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The metallome has been involved in the pathological investigation into ocular tissue for decades; however, as technologies advance, more information can be ascertained from individual tissue sections that were not previously possible. Herein, a demonstration of complementary techniques has been utilized to describe the distribution and concentrations of essential metals in both wildtype (WT) and rhodopsin (Rho−/−) ocular tissues. The multimodal approach described is an example of complementary datasets that can be produced when employing a multifaceted analytical approach. Heterogenous distributions of copper and zinc were observable within both WT and Rho−/− tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and the distributions of further trace elements notoriously problematic for ICP-MS analysis (phosphorous, Sulfur, chlorine, potassium, calcium, iron, and aluminum) were analysed by particle-induced X-ray emission (PIXE).

Perineuronal nets (PNNs) are dense, negatively charged extracellular matrices that cover the cell body of fast-spiking inhibitory neurons. Synapses can be embedded and stabilized by PNNs believed to prevent synaptic plasticity. We find that in cortical fast-spiking interneurons synaptic terminals localize to perforations in the PNNs, 95% of which contain either excitatory or inhibitory synapses or both. The majority of terminals also colocalize with astrocytic processes expressing Kir4.1 as well as glutamate (Glu) and GABA transporters, hence can be considered tripartite synapses. In the adult brain, degradation of PNNs does not alter axonal terminals but causes expansion of astrocytic coverage of the neuronal somata. However, loss of PNNs impairs astrocytic transmitter and K+ uptake and causes spillage of synaptic Glu into the extrasynaptic space. This data suggests a hitherto unrecognized role of PNNs, to synergize with astrocytes to contain synaptically released signals.

Despite efforts to increase diversity, a glaring underrepresentation of minorities (URM) persists in the fields of science, technology, engineering, and mathematics (STEM). Graduate school can be a stressful step in the STEM pipeline, especially for students previously unaware of the structure and challenges of postgraduate education. To promote successful minority participation in STEM and prepare prospective students for the impending challenges of applying for and attending graduate school, we developed a workshop based on the mentoring and fostering of a champion-oriented mindset entitled, “The Trials and Tribulations of Graduate School: How Do You Make an Impact?.” Students from the HBCU Winston-Salem State University attended the workshop, and a pre/post—a 10-point Likert scale-based survey was administered. The questions used in this seminar were newly designed by the authors as program evaluations. The results suggest that the workshop was well-received by the students and provided information that they considered helpful to help navigate the graduate school process.

Amongst newly developed approaches to analyse molecular data, phylodynamic models are receiving much attention because of their potential to reveal changes to viral populations over short periods. This knowledge can be very important for understanding disease impacts. However, their accuracy needs to be fully understood, especially in relation to wildlife disease epidemiology, where sampling and prior knowledge may be limited. The release of the rabbit haemorrhagic disease virus (RHDV) as biological control in naive rabbit populations in Australia in 1996 provides a unique dataset with which to validate phylodynamic models. By comparing the results obtained for RHDV1 with our current understanding of the RHDV epidemiology in Australia, we evaluated the performances of these recently developed models. In line with our expectations, coalescent analyses detected a sharp increase in the virus trajectory in the first few months after the virus release, followed by a more gradual increase. The phylodynamic analyses with a birth-death tree prior generated effective reproductive number estimates (the average number of secondary infections per each infectious case, Re) larger than one for most of the epochs considered. However, the possible range of the initial Re included estimates lower than one despite the known rapid spread of RHDV1 in Australia. Furthermore, the analyses that took into account the geographical structuring failed to converge. We argue that the difficulties that we encountered most likely stem from the fact that the samples available from 1996 to 2014 were too sparse with respect to geographic and within outbreak coverage to adequately infer some of the model parameters. In general, while these Bayesian analyses proved to be greatly informative in some regards, we caution that their interpretation may not be straight forward and recommend further research in evaluating the robustness of these models to assumption violations and sensitivity to sampling regimes.

Background The rapid technical development and portability of ultrasound systems over recent years has had a profound impact on the area of point-of-care-ultrasound (POCUS), both in general medicine and in obstetrics and gynecology. The use of POCUS enables the clinician to perform the ultrasound scan either at the medical office or the patient’s bedside and used as an extension of the physical examination. Real-time images can immediately be correlated with the patient’s symptoms, and any changes in a (critical) patient’s condition can be more rapidly detected. POCUS in OBGYN POCUS is also suitable for time-critical scenarios, and depending on the situation and its dynamics, the course and results of any therapy may be observed in real time. POCUS should be considered to be a routine extension of practice for most OB/GYN clinicians as it can give immediate answers to what could be life-threatening situations for the mother and/or baby. With its proven usefulness, the applications and use of POCUS should be incorporated in teaching programs for medical students, OBGYN residents and emergency physicians.

Despite an increase in programming to promote persons excluded by their ethnicity or race (PEER) scholars, minorities remain underrepresented in many STEM programs. The academic pipeline is largely leaky for underrepresented minority (URM) scholars due to a lack of effective mentorship. Many URM students experience microaggressions and discrimination from their mentors due to a lack of quality mentorship training. In this workshop, we provide a framework to show trainees what effective mentoring looks like. Mentees, especially URM trainees, can flourish in effective mentoring environments where they feel welcomed and can comfortably develop new ideas without feeling threatened by external factors. Effective mentoring environments provide motivational support, empathy, cultural competency, and training. This workshop explains facets of effective mentoring to students, as well as highlights to URM trainees why mentors can serve as valuable resources.

As a medical imaging modality, ultrasound is used by a wide cross-section of practitioners including radiologists, obstetricians, gynecologists, gastroenterologists, urologists and cardiologists. The increasing popularity of ultrasound as a diagnostic tool is due not only to the ease of use and portability of systems, but also to the perceived safety aspect of the examination. This latter point needs to be examined. As with any reusable medical device, the ultrasound transducer, also known as a probe, could potentially be a vector for the transmission of pathogenic viruses and fungi between patients if not correctly disinfected after each use. This transmission risk is magnified for an endocavity transducer that has come in contact with the vagina, anal canal or oral cavity, as it could be contaminated with organisms transmitted by blood or mucosal, genital or rectal secretions. Based on the Spaulding system, transducers that come in contact with mucous membranes are classified as semi-critical devices that require high-level disinfection (HLD) after each patient procedure. This HLD process should eliminate all microorganisms except high numbers of bacterial endospores. Only a small number of countries worldwide have implemented transducer reprocessing guidelines that adhere to the Spaulding classification and recommend HLD for endocavity transducers. Overall, there is a lack of conformity among global health agencies regarding the use of HLD for endocavity transducers. This is primarily due to the perception that the infection transmission risk is negligible and that if an endocavity transducer has been covered with a single-use sheath for the procedure, then low-level disinfection provides sufficient protection against pathogen transmission. The objective of this study was to review the published risk of infection transmission from endocavity transducers. By highlighting the outbreaks and case reports that implicate pathogen transmission from transducers, we posit that HLD should be a global standard of practice for the reprocessing of endocavity transducers. It requires substantial time for national health administrations to develop and legislate new recommendations, and for practice changes to be accepted and implemented by healthcare providers. We recommend that Joint Commission International (JCI) and other equivalent organizations enforce the use of HLD of endocavity ultrasound transducers during their accreditation reviews.Als bildgebendes Verfahren in der Medizin wird Ultraschall von Ärzten verschiedenster Fachrichtungen eingesetzt, darunter Radiologen, Geburtshelfer, Gynäkologen, Gastroenterologen, Urologen und Kardiologen. Die zunehmende Beliebtheit von Ultraschall als diagnostisches Hilfsmittel ist nicht nur auf die einfache Handhabung und Tragbarkeit der Systeme zurückzuführen, sondern auch auf die vermeintlichen Sicherheitsaspekte der Untersuchung. Dieser letztgenannte Punkt muss untersucht werden. Wie bei jedem wiederverwendbaren medizinischen Gerät könnte der Ultraschallkopf, der auch als Sonde bezeichnet wird, potenziell ein Vektor für die Übertragung pathogener Viren und Pilze zwischen den Patienten sein, wenn er nicht nach jedem Gebrauch korrekt desinfiziert wird. Dieses Übertragungsrisiko ist bei einer endokavitären Sonde, die mit der Vagina, dem Analkanal oder der Mundhöhle in Kontakt gekommen ist, erhöht, da diese mit Organismen kontaminiert sein könnte, die durch Blut oder durch Schleimhaut-, Genital- oder Rektalsekrete übertragen werden. Auf der Grundlage des Spaulding-Klassifikationssystems werden Schallköpfe, die mit Schleimhäuten in Kontakt kommen, als semikritische Geräte eingestuft, die nach jedem Patienteneingriff ein High-level-Desinfektionsverfahren (HLD) erfordern. Dieses HLD-Verfahren sollte alle Mikroorganismen mit Ausnahme vieler bakterieller Endosporen eliminieren. Nur wenige Länder weltweit haben Richtlinien für die Aufbereitung von Schallköpfen eingeführt, die sich an die Spaulding-Klassifikation halten und HLD für endokavitäre Sonden empfehlen. Insgesamt besteht unter den globalen Gesundheitsbehörden ein Mangel an Konformität hinsichtlich des Einsatzes der HLD für endokavitäre Sonden. Dies ist in erster Linie auf die Auffassung zurückzuführen, dass das Risiko der Infektionsübertragung vernachlässigbar ist und dass, wenn eine endokavitäre Sonde für den Eingriff mit einer Einweghülle abgedeckt wurde, eine Desinfektion auf niedrigem Niveau einen ausreichenden Schutz gegen die Übertragung von Krankheitserregern bietet. Das Ziel dieser Studie war es, Publikationen zum Risiko der Infektionsübertragung durch endokavitäre Sonden zu überprüfen. Indem wir die Ausbrüche und Fallberichte hervorheben, die eine Erregerübertragung durch Schallköpfe nahelegen, stellen wir fest, dass HLD weltweit Praxisstandard für die Aufbereitung von endokavitären Sonden werden sollte. Die Entwicklung und Verabschiedung neuer Empfehlungen durch die nationalen Gesundheitsbehörden sowie die Akzeptanz und Umsetzung von praktischen Änderungen bei Gesundheitsdienstleistern erfordern einen erheblichen Zeitaufwand. Wir empfehlen, dass die Joint Commission International (JCI) und andere gleichwertige Organisationen während ihrer Akkreditierungsprüfungen den Einsatz der HLD bei endokavitären Ultraschallsonden einfordern.

BackgroundNumerous studies in veterinary species have recently linked vitamin D status with non-skeletal health disorders. Previous studies have indicated that dogs cannot produce endogenous vitamin D via cutaneous production and rely solely on dietary intake of vitamin D. The seasonal variation of vitamin D seen in humans due to changes in UV exposure therefore is unlikely to be replicated in these animals.ObjectivesThe objective of this study was to investigate the natural variation in 25-hydroxyvitamin-D concentration in dogs subject to seasonal UV exposure.MethodsThis longitudinal study followed 18 healthy dogs fed a standardized diet over one year, with blood samples obtained monthly. Two key vitamin D metabolites, 25-hydroxyvitamin-D2 and 25-hydroxyvitamin-D3, were assessed by liquid chromatography tandem mass spectrometry in serum samples. Various other biochemical parameters were also measured. Seasonality was assessed using Cosinor statistical analysis.ResultsAlthough the dogs were subject to seasonally varying UV radiation, 25-hydroxyvitamin-D and related biomarkers (including calcium and parathyroid hormone) remained stable over time and did not follow a seasonal pattern. 25-hydroxyvitamin-D was not positively correlated to exposure to UV radiation. Nonetheless, variation in 25-hydroxyvitamin-D concentration between individual dogs was detected.ConclusionsGiven the standardization of diet, we concluded that the seasonal stability of 25-hydroxyvitamin-D concentration (vitamin D status) was likely a direct result of lack of cutaneous vitamin D production in this species and highlights the importance of dietary intake. The variation in 25-hydroxyvitamin-D concentration between animals warrants further investigatio

In view of the challenges of the current coronavirus (COVID-19) pandemic and to protect both patients and ultrasound providers (physicians, sonographers, allied professionals), ISUOG has compiled the following expert-opinion-based guidance for the performance of ultrasound investigations in pregnancy and for gynecological indications.

The severe acute respiratory syndrome coronavirus (SARS‐CoV‐2), an enveloped virus, is the causative agent of the disease known as COVID‐19 (coronavirus disease‐2019). Proper infection prevention and control measures and good hygiene practices are essential to prevent spread of COVID‐19 and protect both patients and the healthcare worker. These guidelines are relevant to all ultrasound practitioners and provides guidance on cleaning and disinfection of ultrasound equipment, the environment and PPE (protective personal equipment) during the COVID‐19 outbreak in the Australasian region.

Background Ultrasound probe covers should be used for any ultrasound procedure where there is contact with body fluids or mucous membranes. The type and quality of probe covers used in clinical practice differ widely and studies in the early 1990s showed that condoms were more superior for use with transvaginal examinations than commercial probe covers. Since then, although products have changed, there have been no further studies to assess the breakage rate of different probe covers. The objectives of this study were to assess the integrity of the most commonly used probe covers for transvaginal ultrasound examinations under clinical conditions and report the breakage rate. Methods The study was conducted in public and private hospitals and private practices. A total of 500 covers for each of 10 brands of commercial covers and condoms (latex and latex free) were distributed to ultrasound practitioners. The transvaginal ultrasound examination practice was unchanged except that all covers were placed in a container for assessment instead of discarding post ultrasound examination. All covers were collected and subjected to a water leak test. Covers that broke upon deployment onto the ultrasound probe prior to the ultrasound examination were recorded. All covers that were broken or had microtears or leaks were recorded as well as photographed. Statistical analysis was performed along with Chi-squared analysis of the data and significance considered at P Results None of the commercial covers broke upon deployment onto the ultrasound probe prior to ultrasound examination. A total of 5000 probe covers were examined post-transvaginal ultrasound examinations. The breakage rate for condoms ranged from 0.4% to 13% and for commercial covers 0–5%. Statistical analysis of the data by comparison of p-values revealed that the best performing group were the commercial non-latex probe covers and worst performing group were the non-latex condoms. Conclusion The breakage rates for commercial covers were not as high as previously reported and do not break upon deployment onto the ultrasound probe. This is the first comprehensive study that thoroughly evaluated the integrity of commercial covers and condoms used for transvaginal ultrasound examination in a clinical setting, with regards to brand, numbers and types of covers assessed.

Multi-strain, host-disease dynamics describe a system where multiple strains of a pathogen compete for susceptible individuals of a single host. The theoretical properties of these systems have been well studied, but there are few empirical studies in wildlife hosts. We examined the impacts of two novel strains of rabbit haemorrhagic disease virus (RHDV) recently introduced into Australia, one inadvertently (RHDV2) and one deliberately for rabbit biocontrol (RHDV-K5), by analysing long-term monitoring data for introduced European rabbits (Oryctolagus cuniculus) from 18 sites throughout Australia. We examined population-level impacts using rabbit spotlight counts pre- and post-arrival of the two strains. We also analysed serological data to determine potential interactions among the introduced and existing field strains of RHDV, as well as a pre-existing benign strain of calicivirus (RCV-A1). Serological analyses suggested that RHDV2 arrived in Australia during spring 2014 and spread rapidly through the Australian rabbit population within two years. Following the establishment of RHDV2, rabbit abundance was reduced by an average of 60%, with impacts most pronounced in southern and western Australia. In contrast, the deliberate release of RHDV-K5 had little impact on rabbit populations. Although RHDV2 has spread rapidly throughout Australia, our serological analyses do not support the observation that RHDV2 is rapidly replacing existing field strains of RHDV, as was previously reported in Australia and Europe. Nevertheless, RHDV2 has negatively impacted the ability of RHDV and RCV-A1 to spread within rabbit populations, most likely due to its ability to infect juvenile rabbits, thereby removing them from the pool of susceptible individuals available to be infected by competing strains. Synthesis and applications. The impact of the release of a novel strain of rabbit haemorrhagic disease virus (RHDV-K5) for rabbit biocontrol in Australia has been suppressed by the emergence of a competing strain, RHDV2. Hence, the success of further releases of similar RHDV strains for rabbit biocontrol appear doubtful. Despite this, RHDV2 has suppressed rabbit abundances by an average of 60%, with impacts most pronounced in southern and western Australia. Whether the incursion of RHDV2 leads to the competitive exclusion of other endemic RHDV strains remains to be resolved. However, the existence of partial cross-immunity could allow some level of coexistence between RHDV2 and RHDV strains, at least in the medium term.

Retinal detachment is a serious and common condition, but genetic studies to date have been hampered by the small size of the assembled cohorts. In the UK Biobank dataset, where retinal detachment was ascertained by self-report or hospital records, genetic correlations between retinal detachment and high myopia or cataract operation were respectively 0.46 (SE=0.08) and 0.44 (SE=0.07). These correlations are consistent with known epidemiological associations. Through meta-analysis of genome-wide association studies using UK Biobank retinal detachment cases (N=3977) and two cohorts, each comprising ~1000 clinically-ascertained rhegmatogenous retinal detachment patients, we uncovered 11 genome-wide significant association signals. These are near or within ZC3H11B, BMP3, COL22A1, DLG5, PLCE1, EFEMP2, TYR, FAT3, TRIM29, COL2A1 and LOXL1. Replication in the 23andMe dataset, where retinal detachment is self-reported by participants, firmly establishes six retinal detachment risk loci: FAT3, COL22A1, TYR, BMP3, ZC3H11B and PLCE1. Based on the genetic associations with eye traits described to date, the first two specifically impact risk of a retinal detachment, while the last four point to shared aetiologies with macular condition, myopia and glaucoma. Fine-mapping prioritised the lead common missense variant (TYR S192Y) as causal variant at the TYR locus and a small set of credible causal variants at the FAT3 locus. The larger study size presented here, enabled by resources linked to health records or self-report, provides novel insights into retinal detachment aetiology and underlying pathological pathways.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

To genetically assess the Australian distribution and frequency of Eimeria species in wild rabbits, with a primary focus on Eimeria intestinalis and Eimeria flavescens as possible additional agents of rabbit biocontrol, the distal colon and faecal samples from wild rabbits sourced from 26 Australian locations with mean annual rainfalls of between 252 mm and 925 mm were analysed using amplicon sequencing of the ITS1 region. Contrary to previous microscopy studies which had only detected E. flavescens on mainland Australia at Wellstead in south-west Western Australia, we detected this species at all 23 effectively sampled sites. The more pathogenic E. intestinalis was only found at 52.2% of sites. Three unique Eimeria genotypes were detected that did not align to the 11 published sequences using a pairwise-match threshold of 90%, and may represent unsequenced known species or novel species. One genotype we termed E. Au19SH and was detected at 20 sites, E. Au19CO was detected at eight sites, and E. Au19CN was detected in one rabbit at Crows Nest (Qld). Site diversity ranged from only five Eimeria species at Boboyan (ACT) to 13 unique sequences at Cargo (NSW). Eimeria diversity in individual rabbits ranged from 11 unique sequences in a rabbit at Wellstead (WA) and a rabbit at Cargo (NSW), to one in 17 rabbits and zero in six rabbits. The three rabbit age classes averaged 4.3 Eimeria species per rabbit. No relationship was found between the number of Eimeria species detected and mean annual rainfall. As Eimeria species were found to be fairly ubiquitous at most sites they appear to be an unlikely additional candidate to assist the control of pest rabbits in Australia.

A growing body of evidence indicates a potential role for the gut-brain axis as a novel therapeutic target in treating seizures. The present study sought to characterize the gut microbiome in Theiler murine encephalomyelitis virus (TMEV)-induced seizures, and to evaluate the effect of microbial metabolite S-equol on neuronal physiology as well as TMEV-induced neuronal hyperexcitability ex vivo.We infected C57BL/6J mice with TMEV and monitored the development of acute behavioral seizures 0-7 days postinfection (dpi). Fecal samples were collected at 5-7 dpi and processed for 16S sequencing, and bioinformatics were performed with QIIME2. Finally, we conducted whole-cell patch-clamp recordings in cortical neurons to investigate the effect of exogenous S-equol on cell intrinsic properties and neuronal hyperexcitability.We demonstrated that gut microbiota diversity is significantly altered in TMEV-infected mice at 5-7 dpi, exhibiting separation in beta diversity in TMEV-infected mice dependent on seizure phenotype, and lower abundance of genus Allobaculum in TMEV-infected mice regardless of seizure phenotype. In contrast, we identified specific loss of S-equol-producing genus Adlercreutzia as a microbial hallmark of seizure phenotype following TMEV infection. Electrophysiological recordings indicated that exogenous S-equol alters cortical neuronal physiology. We found that entorhinal cortex neurons are hyperexcitable in TMEV-infected mice, and exogenous application of microbial-derived S-equol ameliorated this TMEV-induced hyperexcitability.Our study presents the first evidence of microbial-derived metabolite S-equol as a potential mechanism for alteration of TMEV-induced neuronal excitability. These findings provide new insight for the novel role of S-equol and the gut-brain axis in epilepsy treatment.

The increasing popularity of citizen science in ecological research has created opportunities for data collection from large teams of observers that are widely dispersed. We established a citizen science program to complement the release of a new variant of the rabbit biological control agent, rabbit haemorrhagic disease virus (RHDV), known colloquially as K5, across Australia. We evaluated the impact of K5 on the national rabbit population and compared citizen science and professionally-collected spotlight count data. Of the citizen science sites (n = 219), 93% indicated a decrease in rabbit abundance following the release of K5. The overall finite monthly growth rate in rabbit abundance was estimated as 0.66 (95%CI, 0.26, 1.03), averaging a monthly reduction of 34% at the citizen science sites one month after the release. No such declines were observed at the professionally monitored sites (n = 22). The citizen science data submissions may have been unconsciously biased or the number of professional sites may have been insufficient to detect a change. Citizen science participation also declined by 56% over the post-release period. Future programs should ensure the use of blinded trials to check for unconscious bias and consider how incentives and/or the good will of the participants can be maintained throughout the program.