Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome:a systematic review

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer-reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta-analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty-three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4–226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.</p

A Workflows Roadmap for the Geosciences

The EarthCube Workflows Community Group was formed in March 2012 as part of the NSF EarthCube initiative in response to initial discussions in EarthCube that occurred during 2011. Workflows are used to manage complex computations that have many steps or use large data. Workflow systems assist scientists to select models appropriate for their data, configure them with appropriate parameters, and execute them efficiently. The EarthCube community saw great value in workflow technologies for the future of geosciences. The goal of the EarthCube Workflows Community Group was to begin to elicit requirements for workflows in geosciences, ascertain the state of the art and current practices, identify current gaps in both the use of and capabilities of current workflow systems in the earth sciences through use case studies, and identify grand challenges for the next decade along with the possible paths to addressing those challenges. The group was asked to produce a roadmap for workflows in geosciences. Three other Community Groups were formed (Data, Semantics and Ontologies, and Governance), and each was asked to create a roadmap in their area. The group held a series of virtual and face-to-face workshops to solicit participation from the geosciences community and other relevant researchers. The EarthCube Workflows Community Group set up a public web site where all their activities were made open for participation from the community and all documents were posted for public access and editing (https://sites.google.com/site/earthcubeworkflow/). Presentations and discussions were recorded and posted on the site. A key result of the work of the EarthCube Workflows Community Group activities in Spring and Summer 2012 was the creation of a workflows roadmap for the geosciences. An initial roadmap document for the EarthCube community that was first released in June 2012 and presented to the EarthCube community. A revised roadmap was delivered to the community in August 2012. The roadmap serves as a living document created as a group effort with provisions and a process to update and extend it over time.This document represents the final roadmap of the NSF EarthCube Community Group for workflows in the geosciences. Community feedback is always welcome, as the roadmap will be revised and extended while EarthCube activities continue.This work was supported through National Science Foundation under grant # EAR-1238216 as part of the NSF EarthCube initiative. EarthCube is an innovative and longterm cross-directorate initiative of the US National Science Foundation

Essential oil analysis and antibacterial activity of Ferula assa-foetida L. aerial parts from Neishabour mountains

Abstract Background and objectives: Ferula assa-foetida (asafoetida) is a native Iranian species which grows in different regions and climates in Iran. The plant is well known in Iranian Traditional Medicine as well as folk medicine for treatment of diseases. Several studies have been carried out on the essential oil of this species collected from different areas of Iran. This study is the first report about the essential oil of the plant collected from Neishabour mountains that is a potent area for growing this valuable plant species. Methods: Essential oil of the aerial part of Ferula assa-foetida which was collected from Neishabour, Iran, was analyzed by gas chromatography-mass spectroscopy (GC/MS). The minimum inhibitory concentrations of the essential oil was investigated against both Grampositive (Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia) bacteria using microdilution method. Results: Twenty three components representing 97.06% of the total oil were identified. (E)-1-propenyl sec-butyl disulfide (53.77%), (Z)-1-propenyl sec-butyl disulfide (35.6%) and α-pinene (3.4%) were identified as major components. The MIC of the essential oil ranged from 12-24 mg/mL against all tested bacteria. Conclusion: The results indicated that among various compounds identified in the essential oil of F. assa-foetida L. from Neishabour mountains, disulphide compounds were the major constituents of the oil. In comparison to other reports of this plant around the country, disulphide compounds could be the reason of its moderate antibacterial effect

Systemic therapy of Cushing’s syndrome

Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio

The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use

Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions

Epithelial Proinflammatory Response and Curcumin-Mediated Protection from Staphylococcal Toxic Shock Syndrome Toxin-1

Staphylococcus aureus initiates infections and produces virulence factors, including superantigens (SAgs), at mucosal surfaces. The SAg, Toxic Shock Syndrome Toxin-1 (TSST-1) induces cytokine secretion from epithelial cells, antigen presenting cells (APCs) and T lymphocytes, and causes toxic shock syndrome (TSS). This study investigated the mechanism of TSST-1-induced secretion of proinflammatory cytokines from human vaginal epithelial cells (HVECs) and determined if curcumin, an anti-inflammatory agent, could reduce TSST-1-mediated pathology in a rabbit vaginal model of TSS. TSST-1 caused a significant increase in NF-κB-dependent transcription in HVECs that was associated with increased expression of TNF- α, MIP-3α, IL-6 and IL-8. Curcumin, an antagonist of NF-κB-dependent transcription, inhibited IL-8 production from ex vivo porcine vaginal explants at nontoxic doses. In a rabbit model of TSS, co-administration of curcumin with TSST-1 intravaginally reduced lethality by 60% relative to 100% lethality in rabbits receiving TSST-1 alone. In addition, TNF-α was undetectable from serum or vaginal tissue of curcumin treated rabbits that survived. These data suggest that the inflammatory response induced at the mucosal surface by TSST-1 is NF-κB dependent. In addition, the ability of curcumin to prevent TSS in vivo by co-administration with TSST-1 intravaginally suggests that the vaginal mucosal proinflammatory response to TSST-1 is important in the progression of mTSS