Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

Normal, dust-obscured galaxies in the epoch of reionization.

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1-3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4-7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare population of extreme starburst galaxies8-12 and companions of rare quasars13,14. These studies conclude that the contribution of dust-obscured galaxies to the cosmic star formation rate density at z > 6 is sub-dominant. Recent ALMA and Spitzer observations have identified a more abundant, less extreme population of obscured galaxies at z = 3-6 (refs. 15,16). However, this population has not been confirmed in the reionization epoch so far. Here, we report the discovery of two dust-obscured star-forming galaxies at z = 6.6813 ± 0.0005 and z = 7.3521 ± 0.0005. These objects are not detected in existing rest-frame UV data and were discovered only through their far-infrared [C II] lines and dust continuum emission as companions to typical UV-luminous galaxies at the same redshift. The two galaxies exhibit lower infrared luminosities and star-formation rates than extreme starbursts, in line with typical star-forming galaxies at z ≈ 7. This population of heavily dust-obscured galaxies appears to contribute 10-25% to the z > 6 cosmic star formation rate density.

From asking to observing. Behavioural measures of socio-emotional and motivational skills in large-scale assessments.

Socio-emotional and motivational skills are routinely measured using self-reports in large-scale educational assessments. Measures exploiting test-takers' behaviour during the completion of questionnaires or cognitive tests are increasingly used as alternatives to self-reports in the economics of education literature. We compute behavioural measures of socio-emotional and motivational skills using data from the Programme for International Student Assessment (PISA). We find that these measures capture important aspects of students' academic profiles: some are importantly associated with contemporaneous performance and educational attainment and most measures have a high degree of stability over time. However, these measures are only limitedly correlated among themselves and have low correlations with self-report measures of the same constructs. This is likely a reflection of the fact that behavioural measures are representations of the test taker current 'state', rather than descriptions of the participant view of their own 'trait' like the self-report measures. Moreover, the low correlation across measures suggests that they capture different behavioural responses to the test-taking situation. These differences are still limitedly understood because the measures are constructed ex-post using collateral information collected during the administration of assessments rather than developed ex ante in line with theoretical models of human cognition and affect.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Performance decline in a low-stakes test at age 15 and educational attainment at age 25: Cross-country longitudinal evidence.

INTRODUCTION: Educational attainment is associated with important life outcomes including labour market performance, health status, well-being, civic and political participation. An important question is whether it is possible to identify early those students who lack the achievement motivation that is needed to complete a higher education degree. METHODS: Longitudinal follow-ups of representative samples of participants in the 2000 and 2003 Programme for International Student Assessment (PISA) from Australia, Denmark and Switzerland (N = 3110; 1130; and 1962; age = 15 to 27; % females 51%, 51%, 49%; ethnicity/race unknown) were used to identify the association between a measure of effort on a cognitively demanding low-stake task at age 15 - performance decline during the test - and educational attainment at age 25-27. RESULTS: A one SD difference in performance decline was associated with a 5-6 percentage point difference in the probability of obtaining tertiary-level qualifications (r = -0.15 in Australia; -0.11 in Denmark and -0.11 in Switzerland). We find no evidence of differences in this relationship across genders, socio-economic status and baseline levels of ability in the three countries. The association between performance decline and educational attainment is homogeneous across these groups. Self-reported measures of achievement motivation were not predictive of educational attainment in the three countries. CONCLUSIONS: Our work contributes new longitudinal evidence to the body of research in education employing behavioural measures of motivation and engagement. It can be used to understand the potential long-term consequences of disparities in students' preparation to sustain effort over cognitively demanding tasks.

Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

Post-partum weight loss and glucose metabolism in women with gestational diabetes: the DEBI Study.

AIMS: Women with gestational diabetes are at high risk for developing diabetes; post-partum weight loss may reduce the risk of diabetes. We evaluated the association of post-partum weight change with changes in glucose, insulin and homeostasis model assessment of insulin resistance in a subsample (n = 72) of participants from Diet Exercise and Breastfeeding Intervention (DEBI), a randomized pilot trial of lifestyle intervention for women with gestational diabetes. METHODS: Glucose and insulin were measured fasting and 2 h after an oral glucose tolerance test at 6 weeks and 12 months post-partum. Women were categorized by weight change (lost > 2 kg vs. maintained/gained) between 6 weeks and 12 months post-partum. RESULTS: Compared with women who maintained or gained weight, women who lost > 2 kg experienced significantly lower increases in fasting glucose [age-adjusted means: 0.1 mmol/l (95% CI -0.03 to 0.3) vs. 0.4 mmol/l (95% CI 0.3-0.6); P < 0.01] and 2-h insulin [10.0 pmol/l (95% CI -56.9 to 76.9) vs. 181.2 pmol/l (95% CI 108.3-506.9); P < 0.01] and a significant reduction in 2-h glucose [-0.9 mmol/l (95% CI -1.4 to -0.3) vs. 0.3 mmol/l (95% CI -0.3 to 0.9); P < 0.01]. In multiple linear regression models adjusted for age, Hispanic ethnicity, medication use, meeting the Institute of Medicine's recommendations for gestational weight gain, breastfeeding and randomized group, a 1-kg increase in weight was significantly associated with increases in fasting and 2-h glucose (P < 0.05), but was not associated with insulin or homeostasis model assessment of insulin resistance. CONCLUSIONS: In women with gestational diabetes, modest post-partum weight loss may be associated with improvements in glucose metabolism.

Bifidobacterium aesculapii sp. nov., from the faeces of the baby common marmoset (Callithrix jacchus).

Six Gram-positive-staining, microaerophilic, non-spore-forming, fructose-6-phosphate phosphoketolase-positive bacterial strains with a peculiar morphology were isolated from faecal samples of baby common marmosets (Callithrix jacchus). Cells of these strains showed a morphology not reported previously for a bifidobacterial species, which resembled a coiled snake, always coiled or ring shaped or forming a 'Y' shape. Strains MRM 3/1(T) and MRM 4/2 were chosen as representative strains and characterized further. The bacteria utilized a wide range of carbohydrates and produced urease. Glucose was fermented to acetate and lactate. Strain MRM 3/1(T) showed a peptidoglycan type unique among members of the genus Bifidobacterium. The DNA base composition was 64.7 mol% G+C. Almost-complete 16S rRNA, hsp60, clpC and rpoB gene sequences were obtained and phylogenetic relationships were determined. Comparative analysis of 16S rRNA gene sequences showed that strains MRM 3/1(T) and MRM 4/2 had the highest similarities to Bifidobacterium scardovii DSM 13734(T) (94.6%) and Bifidobacterium stellenboschense DSM 23968(T) (94.5%). Analysis of hsp60 showed that both strains were closely related to B. stellenboschense DSM 23968(T) (97.5% similarity); however, despite this high degree of similarity, our isolates could be distinguished from B. stellenboschense DSM 23968(T) by low levels of DNA-DNA relatedness (30.4% with MRM 3/1(T)). Strains MRM 3/1(T) and MRM 4/2 were located in an actinobacterial cluster and were more closely related to the genus Bifidobacterium than to other genera in the family Bifidobacteriaceae. On the basis of these results, strains MRM 3/1(T) and MRM 4/2 represent a novel species within the genus Bifidobacterium, for which the name Bifidobacterium aesculapii sp. nov. is proposed; the type strain is MRM 3/1(T) ( = DSM 26737(T) = JCM 18761(T)).

Sex ratio variations among the offspring of women with diabetes in pregnancy.

AIMS: It has long been hypothesized that natural selection would favour a reproductive strategy biased towards females under adverse circumstances in order to maximize the number of surviving grandchildren. An excess of daughters in women with Type 1 diabetes and a greater likelihood of gestational diabetes in women carrying male fetuses have also been reported. This study aims to compare the sex ratio across categories of maternal glycaemia. METHODS: Among 288,009 mother-infant pairs delivering at Kaiser Permanente Northern California in 1996-2008, sex ratios were calculated for the following categories: pregravid diabetes, gestational diabetes, mild pregnancy hyperglycaemia (defined as an abnormal screening but normal diagnostic test for gestational diabetes) and normoglycaemia. Odds ratios for delivering a male were estimated with logistic regression; normoglycaemic pregnancies comprised the reference. RESULTS: Women with pregravid diabetes delivered the fewest males (ratio male/female = 1.01), followed by women with normoglycaemic pregnancies and those with an abnormal screening only (both sex ratios = 1.05); women with gestational diabetes delivered the most males (sex ratio = 1.07). Odds ratio estimates suggested the same pattern, but none attained statistical significance. CONCLUSIONS: The crude sex ratios in this cohort suggest a possible gradient by category of maternal glycaemia. Women with gestational diabetes, a condition characterized by excessive fuel substrates, appear to deliver more males. Women with pregravid diabetes delivered the fewest males, possibly reflecting the unfavourable state of chronic disease.

Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern Italy.

OBJECTIVES: The introduction of vaccination against hepatitis B initially reduced the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections, but the decreasing trend of HDV infection seems to have stopped. The aim of this study was to assess the prevalence of HDV infection in the general population living in the catchment area of Legnano Hospital in northern Italy. METHODS: Of the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were subsequently tested for anti-HDV antibodies. RESULTS: Of the 488 subjects who tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30 and 60 years. The difference in prevalence between males (7.1%) and females (1.9%) was statistically significant (p < 0.05), but not that between Italian (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV seropositivity between the patients with acute (0%) and chronic infections (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not statistically significant, but there was a significant difference (p < 0.01) between those with asymptomatic (2.1%) and clinically symptomatic infections (10.3%). Intravenous drug abuse was the main source of infection. CONCLUSIONS: In the catchment area of our hospital, the prevalence of HDV infection does not seem to be due to patients of non-Italian origin, but to Italian patients who are not vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s. Nevertheless, the increase in the number of immigrants from non-EU countries in recent years is soon likely to lead to a change in the epidemiology of HDV.

The impact of land use/land cover changes on land degradation dynamics: a Mediterranean case study.

In the last decades, due to climate changes, soil deterioration, and Land Use/Land Cover Changes (LULCCs), land degradation risk has become one of the most important ecological issues at the global level. Land degradation involves two interlocking systems: the natural ecosystem and the socio-economic system. The complexity of land degradation processes should be addressed using a multidisciplinary approach. Therefore, the aim of this work is to assess diachronically land degradation dynamics under changing land covers. This paper analyzes LULCCs and the parallel increase in the level of land sensitivity to degradation along the coastal belt of Sardinia (Italy), a typical Mediterranean region where human pressure affects the landscape characteristics through fires, intensive agricultural practices, land abandonment, urban sprawl, and tourism concentration. Results reveal that two factors mainly affect the level of land sensitivity to degradation in the study area: (i) land abandonment and (ii) unsustainable use of rural and peri-urban areas. Taken together, these factors represent the primary cause of the LULCCs observed in coastal Sardinia. By linking the structural features of the Mediterranean landscape with its functional land degradation dynamics over time, these results contribute to orienting policies for sustainable land management in Mediterranean coastal areas.

Screening for mutations in the ISL1 gene in patients with thyroid dysgenesis.

CONTEXT: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000- 4000 newborns. In 80-85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland, all conditions indicated as "thyroid dysgenesis" (TD). A higher prevalence of congenital heart diseases has been documented in children with CH compared to the general population. This association suggests a possible pathogenic role of genes involved in both heart and thyroid development. Among these, it can be included Isl1, a transcription factor containing a LIM homeodomain that is expressed in both thyroid and heart during morphogenesis. OBJECTIVE: In the present study, we investigate the role of ISL1 in the pathogenesis of TD. SETTINGS AND PATIENTS: By single stranded conformational polymorphism, we screened for mutations the entire ISL1 coding sequence in 96 patients with TD and in 96 normal controls. RESULTS: No mutations have been found in patients and controls. CONCLUSION: Our data indicate that, despite the relevant role of ISL1 in thyroid and heart morphogenesis, mutations in its coding region are not associated with TD in our group of patients.

Rotator cuff re-tear or non-healing: histopathological aspects and predictive factors.

PURPOSE: The aim of the study was to evaluate the histopathological changes that occur in the tendon and subacromial bursal tissue in patients with rotator cuff tear trying to correlate these changes to their healing capability. METHODS: Eighty-four patients were clinically evaluated with the Constant Scale. Radiographs and MRI were performed preoperatively and ultrasound were performed postoperatively. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed, and the specimens were histopathologically analyzed. RESULTS: Tendons histopathological features consisted of loss of structural organization, poor or absent neoangiogenesis, chondral metaplasia, and fibrosis. Bursal features consisted of neoangiogenesis, absence of chondral metaplasia, hyperplasia/hypertrophy, and absence of necrosis. Direct correlation was seen between tendon and bursal hyperplasia and time of the onset of symptoms; between tendon chondral metaplasia, fibrosis, bursal neoangiogenesis, inflammation, and patient age; between tendon neoangiogenesis, hyperplasia, necrosis, fibrosis, bursal necrosis, inflammation, and lesion size; on the contrary, tendon fibrosis, necrosis, and bursal tissue inflammation decrease as time passes from the onset of symptoms. Tendon fibers disarray, neoangiogenesis, and inflammation decreases as the patient's age increases. Bursal tissue fibrosis decreases as lesion size increases. CONCLUSIONS: Simple histopathological techniques should be employed routinely to assess the tissue quality, with the aim to predict future clinical evolution (repair or non-repair). Comparing the histopathological data with the demographical information and the descriptive statistics, it is possible to define the RCT repair at risk and identify which RCT will be able to heal.

A supernova origin for dust in a high-redshift quasar.

Interstellar dust plays a crucial role in the evolution of the Universe by assisting the formation of molecules, by triggering the formation of the first low-mass stars, and by absorbing stellar ultraviolet-optical light and subsequently re-emitting it at infrared/millimetre wavelengths. Dust is thought to be produced predominantly in the envelopes of evolved (age >1 Gyr), low-mass stars. This picture has, however, recently been brought into question by the discovery of large masses of dust in the host galaxies of quasars at redshift z > 6, when the age of the Universe was less than 1 Gyr. Theoretical studies, corroborated by observations of nearby supernova remnants, have suggested that supernovae provide a fast and efficient dust formation environment in the early Universe. Here we report infrared observations of a quasar at redshift 6.2, which are used to obtain directly its dust extinction curve. We then show that such a curve is in excellent agreement with supernova dust models. This result demonstrates a supernova origin for dust in this high-redshift quasar, from which we infer that most of the dust at high redshifts probably has the same origin.

[Stem cells and colorectal cancerogenesis: new insight]. / Cellule staminali e carcinogenesi colorettale: recenti acquisizioni.

Intestinal stem cells are monoclonal, multipotent cells residing in the niches of intestinal cripts where they regulate colonic epithelial turnover. It has been recently demonstrated that alterations in signalling transduction of the intestinal stem cells is implicated in the onset of colorectal cancer. Chronic inflammation may be one of the mechanisms involved in cancerogenesis because failure of resident stem cells in repairing the epithelial damage for the chronic insult, recruits bone marrow stem cells, which can develop genetic mutations due to the inflamed environment, leading to cancer. The main mutations associated with colorectal cancer affect the most important cellular signalling pathway, the Wnt. Mutations of adenomatous polyposis coli (APC) tumor suppressor gene and b catenin oncogene are the most common and severe alterations of this pathway. Tissue invasion and metastatization require a two-side transition of cancer stem cells, from epithelial phenotypes to mesenchimal one (epithelial transition tumor, EMT) and from the mesenchimal phenotype to the epithelial one (mesenchymal transition tumor, MET) under the regulatory effects of the environment, the intracellular b catenin distribution and P16 cell cycle inhibitor. Stem cells provide normal intestinal epithelial turnover, but may also promote intestinal cancerogenesis, and, since the cancer stem cells during the mesenchimal status are resistant to the chemotherapy (which is active only on proliferating cells), they represent the true target of future therapeutic approaches in oncology.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Mutations in TAZ/WWTR1, a co-activator of NKX2.1 and PAX8 are not a frequent cause of thyroid dysgenesis.

AIM: In 80-85% of cases, congenital hypothyroidism is associated with thyroid dysgenesis (TD), but only in a small percentage of cases mutations in thyroid transcription factors (NKX2.1, PAX8, FOXE1, and NKX2.5) have been associated with the disease. Several studies demonstrated that the activity of the transcription factors can be modulated by the interaction with other proteins, such as coactivators and co-repressors, and TAZ (transcriptional co-activator with PDZ-binding motif or WWTR1) is a co-activator interacting with both NKX2.1 and PAX8. In the present study we investigate the role of TAZ in the pathogenesis of TD. MATERIAL AND METHODS: By Single Stranded Conformational Polymorphism, we screened the entire TAZ coding sequence for mutations in 96 patients with TD and in 96 normal controls. RESULTS: No mutations were found in patients and controls, but we found several polymorphisms in both groups. No significant differences could be demonstrated in the prevalence of the mutations between patients and controls. CONCLUSIONS: Our data indicate that TAZ mutations are not a cause of TD in the series of patients studied.

Emergency use of wearable left ventricular assist devices in patients not eligible for heart transplantation.

BACKGROUND: We reviewed our experience concerning the clinical outcomes of emergency implantation of left ventricular assist devices (LVAD) in patients not eligible for heart transplantation (HTX). PATIENTS AND METHODS: Between January 1998 and September 2006, 62 patients were referred for emergency HTX including 35 (55%) who received cardiac allografts; 9 (14%) died on the waiting list. The other 18 subjects (31%) did not meet listing criteria due to pulmonary hypertension with massive transpulmonary gradients (TPG), severe diabetes, or another factor; 7 patients had wearable LVAD implants and the remaining 11 who had contraindications both to HTX and to LVAD implantation remained on medical therapy. RESULTS: Twelve month actuarial survivals were 47% in LVAD G1 vs 1% in medical therapy G2 (P< .005). Four G1 patients died either due to cerebrovascular vascular episodes or to thromboembolic events. The beneficial use of LVAD in 3 patients led to consistent improvement in hemodynamic performance allowing listing for HTX. Two of them have been successfully transplanted; 1 is still waiting. Due to refractory heart failure, 90% of G2 died within the first months after evaluation. CONCLUSION: Our limited experience indicated that emergency use of LVAD ensued a satisfactory outcome allowing better actuarial survival.