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Background: The residency program director (PD) position is a valued leadership appointment in academic medicine. PDs are responsible for the success of their program and its residents. The objective of this study is to provide a cross-sectional analysis of baseline demographics and academic backgrounds of current neurosurgery program directors., Methods: Data was compiled on neurosurgery PDs and their residency programs, as of the end of May 2021, using publicly available resources including Doximity, FREIDA, and Healthgrades. The Mann-Whitney and Fisher exact tests were used for statistical analysis., Results: Of 113 PDs identified, 91.15% are male (P < 0.01). The majority of PDs (88.5%) received their medical degrees from U.S. medical schools. The average age of current PDs is 54 years, and the average age at appointment was 48 years. Compared to their male counterparts, female PDs are more likely to be younger at appointment (41 vs. 48 years; P = 0.001) and while holding the same position (45 vs. 55 years; P = 0.001). As a result, female PDs experience less time to appointment after residency (8.6 years vs. 14.7 years, P = 0.013). There are no significant differences regarding the gender of the PD and university affiliation, current appointment, completion of a fellowship, and resident gender ratios., Conclusions: The position of neurosurgery residency PD is dominated by fellowship-trained men in their late 40s to 50s. The gender ratio of neurosurgery residents is consistent with the underrepresentation of women in this position. With increasing female representation in neurosurgery, more women may assume this leadership position and begin to hasten the gender balance., (Copyright © 2022. Published by Elsevier Inc.)

Abstract Efficient manufacture of recombinant adeno-associated virus (rAAV) vectors for gene therapy remains challenging. Packaging cell lines containing stable integration of the AAV rep/cap genes have been explored, however rAAV production needs to be induced using wild-type adenoviruses to promote episomal amplification of the integrated rep/cap genes by mobilizing a cis-acting replication element (CARE). The adenovirus proteins responsible are not fully defined, and using adenovirus during rAAV manufacture leads to contamination of the rAAV preparation. ‘TESSA’ is a helper adenovirus with a self-repressing Major Late Promoter (MLP). Its helper functions enable efficient rAAV manufacture when the rep and cap genes are provided in trans but is unable to support rAAV production from stable packaging cells. Using rAAV-packaging cell line HeLaRC32, we show that expression of the adenovirus L4 22/33K unit is essential for rep/cap amplification but the proteins are titrated away by binding to replicating adenovirus genomes. siRNA-knockdown of the adenovirus DNA polymerase or the use of a thermosensitive TESSA mutant decreased adenovirus genome replication whilst maintaining MLP repression, thereby recovering rep/cap amplification and efficient rAAV manufacture. Our findings have direct implications for engineering more efficient adenovirus helpers and superior rAAV packaging/producer cells.

Abstract The removal of toxic dye pigments from the environment is of utmost importance since even trace amounts of these pollutants can lead to harmful impacts on ecosystems. Heterogeneous photocatalysis is a potential technique for eliminating microbiological, inorganic, and organic pollutants from wastewater. Here, we report the band gap alteration of ZnO by making its composites with CuSe to enhance photocatalytic activity. The purpose is to develop metal oxide nanocomposites (ZnO/CuSe) as an effective and efficient material for the photodegradation of methyl blue. The photocatalysts, ZnO nanorods, CuSe, and ZnO/CuSe nanocomposites of different weight ratios were synthesized by the simple and cost-effective technique of precipitation. UV–Vis spectra verified that the ZnO/CuSe photocatalyst improved absorption in the visible region. The optical bandgap of ZnO/CuSe nanocomposites reduced from 3.37 to 2.68 eV when CuSe concentration increased from 10 to 50%. ZnO/CuSe composites demonstrated better photocatalytic activity than ZnO when exposed to UV–visible light. The pure ZnO nanorods could absorb UV light and the nanocomposites could absorb visible light only; this was attributed to the transfer of excited high-energy electrons from ZnO to CuSe.

Abstract Active machine learning is widely used in computational studies where repeated numerical simulations can be conducted on high performance computers without human intervention. But translation of these active learning methods to physical systems has proven more difficult and the accelerated pace of discoveries aided by these methods remains as yet unrealized. Through the presentation of a general active learning framework and its application to large-scale boundary layer wind tunnel experiments, we demonstrate that the active learning framework used so successfully in computational studies is directly applicable to the investigation of physical experimental systems and the corresponding improvements in the rate of discovery can be transformative. We specifically show that, for our wind tunnel experiments, we are able to achieve in approximately 300 experiments a learning objective that would be impossible using traditional methods.

Faisalabad is a major industrial area in Pakistan’s Punjab province that discharges wastewater into the Chenab River. Industrial effluents in Faisalabad are predicted to pose a significant threat to the riparian vegetation of the Chenab River and nearby vegetation. Heavy metal pollution of plants, water, and soils is one of the biggest problems worldwide that needs to be addressed because heavy metals above normal levels are extremely dangerous to both riparian vegetation and wildlife. The results indicated high levels of pollution in the industrial effluents as well as in the river in terms of salinity, metal toxicity, TSS, TDS, SAR, the acidic and alkaline nature of the industrial effluents, and the spread of industrial effluents up to 15 square kilometres in the Chenab River. Despite the higher pollution, four plants were found at all sites: Calotropis procera, Phyla nodiflora, Eclipta alba and Ranunculus sceleratus. It was found that most of the selected plants were phytoaccumulators, making them best suited to survive in harsh environments such as those with industrial pollution. The Fe concentration in the plant constituents was the highest, along with Zn, Pb, Cd, and Cu, all of which were above the permissible limits of the WHO. The metal transfer factor (MTF) was higher in most of the plants studied, and even exceeded 10 at some severely affected sites. Calotropis procera proved to be the most suitable plant for growth on drainage systems and also at river sites, as it had the highest importance value across all sites and seasons.

Introduction: Geriatric patients are often frail and may lose independence through a variety of mechanisms including cognitive decline, reduced mobility, and falls. Our goal was to measure the effect of a multidisciplinary home health program that assessed frailty and safety and then coordinated ongoing delivery of community resources on short-term, all-cause emergency department (ED) utilization across three study arms that attempted to stratify frailty by fall risk. Methods: Subjects became eligible for this prospective observational study via one of three pathways: 1) by visiting the ED after a fall (2,757 patients); 2) by self-identifying as at risk for falling (2,787); or 3) by calling 9-1-1 for a “lift assist” after falling and being unable to get up (121). The intervention consisted of sequential home visits by a research paramedic who used standardized assessments of frailty and risk of falling (including providing home safety guidance), and a home health nurse who aligned resources to address the conditions found. Outcomes of interest were all-cause ED utilization at 30, 60, and 90 days post-intervention compared with subjects who enrolled via the same study pathway but declined the study intervention (controls). Results: Subjects in the fall-related ED visit arm were significantly less likely to have one or more subsequent ED encounters post-intervention than controls at 30 days (18.2% vs 29.2%, P

Cholesteatoma is a rare progressive disease of the middle ear. Most cases are sporadic, but some patients report a positive family history. Identifying functionally important gene variants associated with this disease has the potential to uncover the molecular basis of cholesteatoma pathology with implications for disease prevention, surveillance, or management. We performed an observational WES study of 21 individuals treated for cholesteatoma who were recruited from ten multiply affected families. These family studies were complemented with gene-level mutational burden analysis. We also applied functional enrichment analyses to identify shared properties and pathways for candidate genes and their products. Filtered data collected from pairs and trios of participants within the ten families revealed 398 rare, loss of function (LOF) variants co-segregating with cholesteatoma in 389 genes. We identified six genes DENND2C, DNAH7, NBEAL1, NEB, PRRC2C, and SHC2, for which we found LOF variants in two or more families. The parallel gene-level analysis of mutation burden identified a significant mutation burden for the genes in the DNAH gene family, which encode products involved in ciliary structure. Functional enrichment analyses identified common pathways for the candidate genes which included GTPase regulator activity, calcium ion binding, and degradation of the extracellular matrix. The number of candidate genes identified and the locus heterogeneity that we describe within and between multiply affected families suggest that the genetic architecture for familial cholesteatoma is complex.

Bergmann's and Allen's rules predict changes in body size and appendage length across temperature gradients for species with broad geographic distributions. Larger bodies and longer limbs facilitate cooling whereas smaller bodies and compact limbs limit heat loss. Although these patterns are highly repeatable (hence "rules" of ecology) the patterns and underlying mechanisms are less-well understood in humans. Here I show that variation in running performance among human male triathletes is consistent with both Bergmann's and Allen's rules. Males (but not females) with relatively larger body size and longer limbs performed better at hot compared to cold race venues and vice-versa. Consistent with results in other taxa, sex-specificity may reflect selection for sexual dimorphism. Results suggest that ecological patterns detected over large-spatial scales may arise from fine-scale variation in locomotor performance.

The Paediatric and congenital Interventional Cardiology Early-Career Society (PICES) was conceived in a hallway conversation during the 2011 Society for Cardiovascular Angiography and Interventions (SCAI) meeting in Baltimore, MD and was subsequently formally established in July of 2011 [1]. Since its inception, the organization has focused on promoting clinical education, fostering multicentre research collaboration, developing leadership skills, and promoting professional networking among the early-career (within 10 years of their training) paediatric/congenital interventional cardiologists as well as fellows-in-training. Membership is available free of charge to anyone in congenital cardiology training, congenital interventional cardiology training, or an interventional cardiology faculty early within their career. PICES is a special interest group of the SCAI, and multiple previous and current PICES executive committee members have served on the Congenital Heart Disease (CHD) council of the SCAI. Currently the society consists of more than 200 members with approximately 60% United States and 40% international representation.

Abstract Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer’s disease.

The foundation of wisdom is rooted in experience, and thus we reflexively call upon our senior leaders, mentors, coaches, and family members for guidance in our personal and professional lives. Witnessing the weathered perspectives of others allows for an internal audit of one’s own strengths and deficiencies, which ultimately inspires personal growth. This experience is heightened when both the mentor and the mentee, for example, share a common goal. The field of congenital interventional cardiology, with its constant evolution and diverse technical approaches, requires a lifetime of learning, as well as safe passage of knowledge to the next generation. While there are published recommendations for what to consider when completing this task, hearing the sentiments of those with experience may be more profitable for future fellows and current interventionalists. In part one of a series, we hope to accomplish this goal by presenting an opportunity to learn from our experienced colleagues on the topic of congenital interventional cardiology training. Specifically, we aim to share expert opinions on how to succeed as a congenital interventional fellow, illustrate the diversity of teaching styles and expectations in various healthcare systems, and for the mid-career interventionalists, provide insight into the character traits of a successful mentor of interventional fellows.

Introduction Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs—to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.Methods and analysis In this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care.Ethics and dissemination This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS.

Although combat has been found to be associated with adverse health outcomes, little is known about the impact of specific combat exposures, particularly among specialized personnel. This study examined the association of different types of combat exposures with behavioral health outcomes, and whether these associations differed by Army occupational specialization: General Purpose Forces infantrymen (n = 5,361), Ranger Qualified infantrymen (n = 308), and Special Forces personnel (n = 593). Multivariable regression models estimated the association of combat severity, type of combat event (fighting, killing, threat to oneself, death/injury of others), and type of killing with mental health disorders, trouble sleeping, and problem drinking. Combat severity, each type of combat event, and killing noncombatants were associated with adverse health outcomes after adjusting for covariates and other combat exposures. Except for trouble sleeping, these associations did not differ by occupational specialization, though the prevalence and odds of outcomes were generally lower for Special Forces personnel.

Background: Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model, and then examined the feasibility of modelling stroke in such rats. Methods: Twelve-month old male Wistar-Han rats (n=15) were fed a 60% fat diet for 8 months during which monthly serial blood samples were taken to assess the development of metabolic syndrome and pro-inflammatory markers. Following this, to pilot the suitability of these rats for undergoing surgical models of stroke, they underwent 30min of middle cerebral artery occlusion (MCAO) alongside younger controls fed a standard diet (n=10). Survival, weight and functional outcome were monitored, and blood vessels and tissues collected for analysis. Results: A high fat diet in aged rats led to substantial obesity. These rats did not develop type 2 diabetes or hypertension. There was thickening of the thoracic arterial wall and vacuole formation in the liver; but of the cytokines examined changes were not seen. MCAO surgery and behavioural assessment was possible in this model (with some caveats discussed in manuscript). Conclusions: This study shows MCAO is possible in aged, obese rats. However, this model is not ideal for recapitulating the complex comorbidities commonly seen in stroke patients.

We tested the efficacy of a stereo camera (SC) system adapted for use with a remotely operated vehicle (ROV) to estimate fish length distributions at reef sites in the northern Gulf of Mexico. A pool experiment was conducted to test the effect of distance (1, 2, 3 or 5 m), angle of incidence (AOI; 0° to 40° at 5° increments), and SC baseline distance (BD; BD1 = 406, BD2 = 610, and BD3 = 762 mm camera separation) on the accuracy and precision of fish model length (288, 552, or 890 mm fork length) estimates compared to a red laser scaler (RLS). A field experiment was then conducted at 20 reef sites with SCs positioned at BD1 to compare fish length distribution estimates between the SC and RLS systems under in situ conditions. In the pool experiment, mean percent errors were consistently within the a priori selected threshold of ±5% at AOIs ≤10° at all distances with all four systems. However, SCs produced accurate estimates at AOIs up to 30° at all distances tested; 2-3 m was optimal. During reef site surveys, SCs collected 10.4 times as many length estimates from 4.3 times as many species compared to the RLS. Study results demonstrate that, compared to laser scalers, ROV-based SC systems can substantially increase the number of available fish length estimates by producing accurate length estimates at a wider range of target orientations while also enabling measurements from a greater portion of the cameras' field of view.

Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function.

Abstract Background There is no ‘gold-standard’ for the evaluation of dexterity for the health professional or podiatrist populations. This has resulted in a broad array of generalised tests to evaluate dexterity. Thus, the aim was to determine which objective generalised dexterity tests are best suited to evaluating dexterity in a podiatry student population. Methods A cohort of Novice podiatry students and Experienced podiatrists were recruited and evaluated on a battery of dexterity tests selected to evaluate a variety of different elements. Group differences were evaluated statistically and regression undertaken on significant test outcomes. Results A total of 108 participants were recruited with 54 participants in each of the Novice and Experienced groups. Five of the eight tests were able to discriminate dexterous ability of participants in the Novice and Experienced groups. These included the Grip-lift task, GPT, P-MVC, G-MVC and the AsTex® sensory discrimination test. These tests comprised a total of 11 significant dependent variables (p

Abstract Background Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice. Methods Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15–21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses. Results We found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p

Medication-induced cutaneous hyperpigmentation has variable clinical presentations and is dependent on the specific drug involved. Most commonly, an attentive patient observes such changes early in the course; when missed by the patient, such changes are usually noted by an observant clinician. Clinical diagnosis can be challenging if the patient is on multiple medications because other causes must be excluded. This condition occurs via multiple mechanisms. Frequently, the pigmentary change is reversible with discontinuation of the drug. Causative medications include nonsteroidal; anti-inflammatory agents, antimalarials, antibiotics, psychotropics, amiodarone, and chemotherapeutic agents. The; antimicrobials responsible for hyperpigmentation are antimalarials, tetracyclines, tigecycline, dapsone, rifampicin, and antiretrovirals such as zidovudine. Sunlight exposure can worsen the pigmentation seen with some of the above antimicrobials (e.g., dapsone). Here, we describe an older adult white woman presenting with acute cutaneous; hyperpigmentation of the bilateral lower extremities while on levofloxacin therapy. Hyperpigmentation resolved after cessation of the agent. Our case highlights this unique acute presentation after only a few days of oral levofloxacin.

Background: Surgical and transcatheter bioprosthetic valves (BPVs) in the pulmonary position in patients with congenital heart disease may ultimately fail and undergo transcatheter reintervention. Angiographic assessment of the mechanism of BPV failure has not been previously described. Aims: The aim of this study was to determine the mode of BPV failure (stenosis/regurgitation) requiring transcatheter reintervention and to describe the angiographic characteristics of the failed BPVs and report the types and efficacy of reinterventions. Materials and Methods: This is a retrospective single-center review of consecutive patients who previously underwent pulmonary BPV placement. (surgical or transcatheter) and subsequently underwent percutaneous reintervention from 2005 to 2014. Results: Fifty-five patients with surgical. (41) and transcutaneous pulmonary valve. (TPV) (14) implantation of BPVs underwent 66 catheter reinterventions. The surgically implanted valves underwent fifty reinterventions for indications including 16 for stenosis, seven for regurgitation, and 27 for both, predominantly associated with leaflet immobility, calcification, and thickening. Among TPVs, pulmonary stenosis. (PS) was the exclusive failure mode, mainly due to loss of stent integrity. (10) and endocarditis. (4). Following reintervention, there was a reduction of right ventricular outflow tract gradient from 43 ± 16 mmHg to 16 ± 10. mmHg (P < 0.001) and RVp/AO ratio from 0.8 ± 0.2 to 0.5 ± 0.2 (P < 0.001). Reintervention with TPV placement was performed in 45. (82%) patients. (34 surgical, 11 transcatheter) with no significant postintervention regurgitation or paravalvular leak. Conclusion: Failing surgically implanted BPVs demonstrate leaflet calcification, thickness, and immobility leading to PS and/or regurgitation while the mechanism of TPV failure in the short- to mid-term is stenosis, mainly from loss of stent integrity. This can be effectively treated with a catheter.based approach, predominantly with the valve-in-valve technique.

Access to therapeutic oxygen remains a challenge in the effort to reduce pneumonia mortality among children in low- and middle-income countries. The use of oxygen concentrators is common, but their effectiveness in delivering uninterrupted oxygen is gated by reliability of the power grid. Often cylinders are employed to provide continuous coverage, but these can present other logistical challenges. In this study, we examined the use of a novel, low-pressure oxygen storage system to capture excess oxygen from a concentrator to be delivered to patients during an outage. A prototype was built and tested in a non-clinical trial in Jinja, Uganda. The trial was carried out at Jinja Regional Referral Hospital over a 75-day period. The flow rate of the unit was adjusted once per week between 0.5 and 5 liters per minute. Over the trial period, 1284 power failure episodes with a mean duration of 3.1 minutes (range 0.08 to 1720 minutes) were recorded. The low-pressure system was able to deliver oxygen over 56% of the 4,295 power outage minutes and cover over 99% of power outage events over the course of the study. These results demonstrate the technical feasibility of a method to extend oxygen availability and provide a basis for clinical trials.

In animals, color signals that convey information about quality are often associated with costs linked to the expression of coloration and may therefore be honest signals of sender quality. Honest indicators are often seen in sexual signals that are used by males to advertise quality to females. Carotenoid and pterin pigments are responsible for yellow, orange, and red coloration in a variety of taxa, but can also serve important roles as antioxidants by reducing free radicals in the body. In this study, we test the effects of a novel full-bodied orange color phenotype of the brown anole, Anolis sagrei, on mate choice, physiology, and survival. We found no evidence that lizards expressing the orange phenotype were preferred by females. Additionally, they did not differ in immune function, running endurance, or maximum sprint speed from lizards that did not express the novel phenotype. Pigment extractions revealed that orange body coloration resulted from pterin pigments and not carotenoids. Visual models suggest that the orange phenotype is less conspicuous to bird predators than the brown phenotype and may provide an adaptive explanation for the persistence of this trait. Given its small, yet positive effect on fitness, we expect the orange color phenotype to increase in frequency in subsequent decades.

Nocardia spp. are worldwide, ubiquitous zoonotic bacteria that have the ability to infect humans as well as domestic animals. Herein, we present a case of a five-year-old female spayed domestic shorthair cat (from the island of Nevis) with a history of a traumatic skin wound on the ventral abdomen approximately two years prior to presenting to the Ross University Veterinary Clinic. The cat presented with severe dermatitis and cellulitis on the ventral caudal abdomen, with multiple draining tracts and sinuses exuding purulent material. Initial bacterial culture yielded Corynebacterum spp. The patient was treated symptomatically with antibiotics for 8 weeks. The cat re-presented 8 weeks after the initial visit with worsening of the abdominal lesions. Surgical intervention occurred at that time, and histopathology and tissue cultures confirmed the presence of Nocardia spp.-induced pyogranulomatous panniculitis, dermatitis, and cellulitis. Pre-operatively, the patient was found to be feline immunodeficiency virus (FIV)-positive. The patient was administered trimethoprim/sulfamethoxazole (TMS) after antimicrobial sensitivity testing. PCR amplification and 16S rRNA gene sequencing confirmed Nocardia jiangxiensis as the causative agent. To our knowledge, N. jiangxiensis has not been previously associated with disease. This case report aims to highlight the importance of a much-needed One Health approach using advancements in technology to better understand the zoonotic potential of Nocardia spp. worldwide.

Planctomycetes are distinguished from other Bacteria by compartmentalization of cells via internal membranes, interpretation of which has been subject to recent debate regarding potential relations to Gram-negative cell structure. In our interpretation of the available data, the planctomycete Gemmata obscuriglobus contains a nuclear body compartment, and thus possesses a type of cell organization with parallels to the eukaryote nucleus. Here we show that pore-like structures occur in internal membranes of G.obscuriglobus and that they have elements structurally similar to eukaryote nuclear pores, including a basket, ring-spoke structure, and eight-fold rotational symmetry. Bioinformatic analysis of proteomic data reveals that some of the G. obscuriglobus proteins associated with pore-containing membranes possess structural domains found in eukaryote nuclear pore complexes. Moreover, immunogold labelling demonstrates localization of one such protein, containing a β-propeller domain, specifically to the G. obscuriglobus pore-like structures. Finding bacterial pores within internal cell membranes and with structural similarities to eukaryote nuclear pore complexes raises the dual possibilities of either hitherto undetected homology or stunning evolutionary convergence.

The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface. Liposomal vaccine particles were engineered to display the malaria circumsporozoite (CSP) antigen on their surface, with helper CD4+ epitopes from distinct vaccine or viral antigens contained within the particle core, ensuring the B cell response is raised but focused against CSP. In vivo vaccination studies were then conducted in C57Bl/6 mice as models of either vaccine-induced pre-existing CD4+ T cell immunity (using ovalbumin-OVA) or virus-induced pre-existing CD4+ T cell immunity (murine cytomegalovirus-MCMV). Following the establishment of pre-existing by vaccination (OVA in the adjuvant TiterMax® Gold) or infection with MCMV, mice were administered CSP-coated liposomal vaccines containing the relevant OVA or MCMV core CD4+ T cell epitopes. In mice with pre-existing anti-OVA CD4+ T cell immunity, these vaccine particles elicited rapid, high-titre, isotype-switched CSP-specific antibody responses-consistent with the involvement of anti-OVA T helper cells in confirming activation of anti-CSP B cells. Responses were further improved by entrapping TLR9 agonists, combining humoral vaccination signals 'one', 'two' and 'three' within one particle. Herpes viruses can establish chronic infection and elicit significant, persistent cellular immune responses. We then demonstrate that this principle can be extended to re-purpose pre-existing anti-MCMV immunity to enhance anti-CSP vaccine responses-the first description of a strategy to specifically exploit anti-cytomegalovirus immunity to augment vaccination against a target antigen.

Gaseous oxidized mercury (GOM) dry deposition measurements using aerodynamic surrogate surface passive samplers were collected in central and eastern Texas and eastern Oklahoma, from September 2011 to September 2012. The purpose of this study was to provide an initial characterization of the magnitude and spatial extent of ambient GOM dry deposition in central and eastern Texas for a 12-month period which contained statistically average annual results for precipitation totals, temperature, and wind speed. The research objective was to investigate GOM dry deposition in areas of Texas impacted by emissions from coal-fired utility boilers and compare it with GOM dry deposition measurements previously observed in eastern Oklahoma and the Four Corners area. Annual GOM dry deposition rate estimates were relatively low in Texas, ranging from 0.1 to 0.3 ng/m2h at the four Texas monitoring sites, similar to the 0.2 ng/m2h annual GOM dry deposition rate estimate recorded at the eastern Oklahoma monitoring site. The Texas and eastern Oklahoma annual GOM dry deposition rate estimates were at least four times lower than the highest annual GOM dry deposition rate estimate previously measured in the more arid bordering western states of New Mexico and Colorado in the Four Corners area.

Fertilization is followed by complex changes in cytoplasmic composition and extensive chromatin reprogramming which results in the abundant activation of totipotent embryonic genome at embryonic genome activation (EGA). While chromatin reprogramming has been widely studied in several species, only a handful of reports characterize changing transcriptome profiles and resulting metabolic changes in cleavage stage embryos. The aims of the current study were to investigate RNA profiles of in vivo developed (ivv) and in vitro produced (ivt) porcine embryos before (2-cell stage) and after (late 4-cell stage) EGA and determine major metabolic changes that regulate totipotency. The period before EGA was dominated by transcripts responsible for cell cycle regulation, mitosis, RNA translation and processing (including ribosomal machinery), protein catabolism, and chromatin remodelling. Following EGA an increase in the abundance of transcripts involved in transcription, translation, DNA metabolism, histone and chromatin modification, as well as protein catabolism was detected. The further analysis of members of overlapping GO terms revealed that despite that comparable cellular processes are taking place before and after EGA (RNA splicing, protein catabolism), different metabolic pathways are involved. This strongly suggests that a complex metabolic switch accompanies EGA. In vitro conditions significantly altered RNA profiles before EGA, and the character of these changes indicates that they originate from oocyte and are imposed either before oocyte aspiration or during in vitro maturation. IVT embryos have altered content of apoptotic factors, cell cycle regulation factors and spindle components, and transcription factors, which all may contribute to reduced developmental competence of embryos produced in vitro. Overall, our data are in good accordance with previously published, genome-wide profiling data in other species. Moreover, comparison with mouse and human embryos showed striking overlap in functional annotation of transcripts during the EGA, suggesting conserved basic mechanisms regulating establishment of totipotency in mammalian development.

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3' un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3' UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×10(10) viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets.

The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC) is approved for the treatment of myelodysplastic syndromes (MDS), but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS.We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance). We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM) analysis of global methylation in secondary resistance.Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P

Invasive species can dramatically impact natural populations, especially those living on islands. Though numerous examples illustrate the ecological impact of invasive predators, no study has examined the genetic consequences for native populations subject to invasion. Here we capitalize on a natural experiment in which a long-term study of the brown anole lizard (Anolis sagrei) was interrupted by rat invasion. An island population that was devastated by rats recovered numerically following rat extermination. However, population genetic analyses at six microsatellite loci suggested a possible loss of genetic diversity due to invasion when compared to an uninvaded island studied over the same time frame. Our results provide partial support for the hypothesis that invasive predators can impact the genetic diversity of resident island populations.