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Purpose: Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms — known to affect bone density in the general population — has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population. Methods: This is an observational study involving 135 TGD and 107 cisgender participants. Collected data included hormonal profiles and phospho-calcium metabolism, bone geometry and density (Dual Energy X-ray Absorptiometry and peripheral Quantitative Computed Tomography). For the genetic study related to the AR, genomic DNA was extracted from peripheral blood leukocytes. Results: TGD individuals had lower BMD values compared to their cisgender peers. In a subgroup of 129 individuals (86 TGD and 43 cisgender), we assessed the length of the polymorphic tracts of the ARgene and observed no differences between the groups. ARpolymorphisms showed significant correlations only with cortical BMD in both TGD and cisgender assigned females at birth (AFAB) individuals, and negative correlations with trabecular BMD in both cisgender men and women. Conclusions: Our study suggests that ARpolymorphisms do not play a significant role in the low BMD values observed in TGD individuals at baseline. Further research is necessary to better understand the impact of factors such as lifestyle on the bone health of TGD individuals.

Objective and design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection. Patients and measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone. Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395–479, 138–142, and 3.7–4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138–690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135–145 nmol/L) was detected in five patients, without being related to cortisol levels. Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency.

Background: The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. Material and Methods: An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. Results: Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescenceassociated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. Conclusions: Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented. [ABSTRACT FROM AUTHOR]

Introduction: Since COVID-19 pandemic spread, strict preventive measures were adopted to reduce the risk of transmission. Antiseptic dispensers for hand hygiene were diffusely available for patients and hospital staff. To investigate the prophylactic role played by the strict antiseptic rules adopted during pandemic, the rates of nosocomial urinary infections in 2019 and 2020 were compared.Materials and methods: Patients’ clinical pre-operative characteristics, symptoms, fever, and laboratory data were recorded pre- and post-operatively. Urological surgery was classified in five categories: 1. major surgery 2. upper urinary tract endoscopy, 3. lower urinary tract endoscopy, 4. minor surgery, and 5. Nephrostomy and ureteral stenting. Clavien-Dindo complication score was used. Statistical analysis was performed with R 3.4.2 software.Results: Out of 495 patients, 383 (57.1%) underwent surgical intervention in pre-pandemic March–May 2019 period and 212 (42.9%) in the same pandemic 2020 interval. Preoperatively, 40 (14.1%) and 11 (5.2%) and 77 (27.3%) and 37 (17.5%) patients had fever (p< 0.003) and leukocytosis (p< 0.02), in 2019 and 2020 respectively. Urine culture was positive in 29 (10.2%) and 13 (6.2%) patients respectively (p= 0.22). Post-operatively, 54 (19.1%) and 22 (10.4%) patients and 17 (6.1%) and 2 (0.6%) patients showed fever (p< 0.003) and positive urineculture (p< 0.03), in 2019 and 2020 respectively.Discussion and conclusion: Preoperative and post-operative clinical and laboratory signs of nosocomial urinary infection showed a statistically significant lower incidence during the pandemic period in 2020. This observation could be ascribed to the strong preventive measures, to the medical staff high adherence to hygiene and the diffuse availability of hand sanitizers.

In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.

Objectives: Learning and performing new routines are difficult for children with neurodevelopmental disorders. Studies have shown that consistency in child reinforcement and parental support are effective. For example, digital solutions such as serious games can be used to support parents and children in developing these life skills. The objective of this study was to evaluate the effect of a serious game on the performance of daily routines by autistic and ADHD children. Methods: A total of 201 families (parents and children) participated in the study. The study used a combined 3 (intervention) × 3 (diagnosis) × 3 (time) research design with repeated measures. Participants were randomly assigned to three intervention groups (serious game, parental support, and a combination of serious game and parental support) based on their diagnosis (ASD, ADHD, neurotypical). Latent growth modeling and repeated ANOVAS were performed to analyze routine scores collected at three moments (baseline, midpoint, persistence) over an 8-week period. Results: Results show a moderating effect of diagnosis on child routine trajectory. For ADHD participants, we observed a very important significant clinical effect for two interventions (parental support alone and combination of serious game and parental support) where for ASD children, this effect is observed for only one treatment (combination of serious game and parental support). For neurotypical children, results indicate a very important and significant clinical effect when they use the serious game alone. Conclusions: Results show that the serious game can improve children’s routines. However, for some neurodevelopmental profiles (ASD or ADHD), the addition of parental support produces greater clinical improvements.

BackgroundThe role of bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS) remains debatable. Atrial fibrillation (AF) associated strokes may be associated with reduced treatment effect from IVT. This study compares the effect of bridging IVT in AF and non-AF patients.MethodsThis retrospective cohort study comprised anterior circulation large vessel occlusion (LVO) AIS patients receiving EVT alone or bridging IVT plus EVT within 6 hours of symptom onset. Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were successful reperfusion defined as expanded Thrombolysis In Cerebral Infarction (eTICI) grading ≥2b flow, symptomatic intracerebral hemorrhage (sICH), and in-hospital mortality.ResultsWe included 705 patients (314 AF and 391 non-AF patients). The mean age was 68.6 years and 53.9% were male. The odds of good functional outcomes with bridging IVT was higher in the non-AF (adjusted odds ratio (aOR) 2.28, 95% CI 1.06 to 4.91, P=0.035) compared with the AF subgroups (aOR 1.89, 95% CI 0.89 to 4.01, P=0.097). However, this did not constitute a significant effect modification by the presence of AF on bridging IVT (interaction aOR 0.12, 95% CI −1.94 to 2.18, P=0.455). The rate of successful reperfusion, sICH, and mortality were similar between bridging IVT and EVT for both AF and non-AF patients.ConclusionThe presence of AF did not modify the treatment effect of bridging IVT. Further individual patient data meta-analysis of randomized trials may shed light on the comparative efficacy of bridging IVT in AF versus non-AF LVO strokes.

ABSTRACTThis study investigated the effect of clove essential oil used prior to stunning by cranial percussion and hypothermia on Nile tilapia (Oreochromis niloticus) welfare and fillet quality. A total of 100 tilapias were divided into four groups in a 2 × 2 factorial design, exploring two stunning methods with and without clove essential oil. Behavioral responses, glucose, lactate, pH, water holding capacity, color parameters, lipid and protein oxidation, and oxidative stress were analyzed. The application of clove essential oil resulted in 100% numbing in swimming and stimulus response behaviors, and 96% in balance and eye vestibule reflex variables. Significant reductions in glucose (12.12 mg dL−1) for hypothermia group (p = 0.001) and lactate (3.36 mmol L−1) for cranial percussion (p = 0.004), 0.028 nmol lipid oxidation in hypothermia treatment (p = 0.009), and 0.134 nmol carbonyls/mg protein (p = 0.001) were observed. There was a reduction in luminosity (p = 0.010) and red intensity (p = 0.001) in the group of fish fillet that received cranial percussion, however, there was no difference in the group stunned by hypothermia. Clove essential oil demonstrates effectiveness in pre-slaughter stress mitigation, influencing the antioxidant system positively. Its usage in pre-slaughter protocols could contribute to improved fillet quality, presenting a promising alternative for enhancing tilapia welfare during slaughter.

The directed assembly of nanomaterials into 3D architectures is a powerful tool to produce macroscopic materials with tailored physical properties. We show in this article that such a process can be advantageously performed for the fabrication of lightweight electrically conductive materials. Silver nanowire aerogels (AgNWAs) with very low densities (down to ∼6 mg cm–3) were ice-templated and freeze-dried, leading to 3D shaped cellular materials based on one-dimensional nanoscopic building blocks. Due to their intrinsic moderate mechanical resistance, the potential use of pure AgNWAs in real life applications appears rather limited. We demonstrate that the addition of carboxymethylcellulose (CMC) in a 1:1 weight ratio leads to the fabrication of hybrid aerogels with highly improved mechanical properties. The molecular weight of the CMC is shown to be a critical parameter to ensure a good dispersion of the AgNWs, and thus to reach excellent performances such as a very low resistivity (0.9 ± 0.2 Ω·cm at 99.2 vol % porosity). The combination of silver nanowires with CMC-700k results in a gain higher than 7100% of the Young’s modulus, from 10.4 ± 0.9 kPa (at very low density, i.e., 12 mg cm−3) for the AgNWAs to 740 ± 40 kPa for the AgNW:CMC aerogel. Electromechanical characterizations allowed us to quantify the piezoelectric properties of these hybrid aerogels. The very good elasticity and the piezoelectric behavior stability up to 100 cycles of compression under high (50%) deformation were revealed, which may be of interest for various applications such as pressure sensors.

Background The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB.Materials and Methods We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected.Results We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30–72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1–36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm). An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%). Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) – one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up.Conclusion The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

IMPORTANCE: The outcome and interpretation of noninferiority trials depend on the magnitude of the noninferiority margin and whether a relative or absolute noninferiority margin is used and may be affected by imprecision in event rate estimation. OBJECTIVE: To assess the consequence of imprecise event rate estimations on interpretation of peer-reviewed randomized clinical trials. DATA SOURCES: PubMed/MEDLINE was searched for articles published between January 1, 2015, and April 30, 2021. STUDY SELECTION: Noninferiority randomized clinical trials of coronary stents published in selected journals with clinical events as the primary end point. DATA EXTRACTION AND SYNTHESIS: Two reviewers (M.S. and F.V.) independently extracted data on trial characteristics, noninferiority assumptions, primary end point clinical outcomes, and study conclusions. Overestimation or underestimation of the control event rate was evaluated by dividing the assumed control event rate by the observed control event rate. For noninferiority end points with absolute margins, the assumed corresponding relative margin was defined as the ratio of the absolute margin and the assumed event rate, and the observed corresponding relative margin as the ratio between the absolute margin and the observed event rate in the control arm. Noninferiority comparisons with absolute margins were reanalyzed using the assumed corresponding relative margin and the Farrington-Manning score test for relative risk. MAIN OUTCOMES AND MEASURES: Overestimation or underestimation, assumed and observed corresponding relative margins, and relative reanalysis of the primary end points of trials with absolute margins. RESULTS: A total of 106 989 patients from 58 trials were included. The event rate in the control arms was overestimated by a median (IQR) of 28% (2%-74%). Most noninferiority trials used absolute rather than relative margins (55 of 58 trials [94.8%]). Owing to overestimation, absolute noninferiority margins became more permissive than originally assumed (median [IQR] of observed relative noninferiority margin, 1.62 [1.50-1.80] vs assumed relative noninferiority margin, 1.47 [1.39-1.55]; P &lt; .001). Among trial comparisons that met noninferiority with an absolute noninferiority margin, 17 of 50 trials (34.0%) would not have met noninferiority with a corresponding assumed relative noninferiority margin. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, assumed event rates were often overestimated in noninferiority coronary stent trials. Because most of these trials use absolute margins to define noninferiority, such overestimation results in excessively permissive relative noninferiority margins.

Introduction: BCG and MMC shortage and Covid-19 pandemic, more recently, limit accessibility to maintenance regimen in intravesical prophylaxis against recurrence of non-muscle invasive bladder cancer (NMIBC). Ellagic acid (EA) and Annona muricata (AM) exert antitumor activity against different human tumours. An observational prospective study on the prophylactic effect of oral administration of EA+AM in patients avoiding maintenance regimen is presented.Materials and methods: Patients affected by NMIBC and not undergoing maintenance after a 6-week course of intravesical prophylaxis with MMC or BCG were entered. Tis and very high-risk tumours were excluded. After informed consent, the patients were subdivided in relation to the oral assumption or not of EA (100 mg) plus AM (100 mg), daily for 6 months. All patients were submitted to 3-month cytology and cystoscopy.Results: 162 (90%) of 180 entered patients are evaluable, 90 and 72 receiving or not EA+AM. No difference emerged in patients’ characteristics between the two groups. BCG was given in 86 (54%) and chemotherapy in 74 (46%) patients. The recurrence free rate at 3, 6 and 12 months in patients assuming or not EA was 96.5% versus 84.6% (p= 0.003), 85.4% versus 64.8% (p= 0.005) and 74.2% versus 60.6% (p= 0.246), respectively. The recurrence free survival at 12 months in patients assuming or not EA was 63.0% versus 34.5% (p< 0.0001).Discussion and conclusions: Our study suffers several limits: not randomized trial although prospective, limited number of patients and short follow-up, nevertheless it shows the prophylactic effect of oral EA+AM in absence of maintenance after intravesical chemotherapy or immunotherapy induction.

Background and purposeCone-beam CT angiography (CB-CTA) provides a three-dimensional spatial resolution which is, so far, unmatched in clinical practice compared with other conventional techniques such as two-dimensional digital subtracted angiography. We aimed to assess the distribution of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) using CB-CTA.Methods30 consecutive patients with aSAH undergoing vasospasm percutaneous balloon angioplasty (PBA) were recruited and underwent CB-CTA in this single-center prospective cohort series. Intracranial arteries were systematically analyzed by two independent observers from the large trunks to the distal cortical branches and perforators using a high-resolution reconstruction protocol. Intermediate and severe cerebral vasospasm was defined as 30–50% and >50% narrowing in the diameter of the vessel, respectively.Results35 arterial cervical artery territories were analyzed, of which 80% were associated with clinical or radiological signs of delayed cerebral ischemia. The median spatial resolution was 150 µm (range 100–250 µm). Intermediate or severe vasospasm was observed in the proximal (86%, 95% CI 74% to 97%), middle (89%, 95% CI 78% to 99%), and distal (60%, 95% CI 44% to 76%) segments of the large trunks, as well as the cortical branches (11%, 95% CI 1% to 22%). No vasospasm was observed in basal ganglia or cortical perforators, or in arteries smaller than 900 µm. Vasospasm was more severe in middle or distal segments compared with proximal segments in 43% (95% CI 26% to 59%) of cases.ConclusionsOur study demonstrated that symptomatic cerebral vasospasm following aSAH did not involve arteries smaller than 900 µm, and frequently predominated in middle or distal segments. These results offer new insights into the potential management options for vasospasm using PBA.

Introduction: The current scenario of the COVID-19 pandemic is significantly different from that of the first, emergency phase. Several countries in the world are experiencing a second, or even a third, wave of contagion, while awaiting the effects of mass vaccination campaigns. The aim of this report was to provide an update of previously released recommendations on prioritization and restructuring of urological activities.Methods: A large group of Italian urologists directly involved in the reorganization of their urological wards during the first and second phase of the pandemic agreed on a set of updated recommendations for current urology practice.Results: The updated recommendations included strategies for the prioritization of both surgical and outpatient activities, implementation of perioperative pathways for patients scheduled for elective surgery, management of urological conditions in infected patients. Future scenarios with possible implementation of telehealth and reshaping of clinical practice following the effects of vaccination are also discussed.Conclusion: The present update may be a valid tool to be used in the clinical practice, may provide useful recommendations for national and international urological societies, and may be a cornerstone for further discussion on the topic, also considering further evolution of the pandemic after the recently initiated mass vaccination campaigns.

As part of the cost reduction of proton exchange membrane fuel cells, the substitution of the standard platinum catalyst by iron active sites for the oxygen reduction reaction (ORR) appears as a promising route. Herein, we report Pt-free catalysts prepared through an Fe–N-doped carbon cryogel synthesis process. By tuning selected parameters such as the initial pH and precursor molar ratios, various new structures with different chemical compositions and catalytic activities were synthesized and characterized. Carbon cryogels are porous materials, and the achieved hierarchical structures proved favorable for the accessibility of the active sites for O2and H+. The value of the pH medium was identified as a key parameter to control the structure of N-rich carbon cryogels, leading to a specific pH range to diphasic hydrogels. These materials are described and characterized for the first time, and they show promising catalytic activity for the ORR.

Onset of many forms of epilepsy occurs after an initial epileptogenic insult or as a result of an identified genetic defect. Given that the precipitating insult is known, these epilepsies are, in principle, amenable to secondary prevention. However, development of preventive treatments is difficult because only a subset of individuals will develop epilepsy and we cannot currently predict which individuals are at the highest risk. Biomarkers that enable identification of these individuals would facilitate clinical trials of potential anti-epileptogenic treatments, but no such prognostic biomarkers currently exist. Several putative molecular, imaging, electroencephalographic and behavioural biomarkers of epileptogenesis have been identified, but clinical translation has been hampered by fragmented and poorly coordinated efforts, issues with inter-model reproducibility, study design and statistical approaches, and difficulties with validation in patients. These challenges demand a strategic roadmap to facilitate the identification, characterization and clinical validation of biomarkers for epileptogenesis. In this Review, we summarize the state of the art with respect to biomarker research in epileptogenesis and propose a five-phase roadmap, adapted from those developed for cancer and Alzheimer disease, that provides a conceptual structure for biomarker research.

Pumps used in professional appliances process a solution of water, soils residues and detergents. These affect vapor tension, viscosity and rheology of the solution, mainly due to the presence of surfactants and polymers. Only a few studies have been found on how these substances can influence pump performances. Therefore, an experimental analysis has been carried out with aqueous solutions of a detergent component, the Polyox WSR 301, in the concentration range of 100–7000 ppm, to evaluate their influence on pump performances and cavitation. Some properties of the solutions have been preliminary characterized with a rheometer. Then, each solution has been tested in a dedicated test rig, to compare the performance curves of a centrifugal pump used in professional warewashing machines with those obtained with pure water. A non-intrusive method, based on the investigation of high frequency vibrations and noise signals, has been developed to detect cavitation at its early stage of inception. It was observed that polymer mitigates cavitating pump vibrations, with a reduction of the acceleration to less than one g. The analysis has provided the data necessary for the successive development of a control strategy for pump operation in professional appliances.

BackgroundWhile anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms.MethodsOne-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient’s notes and follow-up imaging.ResultsCBCT-A was superior in demonstrating the origin of perforators (P<0.001). The prevalence of perforator origin was estimated at 86% (95% CI 81%–92%) for PcoA, 8% (95% CI 4%–13%) for aneurysm wall, and 5% (95% CI 2%–9%) for ICA. The aneurysm wall origin was exclusively associated with PcoA agenesis, as well as higher risk of perforator infarction after aneurysm coiling compared with other variants (OR=14, 95% CI 2–88, P=0.006).ConclusionsOur study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.

This systematic review was conducted to identify the literature examining the prevalence of problematic internet use (PIU) in individuals with autism spectrum disorder (ASD), the difference in prevalence of PIU between those with and without ASD, and the correlates of PIU in ASD. Ten studies were identified. The eight studies with comparison groups reported that individuals with ASD had more symptoms of or scored higher on PIU. Correlates of PIU included time spent online and age at which individuals first went online, as well as depression, inattention, hyperactivity, impulsivity, opposition, and escapism. Results indicate that additional research is needed to examine PIU in adults with ASD and the causal relation of factors related to PIU in ASD through longitudinal studies.

ABSTRACTThree new species of Luticolaare described from lotic ecosystems in Andakí Municipal Natural Park, located in the Andean-Amazon region on the eastern flank of the eastern Andes mountain range in Colombia. Size and morphological features of the three new species, L. caquetensisKociolek, Simonato & Núñez-Avellaneda sp. nov., L. andakiesiorumSimonato, Kociolek & Plata Díaz sp. nov., and L. sinchiiSala, Kociolek & Simonato sp. nov. are provided, based on light and scanning electron microscopical observations, and compared with similar congeners. Species of the genus are organized into groups depending upon whether they possess or lack marginal channels and/or pseudosepta. All the new species possess pseudosepta and L. caquetensisand L. andakiesiorumlack marginal channels. The two latter species share this combination of features with Luticola affinisLevkov et al.,a species described from Brazil. These species thus form a unique group within the genus, offering additional evidence for the unique biodiversity found in this region.

In pediatric acute myeloid leukemia (AML), intensive chemotherapy and allogeneic hematopoietic stem cell transplantation are the cornerstones of treatment in high-risk cases, with severe late effects and a still high risk of disease recurrence as the main drawbacks. The identification of targeted, more effective, safer drugs is thus desirable. We performed a high-throughput drug-screening assay of 1280 compounds and identified thioridazine (TDZ), a drug that was highly selective for the t(6;11)(q27;q23) MLL-AF6 (6;11)AML rearrangement, which mediates a dramatically poor (below 20%) survival rate. TDZ induced cell death and irreversible progress toward the loss of leukemia cell clonogenic capacity in vitro. Thus, we explored its mechanism of action and found a profound cytoskeletal remodeling of blast cells that led to Ca2+ influx, triggering apoptosis through mitochondrial depolarization, confirming that this latter phenomenon occurs selectively in t(6;11)AML, for which AF6 does not work as a cytoskeletal regulator, because it is sequestered into the nucleus by the fusion gene. We confirmed TDZ-mediated t(6;11)AML toxicity in vivo and enhanced the drug’s safety by developing novel TDZ analogues that exerted the same effect on leukemia reduction, but with lowered neuroleptic effects in vivo. Overall, these results refine the MLL-AF6 AML leukemogenic mechanism and suggest that the benefits of targeting it be corroborated in further clinical trials.

In pediatric acute myeloid leukemia (AML), intensive chemotherapy and allogeneic hematopoietic stem cell transplantation are the cornerstones of treatment in high-risk cases, with severe late effects and a still high risk of disease recurrence as the main drawbacks. The identification of targeted, more effective, safer drugs is thus desirable. We performed a high-throughput drug-screening assay of 1280 compounds and identified thioridazine (TDZ), a drug that was highly selective for the t(6;11)(q27;q23) MLL-AF6(6;11)AML rearrangement, which mediates a dramatically poor (below 20%) survival rate. TDZ induced cell death and irreversible progress toward the loss of leukemia cell clonogenic capacity in vitro. Thus, we explored its mechanism of action and found a profound cytoskeletal remodeling of blast cells that led to Ca2+influx, triggering apoptosis through mitochondrial depolarization, confirming that this latter phenomenon occurs selectively in t(6;11)AML, for which AF6 does not work as a cytoskeletal regulator, because it is sequestered into the nucleus by the fusion gene. We confirmed TDZ-mediated t(6;11)AML toxicity in vivo and enhanced the drug's safety by developing novel TDZ analogues that exerted the same effect on leukemia reduction, but with lowered neuroleptic effects in vivo. Overall, these results refine the MLL-AF6AML leukemogenic mechanism and suggest that the benefits of targeting it be corroborated in further clinical trials.

ABSTRACTCoronary obstruction is a major complication of transcatheter aortic valve replacement (TAVR). Rapid and growing demand for TAVR procedures is accompanied by interest in techniques that may prevent this life-threatening adverse event. BASILICA (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction) is a transcatheter technique that may effectively prevent coronary obstruction. Formal proctorship and assistance by operators already experienced with the performance of BASILICA is beneficial to ensure good clinical outcomes. This review describes the BASILICA procedure and outlines selected technical considerations and pitfalls.AbbreviationsTAVR: transcatheter aortic valve replacement; BASILICA: Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic coronary Artery Obstruction; THV: transcatheter heart valve; VTC: virtual valve to coronary distance; ViV: valve-in-valve; VIVID: valve in valve international data.

La sclérose en plaques (SEP) est la première cause de handicap non traumatique de l’adulte jeune. L’hypersomnolence diurne a été rapportée chez ces patients, altérant la qualité de vie.

A limit of peripheral veno-arterial Extracorporeal Membrane Oxigenator (VA-ECMO) is the inadequate unloading of the left ventricle. The increase of end-diastolic pressure reduces the possibility of a recovery and may cause severe pulmonary edema. In this study, we evaluate our results after implantation of VA-ECMO and Transapical Left Ventricular Vent (TLVV) as a bridge to recovery, heart transplantation or long-term left ventricular assit devices (LVAD). From 2011 to 2014, 24 consecutive patients with profound cardiogenic shock were supported by peripheral VA-ECMO as bridge to decision. In all cases, TLVV was implanted after a mean period of 12.2 ± 3.4 hours through a left mini-thoracotomy and connected to the venous inflow line of the VA-ECMO. Thirty-day mortality was 37.5% (9/24). In all patients, hemodynamics improved after TLVV implantation with an increased cardiac output, mixed venous saturation and a significant reduced heart filling pressures (p< .05). Recovery of the cardiac function was observed in 11 patients (11/24; 45.8%). Three patients were transplanted (3/24; 12.5%) and three patients (3/24; 12.5%) underwent LVAD implantation as destination therapy, all these patients were discharged from the hospital in good clinical conditions. In these critical patients, systematic TLVV improved hemodynamic seemed to provide better in hospital survival and chance of recovery, compared to VA-ECMO results in the treatment of cardiogenic shock reported in the literature . TLVV is a viable alternative to standard VA-ECMO to identify the appropriate long-term strategy (heart transplantation or long-term VAD) reducing the risk of treatment failure. A larger and multicenter experience is mandatory to validate these hypothesis.