Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.492
Filtrar
1.
Pulm Circ ; 14(3): e12435, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39308941

RESUMO

One of the great diagnostic challenges for children with pulmonary arterial hypertension is the need for general anesthesia (GA) to enable successful right heart catheterization. Here, for the first time, we describe how echocardiographic estimates of right ventricular function and pulmonary pressures change in pediatric patients during GA.

2.
Commun Biol ; 7(1): 1146, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277687

RESUMO

Microtubules are essential for various cellular processes. The functional diversity of microtubules is attributed to the incorporation of various α- and ß-tubulin isotypes encoded by different genes. In this work, we investigated the functional role of ß4B-tubulin isotype (TUBB4B) in hearing and vision as mutations in TUBB4B are associated with sensorineural disease. Using a Tubb4b knockout mouse model, our findings demonstrate that TUBB4B is essential for hearing. Mice lacking TUBB4B are profoundly deaf due to defects in the inner and middle ear. Specifically, in the inner ear, the absence of TUBB4B lead to disorganized and reduced densities of microtubules in pillar cells, suggesting a critical role for TUBB4B in providing mechanical support for auditory transmission. In the middle ear, Tubb4b-/- mice exhibit motile cilia defects in epithelial cells, leading to the development of otitis media. However, Tubb4b deletion does not affect photoreceptor function or cause retinal degeneration. Intriguingly, ß6-tubulin levels increase in retinas lacking ß4B-tubulin isotype, suggesting a functional compensation mechanism. Our findings illustrate the essential roles of TUBB4B in hearing but not in vision in mice, highlighting the distinct functions of tubulin isotypes in different sensory systems.


Assuntos
Cílios , Cóclea , Tubulina (Proteína) , Animais , Camundongos , Cílios/metabolismo , Cóclea/citologia , Cóclea/metabolismo , Citoesqueleto/metabolismo , Camundongos Knockout , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética
3.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39225573

RESUMO

A plasma device has been created to study dynamic plasma coupling in an E × B-drifting magnetized plasma. The E × B magnetized plasma device is a 1.2 m diameter by 2 m long cylindrical chamber with two sets of Helmholtz coils in a mirror configuration. A steady-state axial hollow cathode source injects a plasma discharge in electrical contact with a floating conductor at a range that forms a unique axisymmetric equipotential surface or Virtual Cathode Lightsaber (VCL). The VCL generates two plasma populations streaming relative to one another providing a suitable environment for the investigation of dynamic plasma coupling. The plasma density, radial electric field, and plasma rotational velocity outside the VCL are shown to be influenced by the current-voltage relationship of the cathode and applied magnetic field strength. A basic characterization of the device and plasma environment is presented with an emphasis on diagnostics systems and the analytical techniques utilized.

4.
Indian J Orthop ; 58(9): 1297-1302, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39170652

RESUMO

Background: Laterality and bilaterality have been reported as prognostic variables in developmental dysplasia of the hip (DDH) outcomes. However, there is little clarity across the literature on the reporting of laterality in developmental dysplasia of the hip (DDH) due to the variability in severity of the condition. It is widely accepted that the left hip is most frequently affected; however, the true incidence of unilateral left, unilateral right and bilateral cases can be hard to quantify and compare across studies. The purpose of this study was to examine laterality accounting for graded severity in a multi-centre, international prospective observational study of infants with hip dysplasia to demonstrate the complexity of this issue. Methods: A multi-centre, prospective hip dysplasia database was analyzed from 2010 to April 2015. Baseline diagnosis was used to classify patients into a graded laterality category accounting for hip status within the DDH spectrum. Results: A total of 496 patients were included in the analysis; 328 were <6 months old at diagnosis and 168 were between 6 and 18 months old. Of these patients, 421 had at least one frankly dislocated hip. Unilateral left hip dislocations were most common, with 223 patients, followed by unilateral right and bilateral dislocations with 106 and 92 respectively. Stratifying these patients based on status of the contralateral hip, 54 unilateral left and 31 unilateral right dislocated patients also had a dysplastic or unstable contralateral hip. There were significantly fewer bilateral patients in the 6 to 18-month group (p = 0.0005). When classifying laterality by affected hip, bilaterality became the predominant finding, comprising 42% of all patients. Conclusions: Findings from this multi-centre prospective study demonstrate the necessity to account for the graded severity in hip status when reporting DDH laterality. To accurately compare laterality across studies, a standardized, comprehensive classification should be established, as contralateral hip status may impact prognosis and treatment outcomes. Level of Evidence: Level II Prognostic Study.

5.
Chemosphere ; 364: 143144, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39168384

RESUMO

High demand for rare earth elements (REEs) has increased interest in their recovery from unconventional sources, such as acid mine drainage (AMD). AMD contains elevated concentrations of Mn, Fe, and Al, which precipitate as (oxy)hydroxide minerals as pH is raised. These precipitates can remove cations including REEs and Co from solution via sorption and/or coprecipitation. In this study we developed a method to recover these critical minerals by sorption to MnO2, precipitated by oxidation of in situ Mn (II) with added KMnO4 at acidic pH. MnO2 solids were prepared with varying concentrations of KMnO4, SO42-, and Cl-, to elucidate the effects of excess KMnO4, SO42- concentration, and ionic strength on adsorption. When using a stoichiometric ratio of Mn (II) and KMnO4, 100% removal of REEs and Co occurred at approximately pH 3.5, nearly 2 pH units lower than was observed by sorption to Fe and Al hydroxysulfates. When using excess KMnO4 nearly 100% removal of REEs and Co was accomplished at approximately pH 2, although SO42- was found to inhibit REE sorption. From these results, we developed a two-stage process for recovery of REEs from AMD; a preliminary pH adjustment to remove Fe and Al hydroxy-sulfates, followed by adding KMnO4, precipitating MnO2, enabling recovery of REEs and Co. We tested this process in a representative synthetic AMD, achieving a grade of 6.16 mg REEs per g of solid, which is 65 % of the maximum possible grade based on solution composition. Fractionation of REEs was observed, with light REEs (LREEs) preferentially sorbed to MnO2 relative to both medium REEs (MREEs) and heavy REEs (HREEs). In contrast, preferential sorption of HREEs was observed for sorption to Fe and Al oxyhydroxides at all pH ranges. These results suggest the mechanisms of REE sorption differ among the solids and warrant further study.

6.
Curr Protoc ; 4(8): e1110, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39093058

RESUMO

In addition to current challenges in food production arising from climate change, soil salinization, drought, flooding, and human-caused disruption, abrupt sunlight reduction scenarios (ASRS), e.g., a nuclear winter, supervolcano eruption, or large asteroid or comet strike, are catastrophes that would severely disrupt the global food supply and decimate normal agricultural practices. In such global catastrophes, teragrams of particulate matter, such as aerosols of soot, dust, and sulfates, would be injected into the stratosphere and block sunlight for multiple years. The reduction of incident sunlight would cause a decrease in temperature and precipitation and major shifts to climate patterns leading to devastating reductions in agricultural production of traditional food crops. To survive a catastrophic ASRS or endure current and future disasters and famines, humans might need to rely on post-catastrophic foods, or those that could be foraged, grown, or produced under the new climate conditions to supplement reduced availability of traditional foods. These foods have sometimes been referred to as emergency, alternate, or resilient foods in the literature. While there is a growing body of work that summarizes potential post-catastrophic foods and their nutritional profiles based on existing data in the literature, this article documents a list of protocols to experimentally determine fundamental nutritional properties of post-catastrophic foods that can be used to assess the relative contributions of those foods to a balanced human diet that meets established nutritional requirements while avoiding toxic levels of nutrients. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Total digestible glucans Basic Protocol 2: Apparent protein digestibility Basic Protocol 3: Vitamins B1, B3, B9, C, and D2 by HPLC Basic Protocol 4: Total antioxidant activity (DPPH-scavenging activity) Basic Protocol 5: Total phenolic compounds (Folin-Ciocalteu reagent method) Basic Protocol 6: Mineral content by ICP-OES.


Assuntos
Valor Nutritivo , Humanos , Desastres , Análise de Alimentos , Mudança Climática , Abastecimento de Alimentos
8.
Injury ; 55(11): 111837, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39197325

RESUMO

INTRODUCTION: Fractures of the lower trunk are among the most common fractures occurring in the elderly. Super elderly individuals (i.e., those 80 years of age and older) represent a growing segment of the population and are especially prone to these fractures. The contemporary epidemiology of lower trunk fractures in the super elderly population is incompletely described in the literature. MATERIALS AND METHODS: This descriptive epidemiology study used the National Electronic Injury Surveillance System (NEISS) to examine the incidence and recent trends of lower trunk fractures (i.e., fractures of the hip, pelvis, and lumbar spine) occurring among super elderly individuals in the United States (US) from 2011 to 2020. Annual, overall, and age-/sex-specific incidence rates (IRs) were analyzed. Average annual percent change (AAPC) estimates were calculated to indicate the magnitude/direction of trends in annual injury rates. RESULTS: An estimated N=1,226,160 super elderly patients sustained lower trunk fractures over the 10-year study period for an overall IR of 100.2 per 10,000 person-years at-risk (PYR). Hip fractures accounted for the largest percentage of cases (IR=71.7 PYR), followed by lumbar spine fractures (IR=14.7), and pelvic fractures (IR=14.3). The incidence of lower trunk fractures among super elderly females (IR=121.5 PYR) was significantly greater than that of males (IR=65.7 PYR). The incidence of lower trunk fractures among nonagenarians and centenarians was significantly higher than that of octogenarians. Accounting for population growth yielded a significantly increasing annual incidence of lower trunk fractures in super elderly patients over the study period from 86.7 PYR in 2011 to 107.2 PYR in 2020 (AAPC=2.7, p<0.001). The annual incidence of both pelvic (AAPC=5.8) and lumbar spine (AAPC=6.9) fractures increased at a significantly higher rate than that of hip fractures (AAPC=1.4). CONCLUSIONS: This study suggests that the annual incidence of lower trunk fractures in the oldest cohort of patients in the US (80+ years of age) increased significantly during the recent decade from 2011 to 2020, with pelvic and lumbar fractures in particular becoming increasingly common. Increased incidence rates highlight the need for future research aimed at optimizing outcomes and quality of life in this frail and ever-growing segment of the population.

9.
JCI Insight ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115937

RESUMO

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving life expectancy of people living with HIV, but also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the impact of pre-existing metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART. The responses of lean and obese macaques to SIV and ART were similar with respect to plasma and cell-associated viral loads, ART drug levels in plasma and tissues, SIV-specific immune responses, adipose tissue and islet morphology, and colon inflammation, with baseline differences between lean and obese groups largely maintained. Both groups exhibited a striking depletion of CD4+ T cells from adipose tissue that did not recover with ART. However, differential responses to SIV and ART were observed for body weight, omental adipocyte size, and the adiponectin/leptin ratio, a marker of cardiometabolic risk. Thus, obesity and insulin resistance had limited effects on multiple responses to acute SIV infection and ART, while several factors that underlie long-term metabolic comorbidities were influenced by prior obesity and insulin resistance. These studies provide the foundation for future investigations into the efficacy of adjunct therapies such as metformin and glucagon-like peptide-1 receptor agonists in the prevention of metabolic comorbidities in people living with HIV.

10.
Ann Bot ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212164

RESUMO

BACKGROUND AND AIMS: The master transcription factor NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3), also known as SND1, plays a pivotal role in regulating secondary cell wall (SCW) development in interfascicular and xylary fibers in Arabidopsis thaliana. Despite progress in understanding SCW assembly in xylem vessel-like cells, the mechanisms behind its assembly across different cell types remain unclear. Overexpressing NST3 or its homolog NST1 leads to reduced fertility, posing challenges for studying their impact on secondary wall formation. This study aimed at developing a tightly regulated dexamethasone (DEX)-inducible expression system for NST3 and NST1 to elucidate the structure and assembly of diverse SCWs. METHODS: Using the DEX-inducible system, we characterized ectopically formed SCWs for their diverse patterns, mesoscale organization, cellulose microfibril orientation, and molecular composition using spinning disk confocal microscopy, field emission scanning electron microscopy (FESEM), vibrational sum-frequency generation (SFG) spectroscopy and, histochemical staining and time-of-flight secondary ion mass spectrometry (ToF-SIMS), respectively. KEY RESULTS: Upon DEX treatment, NST3 and NST1 transgenic hypocotyls underwent time-dependent transdifferentiation, progressing from protoxylem-like to metaxylem-like cells. NST3-induced plants exhibited normal growth but had rough secondary wall surfaces with delaminating S2 and S3 layers. Mesoscale examination of induced SCWs in epidermal cells revealed that macrofibril thickness and orientation were comparable to xylem vessels, while wall thickness resembled that of interfascicular fibers. Additionally, induced epidermal cells formed SCWs with altered cellulose and lignin contents. CONCLUSIONS: These findings suggest NST3 and/or NST1 induce SCWs with shared characteristics of both xylem and fiber-like cells forming loosely arranged cell wall layers and cellulose organized at multiple angles relative to the cell growth axis and with varied cellulose and lignin abundance. This inducible system opens avenues to explore ectopic SCWs for bioenergy and bioproducts, offering valuable insights into SCW patterning across diverse cell types and developmental stages.

11.
Br J Haematol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977270

RESUMO

The mechanisms of action of l-glutamine for the treatment of sickle cell disease (SCD) are not well understood and there are no validated clinical biomarkers to assess response. We conducted a three-week, dose-ascending trial of glutamine and measured the pharmacokinetic (PK) exposure parameters, peak concentration (Cmax) and area under the curve (AUC). We used a panel of biomarkers to investigate the pharmacodynamics (PD) of glutamine and studied PK-PD relationships. There was no plasma accumulation of glutamine, glutamate, arginine or other amino acids over time, but modestly improved arginine bioavailability was observed. In standard analysis by dose levels over time, there were no measurable effects on blood counts, viscosity, ektacytometry or reactive oxygen species (ROS). In PK-PD analysis, however, higher glutamine exposure (Cmax or AUC) was associated with increased whole blood viscosity and cellular dehydration, yet also with higher haemoglobin concentration, increased haematocrit-to-viscosity ratio, decreased reticulocyte ROS, improved RBC deformability and decreased point of sickling. This novel PK-PD analysis identified biomarkers reflecting the positive and negative effects of glutamine, helping to elucidate its mechanisms of action in SCD. PK-optimized dosing to achieve glutamine exposure (AUC or Cmax) that is associated with salutary biological effects should be studied to support its therapeutic use.

12.
Front Oncol ; 14: 1403703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978736

RESUMO

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

13.
J Exp Bot ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058275

RESUMO

Boron dimerizes RG-II in the plant cell wall and is crucial for plant cell elongation. However, studying RG-II dimerization in plants is challenging because of the severe phenotypes or lethality of RG-II mutants. Boron deprivation abrogates both RG-II dimerization and plant growth, but whether or how these phenotypes are functionally linked has remained unclear. Boric acid analogues can serve as experimental tools to interfere with RG-II cross-linking. Here, we investigated RG-II dimerization and developmental phenotypes in Arabidopsis thaliana seedlings treated with a boric acid analogue, phenylboronic acid (PBA), to test whether the observed developmental phenotypes are attributable to alteration of RG-II dimerization or to other putative functions of boron in plants. We found that PBA treatment altered root development in seedlings while RG-II dimerization and distribution were not affected. Surprisingly, under low boron conditions, PBA treatment i) had no effect on root size but still prevented lateral root development and ii) restored RG-II dimerization. PBA treatment also disrupted auxin levels, potentially explaining the absence of lateral roots in seedlings treated with this analogue. We conclude that PBA interacts both with RG-II and other cellular targets such as auxin signaling components, and that the phenotypes caused by PBA arise from interference with multiple functions of boron.

14.
J Pediatr Orthop ; 44(8): 476-482, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956967

RESUMO

OBJECTIVES: The first case report describing a pediatric fracture of the tibial tubercle was published in 1852 in the Medical Times and Gazette, a Journal of Medical Science, literature, criticism, and news. A century later, in 1955, Sir Watson-Jones introduced the first classification system for this fracture. Despite the existence of several classification systems for pediatric tibial tubercle fractures in the medical literature, a crucial aspect of their validation-reliability and reproducibility-has not yet been systematically evaluated. METHODS: In this study, a modified Watson-Jones (mWJ) classification system of tibial tubercle fractures in children was assessed for intraobserver and interobserver variability. Using the mWJ classification, 3 board-certified pediatric orthopaedic surgeons and 3 orthopaedic surgery residents, classified thirty tibial tubercle fractures based on anteroposterior and lateral radiographs on 2 separate occasions in a 2-week duration. Further comparison was made to evaluate the impact of advanced imaging, specifically computed tomography or magnetic resonance imaging, on diagnostic reliability and reproducibility. RESULTS: The study found substantial intraobserver reliability of the mWJ classification based on radiographs alone, with a Cohen weighted kappa (κ w ) coefficient of 0.733. When advanced imaging was utilized, the reliability of the classification improved to κ w = 0.783. Similarly, interobserver reliability demonstrated substantial consistency among observers when using radiographs alone (κ w = 0.69) and improved agreement with advanced imaging (κ w = 0.75). Notably, there was no significant difference in reliability scores between senior-level attendings and residents when analyzed as separate groups. CONCLUSION: Fracture classification systems are clinically relevant tools that help organize and transfer knowledge efficiently, provide treatment guidance, propose prognostic expectations, and improve communication in academic literature. The present study demonstrated substantial reproducibility of an mWJ fracture classification system both between and within individual surgeon raters. LEVEL OF EVIDENCE: Level III-diagnostic.


Assuntos
Variações Dependentes do Observador , Fraturas da Tíbia , Humanos , Reprodutibilidade dos Testes , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/classificação , Criança , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Pré-Escolar
15.
J Bone Miner Res ; 39(8): 1061-1070, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-38952014

RESUMO

Inpatient zoledronic acid (IP-ZA) administered during the initial fracture hospitalization significantly improves the osteoporosis treatment rate. Clinical outcomes of IP-ZA after hip fracture remain uncertain. Here we report a cohort study that emulated a randomized controlled trial using real-world data and evaluated the risk of all-cause-mortality and radiologically confirmed subsequent new fractures among patients hospitalized for a hip fracture who had received IP-ZA as compared with propensity-matched controls. A total of 654 patients who had received IP-ZA and 6877 controls (for whom anti-osteoporosis treatment was indicated but no IP-ZA started during index hospitalization) were included in the study. The primary cohort comprised 652 IP-ZA patients (IP-ZA group) and 1926 matched controls (untreated group), with 71.7% female 92.1% White participants, with a mean age of 80.9 years. Cumulative all-cause mortality over the 24-month follow-up for the IP-ZA group was 12.3% and 20.7% for the untreated group (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78, p < .001). A total of 585 (89.7%) patients in IP-ZA group received only a single dose of ZA during the 24 months, and the death rate of this single dose group was 13.3%, which was significantly lower than that of the untreated group (HR, 0.70; 95% CI, 0.55-0.89, p = .003). Rates of radiologically confirmed cumulative subsequent new vertebral fractures were 2.0% in the IP-ZA group and 5.4% in the untreated group (HR, 0.40; 95% CI, 0.22-0.71, p = .001). A similarly lower rate of new vertebral fractures was seen in the single dose subgroup (1.9% vs 5.4%; HR, 0.44; 95% 0.24-0.82, p = .008). IP-ZA, administered during the initial hospitalization for hip fracture, was associated with lower all-cause-mortality and risk of radiologically confirmed subsequent new vertebral fractures, and thus offers a mechanism to narrow the treatment gap in patients having sustained a hip fragility fracture.


Hip fracture is a serious complication of osteoporosis affecting approximately 300 000 Americans per year and is associated with a 20%-30% 1-year mortality rate. Most patients with hip fracture are elderly (average age, 80-81 years), with multiple underlying medical conditions and are often unable to timely attend post-hospitalization outpatient follow-up to initiate anti-osteoporosis treatment. As a result, only ~10% of post­hip fracture patients receive treatment for underlying osteoporosis. We have previously reported that zoledronic acid (ZA) administered during initial fracture hospitalization (IP-ZA) is safe and can effectively improve the osteoporosis treatment rate to 70%. The present study analyzed the clinical outcomes of 652 patients who had sustained hip fractures and were treated with IP-ZA and 1926 matched controls and revealed significantly reduced rates of all-cause mortality and vertebral compression fracture (VCF) during a 2-year follow-up period. Of note, nearly 90% of the treated patients received only a single dose of ZA (namely, IP-ZA), suggesting that, for most patients, the only opportunity to receive anti-osteoporosis treatment was during the index fracture hospitalization. Importantly, reduced mortality and VCF rates were readily seen in this single-dose group of patients. Our data suggest that IP-ZA is beneficial for osteoporotic hip fracture.


Assuntos
Difosfonatos , Fraturas do Quadril , Hospitalização , Imidazóis , Ácido Zoledrônico , Humanos , Fraturas do Quadril/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Feminino , Masculino , Idoso de 80 Anos ou mais , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Imidazóis/farmacologia , Idoso , Conservadores da Densidade Óssea/uso terapêutico
16.
Pediatrics ; 154(1)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38841764

RESUMO

Despite >1 in 5 children taking prescription drugs in the United States, off-label drug use is common. To increase the study of drugs in children, regulatory bodies have enacted legislation to incentivize and require pediatric drug studies. As a result of this legislation, novel trial approaches, and an increase in personnel with pediatric expertise, there have been numerous advancements in pediatric drug development. With this review, we aim to highlight developments in pediatric pharmacology over the past 6 years for the most common disease processes that may be treated pharmacologically by the pediatric primary care provider. Using information extracted from label changes between 2018 and 2023, the published literature, and Clinicaltrials.gov, we discuss advances across multiple therapeutic areas relevant to the pediatric primary care provider, including asthma, obesity and related disorders, mental health disorders, infections, and dermatologic conditions. We highlight instances in which new drugs have been developed on the basis of a deeper mechanistic understanding of illness and instances in which labels have been expanded in older drugs on the basis of newly available data. We then consider additional factors that affect pediatric drug use, including cost and nonpharmacologic therapies. Although there is work to be done, efforts focused on pediatric-specific drug development will increase the availability of evidence-based, labeled guidance for commonly prescribed drugs and improve outcomes through the safe and effective use of drugs in children.


Assuntos
Uso Off-Label , Atenção Primária à Saúde , Humanos , Criança , Uso Off-Label/legislação & jurisprudência , Pediatria , Estados Unidos , Desenvolvimento de Medicamentos/legislação & jurisprudência , Asma/tratamento farmacológico
17.
J Neurosci ; 44(28)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38830758

RESUMO

Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable Shank3 complexes is regulated by the binding of zinc to the C-terminal sterile-alpha-motif (SAM) domain of Shank3. Mutations in the SAM domain of Shank3 result in altered synaptic function and morphology, and disruption of zinc in synapses that express Shank3 leads to a reduction of postsynaptic proteins important for synaptic structure and function. This suggests that zinc supports the localization of postsynaptic proteins via Shank3. Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice-which lack synaptic zinc-show behavioral deficits associated with autism spectrum disorder and schizophrenia. Here we show that male and female ZnT3 KO mice have smaller dendritic spines and miniature excitatory postsynaptic current amplitudes than wildtype (WT) mice in the auditory cortex. Additionally, spine size deficits in ZnT3 KO mice are restricted to synapses that express Shank3. In WT mice, synapses that express both Shank3 and ZnT3 have larger spines compared to synapses that express Shank3 but not ZnT3. Together these findings suggest a mechanism whereby presynaptic ZnT3-dependent zinc supports postsynaptic structure and function via Shank3 in a synapse-specific manner.


Assuntos
Córtex Auditivo , Proteínas de Transporte de Cátions , Espinhas Dendríticas , Proteínas do Tecido Nervoso , Sinapses , Animais , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Sinapses/metabolismo , Espinhas Dendríticas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Córtex Auditivo/metabolismo , Feminino , Masculino , Camundongos Knockout , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-38841989

RESUMO

Opinion 130 deals with a Request for an Opinion asking the Judicial Commission to clarify whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate. The Request is approved and an answer is given. The name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate because it is a later homonym of the validly published cyanobacterial name Rhodococcus Hansgirg 1884. The Judicial Commission also clarifies that it has the means to resolve such cases by conserving a name over an earlier homonym. It is concluded that the name Rhodococcus Zopf 1891 (Approved Lists 1980) is significantly more important than the name Rhodococcus Hansgirg 1884 and therefore the former is conserved over the latter. This makes the name Rhodococcus Zopf 1891 (Approved Lists 1980) legitimate.


Assuntos
Rhodococcus , Terminologia como Assunto , Rhodococcus/classificação
19.
Curr Protoc ; 4(6): e1090, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923331

RESUMO

In the event of a sunlight-blocking, temperature-lowering global catastrophe, such as a global nuclear war, super-volcano eruption or large asteroid strike, normal agricultural practices would be severely disrupted with a devastating impact on the global food supply. Despite the improbability of such an occurrence, it is prudent to consider how to sustain the surviving population following a global catastrophe until normal weather and climate patterns resume. Additionally, the ongoing challenges posed by climate change, droughts, flooding, soil salinization, and famine highlight the importance of developing food systems with resilient inputs such as lignocellulosic biomass. With its high proportion of cellulose, the abundant lignocellulosic biomass found across the Earth's land surfaces could be a source of energy and nutrition, but it would first need to be converted into foods. To understand the potential of lignocellulosic biomass to provide energy and nutrition to humans in post-catastrophic and other food crisis scenarios, compositional analyses should be completed to gauge the amount of energy (soluble sugars) and other macronutrients (protein and lipids) that might be available and the level of difficulty in extracting them. Suitable preparation of the lignocellulosic biomass is critical to achieve consistent and comparable results from these analyses. Here we describe a compilation of protocols to prepare lignocellulosic biomass and analyze its composition to understand its potential as a precursor to produce post-catastrophic foods which are those that could be foraged, grown, or produced under the new climate conditions to supplement reduced availability of traditional foods. These foods have sometimes been referred to in the literature as emergency, alternate, or resilient foods. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Convection oven drying (1 to 2 days) Alternate Protocol 1: Air-drying (2 to 3 days) Alternate Protocol 2: Lyophilization (1 to 4 days) Support Protocol 1: Milling plant biomass Support Protocol 2: Measuring moisture content Basic Protocol 2: Cellulose determination Basic Protocol 3: Lignin determination Basic Protocol 4: Crude protein content by total nitrogen Basic Protocol 5: Crude fat determination via soxtec extraction system Basic Protocol 6: Sugars by HPLC Basic Protocol 7: Ash content.


Assuntos
Biomassa , Lignina , Lignina/análise , Lignina/química , Plantas/química , Plantas/metabolismo , Abastecimento de Alimentos , Mudança Climática
20.
Artigo em Inglês | MEDLINE | ID: mdl-38791745

RESUMO

Sickle cell disease (SCD) is a group of chronic, genetic disorders of the red blood cells with significant gaps in access to evidence-based clinical care. Sickle Treatment and Outcomes Research in the Midwest (STORM), a provider network, utilized Project ECHO (Extension for Community Health Outcomes), a telementoring model, to deliver evidence-based education about SCD management. The purpose of this mixed-methods study is to evaluate the utility of Project ECHO as an educational strategy for healthcare providers treating children and adults with SCD. Annual evaluations were administered to STORM TeleECHO participants from 2016 to 2021. Survey data showed a statistically significant change in self-reported provider confidence in the ability to provide care for adult patients with SCD; identify suitable candidates for disease-modifying therapies; and confidence to prescribe disease-modifying therapies. Participants who attended at least 10 sessions were invited to participate in a semi-structured interview. Qualitative data were analyzed using thematic analysis and several themes emerged about the benefits, including (1) increased confidence, (2) integrated best-practice care, (3) connection to provider network and access to experts, (4) high-quality educational presentations and (5) opportunities for collaboration and a sense of community. This suggests that Project ECHO is accessible and leads to increased confidence in providers caring for individuals with SCD. Overall, participant knowledge gains successfully demonstrated the utility of Project ECHO as an educational resource for providers.


Assuntos
Anemia Falciforme , Anemia Falciforme/terapia , Humanos , Adulto , Pessoal de Saúde/educação , Feminino , Masculino , Prática Clínica Baseada em Evidências , Telemedicina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA