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1.
Diabetol Metab Syndr ; 16(1): 106, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769575

RESUMO

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

2.
World J Gastrointest Oncol ; 16(5): 1705-1724, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764833

RESUMO

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

3.
JCO Glob Oncol ; 10: e2300060, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38754053

RESUMO

PURPOSE: Cost containment and efficiency in the provision of health care are primary concerns for health systems that aim to provide affordable, high-quality care. Between 2005 and 2015, Seguro Poplar's Fund against Catastrophic Expenditures (FPGC) funded ALL treatment in Mexico. Before January 1, 2011, FPGC reimbursed a fixed amount per patient according to risk. In 2011, the per capita reimbursement method changed to fee for service. We used this natural experiment to estimate the impact of the reimbursement policy change on average expenditure and quality of care for ALL treatment in Mexico. METHODS: We used nationwide reimbursement data from the Seguro Poplar's FPGC from 2005 to 2015. We created a patient cohort to assess 3-year survival and estimate the average reimbursement before and after the fee-for-service policy. We examined survival and expenditure impacts, controlling for patients' and providers' characteristics, including sex, risk (standard and high), the volume of patients served, type of institution (federally funded v other), and level of care. To quantify the impact, we used a regression discontinuity approach. RESULTS: The average reimbursement for standard-risk patients in the 3-year survival cohort was $16,512 US dollars (USD; 95% CI, 16,042 to 17,032) before 2011 and $10,205 USD (95% CI, 4,659 to 12,541) under the fee-for-service reimbursement scheme after 2011. The average annual reimbursement per patient decreased by 136% among high-risk patients. The reduction was also significant for the standard-risk cohort, although the magnitude was substantially smaller (34%). CONCLUSION: As Mexico's government is currently restructuring the health system, our study provides evidence of the efficiency and effectiveness of the funding mechanism in the Mexican context. It also serves as a proof of concept for using administrative data to evaluate economic performance and quality of care of publicly funded health programs.


Assuntos
Planos de Pagamento por Serviço Prestado , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , México/epidemiologia , Planos de Pagamento por Serviço Prestado/economia , Masculino , Feminino , Leucemia-Linfoma Linfoblástico de Células Precursoras/economia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Criança , Gastos em Saúde/estatística & dados numéricos , Pré-Escolar , Adulto Jovem
4.
World J Transplant ; 14(1): 90149, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38576758

RESUMO

Kidney transplantation is the best option for kidney replacement therapy, even considering that most of the times the grafts do not survive as long as their recipients. In the Khalil et al's experience, published in this issue of the Journal, they analyze their second kidney graft survival and describe those significant predictors of early loss. This editorial comments on the results and put in perspec tive that most of the times, long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason, and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

5.
Environ Monit Assess ; 196(5): 421, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570395

RESUMO

This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.


Assuntos
Diabetes Mellitus Tipo 2 , Hidrocarbonetos Clorados , Neoplasias , Praguicidas , Humanos , Feminino , Hexaclorobenzeno/análise , Carcinógenos , México/epidemiologia , Monitoramento Ambiental , Praguicidas/análise , Hidrocarbonetos Clorados/análise , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia
6.
J Glob Health ; 14: 04068, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606605

RESUMO

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.


Assuntos
Doenças Autoimunes , COVID-19 , Eczema , Hipertensão , Síndrome do Intestino Irritável , Hepatopatias , Infarto do Miocárdio , Estado Pré-Diabético , Doença Pulmonar Obstrutiva Crônica , Distúrbios do Início e da Manutenção do Sono , Adulto , Humanos , Qualidade de Vida , Pandemias , Úlcera , Doença Crônica , Estilo de Vida , COVID-19/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Colesterol
7.
Pharmacol Res Perspect ; 12(3): e1195, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38644566

RESUMO

Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health-related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health-related outcomes in asthma patients.


Assuntos
Asma , Farmacêuticos , Qualidade de Vida , Asma/tratamento farmacológico , Humanos , Adesão à Medicação/estatística & dados numéricos , Assistência Farmacêutica , Papel Profissional , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Revisões Sistemáticas como Assunto
8.
J Orthop Res ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669091

RESUMO

Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with large acetabular defects. Previous clinical studies from our institution showed that these implants tend to lateralize the acetabular center of rotation. However, the clinical impact of lateralization on implant survivorship is debated. Our goal was to develop a finite element model to quantify how lateralization of the native hip center affects periprosthetic strain and implant-bone micromotion distributions in a static level gait loading condition. To build the model, we computationally created a superomedial acetabular defect in a computed tomography 3D reconstruction of a native pelvis and designed a flanged acetabular implant to address this simulated bone defect. We modeled two implants, one with ~1 cm and a second with ~2 cm of hip center lateralization. We applied the maximum hip contact force and corresponding abductor force observed during level gait. The resulting strains were compared to bone fatigue strength (0.3% strain) and the micromotions were compared to the threshold for bone ingrowth (20 µm). Overall, the model demonstrated that the additional lateralization only slightly increased the area of bone at risk of failure and decreased the areas compatible with bone ingrowth. This computational study of patient-specific acetabular implants establishes the utility of our modeling approach. Further refinement will yield a model that can explore a multitude of variables and could be used to develop a biomechanically-based acetabular bone loss classification system to guide the development of patient-specific implants in the treatment of large acetabular bone defects.

9.
Stroke ; 55(5): 1449-1463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648282

RESUMO

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.


Assuntos
Malformações Arteriovenosas Intracranianas , Humanos , Hemorragia Cerebral/terapia , Procedimentos Endovasculares/métodos , Malformações Arteriovenosas Intracranianas/terapia , Radiocirurgia/métodos
10.
World Neurosurg ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537791

RESUMO

BACKGROUND: Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes. METHODS: This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed. RESULTS: A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06-2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00-1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00-1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00-1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes. CONCLUSIONS: HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion.

11.
J Arthroplasty ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537838

RESUMO

BACKGROUND: Dislocation after total hip arthroplasty (THA) is a primary reason for THA revision. During THA through the direct anterior approach (DAA), the iliofemoral ligament, which provides the main resistance to external rotation (ER) of the hip, is commonly partially transected. We asked: (1) what is the contribution of the medial iliofemoral ligament to resisting ER after DAA THA? and (2) how much resistance to ER can be restored by repairing the ligament? METHODS: A fellowship-trained surgeon performed DAA THA on 9 cadaveric specimens. The specimens were computed tomography scanned before and after implantation. Prior to testing, the ER range of motion of each specimen to impingement in neutral and 10° of extension was computationally predicted. Each specimen was tested on a 6-degrees-of-freedom robotic manipulator. The pelvis was placed in neutral and 10° of extension. The femur was externally rotated until it reached the specimen's impingement target. Total ER torque was recorded with the medial iliofemoral ligament intact, after transecting the ligament, and after repair. Torque at extremes of motion was calculated for each condition. To isolate the contribution of the native ligament, the torque for the transected state was subtracted from both the native and repaired conditions. RESULTS: The medial iliofemoral ligament contributed an average of 68% (range, 34 to 87) of the total torque at the extreme of motion in neutral and 80% (58 to 97) in 10° of extension. The repaired ligament contributed 17% (1 to 54) of the total torque at the extreme of motion in neutral and 14% (5 to 38) in 10° of extension, restoring on average 18 to 25% of the native resistance against ER. CONCLUSIONS: The medial iliofemoral ligament was an important contributor to the hip torque at the extreme of motion during ER. Repairing the ligament restored a fraction of its ability to generate torque to resist ER.

12.
J Arthroplasty ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548236

RESUMO

BACKGROUND: Cementless total knee arthroplasty (TKA) has regained interest for its potential for long-term biologic fixation. The density of the bone is related to its ability to resist static and cyclic loading and can affect long-term implant fixation; however, little is known about the density distribution of periarticular bone in TKA patients. Thus, we sought to characterize the bone mineral density (BMD) of the proximal tibia in TKA patients. METHODS: We included 42 women and 50 men (mean age 63 years, range: 50 to 87; mean body mass index 31.6, range: 20.5 to 49.1) who underwent robotic-assisted TKA and had preoperative computed tomography scans with a BMD calibration phantom. Using the robotic surgical plan, we computed the BMD distribution at 1 mm-spaced cross-sections parallel to the tibial cut from 2 mm above the cut to 10 mm below. The BMD was analyzed with respect to patient sex, age, preoperative alignment, and type of fixation. RESULTS: The BMD decreased from proximal to distal. The greatest changes occurred within ± 2 mm of the tibial cut. Age did not affect BMD for men; however, women between 60 and 70 years had higher BMD than women ≥ 70 years for the total cut (P = .03) and the medial half of the cut (P = .03). Cemented implants were used in 1 86-year-old man and 18 women (seven < 60 years, seven 60 to 70 years, and four ≥ 70 year old). We found only BMD differences between cemented or cementless fixation for women < 60 years. CONCLUSIONS: To our knowledge, this is the first study to characterize the preoperative BMD distribution in TKA patients relative to the intraoperative tibial cut. Our results indicate that while sex and age may be useful surrogates of BMD, the clinically relevant thresholds for cementless knees remain unclear, offering an area for future studies.

13.
Biodemography Soc Biol ; 69(1): 4-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38437066

RESUMO

The medical literature has shown that populations under high stress have a lower sex ratio at birth (i.e. number of males for every 100 females). In this paper, I examine the relationship between income, as a source of economic stress, and the sex ratio at a subnational level for the 1895-2010 period. For this, I use census microdata from Argentina -a developing country that experienced rapid growth at the end of the 19th century and stagnated in recent decades- and I estimate from a two-way fixed effects model that exploits the wide temporal and geographic variability in income. The results show that as per capita income increases, the sex ratio at birth also increases. In particular, for every US$ 1,000 increase in per capita income, the sex ratio increases between 0.3 and 0.6 points. These findings make it possible to quantify the lost boys (i.e. those boys who were not born due to high economic stress on their parents) and constitute a call for attention in favor of the implementation of prenatal care policies -especially in periods of stagnation or income decline- to maintain a more balanced sex ratio.


Assuntos
Renda , Razão de Masculinidade , Masculino , Feminino , Gravidez , Recém-Nascido , Humanos , Fatores Socioeconômicos , Dinâmica Populacional , Argentina , Países em Desenvolvimento
14.
Pediatr Neurol ; 154: 44-50, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518503

RESUMO

BACKGROUND: Infants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. METHODS: Infants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. RESULTS: Of 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. CONCLUSIONS: Among infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.


Assuntos
Paralisia Cerebral , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Lactente , Criança , Humanos , Pré-Escolar , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/genética , Paralisia Cerebral/complicações , Imageamento por Ressonância Magnética/métodos , Encéfalo , Hipotermia Induzida/métodos
15.
Int J Infect Dis ; 143: 107020, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548167

RESUMO

OBJECTIVES: De-escalation (DES) from echinocandins to azoles is recommended by several medical societies in Candida infections. We summarise the evidence of DES on clinical and microbiological cure and 30-day survival and compare it with continuing the treatment with echinocandins (non-DES). METHODS: We searched MEDLINE, Embase, Web of Science and Scopus. Studies describing DES in inpatients and reporting any of the outcomes evaluated were included. Pooled estimates of the tree outcomes were calculated with a fixed or random-effects model. Heterogeneity was explored stratifying by subgroups and via meta-regression. This systematic review is registered with PROSPERO (CRD42023475486). RESULTS: Of 1853 records identified, 9 studies were included, totalling 1575 patients. Five studies stepped-down to fluconazole; one to voriconazole and three to any of azoles. The mean day of DES was 5.2 (4.6-6.5) days. The clinical cure OR was 1.29 (95% CI: 0.88-1.88); the microbiological cure 1.62 (95% CI: 0.71-3.71); and 30-day survival 2.17 (95% CI: 1.09-4.32). The 30-day survival data into subgroups showed higher effect on critically ill patients and serious-risk bias studies. Meta-regression did not identify significant effect modifiers. CONCLUSIONS: DES is a safe strategy; it showed no higher 30-day mortality and a trend towards greater clinical and microbiological cure.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/mortalidade , Candidíase/microbiologia , Fluconazol/uso terapêutico , Candida/efeitos dos fármacos , Voriconazol/uso terapêutico , Equinocandinas/uso terapêutico , Resultado do Tratamento , Azóis/uso terapêutico , Azóis/farmacologia
16.
Biomimetics (Basel) ; 9(3)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38534824

RESUMO

The vertebrate basal ganglia play an important role in action selection-the resolution of conflicts between alternative motor programs. The effective operation of basal ganglia circuitry is also known to rely on appropriate levels of the neurotransmitter dopamine. We investigated reducing or increasing the tonic level of simulated dopamine in a prior model of the basal ganglia integrated into a robot control architecture engaged in a foraging task inspired by animal behaviour. The main findings were that progressive reductions in the levels of simulated dopamine caused slowed behaviour and, at low levels, an inability to initiate movement. These states were partially relieved by increased salience levels (stronger sensory/motivational input). Conversely, increased simulated dopamine caused distortion of the robot's motor acts through partially expressed motor activity relating to losing actions. This could also lead to an increased frequency of behaviour switching. Levels of simulated dopamine that were either significantly lower or higher than baseline could cause a loss of behavioural integration, sometimes leaving the robot in a 'behavioral trap'. That some analogous traits are observed in animals and humans affected by dopamine dysregulation suggests that robotic models could prove useful in understanding the role of dopamine neurotransmission in basal ganglia function and dysfunction.

17.
Front Immunol ; 15: 1293931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469299

RESUMO

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Células Matadoras Naturais/patologia , Lenalidomida/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Resposta Patológica Completa
18.
J Pediatr ; 268: 113933, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38309524

RESUMO

OBJECTIVE: To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. STUDY DESIGN: We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36 months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. RESULTS: Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. CONCLUSIONS: Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.


Assuntos
Temperatura Corporal , Esôfago , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Reto , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Masculino , Feminino , Recém-Nascido , Lactente , Esôfago/diagnóstico por imagem , Resultado do Tratamento , Monitorização Fisiológica/métodos , Imageamento por Ressonância Magnética , Pré-Escolar
19.
J Pediatr ; 268: 113957, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38360261

RESUMO

OBJECTIVE: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM). STUDY DESIGN: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM. RESULTS: Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010). CONCLUSIONS: Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.


Assuntos
Anticonvulsivantes , Eletroencefalografia , Hipóxia-Isquemia Encefálica , Convulsões , Humanos , Convulsões/tratamento farmacológico , Estudos Retrospectivos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Masculino , Anticonvulsivantes/uso terapêutico , Recém-Nascido , Feminino , Resultado do Tratamento
20.
Int J Transgend Health ; 25(1): 63-73, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328585

RESUMO

The practices of parents raising children with trans* life experiences influence their subsequent social adjustment. The aim of the study was to identify potential differences in parenting patterns and practices between two groups, one comprising families with transgender children and the other group comprising families with cisgender children. Twenty-eight adults and 15 children and adolescents from Bogotá, Colombia, participated. We performed descriptive, nonparametric comparative, and Bayesian comparative analyses for independent samples. We used a frequentist inferential comparative method with the Mann-Whitney U test with an effect size based on rank-biserial correlation, which revealed no statistically significant difference values. Bayesian comparisons showed minimal evidence in favor of the null hypothesis in all comparisons performed, except for the Behavioral Control or Regulation variable. The main finding of this study suggests that parents of children with trans* life experiences may not be addressing their specific needs, which could lead to a lack of understanding of their situation and support in their transition process.

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