Observation of metal nanoparticles at atomic resolution in Pt-based cancer chemotherapeutics.

The chemotherapeutics cisplatin and oxaliplatin are important tools in the fight against cancer. Both compounds are platinum complexes. Aberration-corrected scanning transmission electron microscopy using the annular dark-field imaging mode now routinely provides single-atom sensitivity with atomic number contrast. Here, this imaging mode is used to directly image the platinum within the two drugs in their dried form on an amorphous carbon support film. The oxaliplatin is found to have wetted the supporting amorphous carbon, forming disordered clusters suggesting that the platinum has remained within the complex. Conversely, the cisplatin sample reveals 1.8-nm-diameter metallic platinum clusters. The size and shape of the clusters do not appear to be dependent on drying rate nor formed by beam damage, which may suggest that they were present in the original drug solution.

[Chronic skin ulcer in a 24-year-old man after a journey to Southeast Asia]. / Chronisches Ulkus nach Südostasienreise bei 24­jährigem Mann.

Our report concerns a 24-year-old man with a chronic exsudative skin lesion after a journey to Southeast Asia. The diagnosis of melioidosis was made by the identification of Burkholderia pseudomallei from the ichor. The diagnosis was confirmed by polymerase change reaction. The patient was treated with meropenem i. v. for about 10 days and with trimethoprim/sulfamethoxazole for the following 12 weeks. Melioidosis is an endemic disease in Southeast Asia and North Australia which in some cases can run a severe course and can have a high fatality rate. The relevance of melioidosis becomes more important against the background of the increasing global movement of travelers and migration.

Phytoremediation for the indoor environment: a state-of-the-art review.

Poor indoor air quality has become of particular concern within the built environment due to the time people spend indoors, and the associated health burden. Volatile organic compounds (VOCs) off-gassing from synthetic materials, nitrogen dioxide and harmful outdoor VOCs such benzene, toluene, ethyl-benzene and xylene penetrate into the indoor environment through ventilation and are the main contributors to poor indoor air quality with health effects. A considerable body of literature over the last four decades has demonstrate the removal of gaseous contaminants through phytoremediation, a technology that relies on plant material and technologies to remediate contaminated air streams. In this review we present a state-of-the-art on indoor phytoremediation over the last decade. Here we present a review of 38 research articles on both active and passive phytoremediation, and describe the specific chemical removal efficiency of different systems. The literature clearly indicates the efficacy of these systems for the removal of gaseous contaminants in the indoor environment, however it is evident that the application of phytoremediation technologies for research purposes in-situ is currently significantly under studied. In addition, it is common for research studies to assess the removal of single chemical species under controlled conditions, with little relevancy to real-world settings easily concluded. The authors therefore recommend that future phytoremediation research be conducted both in-situ and on chemical sources of a mixed nature, such as those experienced in the urban environment like petroleum vapour, vehicle emissions, and mixed synthetic furnishings off-gassing. The assessment of these systems both in static chambers for their theoretical performance, and in-situ for these mixed chemical sources is essential for the progression of this research field and the widespread adoption of this technology.

Nanoscale LiZnN - Luminescent Half-Heusler Quantum Dots.

Colloidal semiconductor quantum dots are a well-established technology, with numerous materials available either commercially or through the vast body of literature. The prevalent materials are cadmium-based and are unlikely to find general acceptance in most applications. While the III-V family of materials is a likely substitute, issues remain about its long-term suitability, and other earth-abundant materials are being explored. In this report, we highlight a nanoscale half-Heusler semiconductor, LiZnN, composed of readily available elements as a potential alternative system to luminescent II-VI and III-V nanoparticle quantum dots.

40Ar/39Ar Age of the Lathrop Wells Volcanic Center, Yucca Mountain, Nevada.

Paleomagnetic and (40)Ar/(39)Ar analyses from the Lathrop Wells volcanic center, Nevada, indicate that two eruptive events have occurred there. The ages (136 +/- 8 and 141 +/- 9 thousand years ago) for these two events are analytically indistinguishable. The small angular difference (4.7 degrees ) between the paleomagnetic directions from these two events suggests they differ in age by only about 100 years. These ages are consistent with the chronology of the surficial geological units in the Yucca Mountain area. These results contradict earlier interpretations of the cinder-cone geomorphology and soil-profile data that suggest that at least five temporally discrete eruptive events occurred at Lathrop Wells approximately 20,000 years ago.

The effect of sesamoid position on outcome following scarf osteotomy for hallux abducto valgus.

BACKGROUND: Hallux valgus is a common forefoot condition, with numerous operations described to correct the deformity. Debate remains as to the relative importance of correcting the position of the sesamoid apparatus. METHODS: Forty-six cases were reviewed. Preoperative and post-operative X-rays were used to measure forefoot width, inter-metatarsal angle (IM), hallux valgus (HV) angle and sesamoid position (Reynolds stations). Satisfaction was assessed via questionnaire. RESULTS: Significant improvements were seen in all radiological parameters. 37/43 patients were satisfied with the result. Comparison between the satisfied and non-satisfied group revealed significant differences in the IM angle (p<0.05) and HV angle (p<0.05). However, patient satisfaction was not associated with post-op sesamoid position or change in sesamoid position (p>0.05). CONCLUSIONS: This study showed that scarf osteotomy, can successfully correct hallux valgus, with high levels of satisfaction. Satisfaction is associated with a greater correction of deformity. Improvement in sesamoid position was not associated with patient satisfaction.

Import of community-associated, methicillin-resistant Staphylococcus aureus to Europe through skin and soft-tissue infection in intercontinental travellers, 2011-2016.

OBJECTIVES: Recently, following import by travel and migration, epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused nosocomial outbreaks in Europe, sometimes with a fatal outcome. We describe clinico-epidemiological characteristics of CA-MRSA detected by the European Network for the Surveillance of imported S. aureus (www.staphtrav.eu) from May 2011 to November 2016. METHODS: Sentinel surveillance at 13 travel clinics enrolling patients with travel-associated skin and soft-tissue infection (SSTI) and analysing lesion and nose swabs at one central laboratory. RESULTS: A total of 564 independent case-patients with SSTI were enrolled and had 374 (67%) S. aureus-positive lesions, of which 14% (51/374) were MRSA. The majority of CA-MRSA isolates from SSTI were Panton-Valentine leucocidin (PVL) -positive (43/51, 84%). The risk of methicillin-resistance in imported S. aureus varied by travel region (p <0.001) and was highest in Latin America (16/57, 28%, 95% CI 17.0-41.5) and lowest in Sub-Saharan Africa (4/121, 3%, 95% CI 0.9-8.3). Major epidemic clones (USA300 / USA300 Latin-American Variant, Bengal Bay, South Pacific) accounted for more than one-third (19/51, 37%) of CA-MRSA imports. CA-MRSA SSTI in returnees was complicated (31/51 multiple lesions, 61%; 22/50 recurrences, 44%), led to health-care contact (22/51 surgical drainage, 43%; 7/50 hospitalization, 14%), was transmissible (13/47 reported similar SSTI in non-travelling contacts, 28%), and associated with S. aureus nasal colonization (28 of 51 CA-MRSA cases, 55%; 24 of 28 colonized with identical spa-type in nose and lesion, 85%). CONCLUSIONS: Travel-associated CA-MRSA SSTI is a transmissible condition that leads to medical consultations and colonization of the infected host.

Breakpoints for posaconazole susceptibility testing: background and discussion about the need of establishing values.

Posaconazole is a new antifungal agent, which exhibits a broad spectrum of activity against fungi including Aspergillus terreus, some zygomycetes and dematiaceous fungi. Out of the group of triazole antifungal agents, it is the only compound for which interpretive breakpoints have not been established have not yet been established for Candida spp. As reliable breakpoints are useful in the practical management of patients with fungal infections, it is desirable to establish the same for all available substances. However, the underlying data of the existing breakpoints for other antifungal agents are of varying quality because of limited clinical data available. Furthermore, these breakpoints are not equally suitable for all testing methods available and they may not be suitable for all species to be tested. From the practical point of view, it is therefore important not only to establish breakpoints for the reference method but also for the inexpensive and easy to perform testing methods, which are suitable for smaller laboratories.

3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection.

With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.

Impact of antifreeze proteins and antifreeze glycoproteins on bovine sperm during freeze-thaw.

There are no reports on the use of antifreeze proteins (AFP) and antifreeze glycoproteins (AFGP) for the use of bull sperm cryopreservation despite studies in the ram, mouse and chimpanzee. The effect of freezing and thawing on bull sperm viability, osmotic resistance and acrosome integrity were observed following the addition of AFP1, AFPIII and AFGP at four concentrations (0.1, 1, 10 and 100 microg/ml). In a second part of the experiment, fluorescein was conjugated to the AFPs and AFGP and observations were made using fluorescence microscopy to determine whether binding occurred between the sperm cell membranes and the proteins. In the final part of the study the cryopreservation media were cooled in the presence of the AFPs and AFGPs at the four concentrations on a cryomicroscope to mimic similar cooling curves as those used in the presence of sperm. Following freeze-thaw, AFPI resulted in increased osmotic resistant cells at 0.1-10 microg/ml compared to the control (P<0.01). AFPI and AFPIII did bind to the sperm cells. There was no visual difference in ice structure between the control, AFPIII and AFGP but AFPI resulted in parallel crystals at 0.1, 1 and 10 microg/ml. We suggest that the increased osmotic resistance in the spermatozoa cryopreserved in AFPI is due to the cells orientating between the ice crystals, reducing mechanical stress to the cell membrane. Previous research has shown that osmotic resistance correlates with bull fertility, suggesting that bull spermatozoa cryopreserved in the presence of AFPI may have increased fertility in vivo.

The Biosynthesis of Infrared-Emitting Quantum Dots in Allium Fistulosum.

The development of simple routes to emissive solid-state materials is of paramount interest, and in this report we describe the biosynthesis of infrared emitting quantum dots in a living plant via a mutual antagonistic reaction. Exposure of common Allium fistulosum to mercury and tellurium salts under ambient conditions resulted in the expulsion of crystalline, non-passivated HgTe quantum dots that exhibited emissive characteristics in the near-infrared spectral region, a wavelength range that is important in telecommunications and solar energy conversion.

Assessment of mumps virus growth on various continuous cell lines by virological, immunological, molecular and morphological investigations.

Vero cells have been used as a convenient laboratory substrate for the isolation of mumps virus but may not be very sensitive and may select for particular adapted variants from clinical specimens. Continuous cell lines were evaluated for their ability to support the replication of mumps virus. Criteria included the production of infectious virus, detection of intracellular mumps proteins by immunofluorescence and electron microscopy and detection of specific nucleic acid by RT-PCR. Of the cells tested, CaCo-2, PLC/PRF/5, and Vero cells produced infectious virus, with Vero and CaCo-2 being the most permissive. The other substrates tested included cells of murine, canine and human origin showed signs of intracellular proteins and RNA but the amounts produced were much lower, and no infectious virus was detected in some cases. The virus use was a low passage of a Vero derived wild type strain, and it will ultimately be necessary to continue the studies with an unpassaged clinical specimen to identify a cell line able to isolate mumps virus at high efficiency and in unmodified form.

Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe.

Staphylococcus aureus is emerging globally. Treatment of infections is complicated by increasing antibiotic resistance. We collected clinical data and swabs of returnees with skin and soft tissue infections (SSTI) at 13 travel-clinics in Europe (www.staphtrav.eu). Sixty-two percent (196/318) SSTI patients had S. aureus-positive lesions, of which almost two-thirds (122/196) were Panton-Valentine leukocidin (PVL) positive. PVL was associated with disease severity, including hospitalization for SSTI (OR 5.2, 95% CI 1.5-18.2). In returnees with SSTI, longer travel and more intense population contact were risk factors for nasal colonization with PVL-positive S. aureus. Imported S. aureus frequently proved resistant to trimethoprim-sulfamethoxazole (21%), erythromycin (21%), tetracycline (20%), ciprofloxacin (13%), methicillin (12%) and clindamycin (8%). Place of exposure was significantly (p < 0.05) associated with predominant resistance phenotypes and spa genotypes: Latin America (methicillin; t008/CC24/304), Africa (tetracycline, trimethoprim-sulfamethoxazole; t084/CC84, t314/singleton, t355/CC355), South Asia (trimethoprim-sulfamethoxazole, ciprofloxacin; t021/CC21/318), South-East Asia (clindamycin; t159/CC272). USA300-like isolates accounted for 30% of all methicillin-resistant S. aureus imported to Europe and were predominantly (71%) acquired in Latin America. Multi-resistance to non-ß-lactams were present in 24% of imports and associated with travel to South Asia (ORcrude 5.3, 95% CI 2.4-11.8), even after adjusting for confounding by genotype (ORadjusted 3.8, 95% 1.5-9.5). Choosing randomly from compounds recommended for the empiric treatment of severe S. aureus SSTI, 15% of cases would have received ineffective antimicrobial therapy. These findings call for the development of regionally stratified guidance on the antibiotic management of severe imported S. aureus disease and put the infected and colonized traveller at the centre of interventions against the global spread of multi-resistant S. aureus.

Predominance of dfrG as determinant of trimethoprim resistance in imported Staphylococcus aureus.

To investigate the global occurrence of trimethoprim-sulfamethoxazole resistance and the genetic mechanisms of trimethoprim resistance, we analysed Staphylococcus aureus from travel-associated skin and soft-tissue infections treated at 13 travel clinics in Europe. Thirty-eight per cent (75/196) were trimethoprim-resistant and 21% (41/196) were resistant to trimethoprim-sulfamethoxazole. Among methicillin-resistant S. aureus, these proportions were 30% (7/23) and 17% (4/23), respectively. DfrG explained 92% (69/75) of all trimethoprim resistance in S. aureus. Travel to South Asia was associated with the highest risk of acquiring trimethoprim-sulfamethoxazole-resistant S. aureus. We conclude that globally dfrG is the predominant determinant of trimethoprim resistance in human S. aureus infection.

Human dermal microvascular endothelial cells behave like umbilical vein endothelial cells in T-cell adhesion studies.

The adhesion of T lymphocytes to human dermal microvascular endothelial cells (DMVEC) in vitro has been tested after stimulation of the DMVEC with gamma interferon (IFN-gamma), interleukin 1 (IL-1), or a bacterial lipopolysaccharide (LPS). These agents enhanced T-cell adhesion in a manner similar to that previously observed with human umbilical vein endothelial cells (UVEC). Moreover, phorbol ester stimulation of T cells enhanced T-cell adhesion to both DMVEC and UVEC. Unstimulated and phorbol ester-enhanced T-cell adhesion to both DMVEC and UVEC was strongly inhibited by monoclonal antibody (Mab) 60.3 against the surface membrane CDw18 glycoprotein complex. In contrast, Mab 60.3 had a much weaker inhibitory effect on the binding enhancement due to IL-1, LPS, or IFN-gamma, suggesting that these agents may enhance adhesion by a mechanism at least partially independent of CDw18. These observations suggest that DMVEC behave in a similar fashion to UVEC in T-cell adhesion studies, and support previous conclusions that modulation of lymphocyte endothelial cell adhesion by cytokines, bacterial products, and phorbol esters may be relevant to lymphocyte adhesion and migration in vivo.

Pharmacokinetics and pharmacodynamics of a new cardiotonic vasodilator agent, 349U85, in normal subjects.

OBJECTIVE: To assess the pharmacodynamics and pharmacokinetics of single oral doses of a new vasodilator-cardiotonic agent, 349U85 hydrochloride [6-piperidino-2(1H)-quinolinone hydrochloride], in healthy male subjects. METHODS: This randomized, parallel, double-blind, placebo-controlled, dose escalation trial was conducted at a university-based clinical research center among 27 healthy male subjects. Data measurements used in the study included cardiac index, supine and standing blood pressure, 24-hour ambulatory electrocardiography, and 12-lead electrocardiography. RESULTS: Doses from 2 mg to 250 mg were well tolerated. Cardiac index, supine heart rate, and orthostatic hypotension, indicators of inotropic, chronotropic, and vasodilator effects, respectively, correlated to plasma concentrations of 349U85 and of its metabolite, 661U88. Results suggest that 349U85 may be more responsible for inotropic effects, whereas 661U88 may be more responsible for vasodilatory and chronotropic effects. These results are consistent with the preclinical pharmacologic profile for these two compounds. Headache, orthostatic dizziness, and hypotension tended to occur more frequently at higher doses and were temporally related to drug administration. Pharmacokinetic analyses indicate nonlinearity of 349U85 and 661U88, suggestive of saturation of metabolism and large interindividual variability in maximum plasma drug concentration and area under the plasma concentration-time curve. The source of the variability is not known. The time to maximum distribution was approximately 0.7 hours for both 349U85 and 661U88; the terminal elimination half-life was 1 hour for 349U85 and 3 hours for 661U88. Holter monitoring revealed asymptomatic increases in ventricular and supraventricular ectopic activity in some volunteers; ectopy appeared to be related to the dose of 349U85 and generally occurred at higher doses.

Consequences of breast irradiation in patients with pre-existing collagen vascular diseases.

Exaggerated acute and late effects were observed in three of four women with pre-existing collagen vascular disease (CVD) within 2 years after definitive megavoltage radiation therapy for breast carcinoma. Five women with breast carcinoma, who developed CVD 3 months to 10 years after radiation therapy, had no complications. An abnormally severe reaction was observed during treatment of one patient with discoid lupus. The patient developed moist desquamation that persisted for a month, requiring early termination of treatment. One year after treatment, the patient developed paresthesias in the ipsilateral arm. A planned reduction of the prescribed dose in a second patient with progressive systemic sclerosis did not prevent intense erythema at the end of treatment, followed 14 months later by chest wall necrosis, which eventually required multiple surgeries including chest wall resections. The third patient, who had systemic lupus erythematosis, developed necrosis 2 years after treatment, which progressed over 12 years to osteoradionecrosis of the clavicle, sternum and rib cage. Multiple surgeries to repair the defect were complicated by flap necrosis and pleurocutaneous fistulas. The fourth patient died 6 months after radiotherapy without apparent sequelae. None of the patients had evidence of recurrent carcinoma. A history of collagen vascular disease appears to be a contraindication to breast conservation or for elective irradiation for breast cancer.

A system for individualized dosing of intravenous aminophylline using a programmable calculator.

A program that calculates a value of clearance for an individual patient prior to reaching steady state in the early stages of aminophylline therapy is presented. The program is written for the Texas Instruments TI-59 programmable calculator and may be used with or without the PC-100C printer. The program can provide clinically useful information concerning projected plasma concentrations prior to reaching steady state with an accurate history of the dose administration and serum concentration determination. If the patient has not received xanthene therapy prior to admission, only one serum sample is required. If there has been prior drug exposure, a second serum sample is required. An iterative technique, which would be impractical to use without calculator assistance, is employed to make these determinations.