Pt─O Bond Accelerated Cu0/Cu+ Activity for Boosting Low-Energy Bipolar Hydrogen Production.

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Who enrolls and why? Examining center-specific underlying patterns behind enrollment: a New York City-based traumatic brain injury model systems study.

BACKGROUND: To elucidate the sociodemographic and study factors involved in enrollment in the Traumatic Brain Injury Model System (TBIMS) database, this study examined the effect of a variety of variables on enrollment at a local TBIMS center. METHODS: A sample of 654 individuals from the local TBIMS center was studied examining enrollment by age, gender, race, ethnicity, homelessness status at date of injury, history of homelessness, health insurance status, presence of social support, primary language, consenting in hospital or after discharge, and the need for an interpreter. Binary logistic regression was conducted to identify variables that predict center-based enrollment into TBIMS. RESULTS: Results demonstrated that older age was associated with decreasing enrollment (OR = 0.99, p = 0.01), needing an interpreter made enrollment less likely (OR = 0.33, p < 0.01), being primarily Spanish speaking predicted enrollment (OR = 3.20, p = 0.02), Hispanic ethnicity predicted enrollment (OR = 7.31, p = 0.03), and approaching individuals in the hospital predicted enrollment (OR = 6.94, p < 0.01). Here, OR denotes the odds ratio estimate from a logistic regression model and P denotes the corresponding p-value. CONCLUSIONS: These results can be useful in driving enrollment strategies at this center for other similar TBI research, and to contribute a representative TBI sample to the national database.

Total Knee Arthroplasty in the Post-Traumatic Knee: Revision Risks and Functional Outcomes Compared to Osteoarthritic Knees. A Report of Primary Procedures From the Dutch Arthroplasty Register.

BACKGROUND: Total knee arthroplasty (TKA) for post-traumatic arthritis (PTA) poses higher challenges and increased risks of complications compared to TKA for osteoarthritis (OA). This study aimed to compare implant survivorships, reasons for revision, and patient-reported outcome measures between OA and PTA as indications for TKA. METHODS: We selected all primary TKAs for PTA or OA between 2007 and 2020 from the Dutch Arthroplasty Register (Landelijke Registratie Orthopedische Interventies). The study included 3,897 TKA procedures for PTA (median follow-up 4.6 years; interquartile range: 2.2, 7.3) and 255,259 procedures for OA (median follow-up 4.7 years; interquartile range 2.2, 7.6). A total of 10,480 revision procedures were performed across both groups (238 in PTA knees; 10,242 in OA knees). We analyzed the prevalence of preoperative comorbidities and postoperative complications, as well as the reasons for revision, and calculated the implant survival rates. RESULTS: The survival revision rate in the OA group was significantly lower at both follow-up moments (5- and 10- years). The likelihood for revision was increased in TKA for PTA compared to TKA for OA (hazards ratio: 1.16 [95% confidence interval 1.02 to 1.33], P = .03). The most common reason for a revision was instability and arthrofibrosis in the PTA group compared to patellar pain for the OA group. CONCLUSION: This study demonstrated an increased risk for revision for any reason in TKA for PTA compared to OA. Revision for instability and arthrofibrosis were more prevalent in the PTA group, while revision for patellar pain was less prevalent compared to TKA for OA.

Analysis of interventional treatment options of the common femoral artery - a retrospective single center experience.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

Performance and mechanism of La-Fe metal-organic framework as a highly efficient adsorbent for fluoride removal from mine water.

Water fluoride pollution has caused non-negligible harm to the environment and humans, and thus it is crucial to find a suitable treatment technology. In this study, La-Fe@PTA adsorbent was synthesized for the defluoridation of mine water. The results showed that the optimum conditions for defluoridation by La-Fe@PTA were pH close to 7.0, the initial F- concentration of 10 mg/L, the dosage of 0.5 g/L and the adsorption time of 240 min. Compared with SO42‒, Cl‒, NO3‒, Ca2+ and Mg2+, CO32‒ and HCO3‒ presented severer inhibition on fluoride uptake by La-Fe@PTA. The adsorption process fits well with the pseudo-second-order kinetic model and Freundlich model, and the maximum adsorption capacity of Langmuir model was 95 mg/g. Fixed-bed adsorption results indicated that fluoride in practical fluorinated mine water could be effectively removed from 3.6 mg/L to less than 1.5 mg/L within 130 bed volume (BV) by using 1.5 g La-Fe@PTA. Furthermore, the adsorbent still had good adsorption capacity after regeneration, which confirms the great application potential of La-Fe@PTA as a fluoride ion adsorbent. The mechanism analysis showed that La-Fe@PTA adsorption of fluorine ions is a physicochemical reaction driven by electrostatic attraction and ion exchange.

Population Pharmacokinetic Modeling of Free Plasma and Free Brain Concentrations of Ceftaroline in Healthy and Methicillin-Resistant Staphylococcus aureus-Infected Wistar Rats.

A population pharmacokinetic model was developed to describe alterations in ceftaroline brain disposition caused by meningitis in healthy and methicillin-resistant Staphylococcus aureus (MRSA)-infected rats. Blood and brain microdialysate samples were obtained after a single bolus dose of ceftaroline fosamil (20 mg/kg) administered intravenously. Plasma data were modeled as one compartment, and brain data were added to the model as a second compartment, with bidirectional drug transport between plasma and brain (Qin and Qout). The cardiac output (CO) of the animals showed a significant correlation with the relative recovery (RR) of plasma microdialysis probes, with animals with greater CO presenting lower RR values. The Qin was approximately 60% higher in infected animals, leading to greater brain exposure to ceftaroline. Ceftaroline brain penetration was influenced by MRSA infection, increasing from 17% (Qin/Qout) in healthy animals to 27% in infected animals. Simulations of a 2-h intravenous infusion of 50 mg/kg every 8 h achieved >90% probability of target attainment (PTA) in plasma and brain for the modal MRSA MIC (0.25 mg/L), suggesting that the drug should be considered an option for treating central nervous system infections.

Engineering Interfacial Pt─O─Ti Site at Atomic Step Defect for Efficient Hydrogen Evolution Catalysis.

The hydrogen evolution reaction (HER) activity of defect-stabilized low-Pt-loading catalysts is closely related with defect type in support materials, while the knowledge about the effect of higher-dimensional defects on the property and activity of trapped Pt atomic species is scarce. Herein, small size (5-10 nm) TiO2 nanoparticles with abundant surface step defects (one kind of line defect) are used to direct the uniform anchoring of Pt atomic clusters (Pt-ACs) via Pt─O─Ti linkage. The as-made low-Pt catalysts (Pt-ACs/S-TiO2 -NP) exhibit exceptional HER intrinsic activity due to the unique step-site Pi-O-Ti species, in which the mass activity and turnover frequency are as high as 21.46 A mg Pt -1 and 21.69 s-1 at the overpotential of 50 mV, both far beyond those of benchmark Pt/C catalysts and other Pt-ACs/TiO2 samples with less step sites. Spectroscopic measurements and theoretical calculations reveal that the step-defect-located Pt─O─Ti sites can simultaneously induce the charge transfer from TiO2 substrate to the trapped Pt-ACs and the downshift of d-band center, which helps the proton reduction to H* intermediates and the following hydrogen desorption process, thus improving the HER. The work provides a deep insight on the interactions between high-dimensional defect and well-dispersed atomic metal motifs for superior HER catalysis.

A Systematic Review and Meta-analysis of Atherectomy Plus Balloon Angioplasty Versus Balloon Angioplasty Alone for Infrapopliteal Arterial Disease.

OBJECTIVE: The article aimed to compare the efficiency and safety of atherectomy plus balloon angioplasty (BA) with BA alone for the treatment of infrapopliteal arterial disease. METHODS: According to the inclusion and exclusion criteria, PubMed, Embase, and Cochrane Library database were searched for studies comparing atherectomy plus angioplasty and angioplasty alone in treating infrapopliteal artery lesions until November 2022. The endpoints included technical success, primary patency, clinically-driven target lesion revascularization (CD-TLR), periprocedural complications, distal embolization, target limb major amputation, and all-cause mortality. RESULTS: Ten studies met the requirements of our meta-analysis, including 7723 patients in the atherectomy plus BA group and 2299 patients in the BA alone group. The meta-analysis showed that atherectomy plus BA was associated with reduced CD-TLR (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.34, 0.78, p=0.002) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12-month follow-up. No statistically significant difference was found in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. Subgroup analysis found a higher rate of primary patency at 6 and 12 months (6 months: OR: 2.26, 95% CI: 1.11, 4.60, p=0.02; 12 months: OR: 2.38, 95% CI: 1.16, 4.86, p=0.02), and lower rates of CD-TLR (OR: 0.45, 95% CI: 0.25, 0.82, p=0.009) and target limb major amputation (OR: 0.43, 95% CI: 0.19, 1.01, p=0.05) at 12 months in patients treated with atherectomy plus drug-coated balloon (DCB) but not in patients treated with atherectomy plus plain old balloon angioplasty (POBA). CONCLUSIONS: This meta-analysis suggests that compared with BA alone, atherectomy plus BA may reduce the need for CD-TLR and the incidence of target limb major amputation at 12-month follow-up in the treatment of infrapopliteal artery occlusive lesions, even though there are no significant advantages in technical success, primary patency, periprocedural complications, distal embolization, or all-cause mortality. To go further, atherectomy plus DCB shows significant benefits in primary patency, CD-TLR, and target limb major amputation rate but atherectomy plus POBA does not'. However, due to the limitations of this article, more randomized controlled trials (RCTs) are needed to confirm these conclusions. CLINICAL IMPACT: According to our research, atherectomy combined with BA has the advantages of higher primary patency rate, lower CD-TLR and target limb significant amputation rate in treating infrapopliteal artery occlusive lesions, which may replace the current mainstream surgical method ---BA alone. For the clinician, although the surgery may take longer, it will significantly improve the prognosis and quality of life of patients and hold considerable significance for the management of patients with infrapopliteal arterial disease. Based on the characteristics of infrapopliteal artery disease, this study explored the feasibility of atherectomy combined with BA for infrapopliteal artery disease. Moreover, we found that atherectomy combined with DCB had better clinical efficacy, which should be the innovation of this study.

Prolonged duration of post-traumatic amnesia: A sensitive classification for predicting cognitive outcomes in children recovering from traumatic brain injury.

OBJECTIVE: A paucity of data exists regarding the duration of post-traumatic amnesia (PTA) as a predictor of cognitive functioning among children after traumatic brain injury (TBI). The study aimed to assess the relationship between PTA duration and areas of neurocognitive function among the pediatric population in the sub-acute phase of recovery and rehabilitation. METHODS: Data were collected from medical files on 103 children aged 5.5-16.5 hospitalized at a pediatric rehabilitation department with a diagnosis of moderate-severe TBI (msTBI) between the years 2004-2019. The Children Orientation and Amnesia Test was used to evaluate PTA duration. Measures of high-order cognitive abilities of attention and executive function were collected using the Test of Everyday Attention-Child version (TEA-Ch). RESULTS: Three PTA duration groups were assembled out of a cluster analysis: "Long PTA" (M = 21 days), "Very Long PTA" (M = 47 days), and "Extremely Long PTA" (M = 94 days). Analyses revealed that the "Long PTA" group preformed significantly better than the "Very Long PTA" and "Extremely Long PTA" groups on all TEA-Ch measures, that is, Selective Attention, Attentional Control Switching, and Sustained Attention. CONCLUSIONS: This study is the first to demonstrate that PTA duration is a useful predictor of high-order cognitive functions among children with msTBI in the sub-acute phase of recovery and rehabilitation. The findings emphasize the importance of using a more sensitive classification of prolonged PTA durations to improve outcome prediction and allocation of resources to those who can benefit most after severe brain injuries.

Unveiling the etiology of peritonsillar abscess using next generation sequencing.

BACKGROUND: Peritonsillar abscess (PTA) is a severe deep neck space infection with an insufficiently characterized bacterial etiology. We aimed to reveal the bacteria associated with PTA applying next generation sequencing (NGS). Tonsil biopsies and pus samples of 91 PTA patients were analysed applying NGS method. RESULTS: Over 400 genera and 800 species belonging to 34 phyla were revealed. The most abundant species in both sample types were Streptococcus pyogenes, Fusobacterium necrophorum and Fusobacterium nucleatum. When present, S. pyogenes was normally a predominant species, although it was recovered as a minor population in some samples dominated by F. nucleatum and occasionally F. necrophorum. S. pyogenes and F. necrophorum were the predominant species (> 10% in a community) in 28 (31%) pus samples, while F. nucleatum in 21 (23%) and S. anginosus in 8 (9%) pus samples. We observed no substantial differences between the microbial findings in pus and tonsil biopsies. CONCLUSIONS: The most probable causative agents of PTA according to our NGS-study include Streptococcus pyogenes, Fusobacterium necrophorum and Fusobacterium nucleatum. Some other streptococci (S. anginosus) and anaerobes (Prevotella, Porphyromonas) may contribute to the infection as well. Pus of the peritonsillar abscess is more representative specimen for microbiological examination than the tonsillar tissue. Our results are important in the context of optimizing the handling of the PTA patients.

Genomic, phenotypic, and clinical safety of Limosilactobacillus reuteri ATCC PTA 4659.

Evaluating the safety of probiotic microorganisms is an important part of the development of probiotic products. In this study, we have performed a systematic safety assessment of Limosilactobacillus reuteri American Type Culture Collection (ATCC) PTA 4659 based on genome analysis, antibiotic susceptibility testing, phenotypic characterization, and a human clinical safety study. Genome sequence analysis showed that the strain is free from virulence and antibiotic resistance genes. Connected to this, phenotypic characterization showed that the strain is susceptible to the main classes of antibiotics. Limosilactobacillus reuteri ATCC PTA 4659 was shown to produce histamine, which has previously been described as an anti-inflammatory mediator produced by certain L. reuteri strains. However, the amount of histamine, a biogenic amine, poses no safety concern of a potential product. The strain was investigated in a human clinical safety study and was shown to survive passage through the gastrointestinal tract, both when administered at high [1 × 1011 colony-forming units (CFU)/day] and low doses (1 × 109 CFU/day). The clinical safety evaluation showed that the doses administered are safe for human consumption. Furthermore, carbohydrate utilization, mucus adhesion, and tolerance to acid and bile were studied. It was shown that L. reuteri ATCC PTA 4659 has a very high adhesion to mucus and tolerance to both gastric pH and bile, all potentially important properties for a probiotic strain. Altogether, this study has demonstrated that Limosilactobacillus reuteri ATCC PTA 4659 is safe for human consumption and along with its phenotypic characteristics and previously described anti-inflammatory effects, makes it a promising strain for future probiotic development. NCT01033539.

Outcomes of cochlear implantation in children with Usher syndrome: a long-term observation.

PURPOSE: To evaluate auditory performance and speech intelligibility of children with Usher syndrome up to 10 years after cochlear implantation. METHODS: Thirty-five children with USH were compared to 46 non-syndromic patients regarding age at implantation. Auditory performance and speech intelligibility was assessed with standard tools. Genetic counseling, vestibular tests, imaging studies, and ophthalmological findings were evaluated, depending on the availability. RESULTS: The mean age of implantation in USH children was 6.3 years (SD 4.6, range 0.3-17.6 years). Post-implantation values of the studied parameters were compared between USH and NS children and presented as follows: PTA = 25.0 dB HL vs. 28.4, CAP = 5.3 vs. 5.1, SIR = 4.1 vs. 3.9, MAIS = 82.3% vs. 80.5%, MUSS = 81.8% vs. 76.6%. There were no statistically significant differences between the USH and NS groups (p > 0.005). USH patients reached a higher score ceiling earlier compared to NS patients. Children implanted before 3 years of age achieved significantly higher results than older children in USH and NS groups (p < 0.005). In all patients with USH, the electroretinogram was abnormal. Vestibular examination was abnormal in 29 of 31 patients with USH1. Imaging studies revealed no inner ear or auditory nerve anomalies in patients with USH. CONCLUSION: Cochlear implantation successfully improves auditory performance and speech intelligibility in patients with USH, especially those implanted under 3 years of age. The electroretinogram is the only reliable test to establish a diagnosis of USH. Logopedic outcomes are associated with early implantation, and early diagnosis of USH contributes to optimizing speech therapy.

Functionalization of and through Melanin: Strategies and Bio-Applications.

A unique feature of nanoparticles for bio-application is the ease of achieving multi-functionality through covalent and non-covalent functionalization. In this way, multiple therapeutic actions, including chemical, photothermal and photodynamic activity, can be combined with different bio-imaging modalities, such as magnetic resonance, photoacoustic, and fluorescence imaging, in a theragnostic approach. In this context, melanin-related nanomaterials possess unique features since they are intrinsically biocompatible and, due to their optical and electronic properties, are themselves very efficient photothermal agents, efficient antioxidants, and photoacoustic contrast agents. Moreover, these materials present a unique versatility of functionalization, which makes them ideal for the design of multifunctional platforms for nanomedicine integrating new functions such as drug delivery and controlled release, gene therapy, or contrast ability in magnetic resonance and fluorescence imaging. In this review, the most relevant and recent examples of melanin-based multi-functionalized nanosystems are discussed, highlighting the different methods of functionalization and, in particular, distinguishing pre-functionalization and post-functionalization. In the meantime, the properties of melanin coatings employable for the functionalization of a variety of material substrates are also briefly introduced, especially in order to explain the origin of the versatility of melanin functionalization. In the final part, the most relevant critical issues related to melanin functionalization that may arise during the design of multifunctional melanin-like nanoplatforms for nanomedicine and bio-application are listed and discussed.

CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy.

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αß T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.

Population Pharmacokinetic Modeling and Probability of Target Attainment of Ceftaroline in Brain and Soft Tissues.

Ceftaroline, approved to treat skin infections and pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA), has been considered for the treatment of central nervous system (CNS) infections. A population pharmacokinetic (popPK) model was developed to describe ceftaroline soft tissue and cerebrospinal fluid (CSF) distributions and investigate the probability of target attainment (PTA) of the percentage of the dosing interval that the unbound drug concentration exceeded the MIC (%fT>MIC) to treat MRSA infections. Healthy subjects' plasma and microdialysate concentrations from muscle and subcutaneous tissue following 600 mg every 12 h (q12h) and q8h and neurosurgical patients' plasma and CSF concentrations following single 600-mg dosing were used. Plasma concentrations were described by a two-compartment model, and tissue concentrations were incorporated as three independent compartments linked to the central compartment by bidirectional transport (clearance in [CLin] and CLout). Apparent volumes were fixed to physiological interstitial values. Healthy status and body weight were identified as covariates for the volume of the central compartment, and creatinine clearance was identified for clearance. The CSF glucose concentration (GLUC) was inversely correlated with CLin,CSF. Simulations showed a PTA of >90% in plasma and soft tissues for both regimens assuming an MIC of 1 mg/L and a %fT>MIC of 28.8%. Using the same target, patients with inflamed meninges (0.5 < GLUC ≤ 2 mmol/L) would reach PTAs of 99.8% and 97.2% for 600 mg q8h and q12h, respectively. For brain infection with mild inflammation (2 < GLUC ≤ 3.5 mmol/L), the PTAs would be reduced to 34.3% and 9.1%, respectively. Ceftaroline's penetration enhanced by meningeal inflammation suggests that the drug could be a candidate to treat MRSA CNS infections.

Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for in vitro sensitive pathogens were assigned to either the II (2 g every 8 h over 0.5 h) or the CI (6 g over 24 h after a loading dose of 2 g) group. A population pharmacokinetic model was developed using unbound plasma, and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. The area under the concentration-time curve from 0 to 24 h (AUC0-24) ELF/plasma penetration ratio was 0.73, at steady state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed that for the minimal pharmacodynamic (PD) targets of 50% T > 1× MIC (II group) and 100% T > 1× MIC (CI group), PK/PD breakpoints were 4 mg/L in plasma and 2 mg/L in ELF and 4 mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with creatinine clearance (CLCR) < 60 mL/min/1.73 m2. While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in the case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.

Iliac "paving & cracking" technique for transcatheter aortic valve implantation.

Challenging femoral/iliac access (CA) can lead to vascular complications which can hamper the clinical benefit of transfemoral (TF) transcatheter aortic valve implantation (TAVI). In this sense, iliac artery rupture is a severe complication associated with significant morbidity and mortality. We report a case of TF-TAVI managed with the "paving and cracking technique" to overcome CA.

Prognostic impact of resting heart rate in patients with peripheral artery disease.

OBJECTIVES: Resting heart rate has been increasingly identified as a marker of cardiovascular risk and has been extensively studied as a predictor of coronary artery disease progression. In peripheral artery disease, the prognostic impact of resting heart rate remains elusive. METHODS: Consecutive patients undergoing invasive peripheral procedures were included. Data included resting heart rate determination by averaging manual radial pulse palpation measurements taken 24 h before and after an invasive peripheral procedure. RESULTS: A total of 1720 patients were included (mean age 70±11 years, 38% were female, 39% had critical limb ischemia). During a median follow-up of 729 days, 364 (21.2%) patients died. Resting heart rate emerged as an independent predictor of mortality, even after adjusting for clinical characteristics, peripheral artery disease manifestation and anatomic extent, traditional risk factors, co-morbidities, and disease-modifying therapies: hazard ratio for heart rate >75 bpm was 1.010 (95% confidence interval 1.001-1.109), with each bpm increase in resting heart rate conferring a 1.1% increase in the risk of all-cause mortality (95% confidence interval 0.1-10.9%, adjusted p = 0.030). CONCLUSIONS: Resting heart rate is an independent predictor of mortality in patients with peripheral artery disease; our findings extend heart rate as a possible marker of prognosis to non-coronary atherosclerotic vascular disease.

The Norsesquiterpene Glycoside Ptaquiloside as a Poisonous, Carcinogenic Component of Certain Ferns.

Previous studies related to the ptaquiloside molecule, a carcinogenic secondary metabolite known from the world of ferns, are summarised. Ptaquiloside (PTA) belongs to the group of norsesquiterpenes of the illudane type. The name illudane refers to the fungal taxa from which the first representatives of the molecular group were identified. Ptaquiloside occurs mainly in Pteridium fern species, although it is also known in other fern taxa. The species of the genus Pteridium are common, frequent invasive species on all continents, and PTA is formed in smaller or larger amounts in all organs of the affected species. The effects of PTA and of their derivatives on animals and humans are of great toxicological significance. Its basic chemical property is that the molecule can be transformed. First, with the loss of sugar moiety, ptaquilosine is formed, and then, under certain conditions, a dienone derivative (pteridienone) may arise. The latter can alkylate (through its cyclopropane groups) certain molecules, including DNA, in animal or human organisms. In this case, DNA adducts are formed, which can later have a carcinogenic effect through point mutations. The scope of the PTA is interdisciplinary in nature since, for example, molecules from plant biomass can enter the body of animals or humans in several ways (directly and indirectly). Due to its physico-chemical properties (excellent water solubility), PTA can get from the plant into the soil and then into different water layers. PTA molecules that enter the soil, but mainly water, undergo degradation (hydrolytic) processes, so it is very important to clarify the toxicological conditions of a given ecosystem and to estimate the possible risks caused by PTA. The toxicoses and diseases of the animal world (mainly for ruminant farm animals) caused by PTA are briefly described. The intake of PTA-containing plants as a feed source causes not only various syndromes but can also enter the milk (and meat) of animals. In connection with the toxicological safety of the food chain, it is important to investigate the transport of carcinogenic PTA metabolites between organisms in a reassuring manner and in detail. This is a global, interdisciplinary task. The present review aims to contribute to this.