Feasibility of a combined mobile-health electrocardiographic and rapid diagnostic test screening for chagas-related cardiac alterations

Background: Chronic Chagas cardiomyopathy (CChC) is the most common cause of death related to Chagas disease (CD). The aim of this study was to assess the feasibility of a combined rapid diagnostic test (RDT) and electrocardiographic (ECG) screening in a remote rural village of the Bolivian Chaco, with a high prevalence of CChC. Methods: Consecutive healthy volunteers > 15 years were enrolled in the community of Palmarito (municipality of Gutierrez, Santa Cruz Department, Bolivia) in February 2019. All patients performed an RDT with Chagas Stat-Pak(®) (CSP, Chembio Diagnostic System, Medford, NY, USA) and an ECG by D-Heart(®) technology, a low-cost, user-friendly smartphone-based 8-lead Bluetooth ECG. RDTs were read locally while ECGs were sent to a cardiology clinic which transmitted reports within 24 h from recording. Results: Among 140 people (54 men, median age 38(interquartile range 23–54) years), 98 (70%) were positive for Trypanosoma cruzi infection, with a linear, age-dependent, increasing trend (p < 0.001). Twenty-five (18%) individuals showed ECG abnormalities compatible with CD. Prevalence of ECG abnormalities was higher in infected individuals and was associated with higher systolic blood pressure and smoking. Following screening, 22 (16%) individuals underwent clinical evaluation and chest X-ray and two were referred for further evaluation. At multivariate analysis, positive CSP results (OR = 4.75, 95%CI 1.08–20.96, p = 0.039) and smoking (OR = 4.20, 95%CI 1.18–14.92, p = 0.027) were independent predictors of ECG abnormalities. Overall cost for screening implementation was <10 $. Conclusions: Combined mobile-Health and RDTs was a reliable and effective low-cost strategy to identify patients at high risk of disease needing cardiologic assessment suggesting potential future applications

Unsharp Quantum Reality

The positive operator (valued) measures (POMs) allow one to generalize the notion of observable beyond the traditional one based on projection valued measures (PVMs). Here, we argue that this generalized conception of observable enables a consistent notion of unsharp reality and with it an adequate concept of joint properties. A sharp or unsharp property manifests itself as an element of sharp or unsharp reality by its tendency to become actual or to actualize a specific measurement outcome. This actualization tendency-or potentiality-of a property is quantified by the associated quantum probability. The resulting single-case interpretation of probability as a degree of reality will be explained in detail and its role in addressing the tensions between quantum and classical accounts of the physical world will be elucidated. It will be shown that potentiality can be viewed as a causal agency that evolves in a well-defined way

Thymidine phosphorylase expression in normal, hyperplastic and neoplastic prostates: correlation with tumour associated macrophages, infiltrating lymphocytes, and angiogenesis

Thymidine phosphorylase is an angiogenic factor primarily expressed by cancer cells, stromal cells and tumour-associated macrophages in many human malignancies. These different types of thymidine phosphorylase-expressing cells, however, may have a distinct place in the angiogenic process, and this question was addressed in the present study. A series of 20 normal/hyperplastic prostate glands and 60 prostate carcinomas was investigated by immunohistochemistry, using specific antibodies for thymidine phosphorylase (P-GF.44C), tumour-associated macrophages (CD68), endothelium (CD31) and prostate specific antigen (ER-PR8). Thymidine phosphorylase expression by normal and hyperplastic epithelial or stromal cells occurred almost exclusively in the context of an intense lymphocytic infiltrate. High thymidine phosphorylase cancer cells and thymidine phosphorylase stromal cells expression was associated with high angiogenesis in prostate carcinomas, and this significant association was extended to include both tumour-associated macrophages and tumour-infiltrating lymphocytes. Thymidine phosphorylase expression and tumour-infiltrating lymphocytes were related inversely with prostate specific antigen reactivity. In conclusion, thymidine phosphorylase is a major angiogenic factor in prostate carcinomas and its up-regulation is likely to occur in the context of a host immune response

Chagas disease in Italy: breaking an epidemiological silence

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Somatic mutations of KIT in familial testicular germ cell tumours

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino acid substitutions in exon 17 and one was a 12bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with 3 out 116 unilateral cases (p = 0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes

Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719

Prognostic factors in prostate cancer

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking

Auswirkungen eines Tinnitusperzepts auf das Tondiskriminationslernen der Wüstenrennmaus

Die Entstehungsmechanismen eines zentralen Tinnitus sind nach wie vor weitgehend unverstanden, gehen aber mit neuroplastischen Veränderungen der funktionellen Organisation des auditorischen Cortex (AC) einher. Hier untersuchen wir, ob Tinnitus-assoziierte, maladaptive plastische Veränderungen im AC mit solchen interferieren können, welche mit einem auditorischen Diskriminationslernen einhergehen.Von insgesamt 18 Wüstenrennmäusen wurden 12 (Trauma Gruppe T) in Narkose einem Schalltrauma (2 kHz, 115 dB SPL, 75 min) unterzogen, 6 Kontrolltiere (Gruppe K) einem Scheintrauma (2 kHz, 65 dB SPL, 75 min). Anschließend wurden sie operant auf eine Reinton-Diskrimination (2 vs. 5 kHz aversives GO-NOGO shuttle-box Paradigma) konditioniert. Von den T-Tieren entwickelten 7 ein Tinnitus-Perzept (TT), bei 5 Tieren konnte im Verhaltenstest (gap-startle-Paradigma) kein Tinnitus nachgewiesen werden (TNT).Zwischen der K und der TT-Gruppe konnten im Mittel keine signifikanten Unterschiede in der Lernleistung nachgewiesen werden, die TNT-Gruppe zeigte eine signifikant schlechtere Lernleistung. Eine Detailanalyse ergab, dass die TT-Tiere, deren wahrgenommene minimale Tinnitusfrequenz (TF) bei 2 kHz lag, auch signifikant schlechter lernten als die K-Gruppe.Offenbar zeigen Tiere, deren TF einem der konditionierten Reize entsprach, eine schlechtere Trainingsleistung als solche mit anderen TFs. Dies deutet auf eine mögliche Interferenz der von den beiden Prozessen ausgelösten plastischen Veränderungen im AC hin. Die schlechtere Lernleistung der TNT-Tiere ist dagegen möglicherweise auf den traumabedingten Hörverlust zurückzuführen, die im Mittel scheinbar bessere Leistung der Tinnitustiere könnte dagegen auf der beobachteten insgesamt höheren Sprungneigung dieser Tiere im Lerntraining beruhen.Der Erstautor gibt keinen Interessenkonflikt an

Rheology of rounded mammalian cells over continuous high-frequencies

Understanding the viscoelastic properties of living cells and their relation to cell state and morphology remains challenging. Low-frequency mechanical perturbations have contributed considerably to the understanding, yet higher frequencies promise to elucidate the link between cellular and molecular properties, such as polymer relaxation and monomer reaction kinetics. Here, we introduce an assay, that uses an actuated microcantilever to confine a single, rounded cell on a second microcantilever, which measures the cell mechanical response across a continuous frequency range ≈ 1–40 kHz. Cell mass measurements and optical microscopy are co-implemented. The fast, high-frequency measurements are applied to rheologically monitor cellular stiffening. We find that the rheology of rounded HeLa cells obeys a cytoskeleton-dependent power-law, similar to spread cells. Cell size and viscoelasticity are uncorrelated, which contrasts an assumption based on the Laplace law. Together with the presented theory of mechanical de-embedding, our assay is generally applicable to other rheological experiments.ISSN:2041-172