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Background: Fractures of the clavicle are the most common birth injury among newborns. Aim of this systematic review was to provide a comprehensive analysis of the role of ultrasound (US) in diagnosing clavicular fractures in neonates. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed and Embase, including studies focusing on US in neonatal clavicle fracture. Age at US, number of cases examined by US and X-ray, US and X-ray diagnoses, US probe used, fracture site were systematically extracted. Results: A total of 231 articles were found. We ultimately selected 7 publications that satisfied the inclusion criteria, involving 136 patients examined between 3 days and 3 weeks of age, with 135 confirmed fractures. US was performed on all patients and correctly diagnosed all fractures (135/135, 100%). X-ray was performed on 94/136 patients (69.1%) and correctly diagnosed 89/93 fractures (95.7%). Fracture site was: medial in 2/79, middle in 37/79, and lateral in 40/79. In the remaining 57 cases, site was not reported. Conclusions: This review indicates that ultrasound is extremely reliable in diagnosing clavicle fractures in newborns and should be considered as the gold standard in this context.

Abstract Objectives Pathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1‐related disorders. Methods We performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy. Results The patient presented with drug‐resistant, electro‐clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy. Interpretation This is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease.

IntroductionPerinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children.ResultsInvolvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia.ConclusionsMetabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

IntroductionX-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD.MethodsIn June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS.DiscussionGenetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience.ConclusionThe primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD.EthicsThe study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Background: Fractures of the clavicle are the most common birth injury among newborns. Aim of this systematic review was to provide a comprehensive analysis of the role of ultrasound (US) in diagnosing clavicular fractures in neonates. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed and Embase, including studies focusing on US in neonatal clavicle fracture. Age at US, number of cases examined by US and X-ray, US and X-ray diagnoses, US probe used, fracture site were systematically extracted. Results: A total of 231 articles were found. We ultimately selected 7 publications that satisfied the inclusion criteria, involving 136 patients examined between 3 days and 3 weeks of age, with 135 confirmed fractures. US was performed on all patients and correctly diagnosed all fractures (135/135, 100%). X-ray was performed on 94/136 patients (69.1%) and correctly diagnosed 89/93 fractures (95.7%). Fracture site was: medial in 2/79, middle in 37/79, and lateral in 40/79. In the remaining 57 cases, site was not reported. Conclusions: This review indicates that ultrasound is extremely reliable in diagnosing clavicle fractures in newborns and should be considered as the gold standard in this context. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To analyze the anatomic influence of the ribs related to the severity of thoracic spine burst fractures. Methods: A retrospective review of 28 patients with thoracic spine burst fractures hospitalized by the Spine Group of the Hospital Ortopédico de Passo Fundo between January 2002 and December 2016 was conducted. The kyphosis, vertebral collapse, and narrowing of the vertebral canal measurements were compared between patients who had fractures at the true and false rib levels (T1 to T10) and those with fractures at the floating rib levels (T11 to T12). Results: The kyphosis, vertebral collapse, and narrowing of the vertebral canal values, measured only for vertebrae pertaining to the rib cage, were low. In addition, there were no statistically significant differences between the measurements of the group of patients with fractures at the level of the true and false ribs (T1 to T10) and the group of patients whose fractures were at the level of the floating ribs (T11 and T12). Conclusion: The differences between the traumatic structural changes in the vertebrae with true and false ribs (T1 to T10) and the vertebrae with floating ribs (T11 and T12) were not significant in the present study. Level of Evidence II; Retrospective study.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

Introdução: A transição epidemiológica e demográfica, o sedentarismo e o estímulo ao desenvolvimento de atividades físicas regulares sem a devida orientação de profissionais podem estar relacionados a distúrbios osteoarticulares e musculares. Objetivo: Analisar o efeito da suplementação de vitamina E (α-tocoferol), vitamina C (ácido ascórbico) e ácido graxo Ômega 3 no dano oxidativo de 20 atletas masculinos em uma prova de ciclismo de longa duração. Métodos: Realizou-se um estudo clínico randomizado de 20 atletas participantes de uma prova de ciclismo de 200 km. Resultados: O grupo suplementado apresentou uma menor dano lipídico (redução de TBARS p

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1–7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth. [ABSTRACT FROM AUTHOR]

Infere-se que muitas pesquisas comprovam o papel de vários fatores de saúde, estilo de vida e doenças na expressão da sonolência diurna excessiva. O presente estudo teve por objetivo demonstrar o perfil clínico-epidemiológico da sonolência diurna excessiva com base nos seus achados na literatura mediante aplicação de duas escalas subjetivas utilizadas em protocolos de pesquisa e centros de avaliação do sono, são elas: a Escala de Sonolência de Epworth e Índice de Qualidade do Sono de Pittsburgh. Trata-se de uma revisão bibliográfica, em que foram elegíveis artigos primários, com data de publicação de 1999 até 2018, em que se utilizou as seguintes bases de dados referenciais: Biblioteca Virtual de Saúde (Bvs), Web of Science; Periódico da Capes; Scopus; SciELO; Social Science Research Network (SSRN); PubMed; LILACS e MEDLINE Complete. Na seleção crítica dos artigos de estudos transversais, recorreu-se à Appraisal tool for Cross-Sectional Studies (AXIS). Verificou-se que medidas autorrelatadas são prontamente obtidas com questionários validados como a Escala de Epworth (ESS) e Pittsburgh Sleep Quality Index (PSQI). Outrossim, a literatura evidencia a relevância da análise e diagnóstico da sonolência diurna excessiva mediante o uso de exames eletrofisiológicos incluindo videopolissonografia noturna, teste de latências múltiplas do sono, teste de manutenção da vigília e actigrafia. A fadiga foi relacionada à depressão, à ansiedade e à qualidade do sono, mas não a sonolência diurna excessiva. Por último, indivíduos obesos, quando operados pela cirurgia metabólica pela técnica de desvio biliopancreático apresentaram normalização da sonolência diurna excessiva.

Objetivo: Avaliar a qualidade de vida (QV) dos profissionais da área médica de acordo com a especialidade escolhida (clínica ou cirúrgica). Métodos: Estudo transversal analítico, realizado em 2016, com médicos de clínicas e hospitais de Rio Verde, Goiás, Brasil. Utilizaram-se dois questionários: um sobre aspectos sociodemográficos e outro para avaliação da QV, o World Health Organization Quality of Life-Bref (WHOQOL-abreviado). Entregaram-se 287 questionários, sendo 144 respondidos. Dados comparativos dos domínios receberam análise ANOVA, MANOVA, MANCOVA, correlação de Pearson e regressão linear, considerando-se p˂0,05. Resultados: Encontrou-se média de idade de 37,7±10,09 anos e a maioria do sexo masculino (63,1%; n=91). O domínio físico foi, significantemente, melhor avaliado nos valores médios de QV pelo sexo masculino (p=0,002), assim como o domínio meio ambiente (p=0,031). Quando se comparou valores médios da QV e seus domínios de acordo com a atuação clínica e/ou cirúrgica dos médicos, não houve diferença significativa. Ao se comparar médicos plantonistas e não plantonistas, verificou-se que os domínios relação social (p=0,049), meio ambiente (p=0,001) e QV (p=0,024), independentes da carga horária, apresentaram piora no caso dos médicos plantonistas. Quanto maior o tempo de formado, maior a percepção do domínio meio ambiente (p=0,02). Sem diferença significativa quanto à faixa salarial. Conclusão: Não houve diferença na qualidade de vida global entre os médicos clínicos e cirurgiões avaliados, porém, quando comparado entre o sexo, o masculino obteve desempenho mais satisfatório nos domínios físico e meio ambiente. Evidenciou-se que a faixa salarial não influencia na qualidade de vida desses profissionais.

Objective: To evaluate the performance of a CO-oximeter to determine the smoking status in relation to an exhaled carbon monoxide meter in subjects attending Primary Health Care. Methods: A cross-sectional study was carried out in outpatients aged 18 years or older, attending Primary Health Care Units of Anápolis-GO. Subjects were submitted to clinical evaluation, exhaled carbon monoxide dosing, and carbon monoxide measurement by pulse CO-oximetry. Results: A total of 449 individuals were included, 106 smokers (23.6%), 89 ex-smokers (19.8%), 203 never smokers (45.2%) and 51 passive smokers (11.4%). CO-oximetry with cutoff point of ≥4% showed a specificity of 77.3% (95% CI 72.5% -81.6%), a sensitivity of 52.8% (CI 95% 42.9% - 62,6%), positive and negative predictive values of 45.3% (95% CI: 38.9% -51.9%), 82.1% (95% CI: 78.8% -85%), respectively and area under ROC curve of 0.73 (95% CI 0.67-0.78). The exhaled carbon monoxide dosage with cut-off point of ≥5ppm showed a specificity of 96.2% (95% CI 93.6% -98%), sensitivity of 79.2% (95% CI 70.3% -86, 5%), positive and negative predictive value of 88.2% (95% CI 81.3% -92.8%), 92.9% (95% CI 89.9% -95%), respectively, and area under ROC curve of 0.91 (95% CI 0.87-0.95). COHb(%) ≥4 showed OR: 4.3; (95%CI 2.7-7.1); p

Introduction: Both human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) are part of the National List of Compulsory Notification of Diseases. Despite the compulsory reporting of HIV infection from 2014, there has been a drop in the detection of new cases in the last five years. Objective: Analyze the epidemiological data of HIV/AIDS case reports in the city of Passo Fundo, Rio Grande do Sul, from 2007 to 2017 in relation to gender, neighborhoods, notifying units and treatment units. Methods: Retrospective descriptive study, accomplished at the Health Surveillance Sector from the compulsory notifications available in the Information System of Notifiable Diseases (Sistema de Informação de Agravos de Notificação – SINAN). A spreadsheet was made in the Microsoft Excel® Program (2016). Data were analyzed using the SPSS® Program, descriptively through measures of prevalence, incidence and distribution. Results: There were 1,068 notifications. There was a predominance of males (55.5%) and in the age group from 27 to 43 years. Of the 31 notifying health units, three concentrated 95% of the cases: Specialized Care Service (74.7%); Hospital São Vicente de Paulo (16%); and Hospital das Clínicas of Passo Fundo (4%). The same three units concentrated 98.0% of the treatments: 88, 9 and 1%, respectively. The primary care accounted for 5.0% of the notifications. Conclusion: The higher prevalence in young adult men denotes the importance of prevention aimed at this audience. Notifications were mostly from hospitals and a public referral center, with little involvement of primary care in reporting HIV/AIDS.

We report a case of a baby, who, after pregnancy complicated by maternal Addison's disease and Hashimoto's thyroiditis and natural delivery, unexpectedly presented a cardiorespiratory collapse and died 1 hour after birth without responding to prolonged neonatal resuscitation maneuvers. The cause of death was reliably established by carrying out a forensic postmortem examination. More specifically, the histological examination of the lungs showed the presence of abundant endoalveolar and endobronchial cornea scales caused by absorption of amniotic fluid. The neuropathological examination of the brainstem highlighted severe hypodevelopment of the retrotrapezoid/parafacial respiratory group, which is a complex of neurons located in the caudal pons that is involved in respiratory rhythm coordination, especially expiration, in conditions of enhanced respiratory drive, as well as in chemoreception. This neuropathological finding shed new light on the mechanisms underlying the massive amniotic fluid aspiration which led to this early death.

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as “cases” if they developed EOS, and as “controls”if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Background: “breathomics” enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: “breathomics” can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities. The risk of HCMV transmission to the fetus in pregnant women receiving immunosuppressive agents is unknown. We describe two cases of pregnant women with evidence of pre-conception HCMV protective immunity receiving azathioprine for ulcerative colitis or systemic lupus erythematosus. Both women reactivated the HCMV and transmitted the infection to the fetuses. One newborn showed unilateral hearing deficits and brain abnormalities while the other was asymptomatic. The mother of the symptomatic newborn had low levels of total and HCMV-specific blood CD4+ T cells. Women receiving immunosuppressive agents deserve information about the risk of HCMV congenital infection and should be monitored for HCMV infection during pregnancy. Their newborns should be screened for HCMV congenital infection.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment. [ABSTRACT FROM AUTHOR]

Objectives: Pathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1‐related disorders. Methods: We performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy. Results: The patient presented with drug‐resistant, electro‐clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy. Interpretation: This is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease. [ABSTRACT FROM AUTHOR]

1-Triacontanol (TRIA) is gaining a lot of interest in agricultural practice due to its use as bio-stimulant and different types of TRIA-containing products have been presented on the market. Up to date, TRIA determination is performed by GC analysis after chemical derivatization, but in aqueous samples containing low amounts of TRIA determination can be problematic and the derivatization step can be troublesome. Hence, there is the need for an analysis method without derivatization. TRIA-based products are in general plant extracts that can be obtained with different extraction procedures. These products can contain different ranges of concentration of TRIA from units to thousands of mg/kg. Thus, there is the need for a method that can be applied to different sample matrices like plant materials and different plant extracts. In this paper we present a HPLC-ELSD method for the analysis of TRIA without derivatization. The method has been fully validated and it has been tested analyzing the content of TRIA in different dried vegetal matrices, plant extracts, and products. The method is characterized by high sensitivity (LOD = 0.2 mg/L, LOQ = 0.6 mg/L) and good precision (intra-day:

Global changes are recognized as one of the main drivers of biodiversity changes over time, especially in mountain ecosystems. A key approach to detect and investigate the effect of climate and land use change on these ecosystems is represented by vegetation surveys. In this study, based on the resurvey of historical vegetation data, we assessed temporal beta-diversity patterns within and between subalpine and alpine vegetation types in the Dolomiti Bellunesi National Park. Resurvey was focussed on plots sampled in four main vegetation types: 1 and 2) Mesophytic and xerophytic grasslands on neutral or base-rich soils respectively dominated by Sesleria caerulea and Carex sempervirens and by Sesleria caerulea and Helictotrichon parlatorei; 3) Acidophytic grasslands dominated by Nardus stricta; 4) Snowbeds with dominance of dwarf willows (Salix herbacea or S. retusa) or Luzula alpinopilosa. Our results revealed a pattern of floristic homogenization in grasslands and snowbeds indicating a decreasing heterogeneity, both within and between different vegetation types that can be associated with different components of global change. The highest temporal beta diversity and floristic homogenization were detected in snowbeds. In general, the magnitude of temporal changes differ between communities, thus claiming for conservation activities that are tailored to each vegetation type. [ABSTRACT FROM AUTHOR]

In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component. Such solvents have gained much attention of the scientific community in the green chemistry area, being considered useful alternatives to common organic solvents. NADES can be used also as administration vehicles, and this can be attractive for nutraceutical products when eutectics are formed with food grade ingredients. In this work, different NADES were prepared using mainly food grade constituents and were tested as solvents for the alkaloid berberine. Three selected NADES/berberine solutions and an aqueous suspension were orally administered to mice with in dose of 50 mg/Kg. Blood levels of berberine were measured by a LC-MS/MS method. The pharmacokinetic analysis revealed a 2–20 fold increase in blood concentration of NADES/berberine with significant changes in pharmacokinetic profile. Natural Deep Eutectic Solvents may thus be considered attractive solubilizing agents and may also play a role in the increase of absorption of poorly bioavailable natural products such as berberine.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA. [ABSTRACT FROM AUTHOR]

Introduction: Inherited deficiencies in the coagulation pathway provide diversified models to investigate the molecular bases of perinatal lethality associated with null‐like variants. Differently from X‐linked haemophilias, homozygous/doubly heterozygous null variants in the rare autosomally inherited deficiency of factor X (FX) might be incompatible with perinatal survival. Aim: To provide experimental evidence about the null/close‐to‐null FX function. Methods: The residual secreted (ELISA) and functional (thrombin generation assays) protein levels associated with the novel nonsense (c.1382G>A; p.Trp461Ter) and missense (c.752T>C; p.Leu251Pro) variants, found in the proposita with life‐threatening symptoms at birth, were characterized through recombinant (r)FX expression. Results: The rFX‐461Ter showed very low secretion and undetectable function. Expression and function of the predicted readthrough‐deriving missense variants (rFX‐461Tyr, rFX‐461Gln) were also severely impaired. These unfavourable features, due to nucleotide and protein sequence constraints, precluded functional readthrough over the 461 stop codon. Differently, the poorly secreted rFX‐251Pro variant displayed residual function that was characterized by anti‐TFPI aptamer‐based amplification or selective inhibition of activated FX function by fondaparinux in plasma and found to be reduced by approximately three orders of magnitude. Similarly to the rFX‐251Pro, a group of catalytic domain missense variants cause poorly secreted molecules with modest function in FX‐deficient patients with life‐threatening symptoms. Conclusions: Our data, contributing to the knowledge of the very severe FX deficiency forms, support life‐saving requirement of trace FX function, clearly exemplified by the dysfunctional but not completely inactive rFX‐251Pro variant that, albeit with severely reduced function, is compatible with a residual activity ensuring minimal haemostasis and permitting perinatal survival. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quince (Cydonia oblonga) fruits can be considered as starting material for the extraction of health‐promoting phytochemicals, to be exploited in food and nutraceuticals. In the present work, liquid chromatography coupled with diode array detection and tandem mass spectrometry analysis allowed the study of the phytochemical composition of quince fruits and to compare it with those of six commercial apple varieties. RESULTS: The distribution and quantification of secondary metabolites in peel and pulp were studied and compared with six commercial apple varieties. Furthermore the in vitro antioxidant activity was determined by 2,2‐diphenyl‐2‐picrylhydrazyl (DPPH) assay. Quince fruit presented significant amounts of shikimic and quinic acid derivatives, as well as flavonoids and procyanidins. Compared with apple, quince fruit composition was characterized by the presence of 4‐caffeoylshikimic acid, 4‐caffeoyl quinic acid, quercetin‐3,7‐diglucoside, kaempferol‐3‐O‐rhamnoside and kaempferol‐7‐O‐glucoside, and the dihydrochalcones were not detectable. The peel showed the highest contents of phenolics, whereas 3‐O‐caffeoylquinic acid was the most abundant compound in the quince pulp. The Pearson correlation index was calculated considering the quantitative amount of the phenolic constituents and the radical scavenging activity toward DPPH· both for peel and pulp extracts. CONCLUSIONS: This study highlighted the presence of significant amounts of valuable secondary metabolites in quince fruit, in particular the procyanidins and caffeoyl esters with shikimic and quinic acid. Notably, owing to the higher content in phenolic compounds and the stronger antioxidant capacity compared with the other fruits considered, the use of C. oblonga as a source of antioxidant can be valuable in nutraceuticals, revealing new possible applications of quince fruit. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we investigated the fragmentation of the main triterpene acids of apple using an liquid chromatography atmospheric pressure chemical ionization mass spectrometry (LC‐APCI‐MSn) approach and high‐resolution mass spectrometry (HR‐MS) (Q‐TOF). Triterpenes were isolated using semipreparative high‐performance liquid chromatography, and chemical structures were elucidated by HR‐MS and nuclear magnetic resonance spectroscopy. Finally, compounds were used to study MSn behavior in ion trap. Isolated triterpenes present similar structures, bearing carboxyl group linked to C‐17 and different substitutions. We observed significant changes in MS2 spectra, which were useful for further compound identification. The observed fragments allowed the discrimination of different derivatives, namely, pomaceic, annurcoic, euscaphic, pomolic, corosolic, maslinic, betulinic, oleanolic, and ursolic acids. The proposed method allows a rapid identification of triterpene acids, and it could be useful for the analysis of these compounds in apple fruits and in other natural sources. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we investigated the fragmentation of the main triterpene acids of apple using an liquid chromatography atmospheric pressure chemical ionization mass spectrometry (LC‐APCI‐MSn) approach and high‐resolution mass spectrometry (HR‐MS) (Q‐TOF). Triterpenes were isolated using semipreparative high‐performance liquid chromatography, and chemical structures were elucidated by HR‐MS and nuclear magnetic resonance spectroscopy. Finally, compounds were used to study MSn behavior in ion trap. Isolated triterpenes present similar structures, bearing carboxyl group linked to C‐17 and different substitutions. We observed significant changes in MS2 spectra, which were useful for further compound identification. The observed fragments allowed the discrimination of different derivatives, namely, pomaceic, annurcoic, euscaphic, pomolic, corosolic, maslinic, betulinic, oleanolic, and ursolic acids. The proposed method allows a rapid identification of triterpene acids, and it could be useful for the analysis of these compounds in apple fruits and in other natural sources. [ABSTRACT FROM AUTHOR]

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In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component. Such solvents have gained much attention of the scientific community in the green chemistry area, being considered useful alternatives to common organic solvents. NADES can be used also as administration vehicles, and this can be attractive for nutraceutical products when eutectics are formed with food grade ingredients. In this work, different NADES were prepared using mainly food grade constituents and were tested as solvents for the alkaloid berberine. Three selected NADES/berberine solutions and an aqueous suspension were orally administered to mice with in dose of 50 mg/Kg. Blood levels of berberine were measured by a LC-MS/MS method. The pharmacokinetic analysis revealed a 2-20 fold increase in blood concentration of NADES/berberine with significant changes in pharmacokinetic profile. Natural Deep Eutectic Solvents may thus be considered attractive solubilizing agents and may also play a role in the increase of absorption of poorly bioavailable natural products such as berberine. [ABSTRACT FROM AUTHOR]

We herein review the Adriatic opisthobranch fauna, provide an updated checklist of 223 species and assess their distribution at regional and country levels. New Adriatic records are provided for 67 opisthobranch taxa, adding three new records for the Italian coastline, five new records for Albania, eight for Croatia and 15 for Montenegro. The presence of Hermaea bifida (Montagu, 1815), Hermaea variopicta (Costa A., 1869) and Facelina annulicornis (Chamisso & Eysenhardt, 1821) is reported for the first time from anywhere in the Adriatic Sea. Including the new findings, our inventory includes 28 species from Albania, 163 from Croatia, 178 from the Italian coastline of the Adriatic, 41 from Montenegro and 74 from Slovenia. No records were available from Bosnia and Hercegovina. Ninety species (40.4%) are widespread, and were recorded from all three main divisions (Northern, Western and Eastern Adriatic), whilst 79 species (35.4%) were reported from only one of them. At sub-division levels, the Albanian inventory is the most dissimilar to the other country/regional lists, presumably because of the lack of targeted field surveys. The highest similarity is observed amongst the Western Adriatic, Croatia and the Italian Ionian coastline. Seven alien, one possible alien and three cryptogenic opisthobranchs were reliably recorded from the Adriatic Sea. The first Mediterranean records of five species were in the Adriatic Sea, of which four species have not been found elsewhere in the Mediterranean. Shipping and aquaculture are the probable pathways for most of the alien species. A steady rate of one to two alien introductions per decade since the 1970s was evident. The Northern Adriatic coasts are the most affected by alien invasions, probably due to repeated local introductions along with shellfish transfers (oysters, mussels, Manila clams), and heavy maritime transport. [ABSTRACT FROM AUTHOR]

The distribution of the endemic brown alga Fucus virsoides was assessed along the northern Adriatic coastline. A high-resolution geographic information system database was created using visual census methods to identify the presence and abundance of algae, including the geomorphology of the substrate. Samples of F. virsoides were collected for analysis of the quantitative spatial distribution. The abundance of F. virsoides was related to several environmental variables, including the relative exposure index (REI). The results support the hypothesis that the distribution of F. virsoides in the Gulf of Trieste is influenced mainly by the stability of mediolittoral substrata, wave exposure and the vicinity of freshwater inputs. Populations of this species are widespread in the Gulf of Trieste. Many of them were found growing inside small harbours or along a boatyard, where fluctuations in salinity and nutrient concentrations are frequent. Therefore, we conclude that F. virsoides cannot be considered an ecological indicator for seawater pollution nor for climate change, since it is subjected naturally to high pollution levels and environmental variability. [ABSTRACT FROM AUTHOR]

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as "cases" if they developed EOS, and as "controls"if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis. [ABSTRACT FROM AUTHOR]

Background: "breathomics" enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: "breathomics" can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile. [ABSTRACT FROM AUTHOR]