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the aims of the review, we believe that the targeted approach was appropriate. The evidence presented in this article highlights the need for alternatives to strict QALY-based approaches to prevent avoidable health inequities when determining cost-effectiveness of healthcare interventions for non-ambulatory populations against fixed cost-effectiveness thresholds. An alternative metric, the Equal Value of Life Years Gained (evLYG), has been proposed as a supplementary measure for use alongside the QALY for its potential to alleviate bias against disabled patient populations during the assessment of healthcare treatments.

Pituitary insufficiency is a common toxicity of cranial radiotherapy received in childhood for central nervous system, head and neck, and hematological malignancies. There is a recognized deficiency pattern and correlation with prescribed radiotherapy dose; however, correlation with measured pituitary dose (which can be minimized with modern radiotherapy techniques) has not previously been assessed.

Retrospective analysis was carried out of measured pituitary dose and endocrine outcomes of patients receiving cranial, total body, or head and neck photon beam radiotherapy at a tertiary center from July 2008 to October 2019.

Complete data for 102 patients were available. Median (IQR) age at radiotherapy was 9.0 (6.0-12.0) and follow-up 5.7 years (3.5-9.1). Most patients received focal brain radiotherapy (36.3%) or total body irradiation (32.4%); most frequent diagnoses were acute lymphoblastic leukemia (25.5%) and medulloblastoma (17.6%). The majority developed pituitary insufficiency (64; 62.7%); 41% had ufficiency even at lower doses, despite modern radiotherapy techniques. These data highlight the importance of minimizing pituitary dose and early specialist endocrine follow-up.

The investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS).

The fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1mg/kg/day). Depressive behaviors of these rats were determined through an open-field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS-stimulated microglia and CRS-stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor.

(i) SGKL improved the altered behaviors in CRS-stimulated rats; (ii) SGKL ameliorated the CRS-induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF-α, IL-1β, and IL-6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α-diversity indices and shifted β-diversity in CRS-stimulated rats; (v) at the genus level, SGKL decreased the CRS-enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL-treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS-decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS-induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats.

SGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.

SGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.Unbalanced Ca2+ homeostasis serves an essential role in the occurrence and development of septic myocardial injury. However, the mechanism of Ca2+ homeostasis in septic myocardial depression is poorly understood due to the complexity of Ca2+ transporters in excitable cells. It was therefore hypothesized that cardiac dysfunction, myocardial injury and cardiac apoptosis in septic myocardial depression are associated with elevated intracellular Ca2+ concentrations caused by stromal interaction molecule 1 (STIM1)/Orai calcium release‑activated calcium modulator 1 (Orai1)‑mediated store‑operated Ca2+ entry (SOCE). LXH254 mouse A septic myocardial depression model was established using the cecal ligation and puncture operation (CLP) in mice and was simulated in H9C2 cells via lipopolysaccharide (LPS) stimulation. Cardiac function, myocardial injury, cardiac apoptosis and the expression levels of Bax, Bcl‑2, STIM1 and Orai1 were quantified in vivo at 6, 12 and 24 h. Changes in the intracellular Ca2+ concentration, SOCE and the dction, cardiac injury and myocardial depression may be related to increased intracellular Ca2+ concentration resulting from STIM1/Orai1‑mediated SOCE, which may provide a potential method to alleviate septic myocardial depression.

Intravenous thrombolysis (IVT) with tenecteplase has been associated with better clinical outcomes in acute ischemic stroke (AIS) patients with confirmed large vessel occlusions compared to IVT with alteplase. However, the utility of tenecteplase for the treatment of all AIS patients eligible for IVT has not been established.

We compared the safety and efficacy of tenecteplase versus alteplase in AIS patients by analyzing propensity score matched data from 20 centers participating in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients receiving IVT with tenecteplase were matched with up to 3 patients receiving alteplase from the same center. The primary outcome of interest was the distribution of 3-month functional outcomes. Secondary outcomes included the rates of patients with symptomatic intracranial hemorrhage (SICH) in the first 24hours, excellent (modified Rankin Scale [mRS] score=0-1) or good (mRS score=0-2) functional outcome, and all-cause mortalitonth clinical outcomes compared to IVT with alteplase in AIS patients, with no increased risk of symptomatic intracranial bleeding. ANN NEUROL 2022;92349-357.The Autistic community values neurodiversity-positive approaches rather than behavioral interventions for Autistic children; however, little is known about what that would look like in occupational therapy. Frequently, researchers seek parent perspectives for understanding Autistic children's preferences, while to date insufficient attention has been paid to Autistic adults as valuable informants on the Autistic experience of Autistic children. The objective of the study was to understand Autistic adult perspectives on pediatric occupational therapy for Autistic children. We sought and thematically analyzed data from a large Facebook group and an occupational therapy podcast on Autistic values, needs, and experiences in pediatric occupational therapy. Participants described wanting therapy that supported Autistic identities rather than trying to "fix" children, changing environments or tasks to promote participation, and setting goals that address self-advocacy and autonomy. Occupational therapy practitioners should critically reflect on their practice's alignment with Autistic values and start to shift their practice as needed.Mitochondria are the critical organelles involved in various cellular functions. Mitochondrial biogenesis is activated by multiple cellular mechanisms which require a synchronous regulation between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). The mitochondrial DNA copy number (mtDNA‑CN) is a proxy indicator for mitochondrial activity, and its alteration reflects mitochondrial biogenesis and function. Despite the precise mechanisms that modulate the amount and composition of mtDNA, which have not been fully elucidated, mtDNA‑CN is known to influence numerous cellular pathways that are associated with cancer and as well as multiple other diseases. In addition, the utility of current technology in measuring mtDNA‑CN contributes to its extensive assessment of diverse traits and tumorigenesis. The present review provides an overview of mtDNA‑CN variations across human cancers and an extensive summary of the existing knowledge on the regulation and machinery of mtDNA‑CN. The current information on the advanced methods used for mtDNA‑CN assessment is also presented.The Weekly Calendar Planning Activity (WCPA) may improve understanding of functional cognition in people with Parkinson disease (PwPD) without dementia. We aimed to determine if WCPA performance (a) discriminates between PwPD with and without cognitive impairment and healthy controls and (b) correlates with other indicators of cognition and daily function. This was a cross-sectional study. Parkinson disease (PD) participants without dementia were divided into normal cognition (PD-NC, n = 25) and possible mild cognitive impairment (PD-MCI, n = 21) groups. Their WCPA performance was compared with that of a normative sample (n = 196) and correlated with neuropsychological test performance and self-reported cognition and participation. Both the PD-MCI and PD-NC groups had impaired WCPA performance. WCPA performance correlated with executive function, processing speed, and self-reported cognition and participation. The WCPA can detect functional cognitive deficits in PwPD without dementia and can inform occupational therapy interventions to support functional cognition, occupational performance, and participation in this population.

Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.

Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline-induced PH (MCT-PH) male rats were treated with 17β-estradiol (E

) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.

Many circulating miRNAs, including miR-21-5p and miR-574-5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls. However, miR-574-5p showed no difference in the lungs of MCT-PH rats and controls. miR-21-5p was selected for further analysis in rats as E

strongly regulated it. E

decreased miR-21-5p expression in the lungs of MCT-PH rats by ERβ. E

reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E

and miR-21-5p antagonist.

miR-21-5p level was remarkably associated with PH severity in patients. Moreover, the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E

on MCT-PH through ERβ.

miR-21-5p level was remarkably associated with PH severity in patients. Moreover, the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT-PH through ERβ.