Task-related measures of short-interval intracortical inhibition and GABA levels in healthy young and older adults: A multimodal TMS-MRS study.

Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABAA receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABAA receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABAA receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABAA receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant.

Age-Related Declines in Motor Performance are Associated With Decreased Segregation of Large-Scale Resting State Brain Networks.

Aging is typically associated with substantial declines in motor functioning as well as robust changes in the functional organization of brain networks. Previous research has investigated the link between these 2 age-varying factors but examinations were predominantly limited to the functional organization within motor-related brain networks. Little is known about the relationship between age-related behavioral impairments and changes in functional organization at the whole brain (i.e., multiple network) level. This knowledge gap is surprising given that the decreased segregation of brain networks (i.e., increased internetwork connectivity) can be considered a hallmark of the aging process. Accordingly, we investigated the association between declines in motor performance across the adult lifespan (20-75 years) and age-related modulations of functional connectivity within and between resting state networks. Results indicated that stronger internetwork resting state connectivity observed as a function of age was significantly related to worse motor performance. Moreover, performance had a significantly stronger association with the strength of internetwork as compared with intranetwork connectivity, including connectivity within motor networks. These findings suggest that age-related declines in motor performance may be attributed to a breakdown in the functional organization of large-scale brain networks rather than simply age-related connectivity changes within motor-related networks.

Utility of a machine-guided tool for assessing risk behaviour associated with contracting HIV in three sites in South Africa.

Introduction: Digital data collection and the associated mobile health technologies have allowed for the recent exploration of artificial intelligence as a tool for combatting the HIV epidemic. Machine learning has been found to be useful both in HIV risk prediction and as a decision support tool for guiding pre-exposure prophylaxis (PrEP) treatment. This paper reports data from two sequential studies evaluating the viability of using machine learning to predict the susceptibility of adults to HIV infection using responses from a digital survey deployed in a high burden, low-resource setting. Methods: 1036 and 593 participants were recruited across two trials. The first trial was a cross-sectional study in one location and the second trial was a cohort study across three trial sites. The data from the studies were merged, partitioned using standard techniques, and then used to train and evaluate multiple different machine learning models and select and evaluate a final model. Variable importance estimates were calculated using the PIMP and SHAP methodologies. Results: Characteristics associated with HIV were consistent across both studies. Overall, HIV positive patients had a higher median age (34 [IQR: 29-39] vs 26 [IQR 22-33], p < 0.001), and were more likely to be female (155/703 [22%] vs 107/927 [12%], p < 0.001). HIV positive participants also had more commonly gone a year or more since their last HIV test (183/262 [70%] vs 540/1368 [39%], p < 0.001) and were less likely to report consistent condom usage (113/262 [43%] vs 758/1368 [55%], p < 0.001). Patients who reported TB symptoms were more likely to be HIV positive. The trained models had accuracy values (AUROCs) ranging from 78.5% to 82.8%. A boosted tree model performed best with a sensitivity of 84% (95% CI 72-92), specificity of 71% (95% CI 67-76), and a negative predictive value of 95% (95% CI 93-96) in a hold-out dataset. Age, duration since last HIV test, and number of male sexual partners were consistently three of the four most important variables across both variable importance estimates. Conclusions: This study has highlighted the synergies present between mobile health and machine learning in HIV. It has been demonstrated that a viable ML model can be built using digital survey data from an low-middle income setting with potential utility in directing health resources.

Scaffold Geometry-Imposed Anisotropic Mechanical Loading Guides the Evolution of the Mechanical State of Engineered Cardiovascular Tissues in vitro.

Cardiovascular tissue engineering is a promising approach to develop grafts that, in contrast to current replacement grafts, have the capacity to grow and remodel like native tissues. This approach largely depends on cell-driven tissue growth and remodeling, which are highly complex processes that are difficult to control inside the scaffolds used for tissue engineering. For several tissue engineering approaches, adverse tissue growth and remodeling outcomes were reported, such as aneurysm formation in vascular grafts, and leaflet retraction in heart valve grafts. It is increasingly recognized that the outcome of tissue growth and remodeling, either physiological or pathological, depends at least partly on the establishment of a homeostatic mechanical state, where one or more mechanical quantities in a tissue are maintained in equilibrium. To design long-term functioning tissue engineering strategies, understanding how scaffold parameters such as geometry affect the mechanical state of a construct, and how this state guides tissue growth and remodeling, is therefore crucial. Here, we studied how anisotropic versus isotropic mechanical loading-as imposed by initial scaffold geometry-influences tissue growth, remodeling, and the evolution of the mechanical state and geometry of tissue-engineered cardiovascular constructs in vitro. Using a custom-built bioreactor platform and nondestructive mechanical testing, we monitored the mechanical and geometric changes of elliptical and circular, vascular cell-seeded, polycaprolactone-bisurea scaffolds during 14 days of dynamic loading. The elliptical and circular scaffold geometries were designed using finite element analysis, to induce anisotropic and isotropic dynamic loading, respectively, with similar maximum stretch when cultured in the bioreactor platform. We found that the initial scaffold geometry-induced (an)isotropic loading of the engineered constructs differentially dictated the evolution of their mechanical state and geometry over time, as well as their final structural organization. These findings demonstrate that controlling the initial mechanical state of tissue-engineered constructs via scaffold geometry can be used to influence tissue growth and remodeling and determine tissue outcomes.

Molecular and Serological Intraocular Fluid Analysis of Coxiella burnetii-seropositive Patients with Concurrent Idiopathic Uveitis.

PURPOSE: Previous studies have suggested a link between Q fever and uveitis. We determined whether Coxiella burnetii causes intraocular infection in C. burnetii-seropositive patients with idiopathic uveitis. METHODS: From a retrospective observational case series, paired aqueous humor and serum samples from 10 C. burnetii-seropositive patients with idiopathic uveitis were examined for intraocular antibody production by using the Goldmann-Witmer coefficient and by polymerase chain reaction (PCR). RESULTS: Although intraocular IgG against C. burnetii was detected, no intraocular antibody production was observed (low Goldmann Wittmer coefficients). All PCR results were negative. CONCLUSIONS: Uveitis due to an intraocular infection with C. burnetii is unlikely.

Purification of mitochondrial NADH dehydrogenase from Drosophila hydei and comparison with the 'heat-shock' polypeptides.

Mitochondrial NADH dehydrogenase (NADH:(acceptor) oxidoreductase, EC .6.99.3) from either Drosophila hydei larvae or embryos has been purified 150- and 120-fold, respectively. The purified enzyme appeared homogeneous and showed a molecular weight of 57 000. The molecular weight of the nondenatured enzyme was 79 000. On isoelectro-focussing of the preparation, two fractions were observed, a major one with an isoelectric point of 6.2 and a minor fraction with an isoelectric point of 4.9. Straight-line kinetics in Lineweaver-Burk plots were observed for the purified enzyme with a Km of 0.040 mM. The Km was not changed during the purification procedure, suggesting that the enzyme was not denatured or inactivated. The pH optimum of the purified enzyme was 5.6. The molecular weight of the purified mitochondrial NADH dehydrogenase does not correspond to that of one of the 'heat-shock' polypeptides.

Effects of isradipine on peripheral hemodynamic reflex responses in mild-to-moderate essential hypertension.

In a randomized double-blind, placebo-controlled, crossover study of isradipine (5 mg twice daily), effects on peripheral hemodynamic reflex responses were studied in nine patients (mean age 48 years) at baseline and after six weeks of active treatment. Assessments included vital signs, resting blood flow in the calf and finger (using an electrocardiograph-triggered venous occlusion plethysmograph), reflex responses during isometric exercise and cold pressor resistance, and venous capacitance in the forearm and calf. Isradipine lowered systolic and diastolic blood pressure as well as mean arterial pressure in patients with mild-to-moderate essential hypertension without reflex tachycardia or venoconstriction. All of the reflex responses studied were attenuated. It is concluded that vasodilatation of the peripheral circulation induced by isradipine contributes partially to the blood pressure-lowering effect.

Inhibitory effects of pirenzepine on muscarinic stimulation of rat pancreas.

The binding properties and pharmacological effects of pirenzepine were compared to those of atropine in isolated pancreatic acini and pancreatic membranes of rats. In the first preparation, pirenzepine and atropine blocked [N-methyl-3H]scopolamine ([3H]NMS) binding, pirenzepine being 110 times less potent than atropine (KD for pirenzepine 0.38 microM and for atropine 3.5 microM). A similar difference in potency was observed with respect to carbamylcholine stimulation of amylase secretion (IC50 for pirenzepine 4.5 microM and for atropine 30 nM) and calcium efflux (IC50 for pirenzepine 2.8 microM and for atropine 4 nM). Correspondingly, in rat pancreatic membranes, the KD values for pirenzepine and atropine were 250 and 1.5 nM, respectively. These data are compatible with the hypothesis that the in vitro antimuscarinic effect of pirenzepine on the rat pancreas is linked to the occupancy of a single homogeneous class of receptors with a low affinity for the antagonist.

Exercise and heart transplantation. A review.

Results of heart transplantation as therapy for end-stage cardiac diseases are encouraging not only because of actuarial survival curves but also because of the recovered quality of life for the heart transplant recipient. Although heart transplantation drastically improves the physical capacity of the patients, heart recipients still have a reduced maximal aerobic capacity compared to healthy people. Altered resting and exercise haemodynamics, due to cardiac denervation, are a common finding after orthotopic heart transplantation: increases in heart rate and stroke volume at exercise are first linked with the augmented venous return and later with the increased plasmatic nor-adrenaline level. Maximal heart rate and stroke volume are both reduced when compared to innervated heart. Reduced cardiac output response to exercise therefore results in early anaerobic metabolism, acidosis, hyperventilation and diminished physical capacity. In spite of an altered ventilatory adaptation to exercise, characterised by hyperpnoea in most transplant patients, ventilation is not the limiting factor for exercise in heart recipients without associated obstructive pulmonary disease. Endurance training restores lean tissue, decreases submaximal minute ventilation, increases peak work output, maximal ventilation and peak heart rate. Guidelines for prescribing exercise are not yet standardised due to the limited number of studies on a sufficient cohort of heart recipients. Nevertheless, recommendations similar to those used for persons with coronary heart disease, with modifications due to the denervated heart, seem to be used. The cardiocirculatory and pulmonary capacity of heart transplant recipients allow them to undertake endurance sports activities such as walking, jogging, cycling and swimming, and these should be encouraged.

Helminth and protozoan parasites in dogs and cats in Belgium.

This study investigates the level of helminthic and protozoal infestation over the last 10 years in strays, well-cared-for dogs and cats. Determination of the prevalence of infections was based either on faecal examination or on worm counts at necropsy. Of 2324 faecal flotations (NaCl sp.gr. 1.20) of stray dogs, 34.2% had eggs or proglottids of one or more worm species consisting of Toxocara canis (17.4%), Toxascaris leonina (10.1%), Uncinaria stenocephala (11.4%), Trichuris vulpis (7.0%) and cestodes (2.1%). Isospora oocysts were observed in 5.2% of the dogs. The data on the distribution of the various worm species in the positive dogs indicate that T. canis eggs were by far the most common (50.9%). Necropsy data from 212 infected dogs indicate that 38.9% were infected with T. canis and 33.7% with T. leonina. The overall prevalence of worm infestation of 246 well-cared-for kennel dogs, based on worm egg counts by the McMaster technique, was 36.1%. Of 30 feline faecal samples examined by flotation, 83.3% were positive for parasites, including Toxocara cati (60%), Ancylostoma tubaeformae (36.6%), Taenia (Hydatigera) taeniaeformis (20%) and coccidia (30%). Toxocara cati was the most frequently found worm species at the necropsy of 25 cats (52%). Toxoplasma was not observed.

Efficacy of diclazuril in the prevention and cure of intestinal and hepatic coccidiosis in rabbits.

The efficacy of diclazuril against intestinal and hepatic coccidiosis was studied in artificially infected rabbits. Prophylaxis against intestinal coccidiosis was evaluated using a mixed infection of Eimeria intestinalis, Eimeria magna and Eimeria perforans. Continuous medication in the feed at 1 p.p.m. was 100% effective in reducing oocyst output and faecal scores, and weight gain and feed efficiency were normal. Hepatic coccidiosis induced by Eimeria stiedai was prevented at 0.5 and 1 p.p.m. as shown by negative oocyst counts, normal liver weight, absence of liver lesions, and normal body-weight gain and feed efficiency. Medication at 1 p.p.m. for 7 consecutive days during the prepatent phase of hepatic coccidiosis resulted in large reductions in oocyst counts and lesion scores with a normal liver weight and growth performance. Diclazuril at 1 p.p.m. in the feed prevented both intestinal and hepatic coccidiosis in rabbits and can be advocated for safe mass medication.

Efficacy of diclazuril against Eimeria dispersa in turkeys.

Diclazuril, a new anticoccidial drug, was tested for its efficacy against Eimeria dispersa in turkeys. A dose-titration study indicated that diclazuril at dosages of 0.5, 1, and 2 ppm in the feed was highly effective in terms of weight gain and suppression of lesions, abnormal droppings, and oocyst shedding.

Efficacy of diclazuril against turkey coccidiosis in a floor-pen experiment.

Diclazuril, a new anticoccidial drug, was tested for its efficacy in turkeys against mixed Eimeria infections. A floor-pen trial indicated that diclazuril at dosages of 0.5 ppm and 1 ppm in the feed was highly effective against the major pathogenic species E. adenoeides, E. gallopavonis, and E. meleagrimitis in suppressing intestinal and cecal lesions and oocyst shedding. Weight gain and feed conversion improved, particularly at 1 ppm.

Efficacy of diclazuril against turkey coccidiosis in dose-titration studies.

Diclazuril, a new anticoccidial drug, was tested for its efficacy in turkeys against single Eimeria infections. Dose-titration studies indicated that diclazuril at dosages of 0.1, 0.5, 1, and 2 ppm was highly effective against the major pathogenic species-E. adenoeides, E. gallopavonis, and E. meleagrimitis-in terms of weight gain and suppression of lesions, abnormal droppings, and oocyst shedding.

Classification of normal and abnormal electrogastrograms using multilayer feedforward neural networks.

A neural network approach is proposed for the automated classification of the normal and abnormal EGG. Two learning algorithms, the quasi-Newton and the scaled conjugate gradient method for the multilayer feedforward neural networks (MFNN), are introduced and compared with the error backpropagation algorithm. The configurations of the MFNN are determined by experiment. The raw EGG data, its power spectral data, and its autoregressive moving average (ARMA) modelling parameters are used as the input to the MFNN and compared with each other. Three indexes (the percent correct, sum-squared error and complexity per iteration) are used to evaluate the performance of each learning algorithm. The results show that the scaled conjugate gradient algorithm performs best, in that it is robust and provides a super-linear convergence rate. The power spectral representation and the ARMA modelling parameters of the EGG are found to be better types of the input to the network for this specific application, both yielding a percent correctness of 95% on the test set. Although the results are focused on the classification of the EGG, this paper should provide useful information for the classification of other biomedical signals.

Thrombotic thrombocytopenic purpura: a rare but potential life-threatening complication following ticlopidine administration.

Thrombotic thrombocytopenic purpura (TTP) is a known, although rare, complication of ticlopidine treatment. It typically appears within the first days or weeks after initiation of therapy. We describe a case of TTP in a 75-year-old patient, due to ticlopidine, occurring three weeks after coronary stent implantation. The patient responded favourably to fresh frozen plasma exchanges. We are reporting this case to emphasize that prognosis depends on prompt diagnosis and early treatment, implying careful biochemical monitoring.

Anthelmintic efficacy of flubendazole paste against nematodes and cestodes in dogs and cats.

Small dogs and cats, naturally infected with nematodes and cestodes, were used in a critical test under laboratory conditions to determine the palatability and efficacy of flubendazole as a past formulation. Subsequently, a control test in dogs was conducted under field conditions. A 4.4% past formulation was given at a dosage of 22 mg/kg of body weight once a day for 2 or 3 consecutive days. In a critical test in dogs, the efficacy against Toxocara canis was 97.4% after a 2-day administration and 100% after 3 days. Toxascaris leonina seemed to be the most susceptible worm species, since either 2 or 3 treatments were 100% active. The efficacy against Uncinaria stenocephala was 97.5% after 2 treatments; the same dose level for 3 days improved the efficacy to 100%. The efficacy was 100% for the removal of Trichuris vulpis after a daily dosage for 2 days and 96.7% after 3 days. One of 2 dogs infected with Taenia pisiformis was cleared of the infection after a 2-day treatment, and 3 of 4 dogs were cleared after a 3-day regimen. All cats were cleared of Toxocara cati after 2 or 3 days of treatment. One of 2 cats infected with Hydatigera taeniaeformis was cleared of the infection after a 2-day treatment; a 3-day treatment in 7 cats was 100% effective. The results in the laboratory test in dogs were confirmed under field conditions by a control test, based on the reduction of eggs per gram of feces count after treatment. The paste formulation was well accepted by all dogs and cats without any side effects.

Diclazuril, a new broad spectrum anticoccidial drug in chickens. 2. Battery trials.

Battery trials have confirmed the broad spectrum anticoccidial activity of diclazuril as previously reported in dose titration studies. The advocated dose level of 1 ppm in the diet demonstrated excellent activity against the economically most important Eimeria species. At this dose level, body weight gains were comparable to those of uninfected, unmedicated controls and the oocyst production was negative in most species. Lesion scores and dropping scores were nil or highly reduced. An E. maxima-147 strain, less sensitive to ionophores, also responded well to diclazuril. It was concluded that diclazuril is a promising anticoccidial for the control of all species of coccidia that cause losses to the poultry industry.

Diclazuril, a new broad-spectrum anticoccidial for chickens. 3. Floor-pen trials.

Diclazuril is a benzeneacetonitrile showing great promise as a broad-spectrum anticoccidial agent for chickens, turkeys, and rabbits. The high anticoccidial activity of diclazuril in chickens, as first reported in dose-titration studies and battery trials, was confirmed in three floor-pen trials. The efficacy was demonstrated against six major pathogenic species of Eimeria after artificial infection with one or more species. The experimental data indicated that diclazuril, at dose levels of .5, .75, 1, and 2 ppm, had a high anticoccidial activity in terms of preventing mortality, suppressing or reducing lesion scores, and allowing for normal weight gains as well as productivity. The performances obtained with diclazuril was generally comparable with that of salinomycin at 60 ppm and that of lasalocid at 90 ppm.

Efficacy of flubendazole against gastrointestinal and lung nematodes in pigs.

Three trials were carried out on landrace pigs of various ages to assess the anthelmintic efficacy of flubendazole. The pigs were either artificially infected with Metastrongylus apri or naturally or artificially infected with the gastrointestinal nematodes Ascaris suum, Oesophagostomum dentatum or Hyostrongylus rubidus. For mass medication of young pigs and fatteners a dose regimen of 30 ppm flubendazole in the feed for 10 consecutive days was 100 per cent effective against the four nematode species. For individual medication a single dose of 5 mg/kg bodyweight administered in a small amount of feed was also 100 per cent effective. No side effects were observed.