Characterization of Vaccine Breakthrough Cases during Measles Outbreaks in Milan and Surrounding Areas,Italy, 2017–2021

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles.     

The Isolation and Characterization of a Broad Host Range Bcep22-like Podovirus JC1

Bacteriophage JC1 is a Podoviridae phage with a C1 morphotype, isolated on host strain Burkholderia cenocepacia Van1. Phage JC1 is capable of infecting an expansive range of Burkholderia cepacia complex (Bcc) species. The JC1 genome exhibits significant similarity and synteny to Bcep22-like phages and to many Ralstonia phages. The genome of JC1 was determined to be 61,182 bp in length with a 65.4% G + C content and is predicted to encode 76 proteins and 1 tRNA gene. Unlike the other Lessieviruses, JC1 encodes a putative helicase gene in its replication module, and it is in a unique organization not found in previously analyzed phages. The JC1 genome also harbours 3 interesting moron genes, that encode a carbon storage regulator (CsrA), an N-acetyltransferase, and a phosphoadenosine phosphosulfate (PAPS) reductase. JC1 can stably lysogenize its host Van1 and integrates into the 5′ end of the gene rimO. This is the first account of stable integration identified for Bcep22-like phages. JC1 has a higher global virulence index at 37 °C than at 30 °C (0.8 and 0.21, respectively); however, infection efficiency and lysogen stability are not affected by a change in temperature, and no observable temperature-sensitive switch between lytic and lysogenic lifestyle appears to exist. Although JC1 can stably lysogenize its host, it possesses some desirable characteristics for use in phage therapy. Phage JC1 has a broad host range and requires the inner core of the bacterial LPS for infection. Bacteria that mutate to evade infection by JC1 may develop a fitness disadvantage as seen in previously characterized LPS mutants lacking inner core.     

Development of a Kinetic Model for the Redox Reactions of Co2.4Ni0.6O4 and SiO2/Co2.4Ni0.6O4 Oxides for Thermochemical Energy Storage

One of the possible solutions for the transition of the actual energetic model is the use of thermal energy storage technologies. Among them, thermochemical energy storage based on redox reactions involving metal oxides is very promising due to its high energy density. This paper deals with the development of the kinetic study based on data extracted from the thermogravimetric analysis of a cobalt-nickel mixed oxide (Co_2.4Ni_0.6O₄) without and with the addition of SiO₂ particles to improve the cyclability. The results show that in the reduction reaction the activation energy is not affected by the addition of SiO₂ particles while in the oxidation reaction an increase in the activation energy is observed. The theoretical models fitting with the experimental data are different for each material in the reduction reaction. The mixed oxide is controlled by a nucleation and growth mechanism for conversion ratios higher than 0.5, while the added material is controlled by diffusion mechanisms. In the oxidation reaction, the two materials are controlled by a nucleation and growth mechanism for conversion ratios higher than 0.5.     

Using the Smith-Watson-Topper Parameter and Its Modifications to Calculate the Fatigue Life of Metals: The State-of-the-Art

The Smith-Watson-Topper parameter (SWT) in its original form was designed to estimate the fatigue life of metal materials in a uniaxial load state (tension–compression) in the range up to fatigue crack initiation, with non-zero mean values. This parameter is based on the analysis of both stress and strain. Therefore, the stress–strain criterion is the focus, rather than the energy criterion. This paper presents the original SWT model and its numerous modifications. The first part presents different versions of this parameter defined by the normal parameters. Then, it presents versions defined through the tangent parameter and the most promising parameter defined through the tangent and normal parameters. It was noted that the final form of the equivalent value is defined either by stress or by an energy parameter. Therefore, the possible characteristics from which the fatigue life can be determined are also presented.     

Voice Hearing in Borderline Personality Disorder Across Perceptual,Subjective, and Neural Dimensions

BackgroundAuditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as “pseudohallucinations,” but they nevertheless have a detrimental impact on well-being.MethodsThe current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively.ResultsPerceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level–dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices.ConclusionIn summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as “pseudohallucinations.” These highlight a need to reconsider this experience as a treatment priority.     

接种抗HPV-16癌基因蛋白疫苗治疗外阴上皮内瘤样变

背景及目的：最近，关于叶酸的安全性引起了广泛的关注，尤其是其与肿瘤风险的关系。本研究是通过两项随机对照试验评价叶酸和维生素B治疗对肿瘤发生率和全因死亡率的影响。     

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

ABSTRACT: BACKGROUND: Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2--3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. METHODS: Term newborns (gestational age >= 36 weeks and birth weight >= 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. DISCUSSION: This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25.     

Evaluation of Food Labelling the Products with Information Regarding the Level of Sugar: A Preliminary Study

The aim of this article is to explore the reasons for seeking selected information on a food label, with particular emphasis on certain information about sugar. In order to meet the aim, in 2020, a survey was conducted among consumers aged 18–45. Predictive models (Logistic Regression) were developed for noticing “light” products and reading food labels. The results of our study indicate that consumers are mainly discouraged from reading label information by a large amount of information, the lack of time, and a general reluctance to be interested in label information. When it comes to the factors that lead people to read label information, the naturalness of the product, its organic origin, and physical activity are important. Moreover, respondents who declared that they noticed products on the market defined as “light” were those who were interested in the naturalness of the product, but also consumers declaring that they have nutritional knowledge. The results of the study indicate the need to intensify information campaigns in order to emphasize how important it is for consumers to read the information on food labels. The amount and complexity of information currently appearing on the food label may unfortunately discourage consumers from reading it, so it is important to continuously improve this form of communication with the consumer.