ANTIBACTERIAL EFFECTS OF SINGLE AND COMBINED CRUDE EXTRACTS OF SYNADENIUM GLAUCESCENS AND COMMIPHORA SWYNNERTONII.

Background: Synadenium glaucescens and Commiphora swynnertonii are among the reported plants used traditionally for treatment of bacterial infections. This study reports antibacterial effects of single and combined extracts from leaves, stem and root barks of Commiphora swynnertonii and Synadenium glaucescens. Materials and Methods: Plants were collected from Manyara and Njombe regions in Tanzania. Extraction was done using dichloromethane and methanol. The extracts were assessed for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa). Minimum Inhibitory Concentrations (MIC) was determined by broth microdilution, while Fractional Inhibitory Concentration (FIC) indices were calculated from MIC values of combined extracts to determine combination effects. Results: Strong antibacterial activities were demonstrated by all extracts of S. glaucescens (MIC 0.011-0.375mg/mL) against Gram-positive bacteria and methanol extracts of C. swynnertonii (MIC 0.047-0.375mg/mL). Synergistic effect was observed when combining methanol extracts of C. swynnertonii stem bark with S. glaucescens leaves against S. aureus (∑FIC 0.5), Other synergistic effects were observed against E. faecalis with dichloromethane extracts of C. swynnertonii stem bark and S. glaucescens stem bark (∑FIC 0.5), and C. swynnertonii root bark and S. glaucescens root bark (FIC index 0.3). For the remaining combinations, mainly additive effects were observed. Conclusion: Synergistic effects on bacteria were observed by combining different plant parts of S. glaucescens and C. swynnertonii suggesting that it could be beneficial to combine such extracts when used for antibacterial purposes.

Wave chaos enhanced light trapping in optically thin solar cells.

Enhancing the energy output of solar cells increases their competitiveness as a source of energy. Producing thinner solar cells is attractive, but a thin absorbing layer demands excellent light management in order to keep transmission- and reflection-related losses of incident photons at a minimum. We maximize absorption by trapping light rays to make the mean average path length in the absorber as long as possible. In chaotic scattering systems, there are ray trajectories with very long lifetimes. In this paper, we investigate the scattering dynamics of waves in a model system using principles from the field of quantum chaotic scattering. We quantitatively find that the transition from regular to chaotic scattering dynamics correlates with the enhancement of the absorption cross section and propose the use of an autocorrelation function to assess the average path length of rays as a possible way to verify the light-trapping efficiency experimentally.

Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Chaos: A new mechanism for enhancing the optical generation rate in optically thin solar cells.

The photogenerated current of solar cells can be enhanced by light management with surface structures. For solar cells with optically thin absorbing layers, it is especially important to take advantage of this fact through light trapping. The general idea behind light trapping is to use structures, either on the front surface or on the back, to scatter light rays to maximize their path length in the absorber. In this paper, we investigate the potential of chaotic scattering for light trapping. It is well known that the trajectories close to the invariant set of a chaotic scatterer spend a very long time inside of the scatterer before they leave. The invariant set, also called the chaotic repeller, contains all rays of infinite length that never enter or leave the region of the scatterer. If chaotic repellers exist in a system, a chaotic dynamics is present in the scatterer. As a model system, we investigate an elliptical dome structure placed on top of an optically thin absorbing film, a system inspired by the chaotic Bunimovich stadium. A classical ray-tracing program has been developed to classify the scattering dynamics and to evaluate the absorption efficiency, modeled with Beer-Lambert's law. We find that there is a strong correlation between the enhancement of absorption efficiency and the onset of chaotic scattering in such systems. The dynamics of the systems was shown to be chaotic by their positive Lyapunov exponents and the noninteger fractal dimension of their scattering fractals.

Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates.

BACKGROUND: The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated. OBJECTIVES: To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals. ANIMALS: Two-hundred and seventy-three ill foals and 25 healthy control foals. METHODS: Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis. RESULTS: One-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study. CONCLUSIONS AND CLINICAL IMPORTANCE: The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis.

Kinematic discrimination of ataxia in horses is facilitated by blindfolding.

BACKGROUND: Agreement among experienced clinicians is poor when assessing the presence and severity of ataxia, especially when signs are mild. Consequently, objective gait measurements might be beneficial for assessment of horses with neurological diseases. OBJECTIVES: To assess diagnostic criteria using motion capture to measure variability in spatial gait-characteristics and swing duration derived from ataxic and non-ataxic horses, and to assess if variability increases with blindfolding. STUDY DESIGN: Cross-sectional. METHODS: A total of 21 horses underwent measurements in a gait laboratory and live neurological grading by multiple raters. In the gait laboratory, the horses were made to walk across a runway surrounded by a 12-camera motion capture system with a sample frequency of 240 Hz. They were made to walk normally and with a blindfold in at least three trials each. Displacements of reflective markers on head, fetlock, hoof, fourth lumbar vertebra, tuber coxae and sacrum derived from three to four consecutive strides were processed and descriptive statistics, receiver operator characteristics (ROC) to determine the diagnostic sensitivity, specificity and area under the curve (AUC), and correlation between median ataxia grade and gait parameters were determined. RESULTS: For horses with a median ataxia grade ≥2, coefficient of variation for the location of maximum vertical displacement of pelvic and thoracic distal limbs generated good diagnostic yield. The hoofs of the thoracic limbs yielded an AUC of 0.81 with 64% sensitivity and 90% specificity. Blindfolding exacerbated the variation for ataxic horses compared to non-ataxic horses with the hoof marker having an AUC of 0.89 with 82% sensitivity and 90% specificity. MAIN LIMITATIONS: The low number of consecutive strides per horse obtained with motion capture could decrease diagnostic utility. CONCLUSIONS: Motion capture can objectively aid the assessment of horses with ataxia. Furthermore, blindfolding increases variation in distal pelvic limb kinematics making it a useful clinical tool.

Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy.

INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. AIM: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy. METHODS: Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score). RESULTS: In patients with haemophilia, cartilage degradation, measured by C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in haemophilia patients (P < 0.05). Bone formation (PINP) was reduced by 25% (P < 0.05) in haemophilia patients, whereas bone resorption (CTX-I) was increased by 30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01), whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophilia patients relative to control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could distinguish haemophilia patients from control subjects with 85.3% accuracy (P < 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint. CONCLUSION: Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophilia patients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.

The effects of oil spills on marine fish: Implications of spatial variation in natural mortality.

The effects of oil spills on marine biological systems are of great concern, especially in regions with high biological production of harvested resources such as in the Northeastern Atlantic. The scientific studies of the impact of oil spills on fish stocks tend to ignore that spatial patterns of natural mortality may influence the magnitude of the impact over time. Here, we first illustrate how spatial variation in natural mortality may affect the population impact by considering a thought experiment. Second, we consider an empirically based example of Northeast Arctic cod to extend the concept to a realistic setting. Finally, we present a scenario-based investigation of how the degree of spatial variation in natural mortality affects the impact over a gradient of oil spill sizes. Including the effects of spatial variations in natural mortality tends to widen the impact distribution, hence increasing the probability of both high and low impact events.

Experiencia con el balón de Bakri en hemorragia obstétrica / Brakri balloon experience in obstetric hemorrhage

Resumen OBJETIVO: reportar la experiencia con el balón de Bakri en el control de la hemorragia obstétrica, su relación con la cantidad y concentraciones de hemoglobina antes y después de su aplicación. MATERIALES Y MÉTODOS: estudio prospectivo y observacional efec- tuado en dos unidades hospitalarias del 1 de enero al 31 de diciembre de 2016. A todas las pacientes se les aplicó el balón de Bakri por falta de respuesta a los uterotónicos. Variables de estudio: datos clínicos, cantidad de pérdida sanguínea antes y después de la aplicación del balón, cantidad de sangrado en el posparto y transcesárea, tiempo trascurrido entre el diagnóstico y la colocación, tiempo de llenado y volumen administrado, concentraciones de hemoglobina y pruebas de coagulación al ingreso a la unidad de atención, postsangrado y posterior a la aplicación, indicación de hemocomponentes, cantidad y tiempo de permanencia del balón, éxito y complicaciones. Se realizó análisis estadístico de todas estas variables. RESULTADOS: se incluyeron 20 pacientes con hemorragia posparto y transcesárea. La cantidad de sangrado después de la aplicación, tanto en los casos de posparto como transcesárea, fue menor y se obtuvo una adecuada respuesta. El tiempo medio entre el diagnóstico de la hemorragia y la colocación del balón fue de 30 minutos, tiempo medio de llenado de 5 minutos y cantidad media de llenado de 400 mL. El tiempo medio de permanencia del balón fue de 29.5 horas. En 95% de los casos se consiguió una respuesta favorable para el control de la hemorragia, sin complicaciones. CONCLUSIONES: la aplicación del balón de Bakri resultó en una medida útil, rápida y sin complicaciones para controlar la hemorragia obstétrica.

Abstract OBJECTIVE: To present the results obtained by using the Bakri Balloon to control obstetric hemorrhage. MATERIALS AND METHOD: Prospective, observational study within two inpatient medical care units from January 1 to December 31 2016. All of them were applied the Bakri Balloon because of failure to respond to uterotonic drug therapy. The following were analized: clinical data, amount of bleeding before and after the balloon, amount of postpartum or transcesarean bleeding, time between diagnosis and insertion, insufflation time and supplied volumen, hemoglobin levels and coagulation tests results initially, post-hemorrhage and post insertion, use of and amount of haemocomponents ministered, and the balloons use time, success, and complications. RESULTS: 20 patients with postpartum and transesarean hemorrhage are included. The amount of bleeding after insertion, both in postpartum and trans cesarean was reduced and there was an adequate response in hemoglobin levels. The average time between hemorrhage diagnosis and balloon insertion was thirty minutes; average insufflation time, five minutes, and average volumen supplied 400 mL. Balloon's average use time, 29.5 hours. In 95% of the cases there was a positive response for hemorrhage control, with no complications derived from use. CONCLUSIONS: The Bakri Balloon proved to be a useful, quick and complication-free therapy for controlling obstetric hemorrhage.

Charge Radii of Neutron Deficient

Bunched-beam collinear laser spectroscopy is performed on neutron deficient ^{52,53}Fe prepared through in-flight separation followed by a gas stopping. This novel scheme is a major step to reach nuclides far from the stability line in laser spectroscopy. Differential mean-square charge radii δ⟨r^{2}⟩ of ^{52,53}Fe are determined relative to stable ^{56}Fe as δ⟨r^{2}⟩^{56,52}=-0.034(13) fm^{2} and δ⟨r^{2}⟩^{56,53}=-0.218(13) fm^{2}, respectively, from the isotope shift of atomic hyperfine structures. The multiconfiguration Dirac-Fock method is used to calculate atomic factors to deduce δ⟨r^{2}⟩. The values of δ⟨r^{2}⟩ exhibit a minimum at the N=28 neutron shell closure. The nuclear density functional theory with Fayans and Skyrme energy density functionals is used to interpret the data. The trend of δ⟨r^{2}⟩ along the Fe isotopic chain results from an interplay between single-particle shell structure, pairing, and polarization effects and provides important data for understanding the intricate trend in the δ⟨r^{2}⟩ of closed-shell Ca isotopes.

Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia.

Essentials Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. Basement membrane and interstitial matrix turnover changed significantly following hemarthrosis. SUMMARY: Background Hemophilic arthropathy is a severe complication of hemophilia. It is caused by recurrent bleeding into joint cavities, which leads to synovial inflammation, fibrosis, cartilage degradation and bone remodeling. Extracellular matrix remodeling of affected tissues is a hallmark of these pathological processes. Objectives The aim of this study was to use serological biomarkers of collagen turnover to evaluate extracellular matrix remodeling in a factor VIII-deficient rat model of hemophilic arthropathy. Methods F8-/- rats and wild-type littermate controls were subjected to repeated knee bleeds induced by needle puncture on days 0 and 14. Development of arthropathy was confirmed by histology after termination on day 28. Serum samples were collected at baseline and throughout the study and analyzed for biomarkers of collagen turnover, including collagens of the basement membrane (type IV collagen), the interstitial matrix (collagen types III, V and VI) and cartilage (type II collagen). Results In F8-/- rats, induced knee bleeding and subsequent development of arthropathy caused significant alterations in collagen turnover, measured as changes in serological biomarkers of basement membrane turnover, interstitial matrix turnover and cartilage degradation. Biomarkers of type II collagen degradation correlated significantly with cartilage degradation and degree of arthropathy. Hemophilic rats had a 50% higher turnover of the basement membrane than wild-type littermates at baseline. Conclusions Joint bleeding and hemophilic arthropathy cause changes in turnover of extracellular matrix collagens in hemophilic rats. Biomarkers of collagen turnover may be used to monitor joint bleeding and development of blood-induced joint disease in hemophilia.

Impact of Nuclear Mass Uncertainties on the r Process.

Nuclear masses play a fundamental role in understanding how the heaviest elements in the Universe are created in the r process. We predict r-process nucleosynthesis yields using neutron capture and photodissociation rates that are based on the nuclear density functional theory. Using six Skyrme energy density functionals based on different optimization protocols, we determine for the first time systematic uncertainty bands-related to mass modeling-for r-process abundances in realistic astrophysical scenarios. We find that features of the underlying microphysics make an imprint on abundances especially in the vicinity of neutron shell closures: Abundance peaks and troughs are reflected in trends of neutron separation energy. Further advances in the nuclear theory and experiments, when linked to observations, will help in the understanding of astrophysical conditions in extreme r-process sites.

Lungeing on hard and soft surfaces: Movement symmetry of trotting horses considered sound by their owners.

REASONS FOR PERFORMING STUDY: Lungeing is often part of the clinical lameness examination. The difference in movement symmetry, which is a commonly employed lameness measure, has not been quantified between surfaces. OBJECTIVES: To compare head and pelvic movement symmetry between surfaces and reins during lungeing. STUDY DESIGN: Quantitative gait analysis in 23 horses considered sound by their owners. METHODS: Twenty-three horses were assessed in-hand and on the lunge on both reins on hard and soft surfaces with inertial sensors. Seven movement symmetry parameters were quantified and used to establish 2 groups, namely symmetrical (n = 9) and forelimb-lame horses (n = 14), based on values from straight-line assessment. Movement symmetry values for left rein measurements were side corrected to allow comparison of the amount of movement symmetry between reins. A mixed model (P<0.05) was used to study effects on movement symmetry of surface (hard/soft) and rein (inside/outside with respect to movement symmetry on the straight). RESULTS: In forelimb-lame horses, surface and rein were identified as significantly affecting all head movement symmetry measures (rein, all P<0.0001; surface, all P<0.042). In the symmetrical group, no significant influence of surface or rein was identified for head movement symmetry (rein, all P>0.245; surface, all P>0.073). No significant influence of surface or rein was identified for any of the pelvic movement symmetry measures in either group. CONCLUSIONS: While more symmetrical horses showed a consistent amount of movement symmetry across surfaces/reins, horses objectively quantified as lame on the straight showed decreased movement symmetry during lungeing, in particular with the lame limb on the inside of a hard circle. The variation within group questions straight-line movement symmetry as a sole measure of lameness without quantification of movement symmetry on the lunge, ideally on hard and soft surfaces to evaluate differences between reins and surfaces. In future, thresholds for lungeing need to be determined using simultaneous visual and objective assessment.

Mutations in the TLR3 signaling pathway and beyond in adult patients with herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) in children has previously been linked to defects in type I interferon production downstream of Toll-like receptor (TLR)3. In the present study, we used whole-exome sequencing to investigate the genetic profile of 16 adult patients with a history of HSE. We identified novel mutations in IRF3, TYK2 and MAVS, molecules involved in generating innate antiviral immune responses, which have not previously been associated with HSE. Moreover, data revealed mutations in TLR3, TRIF, TBK1 and STAT1 known to be associated with HSE in children but not previously described in adults. All discovered mutations were heterozygous missense mutations, the majority of which were associated with significantly decreased antiviral responses to HSV-1 infection and/or the TLR3 agonist poly(I:C) in patient peripheral blood mononuclear cells compared with controls. Altogether, this study demonstrates novel mutations in the TLR3 signaling pathway in molecules previously identified in children, suggesting that impaired innate immunity to HSV-1 may also increase susceptibility to HSE in adults. Importantly, the identification of mutations in innate signaling molecules not directly involved in TLR3 signaling suggests the existence of innate immunodeficiencies predisposing to HSE beyond the TLR3 pathway.

Spatial ecology of coastal Atlantic cod Gadus morhua associated with parasite load.

Acoustic tags and receivers were used to investigate the spatial ecology of coastal Atlantic cod Gadus morhua (n = 32, mean fork length: 50 cm, range: 33-80 cm) on the Norwegian Skagerrak coast in 2012. Monthly home ranges (HR), swimming activity and depth use varied considerably among individuals and through the months of June, July and August. HR sizes for the period ranged from 0.25 to 5.20 km2 (mean = 2.30 km2. Two thirds of the tagged G. morhua were infected with black spot disease Cryptocotyle lingua parasites; these fish had larger HRs and occupied deeper water compared with non-infected fish. The infected fish also tended to be more active in terms of horizontal swimming. From an ecological and evolutionary perspective, any environmental change that modifies G. morhua behaviour may therefore also alter the parasite load of the population, and its conservation and fishery status.

Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sézary syndrome).

BACKGROUND: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited. We investigated the response rate, safety and tolerability of oral forodesine treatment in subjects with cutaneous manifestations of CTCL, stages IB, IIA, IIB, III and IVA. The safety population encompassing all stages was used for analysis of accountability, demographics and safety. The efficacy population differed from the safety population by exclusion of stage IB and IIA patients. RESULTS: All 144 patients had performance status 0-2. The median duration of CTCL from diagnosis was 53 months (5-516 months). The median number of pretreatments was 4 (range: 3-15). No complete remissions were observed. In the efficacy group of patients, 11% achieved partial remission and 50% had stable disease. The median time to response was 56 days and the median duration of response was 191 days. A total of 96% of all treated patients reported one or more adverse events (AEs) and 33% reported a serious AE. The majority of AEs were classified as mild or moderate in severity. The most commonly reported AEs (>10%) were peripheral edema, fatigue, insomnia, pruritus, diarrhea, headache and nausea. Overall eight patients died during the study: five due to sepsis and infections, one due to a second malignancy (esophageal cancer), one due to disease progression and one due to liver failure. CONCLUSION: Oral forodesine at a dose of 200 mg daily is feasible and shows partial efficacy in this highly selected CTCL population and some durable responses.

Rater agreement on gait assessment during neurologic examination of horses.

BACKGROUND: Reproducible and accurate recognition of presence and severity of ataxia in horses with neurologic disease is important when establishing a diagnosis, assessing response to treatment, and making recommendations that might influence rider safety or a decision for euthanasia. OBJECTIVES: To determine the reproducibility and validity of the gait assessment component in the neurologic examination of horses. ANIMALS: Twenty-five horses referred to the Royal Veterinary College Equine Referral Hospital for neurological assessment (n = 15), purchased (without a history of gait abnormalities) for an unrelated study (n = 5), or donated because of perceived ataxia (n = 5). METHODS: Utilizing a prospective study design; a group of board-certified medicine (n = 2) and surgery (n = 2) clinicians and residents (n = 2) assessed components of the equine neurologic examination (live and video recorded) and assigned individual and overall neurologic gait deficit grades (0-4). Inter-rater agreement and assessment-reassessment reliability were quantified using intraclass correlation coefficients (ICC). RESULTS: The ICCs of the selected components of the neurologic examination ranged from 0 to 0.69. "Backing up" and "recognition of mistakes over obstacle" were the only components with an ICC > 0.6. Assessment-reassessment agreement was poor to fair. The agreement on gait grading was good overall (ICC = 0.74), but poor for grades ≤ 1 (ICC = 0.08) and fair for ataxia grades ≥ 2 (ICC = 0.43). Clinicians with prior knowledge of a possible gait abnormality were more likely to assign a grade higher than the median grade. CONCLUSION AND CLINICAL IMPORTANCE: Clinicians should be aware of poor agreement even between skilled observers of equine gait abnormalities, especially when the clinical signs are subtle.

Innate DNA sensing is impaired in HIV patients and IFI16 expression correlates with chronic immune activation.

The innate immune system has been recognized to play a role in the pathogenesis of HIV infection, both by stimulating protective activities and through a contribution to chronic immune activation, the development of immunodeficiency and progression to AIDS. A role for DNA sensors in HIV recognition has been suggested recently, and the aim of the present study was to describe the influence of HIV infection on expression and function of intracellular DNA sensing. Here we demonstrate impaired expression of interferon-stimulated genes in responses to DNA in peripheral blood monuclear cells from HIV-positive individuals, irrespective of whether patients receive anti-retroviral treatment. Furthermore, we show that expression levels of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic guanosine monophosphate-adenosine monophosphate synthase were increased in treatment-naive patients, and for IFI16 expression was correlated with high viral load and low CD4 cell count. Finally, our data demonstrate a correlation between IFI16 and CD38 expression, a marker of immune activation, in CD4(+) central and effector memory T cells, which may indicate that IFI16-mediated DNA sensing and signalling contributes to chronic immune activation. Altogether, the present study demonstrates abnormal expression and function of cytosolic DNA sensors in HIV patients, which may have implications for control of opportunistic infections, chronic immune activation and T cell death.

Landscape of two-proton radioactivity.

Ground-state two-proton (2p) radioactivity is a decay mode found in isotopes of elements with even atomic numbers located beyond the two-proton drip line. So far, this exotic process has been experimentally observed in a few light- and medium-mass nuclides with Z≤30. In this study, using state-of-the-art nuclear density functional theory, we globally analyze 2p radioactivity and for the first time identify 2p-decay candidates in elements heavier than strontium. We predict a few cases where the competition between 2p emission and α decay may be observed. In nuclei above lead, the α-decay mode is found to be dominating and no measurable candidates for the 2p radioactivity are expected.