A global one health perspective on leptospirosis in humans and animals.

Leptospirosis is a quintessential one health disease of humans and animals caused by pathogenic spirochetes of the genus Leptospira. Intra- and interspecies transmission is dependent on 1) reservoir host animals in which organisms replicate and are shed in urine over long periods of time, 2) the persistence of spirochetes in the environment, and 3) subsequent human-animal-environmental interactions. The combination of increased flooding events due to climate change, changes in human-animal-environmental interactions as a result of the pandemic that favor a rise in the incidence of leptospirosis, and under-recognition of leptospirosis because of nonspecific clinical signs and severe signs that resemble COVID-19 represents a "perfect storm" for resurgence of leptospirosis in people and domestic animals. Although often considered a disease that occurs in warm, humid climates with high annual rainfall, pathogenic Leptospira spp have recently been associated with disease in animals and humans that reside in semiarid regions like the southwestern US and have impacted humans that have a wide spectrum of socioeconomic backgrounds. Therefore, it is critical that physicians, veterinarians, and public health experts maintain a high index of suspicion for the disease regardless of geographic and socioeconomic circumstances and work together to understand outbreaks and implement appropriate control measures. Over the last decade, major strides have been made in our understanding of the disease because of improvements in diagnostic tests, molecular epidemiologic tools, educational efforts on preventive measures, and vaccines. These novel approaches are highlighted in the companion Currents in One Health by Sykes et al, AJVR, September 2022.

Variation in blood mercury concentrations in brown skuas (Stercorarius antarcticus) is related to trophic ecology but not breeding success or adult body condition.

Mercury is a pervasive environmental contaminant that can negatively impact seabirds. Here, we measure total mercury (THg) concentrations in red blood cells (RBCs) from breeding brown skuas (Stercorarius antarcticus) (n = 49) at Esperanza/Hope Bay, Antarctic Peninsula. The aims of this study were to: (i) analyse RBCs THg concentrations in relation to sex, year and stable isotope values of carbon (δ13C) and nitrogen (δ15N); and (ii) examine correlations between THg, body condition and breeding success. RBC THg concentrations were positively correlated with δ15N, which is a proxy of trophic position, and hence likely reflects the biomagnification process. Levels of Hg contamination differed between our study years, which is likely related to changes in diet and distribution. RBC THg concentrations were not related to body condition or breeding success, suggesting that Hg contamination is currently not a major conservation concern for this population.

Supporting individuals with intellectual and developmental disability during the first 100 days of the COVID-19 outbreak in the USA.

BACKGROUND: It is unknown how the novel Coronavirus SARS-CoV-2, the cause of the current acute respiratory illness COVID-19 pandemic that has infected millions of people, affects people with intellectual and developmental disability (IDD). The aim of this study is to describe how individuals with IDD have been affected in the first 100 days of the COVID-19 pandemic. METHODS: Shortly after the first COVID-19 case was reported in the USA, our organisation, which provides continuous support for over 11 000 individuals with IDD, assembled an outbreak committee composed of senior leaders from across the health care organisation. The committee led the development and deployment of a comprehensive COVID-19 prevention and suppression strategy, utilising current evidence-based practice, while surveilling the global and local situation daily. We implemented enhanced infection control procedures across 2400 homes, which were communicated to our employees using multi-faceted channels including an electronic resource library, mobile and web applications, paper postings in locations, live webinars and direct mail. Using custom-built software applications enabling us to track patient, client and employee cases and exposures, we leveraged current public health recommendations to identify cases and to suppress transmission, which included the use of personal protective equipment. A COVID-19 case was defined as a positive nucleic acid test for SARS-CoV-2 RNA. RESULTS: In the 100-day period between 20 January 2020 and 30 April 2020, we provided continuous support for 11 540 individuals with IDD. Sixty-four per cent of the individuals were in residential, community settings, and 36% were in intermediate care facilities. The average age of the cohort was 46 ± 12 years, and 60% were male. One hundred twenty-two individuals with IDD were placed in quarantine for exhibiting symptoms and signs of acute infection such as fever or cough. Sixty-six individuals tested positive for SARS-CoV-2, and their average age was 50. The positive individuals were located in 30 different homes (1.3% of total) across 14 states. Fifteen homes have had single cases, and 15 have had more than one case. Fifteen COVID-19-positive individuals were hospitalised. As of 30 April, seven of the individuals hospitalised have been discharged back to home and are recovering. Five remain hospitalised, with three improving and two remaining in intensive care and on mechanical ventilation. There have been three deaths. We found that among COVID-19-positive individuals with IDD, a higher number of chronic medical conditions and male sex were characteristics associated with a greater likelihood of hospitalisation. CONCLUSIONS: In the first 100 days of the COVID-19 outbreak in the USA, we observed that people with IDD living in congregate care settings can benefit from a coordinated approach to infection control, case identification and cohorting, as evidenced by the low relative case rate reported. Male individuals with higher numbers of chronic medical conditions were more likely to be hospitalised, while most younger, less chronically ill individuals recovered spontaneously at home.

Funding trends in hormetic research.

The topic of hormesis research funding has been a focus of deliberation within the scientific community for several decades. A common assumption/belief is that most hormesis research is funded by the private sector. With this assumption may emerge questions revolving around potential bias of such research. To provide some clarification to this issue, all hormesis research articles were obtained through online databases for 5-year increments starting with 1995 and ending with 2015 and were subsequently categorized by their funding source. A total of 710 articles were found for those years and 383 of those reported information on funding sources. Reporting funding is not required by law and until more recently was not encouraged or required by funders, research institutions, and/or scientific publishers. The analysis revealed that the assumption that the majority of hormesis research has been privately funded was not supported, with the public sector (i.e. federal and state governmental agencies) exclusively contributing to 78% of the reported research funding. Going forward, funding transparency for scientific research as a whole is essential within the scientific community as it may affect how research may be perceived, accepted, and applied.

Non-accidental properties, metric invariance, and encoding by neurons in a model of ventral stream visual object recognition, VisNet.

When objects transform into different views, some properties are maintained, such as whether the edges are convex or concave, and these non-accidental properties are likely to be important in view-invariant object recognition. The metric properties, such as the degree of curvature, may change with different views, and are less likely to be useful in object recognition. It is shown that in a model of invariant visual object recognition in the ventral visual stream, VisNet, non-accidental properties are encoded much more than metric properties by neurons. Moreover, it is shown how with the temporal trace rule training in VisNet, non-accidental properties of objects become encoded by neurons, and how metric properties are treated invariantly. We also show how VisNet can generalize between different objects if they have the same non-accidental property, because the metric properties are likely to overlap. VisNet is a 4-layer unsupervised model of visual object recognition trained by competitive learning that utilizes a temporal trace learning rule to implement the learning of invariance using views that occur close together in time. A second crucial property of this model of object recognition is, when neurons in the level corresponding to the inferior temporal visual cortex respond selectively to objects, whether neurons in the intermediate layers can respond to combinations of features that may be parts of two or more objects. In an investigation using the four sides of a square presented in every possible combination, it was shown that even though different layer 4 neurons are tuned to encode each feature or feature combination orthogonally, neurons in the intermediate layers can respond to features or feature combinations present is several objects. This property is an important part of the way in which high capacity can be achieved in the four-layer ventral visual cortical pathway. These findings concerning non-accidental properties and the use of neurons in intermediate layers of the hierarchy help to emphasise fundamental underlying principles of the computations that may be implemented in the ventral cortical visual stream used in object recognition.

Computations in the deep vs superficial layers of the cerebral cortex.

A fundamental question is how the cerebral neocortex operates functionally, computationally. The cerebral neocortex with its superficial and deep layers and highly developed recurrent collateral systems that provide a basis for memory-related processing might perform somewhat different computations in the superficial and deep layers. Here we take into account the quantitative connectivity within and between laminae. Using integrate-and-fire neuronal network simulations that incorporate this connectivity, we first show that attractor networks implemented in the deep layers that are activated by the superficial layers could be partly independent in that the deep layers might have a different time course, which might because of adaptation be more transient and useful for outputs from the neocortex. In contrast the superficial layers could implement more prolonged firing, useful for slow learning and for short-term memory. Second, we show that a different type of computation could in principle be performed in the superficial and deep layers, by showing that the superficial layers could operate as a discrete attractor network useful for categorisation and feeding information forward up a cortical hierarchy, whereas the deep layers could operate as a continuous attractor network useful for providing a spatially and temporally smooth output to output systems in the brain. A key advance is that we draw attention to the functions of the recurrent collateral connections between cortical pyramidal cells, often omitted in canonical models of the neocortex, and address principles of operation of the neocortex by which the superficial and deep layers might be specialized for different types of attractor-related memory functions implemented by the recurrent collaterals.

High-Precision Half-Life Measurements for the Superallowed ß

Precision measurements of superallowed Fermi ß-decay transitions, particularly for the lightest superallowed emitters ^{10}C and ^{14}O, set stringent limits on possible scalar current contributions to the weak interaction. In the present work, a discrepancy between recent measurements of the ^{10}C half-life is addressed through two high-precision half-life measurements, via γ-ray photopeak and ß counting, that yield consistent results for the ^{10}C half-life of T_{1/2}=19.2969±0.0074 s and T_{1/2}=19.3009±0.0017 s, respectively. The latter is the most precise superallowed ß-decay half-life measurement reported to date and the first to achieve a relative precision below 10^{-4}. A fit to the world superallowed ß-decay data including the ^{10}C half-life measurements reported here yields b_{F}=-0.0018±0.0021 (68% C.L.) for the Fierz interference term and C_{S}/C_{V}=+0.0009±0.0011 for the ratio of the weak scalar to vector couplings assuming left-handed neutrinos.

Impact-induced muscle damage and urinary pterins in professional rugby: 7,8-dihydroneopterin oxidation by myoglobin.

Muscle damage caused through impacts in rugby union is known to increase oxidative stress and inflammation. Pterins have been used clinically as markers of oxidative stress, inflammation, and neurotransmitter synthesis. This study investigates the release of myoglobin from muscle tissue due to force-related impacts and how it is related to the subsequent oxidation of 7,8-dihydroneopterin to specific pterins. Effects of iron and myoglobin on 7,8-dihydroneopterin oxidation were examined in vitro via strong cation-exchange high-performance liquid chromatography (SCX-HPLC) analysis of neopterin, xanthopterin, and 7,8-dihydroxanthopterin. Urine samples were collected from 25 professional rugby players pre and post four games and analyzed for myoglobin by enzyme-linked immunosorbent assay, and 7,8-dihydroneopterin oxidation products by HPLC. Iron and myoglobin oxidized 7,8-dihydroneopterin to neopterin, xanthopterin, and 7,8-dihydroxanthopterin at concentrations at or above 10 µM and 50 µg/mL, respectively. All four games showed significant increases in myoglobin, neopterin, total neopterin, biopterin, and total biopterin, which correlated between each variable (P < 0.05). Myoglobin and iron facilitate 7,8-dihydroneopterin oxidation to neopterin and xanthopterin. In vivo delocalization of myoglobin due to muscle damage may contribute to oxidative stress and inflammation after rugby. Increased concentrations of biopterin and total biopterin may indicate production of nitric oxide and monoamine neurotransmitters in response to the physical stress.

Inhibition of monoamine oxidase isoforms modulates nicotine withdrawal syndrome in the rat.

AIMS: There have been many reports of monoamine oxidase (MAO) inhibition by non-nicotine ingredients in tobacco smoke, persisting for days after smoking cessation. This study determined the effect of inhibiting MAO and its isoforms on nicotine withdrawal syndrome. MAIN METHODS: Rats were rendered nicotine-dependent by seven days of subcutaneous (s.c.) 9 mg/kg/day infusion of nicotine bitartrate. Twenty-two hours after termination of infusion, they were observed over 20 min for somatically expressed nicotine withdrawal signs. Three hours before observation, rats were injected intraperitoneally (i.p.) with 4 mg/kg each of the MAO A antagonist clorgyline and the MAO B antagonist deprenyl, or with saline alone. A similar experiment was performed with non-dependent, saline-infused rats. Another experiment compared nicotine-dependent rats that received injections of either saline or 4 mg/kg clorgyline alone. A further experiment compared rats receiving either saline or 4 mg/kg deprenyl alone. KEY FINDINGS: Combined treatment with both MAO inhibitors markedly and significantly exacerbated somatically expressed nicotine withdrawal signs in nicotine infused rats, while having no significant effects in saline-infused rats. Rats injected s.c. with 4 mg/kg clorgyline alone had significantly more withdrawal signs than saline-injected rats, while deprenyl-injected rats had significantly fewer signs than saline controls. Assays confirmed that clorgyline thoroughly reduced MAO A enzymatic activity and deprenyl thoroughly reduced MAO B activity. SIGNIFICANCE: The results suggest that inhibition of MAO A may contribute to the intensity of withdrawal syndrome in smoking cessation.

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo.

Aberrant activation of Wingless-type (Wnt)/ß-catenin signaling is widespread in human cervical cancer. However, the underlying mechanisms of Wnt activation and the therapeutic potential of Wnt inhibition remain largely unknown. Here, we demonstrate that the Wnt inhibitory factor 1 (WIF1), a secreted Wnt antagonist, is downregulated in all human primary cervical tumors and cell lines analyzed. Our data reveal that WIF1 downregulation occurs due to promoter hypermethylation and is an early event in cervical oncogenesis. WIF1 re-expression upon 5-aza-2'-deoxycytidine treatment or WIF1 gene transfer induces significant apoptosis and G(2)/M arrest, and inhibits cervical cancer cell proliferation in vitro. Consistent with this, treatment of established mice tumor xenografts with peritumoral WIF1 gene transfer results in a significant inhibition of cancer growth and invasion. WIF1 treatment causes a significant decrease in intracellular WNT1 and TCF-4 proteins revealing novel Wnt-regulatory mechanisms. Thus, WIF1 causes a major cellular re-distribution of ß-catenin and a significant inhibition of the Wnt/ß-catenin pathway in tumor cells, as documented by a remarkable reversion in the expression of Wnt/ß-catenin transcriptional target genes (E-cadherin, c-Myc, cyclin D1, CD44 and VEGF). Consequently, multiple critical events in tumor progression and metastasis such as cell proliferation, angiogenesis and invasion were inhibited by WIF1. In addition, WIF1 modulated the expression of specific anti-apoptotic and apoptotic proteins, thereby inducing significant apoptosis in vivo. Our findings demonstrate for the first time that WIF1 downregulation by epigenetic gene silencing is an important mechanism of Wnt activation in cervical oncogenesis. Of major clinical relevance, we show that peritumoral WIF1 gene transfer reduces not only cancer growth but also invasion in well-established tumors. Therefore, our data provide novel mechanistic insights into the role of WIF1 in cervical cancer progression, and the important preclinical validation of WIF1 as a potent drug target in cervical cancer treatment.

Measurement of the two-halo neutron transfer reaction (1)H((11)Li, (9)Li)(3)H at 3A MeV.

The p((11)Li, (9)Li)t reaction has been studied for the first time at an incident energy of 3A MeV at the new ISAC-2 facility at TRIUMF. An active target detector MAYA, built at GANIL, was used for the measurement. The differential cross sections have been determined for transitions to the (9)Li ground and first excited states in a wide range of scattering angles. Multistep transfer calculations using different (11)Li model wave functions show that wave functions with strong correlations between the halo neutrons are the most successful in reproducing the observation.

An exploratory study of parents' approaches to health promotion in families of adolescents with physical disabilities.

BACKGROUND: The life expectancy of children with physical disabilities now extends into adulthood and has been accompanied by the transfer of rehabilitation services from institutions to the home. Thus, families must increasingly partner with health service providers to promote their child's health and prevent the development of secondary conditions that may contribute to heart disease, stroke, respiratory diseases, low endurance and emotional difficulties. AIM: To investigate within a family context the health promotion efforts of parents on behalf of a child with a physical disability. METHOD: The Long Interview Method was used to interview 15 families (11 two-parent and 4 single-parent) having a child 11-16 years of age with a physical disability including cerebral palsy (7), spina bifida (3), muscular dystrophy (3) and other conditions (2). RESULTS: Parents' health promotion efforts were characterized by three main themes. First, parents emphasized traditional lifestyle health behaviours including nutrition, physical activity, tobacco, alcohol and drug use, and personal hygiene. Second, parents tried to foster their adolescent's social life and friendships. They expressed particular concern about how, and if, their child would develop a sense of purpose and have a productive future. Third, parents invested a great deal of effort into observing daily routines, making arrangements for their child's social inclusion and supporting their child in a way that balanced independence with safety and energy conservation. CONCLUSIONS: Parents recognize that their child with a physical disability faces greater obstacles, and work hard at health promotion. Healthcare workers need to work with parents to: (1) provide information about specific lifestyle health behaviours including nutrition, physical activity and sexuality; (2) advocate for resources to foster social inclusion; and (3) discuss family strategies that balance parental involvement with their child's need for independence and energy conservation for daily activities.

The risk of antimalarials in patients with renal failure.

We present here a patient with end stage renal failure who received two weeks antimalarial prophylaxis at full dose leading to life threatening toxicity with severe acute megaloblastic anaemia, symptomatic pancytopenia and exfoliative dermatitis. Prompt recognition and treatment can rapidly reverse these fatal effects but more importantly, education of patients before travel is imperative in preventing such events.

Production cross-sections of 181-186Re isotopes from proton bombardment of natural tungsten.

Cross-sections for the production of (181)Re, (182m)Re, (182g)Re, (183)Re, (184)Re, and (186)Re from proton bombardment of natural tungsten have been measured using the stacked foil technique for proton energies up to 17.6 MeV. Results are compared with the theoretical excitation functions as calculated by the EMPIRE II code (version 2.19) and experimental literature values. Results are in strong agreement with some of the previously reported literature as well at theoretical calculations for multiple reactions providing for more reliable estimates for the (186)W(p,n)(186)Re reaction.

A complication of steroid therapy in acute leukaemia--a case report.

Common complications associated with steroid therapy are well documented. We report a rare and fatal complication, in which oesophageal erosion secondary to the use of steroids was associated with pneumopericardium.

Evolution of mammalian X chromosome-linked imprinting.

We analyse the evolution of X chromosome-linked imprinting by modifying our previous model of imprinting of autosomal genes that influence the trade-off between maternal fecundity and offspring viability through alterations in maternal investment (Mills and Moore, 2004). Unlike previous genetic models, we analyse X-linked imprinting in the context of populations at equilibrium for either autosomal or X-linked biallelically expressed alleles at loci that influence the fecundity/viability trade-off. We show that selection under parental conflict over maternal investment in offspring can parsimoniously explain the occurrence of sex-specific gene expression patterns, without a requirement to postulate direct selection for sexual dimorphism mediated through imprinting. We note that sex chromosome imprinting causes a small distortion of the post-weaning sex ratio, providing a possible selection pressure against the evolution of X-linked imprints. We discuss our conclusions in the context of recent reports of imprinting of mouse X-linked Xlr genes.

Influence of herbicide tolerant soybean production systems on insect pest populations and pest-induced crop damage.

Conventional soybean weed management and transgenic herbicide-tolerant management were examined to assess their effects on soybean insect pest populations in south Georgia in 1997 and 1998. Soybean variety had very little impact on the insect species observed, except that maturity group effects were observed for stink bug, primarily Nezara viridula (L.), population densities on some sampling dates. Stink bugs were more abundant on the early maturing varieties in mid-season. Velvetbean caterpillar, Anticarsia gemmatalis Hübner, potato leafhopper, Empoasca fabae (Harris), and grasshoppers Melanoplus spp. were more numerous on either conventional or herbicide-tolerant varieties on certain dates, although these differences were not consistent throughout the season. Soybean looper, Pseudoplusia includens (Walker), threecornered alfalfa hopper, Spissistilus festinus (Say), and whitefringed beetles, Graphognathus spp , demonstrated no varietal preference in this study. Few weed treatment differences were observed, but if present on certain sampling dates, then pest numbers were higher in plots where weeds were reduced (either postemergence herbicides or preplant herbicide plus postemergence herbicide). The exception to this weed treatment effect was grasshoppers, which were more numerous in weedy plots when differences were present. In post emergence herbicide plots, there were no differences in insect pest densities between the conventional herbicides (e.g., Classic, Select, Cobra, and Storm) compared with specific gene-inserted herbicide-tolerant materials (i.e., Roundup and Liberty). Defoliation, primarily by velvetbean caterpillar, was different between soybean varieties at some test sites but not different between herbicide treatments. We did not observe differences in seasonal abundance of arthropod pests between conventional and transgenic herbicide-tolerant soybean.

Percutaneous management of unstable pelvic ring disruptions.

Percutaneous pelvic fixation stabilizes pelvic ring disruptions without extensive pelvic dissection. For this reason, these anterior and posterior percutaneous pelvic fixation techniques allow acute and definitive treatment. Successful percutaneous pelvic fixation techniques depend on accurate closed reduction, excellent intraoperative fluoroscopic imaging, and detailed preoperative planning. Early pelvic stability diminishes haemorrhage, provides patient comfort, and allows early patient mobilization from recumbency.

Plantar-flexion tarsometatarsal joint injuries in children.

We are reporting a series of eight patients ranging in age from 3 to 10 years who sustained plantar-flexion injuries of the foot, resulting in injuries to the tarsometatarsal (TMT) interval. All injuries were identified within 3 days and treated with molded short leg immobilization. We evaluated all patients an average of 32 months after injury with physical examination and the Midfoot Functional Rating (MFR) score. Seven patients had no limitations in their activities of daily living or athletic endeavors. These seven patients had MFR scores of 100. One patient had complaints of midfoot pain with running for >5 min and radiographic evidence of degenerative changes across the TMT interval at 3-year follow-up. These results suggest that although indirect pediatric TMT injuries have a generally favorable prognosis, early degenerative changes can occur and may be responsible for chronic pain and activity limitation. Degenerative changes in this weight-bearing region in a young patient can have lifelong implications. Patients and parents may benefit from discussion of the potential for future midfoot compromise following this injury.

Results of anterior cruciate ligament reconstruction in the adolescent female.

This study evaluated the functional results and complications of anterior cruciate ligament (ACL) surgery in adolescent females. We studied 22 consecutive female patients younger than 20 years who underwent arthroscopic ACL reconstruction. Average follow-up was 31 months. One hundred percent of the patients were satisfied. Seven patients returned to intercollegiate or high school sports. The mean Lysholm score was 94, and the International Knee Documentation Committee score was 40% normal, 60% nearly normal. KT-1000 arthrometer side-to-side differences were