Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson's disease patients mutated in TMEM175.

Parkinson's disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated. Here, we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in plasma and in dermal fibroblasts of PD patients carrying mutations in TMEM175 gene. We revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these patients, supporting a role of this channel in regulating these cellular processes.

Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Anticancer Activity and Mechanism of Action of Bark Decoction in Gastric Adenocarcinoma Cancer Cell Line.

, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant's flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells.

Mechanisms of antibody-dependent enhancement of infectious disease.

Antibody-dependent enhancement (ADE) of infectious disease is a phenomenon whereby host antibodies increase the severity of an infection. It is well established in viral infections but ADE also has an underappreciated role during bacterial, fungal and parasitic infections. ADE can occur during both primary infections and re-infections with the same or a related pathogen; therefore, understanding the underlying mechanisms of ADE is critical for understanding the pathogenesis and progression of many infectious diseases.

[Zr]ZrCl for direct radiolabeling of DOTA-based precursors.

Introduction: Zirconium-89 (Zr) is a positron emitter with several advantages over other shorter-lived positron emission tomography (PET) compatible radiometals such as gallium-68 or copper-64. These include practically unlimited availability, extremely low cost, greatly facilitated distribution logistics, positron energy fit for medical PET imaging, and sufficiently long physical half-life to enable PET imaging at later time points for patient-specific dosimetry estimations. Despite these apparent benefits, the reception of Zr in the nuclear medicine community has been tepid.

Socioeconomic risk and the longitudinal child lifetime prevalence of child protection involvement.

Background: North American studies find that geographic indicators of disadvantage, such as concentrated poverty, significantly increase the risk of child protection involvement. Despite having one of the most extensive family support systems and progressive income redistribution policies in North America, the Canadian province of Québec still faces geographic variations in socioeconomic conditions that remain a major risk factor for child protection involvement.

Objective: This study asks how child protection involvement is distributed across socioeconomically distinct geographic areas of the province.

Biodistribution of the cationic host defense peptide LL-37 using SPECT/CT.

Human cathelicidin LL-37, a cationic host defense peptide (CHDP), has several important physiological roles, including antimicrobial activity, immune modulation, and wound healing, and is a being investigated as a therapeutic candidate for several indications. While the effects of endogenously produced LL-37 are well studied, the biodistribution of exogenously administered LL-37 are less known. Here we assess the biodistribution of a gallium-67 labeled variant of LL-37 using nuclear imaging techniques over a 48 h period in healthy mice.

Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002.

Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models. However, little is known about its absorption, distribution, and excretion in live organisms.

Hyaluronic acid turnover controls the severity of cerebral cavernous malformations in bioengineered human micro-vessels.

Cerebral cavernous malformations (CCMs) are vascular lesions that predominantly form in blood vessels of the central nervous system upon loss of the CCM multimeric protein complex. The endothelial cells within CCM lesions are characterized by overactive MEKK3 kinase and KLF2/4 transcription factor signaling, leading to pathological changes such as increased endothelial cell spreading and reduced junctional integrity. Concomitant to aberrant endothelial cell signaling, non-autonomous signals from the extracellular matrix (ECM) have also been implicated in CCM lesion growth and these factors might explain why CCM lesions mainly develop in the central nervous system.

The Role of New Morphological Parameters Provided by the BC 6800 Plus Analyzer in the Early Diagnosis of Sepsis.

Background: Late diagnosis of sepsis is associated with adverse consequences and high mortality rate. The aim of this study was to evaluate the diagnostic value of hematologic research parameters, that reflect the cell morphology of blood cells, available on the BC 6800 plus automated analyzer (Mindray) for the early detection of sepsis.

Materials And Methods: A complete blood count (CBC) was performed by Mindray BC 6800 Plus Analyzer in 327 patients (223 with a confirmed diagnosis of sepsis following sepsis-3 criteria, 104 without sepsis), admitted at the Intensive Care Unit of the Novara's Hospital (Italy) and in 56 patients with localized infection.

Activity of (Taro) Corms against Gastric Adenocarcinoma Cells: Chemical Study and Molecular Characterization.

(L.) Schott is a tuberous plant, also known as taro, employed as food worldwide for its renowned nutritional properties but also traditionally used in several countries for medical purposes. In this study, methanolic extracts were prepared from the corms and leaves of , subsequently fractionated via molecular exclusion chromatography (RP-HPLC) and their anti-tumor activity assessed in an in vitro model of gastric adenocarcinoma (AGS cells).

A Green Bioactive By-Product Almond Skin Functional Extract for Developing Nutraceutical Formulations with Potential Antimetabolic Activity.

(1) Background: almond peels are rich in polyphenols such as catechin and epicatechin, which are important anti-free-radical agents, anti-inflammatory compounds, and capable of breaking down cholesterol plaques. This work aims to evaluate the biological and technological activity of a "green" dry aqueous extract from Sicilian almond peels, a waste product of the food industry, and to develop healthy nutraceuticals with natural ingredients. Eudraguard Natural is a natural coating polymer chosen to develop atomized formulations that improve the technological properties of the extract.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO/FiO), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach.

Methods: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022.

Circulating Extracellular Vesicles in Subarachnoid Hemorrhage Patients: Characterization and Cellular Effects.

Circulating extracellular vesicles (EVs) may play a pathophysiological role in the onset of complications of subarachnoid hemorrhage (SAH), potentially contributing to the development of vasospasm (VP). In this study, we aimed to characterize circulating EVs in SAH patients and examine their effects on endothelial and smooth muscle cells (SMCs). In a total of 18 SAH patients, 10 with VP (VP), 8 without VP (NVP), and 5 healthy controls (HC), clinical variables were recorded at different time points.

A core outcome set for appendicitis: A consensus approach utilizing modified Delphi methodology.

Background: Appendicitis is one of the most common pathologies encountered by general and acute care surgeons. The current literature is inconsistent, as it is fraught with outcome heterogeneity, especially in the area of nonoperative management. We sought to develop a core outcome set (COS) for future appendicitis studies to facilitate outcome standardization and future data pooling.

Recurrent child protection post-investigation services for First Nations children in the province of Quebec.

Background: The longitudinal trajectory of Indigenous children within child protection (CP) services, including their recurrent involvement, has yet to be documented.

Objectives: 1) To document whether First Nations children were at increased risk of a first recurrence of post-investigation CP services compared to children from the majority group. 2) To identify the characteristics associated with recurrence for First Nations children, and to compare these results to those for children from the majority group.

Couroupita guianensis bark decoction: From Amazonian medicine to the UHPLC-HRMS chemical profile and its role in inflammation processes and re-epithelialization.

Ethnopharmacological Relevance: In the Amazon rainforest, the shamans of the Mayantuyacu site use the healing virtues of decoctions and teas from different parts of the Couroupita guianensis Aubl. (Lecythidaceae) trees as remedies in Ashaninka medicine. However, composition of the remedy and the underlying mechanism remain unclear.

Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release.

Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms.

Homotypical and Heterotypical Intergenerational Continuity of Child Maltreatment: Evidence from a Cohort of Families Involved with Child Protection Services.

Child maltreatment (CM) in one generation can predict CM in the next generation, a concept known as intergenerational continuity. Yet, the form taken by the intergenerational continuity of CM remains unclear and fathers are mostly absent from this literature. This longitudinal study aimed to document patterns of intergenerational continuity of substantiated CM, on the maternal and paternal sides, by examining the presence of: homotypical CM, which is the same type of CM in both generations; and heterotypical CM, which is different CM types in both generations.

Light curves and colours of the ejecta from Dimorphos after the DART impact.

On 26 September 2022, the Double Asteroid Redirection Test (DART) spacecraft struck Dimorphos, a satellite of the asteroid 65803 Didymos. Because it is a binary system, it is possible to determine how much the orbit of the satellite changed, as part of a test of what is necessary to deflect an asteroid that might threaten Earth with an impact. In nominal cases, pre-impact predictions of the orbital period reduction ranged from roughly 8.

Childhood Prevalence of Involvement with the Child Protection System in Quebec: A Longitudinal Study.

The goal of this study, the first of its kind in Canada, was to estimate the child lifetime prevalence of child protection involvement in Quebec. Using administrative and population data spanning 17 years, we performed a survival analysis of initial incidents of child protection reports, confirmed reports, confirmation of a child's security or development being compromised, and placement outside the home for one day or more. We found that before reaching the age of 18 years, over 18% of children were reported to child protection at least once, one in every ten children (10.

Common and Rare Variants in TMEM175 Gene Concur to the Pathogenesis of Parkinson's Disease in Italian Patients.

Parkinson's disease (PD) represents the most common neurodegenerative movement disorder. We recently identified 16 novel genes associated with PD. In this study, we focused the attention on the common and rare variants identified in the lysosomal K channel TMEM175.

COVID Stressed, but Not due to the Virus.

Introduction: Acute care surgeons can experience posttraumatic stress disorder (PTSD) due to the cumulative stress of practice. This study sought to document the potential impact of the COVID-19 pandemic on PTSD in acute care surgeons and to identify potential contributing factors.

Methods: The six-item brief version of the PTSD Checklist-Civilian Version (PCL-6), a validated instrument capturing PTSD symptomology, was used to screen Eastern Association for the Surgery of Trauma members.

Correlated color temperature is not a suitable proxy for the biological potency of light.

Using a simulation based on a real, five-channel tunable LED lighting system, we show that Correlated Color Temperature (CCT) is not a reasonable predictor of the biological potency of light, whether characterized with CIE melanopic Equivalent Daylight Illuminance (mel-EDI), Equivalent Melanopic Lux (EML) (a scalar multiple of mel-EDI), or Circadian Stimulus (CS). At a photopic corneal illuminance of 300 lx and R ≥ 70, spectra can vary in CS from 17 to 41% across CCTs from 2500 to 6000 K, and up to 23% at a single CCT, due to the choice of spectrum alone. The CS range is largest, and notably discontinuous, at a CCT of 3500 K, the location of the inflection point of the CS model.