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BACKGROUND: To determine the association of trainees involvement with surgical outcomes of abdominal and laparoscopic myomectomy including operative time, rate of transfusion, and complications. METHODS: A retrospective cohort study of 1145 patients who underwent an abdominal or laparoscopic myomectomy from 2008-2012 using the American College of Surgeons National Surgical Quality Improvement Program database (Canadian Task Force Classification II-2). RESULTS: Overall, 64% of myomectomies involved trainees. Trainees involvement was associated with a longer operative time for abdominal myomectomies (mean difference 20.17 minutes, 95% Confidence Interval (CI) [11.37,28.97], p < 0.01) overall and when stratified by fibroid burden. For laparoscopic myomectomy, there was no difference in operative time between trainees vs no trainees involvement (mean difference 4.64 minutes, 95% CI [-18.07,27.35], p = 0.67). There was a higher rate of transfusion with trainees involvement for abdominal myomectomies (10% vs 2%, p < 0.01; Odds Ratio (OR) 5.62, 95% CI [2.53,12.51], p < 0.01). Trainees involvement was not found to be associated with rate of transfusion for laparoscopic myomectomy (4% vs 5%, p = 0.86; OR 0.82, 95% CI [0.16,4.14], p = 0.81). For abdominal myomectomy, there was a higher rate of overall complications (15% vs 5%, p < 0.01; OR 2.96, 95% CI [1.77,4.93], p < 0.01) and minor complications (14% vs 4%, p < 0.01; OR 3.71, 95% CI [2.09,6.57], p < 0.01) with no difference in major complications (3% vs 2%, p = 0.23). For laparoscopic myomectomy, there was no difference in overall (6% vs 10% p = 0.41; OR 0.59, 95% CI [0.18,2.01], p = 0.40), major (2% vs 0%, p = 0.38), or minor (5% vs 10%, p = 0.32; OR 0.52, 95% CI [0.15,1.79], p = 0.30) complications. CONCLUSION: Trainees involvement was associated with increased operative time, rate of transfusion, and complications for abdominal myomectomy, however, did not impact surgical outcomes for laparoscopic myomectomy.
TITLE: Trainees Involvement in MyomectomyThe goal of our study was to determine the association of trainees involvement with surgical outcomes of fibroid excision surgery or myomectomy. We conducted a study of abdominal and laparoscopic myomectomies using an international surgical database. We found that trainees involvement in myomectomy was associated with increased operative time, rate of transfusion, and complications for abdominal myomectomy. However, trainees involvement did not impact surgical outcomes for laparoscopic myomectomy.
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Laparoscopia , Miomectomia Uterina , Neoplasias Uterinas , Feminino , Humanos , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Secondary spinal cord injury (SCI) often causes the aggravation of inflammatory reaction and nerve injury, which affects the recovery of motor function. Bone-marrow-derived macrophages (BMDMs) were recruited to the injured area after SCI, and the M1 polarization is the key process for inducing inflammatory response and neuronal apoptosis. We previously showed that photobiomodulation (PBM) can inhibit the polarization of M1 phenotype of BMDMs and reduce inflammation, but the underlying mechanisms are unclear. The purpose of this study is to explore the potential target and mechanism of PBM in treating SCI. METHODS: Transcriptome sequencing and bioinformatics analysis showed that long noncoding RNA taurine upregulated gene 1 (lncRNA TUG1) was a potential target of PBM. The expression and specific mechanism of lncRNA TUG1 were detected by qPCR, immunofluorescence, flow cytometry, western blotting, fluorescence in situ hybridization, and luciferase assay. The Basso mouse scale (BMS) and gait analysis were used to evaluate the recovery of motor function in mice. RESULTS: Results showed that lncRNA TUG1 may be a potential target of PBM, regulating the polarization of BMDMs, inflammatory response, and the axial growth of DRG. Mechanistically, TUG1 competed with TLR3 for binding to miR-1192 and attenuated the inhibitory effect of miR-1192 on TLR3. This effect protected TLR3 from degradation, enabling the high expression of TLR3, which promoted the activation of downstream NF-κB signal and the release of inflammatory cytokines. In vivo, PBM treatment could reduce the expression of TUG1, TLR3, and inflammatory cytokines and promoted nerve survival and motor function recovery in SCI mice. CONCLUSIONS: Our study clarified that the lncRNA TUG1/miR-1192/TLR3 axis is an important pathway for PBM to inhibit M1 macrophage polarization and inflammation, which provides theoretical support for its clinical application in patients with SCI.
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MicroRNAs , RNA Longo não Codificante , Traumatismos da Medula Espinal , Receptor 3 Toll-Like , Animais , Camundongos , Citocinas/genética , Hibridização in Situ Fluorescente , Inflamação/genética , Inflamação/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Traumatismos da Medula Espinal/genética , Receptor 3 Toll-Like/genéticaRESUMO
BACKGROUND: African Americans (AAs) are disproportionately affected by cardiovascular disease (CVD), they are 20% more likely to die from CVD than whites, chronic exposure to inflammation and oxidative stress contributes to CVD. In previous studies, enhancing parasympathetic cholinergic activity has been shown to decrease inflammation. Considering that AAs have decreased parasympathetic activity compared to whites, we hypothesize that stimulating it with a central acetylcholinesterase (AChE) inhibitor, galantamine, would prevent lipid-induced oxidative stress. OBJECTIVE: To test the hypothesis that acute dose of galantamine, an AChE inhibitor, decreases lipid-induced oxidative stress in obese AAs. METHODS: Proof-of-concept, double-blind, randomized, placebo-controlled, crossover study that tested the effect of a single dose of 16 mg of galantamine versus placebo on lipid-induced oxidative stress in obese AAs. Subjects were studied on two separate days, one week apart. In each study day, 16 mg or matching placebo was administered before 20% intralipids infusion at doses of 0.8 mL/m2/min with heparin at doses of 200 U/h for 4 h. Outcomes were assessed at baseline, 2 and 4 h during the infusion. MAIN OUTCOME MEASURES: Changes in F2-isoprostane (F2-IsoPs), marker of oxidative stress, measured in peripheral blood mononuclear cells (PBMC) and in plasma at baseline, 2, and 4-h post-lipid infusion. Secondary outcomes include changes in inflammatory cytokines (IL-6, TNF alpha). RESULTS: A total of 32 obese AA women were screened and fourteen completed the study (age 37.8 ± 10.70 years old, BMI 38.7 ± 3.40 kg/m2). Compared to placebo, 16 mg of galantamine significantly inhibited the increase in F2-IsoPs in PBMC (0.007 ± 0.008 vs. - 0.002 ± 0.006 ng/sample, P = 0.016), and plasma (0.01 ± 0.02 vs. - 0.003 ± 0.01 ng/mL, P = 0.023). Galantamine also decreased IL-6 (11.4 ± 18.45 vs. 7.7 ± 15.10 pg/mL, P = 0.021) and TNFα levels (18.6 ± 16.33 vs. 12.9 ± 6.16 pg/mL, P = 0.021, 4-h post lipid infusion) compared with placebo. These changes were associated with an increased plasma acetylcholine levels induced by galantamine (50.5 ± 10.49 vs. 43.6 ± 13.38 during placebo pg/uL, P = 0.025). CONCLUSIONS: In this pilot, proof-of-concept study, enhancing parasympathetic nervous system (PNS) cholinergic activity with galantamine inhibited lipid-induced oxidative stress and inflammation induced by lipid infusion in obese AAs. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02365285.
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Doenças Cardiovasculares , Galantamina , Acetilcolinesterase , Adulto , Negro ou Afro-Americano , Colinérgicos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Galantamina/farmacologia , Galantamina/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Interleucina-6 , Leucócitos Mononucleares , Lipídeos , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Estresse OxidativoRESUMO
OBJECTIVE: Pregnant women with asthma have increased frequency of respiratory viral infections and exacerbations. Because of these risks, women with asthma may be subject to increased surveillance during pregnancy and may, therefore, be at increased risk of antibiotic receipt. The objective of this study was to assess the relationship between maternal asthma and outpatient prenatal antibiotic prescription fills to inform antibiotic stewardship. METHODS: We included women who delivered a singleton, term, non-low birthweight, and otherwise healthy infant enrolled in the Tennessee Medicaid Program. Maternal asthma and prenatal antibiotic fills were ascertained from healthcare encounters and outpatient pharmacy claims. We examined the association between maternal asthma and prenatal antibiotic fills using modified Poisson regression. RESULTS: Our study population included 168354 pregnant women, 4% of whom had asthma. Women with asthma had an increased risk of filling at least one prenatal antibiotic prescription (adjusted risk ratio [aRR] 1.27, 95% confidence interval [CI] 1.25-1.28) and had an increased number of fills during pregnancy (aRR 1.54, 95% CI 1.51-1.57) compared to women without asthma. Among those who filled at least one antibiotic prescription, women with asthma had earlier first prenatal antibiotic prescription fill and increased likelihood of filling at least one course of broad-spectrum antibiotics during pregnancy (versus narrow-spectrum). CONCLUSIONS: Pregnant women with asthma had more outpatient antibiotic prescription fills than pregnant women without asthma. These findings highlight that pregnant women with asthma disproportionately fill more antibiotic prescriptions during pregnancy, providing data that may inform antibiotic stewardship.
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Asma , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Feminino , Humanos , Lactente , Medicaid , Pacientes Ambulatoriais , Gravidez , Prescrições , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: This study aimed to evaluate risk factors for endometrial intraepithelial neoplasia/malignancy in premenopausal women with abnormal uterine bleeding or oligomenorrhea. Specifically, we aimed to elucidate whether body mass index (BMI) or age confers a higher risk. STUDY DESIGN: A retrospective cohort study was performed at a large academic center examining risk factors for endometrial hyperplasia/malignancy in premenopausal women undergoing endometrial sampling. RESULTS: Of the 4170 women ages 18-51 who underwent endometrial sampling from 1987 to 2019, 77 (1.85%) were found to have endometrial intraepithelial neoplasia or malignancy. Clinical predictors of EIN/malignancy in this population included obesity (OR: 3.84, 95%, p < .001), Body mass index [(OR30 vs. 25:2.11, p < .001) and OR35 vs. 30: 1.65, p < .001], Diabetes (OR: 3.6, p-value <.001), hormonal therapy use (OR: 2.93, p < .001), personal history of colon cancer (OR: 9.90, p = .003), family history of breast cancer (OR: 2.65, p < .001), family history of colon cancer (OR: 3.81, p < .001), and family history of endometrial cancer (OR: 4.92, p = .033). Age was not significantly associated with an increased risk of disease. Adjusting for other factors, a model using BMI to predict the risk of EIN/malignancy was more discriminative than a model based on age. CONCLUSIONS: Increased BMI, may be more predictive of endometrial hyperplasia/malignancy than age in premenopausal women with abnormal uterine bleeding. Modification of evaluation guidelines in a contemporary demographic setting could be considered.
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Neoplasias do Colo , Hiperplasia Endometrial , Neoplasias do Endométrio , Doenças Uterinas , Neoplasias Uterinas , Adolescente , Adulto , Índice de Massa Corporal , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Hiperplasia Endometrial/complicações , Hiperplasia Endometrial/diagnóstico , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Endométrio/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Uterinas/patologia , Hemorragia Uterina/epidemiologia , Neoplasias Uterinas/patologia , Adulto JovemRESUMO
Experts have proven that photobiological regulation therapy for spinal cord injury promotes the spinal repair following injury. The traditional irradiation therapy mode is indirect (percutaneous irradiation), which could significantly lower the effective use of light energy. In earlier studies, we developed an implantable optical fiber that one can embed above the spinal cord lamina, and the light directly is cast onto the surface of the spinal cord in a way that can dramatically improve energy use. Nonetheless, it remains to be seen whether near-infrared light diffused by embedded optical fiber can have side effects on the surrounding nerve cells. Given this, we implanted optical fiber on the lamina of a normal spinal cord to observe the structural integrity of the tissue using morphological staining; we also used immunohistochemistry to detect inflammatory factors. Considering the existing studies, we meant to determine that the light energy diffused by embedded optical fiber has no side effect on the normal tissue. The results of this study will lay a foundation for the clinical application of the treatment of spinal cord injury by near-infrared light irradiation.
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Fibras Ópticas , Traumatismos da Medula Espinal , Animais , Neurônios , Medula Espinal , Traumatismos da Medula Espinal/radioterapia , SuínosRESUMO
The study aimed to design a reliable and straightforward PBM method by implanting a medical scattering fiber above surgically exposed spinal cord in SCI patients. Moreover, the safety of this method was examined. Twelve patients with acute SCI (ASIA B) requiring posterior decompression were recruited. The medical scattering fiber was implanted above the spinal cord, and was continuously irradiated at 810 nm, 300 mW, 30 min/day, once per day for 7 days. The vital signs (temperature, blood pressure, respiratory rate, heart rate, and oxygen saturation), infection indicators (WBC, NEUT, hs-CRP, and PCT), photo-allergic reaction indicators (Eosinophil and Basophil), coagulation function indicators (PT, APTT, TT) and neurological stability indicators (ASIA sensory and motor scores) were recorded to evaluate the safety of PBM. Three months after surgery, 12 patients completed follow-up. In our study, direct PBM on SCI site did not cause clinically pathologic changes in vital signs of the patients. All patients had higher WBC, NEUT, and hs-CRP at day 3 during irradiation than those before surgery, and returned to normal at day 7. The changes in Eosinophil and Basophil that were closely associated with allergic reactions were within normal limits throughout the course of irradiation. The coagulation function (PT, APTT, and TT) of patients were also in the normal range. The ASIA sensory and motor scores of all patients had no changes throughout the irradiation process. However, in the follow-up, both ASIA sensory and motor scores of all patients had minor improvement than those in pre-irradiation, and 7 patients had adverse events, but they were not considered to be related to PBM. Our study might firstly employ direct PBM in the SCI by using scattered optical fibers. In a limited sample size, our study concluded that direct PBM at the site of SCI would not produce adverse effects within the appropriate irradiation parameters. The method is safe, feasible, and does not add additional trauma to the patient. Our preliminary study might provide a new methodology for the clinical PBM treatment of acute SCI.
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Proteína C-Reativa , Terapia com Luz de Baixa Intensidade , Traumatismos da Medula Espinal , Humanos , Recuperação de Função Fisiológica , Medula Espinal/patologia , Traumatismos da Medula Espinal/radioterapia , Traumatismos da Medula Espinal/patologiaRESUMO
BACKGROUND: The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. METHODS: We conducted a population-based cohort study of 84â 214 mother-child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. RESULTS: Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0-2], 1.26 [95% confidence interval {CI}, 1.20-1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum-only antibiotic use, broad spectrum-only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05-1.24]). There were effect modifications (Pâ <â .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. CONCLUSIONS: Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.
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Asma , Efeitos Tardios da Exposição Pré-Natal , Antibacterianos/efeitos adversos , Asma/induzido quimicamente , Asma/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. RESULTS: PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. CONCLUSION: Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.
Assuntos
Astrócitos/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Microglia/efeitos da radiação , Recuperação de Função Fisiológica/efeitos da radiação , Traumatismos da Medula Espinal/patologia , Animais , Astrócitos/metabolismo , Janus Quinase 2/metabolismo , Janus Quinase 2/efeitos da radiação , Lipocalina-2/metabolismo , Lipocalina-2/efeitos da radiação , Masculino , Microglia/metabolismo , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Traumatismos da Medula Espinal/metabolismo , Regulação para CimaRESUMO
The COVID-19 pandemic widely disrupted the delivery of healthcare services, including genetic counseling. To ensure continuity of care, the reproductive genetic counselors at a large academic medical center in the United States rapidly transitioned their practice from 90% in-person patient consultations to a predominantly telehealth model. The present study describes this transition in regard to patient access to genetic counseling and genetic screening. A chart review of patients seen by the reproductive genetic counselors from January 2020 to August 2020 was completed. The time frame included the three months prior to the COVID-19 pandemic and the first five months during COVID-19. Patient demographics and clinical and appointment data were compared between the pre-COVID-19 and during-COVID-19 timeframes. Overall, 88.6% of patients were seen via telehealth during COVID-19 and there was no significant difference based upon patient age (p = .20), indication for appointment (p = .06), or gestational age (p = .06). However, non-English speaking patients were more often seen in-person than by telehealth (p < .001), and more patients residing farther from the clinic were seen via telehealth (p = .004). During-COVID-19 results for prenatal cell-free DNA screening and expanded carrier screening were delayed (p < .001). Additionally, after consenting to screening, patients seen during COVID-19 were more likely to not complete a sample collection for their intended screening when compared to those seen pre-COVID-19 (OR = 6.15, 95% CI = 1.43-26.70, p = .015). Overall, this study supports that access to genetic counseling services and genetic screening can be maintained during a global pandemic like COVID-19. Genetic counselors are well-equipped to pivot swiftly during challenging times; however, they must continue to work to address other barriers to accessing genetic services, especially for non-English speaking populations. Future studies are needed to pose solutions to the obstacles confronted in this service delivery model during a global pandemic.
Assuntos
Centros Médicos Acadêmicos , COVID-19 , Aconselhamento Genético/organização & administração , COVID-19/epidemiologia , Feminino , Humanos , Pandemias , Gravidez , Telemedicina , Tennessee/epidemiologiaRESUMO
Macrophages play key roles in the secondary injury stage of spinal cord injury (SCI). M1 macrophages occupy the lesion area and secrete high levels of inflammatory factors that hinder lesion repair, and M2 macrophages can secrete neurotrophic factors and promote axonal regeneration. The regulation of macrophage secretion after SCI is critical for injury repair. Low-level laser therapy (810-nm) (LLLT) can boost functional rehabilitation in rats after SCI; however, the mechanisms remain unclear. To explore this issue, we established an in vitro model of low-level laser irradiation of M1 macrophages, and the effects of LLLT on M1 macrophage polarization and neurotrophic factor secretion and the related mechanisms were investigated. The results showed that LLLT irradiation decreased the expression of M1 macrophage-specific markers, and increased the expression of M2 macrophage-specific markers. Through forward and reverse experiments, we verified that LLLT can promote the secretion of various neurotrophic factors by activating the PKA-CREB pathway in macrophages and finally promote the regeneration of axons. Accordingly, LLLT may be an effective therapeutic approach for SCI with clinical application prospects.
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Axônios/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Terapia com Luz de Baixa Intensidade , Macrófagos/metabolismo , Macrófagos/efeitos da radiação , Fatores de Crescimento Neural/metabolismo , Regeneração Nervosa , Animais , Axônios/efeitos dos fármacos , Axônios/efeitos da radiação , Meios de Cultivo Condicionados/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Isoquinolinas/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Fatores de Crescimento Neural/genética , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/efeitos da radiação , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sulfonamidas/farmacologiaRESUMO
Infant respiratory syncytial virus (RSV) bronchiolitis in the first 6 months of life was associated with increased odds of pneumonia, otitis media, and antibiotic prescription fills in the second 6 months of life. These data suggest a potential value of future RSV vaccination programs on subsequent respiratory health.
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Bronquiolite , Otite Média , Pneumonia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Antibacterianos/uso terapêutico , Bronquiolite/epidemiologia , Humanos , Lactente , Otite Média/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais RespiratóriosRESUMO
BACKGROUND: Aspects of infant antibiotic exposure and its association with asthma development have been variably explored. We aimed to evaluate comprehensively and simultaneously the impact of dose, timing, and type of infant antibiotic use on the risk of childhood asthma. METHODS: Singleton, term-birth, non-low-birth-weight, and otherwise healthy children enrolled in the Tennessee Medicaid Program were included. Infant antibiotic use and childhood asthma diagnosis were ascertained from prescription fills and healthcare encounter claims. We examined the association using multivariable logistic regression models. RESULTS: Among 152 622 children, 79% had at least 1 antibiotic prescription fill during infancy. Infant antibiotic use was associated with increased odds of childhood asthma in a dose-dependent manner, with a 20% increase in odds (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.19-1.20]) for each additional antibiotic prescription filled. This significant dose-dependent relationship persisted after additionally controlling for timing and type of the antibiotics. Infants who had broad-spectrum-only antibiotic fills had increased odds of developing asthma compared with infants who had narrow-spectrum-only fills (aOR, 1.10 [95% CI, 1.05-1.19]). There was no significant association between timing, formulation, anaerobic coverage, and class of antibiotics and childhood asthma. CONCLUSIONS: We found a consistent dose-dependent association between antibiotic prescription fills during infancy and subsequent development of childhood asthma. Our study adds important insights into specific aspects of infant antibiotic exposure. Clinical decision making regarding antibiotic stewardship and prevention of adverse effects should be critically assessed prior to use during infancy.
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Antibacterianos , Asma , Antibacterianos/efeitos adversos , Asma/epidemiologia , Criança , Humanos , Lactente , Modelos Logísticos , Razão de Chances , Fatores de Risco , Tennessee/epidemiologiaRESUMO
Spinal cord injury (SCI) stimulates reactive astrogliosis and the infiltration of macrophages, which interact with each other at the injured area. We previously found Photobiomodulation (PBM) significantly decreases the number of M1 macrophages at the injured area of SCI. But the exact nature of the astrocyte response following PBM and relationship with the macrophage have not been explored in detail. In this study, a BALB/c mice model with standardized bilateral spinal cord compression and a macrophage-astrocyte co-culture model were applied to study effects of PBM on astrocytes. Results showed that PBM inhibit the expression of the astrocyte markers glial fibrillary acidic protein (GFAP) and the secretion of chondroitin sulfate proteoglycans (CSPG) in the para-epicenter area, decrease the number of M1 macrophage in vivo. The in vitro experiments indicated M1 macrophages promote the cell viability of astrocytes and the expression of CSPG. However, PBM significantly inhibited the expression of GFAP, decreased activation of astrocyte, and downregulated the expression of CSPG by regulating M1 macrophages. These results demonstrate that PBM may regulate the interaction between macrophages and astrocytes after spinal cord injury, which inhibited the formation of glial scar.
Assuntos
Astrócitos/efeitos da radiação , Polaridade Celular/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Macrófagos/efeitos da radiação , Animais , Astrócitos/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Meios de Cultivo Condicionados/farmacologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Atividade Motora/efeitos dos fármacos , Atividade Motora/efeitos da radiação , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Recuperação de Função Fisiológica/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/radioterapiaRESUMO
In spinal cord injury (SCI), inflammation is a major mediator of damage and loss of function and is regulated primarily by the bone marrow-derived macrophages (BMDMs). Photobiomodulation (PBM) or low-level light stimulation is known to have anti-inflammatory effects and has previously been used in the treatment of SCI, although its precise cellular mechanisms remain unclear. In the present study, the effect of PBM at 810 nm on classically activated BMDMs was evaluated to investigate the mechanisms underlying its anti-inflammatory effects. BMDMs were cultured and irradiated (810 nm, 2 mW/cm2) following stimulation with lipopolysaccharide and interferon-γ. CCK-8 assay, 2',7'-dichlorofluorescein diacetate assay, and ELISA and western blot analysis were performed to measure cell viability, reactive oxygen species production, and inflammatory marker production, respectively. PBM irradiation of classically activated macrophages significantly increased the cell viability and inhibited reactive oxygen species generation. PBM suppressed the expression of a marker of classically activated macrophages, inducible nitric oxide synthase; decreased the mRNA expression and secretion of pro-inflammatory cytokines, tumor necrosis factor alpha, and interleukin-1 beta; and increased the secretion of monocyte chemotactic protein 1. Exposure to PBM likewise significantly reduced the expression and phosphorylation of NF-κB p65 in classically activated BMDMs. Taken together, these results suggest that PBM can successfully modulate inflammation and polarization in classically activated BMDMs. The present study provides a theoretical basis to support wider clinical application of PBM in the treatment of SCI.
Assuntos
Polaridade Celular , Inflamação/radioterapia , Macrófagos/patologia , Animais , Polaridade Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Quimiocinas/genética , Quimiocinas/metabolismo , Regulação da Expressão Gênica/efeitos da radiação , Ativação de Macrófagos/efeitos da radiação , Macrófagos/efeitos da radiação , Camundongos Endogâmicos BALB C , Fosforilação/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Multi-grade osteoarthritis (OA) deterioration monitoring in the daily paradigm using Vibroarthrography (VAG) is very challenging due to two difficulties: (1) the composition of VAG signals is complex in the daily paradigm where friction is intensified because of weight-bearing movements. (2) VAG signal samples near the decision boundary of adjacent deterioration grades are easy to be misclassified. The majority of existing works only focus on the binary classification of OA, providing inadequate assistance in instructing physicians to develop treatment plans based on the presence or absence of OA. Thus, we propose a novel framework for fine-grained multi-grade OA deterioration monitoring in the daily paradigm. METHODS: We propose an end-to-end deep learning framework termed Fine-grained Multi-grade OA Deterioration Monitor (FMOADM), which consists of Multiscale-temporal Feature Extraction (MTFE) and Confusion-Free Master-Slave (CF-MS) Classification. Specifically, MTFE is adopted to extract multiscale-temporal discriminative features from the complicated VAG signals. And center loss is introduced by CF-MS to alleviate confusion at the boundary of adjacent deterioration grades in the feature space. Meanwhile, a master-slave structure is proposed for further fine-grained classification, where the master classifier integrates a channel attention mechanism and the slave classifier is designed to update MTFE parameters. As a result, the proposed method ensures fine-grained multi-grade OA monitoring performance via multiscale-temporal discriminative features and boundary confusion alleviation. RESULTS: Experimental results on the VAG-OA dataset demonstrate that our framework outperforms counterpart methods in the daily paradigm. The proposed framework achieved 78% in precision, obtaining an 8% improvement over the state-of-the-art method. CONCLUSION: The proposed framework benefits efficient multi-grade OA deterioration monitoring, empowering physicians to develop treatment plans based on fine-grained monitoring results. It takes knee joint health monitoring in daily activities a step further toward feasible.
Assuntos
Osteoartrite , Humanos , Osteoartrite/fisiopatologia , Osteoartrite/diagnóstico por imagem , Aprendizado Profundo , Algoritmos , Monitorização Fisiológica/métodos , Processamento de Sinais Assistido por Computador , Vibração , Redes Neurais de ComputaçãoRESUMO
Meniscal injury represents a common type of knee injury, accounting for over 50% of all knee injuries. The clinical diagnosis and treatment of meniscal injury heavily rely on magnetic resonance imaging (MRI). However, accurately diagnosing the meniscus from a comprehensive knee MRI is challenging due to its limited and weak signal, significantly impeding the precise grading of meniscal injuries. In this study, a visual interpretable fine grading (VIFG) diagnosis model has been developed to facilitate intelligent and quantified grading of meniscal injuries. Leveraging a multilevel transfer learning framework, it extracts comprehensive features and incorporates an attributional attention module to precisely locate the injured positions. Moreover, the attention-enhancing feedback module effectively concentrates on and distinguishes regions with similar grades of injury. The proposed method underwent validation on FastMRI_Knee and Xijing_Knee dataset, achieving mean grading accuracies of 0.8631 and 0.8502, surpassing the state-of-the-art grading methods notably in error-prone Grade 1 and Grade 2 cases. Additionally, the visually interpretable heatmaps generated by VIFG provide accurate depictions of actual or potential meniscus injury areas beyond human visual capability. Building upon this, a novel fine grading criterion was introduced for subtypes of meniscal injury, further classifying Grade 2 into 2a, 2b, and 2c, aligning with the anatomical knowledge of meniscal blood supply. It can provide enhanced injury-specific details, facilitating the development of more precise surgical strategies. The efficacy of this subtype classification was evidenced in 20 arthroscopic cases, underscoring the potential enhancement brought by intelligent-assisted diagnosis and treatment for meniscal injuries.
RESUMO
Accurate fine-grained grading of lumbar intervertebral disc (LIVD) degeneration is essential for the diagnosis and treatment design of high-incidence low back pain. However, the grading accuracy is still challenged by lacking the fine-grained degenerative details, which is mainly due to the existing grading methods are easily dominated by the salient nucleus pulposus regions in LIVD, overlooking the inconspicuous degeneration changes of the surrounding structures. In this study, a novel regional feature recalibration network (RFRecNet) is proposed to achieve accurate and reliable LIVD degeneration grading. Detection transformer (DETR) is first utilized to detect all LIVDs and then input to the proposed RFRecNet for the fine-grained grading. To obtain sufficient features from both the salient nucleus pulposus and the surrounding regions, a regional cube-based feature boosting and suppression (RC-FBS) module is designed to adaptively recalibrate the feature extraction and utilization from the various regions in LIVD, and a feature diversification (FD) module is proposed to capture the complementary semantic information from the multi-scale features for the comprehensive fine-grained degeneration grading. Extensive experiments were conducted on a clinically collected dataset, which consists of 500 MR scans with a total of 10225 LIVDs. An average grading accuracy of 90.5%, specificity of 97.5%, sensitivity of 90.8%, and Cohen's kappa correlation coefficient of 0.876 are obtained, which indicate that the proposed framework is promising to provide doctors with reliable and consistent fine-grained quantitative evaluation results of the LIVD degeneration conditions for the optimal surgical plan design.