MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival.

Mitochondrial Ca(2+) (Ca(2+)(m)) uptake is mediated by an inner membrane Ca(2+) channel called the uniporter. Ca(2+) uptake is driven by the considerable voltage present across the inner membrane (ΔΨ(m)) generated by proton pumping by the respiratory chain. Mitochondrial matrix Ca(2+) concentration is maintained five to six orders of magnitude lower than its equilibrium level, but the molecular mechanisms for how this is achieved are not clear. Here, we demonstrate that the mitochondrial protein MICU1 is required to preserve normal [Ca(2+)](m) under basal conditions. In its absence, mitochondria become constitutively loaded with Ca(2+), triggering excessive reactive oxygen species generation and sensitivity to apoptotic stress. MICU1 interacts with the uniporter pore-forming subunit MCU and sets a Ca(2+) threshold for Ca(2+)(m) uptake without affecting the kinetic properties of MCU-mediated Ca(2+) uptake. Thus, MICU1 is a gatekeeper of MCU-mediated Ca(2+)(m) uptake that is essential to prevent [Ca(2+)](m) overload and associated stress.

Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria.

Mechanisms that regulate cellular metabolism are a fundamental requirement of all cells. Most eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Nevertheless, regulation of mitochondrial activity is incompletely understood. Here we identified an unexpected and essential role for constitutive InsP(3)R-mediated Ca(2+) release in maintaining cellular bioenergetics. Macroautophagy provides eukaryotes with an adaptive response to nutrient deprivation that prolongs survival. Constitutive InsP(3)R Ca(2+) signaling is required for macroautophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to diminished mitochondrial Ca(2+) uptake. Mitochondrial uptake of InsP(3)R-released Ca(2+) is fundamentally required to provide optimal bioenergetics by providing sufficient reducing equivalents to support oxidative phosphorylation. Absence of this Ca(2+) transfer results in enhanced phosphorylation of pyruvate dehydrogenase and activation of AMPK, which activates prosurvival macroautophagy. Thus, constitutive InsP(3)R Ca(2+) release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration and maintenance of normal cell bioenergetics.

Transcriptomic responses of Antarctic clam Laternula elliptica to nanoparticles, at single and combined exposures reveal ecologically relevant biomarkers.

In recent years micro- and nanoplastics and metal-oxide nanomaterials have been found in several environmental compartments. The Antarctic soft clam Laternula elliptica is an endemic Antarctic species having a wide distribution in the Southern Ocean. Being a filter-feeder, it could act as suitable bioindicator of pollution from nanoparticles also considering its sensitivity to various sources of stress. The present study aims to assess the impact of polystyrene nanoparticles (PS-NP) and the nanometal titanium-dioxide (n-TiO2) on genome-wide transcript expression of L. elliptica either alone and in combination and at two toxicological relevant concentrations (5 and 50 µg/L) during 96 h exposure. Transcript-target qRT-PCR was performed with the aim to identify suitable biomarkers of exposure and effects. As expected, at the highest concentration tested, the clustering was clearer between control and exposed clams. A total of 221 genes resulted differentially expressed in exposed clams and control ones, and 21 of them had functional annotation such as ribosomal proteins, antioxidant, ion transport (osmoregulation), acid-base balance, immunity, lipid metabolism, cell adhesion, cytoskeleton, apoptosis, chromatin condensation and cell signaling. At functional level, relevant transcripts were shared among some treatments and could be considered as general stress due to nanoparticle exposure. After applying transcript-target approach duplicating the number of clam samples, four ecologically relevant transcripts were revealed as biomarkers for PS-NP, n-TiO2 and their combination at 50 µg/L, that could be used for monitoring clams' health status in different Antarctic localities.

Evolution, Expression Patterns, and Distribution of Novel Ribbon Worm Predatory and Defensive Toxins.

Ribbon worms are active predators that use an eversible proboscis to inject venom into their prey and defend themselves with toxic epidermal secretions. Previous work on nemertean venom has largely focused on just a few species and has not investigated the different predatory and defensive secretions in detail. Consequently, our understanding of the composition and evolution of ribbon worm venoms is still very limited. Here, we present a comparative study of nemertean venom combining RNA-seq differential gene expression analyses of venom-producing tissues, tandem mass spectrometry-based proteomics of toxic secretions, and mass spectrometry imaging of proboscis sections, to shed light onto the composition and evolution of predatory and defensive toxic secretions in Antarctonemertes valida. Our analyses reveal a wide diversity of putative defensive and predatory toxins with tissue-specific gene expression patterns and restricted distributions to the mucus and proboscis proteomes respectively, suggesting that ribbon worms produce distinct toxin cocktails for predation and defense. Our results also highlight the presence of numerous lineage-specific toxins, indicating that venom evolution is highly divergent across nemerteans, producing toxin cocktails that might be finely tuned to subdue different prey. Our data also suggest that the hoplonemertean proboscis is a highly specialized predatory organ that seems to be involved in a variety of biological functions besides predation, including secretion and sensory perception. Overall, our results advance our knowledge into the diversity and evolution of nemertean venoms and highlight the importance of combining different types of data to characterize toxin composition in understudied venomous organisms.

High Variability in Type and Indications for Bone Void Filler in Tibial Plateau Fracture Repair.

Tibial plateau fractures are a common injury treated by orthopaedic trauma surgeons. Depression of the articular surface of the tibial plateau is often an associated injury pattern. The methods used to address depressed tibial plateau fractures can vary, as it has yet to be determined if the type of bone void filler utilized affects the long-term functional outcomes of patients with tibial plateau fractures. A 28-question survey was created to better elucidate the current practices used by orthopaedic surgeons and the factors influencing the selection of bone void fillers for treatment of these injuries. The survey was distributed online to Orthopaedic Trauma Association (OTA) members. There were 106 orthopaedic surgeons that completed the survey with a wide range of responses. The survey determined the current practice of orthopaedic surgeons varies widely when selecting bone void fillers in the treatment of depressed tibial plateau fractures. (Journal of Surgical Orthopaedic Advances 32(3):156-159, 2023).

Performance Metric Analysis for a Jamming Detection Mechanism under Collaborative and Cooperative Schemes in Industrial Wireless Sensor Networks.

The emergence of Industry 4.0 technologies, such as the Internet of Things (IoT) and Wireless Sensor Networks (WSN), has prompted a reconsideration of methodologies for network security as well as reducing operation and maintenance costs, especially at the physical layer, where the energy consumption plays an important role. This article demonstrates through simulations and experiments that, while the cooperative scheme is more efficient when a WSN is at normal operating conditions, the collaborative scheme offers more enhanced protection against the aggressiveness of jamming in the performance metrics, thus making it safer, reducing operation and maintenance costs and laying the foundations for jamming mitigation. This document additionally offers an algorithm to detect jamming in real time. Firstly, it examines the characteristics and damages caused by the type of aggressor. Secondly, it reflects on the natural immunity of the WSN (which depends on its node density and a cooperative or collaborative configuration). Finally, it considers the performance metrics, especially those that impact energy consumption during transmission.

Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy whose chemoresistance and relapse persist as a problem despite significant advances in its chemotherapeutic treatments. Mitochondrial metabolism has emerged as an interesting therapeutic target given its essential role in maintaining bioenergetic and metabolic homeostasis. T-ALL cells are characterized by high levels of mitochondrial respiration, making them suitable for this type of intervention. Mitochondrial function is sustained by a constitutive transfer of calcium from the endoplasmic reticulum to mitochondria through the inositol 1,4,5-trisphosphate receptor (InsP3R), making T-ALL cells vulnerable to its inhibition. Here, we determine the bioenergetic profile of the T-ALL cell lines CCRF-CEM and Jurkat and evaluate their sensitivity to InsP3R inhibition with the specific inhibitor, Xestospongin B (XeB). Our results show that T-ALL cell lines exhibit higher mitochondrial respiration than non-malignant cells, which is blunted by the inhibition of the InsP3R. Prolonged treatment with XeB causes T-ALL cell death without affecting the normal counterpart. Moreover, the combination of XeB and glucocorticoids significantly enhanced cell death in the CCRF-CEM cells. The inhibition of InsP3R with XeB rises as a potential therapeutic alternative for the treatment of T-ALL.

Scalable Total Synthesis, IP3R Inhibitory Activity of Desmethylxestospongin†B, and Effect on Mitochondrial Function and Cancer Cell Survival.

The scalable synthesis of the oxaquinolizidine marine natural product desmethylxestospongin B is based on the early application of Ireland-Claisen rearrangement, macrolactamization, and a late-stage installation of the oxaquinolizidine units by lactam reduction. The synthesis serves as the source of material to investigate calcium signaling and its effect on mitochondrial metabolism in various cell types, including cancer cells.

Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer.

INTRODUCTION: Cardiotoxicity is an adverse reaction associated with the use of anthracyclines. OBJECTIVE: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer. METHOD: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables. RESULTS: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001). CONCLUSIONS: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.

INTRODUCCIÓN: La cardiotoxicidad es una reacción adversa asociada al uso de antraciclinas. OBJETIVO: Estimar los factores asociados al desarrollo de cardiotoxicidad por antraciclinas en pacientes pediátricos supervivientes de cáncer. MÉTODO: Cohorte retroprolectiva de niños con diagnóstico de cáncer tratados con antraciclinas. Se realizó determinación ecocardiográfica basal de la fracción de expulsión (FEVi0) antes del inicio del tratamiento y a los 12 meses (FEVi1). Del expediente se obtuvieron las características demográficas y el tratamiento. Se realizó un modelo de regresión logística múltiple (RLM); la FEVi1 < 50 % fue la variable dependiente, que se ajustó por las principales variables confusoras. RESULTADOS: Se incluyeron 65 pacientes, 36.9 % fue del sexo femenino y 56.8 % presentó un tumor sólido. La FEVi0 fue de 74.79 ± 7.3 % y la FEVi1, de 67.96 ± 6.7 % (p = 0.001); 60 % desarrolló cardiotoxicidad. En la RLM solo la dosis acumulada > 430 mg se asoció a cardiotoxicidad (p = 0.001). CONCLUSIONES: En los niños mexicanos se debe evitar una dosis acumulada > 430 mg de antraciclinas para evitar la cardiotoxicidad.

HSP70 from the Antarctic sea urchin Sterechinus neumayeri: molecular characterization and expression in response to heat stress.

BACKGROUND: Heat stress proteins are implicated in stabilizing and refolding denatured proteins in vertebrates and invertebrates. Members of the Hsp70 gene family comprise the cognate heat shock protein (Hsc70) and inducible heat shock protein (Hsp70). However, the cDNA sequence and the expression of Hsp70 in the Antarctic sea urchin are unknown. METHODS: We amplified and cloned a transcript sequence of 1991 bp from the Antarctic sea urchin Sterechinus neumayeri, experimentally exposed to heat stress (5  and 10 °C for 1, 24 and 48 h). RACE-PCR and qPCR were employed to determine Hsp70 gene expression, while western blot and ELISA methods were used to determine protein expression. RESULTS: The sequence obtained from S. neumayeri showed high identity with Hsp70 members. Several Hsp70 family features were identified in the deduced amino acid sequence and they indicate that the isolated Hsp70 is related to the cognate heat shock protein type. The corresponding 70 kDa protein, called Sn-Hsp70, was immune detected in the coelomocytes and the digestive tract of S. neumayeri using a monospecific polyclonal antibody. We showed that S. neumayeri do not respond to acute heat stress by up-regulation of Sn-Hsp70 at transcript and protein level. Furthermore, the Sn-Hsp70 protein expression was not induced in the digestive tract. CONCLUSIONS: Our results provide the first molecular evidence that Sn-Hsp70 is expressed constitutively and is non-induced by heat stress in S. neumayeri.

Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.

L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease.

LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation.

Dysregulation of mitochondrial Ca(2+)-dependent bioenergetics has been implicated in various pathophysiological settings, including neurodegeneration and myocardial infarction. Although mitochondrial Ca(2+) transport has been characterized, and several molecules, including LETM1, have been identified, the functional role of LETM1-mediated Ca(2+) transport remains unresolved. This study examines LETM1-mediated mitochondrial Ca(2+) transport and bioenergetics in multiple cell types, including fibroblasts derived from patients with Wolf-Hirschhorn syndrome (WHS). The results show that both mitochondrial Ca(2+) influx and efflux rates are impaired in LETM1 knockdown, and similar phenotypes were observed in ΔEF hand, (D676A D688K)LETM1 mutant-overexpressed cells, and in cells derived from patients with WHS. Although LETM1 levels were lower in WHS-derived fibroblasts, the mitochondrial Ca(2+) uniporter components MCU, MCUR1, and MICU1 remain unaltered. In addition, the MCU mitoplast patch-clamp current (IMCU) was largely unaffected in LETM1-knockdown cells. Silencing of LETM1 also impaired basal mitochondrial oxygen consumption, possibly via complex IV inactivation and ATP production. Remarkably, LETM1 knockdown also resulted in increased reactive oxygen species production. Further, LETM1 silencing promoted AMPK activation, autophagy, and cell cycle arrest. Reconstitution of LETM1 or antioxidant overexpression rescued mitochondrial Ca(2+) transport and bioenergetics. These findings reveal the role of LETM1-dependent mitochondrial Ca(2+) flux in shaping cellular bioenergetics.

Global conservation status of sponges.

Sponges are important for maintaining ecosystem function and integrity of marine and freshwater benthic communities worldwide. Despite this, there has been no assessment of their current global conservation status. We assessed their status, accounting for the distribution of research effort; patterns of temporal variation in sponge populations and assemblages; the number of sponges on threatened species lists; and the impact of environmental pressures. Sponge research effort has been variable; marine sponges in the northeastern Atlantic and Mediterranean and freshwater sponges in Europe and North America have received the most attention. Although sponge abundance has increased in some locations since 1990, these were typically on coral reefs, in response to declines in other benthic organisms, and restricted to a few species. Few data were available on temporal trends in freshwater sponge abundance. Despite over 8500 described sponge species, only 20 are on threatened species lists, and all are marine species from the northeastern Atlantic and Mediterranean. Of the 202 studies identified, the effects of temperature, suspended sediment, substratum loss, and microbial pathogens have been studied the most intensively for marine sponges, although responses appear to be variable. There were 20 studies examining environmental impacts on freshwater sponges, and most of these were on temperature and heavy metal contamination. We found that most sponges do not appear to be threatened globally. However, little information is available for most species and more data are needed on the impacts of anthropogenic-related pressures. This is a critical information gap in understanding sponge conservation status.

Constitutive cAMP response element binding protein (CREB) activation by Alzheimer's disease presenilin-driven inositol trisphosphate receptor (InsP3R) Ca2+ signaling.

Mutations in presenilins (PS) account for most early-onset familial Alzheimer's disease (FAD). Accumulating evidence suggests that disrupted Ca(2+) signaling may play a proximal role in FAD specifically, and Alzheimer's disease (AD) more generally, but its links to the pathogenesis of AD are obscure. Here we demonstrate that expression of FAD mutant PS constitutively activates the transcription factor cAMP response element binding protein (CREB) and CREB target gene expression in cultured neuronal cells and AD mouse models. Constitutive CREB activation was associated with and dependent on constitutive activation of Ca(2+)/CaM kinase kinase ß and CaM kinase IV (CaMKIV). Depletion of endoplasmic reticulum Ca(2+) stores or plasma membrane phosphatidylinositol-bisphosphate and pharmacologic inhibition or knockdown of the expression of the inositol trisphosphate receptor (InsP(3)R) Ca(2+) release channel each abolished FAD PS-associated constitutive CaMKIV and CREB phosphorylation. CREB and CaMKIV phosphorylation and CREB target gene expression, including nitric oxide synthase and c-fos, were enhanced in brains of M146V-KI and 3xTg-AD mice expressing FAD mutant PS1 knocked into the mouse locus. FAD mutant PS-expressing cells demonstrated enhanced cell death and sensitivity to Aß toxicity, which were normalized by interfering with the InsP(3)R-CAMKIV-CREB pathway. Thus, constitutive CREB phosphorylation by exaggerated InsP(3)R Ca(2+) signaling in FAD PS-expressing cells may represent a signaling pathway involved in the pathogenesis of AD.

Microbiome profile of the Antarctic clam Laternula elliptica.

The filter feeder clam Laternula elliptica is a key species in the Antarctic ecosystem. As a stenothermal benthic species, it has a poor capacity for adaptation to small temperature variations. Despite their ecological importance and sensitivity to climate change, studies on their microbiomes are lacking. The goal of this study was to characterize the bacterial communities of L. elliptica and the tissues variability of this microbiome to provide an initial insight of host-microbiota interactions. We investigated the diversity and taxonomic composition of bacterial communities of L. elliptica from five regions of the body using high-throughput 16S rRNA gene sequencing. The results showed that the microbiome of L. elliptica tended to differ from that of the surrounding seawater samples. However, there were no significant differences in the microbial composition between the body sites, and only two OTUs were present in all samples, being considered core microbiome (genus Moritella and Polaribacter). No significant differences were detected in diversity indexes among tissues (mean 626.85 for observed OTUs, 628.89 Chao1, 5.42 Shannon, and 0.87 Simpson). Rarefaction analysis revealed that most tissues reached a plateau of OTU number according to sample increase, with the exception of Siphon samples. Psychromonas and Psychrilyobacter were particularly abundant in L. elliptica whereas Fluviicola dominated seawater and siphons. Typical polar bacteria were Polaribacter, Shewanella, Colwellia, and Moritella. We detected the prevalence of pathogenic bacterial sequences, particularly in the family Arcobacteraceae, Pseudomonadaceae, and Mycoplasmataceae. The prokaryotic diversity was similar among tissues, as well as their taxonomic composition, suggesting a homogeneity of the microbiome along L. elliptica body. The Antarctic clam population can be used to monitor the impact of human activity in areas near Antarctic stations that discharge wastewater.

The Use of Knotless Suture Tape Construct vs Screw Fixation for Lisfranc Injuries: A Cadaveric Biomechanical Study.

BACKGROUND: Lisfranc injuries are often treated with open reduction and internal fixation using rigid fixation techniques. The use of flexible fixation to stabilize the Lisfranc joint is a newer technique. The purpose of this cadaveric study is to compare the amount of diastasis at the Lisfranc interval under diminished physiologic loads when treated with a knotless suture tape construct and a solid screw. METHODS: Ten cadavers (20 feet) had native motion at the intact Lisfranc interval assessed at multiple increasing loads (69, 138, and 207 N). The Lisfranc ligamentous complex was then disrupted, and testing repeated to evaluate the amount of diastasis. Randomization was performed to determine the type of fixation for each cadaver: solid screw or knotless suture tape construct. Once fixation was completed, specimens were cyclically loaded for 10 000 cycles at loads, and diastasis was quantified after each load cycle to compare the interventions. Diastasis was measured using motion tracking cameras and retroreflective marker sets. A non-inferiority statistical analysis was performed. RESULTS: Diastasis mean values were confirmed to be >2 mm for all load bearing conditions in the injury model. Posttreatment, diastasis was significantly reduced when compared to the sectioned conditions (P < .01) for both treatment options. Non-inferiority analyses showed that the knotless suture tape construct did not perform inferior to screw fixation for diastasis at the Lisfranc interval at any of the compared load states. CONCLUSION: Under the loads tested, there is no significant difference in diastasis at the Lisfranc interval when treating ligamentous Lisfranc injuries with a knotless suture tape construct or solid screws. Both reduced diastasis from the injured state and were not different from the intact state. CLINICAL RELEVANCE: In this cadaveric model with ligamentous Lisfranc injury, diastasis of a knotless suture tape construct is compared to solid screw fixation as tested.

Detection of plastic, cellulosic micro-fragments and microfibers in Laternula elliptica from King George Island (Maritime Antarctica).

It is generally acknowledged that microplastic pollutants are prevalent in ocean waters and sediments across a range of tropical, temperate, subpolar, and polar regions. The waters surrounding King George Island are significantly impacted by human activities, particularly those related to scientific stations, fishing, and tourism. Organisms, such as Laternula elliptica, can be used as environmental monitors due to the likelihood that they will bioaccumulate pollutants. The goal of this study was to quantify and identify plastic and cellulosic micro-fragments and microfibers present in the soft body of clams (n = 21), collected from Fildes Bay near sewage and wastewater discharges. Plastic and cellulose microfragments and microfibers were counted, and their compositions were determined using FT-IR. All 21 individuals sampled contained fragments and fibers, with a total of 900 items detected (42.86 ± 25.36 mean ± SD items per individual), or 1.82 items g.wet mass-1. 58 % of items were cellulose and 22 % plastic. Considering the plastic polymer compositions, 28.57 % were polyethylene terephthalate (PET), 21.43 % acrylic, 14.29 % high-density polyethylene (HDPE), 14.29 % Polypropylene (PP), 7.14 % ultra-high drawn polyethylene filament (UHMWPE), 7.14 % polyester and 7.14 % Polyethylene. The quantities and prevalence of MP in L. elliptica were higher than those found in other Antarctic marine species, and even in bivalves from populated regions of the world. Our work assessed the pollution status of L. elliptica near an effluent of wastewater plants and found that 95 % of individuals displayed MP and 100 % microfibers that could impact their population.

Exposure to nanoplastics and nanomaterials either single and combined affects the gill-associated microbiome of the Antarctic soft-shelled clam Laternula elliptica.

Nanoplastics and engineering nanomaterials (ENMs) are contaminants of emerging concern (CECs), increasingly being detected in the marine environment and recognized as a potential threat for marine biota at the global level including in polar areas. Few studies have assessed the impact of these anthropogenic nanoparticles in the microbiome of marine invertebrates, however combined exposure resembling natural scenarios has been overlooked. The present study aimed to evaluate the single and combined effects of polystyrene nanoparticles (PS NP) as proxy for nanoplastics and nanoscale titanium dioxide (nano-TiO2) on the prokaryotic communities associated with the gill tissue of the Antarctic soft-shell clam Laternula elliptica, a keystone species of marine benthos Wild-caught specimens were exposed to two environmentally relevant concentrations of carboxylated PS NP (PS-COOH NP, ∼62 nm size) and nano-TiO2 (Aeroxide P25, ∼25 nm) as 5 and 50 µg/L either single and combined for 96h in a semi-static condition.Our findings show a shift in microbiome composition in gills of soft-shell clams exposed to PS NP and nano-TiO2 either alone and in combination with a decrease in the relative abundance of OTU1 (Spirochaetaceae). In addition, an increase of gammaproteobacterial OTUs affiliated to MBAE14 and Methylophagaceae (involved in ammonia denitrification and associated with low-quality water), and the OTU Colwellia rossensis (previously recorded in polluted waters) was observed. Our results suggest that nanoplastics and nano-TiO2 alone and in combination induce alterations in microbiome composition by promoting the increase of negative taxa over beneficial ones in the gills of the Antarctic soft-shell clam. An increase of two low abundance OTUs in PS-COOH NPs exposed clams was also observed. A predicted gene function analysis revealed that sugar, lipid, protein and DNA metabolism were the main functions affected by either PS-COOH NP and nano-TiO2 exposure. The molecular functions involved in the altered affiliated OTUs are novel for nano-CEC exposures.

Outcomes of isolated patellofemoral arthroplasty.

Osteoarthritis of the patellofemoral compartment can cause significant functional impairment. Isolated patellofemoral osteoarthritis affects greater than 10% of males and females over the age of 60. Patellofemoral arthroplasty (PFA) was developed as a joint-preserving procedure that maintains natural knee kinematics in those with isolated patellofemoral disease. First-generation implants were fraught with complications, a high rate of revision, and early conversion to total knee arthroplasty (TKA). Second-generation implants have demonstrated significant improvements in patient-reported outcome measures, complication rates and implant survivorship. Factors that can affect outcomes include surgical indications, patient selection, and PFA prosthesis design. Modern PFA for isolated patellofemoral osteoarthritis has comparable outcomes to TKA for isolated patellofemoral osteoarthritis. In this article, we discuss the use of PFA, implant design, the indications and factors affecting outcomes, and comparison to TKA.

Impact of a Nurse-Led Multidisciplinary Heart Failure Clinic in a Low-Resource Setting: Experience in a Latin American Public Healthcare System.

Background: Nurse-led multidisciplinary heart failure clinics (MDHFCs) play an important role in patient care in developed countries, due to their proven benefits relating to mortality, hospitalization, and quality of life. However, evidence is limited regarding the role of MDHFCs in a limited-resource setting. Methods: Patients with heart failure (HF) with reduced ejection fraction (n = 89) were enrolled in a prospective, longitudinal cohort, from January 2018 to January 2019. The following endpoints were collected at baseline and after 6 months of follow-up: (i) quality of life, measured using the Minnesota Living with Heart Failure Questionnaire; (ii) medication adherence using the Morisky Medication Adherence Scale, 8-item; (iii) titration of HF medications; (iv) self-care behavior using the European Heart Failure Self-care Behavior Scale; and (v) mortality and hospitalizations up to 12 months after. Results: The questionnaire score was reduced from 66.5 (interquartile range [IQR], 46-86) at baseline to 26 (IQR, 13-45) at 6 months (P < 0.001). New York Heart Association (NYHA) functional class improved at 6 months (NYHA I: 41.9%; NYHA II: 39.5%; NYHA III: 17.2%), compared to baseline (NYHA I: 20%; NYHA II: 49%; NYHA III: 31%; P < 0.001). Medication adherence using the 8-item Morisky Medication Adherence Scale improved the score from 6 (IQR, 4-7) at baseline to 7 (IQR, 6.25-8; P = 0.001) at 6 months. Uptitration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (25% vs 18% at target dose) and beta-blockers (25% vs 11% at target dose) was documented. After 6 months of follow-up, the European Heart Failure Self-care Behavior Scale was applied, showing a score of 18.5 (IQR, 15-22). The mortality reported at 12 months of follow-up was 9.7%, and the incidence of hospitalization was 44%. Conclusion: An MDHFC is a feasible strategy to manage an HF clinic in a low-resource setting.

Contexte: Les cliniques multidisciplinaires d'insuffisance cardiaque dirigées par du personnel infirmier jouent un rôle important dans les soins aux patients dans les pays développés en raison de leurs bienfaits démontrés en matière de mortalité, d'hospitalisation, et de qualité de vie. Les preuves quant au rôle de ce type de cliniques dans un contexte de pénurie de ressources sont toutefois limitées. Méthodologie: Des patients atteints d'insuffisance cardiaque (IC) présentant une fraction d'éjection réduite (n = 89) ont été inscrits à une étude de cohortes prospective et longitudinale allant de janvier 2018 à janvier 2019. Les critères d'évaluation suivants ont été mesurés à l'inscription et après six mois de suivi : i) qualité de vie, mesurée par le questionnaire Minnesota Living with Heart Failure Questionnaire; ii) adhésion au traitement médicamenteux, mesuré selon l'échelle en huit points Morisky Medication Adherence Scale; iii) modification de la dose de médicaments contre l'IC; iv) comportements d'autosoins, mesurés selon l'échelle European Heart Failure Self-care Behavior Scale; et v) taux de mortalité et d'hospitalisation jusqu'à 12 mois. Résultats: Le score au questionnaire a diminué pour passer de 66,5 (écart interquartile [EI] : 46 à 86) au départ à 26 (EI : 13 à 45) à six mois (p < 0,001). La catégorie fonctionnelle de la New York Heart Association (NYHA) s'est améliorée à six mois (NYHA I : 41,9 %; NYHA II : 39,5 %; NYHA III : 17,2 %), comparativement au départ (NYHA I : 20 %; NYHA II : 49 %; NYHA III : 31 %; p < 0,001). Le score de l'adhésion au traitement médicamenteux mesuré par l'échelle en huit points Morisky Medication Adherence Scale s'est amélioré, passant de 6 (EI : 4 à 7) au départ à 7 (EI : 6,25 à 8; p = 0,001) à six mois. On a noté une augmentation de la dose d'inhibiteurs de l'enzyme de conversion de l'angiotensine ou de bloqueurs des récepteurs de l'angiotensine (25 % vs 18 % à la dose cible) et de bêtabloquants (25 % vs 11 % à la dose cible). Après six mois de suivi, l'échelle European Heart Failure Self-care Behavior Scale a été appliquée, ce qui a donné un score de 18,5 (EI : 15 à 22). Le taux de mortalité rapporté à 12 mois de suivi était de 9,7 %, et le taux d'hospitalisation était de 44 %. Conclusion: Une clinique multidisciplinaire d'insuffisance cardiaque dirigée par du personnel infirmier est une stratégie réaliste pour gérer une clinique d'IC dans un contexte de pénurie de ressources.