Adult pilomyxoid astrocytoma presenting in the temporal lobe.

Pilomyxoid astrocytoma (PMA) is a rare variant of astrocytoma that is usually present in the hypothalamic and chiasmatic areas in the paediatric population. PMA shares many similar histopathological features to Pilocytic astrocytoma (PA), with some notable differences in its radiological and histopathological findings. On the contrary, PMA has been reported to behave more aggressively in its clinical progression than PA. Here, we describe a rare case of PMA in a 25-year-old female involving the temporal lobe, presenting with recurrent partial seizures. To our knowledge, this is the first reported case of PMA presenting in the temporal lobe in an adult female with an atypical location of the tumour, uncommon age group, and unusual radiological features being unique in this case report.

Development and Implementation of Dried Blood Spot-Based COVID-19 Serological Assays for Epidemiologic Studies.

Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at-home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months postinfection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an 8-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible. IMPORTANCE Estimation of community-level antibody responses to SARS-CoV-2 from infection or vaccination is critical to inform public health responses. Traditional studies of antibodies rely on collection of blood via venipuncture, an invasive procedure not amenable to pandemic-related social-distancing measures. Dried blood spots (DBS) are an alternative to venipuncture, since they can be self-collected by study participants at home and do not require refrigeration for shipment or storage. However, DBS-based assays to measure antibody levels to SARS-CoV-2 have not been widely utilized. Here, we show that DBS are comparable to blood as a sampling method for antibody responses to SARS-CoV-2 infection and vaccination over time measured using four distinct serological assays. The DBS format enabled antibody surveillance in a longitudinal cohort where study participants self-collected samples, ensuring the participants' safety during an ongoing pandemic. Our work demonstrates that DBS are an excellent sampling method for measuring antibody responses whenever venipuncture is impractical.

Microscale residual stresses in additively manufactured stainless steel.

Additively manufactured (AM) metallic materials commonly possess substantial microscale internal stresses that manifest as intergranular and intragranular residual stresses. However, the impact of these residual stresses on the mechanical behaviour of AM materials remains unexplored. Here we combine in situ synchrotron X-ray diffraction experiments and computational modelling to quantify the lattice strains in different families of grains with specific orientations and associated intergranular residual stresses in an AM 316L stainless steel under uniaxial tension. We measure pronounced tension-compression asymmetries in yield strength and work hardening for as-printed stainless steel, and show they are associated with back stresses originating from heterogeneous dislocation distributions and resultant intragranular residual stresses. We further report that heat treatment relieves microscale residual stresses, thereby reducing the tension-compression asymmetries and altering work-hardening behaviour. This work establishes the mechanistic connections between the microscale residual stresses and mechanical behaviour of AM stainless steel.

Effects of pH on the Antibiotic Resistance of Bacteria Recovered from Diabetic Foot Ulcer Fluid An In Vitro Study.

BACKGROUND: This study investigated the resistance of bacteria isolated from diabetic foot ulcers (DFUs) to antibiotics frequently used in the management of the diabetic foot infections, at a range of pH values (pH 6.5, 7.5, and 8.5) known to exist in DFU wound fluid. This study aimed to determine whether changes (or atypical stasis) in wound fluid pH modulate the antibiotic resistance of DFU isolates, with potential implications in relation to the suppression/eradication of bacterial infections in DFUs. METHODS: Thirty bacterial isolates were recovered from DFU wound fluid, including Staphylococcus spp, Staphylococcus aureus, Escherichia coli, Streptococcus spp, Pseudomonas spp, and Pseudomonas aeruginosa. The resistances of these isolates to a panel of antibiotics currently used in the treatment of infected or potentially infected DFUs, ie, ciprofloxacin, amoxicillin-clavulanate, doxycycline, and piperacillin-tazobactam, at the previously mentioned pH values were determined by a modification of the Kirby-Bauer assay. RESULTS: The resistance of DFU isolates to clinically relevant antibiotics was significantly affected by the pH levels in DFU wound fluid. CONCLUSIONS: These findings highlight the importance of a more comprehensive understanding of the conditions in DFUs to inform clinical decision making in the selection and application of antibiotics in treating these difficult-to-heal wounds. The scale of the differences in the efficacies of antibiotics at the different pH values examined is likely to be sufficient to suggest reconsideration of the antibiotics of choice in the treatment of DFU infection.

Application-Specific Computational Materials Design via Multiscale Modeling and the Inductive Design Exploration Method (IDEM).

The development of materials is a laborious, iterative, expensive, and intuitive process, often requiring decades to transition from early laboratory studies to commercial applications. This research seeks to address this issue by demonstrating a systematic process for linking process-structure-property-performance (PSPP) relations. We argue that the limitations on time for the material development process arise in large part due to lack of effective approaches for exploring the material design space that anticipates application requirements, objectives, and constraints. The material design process employed here utilizes hierarchical multiscale modeling, analytical models, and associated metamodels to construct a set of bottom-up deductive mappings, along with the inductive design exploration method (IDEM) to account for uncertainty in pursuing top-down inductive decision support problems that address application-specific design objectives. The demonstrated problem considers the simultaneous design of ultra-high-performance concrete material and a structural panel able to withstand a 1.5-MPa-ms reflected blast wave impulse. A set of PSPP mappings were constructed across micro-, meso-, and macro-length-scales using analytical expressions and a hierarchical multiscale finite element model at the single fiber, multiple fiber, and structural length scales. The set of PSPP deductive mappings considered seven design variables-panel thickness, fiber pitch, ratio of water to cementitious materials, curing temperature, and volume fractions of fibers, cement, and silica fume-across four hierarchical levels. After the set of deductive PSPP mappings were constructed and validated, ranged sets of feasible values for each design variable were determined via IDEM. Starting with the highest and next-to-higher hierarchical levels as the output and input spaces, respectively, IDEM was implemented via application of three steps-discretization of input variables, projection of discretized sets of input variables with account of uncertainty to a range in the output space, and determination of which sets of discrete input values satisfy the output space requirement(s). By recursively applying these three steps, the PSPP relations were robustly searched for properties, structures, and processes that satisfy the performance requirement(s). The advantages of this approach are the identification of ranged sets of values of design variables and the ability to account for propagated uncertainty. By defining additional mass and cost objectives, the feasible input space was then searched to find the preferred combination of values of design variables that minimized mass and minimized cost while maintaining a robust material and structural design.

External ventricular drain infections at the Canberra Hospital: A retrospective study.

External ventricular drains (EVD) are crucial for the emergency management of hydrocephalus and raised intracranial pressure. Infection is the most morbid and costly cause of EVD malfunction and can cost up to $50,000 US to treat per case. In 2007, Canberra Hospital changed EVD management protocols requiring set-up of EVD transducer systems in theatre, cessation of prophylactic antibiotics after 24hours, cerebrospinal fluid (CSF) samples second or third daily and discontinuation of elective EVD changes. The current study aimed to retrospectively audit EVD inserted between 2006 and 2010 in order to determine the impact of these changes. There was a non-significant downward trend in infection rates from 20.93% to 11.50% (p=0.343) after the protocol changes. Patient age (OR=1.032, p=0.064, confidence interval (CI): 0.998-1.067) and sex (OR=1.405, p=0.595, CI: 0.401-4.917) were not significantly associated with infection. However, multiple drains were associated with a significant increase in infections rates (OR=21.96, p=0.001, CI: 6.103-79.023) and systemic perioperative antibiotic prophylaxis was associated with decreased rates of infections (OR=0.269, p=0.044, CI: 0.075-0.964). Our study showed a non-significant downwards trend in infections with introduction of changes to hospital protocol and illustrated some risk factors for infection in the Australian setting.

Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature.

BACKGROUND/OBJECTIVES: Nitrous oxide (N2 O) is known to have abuse potential, although debate regarding the toxic effects of such abuse continues. Our objective was to review the case literature and present the neurologic, psychiatric and medical consequences of N2 O abuse. METHODS: A systematic literature review was completed for case reports using keywords "nitrous oxide" with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction." Non-English-language cases and cases not involving direct toxic effects of N2 O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2 O abuse, laboratory studies, imaging, ancillary tests, treatments and outcomes were collected from case reports. RESULTS: Our review returned 335 Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey Literature results, and after exclusion and removal of duplicates, 91 individual cases across 77 publications were included. There were also 11 publications reporting 29 cases of death related to N2 O abuse. The majority of cases (N = 72) reported neurologic sequelae including myeloneuropathy and subacute combined degeneration, commonly (N = 39) with neuroimaging changes. Psychiatric (N = 11) effects included psychosis while other medical effects (N = 8) included pneumomediastinum and frostbite. Across all cases N2 O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally elevated homocysteine and methylmalonic acid. CONCLUSIONS/SCIENTIFIC SIGNIFICANCE: N2 O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict 2016;25:358-369).

Chemomechanical Origin of Hydrogen Trapping at Grain Boundaries in fcc Metals.

Hydrogen embrittlement of metals is widely observed, but its atomistic origins remain little understood and much debated. Combining a unique identification of interstitial sites through polyhedral tessellation and first-principles calculations, we study hydrogen adsorption at grain boundaries in a variety of face-centered cubic metals of Ni, Cu, γ-Fe, and Pd. We discover the chemomechanical origin of the variation of adsorption energetics for interstitial hydrogen at grain boundaries. A general chemomechanical formula is established to provide accurate assessments of hydrogen trapping and segregation energetics at grain boundaries, and it also offers direct explanations for certain experimental observations. The present study deepens our mechanistic understanding of the role of grain boundaries in hydrogen embrittlement and points to a viable path towards predictive microstructure engineering against hydrogen embrittlement in structural metals.

Protein, cell and bacterial response to atmospheric pressure plasma grafted hyaluronic acid on poly(methylmethacrylate).

Hyaluronic acid (HA) has been immobilised on poly(methyl methacrylate) (PMMA) surfaces using a novel dielectric barrier discharge (DBD) plasma process for the purposes of repelling protein, cellular and bacterial adhesion in the context of improving the performance of ophthalmic devices. Grafting was achieved by the following steps: (1) treatment of the PMMA with a DBD plasma operating at atmospheric pressure, (2) amine functionalisation of the activated polymer surface by exposure to a 3-aminopropyltrimethoxysilane (APTMS) linker molecule and (3) reaction of HA with the surface bound amine. The mechanism and effectiveness of the grafting process was verified by surface analysis. XPS data indicates that the APTMS linker molecule binds to PMMA via the Si-O chemistry and has the required pendant amine moiety. The carboxylic acid moiety on HA then binds with this -NH2 group via standard carbodiimide chemistry. ToF-SIMS confirms the presence of a coherent HA layer the microstructure of which is verified by AFM. The plasma grafted HA coating surfaces showed a pronounced decrease in protein and cellular adhesion when tested with bovine serum albumin and human corneal epithelial cells, respectively. The ability of these coatings to resist bacterial adhesion was established using Staphylococcus aureus NTC8325. Interestingly, the coatings did not repel bacterial adhesion, indicating that the mechanism of adhesion of bacterial cells is different to that for the surface interactions of mammalian cells. It is proposed that this difference is a consequence of the specific HA conformation that occurs under the conditions employed here. Hence, it is apparent that the microstructure/architecture of the HA coatings is an important factor in fabricating surfaces intended to repel proteins, mammalian and bacterial cells.

The pH of wound fluid in diabetic foot ulcers -- the way forward in detecting clinical infection?

Infections within diabetic foot ulcers are often hard to detect and extremely difficult to treat. The normal signs and symptoms of infection including purulence, erythema, pain, tenderness, warmth and induration are frequently absent in such wounds necessitating exploration of other ways of rapidly and accurately detecting infection. This study considers diabetic wound fluid pH as a possible alternative means of monitoring infection status. CINAHL, Ovid SP and MEDLINE were searched for papers in English published between January 2004 to May 2014. Key search terms included wound fluid, exudate, wound, ulcer, diabetes, pH, healing, infection, bacteria. This paper considers the potential benefits of augmenting and supporting current clinical practice in the early determination of wound healing trajectory and infection status, by monitoring wound fluid pH. The evidence collected highlights the need for further research and suggests the potential of wound fluid analysis as a possible surrogate marker for detecting infection in diabetic foot ulcers.

A randomized, double-blind, placebo-controlled trial of venlafaxine for the treatment of depressed cocaine-dependent patients.

OBJECTIVE: This study tested the hypothesis that the antidepressant venlafaxine would be an effective treatment for cocaine abusers with concurrent depressive disorders. METHODS: This was a randomized, 12-week, double-blind, placebo-controlled trial of outpatients (N = 130) meeting DSM-IIIR criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with venlafaxine, up to 300 mg/day versus placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included Clinical Global Impression Scale (CGI), self-reported cocaine use, urine toxicology and the Hamilton Depression Scale (Ham-D). RESULTS: Mood response, defined as a 50% reduction in the Ham-D between randomization and end of study, was 41% (26/64) on venlafaxine, and 33% (22/66) on placebo (p = .39). Measures of depression (Ham-D and CGI) improved more rapidly on venlafaxine than placebo, but these differences disappeared by weeks 6-8. Cocaine outcomes did not differ between treatment groups, and the proportion of patients achieving three or more consecutive weeks of urine-confirmed abstinence was low (venlafaxine: 16%; placebo: 15%). Reduction in cocaine use was associated with mood response. CONCLUSIONS: Overall, venlafaxine was not superior to placebo on either mood or cocaine use outcomes. Mood improvement was associated with improvement in cocaine use. However, placebo mood response was only moderate, and the proportion of patients achieving sustained abstinence was low. This suggests that the subgroup of cocaine-dependent patients with depressive disorders is relatively treatment resistant, and that further research is needed to improve outcomes for these patients.

A study of Salmonella in pigs from birth to carcass: serotypes, genotypes, antibiotic resistance and virulence profiles.

A study was undertaken to investigate Salmonella in pigs at each step from birth to carcass. Environmental and/or pig samples were taken at birth, farrowing, 1st weaning, 2nd weaning, finishing, transport, lairage, bleeding and chilling of carcasses and tested for Salmonella. All isolates were characterised in terms of serotype, phage type (where relevant) and subtyping with pulsed field gel electrophosesis (PFGE). Isolates were tested for antibiotic resistance, resistance (intI1, bla(CIT), bla(Tem), bla(PSE-1), bla(OXA-1), floR, catA1, aadA1, aadA2, tetA, tetB, tetG, sul1and aphA1) and virulence (invA, rck, spvC and pefA) genes. PCR was also performed to test for the presence of the left junction, thdF-S001 and the right junction, S004-int2 or S004-yidY of Salmonella genomic island 1 (SGI1). Overall 4.3%, 27.5% and 5% of environmental, throat/rectal and carcass samples were Salmonella positive, respectively. S. Typhimurium DT193 was detected during production, while S. Typhimurium DT17 and U311 were present in lairage at the abattoir, where strain characterisation suggested cross contamination of the live animals occurred. The carcasses were also cross contaminated with S. Brandenburg during processing. PFGE grouped the isolates by serotype and/or phage type. The DT193 isolates displayed the ACSSuTTmMn/Gm resistance phenotype and carried the invA, spvC, rck, bla-tem, aadA2, tetA, strA virulence/antibiotic resistance markers; U311 showed an ASSuTMn resistance pattern and carried invA and tetB; DT17 was sensitive to all antibiotics tested but invA, spv and rck positive while S. Brandenburg displayed neither resistance nor virulence gene carriage. None of the isolates possessed class 1 integrons and all isolates were negative for the left and right junctions of SGI1. It was concluded that control activities should target improved biosecurity at farm level and better sanitation in lairage. This study also provides further evidence that multiple drug resistance may be associated with non-SGI1 Salmonella strains. The continued emergence of non-DT104 S. Typhimurium isolates exhibiting multidrug resistance is a cause for concern as is the persistence of highly virulent Salmonella strains in the abattoir environment.

Thermal inactivation of Yersinia enterocolitica in pork slaughter plant scald tank water.

The objective of this study was to establish the time-temperature combinations required to ensure the thermal inactivation of Yersinia enterocolitica during scalding of pork carcasses. A 2 strain cocktail of Y. enterocolitica (bioserotypes 2/O:5,27 and 1A/O:6,30) was heat treated at 50, 55 and 60°C in samples of scald tank water obtained from a commercial pork slaughter plant. Samples were removed at regular intervals and surviving cells enumerated using (i) Cefsulodin-Irgasan-Novobiocin Agar (CIN) supplemented with ampicillin and arabinose and (ii) Tryptone Soya Agar (TSA), overlaid with CIN agar with ampicillin and arabinose. The data generated was used to estimate D- and z-values and the formula Dx=log(-1)(log D60-((t2-t1)/z)) was applied to calculate thermal death time-temperature combinations from 55 to 65°C. D50, D55 and D60-values of 45.9, 10.6 and 2.7min were calculated from the cell counts obtained on CIN agar, respectively. The corresponding D-values calculated from the TSA/CIN counts were 45.1, 11 and 2.5min, respectively. The z-value was 7.8. It was concluded that a time-temperature combination of 2.7min at 60°C is required to achieve a 1 log reduction in Y. enterocolitica in pork scald tank water. The predicted equivalent at 65°C was 0.6min. This study provides data and a model to enable pork processors to identify and apply parameters to limit the risk of carcass cross-contamination with Y. enterocolitica in pork carcass scald tanks.

Characterization of farm, food, and clinical Shiga toxin-producing Escherichia coli (STEC) O113.

Thirty-nine Shiga toxin-producing Escherichia coli (STEC) O113 Irish farm, abattoir, and clinical isolates were analyzed in conjunction with eight Australian, New Zealand, and Norwegian strains for H (flagellar) antigens, virulence gene profile (eaeA, hlyA, tir, espA, espB katP, espP, etpD, saa, sab, toxB, iha, lpfA(O157/OI-141,) lpfA(O113,) and lpfA(O157/OI-154)), Shiga toxin gene variants (stx(1c), stx(1d), stx(2), stx(2c), stx(2dact), stx(2e), stx(2f,) and stx(2g)) and were genotyped using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All of the Irish strains were O113:H4, regardless of source, while all non-Irish isolates carried the H21 flagellar antigen. The stx(1) gene was present in 30 O113:H4 strains only, whereas the stx(2d) gene was common to all isolates regardless of source. In contrast, eaeA was absent, while hlyA was found in the Australian, New Zealand, Norwegian, and two of the Irish human clinical isolates. saa was present in the O113:H21 but not in the O113:H4 serotype. To the best of the author's knowledge, this is the first report of clinically significant STEC lacking both the eaeA and saa genes. PFGE analysis was inconclusive; however, MLST grouped the strains into three sequence types (ST): ST10, ST56, and ST223. Based on our findings, it was concluded that the stx(2d) gene is common in STEC O113, which are generally eaeA negative. Furthermore, STEC O113:H4 is a new, emerging bovine serotype of human clinical significance.

Serotypes and virulotypes of non-O157 shiga-toxin producing Escherichia coli (STEC) on bovine hides and carcasses.

Four hundred and fifty beef animal hides and a similar number of carcasses were screened for STEC in 3 beef abattoirs over a 12 month period using PCR and culture based methods. 67% (301/450) of hides and 27% (122/450) of carcasses were STEC PCR positive. Forty isolates representing 12 STEC serotypes (O5:H-, O13:H2, O26:H11, O33:H11, O55:H11, O113:H4, O128:H8, O136:H12, O138:H48, O150:H2, O168:H8 and ONT:H11) and 15 serotype-virulotype combinations were identified. This study provides much needed non-O157 STEC surveillance data and also provides further evidence of bovines as a source of clinically significant STEC as well as identifying 3 emerging serotypes O5:H- (eae-ß1), O13:H2 (eae-ζ), and O150:H2 (eae-ζ) that should be considered when developing beef testing procedures for non-O157 STEC.

UVc-irradiation sublethal stress does not alter antibiotic susceptibility of staphylococci (MRSA, MSSA, and coagulase-negative staphylococci) to ß-lactam, macrolide, and fluoroquinolone antibiotic agents.

Skin tanning, either by exposure to natural sunlight or through use of UV sunbeds, has become a popular practice in the US, where it is estimated that approximately 1 million times per day someone in the US uses UV radiation for skin tanning, equating to 30 million Americans (circa 10% of the US population) who use a tanning bed. As well as exposing the host to periods of UV radiation, such practices also expose commensal skin bacteria, including Staphylococcus aureus, to such UV radiation. Previous work has indicated that environmental stresses on bacteria may lead to an upregulation of stress responses, in an attempt for the organism to combat the applied stress and remain viable. UV light may act as an environmental stress on bacteria, and so it was the aim of this study to examine the effect of UVc light on the antibiotic susceptibility of commensal skin bacteria, to determine if UV radiation would increase the antibiotic resistance of such skin flora and thus lead to a potential skin flora with increased antibiotic resistance. Previously, it has been shown that UVc light has a greater mutational effect on bacteria compared to lower-energy UV forms, including UVa and UVb light. Therefore, we decided to employ UVc light in our study to amplify the potential for mutational events occurring in skin staphylococci organisms (n=8) including methicillin-sensitive Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (n=4), and coagulase-negative staphylococci (Staphylococcus haemolyticus) (n=2) were exposed to varying degrees of sublethal radiation via UVc light, and their minimum inhibitory concentration (MIC) susceptibility was determined by broth dilution assay against three classes of commonly used antibiotics, namely ß-lactams (penicillin), macrolides (erythromycin), and fluoroquinolones (ciprofloxacin). There was no significant difference between antibiotic susceptibility before UVc exposure and until maximum sublethal stress, prior to cell death due to fatal UVc exposure with the cells. These results indicate that UV environmental stress/exposure does not upregulate antibiotic resistance, and therefore these data indicate that UVc radiation does not lead to a more antibiotic-resistant population in the staphylococci organisms post-exposure.