Effectiveness of photo-ozone therapy against equine Pythium insidiosum.

Cutaneous pythiosis is a life-threatening infectious disease. Low-level laser therapy (LLLT) and ozone (O3) have been used individually in the treatment of infected wounds. The goals of the study were a) to characterize the antimicrobial action of the photo-ozone therapy (LLLT-O3) against equine Pythium insidiosum, and b) to assess the cytotoxic potential of the LLLT-O3 in keratinocytes. Specimens of pathogen were isolated from 10 horses. After culturing, 120 hyphae plugs were distributed among four groups (n=30 hyphae plugs/group): LLLT (laser irradiation for 160 sec;), O3 (exposition to O3 for 15 min;), LLLT-O3 (LLLT and O3 treatments in sequence) and control (untreated plugs). The hyphae growth was measured during the first 14 days post-treatment. Where there was an absence of hyphae growth, the plug was recultured for an additional 7 days. The cytotoxic potential of the treatments against HaCaT keratinocytes was assessed by colorimetric assays. The LLLT-O3 and O3 treatments inactivated, respectively, 92.3% (28/30) and 30% (9/30) of the samples. No growth was detected after 7 days reculture of inactivated hyphae plugs on new media. Hyphae growth was visualized in 100% of the control and LLLT hyphae plugs. The viability of HaCaT cells was not affected by the isolated treatments (LLLT and O3), while the LLLT-O3 showed slight cytotoxic effect (20%) when compared to the control group (P<0.05). Photo-ozone therapy inactivated equine P. insidiosum hyphae with minimal cytotoxicity in skin cells in vitro.

Genetics in Parkinson's disease, state-of-the-art and future perspectives.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is clinically characterized by the presence of motor (bradykinesia, rigidity, rest tremor and postural instability) and non-motor symptoms (cognitive impairment, autonomic dysfunction, sleep disorders, depression and hyposmia). The aetiology of PD is unknown except for a small but significant contribution of monogenic forms. SOURCES OF DATA: No new data were generated or analyzed in support of this review. AREAS OF AGREEMENT: Up to 15% of PD patients carry pathogenic variants in PD-associated genes. Some of these genes are associated with mendelian inheritance, while others act as risk factors. Genetic background influences age of onset, disease course, prognosis and therapeutic response. AREAS OF CONTROVERSY: Genetic testing is not routinely offered in the clinical setting, but it may have relevant implications, especially in terms of prognosis, response to therapies and inclusion in clinical trials. Widely adopted clinical guidelines on genetic testing are still lacking and open to debate. Some new genetic associations are still awaiting confirmation, and selecting the appropriate genes to be included in diagnostic panels represents a difficult task. Finally, it is still under study whether (and to which degree) specific genetic forms may influence the outcome of PD therapies. GROWING POINTS: Polygenic Risk Scores (PRS) may represent a useful tool to genetically stratify the population in terms of disease risk, prognosis and therapeutic outcomes. AREAS TIMELY FOR DEVELOPING RESEARCH: The application of PRS and integrated multi-omics in PD promises to improve the personalized care of patients.

Recommendations for pre-symptomatic genetic testing for hereditary transthyretin amyloidosis in the era of effective therapy: a multicenter Italian consensus.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a late-onset, autosomal dominant disease caused by progressive extracellular deposition of transthyretin amyloid fibrils, leading to organ damage and death. For other late-onset fatal diseases, as Huntington's disease, protocols for pre-symptomatic genetic testing (PST) are available since decades. For ATTRv, limited experience has been reported to date, mostly gathered before the availability of approved therapies. We aimed at developing recommendations for a safe and feasible PST protocol in ATTRv in the era of emerging treatments, taking also into account Italian patients' characteristics and healthcare system rules. After an initial survey on ongoing approaches to PST for ATTRv in Italy, two roundtable meetings were attended by 24 experts from 16 Italian centers involved in the diagnosis and care of this disease. Minimal requirements for PST offer and potential critical issues were highlighted. By November 2019, 457 families affected by ATTRv with 209 molecularly confirmed pre-symptomatic carriers were counted. The median age at PST was 41.3 years of age, regardless of the specific mutation. Half of the Italian centers had a multidisciplinary team, including a neurologist, an internist, a cardiologist, a medical geneticist and a psychologist, although in most cases not all the specialists were available in the same center. A variable number of visits was performed at each site. Experts agreed that PST should be offered only in the context of genetic counselling to at risk individuals aged 18 or older. Advertised commercial options for DNA testing should be avoided. The protocol should consist of several steps, including a preliminary clinical examination, a pre-test information session, an interval time, the genetic test and a post-test session with the disclosure of the test results, in the context of an experienced multidisciplinary team. Recommendations for best timing were also defined. Protocols for PST in the context of ATTRv can be refined to offer at risk individuals the best chance for early diagnosis and timely treatment start, while respecting autonomous decisions and promoting safe psychological adjustment to the genetic result.

Fractal signatures of the COVID-19 spread.

Recent quantitative approaches for studying several aspects of urban life and infrastructure have shown that scale properties allow the understanding of many features of urban infrastructure and of human activity in cities. In this paper, we show that COVID-19 virus contamination follows a similar pattern in different regions of the world. The superlinear power-law behavior for the number of contamination cases as a function of the city population, with exponent ß of the order of 1.15 is always obtained. Due to the strong indication that scaling is a determinant feature of covid-19 spread, we propose an epidemiological model that embodies a fractal structure, allowing a more detailed description of the observed data about the virus spread in different countries and regions. The hypothesis that fractal structures can be formed in cities as well as in larger networks is tested, indicating that indeed self-similarity may be found in networks connecting several cities.

Er,Cr:YSGG laser associated with acidulated phosphate fluoride gel (1.23% F) for prevention and control of dentin erosion progression.

To evaluate the effect of Er,Cr:YSGG laser, associated with fluoride application, on the prevention/control of dentin erosion. Dentin slabs were embedded in acrylic resin, flattened, and polished. Half of the specimens were previously eroded (10 min immersion in 1% citric acid solution) and half were kept sound. The specimens (n = 10 each substrate) were randomly allocated into the experimental groups, according to the following treatments: control (no treatment); APF gel (1.23% F, 1 min); Er,Cr:YSGG laser irradiation (P1: 0.25 W, 20 Hz, 2.8 J/cm2, tip S75, beam diameter of 750 µm, 1 mm away from the surface); Er,Cr:YSGG laser irradiation (P2: 0.50 W, 20 Hz, 5.7 J/cm2, tip S75, beam diameter of 750 µm, 1 mm away from the surface); APF gel + Er,Cr:YSGG laser P1 and; APF gel + Er,Cr:YSGG laser P2. Afterwards, the specimens underwent an erosion-remineralization cycling, consisting of a 5-min immersion into 0.3% citric acid, followed by 60-min exposure to artificial saliva. This procedure was repeated 4×/day, for 5 days. Surface loss (SL, in µm) was determined by optical profilometry. Specimens from each group were analyzed by environmental scanning electron microscopy (n = 3). Data were statistically analyzed (α = 0.05). For the eroded specimens, APF gel presented the lowest SL, being different from the control. For the sound specimens, none of the groups differed from the control, except for Er,Cr:YSGG laser P2, which presented the highest SL. When substrates were compared, only the eroded specimens of the control and APF + Er,Cr:YSGG laser P1 Groups showed higher SL. Selective structure removal was observed for the laser-treated groups. None of the Er,Cr:YSGG laser parameters were effective in the prevention/control dentin erosion. The laser was also unable to enhance the protection of fluoride against dentin erosion.

Author Correction: A method to generate small-scale, high-resolution sedimentary bedform architecture models representing realistic geologic facies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A method to generate small-scale, high-resolution sedimentary bedform architecture models representing realistic geologic facies.

Small-scale (mm to m) sedimentary structures (e.g. ripple lamination, cross-bedding) have received a great deal of attention in sedimentary geology. The influence of depositional heterogeneity on subsurface fluid flow is now widely recognized, but incorporating these features in physically-rational bedform models at various scales remains problematic. The current investigation expands the capability of an existing set of open-source codes, allowing generation of high-resolution 3D bedform architecture models. The implemented modifications enable the generation of 3D digital models consisting of laminae and matrix (binary field) with characteristic depositional architecture. The binary model is then populated with petrophysical properties using a textural approach for additional analysis such as statistical characterization, property upscaling, and single and multiphase fluid flow simulation. One example binary model with corresponding threshold capillary pressure field and the scripts used to generate them are provided, but the approach can be used to generate dozens of previously documented common facies models and a variety of property assignments. An application using the example model is presented simulating buoyant fluid (CO2) migration and resulting saturation distribution.

Tratamento alternativo em gatos acometidos por DITUIF / Alternative treatment in cats affected by FLUTD

This report describes two cases of male cats affected by FLUTD (Feline lower urinary tract disease). The first patient had been affected by numerous relapses after passing through various therapeutic treatments and surgical interventions, and was subjected to the alternative protocol after being recommended for euthanasia, the second patient had no history of urinary tract disorders in the past, and was not subjected to any kind of previous treatment. The two patients had a significant improvement in their clinical condition, were not affected by relapses after participation in the alternative design, and were accompanied for about a year after their treatment.(AU)

Final design of the beam source for the MITICA injector.

The megavolt ITER injector and concept advancement experiment is the prototype and the test bed of the ITER heating and current drive neutral beam injectors, currently in the final design phase, in view of the installation in Padova Research on Injector Megavolt Accelerated facility in Padova, Italy. The beam source is the key component of the system, as its goal is the generation of the 1 MeV accelerated beam of deuterium or hydrogen negative ions. This paper presents the highlights of the latest developments for the finalization of the MITICA beam source design, together with a description of the most recent analyses and R&D activities carried out in support of the design.

Electrostatic sensors for SPIDER experiment: design, manufacture of prototypes, and first tests.

A system of electrostatic sensors has been designed for the SPIDER (Source for the production of Ions of Deuterium Extracted from RF plasma) experiment, prototype RF source of the ITER NBI (neutral beam injection). A prototype of the sensor system was manufactured and tested at the BATMAN (BAvarian Test MAchine for Negative ions) facility, where the plasma environment is similar to that of SPIDER. Different aspects concerning the mechanical manufacturing and the signal conditioning are presented, among them the RF compensation adopted to reduce the RF effects which could lead to overestimated values of the electron temperature. The first commissioning tests provided ion saturation current values in the range assumed for the design, so the deduced plasma density estimate is consistent with the expected values.

Progress in the MITICA beam source design.

In the framework of the development of the ITER neutral beam (NB) system, a test facility is planned to be built in Padova. A full size prototype of the ITER heating NB injector (MITICA) shall be built and tested at full beam power (17 MW) as per ITER requirements. The design of the MITICA beam source has further progressed following updated optimization and overall integration criteria. In the paper, the major design choices and revisions are presented, together with some results of numerical analyses carried out in order to assess the electrostatic and thermo-mechanical behaviour of the source.

Pathologic findings of highly pathogenic avian influenza virus A/Duck/Vietnam/12/05 (H5N1) in experimentally infected pekin ducks, based on immunohistochemistry and in situ hybridization.

The ongoing H5N1 Asian epidemic is currently affecting a number of avian species including ducks. These birds are an important part of the poultry industry in the affected countries, and it is likely that they are acting as a reservoir of infection. Ten Pekin ducks were challenged with 100 microl containing 10(7) 50% egg infective dose of the highly pathogenic avian influenza virus (HPAIV) A/Duck/Vietnam/12/05 (H5N1), administered by an intra-nasal and oral route. Clinical symptoms were recorded twice a day up to 14 days postinfection (dpi). Clinical signs were first noted at 2 dpi, with conjunctivitis and slight depression, and progressed over a period of 1-3 days to severe neurologic signs consisting of torticollis, incoordination, tremors, and seizures. Survival times varied from 3 to 7 dpi. On postmortem examination, hemorrhages were observed in the duodenum, ceca, proventriculus, ventriculus, trachea, pancreas, and brain. Histologic lesions, as well as immunohistochemistry positivity, were recorded in the pancreas and brain. In situ hybridization revealed viral antigen associated with acinar pancreatic cells, bronchial epithelial cells, and with cells of the central nervous system as well as neurons of the submucosal plexus of the duodenum. Our experimental findings agree with those previously observed in ducks naturally infected with HPAIV H5N1 viruses, confirming the acquired viral neurotropism and pancreatotropism, as previously noted in other avian species, as well as in humans.

Níveis de fibra em detergente neutro na dieta de cordeiros: consumo, digestibilidade e fermentação ruminal / Levels of neutral detergent fiber in lambs diets: intake, digestibility and ruminal fermentation

Foram utilizados oito cordeiros castrados (35,0±6,0kg peso vivo) em um delineamento duplo quadrado latino 4 ´ 4 para avaliar o efeito de quatro níveis de fibra em detergente neutro (FDN) na dieta (25, 31, 37 e 43 por cento da matéria seca (MS)) sobre o consumo e parâmetros digestivos. O consumo de nitrogênio (N) variou de forma quadrática; o de MS, matéria orgânica (MO) e energia diminuíram (P<0,05) e de FDN aumentou (P<0,01) linearmente com o aumento de fibra na dieta. A digestibilidade da FDN e do N, assim como o pH e as concentrações de peptídeos no fluído ruminal foram similares em todos os tratamentos. A digestibilidade aparente da MS, da MO e da energia, assim como as concentrações ruminais de açúcares diminuíram linearmente (P<0,01) e a síntese de proteína microbiana ruminal, as concentrações ruminais de amônia e de aminoácidos variaram quadraticamente (P<0,05) com o aumento do teor de FDN das dietas. A redução do consumo e da digestibilidade foram mais evidentes somente pela inclusão do nível mais alto de FDN (43 por cento) e, sob o aspecto nutricional, a inclusão em torno de 30 por cento de FDN representa o nível mais adequado para formulação de dietas a base de silagem de sorgo e concentrado oferecido a cordeiros confinados.

Eight castrated raw lambs (35.0± 6.0kg live weight) were used in a replicated 4 ´ 4 latin square design to evaluate the effect of four neutral detergent fiber (NDF) levels (25, 31, 37 and 43 percent of dry matter (DM)) on intake and digestion traits. Nitrogen (N) intake varied quadratically; intake of DM, organic matter (OM) and energy decreased (P<0.05) and that of NDF increased (P<0.01) as fibre level increased. NDF and N digestibility, as well as pH and ruminal concentrations of peptides were similar for all treatments. Apparent digestibility of DM, OM and energy, as well as ruminal concentrations of sugars decreased (P<0.01) and, ruminal microbial protein synthesis and ruminal concentrations of ammonia and amino acids varied in a quadratic way (P<0.05) with increased levels of NDF. The effect of NDF in decreasing intake and digestibillity was more evident only at the highest level (43 percent). The inclusion of about 30 percent NDF represents the most adequate level for sorghum silage and concentrate based diets fed to feedlot lambs.

Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients.

BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. METHODS: Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. RESULTS: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin.

CSF monoamine metabolite and beta endorphin levels in recently detoxified alcoholics and healthy controls: prediction of alcohol cue-induced craving?

BACKGROUND: Abnormalities in central neurotransmitter systems have been described in alcohol-dependent individuals and may contribute to alcohol craving. This study compared cerebrospinal fluid (CSF) levels of monoamine metabolites and beta endorphin levels in samples from early-onset alcohol-dependent patients (n = 20), late-onset alcohol-dependent patients (n = 14), and healthy controls (n = 23). It also evaluated whether these CSF measures levels predicted the degree of craving experienced in response to an alcohol cue. METHODS: Individuals meeting DSM-III and -IV R-criteria for alcohol dependence, 1 to 3 months postdetoxification, and healthy controls underwent a lumbar puncture. Patients also completed a cue exposure test day between 3 and 15 days later. RESULTS: Alcohol-dependent patients had lower CSF levels of the norepinephrine metabolite MHPG compared with the healthy subjects, but this difference disappeared when differences in age between the groups were accounted for. No other group comparisons between patients and healthy subjects reached significance. CSF levels of the dopamine metabolite HVA were significantly higher in the early-onset patients compared with the late-onset patients and controls. The CSF measures did not predict the precue levels of craving, or the increase in craving after alcohol cue exposure. CONCLUSIONS: These results are inconclusive about the role of monoaminergic dysregulation in recovering alcoholics. They also question the utility of these CSF measures to predict alcohol cue reactivity in patients who have been sober at least 1 month.

Triterpenes and saponins from Rudgea viburnioides.

A novel triterpene, viburgenin (1), has been isolated from an extract of the ripe fruit rinds of Rudgea viburnioides, together with the known saponins, arjunglucoside I and trachelosperosides B-1 and E-1, and the triterpenes trachelosperogenin B (2) and arjungenin. Compound 2 was previously obtained as a product from enzymatic hydrolysis, and it is reported for the first time as a natural product. The structure of compound 1 was determined as 2alpha,3beta, 19alpha,23,24-pentahydroxyurs-12-ene by extensive use of 1D and 2D NMR spectroscopic methods. Compound 1 exhibited moderate antifungal activity against Cladosporium cladosporioides.

Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics.

BACKGROUND: This study evaluated the dose-related ethanol-like subjective effects of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics. METHODS: Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving. RESULTS: Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol. CONCLUSION: The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.

Complications of alcohol withdrawal: pathophysiological insights.

Disease processes or events that accompany acute alcohol withdrawal (AW) can cause significant illness and death. Some patients experience seizures, which may increase in severity with subsequent AW episodes. Another potential AW complication is delirium tremens, characterized by hallucinations, mental confusion, and disorientation. Cognitive impairment and delirium may lead to a chronic memory disorder (i.e., Wernicke-Korsakoff syndrome). Psychiatric problems associated with withdrawal include anxiety, depression, and sleep disturbance. In addition, alterations in physiology, mood, and behavior may persist after acute withdrawal has subsided, motivating relapse to heavy drinking. Recent advances in neurobiology may support the development of improved medications to decrease the risk of AW complications and support long-term sobriety.