Bone flap infections after craniotomy: a review of 63 cases and the implications for definitions, classification and surveillance methodologies.

BACKGROUND: Bone flap infections (BFIs) occur following neurosurgical procedures such as craniotomies. However, they are poorly defined and often not clearly differentiated from other surgical site infection in neurosurgery. AIM: To review data from a national adult neurosurgical centre to explore some clinical aspects to better inform definitions, classification and surveillance methodologies. METHODS: We retrospectively reviewed data on clinical samples sent for culture from patients with suspected BFI. We also accessed information recorded prospectively from national and local databases for evidence of BFI or related conditions based on terms used in surgical operative notes or discharge summaries and documented monomicrobial and polymicrobial infections related to craniotomy sites. FINDINGS: Between January 2016 and December 2020, we documented 63 patients with a mean age of 45 years (16-80). Craniectomy for infection of the skull was the most common terminology used to describe BFI in the coding used in a national database, 40/63 (63%), but other terms were used. A malignant neoplasm was the most common underlying condition necessitating craniectomy in 28/63 (44%) cases. Specimens submitted for microbiological investigation included 48/63 (76%) bone flaps, 38/63 (60%) fluid/pus, and 29/63 (46%) tissue. Fifty-eight (92%) patients had at least one culture-positive specimen; 32 (55%) were monomicrobial and 26 (45%) were polymicrobial. Gram-positive bacteria predominated and Staphylococcus aureus was the most common. CONCLUSION: Greater clarity on how to define BFI is required to enable better classification and the carrying out of appropriate surveillance. This will inform preventative strategies and more effective patient management.

A decade of Clostridioides difficile infection: a constant challenge to maintain the status quo.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea. We retrospectively investigated data from a comprehensive, multidisciplinary C. difficile surveillance programme focusing on hospitalized patients in a tertiary Irish hospital over 10 years. METHODS: Data from 2012 to 2021 were extracted from a centralized database, including patient demographics, admission, case and outbreak details, ribotypes (RTs), and (since 2016) antimicrobial exposures and CDI treatments. Counts of CDI by origin of infection were explored using ꭓ2 analyses, Poisson regression was used to investigate trends in rates of CDI and possible risk factors. Time to recurrent CDI was examined by a Cox proportional hazards regression. RESULTS: Over 10 years, 954 CDI patients had a 9% recurrent CDI rate. CDI testing requests occurred in only 22% of patients. Most CDIs were HA (82.2%) and affected females (odds ratio: 2.3, P<0.01). Fidaxomicin significantly reduced the hazard ratio of time to recurrent CDI. No trends in HA-CDI incidence were observed despite key time-point events and increasing hospital activity. In 2021, community-associated (CA)-CDI increased. RTs did not differ for HA versus CA for the most common RTs (014, 078, 005 and 015). Average length-of-stay differed significantly between HA (67.1 days) and CA (14.6 days) CDI. CONCLUSION: HA-CDI rates remained unchanged despite key events and increased hospital activity, whereas by 2021, CA-CDI was at its highest in a decade. The convergence of CA and HA RTs, and the proportion of CA-CDI, question the relevance of current case definitions when increasingly patients receive hospital care without an overnight hospital stay.

Pattern formation in Faraday instability-experimental validation of theoretical models.

Two types of resonance-derived interfacial instability are reviewed with a focus on recent work detailing the effect of side walls on interfacial mode discretization. The first type of resonance is the mechanical Faraday instability, and the second is electrostatic Faraday instability. Both types of resonance are discussed for the case of single-frequency forcing. In the case of mechanical Faraday instability, inviscid theory can forecast the modal forms that one might expect when viscosity is taken into account. Experiments show very favourable validation with theory for both modal forms and onset conditions. Lowering of gravity is predicted to shift smaller wavelengths or choppier modes to lower frequencies. This is also validated by experiments. Electrostatic resonant instability is shown to lead to a pillaring mode that occurs at low wavenumbers, which is akin to Rayleigh Taylor instability. As in the case of mechanical resonance, experiments show favourable validation with theoretical predictions of patterns. A stark difference between the two forms of resonance is the observation of a gradual rise in the negative detuning instability in the case of mechanical Faraday and a very sharp one in the case of electrostatic resonance. This article is part of the theme issue 'New trends in pattern formation and nonlinear dynamics of extended systems'.

Multidisciplinary neurosurgical rounds incorporating antimicrobial stewardship. Are they of benefit?

Background: In an era of increasing antimicrobial resistance, appropriate antimicrobials are essential to optimise patient outcomes. In 2017, antimicrobial use prevalence (AMU) on the two neurosurgical wards in our tertiary teaching hospital varied from 23% on ward A to 33% on ward B with 67% and 100% 'appropriate' prescriptions, respectively. In July 2018, a weekly antimicrobial stewardship multidisciplinary round led by a senior neurosurgery registrar commenced, attended by the antimicrobial stewardship team (AST). Research question: This report evaluates whether a multi-disciplinary approach on neurosurgical prescribing was beneficial, specifically in reducing AMU. Materials and methods: The following data was collected on AST rounds for 30 weeks in total from August 2018 to July 2019: number of patients on antimicrobials, appropriateness and stewardship actions. A questionnaire was distributed to neurosurgical doctors on two occasions to canvass opinions and attitudes on antimicrobial prescribing. Results: 1716 prescriptions were reviewed (mean 57.2 per week). Of these 321 (18.7%) included antimicrobial prescriptions; 200 on ward A (19.8%), and 121 on ward B (17%), representing a decrease in AMU from 2017. The majority of antimicrobial prescriptions, 271 (84.4%) were deemed appropriate. Stewardship actions were taken in 215 (67%) prescriptions.Fifteen questionnaires were completed by neurosurgical doctors. The majority, 87%, stated the AST round was helpful overall. 93% indicated that informal training on the AST round was a source of education in antibiotic prescribing. Discussion and conclusion: The weekly AST round provided a timely opportunity for multidisciplinary discussion, implementation of antimicrobial stewardship actions and opportunistic antimicrobial stewardship education.

Rapid Synthesis of the epi-Biotin Sulfone via Tandem S,N-Carbonyl Migration/aza-Michael/Spirocyclization and Haller-Bauer Reaction.

A synthesis of 2-epi-biotin sulfone was accomplished from commercially available l-cysteine. The synthesis features an unprecedented tandem S,N-carbonyl migration/aza-Michael/spirocyclization reaction from an l-cysteine-derived enone with aq. ammonia, in which three new sigma bonds and two rings are formed. In addition, the synthesis includes a highly diastereoselective late-stage Haller-Bauer reaction of sulfone for direct introduction of the carbon side chain.

Receptor based virtual screening of potential novel inhibitors of tigar [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator.

TP53 (tumor protein 53)-induced glycolysis and apoptosis regulator (TIGAR) belongs to the phosphatases family of proteins that modulates the level of reactive oxygen species in tumor cells. This protein plays a vital role as a negative regulator of glycolysis, thus lowering ROS levels in the cells, which helps the cancerous cells to resist programmed cell death. Besides, TIGAR also mediates the DNA damage repair in cancer cells by increasing tumor cell survival. In the current study, we have screened natural products that compete with the substrate to bind to the active site of TIGAR. Extra precision and MMGBSA scoring function were used to screen the lead molecules. Five compounds were considered as lead molecules with 2-(2-(3,4-dihydroxy phenyl)-3,5-dihydroxy-8-(4-hydroxyphenyl)-4-oxo-4H-furo[2,3-h]chromen-9-yl) acetic acid(DDFA) as a top lead with a docking score of -9.428, and -53.16 MMGBSA, bind to the positively charged amino acids present in the active site. Further, the molecular dynamics simulation studies indicated the structural stability attained by TIGAR protein upon the binding of DDFA, suggesting it to be a potent inhibitor of TIGAR, and could be employed as an anticancer drug during combinational therapy.

Primary pyogenic ventriculitis caused by Streptococcal pneumoniae in adults.

Primary pyogenic ventriculitis is more commonly manifested in children. Its presentation in adults due to Streptococcus pneumonia is rarely reported. It is mainly due to adequate vaccination cover and initiation of appropriate antibiotics. Ventriculitis is one of the complications of bacterial meningitis, requires long-term antibiotics and surgical intervention. Here, we are reporting a 67-year-old diabetic lady presented with a decrease in sensorium, seizure, and fever, diagnosed as bacterial ventriculitis. Her cerebro spinal fluid (CSF) picture suggestive of pyogenic meningitis, CSF, blood culture grew Streptoccous pneumoniae; MRI revealed -ventriculitis. She was treated with Injection Ceftriaxazone for 6 week duration. Serial MRI showed clearing of ventricular debris and she improved. This highlights the atypical presentation of pyogenic meningitis without nuchal rigidity, status epilepticus, and clinical improvement without the need of surgical intervention.

Food for thought. Malnutrition risk associated with increased risk of healthcare-associated infection.

BACKGROUND: Infection and malnutrition are interconnected. UK and Irish guidelines recommend the Malnutrition Universal Screening Tool (MUST) for nutritional risk screening. Patients with a MUST score of ≥2 are considered at high risk of malnutrition and referral for nutritional assessment is recommended. AIM: To explore the association between healthcare-associated infection (HCAI) and the MUST score categories of patients. METHODS: This was a cross-sectional study in May 2017 on ten representative wards in our institution. Patient demographics, MUST score, presence of medical devices, HCAI and antimicrobial use were collected. FINDINGS: Of 240 patients, the HCAI prevalence was 10.4% (N = 25) and 26% (N = 63) were at high risk of malnutrition (MUST score ≥2). Patients with HCAI were more likely to have had surgery (odds ratio (OR): 5.5; confidence interval (CI): 2.1-14.3; P < 0.001), a central vascular catheter (OR: 10.0; CI: 3.6-27.2; P < 0.001), or a urinary catheter in situ (OR: 7.5; CI: 2.8-20.0; P < 0.001), and to have a high risk of malnutrition (OR: 4.3; CI: 1.7-11.2; P < 0.001). A higher MUST score remained a significant predictor of a patient having HCAI on multivariate regression analysis (CI: 0.2-0.6; P < 0.001). CONCLUSION: Patients at risk of malnutrition when assessed with the MUST were more likely to have HCAI. However, prospective studies are required to investigate the temporal association between MUST and HCAI and which interventions best address malnutrition risk and HCAI reduction in different settings.

Bacteraemia in the ED: Are We Meeting Targets?

AIM: An audit was performed in an Irish Emergency department (ED) to evaluate adherence to established antimicrobial guidelines and to determine the most common presentations of sepsis. METHODS: Data on ED patients with clinically significant bacteraemia on blood cultures were recorded for three months . The antimicrobial given to the patient was compared to that which the hospital guidelines would recommend for the ED diagnosis. RESULTS: Eleven patients out of 53 had no antimicrobial guidelines for diagnosis. Of the 42/53 patients, non-adherence to antimicrobial guidelines by physicians was observed in 81% (n=34/42) patients and adherence was observed in 19% (n=8/42) patients. Escherichia coli 35.70% (n=18), was the most frequent organism isolated. CONCLUSIONS: Non-adherence to antimicrobial guidelines resulted in 68% (n=23/34) of organisms covered by the antibiotic. Adherence to antimicrobial guidelines resulted in 87% (n=7/8) of organisms covered by the antibiotic.

Effect of soluble surfactants on the stability of stratified flows through soft-gel-coated walls.

The effect of a soluble surfactant on the linear stability of layered two-phase Poiseuille flows through soft-gel-coated parallel walls is studied in this paper. The focus is on determining the effect of the elastohydrodynamic coupling between the fluids and the soft-gel layers on the various flow instabilities. The fluids are assumed Newtonian and incompressible, while the soft gels are modeled as linear viscoelastic solids. The effect of a soluble surfactant on the different instabilities is specifically investigated. The soft-gel-coated plates are maintained at two different solute concentrations. The dynamics of the soluble surfactant in the fluids is captured using a species transport equation. A linear stability analysis is carried out to identify different instabilities in the system. The linearized governing equations are solved numerically using a Chebyshev spectral Collocation technique. The effect of deformability of the soft gels on three distinct instability modes, (a) a liquid-liquid long-wave mode, (b) a liquid-liquid short-wave mode, and (c) a liquid-liquid Marangoni short-wave mode, is analyzed. An analytical expression for the growth rate is obtained in the long-wave length limit using an asymptotic analysis. From the long-wave analysis a stability map is obtained, in which dominant effects in different regions are identified. The Marangoni stresses can either stabilize or destabilize the interfacial instability depending on the direction of mass transfer. They have a predominantly stabilizing effect on the interfacial instability when the mass transfer is from the more viscous broader fluid to the less viscous thinner fluid. Placing a gel closer to the more viscous fluid has a stabilizing effect on this instability. The Marangoni stresses and soft-gel layers can have opposing effects on the stability of the long-wave mode. The dominant of these two opposing effects is determined by the prevailing parameters. Insights into the dominant physical causes of different instabilities are presented.

Modeling reproduction of whitetail deer and its applications.

Many environmental factors, such as annual precipitation, temperature variations, and the embedded stochasticity of natural systems, affect resource availability from one region to the next, such that animal survival and reproduction rates differ by region. For species exhibiting phenotypic plasticity, embedding phenotypes in a model of population dynamics becomes important, as region-driven plastic responses play a significant role when estimating parameters values. In this paper, we discuss how to include observable characteristics and climate patterns in estimates of reproduction rates of whitetail deer (Odocoileus virginianus). Using many studies already available in the literature, we establish a strong correlation between reproduction rate and both body weight and USDA plant hardiness zone. We demonstrate the accuracy of the estimated whitetail deer fecundity rates for various geographical regions in North America and show that Bergmann's rule is necessary to maintain similar biological fitness between various spatial distributions of deer populations. We demonstrate that the standard deviation of the weight distribution has almost no effect on reproduction rate estimates for adult deer populations. However, statistical analysis reveals sensitivity of fawn reproduction rates to environmental stochasticity. We incorporate the reproduction function in a stage- and gender-based model and prove the existence of a stable solution. Finally, we demonstrate a possible application of the model using harvested deer weights, without collecting reproduction data directly.

Syn vs Anti Carboxylic Acids in Hybrid Peptides: Experimental and Theoretical Charge Density and Chemical Bonding Analysis.

A comparative study of syn vs anti carboxylic acids in hybrid peptides based on experimental electron density studies and theoretical calculations shows that, in the anti form, all three bond angles surrounding Ccarboxyl of the -COOH group are close to ∼120°, as expected for a C-sp2 atom, whereas in the syn form, the ∠Cα-C(O)-Ohydroxyl angle is significantly smaller by 5-10°. The oxygen atom in the carboxyl group is more electronegative in the anti form, so the polarity of the acidic O-H bond is higher in the anti form compared to the syn form, as observed within the limitations of H atom treatment in X-ray diffraction. Consequently, the investigated anti carboxylic acid forms the strongest O-H···O hydrogen bond among all model compounds. Furthermore, according to natural bond orbital analysis, the oxygen lone pairs are clearly nonequivalent, as opposed to the general notion of hybridization of equivalent sp2 and sp3 lone pairs on carbonyl or hydroxyl oxygen atoms. The hybridization of the lone pairs is directly related to the directionality and strength of hydrogen bonds.

Using measured stocks of biomass and litter carbon to constrain modelled estimates of sequestration of soil organic carbon under contrasting mixed-species environmental plantings.

Reforestation of agricultural land with mixed-species environmental plantings of native trees and shrubs contributes to abatement of greenhouse gas emissions through sequestration of carbon, and to landscape remediation and biodiversity enhancement. Although accumulation of carbon in biomass is relatively well understood, less is known about associated changes in soil organic carbon (SOC) following different types of reforestation. Direct measurement of SOC may not be cost effective where rates of SOC sequestration are relatively small and/or highly spatially-variable, thereby requiring intensive sampling. Hence, our objective was to develop a verified modelling approach for determining changes in SOC to facilitate the inclusion of SOC in the carbon accounts of reforestation projects. We measured carbon stocks of biomass, litter and SOC (0-30cm) in 125 environmental plantings (often paired to adjacent agricultural sites), representing sites of varying productivity across the Australian continent. After constraining a carbon accounting model to observed measures of growth, allocation of biomass, and rates of litterfall and litter decomposition, the model was calibrated to maximise the efficiency of prediction of SOC and its fractions. Uncertainties in both measured and modelled results meant that efficiencies of prediction of SOC across the 125 contrasting plantings were only moderate, at 39-68%. Data-informed modelling nonetheless improved confidence in outputs from scenario analyses, confirming that: (i) reforestation on agricultural land highly depleted in SOC (i.e. previously under cropping) had the highest capacity to sequester SOC, particularly where rainfall was relatively high (>600mmyear-1), and; (ii) decreased planting width and increased stand density and the proportion of eucalypts enhanced rates of SOC sequestration. These results improve confidence in predictions of SOC following environmental reforestation under varying conditions. The calibrated model will be a useful tool for informing land managers and policy makers seeking to understand the dynamics of SOC following such reforestation.

The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading.

Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loading, however, promotes steatohepatitis, an advanced stage of chronic liver disease that precedes hepatocellular carcinoma (HCC), by depleting mitochondrial GSH (mGSH) due to a cholesterol-mediated impairment in mGSH transport. Whether and how HCC cells overcome the restriction of mGSH transport imposed by mt-cholesterol loading to support mGSH uptake remains unknown. Although the transport of mGSH is not fully understood, SLC25A10 (dicarboxylate carrier, DIC) and SLC25A11 (2-oxoglutarate carrier, OGC) have been involved in mGSH transport, and therefore we examined their expression and role in HCC. Unexpectedly, HCC cells and liver explants from patients with HCC exhibit divergent expression of these mitochondrial carriers, with selective OGC upregulation, which contributes to mGSH maintenance. OGC but not DIC downregulation by siRNA depleted mGSH levels and sensitized HCC cells to hypoxia-induced ROS generation and cell death as well as impaired cell growth in three-dimensional multicellular HCC spheroids, effects that were reversible upon mGSH replenishment by GSH ethyl ester, a membrane permeable GSH precursor. We also show that OGC regulates mitochondrial respiration and glycolysis. Moreover, OGC silencing promoted hypoxia-induced cardiolipin peroxidation, which reversed the inhibition of cholesterol on the permeabilization of MOM-like liposomes induced by Bax or Bak. Genetic OGC knockdown reduced the ability of tumor-initiating stem-like cells to induce liver cancer. These findings underscore the selective overexpression of OGC as an adaptive mechanism of HCC to provide adequate mGSH levels in the face of mt-cholesterol loading and suggest that OGC may be a novel therapeutic target for HCC treatment.

Rapid prediction of particulate, humus and resistant fractions of soil organic carbon in reforested lands using infrared spectroscopy.

Reforestation of agricultural lands with mixed-species environmental plantings can effectively sequester C. While accurate and efficient methods for predicting soil organic C content and composition have recently been developed for soils under agricultural land uses, such methods under forested land uses are currently lacking. This study aimed to develop a method using infrared spectroscopy for accurately predicting total organic C (TOC) and its fractions (particulate, POC; humus, HOC; and resistant, ROC organic C) in soils under environmental plantings. Soils were collected from 117 paired agricultural-reforestation sites across Australia. TOC fractions were determined in a subset of 38 reforested soils using physical fractionation by automated wet-sieving and 13C nuclear magnetic resonance (NMR) spectroscopy. Mid- and near-infrared spectra (MNIRS, 6000-450 cm-1) were acquired from finely-ground soils from environmental plantings and agricultural land. Satisfactory prediction models based on MNIRS and partial least squares regression (PLSR) were developed for TOC and its fractions. Leave-one-out cross-validations of MNIRS-PLSR models indicated accurate predictions (R2 > 0.90, negligible bias, ratio of performance to deviation > 3) and fraction-specific functional group contributions to beta coefficients in the models. TOC and its fractions were predicted using the cross-validated models and soil spectra for 3109 reforested and agricultural soils. The reliability of predictions determined using k-nearest neighbour score distance indicated that >80% of predictions were within the satisfactory inlier limit. The study demonstrated the utility of infrared spectroscopy (MNIRS-PLSR) to rapidly and economically determine TOC and its fractions and thereby accurately describe the effects of land use change such as reforestation on agricultural soils.

Linear stability of layered two-phase flows through parallel soft-gel-coated walls.

The linear stability of layered two-phase Poiseuille flows through soft-gel-coated parallel walls is studied in this work. The focus is on determining the effect of the elastohydrodynamic coupling between the fluids and the soft-gel layers on the different instabilities observed in flows between parallel plates. The fluids are assumed Newtonian and incompressible, while the soft gels are modeled as linear viscoelastic solids. A long-wave asymptotic analysis is used to obtain an analytical expression for the growth rate of the disturbances. A Chebyshev collocation method is used to numerically solve the general linearized equations. Three distinct instability modes are identified in the flow: (a) a liquid-liquid long-wave mode; (b) a liquid-liquid short-wave mode; (c) a gel-liquid short-wave mode. The effect of deformability of the soft gels on these three modes is analyzed. From the long-wave analysis of the liquid-liquid mode a stability map is obtained, in which four different regions are clearly demarcated. It is shown that introducing a gel layer near the more viscous fluid has a predominantly stabilizing effect on this mode seen in flows between rigid plates. For parameters where this mode is stable for flow between rigid plates, introducing a gel layer near the less viscous and thinner fluid has a predominantly destabilizing effect. The liquid-liquid short-wave mode is destabilized by the introduction of soft-gel layers. Additional instability modes at the gel-liquid interfaces induced by the deformability of the soft-gel layers are identified. We show that these can be controlled by varying the thickness of the gel layers. Insights into the physical mechanism driving different instabilities are obtained using an energy budget analysis.

The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan.

Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long non-coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long non-coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.