes in response to elevated local calcium levels. The biotinylated proteins can be identified via mass spectrometry and visualized using microscopy. In neurons, Cal-ID labeling is triggered by neuronal activity, leading to prominent protein biotinylation that enables transcription-independent activity labeling in the brain. In summary, Cal-ID produces a biochemical record of calcium signals and neuronal activity with high spatial resolution and molecular specificity.
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Biotinilação , Sinalização do Cálcio , Cálcio , Neurônios , Cálcio/metabolismo , Neurônios/metabolismo , Animais , Carbono-Nitrogênio Ligases/metabolismo , Carbono-Nitrogênio Ligases/química , Humanos , Camundongos , Células HEK293 , Proteínas Repressoras , Proteínas de Escherichia coliRESUMO
BACKGROUND: Cervical artery dissection (CeAD) represents up to 15% to 25% of ischemic strokes in people under the age of 50 years. Noninvasive vessel imaging is increasingly used in clinical practice, but the impact on the frequency of detection of CeAD is unknown. In 2006, the yearly incidence rate of CeAD was estimated at 2.6 per 100â 000 person-years, but the current incidence is unknown. METHODS: In this population-based retrospective observational cohort study, we utilized the resources of the Rochester Epidemiology Project to ascertain all adult residents of Olmsted County, MN, diagnosed with internal carotid artery dissection and common carotid artery dissection or vertebral artery dissection from 2002 to 2020. Patients with only intracranial involvement or CeAD following major trauma were excluded. Age-adjusted sex-specific and age- and sex-adjusted incidence rates were estimated using the US White 2010 decennial census, with rates expressed per 100â 000 person-years. We assessed longitudinal trends by dividing the data into 5-year time intervals, with the last being a 4-year interval. RESULTS: We identified 123 patients with a diagnosis of CeAD. There were 63 patients with internal carotid artery dissection, 54 with vertebral artery dissection, 2 with concurrent internal carotid artery dissection and vertebral artery dissection, and 4 with common carotid artery dissection. There were 63 (51.2%) female patients and 60 (48.8%) male patients. The average age at diagnosis was 50.2 years (SD, 15.1 [95% CI, 20.1-90.5] years). The incidence rate of spontaneous CeAD encompassing all locations was 4.69 per 100â 000 person-years (2.43 for internal carotid artery dissection and 2.01 for vertebral artery dissection). The incidence rate increased from 2.30 per 100â 000 person-years from 2002 to 2006 to 8.93 per 100â 000 person-years from 2017 to 2020 (P<0.0001). The incidence rate for female patients rose from 0.81 per 100â 000 person-years from 2002 to 2006 to 10.17 per 100â 000 person-years from 2017 to 2020. CONCLUSIONS: The incidence rate of spontaneous CeAD increased nearly 4-fold over a 19-year period from 2002 to 2020. The incidence rate in women rose over 12-fold. The increase in incidence rates likely reflects the increased use of noninvasive vascular imaging.
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Dissecação da Artéria Carótida Interna , Acidente Vascular Cerebral , Dissecação da Artéria Vertebral , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artérias , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dissecação da Artéria Carótida Interna/epidemiologia , Dissecação da Artéria Carótida Interna/etiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/epidemiologia , Dissecação da Artéria Vertebral/complicações , Adulto Jovem , Idoso , Idoso de 80 Anos ou maisRESUMO
Uterine leiomyoma (LM), also known as uterine fibroids, are common gynecological tumors and can reach a prevalence of 70% among women by the age of 50 years. Notably, the LM burden is much higher in Black women with earlier onset, a greater tumor number, size, and severity compared to White women. Published knowledge shows that there are genetic, environmental, and lifestyle-based risk factors associated with racial disparity for LM. Significant strides have been made on genomic, epigenomic, and transcriptomic data levels in Black and White women to elucidate the underlying pathomolecular reasons of racial disparity in LM development. However, racial disparity of LM remains a major area of concern in gynecological research. This review highlights risk factors of LM and their role in different races. Furthermore, we discuss the genetics and uterine myometrial microenvironment in LM development. Comparative findings revealed that a major racial difference in the disease is linked to myometrial oxidative burden and altered ROS pathways which is relevant to the oxidized guanine in genomic DNA and MED12 mutations that drive the LM genesis. Considering the burden and morbidity of LM, we anticipate that this review on genetic risk and myometrial microenvironment will strengthen understanding and propel the growth of research to address the racial disparity of LM burden.
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Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Negro ou Afro-Americano , Perfilação da Expressão Gênica , Leiomioma/genética , Leiomioma/metabolismo , Miométrio/metabolismo , Microambiente Tumoral , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Útero/metabolismo , BrancosRESUMO
PURPOSE: Female CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. METHODS: Including 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women. RESULTS: We found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward. CONCLUSION: A significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.
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We report on observations of coherent, sustained oscillations in the absorption of continuous-wave light at 388 nm that excites the 6S1/2 â 8P3/2 transition in cesium (Cs) vapor. The oscillation frequency is close to the spacing of hyperfine levels of the 8P3/2 level that are excited simultaneously by the 388 nm field. We observe a threshold behavior of the oscillation amplitude with pump power and suggest that the effect is associated with infrared directional emission due to amplified spontaneous emission (ASE) from the 8P3/2 â 8S1/2 transition that is assisted by retro-reflections from cell windows. The effect may be used to probe a lasing process in an atomic vapor, by checking the temporal properties of the pump field transmitted through the vapor.
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We report an estimation of the injected mass composition of ultrahigh energy cosmic rays (UHECRs) at energies higher than 10 EeV. The composition is inferred from an energy-dependent sky distribution of UHECR events observed by the Telescope Array surface detector by comparing it to the Large Scale Structure of the local Universe. In the case of negligible extragalactic magnetic fields (EGMFs), the results are consistent with a relatively heavy injected composition at Eâ¼10 EeV that becomes lighter up to Eâ¼100 EeV, while the composition at E>100 EeV is very heavy. The latter is true even in the presence of highest experimentally allowed extragalactic magnetic fields, while the composition at lower energies can be light if a strong EGMF is present. The effect of the uncertainty in the galactic magnetic field on these results is subdominant.
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OBJECTIVE: To evaluate the prevalence and rate of a missed diagnosis of sacroiliitis on abdominal computed tomography (CT) in patients with inflammatory bowel disease (IBD). Factors associated with sacroiliitis were also assessed. METHOD: This retrospective study included 210 patients with IBD (mean age 31.1 years) who underwent abdominal CT. Based on a validated abdominal CT scoring tool, bilateral sacroiliac (SI) joints on abdominal CT in the whole study population were retrospectively reviewed. Subsequently, patients were classified into the 'patients with sacroiliitis' group and the 'patients without sacroiliitis' group. Univariate and multivariate regression analyses were used to clarify the factors associated with sacroiliitis. RESULTS: Sacroiliitis was identified in 26 out of 210 patients (12.4%). However, sacroiliitis was recognized on the primary reading in only five of these 26 patients (19.2%) and was missed on the initial report in the remaining 21 patients (80.8%). Among the 21 patients, 20 (95.2%) were finally diagnosed with axial spondyloarthritis (axSpA). There was a higher prevalence of female sex (p = 0.04), upper gastrointestinal involvement (p = 0.04), and back pain (p < 0.01) in patients with sacroiliitis than in those without sacroiliitis. However, on multivariate analysis, back pain was the only factor associated with sacroiliitis (p = 0.01). CONCLUSION: Physicians should carefully evaluate SI joints on abdominal CT in patients with IBD to enable early detection of sacroiliitis, potentially leading to an early diagnosis of axSpA. In addition, if patients with IBD present with back pain, the possibility of sacroiliitis should be considered.
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Doenças Inflamatórias Intestinais , Sacroileíte , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Sacroileíte/diagnóstico por imagem , Sacroileíte/epidemiologia , Adulto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/complicações , Prevalência , Pessoa de Meia-Idade , Adulto Jovem , Diagnóstico Ausente/estatística & dados numéricos , Articulação Sacroilíaca/diagnóstico por imagem , Espondiloartrite Axial/epidemiologia , Espondiloartrite Axial/diagnóstico por imagemRESUMO
Compared to aquatic ecosystem, terrestrial systems have been subjected to fewer investigations on the exposure to halogenated flame retardants (HFRs). Our study utilized peregrine falcon eggs collected from multiple habitats across North America to retrospectively explore both spatial distribution and temporal changes in legacy (e.g., polybrominated diphenyl ethers) and alternative HFRs over a 30 year period (1984-2016). The results reveal intensive HFR exposure in terrestrial ecosystems and chemical-specific spatiotemporal distribution patterns. The correlations between egg levels of the selected HFRs and human population density clearly illustrated a significant urban influence on the exposure of this wildlife species to these HFRs and subsequent maternal transfer to their eggs. Temporal analyses suggest that, unlike aquatic systems, terrestrial ecosystems may undergo continual exposure to consistently high levels of legacy HFRs for a long period of time. Our findings collectively highlight the effectiveness of using peregrine eggs to monitor terrestrial exposure to HFRs and other bioaccumulative chemicals and the need for continuous monitoring of HFRs in terrestrial ecosystems.
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INTRODUCTION AND HYPOTHESIS: Patient-reported outcomes are relevant outcomes in studies on pelvic organ prolapse (POP) surgery, as anatomical recurrence alone does not have a significant correlation with perceived improvement. In the present study, the patient's impression of improvement after 1 year is studied after vaginal hysterectomy (VH) versus sacrospinous hysteropexy (SSH) in large cohorts from daily clinical practice. We hypothesize that there is no difference between the groups. METHODS: This is a secondary analysis on prospectively collected data in a multicenter cohort of patients who underwent VH or SSH for symptomatic POP. All patients had a POP-Q stage ≥ 2 in at least one compartment at baseline and were treated with VH or SSH between 2002 and 2019. The primary outcome was the patient-reported score on the patient global impression of improvement index (PGI-I) 1 year after surgery. The secondary outcome was a composite outcome of surgical success, defined as the absence of recurrent POP beyond the hymen with bothersome bulge symptoms and/or repeat surgery. RESULTS: A total of 378 women (196 VH and 182 SSH) were included. The median score on the PGI-I did not differ between VH and SSH. At 1 year post-operatively, 77 women after VH (73%) and 77 women after SSH (75%) considered their condition (very) much improved (p = 0.86). There was no difference in composite outcome of surgical success (126 out of 137 women [92%] after VH, 118 out of 125 women [94%] after SSH; p = 0.44). CONCLUSIONS: Our study shows that there was no difference in the type of surgery, VH or SSH, with regard to the patient's impression of improvement 1 year postoperatively in a large cohort from daily clinical practice.
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Histerectomia Vaginal , Medidas de Resultados Relatados pelo Paciente , Prolapso de Órgão Pélvico , Humanos , Feminino , Histerectomia Vaginal/métodos , Prolapso de Órgão Pélvico/cirurgia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Estudos Prospectivos , Procedimentos Cirúrgicos em Ginecologia/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The maternal mortality ratio (MMR) in Indonesia is among the highest in Southeast Asia. We aim to describe trends in the MMR and causes of maternal deaths in Indonesia over the past decades, regionally and nationally. METHODS: We performed a systematic review and conducted a search using PubMed, Embase, Global Health, CINAHL, Cochrane, Portal Garuda, and Google Scholar from the inception of the database to April 2023. We included all studies on the incidence and/or the causes of maternal deaths in Indonesia. The MMR was defined as the number of maternal deaths per 100,000 live births. Maternal death causes were assessed and reclassified according to the WHO International Classification of Disease Maternal Mortality (ICD-MM). RESULTS: We included 63 studies that reported the MMR (54 studies) and/or the causes of maternal deaths (44 studies) in Indonesia from 1970 to 2022, with a total of 254,796 maternal deaths. The national MMR declined from 450 to 249 (45%) between 1990 and 2020. Great differences in MMR exist across the country, with the lowest in Java-Bali and the highest (more than twice the national MMR) in Sulawesi and Eastern Indonesia. Between 1990 and 2022, the proportion of deaths due to hemorrhage and sepsis decreased, respectively from 48 to 18% and 15-5%, while the share of deaths due to hypertensive disorders and non-obstetric causes increased, respectively from 8 to 19% and 10-49%. CONCLUSION: Despite the steady decline of maternal deaths in Indonesia, it remains one of the highest in Southeast Asia, with enormous disparities within the country. Hypertensive disorders and non-communicable diseases make up a growing share of maternal deaths, making maternal death reduction strategies increasingly challenging. National Maternal Death Surveillance and Response needs to be prioritized to eliminate preventable maternal deaths in Indonesia. REGISTRATION OF SYSTEMATIC REVIEWS: PROSPERO, CRD42022320213.
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Causas de Morte , Mortalidade Materna , Humanos , Indonésia/epidemiologia , Mortalidade Materna/tendências , Feminino , Gravidez , Causas de Morte/tendências , Complicações na Gravidez/mortalidade , Complicações na Gravidez/epidemiologiaRESUMO
PURPOSE: Asymptomatic patients with clinically non-functional pituitary neuroendocrine tumors (CNF-PitNETs) are usually followed up. However, the natural course of CNF-PitNETs according to sex and age remains unclear. Therefore, this study assessed growth patterns of CNF-PitNETs according to sex and age. METHODS: In this longitudinal study, we enrolled 431 consecutive patients with CNF-PitNETs who were treated at Seoul National University Hospital from 1997 to 2021. The patients underwent hormone function testing and visual field testing, and were subsequently followed up with imaging over a median duration of 66 months. RESULTS: The median age of the patients was 53.0 years, and 37.1% (n = 160) were men. Men were older and harbored more macroadenomas than women. The annual tumor volume change was higher in men than in women (0.21 vs. 0.04 cm3/year, P < 0.001). The estimated cutoff value of age for significant tumor growth was 51 years. In men, the annual tumor volume change was similar across all age groups. In women, those aged ≤ 50 years showed significantly lower annual tumor volume change than those aged > 50 years (0.01, 0.11, and 0.17 cm3/year, P = 0.001). When comparing sexes within the same age group, the annual tumor volume changes was significantly lower for women than for men, only in patients aged ≤ 50 years (0.01 vs. 0.15 cm3/year, P < 0.001). CONCLUSIONS: Among patients with CNF-PitNET, tumor growth was slower in women aged ≤ 50 years than in men and women aged > 50. These findings may guide the customization of surveillance strategies for CNF-PitNETs according to sex and age.
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Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/diagnóstico , Pessoa de Meia-Idade , Estudos Longitudinais , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/diagnóstico , Fatores Sexuais , Fatores Etários , Idoso , Adulto , Carga Tumoral , Seguimentos , PrognósticoRESUMO
OBJECTIVE: To investigate the accuracy of artificial intelligence-assisted growth prediction using a convolutional neural network (CNN) algorithm and longitudinal lateral cephalograms (Lat-cephs). MATERIALS AND METHODS: A total of 198 Japanese preadolescent children, who had skeletal Class I malocclusion and whose Lat-cephs were available at age 8 years (T0) and 10 years (T1), were allocated into the training, validation, and test phases (n = 161, n = 17, n = 20). Orthodontists and the CNN model identified 28 hard-tissue landmarks (HTL) and 19 soft-tissue landmarks (STL). The mean prediction error values were defined as 'excellent,' 'very good,' 'good,' 'acceptable,' and 'unsatisfactory' (criteria: 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively). The degree of accurate prediction percentage (APP) was defined as 'very high,' 'high,' 'medium,' and 'low' (criteria: 90%, 70%, and 50%, respectively) according to the percentage of subjects that showed the error range within 1.5 mm. RESULTS: All HTLs showed acceptable-to-excellent mean PE values, while the STLs Pog', Gn', and Me' showed unsatisfactory values, and the rest showed good-to-acceptable values. Regarding the degree of APP, HTLs Ba, ramus posterior, Pm, Pog, B-point, Me, and mandibular first molar root apex exhibited low APPs. The STLs labrale superius, lower embrasure, lower lip, point of lower profile, B', Pog,' Gn' and Me' also exhibited low APPs. The remainder of HTLs and STLs showed medium-to-very high APPs. CONCLUSION: Despite the possibility of using the CNN model to predict growth, further studies are needed to improve the prediction accuracy in HTLs and STLs of the chin area.
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Pontos de Referência Anatômicos , Inteligência Artificial , Cefalometria , Má Oclusão Classe I de Angle , Redes Neurais de Computação , Humanos , Cefalometria/métodos , Criança , Feminino , Masculino , Pontos de Referência Anatômicos/diagnóstico por imagem , Má Oclusão Classe I de Angle/diagnóstico por imagem , Algoritmos , Desenvolvimento Maxilofacial , Previsões , Mandíbula/diagnóstico por imagem , Mandíbula/crescimento & desenvolvimentoRESUMO
While there is generally no consensus about how nutrients determine milk synthesis in the mammary gland, it is likely that the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) plays a role as a key integrator of nutritional and mitogenic signals that can influence a multitude of catabolic and anabolic pathways. The objectives of this study were to evaluate acute changes (<24 h) in translational signaling, in addition to chronic changes (14 d) in mammary gland structure and composition, in response to a severe feed restriction. Fourteen lactating Holstein dairy cows were assigned to either ad libitum feeding (n = 7) or a restricted feeding program (n = 7). Feed-restricted cows had feed removed after the evening milking on d 0. Mammary biopsies and blood samples were collected 16 h after feed removal, after which cows in the restricted group were fed 60% of their previously observed ad libitum intake for the remainder of the study. On d 14, animals were slaughtered and their mammary glands dissected. In response to feed removal, an acute increase in plasma nonesterified fatty acid concentration was observed, concurrent to a decrease in milk yield. In mammary tissue, we observed downregulation of the mTORC1-S6K1 signaling cascade, in addition to reductions in mRNA expression of markers of protein synthesis, endoplasmic reticulum biogenesis, and cell turnover (i.e., transcripts associated with apoptosis or cell proliferation). During the 14 d of restricted feeding, animals underwent homeorhetic adaptation to 40% lower nutrient intake, achieving a new setpoint of 14% reduced milk yield with 18% and 29% smaller mammary secretory tissue DM and CP masses, respectively. On d 14, no treatment differences were observed in markers of protein synthesis or mammary cell turnover evaluated using gene transcripts and immunohistochemical staining. These findings implicate mTORC1-S6K1 in the early phase of the adaptation of the mammary gland's capacity for milk synthesis in response to changes in nutrient supply. Additionally, changes in rates of mammary cell turnover may be transient in nature, returning to basal levels following brief alterations that have sustained effects.
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Lactação , Glândulas Mamárias Animais , Leite , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Feminino , Bovinos , Glândulas Mamárias Animais/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Leite/química , Leite/metabolismo , Dieta/veterinária , Ração AnimalRESUMO
Type 2 diabetes (T2D) is a chronic multifactorial disease characterized by a combination of insulin resistance and impaired glucose regulation. The alleviative effects of probiotics on T2D have been widely studied. However, studies on the effects of postbiotics, known as inactivated probiotics, on dairy products are limited. This study aimed to evaluate the effectiveness of postbiotic Lactiplantibacillus plantarum LRCC5314 in milk powder (MP-LRCC5314) in a stress-induced T2D (stress-T2D) mouse model. Compared with probiotic MP-LRCC5314, postbiotic MP-LRCC5314 significantly influenced stress-T2D-related factors. The administration of heat-killed MP-LRCC5314 reduced corticosterone levels, increased short-chain fatty acid production by modulating gut microbiota, and regulated immune response, glucose metabolism, stress-T2D-related biomarkers in the brain, gut, and adipose tissues, as well as glucose and insulin sensitivity. In addition, heat-killed MP-LRCC5314 treatment led to a decrease in pro-inflammatory cytokine levels and an increase in anti-inflammatory cytokine levels. Overall, these findings suggest that adding postbiotic MP-LRCC5314 to milk powder could serve as a potential supplement for stress-T2D mitigation.
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Diabetes Mellitus Tipo 2 , Leite , Probióticos , Animais , Camundongos , Diabetes Mellitus Tipo 2/veterinária , Lactobacillus plantarumRESUMO
Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.
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Lipopolissacarídeos , Oligossacarídeos , Camundongos , Animais , Oligossacarídeos/farmacologia , Inflamação/tratamento farmacológico , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Trissacarídeos/farmacologia , Lactose/análogos & derivadosRESUMO
OBJECTIVES: This study aimed to investigate the association between adherence to 24-h movement guidelines and metabolic syndrome (MetS) before and during the COVID-19 pandemic. STUDY DESIGN: Repeated cross-sectional design. METHODS: We selected 10,882 adults (2019: n = 5710; 2020: n = 5172) aged ≥20 years from the Korea National Health and Nutrition Examination Survey. Domain-specific physical activity and sedentary behavior were assessed using a global physical activity questionnaire. We also measured the typical sleep duration (h/day) on weekdays and weekends. MetS was defined as the presence of more than three risk factors. RESULTS: During the COVID-19 pandemic, transportation-related physical activity decreased, while the prevalence of abdominal obesity (+3.3 %) and low HDL-C levels (+3.1 %) increased significantly. An elevated risk of MetS was observed in the lower aerobic (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.04-1.58; P = 0.019) and muscular exercise (OR, 1.31; 95% CI, 1.04-1.66; P = 0.023) groups and in the high sedentary behavior (OR, 1.23; 95% CI, 1.00-1.51; P = 0.049) during the pandemic. Sensitivity analysis stratified by sex showed similar patterns with more pronounced changes in MetS components in males. The models also showed significant associations between aerobic physical activity, strength exercises, and sedentary behavior with MetS in males and females. CONCLUSIONS: Although sedentary behavior and sleep time remained unchanged, a significant decrease in transportation-related physical activity was observed during the pandemic. Moreover, our findings revealed that aerobic physical activity, strength exercise, and sedentary time during the pandemic were associated with an increased MetS risk. These results highlight the importance of promoting physical activity, particularly during periods of social restriction, to mitigate the pandemic's negative effects on metabolic health.
Assuntos
COVID-19 , Síndrome Metabólica , Adulto , Masculino , Feminino , Humanos , Síndrome Metabólica/epidemiologia , Pandemias , Inquéritos Nutricionais , Estudos Transversais , COVID-19/epidemiologia , COVID-19/complicações , República da Coreia/epidemiologiaRESUMO
OBJECTIVE: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. STUDY DESIGN: This was a retrospective observational study. METHODS: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. RESULTS: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831). CONCLUSIONS: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.
Assuntos
Pólipos Adenomatosos , Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Gastrite Atrófica/patologia , Estudos Retrospectivos , Estudos Longitudinais , Detecção Precoce de Câncer , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Inquéritos Nutricionais , Saúde Pública , Fatores Econômicos , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
AIMS: To understand the strategies used to continue providing psychosocial support to cancer patients during the pandemic, including outcomes and implications beyond the pandemic. DESIGN: A systematic review of original research. DATA SOURCES: ProQuest Health & Medicine, CINAHL Complete (via EBSCOhost), Scopus, and PubMed were searched for original work published between January 2020 and December 2022. METHODS: Abstract and title screening identified eligible articles for full-text review. Following a full-text review, data were extracted from eligible articles, and a risk of bias assessment was conducted. A synthesis without meta-analysis was performed. RESULTS: Thirty-four articles met the selection criteria. These articles provide evidence that systematic adaptations during the pandemic improved the assessment and screening of psychological needs and/or increased the number of clients accessing services. Additionally, while the pandemic was associated with decreased psychosocial well-being for cancer patients, five intervention studies reported improvements in psychosocial well-being. Barriers, strategies, and recommendations were described. CONCLUSION: Adapting psychosocial support during a pandemic can be successful, achieved relatively quickly, and can increase the uptake of support for people experiencing cancer. IMPLICATIONS FOR PATIENT CARE: It is imperative that these adaptations continue beyond the pandemic to maximize adaptive psychosocial outcomes for a group vulnerable to ongoing mental health concerns. IMPACT: While the COVID-19 pandemic was associated with increased psychosocial need for cancer patients, evidence in the review suggested that adaptations made to service delivery facilitated increased access for patients who may not previously have been able to access support. Additionally, improvements in psychosocial well-being were achieved. These findings are relevant for clinicians and decision-makers who fund and design psychosocial support services for cancer patients. REPORTING METHOD: The review was guided by PRISMA Guidelines and the SWiM Reporting Guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.