Lipoprotein metabolism in familial hypercholesterolemia

Familial hypercholesterolemia (FH) is one of the most common genetic disorders in humans. It is an extremely atherogenic metabolic disorder characterized by lifelong elevations of circulating LDL-C levels often leading to premature cardiovascular events. In this review, we discuss the clinical phenotypes of heterozygous and homozygous FH, the genetic variants in four genes (LDLR/APOB/PCSK9/LDLRAP1) underpinning the FH phenotype as well as the most recent in vitro experimental approaches used to investigate molecular defects affecting the LDL receptor pathway. In addition, we review perturbations in the metabolism of lipoproteins other than LDL in FH, with a major focus on lipoprotein (a). Finally, we discuss the mode of action and efficacy of many of the currently approved hypocholesterolemic agents used to treat patients with FH, with a special emphasis on the treatment of phenotypically more severe forms of FH. © 2021 THE AUTHORS

Hiding behaviour of Oxynoe olivacea (Mollusca: Opisthobranchia: Sacoglossa) in the invasive seaweed Caulerpa taxifolia

The occurrence of the invasive seaweed Caulerpa taxifolia in the Straits of Messina (Italy) provides an excellent opportunity to examine the spatial and temporal patterns of abundance of the endemic Mediterranean sacoglossan Oxynoe olivacea. Densities of this species were recorded in March, June and October 2000 on three different habitats: the underside of boulders (UNB), the upper side of boulders (UPB), and the surface of concrete blocks (CB). Results showed that in March, O. olivacea was consistently more abundant on UNB whereas in June it was present exclusively on CB. The density of O. olivacea was similar in the three habitats in October. The hiding behaviour of O. olivacea and its seeming disappearance in March did not coincide with a decline of abundance of phylloids of C. taxifolia. The results represent an important basis for further studies devoted to the investigation of abundance of these marine invertebrates, which has been traditionally thought of as unpredictable

Predictive Factors of Surgical Site Infection in Prosthetic Joint Surgery: A Prospective Study on 760 Arthroplasties

Purpose. The success of total joint arthroplasty (TJA) has led to consistent growth in the use of arthroplasty in progressivelyyounger patients. However, more than 10 percent of patients require revision surgery due to implant failure caused by asepticor septic inflammation. Among the latter, surgical site infection (SSI) represents one of the worst complications of TJA,potentially resulting in the removal of the prosthesis. The aim of our study was to identify potential risk factors for SSIs in apopulation of patients undergoing TJA. Methods. TJA were prospectively recruited at Casa di Cura Santa Maria Maddalenafrom February 2019 to April 2020. Age, sex, major comorbidities, American Society of Anesthesiologists (ASA) class, length ofsurgery, type of surgical suture, total hospital length of stay, and clinical laboratory data were collected. The study populationwas then divided into two groups: Group A, normal postoperative course, and Group B, patients who developed SSI at follow-up (17-25 days). Results. 25/760 (3.3%) patients developed SSIs at follow-up. Clinical and demographic parameters were notdifferent between the two groups. Total leucocyte and neutrophil values at discharge resulted to be significatively higher inGroup B compared to Group A (p = 0:025 and p = 0:016, respectively). Values of 7860/μL for total leucocyte and 5185/μL forneutrophil count at discharge significantly predicted the future development of SSI (AUC 0.623 and AUC 0.641, respectively; p< 0:05) independently from confounding factors (total leukocytes: O:R: = 3, 69 [95% C.I. 1,63-8,32]; neutrophils: O:R: = 3, 98[95% C.I. 1,76-8,97]). Deep SSIs has been diagnosed significantly before superficial SSIs (p = 0,008), with a median advance of9 days. Conclusion. Total leukocytes and neutrophils at discharge seem useful to identify a population at risk for thedevelopment of septic inflammation at the surgical site following TJA. Further studies with larger populations are needed to develop a predictive SSIs risk score that should include those variables

Global warming-related response after bacterial challenge in Astroides calycularis, a Mediterranean thermophilic coral

A worldwide increase in the prevalence of coral diseases and mortality has been linked to ocean warming due to changes in coral-associated bacterial communities, pathogen virulence, and immune system function. In the Mediterranean basin, the worrying upward temperature trend has already caused recurrent mass mortality events in recent decades. To evaluate how elevated seawater temperatures affect the immune response of a thermophilic coral species, colonies of Astroides calycularis were exposed to environmental (23 °C) or elevated (28 °C) temperatures, and subsequently challenged with bacterial lipopolysaccharides (LPS). Using immunolabeling with specific antibodies, we detected the production of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB), molecules involved in coral immune responses, and heat shock protein 70 (HSP70) activity, involved in general responses to thermal stress. A histological approach allowed us to characterize the tissue sites of activation (epithelium and/or gastroderm) under different experimental conditions. The activity patterns of the examined markers after 6 h of LPS stimulation revealed an up-modulation at environmental temperature. Under warmer conditions plus LPS-challenge, TLR4-NF-kB activation was almost completely suppressed, while constituent elevated values were recorded under thermal stress only. An HSP70 up-regulation appeared in both treatments at elevated temperature, with a significantly higher activation in LPS-challenge colonies. Such an approach is useful for further understanding the molecular pathogen-defense mechanisms in corals in order to disentangle the complex interactive effects on the health of these ecologically relevant organisms related to global climate change

Dysfunctional mitochondria accumulate in a skeletal muscle knockout model of Smn1, the causal gene of spinal muscular atrophy

The approved gene therapies for spinal muscular atrophy (SMA), caused by loss of survival motor neuron 1 (SMN1), greatly ameliorate SMA natural history but are not curative. These therapies primarily target motor neurons, but SMN1 loss has detrimental effects beyond motor neurons and especially in muscle. Here we show that SMN loss in mouse skeletal muscle leads to accumulation of dysfunctional mitochondria. Expression profiling of single myofibers from a muscle specific Smn1 knockout mouse model revealed down-regulation of mitochondrial and lysosomal genes. Albeit levels of proteins that mark mitochondria for mitophagy were increased, morphologically deranged mitochondria with impaired complex I and IV activity and respiration and that produced excess reactive oxygen species accumulated in Smn1 knockout muscles, because of the lysosomal dysfunction highlighted by the transcriptional profiling. Amniotic fluid stem cells transplantation that corrects the SMN knockout mouse myopathic phenotype restored mitochondrial morphology and expression of mitochondrial genes. Thus, targeting muscle mitochondrial dysfunction in SMA may complement the current gene therapy

Assessing vermetid reefs as indicators of past sea levels in the Mediterranean

The endemic Mediterranean reef building vermetid gastropods Dendropoma petraeum complex (Dendropoma spp) and Vermetus triquetrus develop bio-constructions (rims) on rocky shorelines at about Mean Sea Level (MSL) and are therefore commonly used as relative sea-level (RSL) markers. In this study, we use elevations and age data of vermetid reefs to (1) re-assess the vertical uncertainties of these biological RSL indicators, and (2) evaluate the vertical growth rates along a Mediterranean east-west transect, in attempt to explain the differences found in both growth rates and uncertainties. In Israel, Differential Global Positioning System (DGPS) and laser measurements relative to the local datum show that the reef surfaces mainly occupy the upper intertidal zone with variations in elevation from +0.51 ± 0.07 m to +0.13 ± 0.05 m along the coast. However, in specific sites the vertical uncertainty exceeds the tidal range. In some places the local vermetid species D. anguliferum and V. triquetrus appear to alternate along the vertical rim profiles. This study documents a spatial variability of vertical growth rates, ranging from ~1 mm yr−1 in Israel and Crete, to ~0.1–0.2 mm yr−1 in NW Sicily and Spain. The order of magnitude of the difference in growth rates correlates with the east-west spatial thermal gradient of Sea-Surface Temperature (SST). Preferential skeleton deposition of D. petraeum and V. triquetrus measured by growth axis δ18O analysis shows that most calcification occurs at SST above the mean annual value. These findings indicate that vermetid reefs are a site-specific RSL indicator, displaying various vertical uncertainties and inner-structure complexities. Local data on the indicative range of vermetids are required when reconstructing relative sea-level changes using fossil vermetids

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated

Proposta de guia para a restauração de campos nativos no sul do Brasil.

O guia técnico para restauração de campos nativos integra as ações de pesquisa e extensão conjuntas entre os projetos “Nexo Pampa” (Embrapa Clima Temperado) e o projeto “PANexus: governança da sociobiodiversidade para as seguranças hídrica, energética e alimentar na Mata Atlântica Sul” Círculo de Referência em Agroecologia, Sociobiodiversidade, Soberania e Segurança Alimentar e Nutricional (AsSsAN Círculo de Referência), Universidade Federal do Rio Grande do Sul (UFRGS)

Microgenomic Analysis in Skeletal Muscle: Expression Signatures of Individual Fast and Slow Myofibers

BACKGROUND: Skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ. METHODOLOGY/PRINCIPAL FINDINGS: We have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification. CONCLUSIONS/SIGNIFICANCE: As gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological condition

European Red List of Habitats Part 1. Marine habitats

The European Red List of Habitats provides an overview of the risk of collapse (degree of endangerment) of marine, terrestrial and freshwater habitats in the European Union (EU28) and adjacent regions (EU28+), based on a consistent set of categories and criteria, and detailed data and expert knowledge from involved countries1. A total of 257 benthic marine habitat types were assessed. In total, 19% (EU28) and 18% (EU28+) of the evaluated habitats were assessed as threatened in categories Critically Endangered, Endangered and Vulnerable. An additional 12% were Near Threatened in the EU28 and 11% in the EU28+. These figures are approximately doubled if Data Deficient habitats are excluded. The percentage of threatened habitat types differs across the regional seas. The highest proportion of threatened habitats in the EU28 was found in the Mediterranean Sea (32%), followed by the North-East Atlantic (23%), the Black Sea (13%) and then the Baltic Sea (8%). There was a similar pattern in the EU28+. The most frequently cited pressures and threats were similar across the four regional seas: pollution (eutrophication), biological resource use other than agriculture or forestry (mainly fishing but also aquaculture), natural system modifications (e.g. dredging and sea defence works), urbanisation and climate change. Even for habitats where the assessment outcome was Data Deficient, the Red List assessment process has resulted in the compilation of a substantial body of useful information to support the conservation of marine habitats