Special AT-rich sequence-binding protein 2 immunohistochemistry in the diagnosis of osteosarcoma in dogs.

Malignant osteoblasts can have markedly pleomorphic phenotypes and variable amounts of tumour-associated matrix, complicating the ability of pathologists to accurately differentiate osteosarcoma (OSA) from other types of neoplasms using only histopathology. Current immunohistochemical markers for animals have limited sensitivity and specificity in identifying OSA or produce inconsistent results. Immunohistochemistry (IHC) for special AT-rich sequence-binding protein 2 (SATB2) has been used in human medicine to aid in identification of normal and neoplastic osteoblasts, and the objective of this study was to determine whether this marker could also be useful for the diagnosis of canine OSA. Initially, SATB2 IHC was performed on eight samples from cases of well-differentiated canine OSA and on other tumour types for which OSA is a differential diagnosis, as well as on normal tissues, to assess sensitivity and cross-reactivity. Following confirmation that SATB2 is immunoreactive for normal and neoplastic canine osteoblasts and negative in other non-osseous mesenchymal cell types and organs, SATB2 IHC was tested on 123 cases of poorly differentiated malignant neoplasms as part of a panel with other immunohistochemical markers, as appropriate, based on histomorphology and differential diagnoses. The conclusion is that SATB2 IHC is a sensitive and specific marker for identifying canine OSA when used in a panel with other immunohistochemical markers and in conjunction with supportive clinical history.

High-density lipoprotein over midlife and future cognition in women: The SWAN HDL ancillary study.

CONTEXT: Limited data provides evidence-based insights on the association between comprehensive metrics of high-density lipoproteins (HDL) and cognitive performance, especially in midlife women for whom benefit might be the greatest. OBJECTIVE: To assess the associations of serum HDL metrics including HDL lipid content [HDL cholesterol, phospholipid (HDL-PL), triglyceride], proteins/subclasses [apolipoprotein A-1 (apoA-1); small, medium, large, total HDL particle (HDL-P); and HDL size], and cholesterol efflux capacity with cognitive performance in midlife women. METHODS: This prospective cohort study was conducted among 503 midlife women (1234 observations) from the Study of Women's Health Across the Nation HDL ancillary study. Joint models were applied to examine associations of HDL metrics assessed at midlife (50.2 ± 2.9 years, baseline of the current study) and their changes over midlife (6.1 ± 3.9 years of duration) with subsequent cognitive performance [working memory (Digit Span Backward Test), processing speed (Symbol Digit Modalities Test), and episodic memory immediate and delayed recall (East Boston memory test)] assessed repeatedly (maximum 5 times) 1.5 ± 1 years later over 7.72 ± 4.10 years of follow up. RESULTS: Higher total HDL-P and smaller HDL size at midlife were associated with a better subsequent immediate recall, delayed recall and/or processing speed. Greater increase in HDL-PL, apoA-1, medium HDL-P, and total HDL-P and less increase in HDL size over midlife were associated with a better subsequent immediate and/or delayed recall. CONCLUSIONS: Enhancing specific serum HDL metrics during midlife could be promising in cognitive restoration, particularly memory, the initial and predominant symptom of Alzheimer's disease.

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy.

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or 'wolframinopathies', exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the 'plus' phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Long-Term Risk of Subsequent Neoplasms in 5-Year Survivors of Childhood Neuroblastoma: A Dutch Childhood Cancer Survivor Study-LATER 3 Study.

PURPOSE: Neuroblastoma survivors have an increased risk of developing subsequent malignant neoplasms (SMNs), but the risk of subsequent nonmalignant neoplasms (SNMNs) and risk factors are largely unknown. We analyzed the long-term risks and associated risk factors for developing SMNs and SNMNs in a well-characterized cohort of 5-year neuroblastoma survivors. METHODS: We included 563 5-year neuroblastoma survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort, diagnosed during 1963-2014. Subsequent neoplasms were ascertained by linkages with the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (Palga) and medical chart review. We calculated standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative incidences. Multivariable competing risk regression analysis was used to evaluate risk factors. RESULTS: In total, 23 survivors developed an SMN and 60 an SNMN. After a median follow-up of 23.7 (range, 5.0-56.3) years, the risk of SMN was elevated compared with the general population (SIR, 4.0; 95% CI, 2.5 to 5.9; AER per 10,000 person-years, 15.1). The 30-year cumulative incidence was 3.4% (95% CI, 1.9 to 6.0) for SMNs and 10.4% (95% CI, 7.3 to 14.8) for SNMNs. Six survivors developed an SMN after iodine-metaiodobenzylguanidine (131IMIBG) treatment. Survivors treated with 131IMIBG had a higher risk of developing SMNs (subdistribution hazard ratio [SHR], 5.7; 95% CI, 1.8 to 17.8) and SNMNs (SHR, 2.6; 95% CI, 1.2 to 5.6) compared with survivors treated without 131IMIBG; results for SMNs were attenuated in high-risk patients only (SMNs SHR, 3.6; 95% CI, 0.9 to 15.3; SNMNs SHR, 1.5; 95% CI, 0.7 to 3.6). CONCLUSION: Our results demonstrate that neuroblastoma survivors have an elevated risk of developing SMNs and a high risk of SNMNs. 131IMIBG may be a treatment-related risk factor for the development of SMN and SNMN, which needs further validation. Our results emphasize the need for awareness of subsequent neoplasms and the importance of follow-up care.

Do marked discharge summaries with recommendation text boxes enhance patient safety? A nationwide survey.

BACKGROUND: Danish hospital physicians are required to mark their discharge summaries addressing whether the patient's general practitioner (GP) is recommended to follow up as well as suggest follow-up actions. AIM: To investigate whether a new form of discharge summaries may contribute to improve the perceived patient safety following transition from hospitals to general practice. DESIGN & SETTING: This paper reports data from a questionnaire sent to a representative sample of GPs in Denmark. METHOD: A questionnaire was prepared for GPs based on background material, focus group interviews and discussions with relevant professionals. It was subsequently pilot tested by fellow researchers and GPs and revised prior to the presently reported survey. RESULTS: Of 310 participating GPs, 197 (63%) 'totally agree' or 'partly agree' that the marked discharge summaries with a recommendation text box contribute to a better handover to general practice, and 223 (72%) 'totally agree' or 'partly agree' that they improve patient safety. CONCLUSION: The majority of responding GPs believe that the marked discharge summaries with a recommendation text box enhance patient safety and facilitate the transition of care to general practice following hospital discharge.

Protocol for an open-source system to integrate calcium imaging, pupillometry, and locomotion-estimated tracking in head-fixed mice.

A wide selection of behavioral assays in systems neuroscience relies on head-fixation protocols to integrate in vivo multi-photon imaging approaches. For this, simultaneous pupillometry and locomotion tracking in head-fixed mice are used to measure behavioral responses and identify neural correlates. Here, we present an open-source protocol for assembling a complete head-fixation system that integrates pupillometry and locomotion-estimated tracking with multi-photon calcium imaging. We include detailed procedures for head-fixation and for data collection.

Optimization and application of digital droplet PCR for the detection of SARS-CoV-2 in saliva specimen using commercially available kit.

The coronavirus disease-19 pandemic has resulted in a significant global health crisis, causing hundreds of millions of cases and millions of deaths. Despite being declared endemic, SARS-CoV-2 infection continues to pose a significant risk, particularly for immunocompromised individuals, highlighting the need for a more sensitive and specific detection. Reverse transcription digital droplet polymerase chain reaction (RT-ddPCR) possesses a sensitive and absolute quantification compared to the gold standard. This study is the first to optimize RT-ddPCR for detecting SARS-CoV-2 in saliva specimens using a commercially available RT-qPCR kit. Optimization involved the assessment of the RT-ddPCR reaction mixture, annealing temperature adjustments, and validation using 40 stored saliva specimens. RT-qPCR was used as a reference method in this study. Compatibility assessment revealed that ddPCR Supermix for Probes (no dUTP) was preferable with an optimal annealing temperature of 57.6°C. Although a 25% higher primer/probe concentration provides a higher amplitude in droplet separation of positive control, the number of copy numbers decreased. An inverse correlation between Ct value and copy number concentration was displayed, presenting that the lower the Ct value, the higher the concentration, for the N and E genes with r2 values of 0.98 and 0.85, respectively. However, ORF1ab was poorly correlated (r2 of 0.34). The sensitivity of targeted and E genes was 100% and 93.3%, respectively; as for the specificity, the percentage ranged from 80.8% to 91.3%. This study implicates the applicability of a modified method in the ddPCR platform for similar types of pathogens using saliva specimens.

Screening of Sensorial and Inflammatory Changes in Patients Submitted to Orthognathic Surgery.

BACKGROUND: Despite the high levels of success after orthognathic surgery, the immediate postoperative pain and edema, besides the neurosensorial deficits, are common complications. OBJECTIVE: This study aimed to evaluate the pattern of sensory and inflammatory responses in patients undergoing orthognathic surgery. METHODS: This prospective observational study included 20 patients undergoing bimaxillary orthognathic surgery, who were evaluated in the preoperative period and on Days 1, 2, 3, 4, 5, 6, 7, and 30 after surgery, using a battery of tests to assess sensorial and inflammatory changes. RESULTS: Subjective and objective evaluations of edema indicated a trend toward edema resolution within 30 days, with a significant decrease in mouth opening on days 1, 7, and 30 after surgery. Regarding nasal obstruction, a significant increase in Nasal Obstruction Symptom Evaluation (NOSE) scores was demonstrated on the first, second, and third days, returning to preoperative levels after 30 days. There was a significant increase in visual analogic scale (VAS) scores from the first to the seventh day after surgery, with a reduction within 30 days. For mechanical and thermal sensitivity tests, the lower lip and chin regions had poorer results, without recovery after 30 days. Positive correlations were observed between painful and inflammatory parameters, as well as between subjective and objective evaluations. Analysis of saliva biomarkers did not show significant differences for pre- and postoperative CCL3 or CCL4 levels. CONCLUSION: Data provide new evidence about the early inflammatory and sensorial complications after orthognathic surgery.

Maternal hypertensive disorders of pregnancy and electrocardiographic findings among newborns: The Copenhagen Baby Heart Study.

BACKGROUND: Maternal preeclampsia is associated with both congenital heart defects and changes in left ventricular structure and function in the offspring. Whether preeclampsia and gestational hypertension also affect the offspring's cardiac conduction system is unknown. OBJECTIVES: This study assesses whether infants exposed to maternal hypertensive disorders of pregnancy (HDPs) exhibit changes in their electrocardiogram (ECG) compared with infants unexposed to HDPs. METHODS: This population-based cohort study included newborns from the Copenhagen Baby Heart Study who had an ECG performed within 30 days of birth and had available obstetric information. ECG parameters of newborns exposed to maternal HDPs were compared with those of unexposed newborns using linear regression. RESULTS: Our study cohort included 11,826 newborns, including 441 exposed to maternal preeclampsia and 320 exposed to gestational hypertension. Infants exposed to preeclampsia had prolonged QRS durations (adjusted mean difference 0.6 ms, 95% confidence interval [CI] 0.04, 1.16) and lower maximum amplitudes of the R-wave in V1 (adjusted mean difference, linear scale 0.95, 95% CI 0.90, 1.00), compared with unexposed infants. Exposure to maternal preeclampsia was not associated with changes in other ECG parameters. Exposure to gestational hypertension was associated with increased QT interval durations (QTc Bazett, adjusted mean difference 2.48 ms, 95% CI -0.23, 5.20; QTc Fridericia, adjusted mean difference 2.32 ms, 95% CI -0.19, 4.83). CONCLUSIONS: Our findings suggest that the newborn cardiac conduction system is affected by exposure to maternal preeclampsia. This could reflect the previously described thickening of the left ventricular myocardium in infants exposed to preeclampsia.

Evaluating the updated LATE-NC staging criteria using data from NACC.

INTRODUCTION: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data. METHODS: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models. RESULTS: Of 1352 participants, 502 (37%) had LATE-NC (23% stage 1a, 6% stage 1b, 58% stage 2, 13% stage 3). LATE-NC stages were associated with cognition, hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), Lewy bodies (LBs), and hippocampal atrophy. While stage 1b was associated with cognition and HS-A consistent with other stages, it was not associated with ADNC or LBs. All LATE-NC stages remained significantly associated with worse cognition when accounting for other NCs. DISCUSSION: The updated LATE-NC staging criteria capture variations in early TDP-43 pathology spread which are consequential for cognition and associations with other NCs. HIGHLIGHTS: We applied the updated limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria to data from the National Alzheimer's Coordinating Center. LATE-NC stage 1b was identified in 22% of participants with stage 1. In contrast to other LATE-NC stages, stage 1b was not associated with Alzheimer's disease neuropathologic change (ADNC) or Lewy bodies. Stages 1a and 1b were significantly associated with dementia and memory impairment. Stages 1b+ were more strongly tied to dementia than all other neuropathologic changes except high likelihood ADNC.

Synthesis and toxicity of monothiooxalamides against human red blood cells, brine shrimp (Artemia salina), and fruit fly (Drosophila melanogaster).

A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by 1H and 13C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (I). In this study, the in vitro hemolytic activity of compounds from the 2-aminopyridine (I) and 2-aminobenzimidazole (II) families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and in vivo toxicity against Drosophila melanogaster. Compounds with morpholine fragments (1g, 1h, 2g, and 2h) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide 2g showed lower toxicity and can be considered for further biological screening and application trials.

Characteristics of trans and non-binary children and adolescents who attended a tertiary hospital. / Características de niños, niñas y adolescentes trans y no binarios atendidos en un hospital de tercer nivel.

Introduction. The trans population in Argentina represents 0.43%. Our objective was to describe the characteristics of trans and non-binary children and adolescents. Population and methods. A cross-sectional study was designed. The population was all trans or nonbinary persons under 24 years of age seen by an interdisciplinary team in a tertiary university hospital from January 2019 to May 2023. The sample was obtained from the database of patients seen by reviewing electronic medical records (EMR). Results. The EMRs of 107 individuals were analyzed; the average age at first consultation was 15.3 years, and the age of self-perceived transgender identity was 11.1 years. Seventy-two percent perceived themselves as having a trans male identity; in 89.7%, their gender expression was by their self-perception, and 46.3% had a bisexual sexual orientation. Seventy-six percent acknowledged having family support; 87.3%, school support; and 92.5%, peer support. 44.8% had a hormonal strategy, 14.1% had surgery, 57.1% had mental health intervention, and 29.1% received psychiatric medication. Only three patients (2.8%) detransitioned their gender identity. Conclusion. Most individuals were trans men and perceived good support from their environments. Almost half received a hormonal strategy; less than a quarter received a surgical intervention; more than half received a mental health intervention. The detransition was infrequent.

Introducción. La población trans en Argentina representa el 0,43 %. Nuestro objetivo fue describir las características de niñas, niños y adolescentes trans y no binarios. Población y métodos. Se diseñó un estudio de corte transversal. La población fueron todas las personas menores de 24 años trans o no binarias atendidas por un equipo interdisciplinario en un hospital universitario de tercer nivel desde enero de 2019 hasta mayo de 2023. La muestra se obtuvo de la base de datos de pacientes atendidos a través de la revisión de las historias clínicas electrónicas (HCE). Resultados. Se analizaron las HCE de 107 personas; el promedio de la primera consulta fue 15,3 años y la edad de autopercepción de identidad de género trans, 11,1 años. El 72 % se percibió con una identidad varón trans; en el 89,7 %, su expresión de género fue acorde a su autopercepción y el 46,3 % tuvo una orientación sexual bisexual. El 76 % reconoció tener contención familiar; el 87,3 %, contención escolar; y el 92,5 %, contención de sus pares. El 44,8 % realizó una estrategia hormonal; el 14,1 %, intervención quirúrgica; el 57,1 %, intervención con salud mental; y el 29,1 % recibió medicación psiquiátrica. Solo 3 pacientes (2,8 %) detransicionaron su identidad de género. Conclusión. La mayoría de las personas eran varones trans y percibieron una buena contención de sus entornos. Casi la mitad recibió una estrategia hormonal; menos de un cuarto, una intervención quirúrgica; más de la mitad, una intervención con salud mental. La detransición fue infrecuente.

Epigenetic alteration of uterine Leukemia Inhibitory Factor gene after glyphosate or a glyphosate-based herbicide exposure in rats.

Glyphosate-based herbicides (GBHs) or its active ingredient, glyphosate (Gly), induce implantation failure in rats. We aimed to elucidate a mechanism of action of these compounds assessing the transcriptional and epigenetic status of the receptivity marker, leukemia inhibitory factor (Lif) gene. F0 rats were orally exposed to GBH or Gly at 3.8 or 3.9mg Gly/kg/day, respectively, from gestational day (GD) 9 until weaning. F1 females were mated and uterine samples collected at GD5. Methylation-sensitive restriction enzymes (MSRE) sites and transcription factors were in silico predicted in regulatory regions of Lif gene. DNA methylation status and histone modifications (histone 3 and 4 acetylation (H3Ac and H4Ac) and H3 lysine-27-trimethylation (H3K27me3)) were assessed. GBH and Gly decreased Lif mRNA levels and caused DNA hypermethylation. GBH increased H3Ac levels, whereas Gly reduced them; both compounds enhanced H3K27me3 levels. Finally, both GBH and Gly induced similar epigenetic alterations in the regulatory regions of Lif.

HSF1 is a prognostic determinant and therapeutic target in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a lethal primary liver tumor characterized by clinical aggressiveness, poor prognosis, and scarce therapeutic possibilities. Therefore, new treatments are urgently needed to render this disease curable. Since cumulating evidence supports the oncogenic properties of the Heat Shock Factor 1 (HSF1) transcription factor in various cancer types, we investigated its pathogenetic and therapeutic relevance in iCCA. METHODS: Levels of HSF1 were evaluated in a vast collection of iCCA specimens. The effects of HSF1 inactivation on iCCA development in vivo were investigated using three established oncogene-driven iCCA mouse models. In addition, the impact of HSF1 suppression on tumor cells and tumor stroma was assessed in iCCA cell lines, human iCCA cancer-associated fibroblasts (hCAFs), and patient-derived organoids. RESULTS: Human preinvasive, invasive, and metastatic iCCAs displayed widespread HSF1 upregulation, which was associated with a dismal prognosis of the patients. In addition, hydrodynamic injection of a dominant-negative form of HSF1 (HSF1dn), which suppresses HSF1 activity, significantly delayed cholangiocarcinogenesis in AKT/NICD, AKT/YAP, and AKT/TAZ mice. In iCCA cell lines, iCCA hCAFs, and patient-derived organoids, administration of the HSF1 inhibitor KRIBB-11 significantly reduced proliferation and induced apoptosis. Cell death was profoundly augmented by concomitant administration of the Bcl-xL/Bcl2/Bcl-w inhibitor ABT-263. Furthermore, KRIBB-11 reduced mitochondrial bioenergetics and glycolysis of iCCA cells. CONCLUSIONS: The present data underscore the critical pathogenetic, prognostic, and therapeutic role of HSF1 in cholangiocarcinogenesis.

Amiloride Sensitizes Prostate Cancer Cells to the Reversible Tyrosine Kinase Inhibitor Lapatinib by Modulating ERBB3 Subcellular Localization.

Neoadjuvant therapy (NAT) has been studied in clinically localized prostate cancer (PCa) to improve the outcomes from radical prostatectomy (RP) by 'debulking' of high-risk PCa; however, using androgen deprivation at this point risks castration resistant PCa (CRPC) clonal proliferation with potentially profound side effects such as fatigue, loss of libido, hot flashes, loss of muscle mass, and weight gain. Our goal is to identify alternative NAT that reduce hormone sensitive PCa (HSPC) without affecting androgen receptor (AR) transcriptional activity. PCa is associated with increased expression and activation of the epidermal growth factor receptor (EGFR) family, including HER2 and ErbB3. Dimerization between these receptors is required for activation of downstream targets involved in tumor progression. The FDA-approved HER2 inhibitor lapatinib has been tested in PCa but was ineffective due to continued activation of ErbB3. We now demonstrate that this is due to ErbB3 being localized to the nucleus in HSPC and thus protected from lapatinib which affect membrane localized HER2/ErbB3 dimers. Here, we show that the well-established, well-tolerated diuretic amiloride hydrochloride dose dependently prevented ErbB3 nuclear localization via formation of plasma membrane localized HER2/ErbB3 dimers. This in turn allowed lapatinib inactivation of these dimers via inhibition of its target HER2, which dephosphorylated downstream survival and proliferation regulators AKT and ERK1/2. Amiloride combined with lapatinib significantly increased apoptosis but did not affect AR transcriptional activity. Thus, our data indicate that a combination of amiloride and lapatinib could target HSPC tumors without problems associated with androgen deprivation therapy in localized PCa.

A randomised crossover trial of nitrate and breakfast on prefrontal cognitive and haemodynamic response functions.

It remains unknown whether dietary nitrate and breakfast may enhance working memory (WM) performance by augmenting physiological mechanisms and subjective psychological well-being. We performed a 3-arm randomised within-subject crossover study, with pretest-posttest comparisons, to test whether nitrate consumption via breakfast with a beetroot juice shot or regular breakfast compared to no breakfast improved WM (measured with n-back tests) and cognitive task-related changes in prefrontal cortical haemodynamic response (oxygenated- and deoxygenated-haemoglobin derived from functional near-infrared spectroscopy). In addition, effects on peripheral vascular function and self-reported psychological factors were assessed. In 60 adolescents (13-15 years old; 66% girls), WM improved in all conditions, with no intervention effects. Intervention effects were seen for oxygenated-haemoglobin changes, such that it increased after the breakfast with a nitrate shot during the WM tests and decreased after the regular breakfast. Thus, different neurophysiological mechanisms may be at play to preserve WM in adolescents depending on their breakfast composition. The trial was registered in the ISRCTN registry (ISRCTN16596056) on 21/02/2022.

Specific microRNA Profile Associated with Inflammation and Lipid Metabolism for Stratifying Allergic Asthma Severity.

The mechanisms underlying severe allergic asthma are complex and unknown, meaning it is a challenge to provide the most appropriate treatment. This study aimed to identify novel biomarkers for stratifying allergic asthmatic patients according to severity, and to uncover the biological mechanisms that lead to the development of the severe uncontrolled phenotype. By using miRNA PCR panels, we analyzed the expression of 752 miRNAs in serum samples from control subjects (n = 15) and mild (n = 11) and severe uncontrolled (n = 10) allergic asthmatic patients. We identified 40 differentially expressed miRNAs between severe uncontrolled and mild allergic asthmatic patients. Functional enrichment analysis revealed signatures related to inflammation, angiogenesis, lipid metabolism and mRNA regulation. A random forest classifier trained with DE miRNAs achieved a high accuracy of 97% for severe uncontrolled patient stratification. Validation of the identified biomarkers was performed on a subset of allergic asthmatic patients from the CAMP cohort at Brigham and Women's Hospital, Harvard Medical School. Four of these miRNAs (hsa-miR-99b-5p, hsa-miR-451a, hsa-miR-326 and hsa-miR-505-3p) were validated, pointing towards their potential as biomarkers for stratifying allergic asthmatic patients by severity and providing insights into severe uncontrolled asthma molecular pathways.

Thin-Layer TiO2 Membrane Fabrication by Condensed Layer Deposition.

A novel approach to the fabrication of thin-film supported metal oxide membranes was investigated. Nanocoatings were obtained by the condensed layer deposition of TiO2 on tubular microporous supports, applying multiple consecutive layers of TiO2/polyaniline. The surface, cross-sectional structure, and morphology of the materials were investigated by electron microscopy. Their membrane-related properties were explored by permeability measurements, rejection, and fouling analysis, using polyethylene glycol (PEG) as test molecules. The SEM images showed that TiO2 was successfully deposited on the surface, creating a layer with partial coverage of the support after each layer was deposited; consequently, the permeability of the membranes decreased gradually. Overall, the results of the flux and permeability of the membranes confirmed the coating. The transmembrane pressure (TMP) increased with each coating layer, while the rejection of the membrane showed gradual improvement.

Three-dimensional analysis of the potency of Cocos nucifera in demineralizing the artificial enamel carious lesion: a micro-CT study.

BACKGROUND: Herbal based ingredients form a more sustainable and effective means for management of ailments related to the human body. Previously plant-based extracts of Cocos nucifera had effective remineralization potential. Hence to identify the changes in enamel mineral density and volume during the remineralization procedure, this study was done with an aim of three-dimensional micro-CT analysis to identify the potency of Cocos nucifera in remineralizing the artificial enamel carious lesion. The aim of the present study was a three-dimensional micro-CT analysis to identify of the potency of Cocos nucifera in remineralizing the artificial enamel carious lesion. METHODS: This is an in-vitro study, performed in a laboratory setting. Tooth slabs (N.=35) measuring 3×3×1.5 mm were prepared from extracted molar tooth. The prepared slabs were allotted to their respective groups by block randomization. Demineralization of the tooth slabs were done for a period of 72 hours. Following this the samples were washed with deionized water and remineralization was carried out for a period of 14 days. The groups tested were: 1) only remineralization solution(control); 2) 1: 1 lyophilized coconut (2.5 g LC in 25 mL remineralization solution); 3) 2:1 Lyophilized coconut (5 g LC in 25 mL remineralization solution); 4) 1:1 coconut milk (2.5 g CM in 25 mL remineralization solution); and 5) 2:1 coconut milk (2:1 CM - 5 g CM in 25 mL remineralization solution). Micro-CT scanning and analysis of the samples was performed postdemineralization and postremineralization procedure to evaluate the changes in the enamel volume and enamel mineral density. Within each of the five-group tested, the changes in the enamel volume and density before and after remineralization procedure was statistically analyzed using Paired t-test. One way ANOVA and Post-hoc Tukey test were done to analyze the intergroup statistical significance between the various treatment groups postremineralization procedure. RESULTS: The mean difference of the enamel volume indicates that the control group showed the highest differences (-4.57±0.347) this was seconded by the 1:1 coconut milk, 1:1 lyophilized coconut and the lowest was noted in the 2:1 coconut milk group. The mean differences of the changes in the enamel mineral density between the demineralized and remineralized enamel surface indicates that 2:1 Coconut milk showed highest changes in the surface enamel postdemineralization (-22.32±5.37) and 1:1 coconut milk showed the least of the changes in the surface of the enamel (4.00±3.42). CONCLUSIONS: Coconut extracts obtained from various extraction procedures showed quantitative increase in remineralization of artificially created enamel carious lesion. Further in-vitro studies could be done to the clinical efficiency of the same in oral environment.

Gender differences in the association between education and late-life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest-old.

INTRODUCTION: Few studies have examined the relationship between education and cognition among the oldest-old. METHODS: Cognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models. RESULTS: Higher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender. DISCUSSION: Education is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time. HIGHLIGHTS: In the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals.