One year of surgical mask testing at the University of Bologna labs: Lessons learned from data analysis.

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

The Italian dementia with Lewy bodies study group (DLB-SINdem): toward a standardization of clinical procedures and multicenter cohort studies design.

Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients' reduced quality of life and high mortality. Furthermore, DLB is often misdiagnosed as Alzheimer's disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer's disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.

Adalimumab retreatment successfully restores clinical response and health-related quality of life in patients with moderate to severe psoriasis who undergo therapy interruption.

BACKGROUND: Published evaluations of skin disease signs and health-related quality of life (HRQoL) upon therapy withdrawal and retreatment in psoriatic patients are limited to results of drug withdrawal after short-term treatment. Analyses are lacking that evaluate patients' response to retreatment for patients treated successfully long-term. OBJECTIVE: To study the efficacy and safety of adalimumab in patients with long-term clinical responses to adalimumab who then discontinue therapy and are retreated with the same dosing regimen as the initial course. Skin disease signs and patients' HRQoL are evaluated. METHODS: This post hoc analysis of an open-label study (NCT00195676) included patients who had responded favourably to adalimumab during initial treatment (≥75% improvement in Psoriasis Area and Severity Index [PASI 75 response]) and had maintained good clinical response for an extended period (up to 252 weeks); patients had Physician's Global Assessment (PGA) 0 or 1 before treatment interruption. Following drug withdrawal (up to 40 weeks), all patients were retreated with adalimumab 80 mg initial dose, followed by 40 mg every-other-week for 16 weeks. PASI response and HRQoL were evaluated. RESULTS: Of the 133 patients in this analysis, 24 (18%) relapsed during therapy withdrawal. After 16 weeks of retreatment, 75% who relapsed and 89.9% who did not relapse, had a PASI 75 response; 89.5% achieved European Consensus Programme treatment goals after 16 weeks of retreatment. During drug withdrawal, HRQoL disproportionally worsened compared to skin disease signs; HROoL also considerably worsened for patients who did not relapse. Patients regained HRQoL upon retreatment with adalimumab. No new safety signals were identified in this study. CONCLUSION: Retreatment with adalimumab was successful in improving psoriasis skin signs and HRQoL in this subgroup with initial and extended responses to therapy followed by relapse after treatment withdrawal. Patient's HRQoL should be considered, as it may substantially worsen during therapy interruption.

A large community outbreak of Legionnaires disease in Vila Franca de Xira, Portugal, October to November 2014.

An outbreak of Legionnaires' disease with 334 confirmed cases was identified on 7 November 2014 in Vila Franca de Xira, Portugal and declared controlled by 21 November. Epidemiological, environmental and microbiological analysis identified industrial wet cooling systems to be the probable source of infection. Preliminary results from sequence-based typing of clinical specimens and environmental isolates confirmed this link. A series of meteorological phenomena are likely to have contributed to the scale of this outbreak.

Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis.

BACKGROUND: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. OBJECTIVE: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients' Paced-Auditory-Serial-Addition-Test (PASAT) scores. METHODS: Relapsing-remitting MS (RRMS) patients (n = 25) and controls (n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. RESULTS: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. CONCLUSIONS: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.

CT Findings in Laryngeal Trauma and the Clinical Implications.

PURPOSE: Acute traumatic osseous and cartilaginous injuries to the larynx are rare injuries presenting to the emergency department. Despite the low reported incidence, laryngeal trauma carries a high morbidity and mortality. The purpose of this study is to identify fracture and soft tissue injury patterns in laryngeal trauma and explore associations with patient demographics, mechanisms of injury, urgent airway and surgical intervention. METHODS: A retrospective review of patients with laryngeal injury who underwent multidetector computed tomography (MDCT) imaging was performed. The CT findings of laryngeal and hyoid fracture location, fracture displacement, and soft tissue injuries were recorded. Clinical data including patient demographics, mechanisms of injury, frequency of airway and surgical intervention were also recorded. Correlation of imaging characteristics with patient demographics, mechanism of injury and interventions were assessed for statistical significance using χ2 and Fisher's exact tests. RESULTS: The median patient age was 40 years old with a strong male predominance. The most common mechanisms of injury included motor vehicle collisions and penetrating gunshot wounds. Thyroid cartilage fractures were the most common fracture type. Findings of fracture displacement and airway hematoma had a higher correlation with requiring urgent airway management. CONCLUSION: Radiologists' early recognition and prompt communication of laryngeal trauma to the clinical service is important to reduce associated morbidity and mortality. Displaced fractures and laryngeal hematomas should be promptly conveyed to the clinical service as they are associated with more complex injuries and higher rates of urgent airway management and surgical intervention.

Multicentric/multifocal breast cancer with a single histotype: is the biological characterization of all individual foci justified?

BACKGROUND: Invasive multiple breast cancers with a single histological feature (MBCSH) are routinely assessed for biological parameters to indicate adjuvant treatments only in the largest invasive carcinomas. However, the heterogeneity of individual foci in multiple carcinomas has not been widely studied. We analyzed whether such biological features are differently expressed in different MBCSH foci. PATIENT AND METHODS: One hundred and thirteen invasive MBCSH were tested over a 5-year period. The expression of estrogen (ER) and progesterone (PgR) receptors, Ki-67 proliferative index, expression of HER2 and tumor grading were prospectively determined in each tumor focus, and mismatches among foci were recorded. RESULTS: Mismatches in ER status were present in 5 (4.4%) cases and PgR in 18 (15.9%) cases. Mismatches in tumor grading were present in 21 cases (18.6%), proliferative index (Ki-67) in 17 (15%) cases and HER2 status in 11 (9.7%) cases. CONCLUSIONS: In our experience, invasive MBCSH showed heterogeneity among foci. In our clinical practice, such assessment led to 14 (12.4%) patients receiving different adjuvant treatments compared with what would have been indicated if we had only taken into account the biologic status of the primary tumor.

The Natural History of Small Vestibular Schwannomas.

Objective The incidence of vestibular schwannomas is increasing, and the average tumor size at diagnosis is decreasing. Therefore, understanding the specific growth pattern of small vestibular schwannomas is becoming increasingly important to guide clinical management. The objectives of this study were to evaluate the growth patterns of very small intracanalicular vestibular schwannomas measuring ≤ 4 mm in linear diameter and to assess the likelihood of these lesions ever requiring treatment.  Methods A retrospective review was performed. A search of all MRI brain and internal auditory canal studies suggestive of a vestibular schwannoma from 1995 to 2019 was performed at our institution. This resulted in 372 cases, which were then evaluated for the presence of a vestibular schwannoma measuring ≤ 4 mm. All patients had to have at least one follow-up MRI to be included. Images were reviewed by a neuroradiologist. Results Eight ≤ 4 mm vestibular schwannomas were found that met all search criteria. The distribution of tumor sizes was as follows: three 2 mm, one 3 mm and four 4 mm. None of the ≤ 4 mm vestibular schwannomas identified demonstrated any significant growth in the linear dimension defined as greater than 2 mm of growth over observation times of 1-13 years (mean 6.3 years). None of the lesions ever required a treatment intervention per available medical records. Conclusion None of the ≤ 4 mm intracanalicular vestibular schwannomas identified in this study grew significantly or required treatment. Overall, the findings in this study suggest that vestibular schwannomas measuring ≤ 4 mm are unlikely to grow and ever require treatment.

Regional brain atrophy and functional disconnection across Alzheimer's disease evolution.

OBJECTIVE: To assess the contribution of regional grey matter (GM) atrophy and functional disconnection in determining the level of cognitive decline in patients with Alzheimer's disease (AD) at different clinical stages. METHODS: Ten patients with amnesic mild cognitive impairment (a-MCI), 11 patients with probable AD and 10 healthy controls were recruited. T1 volumes were obtained from each subject and postprocessed according to an optimised voxel based morphometry protocol. Resting state functional MRI data were also collected from the same individuals and analysed to produce connectivity maps after identification of the default mode network (DMN) by independent component analysis. RESULTS: Compared with healthy controls, both AD and a-MCI patients showed a similar regional pattern of brain disconnection between the posterior cingulate cortex (PCC) and the medial prefrontal cortex and the rest of the brain. Conversely, the distribution of GM atrophy was significantly more restricted in a-MCI than in AD patients. Interestingly, the PCC showed reduced connectivity in a-MCI patients in the absence of GM atrophy, which was, in contrast, detectable at the stage of fully developed AD. CONCLUSIONS: This study indicates that disconnection precedes GM atrophy in the PCC, which is a critical area of the DMN, and supports the hypothesis that GM atrophy in specific regions of AD brains likely reflects a long term effect of brain disconnection. In this context, our study indicates that GM atrophy in PCC accompanies the conversion from MCI to AD.

Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers.

BACKGROUND: Telomeres, located at chromosome ends, are progressively shortened during each cell cycle by replication-dependent loss of DNA termini. Although maintenance of telomere length is critical for cell-replicative potential and tumourigenesis, the erosion of telomeres can lead to genetic instability, a pivotal mechanism in the neoplastic process. PATIENTS AND METHODS: A total of 118 colorectal cancer (CRC) samples (53 right-colon, 30 left-colon, and 35 rectal tumours) and corresponding adjacent non-cancerous tissues were evaluated for telomere length, p53 mutation, and microsatellite instability (MSI). Telomere length was estimated by real-time PCR. RESULTS: Telomeres were significantly shorter in CRCs than in adjacent tissues, regardless of tumour stage and grade, site, or genetic alterations (P<0.0001). Moreover, in normal tissues, but not in tumours, telomere length inversely correlated with age (r=-0.24, P=0.017). Telomere length in CRCs did not differ with tumour progression or p53 status; however, in CRCs carrying the wild-type p53, telomeres were significantly shorter in tumours with MSI than in those with stable microsatellites (P=0.027). Furthermore, telomere length differed according to tumour location, being longer in rectal cancers (P=0.03). CONCLUSIONS: These findings suggest that telomere shortening is a key initial event in colorectal carcinogenesis. The extent of telomere erosion is related to tumour origin site and may be influenced by the mismatch repair pathway.

Sex-related variation in migration phenology in relation to sexual dimorphism: a test of competing hypotheses for the evolution of protandry.

Timing of arrival/emergence to the breeding grounds is under contrasting natural and sexual selection pressures. Because of differences in sex roles and physiology, the balance between these pressures on either sex may differ, leading to earlier male (protandry) or female (protogyny) arrival. We test several competing hypotheses for the evolution of protandry using migration data for 22 bird species, including for the first time several monochromatic ones where sexual selection is supposedly less intense. Across species, protandry positively covaried with sexual size dimorphism but not with dichromatism. Within species, there was weak evidence that males migrate earlier because, being larger, they are less susceptible to adverse conditions. Our results do not support the 'rank advantage' and the 'differential susceptibility' hypotheses, nor the 'mate opportunity' hypothesis, which predicts covariation of protandry with dichromatism. Conversely, they are compatible with 'mate choice' arguments, whereby females use condition-dependent arrival date to assess mate quality.

Moult speed affects structural feather ornaments in the blue tit.

Growing evidence suggests that structural feather colours honestly reflect individual quality or body condition but, contrary to pigment-based colours, it is not clear what mechanism links condition to reflectance in structural feather colours. We experimentally accelerated the moult speed of a group of blue tits (Cyanistes caeruleus) by exposing them to a rapidly decreasing photoperiod and compared the spectral characteristics of their structural feather colours with those of control birds. Blue tits were sexually dimorphic on the UV/blue crown and on the white cheek feathers. Moult speed, however, dramatically reduced brightness and the saturation only on the UV/blue crown feathers, whereas structural white on the cheek feathers was basically unaffected by moult speed. Given that the time available for moulting is usually confined to the period between the end of the breeding season and migration or wintering, UV/blue colours, but not structural white, may convey long-term information about an individual's performance during the previous breeding season. The trade-off between fast moulting and structural colour expression may represent a previously unrecognized selective advantage for early-breeding birds.

Tracking the origin of an invasive species: Drosophila subobscura in Argentina.

Biological invasions are excellent opportunities to study the evolutionary forces leading to the adaptation of a species to a new habitat. Knowledge of the introduction history of colonizing species helps tracking colonizing routes and assists in defining management strategies for invasive species. The Palearctic species Drosophila subobscura is a good model organism for tracking colonizations since it was detected in Chile and western North America three decades ago and later on in the Atlantic coast of Argentina. To unravel the origin of the Argentinean colonizers two populations have been analysed with several genetic markers. Chromosomal arrangements and microsatellite alleles found in Argentina are almost similar to those observed in Chile and USA. The lethal allelism test demonstrates that the lethal gene associated with the O(5) inversions in Argentina is identical to that found in Chile and USA, strongly supporting the hypothesis that all the American colonizing populations originated from the same colonization event. A secondary bottleneck is detected in the Argentinean populations and the genetic markers suggest that these populations originated from the invasion of 80-150 founding individuals from Chile.

Rapid evolution of a geographic cline in size in an introduced fly.

The introduction and rapid spread of Drosophila subobscura in the New World two decades ago provide an opportunity to determine the predictability and rate of evolution of a geographic cline. In ancestral Old World populations, wing length increases clinally with latitude. In North American populations, no wing length cline was detected one decade after the introduction. After two decades, however, a cline has evolved and largely converged on the ancestral cline. The rate of morphological evolution on a continental scale is very fast, relative even to rates measured within local populations. Nevertheless, different wing sections dominate the New versus Old World clines. Thus, the evolution of geographic variation in wing length has been predictable, but the means by which the cline is achieved is contingent.

The chromosomal polymorphism of Drosophila subobscura: a microevolutionary weapon to monitor global change.

The Palaearctic species Drosophila subobscura recently invaded the west coast of Chile and North America. This invasion helped to corroborate the adaptive value of the rich chromosomal polymorphism of the species, as the same clinal patterns than those observed in the original Palaearctic area were reproduced in the colonized areas in a relatively short period of time. The rapid response of this polymorphism to environmental conditions makes it a good candidate to measure the effect of the global rising of temperatures on the genetic composition of populations. Indeed, the long-term variation of this polymorphism shows a general increase in the frequency of those inversions typical of low latitudes, with a corresponding decrease of those typical of populations closer to the poles. Although the mechanisms underlying these changes are not well understood, the system remains a valid tool to monitor the genetic impact of global warming on natural populations.

Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia.

Anoxia is considered a good model for studying amnesia. However, not all individuals who experience anoxic events develop memory problems. Moreover, the question still remains about whether, after anoxia, damage is limited to the hippocampus in patients with amnesia and without other significant cognitive deficits. Here we investigated brain damage in a selected sample of adults affected exclusively by an amnesic syndrome after an anoxic episode. The cerebral MR images of these patients were submitted to visual inspection, volumetric measurements of the mesial temporal structures following manual segmentation, and to Voxel-Based Morphometry of the whole brain. We studied five anoxic patients and thirty-three well-matched healthy subjects. Our aim was to: (a) quantify regional atrophic changes associated with chronic anoxic damage compared to control subjects (Group Comparison Analysis); (b) identify regions of common abnormality across all patients (Conjunction Analysis in the VBM); (c) investigate whether measures of regional volume reduction correlated with neuropsychological memory scores; (d) compare the results obtained with visual inspection and ROI analyses with those obtained with VBM. We found that anoxic patients presented a significant reduction of gray matter volume in the hippocampus bilaterally compared to healthy subjects. The only common atrophic region across all patients was the hippocampus bilaterally. Correlation analysis showed only a trend between the Prose immediate free recall test and the left hippocampus. Our findings confirm that the hippocampus is very sensitive to damage stemming from anoxia. Patients with hypoxic amnesia may present damage in other brain regions, but only hippocampal atrophy is common in all of them.

Proteins that bind methylated DNA and human cancer: reading the wrong words.

DNA methylation and the machinery involved in epigenetic regulation are key elements in the maintenance of cellular homeostasis. Epigenetic mechanisms are involved in embryonic development and the establishment of tissue-specific expression, X-chromosome inactivation and imprinting patterns, and maintenance of chromosome stability. The balance between all the enzymes and factors involved in DNA methylation and its interpretation by different groups of nuclear factors is crucial for normal cell behaviour. In cancer and other diseases, misregulation of epigenetic marks is a common feature, also including DNA methylation and histone post-translational modifications. In this scenario, it is worth mentioning a family of proteins characterized by the presence of a methyl-CpG-binding domain (MBDs) that are involved in interpreting the information encoded by DNA methylation and the recruitment of the enzymes responsible for establishing a silenced state of the chromatin. The generation of novel aberrantly hypermethylated regions during cancer development and progression makes MBD proteins interesting targets for their biological and clinical implications.

Variability of PM10 in industrialized-urban areas. New coefficients to establish significant differences between sampling points.

One of the main problems that arise in the assessment of air quality in an area is to estimate the number of representative sampling points of each microenvironment within it. We present a new model that reduces the variability and increases the quality of the comparison of the sampling points. The study is based on the comparison between a city in eastern Spain, Vila-real, a macro city in México, Monterrey and the Piemonte region regarding the assessment of PM10 in microenvironments. Vila-real is located in the province of Castellón. This province is a strategic area in the framework of European Union (EU) pollution control. On the other hand, Monterrey in México, located in the northern state of Nuevo León, has several problems with particulate material in the atmosphere produced by the extraction of building materials in the hill that surround the city. Finally, the Piemonte region, which is located in the north of Italy, has to be in consideration due to higher concentrations of PM10 in the Po river basin. In the case of Vila-real the PM10 samples were collected by a medium volume sampler according to European regulations. Particle concentration levels were determined gravimetrically (EN 12341:1999). In the case of Monterrey the PM10 concentrations were determined by Beta Ray Attenuation according to US-EPA regulations. In the Piemonte region, the average concentration of PM10 was also obtained by means of the Beta Ray Attenuation as well as using gravimetric instruments. The methodology carried out in this paper is a useful tool for developing future Air Quality Plans in other industrialised areas.

Bilateral damage to the mammillo-thalamic tract impairs recollection but not familiarity in the recognition process: a single case investigation.

Focal damage confined to the hippocampus may result in recognition deficits characterized by a dissociation between impaired recollection and preserved familiarity. Here, we report a single case of an amnesic patient with bilateral damage to the anterior part of the thalamus, who presented with a neuropsychological profile suggesting such a dissociation. We hypothesized that this focal damage involved the so-called Delay and Brion's circuit, which has been theorized to subserve episodic memory processes, but at a different anatomical level than in patients with hippocampal lesions. Using two independent experimental paradigms (remember/know and confidence receiver operating characteristics [ROC]) and recruiting a sex- and age-matched group of healthy controls, we demonstrated that this patient's recognition deficits were due to a selective impairment of recollection with a normal familiarity process. The patient underwent an ad hoc brain MRI study, and a quantitative analysis of his MR images was performed. Tissue damage extended bilaterally to the mammillo-thalamic tract, with complete preservation of the medio-dorsal thalamic nuclei. Our findings support the idea that the same functional specialization hypothesized for the different sub-regions of the mesial temporal lobe might also extend to the thalamus. This case will be discussed in light of its implications in support of recent theories, which regard recollection and familiarity as independent processes associated with different neural circuits.