Polycomb group (PcG) proteins prevent the assembly of abnormal synaptonemal complex structures during meiosis.

The synaptonemal complex (SC) is a proteinaceous scaffold that is assembled between paired homologous chromosomes during the onset of meiosis. Timely expression of SC coding genes is essential for SC assembly and successful meiosis. However, SC components have an intrinsic tendency to self-organize into abnormal repetitive structures, which are not assembled between the paired homologs and whose formation is potentially deleterious for meiosis and gametogenesis. This creates an interesting conundrum, where SC genes need to be robustly expressed during meiosis, but their expression must be carefully regulated to prevent the formation of anomalous SC structures. In this manuscript, we show that the Polycomb group protein Sfmbt, the Drosophila ortholog of human MBTD1 and L3MBTL2, is required to avoid excessive expression of SC genes during prophase I. Although SC assembly is normal after Sfmbt depletion, SC disassembly is abnormal with the formation of multiple synaptonemal complexes (polycomplexes) within the oocyte. Overexpression of the SC gene corona and depletion of other Polycomb group proteins are similarly associated with polycomplex formation during SC disassembly. These polycomplexes are highly dynamic and have a well-defined periodic structure. Further confirming the importance of Sfmbt, germ line depletion of this protein is associated with significant metaphase I defects and a reduction in female fertility. Since transcription of SC genes mostly occurs during early prophase I, our results suggest a role of Sfmbt and other Polycomb group proteins in downregulating the expression of these and other early prophase I genes during later stages of meiosis.

NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning.

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken Germline depletion of Salsa and splice site mutations within gurken first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a gurken construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.

Hydroethanolic Extract of Grape Peel from Vitis labrusca Winemaking Waste: Antinociceptive and Anti-Inflammatory Activities.

Research background: Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach: A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions: In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution: This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.

Topical Administration of 15-Deoxy-Δ 12,14-Prostaglandin J2 Using a Nonionic Cream: Effect on UVB-Induced Skin Oxidative, Inflammatory, and Histopathological Modifications in Mice.

UVB radiation is certainly one of the most important environmental threats to which we are subjected to. This fact highlights the crucial protective role of the skin. However, the skin itself may not be capable of protecting against UVB depending on irradiation intensity and time of exposition. Sun blockers are used to protect our skin, but they fail to fully protect it against oxidative and inflammatory injuries initiated by UVB. To solve this issue, topical administration of active molecules is an option. 15-Deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) is an arachidonic acid-derived lipid with proresolution and anti-inflammatory actions. However, as far as we are aware, there is no evidence of its therapeutic use in a topical formulation to treat the deleterious events initiated by UVB, which was the aim of the present study. We used a nonionic cream to vehiculate 15d-PGJ2 (30, 90, and 300 ng/mouse) (TFcPGJ2) in the skin of hairless mice. UVB increased skin edema, myeloperoxidase activity, metalloproteinase-9 activity, lipid peroxidation, superoxide anion production, gp91phox and COX-2 mRNA expression, cytokine production, sunburn and mast cells, thickening of the epidermis, and collagen degradation. UVB also diminished skin ability to reduce iron and scavenge free radicals, reduced glutathione (GSH), sulfhydryl proteins, and catalase activity. TFcPGJ2 inhibited all these pathological alterations in the skin caused by UVB. No activity was observed with the unloaded topical formulation. The protective outcome of TFcPGJ2 indicates it is a promising therapeutic approach against cutaneous inflammatory and oxidative pathological alterations.

Renicolidae infection in Manx shearwater (Puffinus puffinus): is parasitism implicated on renal lesions?

Renicolid digeneans are frequently observed in the renal tubules and ureters of seabirds, such Puffinus puffinus, a migratory species distributed along the Brazilian coast. However, few studies have focused on the relationship between renicolid infection and health status in P. puffinus. Thus, the aim of this study was to describe (i) renal and systemic alterations, (ii) the renicolids and (iii) the biological aspects associated with the presence of renicolids in P. puffinus. Gross and histological assays were performed in 93 P. puffinus stranded on the Paraná coast, southern Brazil, and renicolids were submitted to morphological and molecular assays. A high prevalence of renicolids in P. puffinus (71/93) was observed. In the kidney, the main microscopic findings were lymphocytic interstitial infiltrate, ductal ectasia and tubular necrosis. The renal lesions were significantly associated with the parasite infection. The morphological (n = 84) and molecular analyses (n = 2) confirmed the species as Renicola sloanei (100% and 95.9% of nucleotide identity with R. sloanei strains from P. puffinus and from Spheniscus demersus, respectively). In both parasitized and non-parasitized animals, cardiac and skeletal muscle degeneration and necrosis were the most frequent systemic changes. Therefore, the results suggest renicolids being a possible cause for the demonstrated renal alterations. A contribution of this parasite to a decreased health status of Puffinus puffinus along their migratory route is possible.

Non-alcoholic Fatty Liver Disease and Its Links with Inflammation and Atherosclerosis.

PURPOSE OF REVIEW: We summarize best data of the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). RECENT FINDINGS: NAFLD has been linked with insulin resistance, obesity, and metabolic syndrome, conditions known to be associated with CVD and subclinical atherosclerosis. The rising evidence of the association between NAFLD and subclinical CVD may suggest that NAFLD is not only a marker but also may be actively involved in pathogenesis of CVD. It is an overview of previous studies assessing relationships between NAFLD and markers of cardiovascular disease, as the presence of coronary artery calcification, increased arterial stiffness, and elevated carotid media thickness, in order to better understand the interplay between these conditions.

Acute Kidney Injury and Risk of Death After Elective Surgery: Prospective Analysis of Data From an International Cohort Study.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with a high mortality rate. However, the relationship among AKI, its associations, and mortality is not well understood. METHODS: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals. RESULTS: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass. CONCLUSIONS: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.

Biocompatible silver nanoparticles prepared with amino acids and a green method.

The synthesis of nanoparticles is usually carried out by chemical reduction, which is effective but uses many toxic substances, making the process potentially harmful to the environment. Hence, as part of the search for environmentally friendly or green synthetic methods, this study aimed to produce silver nanoparticles (AgNPs) using only AgNO3, Milli-Q water, white light from a xenon lamp (Xe) and amino acids. Nanoparticles were synthetized using 21 amino acids, and the shapes and sizes of the resultant nanoparticles were evaluated. The products were characterized by UV-Vis, zeta potential measurements and transmission electron microscopy. The synthesis of silver nanoparticles with tryptophan and tyrosine, methionine, cystine and histidine was possible through photoreduction method. Spherical nanoparticles were produced, with sizes ranging from 15 to 30 nm. Tryptophan does not require illumination nor heating, and the solution color changes immediately after the mixing of reagents if sodium hydroxide is added to the solution (pH = 10). The Xe illumination acts as sodium hydroxide in the nanoparticles synthesis, releases H+ and allows the reduction of silver ions (Ag+) in metallic silver (Ag0).

Aminolevulinic acid with gold nanoparticles: a novel theranostic agent for atherosclerosis.

In this study, 5-aminolevulinic acid (ALA) gold nanoparticles (ALA:AuNPs) functionalized with polyethylene glycol (PEG) were synthesized and administered to rabbits to evaluate their use in clinical practice as theranostic agents for atherosclerosis. This was done by measuring the porphyrin fluorescence extracted from the rabbits' blood and feces. An increase in blood and feces porphyrin emission after ALA:AuNP administration suggests that ALA was incorporated by gold nanoparticles, its structure was preserved, and a rapid conversion into endogenous porphyrins occurred, overloading the synthetic pathway that led to protoporphyrin IX (PPIX) accumulation. This finding indicated that this method can aid in the early diagnosis and therapy of atherosclerosis with high sensitivity.

Identification of a novel nidovirus in an outbreak of fatal respiratory disease in ball pythons (Python regius).

BACKGROUND: Respiratory infections are important causes of morbidity and mortality in reptiles; however, the causative agents are only infrequently identified. FINDINGS: Pneumonia, tracheitis and esophagitis were reported in a collection of ball pythons (Python regius). Eight of 12 snakes had evidence of bacterial pneumonia. High-throughput sequencing of total extracted nucleic acids from lung, esophagus and spleen revealed a novel nidovirus. PCR indicated the presence of viral RNA in lung, trachea, esophagus, liver, and spleen. In situ hybridization confirmed the presence of intracellular, intracytoplasmic viral nucleic acids in the lungs of infected snakes. Phylogenetic analysis based on a 1,136 amino acid segment of the polyprotein suggests that this virus may represent a new species in the subfamily Torovirinae. CONCLUSIONS: This report of a novel nidovirus in ball pythons may provide insight into the pathogenesis of respiratory disease in this species and enhances our knowledge of the diversity of nidoviruses.

Knowing your audience affects male-male interactions in Siamese fighting fish (Betta splendens).

Aggressive interactions between animals often occur in the presence of third parties. By observing aggressive signalling interactions, bystanders may eavesdrop and gain relevant information about conspecifics without the costs of interacting. On the other hand, interactants may also adjust their behaviour when an audience is present. This study aimed to test how knowledge about fighting ability of an audience affects aggressive interactions in male Siamese fighting fish. Subjects were positioned between two dyads of non-interacting males and allowed to observe both dyads shortly before the view to one of the dyads was blocked, and the dyads were allowed to interact. Subjects were subsequently exposed to an unknown opponent in the presence of either the winner or the loser of the seen or unseen interaction. The results suggest a complex role of the characteristic of an audience in the agonistic behaviours of a subject engaged in an interaction. The presence of a seen audience elicited more aggressive displays towards the opponent if the audience was a loser. This response was different in the presence of an unseen audience. Subjects then directed a higher aggressiveness against their opponent if the audience was a winner. These results also suggest a potentially more complex and interesting process allowing individuals to gain information about the quality and threat level of an unknown audience while it is interacting with a third party. The importance of information acquisition for an individual to adapt its behaviour and the role of communication networks in shaping social interactions are discussed.

Nasal adenocarcinoma and secondary chronic sinusitis in a hyacinth macaw (Anodorhynchus hyacinthinus).

An adult male hyacinth macaw (Anodorhynchus hyacinthinus) that presented for acute onset nasal discharge and dyspnea had purulent discharge from the right naris and serosanguineous discharge from the left naris on physical examination. Results of a complete blood count revealed severe leukocytosis with a mature heterophilia. Computed tomography scans showed a large amount of soft-tissue attenuating material within the infraorbital sinus and associated diverticula. Aerobic culture results of the nasal discharge showed a mixed population of Staphylococcus intermedius and Pasteurella species, including Pasteurella pneumotropica; all isolated bacteria were susceptible to enrofloxacin. Clinical signs did not resolve over the course of 9 weeks of antibiotic treatment. The macaw died after cardiopulmonary arrest while hospitalized. At necropsy, a 2 x 2 x 3-cm firm, tan, friable, space-occupying mass surrounded by a thick exudate was present in the left preorbital diverticulum of the infraorbital sinus. The cranioventral one-third of the trachea contained a 4 x 0.5-cm white-yellow plaque. On histologic examination, the sinus mass was diagnosed as a nasal adenocarcinoma, and the tracheal plaque was caused by fungal infection, most likely with an Aspergillus species.

Implementation and impact of integrated health and social care services: an umbrella review.

Governments in many European countries have been working towards integrating health and social care services to eliminate the fragmentation that leads to poor care coordination for patients. We conducted a systematic review to identify and synthesize knowledge about the integration of health and social care services in Europe. We identified 490 records, in 14 systematic reviews that reported on 1148 primary studies and assessed outcomes of integration of health care and social care. We categorized records according to three purposes: health outcomes, service quality and integration procedures outcomes. Health outcomes include improved clinical outcomes, enhanced quality of life, and positive effects on quality of care. Service quality improvements encompass better access to services, reduced waiting times, and increased patient satisfaction. Integration procedure outcomes involve cost reduction, enhanced collaboration, and improved staff perceptions; however, some findings rely on limited evidence. This umbrella review provides a quality-appraised overview of existing systematic reviews.

Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

Trilobolide-6-O-isobutyrate from Sphagneticola trilobata acts by inducing oxidative stress, metabolic changes and apoptosis-like processes by caspase 3/7 activation of human lung cancer cell lines.

BACKGROUND: Lung cancer, a chronic and heterogeneous disease, is the leading cause of cancer-related death on a global scale. Presently, despite a variety of available treatments, their effectiveness is limited, often resulting in considerable toxicity and adverse effects. Additionally, the development of chemoresistance in cancer cells poses a challenge. Trilobolide-6-O-isobutyrate (TBB), a natural sesquiterpene lactone extracted from Sphagneticola trilobata, has exhibited antitumor effects. Its pharmacological properties in NSCLC lung cancer, however, have not been explored. PURPOSE: This study evaluated the impact of TBB on the A549 and NCI-H460 tumor cell lines in vitro, examining its antiproliferative properties and initial mechanisms of cell death. METHODS: TBB, obtained at 98 % purity from S. trilobata leaves, was characterized using chromatographic techniques. Subsequently, its impact on inhibiting tumor cell proliferation in vitro, TBB-induced cytotoxicity in LLC-MK2, THP-1, AMJ2-C11 cells, as well as its effects on sheep erythrocytes, and the underlying mechanisms of cell death, were assessed. RESULTS: In silico predictions have shown promising drug-likeness potential for TBB, indicating high oral bioavailability and intestinal absorption. Treatment of A549 and NCI-H460 human tumor cells with TBB demonstrated a direct impact, inducing significant morphological and structural alterations. TBB also reduced migratory capacity without causing toxicity at lower concentrations to LLC-MK2, THP-1 and AMJ2-C11 cell lines. This antiproliferative effect correlated with elevated oxidative stress, characterized by increased levels of ROS, superoxide anion radicals and NO, accompanied by a decrease in antioxidant markers: SOD and GSH. TBB-stress-induced led to changes in cell metabolism, fostering the accumulation of lipid droplets and autophagic vacuoles. Stress also resulted in compromised mitochondrial integrity, a crucial aspect of cellular function. Additionally, TBB prompted apoptosis-like cell death through activation of caspase 3/7 stressors. CONCLUSION: These findings underscore the potential of TBB as a promising candidate for future studies and suggest its viability as an additional component in the development of novel anticancer drugs prototypes.

Treatment of Pain in Ferrets.

Ferrets often require pain management as part of comprehensive veterinary care. Recognition and objective quantification of pain, such as the ferret grimace scale, are the first steps of an analgesic plan. As in other species, a multimodal approach to pain management is preferred, which includes combining analgesic drugs of multiple classes and/or techniques to affect different areas of the pain pathway. This article reviews the current published literature on analgesic medications in domestic ferrets, including specific drugs, doses, dosing intervals, and routes of administration.

Polyvinylpyrrolidone Nanofibers Incorporating Mesoporous Bioactive Glass for Bone Tissue Engineering.

Composite biomaterials that combine osteoconductive and osteoinductive properties are a promising approach for bone tissue engineering (BTE) since they stimulate osteogenesis while mimicking extracellular matrix (ECM) morphology. In this context, the aim of the present research was to produce polyvinylpyrrolidone (PVP) nanofibers containing mesoporous bioactive glass (MBG) 80S15 nanoparticles. These composite materials were produced by the electrospinning technique. Design of experiments (DOE) was used to estimate the optimal electrospinning parameters to reduce average fiber diameter. The polymeric matrices were thermally crosslinked under different conditions, and the fibers' morphology was studied using scanning electron microscopy (SEM). Evaluation of the mechanical properties of nanofibrous mats revealed a dependence on thermal crosslinking parameters and on the presence of MBG 80S15 particles inside the polymeric fibers. Degradation tests indicated that the presence of MBG led to a faster degradation of nanofibrous mats and to a higher swelling capacity. The assessment of in vitro bioactivity in simulated body fluid (SBF) was performed using MBG pellets and PVP/MBG (1:1) composites to assess if the bioactive properties of MBG 80S15 were kept when it was incorporated into PVP nanofibers. FTIR and XRD analysis along with SEM-EDS results indicated that a hydroxy-carbonate apatite (HCA) layer formed on the surface of MBG pellets and nanofibrous webs after soaking in SBF over different time periods. In general, the materials revealed no cytotoxic effects on the Saos-2 cell line. The overall results for the materials produced show the potential of the composites to be used in BTE.

Biogenic silver nanoparticle exhibits schistosomicidal activity in vitro and reduces the parasitic burden in experimental schistosomiasis mansoni.

Schistosomiasis is a neglected tropical parasitic disease that affects millions of people, being the second most prevalent parasitic disease worldwide. The current treatment has limited effectiveness, drug-resistant strains, and is not effective in different stages of the disease. This study investigated the antischistosomal activity of biogenic silver nanoparticles (Bio-AgNp) against Schistosoma mansoni. Bio-AgNp presented direct schistosomicidal activity on newly transformed schistosomula causing plasma membrane permeabilization. In S. mansoni adult worms, reduced the viability and affected the motility, increasing oxidative stress parameters, and inducing plasma membrane permeabilization, loss of mitochondrial membrane potential, lipid bodies accumulation, and autophagic vacuoles formation. During the experimental schistosomiasis mansoni model, Bio AgNp restored body weight, reduced hepatosplenomegaly, and decrease the number of eggs and worms in feces and liver tissue. The treatment also ameliorates liver damage and reduces macrophage and neutrophil infiltrates. A reduction in count and size was evaluated in the granulomas, as well as a change to an exudative-proliferative phase, with a local increase of IFN-γ. Together our results showed that Bio-AgNp is a promising therapeutic candidate for studies of new therapeutic strategies against schistosomiasis.

Clown Nose: A Rare Hypopharyngeal Cancer Metastasis.

Cutaneous metastases from squamous cell carcinomas of the head and neck region are uncommon, and their location at the nasal tip is exceptionally rare. A patient, previously treated with surgery and chemoradiation for a hypopharyngeal squamous cell carcinoma, developed several red nodular skin lesions at the nasal tip. Biopsy revealed cutaneous metastasis from the primary tumor. This manifestation was previously described as a "clown nose," given their appearance and location. Skin lesions should raise suspicion of malignancy, despite their location at uncommon places, particularly in patients with previous diagnosed cancer. Clinicians must be aware that metastases from head and neck cancer can present as a "clown nose."