Detail study on the interaction between perfluorooctanoic acid (PFOA) with human hemoglobin (Hb).

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are often referred to as legacy perfluoroalkyl substances (PFAS). Human exposure to PFAS leads to severe negative health impacts including cancers, infertility, and dysfunction in the kidneys. Steady-state absorbance, fluorescence, and circular dichroism (CD) methods were used to study the interactions between PFOA and Hb. The results demonstrate the presence of multiple PFOA binding sites on the Hb protein. The detailed analysis of the ferric hemoglobin protein (met Hb) absorbance data as a function of PFOA concentration indicates the presence of at least two binding sites with equilibrium dissociation constants of 0.8 ± (0.2) × 10-6 M and 63 ± (15) × 10-5 M. A competitive binding study with 1,8-ANS showed PFOA can bind to the same binding site as 1,8-ANS on the Hb protein. The titration curve for PFOA binding to Hb in its CO bound form (CO-Hb) yields a single equilibrium dissociation constant of 139 ± (20) × 10-6 M. PFOA binding at low concentrations occurs at the high-affinity sites leading to the destabilization of the protein structure as reflected by changes in the CD spectrum. PFOA interactions with Hb also interfere with the kinetics of CO association to this protein. The rate for CO association to Hb increases at low PFOA concentrations, whereas at elevated PFOA concentrations, the ligand association is biphasic as a new kinetic process with a different rate constant was observed. Overall, this study provides a detailed explanation of PFOA-induced structural and conformational changes to the Hb protein based on the spectroscopy data.

Induced neural phase precession through exogeneous electric fields.

The gradual shifting of preferred neural spiking relative to local field potentials (LFPs), known as phase precession, plays a prominent role in neural coding. Correlations between the phase precession and behavior have been observed throughout various brain regions. As such, phase precession is suggested to be a global neural mechanism that promotes local neuroplasticity. However, causal evidence and neuroplastic mechanisms of phase precession are lacking so far. Here we show a causal link between LFP dynamics and phase precession. In three experiments, we modulated LFPs in humans, a non-human primate, and computational models using alternating current stimulation. We show that continuous stimulation of motor cortex oscillations in humans lead to a gradual phase shift of maximal corticospinal excitability by ~90°. Further, exogenous alternating current stimulation induced phase precession in a subset of entrained neurons (~30%) in the non-human primate. Multiscale modeling of realistic neural circuits suggests that alternating current stimulation-induced phase precession is driven by NMDA-mediated synaptic plasticity. Altogether, the three experiments provide mechanistic and causal evidence for phase precession as a global neocortical process. Alternating current-induced phase precession and consequently synaptic plasticity is crucial for the development of novel therapeutic neuromodulation methods.

Exhaled Pneumocystis jirovecii output and detection of asymptomatic exhalation by facemask sampling in HIV-uninfected, immunocompromised patients.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) transmission is poorly defined. Previous studies have sampled air of rooms occupied by HIV-infected patients with PJP, while natural and direct exhalations of HIV-uninfected subjects remain under-investigated. Here, clinical facemasks were used to examine and quantify potential P. jirovecii exhalations from HIV-uninfected patients with suspected PJP and to determine whether pathogen exhalation was definable clinically or radiologically. METHODS: Forty-five patients in Leicester (England), highly suspected of having PJP based on European Conference on Infections in Leukaemia (ECIL-5) guidelines, each wore one facemask carrying a gelatine/PVA sampling matrix for 1 h while respiring normally. Mask contamination with P. jirovecii was assessed using a modified quantitative polymerase chain reaction targeting mitochondrial large subunit (MtLSU). Radiological findings on chest X-ray (CXR) and computed tomography (CT) were graded and analysed for correlation with P. jirovecii signals alongside relevant clinical and laboratory findings. RESULTS: P. jirovecii was detected in seven of 20 patients diagnosed with PJP and three of 19 patients with suspected but undiagnosed PJP. The median captured signal was 8.59 × 104 MtLSU copies/mask (interquartile range (IQR) = 3.01 × 105-1.81 × 104). Blood ß-D-glucan test results correlated with the mask detection data (r = 0.65; P<0.0001) but other clinical indices and radiological features did not. Five of the 10 P. jirovecii-exhalers exhibited normal CXR with a median exhalation burden 1.28 × 105 copies/mask (IQR = 1.51 × 105-2.27 × 104). Two P. jirovecii-exhalers (7.64 × 104 copies/mask) were asymptomatic. CONCLUSION: P. jirovecii was exhaled sufficiently during normal respiration to be detectable in facemasks worn by HIV-uninfected patients. Neither clinical nor radiological features correlated with P. jirovecii exhalation.

Risk factors for injury and illness in youth floorball players - A prospective cohort study.

OBJECTIVES: To investigate risk factors for injury and illness in female and male youth floorball players (12-17 years) during a 26-week floorball season. DESIGN: Prospective cohort study. SETTING: Recreational youth sport. PARTICIPANTS: 471 players (142 females) 12-17 years. MAIN OUTCOME MEASURES: Weekly survey including questions about stress, sleep quality, well-being, sport exposure and average weekly rating of perceived exertion (RPE). Acute:chronic workload ratio (ACWR) was calculated. The Oslo Sports Trauma Research Center questionnaire on health problems was used. Predictors of new injury and illness were examined using multi-level logistic regression models with weekly measures nested within individuals. RESULTS: Higher stress, poorer sleep quality and well-being increased the odds of a new injury in the subsequent week by 8% (2.0-13.5%), 10% (4.2-15.9%) and 8% (2.4-13.5%) per 1 unit increase. Higher stress, and poorer well-being increased the odds of illness by 8% (2.6-12.6%), and 12% (7.2-16.6%). ACWR below 0.8 or above 1.3 increased the odds of illness by 34% (4.9-70.8%). CONCLUSIONS: Perceived stress, well-being, and sleep quality were associated with injury and illness occurrence in the subsequent week. ACWR outside the range 0.8-1.3 was associated with illness the subsequent week. TRIAL REGISTRATION: Clinical Trials registration NCT03309904.

A Rapid and Satisfactory Outcome with Combined Immunosuppressive Therapy in Acquired Haemophilia A with Underlying Tuberculosis.

Acquired haemophilia A (AHA) is a rare disorder with an incidence of 1.5 cases per million per year in the United Kingdom. The incidence could be underestimated due to difficulty in diagnosis and also due to the fact that people with low titre inhibitor levels are asymptomatic. It is usually a disease affecting elderly but a disease peak in the younger population is known. The common underlying diseases are autoimmune disorders, malignancies, infections, and drugs. However, approximately 50% of the cases do not have a specific aetiology and about 10% will not have bleeding manifestations. Therefore, an isolated prolongation of APTT should be evaluated, especially prior to any haemostatic challenges. We report a case of a middle-aged man who presented with bleeding due to AHA associated with high inhibitory titres and active pulmonary tuberculosis. He was treated with both antituberculous and combined-aggressive immunosuppressive therapy which resulted in satisfactory disease remission.

Dataset from the detailed survey of vintage unreinforced masonry buildings in the State of Queensland, Australia.

Due to an identified need to have realistic geometries and boundary conditions of vintage unreinforced masonry (URM) parapets and gable ends, this data collection study was conducted to document prevalent typologies of URM buildings in the Australian State of Queensland. Street surveys were completed in 7 towns and included measurement of the building geometry and the documentation of the other building construction details that were ascertainable using a brief external evaluation. To collect the data, firstly the historical statistical records from Colonial Australia were interrogated to determine regions with the largest potential stocks of vintage URM buildings. It was found that, excluding the Queensland capital (Brisbane), seven other towns existed that had reported significant URM building construction during late 19th century and early 20th century census. These seven towns were selected for street surveys, and Brisbane was excluded due to the lack of sufficient resources. The street survey included take measurable photographs of building facades using a digital laser-based tool. These photographs were used in subsequent desktop study to calculate façade geometries. Additional relevant building information was extracted from Google Map and other sources, enabling an estimate of the roof shape and building plan dimension to be also obtained. This data report includes spreadsheets containing summary of the 363 surveyed building properties and the drawings that were created using the collected data.

Oxidative stress differentially impacts apical and basolateral secretion of angiogenic factors from human iPSC-derived retinal pigment epithelium cells.

The retinal pigment epithelium (RPE) is a polarized monolayer that secretes growth factors and cytokines towards the retina apically and the choroid basolaterally. Numerous RPE secreted proteins have been linked to the pathogenesis of age-related macular degeneration (AMD). The purpose of this study was to determine the differential apical and basolateral secretome of RPE cells, and the effects of oxidative stress on directional secretion of proteins linked to AMD and angiogenesis. Tandem mass tag spectrometry was used to profile proteins in human iPSC-RPE apical and basolateral conditioned media. Changes in secretion after oxidative stress induced by H2O2 or tert-butyl hydroperoxide (tBH) were investigated by ELISA and western analysis. Out of 926 differentially secreted proteins, 890 (96%) were more apical. Oxidative stress altered the secretion of multiple factors implicated in AMD and neovascularization and promoted a pro-angiogenic microenvironment by increasing the secretion of pro-angiogenic molecules (VEGF, PTN, and CRYAB) and decreasing the secretion of anti-angiogenic molecules (PEDF and CFH). Apical secretion was impacted more than basolateral for PEDF, CRYAB and CFH, while basolateral secretion was impacted more for VEGF, which may have implications for choroidal neovascularization. This study lays a foundation for investigations of dysfunctional RPE polarized protein secretion in AMD and other chorioretinal degenerative disorders.

Bilateral fracture-dislocation of the shoulder following a seizure- A case report & review of literature.

Introduction: and Importance: Bilateral shoulder dislocations are uncommon and those are usually posterior dislocations. Bilateral anterior fracture-dislocations are rarest of their kind following seizure episodes. Case presentation: We present a case of bilateral fracture-dislocations of the shoulder following a seizure episode. Bilateral dislocations were relocated to the emergency unit and managed conservatively as he refused to undergo surgery. The patient was followed up at the Orthopaedic clinic and achieved a full range of movements of the bilateral shoulder the one-year post-intervention. Clinical discussion: A closed reduction is also an option on occasion like this patient. Conclusion: Careful radiological assessment and follow-up with physiotherapy will help to achieve a good outcome.

[MxyR of Mycobacterium tuberculosis Responds to Xylan; an Unusual Ligand for a MarR Family Transcriptional Regulator].

Among the repertoire of MarR family transcriptional regulators in Mycobacterium tuberculosis, gene rv3095 (mxyR) encodes Mycobacterial Xylan Regulator, MxyR. Gene mxyR is divergently oriented from a hydrolase (rv3094c), oxidoreductase (rv3093c) and an ABC transporter (rv3092c) and convergently oriented with xylanase (rv3096). Xylanase is commonly used by plant pathogenic microbes where they degrade xylan, the major component of hemicellulose. We have purified the transcriptional regulatory protein encoded by rv3095 and its molecular interactions were studied in detail using electrophoretic mobility shift assay. MxyR interacts with its upstream intergenic region mxyO with high specificity and at a dissociation constant of 5.01 ± 0.017 nM. Notably, this binding is attenuated by specific carbohydrate ligands such as xylan, L-Arabinose and D-Galactose with an IC50 values of 22.7 ± 1.02 ng/µL, 360.8 ± 24.25 ng/µL and 2320.0 ± 96.97 µg/µL, respectively. Consequently, it is evident that this association changes the conformation of the DNA binding helix α4 making the transcriptional regulator incompatible with binding to its cognate DNA, allowing xylanase and other genes to be transcribed. This study establishes the natural ligands of MxyR of M. tuberculosis providing insight on metabolic regulation of the carbohydrate, xylan.

Elucidation of specific binding sites and extraction of toxic Gen X from HSA employing cyclodextrin.

The presence of per and poly-fluoroalkyl substances (PFAS), commonly referred to as forever chemicals, in aquatic systems is a serious global health problem. While the remediation of PFAS from aqueous media has been extensively investigated, their interactions with and removal from biological systems have received far less attention. We report herein structural alterations to human serum albumin (HSA) upon addition of perfluoro(2-methyl-3-oxahexanoic) acid (Gen X) monitored by changes to the fluorescence and circular dichroism (CD) spectra of HSA. The equilibrium association constant for Gen X binding to HSA is 7( ± 1) × 103 M-1 determined from changes in HSA fluorescence emission data during titration. Site-specific HSA binding fluorophores, 8-anilinonaphthalene-1-sulfonic acid (1,8-ANS), warfarin and dansyl-L-proline were used to investigate the specific binding sites of Gen X on HSA. A competitive displacement study yields association constants for Gen X to HSA at the 1,8-ANS, warfarin, and dansyl-L-proline binding sites to be 6.25 ( ± 0.5) × 104 M-1, 1.1 × 106 M-1, and 2.5( ± 0.2) × 109 M-1 respectively. Addition of ß-cyclodextrin (ß-CD) and heptakis(6-deoxy-6-amino)-ß-cyclodextrin heptahydrochloride to the HSA:Gen X complex leads to the effective extraction of Gen X from the complex with the return of HSA in its native form. Gen X also leads to displacement of site-specific binding fluorophores bound to HSA, while subsequent addition of ß-CD extracts Gen X from HSA with the return of the characteristic fluorescence of the HSA bound site-specific agent. These results illustrate the strong and specific binding sites of Gen X on HSA and demonstrate the principles for the potential application of ß-CD for the remediation of PFAS from biological systems.

In vitro and in vivo evaluation of the wound healing properties and safety assessment of two seaweeds (Sargassum ilicifolium and Ulva lactuca).

Seaweeds have been regarded as a reservoir of biologically active molecules that are important in the pharmaceutical industry. The aim of the present study was to explore the wound healing properties and to assess the safety of the seaweed Sargassum ilicifolium and Ulva lactuca. Enhanced cell proliferation and cell migration activities were observed in L929 cells treated with S. ilicifolium extract compared to U. lactuca extract treated cells and the control group. In-vivo experiments were conducted using five groups (10 in each) of Albino mice (BALB/c). Mice in group I and group II were treated (Orally, 100 mg/kg BW/day) with aqueous extracts of S. ilicifolium and U. lactuca, respectively for 14 days. Treatment group III received a topical application of the aqueous extract of S. ilicifolium (25% w/w) and ointment base (75% w/w) (2 g/kg BW/day, for 14 days). Group IV (Control) received an equal amount of distilled water, orally and mice in group V kept without wounds. The extract from S. ilicifolium showed stronger wound healing properties than the one from Ulva lactuca. Histopathological findings also revealed that the healing process was significantly enhanced in the mice group treated orally with S. ilicifolium aqueous extract. These findings show that S. ilicifolium species possess promising wound healing properties in-vitro and in-vivo.

Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study.

BACKGROUND: Dengue fever prevalence is rising globally and it causes significant morbidity and mortality. Fluid extravasation during the critical phase of dengue haemorrhagic fever (DHF) leads to shock, multi-organ failure and death if not resuscitated appropriately with fluids. The mainstay of management is judicious fluid replacement using a guideline based, calculated fluid quota of maintenance (M) fluid plus 5% deficit (M +  5% deficit) to prevent organ hypoperfusion. METHODS: We conducted an observational follow-up study in Sri Lanka from January-July 2017 to identify the fluid requirements of DHF patients and to identify whether features of fluid overload are present in patients who exceeded the fluid quota. Patients who developed DHF following admission to the place of study, were recruited and the amount of fluid received during the critical phase was documented. RESULTS: A total of 115 DHF patients with a mean age of 30.3 (SD 12.2) years were recruited to the study. There were 65 (56.5%) males and the mean fluid requirement was 5279.7 ml (SD 735) over the 48 h. Majority of the study participants (n = 80, 69.6%) received fluid in excess of the recommended maintenance + 5% deficit and this group had higher body mass index (22.75 vs 20.76, p0.03) and a lower white cell count at the onset of the critical phase (3.22 × 103 vs 4.78 × 103, p < 0.001). The highest fluid requirement was seen within the first 12 and 24 h of the critical phase in patients requiring fluid M +  5%-7.5% deficit and ≥ M +  7.5% deficit respectively. Patients exceeding M + 5% deficit had narrow pulse pressure and hypotension compared to the rest. DHF grades III and IV were seen exclusively in patients exceeding the fluid quota indicating higher amount of fluid was given for resuscitation. Fluid overload was detected in 14 (12.1%) patients and diuretic therapy was required in 6 (5.2%) patients. CONCLUSIONS: The majority of patients received fluid in excess of the recommended quota and this group represents patients with narrow pulse pressure and hypotension. Although, fluid overload was infrequent in the study population, clinicians should be cautious when administering fluid in excess of M +  7.5% deficit.

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients

BackgroundIncreased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in multiple neutrophil functions and circulating cytokine levels over time during COVID-19 may help define disease severity and guide care and decision making. MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil oxidative burst, neutrophil extracellular trap formation (NETosis), phagocytosis and cytokine levels were assessed ex vivo. Lung tissue was obtained immediately post-mortem for immunostaining. ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified in COVID-19 plasma both at the first measurement and at multiple timepoints across hospitalization (p < 0.0001). Neutrophils had exaggerated oxidative burst (p < 0.0001), NETosis (p < 0.0001) and phagocytosis (p < 0.0001) relative to controls. Increased NETosis correlated with both leukocytosis and neutrophilia. Neutrophils and NETs were identified within airways and alveoli in the lung parenchyma of 40% of SARS-CoV-2 infected lungs. While elevations in IL-8 and ANC correlated to COVID-19 disease severity, plasma IL-8 levels alone correlated with death. ConclusionsCirculating neutrophils in COVID-19 exhibit an activated phenotype with increased oxidative burst, NETosis and phagocytosis. Readily accessible and dynamic, plasma IL-8 and circulating neutrophil function may be potential COVID-19 disease biomarkers.

Reactogenicity to ChAdOx1 nCoV-19 vaccine in health care workers: A multicenter observational study in Sri Lanka.

Introduction: The acceptability of a vaccine is an important factor during mass vaccination programs and this is largely dependent on the symptoms of local and systemic reactogenicity. There is paucity of data on the systemic and local reactions experienced by COVD-19 vaccine recipients in South Asia. Objectives: To identify the early local and systemic reactogenicity of ChAdOx1 nCoV-19 vaccine. Method: A multicenter observational study was performed to identify the reactogenicity to ChAdOx1 nCoV-19 vaccine in healthcare workers following the first dose. Results: There were 4478 participants with a median age of 42 years (IQR 34-51) and 2863 (63.9%) were females. At least one symptom of reactogenicity was reported by 4151 (92.7%). Local reactions were reported by 2612 (58.3%). Systemic reactions were bodyache (3244,72.4%), fatigue (2379, 53.1%), headache (2277, 50.8%), fever (2290, 51.1%), feverishness (1912, 42.7%) and chills (2295, 51.3%). Lower age (p<0.0001) and female gender (p 0.002) were associated with a higher frequency of developing systemic reactions. There was no association between reactogenicity and comorbidities. There were 342 (7.6%) reports of palpitations and one case of ventricular bigeminy. There was one report of anaphylaxis and hospital admissions were reported by 24 (0.5%). One vaccine recipient was managed for possible aseptic meningitis. Conclusion: This study demonstrates that early systemic and local reactions are common. Systemic reactions were more frequent in females and in the younger population. Most symptoms were self- limiting and did not require medical attention or hospital admission. ChAdOx1 nCoV-19 vaccine appears safe in the studied population.

Impedance Plethysmography as an Alternative Measure of Reactive Hyperemia.

Peripheral vascular flow in response to induced reactive hyperemia of the radial artery is used as a benchmark for non-invasive assessment of the endothelial function. As an alternative to standard modalities, this study investigates the suitability of impedance plethysmography to estimate peripheral vascular flow variations associated with the reactive hyperemia process. Results indicate a consistent variation of bio-impedance during the reactive hyperemia process at higher measurement frequencies and these variations are compatible with a standard tissue impedance model. Further, calculated features of bioimpedance has shown the capability of differentiating healthy and diabetic groups which is useful in estimating the endothelial dysfunction.

Epidemiological profile of pain and non-steroid anti-inflammatory drug use in collegiate athletes in the United States.

BACKGROUND: Although athletic endeavours are associated with a high amount of physical stress and injury, the prevalence of pain is underreported in the sports medicine literature with only a few studies reporting pain on collegiate athletes or exploring sex difference of pain. Impact of pain on athlete availability, training and performance can be mitigated when key epidemiological information is used to inform adequate pain management strategies. This study aims to 1) provide an epidemiological profile of self-reported pain experienced by the National Collegiate Athletic Association (NCAA) athletes by sex during the first half of the 2019 season, 2) describe their self-reported non-steroidal anti-inflammatory drug (NSAID) use. METHODS: Online survey was completed by athletes at three NCAA institutions from 1 August to 30 September 2019. Descriptive statistics were used to describe player demographic data, self-reported pain and self-reported NSAID use. Pain incidence proportion were calculated. RESULTS: Two hundred thirty female athletes and 83 male athletes completed the survey. Self-reported pain incidence proportion for female athletes was 45.0 (95% CI 41.5-48.5) vs 34.9 (95% CI 29.4-40.4) for male athletes. Majority of the athletes did not report pain (55% female vs 62% male) during the first half of the 2019 season. Female athletes reported pain in their back (35%), knee (26%), and ankle/foot (23%) whilst male athletes reported pain in their knee (35%), back (28%), and shoulder (24%). Of all athletes, 28% female vs 20% male athletes reported currently taking NSAIDs. Of athletes that reported pain, 46% female vs 38% male athletes currently took NSAIDs. 70% female vs 61% male athletes self-purchased NSAIDs, and 40% female vs 55% male athletes consumed alcohol. CONCLUSIONS: Half of female athletes and one in three male athletes reported pain. Most commonly back, knee and foot/ankle pain and knee, back and shoulder pain was reported in female and male athletes respectively. One in four female athletes and one in five male athletes use NSAIDs for pain or prophylactic purpose. Majority self-purchase these medications indicating need for health literacy interventions to mitigate potential adverse effects.

Reporte de resultados negativos a Trichinella spp. por digestión artificial en cerdos domésticos del valle inferior del río Negro, Patagonia Argentina / Report of negative results to Trichinella spp. by artificial digestion in domestic pigs of the lower valley of the Negro River, Argentine Patagonia

Resumen Actualmente, el género Trichinella está constituido por 10 especies y 3 genotipos. La transmisión ocurre únicamente por ingestión de tejido muscular infectado. Entre los potenciales hospedadores se conforma un ciclo doméstico y un ciclo silvestre con posible retroalimentación constante entre ambos. Desde el año 2017 el funcionamiento del Matadero Social de San Javier, en el valle inferior del río Negro, permite a productores acceder a una faena segura que además brinde garantías al consumidor. El objetivo del presente trabajo fue evaluar la presencia de larvas L1 de Trichinella spp. en porcinos domésticos procedentes de criaderos de pequeña y mediana escala. Se analizaron por el método de digestión artificial 10 gramos de diafragma de cada porcino doméstico, conformando pooles de hasta 10 animales. En total 942 porcinos domésticos resultaron negativos a la presencia de larvas L1 de Trichinella spp. No obstante debe tenerse presente que sistemas de producción con las características de los que provienen los animales analizados, estarían potencialmente expuestos a la retroalimentación de Trichinella spp. desde la fauna silvestre. En este marco, resulta necesario garantizar el control veterinario en la faena de porcinos y presas de caza y sostener acciones de vigilancia, actualización y promoción en relación a la prevención de la triquinelosis.

Abstract Currently the Trichinella genus consists of 10 species and 3 genotypes. Transmission occurs only through ingestion of infected muscle tissue. Between the potential hosts there is a domestic cycle and a wild cycle with possible constant feedback between both. Since 2017, the operation of the San Javier Social Slaughterhouse, in the lower valley of the Río Negro, allows producers to access a safe operation that also provides guarantees to the consumer. The aim of the present study was to evaluate the presence of L1 larvae larvae of Trichinella spp. in domestic pigs from small and medium-scale farms. 10 grams of diaphragm from each domestic pig were analyzed by the artificial digestion method, forming pools of up to 10 animals. In total 942 domestic pigs were negative for the presence of L1 larvae of Trichinella spp. However, it should be borne in mind that production systems with the characteristics from which the analyzed animals come, would potentially be exposed to the feedback of Trichinella spp. from wildlife. Then, it is necessary to guarantee veterinary control in the slaughter of pigs and game prey and to support surveillance, updating and promotion actions in relation to the prevention of trichinellosis.

Characterization of a catalase from red-lip mullet (Liza haematocheila): Demonstration of antioxidative activity and mRNA upregulation in response to immunostimulants.

Reactive oxygen species, generated in all the aerobic organisms, can cause oxidative stress. Excessive ROS may become a source of carcinogen due to DNA damage, lipid peroxidation, cell injury, and cell death. In order to prevent these adverse effects of ROS, antioxidant enzymes have evolved in aerobic organisms. Catalase is a major antioxidant enzyme that breaks down excessive H2O2 and inhibits apoptotic cell death. Here we molecularly characterized catalase from red-lip mullet. The cDNA sequence of LhCAT consists of an ORF of 1545 bp, which encodes a 527 amino acid peptide (~60 kDa). Based on bioinformatics analysis, LhCAT possesses a domain architecture characteristic of catalases, including a catalase proximal active site signature and a catalase proximal heme-ligand signature. It also has heme and NADPH binding sites homologous to previously described catalases. Pairwise alignment with its homologs revealed that LhCAT shares 95.1% identity with Oplegnathus fasciatus catalase and 97.4% similarity with Sparus aurata catalase. An uprooted phylogenetic tree demonstrated that LhCAT resides in a clade with catalases from other teleosts and exhibits a close relationship with Oplegnathus fasciatus catalase. Among twelve tissue types, we observed the highest LhCAT mRNA expression in the liver, followed by blood. Immune challenge by Lactococcus garvieae, or Poly I:C in the blood or spleen resulted in up-regulation at 24 h post injection. We also tested the antioxidant activity of recombinant LhCAT against hydrogen peroxide and found its optimal concentration to be 12.5 µg/mL. Collectively, these data suggested that LhCAT play an important role in antioxidant defense and immune response of red-lip mullet.

Detailed clinical characterisation, unique features and natural history of autosomal recessive RDH12-associated retinal degeneration.

BACKGROUND: Defects in retinol dehydrogenase 12 (RDH12) account for 3.4%-10.5 % of Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) and are a potential target for gene therapy. Clinical trials in inherited retinal diseases have unique challenges, and natural history studies are critical to successful trial design. The purpose of this study was to characterise the natural history of RDH12-associated retinal degeneration. METHODS: A retrospective chart review was performed in individuals with retinal degeneration and two likely disease-causing variants in RDH12. RESULTS: 57 subjects were enrolled from nine countries. 33 subjects had clinical records available from childhood. The data revealed an EOSRD, with average age of onset of 4.1 years. Macular atrophy was a universal clinical finding in all subjects, as young as 2 years of age. Scotopic and photopic electroretinography (ERG) responses were markedly reduced in all subjects, and a non-recordable ERG was documented as young as 1 year of age. Assessment of visual acuity, visual field and optical coherence tomography revealed severe loss of function and structure in the majority of subjects after the age of 10 years. Widefield imaging in 23 subjects revealed a unique, variegated watercolour-like pattern of atrophy in 13 subjects and sparing of the peripapillary area in 18 subjects. CONCLUSIONS: This study includes the largest collection of phenotypic data from children with RDH12-associated EOSRD and provides a comprehensive description of the timeline of vision loss in this severe, early-onset condition. These findings will help identify patients with RDH12-associated retinal degeneration and will inform future design of therapeutic trials.

Optimizing antibiotic prescribing: collective approaches to managing a common-pool resource.

BACKGROUND: Antimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way. OBJECTIVES: We aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma. SOURCES: We conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas. CONTENT: The social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms. IMPLICATIONS: We conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development.