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Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF.Data from consecutive patients treated with CB-PVI for symptomatic and drug refractory AF between 2005 and 2012 were analyzed. Patients with a FU of ≥9 years after index CB-PVI were included. All patients were continuously followed-up in our outpatient clinic. Arrhythmia recurrence was defined as AF or atrial tachycardia (AT) lasting30 s beyond a 3-month blanking period.A total of 385 patients (71% male) were included. Mean age was 58 ± 10 years and paroxysmal AF was present in 93% of patients. Mean FU duration was 124 ± 24 months. At the end of the observational period, 73% of all patients were in stable sinus rhythm after a mean of 2 ± 0.8 ablation procedures. Patients with AF/AT recurrence were older (60 ± 8 vs. 57 ± 10 years; p = .019), had a higher CHACB-PVI as index procedure for AF ablation resulted in favorable long-term outcome in symptomatic AF. CB-PVI might be recommended as interventional therapy in patients with lower LA remodeling.

Gasoline exposure has been widely reported in the literature as being toxic to human health. However, the exact underlying molecular mechanisms triggered by its inhalation have not been thoroughly investigated. We herein present a model of sub-chronic, static gasoline vapor inhalation in adult female C57BL/6 mice. Animals were exposed daily to either gasoline vapors (0.86 g/animal/90 min) or ambient air for 5 days/week over 7 consecutive weeks. At the end of the study period, toxic and molecular mechanisms underlying the inflammatory, oxidative, and apoptotic effects triggered by gasoline vapors, were examined in the lungs and liver of gasoline-exposed (GE) mice. Static gasoline exposure induced a significant increase (+21%) in lungs/body weight (BW) ratio in GE versus control (CON) mice along with a pulmonary inflammation attested by histological staining. The latter was consistent with increases in the transcript levels of proinflammatory cytokines [Interleukins (ILs) 4 and 6], respectively by ~ 6- and 4-fold in the lungs of GE mice compared to CON. Interestingly, IL-10 expression was also increased by ~ 10-fold in the lungs of GE mice suggesting an attempt to counterbalance the established inflammation. Moreover, the pulmonary expression of IL-12 and TNF-α was downregulated by 2- and 4-fold, respectively, suggesting the skewing toward Th2 phenotype. Additionally, GE mice showed a significant upregulation in Bax/Bcl-2 ratio, caspases 3, 8, and 9 with no change in JNK expression in the lungs, suggesting the activation of both intrinsic and extrinsic apoptotic pathways. Static gasoline exposure over seven consecutive weeks had a minor hepatic portal inflammation attested by HE staining along with an increase in the hepatic expression of the mitochondrial complexes in GE mice. Therefore, tissue damage biomarkers highlight the health risks associated with vapor exposure and may present potential therapeutic targets for recovery from gasoline intoxication.

Outcomes from Gram-negative bacteremia (GNB) in solid organ transplant (SOT) recipients are poorly understood.This is a single center prospective cohort study comparing the clinical characteristics and outcomes of SOT recipients with GNB to immunocompetent non-SOT patients with GNB between 1/1/2002 through 12/31/2018. Outcomes of interest included incidence of septic shock, respiratory failure, and time to death. A multivariable logistic regression model was used to determine factors associated with incidence of septic shock and respiratory failure. Time to death was evaluated using Cox proportional hazard models.A total of 297 SOT and 1245 immunocompetent non-SOT patients were included. Incidence of septic shock did not significantly differ between the groups (SOT 25.3% vs. non-SOT 24.6%, p = .8225). Overall survival did not significantly differ by transplant status (30-day survival: SOT 76%, 95% confidence interval [CI] 70, 92, non-SOT 74%, 95% CI 71, 77: log rank: p = .76). SOT recipients taking three immunosuppressive medications had significantly lower odds of developing septic shock or respiratory failure requiring intubation and mechanical ventilation than those taking ≤1 agent (shock: adjusted odds ratio [aOR] 0.29, 95% CI 0.09, 0.90, p = .0316; respiratory failure: aOR 0.14, 95% CI: 0.04, 0.49, p = .0020).SOT recipients with GNB do not experience higher rates of septic shock, respiratory failure, or mortality than immnon-SOT recipients with GNB. Among SOT recipients, a greater number of immunosuppressive medications may be associated with improved outcomes during GNB. Future studies are needed to understand the potential relationship between levels of immunosuppression and clinical outcome in SOT recipients with GNB.

The Fracture Risk Assessment Tool (FRAX) is the most widely used tool for fracture prediction. It provides 10-year probabilities for hip and major osteoporotic fracture (MOF). It uses country-specific hip fracture incidence and life expectancy data, and for most countries, MOF/hip fracture incidence rate ratios (IRRs) from Malmo Sweden. However, the risk of MOF varies by age, sex, and geography. The objective is to compare the MOF/hip IRRs across countries, by sex and age. This systematic review targeted observational studies of MOF and hip fractures in individuals >50 years (PROSPERO 2019 CRD42019129259). One reviewer screened potential articles. Two reviewers completed duplicate and independent data abstraction, and assessed study quality based on population representativeness, study design and duration, definition of ethnicity, and fracture characteristics. We calculated the MOF/hip IRRs (95% confidence interval) and Z-values to compare IRRs in various countries to those for Sweden. We included 27 studies, of fair to good quality in the majority, from Europe (15), US and Canada (7), Asia (3), and Australia (2). The IRRs were twofold to 10-fold higher in younger compared to older age categories, and in women compared to men, with few exceptions. Within Europe, and using Sweden as a reference, MOF/Hip IRRs in women 50-54 years from Finland, Italy, Netherlands, Denmark, and UK were significantly lower by 38% to 60%. Findings were similar in men. At older ages, MOF/Hip IRRs were consistently lower in women from European countries compared to Sweden, by 10%-40% and 11%-51%, at 75-79 years and 85-89 years, respectively. Findings were heterogenous in men and in non-European countries. In conclusion, the MOF/hip fracture IRR may vary between countries. The variability at older ages may affect FRAX prediction when country-specific fracture IRRs are not used. Further research is needed to elucidate the implication of our findings to FRAX-derived MOF estimates in various countries. © 2021 American Society for Bone and Mineral Research (ASBMR).

Mediterranean forest mammals are still poorly known, and few localities have been properly studied in the East Mediterranean Region (EMR). According to the IUCN Red List, many recorded species in this region are listed as threatened or endangered. Despite all threats, better management and more investments in species monitoring would surely improve the efficiency of biodiversity conservation projects to protect Mediterranean forest mammals. Protected reserves are of utmost importance for the conservation of native flora and fauna. Hereby, we provide a survey of mammals through a noninvasive technique based on environmental DNA extracted from scats. Samples were collected over 1 year covering all seasons from an important site for biodiversity conservation and scientific researches, the Horsh Ehden Nature Reserve. A total of 18 vertebrate species were recorded, many of them are endemic for the region and/or threatened especially in Lebanon. The use of noninvasive sampling method combined with genetic analysis of scats proved to be a powerful tool for species detection in a highly biodiverse protected area and can be easily replicated in any region around the world to rapidly assess species richness and therefore to apply direct conservation and management strategies toward species of interest.

Objective Our goal was to assess development, cognition and behaviour following an initial complex febrile seizure (FS), at onset and school age, in the context of known risk factors for cognitive development. Methods Two cohorts were recruited. Thirty-five infants with an initial complex FS were assessed within the first year post-seizure and compared to 30 controls (simple FS) based on measures of cognitive, motor and language development, behaviour and emotions. Additionally, 19 school-age children with previous complex FS (11 multiple, eight prolonged) were assessed and compared to 19 controls (simple FS) based on measures of intelligence, learning/memory, executive functioning, behaviour and emotions. Results Within the first year post-onset, infants with complex FS did not significantly differ from controls based on developmental measures. Seizure duration and age at seizure onset did not impact developmental outcome. School-age children with complex FS showed unaltered global intelligence, but lower executive functioning, compared to controls. Children with prolonged FS also showed evidence of a lower level of learning and memory abilities. Neuropsychological scores correlated with seizure duration. Children with complex FS showed more attentional problems and anxious/depressed symptomatology at onset and school age, and more hyperactivity at school age. Significance Infants with complex FS seemed to show normal development within the first year post-seizure onset. However, challenges in executive functioning, learning and memory at school age were found in children with a history of FS. Hence, at school age, cognitive challenges cannot be excluded based on undifferentiated early cognitive development, and may occur even in the absence of the most severe form of FS (i.e., FSE). Beyond the limits of this study (i.e., small sample size, use of parental questionnaires for emotional/behavioural outcome, absence of focal cases in the school-age cohort), our results suggest that a follow-up is necessary beyond the early preschool years in order to understand the long-term outcome.

Human biospecimens provide the basis for research, leading to a better understanding of human disease biology and discovery of new treatments that are tailored to individual patients with cancer or other common complex diseases. The collection, processing, preservation, storage and providing access to these resources are key activities of biobanks. Biobanks must ensure proper quality of samples and data, ethical and legal compliance as well as transparent and efficient access procedures. The standards for biobanking outlined herein are intended to be implemented in biobanks and to supply researchers with high-quality samples fitted for an intended use.

Introduction Success rates of catheter ablation in persistent atrial fibrillation (AF) remain suboptimal. A better and more targeted ablation strategy is urgently needed to optimize outcomes of AF treatment. We sought to assess the safety and efficacy of targeting atrial fibrosis during ablation of persistent AF patients in improving procedural outcomes. Methods The DECAAF II trial (ClinicalTrials. gov identifier number NCT02529319) is a prospective, randomized, multicenter trial of patients with persistent AF. Patients with persistent AF undergoing a first-time ablation procedure were randomized in a 1:1 fashion to receive conventional pulmonary vein isolation (PVI) ablation (Group 1) or PVI + fibrosis-guided ablation (Group 2). Left atrial fibrosis and ablation induced scarring were defined by late gadolinium enhancement magnetic resonance imaging at baseline and at 3-12 months postablation, respectively. The primary endpoint is the recurrence of atrial arrhythmia postablation, including atrial fibrillation, atrial flutter, or atrial tachycardia after the 90-day postablation blanking period. Patients were followed for a period of 12-18 months with a smartphone ECG Device (ECG Check Device, Cardiac Designs Inc.). With an anticipated enrollment of 900 patients, this study has an 80% power to detect a 26% reduction in the hazard ratio of the primary endpoint. Results and conclusion The DECAAF II trial is the first prospective, randomized, multicenter trial of patients with persistent AF using imaging defined atrial fibrosis as a treatment target. The trial will help define an optimal approach to catheter ablation of persistent AF, further our understanding of influencers of ablation lesion formation, and refine selection criteria for ablation based on atrial myopathy burden.

The recent financial and economic meltdown in Lebanon is the result of 30 years of social, economic, financial, and fiscal mismanagement, amplified by the Covid-19 pandemic and further exacerbated by the Beirut port explosion. Lebanese citizens? trust, as well as the international community's trust in the government, have unfortunately been destroyed. Consequently, Lebanon's sole option is to rebuild confidence in the government and public institutions by implementing economic reforms and to seek an IMF program to pave the way for additional financing from other international sources. The most important confidence-building step is a clear financial and economic plan that has the support of all key stakeholders. This article presents a road map for a reforms-driven, export-led growth strategy for Lebanon. Ultimately, the goal is to jump-start the economy and put it on a path of sustainable, inclusive, and equitable economic growth. Such growth should be grounded in a small, open-economy model and driven by low tariffs, a flexible exchange rate regime, and a dynamic export sector built on competitive and comparative advantages. This plan partially builds on proposals and recommendations provided by previous economic plans and policy notes.

Background Although the typical inheritance of spastic paraplegia 7 is recessive, several reports have suggested that SPG7 variants may also cause autosomal dominant hereditary spastic paraplegia (HSP). Objectives We aimed to conduct an exome-wide genetic analysis on a large Canadian cohort of HSP patients and controls to examine the association of SPG7 and HSP. Methods We analyzed 585 HSP patients from 372 families and 1175 controls, including 580 unrelated individuals. Whole-exome sequencing was performed on 400 HSP patients (291 index cases) and all 1175 controls. Results The frequency of heterozygous pathogenic/likely pathogenic SPG7 variants (4.8%) among unrelated HSP patients was higher than among unrelated controls (1.7%; OR 2.88, 95% CI 1.24-6.66, P = 0.009). The heterozygous SPG7 p.(Ala510Val) variant was found in 3.7% of index patients versus 0.85% in unrelated controls (OR 4.42, 95% CI 1.49-13.07, P = 0.005). Similar results were obtained after including only genetically-undiagnosed patients. We identified four heterozygous SPG7 variant carriers with an additional pathogenic variant in known HSP genes, compared to zero in controls (OR 19.58, 95% CI 1.05-365.13, P = 0.0031), indicating potential digenic inheritance. We further identified four families with heterozygous variants in SPG7 and SPG7-interacting genes (CACNA1A, AFG3L2, and MORC2). Of these, there is especially compelling evidence for epistasis between SPG7 and AFG3L2. The p.(Ile705Thr) variant in AFG3L2 is located at the interface between hexamer subunits, in a hotspot of mutations associated with spinocerebellar ataxia type 28 that affect its proteolytic function. Conclusions Our results provide evidence for complex inheritance in SPG7-associated HSP, which may include recessive and possibly dominant and digenic/epistasis forms of inheritance. © 2021 International Parkinson and Movement Disorder Society.

Objective Isolated (or idiopathic) rapid eye movement sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Biomarkers are lacking to predict conversion to a dementia or a motor-first phenotype. Here, we aimed at identifying a brain-clinical signature that predicts dementia in iRBD. Methods A brain-clinical signature was identified in 48 patients with polysomnography-confirmed iRBD using partial least squares between brain deformation and 27 clinical variables. The resulting variable was applied to 78 patients with iRBD followed longitudinally to predict conversion to a synucleinopathy, specifically DLB. The deformation scores from patients with iRBD were compared with 207 patients with PD, DLB, or prodromal DLB to assess if scores were higher in DLB compared to PD. Results One latent variable explained 31% of the brain-clinical covariance in iRBD, combining cortical and subcortical deformation and subarachnoid/ventricular expansion to cognitive and motor variables. The deformation score of this signature predicted conversion to a synucleinopathy in iRBD (p = 0.036, odds ratio [OR] = 2.249; 95% confidence interval [CI] = 1.053-4.803), specifically to DLB (OR = 4.754; 95% CI = 1.283-17.618, p = 0.020) and not PD (p = 0.286). Patients with iRBD who developed dementia had scores similar to clinical and prodromal patients with DLB but higher scores compared with patients with PD. The deformation score also predicted cognitive performance over 1, 2, and 4 years in patients with PD. Interpretation We identified a brain-clinical signature that predicts conversion in iRBD to more severe/dementing forms of synucleinopathy. This pattern may serve as a new biomarker to optimize patient care, target risk reduction strategies, and administer neuroprotective trials. ANN NEUROL 2021;89:341-357.

Cryoballoon (CB)-guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults.A total of 93 consecutive patients aged45 years referred to our center for AF ablation were included in this observational study. All patients received CB-guided PVI according to a standardized institutional protocol. Follow-up was performed in our outpatient clinic using 72-h Holter monitoring and periodic telephone interview. Recurrence was defined as any AF/atrial tachycardia (AT) episode30 s following a 3-month blanking period. A propensity matched control group consisting of patients older than 45 years were used for further evaluation. Mean age was 35 ± 7 years, 22% suffered from persistent AF, 85% were male. Mean follow-up was 2.6 ± 2 years. At the end of the observational period, 83% of patients were free of any AF/AT episodes. There was an excellent overall 12-month success rate of 92%. In comparison to a matched group the overall recurrence rate was noticeably lower in the young group (15% vs. 27%). Increasing age was associated with a hazard ratio of 1.16 for recurrence. In a multivariate analysis model, left atrial diameter remained as significant predictor of AF/AT recurrence. The complication rate was low, no permanent phrenic nerve palsy was observed.CB-guided PVI in young adults is safe and effective with favorable long-term results. It may be considered as first-line therapy in this relatively healthy population.

In cats, assessment of the testicular function is mainly based on sperm evaluation. Whatever the technique used, the volume of collected sperm is often small, which may lead to technical difficulties to achieve the semen evaluation in routine practice. Fine-needle aspiration (FNA) biopsy of the testicular parenchyma is one of the other methods used to assess testicular function. The aim of this study was to explore the relevance of FNA in the assessment of testicular cells in sexually mature cats. Eighteen cats over one year of age were recruited among animals presented for surgical neutering. Semen was collected by electroejaculation before it was evaluated. FNA biopsies of the testicles were taken using a 21-gauge needle. After castration, histological analysis of the testes was performed. Semen evaluation and histological analysis showed no anomalies, which confirmed normal spermatogenesis in all the cats and allowed a proper interpretation of the cytological findings. The cells identified through cytological examination were spermatogonia (1.99 ± 0.17%), primary spermatocytes (10.49 ± 0.74%), round spermatids (34.80 ± 1.57%), elongated spermatids (23.59 ± 2.02%), spermatozoa (21.56 ± 1.86%), Sertoli cells (7.53 ± 1.23%) and Leydig cells (0.04 ± 0.03%). However, spermatocytes II were not identified. This is due to the low proportions of these cells, related to their very short lifespan. Likewise, the very low number of Leydig cells observed is probably due to the damage caused during the aspiration stage. This study showed that fine-needle aspiration is an efficient method to describe cytologically normal testicular populations, a cornerstone for future research aimed to study abnormal spermatogenesis and to correlate it to cytological proportion of germ cells.

Efforts to reduce postoperative venous thromboembolism are challenging due to heterogeneity in thromboprophylaxis practice. As a result, a 'one-size-fits-all' approach that accounts for surgery-specific risk, but fails to account for patient-level variation, is often adopted by healthcare networks. Updated clinical practice guidelines have advocated an individualised risk-stratified approach that balances the risk:benefit ratio associated with thromboprophylaxis; however, there are limited data confirming effectiveness of these recommendations on the incidence of postoperative venous thromboembolism and bleeding. We developed the surgical-thrombo-embolism-prevention protocol, a novel risk-stratified algorithm that classified patients into low-, intermediate-, and high-risk profiles according to surgical procedure and patient baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies were then applied. A staged quality improvement program was developed to implement the protocol. We postulated that compliance with the protocol would reduce postoperative venous thromboembolism rates without increasing the incidence of postoperative bleeding. Between June 2013 and March 2018, we evaluated the efficacy, safety and sustainability of this risk-stratified approach in 24,953 surgical admissions at a dedicated cancer centre. By final implementation, program compliance was 91%. Postoperative venous thromboembolism rates reduced from 3.1 per 1000 surgical admissions to 0.6 per 1000 surgical admissions (relative risk reduction 79%; p < 0.005). Postoperative bleeding rates also declined from 10.0 per 1000 surgical admissions to 6.3 per 1000 surgical admissions (relative risk reduction 37%; p = 0.02). Sustained improvement was evident more than 3 years after implementation. Implementation of the surgical-thrombo-embolism-prevention protocol significantly reduced the incidence of postoperative venous thromboembolism supporting its validation at other institutions.

Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single‐cell RNA‐sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post‐MPA treatment. After stimulation, HPRT1 expression was 2.1‐fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor‐ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy.