UVR: sun, lamps, pigmentation and vitamin D.

Exposure to ultraviolet radiation (UVR) has important and significant consequences on human health. Recently, there has been renewed interest in the beneficial effects of UVR. This perspective gives an introduction to the solar spectrum, UV lamps, UV dosimetry, skin pigment and vitamin D. The health benefits of UVR exposure through vitamin D production or non-vitamin D pathways will be discussed in this themed issue in the following articles.

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate.

BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254 nm) and semi-quantify MTX distribution in skin. RESULTS: AFXL increased topical MTX-delivery (P < 0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07 mg/cm(2) , increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P < 0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85 mg/cm(3) at 500 µm skin-level vs. MAZ-DM: 3.75 mg/cm(3) at 800 µm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47 µm, P ≥ 0.438). CONCLUSION: AFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX-concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. © 2016 Wiley Periodicals, Inc.

Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis.

The empiric treatment of infective endocarditis (IE) varies widely and, in some places, a regimen of penicillin in combination with an aminoglycoside is administered. The increasing incidence of Staphylococcus aureus IE, poor tissue penetration by aminoglycosides and low frequency of penicillin-susceptible S. aureus may potentially lead to functional tobramycin monotherapy. Therefore, this study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE rat model. Catheter-induced IE at the aortic valves were established with S. aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or tobramycin-treated (n = 13) groups. The treatment group received tobramycin once-daily. Animals were evaluated at 1 day post infection (DPI), 2 DPI or 3 DPI. Quantitative bacteriology and cytokine expression were measured for valves, myocardium and serum. A decrease of bacterial load was observed in valves and the spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8) (p ≤ 0.02 and p ≤ 0.01, respectively), but not at 3 DPI (n = 7). Quantitative bacteriology in the myocardium was not different between the groups. Keratinocyte-derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in the tobramycin-treated group (p ≤ 0.03). However, the expression of interleukin (IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was not different between the two groups. In the myocardium, a significant reduction in IL-1b was observed at 2 DPI (p ≤ 0.001) but not at 3 DPI. Tobramycin as functional monotherapy only reduced bacterial load and inflammation transiently, and was insufficient in most cases of S. aureus IE.

Validation of self-reported erythema: comparison of self-reports, researcher assessment and objective measurements in sun worshippers and skiers.

BACKGROUND: Most epidemiological data of sunburn related to skin cancer have come from self-reporting in diaries and questionnaires. We thought it important to validate the reliability of such data. OBJECTIVE: To validate the quality of self-reported erythema by sun worshippers and skiers, and to validate the ability to determine erythema visually compared with objectively measured erythema. METHODS: The skin in a group of sun worshippers in Tenerife and of skiers in Austria was closely monitored over a week. The participants used a diary to record any erythema assessed on different skin sites and underwent a twice daily skin examination by researchers who assessed erythema on the same sites. Lastly, the erythema assessment was validated by objective measurements. RESULTS: We found that the participants' agreed with researchers' assessment of erythema in only 57-61% of cases, and that the researchers detected up to 28% more of the objectively measured erythema than the participants did. We also found that, even for the trained eye (researchers), it was difficult to detect an increase in erythema as only 71-91% of those cases with an increase >15 in measured erythema percentage were detected in the evening. Possibly, detection was impeded by a simultaneous increase in pigmentation. CONCLUSION: Self-assessment of erythema from diaries is unreliable. Erythema is considerably underestimated and possibly neglected. Even for the trained eye, it can be difficult to detect erythema.

High-throughput, accurate Monte Carlo simulation on CPU hardware for PET applications.

Monte Carlo simulations (MCS) represent a fundamental approach to modelling the photon interactions in positron emission tomography (PET). A variety of PET-dedicated MCS tools are available to assist and improve PET imaging applications. Of these, GATE has evolved into one of the most popular software for PET MCS because of its accuracy and flexibility. However, simulations are extremely time-consuming. The use of graphics processing units (GPU) has been proposed as a solution to this, with reported acceleration factors about 400-800. These factors refer to GATE benchmarks performed on a single CPU core. Consequently, CPU-based MCS can also be easily accelerated by one order of magnitude or beyond when exploiting multi-threading on powerful CPUs. Thus, CPU-based implementations become competitive when further optimisations can be achieved. In this context, we have developed a novel, CPU-based software called the PET physics simulator (PPS), which combines several efficient methods to significantly boost the performance. PPS flexibly applies GEANT4 cross-sections as a pre-calculated database, thus obtaining results equivalent to GATE. This is demonstrated for an elaborated PET scanner with 3-layer block detectors. All code optimisations yield an acceleration factor of ≈20 (single core). Multi-threading on a high-end CPU workstation (96 cores) further accelerates the PPS by a factor of 80. This results in a total speed-up factor of ≈1600, which outperforms comparable GPU-based MCS by a factor of ≳2. Optionally, the proposed method of coincidence multiplexing can further enhance the throughput by an additional factor of ≈15. The combination of all optimisations corresponds to an acceleration factor of ≈24 000. In this way, the PPS can simulate complex PET detector systems with an effective throughput of 106photon pairs in less than 10 milliseconds.

Improving antibiotic treatment of bacterial biofilm by hyperbaric oxygen therapy: Not just hot air.

Bacteria and fungi show substantial increased recalcitrance when growing as infectious biofilms. Chronic infections caused by biofilm growing microorganisms is considered a major problem of modern medicine. New strategies are needed to improve antibiotic treatment of biofilms. We have improved antibiotic treatment of bacterial biofilms by reviving the dormant bacteria and thereby make them susceptible to antibiotics by means of reoxygenation. Here we review the rationale for associating lack of oxygen with low susceptibility in infectious biofilm, and how hyperbaric oxygen therapy may result in reoxygenation leading to enhanced bactericidal activity of antibiotics. We address issues of feasibility and potential adverse effects regarding patient safety and development of resistance. Finally, we propose means for supplying reoxygenation to antibiotic treatment of infectious biofilm with the potential to benefit large groups of patients.

Hyperbaric oxygen therapy augments tobramycin efficacy in experimental Staphylococcus aureus endocarditis.

Staphylococcus aureus infective endocarditis (IE) is a serious disease with an in-hospital mortality of up to 40%. Improvements in the effects of antibiotics and host responses could potentially benefit outcomes. Hyperbaric oxygen therapy (HBOT) represents an adjunctive therapeutic option. In this study, the efficacy of HBOT in combination with tobramycin in S. aureus IE was evaluated. A rat model of S. aureus IE mimicking the bacterial load in humans was used. Infected rats treated subcutaneously with tobramycin were randomised into two groups: (i) HBOT twice daily (n = 13); or (ii) normobaric air breathing (non-HBOT) (n = 17). Quantitative bacteriology, cytokine expression, valve vegetation size and clinical status were assessed 4 days post-infection. Adjunctive HBOT reduced the bacterial load in the aortic valves, myocardium and spleen compared with the non-HBOT group (P = 0.004, <0.001 and 0.01, respectively) and improved the clinical score (P <0.0001). Photoplanimetric analysis and weight of valve vegetations showed significantly reduced vegetations in the HBOT group (P <0.001). Key pro-inflammatory cytokines [IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and vascular endothelial growth factor (VEGF)] were significantly reduced in valves from the HBOT group compared with the non-HBOT group. In conclusion, HBOT augmented tobramycin efficacy as assessed by several parameters. These findings suggest the potential use of adjunctive therapy in severe S. aureus IE.

Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging.

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography - electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain's default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition - excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and ß-1, but not with ß-2 and ß-3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

Performance tests of two portable mini gamma cameras for medical applications.

We have developed two prototypes of portable gamma cameras for medical applications based on a previous prototype designed and tested by our group. These cameras use a CsI(Na) continuous scintillation crystal coupled to the new flat-panel-type multianode position-sensitive photomultiplier tube, H8500 from Hamamatsu Photonics. One of the prototypes, mainly intended for intrasurgical use, has a field of view of 44 x 44 mm2, and weighs 1.2 kg. Its intrinsic resolution is better than 1.5 mm and its energy resolution is about 13% at 140 keV. The second prototype, mainly intended for osteological, renal, mammary, and endocrine (thyroid, parathyroid, and suprarenal) scintigraphies, weighs a total of 2 kg. Its average spatial resolution is 2 mm; it has a field of view of 95 x 95 mm2, with an energy resolution of about 15% at 140 keV. The main advantages of these gamma camera prototypes with respect to those previously reported in the literature are high portability and low weight, with no significant loss of sensitivity and spatial resolution. All the electronic components are packed inside the mini gamma cameras, and no external electronic devices are required. The cameras are only connected through the universal serial bus port to a portable PC. In this paper, we present the design of the cameras and describe the procedures that have led us to choose their configuration together with the most important performance features of the cameras. For one of the prototypes, clinical tests on melanoma patients are presented and images are compared with those obtained with a conventional camera.

One versus two-step Roux-en-Y gastric bypass after gastric banding­data analysis of the German Bariatric Surgery Registry.

BACKGROUND: Bariatric surgery outcomes have been examined in Germany since January 1, 2005. All data were registered prospectively in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University Magdeburg. METHODS: The data were collected from an online data bank. Data collection began in 2005 for gastric banding (GB) and Roux-en-Y gastric bypass (RYGB) results. In addition to primary bariatric operations, data regarding the complications of revision procedures and redo operations were analyzed. Participation in the quality assurance study was required for all certified centers in Germany. RESULTS: RYGBs are a popular redo operation after failed gastric banding. In the German Bariatric Surgery Registry (GBSR), we analyzed data from 263 RYGB operations that used a one-step approach after GB and 116 operations that used a two-step approach. The leakage rates for primary RYGB decreased to 1.8%. The incidence of leakage after a one-step RYGB after GB was lower (1.9%) than after the two-step procedure (2.6%). CONCLUSION: RYGBs are popular procedures after failed GB in Germany. The multivariable analysis for overall intraoperative complications revealed a significant difference between the two-step and the one-step procedure. In an unadjusted and multivariate assessment, the one-step procedure had statistically lower general postoperative complications than the two-step approach. Therefore, we suggest performing band removal and RYGB as a one-step procedure. Further analysis is necessary to evaluate the risk factors for the one-step procedure. Follow-up investigations must be performed to determine whether RYGB is an effective and safe option after GB.