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1.
Surg Endosc ; 38(7): 3849-3857, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38831212

RESUMO

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) has been well utilized in treating malignant gastric outlet obstructions (GOO) given its efficacy and lower risk profile compared to surgery. However, its efficacy and potential for use in patients with benign GOO who are poor surgical candidates is not well documented. The aim of this study was to examine the role of EUS-GJ in treatment of benign GOO in select patients. PATIENTS AND METHODS: This is a single-center, open-label, retrospective descriptive study that included all consecutive patients undergoing EUS-GJ to treat benign causes of GOO. Direct antegrade and direct retrograde methods were utilized. RESULTS: A total of 18 patients were included, 38.9% female with an average age of 63.3 years. Extrinsic GOO was present in (10 of 18) 55.5% of patients and intrinsic etiology was present in (8 of 18) 45.5% of patients. Technical success was achieved in 100% (18 of 18) patients and clinical success was achieved in 94% (17 of 18) patients. In total, 13 patients had follow-up endoscopy, 2 patients were treated relatively recently in time, 1 patient was lost to follow-up, and 2 patients died of other chronic illnesses. Stents remained in place for a median of 286 days (range 88-1444 days). In patients whose stents were removed, 75% (3 of 4) had extrinsic etiologies of GOO. CONCLUSIONS: This study reports a favorable long-term patency with excellent technical and clinical success of EUS-GJ in patients with benign GOO. Despite the limitations of sample size and retrospective nature, it adds to the extremely limited literature of EUS-GJ in management of patients with benign GOO.


Assuntos
Endossonografia , Derivação Gástrica , Obstrução da Saída Gástrica , Ultrassonografia de Intervenção , Humanos , Obstrução da Saída Gástrica/cirurgia , Obstrução da Saída Gástrica/etiologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Masculino , Derivação Gástrica/métodos , Endossonografia/métodos , Idoso , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos , Adulto , Idoso de 80 Anos ou mais
3.
JPGN Rep ; 5(2): 175-177, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38756110

RESUMO

Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and critical illness. This patient had previously undergone treatment with 6-mercaptopurine and presented with pancreatitis that eventually worsened to a walled-off necrotic collection with paracolic extensions reaching the pelvis. Given clinical worsening with development of shock, procedural options for source control were weighed with gastroenterology, pediatric surgery, and interventional radiology, before pancreatic necrosectomy was determined to be the treatment of choice, given the adjacency of the collection to the stomach. A total of three separate endoscopic pancreatic necrosectomy procedures were performed and the patient s clinical status improved greatly, with vast improvement later seen on outpatient imaging. This successful treatment course argues for the efficacy of pancreatic necrosectomy even in very large walled off collections, and most importantly, lead to a positive outcome in this young patient.

4.
Can J Diabetes ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38735638

RESUMO

OBJECTIVES: Expert guidelines recommend an aerobic cooldown to lower blood glucose for the management of post-exercise hyperglycemia. This strategy has never been empirically tested. Our aim in this study was to compare the glycemic effects of performing an aerobic cooldown vs not performing a cooldown after a fasted resistance exercise session. We hypothesized that the cooldown would lower blood glucose in the 30 minutes after exercise and would result in less time in hyperglycemia in the 6 hours after exercise. METHODS: Participants completed 2 identical resistance exercise sessions. One was followed by a low-intensity (30% of peak oxygen consumption) 10-minute cycle ergometer cooldown, and the other was followed by 10 minutes of sitting. We compared the changes in capillary glucose concentration during these sessions and continuous glucose monitoring (CGM) outcomes over 24 hours post-exercise. RESULTS: Sixteen participants completed the trial. Capillary glucose was similar between conditions at the start of exercise (p=0.07). Capillary glucose concentration decreased by 0.6±1.0 mmol/L during the 10-minute cooldown, but it increased by 0.7±1.3 mmol/L during the same time in the no-cooldown condition. The resulting difference in glucose trajectory led to a significant interaction (p=0.02), with no effect from treatment (p=0.7). Capillary glucose values at the end of recovery were similar between conditions (p>0.05). There were no significant differences in CGM outcomes. CONCLUSIONS: An aerobic cooldown reduces glucose concentration in the post-exercise period, but the small and brief nature of this reduction makes this strategy unlikely to be an effective treatment for hyperglycemia occurring after fasted exercise.

6.
Immunometabolism (Cobham) ; 6(2): e00040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38680993

RESUMO

Background: Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c. Methods: A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis. Results: Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c. Conclusions: In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children. Trial registration: This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).

7.
J Vis Exp ; (206)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38647284

RESUMO

Endovascular treatment of complex vascular anomalies shifts the risk of open surgical procedures to the benefit of minimally invasive endovascular procedural solutions. Complex open surgical procedures used to be the only option for the treatment of a myriad of conditions like pulmonary and aortic valve replacement as well as cerebral aneurysm repair. However, due to advancements in catheter-delivered devices and operator expertise, these procedures (along with many others) can now be performed through minimally invasive procedures delivered through a central or peripheral vein or artery. The decision to shift from an open procedure to an endovascular approach is based on multi-modal imaging, often including 3D Digital Imaging and Communications in Medicine (DICOM) imaging datasets. Utilizing these 3D images, our lab generates 3D models of the pathologic anatomy, thereby allowing the pre-procedural analysis necessary to pre-plan critical components of the catheterization lab procedure, namely, C-arm positioning, 3D measurement, and idealized road-map generation. This article describes how to take segmented 3D models of patient-specific pathology and predict generalized C-arm positions, how to measure critical two-dimensional (2D) measurements of 3D structures relevant to the 2D fluoroscopy projections, and how to generate 2D fluoroscopy roadmap analogs that can assist in proper C-arm positioning during catheterization lab procedures.


Assuntos
Imageamento Tridimensional , Realidade Virtual , Humanos , Imageamento Tridimensional/métodos , Procedimentos Endovasculares/métodos , Medicina de Precisão/métodos
8.
J Sex Res ; : 1-19, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517458

RESUMO

Despite increasing scientific and policy interest in sexual wellbeing, it remains poorly conceptualized. Many studies purporting to measure it instead measure related but distinct concepts, such as sexual satisfaction. This lack of conceptual clarity impedes understanding, measuring, and improving sexual wellbeing. We present qualitative research from multi-stage, mixed-methods work to develop a new measure of sexual wellbeing (Natsal-SW) for the fourth British National Survey of Sexual Attitudes & Lifestyles. Literature review and discussion generated a conceptual framework with seven proposed domains: respect, self-esteem, comfort, self-determination, safety and security, forgiveness, and resilience. Semi-structured interviews with 40 adults aged 18-64 then explored whether and how these domains aligned with participants' own understandings, experiences, and language of sexual wellbeing. Data were analyzed thematically. Participants conceptualized sexual wellbeing as distinct from sexual satisfaction and sexual health and as multidimensional, dynamic, and socially and structurally influenced. All seven proposed domains resonated with accounts of sexual wellbeing as a general construct. The personal salience of different domains and their dimensions varied between individuals (especially by gender and sexual orientation) and fluctuated individually over time. This study clarifies dimensions of domains that participants considered important, providing an empirical basis to inform development of a new measure of sexual wellbeing.

10.
J Environ Manage ; 352: 120054, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38211432

RESUMO

Adoption of edge-of-field conservation practices, such as denitrifying bioreactors, may be intrinsically linked to barriers associated with cost. However, most previous bioreactor cost efficiency assessments assumed values for either costs and/or nitrate removal. The objective of this work was to use actual construction costs as well as monitored nitrate removal to develop empirical cost efficiencies for eight full-size bioreactors in Illinois, USA. Capital construction costs were obtained via invoices or personal communications. A cash-flow discounting procedure was used to develop an equal annualized cost for each bioreactor assuming two media recharges over a 24-y planning horizon. These costs were combined with monitored nitrate removal based on one to six years of monitoring per site. Construction costs averaged $12,250 ± $7520 across the eight sites (or, $16,020 ± $9960 in 2023 price levels) but considering one of the sites was a paired bioreactor system, costs averaged $10,890 per bioreactor unit. Drainage treatment area-based cost averaged $132/ha-y and treatment area was strongly correlated with capital costs (R2 = 0.90; p = 0.001). The bioreactors averaged $108/m3 of woodchips and available federal government conservation programs could have offset an average of 70% of this cost. Monitored nitrate removal across 27 site-years resulted in a median of $33/kg N-y removed. This mass-based cost efficiency was higher than most previous assessments because the monitored nitrate removal for the study sites was lower than has been previously assumed or modeled. Future reporting about bioreactor recharge timing and cost will help guide assessment and planning. Water quality planning efforts should also consider the increasingly important engineering design costs, which were not included here. Suggested research and outreach to improve bioreactor cost efficiencies involves scaling the physical capacity of this technology for larger treatment areas, revisiting the use of low-cost non-standard fill media, and providing practical construction training.


Assuntos
Desnitrificação , Nitratos , Reatores Biológicos , Illinois
11.
Curr Diab Rep ; 24(4): 61-73, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38294726

RESUMO

PURPOSE OF REVIEW: Maintaining positive health behaviours promotes better health outcomes for people with type 1 diabetes (T1D). However, implementing these behaviours may also lead to additional management burdens and challenges. Diabetes technologies, including continuous glucose monitoring systems, automated insulin delivery systems, and digital platforms, are being rapidly developed and widely used to reduce these burdens. Our aim was to review recent evidence to explore the influence of these technologies on health behaviours and well-being among adults with T1D and discuss future directions. RECENT FINDINGS: Current evidence, albeit limited, suggests that technologies applied in diabetes self-management education and support (DSME/S), nutrition, physical activity (PA), and psychosocial care areas improved glucose outcomes. They may also increase flexibility in insulin adjustment and eating behaviours, reduce carb counting burden, increase confidence in PA, and reduce mental burden. Technologies have the potential to promote health behaviours changes and well-being for people with T1D. More confirmative studies on their effectiveness and safety are needed to ensure optimal integration in standard care practices.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/psicologia , Automonitorização da Glicemia , Promoção da Saúde , Glicemia , Insulina , Comportamentos Relacionados com a Saúde , Tecnologia
12.
Int J Radiat Biol ; 100(1): 28-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37603396

RESUMO

PURPOSE: Over the years, animal models of local heart irradiation have provided insight into mechanisms of and treatments for radiation-induced heart disease in human populations. However, it is not completely clear which manifestations of radiation injury are most commonly seen after whole heart irradiation, and whether certain biological factors impact experimental results. Combining 9 homogeneous studies in rat models of whole heart irradiation from one laboratory, we sought to identify experimental and/or biological factors that impact heart outcomes. We evaluated the usefulness of including (1) heart rate and (2) bodyweight as covariates when analyzing biological parameters, and (3) we determined which echocardiography, histological, and immunohistochemistry parameters are most susceptible to radiation effects. Finally, (4) as an educational example, we illustrate a hypothetical sample size calculation for a study design commonly used in evaluating radiation modifiers, using the pooled estimates from the 9 rat studies only for context. The results may assist investigators in the design and analyses of pre-clinical studies of whole heart irradiation. MATERIALS AND METHODS: We made use of data from 9 rat studies from our labs, 8 published elsewhere in 2008-2017, and one unpublished study. Echocardiography, histological, and immunohistochemical parameters were collected from these studies. Using mixed effects analysis of covariance models, we estimated slopes for heart rate and bodyweight and estimated the radiation effect on each of the parameters. RESULTS: Bodyweight was related to most echocardiography parameters, and heart rate had an effect on echocardiography parameters related to the diameter of the left ventricle. For some parameters, there was evidence that heart rate and bodyweight relationships with the parameter depended on whether the rats were irradiated. Radiation effects were found in systolic measures of echocardiography parameters related to the diameter of the left ventricle, with ejection fraction and fractional shortening, with atrial wall thickness, and with histological measures of capillary density, collagen deposition, and mast cells infiltration in the heart. CONCLUSION: Accounting for bodyweight, as well as heart rate, in analyses of echocardiography parameters should reduce variability in estimated radiation effects. Several echocardiography and histological parameters were particularly susceptible to whole heart irradiation, showing robust effects compared to sham-irradiation. Lastly, we provide an example approach for a sample size calculation that will contribute to a rigorous study design and reproducibility in experiments studying radiation modifiers.


Assuntos
Cardiopatias , Lesões por Radiação , Ratos , Humanos , Animais , Reprodutibilidade dos Testes , Coração/efeitos da radiação , Átrios do Coração/patologia , Fatores Biológicos
13.
Pediatr Pulmonol ; 59(1): 48-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37772681

RESUMO

RATIONALE: Metformin is a commonly used antidiabetes medication with suggested anti-inflammatory and antioxidative effects. Metformin use has been associated with lower risk of asthma exacerbations and hospitalizations in adults. Here, we aimed to evaluate how asthma exacerbation rates changed after adolescents and young adults were prescribed metformin, and to learn if those changes were related to metformin prescription adherence. METHODS: Using secondary data of patients between 12 and 20 years old with asthma diagnosis and a metformin prescription from the Arkansas All Payers Claim Database and Arkansas School body mass index (BMI) database, we estimated the change in annualized asthma exacerbation rates after metformin prescription. We also evaluated the association of prescription adherence to the changes in those rates using univariate and multivariate regression models. RESULTS: A total of 464 patients met inclusion criteria. Outpatient exacerbation rates decreased after metformin prescription (13.4% only before vs. 7.8% only after, p = .009), and the annualized rate decreased more after metformin prescription as adherence increased (rank r = -.165, p < .001). After adjusting for potential confounders-age, sex, BMI, and inhaled corticoid steroid use-the strength of the association was attenuated. CONCLUSIONS: Asthma exacerbation rates decreased after metformin prescription, but a larger sample of patients who have experienced exacerbations and including patients with asthma who have not been prescribed metformin is needed to better know whether these decreases are driven by metformin use.


Assuntos
Antiasmáticos , Asma , Metformina , Humanos , Adolescente , Adulto Jovem , Criança , Adulto , Metformina/uso terapêutico , Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Progressão da Doença
14.
Obesity (Silver Spring) ; 31(11): 2740-2749, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37731271

RESUMO

OBJECTIVE: The objective of this study was to quantify the effects of a 4-week, supervised, high-intensity interval training (HIIT) on intrahepatic triglyceride content (IHTG, percentage), cardiorespiratory fitness (CRF), and cardiometabolic markers in adolescents with obesity. METHODS: A total of 40 adolescents (age 13-18 y, BMI 36.7 ± 5.8 kg/m2 ) at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) based on obesity and elevated Fibroscan measured controlled attenuation parameter (CAP) scores were randomized to HIIT three times a week for 4 weeks (n = 34) or observation (control; n = 6). Liver magnetic resonance imaging proton-density fat-fraction (MRI-PDFF), CAP, oral glucose tolerance test, serum alanine aminotransferase, dual-energy x-ray absorptiometry, and CRF tests were performed before and after intervention. Within- and between-group differences were compared. RESULTS: A total of 13 (38%) and 4 (66%) children had MASLD by MRI-PDFF (IHTG ≥ 5%) in the HIIT and control groups, respectively. The implemented HIIT protocol had no impact on CRF or IHTG (baseline 5.26%, Δ = -0.31 percentage points, 95% CI: -0.77 to 0.15; p = 0.179), but it decreased the 2-h glucose concentration (baseline 116 mg/dL, Δ = -11 mg/dL; 95% CI: -17.6 to -5.5; p < 0.001). When limiting the analysis to participants with MASLD (n = 17), HIIT decreased IHTG (baseline 8.81%, Δ = -1.05 percentage points, 95% CI: -2.08 to -0.01; p = 0.048). Between-group comparisons were not different. CONCLUSIONS: The implemented exercise protocol did not reduce IHTG, but it led to modest improvement in markers of cardiometabolic health.


Assuntos
Doenças Cardiovasculares , Doenças Metabólicas , Obesidade Infantil , Adolescente , Humanos , Exercício Físico , Fígado/diagnóstico por imagem , Sobrepeso , Obesidade Infantil/diagnóstico por imagem , Obesidade Infantil/terapia
15.
J Opioid Manag ; 19(4): 329-341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37644791

RESUMO

OBJECTIVES: (1) To explore the characteristics of patients with opioid use disorder (OUD) maintained on either methadone or buprenorphine and (2) to determine the relative acceptability of integrating Tai Chi (TC) practice into an ongoing medication-assisted treatment for opioid use disorder (MOUD) program. DESIGN: Survey study. SETTING: The University of Arkansas for Medical Sciences Center for Addiction Services and Treatment Program. PATIENTS: 97 patients receiving MOUD treatment. MAIN OUTCOMES: Drug use history, treatment status, physical limitation, mental health, pain, and whether participants were interested in using TC to improve health outcomes. RESULTS: At least 30.9 percent of the sample reported moderate or higher level of limitation in performing rigorous physical activities, pain intensity, and pain interference. Between 37.1 and 61.5 percent of the sample reported various psychiatric symptoms. Methadone patients reported higher levels of physical limitations, especially in rigorous activities (p = .012), climbing several flights of stairs (p = .001), and walking more than a mile (p = .011), but similar levels of pain (ps = .664-.689) and psychiatric symptoms (ps = .262-.879) relative to buprenorphine patients. At least 40.2 percent of participants expressed moderate or higher level of interest in TC for improving health outcomes, with methadone patients more interested in participating to ease mental and sleep problems (p = .005) and improve physical fitness (p = .015) compared to buprenorphine patients. CONCLUSIONS: High prevalence of physical limitation, pain, and psychiatric comorbidities were found in OUD patients. Since patients were interested in TC to improve their health outcomes, this low-cost intervention, if proven effective, can be integrated into ongoing MOUD programs to improve health in this population.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Tai Chi Chuan , Humanos , Analgésicos Opioides/efeitos adversos , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Metadona/uso terapêutico , Buprenorfina/uso terapêutico , Dor/tratamento farmacológico
16.
Oper Dent ; 48(4): 425-434, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37399004

RESUMO

OBJECTIVE: The purpose of this study was to compare the optical and mechanical properties of newer ceramic CAD/CAM materials to more established materials on the market. METHODS AND MATERIALS: The following ceramic materials were tested: lithium disilicate/lithium-aluminum silicate (Tessera, Dentsply/Sirona), lithium disilicate (Initial LiSi Block, GC), IPS e.max CAD, Ivoclar Vivadent), and 4Y polycrystalline stabilized zirconia (IPS e.max ZirCAD MT, Ivoclar Vivadent; Katana STML, Kuraray; YZ ST, VITA). Optical properties (translucency, opalescence) were determined using a dental spectrophotometer on 0.5-, 1.0-, 1.5-, or 2.0-mm specimens. Mechanical properties (flexural strength, flexural modulus, flexural fatigue strength, Weibull modulus, and characteristic strength) were determined with beams undergoing 3-point bend testing. The data were analyzed with multiple analyses of variance and Tukey's post hoc tests (α=0.05). RESULTS: Significant differences were found between groups based on type of ceramic or property (p<0.05). CONCLUSIONS: In general, the lithium disilicate based-ceramic materials had greater optical properties and lower mechanical properties than the zirconia-based ceramic materials.


Assuntos
Cerâmica , Porcelana Dentária , Teste de Materiais , Propriedades de Superfície , Porcelana Dentária/química , Cerâmica/química , Zircônio/química , Desenho Assistido por Computador
17.
J Parkinsons Dis ; 13(6): 961-973, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522218

RESUMO

BACKGROUND: Freezing of gait (FOG) is a debilitating, variably expressed motor symptom in people with Parkinson's disease (PwPD) with limited treatments. OBJECTIVE: To determine if the rate of progression in spatiotemporal gait parameters in people converting from a noFOG to a FOG phenotype (FOGConv) was faster than non-convertors, and determine if gait parameters can help predict this conversion. METHODS: PwPD were objectively monitored longitudinally, approximately every 6 months. Non-motor assessments were performed at the initial visit. Steady-state gait in the levodopa ON-state was collected using a gait mat (Protokinetics) at each visit. The rate of progression in 8 spatiotemporal gait parameters was calculated. FOG convertors (FOGConv) were classified if they did not have FOG at initial visit and developed FOG at a subsequent visit. RESULTS: Thirty freezers (FOG) and 30 non-freezers were monitored an average of 3.5 years, with 10 non-freezers developing FOG (FOGConv). FOGConv and FOG had faster decline in mean stride-length, swing-phase-percent, and increase in mean total-double-support percent, coefficient of variability (CV) foot-strike-length and CV swing-phase-percent than the remaining non-freezers (noFOG). On univariate modeling, progression rates of mean stride-length, stride-velocity, swing-phase-percent, total-double-support-percent and of CV swing-phase-percent had high discriminative power (AUC > 0.83) for classification of the FOGConv and noFOG groups. CONCLUSION: FOGConv had a faster temporal decline in objectively quantified gait than noFOG, and progression rates of spatiotemporal gait parameters were more predictive of FOG phenotype conversion than initial (static) parameters Objectively monitoring gait in disease prediction models may help define FOG prone groups for testing putative treatments.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/etiologia , Marcha , Levodopa
18.
Clin Park Relat Disord ; 9: 100202, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37288072

RESUMO

Background: In people with Parkinson's disease (PwPD), Freezing of Gait (FOG) episodes can be levodopa responsive (OFF-FOG) or levodopa unresponsive (ONOFF-FOG). Steady-state gait abnormalities, outside of the freezing episodes themselves also exist and the response to levodopa in these different groups has not been previously documented. Objectives: To define the levodopa responsiveness in steady-state gait in OFF-FOG and ONOFF-FOG individuals. Methods: Steady-state gait was collected in both the effective levodopa OFF-state (doses withheld > 8 h) and ON-state (1 h after levodopa dosing) in 32 PwPD; 10 with OFF-FOG and 22 with ONOFF-FOG. Levodopa response was compared between the two groups in the mean and variability (CV) of 8 spatiotemporal gait parameters. Results: Both OFF-FOG and ONOFF-FOG participants showed improvement in mean stride-length and stride-velocity with levodopa. Improvement was seen in the OFF-FOG but not the ONOFF-FOG groups in mean stride-width and CV Integrated pressure with levodopa. Discussion: In this study we show that steady-state gait deficits improve with levodopa in PwPD with OFF-FOG and ONOFF-FOG, even though episodes of FOG did not resolve in the ONOFF-FOG group. Lowering levodopa in people with ONOFF-FOG, or levodopa-unresponsive freezing of gait, should be undertake with caution and objective gait titration at different levodopa doses may be beneficial. Further work is needed to elucidate the pathophysiologic mechanisms of these differences.

19.
Radiat Res ; 200(2): 107-115, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37327124

RESUMO

Historically, animal numbers have most often been in the hundreds for experiments designed to estimate the dose reduction factor (DRF) of a radiation countermeasure treatment compared to a control treatment. Before 2010, researchers had to rely on previous experience, both from others and their own, to determine the number of animals needed for a DRF experiment. In 2010, a formal sample size formula was developed by Kodell et al. This theoretical work showed that sample sizes for realistic, yet hypothetical, DRF experiments could be less than a hundred animals and still have sufficient power to detect clinically meaningful DRF values. However, researchers have been slow to use the formula for their DRF experiments, whether from ignorance to its existence or hesitancy to depart from "tried and true" sample sizes. Here, we adapt the sample size formula to better fit usual DRF experiments, and, importantly, we provide real experimental evidence from two independent DRF experiments that sample sizes smaller than what have typically been used can still statistically detect clinically meaningful DRF values. In addition, we update a literature review of DRF experiments which can be used to inform future DRF experiments, provide answers to questions that researchers have asked when considering sample size calculations rather than solely relying on previous experience, whether their own or others', and, in the supplementary material, provide R code implementing the formula, along with several exercises to familiarize the user with the adapted formula.


Assuntos
Tamanho da Amostra , Animais , Estudos de Viabilidade
20.
Life Sci Space Res (Amst) ; 37: 78-87, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37087182

RESUMO

PURPOSE: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model. MATERIALS AND METHODS: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions (16O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury. RESULTS: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild. CONCLUSION: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models.


Assuntos
Radiação Cósmica , Prótons , Humanos , Coelhos , Masculino , Ratos , Camundongos , Animais , Lactente , Oxigênio , Íons , Coração/efeitos da radiação , Relação Dose-Resposta à Radiação
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