• Clemensen Hermansen opublikował 5 miesięcy, 1 tydzień temu

    Studies have evaluated the impact of the use of digital health technologies to improve CVD outcomes through several modalities text-messaging programmes, smartphone applications (apps) and wearable devices. Text-messaging programmes are to date the most studied type of digital health interventions, and studies have demonstrated reduced CVD risk and improved medication adherence. Literature supporting the use of smartphone apps is also growing but remains limited, with some studies favouring the use of health apps but others showing negative results. Wearable devices are the latest type of technology investigated, and studies have shown positive outcomes in terms of physical activity and detection of arrhythmias. Digital health is a growing and evolving area of investigation. To date, the scientific evidence overall supports the use of such technologies in CVD care and management. Future research using new models are needed to continue to evaluate these new technologies.

    To evaluate and compare the rate and characteristics of vitreoretinal disorders in fellow eyes of lamellar macular holes (LMH) versus epiretinal membrane foveoschisis (ERMF).

    Included patients in this retrospective study were divided into two groups based on spectral-domain optical coherence tomography (SD-OCT) features of their primary eye LMH (group A) and ERMF (group B).

    Ninety-four patients were enrolled 59 (62.8%) in group A and 35 (37.2%) in group B. Fellow eyes in group A had a higher rate of retinal detachment (8/59 [13.6%] vs. 0/35 [0%], P = 0.024), and full-thickness macular hole (FTMH) (11/59 [18.6%] vs. 2/35 [5.7%], P = 0.079), compared with fellow eyes in group B. In group A, 4/59 patients (6.8%) showed a bilateral LMH while none from group B had a LMH in their fellow eye (0/35 [0%]), P = 0.293. Additionally, epiretinal proliferation was noted in 30/59 (50.8%) fellow eyes in group A versus 3/35 (8.6%) fellow eyes in group B, P < 0.001. Longitudinal data were available for 80/94 patients. Over a mean follow-up of 37.4 ± 29.9months, 1/48 (2.1%) fellow eyes from group A developed a FTMH and 2/48 (4.2%) developed a LMH, while no FTMH or LMH occurred in fellow eyes of group B.

    Fellow eyes of LMH showed a high rate of macular and peripheral vitreoretinal disorders. In addition, epiretinal proliferation was detected in a higher number of fellow eyes of LMH versus ERMF. These findings suggest a bilateral process in eyes of patients with LMH.

    Fellow eyes of LMH showed a high rate of macular and peripheral vitreoretinal disorders. In addition, epiretinal proliferation was detected in a higher number of fellow eyes of LMH versus ERMF. These findings suggest a bilateral process in eyes of patients with LMH.

    To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD).

    Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V

    ), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V

    and V

    ) were compared with data at V

    .

    One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5days within V

    and V

    and 80.8 ± 39.7days within V

    and V

    , respectively (P< 0.0001). BCVA was statistically worse at the V

    visit as compared with the immediately preceding (V

    ) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V

    and V

    visits, respectively; P= 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V

    visit, while 77 (68.7%) eyes exhibited signs of exudation at the V

    visit (P= 0.022). No differences in terms of BCVA and OCT findings were detected between the V

    and V

    visits. In multiple regression analysis, the difference in BCVA between V

    and V

    visits was significantly associated with the interval time within these two visits (P= 0.026).

    The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.

    The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.Infants show shifting patterns of visual engagement to faces over the first years of life. To explore the adaptive implications of this engagement, we collected eye-tracking measures on cross-sectional samples of 10-25-month-old typically developing toddlers (TD;N = 28) and those with autism spectrum disorder (ASD;N = 54). Concurrent language assessments were conducted and relationships between visual engagement and expressive and receptive language were analyzed between groups, and within ASD subgroups. TD and ASD toddlers exhibited greater mouth- than eye-looking, with TD exhibiting higher levels of mouth-looking than ASD. Mouth-looking was positively associated with expressive language in TD toddlers, and in ASD toddlers who had acquired first words. Mouth-looking was unrelated to expressive language in ASD toddlers who had not yet acquired first words.The effects of soil compaction on porosity (α), bulk density (ρs), and saturated hydraulic conductivity (Ksat) can create a physical barrier in the soil, reducing the vertical movement of toxic elements in the soil profile. However, the indirect effects of compaction in altering the forms and availability of heavy metals in soil have not been well-studied. This study examined the influence of compaction on forms of lead (Pb) in soils with contrasting texture. Four levels of compaction were imposed on a sandy loam and a clayey soil, which were artificially contaminated based on their maximum Pb adsorption capacity. Compaction had different effects on Pb forms depending on soil texture. In the sandy loam soil, compaction had a dual beneficial effect in mitigating the impact of Pb contamination, since it decreased Ksat, reducing metal transport to deeper soil layers, and also prevented transformation to more available Pb forms (soluble and exchangeable). Instead, there was an increase in the most environmentally stable forms of Pb (inner sphere adsorption on iron and manganese oxides). In the clayey soil, compaction caused a significant increase in soluble and exchangeable Pb, accompanied by a significant reduction in environmentally stable Pb (inner sphere adsorption on gibbsite and kaolinite). In addition, studies about Pb contents under compacted soil layers should be investigated, mainly in clayey soils with edible crops, and environmental remediation practices that involve the machines traffic (for example, phytoremediation-successive cultivation of Pb-hyperaccumulating plants) should be used with care to minimise the compaction of clayey soils.Motion and generation of forces by single cells and cell collectives are essential elements of many biological processes, including development, wound healing and cancer cell migration. Quantitative wound healing assays have demonstrated that cell monolayers can be both dynamic and elastic at the same time. However, it is very challenging to model this combination with conventional approaches. Here we introduce an elastic phase field approach that allows us to predict the dynamics of elastic sheets under the action of active stresses and localized forces, e.g. from leader cells. Our method ensures elastic reversibility after release of forces. We demonstrate its potential by studying several paradigmatic situations and geometries relevant for single cells and cell monolayers, including elastic bars, contractile discs and expanding monolayers with leader cells.

    Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu.

    One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A.

    Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depressi development of depression in PsA patients.

    Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.Non-SMC condensin I complex subunit H (NCAPH) is a structural component of chromosomes during mitosis, which up-regulates in various cancers. However, the role of NCAPH in breast cancer still hasn’t been clearly explored. Our aim is to confirm the value of NCAPH as a prognostic biomarker of breast cancer. We revealed the high expression of NCAPH in breast cancer by using Oncomine, Ualcan and GOBO analysis. Quantitative Real-time PCR (qRT-PCR) analysis was conducted to detect the mRNA expression of NCAPH in MCF-7 and MCF-10A cells, and thus higher mRNA level of NCAPH in MCF-7 cells was confirmed. STRING and gene enrich analysis were conducted to explore the interaction between NCAPH and other proteins, hence the functionality of NCAPH in mitosis is demonstrated. With Kaplan-Meier plotter we found that upregulation of NCAPH is indicative of a poor prognosis especially in hormone receptor positive breast cancer. We confirmed the potential competence of NCAPH as a promising biomarker in breast cancer prognosis.Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due to influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV) are also at a higher risk of developing invasive pulmonary aspergillosis (IPA). Recently, reports of IPA have also emerged among SARS-CoV-2 infected patients admitted to intensive care units (ICUs). Here, we report a fatal case of probable IPA in an acute myeloid leukemia patient co-infected with SARS-CoV-2 and complicated by acute respiratory distress syndrome (ARDS). Probable IPA is supported by multiple pulmonary nodules with ground glass opacities which indicate halo sign and positive serum galactomannan results. Screening studies are needed to evaluate the prevalence of IPA in immunocompromised patients infected with SARS-CoV-2. Consequently, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples of COVID-19 patients with timely and targeted antifungal therapy based on early clinical suspicion of IPA are highly recommended.Type IV pili (T4P) are bacterial appendages used for cell adhesion and surface motility. In metal-reducing bacteria in the genus Geobacter, they have the unique property of being conductive and essential to wire cells to extracellular electron acceptors and other cells within biofilms. These electroactive bacteria use a conserved pathway for biological assembly and disassembly of a short and aromatic dense peptide subunit (pilin). The polymerization of the pilins clusters aromatic residues optimally for charge transport and exposes ligands for metal immobilization and reduction. The simple design yet unique functionalities of conductive T4P afford opportunities for the scaled-up production of recombinant pilins and their in vitro assembly into electronic biomaterials of biotechnological interest. This review summarizes current knowledge of conductive T4P biogenesis and functions critical to actualize applications in bioelectronics, bioremediation, and nanotechnology.After acute ischemic stroke (AIS), peripheral monocytes infiltrate into the lesion site within 24 h, peak at 3 to 7 days, and then differentiate into macrophages. Traditionally, monocytes/macrophages (MMs) are thought to play a deleterious role in AIS. Depletion of MMs in the acute phase can alleviate brain injury induced by ischemia. However, several studies have shown that MMs have anti-inflammatory functions, participate in angiogenesis, phagocytose necrotic neurons, and promote neurovascular repair. Therefore, MMs play dual roles in ischemic stroke, depending mainly upon the MM microenvironment and the window of time post-stroke. Because activated microglia and MMs are similar in morphology and function, previous studies have often investigated them together. However, recent studies have used special methods to distinguish MMs from microglia and have found that MMs have properties which differ from microglia. Here, we review the unique role of MMs and the interaction between MMs and neurovascular units, including neurons, astrocytes, microglia, and microvessels. Future therapeutics targeting MMs should regulate the polarization and subset transformation of the MMs at different stages of AIS rather than comprehensively suppressing MM infiltration and differentiation. In addition, more studies are needed to elucidate the cellular and molecular mechanisms of MM subsets and polarization during ischemic stroke.

    To evaluate and detail the management of a difficult, long-term, open abdomen in a resource constraint setting with the use of Hydrocolloid dressing.

    An observational retrospective study was conducted at a single level-1 trauma center. Over a 5-year period, all the open abdomen patients were evaluated and the cohorts who were treated with Hydrocolloid dressings were described in detail from their admission to their discharge.

    During this period, there were 147 open abdomens. 7.5% (11) patients required long-term open abdomen management, in which Hydrocolloid dressing was utilized. Of this group, there were no entero/colonic-atmospheric fistulas, and there was either de-novo complete skin coverage, successful skin graft placement, or definitive abdominal wall repair in all the patients. De-novo complete skin coverage took an average of 7.4months. All the patients were discharged home after an average of 107days hospitalized.

    Despite not being an optimal management of an open abdomen, there are always a small group of these patients who lose abdominal domain, are critically ill or injured, and have prolonged hospitalization with an open abdomen. In this cohort, and especially in resource constraint settings, Hydrocolloid dressing is a cost-efficient, simple, and effective method to treat the 'long-term’ open abdomens.

    Despite not being an optimal management of an open abdomen, there are always a small group of these patients who lose abdominal domain, are critically ill or injured, and have prolonged hospitalization with an open abdomen. In this cohort, and especially in resource constraint settings, Hydrocolloid dressing is a cost-efficient, simple, and effective method to treat the 'long-term’ open abdomens.

    Hypertriglyceridaemia is a highly prevalent disorder worldwide. Genetic and Mendelian randomization studies have suggested that triglyceride (TG)-rich lipoproteins are causal risk factors for coronary heart disease and contribute to the residual cardiovascular risk observed in patients optimally treated with statins. However, clinical trials failed to show cardiovascular benefits of TG-lowering; in this context, trials with omega-3 fatty acids provided contrasting results. Few trials have tested the supplementation of EPA alone rather than the combination of EPA + DHA. The JELIS study showed that EPA 1.8g/day significantly reduced CV events in hypercholesterolaemic patients given statins, an effect that was independent on lipid reduction.

    The REDUCE-IT trial showed that high-dose (4g/day) EPA significantly reduces the incidence of major cardiovascular events compared with placebo in patients with elevated TG levels. The clinical benefit was higher than expected by the reduction of TG-rich lipoprotein leveation on a background of optimal LDL-C-lowering therapy as a key approach to achieve a further and significant reduction of CV events in very-high CV risk patients with persistent hypertriglyceridaemia. The effect on lipids does not appear to fully explain the CV benefit, and additional mechanisms of action of EPA likely contribute to the cardiovascular protection, including the reduction of inflammation and platelet aggregation. Current guidelines recommend using high-dose EPA in combination with a statin in high/very-high CV risk patients with mild-to-moderate elevation of plasma TG to reduce the residual CV risk.Interleukin enhancer-binding factor 2 (ILF2) forms a heterodimer with interleukin enhancer-binding factor 3 (ILF3) via double-stranded RNA-binding motif and zinc finger associated domain and thus regulates gene expression and cancer cell growth. However, how ILF2 is degraded in cells remains elusive. In this work, using stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomics, we find that ILF2 is downregulated in cells expressing cereblon (CRBN). Using affinity purification and immunoblotting analysis, we demonstrate that CRBN interacts with ILF2 and functions as a substrate receptor of the cullin-4 RING E3 ligase complex. Biochemical experiments disclose that CRBN expression reduces ILF2 protein level and this reduction is diminished when the proteasome is inhibited. Upon protein synthesis inhibition, the degradation of ILF2 is enhanced by CRBN. Moreover, CRBN promotes the ubiquitination of ILF2 and thus results in the ubiquitin-mediated proteasomal degradation. Analyses of previously identified post-translational modification sites and the crystal structure of ILF2 discover the potential ubiquitination sites on ILF2. Through mutagenesis and biochemical experiments, we further reveal that the K45R mutation completely abolishes the effect of CRBN on ILF2, suggesting that this is the key residue responsible for its ubiquitination. Taken together, we identify an E3 ligase that regulates ILF2 and uncover a molecular pathway for its degradation. This work might be helpful to elucidate the molecular mechanism by which CRBN regulates diverse cellular functions.The purpose was to determine if increasing serum 25(OH)D and calcium in postmenopausal women increased skeletal muscle size, strength, balance, and functional task performance while decreasing muscle fatigue. PCSA of the vastus lateralis increased and ascent of stairs time decreased after 6 months of increased serum 25(OH)D.

    The Institute of Medicine recommends ≥ 20 ng/ml of serum 25-hydroxyvitamin D [25(OH)D] for bone and overall health. Serum 25(OH)D levels have been associated with physical performance, postural sway, and falls. The purpose of this study was to determine if increasing postmenopausal women’s serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml improved skeletal muscle size, strength, balance, and functional performance while decreasing skeletal muscle fatigue.

    Twenty-six post-menopausal women (60-85 years old) with baseline serum 25(OH)D levels between 20 and 30 ng/ml were recruited. Oral over-the-counter (OTC) vitamin D3 and calcium citrate were prescribed to increase subjects’ serum 25 non-significantly, suggesting balance may improve from increased serum 25(OH)D and calcium citrate levels.

    Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.

    Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.Drying-induced cracking is widely encountered in nature and is of fundamental interest in industrial applications. During desiccation, the evolution of water content is nonlinear. Considering the inhomogeneous procedure of desiccation, it is worth considering whether water content will affect the crack pattern formation. To address this concern, in this paper, we report an experimental investigation on the effect of water content on the failure mode in drying colloidal films. A distinct failure transition from random cracking to curling is found when the initial water content increases gradually. When the water content is below a critical value for given film thickness, random desiccation cracking driven by shrinkage is observed. Beyond this critical water content, the film curls with the advent of several main cracks. It is also found that the critical water content corresponding to the transition point depends on the film thickness. In order to qualitatively interpret the experimental observation, a theoretical model is established by adopting the fracture mechanics based on the energy method. The model is found to agree well with the experimental results, elucidating the effects of initial water content on the crack patterns and the transition of failure modes.

    The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the 2020 European Society of Cardiology (ESC) Congress-The Digital Experience.

    The studies reviewed include clinical trials on novel RNA interference-based lipid-lowering therapies AKCEA-APOCIII-L

    and vupanorsen (AKCEA-ANGPTL3-L

    ); the EVAPORATE trial assessing the effects of icosapent ethyl on coronary plaque volume progression; the LoDoCo2 trial evaluating the efficacy of low-dose colchicine in cardiovascular disease risk reduction among patients with chronic coronary artery disease; as well as the EMPEROR-Reduced trial evaluating cardiovascular and renal outcomes with empagliflozin in patients with heart failure and reduced ejection fraction. In addition, we review the BPLTTC analysis on blood pressure treatment across blood pressure levels and CVD status and discuss findings from the BRACE CORONA study that examined continuing versus suspending angiotensin-converting enzyme inhibitor or s suspending angiotensin-converting enzyme inhibitor or angiotensin receptor blockers in patients on these antihypertensive medications who were hospitalized with COVID-19 infection. The studies presented at the 2020 digital ESC Congress highlight the continuing advancements in the field of CVD prevention.

    The demographics of head and neck cancer (HNC) survivors are changing, contributing to a growing number of survivors and a greater length of survivorship. Curative treatment involves intense multimodal therapy, which contributes to both short-term toxicities and long-term treatment-related effects. Delivering high-quality, relevant cancer survivorship care is a growing national priority. Various survivorship models and tools, such as survivorship care plans, have been utilized in an attempt to enhance care and optimize outcomes. However, an essential, yet understudied, component of high-quality survivorship care is the identification and management of late and long-term treatment-related effects. In this article, we will describe the current advancements in survivorship care as well as the research related to late and long-term treatment effects. While there is a growing body of literature that describes the prevalence of treatment-related effects and their impact on quality of life, more work is needed. Reers the potential to alleviate these effects for future survivors, we need clinically meaningful assessment tools and therapies to provide the survivors we evaluate and treat daily. Targeted patient-reported outcomes and objective measures validated through clinical research are needed to help us systematically identify and treat late and long-term effects. In order to tailor and optimize the care we provide to our HNC survivors, we will need to leverage these tools as well as the expertise of all members of our multidisciplinary survivorship teams.

    Pulmonary vein stenosis (PVS) is a rare entity that until the last 2 decades was seen primarily in infants and children. Percutaneous and surgical interventions have limited success due to relentless restenosis, and mortality remains high. In adults, acquired PVS following ablation for atrial fibrillation has emerged as a new syndrome. This work will review these two entities with emphasis on current treatment.

    Greater emphasis on understanding and addressing the mechanism of restenosis for congenital PVS has led to the use of drug-eluting stents (DES) and systemic drug therapy to target neo-intimal growth. Frequent reinterventions are positively affecting outcomes. Longer-term outcomes of percutaneous treatment for acquired PVS are emerging. Treatment of congenital PVS continues to be plagued by restenosis. DES show promise, but frequent reinterventions are required. Larger upstream vein diameter predicts success for congenital and acquired PVS interventions. Efforts to induce/maintain vessel growth are important for future treatment strategies.

    Greater emphasis on understanding and addressing the mechanism of restenosis for congenital PVS has led to the use of drug-eluting stents (DES) and systemic drug therapy to target neo-intimal growth. Frequent reinterventions are positively affecting outcomes. Longer-term outcomes of percutaneous treatment for acquired PVS are emerging. Treatment of congenital PVS continues to be plagued by restenosis. DES show promise, but frequent reinterventions are required. Larger upstream vein diameter predicts success for congenital and acquired PVS interventions. Efforts to induce/maintain vessel growth are important for future treatment strategies.

    Psychiatrists were surveyed to obtain an overview of how they currently use technology in clinical practice, with a focus on psychiatrists who treat patients with bipolar disorder.

    Data were obtained using an online-only survey containing 46 questions, completed by a convenience sample of 209 psychiatrists in 19 countries. Descriptive statistics, and analyses of linear associations and to remove country heterogeneity were calculated.

    Virtually all psychiatrists seek information online with many benefits, but some experience information overload. 75.2% of psychiatrists use an EMR/EHR at work, and 64.6% communicate with patients using a new technology, primarily email (48.8%). 66.0% do not ask patients if they use the Internet in relation to bipolar disorder. 67.3% of psychiatrists feel it is too early to tell if patient online information seeking about bipolar disorder is improving the quality of care. 66.3% of psychiatrists think technology-based treatments will improve the quality of care for some or mmitations of clinical products.

    Digital technology is routinely used by psychiatrists in clinical practice. There is near unanimous agreement about the benefits of psychiatrist online information-seeking, but research on information overload is needed. There is less agreement about the appropriate use of other clinical technologies, especially those involving patients. It is too early to tell if technology-based treatments or patient Internet activities will improve the quality of care. The digital divide remains between use of technology for psychiatrists with patients living in urban and rural or suburban areas. Psychiatrists need more formal training in technology to understand risks, benefits and limitations of clinical products.

    Establishing a diagnosis of ischemic heart disease (IHD) in women, including assessment for coronary microvascular dysfunction (CMD) when indicated, can be challenging. Access to performance of invasive testing when appropriate may be limited, and noninvasive imaging assessments have evolved. This review will summarize the various noninvasive imaging modalities available for the diagnosis of IHD and CMD in women, outlining indications, performance modalities, advantages, and limitations.

    While stress echocardiography and single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) are widely available and can detect IHD in women, their ability to specifically identify CMD is limited. Novel developments in cardiac magnetic resonance (CMR) imaging, including spectroscopy, and positron emission tomography (PET) have changed the diagnostic landscape. Coronary computed tomographic angiography (CCTA), while unable to diagnose CMD, is developing an emerging role in the risk stratificatiogical advances in diagnostic imaging, practitioners are limited by user expertise and center availability when choosing a diagnostic imaging modality. Knowledge of this evolving field is imperative as it highlights the need for sex-specific assessment of cardiovascular syndromes.Extracorporeal cardiopulmonary resuscitation (ECPR) is controversial, given both the lack of evidence for improved outcomes and clarity on appropriate candidacy during time-sensitive cardiac arrest situations. The primary objective of our study was to identify factors predicting successful outcomes in ECPR patients.Between March 2007 and November 2018, 112 patients were placed on extracorporeal life support (ECLS) during active CPR (ECPR) at our institution. The primary outcome was survival to hospital discharge. Survivors and non-survivors were compared in terms of pre-cannulation comorbidities, laboratory values, and overall outcomes. Multivariable logistic regression was used to identify pre-cannulation predictors of in-hospital mortality. Among 112 patients, 44 (39%) patients survived to decannulation and 31 (28%) survived to hospital discharge. The median age was 60 years (IQR 45-72) with a median ECLS duration of 2.2 days (IQR 0.6-5.1). Patients who survived to discharge had lower rates of chronic kidney disease than non-survivors (19% vs. 41%, p = 0.046) and lower baseline creatinine values [median 1.2 mg/dL (IQR 0.8-1.7) vs. 1.7 (0.7-2.7), p = 0.008]. Median duration from CPR initiation to cannulation was 40 min (IQR 30-50) with no difference between survivors and non-survivors (p = 0.453). When controlling for age and CPR duration, multivariable logistic regression with pre-procedural risk factors identified pre-arrest serum creatinine as an independent predictor of mortality [OR 3.25 (95% CI 1.22-8.70), p = 0.019] and higher pre-arrest serum albumin as protective [OR 0.32 (95% CI 0.14-0.74), p = 0.007]. In our cohort, pre-arrest creatinine and albumin were independently predictive of in-hospital mortality during ECPR, while age and CPR duration were not.Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors. We find no evidence of mouse-specific clonal evolution in glioma PDOXs. Our cohort captures individual molecular genotypes for precision medicine including mutations in IDH1, ATRX, TP53, MDM2/4, amplification of EGFR, PDGFRA, MET, CDK4/6, MDM2/4, and deletion of CDKN2A/B, PTCH, and PTEN. Matched longitudinal PDOX recapitulate the limited genetic evolution of gliomas observed in patients following treatment. At the histological level, we observe increased vascularization in the rat host as compared to mice. PDOX-derived standardized glioma organoids are amenable to high-throughput drug screens that can be validated in mice. We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology.

    Dorsal screw-rod instrumentations are used for a variety of spinal disorders. Cross-links (CL) can be added to such constructs, however, no clear recommendations exist. This study aims to provide an overview of the available evidence on the effectiveness of CL, potentially allowing to formulate recommendations on their use.

    A systematic literature review was performed on PubMed and 37 original articles were included and grouped into mechanical, biomechanical, finite element and clinical studies. The change in range of motion (ROM) was analyzed in mechanical and biomechanical studies, ROM, stiffness and stress distribution were evaluated in finite element studies and clinical outcome parameters were analyzed in clinical studies.

    A relative consistent reduction in ROM in axial rotation with CL-augmentation was reported, while minor and less consistent effects were observed in flexion-extension and lateral bending. The use of CLs was clinical beneficial in C1/2 fusion, while the limited clinical studies on other anatomic regions show no significant benefit for CL-augmentation.

    While CL provides some additional axial rotation stability in most situations, lateral bending and flexion-extension are less affected. Based on clinical data, CL-augmentation can only be recommended for C1/2 instrumentations, while for other cases, further clinical studies are needed to allow for evidence-based recommendations.

    While CL provides some additional axial rotation stability in most situations, lateral bending and flexion-extension are less affected. Based on clinical data, CL-augmentation can only be recommended for C1/2 instrumentations, while for other cases, further clinical studies are needed to allow for evidence-based recommendations.The objective of this study was to determine the infection rate and genetic diversity of Cryptosporidium spp. in minks, foxes, and raccoon dogs, farmed in the Xinjiang Uygur Autonomous Region, Northwest China. Fresh fecal specimens were collected from individual cages of farmed minks (n = 214), blue foxes (n = 35), and raccoon dogs (n = 39) and examined using nested PCR based on the Cryptosporidium spp. small subunit rRNA gene. Cryptosporidium spp. was detected in 35 cages (12.2%, 35/288), with a higher infection rate detected in raccoon dogs (20.5%) compared with minks (12.1%) and blue foxes (2.9%). Sequence analysis showed that Cryptosporidium canis was the only species identified in blue foxes and raccoon dogs, while in the 26 Cryptosporidium-positive mink specimens, Cryptosporidium mink genotype (n = 17), C. canis (n = 7), and Cryptosporidium parvum (n = 2) were identified. Further analysis based on the 60-kDa glycoprotein (gp60) gene determined that both C. parvum isolates belonged to the subtype IIdA15G1, while eight of the 17 Cryptosporidium mink genotype isolates were a novel subtype that we have named XeA5G1. To the best of our knowledge, this is the first report of C. parvum subtype IIdA15G1 infection in minks. Since all the Cryptosporidium species/genotypes identified in minks, foxes, and raccoon dogs from Xinjiang have been previously found in humans, our results suggest that these fur animals may play a role in the transmission of zoonotic Cryptosporidium.A novel species of coccidia, resembling a member of the genus Eimeria, was found in bats, Scotophilus leucogaster, collected in southern Saudi Arabia has been described on the basis of unsporulated oocysts and DNA sequencing of the Internal Transcribed Spacer 1 (ITS1) and partial 18S rDNA regions. Unsporulated oocysts of this form are ovoidal to spheroidal and had a 2-layered wall, 1.5-2.0 (1.9 ± 0.2); the outer layer was light blue with striations, and thicker than the inner, darker layer. No micropyle was present. Unsporulated oocysts (N = 150) measured 27.2 × 22.1 (25-30 × 20-25), length width ratio, 1.2 (1.1-1.4). There was no evidence of an oocyst residuum and/or polar granule. This parasite was detected in 2/7 (29%) S. leucogaster collected from southern Saudi Arabia. Oocysts incubated at 25 °C in 2.5% K2Cr2O7 did not sporulate after > 1 month. Unsporulated oocyst measurements were compared with other coccidian parasites of bats that discharge oocysts in their feces. Sequences of the ITS1 and the 18S rDNA regions obtained from the unsporulated oocysts grouped this coccidium from S. leucogaster with eimerian species from various rodent and squirrel species. It is critical that future investigators obtain fully sporulated oocysts of this coccidium for full description of the parasite recovered in our study so it can be correctly assigned to genus and given an accurate binomial.Buffalo-derived Theileria parva can 'break through’ the immunity induced by the infection and treatment vaccination method (ITM) in cattle. However, no such 'breakthroughs’ have been reported in northern Tanzania where there has been long and widespread ITM use in pastoralist cattle, and the Cape buffalo (Syncerus caffer) is also present. We studied the exposure of vaccinated and unvaccinated cattle in northern Tanzania to buffalo-derived T. parva using p67 gene polymorphisms and compared this to its distribution in vaccinated cattle exposed to buffalo-derived T. parva in central Kenya, where vaccine 'breakthroughs’ have been reported. Additionally, we analysed the CD8+ T cell target antigen Tp2 for positive selection. Our results showed that 10% of the p67 sequences from Tanzanian cattle (n = 39) had a buffalo type p67 (allele 4), an allele that is rare among East African isolates studied so far. The percentage of buffalo-derived p67 alleles observed in Kenyan cattle comprised 19% of the parasites (n = 36), with two different p67 alleles (2 and 3) of presumptive buffalo origin. The Tp2 protein was generally conserved with only three Tp2 variants from Tanzania (n = 33) and five from Kenya (n = 40). Two Tanzanian Tp2 variants and two Kenyan Tp2 variants were identical to variants present in the trivalent Muguga vaccine. Tp2 evolutionary analysis did not show evidence for positive selection within previously mapped epitope coding sites. The p67 data indicates that some ITM-vaccinated cattle are protected against disease induced by a buffalo-derived T. parva challenge in northern Tanzania and suggests that the parasite genotype may represent one factor explaining this.Fascioliasis, a food- and water-borne trematodiasis, has been identified as a public health threat by the World Health Organization, with millions of people estimated to be infected or at risk of infection worldwide. We developed an immunochromatographic test (ICT) as a point-of-care (POC) tool for the rapid serodiagnosis of human fascioliasis caused by Fasciola gigantica and evaluated their diagnostic ability. Two tests were developed using antigens from adult F. gigantica excretory-secretory (ES) product and recombinant F. gigantica cathepsin L (rFgCL). Sera from 12 patients with parasitologically proven fascioliasis caused by F. gigantica, 18 with clinically suspected fascioliasis, 65 with other parasitic infections, and 30 healthy controls were used. Using a cutoff of > 0.5 for antibody detection, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the ES-based ICT method were 100%, 98.9% 96.8%, 100%, and 99.2%, respectively, and those of the rFgCL-based ICT method were 86.7%, 93.7%, 81.3%, 95.7%, and 92.0%, respectively. The concordance between the two methods was 91.2%. Tests using F. gigantica ES and rFgCL antigens can be employed quickly and easily as POC diagnostic tools. They can be used to support the clinical diagnosis of human fascioliasis gigantica and in large-scale surveys in endemic areas throughout tropical regions without necessitating additional facilities or ancillary supplies.The aim of this study was to establish an animal model of Neospora caninum infection in pregnant BALB/c mice infected with different doses of N. caninum tachyzoites. After infection, the female BALB/c mice were housed with male BALB/c mice. The aim of this study was to observe clinical signs and pathological changes, detect Nc5 gene expression in the main organs, and measure the wet weight and coefficient of the placenta of the pregnant mice. In addition, the level of cytokines and placental hormones in the serum was measured in pregnant mice. Our results showed that the optimal dose of the mice in the infected model was 105 tachyzoites. The infected pregnant mice presented with various clinical signs, including depression, ataxia, and variable mortality. Pathological observations of the brain, liver, and spleen in the mice exhibited hyperemia, bleeding, and swelling. Moreover, N. caninum tissue cysts or tachyzoites were observed in the brain, liver, and spleen tissues by hematoxylin-eosin (HE). The Nc5 gene was detected in the brain, liver, spleen, and placental tissues of the mice. With the increase in infection days, the weight of the placenta in the model mice increased, and the placenta ratio decreased gradually. Compared with the control group, the placenta weight and placental ratio were significantly different (P less then 0.05). Furthermore, the levels of the placental hormones, corticotropin-releasing hormone (CRH), chorionic gonadotropin (CG), prolactin (PRL), and estriol (E3), and cytokines IFN-γ, IL-4, and TGF-β were differentially expressed between the model and the control group (P less then 0.05 or P less then 0.01), which indicated that infection with N. caninum caused an imbalance in the regulatory function of the placental hormones and cytokines in pregnant mice. A pregnant mouse model of N. caninum infection was successfully established in this study, providing a foundation for the study of the pathogenic mechanisms of N. caninum.Plastic pollution is an emerging issue faced worldwide owing to rapid urbanization and extensive use of plastic products. The objective of this study was to determine and highlight the spatial distribution of microplastics (MPs) in the top soils of different land use types of an urbanized city, i.e., Lahore, Pakistan, influenced by different human activities. Soil samples (n = 40) were collected from eight different land use groups including agricultural areas, drains, dumping sites, industrial areas, lawns, parks, roadsides, and wastelands to represent the influence of corresponding human actions. After cleaning the samples through wet peroxide digestion and density separation, MPs were identified under a stereomicroscope. The range of MPs in top soils within Lahore district varied from 1750 to 12,200 MPs/kg with an average of 4483 ± 2315 MPs/kg. The highest concentration of MPs was present in the parks while the lowest numbers of MPs were enumerated in soil from dumping sites. About 99% of the identified MPs particles were fibers, sheets, and fragments in shape while foams and beads accounted for the rest. Moreover, among the size ranges, the large size MPs (300-5000 μm) were found in the majority (41.16%) followed by the fine size MPs (50-150 μm; 30.67%) and medium size MPs (150-300 μm; 28.17%). The current level of MPs pollution attracts the attention of researchers for a more comprehensive investigation in the future. It also incites the policy-makers to implement the regulations to prevent plastic pollution and its environmental implications.

    Anatomic tunnel placement in ACL reconstruction is crucial to restore knee function. The aims of this study were to (i) evaluate the accuracy of tunnel placement for primary state-of-the-art ACL reconstruction, and (ii) examine the correlation between incorrect tunnel placement, graft appearance, and notch impingement.

    In this retrospective study, all patients underwent primary single-bundle ACL reconstruction with independent drilling of the femoral and tibial tunnels according to anatomical landmarks. The accuracy of tunnel placement and the rate of notch impingement were analysed with MRI. The study cohort was subdivided according to the morphology of the graft intact, degeneration, and re-rupture. The objective outcome was evaluated with the IKDC objective score, and the subjective outcomes were evaluated with the IKDC subjective score, the Lysholm knee score, the KOOS, and the Tegner activity scale score.

    Eighty-seven consecutive patients with a mean follow-up of 3.8 ± 1.4years were evaluated. Theracy of femoral tunnel placement in modern single-bundle ACL reconstruction is greater, the risk of malpositioning and graft impingement remains. In our patient cohort, there was a clear correlation between ACL graft impingement, degenerative changes in MRI, and incorrect tunnel positioning. The surgeon must focus on accurate tunnel placement specific to individual patient anatomy.

    Level III.

    Level III.

    Magnetic resonance imaging (MRI) findings of subchondral bone marrow edema (SBME) in osteochondral lesions of the talus (OLT) after arthroscopic microfracture are associated with poor clinical outcomes. However, the relationship between SBME volume change and clinical outcomes has not been analyzed. It was hypothesized that clinical outcomes correlated with SBME volume change and extent of cartilage regeneration in patients with OLT.

    64 patients who underwent arthroscopic microfracture for OLT were followed up for more than 2years. SBME volume change was measured by comparing preoperative and 2-year follow-up MRI. Clinical outcomes were assessed using the visual analogue scale (VAS) and the American orthopedic foot and ankle society ankle-hindfoot scale (AOFAS) at the 2-year and final follow-up. To compare clinical outcomes, patients were categorized into two groups decreased SBME (DSBME) group (cases without SBME on either MRI or with a decreased SBME volume between the MRIs) and increased SBME (ISBME) gnot affect clinical outcomes.

    SBME volume change correlated with clinical outcomes after arthroscopic microfracture for OLT. Clinical outcomes were worse in patients with new postoperative SBME and increased postoperative SBME volume. In patients with an unsatisfactory clinical course that show decreased SBME via postoperative MRI, an extended follow-up in a conservative manner could be considered.

    Level III.

    Level III.Climate change causes species range expansions to higher latitudes and altitudes. It is expected that, due to differences in dispersal abilities between plants and soil biota, range-expanding plant species will become associated with a partly new belowground community in their expanded range. Theory on biological invasions predicts that outside their native range, range-expanding plant species may be released from specialist natural enemies, leading to the evolution of enhanced defence against generalist enemies. Here we tested the hypothesis that expanded range populations of the range-expanding plant species Centaurea stoebe accumulate fewer root-feeding nematodes than populations from the original range. Moreover, we examined whether Centaurea stoebe accumulates fewer root-feeding nematodes in expanded range soil than in original range soil. We grew plants from three expanded range and three original range populations of C. stoebe in soil from the original and from the new range. We compared nematode communities of C. stoebe with those of C. jacea, a congeneric species native to both ranges. Our results show that expanded range populations of C. stoebe did not accumulate fewer root-feeding nematodes than populations from the original range, but that C. stoebe, unlike C. jacea, accumulated fewest root-feeding nematodes in expanded range soil. Moreover, when we examined other nematode feeding groups, we found intra-specific plant population effects on all these groups. We conclude that range-expanding plant populations from the expanded range were not better defended against root-feeding nematodes than populations from the original range, but that C. stoebe might experience partial belowground enemy release.In this study, K. oxytoca KMS004 (ΔadhE Δpta-ackA) was further reengineered by the deletion of frdABCD and pflB genes to divert carbon flux through D-(-)-lactate production. During fermentation of high glucose concentration, the resulted strain named K. oxytoca KIS004 showed poor in growth and glucose consumption due to its insufficient capacity to generate acetyl-CoA for biosynthesis. Evolutionary adaptation was thus employed with the strain to overcome impaired growth and acetate auxotroph. The evolved K. oxytoca KIS004-91T strain exhibited significantly higher glucose-utilizing rate and D-(-)-lactate production as a primary route to regenerate NAD+. D-(-)-lactate at concentration of 133 g/L (1.48 M), with yield and productivity of 0.98 g/g and 2.22 g/L/h, respectively, was obtained by the strain. To the best of our knowledge, this strain provided a relatively high specific productivity of 1.91 g/gCDW/h among those of other previous works. Cassava starch was also used to demonstrate a potential low-cost renewable substrate for D-(-)-lactate production. Production cost of D-(-)-lactate was estimated at $3.72/kg. Therefore, it is possible for the KIS004-91T strain to be an alternative biocatalyst offering a more economically competitive D-(-)-lactate production on an industrial scale. KEY POINTS • KIS004-91T produced optically pure D-(-)-lactate up to 1.48 M in a low salts medium. • It possessed the highest specific D-(-)-lactate productivity than other reported strains. • Cassava starch as a cheap and renewable substrate was used for D-(-)-lactate production. • Costs related to media, fermentation, purification, and waste disposal were reduced.Salmonella spp. can cause animal and human salmonellosis. In this study, we established a simple method to detect all Salmonella species by amplifying a specific region within the flgE gene encoding the flagellar hook protein. Our preliminary sequence analysis among flagella-associated genes of Salmonella revealed that although Salmonella Gallinarum and Salmonella Pullorum are lacking flagella, they did have flagella-associated genes, including flgE. To investigate in detail, a comparative flgE sequence analysis was conducted using different bacterial strains including flagellated and non-flagellated Salmonella as well as non-Salmonella strains. Two unique regions (481-529 bp and 721-775 bp of the reference sequence) within the flgE open reading frame were found to be highly conserved and specific to all Salmonella species. Next, we designed a pair of PCR primers (flgE-UP and flgE-LO) targeting the above two regions, and performed a flgE-tailored PCR using as template DNA prepared from a total of 76 bacterial strains (31 flagellated Salmonella strains, 26 non-flagellated Salmonella strains, and 19 other non-Salmonella bacteria strains).

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