Ruminant pestiviruses in North Africa

Ruminant pestiviruses are widely distributed worldwide, causing congenital disease and massive economic losses. Although ruminant production is an important economic sector in North Africa, the knowledge about pestiviruses is scarce. The present study aimed at assessing the presence of Pestivirus in cattle in Algeria, and to review the data available on ruminant pestiviruses in North Africa. A cross-sectional study was conducted on dairy farms from North-Western Algeria. Blood samples from 234 dairy cattle from 31 herds were collected. All sera were analysed for the presence of antibodies using a commercial iELISA. The presence of Pestivirus RNA was also assessed by using a Reverse Transcription-PCR, and PCR-positive samples were sequenced. Risk factors related to Pestivirus infection were also analysed. The review of the presence of ruminant pestiviruses in North Africa was performed using a systematic search and compilation methodology of the peer-reviewed literature available in order to identify gaps of knowledge for future research. The seroprevalence at population and farm levels obtained in the present study (59.9% and 93.5%, respectively) concur with data reported in neighbouring countries. Risk factors associated with Pestivirus infection in cattle were the presence of sheep in the herd and the animal category (cow vs heifer). Furthermore, we confirmed the presence of BVDV-1a in Algeria. The scarce data suggest an endemic epidemiological scenario of pestivirus in livestock. The lack of studies about the epidemiology and molecular variability of ruminant pestiviruses in livestock and wildlife in North Africa is of concern for animal health and wildlife conservation, and needs to be addressed.info:eu-repo/semantics/acceptedVersio

Assessing the challenges of global long-term mitigation scenarios

The implications of global mitigation to achieve different long-term temperature goals (LTTGs) can be investigated in integrated assessment models (IAMs), which provide a large number of outputs including technology deployment levels, economic costs, carbon prices, annual rates of decarbonisation, degree of global net negative emissions required, as well as utilisation levels for fossil fuel plants. All of these factors can be considered in detail when judging the real-world feasibility of the mitigation scenarios produced by these models. This study presents a model inter-comparison of three widely used IAMs (TIAM, MESSAGE and WITCH) to analyse multiple mitigation scenarios exploring a range of LTTGs and a range of constraints, including delayed mitigation action, limited end-use electrification and delayed deployment of carbon capture technologies. The scenario outputs across the three models are examined and discussed and a matrix of the different factors concerning scenario feasibility is presented

Comparative Analysis of Patient Characteristics in Cardiogenic Shock Studies: Differences Between Trials and Registries

OBJECTIVES: This study sought to evaluate the differences in cardiogenic shock patient characteristics in trial patients and real-life patients. BACKGROUND: Cardiogenic shock (CS) is a leading cause of mortality in patients presenting with acute myocardial infarction (AMI). However, the enrollment of patients into clinical trials is challenging and may not be representative of real-world patients. METHODS: We performed a systematic review of studies in patients presenting with AMI-related CS and compared patient characteristics of those enrolled into randomized controlled trials (RCTs) with those in registries. RESULTS: We included 14 RCTs (n = 2,154) and 12 registries (n = 133,617). RCTs included more men (73% vs 67.7%, P \u3c 0.001) compared with registries. Patients enrolled in RCTs had fewer comorbidities, including less hypertension (61.6% vs 65.9%, P \u3c 0.001), dyslipidemia (36.4% vs 53.6%, P \u3c 0.001), a history of stroke or transient ischemic attack (7.1% vs 10.7%, P \u3c 0.001), and prior coronary artery bypass graft surgery (5.4% vs 7.5%, P \u3c 0.001). Patients enrolled in RCTs also had lower lactate levels (4.7 ± 2.3 mmol/L vs 5.9 ± 1.9 mmol/L, P \u3c 0.001) and higher mean arterial pressure (73.0 ± 8.8 mm Hg vs 62.5 ± 12.2 mm Hg, P \u3c 0.001). Percutaneous coronary intervention (97.5% vs 58.4%, P \u3c 0.001) and extracorporeal membrane oxygenation (11.6% vs 3.4%, P \u3c 0.001) were used more often in RCTs. The in-hospital mortality (23.9% vs 38.4%, P \u3c 0.001) and 30-day mortality (39.9% vs 45.9%, P \u3c 0.001) were lower in RCT patients. CONCLUSIONS: RCTs in AMI-related CS tend to enroll fewer women and lower-risk patients compared with registries. Patients enrolled in RCTs are more likely to receive aggressive treatment with percutaneous coronary intervention and extracorporeal membrane oxygenation and have lower in-hospital and 30-day mortality

A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: results from the International Takotsubo Registry

AIMS. Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage. METHODS AND RESULTS: Patients with TTS were recruited from the International Takotsubo Registry ( www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96-0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87-0.93). CONCLUSION: The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity

Happy heart syndrome. role of positive emotional stress in takotsubo syndrome

AIMS: Takotsubo syndrome (TTS) is typically provoked by negative stressors such as grief, anger, or fear leading to the popular term 'broken heart syndrome'. However, the role of positive emotions triggering TTS remains unclear. The aim of the present study was to analyse the prevalence and characteristics of patients with TTS following pleasant events, which are distinct from the stressful or undesirable episodes commonly triggering TTS. METHODS AND RESULTS: Takotsubo syndrome patients with preceding pleasant events were compared to those with negative emotional triggers from the International Takotsubo Registry. Of 1750 TTS patients, we identified a total of 485 with a definite emotional trigger. Of these, 4.1% (n = 20) presented with pleasant preceding events and 95.9% (n = 465) with unequivocal negative emotional events associated with TTS. Interestingly, clinical presentation of patients with 'happy heart syndrome' was similar to those with the 'broken heart syndrome' including symptoms such as chest pain [89.5% (17/19) vs. 90.2% (412/457), P = 1.0]. Similarly, electrocardiographic parameters, laboratory findings, and 1-year outcome did not differ. However, in a post hoc analysis, a disproportionate higher prevalence of midventricular involvement was noted in 'happy hearts' compared with 'broken hearts' (35.0 vs. 16.3%, P = 0.030). CONCLUSION: Our data illustrate that TTS can be triggered by not only negative but also positive life events. While patient characteristics were similar between groups, the midventricular TTS type was more prevalent among the 'happy hearts' than among the 'broken hearts'. Presumably, despite their distinct nature, happy and sad life events may share similar final common emotional pathways, which can ultimately trigger TTS

An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11 months but was extended in a minority of cases up to 7 years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1 month) was favoured by age <60 years (p < 0.005), no previous observation (p < 0.0002), duration less than 3 months (p < 0.0001), absence of CSCR in the fellow eye (p = 0.04), leakage outside of the arcade (p = 0.05) and fluid height >500 \u3bcm (p = 0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1 month was favoured by first episode (p = 0.04), height of subretinal fluid >500 \u3bcm (p < 0.0001) and short duration of observation (p = 0.02). Finally, there was no statistically significant difference among the treatments at 12 months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification

Functional KV10.1 Channels Localize to the Inner Nuclear Membrane

Ectopically expressed human KV10.1 channels are relevant players in tumor biology. However, their function as ion channels at the plasma membrane does not totally explain their crucial role in tumors. Both in native and heterologous systems, it has been observed that a majority of KV10.1 channels remain at intracellular locations. In this study we investigated the localization and possible roles of perinuclear KV10.1. We show that KV10.1 is expressed at the inner nuclear membrane in both human and rat models; it co-purifies with established inner nuclear membrane markers, shows resistance to detergent extraction and restricted mobility, all of them typical features of proteins at the inner nuclear membrane. KV10.1 channels at the inner nuclear membrane are not all transported directly from the ER but rather have been exposed to the extracellular milieu. Patch clamp experiments on nuclei devoid of external nuclear membrane reveal the existence of channel activity compatible with KV10.1. We hypothesize that KV10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K+, or indirectly interact with heterochromatin, both factors known to affect gene expression

Rapid Internalization of the Oncogenic K+ Channel KV10.1

KV10.1 is a mammalian brain voltage-gated potassium channel whose ectopic expression outside of the brain has been proven relevant for tumor biology. Promotion of cancer cell proliferation by KV10.1 depends largely on ion flow, but some oncogenic properties remain in the absence of ion permeation. Additionally, KV10.1 surface populations are small compared to large intracellular pools. Control of protein turnover within cells is key to both cellular plasticity and homeostasis, and therefore we set out to analyze how endocytic trafficking participates in controlling KV10.1 intracellular distribution and life cycle. To follow plasma membrane KV10.1 selectively, we generated a modified channel of displaying an extracellular affinity tag for surface labeling by α-bungarotoxin. This modification only minimally affected KV10.1 electrophysiological properties. Using a combination of microscopy and biochemistry techniques, we show that KV10.1 is constitutively internalized involving at least two distinct pathways of endocytosis and mainly sorted to lysosomes. This occurs at a relatively fast rate. Simultaneously, recycling seems to contribute to maintain basal KV10.1 surface levels. Brief KV10.1 surface half-life and rapid lysosomal targeting is a relevant factor to be taken into account for potential drug delivery and targeting strategies directed against KV10.1 on tumor cells