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1.
Aust Crit Care ; 37(3): 422-428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37316370

RESUMO

BACKGROUND: Data on nutrition delivery over the whole hospital admission in critically ill patients with COVID-19 are scarce, particularly in the Australian setting. OBJECTIVES: The objective of this study was to describe nutrition delivery in critically ill patients admitted to Australian intensive care units (ICUs) with coronavirus disease 2019 (COVID-19), with a focus on post-ICU nutrition practices. METHODS: A multicentre observational study conducted at nine sites included adult patients with a positive COVID-19 diagnosis admitted to the ICU for >24 h and discharged to an acute ward over a 12-month recruitment period from 1 March 2020. Data were extracted on baseline characteristics and clinical outcomes. Nutrition practice data from the ICU and weekly in the post-ICU ward (up to week four) included route of feeding, presence of nutrition-impacting symptoms, and nutrition support received. RESULTS: A total of 103 patients were included (71% male, age: 58 ± 14 years, body mass index: 30±7 kg/m2), of whom 41.7% (n = 43) received mechanical ventilation within 14 days of ICU admission. While oral nutrition was received by more patients at any time point in the ICU (n = 93, 91.2% of patients) than enteral nutrition (EN) (n = 43, 42.2%) or parenteral nutrition (PN) (n = 2, 2.0%), EN was delivered for a greater duration of time (69.6% feeding days) than oral and PN (29.7% and 0.7%, respectively). More patients received oral intake than the other modes in the post-ICU ward (n = 95, 95.0%), and 40.0% (n = 38/95) of patients were receiving oral nutrition supplements. In the week after ICU discharge, 51.0% of patients (n = 51) had at least one nutrition-impacting symptom, most commonly a reduced appetite (n = 25; 24.5%) or dysphagia (n = 16; 15.7%). CONCLUSION: Critically ill patients during the COVID-19 pandemic in Australia were more likely to receive oral nutrition than artificial nutrition support at any time point both in the ICU and in the post-ICU ward, whereas EN was provided for a greater duration when it was prescribed. Nutrition-impacting symptoms were common.


Assuntos
COVID-19 , Estado Terminal , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Teste para COVID-19 , Pandemias , Ingestão de Energia , Tempo de Internação , Austrália , Hospitalização , Unidades de Terapia Intensiva
2.
J Physiol ; 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432936

RESUMO

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury.

3.
N Engl J Med ; 382(11): 989-998, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-31613432

RESUMO

BACKGROUND: Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). METHODS: We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28. RESULTS: The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). CONCLUSIONS: In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the Health Research Council of New Zealand; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).


Assuntos
Oxigenoterapia , Respiração Artificial , Adulto , Idoso , Tratamento Conservador , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Oxigênio/administração & dosagem , Oxigenoterapia/métodos , Resultado do Tratamento , Desmame do Respirador
4.
Aust Crit Care ; 36(6): 955-960, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-36806392

RESUMO

BACKGROUND: The COVID-19 pandemic highlighted major challenges with usual nutrition care processes, leading to reports of malnutrition and nutrition-related issues in these patients. OBJECTIVE: The objective of this study was to describe nutrition-related service delivery practices across hospitalisation in critically ill patients with COVID-19 admitted to Australian intensive care units (ICUs) in the initial pandemic phase. METHODS: This was a multicentre (nine site) observational study in Australia, linked with a national registry of critically ill patients with COVID-19. Adult patients with COVID-19 who were discharged to an acute ward following ICU admission were included over a 12-month period. Data are presented as n (%), median (interquartile range [IQR]), and odds ratio (OR [95% confidence interval {CI}]). RESULTS: A total of 103 patients were included. Oral nutrition was the most common mode of nutrition (93 [93%]). In the ICU, there were 53 (52%) patients seen by a dietitian (median 4 [2-8] occasions) and malnutrition screening occurred in 51 (50%) patients most commonly with the malnutrition screening tool (50 [98%]). The odds of receiving a higher malnutrition screening tool score increased by 36% for every screening in the ICU (1st to 4th, OR: 1.39 [95% CI: 1.05-1.77] p = 0.018) (indicating increasing risk of malnutrition). On the ward, 51 (50.5%) patients were seen by a dietitian (median time to consult: 44 [22.5-75] hours post ICU discharge). The odds of dietetic consult increased by 39% every week while on the ward (OR: 1.39 [1.03-1.89], p = 0.034). Patients who received mechanical ventilation (MV) were more likely to receive dietetic input than those who never received MV. CONCLUSIONS: During the initial phases of the COVID-19 pandemic in Australia, approximately half of the patients included were seen by a dietitian. An increased number of malnutrition screens were associated with a higher risk score in the ICU and likelihood of dietetic consult increased if patients received MV and as length of ward stay increased.


Assuntos
COVID-19 , Desnutrição , Adulto , Humanos , Estado Terminal , Pandemias , Austrália/epidemiologia , Hospitalização , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Unidades de Terapia Intensiva
5.
Breast Cancer Res Treat ; 191(1): 63-75, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34698969

RESUMO

PURPOSE: Invasion of carcinoma cells into surrounding tissue affects breast cancer staging, influences choice of treatment, and impacts on patient outcome. KIF21A is a member of the kinesin superfamily that has been well-studied in congenital extraocular muscle fibrosis. However, its biological relevance in breast cancer is unknown. This study investigated the functional roles of KIF21A in this malignancy and examined its expression pattern in breast cancer tissue. METHODS: The function of KIF21A in breast carcinoma was studied in vitro by silencing its expression in breast cancer cells and examining the changes in cellular activities. Immunohistochemical staining of breast cancer tissue microarrays was performed to determine the expression patterns of KIF21A. RESULTS: Knocking down the expression of KIF21A using siRNA in MDA-MB-231 and MCF7 human breast cancer cells resulted in significant decreases in tumor cell migration and invasiveness. This was associated with reduced Patched 1 expression and F-actin microfilaments. Additionally, the number of focal adhesion kinase- and paxillin-associated focal adhesions was increased. Immunohistochemical staining of breast cancer tissue microarrays showed that KIF21A was expressed in both the cytoplasmic and nuclear compartments of carcinoma cells. Predominance of cytoplasmic KIF21A was significantly associated with larger tumors and high grade cancer, and prognostic of cause-specific overall patient survival and breast cancer recurrence. CONCLUSION: The data demonstrates that KIF21A is an important regulator of breast cancer aggressiveness and may be useful in refining prognostication of this malignant disease.


Assuntos
Neoplasias da Mama , Cinesinas , Neoplasias da Mama/genética , Citoplasma , Feminino , Humanos , Cinesinas/genética , Recidiva Local de Neoplasia/genética , Prognóstico
6.
Brain Cogn ; 154: 105789, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509124

RESUMO

Transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (DLPFC) was used to improve foreign-langue learning while using mental imagery. Participants underwent two sessions of 1 mA, 1.5 mA, or sham stimulation prior to learning Swahili-English word pairs two consecutive days. During learning, participants were encouraged to create a mental image of the associated English word. Twenty-four hours after learning and one week later, participants received a cued recall test. A linear dose-response effect of stimulation was found across both tests that occurred long after the immediate effects of stimulation. Follow-up comparisons revealed that only the 1.5 mA condition differed from the sham group. Exploratory moderating effects revealed interactions with sleep quality and handedness. Those with poorer sleep and who were left-handed showed greater recall after 1.5 mA of stimulation than those with better sleep and right-handers. A follow-up behavioral study probing strategy usage indicated that mental imagery strategy use did not strongly impact learning but point to other possible mechanisms including the importance of attending to multimodal perceptual details and memory consolidation. This preliminary evidence supports the role of the DLPFC or connected regions in foreign language vocabulary learning and verbal memory encoding.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Idioma , Rememoração Mental , Córtex Pré-Frontal , Vocabulário
7.
Am J Physiol Regul Integr Comp Physiol ; 319(6): R653-R665, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33074015

RESUMO

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (P < 0.001), increased arterial pressure (P < 0.001), and reduced femoral (P < 0.005) and carotid (P < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia (P < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.


Assuntos
Asfixia Neonatal/tratamento farmacológico , Glicemia/efeitos dos fármacos , Dexametasona/toxicidade , Coração Fetal/efeitos dos fármacos , Glucocorticoides/toxicidade , Hemodinâmica/efeitos dos fármacos , Hiperglicemia/induzido quimicamente , Nascimento Prematuro/tratamento farmacológico , Animais , Animais Recém-Nascidos , Pressão Arterial/efeitos dos fármacos , Asfixia Neonatal/sangue , Asfixia Neonatal/fisiopatologia , Biomarcadores/sangue , Glicemia/metabolismo , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Coração Fetal/fisiopatologia , Idade Gestacional , Glucocorticoides/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/fisiopatologia , Nascimento Prematuro/sangue , Nascimento Prematuro/fisiopatologia , Carneiro Doméstico , Fatores de Tempo
8.
Am J Respir Crit Care Med ; 200(11): 1363-1372, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31356105

RESUMO

Rationale: Open lung ventilation strategies have been recommended in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine whether a maximal lung recruitment strategy reduces ventilator-free days in patients with ARDS.Methods: A phase II, multicenter randomized controlled trial in adults with moderate to severe ARDS. Patients received maximal lung recruitment, titrated positive end expiratory pressure and further Vt limitation, or control "protective" ventilation.Measurements and Main Results: The primary outcome was ventilator-free days at Day 28. Secondary outcomes included mortality, barotrauma, new use of hypoxemic adjuvant therapies, and ICU and hospital stay. Enrollment halted October 2, 2017, after publication of ART (Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial), when 115 of a planned 340 patients had been randomized (57% male; mean age, 53.6 yr). At 28 days after randomization, there was no difference between the maximal lung recruitment and control ventilation strategies in ventilator-free days (median, 16 d [interquartile range (IQR), 0-21 d], n = 57, vs. 14.5 d [IQR, 0-21.5 d], n = 56; P = 0.95), mortality (24.6% [n = 14/56] vs. 26.8% [n = 15/56]; P = 0.79), or the rate of barotrauma (5.2% [n = 3/57] vs. 10.7% [n = 6/56]; P = 0.32). However, the intervention group showed reduced use of new hypoxemic adjuvant therapies (i.e., inhaled nitric oxide, extracorporeal membrane oxygenation, prone; median change from baseline 0 [IQR, 0-1] vs. 1 [IQR, 0-1]; P = 0.004) and increased rates of new cardiac arrhythmia (n = 17 [29%] vs. n = 7 [13%]; P = 0.03).Conclusions: Compared with control ventilation, maximal lung recruitment did not reduce the duration of ventilation-free days or mortality and was associated with increased cardiovascular adverse events but lower use of hypoxemic adjuvant therapies.Clinical trial registered with www.clinicaltrials.gov (NCT01667146).


Assuntos
Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/métodos , Respiração com Pressão Positiva/mortalidade , Respiração Artificial/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , Análise de Sobrevida
9.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255257

RESUMO

Progressive fetal infection/inflammation is strongly associated with neural injury after preterm birth. We aimed to test the hypotheses that progressively developing fetal inflammation leads to neuroinflammation and impaired white matter development and that the histopathological changes can be detected using high-field diffusion tensor magnetic resonance imaging (MRI). Chronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive intravenous saline (control; n = 6) or a progressive infusion of lipopolysaccharide (LPS, 200 ng intravenous over 24 h then doubled every 24 h for 5 days to induce fetal inflammation, n = 7). Sheep were killed 10 days after starting the infusions, for histology and high-field diffusion tensor MRI. Progressive LPS infusion was associated with increased circulating interleukin (IL)-6 concentrations and moderate increases in carotid artery perfusion and the frequency of electroencephalogram (EEG) activity (p < 0.05 vs. control). In the periventricular white matter, fractional anisotropy (FA) was increased, and orientation dispersion index (ODI) was reduced (p < 0.05 vs. control for both). Histologically, in the same brain region, LPS infusion increased microglial activation and astrocyte numbers and reduced the total number of oligodendrocytes with no change in myelination or numbers of immature/mature oligodendrocytes. Numbers of astrocytes in the periventricular white matter were correlated with increased FA and reduced ODI signal intensities. Astrocyte coherence was associated with increased FA. Moderate astrogliosis, but not loss of total oligodendrocytes, after progressive fetal inflammation can be detected with high-field diffusion tensor MRI.


Assuntos
Gliose/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Animais , Gliose/fisiopatologia , Gliose/veterinária , Inflamação/fisiopatologia , Inflamação/veterinária , Leucoencefalopatias/fisiopatologia , Leucoencefalopatias/veterinária , Ovinos , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia
10.
Fam Process ; 59(3): 1293-1307, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31497888

RESUMO

This study investigated the longitudinal associations between mastery, conflict management behaviors, and depressive symptoms using an actor-partner interdependence model with 371 middle-aged couples over a span of 24 years. Results indicated that for both husbands and wives, individuals who possessed higher levels of mastery generally displayed more constructive conflict management behaviors during marital conflicts in middle years. In turn, individuals with more constructive behaviors averaged fewer depressive symptoms in their later adulthood. A partner effect was also noted, as individuals' constructive behaviors were linked to their spouse's depressive symptoms. This finding emphasizes the importance of utilizing a dyadic context to understand intra-individual and inter-individual (or crossover) influences between husbands and wives in enduring marriages. A better understanding of how couples affect each other's mental health can inform the development and implementation of health promotion interventions and prevention efforts targeting middle-aged couples.


Este estudio investigó las asociaciones longitudinales entre el control, las conductas de manejo de conflictos y los síntomas depresivos usando un modelo de interdependencia actor-pareja con 371 parejas de mediana edad durante un periodo de 24 años. Los resultados indicaron que tanto en el caso de los esposos como en el de las esposas, las personas que tuvieron niveles más altos de control generalmente demostraron conductas más constructivas de manejo de conflictos durante los conflictos conyugales en la mediana edad. A su vez, las personas con más conductas constructivas promediaron menos síntomas depresivos en su tercera edad. También se observó un efecto de pareja, ya que las conductas constructivas de las personas estuvieron asociadas con los síntomas depresivos de su cónyuge. Este resultado enfatiza la importancia de utilizar un contexto diádico para comprender las influencias intraindividuales e interindividuales (o cruces) entre los esposos y las esposas en los matrimonios duraderos. Una mejor comprensión de cómo las parejas influyen mutuamente en su salud mental puede contribuir al desarrollo y la implementación de intervenciones de promoción de la salud y de esfuerzos de prevención dirigidos a las parejas en la mediana edad.


Assuntos
Depressão/psicologia , Conflito Familiar/psicologia , Casamento/psicologia , Negociação/psicologia , Cônjuges/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Saúde Mental , Pessoa de Meia-Idade
11.
P T ; 43(2): 92-104, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29386866

RESUMO

Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.

12.
Am J Pathol ; 186(1): 199-209, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26608452

RESUMO

Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV.


Assuntos
Mucolipidoses/patologia , Nervo Óptico/patologia , Distrofias Retinianas/patologia , Animais , Western Blotting , Modelos Animais de Doenças , Eletrorretinografia , Imunofluorescência , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucolipidoses/complicações , Tomografia de Coerência Óptica , Canais de Potencial de Receptor Transitório/deficiência , Canais de Potencial de Receptor Transitório/genética
13.
J Lat Psychol ; 12(2): 186-200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39006970

RESUMO

Introduction: Experiences of stressful life events (SLEs) during childhood are associated with greater risk for youth psychopathology. Although SLEs are reported in greater frequency by Latinx families, Latinx populations remain largely absent in the SLE literature. Furthermore, Latinx populations face added stressors related to socio-political climate, acculturation, and racism and discrimination. The purpose of this study was to explore the intersection between parent-reported SLEs and acculturation (i.e., socio-political climate-related) stressors for Latinx youth. Greater frequency of caregiver reported SLEs were hypothesized to predict higher depressive symptoms in their children three years later, and acculturation stress was hypothesized to amplify these effects. Method: The community-recruited, low-income sample for this study consisted of 198 Latinx caregivers (98.5% mothers, 77.3% foreign-born) and their children (M age = 7.4, 47.5% female). Study hypotheses were tested using MPlus. Results: Consistent with prior literature, more SLEs reported at age 7 by parents were associated with more child-reported depressive symptoms at age 10 but only among boys. However, for both boys and girls, there was a significant interaction between acculturation stress and family SLEs. Specifically, as the amount of acculturation stress reported at age 7 increased, the negative impact of family SLEs on child-reported depressive symptoms at age 10 was magnified, regardless of gender. Conclusion: Adding to the literature on SLEs within Latinx families, these results indicate that acculturation and socio-political climate stressors need be considered in discussions of the effects of life stress on Latinx youth and their families.

14.
J Cereb Blood Flow Metab ; : 271678X241236014, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38415649

RESUMO

Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.

15.
Lancet Psychiatry ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38795722

RESUMO

In recent history, the world has witnessed a trend towards liberalization of abortion laws driven by an increasing understanding of the negative personal and public health consequences of criminalizing abortion. By contrast, several countries have recently implemented restrictive reproductive laws, joining the 112 countries where access to abortion care is banned completely or with narrow exceptions. On June 24, 2022, the US Supreme Court ruling in Dobbs v Jackson Women's Health Organization overturned its landmark decisions in Roe v Wade that established abortion until the point of viability of the fetus as a constitutional right. After Roe v Wade having been overturned, it is projected that many women in the USA will be prevented from accessing safe abortion care. Importantly, abortion bans not only impose constraints on patient autonomy, they also restrict physicians' ability to practice evidence-based medicine, which will negatively impact psychiatric care. It is therefore crucial for the practicing psychiatrist to be familiar with this new legal landscape. In this Personal View, we aim to provide a topical overview to help clinicians gain a clear understanding of legal, clinical, and ethical responsibilities, focusing on the USA. We also discuss the reality that psychiatrists might be called upon to determine medical necessity for an abortion on psychiatric grounds, which is new for most US psychiatrists. We predict that psychiatrists will be confronted with very difficult situations in which lawful and ethical conduct might be incongruent, and that abortion bans will result in greater numbers of patients needing psychiatric care from a system that is ill-prepared for additional demands.

16.
Sports Med Open ; 10(1): 49, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689130

RESUMO

BACKGROUND: Psychological readiness is an important consideration for athletes and clinicians when making return to sport decisions following anterior cruciate ligament reconstruction (ACLR). To improve our understanding of the extent of deficits in psychological readiness, a systematic review is necessary. OBJECTIVE: To investigate psychological readiness (measured via the Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI)) over time after ACL tear and understand if time between injury and surgery, age, and sex are associated with ACL-RSI scores. METHODS: Seven databases were searched from the earliest date available to March 22, 2022. Articles reporting ACL-RSI scores after ACL tear were included. Risk of bias was assessed using the ROBINS-I, RoB-2, and RoBANS tools based on the study design. Evidence certainty was assessed for each analysis. Random-effects meta-analyses pooled ACL-RSI scores, stratified by time post-injury and based on treatment approach (i.e., early ACLR, delayed ACLR, and unclear approach). RESULTS: A total of 83 studies were included in this review (78% high risk of bias). Evidence certainty was 'weak' or 'limited' for all analyses. Overall, ACL-RSI scores were higher at 3 to 6 months post-ACLR (mean = 61.5 [95% confidence interval (CI) 58.6, 64.4], I2 = 94%) compared to pre-ACLR (mean = 44.4 [95% CI 38.2, 50.7], I2 = 98%), remained relatively stable, until they reached the highest point 2 to 5 years after ACLR (mean = 70.7 [95% CI 63.0, 78.5], I2 = 98%). Meta-regression suggests shorter time from injury to surgery, male sex, and older age were associated with higher ACL-RSI scores only 3 to 6 months post-ACLR (heterogeneity explained R2 = 47.6%), and this reduced 1-2 years after ACLR (heterogeneity explained R2 = 27.0%). CONCLUSION: Psychological readiness to return to sport appears to improve early after ACL injury, with little subsequent improvement until ≥ 2-years after ACLR. Longer time from injury to surgery, female sex and older age might be negatively related to ACL-RSI scores 12-24 months after ACLR. Due to the weak evidence quality rating and the considerable importance of psychological readiness for long-term outcomes after ACL injury, there is an urgent need for well-designed studies that maximize internal validity and identify additional prognostic factors for psychological readiness at times critical for return to sport decisions. REGISTRATION: Open Science Framework (OSF), https://osf.io/2tezs/ .

17.
J Clin Transl Sci ; 7(1): e57, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008610

RESUMO

Introduction: Optimizing the effectiveness of a team-based approach to unite multiple disciplines in advancing specific translational areas of research is foundational to improving clinical practice. The current study was undertaken to examine investigators' experiences of participation in transdisciplinary team science initiatives, with a focus on challenges and recommendations for improving effectiveness. Methods: Qualitative interviews were conducted with investigators from twelve multidisciplinary teams awarded pilot research funding by the University of Kentucky College of Medicine to better understand the barriers and facilitators to effective team science within an academic medical center. An experienced qualitative researcher facilitated one-on-one interviews, which lasted about one hour. Structured consensus coding and thematic analysis were conducted. Results: The sample was balanced by gender, career stage (five were assistant professor at the time of the award, seven were senior faculty), and training (six were PhDs; six were MD physicians). Key themes at the team-level centered on the tension between clinical commitments and research pursuits and the limitations for effective team functioning. Access to tangible support from home departments and key university centers was identified as a critical organizational facilitator of successful project completion. Organizational barriers centered on operationalizing protected time for physicians, gaps in effective mentoring, and limitations in operational support. Conclusions: Prioritizing tailored mentoring and career development support for early career faculty, and particularly physician faculty, emerged as a key recommendation for improving team science in academic medical centers. The findings contribute to establishing best practices and policies for team science in academic medical centers.

18.
Sports (Basel) ; 11(4)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37104151

RESUMO

Clinicians frequently assess asymmetry in strength, flexibility, and performance characteristics as a method of screening for potential musculoskeletal injury. The identification of asymmetry in countermovement jumps may be an ideal method to reveal asymmetry in other lower extremity characteristics such as strength that otherwise may require additional testing, potentially reducing the time and burden on both the athlete and clinicians. The present study aims to examine the ability of asymmetry in both the single-leg and two-leg countermovement jump tests to accurately detect hip abduction, hip adduction, and eccentric hamstring strength asymmetry. Fifty-eight young male elite soccer players from the same professional academy performed a full battery of functional performance tests which included an assessment of hip adductor and abductor strength profiles, eccentric hamstring strength profiles, and neuromuscular performance and asymmetries during countermovement jumps. Bilateral variables attained from both the single-leg and two-leg countermovement jump tests included concentric impulse (Ns), eccentric mean force (N), and concentric mean force (N) computed by the VALD ForceDecks software. Average maximal force (N) was calculated bilaterally for the strength assessments. Asymmetry was calculated for each variable using 100 × |(right leg - left leg)/(right leg)| and grouped into three categories: 0 to <10%, 10% to <20%, and 20% or greater. Analyses were performed for the two higher asymmetry groups. The accuracy to detect strength asymmetry was assessed as the sensitivity, specificity, and predictive values for positive and negative tests. The outcomes from the accuracy assessments suggest that the single-leg countermovement jump concentric impulse variable at the 20% threshold is indicative of a youth male soccer player having hip adduction strength asymmetry while also demonstrating more accuracy and applicability than the two-leg countermovement jump concentric impulse variable.

19.
J Clin Transl Sci ; 7(1): e59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008617

RESUMO

Introduction: Impactful, transdisciplinary scientific discoveries are created by teams of researchers spanning multiple disciplines, but collaboration across disciplines can be challenging. We examined how team dynamics and collaboration are related to successes and barriers faced by teams of researchers from multiple disciplines. Methods: A mixed-methods approach was used to examine 12 research teams granted multidisciplinary pilot awards. Team members were surveyed to assess their team dynamics and individual views about transdisciplinary research. Forty-seven researchers (59.5%) responded, including two to eight members from each funded team. Associations were examined between collaborative dynamics and scholarly product outcomes, including manuscripts, grant proposals, and awarded grants. One member from each team was selected for an in-depth interview to contextualize and extend information about collaborative processes, successes, and barriers to performing transdisciplinary research. Results: Quality of team interactions was positively associated with achievement of scholarly products (r = 0.64, p = 0.02). Satisfaction with team members (r = 0.38) and team collaboration scores (r = 0.43) also demonstrated positive associations with achievement of scholarly products, but these were not statistically significant. Qualitative results support these findings and add further insight into aspects of the collaborative process that were particularly important to foster success on multidisciplinary teams. Beyond scholarly metrics, additional successes from the multidisciplinary teams were identified through the qualitative portion of the study including career development and acceleration for early career researchers. Conclusions: Both the quantitative and qualitative study results indicate that effective collaboration is critical to multidisciplinary research team success. Development and/or promotion of team science-based trainings for researchers would promote these collaborative skills.

20.
Curr Opin Lipidol ; 22(4): 302-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21734573

RESUMO

PURPOSE OF REVIEW: Serum amyloid A (SAA) is a family of acute-phase proteins which are shown to correlate with cardiovascular disease, but whether this SAA contributes causally to atherosclerosis development or reflects underlying disease or risk factors remains unclear. RECENT FINDINGS: SAA has been detected within atherosclerotic lesions and within adipose tissue where it is hypothesized that it may play a contributory role in disease development. In the acute-phase response SAA is synthesized by the liver and transported primarily in association with HDL. However, there is a growing literature suggesting that localized synthesis of SAA within the vasculature, or adipose tissue, may play a distinct role in disease development. Furthermore, SAA can be found in association with apoB-containing lipoproteins, in which its biological activity may be different. SUMMARY: This review will discuss recent experimental evidence supporting a causal role of SAA with atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Proteína Amiloide A Sérica/metabolismo , Animais , Aterosclerose/fisiopatologia , Humanos , Lipoproteínas LDL/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Proteoglicanas/metabolismo
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