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Background: The aim of this systematic review is to investigate effectiveness and safety of sedation–analgesia techniques in controlling pain during botulinum injections in patients with cerebral palsy (CP). Methods: The Pubmed, Cinahl, and Scopus databases were searched. Inclusion criteria were as follows: cerebral palsy; any type of outcome measure regarding pain and side effects assessment; any type of studies; and English language. RoB2 and Robins-I were applied to assess the risk of bias. Tables and forest plots synthetized the findings. Results: Seventeen reports were included; most regarded pain control, and ten investigated side effects. Three were RCTs, three were controlled, and twelve were observational studies. Several techniques were used, often in combination, such as non-pharmacological approaches (clown care or virtual reality); topical anesthesia with Emla®®, vapocoolant spray, or ice; and light-to-deep sedation with inhaled nitrous oxide, intranasal fentanyl, rectal, enteral, or intravenous midazolam, or intravenous ketamine or propofol. Vomiting and oxygen desaturation were uncommon complications. Conversely, the pooled incidence of other minor side effects was 6.39% (95% CI: 1.47–14.42%) under the random-effects model, with considerable heterogeneity. Conclusions: All the techniques are safe, if administered in an appropriate setting. Deep sedation is more effective in pain control but requires an anesthetist. A combined individualized approach is preferrable. PROSPERO CRD42025639999.

Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT), often accompanied by non-alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters') with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks), inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks), genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by adaptations in expression of gene clusters that control lipid metabolism and inflammatory processes in an orchestrated and interrelated manner.

There is growing evidence that genomic and proteomic research holds great potential for changing irrevocably the practice of medicine. The ability to identify important genomic and biological markers for risk assessment can have a great impact in public health from disease prevention, to detection, to treatment selection. However, the potentially large number of markers and the complexity in the relationship between the markers and the outcome of interest impose a grand challenge in developing accurate risk prediction models. The standard approach to identifying important markers often assesses the marginal effects of individual markers on a phenotype of interest. When multiple markers relate to the phenotype simultaneously via a complex structure, such a type of marginal analysis may not be effective. To overcome such difficulties, we employ a kernel machine Cox regression framework and propose an efficient score test to assess the overall effect of a set of markers, such as genes within a pathway or a network, on survival outcomes. The proposed test has the advantage of capturing the potentially nonlinear effects without explicitly specifying a particular nonlinear functional form. To approximate the null distribution of the score statistic, we propose a simple resampling procedure that can be easily implemented in practice. Numerical studies suggest that the test performs well with respect to both empirical size and power even when the number of variables in a gene set is not small compared to the sample size.

Background/Objectives: International guidelines recommend the use of orthoses in subjects with cerebral palsy (CP), even though there is limited evidence of their effectiveness. Little is known about their effectiveness in children and adolescents with other types of neuromotor disability. Methods: The review protocol was recorded on the PROSPERO register (CRD42024509165) and conformed to the PRISMA guidelines. The inclusion criteria were any type of ankle–foot orthoses (AFOs); pediatric subjects with any non-acquired neuromotor disease; any type of outcome measure regarding gait performance; controlled studies; and those in the English language. Screening, selection, risk of bias assessment, and data extraction were performed by a group of independent researchers. Results: Fifty-seven reports were included, with most regarding CP; three involved subjects with Charcot–Marie–Tooth disease or Duchenne dystrophy. Nine were RCTs. A meta-analysis was performed for studies including subjects with CP. The meta-analysis demonstrated the effectiveness of AFOs in increasing stride length (MD −10.21 [−13.92, −6.51]), ankle dorsiflexion at IC (MD 9.66 [7.05, 12.27]), and peak ankle DF in stance (MD 5.72 [2.34, 9.09]) while reducing cadence (MD 0.13 [0.06, 0.17]) and the energy cost of walking (MD −0.02 [−0.03, −0.00]). The peak ankle power generated at push-off was significantly increased with flexible AFOs compared to rigid AFOs (MD 0.38 [0.30, 0.46]), but it decreased with both compared to walking barefoot or with shoes (MD −0.35 [−0.49, −0.22]). Evidence regarding DMD and CMT was limited but suggested opting for individualized flexible AFOs, which preserved peak ankle power generation. Conclusions: AFOs improve gait performance in CP. Flexible AFOs are preferable because they preserve the peak ankle power generated at push-off compared to rigid AFOs.

Background and Objective AtopyReg ® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. Methods Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. Results A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18–90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. Conclusions This baseline data analysis deriving from AtopyReg ® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients’ quality of life.

Background Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT), often accompanied by non-alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. Methodology/Principal Findings ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters') with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks), inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks), genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. Conclusion In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by adaptations in expression of gene clusters that control lipid metabolism and inflammatory processes in an orchestrated and interrelated manner.

We investigate theoretically the formation of a vortex lattice in a superfluid two-spin component Fermi gas in a rotating harmonic trap, in a BCS-type regime of condensed non-bosonic pairs. Our analytical solution of the superfluid hydrodynamic equations, both for the 2D BCS equation of state and for the 3D unitary quantum gas, predicts that the vortex free gas is subject to a dynamic instability for fast enough rotation. With a numerical solution of the full time dependent BCS equations in a 2D model, we confirm the existence of this dynamic instability and we show that it leads to the formation of a regular pattern of quantum vortices in the gas.

The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.

In a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers. Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field. Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Samples can be obtained from blood and most other bodily fluids. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids. In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients.