Background Large‐vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines ...blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance‐identified stroke code activations <18 hours from symptom onset were recruited at Brandon Regional Hospital (Brandon, FL) between May 2021 and August 2022. Previously determined cutoff concentrations of plasma glial fibrillary acidic protein (213 pg/mL) and d ‐dimer (600 ng/mL) were used in combination with prehospital stroke scales to detect LVO. We compared rates of LVO detection against a reference standard using computed tomography/magnetic resonance angiography. Results A total of 382 patients with suspected stroke were recruited. The final cohort was composed of 323 patients with suspected stroke with the following distribution: LVO ischemic stroke (n = 29, 9%), non‐LVO ischemic stroke (n = 48, 15%), hemorrhagic stroke (n = 13, 4%), transient ischemic attack (n = 12, 3.9%), and stroke mimics (n = 220, 68.1%). Combining blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with the scale field assessment stroke triage for emergency destination yielded the best performance for LVO detection, with specificity of 94% and sensitivity of 71%. Performance was found to be higher in a subanalysis focusing on patients presenting <6 hours from symptom onset, with 93% specificity and 81% sensitivity. Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage. Conclusion The present work prospectively validated the potential utility of previously defined glial fibrillary acidic protein and d ‐dimer cutoff levels (ie, 213 pg/mL and 600 ng/mL, respectively), demonstrating their value for discrimination of LVO stroke from differential diagnoses during code stroke workups. (ClinicalTrials.gov number, NCT04292600.)
This study evaluated the effects of HgCl2 on renal parameters in nonlactating and lactating rats and their pups, as well as the preventive role of ZnCl2 . Rats received 27 mg kg(-1) ZnCl2 for five ...consecutive days and 5 mg kg(-1) HgCl2 for five subsequent days (s.c.). A decrease in δ-aminolevulinic acid dehydratase (δ-ALA-D) activity in the blood and an increase in urine protein content in renal weight as well as in blood and urine Hg levels were observed in lactating and nonlactating rats from Sal-Hg and Zn-Hg groups. ZnCl2 prevented partially the δ-ALA-D inhibition and the proteinuria in nonlactating rats. Renal Hg levels were increased in all HgCl2 groups, and the ZnCl2 exposure potentiated this effect in lactating rats. Nonlactating rats exposed to HgCl2 exhibited an increase in plasma urea and creatinine levels, δ-ALA-D activity inhibition and histopathological alterations (necrosis, atrophic tubules and collagen deposition) in the kidneys. ZnCl2 exposure prevented the biochemical alterations. Hg-exposed pups showed lower body and renal weight and an increase in the renal Hg levels. In conclusion, mercury-induced nephrotoxicity differs considerably between lactating and nonlactating rats. Moreover, prior exposure with ZnCl2 may provide protection to individuals who get exposed to mercury occupationally or accidentally.
We consider the electronic structure near vacancies in the half-filled honeycomb lattice. It is shown that vacancies induce the formation of localized states. When particle-hole symmetry is broken, ...localized states become resonances close to the Fermi level. We also study the problem of a finite density of vacancies, obtaining the electronic density of states, and discussing the issue of electronic localization in these systems. Our results also have relevance for the problem of disorder in d-wave superconductors.
Abstract In order to study the structural formation yield of germanium-vacancy (GeV) centers from implanted Ge in diamond, we have investigated its lattice location by using the β − emission ...channeling technique from the radioactive isotope 75 Ge ( t 1/2 = 83 min) produced at the ISOLDE/CERN facility. 75 Ge was introduced via recoil implantation following 30 keV ion implantation of the precursor isotope 75 Ga (126 s) with fluences around 2 × 10 12 –5 × 10 13 cm −2 . While for room temperature implantation fractions around 20% were observed in split-vacancy configuration and 45% substitutional Ge, following implantation or annealing up to 900 °C, the split-vacancy fraction dropped to 6%–9% and the substitutional fraction reached 85%–96%. GeV complexes thus show a lower structural formation yield than other impurities, with substitutional Ge being the dominant configuration. Moreover, annealing or high-temperature implantation seem to favor the formation of substitutional Ge over GeV. Our results strongly suggest that GeV complexes are thermally unstable and transformed to substitutional Ge by capture of mobile carbon interstitials, which is likely to contribute to the difficulties in achieving high formation yields of these optically active centers.
Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, 'sporadic' bilateral adrenal hyperplasia (BAH) is the most frequent cause of PA and remains ...without genetic etiology in most cases. Our aim was to investigate new genetic defects associated with BAH and PA. We performed whole-exome sequencing (paired blood and adrenal tissue) in six patients with PA caused by BAH that underwent unilateral adrenalectomy. Additionally, we conducted functional studies in adrenal hyperplastic tissue and transfected cells to confirm the pathogenicity of the identified genetic variants. Rare germline variants in phosphodiesterase 2A (PDE2A) and 3B (PDE3B) genes were identified in three patients. The PDE2A heterozygous variant (p.Ile629Val) was identified in a patient with BAH and early-onset HT at 13 years of age. Two PDE3B heterozygous variants (p.Arg217Gln and p.Gly392Val) were identified in patients with BAH and HT diagnosed at 18 and 33 years of age, respectively. A strong PDE2A staining was found in all cases of BAH in zona glomerulosa and/or micronodules (that were also positive for CYP11B2). PKA activity in frozen tissue was significantly higher in BAH from patients harboring PDE2A and PDE3B variants. PDE2A and PDE3B variants significantly reduced protein expression in mutant transfected cells compared to WT. Interestingly, PDE2A and PDE3B variants increased SGK1 and SCNN1G/ENaCg at mRNA or protein levels. In conclusion, PDE2A and PDE3B variants were associated with PA caused by BAH. These novel genetic findings expand the spectrum of genetic etiologies of PA.
A microscopic theory for rare-earth ferromagnetic hexaborides, such as Eu(1-x)Ca(x)B6, is proposed on the basis of the double-exchange Hamiltonian. In these systems, the reduced carrier ...concentrations place the Fermi level near the mobility edge, introduced in the spectral density by the disordered spin background. We show that the transport properties such as Hall effect, magnetoresitance, frequency dependent conductivity, and DC resistivity can be quantitatively described within the model. We also make specific predictions for the behavior of the Curie temperature, Tc, as a function of the plasma frequency, omega_p.
Background
Percutaneous cement discoplasty (PCD) is a minimally invasive procedure. We aim to explore the efficacy and indication(s) of PCD in patients with degenerative disc disease (DDD).
Methods
...The search was conducted across Ovid MEDLINE, Ovid Embase, and PubMed. Data on study design, patient demographics, pre- and post-procedure Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) scores, and complications were extracted. Inclusion criteria focused on adult patients with degenerative spinal diseases treated with cement discoplasty. The overall effect size was evaluated using a forest plot, and heterogeneity was assessed using the I
2
statistic and chi-squared test.
Results
The search strategy yielded six studies, which included 336 patients (73.8% female, 26.2% male) with a mean average age of 74.6 years. VAS scores were reported in all studies, showing a significant difference between pre- and post-PCD pain scores (Weighted Mean Difference WMD: -3.45; 95% CI: -3.83, -3.08; I
2
= 15%; P < .001). ODI scores were reported in 83% of studies, with a significant difference between pre- and post-PCD scores (WMD: -22.22; 95% CI: -25.54, -18.89; I
2
= 61%; p < .001). Complications reported included infections, thrombophlebitis, vertebral fractures, disc extrusion, and the need for further operations.
Conclusions
The analysis showed clinically significant improvements in pain and functional disability based on VAS and ODI scores. However, due to methodological limitations and a high risk of bias, the validity and generalizability of the findings are uncertain. Despite these issues, the results provide preliminary insights into PCD's potential efficacy and can guide future research to address current limitations.
Abstract
Background
Sleep/wake disturbance is a common and debilitating symptom of Alzheimer’s disease (AD) that precedes cognitive loss. The lateral hypothalamic area (LHA) is critical in ...orchestrating the sleep/wake cycle through the neuropeptide orexin and melanin‐concentrating hormone. We previously demonstrated that LHA neurons accumulate AD‐tau from Braak stage (BB) 0 and losses ∼72% of neurons by BB6. Little is known about the molecular changes underlying LHA vulnerability during AD progression. We investigated RNA expression changes in LHA across Braak stages to close this gap.
Method
We dissected LHA from 30um‐thick sections of the brain from healthy control (HC) and subjects at progressive AD stages and extracted RNA using conventional techniques. We ran RNA transcriptomic assay using customized and neuropathology nCounter
®
(Nanostring) panels. The Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when log2 fold‐change was > = |1| and the p‐value was <0.05.
Result
We found an upregulation of HCRTR1, LDHC, NKX6, and SLC11A1 from early stages (BB2‐3), whereas HCRTR2 RNA levels remained stable. Circadian gene PER2 was downregulated from the intermediate stages (BB4). Gene Ontology analyses detected dysregulation of neuropeptide‐ligand interaction pathways from early AD. Linoleic acid metabolism, fat digestion and absorption, and immune pathways became dysregulated at intermediate stages, while glycolysis and gluconeogenesis pathways were in late stages (BB5‐6). Of note, it is critical to consider that the massive LHA neuronal loss during AD progression may confound the interpretation of changes in late stages because of the few remaining neurons.
Conclusion
nCounter
®
is suitable for identifying transcriptome changes in LHA, even at early AD stages. Molecular profiling of LHA across the Braak stage revealed that the earliest changes are associated with an imbalance in neurotransmitter receptors, while the decline in metabolism and increased inflammation marked the intermediate stage. The late‐stage AD is characterized by hypoglycemia and energy deficit. Notably, discrepancies in receptor behavior can inform more effective symptomatic treatment for sleep dysfunction in AD.
People living with HIV (PWH) experience an accelerated aging process. There is no anthropometric predictive model for appendicular skeletal muscle mass (ASM) in PWH. This study develops ...anthropometric models to predict and validate ASM measured by dual energy x-ray absorptiometry (DXA) in PWH; DXA scans were obtained for 125 PWH (male = 74; age >18 years) on antiretroviral therapy. Fat mass ratio was used for lipodystrophy diagnosis. A multiple stepwise linear regression considered ASM DXA as the dependent variable and validated by PRESS method. A high power of determination and low standard estimate error were found for ASM DXA -predicted (adjusted r2 = 0.84 to 0.87, standard estimate error = 1.7-1.6 kg) and high PRESS validation coefficients (Q 2PRESS = 0.84-0.86, S PRESS = 1.7-1.6 kg). The variables included were lipodystrophy diagnosis, medial calf circumference, sex, and total body weight. We present novel, reliable, and validated anthropometric models to predict ASM DXA in PWH.
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