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BACKGROUND: We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). METHODS: In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. RESULTS: Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. CONCLUSION: The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.
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Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.
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PURPOSE OF REVIEW: Chronic inducible urticaria (CIndU) is a group of long-persisting and challenging to manage diseases, characterized by recurrent wheals and angioedema induced by definite triggers. In this review, we address recent findings on CIndU pathogenesis, diagnosis as well as its treatment, and we discuss novel potential targets that may lead to the development of more effective therapies for CIndU patients. RECENT ADVANCES: Meaningful advances in the understanding of its pathogenesis have been reported in the last decades. Novel CIndU-specific patient-reported outcome measures enable a closer and better evaluation of patients. CIndU is a hard-to-treat disease that highly impairs quality of life (QoL) of affected patients. Provocation tests allow to diagnose CIndU subtypes. The only licensed and recommended treatment for CIndU are second generation non-sedating H1-antihistamines, which lack efficacy in many cases. Omalizumab off-label use has been assessed in all types of CIndU with overall good outcomes. Promising emerging therapies currently assessed in chronic spontaneous urticaria are paving the path for novel treatments for CIndU.
Subject(s)
Chronic Urticaria , Omalizumab , Humans , Chronic Urticaria/drug therapy , Chronic Urticaria/immunology , Chronic Urticaria/therapy , Omalizumab/therapeutic use , Quality of Life , Anti-Allergic Agents/therapeutic use , Urticaria/drug therapy , Urticaria/etiology , Urticaria/diagnosis , Urticaria/immunology , Urticaria/therapyABSTRACT
Chronic itch is a frequent and debilitating condition that greatly affects the quality of life of those affected. In a subset of patients, damage to the peripheral or central nervous system constitutes the cause of the itch. Small-fiber neuropathy, nerve compression syndromes, post-herpetic neuralgia, scars and burns are possible conditions affecting the peripheral nervous system potentially causing itch, whereas space-occupying lesions affecting the spinal cord and stroke are examples of conditions that may induce central itch. Neuropathic itch starts on normal appearing skin, is often accompanied by pain sensations and other dysesthesias, and usually relieved by local cold application. Its distribution depends on the affected site of the somatosensory system. A comprehensive medical history is paramount to reach the diagnosis, while complementary diagnostics with skin biopsies for the investigation of cutaneous neuromorphological alterations or medical imaging to rule out nerve impingement may be advised in selected cases. Topical agents such as capsaicin or local anesthetics as well as systemic drugs such as gabapentinoids, antidepressants and opioid receptor modulators are used in the treatment of neuropathic itch. This review article provides an overview of the clinical features, underlying causes, diagnostic workup and therapeutic approach in neuropathic itch.
Subject(s)
Pruritus , Humans , Pruritus/therapy , Pruritus/diagnosis , Pruritus/physiopathology , Pruritus/etiology , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/physiopathologyABSTRACT
It is well-established that unstructured unsupervised socializing with peers (UUS) motivates deviance while in that specific context. In this article, we extend this situational view by arguing that repeated UUS may also gradually shape adolescents' norms and decision making beyond the situation. Specifically, we argue that UUS promotes short-term mindsets, i.e., an increased focus on present rewards at the expense of considering future consequences. We test this hypothesis with fixed-effects models, using longitudinal data from a representative sample of 1,675 adolescents from Zurich, Switzerland. Consistent with our preregistered predictions, more frequent UUS is associated with increased short-term mindsets. Thus, our finding suggests that the effects of UUS on later deviance might be driven by becoming more present-oriented. This link offers new insights into the developmental pathways toward adolescent delinquency and offers a potential target for intervention. Supplementary Information: The online version contains supplementary material available at 10.1007/s40865-024-00249-2.
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Layered perovskites with Ruddlesden-Popper-type structures are fundamentally important for low-dimensional properties, for example, photovoltaic hybrid iodides and superconducting copper oxides. Many such halides and oxides are known, but analogous nitrides are difficult to stabilize due to the high cation oxidation states required to balance the anion charges. Here we report the high-pressure synthesis of three single-layer Ruddlesden-Popper (K2NiF4 type) nitrides-Pr2ReN4, Nd2ReN4 and Ce2TaN4-along with their structural characterization and properties. The R2ReN4 materials (R = Pr and Nd) are metallic, and Nd2ReN4 has a ferromagnetic Nd3+ spin order below 15 K. Thermal decomposition gives R2ReN3 with a Peierls-type distortion and chains of Re-Re multiply bonded dimers. Ce2TaN4 has a structural transition driven by octahedral tilting, with local distortions and canted magnetic Ce3+ order evidencing two-dimensional Ce3+/Ce4+ charge ordering correlations. Our work demonstrates that Ruddlesden-Popper nitrides with varied structural, electronic and magnetic properties can be prepared from high-pressure synthesis, opening the door to related layered nitride materials.
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Galactomannans are polysaccharides obtained from legume seed extraction. They present a chemical structure consisting of D-mannose chains linked by glycosidic bonds and galactose branches. The main focus lies in their use as thickeners in the food industry, aimed at improving the dielectric properties of food during heating processes within the radiofrequency and microwave ranges. In this work, the prepared galactomannan samples were electrically analyzed through impedance spectroscopy, which is a powerful physical technique. From the experimental measurements, the dielectric permittivity and loss tangent of the galactomannan solutions were analyzed and the electrical modulus formalism was used to study the dielectric relaxations. Crude galactomannans exhibited higher values of permittivity, conductivity, and losses compared to purified galactomannans. Increasing ethanol concentration in galactomannan purification causes an increase in the permittivity and conductivity of galactomannan solutions. In a 1% solution, at 1 kHz, the permittivity increased from 378.56 to 538.09, while in the 2% solution, this increase was from 656.22 to 1103.24. Regarding the conductivity, at the same frequency, the increase was from 1.6 × 10-3 to 3.3 × 10-3 Ω-1m-1 and from 2.9 × 10-3 to 5.5 × 10-3 Ω-1m-1, respectively. The rise of the ethanol concentration in galactomannan purification led to a decrease in the relaxation time, from 448.56 to 159.15 µs and from 224.81 to 89.50 µs in the solution with 1 and 2%, respectively. The results suggest that galactomannan from Adenanthera pavonina L. has potential for use in the food industry.
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The term "urticaria" was first introduced by William Cullen in the eighteenth century. Urticaria is a common mast cell-mediated cutaneous disease presenting with pruritic wheals, angioedema, or both. It is classified as acute (≤6 weeks) or chronic (>6 weeks) and as spontaneous (no definite triggers) or inducible (definite and subtype-specific triggers). The international urticaria guideline on the definition, classification, diagnosis, and management of urticaria is revised every 4 years. The global network of Urticaria Centers of Reference and Excellence, the biggest and most active consortium of urticaria specialists, offers physicians and patients several research, educational, and digital care initiatives.
Subject(s)
Urticaria , Humans , Disease Management , Urticaria/classification , Urticaria/diagnosis , Urticaria/therapyABSTRACT
As the number of electronic gadgets in our daily lives is increasing and most of them require some kind of human interaction, this demands innovative, convenient input methods. There are limitations to state-of-the-art (SotA) ultrasound-based hand gesture recognition (HGR) systems in terms of robustness and accuracy. This research presents a novel machine learning (ML)-based end-to-end solution for hand gesture recognition with low-cost micro-electromechanical (MEMS) system ultrasonic transducers. In contrast to prior methods, our ML model processes the raw echo samples directly instead of using pre-processed data. Consequently, the processing flow presented in this work leaves it to the ML model to extract the important information from the echo data. The success of this approach is demonstrated as follows. Four MEMS ultrasonic transducers are placed in three different geometrical arrangements. For each arrangement, different types of ML models are optimized and benchmarked on datasets acquired with the presented custom hardware (HW): convolutional neural networks (CNNs), gated recurrent units (GRUs), long short-term memory (LSTM), vision transformer (ViT), and cross-attention multi-scale vision transformer (CrossViT). The three last-mentioned ML models reached more than 88% accuracy. The most important innovation described in this research paper is that we were able to demonstrate that little pre-processing is necessary to obtain high accuracy in ultrasonic HGR for several arrangements of cost-effective and low-power MEMS ultrasonic transducer arrays. Even the computationally intensive Fourier transform can be omitted. The presented approach is further compared to HGR systems using other sensor types such as vision, WiFi, radar, and state-of-the-art ultrasound-based HGR systems. Direct processing of the sensor signals by a compact model makes ultrasonic hand gesture recognition a true low-cost and power-efficient input method.
Subject(s)
Gestures , Hand , Machine Learning , Neural Networks, Computer , Humans , Hand/physiology , Pattern Recognition, Automated/methods , Ultrasonography/methods , Ultrasonography/instrumentation , Ultrasonics/instrumentation , AlgorithmsABSTRACT
Background: With the introduction of the ICD-11 into clinical practice, the reliable distinction between Posttraumatic Stress Disorder (PTSD) and Complex Posttraumatic Stress Disorder (CPTSD) becomes paramount. The semi-structured clinician-administered International Trauma Interview (ITI) aims to close this gap in clinical and research settings.Objective: This study investigated the psychometric properties of the German version of the ITI among trauma-exposed clinical samples from Switzerland and Germany.Method: Participants were 143 civilian and 100 military participants, aged M = 40.3 years, of whom 53.5% were male. Indicators of reliability and validity (latent structure, internal reliability, inter-rater agreement, convergent and discriminant validity) were evaluated. Confirmatory factor analysis (CFA) and partial correlation analysis were conducted separately for civilian and military participants.Results: Prevalence of PTSD was 30% (civilian) and 33% (military) and prevalence of CPTSD was 53% (civilians) and 21% (military). Satisfactory internal consistency and inter-rater agreement were found. In the military sample, a parsimonious first-order six-factor model was preferred over a second-order two-factor CFA model of ITI PTSD and Disturbances in Self-Organization (DSO). Model fit was excellent among military participants but no solution was supported among civilian participants. Overall, convergent validity was supported by positive correlations of ITI PTSD and DSO with DSM-5 PTSD. Discriminant validity for PTSD symptoms was confirmed among civilians but low in the military sample.Conclusions: The German ITI has shown potential as a clinician-administered diagnostic tool for assessing ICD-11 PTSD and CPTSD in primary care. However, further exploration of its latent structure and discriminant validity are indicated.
This study validated the German International Trauma Interview (ITI), a semi-structured clinician-administered diagnostic interview for ICD-11 Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder.Internal reliability, inter-rater agreement, latent structure, and convergent validity were explored in trauma-exposed clinical and military samples from five different in- and outpatient centres in Germany and German-speaking Switzerland.The findings supported the German ITI's reliability, inter-rater agreement, convergent validity and usefulness from a patient perspective. Future research should explore its factor structure and discriminant validity, for which differences between the samples were found.
Subject(s)
Psychometrics , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/diagnosis , Male , Female , Adult , Germany , Psychometrics/standards , Reproducibility of Results , Switzerland , Military Personnel/psychology , Military Personnel/statistics & numerical data , Interview, Psychological , Prevalence , Middle Aged , Factor Analysis, StatisticalABSTRACT
We propose a novel (to our knowledge) and simple real-time optical monitoring (RTOM) system for dynamic spectral analysis of telecommunication signals, involving electro-optic (EO) temporal sampling followed by dispersion-induced frequency-to-time mapping and high-speed photodetection. This system enables tracking of the presence and relative intensity of multiple wavelength-division-multiplexed (WDM) data streams that span over a broad frequency band with high resolution, accuracy, and fast measurement update rates. We derive the design conditions and trade-offs of the proposed scheme and report proof-of-concept experiments and a numerical result that demonstrate successful spectral monitoring of dense-WDM signals with different modulation formats and bit rates, over the full C-band, with the needed resolution to discern channels separated by a few tens of GHz, and with an unprecedented fast measurement update rate in the MHz range.
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AIM: To identify current key areas for nursing research in Switzerland, we revised the Swiss Research Agenda for Nursing (SRAN) initially published in 2008. BACKGROUND: By developing a research agenda, nursing researchers internationally prioritize and cluster relevant topics within the research community. The process should be collaborative and systematic to provide credible information for decisionmakers in health care research, policy, and practice. SOURCES OF EVIDENCE: After a participative, systematic, and critical evaluation within and outside of the Swiss Association for Nursing Science, the updated SRAN 2019-2029 defines four research priorities (new models of care, nursing care interventions, work and care environment, and quality of care and patient safety) and four transversal themes (organization of research, research methodologies, research in health care policy and public health perspectives). CONCLUSION: Adding to other national nursing research agendas, the categories are organized in a framework of key research priorities and transversal themes. They relate to the importance of global and local foci of research as well as challenges in health care services and policy systems. The agenda is an important prerequisite for enhancing the influence of nursing research in Switzerland and provides guidance for the next decade. IMPLICATIONS FOR NURSING PRACTICE: The revised agenda ensures that research projects target key knowledge gaps and the discipline's core questions in respective countries. IMPLICATIONS FOR HEALTH POLICY: Nursing research should inform and influence health policy on all institutional and political levels. Therefore, the integration of public health perspectives in research is one of the most important new aspects of SRAN 2019-2029.
Subject(s)
Nursing Research , Switzerland , Humans , Health Policy , Health Priorities , Middle Aged , AdultABSTRACT
PURPOSE: One of the most pertinent questions in total knee arthroplasty (TKA) is: what could be considered normal coronal alignment? This study aims to define normal, neutral, deviant and aberrant coronal alignment using large data from a computed tomography (CT)-scan database and previously published phenotypes. METHODS: Coronal alignment parameters from 11,191 knee osteoarthritis (OA) patients were measured based on three dimensional reconstructed CT data using a validated planning software. Based on these measurements, patients' coronal alignment was phenotyped according to the functional knee phenotype concept. These phenotypes represent an alignment variation of the overall hip knee ankle angle (HKA), femoral mechanical angle (FMA) and tibial mechanical angle (TMA). Each phenotype is defined by a specific mean and covers a range of ±1.5° from this mean. Coronal alignment is classified as normal, neutral, deviant and aberrant based on distribution frequency. Mean values and distribution among the phenotypes are presented and compared between two populations (OA patients in this study and non-OA patients from a previously published study). RESULTS: The arithmetic HKA (aHKA), combined normalised data of FMA and TMA, showed that 36.0% of knees were neutral within ±1 SD from the mean in both angles, 44.3% had either a TMA or a FMA within ±1-2 SD (normally aligned), 15.3% of the patients were deviant within ±2-3 SD and only 4.4% of them had an aberrant alignment (±3-4 SD in 3.4% and >4 SD in 1.0% of the patients respectively). However, combining the normalised data of HKA, FMA and TMA, 15.4% of patients were neutral in all three angles, 39.7% were at least normal, 27.7% had at least one deviant angle and 17.2% had at least one aberrant angle. For HKA, the males exhibited 1° varus and females were neutral. For FMA, the females exhibited 0.7° more valgus in mean than males and grew 1.8° per category (males grew 2.1° per category). For TMA, the males exhibited 1.3° more varus than females and both grew 2.3° and 2.4° (females) per category. Normal coronal alignment was 179.2° ± 2.8-5.6° (males) and 180.5 > ± 2.8-5.6° (females) for HKA, 93.1 > ± 2.1-4.2° (males) and 93.8 > ± 1.8-3.6° (females) for FMA and 86.7 > ± 2.3-4.6° (males) and 88 > ± 2.4-4.8° (females) for TMA. This means HKA 6.4 varus or 4.8° valgus (males) or 5.1° varus to 6.1° valgus was considered normal. For FMA HKA 1.1 varus or 7.3° valgus (males) or 0.2° valgus to 7.4° valgus was considered normal. For TMA HKA 7.9 varus or 1.3° valgus (males) or 6.8° varus to 2.8° valgus was considered normal. Aberrant coronal alignment started from 179.2° ± 8.4° (males) and 180.5 > ± 8.4° (females) for HKA, 93.1 > ± 6.3° (males) 93.8 > ± 5.4° (females) for FMA and 86.7 > ± 6.9° (males) and 88 > ± 7.2° (females) for TMA. This means HKA > 9.2° varus or 7.6° valgus (males) or 7.9° varus to 8.9° valgus was considered aberrant. CONCLUSION: Definitions of neutrality, normality, deviance as well as aberrance for coronal alignment in TKA were proposed in this study according to their distribution frequencies. This can be seen as an important first step towards a safe transition from the conventional one-size-fits-all to a more personalised coronal alignment target. There should be further definitions combining bony alignment, joint surfaces' morphology, soft tissue laxities and joint kinematics. LEVEL OF EVIDENCE: III.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Male , Female , Humans , Arthroplasty, Replacement, Knee/methods , Knee Joint/diagnostic imaging , Knee Joint/surgery , Lower Extremity , Tibia/diagnostic imaging , Tibia/surgery , Femur/surgery , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Retrospective StudiesABSTRACT
Background: Previous research shows that 61% of children younger than 6 months in low- and middle-income countries (LMICs) are not exclusively breastfed. Although data on the role of pre- and postnatal depression on breastfeeding exclusivity is mixed, fetomaternal attachment might foster breastfeeding exclusivity. Thus, we tested the potential mediating role of fetomaternal attachment and postnatal depression in the relationship between maternal prenatal depression and exclusive breastfeeding. Materials and Methods: Data were collected as part of a prospective, cross-cultural project, Evidence for Better Lives Study, which enrolled 1208 expectant mothers, in their third trimester of pregnancy across eight sites, from LMICs. Of the whole sample, 1185 women (mean age = 28.32, standard deviation [SD] = 5.77) completed Computer-Aided Personal Interviews on prenatal depressive symptoms, fetomaternal attachment, and socioeconomic status. A total of 1054 women provided follow-up data at 3-6 months after birth, about postnatal depressive symptoms, exclusive breastfeeding, and infant health indicators. Path analysis was used to assess parallel mediation. Results: In the whole sample, the effect of prenatal depression on breastfeeding exclusivity was completely mediated by postnatal depression, whereas fetomaternal attachment did not mediate the relationship. The full mediation effect was replicated individually in Pakistan and Sri Lanka. Conclusions: The study results indicate that prenatal depression symptoms contributed to the development of depressive symptoms after birth, negatively affecting the probability of exclusive breastfeeding. Future research should explore this in early prevention interventions, increasing the chances of healthy child development in LMICs. Considering the mixed results around the sites, it is important to better understand the relationship between maternal depression, fetomaternal attachment and breastfeeding behavior in each site's socio-cultural context.
Subject(s)
Breast Feeding , Depression, Postpartum , Infant , Pregnancy , Child , Female , Humans , Adult , Depression, Postpartum/epidemiology , Prospective Studies , Depression/epidemiology , MothersABSTRACT
Evidence on the outcomes of adolescent dating violence (ADV) victimization mainly derives from cross-sectional studies, which have limitations in suggesting causal relationships. Furthermore, the complexity of factors and overlapping dimensions in dating violence research, such as the forms of violence experienced, may have contributed to the variability of findings across the literature. To address these gaps and provide a more comprehensive understanding of the impact of ADV, this study reviews findings from prospective cohort studies, with a focus on the type of violence experienced and the gender of the victim. A systematic search was conducted in nine electronic databases and additional relevant journals. Prospective longitudinal studies were included if dating violence victimization occurred during adolescence and chronologically preceded the outcomes. A quality assessment was conducted using the Mixed Methods Appraisal Tool. A narrative approach was used to synthesize findings. After screening 1,838 records, 14 publications met the selection criteria and were included in this review. Our findings suggest that experiencing ADV is longitudinally associated with many adverse outcomes, including higher internalizing symptoms and externalizing behaviors, poorer well-being, increased substance use, and increased revictimization. However, the associations are not consistently reported across studies when considering the type of ADV experienced and the gender of the victim. This review highlights the limited number of longitudinal studies examining the outcomes of ADV victimization, the unbalanced approach in investigating different forms of violence, and the lack of diverse samples examining this subject. Implications for research, policy, and practice are outlined.
Subject(s)
Adolescent Behavior , Crime Victims , Intimate Partner Violence , Adolescent , HumansABSTRACT
Background: South Africa has the largest HIV epidemic globally, with ~7.5 million people living with HIV in 2021. Adolescent girls (AG) and young women (YW), aged 15-19 years and 20-24 years, are twice as likely to be living with HIV as their male counterparts. The national HIV prevalence for young women was 9.1% (2021), with limited data on disease severity. Objectives: This study assessed very advanced HIV disease (CD4 < 100 cells/µL) in adolescent girls and young women (AGYW) in South Africa. Method: A retrospective descriptive study analysed data collated from the National Health Laboratory Service database for 2017 to 2021 calendar years for AGYW. National and provincial specimen volumes, the percentage of tests with a CD4 < 100 cells/µL and ≥ 100 cells/µL, and the median and interquartile ranges, were calculated. Logistic regression determined the odds ratio for a CD4 < 100 cells/µL, controlling for age category. Results: Data for 1 199 010 CD4 specimens indicated a significant decrease in volumes of 34% from 287 410 (2017) to 189 533 (2021). The percentage of samples with a count < 100 cells/µL ranged from 4.9% to 5.2% for YW versus 5.6% to 6.1% for AG. Provincial data for a CD4 count < 100 cells/µL ranged between 4.5% and 8.3% in AG and 3.6% to 6.3% for YW. Logistic regression indicated a 24% higher likelihood for AG having a CD4 count < 100 cells/µL. Conclusion: The study reported a higher proportion of very advanced HIV disease for AG versus YW nationally, with provincial disparity needing further analysis.
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In this study, we propose a novel micromechanical model for the brain white matter, which is described as a heterogeneous material with a complex network of axon fibers embedded in a soft ground matrix. We developed this model in the framework of RVE-based multiscale theories in combination with the finite element method and the embedded element technique for embedding the fibers. Microstructural features such as axon diameter, orientation and tortuosity are incorporated into the model through distributions derived from histological data. The constitutive law of both the fibers and the matrix is described by isotropic one-term Ogden functions. The hyperelastic response of the tissue is derived by homogenizing the microscopic stress fields with multiscale boundary conditions to ensure kinematic compatibility. The macroscale homogenized stress is employed in an inverse parameter identification procedure to determine the hyperelastic constants of axons and ground matrix, based on experiments on human corpus callosum. Our results demonstrate the fundamental effect of axon tortuosity on the mechanical behavior of the brain's white matter. By combining histological information with the multiscale theory, the proposed framework can substantially contribute to the understanding of mechanotransduction phenomena, shed light on the biomechanics of a healthy brain, and potentially provide insights into neurodegenerative processes.
Subject(s)
White Matter , Humans , White Matter/physiology , Mechanotransduction, Cellular , Stress, Mechanical , Brain/physiology , Biomechanical Phenomena , Finite Element Analysis , Models, BiologicalABSTRACT
Background: Chronic scratching imposes a major stress on the skin and can lead to itch intensity worsening, and consequently, patients may enter an itch-scratch cycle. This repetitive mechanical stress can result in lichenification, worsening of epidermal barrier function, and enhanced cutaneous inflammation. Furthermore, a reduction of intraepidermal nerve fibers was previously described in lichenification. Aim: The aim of this study was to investigate the influence of chronic scratching on the epidermal neuroanatomy and on sensory changes, in particular the prevalence of hyperknesis and alloknesis in patients after mechanical, chemical, and electrical stimuli. Methods: Analyses were performed on pruritic lichenified (chronically scratched), pruritic non-lichenified (not chronically scratched), and non-pruritic non-lesional (unaffected) skin areas of patients with inflammatory pruritus, i.e., atopic dermatitis (n = 35), and neuropathic pruritus, i.e., brachioradial pruritus (n = 34) vs. healthy matched controls (n = 64). Our fine-grained spatial skin characterization enabled specifically studying the differential effects of chronic scratching in inflammatory and neuropathic itch. Results: Analysis of intraepidermal nerve fiber density showed rarefaction of fibers in all three skin areas of patients compared with healthy controls in both diagnoses. Even more, the two pruritic areas had significantly less nerve fibers than the unaffected skin, whereas electrically induced itch was massively increased. Epidermal branching of the remaining nerve fibers in lichenified/chronically scratched skin was increased, particularly in patients with brachioradial pruritus, which may contribute to the pronounced local neuronal sensitivity. Hyperknesis and alloknesis were found to increase independently of lichenification. Conclusion: Our results indicate that chronic scratching may not affect intraepidermal nerve fiber density but leads to a stronger branching pattern of intraepidermal nerve fibers, which may contribute to local hypersensitivity. The increased sensitivity in the pruritic areas suggests mechanisms of peripheral sensitization, whereas the increased sensation of electrically and chemically induced itch in unaffected skin indicates central sensitization for itch.