The non-vesicle cell-free DNA (cfDNA) induces cell transformation associated with horizontal DNA transfer.

BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis. METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy. RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells. CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.

Role of CB2 cannabinoid receptor in the development of food addiction in male mice.

The endocannabinoid system plays an important role in multiple behavioral responses due to its wide distribution in the central nervous system. The cannabinoid CB1 receptor was associated to the loss of behavioral control over food intake occurring during food addiction. The cannabinoid CB2 receptor (CB2R) is expressed in brain areas canonically associated with addictive-like behavior and was linked to drug-addictive properties. In this study, we evaluated for the first time the specific role of the CB2R in food addiction by using a well-validated operant mouse model of long-term training to obtain highly palatable food. We have compared in this model the behavioral responses of wild-type mice, mutant mice constitutively lacking CB2R, and transgenic mice overexpressing CB2R. The lack of CB2R constitutes a protective factor for the development of food addiction and the impulsive and depressive-like behavior associated. In contrast, the overexpression of CB2R induces a vulnerable phenotype toward food addiction after long-term exposure to highly palatable chocolate pellets. Relevant transcriptomic changes were associated to resilience and vulnerability to food addiction depending on the genotype, which provides a mechanistic explanation for these behavioral changes. Therefore, CB2R may constitute a potential therapeutic target for the loss of eating control and the comorbid emotional effects associated to food addiction.

Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.

ABS-SMART (Aortic Balloon Supporting for Superior Mesenteric Artery Recanalization Technique): A New Technical Option for Recanalization of Complete Superior Mesenteric Artery Occlusion in Chronic Mesenteric Ischemia.

OBJECTIVE: To report our experience with a new technique for recanalization of the superior mesenteric artery (SMA)/celiac trunk (CT) with complete occlusion at the origin. TECHNIQUE: We describe our ABS-SMART (Aortic Balloon Supporting for Superior Mesenteric Artery Recanalization Technique) for recanalization of the CT and SMA in cases of complete occlusion of these arteries with a short or inexistent stump, which usually corresponds to chronic lesions with important calcification of the ostium. CONCLUSION: The ABS-SMART is an alternative for the recanalization of visceral arteries in cases where other conventional techniques have failed. It is particularly useful in scenarios characterized by a short occlusion at the origin of the target vessel, with no entry stump or severe calcification at the origin. CLINICAL IMPACT: Catheterization and recanalization of visceral stenoses may pose a challenge in some cases, as for example in the presence of a very narrow angle between the root or origin of the vessel and the aorta, as well as in the case of long and calcified stenoses, or when arteriography is unable to visualize the origin of the vessel. The present study describes our experience with the endovascular revascularization of visceral vessels using an aortic balloon-supported recanalization technique not previously described in the literature, that may be an effective alternative for the treatment of lesions of difficult access, such as total occlusion at the origin of the target vessel, with no entry stump or severe calcification at the origin of the SMA and CT, by improving the chances for technical success.

Perspective from a Hubbard U-density corrected scheme towards a spin crossover-mediated change in gas affinity.

By employing a recently proposed Hubbard U density-corrected scheme within density functional theory, we provide design principles towards the design of materials exhibiting a spin crossover-assisted gas release. Small molecular fragments are used as case study to identify two main mechanisms behind the change in binding energy upon spin transitions. The feasibility of the proposed mechanism in porous crystals is assessed by correlating the change in binding energy of CO2, CO, N2, and H2, upon spin crossover, with the adiabatic energy difference associated with the spin state change of the square-planar metal in Hofmann-type clathrates (M = Fe, Mn, Ni). A few promising cases are identified for the adsorption of intermediate ligand field strength molecules such as N2 and H2. The latter stands out as the most original result as the strong interaction in low spin, as expected from a Kubas mechanism, results in a large change in binding energy. This work provides a general perspective towards the engineering of open-metal site frameworks exhibiting local environments designed to have a spin crossover upon adsorption of specific gas molecules.

Influencing factors on the safety and effectiveness of venom immunotherapy.

BACKGROUND AND OBJECTIVE: The safety profile of venom immunotherapy (VIT) is a relevant issue and considerable differences in safety and efficacy of VIT have been reported. The primary aim of this study was to evaluate the safety of ACE inhibitors and beta-blockers during VIT, which has already been published. For a second analysis, data concerning premedication and venom preparations in relation to systemic adverse events (AE) during the up-dosing phase and the first year of the maintenance phase were evaluated as well as the outcome of field stings and sting challenges. METHODS: The study was conducted as an open, prospective, observational, multicenter study. In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during the up-dosing and 19.7% of patients during the maintenance phase. Taking antihistamines had no effect on the frequency of systemic AE (p=0.11) but large local reactions (LLR) were less frequently seen (OR: 0.74; 95% CI: 0.58-0.96; p=0.02). Aqueous preparations were preferentially used for up-dosing (73.0%) and depot preparations for the maintenance phase (64.5%). The type of venom preparation neither had an influence on the frequency of systemic AE nor on the effectiveness of VIT (p=0.26 and p=0.80, respectively), while LLR were less frequently seen when depot preparations were used (p<0.001). CONCLUSION: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLR but not systemic AE. All venom preparations used were equally effective and did not differ in the frequency of systemic AE.

Air pollution and meteorological variables' effects on COVID-19 first and second waves in Spain.

The aim of this research is to study the influence of atmospheric pollutants and meteorological variables on the incidence rate of COVID-19 and the rate of hospital admissions due to COVID-19 during the first and second waves in nine Spanish provinces. Numerous studies analyze the effect of environmental and pollution variables separately, but few that include them in the same analysis together, and even fewer that compare their effects between the first and second waves of the virus. This study was conducted in nine of 52 Spanish provinces, using generalized linear models with Poisson link between levels of PM10, NO2 and O3 (independent variables) and maximum temperature and absolute humidity and the rates of incidence and hospital admissions of COVID-19 (dependent variables), establishing a series of significant lags. Using the estimators obtained from the significant multivariate models, the relative risks associated with these variables were calculated for increases of 10 µg/m3 for pollutants, 1 °C for temperature and 1 g/m3 for humidity. The results suggest that NO2 has a greater association than the other air pollution variables and the meteorological variables. There was a greater association with O3 in the first wave and with NO2 in the second. Pollutants showed a homogeneous distribution across the country. We conclude that, compared to other air pollutants and meteorological variables, NO2 is a protagonist that may modulate the incidence and severity of COVID-19, though preventive public health measures such as masking and hand washing are still very important. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04190-z.

Development of 27 new microsatellite markers for the shanny Lipophrys pholis.

BACKGROUND: The shanny Lipophrys pholis is an intertidal fish that is widely distributed throughout the Northeast Atlantic. Characterized by limited adult mobility and a long pelagic larval duration, the shanny stands as an ideal model to better understand larval dispersal and connectivity dynamics, which are critical parameters with implications for marine conservation and management. METHODS AND RESULTS: To this aim, we developed 27 highly polymorphic microsatellite markers and characterized a population of 42 individuals, presenting an average allelic diversity of 20.1 alleles per locus and heterozygosity ranging from 0.619 to 1. CONCLUSIONS: This set of newly developed microsatellite markers will be useful in providing critical insights into the processes which shape L. pholis gene flow and connectivity patterns and can be used to investigate local parentage lineages.

Exposed water ice on the nucleus of comet 67P/Churyumov-Gerasimenko.

Although water vapour is the main species observed in the coma of comet 67P/Churyumov-Gerasimenko and water is the major constituent of cometary nuclei, limited evidence for exposed water-ice regions on the surface of the nucleus has been found so far. The absence of large regions of exposed water ice seems a common finding on the surfaces of many of the comets observed so far. The nucleus of 67P/Churyumov-Gerasimenko appears to be fairly uniformly coated with dark, dehydrated, refractory and organic-rich material. Here we report the identification at infrared wavelengths of water ice on two debris falls in the Imhotep region of the nucleus. The ice has been exposed on the walls of elevated structures and at the base of the walls. A quantitative derivation of the abundance of ice in these regions indicates the presence of millimetre-sized pure water-ice grains, considerably larger than in all previous observations. Although micrometre-sized water-ice grains are the usual result of vapour recondensation in ice-free layers, the occurrence of millimetre-sized grains of pure ice as observed in the Imhotep debris falls is best explained by grain growth by vapour diffusion in ice-rich layers, or by sintering. As a consequence of these processes, the nucleus can develop an extended and complex coating in which the outer dehydrated crust is superimposed on layers enriched in water ice. The stratigraphy observed on 67P/Churyumov-Gerasimenko is therefore the result of evolutionary processes affecting the uppermost metres of the nucleus and does not necessarily require a global layering to have occurred at the time of the comet's formation.

Simulations of micro-sphere/shell 2D silica photonic crystals for radiative cooling.

Passive daytime radiative cooling has recently become an attractive approach to address the global energy demand associated with modern refrigeration technologies. One technique to increase the radiative cooling performance is to engineer the surface of a polar dielectric material to enhance its emittance at wavelengths in the atmospheric infrared transparency window (8-13 µm) by outcoupling surface-phonon polaritons (SPhPs) into free-space. Here we present a theoretical investigation of new surface morphologies based upon self-assembled silica photonic crystals (PCs) using an in-house built rigorous coupled-wave analysis (RCWA) code. Simulations predict that silica micro-sphere PCs can reach up to 73 K below ambient temperature, when solar absorption and conductive/convective losses can be neglected. Micro-shell structures are studied to explore the direct outcoupling of the SPhP, resulting in near-unity emittance between 8 and 10 µm. Additionally, the effect of material composition is explored by simulating soda-lime glass micro-shells, which, in turn, exhibit a temperature reduction of 61 K below ambient temperature. The RCWA code was compared to FTIR measurements of silica micro-spheres, self-assembled on microscope slides.

Percutaneous tibial nerve stimulation in patients with severe low anterior resection syndrome: randomized clinical trial.

BACKGROUND: Treatment of low anterior resection syndrome (LARS) is challenging. Percutaneous tibial nerve stimulation (PTNS) can improve select bowel disorders. An RCT was conducted to assess the efficacy of PTNS compared with sham stimulation in patients with severe LARS. METHOD: This was a multicentre, double-blind RCT. Patients with major LARS score were allocated to receive PTNS or sham therapy (needle placement simulation without nerve stimulation). The study included 16 sessions of 30 min once a week for 12 consecutive weeks, followed by four additional sessions once a fortnight for the following 4 weeks. The primary endpoint was efficacy of PTNS defined by the LARS score 12 months after treatment. Secondary endpoints included faecal incontinence, quality of life (QoL), and sexual function. RESULTS: Between September 2016 and July 2018, 46 eligible patients were assigned randomly in a 1 : 1 ratio to PTNS or sham therapy. Baseline characteristics were similar. LARS scores were reduced in both groups, but only patients who received PTNS maintained the effect in the long term (mean(s.d.) score 36.4(3.9) at baseline versus 30.7(11.5) at 12 months; P = 0.018; effect size -5.4, 95 per cent c.i. -9.8 to -1.0), with a mean reduction of 15.7 per cent at 12-month follow-up. The faecal incontinence score was improved after 12 months in the PTNS group (mean(s.d.) score 15.4(5.2) at baseline versus 12.5(6.4) at 12 months; P = 0.018). No major changes in QoL and sexual function were observed in either group. There was no therapy-associated morbidity. Three patients discontinued the study, but none owing to study-related issues. CONCLUSION: PTNS has positive effects in some patients with major LARS, especially in those with faecal incontinence. Registration number: NCT02517853 (http://www.clinicaltrials.gov).

Video discharge instructions for pediatric gastroenteritis in an emergency department: a randomized, controlled trial.

The aim was to evaluate if the addition of video discharge instructions (VDIs) to usual verbal information improved the comprehension of information provided to caregivers of patients who consult for acute gastroenteritis (AGE). We conducted an open-label, parallel, randomized trial, enrolling patients who consulted for AGE at a tertiary hospital. First, caregivers answered a written test concerning AGE characteristics and management. They were randomly allocated to a control group, which received the usual verbal instructions, or to an intervention group, which additionally received VDI. After discharge, caregivers were contacted by telephone and answered the same test, satisfaction questions, and follow-up information. From September 2019 to March 2020, 139 patients were randomized, 118 completed follow-up. The mean score was 3.13 (SD 1.07) over 5 points in the initial test and 3.96 (SD 0.96) in the follow-up test. Patients in the intervention group had a greater improvement (1.17 points, SD 1.11) than those in the control group (0.47 points, SD 0.94, p < 0.001). In the follow-up test, 49.1% in the intervention group and 18.6% in the control group answered all questions correctly (p < 0.001). There were no significant differences in return visits. Caregivers gave high satisfaction scores regardless of the allocation group.Conclusion: Video instructions improve caregivers' understanding of discharge information.Trial registration: [NCT04463355, retrospectively registered July 9, 2020]. What is Known: • Poor comprehension of discharge instructions leads to incorrect treatment after discharge, increased readmissions and a reduction of caregivers' satisfaction. • Video discharge instructions are useful providing concise information independently of the patients' health literacy level or communication skills of the health care provider What is New: • The addition of video discharge instructions to verbal instructions improves caregivers' knowledge about AGE improved with respect to those who only receive verbal instructions • Video instructions do not add extra time to the emergency department visits.

Spotting intruders: Species distribution models for managing invasive intertidal macroalgae.

Invasive macroalgae represent one of the major threats to marine biodiversity, ecosystem functioning and structure, as well as being important drivers of ecosystem services depletion. Many such species have become well established along the west coast of the Iberian Peninsula. However, the lack of information about the distribution of the invaders and the factors determining their occurrence make bioinvasions a difficult issue to manage. Such information is key to enabling the design and implementation of effective management plans. The present study aimed to map the current probability of presence of six invasive macroalgae: Grateloupia turuturu, Asparagopsis armata, Colpomenia peregrina, Sargassum muticum, Undaria pinnatifida, and Codium fragile ssp. fragile. For this purpose, an extensive field survey was carried out along the coast of the north-western Iberian Peninsula. Species distribution models (SDMs) were then used to map the presence probability of these invasive species throughout the study region on the basis of environmental and anthropogenic predictor variables. The southern Galician rias were identified as the main hotspots of macroalgal invasion, with a high probability of occurrence for most of the species considered. Conversely, the probability of presence on the Portuguese coast was generally low. Physico-chemical variables were the most important factors for predicting the distribution of invasive macroalgae contributing between 57.27 and 85.24% to the ensemble models. However, anthropogenic factors (including size of vessels, number of shipping lines, distance from ports, population density, etc.) considerably improved the estimates of the probability of occurrence for most of the target species. This study is one of the few to include anthropogenic factors in SDMs for invasive macroalgae. The findings suggest that management actions aimed at controlling these species should strengthen control and surveillance at ports, particularly in southern Galician rias. Early detection should be of main concern for risk assessment plans on the Portuguese coast.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.3×10^{19} eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19} eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18} eV is [5.66±0.03(stat)±1.40(syst)]×10^{53} erg Mpc^{-3}.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Steno type 1 risk engine and preclinical atherosclerosis in Mediterranean individuals with type 1 diabetes.

BACKGROUND AND AIMS: Tools to detect type 1 diabetes (T1D) individuals at overt cardiovascular disease (CVD) risk are scarce. We aimed to assess the usefulness of the score 'Steno Type 1 Risk Engine' (Steno-Risk) to identify T1D patients with advanced carotid atherosclerosis. MATERIAL AND METHODS: T1D patients without CVD with at least one of the following were included: ≥40 years, diabetic nephropathy, or diabetes duration ≥10 years with ≥1 CVD risk factor. Intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by standardized B-mode ultrasonography. Steno-Risk was used to estimate 10-year risk (<10% low; 10%-20% moderate; ≥20% high risk). Associations between Steno-Risk and preclinical atherosclerosis were assessed after adjusting for other CVD risk factors. RESULTS: We evaluated 302 patients (55% men, age 47.8 ± 9.8 years, T1D duration 26.3 ± 9.3 years). The prevalence of carotid plaque and ≥2 plaques were 36.4% and 19.2%, respectively; without sex differences. Age (57.4 ± 7.4 vs 37.1 ± 6.2 years), T1D duration (31.3 ± 10.4 vs 21.5 ± 7.1 years), hypertension (52.3% vs 6.3%), nephropathy (25.6% vs 5.1%) and retinopathy (53.5% vs 32.9%) were higher in high-risk (n = 86) vs low-risk participants (n = 79; P < .001 for all). Preclinical atherosclerosis (IMT and plaque) increased in parallel with Steno-Risk (P < .001). In logistic regression analysis, both age ≥40 years and Steno-Risk ≥20% were associated with the presence of plaque (OR 4.22 [1.57-11.36] and 3.79 [1.61-6.80]; respectively), but only high Steno-Risk remained independently associated with ≥2 plaques (OR 3.31 [1.61-6.80]). CONCLUSION: Steno-Risk is independently associated with preclinical atherosclerosis. Further studies are needed to ascertain its usefulness in this high-risk population.

Validation of self-reported adherence in chronic patients visiting pharmacies and factors associated with the overestimation and underestimation of good adherence.

BACKGROUND: Studies validating indirect methods to identify nonadherence in chronic patients who visit pharmacies are lacking. The aim of this study was to validate self-reported adherence and assess the variables associated with both overestimation and underestimation of good adherence when using this method. MATERIALS AND METHODS: An observational, cross-sectional study was undertaken to validate self-reported adherence in 132 community pharmacies throughout Spain in 6237 chronic patients. The Morisky-Green test was used as the validation method and through a 2 × 2 table, the validity indicators, predictive values, and likelihood ratios were calculated. To assess the variables associated with both overestimation and underestimation of good adherence, multivariate logistic regression analysis and calculation of the area under the ROC curve were used to evaluate discriminatory capacity. RESULTS: Sensitivity was 27.8% (95% CI: 26.2-29.4) and specificity was 93.9% (95% CI: 93.1-94.7). Discrepancy analysis obtained a significant overestimation of good adherence (p < 0.001). The factors associated with overestimating good adherence were performing a mnemonic trick (p < 0.001), not self-medicating (p < 0.001), a high level of physical activity (p < 0.001), and an older age (p = 0.014). Factors associated with underestimation were self-medication (p < 0.001), desiring more information (p < 0.001), smoking (p = 0.014), not engaging in physical activity in the low (p = 0.006) or high (p < 0.001) categories, having a younger mean age (p = 0.007), and taking two to three (p = 0.029) or four or more (p < 0.001) chronic treatments. CONCLUSION: Self-reported adherence has good specificity but poor sensitivity. The associated profiles of the discrepancies were obtained to identify both good and poor adherence.

Candidate genes and genome-wide association study of grain protein content and protein deviation in durum wheat.

MAIN CONCLUSION: Stable QTL for grain protein content co-migrating with nitrogen-related genes have been identified by the candidate genes and genome-wide association mapping approaches useful for marker-assisted selection. Grain protein content (GPC) is one of the most important quality traits in wheat, defining the nutritional and end-use properties and rheological characteristics. Over the years, a number of breeding programs have been developed aimed to improving GPC, most of them having been prevented by the negative correlation with grain yield. To overcome this issue, a collection of durum wheat germplasm was evaluated for both GPC and grain protein deviation (GPD) in seven field trials. Fourteen candidate genes involved in several processes related to nitrogen metabolism were precisely located on two high-density consensus maps of common and durum wheat, and six of them were found to be highly associated with both traits. The wheat collection was genotyped using the 90 K iSelect array, and 11 stable quantitative trait loci (QTL) for GPC were detected in at least three environments and the mean across environments by the genome-wide association mapping. Interestingly, seven QTL were co-migrating with N-related candidate genes. Four QTL were found to be significantly associated to increases of GPD, indicating that selecting for GPC could not affect final grain yield per spike. The combined approaches of candidate genes and genome-wide association mapping led to a better understanding of the genetic relationships between grain storage proteins and grain yield per spike, and provided useful information for marker-assisted selection programs.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Autosomal Dominant Gene Negative Frontotemporal Dementia-Think of SCA17.

SCA 17 is a rare, autosomal dominant disorder caused by TBP gene CAG/CAA repeat expansion. Ataxia and dementia are common. The presence of frontal dysfunction at outset of the disease may mimic frontotemporal dementia (FTD). Parkinsonism, chorea, dystonia, and pyramidal signs may occur. We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister at age 39 became dysarthric and unsteady. A brother at age 52 demonstrated emotional lability, and became dysarthric, unsteady, and slowed down. Their mother aged 73 had an abnormal antalgic gait due to arthritis; their father was jocular and disinhibited. MAPT testing detected an exon 9 c.726C>T variant in the proband. Subsequent testing in nine siblings and both parents failed to show co-segregation with disease. SCA17 testing revealed a TBP gene 43 repeat expansion that co-segregated in all affected siblings and in the mother whose gait problems were initially attributed to arthritis. In over 80% of cases of FTD with clear autosomal dominant inheritance, causative gene defects involve MAPT, GRN, or C9orf72 mutations. A minority involves VCP, FUS, and CHMP2B. As evident from our case, SCA17 testing should also be considered, especially if cerebellar atrophy if found on imaging. Segregation analysis is crucial. MAPT variant (c.726C>T exon 9) detected in the family was deemed a polymorphism.