Search

Respiratory syncytial virus (RSV) infection represents a global and noteworthy cause of hospitalization and death in infants of less than 1 year of age. The typical clinical manifestation is bronchiolitis, an inflammatory process of the small airways. The symptoms are usually a brief period of low-grade fever, cough, coryza, breathing difficulties, and reduced feeding. The progression of the disease is difficult to predict, even in previous healthy subjects. Symptoms may also be subtle and underestimated, thus leading to sudden unexpected infant death (SUID). In these cases, RSV infection is discovered at autopsy, either histologically or through real-time reverse transcription polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs. Herein, we describe a case of RSV infection in a 6-month-old infant with no risk factors, who rapidly deteriorated and unexpectedly died of respiratory insufficiency in a hospital setting. RT-PCR on nasopharyngeal swabs revealed RSV. The autopsy showed diffuse lymphogranulocytic bronchitis and bronchiolitis, and multiple foci of acute pneumonia. Abnormal muscularization of the intra-acinar pulmonary arteries was also observed, which likely contributed to worsening the lung impairment.

The two primary classes of opioid substances are morphine and its synthetic derivative, heroin. Opioids can cross the placental barrier, reaching fetal circulation. Therefore, at any gestational age, the fetus is highly exposed to pharmacologically active opioid metabolites and their associated adverse effects. This review aimed to investigate all the studies reported in a timeframe of forty years about prenatal and postnatal outcomes of opioid exposition during pregnancy. Clinical and toxicological aspects, as well as pharmacogenetic and epigenetic research focusing on fetal and infant effects of opioid use during pregnancy together with their medico-legal implications are exposed and discussed.

This work presents results from an original open-source low-cost sensor (LCS) system developed to measure tropospheric O3 in a remote high altitude alpine site. Our study was conducted at the Col Margherita Observatory (2543 m above sea level), in the Italian Eastern Alps. The sensor system mounts three commercial low-cost O3/NO2 sensors that have been calibrated before field deployment against a laboratory standard (Thermo Scientific; 49i-PS), calibrated against the standard reference photometer no. 15 calibration scale of the World Meteorological Organization (WMO). Intra- and intercomparison between the sensors and a reference instrument (Thermo Scientific; 49c) have been conducted for 7 months from May to December 2018. The sensors required an individual calibration, both in laboratory and in the field. The sensor's dependence on the environmental meteorological variables has been considered and discussed. We showed that it is possible to reduce the bias of one LCS by using the average coefficient values of another LCS working in tandem, suggesting a way forward for the development of remote field calibration techniques. We showed that it is possible reconstruct the environmental ozone concentration during the loss of reference instrument data in situations caused by power outages. The evaluation of the analytical performances of this sensing system provides a limit of detection (LOD) ppb (parts per billion), limit of quantification (LOQ) ppb, linear dynamic range (LDR) up to 250 ppb, intra-Pearson correlation coefficient (PCC) up to 0.96, inter-PCC >0.8, bias >3.5 ppb and ±8.5 at 95 % confidence. This first implementation of a LCS system in an alpine remote location demonstrated how to obtain valuable data from a low-cost instrument in a remote environment, opening new perspectives for the adoption of low-cost sensor networks in atmospheric sciences.

Fetal inflammatory response syndrome (FIRS) represents the fetal inflammatory reaction to intrauterine infection or injury, potentially leading to multiorgan impairment, neonatal mortality, and morbidity. Infections induce FIRS after chorioamnionitis (CA), defined as acute maternal inflammatory response to amniotic fluid infection, acute funisitis and chorionic vasculitis. FIRS involves many molecules, i.e., cytokines and/or chemokines, able to directly or indirectly damage fetal organs. Therefore, due to FIRS being a condition with a complex etiopathogenesis and multiple organ dysfunction, especially brain injury, medical liability is frequently claimed. In medical malpractice, reconstruction of the pathological pathways is paramount. However, in cases of FIRS, ideal medical conduct is hard to delineate, due to uncertainty in diagnosis, treatment, and prognosis of this highly complex condition. This narrative review revises the current knowledge of FIRS caused by infections, maternal and neonatal diagnosis and treatments, the main consequences of the disease and their prognoses, and discusses the medico-legal implications.

The six natural silicates known as asbestos may induce fatal lung diseases via inhalation, with a latency period of decades. The five amphibole asbestos species are assumed to be biopersistent in the lungs, and for this reason they are considered much more toxic than serpentine asbestos (chrysotile). Here, we refined the atomic structure of an amosite amphibole asbestos fibre that had remained in a human lung for ∼40 years, in order to verify the stability in vivo. The subject was originally exposed to a blend of chrysotile, amosite and crocidolite, which remained in his parietal pleura for ∼40 years. We found a few relicts of chrysotile fibres that were amorphous and magnesium depleted. Amphibole fibres that were recovered were undamaged and suitable for synchrotron X-ray micro-diffraction experiments. Our crystal structure refinement from a recovered amosite fibre demonstrates that the original atomic distribution in the crystal is intact and, consequently, that the atomic structure of amphibole asbestos fibres remains stable in the lungs for a lifetime; during which time they can cause chronic inflammation and other adverse effects that are responsible for carcinogenesis. The amosite fibres are not iron depleted proving that the iron pool for the formation of the asbestos bodies is biological (haemoglobin/plasma derived) and that it does not come from the asbestos fibres themselves.

Methyl chloroform (MCF) is a man-made chlorinated solvent contributing to the destruction of stratospheric ozone and is controlled under the "Montreal Protocol on Substances that Deplete the Ozone Layer" and its amendments, which called for its phase-out in 1996 in developed countries and 2015 in developing countries. Long-term, high-frequency observations of MCF carried out at three European sites show a constant decline in the background mixing ratios of MCF. However, we observe persistent non-negligible mixing ratio enhancements of MCF in pollution episodes, suggesting unexpectedly high ongoing emissions in Europe. In order to identify the source regions and to give an estimate of the magnitude of such emissions, we have used a Bayesian inversion method and a point source analysis, based on high-frequency long-term observations at the three European sites. The inversion identified southeastern France (SEF) as a region with enhanced MCF emissions. This estimate was confirmed by the point source analysis. We performed this analysis using an 11-year data set, from January 2002 to December 2012. Overall, emissions estimated for the European study domain decreased nearly exponentially from 1.1 Gg yrg'1 in 2002 to 0.32 Gg yrg'1 in 2012, of which the estimated emissions from the SEF region accounted for 0.49 Gg yrg'1 in 2002 and 0.20 Gg yrg'1 in 2012. The European estimates are a significant fraction of the total semi-hemisphere (30-90° N) emissions, contributing a minimum of 9.8% in 2004 and a maximum of 33.7% in 2011, of which on average 50% are from the SEF region. On the global scale, the SEF region is thus responsible for a minimum of 2.6% (in 2003) and a maximum of 10.3% (in 2009) of the global MCF emissions.

Mother-to-newborn COVID-19 transmission is mainly postnatal, but single-case reports and small case series have also described SARS-CoV-2 transplacental transmission. Unfortunately, studies regarding vertical transmission of SARS-CoV-2 lack systematic approaches to diagnosis and classification. So far, scientific evidence seems to suggest that the severity of maternal infection increases the risk of vertical transmission. We report two neonates born from COVID-19-positive mothers, of which one of the newborns had a vertical infection. The placental involvement, and consequent intrauterine transmission of SARS-CoV-2, were inversely related to the severity of the maternal disease. The description of cases divergent from current evidence on this topic could provide new insights to better understand SARS-CoV-2 vertical transmission.

The variety of placental morphological findings with SARS-CoV-2 maternal infections has raised the issue of poor agreement in histopathological evaluation. The aims of this study were: to describe the histopathological placental features of a large sample of SARS-CoV-2-positive women who gave birth in Italy during the COVID-19 pandemic, to analyse the factors underlying these lesions, and to analyse the impact of placental impairment on perinatal outcomes. From 25 February 2020 to 30 June 2021, experienced perinatal pathologists examined 975 placentas of SARS-CoV-2-positive mothers enrolled in a national prospective study, adopting the Amsterdam Consensus Statement protocol. The main results included the absence of specific pathological findings for SARS-CoV-2 infections, even though a high proportion of placentas showed signs of inflammation, possibly related to a cytokine storm induced by the virus, without significant perinatal consequences. Further research is needed to better define the clinical implications of placental morphology in SARS-CoV-2 infections, but the results of this large cohort suggest that placentas do not seem to be a preferential target for the new Coronavirus infection.

A case of vertical transmission in a 35-year-old pregnant woman, gravida 4, para 2 with an unknown medical history of carrying primary syphilis is described. A routine 3rd trimester scan was performed at 30 + 5 weeks of pregnancy, which revealed fetal growth restriction (FGR) associated with absent fetal movement, a pathologic neuroscan characterized by cortical calcifications and ominous Doppler waveform analysis of the umbilical artery and ductus venosus. Computerized electronic fetal monitoring (EFM) showed a Class III tracing, according to the American College of Obstetricians and Gynecologists (ACOG) guidelines. An emergency C-section was performed and a female newborn weighing 1470 g was delivered. The Apgar scores were 5 and 8 at the first and fifth min, respectively. Besides the prompted obstetrical and neonatal interventions, the neonate died after 7 days. A histologic examination of the placenta revealed a chorioamnionitis at stage 1/2 and grade 2/3. The parenchyma showed diffuse delayed villous maturation, focal infarcts, and intraparenchymal hemorrhages. The decidua presented with chronic deciduitis with plasma cells. The parents declined the autopsy. Congenital syphilis is an emerging worldwide phenomenon and the multidisciplinary management of the mother and the fetus should be mandatory.

Along with neuronal mechanisms devoted to memory consolidation –including long term potentiation of synaptic strength as prominent electrophysiological correlate, and inherent dendritic spines stabilization as structural counterpart– negative control of memory formation and synaptic plasticity has been described at the molecular and behavioral level. Within this work, we report a role for the epigenetic corepressor Lysine Specific Demethylase 1 (LSD1) as a negative neuroplastic factor whose stress-enhanced activity may participate in coping with adverse experiences. Constitutively increasing LSD1 activity via knocking out its dominant negative splicing isoform neuroLSD1 (neuroLSD1KO mice), we observed extensive structural, functional and behavioral signs of excitatory decay, including disrupted memory consolidation. A similar LSD1 increase, obtained with acute antisense oligonucleotide-mediated neuroLSD1 splicing knock down in primary neuronal cultures, dampens spontaneous glutamatergic transmission, reducing mEPSCs. Remarkably, LSD1 physiological increase occurs in response to psychosocial stress-induced glutamatergic signaling. Since this mechanism entails neuroLSD1 splicing downregulation, we conclude that LSD1/neuroLSD1 ratio modulation in the hippocampus is instrumental to a negative homeostatic feedback, restraining glutamatergic neuroplasticity in response to glutamate. The active process of forgetting provides memories with salience. With our work, we propose that softening memory traces of adversities could further represent a stress-coping process in which LSD1/neuroLSD1 ratio modulation may help preserving healthy emotional references.

Outdoor air pollution is responsible for more than 4 million premature deaths worldwide and its contribution is particularly severe in industrial contaminated sites, where epidemiological studies highlight often mortality rate larger than the national average. In the framework of the CISAS project, this study investigates spatial and temporal variability of air pollution across three industrial contaminated sites in southern Italy classified as “High Risk Area of Environmental Crisis”: Crotone, Milazzo, and Priolo. The environmental analysis employed three investigation approaches:—meteorological characterization of the sites with analyses of local air mass circulation;—statistical evaluation of the continuous measurements of gaseous pollutants and PM concentration;—determination of mass concentration and detailed speciation of the chemical components of atmospheric particulate matter during intensive field campaigns. Continuous trace gases and aerosol measurements (including NOx, SO2, O3, NMHC, PM10, and PM2.5) over the period 2016–2018 were analyzed, and specific intensive field experiments (2016–2017), representative of winter and summer conditions, were carried out in order to determine PM10 and PM2.5 chemical composition. The analyses of PM components (ions, elemental composition, trace organic pollutants, organic carbon, and elemental carbon) show concentrations typical of rural and urban areas. The results concerning gaseous pollutants and PM concentration showed a general compliance of the concentrations of some regulated species with the limits set by the EU Ambient Air Quality (AAQ) Directive. However, in particular in the industrial areas of Milazzo and Priolo, the analysis here reported highlights the need for a stringent regulation on NMHC ambient concentration and composition, further investigation of fine particle composition and atmospheric processing, and a deeper understanding of the role of anthropogenic emissions on ozone formation, also considering the World Health Organization (WHO) limits.

We present an overview of the concentrations and distributions of water-soluble ion species and elemental components in ambient particulate matter for five measurement sites in southern Italy with the aim of investigating the influence of the different site characteristics on PM levels. The sites encompass different characteristics, ranging from urban to coastal and high-altitude remote areas. PM10 and PM2.5 fractions were collected simultaneously using dual channel samplers during the winter period from November 2015 to January 2016 and analyzed for water-soluble ion species, using ion chromatography, and elemental composition, using inductively coupled plasma mass spectrometry (ICP-MS). In all sites, PM2.5 represented the higher contribution to particulate mass, usually more than two times that of the coarse fraction (PM2.5−10). At the coastal site in Capo Granitola (Western Sicily), sea salts constituted about 30% of total PM10 mass. On average, ion species accounted for 30% to 60% of total PM10 mass and 15% to 50% of PM2.5 mass. We found that secondary ion species, i.e., SO42−, NO3− and NH4+ dominated the identifiable components within both PM2.5 and PM10 fractions. The chlorine–sodium ratio was usually lower than that expected from the natural level in sea salt, evidencing aged air masses. At the monitoring site in Naples, a highly urbanized area affected by high levels of anthropogenic source emissions, an increased contribution of ammonium was found, which was imputed to the increased ammonia emissions from industrial combustion sources and road traffic. The concentrations of the investigated elements showed noteworthy differences from one site to another. The PM10 fraction was highly enriched by sources of anthropogenic origin in the samples from the most urbanized areas. In general, the enrichment factors of the elements were similar between the PM10 and PM2.5 fractions, confirming common sources for all elements.

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR). BRCA1/2 loss-of-function is linked to hereditary PCs and homologous recombination DNA-repair system deficiency: poly-ADP-ribose-polymerase inhibitors can be administered to BRCA-mutated PC patients. Recently, docetaxel-refractory metastatic castration-resistant PC patients with BRCA1/2 or ATM somatic mutations had higher response rates to pembrolizumab. PTEN regulates cell cycle/proliferation/apoptosis through pathways including the AKT/mTOR, which upregulates PD-L1 expression in PC. Our systematic literature review (PRISMA guidelines) investigated the potential correlations between PD-L1 and MMR/MSI/BRCA/PTEN statuses in PC, discussing few other relevant genes. Excluding selection biases, 74/677 (11%) PCs showed dMMR/MSI; 8/67 (12%) of dMMR/MSI cases were PD-L1+. dMMR-PCs included ductal (3%) and acinar (14%) PCs (all cases tested for MSI were acinar-PCs). In total, 15/39 (39%) PCs harbored BRCA1/2 aberrations: limited data are available for PD-L1 expression in these patients. 13/137 (10%) PTEN- PCs were PD-L1+; 10/29 (35%) PD-L1+ PCs showed PTEN negativity. SPOP mutations may increase PD-L1 levels, while the potential correlation between PD-L1 and ERG expression in PC should be clarified. Further research should verify how the efficacy of PD-1 inhibitors in metastatic castration-resistant PCs is related to dMMR/MSI, DNA-damage repair genes defects, or PD-L1 expression.

Citrobacter koseri is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to Citrobacter spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, C. koseri is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by C. koseri, has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. C. koseri was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which C. koseri infection was demonstrated.

Residents of the Kathmandu Valley experience severe particulate and gaseous air pollution throughout most of the year, even during much of the rainy season. The knowledge base for understanding the air pollution in the Kathmandu Valley was previously very limited but is improving rapidly due to several field measurement studies conducted in the last few years. Thus far, most analyses of observations in the Kathmandu Valley have been limited to short periods of time at single locations. This study extends the past studies by examining the spatial and temporal characteristics of two important gaseous air pollutants (CO and O3) based on simultaneous observations over a longer period at five locations within the valley and on its rim, including a supersite (at Bode in the valley center, 1345 m above sea level) and four satellite sites: Paknajol (1380 m a.s.l.) in the Kathmandu city center; Bhimdhunga (1522 m a.s.l.), a mountain pass on the valley's western rim; Nagarkot (1901 m a.s.l.), another mountain pass on the eastern rim; and Naikhandi (1233 m a.s.l.), near the valley's only river outlet. CO and O3 mixing ratios were monitored from January to July 2013, along with other gases and aerosol particles by instruments deployed at the Bode supersite during the international air pollution measurement campaign SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley – endorsed by the Atmospheric Brown Clouds program of UNEP). The monitoring of O3 at Bode, Paknajol and Nagarkot as well as the CO monitoring at Bode were extended until March 2014 to investigate their variability over a complete annual cycle. Higher CO mixing ratios were found at Bode than at the outskirt sites (Bhimdhunga, Naikhandi and Nagarkot), and all sites except Nagarkot showed distinct diurnal cycles of CO mixing ratio, with morning peaks and daytime lows. Seasonally, CO was higher during premonsoon (March–May) season and winter (December–February) season than during monsoon season (June–September) and postmonsoon (October–November) season. This is primarily due to the emissions from brick industries, which are only operational during this period (January–April), as well as increased domestic heating during winter, and regional forest fires and agro-residue burning during the premonsoon season. It was lower during the monsoon due to rainfall, which reduces open burning activities within the valley and in the surrounding regions and thus reduces sources of CO. The meteorology of the valley also played a key role in determining the CO mixing ratios. The wind is calm and easterly in the shallow mixing layer, with a mixing layer height (MLH) of about 250 m, during the night and early morning. The MLH slowly increases after sunrise and decreases in the afternoon. As a result, the westerly wind becomes active and reduces the mixing ratio during the daytime. Furthermore, there was evidence of an increase in the O3 mixing ratios in the Kathmandu Valley as a result of emissions in the Indo-Gangetic Plain (IGP) region, particularly from biomass burning including agro-residue burning. A top-down estimate of the CO emission flux was made by using the CO mixing ratio and mixing layer height measured at Bode. The estimated annual CO flux at Bode was 4.9 µg m−2 s−1, which is 2–14 times higher than that in widely used emission inventory databases (EDGAR HTAP, REAS and INTEX-B). This difference in CO flux between Bode and other emission databases likely arises from large uncertainties in both the top-down and bottom-up approaches to estimating the emission flux. The O3 mixing ratio was found to be highest during the premonsoon season at all sites, while the timing of the seasonal minimum varied across the sites. The daily maximum 8 h average O3 exceeded the WHO recommended guideline of 50 ppb on more days at the hilltop station of Nagarkot (159 out of 357 days) than at the urban valley bottom sites of Paknajol (132 out of 354 days) and Bode (102 out of 353 days), presumably due to the influence of free-tropospheric air at the high-altitude site (as also indicated by Putero et al., 2015, for the Paknajol site in the Kathmandu Valley) as well as to titration of O3 by fresh NOx emissions near the urban sites. More than 78 % of the exceedance days were during the premonsoon period at all sites. The high O3 mixing ratio observed during the premonsoon period is of a concern for human health and ecosystems, including agroecosystems in the Kathmandu Valley and surrounding regions.

This paper presents the light-scattering properties of atmospheric aerosol particles measured over the past decade at 28 ACTRIS observatories, which are located mainly in Europe. The data include particle light scattering (σsp) and hemispheric backscattering (σbsp) coefficients, scattering Ångström exponent (SAE), backscatter fraction (BF) and asymmetry parameter (g). An increasing gradient of σsp is observed when moving from remote environments (arctic/mountain) to regional and to urban environments. At a regional level in Europe, σsp also increases when moving from Nordic and Baltic countries and from western Europe to central/eastern Europe, whereas no clear spatial gradient is observed for other station environments. The SAE does not show a clear gradient as a function of the placement of the station. However, a west-to-east-increasing gradient is observed for both regional and mountain placements, suggesting a lower fraction of fine-mode particle in western/south-western Europe compared to central and eastern Europe, where the fine-mode particles dominate the scattering. The g does not show any clear gradient by station placement or geographical location reflecting the complex relationship of this parameter with the physical properties of the aerosol particles. Both the station placement and the geographical location are important factors affecting the intra-annual variability. At mountain sites, higher σsp and SAE values are measured in the summer due to the enhanced boundary layer influence and/or new particle-formation episodes. Conversely, the lower horizontal and vertical dispersion during winter leads to higher σsp values at all low-altitude sites in central and eastern Europe compared to summer. These sites also show SAE maxima in the summer (with corresponding g minima). At all sites, both SAE and g show a strong variation with aerosol particle loading. The lowest values of g are always observed together with low σsp values, indicating a larger contribution from particles in the smaller accumulation mode. During periods of high σsp values, the variation of g is less pronounced, whereas the SAE increases or decreases, suggesting changes mostly in the coarse aerosol particle mode rather than in the fine mode. Statistically significant decreasing trends of σsp are observed at 5 out of the 13 stations included in the trend analyses. The total reductions of σsp are consistent with those reported for PM2.5 and PM10 mass concentrations over similar periods across Europe.

Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic–pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.

Teratomas are the most common congenital tumors, occurring along the midline or paraxial sites, or uncommonly, the mediastinum. Teratomas are classified as mature, containing only differentiated tissues from the three germinal layers; and immature, which also present with neuroectodermal elements, ependymal rosettes, and immature mesenchyme. Herein, we describe a new case of fetal mediastinal immature teratoma detected at 21 weeks of gestational age (wga) + 1 day with thorough cytogenetic analysis. Ultrasound (US) showed a solid and cystic mass located in the anterior mediastinum, measuring 1.8 × 1.3 cm with no signs of hydrops. At 22 wga, US showed a mass of 2.4 cm in diameter and moderate pericardial effusions. Although the prenatal risks and available therapeutic strategies were explained to the parents, they opted for termination of pregnancy. Histology showed an immature teratoma, Norris grade 2. Karyotype on the fetus and tumor exhibited a chromosomal asset of 46,XX. The fetal outcome in the case of mediastinal teratoma relies on the development of hydrops due to mass compression of vessels and heart failure. Prenatal US diagnosis and close fetal monitoring are paramount in planning adequate treatment, such as in utero surgery, ex utero intrapartum therapy (EXIT) procedure, and surgical excision after birth.

This study investigates changes in aerosol radiative effects on two highly urbanized regions across the Euro-Mediterranean basin with respect to a natural desert region as Sahara over a decade through space-based lidar observations. The research is based on the monthly-averaged vertically-resolved aerosol optical depth (AOD) atmospheric profiles along a 1∘×1∘ horizontal grid, obtained from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) instrument measurements aboard the Cloud-Aerosol lidar and Infrared Pathfinder Satellite Observation (CALIPSO). To assess the variability of the anthropogenic aerosols on climate, we compared the aerosol vertical profile observations to a one-dimensional radiative transfer model in two metropolitan climate sensible hot-spots in Europe, namely the Po Valley and Benelux, to investigate the variability of the aerosol radiative effects over ten years. The same analysis is carried out as reference on the Sahara desert region, considered subject just to natural local emission. Our findings show the efficacy of emission reduction policies implemented at government level in strongly urbanized regions. The total atmospheric column aerosol load reduction (not observed in Sahara desert region) in Po Valley and Benelux can be associated with: (i) an increase of the energy flux at the surface via direct effects confirmed also by long term surface temperature observations, (ii) a general decrease of the atmospheric column, and likely (iii) an increase in surface temperatures during a ten-year period. Summarizing, the analysis, based on the decade 2007–2016, clearly show an increase of solar irradiation under cloud-free conditions at the surface of +3.6 % and +16.6% for the Po Valley and Benelux, respectively, and a reduction of −9.0% for the Sahara Desert.

Objective: Skeletal dysplasia with bowing long bones is a rare group of multiple characterized congenital anomalies. Materials and Methods: We introduce a simple, practical diagnostic flowchart that may be helpful in identifying the appropriate pathway of obstetrical management. Results: Herein, we describe four fetal cases of bent bony dysplasia that focus on ultrasound findings, phenotype, molecular tests, distinctive X-ray features, and chondral growth plate histology. The first case was a typical campomelic dysplasia resulting from a de novo mutation in the SOX9 gene. The second fetus was affected by osteogenesis imperfecta Type II carrying a mutation in the COLA1 gene. The third case was a rare presentation of campomelic dysplasia, Cumming type, in which SOX9 examination was normal. Subsequently, a femoral hypoplasia unusual facies syndrome is also discussed. Conclusion: Targeted molecular tests and genetic counseling are required for supplementing ultrasound imaging in order to diagnose the correct skeletal disorders.

We describe and implement a data selection algorithm aimed at identifying background atmospheric CO2 observations from in situ continuous measurements. Several selection criteria for detecting the background data have been developed and are currently used: the main objective of this work was to define a common methodology to extract the atmospheric background signal minimizing heterogeneities due to the use of different selection algorithms. The algorithm used in this study, (BaDS, Background Data Selection) was tested and optimized using data (from 2014 to 2018) from four Italian stations characterized by markedly different environmental conditions (i.e., mountain, coastal and marine): Plateau Rosa (PRS), Mt. Cimone (CMN), Capo Granitola (CGR) and Lampedusa (LMP). Their locations extend from the Alps to the central Mediterranean. The adopted algorithm proved to be effective in separating the local/regional from the background signal in the CO2 time series. About 6% of the data at LMP, 11% at PRS, 20–38% at CMN and 65% at CGR were identified as non-background. LMP and PRS can be used as reference sites for the central Mediterranean, while CMN and CGR were more impacted by regional sources and sinks. Finally, we discuss a possible application of BaDS screened data.

Kingella kingae is a Gram-negative coccobacillus belonging to the Neisseriaceae family. In children less than 4 years old, K. kingae invasive infection can induce septic arthritis and osteomyelitis, and more rarely endocarditis, meningitis, ocular infections, and pneumonia. In adults, it may be a cause of endocarditis. To date, K. kingae acute chorioamnionitis (AC) leading to preterm rupture of membranes (PPROM) and miscarriage has never been reported. Herein, we describe a case of intrauterine fetal death (IUFD) at 22 weeks’ gestation due to K. kingae infection occurred in a patient affected by undifferentiated connective tissue disease (UCTD) in lupus erythematosus systemic (LES) evolution with severe neutropenia. K. kingae was isolated in placental subamnionic swab and tissue cultures as well as fetal ear, nose, and pharyngeal swabs. Placental histological examination showed necrotizing AC and funisitis. In the fetus, neutrophils were observed within the alveoli and in the gastrointestinal lumen. Maternal medical treatment for UCTD was modified according to the K. kingae invasive infection. In the event of IUFD due to AC, microbiological cultures on placenta and fetal tissues should always be carried out in order to isolate the etiologic agent and target the correct medical treatment.

Several studies investigated the possible impacts of the restriction measures related to the containment of the spread of the COrona VIrus Disease (COVID-19) to atmospheric ozone (O _3 ) at global, regional, and local scales during 2020. O _3 is a secondary pollutant with adverse effects on population health and ecosystems and with negative impacts on climate, acting as greenhouse gas. Most of these studies focused on spring 2020 (i.e. March–May) and on observations in the planetary boundary layer (PBL), mostly in the vicinity of urban agglomerates. Here, we analyzed the variability of O _3 above the PBL of northern Italy in 2020 by using continuous observations carried out at a high mountain WMO/GAW global station in Italy (Mt. Cimone–CMN; 44°12′ N, 10°42′ E, 2165 m a.s.l.). Low O _3 monthly anomalies were observed during spring (MAM) and summer (JJA), when periods of low O _3 intertwined with periods with higher O _3 , within climatological ranges. A similar variability was observed for O _3 precursors like NO _2 and 15 anthropogenic non-methane volatile organic carbons, but the systematic O _3 anomalies were not reflected in these variables. The analysis of meteorological variables and diel O _3 cycles did not suggest major changes in the vertical transport related to the thermal circulation system in the mountain area. The analysis of five days back-trajectories suggested that the observed O _3 anomalies cannot be explained by differences in the synoptic-scale circulation with respect to the previous years alone. On the other hand, the characterization of two transport patterns (i.e. air masses from the regional PBL or from the free troposphere) and the analysis of back-trajectories suggested an important contribution of transport from the continental PBL during the periods with the lowest O _3 at CMN. When proxies of air mass transport from the regional PBL are considered, a lower NO _x content was pointed out with respect to the previous years, suggesting a lower O _3 production in a NO _x -limited atmosphere. Our study suggested for the first time that, during MAM and JJA 2020, the reduced anthropogenic emissions related to the COVID-19 restrictions lowered the amount of this short-lived climate forcer/pollutant at remote locations above the PBL over northern Italy. This work suggests the importance of limiting anthropogenic precursor emissions for decreasing the O _3 amount at remote locations and in upper atmospheric layers.

Klebsiella pneumoniae is a Gram-negative, rod-shaped bacterium, responsible for hospital and community acquired pneumonia, urinary tract and wound infections, and bloodstream dissemination. K. pneumoniae infection in pregnancy, leading to acute chorioamnionitis (AC), preterm premature rupture of membranes (PPROM) and early pregnancy loss in the second trimester, has been rarely reported. Herein, we present a case of K. pneumoniae AC that caused intrauterine fetal demise (IUFD) at 19 weeks + 5 days. The 36-year-old mother was admitted at 18 weeks + 1 day of gestation for threatened abortion. IUFD occurred 11 days after. Fetal postmortem showed severe AC and funisitis, neutrophils within alveoli and intestinal lumen, associated with rod-like bacteria. Fetal blood and lung cultures grew K. pneumoniae, β-lactamase-non-producing strain. Antibiogram revealed sensitivity for piperacillin/tazobactam. Three days after IUFD, the mother presented with fever (37.8 °C) which persisted for one week. Maternal blood and urine cultures were negative. According to fetal microbiological results, available 6 days after IUFD, initial treatment with amoxicillin/clavulanic acid was replaced with piperacillin/tazobactam with full patient recovery. Therefore, in the event of PPROM and IUFD, fetal microbiological investigations should always be performed to isolate the proper etiologic agent and start the correct medical treatment.

Stratospheric intrusion (SI) events are a topic of ongoing research, especially because of their ability to change the oxidation capacity of the troposphere and their contribution to tropospheric ozone levels. In this work, a novel tool called STEFLUX (Stratosphere-to-Troposphere Exchange Flux) is presented, discussed, and used to provide a first long-term investigation of SI over two global hot-spot regions for climate change and air pollution: the southern Himalayas and the central Mediterranean Basin. The main purpose of STEFLUX is to obtain a fast-computing and reliable identification of the SI events occurring at a specific location and during a specified time window. It relies on a compiled stratosphere-to-troposphere exchange (STE) climatology, which makes use of the ERA-Interim reanalysis dataset from the ECMWF, as well as a refined version of a well-established Lagrangian methodology. STEFLUX results are compared to the SI observations (SIO) at two high-mountain WMO/GAW global stations in these climate hot spots, i.e., the Nepal Climate Observatory-Pyramid (NCO-P, 5079 m a.s.l.) and Mt. Cimone (2165 m a.s.l.), which are often affected by SI events. Compared to the observational datasets at the two specific measurement sites, STEFLUX is able to detect SI events on a regional scale. Furthermore, it has the advantage of retaining additional information concerning the pathway of stratospheric-affected air masses, such as the location of tropopause crossing and other meteorological parameters along the trajectories. However, STEFLUX neglects mixing and dilution that air masses undergo along their transport within the troposphere. Therefore, the regional-scale STEFLUX events cannot be expected to perfectly reproduce the point measurements at NCO-P and Mt. Cimone, which are also affected by small-scale (orographic) circulations. Still, the seasonal variability in SI events according to SIO and STEFLUX agrees fairly well. By exploiting the fact that the ERA-Interim reanalysis extends back to 1979, the long-term climatology of SI events at NCO-P and Mt. Cimone is also assessed in this work. The analysis of the 35-year record at both stations denies the existence of any significant trend in the SI frequency, except for winter seasons at NCO-P. Furthermore, for the first time, by using the STEFLUX outputs, we investigate the potential impact of specific climate factors (i.e. ENSO, QBO, and solar activity) on SI frequency variability over the Mediterranean Basin and the Himalayas.

Carbon tetrachloride (CCl4) is a long-lived radiatively active compound with the ability to destroy stratospheric ozone. Due to its inclusion in the Montreal Protocol on Substances that Deplete the Ozone Layer (MP), the last two decades have seen a sharp decrease in its large-scale emissive use with a consequent decline in its atmospheric mole fractions. However, the MP restrictions do not apply to the use of carbon tetrachloride as feedstock for the production of other chemicals, implying the risk of fugitive emissions from the industry sector. The occurrence of such unintended emissions is suggested by a significant discrepancy between global emissions as derived from reported production and feedstock usage (bottom-up emissions), and those based on atmospheric observations (top-down emissions). In order to better constrain the atmospheric budget of carbon tetrachloride, several studies based on a combination of atmospheric observations and inverse modelling have been conducted in recent years in various regions of the world. This study is focused on the European scale and based on long-term high-frequency observations at three European sites, combined with a Bayesian inversion methodology. We estimated that average European emissions for 2006–2014 were 2.2 (± 0.8) Gg yr−1, with an average decreasing trend of 6.9 % per year. Our analysis identified France as the main source of emissions over the whole study period, with an average contribution to total European emissions of approximately 26 %. The inversion was also able to allow the localisation of emission "hot spots" in the domain, with major source areas in southern France, central England (UK) and Benelux (Belgium, the Netherlands, Luxembourg), where most industrial-scale production of basic organic chemicals is located. According to our results, European emissions correspond, on average, to 4.0 % of global emissions for 2006–2012. Together with other regional studies, our results allow a better constraint of the global budget of carbon tetrachloride and a better quantification of the gap between top-down and bottom-up estimates.

Abstract Lissencephaly is a genetic heterogeneous autosomal recessive disorder characterized by the classical triad: brain malformations, eye anomalies, and congenital muscular dystrophy. Prenatal diagnosis is feasible by demonstrating abnormal development of sulci and gyri. Magnetic resonance imaging (MRI) may enhance detection of developmental cortical disorders as well as ocular anomalies. We describe a case of early diagnosis of lissencephaly type 2 detected at the time of routine second trimester scan by three-dimensional ultrasound and fetal MRI. Gross pathology confirmed the accuracy of the prenatal diagnosis while histology showed the typical feature of cobblestone cortex. As the disease is associated with poor perinatal prognosis, early and accurate prenatal diagnosis is important for genetic counseling and antenatal care.

Quality of wind prediction is of great importance since a good wind forecast allows the prediction of available wind power, improving the penetration of renewable energies into the energy market. Here, a 1-year (1 December 2012 to 30 November 2013) three-model ensemble (TME) experiment for wind prediction is considered. The models employed, run operationally at National Research Council – Institute of Atmospheric Sciences and Climate (CNR-ISAC), are RAMS (Regional Atmospheric Modelling System), BOLAM (BOlogna Limited Area Model), and MOLOCH (MOdello LOCale in H coordinates). The area considered for the study is southern Italy and the measurements used for the forecast verification are those of the GTS (Global Telecommunication System). Comparison with observations is made every 3 h up to 48 h of forecast lead time. Results show that the three-model ensemble outperforms the forecast of each individual model. The RMSE improvement compared to the best model is between 22 and 30 %, depending on the season. It is also shown that the three-model ensemble outperforms the IFS (Integrated Forecasting System) of the ECMWF (European Centre for Medium-Range Weather Forecast) for the surface wind forecasts. Notably, the three-model ensemble forecast performs better than each unbiased model, showing the added value of the ensemble technique. Finally, the sensitivity of the three-model ensemble RMSE to the length of the training period is analysed.

The concentration of ozone at the Earth's surface is measured at many locations across the globe for the purposes of air quality monitoring and atmospheric chemistry research. We have brought together all publicly available surface ozone observations from online databases from the modern era to build a consistent data set for the evaluation of chemical transport and chemistry-climate (Earth System) models for projects such as the Chemistry-Climate Model Initiative and Aer-Chem-MIP. From a total data set of approximately 6600 sites and 500 million hourly observations from 1971–2015, approximately 2200 sites and 200 million hourly observations pass screening as high-quality sites in regionally representative locations that are appropriate for use in global model evaluation. There is generally good data volume since the start of air quality monitoring networks in 1990 through 2013. Ozone observations are biased heavily toward North America and Europe with sparse coverage over the rest of the globe. This data set is made available for the purposes of model evaluation as a set of gridded metrics intended to describe the distribution of ozone concentrations on monthly and annual timescales. Metrics include the moments of the distribution, percentiles, maximum daily 8-hour average (MDA8), sum of means over 35 ppb (daily maximum 8-h; SOMO35), accumulated ozone exposure above a threshold of 40 ppbv (AOT40), and metrics related to air quality regulatory thresholds. Gridded data sets are stored as netCDF-4 files and are available to download from the British Atmospheric Data Centre (doi:10.5285/08fbe63d-fa6d-4a7a-b952-5932e3ab0452). We provide recommendations to the ozone measurement community regarding improving metadata reporting to simplify ongoing and future efforts in working with ozone data from disparate networks in a consistent manner.

The Kathmandu Valley in south Asia is considered as one of the global "hot spots" in terms of urban air pollution. It is facing severe air quality problems as a result of rapid urbanization and land use change, socioeconomic transformation, and high population growth. In this paper, we present the first full year (February 2013–January 2014) analysis of simultaneous measurements of two short-lived climate forcers/pollutants (SLCF/P), i.e., ozone (O3) and equivalent black carbon (hereinafter noted as BC) and aerosol number concentration at Paknajol, in the city center of Kathmandu. The diurnal behavior of equivalent BC and aerosol number concentration indicated that local pollution sources represent the major contributions to air pollution in this city. In addition to photochemistry, the planetary boundary layer (PBL) and wind play important roles in determining O3 variability, as suggested by the analysis of seasonal changes of the diurnal cycles and the correlation with meteorological parameters and aerosol properties. Especially during pre-monsoon, high values of O3 were found during the afternoon/evening. This could be related to mixing and entrainment processes between upper residual layers and the PBL. The high O3 concentrations, in particular during pre-monsoon, appeared well related to the impact of major open vegetation fires occurring at the regional scale. On a synoptic-scale perspective, westerly and regional atmospheric circulations appeared to be especially conducive for the occurrence of the high BC and O3 values. The very high values of SLCF/P, detected during the whole measurement period, indicated persisting adverse air quality conditions, dangerous for the health of over 3 million residents of the Kathmandu Valley, and the environment. Consequently, all of this information may be useful for implementing control measures to mitigate the occurrence of acute pollution levels in the Kathmandu Valley and surrounding area.

Hyperechogenic bowel (HB) is a nonspecific ultrasound finding that can be associated with human cytomegalovirus (CMV) congenital infection. In this study, we investigated HB pathophysiology in CMV-infected fetuses. We examined small and large intestine as well as pancreas in 8 fetuses at 22 weeks of gestation with congenital CMV infection. Ultrasound findings showed 4 fetuses with HB and 4 without. As negative group, 4 fetuses without CMV infection and without HB were studied. Immunohistochemistry for CMV, lymphocytic infiltrate, B-cell leukemia/lymphoma-2 (bcl-2), CD-117, cystic fibrosis transmembrane regulator (CFTR) were performed. HB fetuses showed multiple and sequential CMV-positive ganglion cells of Auerbach’s myenteric plexus. In the ganglia, bcl-2 was weakly expressed representing a reduced neuronal functionality. CD-117 revealed a regular distribution of Cajal cells, the pacemakers of intestinal contractility. Pancreas showed normal CFTR staining, indicating a preserved exocrine secretion, thus unlikely a contributory factor in HB. In CMV-infected fetuses without HB, CMV-positive cells were scatteredly found in ganglion cells and bcl-2 was strongly expressed. Intestinal CD-117 and pancreatic CFTR expression were similar to fetuses with HB. In conclusion, fetal CMV infection of the bowel may lead to peristalsis impairment (paralytic ileus) due to intestinal plexus involvement, which at ultrasound appeared as HB.