Chagas disease reactivation in a heart transplant patient infected by domestic Trypanosoma cruzi discrete typing unit I (TcIDOM)

Background Trypanosoma cruzi, causative agent of Chagas disease, displays high intraspecific genetic diversity: six genetic lineages or discrete typing units (DTUs) are currently recognized, termed TcI through TcVI. Each DTU presents a particular distribution pattern across the Americas, and is loosely associated with different transmission cycles and hosts. Several DTUs are known to circulate in Central America. It has been previously suggested that TcI infection is benign and does not lead to chronic chagasic cardiomyopathy (CCC). Findings In this study, we genotyped T. cruzi parasites circulating in the blood and from explanted cardiac tissue of an El Salvadorian patient who developed reactivation Chagas disease while on immunosuppressive medications after undergoing heart transplant in the U.S. as treatment for end-stage CCC. Parasite typing was performed through molecular methods (restriction fragment length polymorphism of polymerase reaction chain amplified products, microsatellite typing, maxicircle sequence typing and low-stringency single primer PCR, [LSSP-PCR]) as well as lineage-specific serology. We show that the parasites infecting the patient belong to the TcI DTU exclusively. Our data indicate that the parasites isolated from the patient belong to a genotype frequently associated with human infection throughout the Americas (TcI DOM ). Conclusions Our results constitute compelling evidence in support of TcI DTU’s ability to cause end-stage CCC and help dispel any residual bias that infection with this lineage is benign, pointing to the need for increased surveillance for dissemination of this genotype in endemic regions, the USA and globally

Differences of corruption types in selected Western and central-eastern health systems during the COVID-19 pandemic: a rapid review

YesTo identify, describe, and classify the cases of health corruption present in selected Western [the Netherlands and the United Kingdom (UK)] and Central-Eastern European (Poland and Slovakia) countries during the COVID-19 pandemic. A rapid review of the literature was conducted, evaluating data from 11 March 2020 to 15 April 2021. Information sources included MEDLINE via WoS, IBSS via ProQuest, Scopus, and gray literature. Thirteen cases were identified across the four countries. The primary type of health corruption in Western European countries was procurement corruption, while misuse of (high) level positions was the most prevalent in Central-Eastern European countries. Actors from central governments were most involved in cases. The rule of law and anti-corruption watchdogs reported most cases in the United Kingdom and the Netherlands, while the media reported cases in Poland and Slovakia. The differences in types of corruption in WE and CEE countries emphasize the need to contextualize the approach to tackle corruption. Thus, further research in preventing and tackling corruption is a vital and necessary undertaking despite the inherent of conducting health corruption research

Active vibration control using mechanical and electrical analogies

Mechanical-electrical analogous circuit models are widely used in electromechanical system design as they represent the function of a coupled electrical and mechanical system using an equivalent electrical system. This research uses electrical circuits to establish a discussion of simple active vibration control principles using two scenarios: an active vibration isolation system and an active dynamic vibration absorber (DVA) using a voice coil motor (VCM) actuator. Active control laws such as gain scheduling are intuitively explained using circuit analysis techniques. Active vibration control approaches are typically constraint by electrical power requirements. The electrical analogous is a fast approach for specifying power requirements on the experimental test platform which is based on a vibration shaker that provides the based excitation required for the single Degree- of-Freedom (1DoF) vibration model under study

Effectiveness and safety of mechanical thrombectomy for acute ischaemic stroke in Latin American countries: A systematic review

YesTo describe the use, effectiveness, and safety outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in Latin American countries. Studies reporting MT outcomes for AIS in Latin America were identified in CINAHL, MEDLINE, Web of Science, SciELO, EMBASE, and LILACS databases. Synthesis was conducted according to effectiveness (recanalization rates) and safety measures (mortality and functional independence at 90 days). Seventeen studies were included, mainly from public and university hospitals. MT utilization varied from 2.6% to 50.1%, while successful recanalization ranged from 63% to 95%. Functional independence 90 days after stroke (a modified Rankin scale score of 0 to 2) was achieved in less than 40% across most studies. Mortality rates were below 30%; studies with posterior circulation strokes reported higher mortality rates. The randomized trial reported better health outcomes for functional independence among patients in the MT group (OR 2.28; 95% CI, 1.41 - 3.69), favoring MT over standard care. The included studies had great methodological heterogeneity due to differences in study design, the MT time window, and stroke location. The only randomized trial showed improved functional independence and lower mortality rates with MT than with standard care. The rest of the studies reported similar findings to available literature. Efforts to improve stroke care are reflected in improved patient outcomes in the region. Future studies should consider standard time window criteria and reduce the risk of bias by including representative samples and comparison groups

Combining mobilizing agents with busulfan to reduce chemotherapy-based conditioning for hematopoietic stem cell transplantation

In the context of hematopoietic stem cell (HSC) transplantation, conditioning with myelo- and immune-ablative agents is used to eradicate the patient's diseased cells, generate space in the marrow and suppress immune reactions prior to the infusion of donor HSCs. While conditioning is required for effective and long-lasting HSC engraftment, currently used regimens are also associated with short and long-term side effects on extramedullary tissues and even mortality. Particularly in patients with severe combined immunodeficiency (SCID), who are generally less than 1-year old at the time of transplantation and often suffer from existing comorbidities. There is a pressing need for development of alternative, less toxic conditioning regimens. Hence, we here aimed to improve efficacy of currently used myeloablative protocols by combining busulfan with stem-cell niche-directed therapeutic agents (G-CSF or plerixafor) that are approved for clinical use in stem cell mobilization. T, B and myeloid cell recovery was analyzed in humanized NSG mice after different conditioning regimens. Increasing levels of human leukocyte chimerism were observed in a busulfan dose-dependent manner, showing comparable immune recovery as with total body irradiation in CD34-transplanted NSG mice. Notably, a better T cell reconstitution compared to TBI was observed after busulfan conditioning not only in NSG mice but also in SCID mouse models. Direct effects of reducing the stem cell compartment in the bone marrow were observed after G-CSF and plerixafor administration, as well as in combination with low doses of busulfan. Unfortunately, these direct effects on the stem population in the bone marrow were not reflected in increased human chimerism or immune recovery after CD34 transplantation in NSG mice. These results indicate moderate potential of reduced conditioning regimens for clinical use relevant for all allogeneic transplants.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Predictors of Cervical Cancer Screening among Infrequently Screened Women Completing Human Papillomavirus Self-Collection: My Body My Test-1

Background: Approximately one-half of cervical cancer cases in the United States occur in underscreened or never-screened women. We examined predictors to completing Papanicolaou (Pap) testing and whether a positive human papillomavirus (HPV) self-collection result affects Pap testing adherence among underscreened women. Materials and Methods: Low-income women aged 30-65 years who reported no Pap testing in ≥4 years were recruited in North Carolina. Knowledge, attitudes, and barriers regarding cervical cancer and Pap testing were assessed by telephone questionnaires. We mailed self-collection kits for HPV testing and provided information regarding where to obtain affordable Pap testing. Participants received $45 for completing all activities. We used multivariable logistic regression to assess the predictors of longer reported time since last Pap (≥10 vs. 4-9 years) and of completion of Pap testing following study enrollment (follow-up Pap). Results: Participants (n = 230) were primarily black (55%), uninsured (64%), and with ≤high school education (59%). Cost and finding an affordable clinic were the most commonly reported barriers to screening. White women and those with ≤high school education reported longer intervals since last Pap test. Half of the participants reported completing a follow-up Pap test (55%). Women with a positive HPV self-collection were five times more likely to report completing a follow-up Pap test than those with negative self-collection (odds ratio = 5.1, 95% confidence interval 1.4-25.7). Conclusions: Improving awareness of resources for affordable screening could increase cervical cancer screening in underserved women. Home-based HPV self-collection represents an opportunity to re-engage infrequently screened women into preventive screening services

Spatial representation of temporal information through spike timing dependent plasticity

We suggest a mechanism based on spike time dependent plasticity (STDP) of synapses to store, retrieve and predict temporal sequences. The mechanism is demonstrated in a model system of simplified integrate-and-fire type neurons densely connected by STDP synapses. All synapses are modified according to the so-called normal STDP rule observed in various real biological synapses. After conditioning through repeated input of a limited number of of temporal sequences the system is able to complete the temporal sequence upon receiving the input of a fraction of them. This is an example of effective unsupervised learning in an biologically realistic system. We investigate the dependence of learning success on entrainment time, system size and presence of noise. Possible applications include learning of motor sequences, recognition and prediction of temporal sensory information in the visual as well as the auditory system and late processing in the olfactory system of insects.Comment: 13 pages, 14 figures, completely revised and augmented versio

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20–2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80–0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up