Higher order Levi forms on homogeneous CR manifolds

We investigate the nondegeneracy of higher order Levi forms on weakly nondegenerate homogeneous CR manifolds. Improving previous results, we prove that general orbits of real forms in complex flag manifolds have order less or equal than 3 and the compact ones less or equal 2. Finally we construct by Lie extensions weakly nondegenerate CR vector bundles with arbitrary orders of nondegeneracy

X-linked genodermatoses from diagnosis to tailored therapy

Background: Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods: During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources. Results: Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions: Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses

Omics sciences and precision medicine in melanoma

Background: This article provides an overview of the application of omics sciences in melanoma research. The name omics sciences refers to the large-scale analysis of biological molecules like DNA, RNA, proteins, and metabolites. Methods: In the course of this review, we have adopted a focu-sed research strategy, meticulously selecting the most pertinent and emblematic articles related to the topic. Our methodology included a systematic examination of the scientific literature to guarantee a thorough and precise synthesis of the existing sources. Results: With the advent of high-throughput technologies, omics have become an essential tool for understanding the complexity of melanoma. In this article, we discuss the different omics approaches used in melanoma research, including genomics, transcriptomics, proteomics, and metabolomics. We also highlight the major findings and insights gained from these studies, including the identification of new therapeutic targets and the development of biomarkers for diagnosis and prognosis. Finally, we discuss the challenges and future directions in omics-based melanoma research, including the integration of multiple omics data and the development of personalized medicine approaches. Conclusions: Overall, this article emphasizes the importance of omics science in advancing our understanding of melanoma and its potential for improving patient outcomes

Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases

Autoantibodies detection in patients affected by autoimmune retinopathies

Objective: Autoimmune retinopathies (ARs) encompass a spectrum of immune diseases that are characterized by the presence of autoantibodies against retinal proteins in the bloodstream. These autoantibodies (AAbs) lead to a progressive and sometimes rapid loss of vision. ARs commonly affect subjects over 50 years of age, but also rare cases of kids under 3 years of age have been reported. Patients and methods: In this study, 47 unrelated Caucasian patients were enrolled. All subjects showed negative cancer diagnoses and negative results in their genetic screenings. We studied 8 confirmed retinal antigens using Western blotting analysis, with α-enolase followed by carbonic anhydrase II being the two most frequently found in the patients' sera. Results: Nineteen patients were positive (40.4%), thirteen uncertain (27.7%), and fifteen were negative (31.9%). Their gender did not correlate with the presence of AAbs (p=0.409). Conclusions: AAbs are responsible for retinal degeneration in some cases, while in others, they contribute to exacerbating the progression of the disease; however, their detection is crucial to reaching a better diagnosis and developing more effective treatments for these conditions. Moreover, finding good biomarkers is important not only for AR monitoring and prognosis, but also for helping with early cancer diagnosis

Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study

Background Feline nonflea hypersensitivity dermatitis (NFHD) is a frequent cause of over-grooming, scratching and skin lesions. Multimodal therapy often is necessary. Hypothesis/Objectives To investigate the efficacy of ultramicronized palmitoylethanolamide (PEA-um) in maintaining methylprednisolone-induced remission in NFHD cats. Animals Fifty-seven NFHD cats with nonseasonal pruritus were enrolled originally, of which 25 completed all study requirements to be eligible for analysis. Methods and materials Cats were randomly assigned to PEA-um (15 mg/kg per os, once daily; n = 29) or placebo (n = 28) while receiving a 28 day tapering methylprednisolone course. Cats responding favourably to methylprednisolone were then administered only PEA-um (n = 21) or placebo (n = 23) for another eight weeks, followed by a four week long treatment-free period. Cats were maintained in the study until relapse or study end, whichever came first. Primary outcome was time to relapse. Secondary outcomes were pruritus Visual Analog Scale (pVAS), SCORing Feline Allergic Dermatitis scale (SCORFAD) and owner Global Assessment Score (GAS). Results Mean relapse time was 40.5 days (+/- 7.8 SE) in PEA-um treated cats (n = 13) and 22.2 days (+/- 3.7 SE) for placebo (n = 12; P = 0.04). On Day 28, the severity of pruritus was lower in the PEA-um treated cats compared to placebo (P = 0.03). Mean worsening of pruritus at the final study day was lower in the PEA-um group compared to placebo (P = 0.04), whereas SCORFAD was not different between groups. Mean owner GAS at the final study day was better in the PEA-um than the placebo-treated group (P = 0.05). Conclusion and clinical importance Ultramicronized palmitoylethanolamide could represent an effective and safe option to delay relapse in NFHD cats

Natural Diagonal Riemannian Almost Product and Para-Hermitian Cotangent Bundles

We obtain the natural diagonal almost product and locally product structures on the total space of the cotangent bundle of a Riemannian manifold. We find the Riemannian almost product (locally product) and the (almost) para-Hermitian cotangent bundles of natural diagonal lift type. We prove the characterization theorem for the natural diagonal (almost) para-K\"ahlerian structures on the total spaces of the cotangent bundle.Comment: 10 pages, will appear in Czechoslovak Mathematical Journa

Rationality in Differential Algebraic Geometry

Parametric Cartan theory of exterior differential systems, and explicit cohomology of projective manifolds reveal united rationality features of differential algebraic geometry.Comment: Abel Symposium 201

A Laboratory of Extremophiles: Iceland Coordination Action for Research Activities on Life in Extreme Environments (CAREX) Field Campaign

Existence of life in extreme environments has been known for a long time, and their habitants have been investigated by different scientific disciplines for decades. However, reports of multidisciplinary research are uncommon. In this paper, we report an interdisciplinary three-day field campaign conducted in the framework of the Coordination Action for Research Activities on Life in Extreme Environments (CAREX) FP7EU program, with participation of experts in the fields of life and earth sciences. In situ experiments and sampling were performed in a 20 m long hot springs system of different temperature (57 \ub0C to 100 \ub0C) and pH (2 to 4). Abiotic factors were measured to study their influence on the diversity. The CO2 and H2S concentration varied at different sampling locations in the system, but the SO2 remained the same. Four biofilms, mainly composed by four different algae and phototrophic protists, showed differences in photosynthetic activity. Varying temperature of the sampling location affects chlorophyll fluorescence, not only in the microbial mats, but plants (Juncus), indicating selective adaptation to the environmental conditions. Quantitative polymerase chain reaction (PCR), DNA microarray and denaturing gradient gel electrophoresis (DGGE)-based analysis in laboratory showed the presence of a diverse microbial population. Even a short duration (30 h) deployment of a micro colonizer in this hot spring system led to colonization of microorganisms based on ribosomal intergenic spacer (RISA) analysis. Polyphasic analysis of this hot spring system was possible due to the involvement of multidisciplinary approaches

Database analysis of children and adolescents with Bipolar Disorder consuming a micronutrient formula

<p>Abstract</p> <p>Background</p> <p>Eleven previous reports have shown potential benefit of a 36-ingredient micronutrient formula (known as EMPowerplus) for the treatment of psychiatric symptoms. The current study asked whether children (7-18 years) with pediatric bipolar disorder (PBD) benefited from this same micronutrient formula; the impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on their response was also evaluated.</p> <p>Methods</p> <p>Data were available from an existing database for 120 children whose parents reported a diagnosis of PBD; 79% were taking psychiatric medications that are used to treat mood disorders; 24% were also reported as ADHD. Using Last Observation Carried Forward (LOCF), data were analyzed from 3 to 6 months of micronutrient use.</p> <p>Results</p> <p>At LOCF, mean symptom severity of bipolar symptoms was 46% lower than baseline (effect size (ES) = 0.78) (<it>p </it>< 0.001). In terms of responder status, 46% experienced >50% improvement at LOCF, with 38% still taking psychiatric medication (52% drop from baseline) but at much lower levels (74% reduction in number of medications being used from baseline). The results were similar for those with both ADHD and PBD: a 43% decline in PBD symptoms (ES = 0.72) and 40% in ADHD symptoms (ES = 0.62). An alternative sample of children with just ADHD symptoms (n = 41) showed a 47% reduction in symptoms from baseline to LOCF (ES = 1.04). The duration of reductions in symptom severity suggests that benefits were not attributable to placebo/expectancy effects. Similar findings were found for younger and older children and for both sexes.</p> <p>Conclusions</p> <p>The data are limited by the open label nature of the study, the lack of a control group, and the inherent self-selection bias. While these data cannot establish efficacy, the results are consistent with a growing body of research suggesting that micronutrients appear to have therapeutic benefit for children with PBD with or without ADHD in the absence of significant side effects and may allow for a reduction in psychiatric medications while improving symptoms. The consistent reporting of positive changes across multiple sites and countries are substantial enough to warrant a call for randomized clinical trials using micronutrients.</p