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Clinical Case Reports Apr 2024High-dose intravenous immunoglobulin exhibits great potential in the treatment of Netherton syndrome.
KEY CLINICAL MESSAGE
High-dose intravenous immunoglobulin exhibits great potential in the treatment of Netherton syndrome.
ABSTRACT
Netherton syndrome (NS) is a rare autosomal recessive genodermatosis (OMIM #256500) characterized by superficial scaling, atopic manifestations, and multisystemic complications. It is caused by loss-of-function mutations in the SPINK5 gene, which encode a key kallikrein protease inhibitor. There are two subtypes of the syndrome that differ in clinical presentation and immune profile: ichthyosiform erythroderma and ichthyosis linearis circumflexa. NS is a multisystemic disease with numerous extracutaneous manifestations. Current therapy for patients with NS is mainly supportive, as there is no curative or specific treatment, especially for children with NS, but targeted therapies are being developed. We describe an 8-year-old boy with genetically proven NS treated with intravenous immunoglobulin for recurrent skin and systemic infections from infancy, growth retardation, and associated erythroderma. Under this therapy, his skin status, infectious exacerbations, and quality of life all improved. Knowledge of the cytokine-mediated pathogenesis of NS and the development of new biologic drugs open new possibilities for NS patients. However, the different therapeutic options have been applied in a limited number of cases, and variable responses have been shown. Randomized controlled trials with a sufficient number of patients stratified and treated according to their specific immune profile and clinical phenotype are needed to evaluate the safety and efficacy of treatment options for patients with NS.
PubMed: 38634098
DOI: 10.1002/ccr3.8770 -
Frontiers in Immunology 2024is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis,...
is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis, surgical site infections, osteomyelitis, and pneumonia. These infections are exacerbated by the emergence of antibiotic-resistant clinical isolates such as methicillin-resistant (MRSA), highlighting the need for alternatives to antibiotics to treat bacterial infections. We have previously developed a multi-component toxoid vaccine (IBT-V02) in a liquid formulation with efficacy against multiple strains of prevalent in the industrialized world. However, liquid vaccine formulations are not compatible with the paucity of cold chain storage infrastructure in many low-to-middle income countries (LMICs). Furthermore, whether our IBT-V02 vaccine formulations are protective against isolates from LMICs is unknown. To overcome these limitations, we developed lyophilized and spray freeze-dried formulations of IBT-V02 vaccine and demonstrated that both formulations had comparable biophysical attributes as the liquid formulation, including similar levels of toxin neutralizing antibodies and protective efficacy against MRSA infections in murine and rabbit models. To enhance the relevancy of our findings, we then performed a multi-dimensional screen of 83 clinical isolates from LMICs (e.g., Democratic Republic of Congo, Palestine, and Cambodia) to rationally down-select strains to test in our models based on broad expression of IBT-V02 targets (i.e., pore-forming toxins and superantigens). IBT-V02 polyclonal antisera effectively neutralized toxins produced by the clinical isolates from LMICs. Notably, the lyophilized IBT-V02 formulation exhibited significant efficacy in various preclinical infection models against the clinical isolates from LMICs, which was comparable to our liquid formulation. Collectively, our findings suggested that lyophilization is an effective alternative to liquid vaccine formulations of our IBT-V02 vaccine against infections, which has important implications for protection from isolates from LMICs.
Topics: Animals; Mice; Rabbits; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Developing Countries; Staphylococcal Infections; Anti-Bacterial Agents; Bacterial Vaccines; Toxoids
PubMed: 38633244
DOI: 10.3389/fimmu.2024.1373367 -
Scientific Reports Apr 2024Wearable long-term monitoring applications are becoming more and more popular in both the consumer and the medical market. In wearable ECG monitoring, the data quality...
Wearable long-term monitoring applications are becoming more and more popular in both the consumer and the medical market. In wearable ECG monitoring, the data quality depends on the properties of the electrodes and on how they interface with the skin. Dry electrodes do not require any action from the user. They usually do not irritate the skin, and they provide sufficiently high-quality data for ECG monitoring purposes during low-intensity user activity. We investigated prospective motion artifact-resistant dry electrode materials for wearable ECG monitoring. The tested materials were (1) porous: conductive polymer, conductive silver fabric; and (2) solid: stainless steel, silver, and platinum. ECG was acquired from test subjects in a 10-min continuous settling test and in a 48-h intermittent long-term test. In the settling test, the electrodes were stationary, whereas both stationary and controlled motion artifact tests were included in the long-term test. The signal-to-noise ratio (SNR) was used as the figure of merit to quantify the results. Skin-electrode interface impedance was measured to quantify its effect on the ECG, as well as to leverage the dry electrode ECG amplifier design. The SNR of all electrode types increased during the settling test. In the long-term test, the SNR was generally elevated further. The introduction of electrode movement reduced the SNR markedly. Solid electrodes had a higher SNR and lower skin-electrode impedance than porous electrodes. In the stationary testing, stainless steel showed the highest SNR, followed by platinum, silver, conductive polymer, and conductive fabric. In the movement testing, the order was platinum, stainless steel, silver, conductive polymer, and conductive fabric.
Topics: Humans; Artifacts; Stainless Steel; Platinum; Silver; Prospective Studies; Electrocardiography; Electric Impedance; Electrodes; Polymers
PubMed: 38632263
DOI: 10.1038/s41598-024-56595-0 -
Environment International Apr 2024To overcome ethical and technical challenges impeding the study of human dermal uptake of chemical additives present in microplastics (MPs), we employed 3D human skin...
To overcome ethical and technical challenges impeding the study of human dermal uptake of chemical additives present in microplastics (MPs), we employed 3D human skin equivalent (3D-HSE) models to provide first insights into the dermal bioavailability of polybrominated diphenyl ether (PBDEs) present in MPs; and evaluated different factors influencing human percutaneous absorption of PBDEs under real-life exposure scenario. PBDEs were bioavailable to varying degrees (up to 8 % of the exposure dose) and percutaneous permeation was evident, albeit at low levels (≤0.1 % of the exposure dose). While the polymer type influenced the release of PBDEs from the studied MPs to the skin, the polymer type was less important in driving the percutaneous absorption of PBDEs. The absorbed fraction of PBDEs was strongly correlated (r = 0.88) with their water solubility, while the dermal permeation coefficient P of PBDEs showed strong association with their molecular weight and logK. More sweaty skin resulted in higher bioavailability of PBDEs from dermal contact with MPs than dry skin. Overall, percutaneous absorption of PBDEs upon skin contact with MPs was evident, highlighting, for the first time, the potential significance of the dermal pathway as an important route of human exposure to toxic additive chemicals in MPs.
Topics: Humans; Flame Retardants; Skin Absorption; Halogenated Diphenyl Ethers; Polypropylenes; Microplastics; Polyethylene; Skin; Models, Biological
PubMed: 38631261
DOI: 10.1016/j.envint.2024.108635 -
Human Genomics Apr 2024Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI.
RESULTS
This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing.
CONCLUSIONS
Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.
Topics: Humans; Case-Control Studies; Leukocytes, Mononuclear; Southeast Asian People; Inflammation; Microbiota; Ichthyosis
PubMed: 38627868
DOI: 10.1186/s40246-024-00603-x -
Mycopathologia Apr 2024The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small...
The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.
Topics: Humans; Male; Dermatomycoses; Skin; Trichophyton; Microscopy; Scrotum
PubMed: 38627263
DOI: 10.1007/s11046-024-00839-0 -
Metabolomics : Official Journal of the... Apr 2024Aspalathus linearis (commonly known as rooibos) is endemic to the Cape Floristic Region of South Africa and is a popular herbal drink and skin phytotherapeutic...
INTRODUCTION
Aspalathus linearis (commonly known as rooibos) is endemic to the Cape Floristic Region of South Africa and is a popular herbal drink and skin phytotherapeutic ingredient, with health benefits derived primarily from its unique phenolic content. Several, seemingly habitat-specific ecotypes from the Cederberg (Western Cape) and Northern Cape have morphological, ecological, genetic and biochemical differences.
OBJECTIVES AND METHODS
Despite the commercial popularity of the cultivated variety, the uncultivated ecotypes are largely understudied. To address gaps in knowledge about the biochemical constituency, ultra-performance liquid chromatography-mass spectrometry analysis of fifteen populations was performed, enabling high-throughput metabolomic fingerprinting of 50% (v/v) methanolic extracts. Antioxidant screening of selected populations was performed via three assays and antimicrobial activity on two microbial species was assessed. The metabolomic results were corroborated with total phenolic and flavonoid screening of the extracts.
RESULTS AND DISCUSSION
Site-specific chemical lineages of rooibos ecotypes were confirmed via multivariate data analyses. Important features identified via PLS-DA disclosed higher relative abundances of certain tentative metabolites (e.g., rutin, aspalathin and apiin) present in the Dobbelaarskop, Blomfontein, Welbedacht and Eselbank sites, in comparison to other locations. Several unknown novel metabolites (e.g., m/z 155.0369, 231.0513, 443.1197, 695.2883) are responsible for metabolomic separation of the populations, four of which showed higher amounts of key metabolites and were thus selected for bioactivity analysis. The Welbedacht and Eselbank site 2 populations consistently displayed higher antioxidant activities, with 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activities of 679.894 ± 3.427 µmol Trolox/g dry matter and 635.066 ± 5.140 µmol Trolox/g dry matter, respectively, in correlation with a high number of phenolic and flavonoid compounds. The contribution of the individual metabolites to the pharmacological effectiveness of rooibos remains unknown and as such, further structural elucidation and phytopharmacological testing is thus urgently needed.
Topics: Aspalathus; Antioxidants; Ecotype; Metabolomics; Flavonoids; Phenols
PubMed: 38615312
DOI: 10.1007/s11306-024-02103-4 -
Foods (Basel, Switzerland) Mar 2024The effect of the production area on the quality of Hass avocados grown on the island of Tenerife was studied. For this purpose, several physicochemical parameters, such...
The effect of the production area on the quality of Hass avocados grown on the island of Tenerife was studied. For this purpose, several physicochemical parameters, such as fruit weight, percentage of pulp, seed and skin, proximate composition, minerals, total phenolic compounds (TP), total flavonoid compounds (TF), α-tocopherol, antioxidant capacity, and fatty acid profile were analyzed. The location of the orchards significantly influenced avocado weight; pulp and seed percentage; and fat, fiber, ash, α-tocopherol, TP, phosphorus, potassium, calcium, iron, zinc, and oleic and palmitoleic acid contents. Buenavista (BU) avocados were the smallest (185 g) and presented the highest percentage of pulp (77.1%) and lowest percentage of fiber (5.43%). The highest levels of dry matter (33.8%) and fat (20.4%) were found in avocados harvested in Los Silos (SI) and Santiago del Teide (SA), respectively. Compared with those at the other locations, the avocados harvested in Güímar (GU) had high levels of α-tocopherol (52.2 µg g) and phenolic compounds (56.0 mg GAE 100 g). Avocados from Los Realejos (RE) had the highest percentage of oleic acid and the lowest percentage of palmitoleic acid. Numerous significant correlations were found between the variables studied, especially those between TP, TF, and antioxidant capacity (DPPH) and between fat percentage and dry matter.
PubMed: 38611361
DOI: 10.3390/foods13071058 -
Foods (Basel, Switzerland) Mar 2024Phenolic compounds, especially tannins, are important for red wine quality. Wines made from cold-hardy hybrid grape cultivars have much lower tannin concentrations than...
Phenolic compounds, especially tannins, are important for red wine quality. Wines made from cold-hardy hybrid grape cultivars have much lower tannin concentrations than wines from grape cultivars. This study assessed the phenolics content of berry tissues of three red cold-hardy hybrid cultivars in comparison to cv. 'Pinot noir' throughout development and ripening. Basic chemical properties, iron-reactive phenolics content, and tannin content were evaluated in the juice, skins, and seeds of spp. cvs. 'Crimson Pearl', 'Marquette', and 'Petite Pearl' and 'Pinot noir' at six time points from one week post-fruit set to harvest in 2021 and 2022. 'Crimson Pearl' displayed similar iron-reactive phenolics and tannin contents in juice, skins (22.6-25.4 mg/g dry skin and 8.0-12.2 mg/g dry skin, respectively), and seeds (12.8-29.8 mg/g dry seed and 4.2-22.0 mg/g dry seed, respectively) as 'Petite Pearl' and 'Marquette' at harvest in 2022. The hybrid cultivars showed a similar trend of phenolic accumulation as 'Pinot noir' but resulted in overall lower content in skins and seeds. Despite differences in developmental trends, the three hybrid grape cultivars displayed similar phenolic content at harvest ripeness. This is the first study examining the phenolic content of 'Crimson Pearl' and 'Petite Pearl' throughout berry development and ripening. This study provides important information for the wine industry to make informed decisions on making wine with these cultivars.
PubMed: 38611290
DOI: 10.3390/foods13070986 -
Alternative Therapies in Health and... Apr 2024Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy...
BACKGROUND
Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy in a 14-year-old boy with Netherton syndrome.
CASE PRESENTATION
A 14-year-old male with a lifelong history of dry skin, erythema, scaling, itching, and notable body odor was evaluated. These symptoms, accompanied by irregular hair growth and delayed development, prompted an initial diagnosis of atopic dermatitis at a local hospital. Treatment with antihistamines, moisturizers, and topical corticosteroids failed to alleviate systemic manifestations of red patches and persistent itching. Seeking further evaluation, the patient was presented to our center. Upon examination, the characteristics of "bamboo hair" and "golf tee sign" were observed microscopically in the patient's hair. Whole exome sequencing identified a paternally inherited mutation in the SPINK5 gene, confirming Netherton syndrome. No mutations were found in the mother. Despite initial positive responses to Secukinumab and Dupilumab, therapeutic efficacy waned over time.
RESULTS AND CONCLUSIONS
Initiation of Upadacitinib at a daily dose of 15 mg yielded significant therapeutic benefits within a short timeframe. This study marks the first documented use of Upadacitinib in pediatric Netherton syndrome treatment. This case highlights the efficacy of Upadacitinib in treating Netherton syndrome, particularly in pediatric patients. Further studies are warranted to elucidate its long-term effects and optimal dosing regimens.
PubMed: 38607195
DOI: No ID Found