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Actin beta-like 2 (ACTBL2) was recently identified as a new mediator of migration in ovarian cancer cells. Yet, its impact on tumor-infiltrating and thus migrating leukocytes (TILs) remains to date unknown. This study characterizes the subset of ACTBL2-expressing TILs in epithelial ovarian cancer (EOC) and elucidates their prognostic influence on the overall survival of EOC patients with special regard to different histological subtypes. Comprehensive immunohistochemical analyses of Tissue-Microarrays of 156 ovarian cancer patients revealed, that a tumor infiltration by ACTBL2-positive leukocytes was significantly associated with an improved overall survival (OS) (61.2 vs. 34.4 months; p = 0.006) and was identified as an independent prognostic factor (HR = 0.556; p = 0.038). This significant survival benefit was particularly evident in patients with low-grade serous carcinoma (OS: median not reached vs. 15.6 months, p < 0.001; HR = 0.058, p = 0.018). In the present cohort, ACTBL2-positive TILs were mainly composed of CD44-positive cytotoxic T-cells (CD8+) and macrophages (CD68+), as depicted by double-immunofluorescence and various immunohistochemical serial staining. Our results provide significant evidence of the prognostic impact and cellular composition of ACTBL2-expressing TILs in EOC. Complementary studies are required to analyze the underlying molecular mechanisms of ACTBL2 as a marker for activated migrating leukocytes and to further characterize its immunological impact on ovarian carcinogenesis.
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Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario , Pronóstico , Neoplasias Ováricas/patología , Linfocitos T Citotóxicos/patología , Linfocitos Infiltrantes de Tumor , Leucocitos/patologíaRESUMEN
Despite quantum electrodynamics (QED) being one of the most stringently tested theories underpinning modern physics, recent precision atomic spectroscopy measurements have uncovered several small discrepancies between experiment and theory. One particularly powerful experimental observable that tests QED independently of traditional energy level measurements is the "tune-out" frequency, where the dynamic polarizability vanishes and the atom does not interact with applied laser light. In this work, we measure the tune-out frequency for the 23S1 state of helium between transitions to the 23P and 33P manifolds and compare it with new theoretical QED calculations. The experimentally determined value of 725,736,700(260) megahertz differs from theory [725,736,252(9) megahertz] by 1.7 times the measurement uncertainty and resolves both the QED contributions and retardation corrections.
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BACKGROUND: Hospitalization rates (HR), emergency care prevalence (ECP) and case fatality proportions (CFP) of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients in one municipality have not been studied, including how these differ from other pandemic or seasonal viral diseases, such as influenza A/B or norovirus. These analyses and their comparison with negative-tested hospitalized patients are the purpose of the present study. METHODS: A total of 67,000 cases of hospitalized patients of a tertiary care hospital and data of the regional health institute were analyzed to calculate HR, ECP and CFP of SARS-CoV2, influenza A/B and norovirus genotype 1/2. RESULTS: In the city and district of Fürth (Germany), 824 persons (0.34%) tested SARS-CoV-2-positive through 7 May 2020, 162 of whom (19.7%) were hospitalized. Furthermore, 48 out of 91 patients died in hospital (CFP 11.0%). During the flu/norovirus season 2019/2020 992 inhabitants were flu-positive and 135 norovirus-positive, of whom 202 (20.3%) and 125 (91.9%), respectively, were hospitalized. The ECPs were 4.1%, 2.0% and 0.6%. The CFPs of the SARS-CoV-2-, influenza- and norovirus-positive hospital cohort were 29.1%, 3.0% and 1.6%, while CFPs of the negative-tested were 5.9%, 4.8% and 6.9% with an in-hospital mortality of 2.1% for 2020. CONCLUSIONS: While HRs of SARS-CoV2 and influenza were similar, CFPs differ significantly. CFPs of negative-tested patients were comparable between the three infectious diseases.
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COVID-19 , Infecciones por Caliciviridae , Gripe Humana , COVID-19/epidemiología , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/epidemiología , Humanos , Gripe Humana/epidemiología , Pandemias , SARS-CoV-2RESUMEN
We present an experimental study of a two component Fermi gas following an interaction quench into the superfluid phase. Starting with a weakly attractive gas in the normal phase, interactions are ramped to unitarity at a range of rates and we measure the subsequent dynamics as the gas approaches equilibrium. Both the formation and condensation of fermion pairs are mapped via measurements of the pair momentum distribution and can take place on very different timescales, depending on the adiabaticity of the quench. The contact parameter is seen to respond very quickly to changes in the interaction strength, indicating that short-range correlations, based on the occupation of high-momentum modes, evolve far more rapidly than the correlations in low-momentum modes necessary for pair condensation.
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Flooding affects more people than any other environmental hazard and hinders sustainable development1,2. Investing in flood adaptation strategies may reduce the loss of life and livelihood caused by floods3. Where and how floods occur and who is exposed are changing as a result of rapid urbanization4, flood mitigation infrastructure5 and increasing settlements in floodplains6. Previous estimates of the global flood-exposed population have been limited by a lack of observational data, relying instead on models, which have high uncertainty3,7-11. Here we use daily satellite imagery at 250-metre resolution to estimate flood extent and population exposure for 913 large flood events from 2000 to 2018. We determine a total inundation area of 2.23 million square kilometres, with 255-290 million people directly affected by floods. We estimate that the total population in locations with satellite-observed inundation grew by 58-86 million from 2000 to 2015. This represents an increase of 20 to 24 per cent in the proportion of the global population exposed to floods, ten times higher than previous estimates7. Climate change projections for 2030 indicate that the proportion of the population exposed to floods will increase further. The high spatial and temporal resolution of the satellite observations will improve our understanding of where floods are changing and how best to adapt. The global flood database generated from these observations will help to improve vulnerability assessments, the accuracy of global and local flood models, the efficacy of adaptation interventions and our understanding of the interactions between landcover change, climate and floods.
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Aclimatación , Demografía , Planificación en Desastres , Inundaciones/estadística & datos numéricos , Modelos Teóricos , Imágenes Satelitales , Bases de Datos como Asunto , Clima Extremo , Humanos , Medición de RiesgoRESUMEN
OBJECTIVES: To evaluate whether there is an increased risk for noise-induced hearing loss at high altitude rsp. in hypobaric hypoxia. METHODS: Thirteen volunteers got standard audiometry at 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, and 8000 Hz before and after 10 min of white noise at 90 dB. The system was calibrated for the respective altitude. Measurements were performed at Kathmandu (1400 m) and at Gorak Shep (5300 m) (Solo Khumbu/Nepal) after 10 days of acclimatization while on trek. Temporary threshold shift (TTS) was analyzed by descriptive statistics and by factor analysis. RESULTS: TTS is significantly more pronounced at high altitudes. Acclimatization does not provide any protection of the inner ear, although it increases arterial oxygen saturation. CONCLUSION: The thresholds beyond which noise protection is recommended (> 80 dB) or necessary (> 85 dB) are not sufficient at high altitudes. We suggest providing protective devices above an altitude of 1500 m ("ear threshold altitude") when noise level is higher than 75 dB and using them definitively above 80 dB. This takes the individual reaction on hypobaric hypoxia at high altitude into account.
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Altitud , Umbral Auditivo , Exposición a Riesgos Ambientales/efectos adversos , Ruido/efectos adversos , Oxígeno , Aclimatación , Adulto , Audiometría , Expediciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: The effects of the maternal nutritional environment on the growth and metabolism of the offspring, and its impacts on health in adult life are defined as metabolic programming. Thus, the objective of this study was to evaluate the effects of Roux-en-Y gastric bypass (RYGB) on the morphology of muscle fiber and neuromuscular junction (NMJ) of the offspring of rats submitted to RYGB. METHODS: Three-week-old Wistar rats were separated into two groups: 1) CAF SHAM which received a cafeteria diet and was submitted to a sham operation and 2) CAF RYGB, which received a cafeteria diet and was submitted to RYGB. The first generation (F1) offspring (male) was named according to the treatment of mothers as CAF SHAM-F1 and CAF RYGB-F1 and received a standard diet after weaning. At 17 weeks, the animals were euthanized, and the extensor digitorum longus muscle (EDL) was collected and processed in light microscopy and transmission electron microscopy for morphological and morphometric analysis. RESULTS: The CAF RYGB-F1 group showed a reduction in the weight of the EDL muscle and also a reduction in the area of type I, IIa and IIb fibers and a nucleus/fiber ratio. This same group also showed an increase in the capillary density and myofibrillar disorganization and in the Z-line, as well as a reduction in the area of the NMJs. CONCLUSION: The RYGB surgery in mothers produced morphological changes in the skeletal striated muscles of the offspring.
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Cirugía Bariátrica/efectos adversos , Músculo Esquelético/patología , Obesidad/cirugía , Animales , Tejido Conectivo/patología , Femenino , Músculo Esquelético/ultraestructura , Unión Neuromuscular/patología , Embarazo , Ratas WistarRESUMEN
We present an experimental and theoretical study of the phonon mode in a unitary Fermi gas. Using two-photon Bragg spectroscopy, we measure excitation spectra at a momentum of approximately half the Fermi momentum, both above and below the superfluid critical temperature T_{c}. Below T_{c}, the dominant excitation is the Bogoliubov-Anderson (BA) phonon mode, driven by gradients in the phase of the superfluid order parameter. The temperature dependence of the BA phonon is consistent with a theoretical model based on the quasiparticle random phase approximation in which the dominant damping mechanism is via collisions with thermally excited quasiparticles. As the temperature is increased above T_{c}, the phonon evolves into a strongly damped collisional mode, accompanied by an abrupt increase in spectral width. Our study reveals strong similarities between sound propagation in the unitary Fermi gas and bosonic liquid helium.
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Infection and inflammation of the mammary gland, and especially prevention of mastitis, are still major challenges for the dairy industry. Different approaches have been tried to reduce the incidence of mastitis. Genetic selection of cows with lower susceptibility to mastitis promises sustainable success in this regard. Bos taurus autosome (BTA) 18, particularly the region between 43 and 59 Mb, harbors quantitative trait loci (QTL) for somatic cell score, a surrogate trait for mastitis susceptibility. Scrutinizing the molecular bases hereof, we challenged udders from half-sib heifers having inherited either favorable paternal haplotypes for somatic cell score (Q) or unfavorable haplotypes (q) with the Staphylococcus aureus pathogen. RNA sequencing was used for an in-depth analysis of challenge-related alterations in the hepatic transcriptome. Liver exerts highly relevant immune functions aside from being the key metabolic organ. Hence, a holistic approach focusing on the liver enabled us to identify challenge-related and genotype-dependent differentially expressed genes and underlying regulatory networks. In response to the S. aureus challenge, we found that heifers with Q haplotypes displayed more activated immune genes and pathways after S. aureus challenge compared with their q half-sibs. Furthermore, we found a significant enrichment of differentially expressed loci in the genomic target region on BTA18, suggesting the existence of a regionally acting regulatory element with effects on a variety of genes in this region.
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Predisposición Genética a la Enfermedad , Hígado/metabolismo , Mastitis Bovina/inmunología , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus , Transcriptoma , Animales , Bovinos , Industria Lechera , Susceptibilidad a Enfermedades/veterinaria , Femenino , Haplotipos , Glándulas Mamarias Animales/metabolismo , Mastitis Bovina/genética , Fenotipo , Sitios de Carácter Cuantitativo , Selección Genética , Análisis de Secuencia de ARN , Infecciones Estafilocócicas/genética , Staphylococcus aureus/genética , Vacunación/veterinariaRESUMEN
BACKGROUND: In dairy herds, mastitis causes detrimental economic losses. Genetic selection offers a sustainable tool to select animals with reduced susceptibility towards postpartum diseases. Studying underlying mechanisms is important to assess the physiological processes that cause differences between selected haplotypes. Therefore, the objective of this study was to establish an in vivo infection model to study the impact of selecting for alternative paternal haplotypes in a particular genomic region on cattle chromosome 18 for mastitis susceptibility under defined conditions in uniparous dairy cows. RESULTS: At the start of pathogen challenge, no significant differences between the favorable (Q) and unfavorable (q) haplotypes were detected. Intramammary infection (IMI) with Staphylococcus aureus 1027 (S. aureus, n = 24, 96 h) or Escherichia coli 1303 (E. coli, n = 12, 24 h) was successfully induced in all uniparous cows. This finding was confirmed by clinical signs of mastitis and repeated recovery of the respective pathogen from milk samples of challenged quarters in each animal. After S. aureus challenge, Q-uniparous cows showed lower somatic cell counts 24 h and 36 h after challenge (P < 0.05), lower bacterial shedding in milk 12 h after challenge (P < 0.01) and a minor decrease in total milk yield 12 h and 24 h after challenge (P < 0.01) compared to q-uniparous cows. CONCLUSION: An in vivo infection model to study the impact of genetic selection for mastitis susceptibility under defined conditions in uniparous dairy cows was successfully established and revealed significant differences between the two genetically selected haplotype groups. This result might explain their differences in susceptibility towards IMI. These clinical findings form the basis for further in-depth molecular analysis to clarify the underlying genetic mechanisms for mastitis resistance.
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Mastitis Bovina/genética , Mastitis Bovina/microbiología , Herencia Paterna , Animales , Bovinos , Industria Lechera , Escherichia coli , Infecciones por Escherichia coli/veterinaria , Femenino , Haplotipos , Masculino , Leche/microbiología , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureusRESUMEN
The original article [1] contained an error whereby the captions to Figs 2 and 3 were mistakenly inverted; this has now been corrected.
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BACKGROUND: A major challenge in modern medicine and animal husbandry is the issue of antimicrobial resistance. One approach to solving this potential medical hazard is the selection of farm animals with less susceptibility to infectious diseases. Recent advances in functional genome analysis and quantitative genetics have opened the horizon to apply genetic marker information for efficiently identifying animals with preferential predisposition regarding health traits. The current study characterizes functional traits with a focus on udder health in dairy heifers. The animals were selected for having inherited alternative paternal haplotypes for a genomic region on Bos taurus chromosome (BTA) 18 genetically associated with divergent susceptibility to longevity and animal health, particularly mastitis. RESULTS: In the first weeks of lactation, the q heifers which had inherited the unfavorable (q) paternal haplotype displayed a significantly higher number of udder quarters with very low somatic cell count (< 10,000 cells / ml) compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. This might result in impaired mammary gland sentinel function towards invading pathogens. Furthermore, across the course of the first lactation, there was indication that q half-sib heifers showed higher somatic cell counts, a surrogate trait for udder health, in whole milkings compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. Moreover, heifers with the haplotype Q had a higher feed intake and higher milk yield compared to those with the q haplotype. Results of this study indicate that differences in milk production and calculated energy balance per se are not the main drivers of the genetically determined differences between the BTA18 Q and q groups of heifers. CONCLUSIONS: The paternally inherited haplotype from a targeted BTA18 genomic region affect somatic cell count in udder quarters during the early postpartum period and might also contribute to further aspects of animal's health and performance traits due to indirect effects on feed intake and metabolism.
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Glándulas Mamarias Animales/fisiología , Herencia Paterna , Animales , Bovinos , Mapeo Cromosómico , Ingestión de Alimentos/genética , Metabolismo Energético/genética , Femenino , Haplotipos/genética , Lactancia/genética , Masculino , Glándulas Mamarias Animales/microbiología , Mastitis Bovina/genética , Periodo PospartoRESUMEN
We present an experimental study of the high-energy excitation spectra of unitary Fermi gases. Using focused beam Bragg spectroscopy, we locally probe atoms in the central region of a harmonically trapped cloud where the density is nearly uniform, enabling measurements of the dynamic structure factor for a range of temperatures both below and above the superfluid transition. Applying sum rules to the measured Bragg spectra, we resolve the characteristic behavior of the universal contact parameter, C, across the superfluid transition. We also employ a recent theoretical result for the kinetic (second-moment) sum rule to obtain the internal energy of gases at unitarity.
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BACKGROUND: The aim of this study was to describe the current obstetric anaesthetic practices in Austria by performing a comprehensive questionnaire survey. METHODS: A questionnaire was sent via email to key anaesthesiologists from obstetric anaesthesia departments of 81 hospitals registered at the Austrian Ministry of Health. RESULTS: Of 81 departments contacted, 65 (80%), covering 84% of annual births in Austria, responded to the 82-question survey. Epidural analgesia was offered universally, at a rate under 30% in 56 (86%) of respondent hospitals. The caesarean section rate was under 30% in 44 (68%) respondent obstetric units. All respondents provided spinal anaesthesia as the primary anaesthetic technique for elective caesarean section. Three (5%) respondents administered long-acting intrathecal morphine and 18 (28%) respondents did not routinely administer any intrathecal opioid. Wound infiltration for acute postoperative pain control was practiced in two (3%) respondent units. A transversus abdominis plane block was offered as rescue analgesia in 14 (22%) departments. Spinal hypotension was treated using a prophylactic phenylephrine infusion in two (3%) respondent hospitals. Prophylactic antibiotics were administered prior to skin incision by 31 (48%) respondents. CONCLUSION: This survey reveals that obstetric anaesthetic practices in Austria differ in part from current European and American guidelines. Findings will direct the national workforce on obstetric anaesthesia that aims to introduce into Austria practice guidelines, based on international collaborations and guideline recommendations.
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Anestesia Obstétrica , Anestesia Raquidea , Analgesia Epidural , Austria , Cesárea , Femenino , Humanos , Embarazo , Encuestas y CuestionariosRESUMEN
Scarcity of donors leads transplant surgeons to consider extended-criteria lungs and occasionally to accept the unlikely. Here we report a case of successful single lung transplantation from a donor 8 months after double lung transplantation.
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Muerte Encefálica , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/métodos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Receptores de Trasplantes , Resultado del TratamientoRESUMEN
There is increasing evidence that nutrition during early mammalian life has a strong influence on health and performance in later life. However, there are conflicting data concerning the appropriate milk diet. This discrepancy particularly applies to ruminants, a group of mammals that switch from monogastric status to rumination during weaning. Little is known regarding how the whole genome expression pattern in the juvenile ruminant gut is affected by alternative milk diets. Thus, we performed a next-generation-sequencing-based holistic whole transcriptome analysis of the jejunum in male pre-weaned German Holstein calves fed diets with restricted or unlimited access to milk during the first 8 weeks of life. Both groups were provided hay and concentrate ad libitum. The analysis of jejunal mucosa samples collected 80 days after birth and four weeks after the end of the feeding regimes revealed 275 differentially expressed loci. While the differentially expressed loci comprised 67 genes encoding proteins relevant to metabolism or metabolic adaptation, the most distinct difference between the two groups was the consistently lower activation of the immune system in calves that experienced restricted milk access compared to calves fed milk ad libitum. In conclusion, different early life milk diets had significant prolonged effects on the intestinal immune system.
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Dieta/métodos , Perfilación de la Expresión Génica , Inmunidad Mucosa , Factores Inmunológicos/biosíntesis , Yeyuno/inmunología , Leche , Animales , Animales Recién Nacidos , Bovinos , Factores Inmunológicos/genética , Masculino , Secuenciación del ExomaRESUMEN
Appearance, distribution, and amount of intramuscular fat (IMF), often referred to as marbling, are highly variable and depend on environmental and genetic factors. On the molecular level, the concerted action of several drivers, including hormones, receptors, transcription factors, etc., determines where clusters of adipocytes arise. Therefore, the aim of future studies remains to identify such factors as biological markers of IMF to increase the ability to identify animals that deposit IMF early in age to increase efficiency of high-quality meat production. In an attempt to unravel the cellular development of marbling, we investigated the abundance of markers for adipogenic differentiation during fattening of cattle and the transcriptome of muscle and dissected IMF. Markers of different stages of adipogenic differentiation are well known from cell culture experiments. They are usually transiently expressed, such as delta-like homolog 1 (DLK1) that is abundant in preadipocytes and absent during differentiation to mature adipocytes. It is even a greater challenge to detect those markers in live animals. Within skeletal muscles, hyperplasia and hypertrophy of adipocytes can be observed throughout life. Therefore, development of marbling requires, on the cellular level, recruitment, proliferation, and differentiation of adipogenic cells to store excess energy in the form of lipids in new cells. In a recent study, we investigated the localization and abundance of early markers of adipogenic differentiation, such as DLK1, in bovine muscle tissue. An inverse relationship between IMF content and number of DLK1-positive cells in bovine muscle was demonstrated. Considering the cellular environment of differentiating adipocytes in muscle and the secretory action of adipocytes and myocytes, it becomes obvious that cross talk between cells via adipokines and myokines may be important for IMF development. Secreted proteins can act on other cells, inhibiting or stimulating their function via autocrine and paracrine actions. Such factors with potential influence on IMF, among them, agouti signaling protein and thrombospondin 4, were identified in transcriptome analyses and further investigated. Furthermore, results from transcriptome analysis indicate involvement of genes that are not directly related to adipogenesis and lipid metabolism, providing new candidates for future research.
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Adipogénesis , Bovinos/fisiología , Metabolismo de los Lípidos , Transcriptoma , Adipocitos/citología , Adipocitos/fisiología , Adipoquinas/metabolismo , Tejido Adiposo/crecimiento & desarrollo , Tejido Adiposo/fisiología , Animales , Biomarcadores/metabolismo , Bovinos/genética , Bovinos/crecimiento & desarrollo , Perfilación de la Expresión Génica/veterinaria , Masculino , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/fisiología , Carne Roja/normas , Eliminación de SecuenciaRESUMEN
This corrects the article DOI: 10.1103/PhysRevLett.113.013002.
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Cardiogenic shock is an acute emergency, which is classically managed by medical support with inotropes or vasopressors and frequently requires invasive ventilation. However, both catecholamines and ventilation are associated with a worse prognosis, and many patients deteriorate despite all efforts. Mechanical circulatory support is increasingly considered to allow for recovery or to bridge until making a decision or definite treatment. Of all devices, extracorporeal membrane oxygenation (ECMO) is the most widely used. Here we review features and strategical considerations for the use of ECMO in cardiogenic shock and cardiac arrest.