Contemporary deep brain stimulation (DBS) for Parkinson's disease is delivered continuously, and adjustments based on patient's changing symptoms must be made manually by a trained clinician. ...Patients may be subjected to energy intensive settings at times when they are not needed, possibly resulting in stimulation-induced adverse effects, such as dyskinesia. One solution is 'adaptive' DBS, in which stimulation is modified in real time based on neural signals that co-vary with the severity of motor signs or of stimulation-induced adverse effects. Here we show the feasibility of adaptive DBS using a fully implanted neural prosthesis.
We demonstrate adaptive deep brain stimulation in two patients with Parkinson's disease using a fully implanted neural prosthesis that is enabled to utilize brain sensing to control stimulation amplitude (Activa PC + S). We used a cortical narrowband gamma (60-90 Hz) oscillation related to dyskinesia to decrease stimulation voltage when gamma oscillatory activity is high (indicating dyskinesia) and increase stimulation voltage when it is low.
We demonstrate the feasibility of 'adaptive deep brain stimulation' in two patients with Parkinson's disease. In short term in-clinic testing, energy savings were substantial (38%-45%), and therapeutic efficacy was maintained.
This is the first demonstration of adaptive DBS in Parkinson's disease using a fully implanted device and neural sensing. Our approach is distinct from other strategies utilizing basal ganglia signals for feedback control.
Food Insecurity and Child Health Thomas, Margaret M C; Miller, Daniel P; Morrissey, Taryn W
Pediatrics,
10/2019, Letnik:
144, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Food insecurity is an important public health problem facing children in the United States. Although a number of previous studies suggest that food insecurity has negative impacts on health, these ...studies have not dealt thoroughly with issues of selection bias. We use propensity scoring techniques to approximate the causal effects of food insecurity on children's health and health care use outcomes.
We use nationally representative data from the 2013-2016 waves of the National Health Interview Study (
= 29 341). Using inverse probability of treatment weighting, a propensity scoring method, we examine a broad range of child health outcomes and account for a comprehensive set of controls, focusing on a sample of children 2 to 17 years old.
Household food insecurity was related to significantly worse general health, some acute and chronic health problems, and worse health care access, including forgone care and heightened emergency department use, for children. Compared to rates had they not been food insecure, children in food-insecure household had rates of lifetime asthma diagnosis and depressive symptoms that were 19.1% and 27.9% higher, rates of foregone medical care that were 179.8% higher, and rates of emergency department use that were 25.9% higher. No significant differences emerged for most communicable diseases, such as ear infections or chicken pox, or conditions that may develop more gradually, including anemia and diabetes.
Policies used to reduce household food insecurity among children may also reduce children's chronic and acute health problems and health care needs.
We assessed anxiety consistent (i.e., “traditional”) and inconsistent (i.e., “atypical”) with diagnostic and statistical manual (DSM) definitions in autism spectrum disorder (ASD). Differential ...relationships between traditional anxiety, atypical anxiety, child characteristics, anxiety predictors and ASD-symptomology were explored. Fifty-nine participants (7–17 years, M
age
= 10.48 years; IQ > 60) with ASD and parents completed semi-structured interviews, self- and parent-reports. Seventeen percent of youth presented with traditional anxiety, 15 % with atypical anxiety, and 31 % with both. Language ability, anxious cognitions and hypersensitivity predicted traditional anxiety, whereas traditional anxiety and ASD symptoms predicted atypical anxiety. Findings suggest youth with ASD express anxiety in ways similar and dissimilar to DSM definitions. Similarities support the presence of comorbid anxiety disorders in ASD. Whether dissimilarities are unique to ASD requires further examination.
The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the ...invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms ...governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocytespecific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.
In this article, the authors present an analysis of radiocarbon dates from a stratified deposit at the Greek Geometric period settlement of Zagora on the island of Andros, which are among the few ...absolute dates measured from the period in Greece. The dates assigned to Greek Geometric ceramics are based on historical and literary evidence and are found to contradict absolute dates from the central Mediterranean which suggest that the traditional dates are too young. The results indicate the final period at Zagora, the Late Geometric, should be seen as starting at least a century earlier than the traditional date of 760 BC.
Short stature remains the most common reason for referral to a pediatric Endocrinologist and its management remains a challenge. One of the main controversies is the diagnosis of idiopathic short ...stature and the role of new technologies for genetic investigation of children with inadequate growth.
Complexities in management of children with short stature includes selection of who should receive interventions such as recombinant human growth hormone, and how should this agent dose be adjusted during treatment. Should anthropometrical data be the primary determinant or should biochemical and genetic data be used to improve growth response and safety? Furthermore, what is considered a suboptimal response to growth hormone therapy and how should this be managed?
Treatment of children with short stature remains a “hot” topic and more data is needed in several areas. These issues are reviewed in this paper.
•Endocrinologists should be familiar with gene technologies to assess short stature.•The diagnosis of milder forms of growth hormone deficiency remains a challenge.•Adequate monitoring of the efficacy and safety of GH should remain a priority.
Anti-angiogenic therapies have generated significant interest for their potential to combat tumor growth. However, tumor overproduction of pro-angiogenic ligands can overcome these therapies, ...hampering success of this approach. To circumvent this problem, we target the resynthesis of phosphoinositides consumed during intracellular transduction of pro-angiogenic signals in endothelial cells (EC), thus harnessing the tumor's own production of excess stimulatory ligands to deplete adjacent ECs of the capacity to respond to these signals. Using zebrafish and human endothelial cells in vitro, we show ECs deficient in CDP-diacylglycerol synthase 2 are uniquely sensitive to increased vascular endothelial growth factor (VEGF) stimulation due to a reduced capacity to re-synthesize phosphoinositides, including phosphatidylinositol-(4,5)-bisphosphate (PIP2), resulting in VEGF-exacerbated defects in angiogenesis and angiogenic signaling. Using murine tumor allograft models, we show that systemic or EC specific suppression of phosphoinositide recycling results in reduced tumor growth and tumor angiogenesis. Our results suggest inhibition of phosphoinositide recycling provides a useful anti-angiogenic approach.
Abstract Background With an increasing proportion of older adults and the associated risk of Alzheimer’s Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ...ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. Methods This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group ( n =57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. Discussion This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. Trial registration ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).
Most cancer-related deaths are due to the development of metastatic disease, and several new molecularly targeted agents in clinical development have the potential to prevent disease progression. ...However, it remains difficult to assess the efficacy of antimetastatic agents in the clinical setting, and an increased understanding of how such agents work at different stages of the metastatic cascade is important in guiding their clinical use. We used optical window chambers combined with photobleaching, photoactivation, and photoswitching to quantitatively measure (a) tumor cell movement and proliferation by tracking small groups of cells in the context of the whole tumor, and (b) E-cadherin molecular dynamics in vivo following perturbation of integrin signaling by inhibiting focal adhesion kinase (FAK) and Src. We show that inhibition of Src and FAK suppresses E-cadherin-dependent collective cell movement in a complex three-dimensional tumor environment, and modulates cell-cell adhesion strength and endocytosis in vitro. This shows a novel role for integrin signaling in the regulation of E-cadherin internalization, which is linked to regulation of collective cancer cell movement. This work highlights the power of fluorescent, direct, in vivo imaging approaches in the preclinical evaluation of chemotherapeutic agents, and shows that inhibition of the Src/FAK signaling axis may provide a strategy to prevent tumor cell spread by deregulating E-cadherin-mediated cell-cell adhesions.
PDF
