Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

[A novel method for non-invasive mechanical ablation of prostate tumors using pulsed focused ultrasound].

AIM: of the study: demonstrate the feasibility of non-invasive mechanical disintegration of human prostate tissue using pulsed high-intensity focused ultrasound (pHIFU), a method termed boiling histotripsy. MATERIALS AND METHODS: An ultrasound experimental system was developed for producing localized mechanical lesions in ex vivo biological tissue samples under ultrasound guidance. A series of experiments was carried out to create small single-focus lesions (volume < 2 mm3) and one large lesion (volume > 50 mm3) in ex vivo prostate tissue samples. After irradiation, two samples were bisected to visualize the region of destruction; the other tissue samples were examined histologically. RESULTS: During pHIFU irradiation under B-mode ultrasound guidance, a region of increased echogenicity caused by formation of vapor-gas bubbles was visualized in the target region. After exposure, small and large lesions filled with a suspension of liquefied tissue were observed. Histological examination confirmed that the prostate tissue in the focal region was disintegrated into subcellular fragments. CONCLUSION: A pilot study showed the feasibility of using boiling histotripsy as a non-invasive method for treating prostate diseases.

An ecosystem-scale perspective of the net land methanol flux: synthesis of micrometeorological flux measurements.

Methanol is the second most abundant volatile organic compound in the troposphere and plays a significant role in atmospheric chemistry. While there is consensus about the dominant role of living plants as the major source and the reaction with OH as the major sink of methanol, global methanol budgets diverge considerably in terms of source/sink estimates reflecting uncertainties in the approaches used to model, and the empirical data used to separately constrain these terms. Here we compiled micrometeorological methanol flux data from eight different study sites and reviewed the corresponding literature in order to provide a first cross-site synthesis of the terrestrial ecosystem-scale methanol exchange and present an independent data-driven view of the land-atmosphere methanol exchange. Our study shows that the controls of plant growth on the production, and thus the methanol emission magnitude, and stomatal conductance on the hourly methanol emission variability, established at the leaf level, hold across sites at the ecosystem-level. Unequivocal evidence for bi-directional methanol exchange at the ecosystem scale is presented. Deposition, which at some sites even exceeds methanol emissions, represents an emerging feature of ecosystem-scale measurements and is likely related to environmental factors favouring the formation of surface wetness. Methanol may adsorb to or dissolve in this surface water and eventually be chemically or biologically removed from it. Management activities in agriculture and forestry are shown to increase local methanol emission by orders of magnitude; they are however neglected at present in global budgets. While contemporary net land methanol budgets are overall consistent with the grand mean of the micrometeorological methanol flux measurements, we caution that the present approach of simulating methanol emission and deposition separately is prone to opposing systematic errors and does not allow taking full advantage of the rich information content of micrometeorological flux measurements.

[Endoscopy of the larynx by hyperspectral imaging]. / Endoskopie des Larynx mit Hyperspectral Imaging.

BACKGROUND: Hyperspectral imaging has been proven to be useful in remote earth sensing, e.g., satellite-based classification of vegetation. After modifying it for in vivo evaluation of the larynx using microscopy, we show its adoption for endoscopes. MATERIALS AND METHODS: In addition to routine microlaryngoscopies under white light inspection, the laryngoscopy was also performed with not only a conventional operation microscope mounted with a tuneable monochromatic light source and a synchronously triggered monochromatic CCD camera (n = 47 patients), but also a similarly modified rigid 0° endoscope (n = 16 patients). Hyperspectral image cubes were obtained between 390 and 680 nm, analyzed using established software tools, and the data using microscope versus endoscope were compared. RESULTS: Under endoscopy, illumination was more even and sterical resolution appeared unchanged at significantly shorter image acquisition times. Hyperspectral classification delineated areas of altered mucosa without further external information irrespective of whether image cubes were generated with microscopy or endoscopy. CONCLUSION: Hyperspectral imaging can be transferred not only to micro(laryngo)scopy but also to endoscopy with rigid optics. This opens the way to a variety of clinically relevant anatomical regions (e.g., upper aerodigestive tract). Its adoption to flexible optics will further broaden this spectrum.

Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms.

The transforming JAK2V617F kinase is frequently associated with myeloproliferative neoplasms and thought to be instrumental for the overproduction of myeloid lineage cells. Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases. We performed a high-throughput in vitro screen to identify point mutations in JAK2V617F that would be predicted to have potential clinical relevance and associated with drug resistance to the JAK2 inhibitor ruxolitinib (INCB018424). Seven libraries of mutagenized JAK2V617F cDNA were screened to specifically identify mutations in the predicted drug-binding region that would confer resistance to ruxolitinib, using a BaF3 cell-based assay. We identified five different non-synonymous point mutations that conferred drug resistance. Cells containing mutations had a 9- to 33-fold higher EC(50) for ruxolitinib compared with native JAK2V617F. Our results further indicated that these mutations also conferred cross-resistance to all JAK2 kinase inhibitors tested, including AZD1480, TG101348, lestaurtinib (CEP-701) and CYT-387. Surprisingly, introduction of the 'gatekeeper' mutation (M929I) in JAK2V617F affected only ruxolitinib sensitivity (fourfold increase in EC(50)). These results suggest that JAK2 inhibitors currently in clinical trials may be prone to resistance as a result of point mutations and caution should be exercised when administering these drugs.

[Reduced vocal cord movement and hypopharyngeal tumor]. / Stimmlippenminderbeweglichkeit und ipsilaterale Raumforderung im Hypopharynx.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western World. It belongs to the low-grade non-Hodgkin lymphomas and is characterized by clonal reproduction of mature small-cell non-functional B-lymphocytes. CLL affects men somewhat more often than women and the average age at onset is over 50 years. In addition to regional lymph node swelling, typical symptoms include hepatosplenomegaly, leukocytosis and skin disorders such as eczema and pruritus. Manifestations in the oropharynx or hypopharynx are rare but should be kept in mind in the differential diagnosis.

[A comparison of low-chirp- and notched-noise-evoked auditory brainstem response]. / Frühe akustisch evozierte Potenziale: Low-Chirp-BERA versus Notched-Noise-BERA.

BACKGROUND: In order to obtain a low-frequency specific auditory brainstem response (ABR) there are less stimuli that plege a satisfying accordance with the ABR threshold and the behavioural threshold. This study investigates the so called low-chirp-ABR as to predict a low-frequency-amblyacousia and compares it to the notched-noise-500 Hz-ABR. MATERIAL AND METHODS: We evaluated behavioural and ABR thresholds to a low-chirp respectively a 500 Hz tone presented in notched noise masking from 32 patients with a severe hearing loss at low-frequencies and 28 patients with normal hearing. RESULTS: The average difference ± single standard deviation between low-chirp-ABR and behavioural threshold is 1.53 dB ± 7.68 dB in the group of patient with low-frequency hearing loss and 2.55 dB ± 5.46 dB in the group of normal hearing. On the contrary the difference between notched-noise-500 Hz- and behavioural thereshold averages 2.67 dB ± 9.29 dB (low-frequency hearing loss) respectively 8.82 dB ± 7.90 dB (normal hearing). In order to verify the equivalence between the several methods we did a equivalence test that shows that low-chip-ABR and behavioural threshold can be considered as equal to obtain a low-frequency threshold. In contrast the comparison of notched-noise-500 Hz-ABR and behavioural threshold proves no equivalence. CONCLUSION: We detected a significant equivalence between low-chirp-ABR and pure-tone audiometric. The ABR to a low-chirp stimulus seems to be rather precise in contrast to the notched-noise-500 Hz-evoked-ABR in order to diagnose a low-frequency-hearing loss.

Viability and membrane potential analysis of Bacillus megaterium cells by impedance flow cytometry.

Single cell analysis is an important tool to gain deeper insights into microbial physiology for the characterization and optimization of bioprocesses. In this study a novel single cell analysis technique was applied for estimating viability and membrane potential (MP) of Bacillus megaterium cells cultured in minimal medium. Its measurement principle is based on the analysis of the electrical cell properties and is called impedance flow cytometry (IFC). Comparatively, state-of-the-art fluorescence-based flow cytometry (FCM) was used to verify the results obtained by IFC. Viability and MP analyses were performed with cells at different well-defined growth stages, focusing mainly on exponential and stationary phase cells, as well as on dead cells. This was done by PI and DiOC(2)(3) staining assays in FCM and by impedance measurements at 0.5 and 10 MHz in IFC. In addition, transition growth stages of long-term cultures and agar plate colonies were characterized with both methods. FCM and IFC analyses of all experiments gave comparable results, quantitatively and qualitatively, indicating that IFC is an equivalent technique to FCM for the study of physiological cell states of bacteria.

[Pressure-related dysphonia, recurring pneumonia and supraglottic tumor]. / Belastungsabhängige Dysphonie, rezidivierende Pleuropneumonie und supraglottische Raumforderung.

Urbach-Wiethe syndrome (hyalinosis cutis et mucosae) is an autosomal-recessive inherited disease. It often presents with typical symptoms such as skin lesions (especially in the face and neck area), dyspnea, and maldigestion. Hoarseness is a leading symptom in young children. These manifestations are caused by the assimilation of glycoproteins in mesenchymal tissue. Our case report shows that hoarseness does not necessarily appear only in children, but can also appear later. Furthermore, the assimilation of glycoproteins in the supraglottic area may also cause dysphonia. Due to the varied features of this disease, interdisciplinary check-ups are necessary at regular intervals.

[Dysphonia in children and adolescents]. / Stimmstörungen bei Kindern und Jugendlichen.

Hoarseness is the leading symptom of dysphonia among children and adolescents. The incidence is evaluated internationally to be 6-25%. In an overview the hereditary and acquired organic and functional causes including secondary organic lesions of the vocal folds, the pathomechanisms and the symptoms typical for this age group are presented. In clinical routine, symptoms of dysphonia in children and adolescents should be consciously looked for and any long-term hoarseness should be examined by specialized physicians, even in this age group, using methods suitable to the age group and the developmental stage. When the appropriate indications are present all therapeutic options currently available should be taken into consideration. Furthermore, this paper provides information for the parents concerning the imminent phoniatric examination.

[Flexible 'chip-on-the-tip' endoscopy for larynx diagnostics]. / Flexible Chip-on-the-tip-Endoskopie zur Larynxdiagnostik.

BACKGROUND: Laryngoscopic procedures can be performed either with rigid or with flexible endoscopes (FE). While the benefit of FEs is a better reflection of the physiological situation, rigid endoscopes (RE) usually offer better image quality. Modern flexible 'chip-on-the-tip' endoscopes promise to combine the advantages of both procedures. MATERIAL AND METHODS: A total of 38 patients with dysphonia were examined with RE, conventional FE, and"chip-on-the-tip" endoscopes (TCE). Image quality was assessed and compared and procedures were evaluated with regard to patient contentment. RESULTS: In all cases image quality of TCE and RE was better than conventional FE. In 55% of cases image quality of TCE and RE was comparable, in 24% RE was judged to be better and in 21% TCE was better. Patient contentment was higher for FE in comparison with RE. CONCLUSION: 'Chip-on-the-tip' endoscopes combine the advantages of both RE and FE with respect to a physiological examination and high image quality.

Carbon monoxide from composting due to thermal oxidation of biomass.

Emissions of carbon monoxide (CO) were observed from decomposing organic wastes and litter under laboratory, pilot composting plant, and natural conditions. Field studies included air from inside a compost heap of about 200 m3, emissions from composting of livestock wastes at a biologically operating farm, and leaf litter pile air samples. The concentration of CO was up to 120 micromol mol(-1) in the compost piles of green waste, and up to 10 micromol mol(-1) in flux chambers above livestock waste windrow composts. The mean CO flux rates were approximately 20 mg CO m(-2) h(-1) for compost heaps of green waste, and varied from 30 to 100 mg CO m(-2) h(-1) for fresh dung windrows. Laboratory studies using a temperature and ventilation-controlled substrate container were performed to elucidate the origin of CO, and included hay samples of fixed moisture content at temperatures between 5 and 65 degrees C, including nonsterilized as well as sterilized samples. The concentration of CO was up to 160 micromol mol(-1) in these experiments, and Arrhenius-type plot analyses resulted in activation energies of 65 kJ mol(-1) for thermochemically produced CO from the nonsterilized compost substrate. Sterilized samples showed dramatically reduced CO2 but virtually unchanged CO emissions, albeit at a slightly lower activation energy, likely a result of the high-temperature sterilization. Though globally and regionally these CO emissions are only a minor source, thermochemically produced CO emissions might affect local air quality in and near composting facilities.