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Obstructive sleep apnea syndrome (OSAS) and obesity are frequently associated with hypertension (HTN), dyslipidemia (DLP), and insulin resistance (IR). In patients with obesity and OSAS scheduled for bariatric surgery (BS), guidelines recommend at least 4 weeks of preoperative continuous positive airway pressure (CPAP). Low-calorie ketogenic diets (LCKDs) promote pre-BS weight loss (WL) and improve HTN, DLP, and IR. However, it is unclear whether pre-BS LCKD with CPAP improves OSAS more than CPAP alone. We assessed the clinical advantage of pre-BS CPAP and LCKD in patients with obesity and OSAS. Seventy patients with obesity and OSAS were randomly assigned to CPAP or CPAP+LCKD groups for 4 weeks. The effect of each intervention on the apnea–hypopnea index (AHI) was the primary endpoint. WL, C-reactive protein (CRP) levels, HTN, DLP, and IR were secondary endpoints. AHI scores improved significantly in both groups (CPAP, p=0.0231; CPAP+LCKD, p=0.0272). However, combining CPAP and LCKD registered no advantage on the AHI score (p=0.863). Furthermore, body weight, CRP levels, and systolic/diastolic blood pressure were significantly reduced in the CPAP+LCKD group after 4 weeks (p=0.0052, p=0.0161, p=0.0008, and p=0.0007 vs baseline, respectively), and CPAP+LCKD had a greater impact on CRP levels than CPAP alone (p=0.0329). The CPAP+LCKD group also registered a significant reduction in serum cholesterol, LDL, and triglyceride levels (p=0.0183, p=0.0198, and p

OBJECTIVE The objective of this study was to describe the clinical and neuroradiological characteristics of a cohort of preterm infants who had undergone external ventricular drain insertion as a temporary measure to treat posthemorrhagic ventricular dilatation. In addition, the authors investigated the factors predicting permanent shunt dependency. METHODS The authors retrospectively reviewed the medical records of a cohort of preterm infants who had undergone external ventricular drain insertion at Gaslini Children’s Hospital (Genoa, Italy) between March 2012 and February 2018. They also analyzed clinical characteristics and magnetic resonance imaging data, including diffusion- and susceptibility-weighted imaging studies, which were obtained before both catheter insertion and removal. RESULTS Twenty-eight infants were included in the study. The mean gestational age was 28.2 ± 2.7 weeks, and the mean birth weight was 1209 ± 476 g. A permanent ventriculoperitoneal shunt was inserted in 15/28 (53.6%) infants because of the failure of external ventricular drainage as a temporary treatment option. Compared with the shunt-free group, the shunt-dependent group had a significantly lower gestational age (29.3 ± 2.3 vs 27.2 ± 2.7 weeks, p = 0.035) and tended toward a lower birth weight (p = 0.056). None of the clinical and neuroradiological characteristics significantly differed between the shunt-free and shunt-dependent groups at the time of catheter insertion. As expected, ventricular parameters as well as the intraventricular extension of intracerebral hemorrhage, as assessed using the intraventricular hemorrhage score, were reportedly higher in the shunt-dependent group than in the shunt-free group before catheter removal. CONCLUSIONS External ventricular drainage is a reliable first-line treatment for posthemorrhagic hydrocephalus. However, predicting its efficacy as a unique treatment remains challenging. A lower gestational age is associated with a higher risk of posthemorrhagic hydrocephalus progression, suggesting that the more undeveloped the mechanisms for the clearance of blood degradation products, the greater the risk of requiring permanent cerebrospinal fluid diversion, although sophisticated MRI investigations are currently unable to corroborate this hypothesis.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

Clinical Practice Points • MDS can occur in patients who have a history of prior exposure to chemotherapy and/or radiotherapy for a previous lymphoma. • MDS can occur with autoimmune disorders not responsive to immunosuppressive treatments. • Cytopenias and immunosuppressive treatments can lead to infections from opportunistic agents. • Mobilizing more cells than the amount needed to be infused could save patients with haematological disease from later cytopenic conditions.

Extracellular vesicles (EVs) are mediators of the immune system response. Encapsulated in EVs, microRNAs can be transferred between cancer and immune cells. To define the potential effects of EVs originated from squamous cell carcinoma cells on immune system response, we performed microRNA profiling of EVs released from two distinct cell lines and treated dendritic cells derived from circulating monocytes (mono-DCs) with these EVs. We confirmed the internalization of EVs by mono-DCs and the down-regulation of microRNA mRNA targets in treated mono-DCs. Differences in surface markers of dendritic cells cultivated in the presence of EVs indicated that their content disrupts the maturation process. Additionally, microRNAs known to interfere with dendritic cell function, and detected in EVs, matched microRNAs from squamous cell carcinoma patients’ plasma: miR-17-5p in oropharyngeal squamous cell carcinoma, miR-21 in oral squamous cell carcinoma, miR-16, miR-24, and miR-181a circulating in both oral and oropharyngeal squamous cell carcinoma, and miR-23b, which has not been previously described in plasma of head and neck squamous cell carcinoma, was found in plasma from patients with these cancer subtypes. This study contributes with insights on EVs in signaling between cancer and immune cells in squamous cell carcinoma of the head and neck.

Sphingomyelinases generate ceramide from sphingomyelin as a second messenger in intracellular signaling pathways involved in cell proliferation, differentiation, or apoptosis. Children from 12 unrelated families presented with microcephaly, simplified gyral pattern of the cortex, hypomyelination, cerebellar hypoplasia, congenital arthrogryposis, and early fetal/postnatal demise. Genomic analysis revealed bi-allelic loss-of-function variants in SMPD4, coding for the neutral sphingomyelinase-3 (nSMase-3/SMPD4). Overexpression of human Myc-tagged SMPD4 showed localization both to the outer nuclear envelope and the ER and additionally revealed interactions with several nuclear pore complex proteins by proteomics analysis. Fibroblasts from affected individuals showed ER cisternae abnormalities, suspected for increased autophagy, and were more susceptible to apoptosis under stress conditions, while treatment with siSMPD4 caused delayed cell cycle progression. Our data show that SMPD4 links homeostasis of membrane sphingolipids to cell fate by regulating the cross-talk between the ER and the outer nuclear envelope, while its loss reveals a pathogenic mechanism in microcephaly.

Pathogenic variants in KAT6A, encoding a histone acetyltransferase, have been identified as a cause of a developmental disorder with a definite clinical spectrum including intellectual disability, speech delay, dysmorphic facial features, microcephaly, cardiac and gastrointestinal defects. Seizures have been described in a minority of patients without a detailed characterization. In this work we focus on epilepsy in KAT6A syndrome, reporting two affected girls with history of seizures, bearing a KAT6A de novo heterozygous variant, of which one is novel. We describe the different epilepsy phenotypes of these two patients and compare them to the other individuals in literature presenting with epilepsy.

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

OBJECTIVE The main purpose of this study was to evaluate the association between age at onset and social support in outpatients with bipolar disorder who were in the recovery phase. We also investigated the association between age at onset and disability. METHODS A total of 180 bipolar disorder I outpatients, of whom 50 had early onset with age at onset ≤18 years old, 108 had middle onset with age at onset between 19 and 39 years old, and 22 had late onset with age at onset ≥40 years old, were assessed with the Medical Outcomes Study Social Support Scale and Sheehan Disability Scale. RESULTS The early onset group had lower tangible social support, longer length of illness, more childless participants, lower income and more suicide attempters than the late onset group. CONCLUSIONS Early onset seems to have inferior outcomes in tangible social support than late onset, but this trend should be considered as a starting point for future studies.

In animal and human neonates, expansion of the extracellular fluid volume is associated with "wet" lung and poor respiratory outcomes. To define fluid status changes during the transition from fetal to neonatal life in infants of diabetic mothers (IDM), we conducted a single-centre (Policlinico Abano Terme, Abano Terme, Italy) study of 66 IDM and a 1:2 matched control group from January 1 to September 30, 2020. Fluid status changes were assessed by computing Δ Hct from umbilical cord blood at birth and capillary heel Hct at 48 h, accounting for body weight decrease. IDM presented with significantly lower cord blood Hct levels in comparison to controls (47.33 ± 4.52 vs 50.03 ± 3.51%, p < 0.001), mainly if delivered by elective cesarean Sect. (45.01 ± 3.77 vs 48.43 ± 3.50%, p = 0.001). Hct levels at 48 h were comparable (55.18 ± 5.42 vs 54.62 ± 7.41%, p = 0.703), concurrently with similar body weight decrease (- 217.21 ± 113.34 vs - 217.51 ± 67.28 g, p = 0.614). This supports significantly higher ∆ Hct in IDM (5.13 ± 5.24 vs 7.29 ± 6.48, p < 0.01) and extra circulating fluid loss of 2-3%.Conclusion: Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung. What is Known: • In neonates, evidence suggests that expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor respiratory outcomes. What is New: • Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung.

The microbiota of fish skin, the primary barrier against disease, is highly dynamic and modulated by several factors. In fish aquaculture, disease outbreaks occur mainly during early-life stages, with associated high economic losses. Antibiotic treatments sometimes remain the best option to control bacterial diseases, despite many reported negative impacts of its use on fish and associated microbiota. Notwithstanding, studies monitoring the effects of disease and antibiotic treatment on the microbiota of fingerlings are scarce. We sequenced the bacterial 16S rRNA V4 gene region using a metabarcoding approach to assess the impact of a mixed infection with Photobacterium damselae ssp. piscicida and Vibrio harveyi and subsequent antibiotic treatment with flumequine, on the skin microbiota of farmed seabass (Dicentrarchus labrax) fingerlings. Both infection and antibiotic treatment led to a significant increase in bacterial diversity and core microbial communities and impacted microbiome structure. Dysbiosis was confirmed by changes in the abundance of potential pathogenic and opportunistic bacterial taxa. Skin bacterial metabolic function was also significantly affected by flumequine administration, suggesting a detriment to fish skin health. Our results add to an increasing body of literature, showing how fish microbiome response to infection and antibiotics cannot be easily predicted.

Schizophrenia (SZ) is a chronic debilitating disease. Subjects with SZ have significant shorter life expectancy. Growing evidence suggests that a process of pathological accelerated aging occurs in SZ, leading to early development of severe clinical diseases and worse morbimortality. Furthermore, unaffected relatives can share certain endophenotypes with subjects with SZ. We aim to characterize accelerated aging as a possible endophenotype of schizophrenia by using a machine learning (ML) model of peripheral biomarkers to accurately differentiate subjects with SZ (n = 35), their unaffected siblings (SB, n = 36) and healthy controls (HC, n = 47). We used a random forest algorithm that included biomarkers related to aging: eotaxins CCL-11 and CCL-24; the oxidative stress markers thiobarbituric acid-reactive substances (TBARS), protein carbonyl content (PCC), glutathione peroxidase (GPx); and telomere length (TL). The ML algorithm of biomarkers was able to distinguish individuals with SZ from HC with prediction accuracy of 79.7%, SZ from SB with 62.5% accuracy and SB from HC with 75.5% accuracy. These results support the hypothesis that a pathological accelerated aging might occur in SZ, and this pathological aging could be an endophenotype of the disease, once this profile was also observed in SB, suggesting that SB might suffer from an accelerated aging in some level.

Acute phosphate nephropathy (APN) is an acute renal failure secondary to the use of oral sodium phosphate (OSP) laxatives, with a high risk of progression to chronicity. We report a 60-year-old woman with mixed connective tissue disease whose serum creatinine increased up to 2.0 mg/dL in her regular control tests, without an evident causative factor. Kidney biopsy showed numerous intratubular calcium phosphate deposits, consistent with APN. She had a history of OSP laxative intake, and a sodium phosphate enema was used before a colonoscopy performed six months earlier. The temporal association between the use of OSP laxatives and acute kidney injury, should lead to the suspicion of APN. The urine sediment is generally normal or with mild to moderate proteinuria. The diagnosis is confirmed with a kidney biopsy. Until now, there is no specific treatment for APN, thus prevention is essential. In high-risk patients for developing APN, the administration of these laxatives should be avoided.

Post-varicella arterial ischemic stroke (AIS) is considered an uncommon cause of pediatric stroke that is considered a self-limiting, monophasic disease. However, in a subset of patients, disease recurs; the prevalence of vasculopathy or AIS recurrence, severity of clinical outcomes, and standardized therapies have not been well characterized. Herein, we determined the clinical-neuroradiological features, long-term evolution, and relationship between acute phase treatment and vasculopathy recurrence in a pediatric population with post-varicella AIS. Clinical, laboratory, and neuroradiological features of 22 children with post-varicella AIS between 2010 and 2019 (16 males, mean age at stroke 4 years, range 1.7–10) were reviewed. Statistical analyses were performed using χ2 and Fisher exact tests. Of the 22 cases, mean time from varicella to stroke was 4.5 months with 3 cases presenting more than 12 months after rash; 21 (95%) were not vaccinated for varicella; 3 (13.6%) had posterior circulation involvement; and 5 (22.7%) had AIS or vasculopathy recurrence, of which 4 recurred 6.1 months to 2.8 years after initial clinical onset. Recurrence was associated with lack of antiviral treatment during the first episode (p = 0.02). Post-varicella AIS can occur months after rash making diagnosis challenging. Because recurrent vasculopathy was seen predominantly in cases not treated with antiviral therapy during initial presentation, it is important to rapidly diagnose post-varicella AIS through clinical criteria and/or virological testing then treat with antivirals to prevent recurrence.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. Moreover, we assessed the relationship between BDNF levels and the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) and healed plaques along the culprit vessel. We enrolled consecutive patients presenting with ST-elevation myocardial infarction (STEMI) or non-ST-elevation (NSTE)-ACS. Serum BDNF levels were assessed by enzyme-linked immunosorbent assay. Plaque characteristics of the culprit vessel were assessed by OCT. Among 126 ACS patients (median age 68.00, interquartile range [IQR] 59.75-75.25 years, male 74.6%, 71 (56.3%) were NSTE-ACS and 55 (43.7%) were STEMI. BDNF levels were higher in STEMI patients compared to NSTE-ACS. OCT assessment was performed in 53 (42.1%) patients. Patients with MØI (n = 27) had higher BDNF levels compared to patients without MØI. Furthermore, patients with healed plaques (n = 13) had lower BDNF levels than patients without healed plaques. At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.

The proposed role of interleukin (IL)-17 in vitiligo pathogenesis, as well as the possible action of anti-IL-17A drugs on vitiligo, are not fully understood. The appearance of vitiligo as a paradoxical effect of treatment with anti-tumor necrosis factor-α drugs is an event well known in the literature, but is rarely described with anti-IL-17A drugs. In this case report, we describe a 42-year-old woman who developed new-onset vitiligo with repigmentation during successful secukinumab therapy for psoriatic arthritis. After 1 year of secukinumab therapy, vitiligo affecting >85% of the skin was evident on clinical and dermatoscopic examination, together with small, repigmented lesions. In depigmented lesions, reflectance confocal microscopy (RCM) showed disappearance of the bright dermal papillary rings normally seen at the dermo-epidermal junction. In repigmented lesions, activated dendritic melanocytes were observed on RCM. The patient continued to receive secukinumab, and continued to experience a slow and progressive repigmentation. Our case shows that anti-IL-17A biological agents for chronic inflammatory diseases may be associated with the development of new-onset vitiligo that improves over time with ongoing therapy. Therefore, physicians should be aware of the possibility of this rare paradoxical skin reaction in patients receiving secukinumab, and that it may not be necessary to discontinue secukinumab to achieve repigmentation.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

Nevus comedonicus (NC) is a rare type of organoid epidermal nevus with comedones and inflammatory cysts 1 . It may be associated with extracutaneous manifestations (cataract, neurological and skeletal anomalies), defining NC syndrome 2 . Acne nevus, a clinically similar mosaic skin condition, is related to FGFR2, whereas postzygotic NEK9 mutations have been identified in four NC patients so far, including only one with NC syndrome 3 4 . Here we report on novel clinical findings, fibrous dysplasia and premature puberty in a case of NC syndrome associated with a NEK9 mutation.

Background A 52-year-old woman presented with shortness of breath and cough. An endobronchial sialolipoma was found at the left entrance of the main bronchus. Sialolipoma is an exceedingly rare type of lipoma reported of the minor salivary glands, especially within the bronchus. Case presentation A 52-year-old woman presented with shortness of breath and cough with 6 months´ evolution. Endobronchial endoscopy revealed a tumour at the left entrance of the main bronchus. The entire removal of the tumour was removed using a cryoprobe device. Pathological examination showed a tumour consistent with the diagnosis of sialolipoma due to the presence of mature adipose cells blended with acinar, ductal, basal, and myoepithelial cells. The patient had a favourable outcome. Conclusion The infrequent tracheobronchial presentation of this tumour can be challenging for correct diagnosis.

Short-term mechanical circulatory support (MCS) devices are designed to provide hemodynamic support for a wide range of clinical conditions such as high-risk cardiac surgery or interventional procedures, post-cardiotomy cardiogenic shock, acute decompensated heart failure. Electrical storm (defined as three or more sustained episodes of ventricular fibrillation-VF- in a 24-h period) is a rare but critical complication following revascularization in patients with ischemic heart disease and it is associated with a very high mortality (80-90%) both during the incident alone and during further observation. Here we report the case of a 38-year-old patient affected by coronary artery disease with moderate to severe left ventricular systolic dysfunction (EF 30-35%) who underwent emergency coronary artery bypass grafting (CABG) complicated by electrical storm and severe haemodynamic instability, successfully managed with a novel approach of biventricular mechanical circulatory support with extracorporeal life support (ECLS) in first instance, subsequently switched to Impella CP and ProtekDuo.

Background Type A aortic dissection is an emergency with high morbidity and mortality when surgery is not performed. Few cases are described in the literature about aortic dissection during pregnancy. A correlation between pregnancy and aortic dissection is mainly reported in patients with family history and connective tissue disorders, such as Marfan’s syndrome (MS), Loeys–Dietz’s syndrome, and Ehlers–Danlos’s syndromes, and patients with bicuspid aortic valve (BAV); exceptional cases are also described in patients without risk factors. Case presentation A 22-year-old young woman with MS, ascending aorta dilation, and BAV became pregnant. During labor, she experienced a short-term chest pain with spontaneous resolution. The electrocardiogram (ECG) and cardiac biomarkers were negative for acute coronary artery disease, but no transthoracic echocardiogram (TTE) was performed. A caesarean section was performed without complications. After 1 month, a routine TTE showed a chronic ascending aortic dissection involving the aortic arch and supra-aortic vessels. Due to a normally functioning aortic valve, the David operation was performed (sparing aortic valve) with the replacement of the aortic arch and supra-aortic vessels. Conclusions Aortic dissection is a rare cardiovascular complication that can occur during pregnancy and is associated with very high-risk mortality. We have reported a rare case of undiagnosed type A aortic dissection involving the aortic arch during unplanned pregnancy in patients with BAV and MS, subsequently treated with the David surgery and replacement of ascending aortic arch and supra-aortic vessels. A closer clinical and instrumental follow-up is necessary in this particular group of patients at risk. Awareness of all physicians involved is mandatory.

Chronic kidney disease (CKD) is a disease characterized by the gradual and functional loss of renal mass, affecting its physiology leading to clinical manifestations. The CKD reaches dogs of several breeds causing important clinical alterations. Some laboratory tests are determinant for the correct diagnosis and thus for the implementation of the most appropriate treatment. The urinalysis, urinary protein-creatinine ratio (UPC) evaluation, urea, and creatinine dosage together with the symmetric dimethylarginine dosage (SDMA), urinary tract ultrasonography and blood pressure monitoring, are the main methods used for diagnosis. In this way, this work aimed to report a case of CKD in a Teckel dog attended at the Veterinary Hospital of the Federal University of Jataí (UFJ), discussing the main clinical manifestations, laboratory, and image alterations, as well as the correct staging according to IRIS (Interest Renal International Society), from which the best treatment option to be adopted is determined.

Background Several somatic mutations in TRAF7 have been reported in cancers, whereas a few germline heterozygous mutations have been recently linked to a neurodevelopmental disorder, characterized by craniofacial dysmorphisms, congenital heart defects, and digital anomalies. Cases We report two subjects harboring de novo heterozygous missense variants in TRAF7, namely the recurrent 1964G>A(p.Arg655Gln) and the novel missense c.1204C>G(p.Leu402Val) variants. In addition to the typical hallmarks of the TRAF7-related disorder, both subjects presented with a recognizable "pear-shaped" skull due to multiple craniosynostosis, sinus pericranii, skull base/cranio-cervical junction anomalies, dysgyria, and inferior cerebellar vermis hypoplasia. Conclusions Hence, we expand the genotypic and phenotypic spectrum of this neurodevelopmental disorder, discussing possible implications for clinical management of subjects with germline TRAF7 mutations.

OBJECTIVE To describe the foramen magnum angle (FMA) as a new parameter for basilar invagination (BI) type B. METHODS The FMA was performed on sagittal slice of magnetic resonance imaging (MRI) as a line from the hard palate to the opisthion (angle vertex), and another line from the opisthion to the basion. The MRIs from 31 participants with BI type B and 96 controls were used. Intraclass correlation coefficient, descriptive data, and receiver operating characteristic (ROC) curve were used for statistical analysis at the 95% confidence interval. RESULTS The interobserver agreement of the FMA was 0.952. Patients with BI type B had a FMA significantly greater (25.9° ± 9.3°) than control participants (11.6° ± 4.9°) (P < 0.001). The area under the ROC curve showed a diagnostic value of 0.947. The FMA showed sensitivity 0.900 and specificity 0.854 for the cutoff criterion 17° (P < 0.001). CONCLUSIONS The FMA had an optimal diagnostic value that provided complementary evidence to investigate BI type B.

Background: The assessment of coronary flow velocity reserve (CFVR) in left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on stress-induced regional wall motion abnormalities (RWMA). Objectives: The purpose of this study was to assess the feasibility and functional correlates of CFVR. Methods: This prospective, observational, multicenter study initially screened 3,410 patients (2,061 [60%] male; age 63 ± 11 years; ejection fraction 61 ± 9%) with known or suspected coronary artery disease and/or heart failure. All patients underwent SE (exercise, n = 1,288; vasodilator, n = 1,860; dobutamine, n = 262) based on new or worsening RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. A subset of 1,867 patients was followed up. Results: The success rate for CFVR on LAD was 3,002 of 3,410 (feasibility = 88%). Reduced (≤2.0) CFVR was found in 896 of 3,002 (30%) patients. At multivariable logistic regression analysis, inducible RWMA (odds ratio [OR]: 6.5; 95% confidence interval [CI]: 4.9 to 8.5; p < 0.01), abnormal left ventricular contractile reserve (OR: 3.4; 95% CI: 2.7 to 4.2; p < 0.01), and B-lines (OR: 1.5; 95% CI: 1.1 to 1.9; p = 0.01) were associated with reduced CFVR. During a median follow-up time of 16 months, 218 events occurred. RWMA (hazard ratio: 3.8; 95% CI: 2.3 to 6.3; p < 0.001) and reduced CFVR (hazard ratio: 1.5; 95% CI: 1.1 to 2.2; p = 0.009) were independently associated with adverse outcome. Conclusions: CFVR is feasible with all SE protocols. Reduced CFVR is often accompanied by RWMA, abnormal LVCR, and pulmonary congestion during stress, and shows independent value over RWMA in predicting an adverse outcome.

Laparoscopic Palomo varicocelectomy is one the most common approaches adopted to treat pediatric varicocele, but postoperative hydrocele still remains a potential problem with this procedure. This study aimed to evaluate the outcome of a new technique of lymphography using indocyanine green (ICG)-enhanced fluorescence to perform lymphatic sparing laparoscopic Palomo varicocelectomy.The records of 25 patients who underwent laparoscopic left varicocelectomy in our unit from March 2017 to March 2018 were retrospectively evaluated. The average patients' age was 13.7 years (range 12-16). All patients had a high degree varicocele associated with left testicular hypotrophy and symptoms. All procedures were performed in laparoscopy using three trocars. After trocars' positioning, 2 mL of ICG solution was directly injected into the left testicle. Using ICG fluorescence, the lymphatic vessels were clearly identified and spared, and then the entire spermatic bundle was clipped and divided according to Palomo's principle.The average operative time was 18 minutes (range 10-25). No conversions to open surgery and no allergy or other adverse reactions induced by ICG were reported. At a maximum follow-up of 18 months, no recurrence of varicocele or postoperative hydrocele was recorded.Our preliminary experience showed that ICG fluorescence lymphography is a safe and effective option to perform lymphatic sparing laparoscopic Palomo varicocelectomy in children and adolescents with high degree varicocele. The intratesticular injection of ICG and use of fluorescence vision allowed identification of lymphatic vessels in 100% of cases. No allergy to ICG or postoperative hydrocele was reported in our experience.

Ultrasound scan is a painless and radiation-free imaging modality and, therefore, it is widely considered the first-choice diagnostic tool in the setting of hepatopathies in paediatric patients. This article focuses on the normal ultrasound anatomy of the liver in neonatal and paediatric age and reviews the ultrasound appearance of the most common diffuse and focal liver affections.

Aims: Patients with heart failure (HF) exhibit ventricular dyssynchrony with negative effects on ventricular systolic and diastolic performance and poor prognosis. There is no consensus about the best approach for estimating the dyssynchrony and for selecting candidates for resynchronization therapy (CRT). We sought to evaluate whether Myocardial Performance Index (MPI), calculated as differences between left and right ventricle (LV, RV), ∆MPI, represents a marker of interventricular dyssynchrony. Methods: The study included 40 patients (22 males, 18 females, mean age 71±13) with NYHA functional class II-III, chronic heart failure (77% ischaemic), in optimal drug therapy for at least three months. All patients underwent a complete two-dimensional and Tissue Doppler Echocardiography (TDE), including an assessment of MPI in both ventricles. Results: Significant correlations were found between ∆MPI and QRS (r = 0.41, p < 0.001), with NYHA (r = 0.66, p < 0.001), with SPWMD (r = 0.32, p < 0.05), with LV ejection fraction (r = -0.32, p < 0.05), with Spv wave at the septal site of LV (r = -0.32, p < 0.05), and with IVMD (r = 0.44, p < 0.001). Ten patients have been re-evaluated six months after CRT implantation, and ∆MPI significantly correlated with the difference between basal LVEF and six months after CRT implantation (r = 0.43, p < 0.04). Conclusion: The ∆MPI could represent an integrative marker of interventricular dyssynchrony and could be considered as a new parameter in the patient selection process to be undergone CRT.

Made available in DSpace on 2020-12-12T01:57:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression. Study design/aims: This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease. Results: Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer. Conclusion: miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection. Division of Pediatric Surgery-Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), Botucatu Department of Pediatric Surgery Barretos Children's Cancer Hospital from Barretos Cancer Center Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), Botucatu Experimental Research Unity (UNIPEX) Faculty of Medicine São Paulo State University (UNESP), Botucatu Faculty of Medicine São Paulo State University (UNESP), Botucatu Department of Genetics Institute of Biosciences, São Paulo State University (UNESP), Botucatu Department of Pathology Faculty of Medicine São Paulo State University (UNESP), Botucatu Division of Pediatric Surgery-Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), Botucatu Department of Surgery and Orthopedics Faculty of Medicine São Paulo State University (UNESP), Botucatu Experimental Research Unity (UNIPEX) Faculty of Medicine São Paulo State University (UNESP), Botucatu Faculty of Medicine São Paulo State University (UNESP), Botucatu Department of Pathology Faculty of Medicine São Paulo State University (UNESP), Botucatu CAPES: 2014/458734-4 FAPESP: 2015/03287-4

INTRODUCTION: Remote monitoring (RM) has significantly transformed the standard of care for patients with cardiac electronic implantable devices It provides easy access to valuable information, such as arrhythmic events, acute decompensation manifestations and device-related issues, without the need of in-person visits METHODS: Starting March 1st, 332 patients were introduced to a RM program during the Italian lockdown in order to limit the risk of in-hospital exposure to Severe Acute Respiratory Syndrome-Coronavirus-2 Patients were categorized into two groups based on the modality of RM delivery [home (n=229) vs office (n= 103) delivered] The study aimed at assessing the efficacy of the new follow-up protocol, assessed as mean RM Activation Time (AT) and need for technical support Additionally, patients' acceptance and anxiety status were quantified via the Home Monitoring Acceptance and Satisfaction Questionnaire and the Generalized Anxiety Disorder 7-item scale RESULTS: AT time was

SummaryBackgroundSocial and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.AimsWe studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.MethodThis is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.ResultsA total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = −0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.ConclusionsOur results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

The long-term impact of low-grade germinal matrix-intraventricular hemorrhage (GMH-IVH) on brain perfusion has not been fully investigated. We aimed to compare cortical and deep gray matter (GM) cerebral blood flow (CBF) obtained with pseudo-continuous arterial spin labeling (pCASL), among preterm neonates with and without low-grade GMH-IVH and full-term controls. 3T-pCASL examinations of 9 healthy full-term neonates (mean gestational age 38.5 weeks, range 38–39) and 28 preterm neonates studied at term-equivalent age were analyzed. Eighteen preterm neonates presented normal brain MRI (mean gestational age 30.50 weeks, range 29–31) and 10 low-grade GMH-IVH according to Volpe’s grading system (mean gestational age 32 weeks, range 28–34). A ROI-based mean CBF quantification was performed in 5 cortical (frontal, parietal, temporal, insula, occipital), and 4 subcortical GM regions (caudate, putamen, pallidum, thalamus) for each cerebral hemisphere. CBF differences were explored using a nonparametric analysis of covariance. Low-grade GMH-IVH hemispheres showed consistently lower CBF in all GM regions when compared with healthy preterm neonates, after controlling the confounding effect of gestational age, postmenstrual age, and birth weight P

Colorectal cancer is one of the most significant types of cancer, ranking second in the world’s mortality cases. As colorectal cancer is often diagnosed at a late stage of disease progression, effe...

Antioxidant components of colostrum prevent oxidative cell damage caused by free radicals that could harm the calf's development. The relationship of antioxidant potential of colostrum with parity is not well defined and could enlighten the importance of these components for the neonate and for the protection of the intestinal epithelium. The purpose of this work was to determine the antioxidant potential of colostrum from primiparous and multiparous Holstein cows in a commercial dairy farm. Samples from the first milk secretion from primiparous (first lactation, n = 8) and multiparous (second and third lactations, n = 8) Holstein cows were collected after birth of calves for determination of immune and antioxidant factors. The cows sampled in this study were vaccinated during pregnancy in order to improve colostrum quality. Colostrum from primiparous cows showed higher values of ceruloplasmin activity, oxygen radical absorbance capacity (ORAC) and transferrin saturation index (TSI) than colostrum from multiparous cows (P < 0.05). The total iron binding capacity (TIBC) and transferrin concentration in the colostrum of primiparous cows showed a non-significant numerical decrease (P = 0.06) in relation to the value in the colostrum of multiparous cows. Concentration of proteins, immunoglobulin G, and activity of lactoperoxidase, lysozyme, glutathione peroxidase and catalase, in turn, did not differ (P > 0.05). Metabolic differences between primiparous and multiparous cows may have affected the antioxidative status of colostrum, since ORAC values were twice higher in first lactation cows. Lower values of transferrin and TIBC and higher TSI in colostrum from primiparous cows suggests a relationship between lower iron stock and higher antioxidant activity. Thus, this work indicates an important role of the antioxidant potential of colostrum for neonates from first-lactation cows. Additionally, the iron stock may be directly related to the higher antioxidant potential of the colostrum from primiparous cows, and further investigations are required.

Brosimum gaudichaudii Trecul, Moraceae, is a Brazilian plant species used in traditional medicine to treat vitiligo or as an additive in natural suntan lotions. Even though it is widely used in Brazil, its safety and efficacy have not been studied. In this study, the hydroalcoholic extract was standardized for its psoralen and 5-methoxypsoralen content, and its biological effects were studied in B16F10 cells. Melanin synthesis capacity of the extract was compared with synthetic psoralen and 5-methoxypsoralen in the same cell line. Safety assessment of the extract was performed by neutral red uptake, comet, and micronucleus cytome assays. The herbal extract was less cytotoxic to the B16F10 cells than pure active ingredients, psoralen, and 5-methoxypsoralen in equivalent doses. Melanin synthesis was enhanced by 300% with the extract compared with the 130% increase with psoralen and 5-methoxypsoralen. The extract prepared with the roots, as well as the synthetic compounds used as control standards, exhibited mutagenic activity on B16F10 cells. Consequently, caution has to be taken with the use of these roots for the treatment of vitiligo in popular herbal medicine.

Objective This study was aimed to investigate the prenatal findings in Aicardi syndrome (AIC) by intrauterine magnetic resonance imaging (iuMRI) suggesting possible diagnostic criteria and differential diagnosis. Methods The iuMRI features of nine AIC confirmed cases were described and then compared with those of postnatal MRI. Furthermore, all iuMRI cases with both corpus callosum (CC) agenesis–dysgenesis and cortical malformation (AIC mimickers) were retrospectively reviewed and compared with iuMRI AIC cases, in order to identify possible neuroradiological predictors of AIC syndrome. For this purpose, Chi-square statistic and binary logistic regression analysis were performed. Results In all AIC cases, iuMRI was able to detect CC agenesis–dysgenesis and cortical development anomalies. Postnatal MRI revealed some additional findings mainly including further cystic lesions and in two cases small coloboma. A statistically significant difference between AIC and AIC mimicker were found regarding sex, nodular heterotopias, posterior fossa abnormalities, coloboma, and cortical gyration abnormalities. The most predictive variables in the logistic regression model were cortical gyration abnormalities, coloboma, and sex. Conclusion The iuMRI findings may suggest prenatal diagnosis of AIC syndrome with significant impact on parental counseling. Among possible differential diagnoses, tubulinopathies emerged.

Background and objectives Individuals with bipolar disorder have an elevated risk of suicide. One hypothesis is that deficits in inhibitory control may play a significant part in suicidal behavior. However, the relationship between inhibitory control and suicide behavior in bipolar disorder is still unclear. This study aims, therefore, to investigate the effects of inhibitory control with other clinical variables on the likelihood that individuals with bipolar disorder have had previous suicide attempts. Methods 96 euthymic individuals with bipolar disorder were recruited and underwent a clinical interview. Inhibitory control was measured through the Stroop Color-Word Test. A logistic regression model was conducted to investigate the effects of multiple hospitalizations, age of disease diagnosis, family history of severe mental disorders, sex and inhibitory control performance, controlling for age and estimated intellectual functioning. Results The model revealed statistically significant main effects of multiple hospitalizations, female sex and family history of psychiatric disorders. Unexpectedly, inhibitory control performance was not a significant predictor, even after designing a new model excluding the clinical variables. Conclusions Current inhibitory control performance was not related to the likelihood of previous suicide attempts in individuals with BD, reinforcing the evidence of major effects of clinical risk factors. It may play an indirect role in suicidal behavior, however, as it may be related to greater illness severity, which, in turn, may be related to more severe episodes and increased suicidal behavior.

Resumo Objetivos Avaliar e comparar as características histológicas de meniscos frescos e meniscos congelados armazenados em banco de tecidos por 1 mês e por 5 anos. Métodos Foi feito um estudo histológico com enxertos meniscais. Avaliamos 10 meniscos, sendo 2 que ficaram armazenados sob congelamento por 5 anos, 4 armazenados congelados por 1 mês, e 4 frescos, recém captados. Foram feitos cortes histológicos corados com hematoxilina e eosina e Tricrômico de Masson, para avaliação das propriedades histológicas. Resultados Os meniscos congelados por 1 mês apresentaram preservação parcial da estrutura das fibras colágenas, sem degeneração hidrópica significativa do tecido. Nos meniscos congelados por 5 anos, observamos dissociação evidente das fibras colágenas, com presença de múltiplos focos de degeneração hidrópica. Discussão Encontramos degeneração bem mais significativa nos meniscos armazenados por 5 anos, o que indica que o longo período de congelamento leva à progressão significativa da degeneração do tecido. Isto pode sugerir que o período de 5 anos, considerado período máximo que o enxerto pode permanecer armazenado antes de ser transplantado, é um período muito longo. Conclusão Nos enxertos armazenados por 1 mês, existiu apenas discreta alteração degenerativa das fibras colágenas, enquanto que nos meniscos com 5 anos de congelamento foi observada degeneração significativa do tecido. Tibiais

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method. The cytotoxic profile was evaluated using the MTT assay, against a human skin cell line (hFB) as a model for normal cells, and against an adenocarcinomic human alveolar basal epithelial (A569) cell line as a lung cancer in vitro model. The results demonstrated that the functionalization of carbon nanotubes with naringenin occurred by non-covalent interactions. The release profiles demonstrated a pH-responsive behavior, showing a prolonged release in the tumor pH environment. The naringenin-functionalized carbon nanotubes showed lower cytotoxicity on non-malignant cells (hFB) than free naringenin, with an improved anticancer effect on malignant lung cells (A549) as an in vitro model of lung cancer., This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the contributions from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Objective To analyze the association between basilar invagination (BI) and stenosis in the hypoglossal canal (HC). Methods A case-control study with magnetic resonance images (MRIs) of the head from a local database was performed. The study used MRIs of 31 patients with BI (type B) and 36 controls, both groups over 18 years of age and without sex distinction. The internal (ID) and external (ED) diameters of the HC were measured on the coronal plane using the Osirix in its free version 3.9.2 (Mac-Apple platform). We used the Kolmogorov-Smirnov test (with Lilliefors adjustment) to evaluate the normality of the variables, the Levine test to verify the homogeneity of the variances, and Student's t test to verify differences between groups. All analyses were within the 95% confidence interval. Results Control group presented right and left ED values of 4.7 ± 0.8 mm and 4.6 ± 0.9 mm, respectively, while the right and left ID showed 4.4 ± 0.9 mm and 4.3 ± 0.8 mm, respectively. The group with BI showed right and left ED values of 3.3 ± 0.9 mm and 3.1 ± 0.9 mm, and the right and left ID had values of 2.8 ± 0.7 mm and 2.7 ± 0.7 mm, respectively. Both ED and ID were smaller in the group with BI (P Conclusions Patients with BI of type B presented the narrowing of HC when compared with control participants.

Post-mortem brain studies suggest that miRNAs may be involved in suicide, but their role as peripheral biomarkers or targets of preventive pharmacological treatments in suicide has yet to be elucidated. We used nCounter miRNA Expression assay to measure miRNAs expression in lymphoblastoid cell lines (LCLs) from patients with Bipolar Disorder (BD) who died by suicide (SC, n = 7) and with low risk of suicide (LR, n = 11). Five miRNAs were differentially expressed in SC compared to LR (false discovery rate p0.05). The two most significant miRNAs were measured with RT-qPCR in the same sample and in 12 healthy controls (HC): miR-4286 was increased while miR-186-5p was decreased in SC compared to LR and HC (ANOVA F = 14.92, p = 0.000043 and F = 3.95, p = 0.032 respectively). miR-4286 was also decreased in postmortem brains from 12 patients with BD who died by suicide compared to 13 controls, even though it did not reach statistical significance (FC=0.51, p = 0.07). Treatment with lithium of human neural progenitor cells reduced the expression of miR-4286 (FC=0.30, p = 0.038). Pathway analysis on predicted miR-4286 targets showed that "insulin resistance" was significantly enriched after correction for multiple testing. This pathway comprised 17 genes involved in lipid and glucose metabolism, several of which were also dysregulated in postmortem brains from patients with BD who died by suicide from the Stanley-foundation array collection. In conclusion, our study suggests that miR-4286 could be a biomarker of suicide but further studies are warranted to investigate its targeted genes and how these could be involved in the neurobiology of suicide.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.

Objectives Systematically review the prevalence of functional impairment (FI) in euthymic patients with bipolar disorder (BD), as assessed only with the Functioning Assessment Short Test (FAST), explore the prevalence of this impairment among all the domains, identify the most compromised of them and the clinical variables associated with low functioning in this population. Methods Meta-analyses were performed, searching for relevant papers published from 2007 to 2019 in Medline, Embase, Cochrane, PsycINFO databases and via hand-searching, without language restrictions. 1128 studies were initially identified, 13 of which were ultimately chosen based on the eligibility criteria. A two-step meta-analysis was performed using the mean difference with a 95% confidence interval for continuous variables and proportion estimation with a fixed-effects model for categorical variables. Results In the first step, all FAST domains showed worse FI in patients than in healthy controls, with significant differences between groups. In the second step, the prevalence of FI domains were as follows: global, 58.6%; occupational, 65.6%; cognitive, 49.2%; autonomy, 42.6%; interpersonal relationships, 42.1%; leisure, 29.2%; and financial issues, 28.8%. Residual depressive symptoms were the most frequently cited variable associated with FI. Conclusions This study reinforces the relevant functional impact of BD in this population and suggests that the occupational domain may be the most impaired. Greater efforts should be directed toward targeting functioning in patient care, as it constitutes the most meaningful endpoint of response to treatment, especially with occupational and cognitive rehabilitation, thus allowing patients to overcome the course of illness and carry fulfilling lives.

Clinically meaningful molecular subtypes for classification of breast cancers have been established, however, initiation and progression of these subtypes remain poorly understood. The recent development of desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) facilitates the convergence of analytical chemistry and traditional pathology, allowing chemical profiling with minimal tissue pretreatment in frozen samples. Here, we characterized the chemical composition of molecular subtypes of breast cancer with DESI-MSI. Regions of interest were identified, including invasive breast cancer (IBC), ductal carcinoma in situ (DCIS), and adjacent benign tissue (ABT), and metabolomic profiles at 200 μm elaborated using Biomap software and the Lasso method. Top ions identified in IBC regions included polyunsaturated fatty acids, deprotonated glycerophospholipids, and sphingolipids. Highly saturated lipids, as well as antioxidant molecules [taurine (m/z 124.0068), uric acid (m/z 167.0210), ascorbic acid (m/z 175.0241), and glutathione (m/z 306.0765)], were able to distinguish IBC from ABT. Moreover, luminal B and triple-negative subtypes showed more complex lipid profiles compared with luminal A and HER2 subtypes. DCIS and IBC were distinguished on the basis of cell signaling and apoptosis-related ions [fatty acids (341.2100 and 382.3736 m/z) and glycerophospholipids (PE (P-16:0/22:6, m/z 746.5099, and PS (38:3), m/z 812.5440)]. In summary, DESI-MSI identified distinct lipid composition between DCIS and IBC and across molecular subtypes of breast cancer, with potential implications for breast cancer pathogenesis. Significance: These findings present the first in situ metabolomic findings of the four molecular subtypes of breast cancer, DCIS, and normal tissue, and add to the understanding of their pathogenesis.

Purpose: The purpose of the present study was to compare visual function assessment, visual evoked potential, and optical coherence tomography with measurement of retinal nerve fiber layer thickness for the diagnosis of optic pathway glioma in children with neurofibromatosis type 1. Methods: This retrospective observational study included patients with neurofibromatosis type 1 who underwent brain magnetic resonance imaging scan, visual evoked potential study, and peripapillary retinal nerve fiber layer evaluation by optical coherence tomography. Patients were tested with pattern-reversal visual evoked potential and with flash visual evoked potential in case of poor cooperation. Optical coherence tomography was performed with HRA Spectralis (Heidelberg Engineering, Heidelberg, Germany). The area under the curve of receiver operating characteristic curves was used to evaluate the accuracy of each parameter for diagnosing optic pathway glioma. Results: In all, 110 patients with neurofibromatosis type 1 were included in the study. Fifty of them had an optic pathway glioma diagnosed with magnetic resonance imaging, while 60 did not. Global retinal nerve fiber layer thickness demonstrated the highest diagnostic power for discriminating patients with and without optic pathway glioma (area under the curve = 0.758, sensitivity = 65.3%, specificity = 83.3%), followed visual acuity (area under the curve = 0.723, sensitivity = 51.1%, specificity = 91.7%) and P100 of visual evoked potential (area under the curve = 0.712, sensitivity = 69.6%, specificity = 63.8%). Conclusion: The results of the present study showed that the measurement of retinal nerve fiber layer thickness was the most efficient test for discriminating patients with and without optic pathway glioma. Brain magnetic resonance imaging remains the gold standard to confirm the diagnosis of optic pathway glioma. Longitudinal studies are required to define if the early detection of tumors with optical coherence tomography could prevent vision loss and morbidity.

Anticoagulation in a neonate is a challenge and the availability of anticoagulant options is extremely limited. Here we describe the use of a direct thrombin inhibitor, bivalirudin, in a full-term neonate with symptomatic cerebral sinovenous thrombosis complicated by bilateral thalamic hemorrhagic stroke and intraventricular hemorrhage, who could not be effectively treated with sodium heparin due to heparin resistance (HR) and showed thrombosis regression after start of bivalirudin treatment, without worsening of the hemorrhage. While the use of bivalirudin in neonates has been previously described, the indication of cerebral sinovenous thrombosis and the setting of HR are unique.

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide.

Myotonic dystrophy type 1 (DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1 (RYR1), sarcoplasmatic/endoplasmatic Ca2+-ATPase (SERCA) and α1S subunit of voltage-gated Ca2+ channels (Cav1.1) is related to Ca2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol (RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy (rs9879/14) on May 20, 2014.