MENGA: a new comprehensive tool for the integration of neuroimaging data and the Allen human brain transcriptome atlas

Brain-wide mRNA mappings offer a great potential for neuroscience research as they can provide information about system proteomics. In a previous work we have correlated mRNA maps with the binding patterns of radioligands targeting specific molecular systems and imaged with positron emission tomography (PET) in unrelated control groups. This approach is potentially applicable to any imaging modality as long as an efficient procedure of imaging-genomic matching is provided. In the original work we considered mRNA brain maps of the whole human genome derived from the Allen human brain database (ABA) and we performed the analysis with a specific region-based segmentation with a resolution that was limited by the PET data parcellation. There we identified the need for a platform for imaging-genomic integration that should be usable with any imaging modalities and fully exploit the high resolution mapping of ABA dataset.In this work we present MENGA (Multimodal Environment for Neuroimaging and Genomic Analysis), a software platform that allows the investigation of the correlation patterns between neuroimaging data of any sort (both functional and structural) with mRNA gene expression profiles derived from the ABA database at high resolution.We applied MENGA to six different imaging datasets from three modalities (PET, single photon emission tomography and magnetic resonance imaging) targeting the dopamine and serotonin receptor systems and the myelin molecular structure. We further investigated imaging-genomic correlations in the case of mismatch between selected proteins and imaging targets

Prevention of vertical transmission of hepatitis B virus infection

Hepatitis B virus (HBV) is the leading cause of chronic viral hepatitis. Annually, almost two million children younger than 5 years acquire the infection, mostly through vertical or horizontal transmission in early life. Vertical transmission of HBV is a high efficacy phenomenon ranging, in the absence of any preventive interventions, from 70% to 90% for hepatitis e antigen positive mothers and from 10% to 40% for hepatitis e antigen-negative mothers. Maternal viraemia is a preeminent risk factor for vertical transmission of HBV. Maternal screening is the first step to prevent vertical transmission of HBV. Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection. Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low- and middle-income countries where the prevalence of the infection is at the highest

Post-COVID-19 acute sarcopenia: physiopathology and management

In this review, we discuss the pathophysiologic and management aspects of acute sarcopenia in relation to SARS-CoV-2 infection. COVID-19 is as a multi-organ infectious disease characterized by a severe inflammatory and highly catabolic status, influencing the deep changes in the body build, especially the amount, structure, and function of skeletal muscles which would amount to acutely developed sarcopenia. Acute sarcopenia may largely impact patients’ in-hospital prognosis as well as the vulnerability to the post-COVID-19 functional and physical deterioration. The individual outcome of the COVID-19 and the degree of muscle mass and functional loss may be influenced by multiple factors, including the patient’s general pre-infection medical and functional condition, especially in older adults. This paper gathers the information about how the SARS-CoV-2 hyper-inflammatory involvement exacerbates the immunosenescence process, enhances the endothelial damage, and due to mitochondrial dysfunction and autophagy, induces myofibrillar breakdown and muscle degradation. The aftermath of these acute and complex immunological SARS-CoV-2-related phenomena, augmented by anosmia, ageusia and altered microbiota may lead to decreased food intake and exacerbated catabolism. Moreover, the imposed physical inactivity, lock-down, quarantine or acute hospitalization with bedrest would intensify the acute sarcopenia process. All these deleterious mechanisms must be swiftly put to a check by a multidisciplinary approach including nutritional support, early physical as well cardio-pulmonary rehabilitation, and psychological support and cognitive training. The proposed holistic and early management of COVID-19 patients appears essential to minimize the disastrous functional outcomes of this disease and allow avoiding the long COVID-19 syndrome. © 2021, The Author(s)

Treatment of multidrug-resistant and extensively drug-resistant tuberculosis in children: The role of bedaquiline and delamanid

Multidrug-resistant (MDR) tuberculosis (TB) has been emerging at an alarming rate over the last few years. It has been estimated that about 3% of all pediatric TB is MDR, meaning about 30,000 cases each year. Although most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with extensively drug-resistant (XDR) TB had limited treatment options and no standard regimen. The main objective of this manuscript is to discuss our present knowledge of the management of MDR-and XDR-TB in children, focusing on the characteristics and available evidence on the use of two promising new drugs: bedaquiline and delamanid. PubMed was used to search for all of the studies published up to November 2020 using key words such as “bedaquiline” and “delamanid” and “children” and “multidrug-resistant tuberculosis” and “extensively drug-resistant tuberculosis”. The search was limited to articles published in English and providing evidence-based data. Although data on pediatric population are limited and more studies are needed to confirm the efficacy and safety of bedaquiline and delamanid, their use in children with MDR-TB/XDR-TB appears to have good tolerability and efficacy. However, more evidence on these new anti-TB drugs is needed to better guide their use in children in order to design effective shorter regimens and reduce adverse effects, drug interactions, and therapeutic failure

Efficacy of topical imiquimod 3.75% in the treatment of actinic keratosis of the scalp in immunosuppressed patients: our case series

AbstractBackground: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients ..

Antibody-dependent cellular cytotoxicity against drug-induced antigens in L5178Y mouse lymphoma.

In vivo treatment with antineoplastic compounds has been reported to lead to the expression of new antigenic specificities which were not detected on parental cells, and which were transmissible as a genetic character. The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. LY/DTIC target cells coated with LY/DTIC-immune serum were specifically lysed by virgin lymphocytes. The genetic background of the effector cells, whether syngeneic, allogeneic or xenogeneic, did not produce significant differences in the percentage of target-cell lysis. ADCC activity was reduced when the immune serum was added directly to the incubation medium, without precoating. Although sera from individual animals exhibited different levels of ADCC activity, they nevertheless followed the general trend of the pooled sera. Peak activity of ADCC was obtained in the sera collected on Days 8 and 30 after LY/DTIC cell challenge. The ADCC activity elicited by LY/DTIC cells may contribute to the rejection of drug-altered tumour cells

Interpreting the long-term variability of the changing-look AGN Mrk 1018

We present a thorough study of the Changing-Look Active Galactic Nucleus (CL-AGN) Mrk 1018, utilizing an extensive dataset spanning optical, UV, and X-ray spectro-photometric data from 2005 to 2019. We analysed X-ray spectra and broad-band photometry, and performed optical-to-X-ray spectral energy distribution (SED) fitting to comprehend the observed changing-look behaviour. We found that over the 14 years in analysis, significant changes in X-ray spectra occurred, as the hardness ratio increases by a factor of ~2. We validated also the broad-band dimming, with optical, UV, and X-ray luminosities decreasing by factors of >7, >24 and ~9, respectively. These dims are attributed to the declining UV emission. We described the X-ray spectra with a two-Comptonization model, revealing a consistent hot comptonizing medium but a cooling warm component. This cooling, linked to the weakening of the magnetic fields in the accretion disk, explains the UV dimming. We propose that the weakening is caused by the formation of a jet, in turn originated from the change of state of the inner accretion flow. Our optical-to-X-ray SED fitting supports this conclusion, as the normalised accretion rate is super-critical ($\mu=$0.06>0.02) in the bright state and sub-critical ($\mu=$0.01<0.02) in the faint state. Instabilities arising at the interface of the state-transition are able to reduce the viscous timescale to the observed ~10 years of Mrk 1018 variability. We explored a possible triggering mechanism for this state transition, involving gaseous clouds pushed onto the AGN sub-pc regions by a recent merging event or by cold chaotic accretion. This scenario, if validated by future simulations, could enhance our understanding of CL-AGN and raises questions about an accretion rate of ~0.02, coupled with minor disturbances in the accretion disk, being the primary factor in the changing-look phenomenon.Comment: 18 pages, 8 figure

Vaccines and Senior Travellers

Background: International tourist travel has been increasingly steadily in recent years, and looks set to reach unprecedented levels in the coming decades. Among these travellers, an increasing proportion is aged over 60&nbsp;years, and is healthy and wealthy enough to be able to travel. However, senior travellers have specific risks linked to their age, health and travel patterns, as compared to their younger counterparts. Methods: We review here the risk of major vaccine-preventable travel-associated infectious diseases, and forms and efficacy of vaccination for these diseases. Results: Routine vaccinations are recommended for older persons, regardless of whether they travel or not (e.g., influenza, pneumococcal vaccines). Older individuals should be advised about the vaccines that are recommended for their age group in the framework of the national vaccination schedule. Travel-specific vaccines must be discussed in detail on a case-by-case basis, and the risk associated with the vaccine should be carefully weighed against the risk of contracting the disease during travel. Travel-specific vaccines reviewed here include yellow fever, hepatitis, meningococcal meningitis, typhoid fever, cholera, poliomyelitis, rabies, Japanese encephalitis, tick-borne encephalitis and dengue. Conclusion: The number of older people who have the good health and financial resources to travel is rising dramatically. Older travellers should be advised appropriately about routine and travel-specific vaccines, taking into account the destination, duration and purpose of the trip, the activities planned, the type of accommodation, as well as patient-specific characteristics, such as health status and current medications