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The birth, maturation, and integration of new neurons in the adult hippocampus regulates specific learning and memory processes, responses to stress, and antidepressant treatment efficacy. This process of adult hippocampal neurogenesis is sensitive to environmental stimuli, including peripheral signals from certain cytokines, hormones, and metabolites, which can promote or hinder the production and survival of new hippocampal neurons. The trillions of microorganisms resident to the gastrointestinal tract, collectively known as the gut microbiota, also demonstrate the ability to modulate adult hippocampal neurogenesis. In doing so, the microbiota-gut-brain axis can influence brain functions regulated by adult hippocampal neurogenesis. Unlike the hippocampus, the gut microbiota is highly accessible to direct interventions, such as prebiotics, probiotics, and antibiotics, and can be manipulated by lifestyle choices including diet. Therefore, understanding the pathways by which the gut microbiota shapes hippocampal neurogenesis may reveal novel targets for non-invasive therapeutics to treat disorders in which alterations in hippocampal neurogenesis have been implicated. This review first outlines the factors which influence both the gut microbiome and adult hippocampal neurogenesis, with cognizance that these effects might happen either independently or due to microbiota-driven mechanisms. We then highlight approaches for investigating the regulation of adult hippocampal neurogenesis by the microbiota-gut-brain axis. Finally, we summarize the current evidence demonstrating the gut microbiota’s ability to influence adult hippocampal neurogenesis, including mechanisms driven through immune pathways, microbial metabolites, endocrine signalling, and the nervous system, and postulate implications for these effects in disease onset and treatment.

We analyzed the first 255 PCR-confirmed cases of monkeypox in Italy in 2022. Preliminary estimates indicate mean incubation period of 9.1 (95% CI 6.5-10.9) days, mean generation time of 12.5 (95% CI 7.5-17.3) days, and reproduction number among men who have sex with men of 2.43 (95% CI 1.82-3.26).

To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions.Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data.Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST).A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively.This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.

Background The SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021. Aim To comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level. Methods We analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility. Results Omicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9–80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7–3.3 days. As of 17 January 2022, Delta variant represented Conclusion Estimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

Tolstoj quadrangle is located in the equatorial area of Mercury, between 22.5°N and 22.5°S of latitude and 144° and 216°E of latitude. In this work we present the preliminary results of a geological map (1:3M scale). The main basemap used for the mapping is the MDIS (Mercury Dual Imaging System) 166 m/pixel BDR (map-projected Basemap reduced Data Record) monochrome mosaic compiled using NAC (Narrow Angle Camera) and WAC (Wide Angle Camera) 750 nm-images. Moreover, to distinguish spectral characteristics and topography of the surface, MDIS global color mosaics (Denevi et al., 2016) and the MDIS global DEM (Becker et al., 2009), have been taken into account. Then, the quadrangle has been mapped using ArcGIS at an average scale of 1:400k for a final out-put of 1:3M. So far, most of the geological contacts and lineaments of Tolstoj quadrangle have been mapped. The preliminary geological map shows the Caloris basin-related features dominating the Tolstoj quadrangle. The southern half of the basin is located in the upper left corner of quadrangle and interior and exterior smooth plains of the Caloris basin are the most extended volcanic deposits emplaced in the area. Also structural framework is mainly linked with the basin with radial and concentric grabens located in its floor and wrinkle ridges widespread both on the interior and exterior Caloris smooth plains. Further, thrusts have been detected on the quadrangle. They are located outside the Caloris basin but they are absent within its floor. Besides smooth plains, products of effusive volcanism, features related to explosive volcanism are also frequently detected. Interestingly, several volcanic vents have been identified in the inner Caloris smooth plains, aligned with the rim of Caloris basin. They were surrounded by extended pyroclastic deposits appearing in bright yellow in MDIS enhanced global color mosaics. However, vents are not clustered only inside Caloris basin, but other crater floors are affected by this type of features. Finally, few hollow fields have been detected, mainly located within crater floors.Once the mapping activity is accomplished, the geological map will be integrated into the global 1:3M geological map of Mercury (Galluzzi et al., 2021), which is being prepared in support to ESA/JAXA (European Space Agency, Japan Aerospace Agency) BepiColombo mission. Acknowledgements: We gratefully acknowledge funding from the Italian Space Agency (ASI) under ASI-INAF agreement 2017-47-H.0 References:Becker K. J., et al. AGU, Fall Meeting, ab-stract#P21A-1189, 2009Denevi et al.:LPS XLVII. Abstract#1264, 2016Galluzzi V. et al.:. Planetary Geologic Mappers 2021, LPI #2610, 202

Background Meningococcus (Neisseria meningitidis) is the causative bacteria of invasive meningococcal disease (IMD), a major cause of meningitis and sepsis. In 2015–16, an outbreak caused by serogroup C meningococci (MenC), belonging to the hyperinvasive strain ST-11(cc-11), resulted in 62 IMD cases in the region of Tuscany, Italy. Aim We aimed to estimate the key outbreak parameters and assess the impact of interventions used in the outbreak response. Methods We developed a susceptible-carrier-susceptible individual-based model of MenC transmission, accounting for transmission in households, schools, discos/clubs and the general community, which was informed by detailed data on the 2015–16 outbreak (derived from epidemiological investigations) and on the implemented control measures. Results The outbreak reproduction number (Re) was 1.35 (95% prediction interval: 1.13–1.47) and the IMD probability was 4.6 for every 1,000 new MenC carriage episodes (95% confidence interval: 1.8–12.2). The interventions, i.e. chemoprophylaxis and vaccination of close contacts of IMD cases as well as age-targeted vaccination, were effective in reducing Re and ending the outbreak. Case-based interventions (including ring vaccination) alone would have been insufficient to achieve outbreak control. The definition of age groups to prioritise vaccination had a critical impact on the effectiveness and efficiency of control measures. Conclusions Our findings suggest that there are no effective alternatives to widespread reactive vaccination during outbreaks of highly transmissible MenC strains. Age-targeted campaigns can increase the effectiveness of vaccination campaigns. These results can be instrumental to define effective guidelines for the control of future meningococcal outbreaks caused by hypervirulent strains.

PDF file 86K, Supplementary Table S2. BNC1 and ADAMTS1 Gene expression changes in pancreatic cancers from previously published microarray dataset

PDF file 57K, Supplemental Figure S3. Kaplan-Meier Curve of Overall Survival Characterized by ADAMTS1 Methylation

Purpose: Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis.Experimental Design: Demographics, tumor characteristics, and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation, and CpG island methylator phenotype (CIMP) status was conducted. A Cox proportional hazard model was built to predict survival.Results: CIMP+ was detected in 27 of 99 (27.3%) duodenal adenocarcinomas and was associated with MSI (P = 0.011) and MLH1 methylation (P < 0.001), but not with KRAS mutations (P = 0.114), as compared with CIMP− tumors. No BRAF V600E mutation was detected. Among the CIMP+ tumors, 15 (55.6%) were CIMP+/MLH1-unmethylated (MLH1-U). Kaplan–Meier analysis showed that tumors classified by CIMP, CIMP/MLH1 methylation status, or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), whereas CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value in both OS (P < 0.001) and TTR (P = 0.023). Patients with CIMP+/MLH1-U tumors had the worst OS and TTR.Conclusions: Our results showed existence of CIMP in duodenal adenocarcinomas. The combination of CIMP+/MLH1-U seems to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI, or CIMP development. Clin Cancer Res; 18(17); 4743–52. ©2012 AACR.

PDF file, 545K, Kaplan-Meier survival estimates of time-to-recurrence in 99 patients with duodenal adenocarcinomas by (A) age, (B) stage, (C) differentiation, and (D) chemotherapy and/or radiotherapy.

PDF file 108K, Supplementary Figure S2. mRNA and Protein Expression in BNC1 Overexpression System

PDF file, 113K, Supplementary Figure Legend; Supplementary Table S1. List of primers used for methylation-specific PCR; S 2. List of KRAS mutations in patients with duodenal Adenocarcinomas; S3. Five year and 10 year cumulative proportion of overall survival and time-to-recurrence for different molecular groups; S4. Univariate and multivariate Cox proportional hazard analysis of overall survival and time-to-recurrence for CIMP, MLH1 methylation or MSI status.

PDF file, 428K, Kaplan-Meier survival estimates of overall survival in 99 patients with duodenal adenocarcinomas by (A) age, (B) stage, and (C) MSI status.

PDF file, 342K, Distributions of MSI, CIMP and MLH1 methylation in 99 patients with duodenal adenocarcinomas.

PDF file 64K, Supplementary Table S1. Primers used for MSP, RT-PCR, Bisulfite sequencing analyses

PDF file, 382K, Summary of promoter hypermethylation frequency in CIMP− and CIMP+ duodenal adenocarcinomas as detected by methylation-specific PCR. Black and gray boxes indicate the presence or absence of hypermethylation, respectively.

PDF file 69K, Supplementary Fig. S1. Schematic representation of the study design used in this project

PDF file 93K, This includes figure legends of supplementary Figure S1-S3

Purpose: Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here, we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer.Experimental Design: We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum.Results: We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreatic cancers (n = 143), up to 100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n = 42) from patients with pancreatic cancer, with a sensitivity for BNC1 of 79% [95% confidence interval (CI), 66%–91%] and for ADAMTS1 of 48% (95% CI, 33%–63%), whereas specificity was 89% for BNC1 (95% CI, 76%–100%) and 92% for ADAMTS1 (95% CI, 82%–100%). Overall sensitivity using both markers is 81% (95% CI, 69%–93%) and specificity is 85% (95% CI, 71%–99%).Conclusions: Promoter DNA methylation of BNC1 and ADAMTS1 is a potential biomarker to detect early-stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early detection of pancreatic cancer and has the potential to improve mortality from this disease. Clin Cancer Res; 19(23); 6544–55. ©2013 AACR.

Neonates possess a molecular variant of fibrinogen, known as fetal fibrinogen, characterized by increased sialic acid, a greater negative charge, and decreased activity compared with adults. Despite these differences, adult fibrinogen is used for the treatment of bleeding in neonates, with mixed efficacy. To determine safe and efficacious bleeding protocols for neonates, more information on neonatal fibrin clot formation and the influence of sialic acid on these processes is needed. Here, we examine the influence of sialic acid on neonatal fibrin polymerization. We hypothesized that the increased sialic acid content of neonatal fibrinogen promotes fibrin B:b knob-hole interactions and consequently influences the structure and function of the neonatal fibrin matrix. We explored this hypothesis through analysis of structural properties and knob:hole polymerization dynamics of normal and desialylated neonatal fibrin networks and compared them with those formed with adult fibrinogen. We then characterized normal neonatal fibrin knob:hole interactions by forming neonatal and adult clots with either thrombin or snake-venom thrombin-like enzymes that preferentially cleave fibrinopeptide A or B. Sialic acid content of neonatal fibrinogen was determined to be a key determinant of resulting clot properties. Experiments analyzing knob:hole dynamics indicated that typical neonatal fibrin clots are formed with the release of more fibrinopeptide B and less fibrinopeptide A than adults. After the removal of sialic acid, fibrinopeptide release was roughly equivalent between adults and neonates, indicating the influence of sialic acid on fibrin neonatal fibrin polymerization mechanisms. These results could inform future studies developing neonatal-specific treatments of bleeding.

The gut microbiota plays crucial roles in maintaining the health and homeostasis of its host throughout lifespan, including through its ability to impact brain function and regulate behaviour during ageing. Studies have shown that there are disparate rates of biologic ageing despite equivalencies in chronologic age, including in the development of neurodegenerative diseases, which suggests that environmental factors may play an important role in determining health outcomes in ageing. Recent evidence demonstrates that the gut microbiota may be a potential novel target to ameliorate symptoms of brain ageing and promote healthy cognition. This review highlights the current knowledge around the relationships between the gut microbiota and host brain ageing, including potential contributions to age-related neurodegenerative diseases. Furthermore, we assess key areas for which gut microbiota-based strategies may present as opportunities for intervention.

Mussolini’s Theatre reveals how Mussolini emotionally and financially invested in the theatre during his reign, believing it would broadly inspire his fascist vision of a cultured people.

Congenital Heart Disease (CHD), malformations of the heart present at birth, is the most common class of life-threatening birth defect (Hoffman (1995) [1] , Gelb (2004) [2] , Gelb (2014) [3] ). A major research challenge is to elucidate the genetic determinants of CHD and mechanistically link CHD ontogeny to a molecular understanding of heart development. Although the embryonic origins of CHD are unclear in most cases, dysregulation of cardiovascular lineage specification, patterning, proliferation, migration or differentiation have been described (Olson (2004) [4] , Olson (2006) [5], Srivastava (2006) [6] , Dunwoodie (2007) [7] , Bruneau (2008) [8]). Cardiac differentiation is the process whereby cells become progressively more dedicated in a trajectory through the cardiac lineage towards mature cardiomyocytes. Defects in cardiac differentiation have been linked to CHD, although how the complex control of cardiac differentiation prevents CHD is just beginning to be understood. The stages of cardiac differentiation are highly stereotyped and have been well-characterized (Kattman et al. (2011) [9], Wamstad et al. (2012) [10], Luna-Zurita et al. (2016) [11], Loh et al. (2016) [12], DeLaughter et al. (2016) [13]); however, the developmental and molecular mechanisms that promote or delay the transition of a cell through these stages have not been as deeply investigated. Tight temporal control of progenitor differentiation is critically important for normal organ size, spatial organization, and cellular physiology and homeostasis of all organ systems (Raff et al. (1985) [14] , Amthor et al. (1998) [15] , Kopan et al. (2014) [16] ). This review will focus on the action of signaling pathways in the control of cardiomyocyte differentiation timing. Numerous signaling pathways, including the Wnt, Fibroblast Growth Factor, Hedgehog, Bone Morphogenetic Protein, Insulin-like Growth Factor, Thyroid Hormone and Hippo pathways, have all been implicated in promoting or inhibiting transitions along the cardiac differentiation trajectory. Gaining a deeper understanding of the mechanisms controlling cardiac differentiation timing promises to yield insights into the etiology of CHD and to inform approaches to restore function to damaged hearts.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging. The gut microbiome can change with age and influence aging-related diseases systemically, including in the brain. The authors show that rejuvenation of the gut microbiome by fecal microbiota transplantation from young mice reverses aging-induced deficits in the hippocampal immune system, metabolome and transcriptome, and rescues selective cognitive deficits.

We report a case series of children with childhood apraxia of speech, by describing behavioral and white matter microstructural changes following 2 different treatment approaches. Five children with childhood apraxia of speech were assigned to a motor speech treatment (PROMPT) and 5 to a language, nonspeech oral motor treatment. Speech assessment and brain MRI were performed pre- and post-treatment. The ventral (tongue/larynx) and dorsal (lips) corticobulbar tracts were reconstructed in each subject. Mean fractional anisotropy and mean diffusivity were extracted. The hand corticospinal tract was assessed as a control pathway. In both groups speech improvements paralleled changes in the left ventral corticobulbar tract fractional anisotropy. The PROMPT treated group also showed fractional anisotropy increase and mean diffusivity decrease in the left dorsal corticobulbar tract. No changes were detected in the hand tract. Our results may provide preliminary support to the possible neurobiologic effect of a multimodal speech motor treatment in childhood apraxia of speech.

We surveyed 181 nursing research leaders from Magnet® hospitals, using mixed methods with the online Hospital-Based Nursing Research Clinical and Economic Outcomes survey, to describe the clinical and economic outcomes of nursing research conducted in hospital settings. We used descriptive statistics to analyze the quantitative findings and a qualitative descriptive approach to study the open-ended responses. Most respondents reported that findings from their hospital-based studies were implemented on their units (88.2%), improved health care processes (88.2%), and reduced hospital costs (79%). Over 50% reported positive impacts on core quality measures, including improving patient/family satisfaction (76.8%), nurse satisfaction (65%), length of stay (59.1%), and infection rates (56.5%). Four themes were identified: study evaluation, improvements in care delivery/clinical outcomes, economic impact, and intrinsic and extrinsic rewards. Much of the research reported by respondents focused on quality measures with findings that resulted in improved clinical and economic outcomes.

BackgroundThe worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. An illustrative example is what occurred in Ethiopia, where nine months after the launch of the national vaccination program in March 2021, only 3% of the population received two doses of COVID-19 vaccine. In the meantime, a new wave of cases caused by the emergence of Delta variant of SARS-CoV-2 was observed between July and November 2021.MethodsWe used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different socio-demographic settings.ResultsWe found that, during the first year of the pandemic, 46.1-58.7% of SARS-CoV-2 infections and 24.9-48% of critical cases occurred in SWSZ were likely associated with infectors under 30 years of age. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase to 66.7-70.6%. However, our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively to the number of available doses. Vaccination of all individuals aged 50□years or older would have averted 40 (95%CI: 18-60), 90 (95%CI: 61-111), and 62 (95%CI: 21-108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged 30□years or more would have averted an average of 86-152 critical cases per 100,000 individuals, depending on the setting considered.ConclusionsDespite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19.

Infants and children with neurological impairment, such as cerebral palsy (CP), often experience abnormal ingestion functions, including oropharyngeal dysphagia and gastroesophageal reflux disease, which led to aspiration-related respiratory complications, morbidity, hospitalization, or death. There is a lack of evidence-based, repeatable, infant-friendly instrumental procedures to assess aspiration-risk in infants with CP or other neurological disorders, with also a lack of clinical assessment measures to support the use of more invasive diagnostic techniques. To this purpose, in the current study we explore the feasibility of lung ultrasound (LUS), to assess lung deaeration possibly related to aspiration during meal, in a cohort of 35 subjects affected by CP or other encephalopathies, and 10 controls in the same age-range. We coupled LUS procedure with meal caregiver administration for each child. Our results support the feasibility of this innovative approach in the clinical setting. Exploratory findings revealed a number of lung abnormalities likely related to abnormal ingestion function in subjects. Subgroup analyses revealed possible differences in LUS abnormalities between CP and other encephalopathies, possibly related to different mechanism of disease or dysfunction. Also, some evidences arose about the possible relationship between such LUS abnormalities and feeding and swallowing abilities in CP or other encephalopathies. LUS showed preliminarily feasibility and effectiveness in detecting meal-related LUS abnormalities in a dynamic manner in the clinical setting. This approach demonstrated usefulness as a potential tool for improving assessment and management in complex care of infants and young children with severe neurological disorders.

BackgroundThe emergence of Omicron (B.1.1.529) variant of SARS-CoV-2 in late 2021 was followed by a marked increase of breakthrough infections. Estimates of vaccine effectiveness (VE) in the long term are key to assess potential resurgence of COVID-19 cases in the future.MethodsWe conducted a systematic review of manuscripts published until June 21, 2022 to identify studies reporting the level of protection provided by COVID-19 vaccines against SARS-CoV-2 infection and symptomatic disease at different time points since vaccine administration. An exponential model was used to perform a secondary data analysis of the retrieved data to estimate the progressive waning of VE associated with different vaccine products, numbers of received doses, and SARS-CoV-2 variants.FindingsOur results show that VE of BNT162b2, mRNA-1273, ChAdOx1 nCoV-19 vaccines against any laboratory confirmed infection with Delta might have been lower than 70% at 9 months from second dose administration. We found a marked immune escape associated with Omicron infection and symptomatic disease, both after the administration of two and three doses. The half-life of protection against symptomatic infection provided by two doses was estimated in the range of 178-456 days for Delta, and between 66 and 73 days for Omicron. Booster doses were found to restore the VE to levels comparable to those acquired soon after administration of the second dose; however, a fast decline of booster VE against Omicron was observed, with less than 20% VE against infection and less than 25% VE against symptomatic disease at 9 months from the booster administration.ConclusionsThis study provides a cohesive picture of the waning of vaccine protection; obtained estimates can inform the identification of appropriate targets and timing for future COVID-19 vaccination programs.

Background Children with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses. Methods A randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2. Discussion This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications. Trial registration Trial registration date 06/12/2019; ClinicalTrials.gov Identifier: NCT04189159.

Undernotification of SARS-CoV-2 infections has been a major obstacle to the tracking of critical quantities such as infection attack rates and the probability of severe and lethal outcomes. We use a model of SARS-CoV-2 transmission and vaccination informed by epidemiological and genomic surveillance data to estimate the number of daily infections occurred in Italy in the first two years of pandemic. We estimate that the attack rate of ancestral lineages, Alpha, and Delta were in a similar range (10–17%, range of 95% CI: 7–23%), while that of Omicron until February 20, 2022, was remarkably higher (51%, 95%CI: 33–70%). The combined effect of vaccination, immunity from natural infection, change in variant features, and improved patient management massively reduced the probabilities of hospitalization, admission to intensive care, and death given infection, with 20 to 40-fold reductions during the period of dominance of Omicron compared to the initial acute phase.

Background Children with neurological impairment may have dysphagia and/or gastro-esophageal reflux disease (GERD), which predispose to complications affecting the airways, increasing risk for aspiration-induced acute and chronic lung disease, or secondarily malnutrition, further neurodevelopmental disturbances, stressful interactions with their caregivers and chronic pain. Only multidisciplinary clinical feeding evaluation and empirical trials are applied to provide support to the management of feeding difficulties related to dysphagia or GERD, but no standardized feeding or behavioral measure exists at any age to assess aspiration risk and support the indication to perform a videofluoroscopic swallowing study (VFSS) or a fibre-optic endoscopic examination of swallowing (FEES), in particular in newborns and infants with neurological impairments. Lung ultrasound (LUS) has been proposed as a non-invasive, radiation-free tool for the diagnosis of pulmonary conditions in infants, with high sensitivity and specificity. Methods A RCT will be conducted in infants aged between 0 and 6 years having, or being at risk for, cerebral palsy, or other neurodevelopmental disease that determines abnormal muscular tone or motor developmental delay assessed by a quantitative scale for infants or if there is the suspicion of GERD or dysphagia based on clinical symptoms. Infants will be allocated in one of 2 groups: 1) LUS-monitored management (LUS-m); 2) Standard care management (SC-m) and after baseline assessment (T0), both groups will undergo an experimental 6-months follow-up. In the first 3 months, infants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 LUS-monitored meal evaluations. Primary and secondary endpoint measures will be collected at 3 and 6 months. Discussion This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the benefits of the use of LUS for monitoring silent and apparent aspiration in the management of dysphagia and its impact on pulmonary illness and growth and (2) to investigate the impact of the LUS management on blood sample and bone metabolism, pain and interaction with caregivers. Trial registration Trial registration date 02/05/2020; ClinicalTrials.gov Identifier: NCT04253951.

The robotic platform for cholecystectomy has been extensively studied in comparison to its laparoscopic counterpart with acceptable outcomes. However, wide acceptance of a robotic approach to cholecystectomy has been limited by increased operative room (OR) times and substantially higher cost. This is a single-institution retrospective review of Veteran patients presenting for elective laparoscopic (LC) and robotic (RC) cholecystectomies for benign biliary disease at the Dallas VA Medical Center. The primary goal was to interrogate 30-day morbidity as well as operative room times, estimated blood loss (EBL), hospital length of stay (LOS), and conversion rates. The entire cohort included 612 patients (age = 55.1 ± 12.9 years, men = 77.9%, BMI = 31.2 ± 6.3 kg/m2) undergoing elective cholecystectomy (LC = 441 and RC = 171) for benign biliary disease (biliary colic = 78.8%, history of biliary pancreatitis = 7.8%, history of cholecystitis = 5.7%). Univariate analysis comparing LC and RC showed the two groups to be of similar age (55.4 ± 12.4 vs. 54.4 ± 14.2 years; p = 0.4), male gender (79.4% vs. 74.3%, p = 0.2), and BMI (31.1 ± 6.4 vs. 31.5 ± 6.3 kg/m2; p = 0.5). Except for dyslipidemia (LC = 48.3% vs. RC = 36.8%; p = 0.01), both groups had the same rate of co-morbid conditions. ASA level III and IV (LC = 60.1 vs. RC = 69.0%, p = 0.04) was higher in the RC group. Both groups underwent surgical intervention for similar indications (biliary colic LC = 80.5% vs. RC = 74.3; p = 0.1). Hospital LOS (1.7 ± 3.2 vs. 0.3 ± 0.9 days, p