The application of a new laminitis scoring method to model the rate and pattern of improvement from equine endocrinopathic laminitis in a clinical setting.

BACKGROUND: Endocrinopathic, or hyperinsulinaemia-associated laminitis (HAL) is a common and debilitating equine foot disease, and although no pharmacological treatments are registered, several are under development. To evaluate the effect of such treatments, an accurate and consistent method is needed to track the clinical signs of laminitis over time, and the natural history of the disease, in terms of a 'normal' pattern of improvement, needs to be understood. This study examined the improvement pattern in clinical cases of naturally-occurring HAL subjected to a range of best-practice interventions, using two different scoring methods. Eighty horses and ponies with suspected HAL were enrolled in a study conducted at 16 veterinary practices across Germany. The severity of laminitis was assessed by independent veterinarians using both the traditional Obel method and a modified Obel method developed by Meier and colleagues. Assessments were made on the day of diagnosis (d 0), then on days 4, 9, 14, 25 and 42 during the intervention period. Pain medications were withheld for 24 h prior to clinical examination in all cases. RESULTS: Time to marked improvement from laminitis varied between individuals, but was difficult to monitor accurately using the Obel method, with the median grade being 2/4 on days 0 and 4, then 0/4 from d 9 onwards. More subtle changes could be identified using the Meier method, however, and the median scores were seen to follow the form of an exponential decay model in most horses, improving from 8/12 on d 0, to 0/12 on d 25. Within this composite scoring method, considerable variation was observed in the rate of improvement of individual clinical signs, with the average time taken for each sign to reach a median score of 0 ranging from 4 days (foot lift and weight shifting) to 25 days (gait when turned in a circle) across all 80 horses. CONCLUSIONS: The Meier method provides a reliable and consistent method for monitoring the clinical status of horses with HAL, and despite the variability, the pattern of improvement described here should provide a useful benchmark against which individual cases and new treatments can be assessed.

Densely Populated Water Droplets in Heavy-Oil Seeps.

Most of the microbial degradation in oil reservoirs is believed to take place at the oil-water transition zone (OWTZ). However, a recent study indicates that there is microbial life enclosed in microliter-sized water droplets dispersed in heavy oil of Pitch Lake in Trinidad and Tobago. This life in oil suggests that microbial degradation of oil also takes place in water pockets in the oil-bearing rock of an oil leg independent of the OWTZ. However, it is unknown whether microbial life in water droplets dispersed in oil is a generic property of oil reservoirs rather than an exotic exception. Hence, we took samples from three heavy-oil seeps, Pitch Lake (Trinidad and Tobago), the La Brea Tar Pits (California, USA), and an oil seep on the McKittrick oil field (California, USA). All three tested oil seeps contained dispersed water droplets. Larger droplets between 1 and 10 µl revealed high cell densities of up to 109 cells ml-1 Testing for ATP content and LIVE/DEAD staining showed that these populations consist of active and viable microbial cells with an average of 60% membrane-intact cells and ATP concentrations comparable to those of other subsurface ecosystems. Microbial community analyses based on 16S rRNA gene amplicon sequencing revealed the presence of known anaerobic oil-degrading microorganisms. Surprisingly, the community analyses showed similarities between all three oil seeps, revealing common OTUs, although the sampling sites were thousands of kilometers apart. Our results indicate that small water inclusions are densely populated microhabitats in heavy oil and possibly a generic trait of degraded-oil reservoirs.IMPORTANCE Our results confirmed that small water droplets in oil are densely populated microhabitats containing active microbial communities. Since these microhabitats occurred in three tested oil seeps which are located thousands of kilometers away from each other, such populated water droplets might be a generic trait of biodegraded oil reservoirs and might be involved in the overall oil degradation process. Microbial degradation might thus also take place in water pockets in the oil-bearing oil legs of the reservoir rock rather than only at the oil-water transition zone.

The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.

BACKGROUND: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 µIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. RESULTS: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 µIU/mL in wk. 0, to 119 ± 19 µIU/mL (P = 0.015) and 117 ± 15 µIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 µIU/mL in the treated group, with no rebound effect. CONCLUSIONS: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.

Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.

PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T­category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (

Cancer survivors' preference for follow-up care providers: a cross-sectional study from the population-based PROFILES-registry.

BACKGROUND: The best practice for the organization of follow-up care in oncology is under debate, due to growing numbers of cancer survivors. Understanding survivors' preferences for follow-up care is elementary for designing patient-centred care. Based on data from prostate cancer and melanoma survivors, this study aims to identify: 1) preferences for follow-up care providers, for instance the medical specialist, the oncology nurse or the general practitioner; 2) characteristics associated with these preferences and 3) the preferred care provider to discuss cancer-related problems. MATERIAL AND METHODS: Survivors diagnosed with prostate cancer (N = 535) and melanoma (N = 232) between 2007 and 2013 as registered in The Netherlands Cancer Registry returned a questionnaire (response rate was 71% and 69%, respectively). A latent class cluster model analysis was used to define preferences and a multinomial logistic regression analysis was used to identify survivor-related characteristics associated with these preferences. RESULTS: Of all survivors, 29% reported no preference, 40% reported a preference for the medical specialist, 20% reported a preference for both the medical specialist and the general practitioner and 11% reported a preference for both the medical specialist and the oncology nurse. Survivors who were older, lower/intermediate educated and women were more likely to have a preference for the medical specialist. Lower educated survivors were less likely to have a preference for both the medical specialist and the general practitioner. Overall, survivors prefer to discuss diet, physical fitness and fatigue with the general practitioner, and hereditary and recurrence with the medical specialist. Only a small minority favored to discuss cancer-related problems with the oncology nurse. CONCLUSION: Survivors reported different preferences for follow-up care providers based on age, education level, gender and satisfaction with the general practitioner, showing a need for tailored follow-up care in oncology. The results indicate an urgency to educate patients about transitions in follow-up care.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique.

OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.

Advanced virtual monoenergetic images: improving the contrast of dual-energy CT pulmonary angiography.

AIM: To investigate the value of advanced virtual monoenergetic image reconstruction (mono-plus) from dual-energy computed tomography (CT) for improving the contrast of CT pulmonary angiography (CTPA). MATERIALS AND METHODS: Forty consecutive patients (25 women, mean 62.5 years, range 28-87 years) underwent 192-section dual-source CTPA with dual-energy CT (90/150 SnkVp) after the administration of 60 ml contrast media (300 mg iodine/ml). Conventional virtual monochromatic images at 60 keV and 17 mono-plus image datasets from 40-190 keV (in 10 keV steps) were reconstructed. Subjective image quality (artefacts, subjective noise) was rated. Attenuation was measured in the pulmonary trunk and in the right lower lobe pulmonary artery; noise was measured in the periscapular musculature. The signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were calculated for each patient and dataset. Comparisons between monochromatic images and mono-plus images were performed by repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction. RESULTS: Interreader agreement was good to excellent for subjective image quality (ICC: 0.616-0.889). As compared to conventional 60 keV images, artefacts occurred less (p=0.001) and subjective noise was rated lower (p<0.001) in mono-plus 40 keV images. Noise was lower (p<0.001), and the SNR and CNR in the pulmonary trunk and right lower lobe pulmonary artery were higher (both, p<0.001) in mono-plus 40 keV images compared to conventional monoenergetic 60 keV images. Transient interruption of contrast (TIC) was found in 14/40 (35%) of patients, with subjective contrast being similar 8/40 (20%) or higher 32/40 (80%) in mono-plus 40 keV as compared to conventional monoenergetic 60 keV images. CONCLUSIONS: Compared to conventional virtual monoenergetic imaging, mono-plus images at 40 keV improve the contrast of dual-energy CTPA.

[Improvement of cost allocation in gastroenterology by introduction of a novel service catalogue covering the complete spectrum of endoscopic procedures]. / Verbesserung der Kostenkalkulation in der Gastroenterologie durch Einführung eines neuen Leistungskatalogs für alle endoskopischen Prozeduren.

BACKGROUND: The German hospital reimbursement system (G-DRG) is incomplete for endoscopic interventions and fails to differentiate between complex and simple procedures. This is caused by outdated methods of personnel-cost allocation. METHODS: To establish an up-to-date service catalogue 50 hospitals made their anonymized expense-budget data available to the German-Society-of-Gastroenterology (DGVS). 2.499.900 patient-datasets (2011-2013) were used to classify operation-and-procedure codes (OPS) into procedure-tiers (e.g. colonoscopy with biopsy/colonoscopy with stent-insertion). An expert panel ranked these tiers according to complexity and assigned estimates of physician time. From June to November 2014 exact time tracking data for a total 38.288 individual procedures were collected in 119 hospitals to validate this service catalogue. RESULTS: In this three-step process a catalogue of 97 procedure-tiers was established that covers 99% of endoscopic interventions performed in German hospitals and assigned validated mean personnel-costs using gastroscopy as standard. Previously, diagnostic colonoscopy had a relative personnel-cost value of 1.13 (compared to gastroscopy 1.0) and rose to 2.16, whereas diagnostic ERCP increased from 1.7 to 3.62, more appropriately reflecting complexity. Complex procedures previously not catalogued were now included (e.g. gastric endoscopic submucosal dissection: 16.74). DISCUSSION: This novel service catalogue for GI-endoscopy almost completely covers all endoscopic procedures performed in German hospitals and assigns relative personnel-cost values based on actual physician time logs. It is to be included in the national coding recommendation and should replace all prior inventories for cost distribution. The catalogue will contribute to a more objective cost allocation and hospital reimbursement - at least until time tracking for endoscopy becomes mandatory.

Cattle movement as a risk factor for epidemics.

Cattle movement is one of the most important risk factors for the occurrence of an epidemic. It is a legal requirement in Switzerland that every cattle movement be reported, and this information is held in the Swiss cattle movement database (Tierverkehrsdatenbank, TVD). Using this data we examined all movements, focusing on the geographical distribution of these movements in relation to the spread of epizootic diseases. We considered the period 01 January 2011 through 30 January 2012, in which a total of 786'462 cattle were moved. Looking at premises individually, a maximum of 901 possible transfers of an infectious agent were found on a specific day after the arrival of another cattle. Furthermore, we found that there were more cattle movements in summer than in winter, due to movements of cattle to and from alpine pastures. There were also prominent regional differences. On the first day after the arrival of a cattle there was a minimum of zero and a maximum of 99'168 possible transfers of an infectious agent. Nevertheless, in most cases there were no cattle moved on the first day following the arrival of a cattle (91.4%). In terms of our epizootics of interest, the following numbers of cattle were moved within the relevant incubation periods: 19'779'551 possible transfers for the Lumpy skin disease, with an incubation period of 28 days; 9'891'665 or 15'025'741 possible transfers for foot and mouth disease, depending on the incubation period of 14 or 21 days; 15'025'741 possible transfers for cattle plague and vesicular stomatitis, both with an incubation period of 21 days. The presented data show a large cattle traffic in Switzerland, and therefore suggest that it is very seldom that an infectious agent is able to start an epidemic.

Les déplacements des bovins en tant que facteur de risque épidémiologique Les déplacements d'animaux constituent un des risques les plus importants pour la survenance d'une épidémie. En Suisse, il est prescrit que chaque déplacement d'un animal de rente doit être annoncé et saisi dans la Banque de Données sur le Trafic des Animaux (BDTA). Sur la base de ces annonces, nous avons examiné tous les déplacements de l'année 2011 et concentré notre attention sur leur répartition géographique par rapport à l'extension des maladies animales contagieuses. Entre le 1er janvier 2011 et le 30 janvier 2012, 786'462 bovins au total ont été déplacés. Ce sont au maximum 901 contacts avec possibilité de transmission d'un agent infectieux qui se sont produits un jour donné après l'arrivée d'un nouvel animal. Vu les déplacements liés à la montée et à la descente de l'alpage, il y a eu plus de déplacements en été qu'en hiver. On constate également des différences régionales. Le premier jour après l'arrivée d'un bovin, il existait au minimum 0 et au maximum 99'168 contacts possibles pour la transmission d'un agent infectieux. Dans la plupart des cas (91.4%), il ne se produisait pas de trafic de bovins le jour suivant l'arrivée d'un animal. En ce qui concerne les maladies contagieuses des bovins revêtant un intérêt en Suisse, on a relevé les contacts de bovins suivants durant la période d'incubation: 19'779'551 pour la lumpy skin disease, avec un temps d'incubation de 28 jours, 9'891'665 ou 15'025'741 pour la fièvre aphteuse, selon qu'on considère un temps d'incubation de 14 ou de 21 jours, 15'025'741 pour la peste bovine et la stomatite vésiculeuse, toutes deux avec un temps d'incubation de 21 jours. Ces chiffres démontrent un grand trafic d'animaux en Suisse. C'est une indication qu'un agent infectieux ne peut que rarement faire démarrer une épidémie.

In vitro evaluation of a novel biofilm remover.

OBJECTIVE: To evaluate a novel device for its efficacy in removing experimental biofilm from root surfaces and its potential for concomitantly removing/roughening the surface substance. METHODS AND MATERIALS: A novel acrylic rotary device (biofilm remover, BR) was tested in vitro in three experiments: surface loss, surface roughness [positive controls: Perioset (PS) and Proxoshape (PR)] and biofilm removal [positive controls: ultrasonic (US) and PS]. Surface loss/surface roughness was evaluated for dentin samples instrumented for three 20 s periods. The calcium removed during instrumentation was analysed after each interval and cumulatively, using atomic absorption spectrophotometry (AAS). Surface roughness was measured using profilometric analysis. Biofilm removal was evaluated on dentin specimens coated with a 64.5 h 6-species in vitro formed biofilm, after one 20 s treatment. Surface loss was analysed using anova with Scheffé post hoc test, and surface roughness/biofilm removal was analysed using Mann-Whitney test (all P ≤ 0.05). RESULTS: Significantly less substance loss [µg (± 1 SD)] was observed with the novel device at all time points, both interval and cumulative (1.0 (± 0.5) versus 9.3 (± 3.2) PS and 9.9 (± 1.9) PR at 60 s). Surface roughness [µm (95% CI)] was significantly lower for BR than for PS and PR [0.00 (-0.01, 0.08) 0.20 (0.16, 0.27) and 0.21 (0.19, 0.24) at 60 s]. Significantly less biofilm bacteria remained after treatment with both BR 4.5 (-0.1, 16.2) and US 1.9 (-0.2, 14.3), compared to PS 52 (27.9, 82.1). CONCLUSIONS: The novel biofilm remover was less damaging to dentin surfaces, while removing biofilm at least as effectively as devices used in this study.

[Genotoxic effects of occupational environment in Kuzbass miners].

The authors studied chromosomal aberrations in blood lymphocytes of 100 miners in coal mines of Kuznetsk coal field, with underground length of service over 15 years. Reference data were collected by cytogenetic analysis in a group of workers with long length of service in Kemerovo thermal power plant, contacting coal dust (n = 104) and in healthy males of the same age group, residents of Kemerovo city, without occupational contact with mutagenes (n = 194). The miners appeared to have maximal frequency of structural chromosomal injuries--5.37%. In the workers of thermal power plant, this value was considerably lower than in the miners (4.23%; p < 0.01), but not exceeding the values obtained in the reference groups (1.07%; p < 0.0001). Analysis of qualitative spectrum of chromosomal structural changes revealed that the miners have higher frequency of both chromosomal and chromatid type aberrations. Differences in chromosomal aberrations frequency between the miners and the thermal power plant workers are mostly due to chromosomal type aberrations. This points to significant role of chemical and radiation factors contribution into chromosomal mutagenesis in miners.

Structural changes in amorphous Ge(x)SiO(y) on the way to nanocrystal formation.

Temperature induced changes of the local chemical structure of bulk amorphous GexSiOy are studied by Ge K-edge x-ray absorption near-edge spectroscopy and Si L2/3-edge x-ray Raman scattering spectroscopy. Different processes are revealed which lead to formation of Ge regions embedded in a Si oxide matrix due to different initial structures of as-prepared samples, depending on their Ge/Si/O ratio and temperature treatment, eventually resulting in the occurrence of nanocrystals. Here, disproportionation of GeOx and SiOx regions and/or reduction of Ge oxides by pure Si or by a surrounding Si sub-oxide matrix can be employed to tune the size of Ge nanocrystals along with the chemical composition of the embedding matrix. This is important for the optimization of the electronic and luminescent properties of the material.

Randomized benchmarking of multiqubit gates.

We describe an extension of single-qubit gate randomized benchmarking that measures the error of multiqubit gates in a quantum information processor. This platform-independent protocol evaluates the performance of Clifford unitaries, which form a basis of fault-tolerant quantum computing. We implemented the benchmarking protocol with trapped ions and found an error per random two-qubit Clifford unitary of 0.162±0.008, thus setting the first benchmark for such unitaries. By implementing a second set of sequences with an extra two-qubit phase gate inserted after each step, we extracted an error per phase gate of 0.069±0.017. We conducted these experiments with transported, sympathetically cooled ions in a multizone Paul trap-a system that can in principle be scaled to larger numbers of ions.

Sentinel node dissection delays recurrence and prolongs melanoma-related survival: an analysis of 673 patients from a single center with long-term follow-up.

BACKGROUND: The status of the sentinel lymph node is an important predictor for survival in melanoma patients, but it is still unclear if early removal of micrometastases by sentinel lymph node dissection (SLND) alters survival. A large series of melanoma patients from a single center with long-term follow-up was analyzed with regard to a possible effect of SLND on the prognosis. MATERIALS AND METHODS: A total of 673 consecutive melanoma patients were assessed treated in our center either without SLND (377 patients, pre-SLN group, between January 1995 and March 2000) or with SLND (296 patients, SLN group, between April 2000 and March 2003). The median follow-up was 64.0 months in the pre-SLN and 72.5 months in the SLN group. RESULTS: The pre-SLN group and SLN group did not differ significantly with regard to characteristics of the primary melanoma thickness and ulceration, sex, and age. Kaplan-Meier analyses showed a significantly better recurrence-free survival (P < .001), distant metastases free survival (P = .006), and overall survival (P = .049) for patients of the SLN group; the 5-year melanoma-specific survival rates were 80.3% in pre-SLN patients and 84.8% in SLN patients. Initial metastases in the in-transit region and distant locations were of similar frequency in the pre-SLN and SLN groups (P = .191 and P = .959, respectively), but initial regional lymph node metastases were significantly more frequent in the pre-SLN group (P < .001). CONCLUSIONS: Our data point toward a subgroup of melanoma patients who might have a prognostic benefit from SLN.

Biofilm reduction and staining potential of a 0.05% chlorhexidine rinse containing essential oils.

OBJECTIVES: To assess the biofilm reduction and discolouration potential of a new 0.05% chlorhexidine (CHX) digluconate solution, containing additional essential oil and alcohol components, compared with that of standard control CHX solutions (0.05% and 0.2% CHX). METHODS: The potential to reduce total viable counts of growing mixed microbial populations was examined using the Zurich biofilm model. Biofilms were created on sterile pellicle-coated hydroxyapatite discs and exposed to test substances at different time points. After 64.5 h, mean colony-forming units and SDs were determined. Colour change measurements using light reflection analysis were carried out on saliva preconditioned bovine dentin and enamel samples, as well as on composite and glass ceramic restorative materials, after successive immersions in a standardized tea brew and the CHX solutions. RESULTS: The test solution was able to reduce biofilm formation by 3 log steps compared with a negative (water) control. This was significantly less effective than the standard control CHX solutions, which reduced viable counts by 6 log steps. Both the test and control solutions exhibited staining on all surfaces. Staining was most pronounced on dentin, followed by enamel and to a significantly lesser degree on the restorative materials. Furthermore, the staining caused by the test solution on these restorative materials was generally lower than that caused by the control solutions. CONCLUSIONS: The test solution exhibited an antimicrobial activity. The composition, however, seems to hamper its effectiveness. Accordingly, it produced statistically significant, although by trend less, staining on restorative materials.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

[Genotoxic and cytotoxic effects in buccal cells of children living in ecologically different Kuzbass areas].

The article presents the results of the study of micronuclei and other types of cytogenetic aberrations in mucous tunic epithelium cells from children living in two different parts of the Kemerovo region (Tashtagol city, above-standard radon concentration exposition, n = 80), and Krasnoye settlement Leninsk-Kuznetsk area (comparison group, n = 41). The samples studied did not differ in the frequency of micronuclei containing cells. Tashtagol children sample showed significant increase in the number of binuclear cells, buccal epithelial cells with nuclear protrusions and with nuclear vacuoles, pyknotic cells, and apoptosis bodies. Reliable increase in average number of cells with chromatin condensation and kayolysis was found in the comparison group. It has been shown that the frequency of metaphase chromosome aberrations registered in peripheral blood lymphocytes corresponds to the amount of nuclear aberrations detected in buccal epithelium cells using micronuclei test.

Glucagon-like peptide-1, insulin-like growth factor-1, and adiponectin in insulin-dysregulated ponies: effects of feeding a high nonstructural carbohydrate diet and association with prospective laminitis.

Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.

Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.