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Identification of human hair follicle antigens targeted in the presumptive autoimmune hair follicle disorder Alopecia Areata and their potential functional relevance In Vitro. Methods development for isolation and identification of Alopecia Areata-relevant human hair follicle antigens using a proteomics approach and their functional assessment using an Ex Vivo hair follicle organ culture model.
Alopecia areata (AA) is a putative autoimmune hair loss disorder. It mainly affects the scalp hair but can also involve body hair, and can also affect the nail and the eye. While there are may be several lines of evidence to support the autoimmune basis of AA, there is still very little information on the hair follicle autoantigen(s) involved in its pathogenesis.
In this project, serum antibodies (AA=10, control=10) were used to immunoprecipitate AA-relevant target antigens from normal human scalp hair follicle extracts. These immunoprecipitates were analysed by LC-MALDI-TOF/TOF mass spectrometry for target protein identification. This part of the project involved substantial methods development.
Trichohyalin was immunoprecipitated by all AA sera, but by only 5 normal sera. Importantly, the mean Mascot scores of the AA group was significantly higher than the normal group (p=0.005). Keratin 16 was also identified from immunoprecipitates as another potential AA-relevant target antigen.
Functional studies by ex vivo whole hair follicle organ culture using commercial antibodies to trichohyalin and keratin 16 significantly inhibited hair fibre elongation compared to controls.
Indirect immunofluorescence studies revealed that AA sera contained higher immunoreactivity against normal human scalp anagen hair follicles compared to normal sera. Immunoreactivities were mainly in the outer root sheath and inner root sheath, and less so to the medulla and hair bulb matrix. Double immunofluorescence studies of AA and normal serum with anti-trichohyalin antibody (AE15) revealed co-localisation of 9 of the AA sera antibodies with trichohyalin in the inner root sheath (mostly in Henle¿s, less in Huxley¿s/inner root sheath cuticle), but only weakly in 3 normal sera.
This study supports the involvement of an antibody response to anagen-specific hair follicles antigens in AA. Moreover, there may be some evidence that these antibodies may have a pathogenic role
Diseño de un sistema integrado de gestión (calidad, medio ambiente y seguridad industrial y salud ocupacional) para la empresa C.I. Recycables S. A. de la ciudad de Cartagena, como respuesta a las exigencias del mercado chino
El diseño de un sistema integrado de gestión para la empresa Recycables S.A., de
la ciudad de Cartagena, le va a permitir hacer un análisis de la situación de la
empresa para responder al mercado nacional e internacional principalmente al
mercado de China donde se exportan el 95% de sus materiales
Con el sistema integrado de gestión se permitirá obtener eficiencia y eficacia en la
prestación de sus servicios, dando como resultado la plena satisfacción de los
clientes, mediante la implementación de la gestión por procesos y la mejora
continua, así como la realización de sus actividades buscando la preservación del
medio ambiente y cumpliendo con la seguridad industrial y salud ocupacional para
sus empleados y respondiendo a todos sus grupos de interés.
El trabajo presenta el manual integrado, sus procesos, procedimientos y formatos
de registros que debe llevar la organización para la estandarización de su sistema
y su mejoramiento continuo, así como el establecimiento de criterios y directivas
para el diseño del SIG con sus indicadores de gestión y la propuesta para la
implementación del SIG con su evaluación económica y financiera.Incluye bibliografía, anexo
Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study
BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02586-9
Effectiveness of a denture hygiene intervention programme among institutionalized elders
Objectives: To evaluate the effectiveness of a denture hygiene intervention programme in terms of improving denture cleanliness and denture stomatitis.
Methods: Residents at seven elderly care homes were invited to participate in a denture hygiene programme. Clinical assessment of denture stomatitis was undertaken and denture cleanliness assessed: (i) qualitatively by the Denture Cleanliness Index ratings and (ii) quantitatively by planimetric assessments of plaque coverage from digital images using Adobe Photoshop®. Individual denture hygiene instruction was provided and denture cleanser (Polident®) supplied. Six weeks later assessments of denture stomatitis and denture cleanliness were undertaken.
Results: Fifty-six participants were recruited; most had evidence of denture stomatitis (82.1%, 46) and 62.5% (35) of dentures were classified as ‘very poorly cleaned’. The mean percentage of plaque coverage was 28.11 (SD 19.64) and 37.5% (21) had evidence of plaque covering more than a third of the denture surface. Denture cleanliness was associated with denture stomatitis (P0.05).Conclusion: A 6-week denture hygiene intervention programme was effective at improving denture stomatitis and denture cleanliness among residents of elderly care homes. However, persistence of problems in denture cleanliness and denture stomatitis existed and this warrants further consideration.published_or_final_versio
Effectiveness of a denture hygiene intervention programme among institutionalized elders
Objectives: To evaluate the effectiveness of a denture hygiene intervention programme in terms of improving denture cleanliness and denture stomatitis.
Methods: Residents at seven elderly care homes were invited to participate in a denture hygiene programme. Clinical assessment of denture stomatitis was undertaken and denture cleanliness assessed: (i) qualitatively by the Denture Cleanliness Index ratings and (ii) quantitatively by planimetric assessments of plaque coverage from digital images using Adobe Photoshop®. Individual denture hygiene instruction was provided and denture cleanser (Polident®) supplied. Six weeks later assessments of denture stomatitis and denture cleanliness were undertaken.
Results: Fifty-six participants were recruited; most had evidence of denture stomatitis (82.1%, 46) and 62.5% (35) of dentures were classified as ‘very poorly cleaned’. The mean percentage of plaque coverage was 28.11 (SD 19.64) and 37.5% (21) had evidence of plaque covering more than a third of the denture surface. Denture cleanliness was associated with denture stomatitis (P0.05).Conclusion: A 6-week denture hygiene intervention programme was effective at improving denture stomatitis and denture cleanliness among residents of elderly care homes. However, persistence of problems in denture cleanliness and denture stomatitis existed and this warrants further consideration.published_or_final_versio
A handbook for using elder academy as a platform of other learning experiences
This handbook will discuss how school syllabus, Other Learning Experiences (OLE) and Elder Academy (EA) can be integrated. It will provide some structures for schools as a reference and help develop a comprehensive learning plan. Besides, the handbook will mention different roles and responsibilities of stakeholders, as well as the suggestions and guidelines for assessment.
The programs and activities in the “Elder Academy at Lingnan” will be taken as examples to demonstrate the guidelines. This can provide a better understanding of the operation mode of the integration between school curricula, OLE and EA. Hence, interested stakeholders can perform their own plans more systematically and effectively.https://commons.ln.edu.hk/osl_book/1000/thumbnail.jp
Lithium and the risk of fractures in patients with bipolar disorder: A population-based cohort study
Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44–0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures
Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes
Abstract
Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133− glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133− cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.http://deepblue.lib.umich.edu/bitstream/2027.42/110124/1/40478_2014_Article_160.pd
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