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

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 ..

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

Secukinumab for Psoriasis in Obese Patients: Minireview and Clinical Experience

Psoriasis (PsO) has been associated with obesity, and its severity increases in obese subjects. The link between psoriatic condition and obesity is based on shared pathophysiological pathways where local and systemic inflammation promote each other; PsO is an inflammatory, immune-mediated disease, and the adipose tissue is the source of proinflammatory adipokines. Moreover, psoriatic arthritis (PsA) is an important comorbidity of PsO that reduces quality of life and makes difficult the patient's management. Treatment of obese subjects with moderate to severe PsO, even more if PsA is present, is challenging because of reduced efficacy of several systemic drugs and increased risk of adverse events. Secukinumab, a monoclonal antibody that selectively binds to and neutralizes interleukin 17A, shows efficacy on PsO in all body weight groups, even in the highest, whose response has a slight downward trend. Clinical features of two obese subjects, affected by PsO and PsA, successfully treated with secukinumab, are described

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates

The Prevalence and Indications of Intravenous Rehydration Therapy in Hospital Settings: A Systematic Review

Objective: We performed a systematic review to explore the prevalence of intravenous (IV) rehydration therapy in hospital settings, and we assessed it by patient groups and populations. Methods: A systematic review of major databases and grey literature was undertaken from inception to 28 March 2022. Studies reporting prevalence of IV rehydration therapy in a hospital setting were identified. The data were synthesised in a narrative approach. (3) Results: Overall, 29 papers met the inclusion criteria. The prevalence of IV rehydration therapy in paediatric patients ranged from 4.5% (hospitalised with diarrhoea and dehydration) to 100% (admitted to the emergency department with mild to moderate dehydration caused by viral gastroenteritis), and in adults this ranged from 1.5% (had single substance ingestion of modafinil) to 100% (hospitalised with hypercalcemia). The most common indication for IV rehydration therapy in paediatric patients was dehydration due to fluid loss from the gastrointestinal tract. Other causes included malnutrition, neuromuscular disease, bronchiolitis, and influenza. In adults, indications for IV rehydration therapy were much more diverse: fever, diarrhoea, drug intoxication, hypercalcemia, cancer, and postural tachycardia syndrome; (4) Conclusions: This systematic review showed that IV rehydration therapy in paediatric patients is often used to treat dehydration and diarrhoea, while in adults it has a broader spectrum of use. While IV rehydration therapy is important in correcting fluid problems and electrolyte status, the maintenance fluid prescribing practices vary considerably, and guidelines are scarce

Tissue carcinoembryonic antigen and oestrogen receptor status in breast carcinoma: an immunohistochemical study of clinical outcome in a series of 252 patients with long-term follow-up.

Carcinoembryonic antigen (CEA) is a well-known tumour marker whose immunohistochemical expression could be prognostically relevant in breast carcinomas. We evaluated CEA immunohistochemical expression, using the specific T84.66 monoclonal antibody, in a series of 252 consecutive cases of infiltrating breast carcinomas (104 N0, 148 N1/2) with median follow-up of 84 months. Oestrogen receptor (ER) status has been evaluated with the immunohistochemical method (ER1D5 antibody, 10% cut-off value): 121 cases were ER negative, 128 cases were ER positive and in three cases ER status was unknown. CEA staining was cytoplasmic; staining intensity and percentage of reacting cells were combined to obtain a final score (CEA score). The difference between the distribution of CEA score within the modalities of the other variables was not statistically significant. Univariate survival analysis has been performed on the series of node-negative and node-positive patients. In the latter subgroup, this has been performed separately for patients treated with systemic adjuvant hormonal therapy or chemotherapy. A multivariate analysis was only performed for node-positive patients treated with adjuvant therapy. CEA immunoreactivity was not prognostically relevant in any subset of analysed patients. The most important prognostic markers were nodal status and tumour size