Formation of negative and positive ions in the radiosensitizer nimorazole upon low-energy electron collisions.

A comprehensive investigation of low-energy electron attachment and electron ionization of the nimorazole radiosensitizer used in cancer radiation therapy is reported by means of a gas-phase crossed beam experiment in an electron energy range from 0 eV to 70 eV. Regarding negative ion formation, we discuss the formation of fifteen fragment anions in the electron energy range of 0 eV-10 eV, where the most intense signal is assigned to the nitrogen dioxide anion NO2 -. The other fragment anions have been assigned to form predominantly from a common temporary negative ion state close to 3 eV of the nitroimidazole moiety, while the morpholine moiety seems to act only as a spectator in the dissociative electron attachment event to nimorazole. Quantum chemical calculations have been performed to help interpreting the experimental data with thermochemical thresholds, electron affinities, and geometries of some of the neutral molecules. As far as positive ion formation is concerned, the mass spectrum at the electron energy of 70 eV shows a weakly abundant parent ion and C5H10NO+ as the most abundant fragment cation. We report appearance energy (AE) measurements for six cations. For the intact nimorazole molecular cation, the AE of 8.16 ± 0.05 eV was obtained, which is near the presently calculated adiabatic ionization energy.

[Pregnant patients wirsth major trauma in the resuscitation room : Special (patho)physiological and therapeutic aspects]. / Polytraumatisierte Schwangere im Schockraum : Spezielle (patho­)physiologische und therapeutische Aspekte.

BACKGROUND: Severely injured pregnant women are rarely encountered even in major trauma centers; at the same time high expectations are set for the best possible outcome of mother and child. OBJECTIVE: Summary of the main pathophysiological aspects of pregnancy and essential therapeutic implications for emergency room treatment from the perspective of anesthetists. METHODOLOGY: Selective literature analysis with a focus on primary physiological literature and the synthesis of pregnancy-adapted recommendations of related guidelines. RESULTS: The essential physiological adaptations to pregnancy and their implications for acute care are presented. CONCLUSION: Teamwork, structured decision making as well as airway management and goal-oriented hemodynamic treatment are the foundations for a good outcome of mother and child.

Misleading symptoms and successful noninvasive rewarming of a patient with severe hypothermia (23.1 °C).

Accidental severe hypothermia is a medical emergency in which symptoms may include coma, apnea, pulmonary edema, ventricular dysrhythmia or asystole. Despite optimal treatment, mortality remains high. This article reports a case of severe hypothermia in a geriatric hypothyroid patient, where despite a body core temperature of 23.1 °C the patient presented conscious and with stable vital signs, pronounced motor response, and a Glasgow Coma Scale score of 9. Blood gas analysis (alpha stat at 37 °C) indicated sufficient pulmonary function. A noninvasive rewarming approach proved successful and resulted in discharge without sequelae. This case highlights that symptoms considered pathognomonic for specific stages of hypothermia should be interpreted with great care in clinical practice. Hypothyroidism may have contributed to this uncommon clinical presentation. Body temperature needs to be taken into account when interpreting blood gas analyses. Even at the stage of severe hypothermia, noninvasive forced-air warming enabled rewarming without complications.

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis.

Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be ß-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAPs) S. mitis/S. oralis strain and its daptomycin-resistant (DAPr) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAPr variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAPs strain following treatment with daptomycin. The parental strain and the DAPr variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 106- and 107-CFU/ml challenge inocula, the parental strain outcompeted the DAPr variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAPs strain was completely eliminated, while the DAPr variant persisted in all target tissues. These data underscore that the acquisition of DAPr in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.

Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide In Vitro and In Vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a topical antiseptic. In the present study, we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced susceptibility to polyhexanide by prolonged stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes and with concomitant decreased susceptibility to daptomycin and other cell wall-active antibiotics. However, the in vitro emergence of reduced susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine. During in vivo polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant S. aureus strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.

IL-10 ameliorates TNF-α induced meniscus degeneration in mature meniscal tissue in vitro.

BACKGROUND: Joint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death. The aim of this study was to examine whether anti-inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF-α-induced meniscus degeneration. METHODS: Meniscus tissue was harvested from the knees of adult cows. After 24 h of equilibrium explants were simultaneously treated with bovine TNF-α and IL-10. After an incubation time of 72 h cell death was measured histomorphometrically (nuclear blebbing, NB) and release of glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were analysed. Transcription levels (mRNA) of matrix degrading enzymes, collagen type X (COL10A1) and nitric oxide synthetase 2 (NOS2) were measured by quantitative real time PCR. TNF-α-dependent formation of the aggrecanase-specific aggrecan neoepitope NITEGE was visualised by immunostaining. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test. RESULTS: Administration of IL-10 significantly prevented the TNF-α-related cell death (P .001), release of NO (P .003) and NOS2 expression (P .04). Release of GAG fragments (P .001), NITEGE formation and expression of MMP3 (P .007), -13 (P .02) and ADAMTS4 (P .001) were significantly reduced. The TNF-α-dependent increase in COL10A1 expression was also antagonized by IL-10 (P .02). CONCLUSION: IL-10 prevented crucial mechanisms of meniscal degeneration induced by a key cytokine of OA, TNF-α. Administration of IL-10 might improve the biological regeneration and provide a treatment approach in degenerative meniscus injuries and in conditions of post-traumatic sports injuries.

Antistaphylococcal ß-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal ß-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.

The atomic structure of low-index surfaces of the intermetallic compound InPd.

The intermetallic compound InPd (CsCl type of crystal structure with a broad compositional range) is considered as a candidate catalyst for the steam reforming of methanol. Single crystals of this phase have been grown to study the structure of its three low-index surfaces under ultra-high vacuum conditions, using low energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS), and scanning tunneling microscopy (STM). During surface preparation, preferential sputtering leads to a depletion of In within the top few layers for all three surfaces. The near-surface regions remain slightly Pd-rich until annealing to ∼580 K. A transition occurs between 580 and 660 K where In segregates towards the surface and the near-surface regions become slightly In-rich above ∼660 K. This transition is accompanied by a sharpening of LEED patterns and formation of flat step-terrace morphology, as observed by STM. Several superstructures have been identified for the different surfaces associated with this process. Annealing to higher temperatures (≥750 K) leads to faceting via thermal etching as shown for the (110) surface, with a bulk In composition close to the In-rich limit of the existence domain of the cubic phase. The Pd-rich InPd(111) is found to be consistent with a Pd-terminated bulk truncation model as shown by dynamical LEED analysis while, after annealing at higher temperature, the In-rich InPd(111) is consistent with an In-terminated bulk truncation, in agreement with density functional theory (DFT) calculations of the relative surface energies. More complex surface structures are observed for the (100) surface. Additionally, individual grains of a polycrystalline sample are characterized by micro-spot XPS and LEED as well as low-energy electron microscopy. Results from both individual grains and "global" measurements are interpreted based on comparison to our single crystals findings, DFT calculations and previous literature.

In vivo environment necessary to support transplanted donor mouse T regulatory cells.

CD4(+) Foxp3(+) T regulatory cells (Tregs ) are essential for maintaining immunological tolerance, which could be harnessed for novel cell-based therapies to prevent allograft rejection and control autoimmunity. However, the use of Tregs for therapy is hindered by the inability to generate sufficient cell numbers to inhibit desired immune response(s) and achieve stable engraftment of the donor-Treg cell inoculums. The present study was undertaken to investigate the in vivo requirements to promote engraftment of adoptively transferred Tregs and induce tolerance. We established that not only is peripheral space required, but competition from endogenous Tregs must be minimized for successful donor-Treg engraftment with IL-2 critical for driving their proliferation and survival. Moreover, these studies revealed a critical level of donor-Treg engraftment was required for tolerance induction to skin transplants. These mouse studies lay the foundation for development of novel Treg approaches for tolerance induction in the clinic involving not only organ or cellular transplantation, but also to re-establish self-tolerance in autoimmune settings.

Diabetes and dementia in older people: a Best Clinical Practice Statement by a multidisciplinary National Expert Working Group.

Both dementia and diabetes mellitus are long-term disabling conditions and each may be a co-morbidity of the other. Type 2 diabetes is associated with a 1.5- to 2-fold higher risk of dementia. Diabetes also may occur for the first time in many individuals with mental ill health, including cognitive impairment and dementia, and this may complicate management and lead to difficulties in self-care. Case finding is often poor for cognitive impairment in medical settings and for diabetes in mental health settings and this needs to be addressed in the development of care pathways for both conditions. Many other deficiencies in quality care (both for dementia and diabetes) currently exist, but we hope that this Best Clinical Practice Statement will provide a platform for further work in this area. We have outlined the key steps in an integrated care pathway for both elements of this clinical relationship, produced guidance on identifying each condition, dealt with the potentially hazardous issue of hypoglycaemia, and have outlined important competencies required of healthcare workers in both medical/diabetes and mental health settings to enhance clinical care.

Combination therapy with iron chelation and vancomycin in treating murine staphylococcemia.

Iron acquisition is a virulence factor for Staphylococcus aureus. We assessed the efficacy of the iron chelator, deferasirox (Def), alone or in combination with vancomycin (Van) against two methicillin-resistant S. aureus (MRSA) strains in vitro and in a murine bacteremia model. In vitro time-kill assays were carried out against MRSA or vancomycin-intermediate S. aureus (VISA) strains. The impact of Def on Van binding to the surface of S. aureus was measured by flow cytometry. Furthermore, we compared the efficacy of Def, Van, or both drugs in treating S. aureus bacteremia in a murine model. Combination therapy reduced MRSA and VISA viability in vitro versus either drug alone or untreated controls (p < 0.005); this outcome was correlated with enhanced Van surface binding to S. aureus cells. In vivo, Def + Van combination therapy significantly reduced the bacterial burden in mice kidneys (p = 0.005) and spleen (p < 0.001), and reduced the severity of infection with MRSA or VISA strains compared to placebo-treated mice. Our results show that Def enhances the in vitro and in vivo capacity of Van-mediated MRSA killing via a mechanism that appears to involve increased binding of Van to the staphylococcal surface. Iron chelation is a promising, novel adjunctive therapeutic strategy for MRSA and VISA infections.

Adsorption and reaction of acetylene on clean and oxygen-precovered Pd(100) studied with high-resolution X-ray photoelectron spectroscopy.

We investigated the adsorption and thermal evolution of acetylene on clean Pd(100) and Pd(100) precovered with 0.25 ML oxygen. The measurements were performed in situ by fast XPS at the synchrotron radiation facility BESSY II. On Pd(100) acetylene molecularly adsorbs at 130 K. Upon heating transformation to a CCH species occurs around 390 K along with the formation of a completely dehydrogenated carbon species. On the oxygen-precovered surface partial CCH formation already occurs upon adsorption at 130 K, and the dehydrogenation temperature and the stability range of CCH are shifted to lower temperatures by ∼200 K.

Isoniazid preventive therapy completion in children under 5 years old who are contacts of tuberculosis cases in Lima, Peru: study protocol for an open-label, cluster-randomized superiority trial.

BACKGROUND: Children < 5 years old in contact with TB cases are at high risk for developing severe and fatal forms of TB. Contact investigation, BCG vaccination, and isoniazid preventive therapy (IPT) are the most effective strategies to prevent TB among children. However, the implementation of IPT faces challenges at several stages of the cascade of care of TB infection among children, particularly those less than 5 years old. In Peru, a large proportion of children do not complete IPT, which highlights the need to design effective interventions that enhance preventive therapy adherence and completion. Although the body of evidence for such interventions has grown, interventions in medium TB incidence settings are lacking. This study aims to test the effectiveness, acceptability, and feasibility of an intervention package to increase information and motivation to complete IPT among children < 5 who have been prescribed IPT. METHODS: An open-label, cluster-randomized superiority trial will be conducted in two districts in South Lima, Peru. Thirty health facilities will be randomized as clusters, 10 to the intervention and 20 to control (standard of care). We aim to recruit 10 children from different households in each cluster. Participants will be caretakers of children aged < 5 years old who initiated IPT. The intervention consists of educational material, and short message services (SMS) reminders and motivators. The primary outcomes will be the proportion of children who picked up > 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker. DISCUSSION: Unfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children < 5 years old. Testing of a context-adapted intervention is needed to improve IPT completion rates and therefore TB prevention in young children. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881228. Registered on March 19, 2019.

Caring for older adults with diabetes mellitus: characteristics of carers and their prime roles and responsibilities.

AIMS: Expanding prevalence of diabetes has a major health impact on older people and the burden experienced by their informal carers. We report research which aimed to examine the burden on carers and highlight their input into diabetes care. METHODS: Of 98 diabetes patients aged over 59 years, 89 regularly received help with day-to-day activities or looking after from someone else and, of these, 83 carers consented to interview. Patients and carers were administered questionnaires related to the management of diabetes and personal strain (including Diabetes Knowledge Questionnaire, EuroQol, Caregiver Strain Scale and General Health Questionnaire). RESULTS: A substantial unmet need of older people with diabetes mellitus, in relation to domestic activities and diabetes care, was highlighted. Patient and carer diabetes knowledge was low. Primary carers were generally female relatives from the same household, not in paid employment. Twenty-seven carers (33%) provided > or = 35 h of care work each week. Most carers experienced a moderate level of stress, but 11 (14%) regularly felt overwhelmed. Thirty-three carers (40%) said they had never received any information on diabetes from professionals. Help most frequently wanted was advice and support in relation to accessing community services and about finances, benefits and/or allowances. CONCLUSIONS: Both patient and carer diabetes education strategies are required. Instruction for carers in the basic care of patients with diabetes is also needed and should be targeted. As many as one in seven carers felt regularly overwhelmed and lacked adequate support. Finally, 26 carers (31%) were entitled to benefits which they did not claim.

Ethene adsorption and dehydrogenation on clean and oxygen precovered Ni(111) studied by high resolution x-ray photoelectron spectroscopy.

The adsorption and thermal evolution of ethene (ethylene) on clean and oxygen precovered Ni(111) was investigated with high resolution x-ray photoelectron spectroscopy using synchrotron radiation at BESSY II. The high resolution spectra allow to unequivocally identify the local environment of individual carbon atoms. Upon adsorption at 110 K, ethene adsorbs in a geometry, where the two carbon atoms within the intact ethene molecule occupy nonequivalent sites, most likely hollow and on top; this new result unambiguously solves an old puzzle concerning the adsorption geometry of ethene on Ni(111). On the oxygen precovered surface a different adsorption geometry is found with both carbon atoms occupying equivalent hollow sites. Upon heating ethene on the clean surface, we can confirm the dehydrogenation to ethine (acetylene), which adsorbs in a geometry, where both carbon atoms occupy equivalent sites. On the oxygen precovered surface dehydrogenation of ethene is completely suppressed. For the identification of the adsorbed species and the quantitative analysis the vibrational fine structure of the x-ray photoelectron spectra was analyzed in detail.

SkinDot: A modified full-skin transplantation technique.

Existing epidermal transplantation procedures applied in burn surgery or wound treatment, such as mesh grafting or the Meek method, do not lead to a restoration of all the skin layers. Dermal skin layers are indispensable in ensuring the quality and function of the transplanted skin as a frictional surface and a carrier of skin appendages such as hair, sweat glands, and sebaceous glands, as well as nerve receptors for detecting pressure, vibration, and temperature. Because of the restricted skin surface area that can be provided by the donor, full-skin transplants cannot be transplanted over a large area. Cultured skin procedures, based on skin cells cultivated in a laboratory, have not yet reached a stage of development where a complex full epidermal transplantation is possible. In particular, the introduction of skin appendages with a functional cell-to-cell communication has not been observed thus far in cultivated skin. Based on the Reverdin transplantation method, in which concave skin islands with epidermal and dermal parts are transplanted, Davis in 1910 described the transplantation of multiple 2-5 mm sized full-skin islands as a new method for the treatment of skin lesions. Further modifying this 100-year-old procedure, we developed a miniaturization and automation of the Davis transplantation method that started in 2011 and called it "SkinDot". In the following article we describe the effectiveness of the full-skin island transplant procedure in two patients. The transplantation of single 2-3 mm full-skin islands results in a full-skin equivalent without any limits on donor area and with a reduced donor morbidity.

Development of an ultrasound-capable phantom with patient-specific 3D-printed vascular anatomy to simulate peripheral endovascular interventions.

PURPOSE: Today, ultrasound-guided peripheral endovascular interventions have the potential to be an alternative to conventional interventions that are still X-ray and contrast agent based. For the further development of this approach, a research environment is needed that represents the individual patient-specific endovascular properties as realistically as possible. Aim of the project was the construction of a phantom that combines ultrasound capabilities and the possibility to simulate peripheral endovascular interventions. MATERIAL AND METHODS: We designed a modular ultrasound-capable phantom with exchangeable patient specific vascular anatomy. For the manufacturing of the vascular pathologies, we used 3D printing technology. Subsequently, we evaluated the constructed simulator with regards to its application for endovascular development projects. RESULTS: We developed an ultrasound-capable phantom with an exchangeable 3D-printed segment of the femoral artery. This modality allows the study of several patient-specific 3D-printed pathologies. Compared to the flow properties of a human artery (male; age 28) the phantom shows realistic flow properties in the duplex ultrasound image. We proved the feasibility of the simulator by performing an ultrasound-guided endovascular procedure. Overall, the simulator showed realistic intervention conditions. CONCLUSIONS: With the help of the constructed simulator, new endovascular procedures and navigation systems, such as ultrasound-guided peripheral vascular interventions, can be further developed. Additionally, in our opinion, the use of such simulators can also reduce the need for animal experiments.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Site blocking and CO/sulfur site exchange processes on stepped Pt surfaces.

The influence of preadsorbed sulfur on the adsorption of CO on Pt(355) and Pt(322) is investigated systematically for sulfur precoverages between 0.02 and 0.30 ML by in situ x-ray photoelectron spectroscopy of the C 1s and S 2p core levels. The two surfaces have the same nominal terrace width of 5 atomic rows, but different step orientation. For both, at low temperatures (130 and 150 K), S preferentially adsorbs at the steps and passivates them for CO adsorption. The required S precoverage is significantly smaller for Pt(322), because of the lower number of steps as a result of the S-induced double-step formation. Upon heating, population of step sites with CO occurs due to irreversible CO/S site exchange. At low S precoverages, the characteristic transition temperatures of 165 K for Pt(355) and 245 K for Pt(322) are significantly different, indicating a higher activation barrier for the CO/S site exchange process for Pt(322). For medium to high S precoverages the transition temperature stays unchanged for Pt(322) but increases for Pt(355). The observed behavior is attributed to a kinetic passivation of the steps by sulfur at low temperatures, which is lifted upon heating.