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1.
Artigo em Inglês | MEDLINE | ID: mdl-38944376

RESUMO

BACKGROUND: Data on the one-year postoperative revision, complication, and economic outcomes in a hospital setting after total shoulder arthroplasty (TSA) are sparse. METHODS: A retrospective cohort study using the Premier Healthcare Database, a hospital-billing data source, evaluated one-year postoperative revision, complication, and economic outcomes of reverse (RTSA) and anatomic (ATSA) TSA for patients who underwent the procedure from 2015 until 2021. All-cause revisits, including revision-related events (categorized as either irrigation and débridement or revision procedures and device removals) and shoulder/non-shoulder complications were collected. The incidences and costs of these revisits were evaluated. Generalized linear models were used to evaluate the associations between patient characteristics and revision and complication occurrences and costs. RESULTS: Among 51,478 RTSA and 34,623 ATSA patients (mean [standard deviation (SD)] ages RTSA 71.5 [8.1] years, ATSA 66.8 [9.0] years), one-year adjusted incidences of all-cause revisits, irrigation/débridement, revision procedures/device removals, and shoulder/non-shoulder complications were RTSA: 45.0% (95% confidence interval (CI): 44.6%-45.5%), 0.1% (95% CI: 0.1%-0.2%), 2.1% (95% CI: 2.0%-2.2%), and 17.8% (95% CI: 17.5%-18.1%) and ATSA: 42.3% (95% CI: 41.8%-42.9%), 0.2% (95% CI: 0.1%-0.2%), 1.9% (95% CI: 1.8%-2.1%), and 14.4% (95% CI: 14.0%-14.8%), respectively; shoulder-related complications were RTSA: 12.4% (95% CI: 12.1%-12.7%) and ATSA: 9.9% (95% CI: 9.6%-10.3%). Significant factors associated with a high risk of revisions and complications included, but were not limited to, chronic comorbidities and noncommercial insurance. Per patient, the mean (SD) total one-year hospital cost was $25,225 ($15,911) and $21,520 ($13,531) for RTSA and ATSA, respectively. Revision procedures and device removals were most costly, averaging $22,920 ($18,652) and $26,911 ($18,619) per procedure for RTSA and ATSA, respectively. Patients with revision-related events with infections had higher total hospital costs than patients without this event (RTSA: $60,887 (95% CI: $56,951-$64,823) and ATSA: $59,478 (95% CI: $52,312-$66,644)), equating to a mean difference of $36,148 with RTSA and $38,426 with ATSA. Significant factors associated with higher costs of revision-related events and complications included age, race, chronic comorbidities, and noncommercial insurance. CONCLUSIONS: Nearly 45% RTSA and 42% ATSA patients returned to the hospital, most often for shoulder/non-shoulder complications (overall 17.8% RTSA and 14.4% ATSA, and shoulder-related 12.4% RTSA and 9.9% ATSA). Revisions and device removals were most expensive ($22,920 RTSA and $26,911 ATSA). Infection complications requiring revision had the highest one-year hospital costs (∼$60,000). This study highlights the need for technologies and surgical techniques that may help reduce TSA healthcare utilization and economic burden.

2.
Pediatr Blood Cancer ; 71(8): e31090, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38807260

RESUMO

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.


Assuntos
RNA Helicases DEAD-box , Neoplasias Renais , Blastoma Pulmonar , Sistema de Registros , Ribonuclease III , Sarcoma , Humanos , RNA Helicases DEAD-box/genética , Ribonuclease III/genética , Blastoma Pulmonar/patologia , Blastoma Pulmonar/terapia , Blastoma Pulmonar/genética , Blastoma Pulmonar/mortalidade , Masculino , Feminino , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Neoplasias Renais/mortalidade , Pré-Escolar , Criança , Lactente , Sarcoma/genética , Sarcoma/patologia , Sarcoma/terapia , Taxa de Sobrevida , Prognóstico , Adolescente , Seguimentos
3.
Nat Commun ; 15(1): 4627, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821962

RESUMO

Stem cells in plants and animals are the source of new tissues and organs. In plants, stem cells are maintained in the central zone (CZ) of multicellular meristems, and large shoot meristems with an increased stem cell population hold promise for enhancing yield. The mobile homeodomain transcription factor WUSCHEL (WUS) is a central regulator of stem cell function in plant shoot meristems. Despite its central importance, the factors that directly modulate WUS protein stability have been a long-standing question. Here, we show that the peptidase DA1 physically interacts with and cleaves the WUS protein, leading to its destabilization. Furthermore, our results reveal that cytokinin signaling represses the level of DA1 protein in the shoot apical meristem, thereby increasing the accumulation of WUS protein. Consistent with these observations, loss of DA1 function results in larger shoot apical meristems with an increased stem cell population and also influences cytokinin-induced enlargement of shoot apical meristem. Collectively, our findings uncover a previously unrecognized mechanism by which the repression of DA1 by cytokinin signaling stabilizes WUS, resulting in the enlarged shoot apical meristems with the increased stem cell number during plant growth and development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Citocininas , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio , Meristema , Meristema/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Citocininas/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Transdução de Sinais , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Estabilidade Proteica
4.
Xenobiotica ; : 1-12, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38794972

RESUMO

In vitro studies using rat, mouse, and human microsomes and hepatocytes on the bacterial ß-glucuronidase inhibitor 1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea) (Inh 1) revealed extensive metabolism in all species.The intrinsic clearances of Inh 1 in human, mouse, and rat hepatic microsomes were 30.9, 67.8, and 201 µL/min/mg, respectively. For intact hepatocytes intrinsic clearances of 21.6, 96.0, and 129 µL/min/106 cells were seen for human, mouse and rat, respectively.The metabolism of Inh 1 involved an uncommon desulphurisation reaction in addition to oxidation, deethylation, and conjugation reactions at multiple sites. Six metabolites were detected in microsomal incubations in human and rat, and seven for the mouse. With hepatocytes, 18 metabolites were characterised, 9 for human, and 11 for mouse and rat.Following IV administration to mice (3 mg/kg), plasma concentrations of Inh 1 exhibited a monophasic decline with a terminal elimination half-life of 0.91 h and low systemic clearance (11.8% of liver blood flow). After PO dosing to mice (3 mg/kg), peak observed Inh 1 concentrations of 495 ng/mL were measured 0.5 h post dose, declining to under 10 ng/mL at 8 h post dose. The absolute oral bioavailability of Inh 1 in the mouse was ca. 26%.

5.
Nat Nanotechnol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783058

RESUMO

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

6.
Breastfeed Med ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695182

RESUMO

Background and Objectives: As cannabis use increases among reproductive-aged women, there is a growing need to better understand the presence of cannabinoids in milk produced by women using cannabis. It is unclear how concentrations of cannabinoids such as delta-9-tetrahydrocannabinol (Δ9-THC) persist in milk after cannabis use and what factors contribute to variation in milk Δ9-THC concentrations. Our objectives were to measure cannabinoids in human milk following cannabis abstention, after single and repeated instances of cannabis use, and identify factors contributing to concentration variation. Methods: The Lactation and Cannabis (LAC) Study prospectively observed 20 breastfeeding participants who frequently used cannabis (≥1/week), had enrolled <6 months postpartum, were feeding their infant their milk ≥5 times/day, and were not using any illicit drugs. Participants collected a baseline milk sample after ≥12 hours of abstaining from cannabis and five milk samples at set intervals over 8-12 hours after initial cannabis use. Participants completed surveys and recorded self-directed cannabis use during the study period. Results: Δ9-THC peaked 120 minutes after a single instance of cannabis use (median, n = 9). More instances of cannabis use during the study period were associated with greater Δ9-THC area-under-the-curve concentrations (ρ = 0.65, p = 0.002), indicating Δ9-THC bioaccumulation in most participants. Baseline Δ9-THC logged concentration was positively associated with self-reported frequency of cannabis use (b = 0.57, p = 0.01). Conclusions: Cannabinoids are measurable in human milk following cannabis use, and concentrations remain elevated with repeated cannabis use over a day. Substantial variation in Δ9-THC milk concentrations reflects individual differences in characteristics and behavior, including average postpartum frequency of cannabis use.

7.
Front Immunol ; 15: 1329092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585272

RESUMO

Background: There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology. Objective: We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis. Methods: This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA. Results: Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding (P=0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater, P≤0.04) of fecal shedding in infants of mothers with COVID-19.


Assuntos
COVID-19 , Lactente , Humanos , Feminino , Masculino , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Aleitamento Materno , Teste para COVID-19 , Lactação , Estudos Longitudinais , RNA Viral , Prevalência , Fezes
8.
BMC Med Educ ; 24(1): 329, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519915

RESUMO

BACKGROUND: A script concordance test (SCT) provides a series of clinical vignettes to assess clinical reasoning in uncertainty. Appraised throughout health education literature, SCTs are cognitive assessments of clinical reasoning, though their use in Doctor of Physical Therapy (DPT) entry-level education has not been investigated. The purpose of this study was to develop and explore the reliability and validity of a SCT for first year DPT students. METHODS: The SCT was developed and implemented over four phases. During phases one and two, DPT program faculty consulted on course content from the first-year curriculum. Thirty clinical vignettes with three follow-up questions each were constructed. The SCT was pilot tested with five clinicians in phase three to assess question clarity. During phase four, the SCT was administered to students and a reference panel via Qualtrics. First year DPT students (n = 44) and reference panel physical therapists with at least two years of experience and advanced certification (n = 15) completed the SCT. Internal consistency was analyzed using Cronbach's Alpha. Differences between student and reference panel percent-correct scores were analyzed with a t-test. Relationships between student SCT scores and academic records were explored with Spearman's Rho. RESULTS: The SCT had an internal consistency of 0.74. A significant difference in scores was found between the students [mean 58.5 (+/-5.31)] and reference panel [65.8 (+/-4.88), p < .01]. No significant correlations between student SCT scores and academic records were found. CONCLUSIONS: The developed SCT was reliable and demonstrated satisfactory internal consistency among test items. The SCT successfully differentiated between groups, with the reference panel demonstrating statistically significant higher percent-correct scores compared to students. SCTs may provide means to measure clinical reasoning in DPT students and lead to novel pedagogical approaches to enhance clinical reasoning.


Assuntos
Competência Clínica , Avaliação Educacional , Humanos , Reprodutibilidade dos Testes , Estudantes , Raciocínio Clínico
9.
Cancer Med ; 13(5): e7094, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468595

RESUMO

BACKGROUND: Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. METHODS: Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. RESULTS: The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. CONCLUSION: The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Prognóstico
10.
J Cannabis Res ; 6(1): 6, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365778

RESUMO

OBJECTIVE: Our primary objective was to understand breastfeeding individuals' decisions to use cannabis. Specifically, we investigated reasons for cannabis use, experiences with healthcare providers regarding use, and potential concerns about cannabis use. METHODS: We collected survey data from twenty breastfeeding participants from Washington and Oregon who used cannabis at least once weekly. We documented individuals' cannabis use and analyzed factors associated with their decisions to use cannabis during lactation. Qualitative description was used to assess responses to an open-ended question about potential concerns. RESULTS: Fifty-five percent of participants (n = 11) reported using cannabis to treat or manage health conditions, mostly related to mental health. Eighty percent of participants (n = 16) reported very few or no concerns about using cannabis while breastfeeding, although participants who used cannabis for medical purposes had significantly more concerns. Most participants (n = 18, 90%) reported receiving either no or unhelpful advice from healthcare providers. Four themes arose through qualitative analysis, indicating that breastfeeding individuals are: 1) identifying research gaps and collecting evidence; 2) monitoring their child's health and development; 3) monitoring and titrating their cannabis use; and 4) comparing risks between cannabis and other controlled substances. CONCLUSIONS: Breastfeeding individuals reported cannabis for medical and non-medical reasons and few had concerns about cannabis use during breastfeeding. Breastfeeding individuals reported using a variety of strategies and resources in their assessment of risk or lack thereof when deciding to use cannabis. Most participants reported receiving no helpful guidance from healthcare providers.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38191998

RESUMO

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

12.
J Integr Complement Med ; 30(2): 173-184, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37566543

RESUMO

Background: Antenatal depression is common and associated with detrimental impacts on women and their families. Disrupted neuroendocrine functioning is reported in women experiencing perinatal mental health disturbances. Preliminary randomized controlled trial (RCT) evidence suggests acupuncture may provide a safe and effective adjunct treatment; however, underlying mechanisms of effect are unclear. We conducted an RCT examination of acupuncture for the management of antenatal depressive symptomologies, which included oxytocinergic and hypothalamic pituitary adrenal (HPA) axis system evaluations. This article reports postintervention changes to cortisol: dehydroepiandrosterone (DHEA) ratios, and oxytocin (OT) hormone concentrations. Methods: Fifty-seven women with Edinburgh Postnatal Depression Scale (EPDS) scores ≥13 were randomized to receive individually tailored depressed specific acupuncture, progressive muscle relaxation (PMR) attention comparator, or treatment as usual (TAU). Weekly 1-h sessions were conducted for 8 weeks (24-31 of pregnancy). Preintervention and postintervention saliva samples were collected. Results: Postintervention mean cortisol: DHEA ratio differences were not significantly predicted by group allocation (n = 46, p = 0.065). Two-group comparisons demonstrated cortisol: DHEA ratios were significantly increased and predicted by group allocation when acupuncture was compared to TAU (p = 0.039); however, not between acupuncture and PMR (p = 0.179), or PMR and TAU (p = 0.421). Postintervention OT concentrations were not significantly predicted by group allocation. Limitations: Small sample size and posthoc analysis Conclusion: Findings suggest positive regulation of the HPA axis may be an underlying mechanism by which acupuncture provided the significant improvements to antenatal depression, stress, and distress observed in this cohort. Trial Registration: Registered on March 19, 2015, with the Australian New Zealand Clinical Trials Registry (ACTRN12615000250538).


Assuntos
Terapia por Acupuntura , Depressão , Gravidez , Feminino , Humanos , Depressão/terapia , Depressão/psicologia , Hidrocortisona/análise , Estudos de Viabilidade , Austrália , Desidroepiandrosterona
13.
Methods Mol Biol ; 2743: 111-122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38147211

RESUMO

Immunofluorescent microscopy enables the examination of cellular expression and localization of proteins. Cellular localization can often impact protein function, as certain molecular interactions occur in specific cellular compartments. Here we describe in detail the processes necessary for identifying phosphatases in the cell through immunofluorescent microscopy. Identification of phosphatase expression and localization could lead to the discovery of protein function in disease states along with potential substrates and binding partners.


Assuntos
Monoéster Fosfórico Hidrolases , Microscopia de Fluorescência
14.
Horm Behav ; 159: 105471, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38128247

RESUMO

Sex differences exist in numerous parameters of the brain. Yet, sex-related factors are part of a large set of variables that interact to affect many aspects of brain structure and function. This raises questions regarding how to interpret findings of sex differences at the level of single brain measures and the brain as a whole. In the present study, we reanalyzed two datasets consisting of measures of oxytocin, vasopressin V1a, and mu opioid receptor binding densities in multiple brain regions in rats. At the level of single brain measures, we found that sex differences were rarely dimorphic and were largely persistent across estrous stage and parental status but not across age or context. At the level of aggregates of brain measures showing sex differences, we tested whether individual brains are 'mosaics' of female-typical and male-typical measures or are internally consistent, having either only female-typical or only male-typical measures. We found mosaicism for measures showing overlap between females and males. Mosaicism was higher a) with a larger number of measures, b) with smaller effect sizes of the sex difference in these measures, and c) in rats with more diverse life experiences. Together, these results highlight the limitations of the binary framework for interpreting sex effects on the brain and suggest two complementary pathways to studying the contribution of sex to brain function: (1) focusing on measures showing dimorphic and persistent sex differences and (2) exploring the relations between specific brain mosaics and specific endpoints.


Assuntos
Encéfalo , Ocitocina , Feminino , Ratos , Masculino , Animais , Encéfalo/metabolismo , Ocitocina/metabolismo , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Ligação Proteica , Caracteres Sexuais
15.
Cancer Immunol Res ; 12(3): 350-362, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38113030

RESUMO

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.


Assuntos
Células Supressoras Mieloides , Neoplasias , Camundongos , Animais , Humanos , Células Mieloides , Neoplasias/terapia , Linfócitos T , Receptores Imunológicos , Microambiente Tumoral , Antígenos CD
16.
Case Rep Otolaryngol ; 2023: 6652012, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143514

RESUMO

Temporal bone osteomas comprise 0.1-1% of benign tumors involving the skull, the majority of which arise in the external auditory canal. More rarely, they can arise from the mastoid portion of the temporal bone. These generally present as a slow growing skull base lesion that can cause cosmetic deformity, headache, and/or hearing loss. Here, we report a case of extracanalicular mastoid osteoma uniquely presenting with posterior fossa and cerebellar compression with associated dizziness and imbalance.

17.
Nat Commun ; 14(1): 8333, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097556

RESUMO

Cytoglobin is a heme protein with unresolved physiological function. Genetic deletion of zebrafish cytoglobin (cygb2) causes developmental defects in left-right cardiac determination, which in humans is associated with defects in ciliary function and low airway epithelial nitric oxide production. Here we show that Cygb2 co-localizes with cilia and with the nitric oxide synthase Nos2b in the zebrafish Kupffer's vesicle, and that cilia structure and function are disrupted in cygb2 mutants. Abnormal ciliary function and organ laterality defects are phenocopied by depletion of nos2b and of gucy1a, the soluble guanylate cyclase homolog in fish. The defects are rescued by exposing cygb2 mutant embryos to a nitric oxide donor or a soluble guanylate cyclase stimulator, or with over-expression of nos2b. Cytoglobin knockout mice also show impaired airway epithelial cilia structure and reduced nitric oxide levels. Altogether, our data suggest that cytoglobin is a positive regulator of a signaling axis composed of nitric oxide synthase-soluble guanylate cyclase-cyclic GMP that is necessary for normal cilia motility and left-right patterning.


Assuntos
Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Humanos , Camundongos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Citoglobina/genética , Padronização Corporal/genética , Óxido Nítrico/metabolismo , Guanilil Ciclase Solúvel/genética , Guanilil Ciclase Solúvel/metabolismo , Cílios/metabolismo , Óxido Nítrico Sintase/metabolismo
18.
BMC Complement Med Ther ; 23(1): 392, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924068

RESUMO

BACKGROUND: Traditional, complementary, and integrative medicine (TCIM) is commonly used by those living with Polycystic Ovary Syndrome (PCOS) but little is known about the use of TCIM such as yoga and Ayurveda in ethnic Indian women with PCOS living worldwide. This survey aimed to explore the prevalence and types of TCIM used and in particular the pattern of use of yoga and Ayurveda including reasons for not using and future interest in using them among non-users. METHOD: An online, international cross-sectional survey was conducted using a pre-designed survey tool. Participants were ethnic Indian women of reproductive age who reported that they were medically diagnosed with PCOS. Descriptive analysis was used to identify the proportion of TCIM users, while a multivariable binary logistic regression was used to analyze their characteristics. RESULTS: Data from 3130 respondents were analysed. The prevalence of TCIM use was 80% (2515/3130). Yoga and Ayurveda were the most frequently practised TCIM modalities with a prevalence of 57% and 37% respectively. We found a high future interest in using yoga (81%) and Ayurveda (70%) among the non-users. The motivation for most Ayurveda use was a recommendation from family/friends (66%), rather than personal choice (38%) or the internet (19%). Most women used Ayurveda because it has natural ingredients (64%) and it is safe (60%) and cited its use to be safe and somewhat helpful. The majority of women were currently practising yoga (73%) up to four times a week (54%) at home (93%). Yoga was primarily used to improve overall health (67%), manage weight (64%), stress (54%) hormonal imbalance (49%) and emotional well-being (48%). Barriers to practising yoga were common among the current users and non-users and included lack of motivation (59% and 59%), time constraints (48% and 39%), and non-availability of yoga teachers specialised in PCOS (31% and 23%). Most women found yoga to be helpful and preferred individual one-on-one (52%) yoga sessions specifically tailored for PCOS (58%). CONCLUSION: This is the first international study that discovered the prevalence and pattern of TCIM use among ethnic Indian women with PCOS living worldwide. We support the urgent need for more research, education, and regulation of different TCIM modalities to promote safe and effective practices globally.


Assuntos
Terapias Complementares , Síndrome do Ovário Policístico , Yoga , Humanos , Feminino , Síndrome do Ovário Policístico/terapia , Estudos Transversais , Inquéritos e Questionários
19.
Artigo em Inglês | MEDLINE | ID: mdl-38011669

RESUMO

OBJECTIVES: Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. METHODS: The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician's effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). RESULTS: 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. CONCLUSIONS: Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT05171270.

20.
Physiol Rep ; 11(20): e15843, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37864278

RESUMO

Ambulatory sleep and blood pressure monitoring are gaining popularity as these can be completed in an individual's home. Little is known regarding the reliability of data and the time it takes to acclimate to the equipment. This study aimed to determine how many nights of wearing the monitoring equipment were required to restore sleep architecture and blood pressure data to baseline. It was hypothesized familiarization would be demonstrated by night 3. Ten male and 10 female subjects completed three nights of sleep and blood pressure recordings. At visit 1, the subjects were familiarized with the equipment and instructed to wear the Sleep Profiler{trade mark, serif} and SunTech Medical Oscar2 ambulatory blood pressure cuff simultaneously for three consecutive nights, then subjects returned the equipment. The percent of time spent in rapid eye-movement (REM) sleep was statistically different on night 3 when compared to night 1. Wake-after-sleep onset and sleep latency were not statistically different between nights 1, 2, and 3. Systolic, diastolic, and pulse pressure were all significantly lower on night 3 compared to night 1. Cortical and autonomic arousals were statistically different on night 3. Ambulatory sleep and blood pressure monitoring need at least 3 nights for familiarization. The percent of time spent in REM sleep was statistically different on night 3 when compared to night 1. Systolic blood pressure, diastolic blood pressure, and pulse pressure were all significantly lower on night 3 compared to night 1. Cortical and autonomic arousals were statistically different on nights 3 and 2, respectively compared to night 1. Based on these findings, ambulatory sleep and blood pressure monitoring takes three nights before the data are reliable and the person is familiarized with the mode of measurement. Therefore, it is recommended to use at least three nights of data collection when using the Sleep Profiler and Oscar2 ambulatory blood pressure cuff in order for results to be valid and reliable.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Sono , Humanos , Masculino , Feminino , Pressão Sanguínea/fisiologia , Reprodutibilidade dos Testes , Sono/fisiologia , Sono REM/fisiologia
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