Does irisin mediate metabolic effects of androgen deficiency? A cross-sectional study in men with chronic spinal cord injury.

Study Design: Retrospective study.

Objectives: To check the hypothesis that irisin could mediate systemic metabolic effects of testosterone in men with chronic spinal cord injury (SCI).

Setting: Spinal Unit of the San Raffaele Institute in Sulmona.

Molecular Characterization of Multidrug-Resistant and Hypervirulent New Delhi Metallo-Beta-Lactamase in Lazio, Italy: A Five-Year Retrospective Study.

Background/objectives: Antimicrobial resistance represents a challenge to public health systems because of the array of resistance and virulence mechanisms that lead to treatment failure and increased mortality rates. Although for years the main driver of carbapenem resistance in Italy has been the KPC carbapenemase, recent years have seen an increase in VIM and NDM metallo-beta-lactamases (MBLs). We conducted a five-year survey of New Delhi Metallo-beta-Lactamase (NDM)-producing (NDM-Kpn) clinical isolates from the Lazio region, Italy; the study aimed to elucidate the molecular mechanisms underpinning their resistant and virulent phenotype.

Hominin brain size increase has emerged from within-species encephalization.

The fact that rapid brain size increase was clearly a key aspect of human evolution has prompted many studies focusing on this phenomenon, and many suggestions as to the underlying evolutionary patterns and processes. No study to date has however separated out the contributions of change through time within vs. between hominin species while simultaneously incorporating effects of body size.

Co-evolutionary dynamics of mammalian brain and body size.

Despite decades of comparative studies, puzzling aspects of the relationship between mammalian brain and body mass continue to defy satisfactory explanation. Here we show that several such aspects arise from routinely fitting log-linear models to the data: the correlated evolution of brain and body mass is in fact log-curvilinear. This simultaneously accounts for several phenomena for which diverse biological explanations have been proposed, notably variability in scaling coefficients across clades, low encephalization in larger species and the so-called taxon-level problem.

Screening of subsp. Strains with Multi-Drug Resistance and Virulence Profiles Isolated from an Italian Hospital between 2020 and 2023.

strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections.

Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice.

Niemann-Pick disease, type C1 (NPC1) is a rare, fatal neurodegenerative disorder caused by pathological variants in , which encodes a lysosomal cholesterol transport protein. There are no FDA approved treatments for this disorder. Both systemic and central nervous system delivery of AAV9- have shown significant disease amelioration in NPC1 murine models.

Severe heart failure in a unique case of cobalamin-C-deficiency resolved with LVAD implantation and subsequent heart transplantation.

Introduction Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. It usually leads to a multisystemic disease; 50% of all patients with cblC have various structural heart defects. Severe congestive heart failure (HF) may also occur and its prognosis is poorly documented.

An In-Depth Investigation of Micropillar Array Columns for the Separation of Finite-Sized Particles by Hydrodynamic Chromatography.

The exact moment approach (EMA) is adopted to predict, without any fitting parameters, the plate height curves for polystyrene microparticles of different sizes in micropillar array columns performed by hydrodynamic chromatography. The EMA allows us to decouple the contribution of horizontal and vertical dispersion terms and thus investigate the influence of pillar height and interpillar distance on separation performance. In the convection-controlled regime, we found that axial dispersion is mainly controlled by the vertical dispersion term, the latter being due to the flow-arresting top and bottom walls.

Punctuational evolution is pervasive in distal site metastatic colonization.

The evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence.

On the modelling of the effective longitudinal diffusion in bi-continuous chromatographic beds.

We report on the possibility to extend to bi-continuous packings the two models for the effective longitudinal diffusion D, or B-term band broadening, recently proposed for discontinuous chromatographic beds. In bi-continuous packings, like monolithic columns, solutes experience a connected end-to-end pathway in both the mobile and stationary zones, as opposed to discontinuous packings, wherein the stationary adsorptive zone is distributed over a set of isolated elements. Since it is unclear whether a densely packed bed of spherical particles should be treated as a continuous or a bi-continuous medium, this extension is also crucial to fully understand the behaviour of packed particle beds.

On the contribution of the top and bottom walls in micro-pillar array columns and related high-aspect ratio chromatography systems.

We report on a steady-state based, and hence highly accurate numerical modelling study of the effect of the top and bottom wall in the current generation of micro-pillar array columns. These have a mesoporous retention layer that not only covers the pillar walls but also the bottom wall. Our results show that the performance of these columns can in general not be improved by also covering the top wall with the same layer, despite the increased column symmetry this approach would offer.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile.

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology.

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters.

An alternative general model for the effective longitudinal diffusion in chromatographic beds filled with ordered porous particles.

The two-zone moment-analysis method for the determination of the dispersion tensor in hierarchical retentive porous media has been adopted to compute and model the effective longitudinal diffusion D, or equivalently the B-term band broadening, in chromatographic beds filled with ordered porous particles. On the one hand, this approach offers accurate numerical results for D while keeping computational expenses low. On the other hand, it also gives direct insight for the analytical modelling, readily revealings the two main essential quantities (resp.

Theoretical computation of the band broadening in micro-pillar array columns.

We have investigated the possibility to establish a theoretical plate height expression for the band broadening in the most widely used micro-pillar array column format, i.e., a cylindrical pillar array wherein the pillar walls and the channel bottom are coated with a thin layer of meso‑porous material.

Deep-sea origin and depth colonization associated with phenotypic innovations in scleractinian corals.

The deep sea (>200 m) is home to a surprisingly rich biota, which in some cases compares to that found in shallow areas. Scleractinian corals are an example of this - they are key species in both shallow and deep ecosystems. However, what evolutionary processes resulted in current depth distribution of the marine fauna is a long-standing question.

Nonadditivity and Nonlinearity of Mobile and Stationary Zone Mass Transfer Resistances in Chromatography.

Using a two-zone moment analysis (TZMA) method based on Brenner's generalized dispersion theory for two-dimensional (2D) and three-dimensional (3D) periodic media, we investigated the mechanisms for dispersion in particulate media for liquid chromatography. This was done using a set of plate height data covering an unprecedented wide range of retention factors, diffusion coefficients, and velocities, all computed with unequaled accuracy. Applying Giddings' additivity test, based on alternatingly making the diffusion coefficient in the mobile and stationary zones infinitely large, the dispersion data clearly indicate a lack of additivity.

Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.

Propionic acidemia (PA) is rare autosomal recessive metabolic disorder caused by defects in the mitochondrially localized enzyme propionyl-coenzyme A (CoA) carboxylase. Patients with PA can suffer from lethal metabolic decompensation and cardiomyopathy despite current medical management, which has led to the pursuit of gene therapy as a new treatment option for patients. Here we assess the therapeutic efficacy of a recently described adeno-associated virus (AAV) capsid, AAV44.

Gene therapy for organic acidemias: Lessons learned from methylmalonic and propionic acidemia.

Organic acidemias (OA) are a group of rare autosomal recessive disorders of intermediary metabolism that result in a systemic elevation of organic acid. Despite optimal dietary and cofactor therapy, OA patients still suffer from potentially lethal metabolic instability and experience long-term multisystemic complications. Severely affected patients can benefit from elective liver transplantation, which restores hepatic enzymatic activity, improves metabolic stability, and provides the theoretical basis for the pursuit of gene therapy as a new treatment for patients.

An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of ()-1,3-butanediol (Avela™).

A study was undertaken to determine the acute effects of a beverage made with Avela™ ()-1,3-butanediol, on blood beta-hydroxybutyrate (BHB) levels (using the Keto-Mojo monitor), gastrointestinal (GI) tolerability (using the modified visual analogue scale GI Symptoms Tool), and sleepiness (using the Stanford Sleepiness Scale). Following a 12-h overnight fast, 26 healthy adults consumed one beverage containing 11.5 g of ()-1,3-butanediol at each of 0, 30, and 60 min, culminating in a total intake of 34.

Moment analysis for predicting effective transport properties in hierarchical retentive porous media.

We report on a new homogenization approach to solve, with drastically improved speed and accuracy, the general advection-diffusion equation in hierarchical porous media with localized diffusion and adsorption/desorption processes, thus opening the way to a much deeper understanding of the band broadening process in chromatographic systems. The proposed robust and efficient moment-based approach allows us to compute the exact local and integral concentration moments and hence provides exact solutions for the effective velocity and dispersion coefficients of migrating solute particles. Innovative to the proposed method is also that it not only produces the exact effective transport parameters of the long-time asymptotic solution, but also their entire transient.

Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.

Methylmalonic Acidemia (MMA) is a heterogenous group of inborn errors of metabolism caused by a defect in the methylmalonyl-CoA mutase (MMUT) enzyme or the synthesis and transport of its cofactor, 5'-deoxy-adenosylcobalamin. It is characterized by life-threatening episodes of ketoacidosis, chronic kidney disease, and other multiorgan complications. Liver transplantation can improve patient stability and survival and thus provides clinical and biochemical benchmarks for the development of hepatocyte-targeted genomic therapies.