Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.  Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Search for Dark-Matter-Nucleon Interactions via Migdal Effect with DarkSide-50.

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c^{2} mass dark matter. We present new constraints for sub-GeV/c^{2} dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12 306±184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c^{2}. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below 3.6 GeV/c^{2}.

Search for Dark Matter Particle Interactions with Electron Final States with DarkSide-50.

We present a search for dark matter particles with sub-GeV/c^{2} masses whose interactions have final state electrons using the DarkSide-50 experiment's (12 306±184) kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section σ[over ¯]_{e}, the axioelectric coupling constant g_{Ae}, and the dark photon kinetic mixing parameter κ. We also set the first dark matter direct-detection constraints on the mixing angle |U_{e4}|^{2} for keV/c^{2} sterile neutrinos.

Xenogeneic collagen matrix versus connective tissue graft for soft tissue augmentation at immediately placed implants: a prospective clinical trial.

The advantages of immediate implant placement for patients include a reduced number of surgical procedures and a shorter overall treatment time. Disadvantages include a higher risk of aesthetic complications. The aim of this study was to compare xenogeneic collagen matrix (XCM) versus a subepithelial connective tissue graft (SCTG) used for soft tissue augmentation in combination with immediate implant placement without provisionalization. Forty-eight patients requiring a single implant-supported rehabilitation were selected and assigned to one of two surgical procedures: immediate implant with SCTG (SCTG group) or immediate implant with XCM (XCM group). Marginal changes in the peri-implant soft tissue and the facial soft tissue thickness (FSTT) were assessed after 12 months. Secondary outcomes included peri-implant health status, aesthetics, patient satisfaction, and perceived pain. All of the implants placed were successfully osseointegrated, resulting in 1-year survival and success rates of 100%. The patients in the SCTG group had a significantly lower mid-buccal marginal level (MBML) recession (P = 0.021) and a greater increase in FSTT (P < 0.001) than the patients in the XCM group. Using xenogeneic collagen matrix during immediate implant placement significantly increased FSTT from the baseline, leading to good aesthetic and patient satisfaction results. However, the connective tissue graft yielded better MBML and FSTT results.

Life-threatening complications of streptococcal sepsis: a PICU contemporary series.

BACKGROUND: Life-threatening streptococcal sepsis nowadays represents an uncommon event in previously healthy infants and children. Critically ill patients suffering from severe streptococcal sepsis complications may present with pre-antibiotic era clinical pictures and require a timely clinical approach to achieve restitutio ad integrum. RESULTS: We report a series of four patient groups affected by an uncommon life-threatening streptococcal sepsis, each of them exhibiting some distinct features. Streptococcus Agalactiae sepsis was associated with cerebral thrombotic/ischaemic lesions, whereas severe cardiogenic shock was prominent in the Streptococcus Viridans group; Streptococcus Faecalis and ß-hemolytic group A Streptococcus patients mostly reported lung complications. CONCLUSIONS: Previous antibiotic treatments should not delay aggressive treatment in the intensive care setting. Early diagnostic suspicion, as well as appropriate and aggressive treatment provided within an intensive care setting are crucial for the clinical outcome.

Outcome and diagnostic reproducibility of the thyroid cytology "indeterminate categories" SIAPEC/SIE 2014 in a consecutive series of 302 cases.

PURPOSE: The clinical impact of the SIAPEC/SIE 2014 classification for thyroid cytology has been addressed in few studies that evaluated the malignancy rate and the relative prevalence of each category. No study analyzed its intra-observer and inter-observer reproducibility, so far. METHODS: We retrospectively collected all "indeterminate" lesions diagnosed before (2011-2014) and after (2015-2018) the application of the SIAPEC/SIE 2014 classification at our Institution. Their relative malignancy risks were calculated based on available histological diagnoses. Cytological and clinical features of TIR3A were compared with the surgical outcome. Finally, a large set of samples was re-evaluated in blind of the original cytological and histological diagnoses by two pathologists, independently. RESULTS: The prevalence of "indeterminate" diagnoses increased in years 2015-2018 (302/1482, 21% with 14% of TIR3A and 7% TIR3B categories) compared to years 2011-2014 (261/1680, 16%). Surgery was performed in 27% TIR3A and in 97% TIR3B cases. Malignancy rates were 40% for TIR3B and 17% for TIR3A, but were greatly influenced by the adoption of the WHO 2017 re-classification of encapsulated follicular-patterned lesions (decreasing to 28% and 6%, respectively). No criteria except for tumor size were associated to malignancy in TIR3A category. Intra-observer agreement of the experienced pathologist was 122/141 (86%), whereas inter-observer agreement between the expert and in-training pathologist was 95/141 (67%). CONCLUSIONS: In this real-life experience, the sub-classification of TIR3A and TIR3B slightly increased the overall prevalence of "indeterminate" diagnoses. Malignancy rates were higher than estimated for both TIR3A and TIR3B categories. Agreement among observers highly depended on pathologist's training.

Two case reports of fetal alcohol syndrome: broadening into the spectrum of cardiac disease to personalize and to improve clinical assessment.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) refers to a broad spectrum of disabilities, in infants and children, resulting from moderate to excessive prenatal alcohol exposure. Significant associations with alcohol exposure were already reported with congenital structural heart defects: i.e. ventricular septal defects, atrial septal defects, conotruncal defects. CASES PRESENTATION: We describe two cases of children with FASD, both admitted to the Center for Rare Diseases and Birth Defects of Policlinico Universitario Agostino Gemelli, in whom asymptomatic cardiac rhythm alterations were detected in absence of structural cardiovascular system anomalies or cardiac channelopathies. CONCLUSIONS: No other reports about cardiac rhythm anomalies in individuals affected by FASD are actually available from the literature. We would like to make an alert for clinician, given the possibility of finding anomalies of heart conduction and rhythm in children affected by FASD even without structural congenital heart disease.

Catastrophic antiphospholipid syndrome as a complication of systemic sclerosis.

A 62-year-old man with a history of systemic sclerosis was admitted with diffuse alveolar hemorrhage and acute kidney injury without clinical data suggestive of glomerulonephritis. Laboratory tests showed anemia, leukocytosis with neutrophilia, thrombocytopenia, elevated serum creatinine and metabolic acidosis. Antinuclear antibodies were positive at a titer of 1/640 (speckled, 1/160; nucleolar, 1/320) while rheumatoid factor, anti Scl-70, anti-centromere, anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane antibodies were negative and serum complement levels were within normal range. During the following days, the patient developed multiple organ failure and, eventually, died. Lupus anticoagulant was revealed positive after the patient's death, suggesting a catastrophic antiphospholipid syndrome. Clinical data and autopsy were consistent with this diagnosis.

National survey of anatomical pathology centres in Italy: the questionnaire.

OBJECTIVES: To obtain a picture of the work done in Italian anatomical pathology centres in 2014, and evaluate differences between the various centres in terms of the workloads of medical and non-medical staff. METHODS: A self-administered questionnaire designed by a SIAPEC working group was e-mailed to 256 centres and subsequently collected by the Anatomical Pathology Service of Bolzano. QlikView software was used to prepare the final database and check the quality of the data, which were processed using version 18.0 of SPSS for Windows statistical software. RESULTS: The questionnaire was completed by 120 of the centres (46.9%), which were staffed by a mean number of 6.6 physicians (range 1-24), 1.6 biologists (range 0-7), 10.8 laboratory technicians (range 2-47) and 2.2 administrative personnel (range 0-9). During 2014, the centres carried out a mean of 15,000 histology examinations (range 3,215-50,680), almost 11,700 immunohistochemistry examinations (range 0-54,359), and a mean of 1,471 molecular biology examinations (range 0-31,322) relating to a mean of 704 patients (range 0-9,434), and a mean of 16,509 cytology examinations (range 0-150,000) relating to 13,383 patients (range 0-120,000). Each centre physician issued a mean of 2,444 histology examinations reports (range 613-11,000); the ratio between the number of immunohistochemistry examinations and the number of histology examinations was 0.8 (range 0-2.7); and each laboratory technician had a mean overall annual workload of 3,072 histology, molecular biology and cytology examinations (range 793-9,882/year). These values varied widely among the participating centres. The mean ratio between the number of histology examinations carried out and the number of physicians was 1,982.77:1 a year in the small centres (< 10,000 histology cases/year), 2,627:1 a year in the medium-sized centres (10-24,999 histology cases/year), and 2,881.34:1 in the large centres (> 25,000 histology cases/year). There were significant differences between the small and medium-sized centres (p = 0.004) and between the small and large centres (p = 0.001), but not between the medium-sized and large centres.The ratio between the total number of histology, molecular biology and cytology examinations and the number of laboratory technicians was 1,963.34 in the small centres (< 10,000 examinations/year), 2,717.11 in the medium-sized centres (10,000-24,999 examinations/year), and 3,531.56 in the large centres (≥ 25,000 examinations/year). There were significant differences between the small and large centres (p = 0.001) and between the medium-sized and large centres (p = 0.004), but not between the small and medium-sized centres. CONCLUSIONS: The data collected by means of this survey provide an important, albeit partial, point of reference concerning the status of Italian anatomical pathology centres and their recent, everyday working situation.

A National Quality Assurance program for breast immunohistochemistry: an Italian perspective.

A national project for the quality assessment of breast immunohistochemistry, involving 155 pathology laboratories distributed all over the Italian territory ( 19 regions), was carried out. The Project lasted one year from December 2014 to December 2015 and it was strongly supported by the Italian Society of Anatomic Pathology (SIAPEC/IAP). Proficiency tests were carried out by the Nordic Immunohistochemical Quality Control (NordiQC) organization. The main aim of the project was to investigate on the general performance of immunohistochemistry (ER, PR and HER2) in the field of breast cancer in the Italian territory, in order to emphasize any difference and give practical support to laboratories in daily practice.The present review article focused on the description of this extraordinary pioneer Italian experience. Besides NordiQC results, further analysis concerning epidemiology and geographical distribution were done.Aim of the study was to analyze the general results and to discuss on the benefits that a national quality control program may have if it became a mandatory service provided by the National Health Care System.In general, the Italian data were in accordance with the general results obtained from the "official" NordiQC HER2, PR and ER assessments. A HER2 scoring consensus between labs and assessor group was achieved in 80% of cases.Interestingly, what emerges from our study is that no substantial differences exist among the three Italian macro-areas (North, Center and South) in the quality of Immunohistochemistry performed for breast cancer. No statistically significant difference was even found between laboratories that perform more or less than 100 tests/year.

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2×10

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.6)×10^{20} protons on target in the neutrino (antineutrino) mode, 89 ν_{e} candidates and seven anti-ν_{e} candidates are observed, while 67.5 and 9.0 are expected for δ_{CP}=0 and normal mass ordering. The obtained 2σ confidence interval for the CP-violating phase, δ_{CP}, does not include the CP-conserving cases (δ_{CP}=0, π). The best-fit values of other parameters are sin^{2}θ_{23}=0.526_{-0.036}^{+0.032} and Δm_{32}^{2}=2.463_{-0.070}^{+0.071}×10^{-3} eV^{2}/c^{4}.

Low-Mass Dark Matter Search with the DarkSide-50 Experiment.

We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20 GeV/c^{2} using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c^{2} for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8-6 GeV/c^{2}.

Constraints on Sub-GeV Dark-Matter-Electron Scattering from the DarkSide-50 Experiment.

We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.

Acute myocarditis as a revealing clue of complete Kawasaki disease.

Not available.

Expression of FK506-binding protein 51 (FKBP51) in Mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of nuclear factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies. OBJECTIVES: We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in patients with MF. METHODS: We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB-target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2). RESULTS: Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores. CONCLUSIONS: We hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL.

Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 µ-like events, and 7.471×10^{20} protons on target in antineutrino mode, which yielded 4 e-like and 66 µ-like events. Reactor measurements of sin^{2}2θ_{13} have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δ_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δ_{CP}=0, π) is excluded at 90% C.L.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

This corrects the article DOI: 10.1038/cdd.2016.22.

Measurement of Coherent π

We report the first measurement of the flux-averaged cross section for charged current coherent π^{+} production on carbon for neutrino energies less than 1.5 GeV, and with a restriction on the final state phase space volume in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso et al., the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. We observe a clear event excess above background, disagreeing with the null results reported by K2K and SciBooNE in a similar neutrino energy region. The measured flux-averaged cross sections are below those predicted by both the Rein-Sehgal and Alvarez-Ruso et al.

Efficacy of high-dose methylprednisolone pulses in a child with noninfectious persistent pleuropericarditis revealing systemic juvenile idiopathic arthritis.

Not available.