Genetic and morphological identification of filarial worm from Iberian hare in Portugal.

The Iberian hare (Lepus granatensis) is an endemic species of the Iberian Peninsula and the only hare species found in Portugal, although also being present in some areas of Spain. The reduction of wild hare populations due to several ecological and sanitary factors, has been raising growing concerns in the recent years. Despite different helminth species were already described in Iberian hares in Portugal, to this date, no filarial worms have been identified in this species. Furthermore, only a few studies on lagomorphs' onchocercid worms are available, referring to other hosts species of hares and/or rabbits. In this study, we describe the presence of filarial worms in the blood vessels of two adult Iberian hares collected in 2019 in continental Portugal. Morphology and sequencing data from the 12S rRNA, coxI, 18S rRNA, myoHC, hsp70 and rbp1 genes, showed that the filaroid species were genetically related with Micipsella numidica. However, the extension of the genetic differences found with M. numidica suggests that the filaroids specimens under study belong to a new species, that we provisionally named Micipsella iberica n. sp.. The body location of this putative new parasite species and its physiological implications indicate that it may constitute a potential menace to the already fragile Iberian hare justifying, therefore, further investigation regarding the morphological characterization, prevalence and real clinical impact of this new parasite in hares.

Implementing harm reduction in non-urban communities affected by opioids and polysubstance use: A qualitative study exploring challenges and mitigating strategies.

BACKGROUND: Harm reduction services, which typically provide overdose education and prevention with distribution of naloxone and other supplies related to safer drug use, help reduce opioid-related overdose and infectious disease transmission. However, structural stigma and the ongoing criminalization of drug use have limited the expansion of harm reduction services into many non-urban communities in the United States that have been increasingly affected by the health consequences of opioid and polysubstance use. METHODS: We conducted qualitative interviews with 22 professionals working with people who use drugs in cities and towns across Rhode Island and Massachusetts to understand challenges and strategies for engaging communities in accepting harm reduction perspectives and services. RESULTS: Our thematic analysis identified several interrelated challenges to implementing harm reduction services in non-urban communities, including: (1) limited understandings of harm reduction practice and preferential focus on substance use treatment and primary prevention, (2) community-level stigma against people who use drugs as well as the agencies supporting them, (3) data reporting and aggregating leading to inaccurate perceptions about local patterns of substance use and related health consequences, and (4) a "prosecutorial mindset" against drug use and harm reduction. From key informants' narratives, we also identified specific strategies that communities could use to address these challenges, including: (1) identifying local champions to advocate for harm reduction strategies, (2) proactively educating communities about harm reduction approaches before they are implemented, (3) improving the visibility of harm reduction services within communities, and (4) obtaining "buy-in" from a wide range of local stakeholders including law enforcement and local government. CONCLUSION: These findings carry important implications for expanding harm reduction services, including syringe service programs and safe injection sites, into non-urban communities that have a demonstrated need for evidence-based interventions to reduce drug-related overdose and infectious disease transmission.

Novel Way to Search for Light Dark Matter in Lepton Beam-Dump Experiments.

A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.

PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation.

VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression anticipated the initiation of vascular enlargement and markedly accelerated the splitting process. Interestingly, quantification during in vivo imaging suggested that a global reduction in shear stress favored the initiation of transluminal pillar formation during VEGF-induced splitting angiogenesis. Quantification of target gene expression showed that VEGF-R2 signaling output was significantly reduced by PDGF-BB co-expression compared to VEGF alone. In conclusion, PDGF-BB co-expression prevents VEGF-induced aberrant angiogenesis by modulating VEGF-R2 signaling and endothelial proliferation, thereby limiting the degree of circumferential enlargement and enabling efficient completion of vascular splitting into normal capillary networks despite high VEGF doses.

Fusarium riograndense sp. nov., a new species in the Fusarium solani species complex causing fungal rhinosinusitis.

Invasive fusariosis has a high mortality and is predominantly observed in patients with leukemia. We report the first case of a novel species of Fusarium, Fusarium riograndense sp. nov, isolated from a lesion in the nasal cavity lesion of a patient with acute lymphoblastic leukemia. The etiological agent was identified by Multilocus Sequencing Typing (MLST), including RPB2, TEF-1α, and ITS-LSU sequences, the gold standard technique to identify new species of Fusarium. MLST and phenotypic data strongly supported its inclusion in the F. solani species complex (FSSC). The new species produced a red pigment in the Sabouraud Dextrose Agar similar to other members of the complex. The macroconiodia developed from phialides on multibranched conidiophores which merge to form effuse sporodochia with a basal foot-cell instead of papilla in basal cell shape. The microconidia were ellipsoidal, 0-1-septated, produced from long monophialides. Chlamydospores were produced singly or in pairs. Amphotericin B (MIC 1µg/mL) was the most active drug, followed by voriconazole (MIC 8µg/mL). The patient was successfully treated with voriconazole. Our findings indicate another lineage within FSSC capable causing of invasive human infection.

REST-Dependent Presynaptic Homeostasis Induced by Chronic Neuronal Hyperactivity.

Homeostatic plasticity is a regulatory feedback response in which either synaptic strength or intrinsic excitability can be adjusted up or down to offset sustained changes in neuronal activity. Although a growing number of evidences constantly provide new insights into these two apparently distinct homeostatic processes, a unified molecular model remains unknown. We recently demonstrated that REST is a transcriptional repressor critical for the downscaling of intrinsic excitability in cultured hippocampal neurons subjected to prolonged elevation of electrical activity. Here, we report that, in the same experimental system, REST also participates in synaptic homeostasis by reducing the strength of excitatory synapses by specifically acting at the presynaptic level. Indeed, chronic hyperactivity triggers a REST-dependent decrease of the size of synaptic vesicle pools through the transcriptional and translational repression of specific presynaptic REST target genes. Together with our previous report, the data identify REST as a fundamental molecular player for neuronal homeostasis able to downscale simultaneously both intrinsic excitability and presynaptic efficiency in response to elevated neuronal activity. This experimental evidence adds new insights to the complex activity-dependent transcriptional regulation of the homeostatic plasticity processes mediated by REST.

Environmental yeast communities in vineyards in the mountains of Santa Catarina State, Brazil.

Yeasts were isolated from three vineyards located in the South Region of Brazil. A cross evaluation was carried out at the oldest vineyard of the study in Pinheiro Preto. Samples of grape berries, grapevine leaves and the soil, along with samples of the winery equipment and effluent, were collected. In the Serra do Marari and Campos Novos vineyards only samples of grape clusters were obtained. The 106 yeast isolates were identified by sequencing the D1/D2 domain of LSU rDNA or ITS1-5.8S-ITS2 region in 22 species. The values for the richness indices varied between the vineyards. A comparison of the taxonomic diversity of the yeasts from these regions using the reciprocal Simpson index showed a significant difference between the Serra do Marari and Campos Novos vineyards (5.72 ± 0.36 and 2.92 ± 0.36, respectively, p < 0.0001). The functional diversity was assessed in relation to the use of carbon and nitrogen sources by the yeasts isolated from each location. In general, we observed that the Pinheiro Preto and Campos Novos vineyards differed consistently from the Serra do Marari vineyard according to these indices (FAD2, FDc and Rao, p < 0.0001). The possible spreading of Saccharomyces cerevisiae from the winery to the vineyard in Pinheiro Preto was observed.

Spectral imbalance in the inertial range dynamics of decaying rotating turbulence.

Direct numerical simulations of homogeneous decaying turbulence with background rotation show the existence of a systematic and significant imbalance between the non-linear energy cascade to small scales and its dissipation. By starting the decay from a statistically stationary and weakly rotating turbulent state, where the dissipation and the energy flux are approximately equal, the data show a growing imbalance between the two until a maximum is reached when the dissipation is about twice the energy flux. This dichotomy of behaviors during decay is reminiscent of the nonequilibrium and the equilibrium regions previously reported for nonrotating turbulence [Valente and Vassilicos, Phys. Rev. Lett. 108, 214503 (2012)PRLTAO0031-900710.1103/PhysRevLett.108.214503]. Note, however, that for decaying rotating turbulence the classical scaling of the dissipation rate ε∝u^{'3}/L (where u^{'} and L are the root mean square fluctuating velocity and the integral length scale, respectively) does not appear to hold during decay, which may be attributed to the effect of the background rotation on the energy cascade. On the other hand, the maximum energy flux holds the scaling Π_{max}∝u^{'3}/L in the initial stage of the decay until the maximum imbalance is reached.

Bone marrow bi-hypoplasia in a dog with a sertoli cell tumor / Hipoplasia dupla de medula óssea em um cão com tumor de células de sertoli

A 20-year-old unneutered male poodle presented prostration, apathy, staggering gait, lack of appetite and tick infestation. The dog was diagnosed with a Sertoli cell tumor in an undescended testicle by cytological, histopathological and immunohistochemical tests. Pancytopenia with moderate nonregenerative anemia, leukopenia and severe thrombocytopenia were detected in the complete blood count. Cytological and histopathological evaluation of the bone marrow revealed a cellularity of 30%, with erythroid (59%), lymphoid (40%) and mast cells (1%), and an absence of granulocytic, monocytic and megakaryocytic lineage cells. In post-mortem examinations, changes related to hemostatic disorders were found. The absence of microorganisms in molecular tests and an estrogen serum concentration over reference values confirmed hyperestrogenism as a possible cause of pancytopenia. The literature describes a Sertoli cell tumor hyperestrogenism that induced pancytopenia, along with bone marrow hypoplasia of all hematopoietic lineages. In contrast, in the present case, the erythroid precursor cells were preserved in the bone marrow, although there were no reticulocytes circulating in the blood. This case, therefore, should be considered in future investigations of pancytopenia induced by Sertoli cell tumor hyperestrogenism.(AU)

Um cão Poodle, macho, de 20 anos, não castrado, apresentou prostração, apatia, andar cambaleante, falta de apetite e infestação por carrapatos. Nesse animal, foi diagnosticado tumor de células de Sertoli em um testículo não descendente, utilizando-se citologia, histopatologia e imuno-histoquímica. Pancitopenia com anemia moderada não regenerativa, leucopenia e trombocitopenia intensas foram detectadas no hemograma. Na avaliação citológica e histopatológica da medula óssea, havia celularidade de 30%, constituída pelas linhagens eritroide (59%) e linfoide (40%) e por mastócitos (1%), com ausência de células das linhagens granulocítica, monocítica e megacariocítica. Em exames post mortem, mudanças relacionadas à hemostasia foram encontradas. A ausência de micro-organismos nos testes moleculares e a concentração sérica de estrogênio acima dos valores de referência confirmaram hiperestrogenismo como a possível causa da pancitopenia. A literatura descreve hiperestrogenismo em tumores de células de Sertoli induzindo pancitopenia associada com hipoplasia da medula óssea de todas as linhagens hematopoiéticas. Em contraste, no presente caso, as células precursoras eritróides estavam preservadas na medula óssea, embora não houvesse reticulócitos no sangue. Assim, o relato apresentado deve ser considerado em futuras investigações de pancitopenia induzida por hiperestrogenismo em tumor de células de Sertoli.(AU)

Avaliação hemogasométrica em cadelas com piometra / Hemogasometric evaluation in bitches with pyometra

A piometra é uma afecção comum em cadelas com uma etiologia hormonal associada à infecção bacteriana, levando ao acúmulo de exsudato uterino. Desequilíbrios ácido-base e hidroeletrolíticos são complicações que contribuem para a progressão da doença, o que piora o estado geral da paciente e pode levá-la ao óbito. O objetivo do presente trabalho foi caracterizar os distúrbios ácido-base e eletrolíticos em cadelas com piometra, além de avaliar se a terapia hídrica pré-cirúrgica (Ringer lactato) é efetiva na correção desses desequilíbrios. Vinte cadelas com piometra foram submetidas à hemogasometria em oito tempos preestabelecidos. Concluiu-se que o distúrbio ácido-base mais frequente foi a alcalose respiratória e que a terapia hídrica no pré-cirúrgico com solução Ringer lactato foi efetiva na correção da acidose metabólica e proporcionou melhora na alcalose respiratória, embora não tenha corrigido quadros de alcalose metabólica.

Pyometra is a common disease in dogs with a hormonal etiology associated with a bacterial infection and leading to accumulation of uterine exudates. Acid-base and electrolyte disturbances are complications that contribute to disease progression, worsening the condition of the patient, possibly leading death. The aim of this study was to characterize the acid-base and electrolyte disturbances in dogs with pyometra, and to evaluate whether preoperative fluid therapy (Ringer's lactate) is effective in correcting these imbalances. Twenty bitches with pyometra were subjected to blood gas analysis in eight pre-set times. It was concluded that the acid-base disorder was the most frequent respiratory alkalosis and fluid therapy in the preoperative Ringer 's lactate solution was effective in the correction of metabolic acidosis, although this has not corrected metabolic alkalosis frames and has provided improved alkalosis breathing .

The association between retinal microvascular changes, metabolic risk factors, and liver histology in pediatric patients with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: The prevalence of childhood obesity is increasing worldwide. Studies in adult populations show that retinal microvascular changes are associated with obesity and components of the metabolic syndrome. In our study we have assessed the effect of body mass index (BMI), metabolic parameters, and adiposity on the retinal microvasculature in children. METHODS: Fifty-four consecutive children with biopsy-proven NAFLD were enrolled in this study. Anthropometric and laboratory parameters were obtained using standardized protocols. Retinal caliber was quantified from digital retinal images using well-known computer-based programs. Twenty-four-hour ambulatory blood pressure monitoring was measured using a standard protocol. RESULTS: In our population, the prevalence of retinopathy was of 53 % (13 males). The 29 patients with retinopathy (mean age 10.91 ± 3.10) showed significantly higher values of triglycerides (mg/day) (105.57 vs. 90.20, p = 0.04), basal insulin (mUI/ml) (17.20 vs. 12.97, p = 0.02), and HOMA-IR (3.37 vs. 2.76, p = 0.04). The patients with a HOMA-IR >2.5 (OR = 3.34, p = 0.02; 95 % IC, 1.07-10.39), and systolic non-dipping (OR 4.16, p = 0.028, 95 % IC, 1.11-13.67), have an increased risk of retinopathy. Moreover, the study of correlation between all stages of liver biopsy (CRN criteria) and the grade of retinopathy showed a positive correlation with fibrosis (r = 0.31) and an NAS score (r = 0.28). CONCLUSIONS: We found an association between metabolic parameters and nocturnal blood pressure on the retinal microvasculature among the obese children with NAFLD. Furthermore, for the first time, we report the positive relationship between hepatic fibrosis in pediatric NAFLD patients and the degree of retinopathy signs.

Origin of the imbalance between energy cascade and dissipation in turbulence.

It is shown in direct numerical simulations of homogeneous isotropic non-stationary turbulence that there is a systematic and significant imbalance between the non-linear energy cascade to fine scales and its dissipation. This imbalance stems from the power required to induce or annihilate fine-scale motions in order to change the level of dissipation. The imbalance is present regardless of transfer time-lags and is applicable to a wide range of Reynolds numbers.

Universal dissipation scaling for nonequilibrium turbulence.

It is experimentally shown that the nonclassical high Reynolds number energy dissipation behavior, C(ε)≡εL/u(3)=f(Re(M))/Re(L), observed during the decay of fractal square grid-generated turbulence (where Re(M) is a global inlet Reynolds number and Re(L) is a local turbulence Reynolds number) is also manifested in decaying turbulence originating from various regular grids. For sufficiently high values of the global Reynolds numbers Re(M), f(Re(M))~Re(M).

Presence of biofilm containing viable multiresistant organisms despite terminal cleaning on clinical surfaces in an intensive care unit.

BACKGROUND: Despite recent attention to surface cleaning and hand hygiene programmes, multiresistant organisms (MROs) continue to be isolated from the hospital environment. Biofilms, consisting of bacteria embedded in exopolymeric substances (EPS) are difficult to remove due to their increased resistance to detergents and disinfectants, and periodically release free-swimming planktonic bacteria back into the environment which may may act as an infection source. AIM: To establish whether reservoirs of MROs exist in the environment as biofilms. METHODS: Following terminal cleaning, equipment and furnishings were removed aseptically from an intensive care unit (ICU) and subjected to culture and scanning electron microscopy (SEM). Samples were placed in 5 mL of tryptone soya broth, sonicated for 5 min before plate culture on horse blood agar, Brillance MRSA and Brilliance VRE agar plates. Samples for SEM were fixed in 3% glutaraldehyde and hexamethyldisilizane (HMDS) prior to sputter-coating with gold and examination in an electron microscope. FINDINGS: Biofilm was demonstrated visually on the sterile supply bucket, the opaque plastic door, the venetian blind cord, and the sink rubber, whereas EPS alone was seen on the curtain. Viable bacteria were grown from three samples, including MRSA from the venetian blind cord and the curtain. CONCLUSION: Biofilm containing MROs persist on clinical surfaces from an ICU despite terminal cleaning, suggesting that current cleaning practices are inadequate to control biofilm development. The presence of MROs being protected within these biofilms may be the mechanism by which MROs persist within the hospital environment.

Test of "crab-waist" collisions at the DAPhiNE Phi factory.

The electron-positron collider DAPhiNE, the Italian Phi factory, has been recently upgraded in order to implement an innovative collision scheme based on large crossing angle, small beam sizes at the crossing point, and compensation of beam-beam interaction by means of sextupole pairs creating a "crab-waist" configuration in the interaction region. Experimental tests of the novel scheme exhibited an increase by a factor of 3 in the peak luminosity of the collider with respect to the performances reached before the upgrade. In this Letter we present the new collision scheme, discuss its advantages, describe the hardware modifications realized for the upgrade, and report the results of the experimental tests carried out during commissioning of the machine in the new configuration and standard operation for the users.

GABAA receptor associated protein (GABARAP) modulates TRPV1 expression and channel function and desensitization.

Transient receptor potential vanilloid (TRPV1) transduces noxious chemical and physical stimuli in high-threshold nociceptors. The pivotal role of TRPV1 in the physiopathology of pain transduction has thrust the identification and characterization of interacting partners that modulate its cellular function. Here, we report that TRPV1 associates with gamma-amino butyric acid A-type (GABA(A)) receptor associated protein (GABARAP) in HEK293 cells and in neurons from dorsal root ganglia coexpressing both proteins. At variance with controls, GABARAP augmented TRPV1 expression in cotransfected cells and stimulated surface receptor clustering. Functionally, GABARAP expression attenuated voltage and capsaicin sensitivity of TRPV1 in the presence of extracellular calcium. Furthermore, the presence of the anchor protein GABARAP notably lengthened the kinetics of vanilloid-induced tachyphylaxia. Notably, the presence of GABARAP selectively increased the interaction of tubulin with the C-terminal domain of TRPV1. Disruption of tubulin cytoskeleton with nocodazole reduced capsaicin-evoked currents in cells expressing TRPV1 and GABARAP, without affecting the kinetics of vanilloid-induced desensitization. Taken together, these findings indicate that GABARAP is an important component of the TRPV1 signaling complex that contributes to increase the channel expression, to traffic and cluster it on the plasma membrane, and to modulate its functional activity at the level of channel gating and desensitization.

Observation of multiple volume reflection of ultrarelativistic protons by a sequence of several bent silicon crystals.

The interactions of 400 GeV protons with different sequences of bent silicon crystals have been investigated at the H8 beam line of the CERN Super Proton Synchrotron. The multiple volume reflection of the proton beam has been studied in detail on a five-crystal reflector measuring an angular beam deflection theta = 52.96 +/- 0.14 microrad. The efficiency was found larger than 80% for an angular acceptance at the reflector entrance of 70 microrad, with a maximal efficiency value of epsilon = 0.90 +/- 0.01 +/- 0.03.

Volume reflection dependence of 400 GeV/c protons on the bent crystal curvature.

The trend of volume reflection parameters (deflection angle and efficiency) in a bent (110) silicon crystal has been investigated as a function of the crystal curvature with 400 GeV/c protons on the H8 beam line at the CERN Super Proton Synchrotron. This Letter describes the analysis performed at six different curvatures showing that the optimal radius for volume reflection is approximately 10 times greater than the critical radius for channeling. A strong scattering of the beam by the planar potential is also observed for a bend radius close to the critical one.

Gasless fetoscopy: a new approach to endoscopic closure of a lumbar skin defect in fetal sheep.

OBJECTIVE: To develop a new endoscopic approach to the correction of a myelomeningocele-like defect in fetal sheep. METHODS: The fetuses of 9 pregnant ewes, with an average gestational age of 115 days, were subjected to a 3.0 x 2.0 cm removal of the skin over the lumbar spine, performed through hysterotomy. The uterus was closed, and three 5-mm endoscopic cannulas, without valve mechanisms, were inserted. In the pilot phase (2 animals), we initially worked exclusively in the amniotic fluid space. In the study phase, we partially withdrew the fetus from the amniotic fluid to completely expose its back. By simply allowing air to enter the amniotic cavity (without gas injection), a working space was created using a uterine lift device. The skin around the defect was dissected, and a biosynthetic cellulose material was applied to cover the area. A continuous suture of the skin was performed to completely hide the material. RESULTS: The combined air/fluid space allowed the skin to be successfully closed in 6 out of 7 cases in the study phase. All fetuses were alive at the end of the procedures. Time to complete the endoscopic part of the procedure fell from 3 to 1 h by the end of this series. Premature birth occurred in 2 of the 4 cases allowed to continue with the pregnancy. CONCLUSION: A new gasless fetoscopic surgery technique was developed as an alternative to current techniques used for fetal endoscopic surgery.