A simple foot pedal device in a horizontal bore imaging facility replicates weightbearing outcomes for Hallux Valgus patients.

BACKGROUND: Weightbearing images are important to the diagnosis of foot pathologies as are the three dimensional views available from CT and MRI. Standard three-dimensional imaging hardware, however, does not have a simple tool to obtain weightbearing images. The current research aimed to design, build and test a simple device to apply load in a horizontal bore imaging facility. METHODS: With the immediate need in hallux valgus studies, hallux valgus subjects were imaged using the new loading device, which could be easily transported and had no additional electronics. RESULTS: Testing showed that the usual angular measures of the foot (intermetatarsal and hallux valgus) replicated the results from the standard of care standing plain film results. With application of load, HV angle changed from 29.9° non-weightbearing to 32.2° weightbearing, while IM angle changed from nonweightbearing 15.8° to weightbearing 16.5°. CONCLUSION: The pedal-like device can provide weightbearing images in a horizontal bore MRI facility.

Early infarct FLAIR hyperintensity is associated with increased hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. METHODS: Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. RESULTS: Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). CONCLUSIONS: Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.

Metabarcoding airborne pollen from subtropical and temperate eastern Australia over multiple years reveals pollen aerobiome diversity and complexity.

eDNA metabarcoding is an emergent tool to inform aerobiome complexity, but few studies have applied this technology with real-world environmental pollen monitoring samples. Here we apply eDNA metabarcoding to assess seasonal and regional differences in the composition of airborne pollen from routine samples collected across successive years. Airborne pollen concentrations over two sampling periods were determined using a continuous flow volumetric impaction air sampler in sub-tropical (Mutdapilly and Rocklea) and temperate (Macquarie Park and Richmond), sites of Australia. eDNA metabarcoding was applied to daily pollen samples collected once per week using the rbcL amplicon. Composition and redundancy analysis of the sequence read counts were examined. The dominant pollen families were mostly consistent between consecutive years but there was some heterogeneity between sites and years for month of peak pollen release. Many more families were detected by eDNA than counted by light microscopy with 211 to 399 operational taxonomic units assigned to family per site from October to May. There were 216 unique and 119 taxa shared between subtropics (27°S) and temperate (33°S) latitudes, with, for example, Poaceae, Myrtaceae and Causurinaceae being shared, and Manihot, Vigna and Aristida being in subtropical, and Ceratodon and Cerastium being in temperate sites. Certain genera were observed within the same location and season over the two years; Chloris at Rocklea in autumn of 2017-18 (0.625, p ≤ 0.004) and 2018-19 (0.55, p ≤ 0.001), and Pinus and Plantago at Macquarie Park in summer of 2017-18 (0.58, p ≤ 0.001 and 0.53, p ≤ 0.003, respectively), and 2018-19 (0.8, p ≤ 0.003 and 0.8, p ≤ 0.003, respectively). eDNA metabarcoding is a powerful tool to survey the complexity of pollen aerobiology and distinguish spatial and temporal profiles of local pollen to a far deeper level than traditional counting methods. However, further research is required to optimise the metabarcode target to enable reliable detection of pollen to genus and species level.

Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus.

AIMS: Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. METHODS AND RESULTS: Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3- and 2,5-dihydroxybenzaldehydes (-DBA) had synergistic interactions depending upon drug and yeast strain. 2,5-DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. CONCLUSIONS: Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a proof-of-concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.

Use of chemosensitization to overcome fludioxonil resistance in Penicillium expansum.

AIM: To overcome fludioxonil resistance of Penicillium expansum, a mycotoxigenic fungal pathogen causing postharvest decay in apple, by using natural phenolic chemosensitizing agents. METHODS AND RESULTS: Fludioxonil-resistant mutants of P. expansum were co-treated with different oxidising and natural phenolic agents. Resistance was overcome by natural phenolic chemosensitizing agents targeting the oxidative stress-response pathway. These agents also augmented effectiveness of the fungicide, kresoxim-methyl. Results indicated that alkyl gallates target mitochondrial respiration and/or its antioxidation system. Fungal mitochondrial superoxide dismutase (Mn-SOD) plays a protective role against alkyl gallates. CONCLUSIONS: Natural chemosensitizing agents targeting the oxidative stress-response system, such as Mn-SOD, can synergize commercial fungicides. SIGNIFICANCE AND IMPACT OF THE STUDY: Redox-active compounds can serve as potent chemosensitizing agents to overcome resistance and lower effective dosages of fungicides. This can reduce costs with coincidental lowering of environmental and health risks.

Tracking seasonal changes in diversity of pollen allergen exposure: Targeted metabarcoding of a subtropical aerobiome.

The importance of grass pollen to the global burden of allergic respiratory disease is well established but exposure to subtropical and temperate pollens is difficult to discern. Current monitoring of airborne pollen relies on light microscopy, limiting identification of taxa to family level. This informs seasonal fluctuations in pollen aerobiology but restricts analysis of aerobiological composition. We aimed to test the utility of DNA metabarcoding to identify specific taxa contributing to the aerobiome of environmental air samples, using routine pollen and spore monitoring equipment, as well as assess temporal variation of Poaceae pollen across an entire season. Airborne pollen concentrations were determined by light microscopy over two pollen seasons in the subtropical city of Brisbane (27°32'S, 153°00E), Australia. Thirty daily pollen samples were subjected to high throughput sequencing of the plastid rbcL amplicon. Amplicons corresponded to plants observed in the local biogeographical region with up to 3238 different operational taxonomic units (OTU) detected. The aerobiome sequencing data frequently identified pollen to genus levels with significant quantitative differences in aerobiome diversity between the months and seasons detected. Moreover, multiple peaks of Chloridoideae and Panicoideae pollen were evident over the collection period confirming these grasses as the dominant Poaceae pollen source across the season. Targeted high throughput sequencing of routinely collected airborne pollen samples appears to offer utility to track temporal changes in the aerobiome and shifts in pollen exposure. Precise identification of the composition and temporal distributions of airborne pollen is important for tracking biodiversity and for management of allergic respiratory disease.

Tomatine and parasitic wasps: potential incompatibility of plant antibiosis with biological control.

alpha-Tomatine, an alkaloid in tomato plants, is toxic to an endoparasite of a major lepidopterous pest of tomatoes. The parasite acquires the alkaloid from its host after the host ingests the alkaloid. This form of interaction creates a potential dilemma to controlling herbivorous pests through chemical antibiosis in plants.

Ipsilateral Prominent Thalamostriate Vein on Susceptibility-Weighted Imaging Predicts Poor Outcome after Intravenous Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The impact of deep cerebral veins on neurologic outcome after intravenous thrombolysis in patients with acute ischemic stroke is unclear. We investigated the relationship between the appearance of deep cerebral veins on susceptibility-weighted imaging and neurologic outcome in patients who underwent thrombolysis. MATERIALS AND METHODS: We retrospectively analyzed 109 consecutive patients with acute ischemic stroke who had pretreatment SWI and received intravenous thrombolysis within 6 hours. We calculated the signal difference ratio (defined as the relative difference in signal intensity between the ipsilateral and contralateral veins) of the thalamostriate vein, septal vein, and internal cerebral vein on pretreatment SWI. RESULTS: Only the signal difference ratio of the thalamostriate vein was significantly associated with poor outcome (3-month modified Rankin Scale score > 2, P = .008). The optimal threshold was relative hypointensity of the ipsilateral vein of >4.8% (sensitivity of 53.7% and specificity of 80.9%). We defined a signal difference ratio of the thalamostriate vein of ≥5% as an ipsilateral prominent thalamostriate vein. Patients with an ipsilateral prominent thalamostriate vein were more likely to have poor outcome (OR = 3.66; 95% CI, 1.25-10.68; P = .02) and a lower rate of successful reperfusion (reperfusion rate of ≥70%; OR = 0.35; 95% CI, 0.13-0.92; P = .03), compared with those without an ipsilateral prominent thalamostriate vein. However, patients with an ipsilateral prominent thalamostriate vein were still less likely to experience poor outcome when reperfusion was achieved compared with when reperfusion did not occur (80.0% versus 44.4%, P = .04). CONCLUSIONS: A pretreatment ipsilateral prominent thalamostriate vein was associated with reduced reperfusion after thrombolysis and poor outcome. More intensive reperfusion approaches may be required for patients with an ipsilateral prominent thalamostriate vein.

Withdrawal reactions following cessation of central alpha-adrenergic receptor agonists.

Interruption of long-term treatment with alpha 2-adrenergic receptor agonists may be associated with reversal of their hemodynamic effects, clinical and biochemical evidence of increased peripheral sympathetic activity, and behavioral responses similar to those seen after narcotic or alcohol withdrawal. Reactions are most commonly observed after short-acting imidazoline drugs such as clonidine and tiamenidine. Reactions are less common after longer acting agents such as guanfacine. A new management approach to withdrawal has been evaluated, which uses a combination of alpha 1-blockade (prazosin) and cardioselective beta-blockade (atenolol) together with a benzodiazepine (chlordiazepoxide). Withdrawal reactions were not observed in eight patients in whom clonidine was withdrawn under cover of these agents. The mechanism of the withdrawal reaction may involve agonist-induced down regulation of alpha 2-adrenergic receptor affinity, number, or both. Experimental studies with the irreversible alpha-antagonist phenoxybenzamine on the turnover of alpha 2-receptors suggest that recovery of receptor number may be much slower in the brain than in the periphery.

Effect of naloxone on the actions of captopril.

Captopril inhibits the metabolism of endogenous opioids in vitro and potentiates their effects in vivo. We examined the hypothesis that endogenous opioids contribute to the actions of captopril in man. The acute cardiovascular and autonomic effects of oral captopril, intravenous naloxone, and their combination were examined in eight healthy men with normotension in a double-blind, placebo-controlled study of a Latin squares design. Naloxone altered neither blood pressure nor heart rate. There were significant falls in systolic blood pressure during captopril dosing alone, but there was no fall in blood pressure during combination therapy. Heart rates were higher during the combination than during captopril alone. The combination caused sedation, but neither captopril nor naloxone alone had any behavioral effects. Modification of the acute circulatory effects of captopril by naloxone suggests a role for endogenous opioids in the responses to converting enzyme inhibition. The sedation caused by the combination raises the possibility that captopril may exert central nervous actions in man.

Acute and chronic effects of the converting enzyme inhibitors enalapril and lisinopril on reflex control of heart rate in normotensive man.

The effects of enalapril maleate and its lysine analogue, lisinopril, on reflex control of heart rate after acute and chronic administration were examined in 10 normotensive males. Both drugs reduced blood pressure without change in heart rate after acute dosing and after seven days. Both drugs impaired the vagally mediated early cardiac acceleration associated with lying down (standing to lying test). A similar effect was observed following edrophonium. After lisinopril bradycardia induced by facial immersion (diving reflex) was significantly attenuated. Edrophonium similarly attenuated the bradycardia. Both these reflexes are parasympathetically mediated. Neither drug altered heart rate or blood pressure changes following Valsalva's manoeuvre and the cold pressor test. Plasma noradrenaline was unchanged. Absence of reflex tachycardia with blood pressure reduction by converting enzyme inhibitors may be related to increased parasympathetic activity either centrally or peripherally without impairment of baroreflexes or sympathetic function.

Implications of hormonal influences on sexual behavior for demographic models of reproduction.

In exploring the implications of hormonal influences on sexual behavior for reproduction, we have focused on androgens because of the convincing evidence for androgenic effects on female sexual motivation. We have been guided by the simple idea, based on clinical findings among hyperandrogenic women, that higher testosterone levels will increase female sexual motivation which in turn will result in increased coital frequency. However, careful consideration of the evidence fails to confirm such a role for testosterone in sexual behavior among normal women at any point in the reproductive span. While some amount of testosterone appears to be important in maintaining female sexual motivation, there is little evidence that variation in testosterone within the normal range is associated with variation in sexual motivation. Reported associations between testosterone and sexual behavior among married women cannot be interpreted as resulting from androgenic effects on sexual motivation. Thus we are left with the task of explaining why testosterone does not appear to play the same role in libido among hyperandrogenic and normal women. As mentioned earlier, some of the difference may attributable to the much higher levels of testosterone among hyperandrogenic women. Sherwin points out that the levels of sexual motivation decline with declining testosterone levels even while testosterone is well above normally occurring levels. It is possible that the brain is simply not sensitive to the variation in testosterone levels found in normal women. Other evidence suggests that the presence of intact ovaries may be equally important. A recent study of androgen replacement in naturally post-menopausal women failed to find a dramatic effect of testosterone on sexual motivation and behavior, despite levels similar to those in studies on surgically menopausal women, pointing to the importance of other factors associated with the presence of ovaries. A similar point can be made with regard to hyperandrogenism related to endogenous sources of testosterone, as in the case of PCOS. High levels of testosterone effectively disrupt ovarian function and interfere with other ovarian processes. Among hyperandrogenic women sexual behavior appears to be related to the direct effects of androgens on motivation, while the indirect effects of estrogen and progesterone are essentially eliminated. Among normal women, on the other hand, there is little evidence for such a dominating role of a direct androgenic effect on sexual behavior. Instead, other ovarian hormones, including estrogen and progesterone may also play a demonstrable role, despite the lack of strong evidence at this point.(ABSTRACT TRUNCATED AT 400 WORDS)

Molecular Phylogeny of Fulgoromorpha (Insecta, Hemiptera, Archaeorrhyncha). The Enigmatic Tettigometridae: Evolutionary Affiliations and Historical Biogeography.

Previous morphologically based studies by several taxonomists disagree on whether the Tettigometridae represent a sister group to all other fulgoromorphans or whether they are a relatively derived family within the Fulgoromorpha. In this study, several parsimony-based analyses using data sets composed of nucleotide sequences of 18S rDNAs (genes encoding 18S rRNAs) support a monophyletic Fulgoromorpha. All analyses depict Tettigometridae as a relatively derived lineage in a monophyletic relationship with Tropiduchidae. Unscored and unweighted data sets position the tettigometrid + tropiduchid clade as sister to Flatidae. The tettigometrid + tropiduchid clade is supported by four synapomorphic sites, two deletions and two transversions. Constraining tettigometrids to a basal fulgoromorphan lineage significantly reduces parsimony, with several hundreds to thousand of trees being more parsimonious. An analysis employing the Barriel method for scoring potential phylogenetic information in regions containing deletions also supports a non-basal tettigometrid + tropiduchid clade. However, this method results in three equally most parsimonious trees and a sister relationship of the tettigometrid + tropiduchid clade to Flatidae becomes ambiguous. The molecular-based results showing a derived Tettigometridae agree with previous morphological interpretations of Bourgoin. The current biogeographical distribution of tettigometrids and morphological features supporting the 18S rDNA-based phylogeny are discussed.

Effect of iron poly (sorbitolgluconic acid) complex on urinary cellular excretion.

The intramuscular injection of 250 mg iron poly (sorbitol-gluconic acid) complex caused no increase in urinary cellular or bacterial excretion in 8 patients with chronic pyelonephritis, 4 patients with non-infective renal disease, and 4 controls. However, in 4 patients with chronic infective disease of the renal tract given 500 g there was a significant increase in cellular excretion. This response was not seen in 2 control patients, nor in 2 patients with non-infective renal disease. Using a differential staining technique, this increase in urinary cellular excretion was found to be due, not to leucocytes, but to renal tubular cells. The precise significance of this is unclear, but there would be concern that the high concentration of excreted iron was providing a 'toxic' insult to susceptible, infection-damaged cells.

The association between lead concentrations in teeth and domestic water lead concentrations.

Tooth lead levels have been measured in 109 children living in Glasgow. A significant association has been demonstrated between molar tooth lead concentrations and domestic drinking water lead concentrations. Tooth lead concentrations were found to be greater the longer a child had liver in older housing with lead plumbing during foetal life and following birth. Tooth lead concentrations were also found to be age-related although no difference with respect to social class could be found.

Delta-aminolaevulinic acid metabolism in normal and lead-exposed humans.

The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid synthetase (ALA.S) and delta-aminolaevulinic acid dehydratase (ALA.D) were measured in the peripheral blood of a group of lead workers and control subjects. The haem precursor delta-aminolaevulinic acid (ALA) was measured in blood and urine, whilst lead levels were measured in whole blood. The inter-relationships between all these parameters were examined and quantified. The results demonstrate that above a blood lead concentration of 2 mumole/l and below an erythrocyte ALA.D activity of 18 nmole ALA utlized/min/ml red blood cells (R.B.C.), Haem synthesis is depressed to such an extent that the activity of leucocyte ALA.S, the rate-limiting enzyme of haem biosynthesis, is increased by negative feedback.

Ratios of plasma and salivary testosterone throughout puberty: production versus bioavailability.

Because diffusion of testosterone (T) into the salivary gland is thought to be largely limited to the free, biologically active fraction, salivary testosterone is expected to provide a better measure of testosterone bioavailability in the body than is plasma testosterone. Matched saliva and blood spot samples were collected from 218 Zimbabwean males (age 11-23) who were at different stages of puberty, as assessed by self-reported Tanner genital stage ratings. Testosterone concentrations in these matched samples were highly correlated (r = 0.83). Both salivary and plasma testosterone (converted from blood spot value) showed expected significant increases across puberty. However, plasma testosterone distinguished among subjects at different stages of genital development more effectively than did salivary testosterone, suggesting the former to be a better marker of testosterone bioavailability. Sex hormone-binding globulin (SHBG) levels were also measured in a subgroup of 93 of these subjects. After controlling for plasma T concentrations, we found a small but significant inverse correlation between blood spot SHBG levels and the proportion of plasma testosterone recovered in salvia, supporting the hypothesis that SHBG-related changes in T bioavailability are detectable in saliva. We conclude that salivary testosterone accurately reflects testicular production of testosterone, but that neither salivary testosterone nor plasma testosterone is clearly superior to the other as a measure of testosterone bioavailability.

Lead exposure and changes in the renin-angiotensin-aldosterone system in man.

We have studied the effects of chronic slight to moderate lead exposure on the renin-angiotensin-aldosterone system in normotensive man. Plasma renin activity (PRA), blood angiotensin I (AI) concentration, angiotensin converting enzyme (ACE) activity and aldosterone concentration were measured in 33 normotensive men, 25 of whom were occupationally exposed to lead. Positive exponential relationships were found between blood lead and PRA, AI, ACE and aldosterone. Linear relationships were observed between PRA and AI, and between AI and ACE. PRA, AI, and ACE did not significantly correlate with aldosterone. Chronic lead exposure enhanced PRA with a resulting increase in AI levels, which in turn may have produced a substrate-induced increase in ACE. The effects of lead on aldosterone may be mediated in part by an independent pathway. These changes may contribute to the development of hypertension in chronically lead-exposed man.

Lead exposure and renal failure: does renal insufficiency influence lead kinetics?

Blood and urine lead concentrations have been measured in 40 subjects with normal and impaired renal function. Derived renal lead clearance varied widely, but was not influenced by the degree of renal impairment. Lead, however, appeared to reduce its own clearance. These findings provide additional evidence of nephrotoxicity from sub-clinical lead exposure.