Altered response to Toll-like receptor 4 activation in fibromyalgia: A low-dose, human experimental endotoxemia pilot study.

In this pilot study, a human intravenous injection of low-dose endotoxin (lipopolysaccharide, LPS) model was used to test if fibromyalgia is associated with altered immune responses to Toll-like receptor 4 (TLR4) activation. Eight women with moderately-severe fibromyalgia and eight healthy women were administered LPS at 0.1 ng/kg in session one and 0.4 ng/kg in session two. Blood draws were collected hourly to characterize the immune response. The primary analytes of interest, leptin and fractalkine, were assayed via commercial radioimmunoassay and enzyme-linked immunosorbent assay kits, respectively. Exploratory analyses were performed on 20 secreted cytokine assays by multiplex cytokine panels, collected hourly. Exploratory analyses were also performed on testosterone, estrogen, and cortisol levels, collected hourly. Additionally, standard clinical complete blood counts with differential (CBC-D) were collected before LPS administration and at the end of the session. The fibromyalgia group demonstrated enhanced leptin and suppressed fractalkine responses to LPS administration. In the exploratory analyses, the fibromyalgia group showed a lower release of IFN-γ, CXCL10, IL-17A, and IL-12 and higher release of IL-15, TARC, MDC, and eotaxin than the healthy group. The results of this study suggest that fibromyalgia may involve an altered immune response to TLR4 activation.

Proceedings of the 2022 UAB CRRT Academy: Non-Invasive Hemodynamic Monitoring to Guide Fluid Removal with CRRT and Proliferation of Extracorporeal Blood Purification Devices.

In 2022, we celebrated the 15th anniversary of the University of Alabama at Birmingham (UAB) Continuous Renal Replacement Therapy (CRRT) Academy, a 2-day conference attended yearly by an international audience of over 100 nephrology, critical care, and multidisciplinary trainees and practitioners. This year, we introduce the proceedings of the UAB CRRT Academy, a yearly review of select emerging topics in the field of critical care nephrology that feature prominently in the conference. First, we review the rapidly evolving field of non-invasive hemodynamic monitoring and its potential to guide fluid removal by renal replacement therapy (RRT). We begin by summarizing the accumulating data associating fluid overload with harm in critical illness and the potential for harm from end-organ hypoperfusion caused by excessive fluid removal with RRT, underscoring the importance of accurate, dynamic assessment of volume status. We describe four applications of point-of-care ultrasound used to identify patients in need of urgent fluid removal or likely to tolerate fluid removal: lung ultrasound, inferior vena cava ultrasound, venous excess ultrasonography, and Doppler of the left ventricular outflow track to estimate stroke volume. We briefly introduce other minimally invasive hemodynamic monitoring technologies before concluding that additional prospective data are urgently needed to adapt these technologies to the specific task of fluid removal by RRT and to learn how best to integrate them into practical fluid-management strategies. Second, we focus on the growth of novel extracorporeal blood purification devices, starting with brief reviews of the inflammatory underpinnings of multiorgan dysfunction and the specific applications of pathogen, endotoxin, and/or cytokine removal and immunomodulation. Finally, we review a series of specific adsorptive technologies, several of which have seen substantial clinical use during the COVID-19 pandemic, describing their mechanisms of target removal, the limited existing data supporting their efficacy, ongoing and future studies, and the need for additional prospective trials.

German brass for Benin Bronzes: Geochemical analysis insights into the early Atlantic trade.

Utilizing geochemical analysis, this study identifies the sources of European brass used in the casting of the renowned Benin Bronzes, produced by the Edo people of Nigeria. It is commonly believed that distinctive brass rings known as "manillas", used as currency in the European trade in West Africa, also served as a metal source for the making of the Bronzes. However, prior to the current study, no research had conclusively connected the Benin artworks and the European manillas. For this research, manillas from shipwrecks in African, American and European waters dating between the 16th and 19th Century were analysed using ICP-MS analysis. Comparing trace elements and lead isotope ratios of manillas and Benin Bronzes identifies Germany as the principal source of the manillas used in the West African trade between the 15th and 18th centuries before British industries took over the brass trade in the late 18th century.

Proton-Induced Spin State Switching in an FeIII Complex.

Reversible proton-induced spin state switching of an FeIII complex in solution is observed at room temperature. A reversible magnetic response was detected in the complex, [FeIII (sal2 323)]ClO4 (1), using Evans' method 1 H NMR spectroscopy which indicated cumulative switching from low-spin to high-spin upon addition of one and two equivalents of acid. Infrared spectroscopy suggests a coordination-induced spin state switching (CISSS) effect, whereby protonation displaces the metal-phenoxo donors. The analogous complex, [FeIII (4-NEt2 -sal2 323)]ClO4 (2), with a diethylamino group on the ligand, was used to combine the magnetic change with a colorimetric response. Comparison of the protonation responses of 1 and 2 reveals that the magnetic switching is caused by perturbation of the immediate coordination sphere of the complex. These complexes constitute a new class of analyte sensor which operate by magneto-modulation, and in the case of 2, also yield a colorimetric response.

Spatio-temporal trends in livestock exposure to per- and polyfluoroalkyl substances (PFAS) inform risk assessment and management measures.

The migration of per- and polyfluoroalkyl substances (PFAS) onto agricultural properties has resulted in the accumulation of PFAS in livestock. The environmental determinants of PFAS accumulation in livestock from the grazing environment are poorly understood, resulting in limited capacity to manage livestock exposure and subsequent transfer of PFAS through the food chain. Analytical- (n = 978 samples of soil, water, pasture, and serum matrices), farm management/practice- and livestock physiology data were collated and interrogated from environmental PFAS investigations across ten farms, from four agro-ecological regions of Victoria (Australia). Statistical analysis identified perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) as key analytes of concern for livestock bioaccumulation. PFOS and PFHxS concentrations in livestock drinking water were positively correlated with serum concentrations while other intake pathways (pasture and soil) had weaker correlations. Seasonal trends in PFAS body burden (serum concentrations) were identified and suggested to be linked to seasonal grazing behaviours and physiological water requirements. The data showed for the first time that livestock exposure to PFAS is dynamic and with relatively short elimination half-lives, there is opportunity for exposure management. Meat from cattle, grazed on PFAS impacted sites, may exceed health-based guideline values for PFAS, especially for markets with low limits (like the European Commission Maximum Limits or EC MLs). This study found that sites with mean livestock drinking water concentrations as low as 0.003 µg PFOS/L may exceed the EC ML for PFOS in cattle meat. Risk assessment can be used to prioritise site cleanup and development of management plans to reduce PFAS body burden by considering timing of stock rotation and/or supplementation of primary exposure sources.

Culture-positive urinary tract infection following micturating cystourethrogram in children.

Objective: To determine the incidence of culture-positive urinary tract infection (UTI) after micturating cystourethrogram (MCUG). We further wanted to identify risk factors for developing a culture-positive UTI following MCUG. Methods: A retrospective review of the available medical records of 500 paediatric patients who underwent MCUG in Perth, Western Australia was performed. Results: Seven (1.4%) patients comprised of four females and three males developed a febrile, culture-positive UTI within 14 days following MCUG. Significant association was found for female patients, patients with neurogenic bladder, and patients with previous culture-positive UTI as developing a culture-positive UTI following MCUG. Multivariate logistic regression determined that patients were more likely to develop culture-positive UTI within 14 days following MCUG if they had a known history of UTI (odds ratio: 5.0, 95% confidence interval: 1.5-17.3, p=0.010) or had a neurogenic bladder (odds ratio: 4.2, 95% confidence interval: 1.0-17.9, p=0.049). Conclusion: The incidence of patients who developed a febrile, culture-positive UTI following MCUG was low at 1.4%. Statistically significant and independent associations for the development of culture positive UTI were found in patients with neurogenic bladder and patients with previous culture-positive UTI. Further prospective studies are necessary to determine necessity of prophylactic antibiotics for high-risk patients, e.g., patients with neurogenic bladder or previous culture-positive UTI.

Clinical spectrum and management options for prostatic utricle in children.

PURPOSE: Prostatic utricle (PU) has been described in children with hypospadias, posterior urethral valves (PUV), variances of sex characteristics and normal external genitalia. Intervention may be required in symptomatic cases, but clinical characteristics vary, requiring individualisation of management. We describe our experience with this condition. METHODS: Retrospective review of males noted to have PU on cystoscopy (2009-2020) at a single centre. Presentation, management and outcomes were recorded (Variances of sex characteristics excluded). RESULTS: Of 1060 male children who underwent cystoscopy for various reasons, PU was recorded in 36 (3.4%), indications for cystoscopy being hypospadias in 28, PUV in 3, urinary tract infections (UTI) in 3 and hydronephrosis in 2. Six (16.7%) developed epididymo-orchitis. All 6 had Ikoma Grade II PU. Case 1 (16 years,UTI) was managed with intravenous antibiotics. Case 2 (8 years,hypospadias) underwent laying open of urethral stricture. Case 3 (5 years,PUV) underwent laparoscopic PU excision. Cases 4 and 5 (3 and 6 years, hypospadias) underwent cystoscopic injection of bulking agent near the insertion of the vasa. Case 6 (3 years,hypospadias) underwent laparoscopic PU excision with vasal disconnection (vasal openings at dome of utricle rather than base) following failed endoscopic management. Median follow-up was 36 (0-206) months. All remained asymptomatic with normal testicular volumes for age at current follow-up. CONCLUSION: Multiple treatment options to address a symptomatic PU have been described and enable surgeons to individualise treatment based on clinical circumstances. It is important to identify variations in anatomy of vasal connection to PU to plan appropriate management. LEVEL OF EVIDENCE: IV (Retrospective study).

Fluid Responsiveness in the Critically Ill Patient.

Accurate assessment of intravascular volume status in critically ill patients remains a very challenging task. Recent data have shown adverse outcomes in critically ill patients with either inadequate or overaggressive fluid therapy. Understanding the tools and techniques available for accurate volume assessment is imperative. This article discusses the concept of fluid responsiveness and reviews methods for assessing fluid responsiveness in critically ill patients.

Online Interactive Platform for COVID-19 Literature Visual Analytics: Platform Development Study.

BACKGROUND: Papers on COVID-19 are being published at a high rate and concern many different topics. Innovative tools are needed to aid researchers to find patterns in this vast amount of literature to identify subsets of interest in an automated fashion. OBJECTIVE: We present a new online software resource with a friendly user interface that allows users to query and interact with visual representations of relationships between publications. METHODS: We publicly released an application called PLATIPUS (Publication Literature Analysis and Text Interaction Platform for User Studies) that allows researchers to interact with literature supplied by COVIDScholar via a visual analytics platform. This tool contains standard filtering capabilities based on authors, journals, high-level categories, and various research-specific details via natural language processing and dozens of customizable visualizations that dynamically update from a researcher's query. RESULTS: PLATIPUS is available online and currently links to over 100,000 publications and is still growing. This application has the potential to transform how COVID-19 researchers use public literature to enable their research. CONCLUSIONS: The PLATIPUS application provides the end user with a variety of ways to search, filter, and visualize over 100,00 COVID-19 publications.

Variation in ureteric re-implantation for Australian children.

BACKGROUND: Management options for vesicoureteric reflux are numerous, increasingly diversifying and debated. There is longstanding anecdotal opinion of inexplicable regional variation in vesicoureteric reflux management in Australia. This study investigates temporal trends in ureteric re-implantation for children, and variation between states and territories. METHODS: Ureteric re-implantation data for children aged 0-14 years were retrieved from the Medicare Benefits Scheme item reports database for the 20-year period from 1998-2017. Claims data were population adjusted for each state then standardized for age using Australian Bureau of Statistics records. National and regional trends were calculated using joinpoint regression. Comparison between eastern (New South Wales, Victoria, Queensland, Tasmania, Australian Capital Territory) and western or central (Western Australia, South Australia) states was performed using the Mann-Whitney U-test. RESULTS: There were 4919 procedure rebate claims during the study period. A national decrease in claim rates of 6.3% per 100 000 children was identified (P < 0.001). This was derived from significant decreases observed in eastern states. There was a threefold higher claim rate in Western Australia and South Australia per annum compared to the remainder of the country (4.0 versus 12.6 per 100 000; P < 0.001). For the most recent 5 years of the study period, this difference increased to a sevenfold higher rate (1.6 versus 11.1; P < 0.001). CONCLUSION: There has been a dramatic nationwide decline in the rate of ureteric re-implantation procedure claims. Regional disparity between each side of the country is widening. Further research is required to determine if this degree of variation is warranted or unwarranted. The observed regional variation facilitates opportunity for a nationwide pragmatic clinical trial.

Torsion of a Wandering Spleen Managed Conservatively: Rare and Interesting.

Wandering spleen is a rare pathology. A 2-year-old child with abdominal pain was diagnosed to have a torted, avascular wandering spleen. On conservative management, she remains well with no radiological evidence of the spleen. Splenic torsion usually warrants surgery. Nonoperative management in selected cases allows the natural process of autosplenectomy.

Modulation of Jahn-Teller distortion and electromechanical response in a Mn3+ spin crossover complex.

Structural, magnetic and electromechanical changes resulting from spin crossover between the spin quintet and spin triplet forms of a mononuclear Mn3+ complex embedded in six lattices with different charge balancing counterions are reported. Isostructural ClO4 - and BF4 - salts (1) and (2) each have two unique Mn3+ sites which follow different thermal evolution pathways resulting in a crossover from the spin quintet form at room temperature to a 1:1 spin triplet:quintet ratio below 150 K. The PF6 - (3) and NO3 - (4) salts which each have one unique Mn3+ site show a complete conversion from spin quintet to spin triplet over the same temperature range. A complete two step spin crossover is observed in the CF3SO3 - lattice (5) with a 1:1 ratio of spin quintet and spin triplet forms at intermediate temperature, while the BPh4 - lattice (6) stabilizes the spin triplet form over most of the temperature range with gradual and incomplete spin state switching above 250 K. An electromechanical piezoresponse was detected in NO3 - complex 4 despite crystallization in a centrosymmetric space group. The role of deformations associated with stress-induced spin triplet-spin quintet switching in breaking the local symmetry are discussed and computational analysis is used to estimate the energy gap between the two spin states.

Multicystic dysplastic kidney - treat each case on its merits.

OBJECTIVES: To assess outcomes of unilateral multicystic dysplastic kidney (MCDK) managed at an Australasian centre over a 15 year period. To assess if MCDK involution could be predicted based on change noted between first two postnatal ultrasound scans 6 months apart. SUBJECTS AND METHODS: A retrospective study was performed. RESULTS: One-hundred-and-six cases of unilateral MCDK were studied. Eighty-four of these presented antenatally. Twenty-two MCDK cases presented postnatally. Urological anomalies associated with MCDK included vesicoureteric reflux (VUR), ureterocele and contralateral pelviureteric junction obstruction (PUJO). Children undergoing surgical intervention for these anomalies were offered concurrent MCDK nephrectomy. Morbidity associated with MCDK under surveillance included febrile culture-positive urinary tract infection in 20 cases (20.7%), hypertension in four (3.7%) and Wilms' tumor in one (0.9%). Thirty-six cases (34%) underwent complete involution, 32 (30.2%) were in the process of involuting and 38 cases (35.8%) underwent nephrectomy because of failure of involution or associated morbidity. If the MCDK reduced in cranio-caudal interpolar length by 20% or more between the first postnatal USS and the next one 6 months later, then it was very likely to involute spontaneously. If the MCDK did not reduce in cranio-caudal interpolar length by 20% between the first postnatal scan and the next one 6 months later, then it was highly likely to fail to involute, and in our study, correlated with the outcome of nephrectomy. CONCLUSION: Although MCDK is a benign condition, it should be carefully investigated and followed-up, as involution may not occur in over a third. In some cases, morbidity may occur. Each case of MCDK should be managed on its own merits. LEVEL OF EVIDENCE: Level II - Prognosis study, Retrospective.

Spin state solvomorphism in a series of rare S = 1 manganese(iii) complexes.

Structural, magnetic and spectroscopic data of four complex salts, [Mn(napsal2323)]NTf2, 1,[Mn(napsal2323)]ClO4, 2, [Mn(napsal2323)]BF4, 3 and [Mn(napsal2323)]NO3, 4, of the [Mn(napsal2323)]+ complex cation indicate that the Mn3+ ion is stabilized in the rare S = 1 spin triplet form in this ligand sphere. Zero-field splitting values of D = +19.6 cm-1 and |E| = 2.02 cm-1 for complex 1 were obtained by High Field Electron Paramagnetic Resonance (HFEPR) measurements conducted over a range of frequencies. Structural and magnetic data also indicate that co-crystallization of complexes 2 and 3 with 0.5 equivalents of ethanol yields the high spin S = 2 forms of the perchlorate and tetrafluoroborate solvates [Mn(napsal2323)]ClO4·0.5(C2H5OH), 2·0.5EtOH and [Mn(napsal2323)]BF4·0.5(C2H5OH), 3·0.5EtOH.

Alterations to the vision-associated transcriptome of zebrafish (Danio rerio) following developmental norethindrone exposure.

Synthetic sex steroids, like the synthetic progestin norethindrone (NET), can affect a wide variety of biological processes via highly conserved mechanisms. NET is prevalent in surface waters, yet the sub-lethal effects of NET exposure are not are net yet well characterized in aquatic biota. A few targeted gene expression and behavioral studies have concluded that NET affects the vision of adult fish; however, early life stage (ELS) fish are often more sensitive to contaminants. Furthermore, many species of fish rely heavily on visual perception for survival during development. The goal of the present study was to characterize the effects of developmental exposure to environmentally relevant concentrations of NET on the visual system of ELS zebrafish, using transcriptomics and histological methods. Results indicate that exposure to relatively low levels of NET in aquatic systems may be sufficient to affect the visual function of developing fish.

Directing self-assembly in solution towards improved cooperativity in Fe(iii) complexes with amphiphilic tridentate ligands.

An amphiphilic iron(iii) complex with a tridentate Schiff-base ligand was prepared by condensation of a hexadecyloxy functionalised salycylaldehyde with a diamine followed by complexation with FeCl2 and anion methathesis with NaClO4. The complex shows spin crossover both in the solid state and solution. However in solution self-assembly and consequently aggregation of individual molecules form concentration dependent particles with sizes of 300 nm for higher concentrations, or 5 nm for lower concentrations. Aggregate formation was confirmed by NANO-flex 180° DLS Size, scan-rate dependent cyclic voltammetry and scanning electron microscopy. Molecular simulations were used to investigate the self-assembly of the complex in solution, including the role of residual water molecules. The simulations showed the self-assembly of reverse micelle-like structures when a small water cluster is inserted in solution, whereas no large aggregates formed in dehydrated environments. The perchlorate anions were found near the metal centres, stabilizing the aggregates around the water pool. Simulations of pre-assembled structures further showed the lack of stability of large aggregates in the absence of water. The larger aggregates promoted efficient communication between the iron(iii) centres and the compound displayed spin crossover in solution at around 220 K with a 10 K hysteresis window, as measured by NMR and SQUID magnetometry.