Junctional epidermolysis bullosa

“Vlinderkinderen” worden ze genoemd, de patiëntjes met epidermolysis bullosa (EB) met een huid zo teer als de vleugels van een vlinder. Er worden zo’n 25 typen EB onderscheiden, waarvan de oorzaak in één van de 15 betrokken genen kan liggen. Junctionele epidermolysis bullosa (JEB) is een EB type met splijting door de junctionele laag tussen opperhuid en lederhuid. De adhesie-eiwitten in de junctionele laag zijn hierbij gestoord of afwezig. In het subtype JEB, type Herlitz (JEB-H) ontbreekt laminine-332 totaal. Kinderen met JEB-H groeien niet, krijgen overal pijnlijke wonden op de huid en in de keel. De aandoening gaat gepaard met uitzichtloos, ondraaglijk lijden en is fataal binnen de eerste 3 levensjaren. Tussen 1988 tot 2011 zijn 22 kinderen met JEB-H begeleid door het Centrum voor Blaarziekten in het UMCG. In het proefschrift worden de diagnostische kenmerken en de lange termijn follow-up van deze patiënten beschreven. Ook werden de ouders geïnterviewd die een kind hadden verloren door EB; waarop wij richtlijnen baseerden voor de begeleiding van ouders die zoiets nog moeten doorstaan. Bij één van de kinderen vroegen de ouders om euthanasie, hetgeen volgens het Groningen protocol werd uitgevoerd. Een ander deel van het proefschrift richt zich op het minder ernstige subtype JEB, type non-Herlitz (JEB-nH), waarbij patiënten wel kunnen overleven tot de volwassen leeftijd. We tonen aan dat volwassen JEB-nH patiënten al op vroege leeftijd een verhoogd risico (25%) hebben op het ontwikkelen van een agressief plaveiselcelcarcinoom, dat in 20% van de patiënten uitzaait. Een andere studie beschrijft dat biopttransplantaties, waarbij kleine huidtransplantaten in chronische wonden worden geplaatst om de wondgenezing te bevorderen, een makkelijke en effectieve behandeling is voor JEB-nH patiënten. Verder tonen we aan dat JEB of late onset veroorzaakt wordt door mutaties in het gen COL17A1.

Junctional epidermolysis bullosa

“Vlinderkinderen” worden ze genoemd, de patiëntjes met epidermolysis bullosa (EB) met een huid zo teer als de vleugels van een vlinder. Er worden zo’n 25 typen EB onderscheiden, waarvan de oorzaak in één van de 15 betrokken genen kan liggen. Junctionele epidermolysis bullosa (JEB) is een EB type met splijting door de junctionele laag tussen opperhuid en lederhuid. De adhesie-eiwitten in de junctionele laag zijn hierbij gestoord of afwezig. In het subtype JEB, type Herlitz (JEB-H) ontbreekt laminine-332 totaal. Kinderen met JEB-H groeien niet, krijgen overal pijnlijke wonden op de huid en in de keel. De aandoening gaat gepaard met uitzichtloos, ondraaglijk lijden en is fataal binnen de eerste 3 levensjaren. Tussen 1988 tot 2011 zijn 22 kinderen met JEB-H begeleid door het Centrum voor Blaarziekten in het UMCG. In het proefschrift worden de diagnostische kenmerken en de lange termijn follow-up van deze patiënten beschreven. Ook werden de ouders geïnterviewd die een kind hadden verloren door EB; waarop wij richtlijnen baseerden voor de begeleiding van ouders die zoiets nog moeten doorstaan. Bij één van de kinderen vroegen de ouders om euthanasie, hetgeen volgens het Groningen protocol werd uitgevoerd. Een ander deel van het proefschrift richt zich op het minder ernstige subtype JEB, type non-Herlitz (JEB-nH), waarbij patiënten wel kunnen overleven tot de volwassen leeftijd. We tonen aan dat volwassen JEB-nH patiënten al op vroege leeftijd een verhoogd risico (25%) hebben op het ontwikkelen van een agressief plaveiselcelcarcinoom, dat in 20% van de patiënten uitzaait. Een andere studie beschrijft dat biopttransplantaties, waarbij kleine huidtransplantaten in chronische wonden worden geplaatst om de wondgenezing te bevorderen, een makkelijke en effectieve behandeling is voor JEB-nH patiënten. Verder tonen we aan dat JEB of late onset veroorzaakt wordt door mutaties in het gen COL17A1.They are called "Butterfly Children", the patients with epidermolysis bullosa (EB) with a skin as fragile as the wings of a butterfly. There are about 25 distinct types of EB caused by mutations in one of the 15 involved genes. Junctional epidermolysis bullosa (JEB) is an EB type characterized by a cleavage through the junctional layer between the epidermis and dermis. The adhesion proteins in the junctional layer are disturbed or absent. In the subtype JEB, type Herlitz (JEB-H) laminin-332 is totally absent. Children with JEB-H do not grow and suffer from painful erosions on their entire skin and in their throat. JEB-H is associated with hopeless, unbearable suffering and is fatal within the first 3 years of life. Twenty-two children with JEB-H were guided by the Center for Blistering Diseases in the UMCG from 1988 to 2011. This thesis presents the diagnostic features and long-term follow-up of these patients. We also interviewed parents who had lost their child to lethal EB, on which we based guidelines for the guidance of future parents. In one of the children, the parents asked for euthanasia, which was performed according to the Groningen protocol. Another part of this thesis focuses on the less severe subtype JEB, type non-Herlitz (JEB-nH), in which patients do survive to adulthood. We show that adult JEB-nH patients have -from an early age on- an increased risk (25%) of developing an aggressive squamous cell carcinoma that metastasizes in 20% of the patients. Another study describes that punch grafting, in which small skin grafts are placed in chronic wounds to promote wound healing, is an easy and effective treatment in JEB-nH patients. Furthermore, we show that JEB of late onset is caused by mutations in the gene COL17A1

Poverty alleviation and policy dynamics in Hong Kong : a study of the community care fund

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Study protocol for a randomised controlled trial evaluating the effectiveness of strengths model case management (SMCM) with Chinese mental health service users in Hong Kong

Introduction Strengths-based approaches mobilise individual and environmental resources that can facilitate the recovery of people with mental illness. Strengths model case management (SMCM), developed by Rapp and Goscha through collaborative efforts at the University of Kansas, offers a structured and innovative intervention. As evidence of the effectiveness of strengths-based interventions come from Western studies, which lacked rigorous research design or failed to assure fidelity to the model, we aim to fill these gaps and conduct a randomised controlled trial (RCT) to test the effectiveness of SMCM for individuals with mental illness in Hong Kong. Methods and analysis This will be an RCT of SMCM. Assuming a medium intervention effect (Cohen’s d=0.60) with 30% missing data (including dropouts), 210 service users aged 18 years or above will be recruited from three community mental health centres. They will be randomly assigned to SMCM groups (intervention) or SMILE groups (control) in a 1:1 ratio. The SMCM groups will receive strengths model interventions from case workers, whereas the SMILE groups will receive generic care from case workers with an attention placebo. The case workers will all be embedded in the community centres and will be required to provide a session with service users in both groups at least once every fortnight. There will be two groups of case workers for the intervention and control groups, respectively. The effectiveness of the SMCM will be compared between the two groups of service users with outcomes at baseline, 6 and 12 months after recruitment. Functional outcomes will also be reported by case workers. Data on working alliances and goal attainment will be collected from individual case workers. Qualitative evaluation will be conducted to identify the therapeutic ingredients and conditions leading to positive outcomes. Trained outcome assessors will be blind to the group allocation. Ethics and dissemination Ethical approval from the Human Research Ethics Committee at the University of Hong Kong has been obtained (HRECNCF: EA1703078). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications

Baicalein antagonizes rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to Parkinsonism

<p>Abstract</p> <p>Background</p> <p>Two active compounds, baicalein and its glycoside baicalin were found in the dried root of <it>Scutellaria baicalensis </it>Georgi, and reported to be neuroprotective <it>in vitro </it>and <it>in vivo</it>. This study aims to evaluate the protective effects of baicalein on the rotenone-induced apoptosis in dopaminergic SH-SY5Y cells related to parkinsonism.</p> <p>Methods</p> <p>Cell viability and cytotoxicity were determined by MTT assay. The degree of nuclear apoptosis was evaluated with a fluorescent DNA-binding probe Hoechst 33258. The production of reactive oxidative species (ROS) and loss of mitochondrial membrane potential (ΔΨm) were determined by fluorescent staining with DCFH-DA and Rhodanmine 123, respectively. The expression of Bax, Bcl-2, cleaved caspase-3 and phosphorylated ERK1/2 was determined by the Western blots.</p> <p>Results</p> <p>Baicalein significantly increased viability and decreased rotenone-induced death of SH-SY5Y cells in a dose-dependent manner. Pre- and subsequent co-treatment with baicalein preserved the cell morphology and attenuated the nuclear apoptotic characteristics triggered by rotenone. Baicalein antagonized rotenone-induced overproduction of ROS, loss of ΔΨm, the increased expression of Bax, cleaved caspase-3 and phosphorylated ERK1/2 and the decreased expression of Bcl-2.</p> <p>Conclusion</p> <p>The antioxidative effect, mitochondrial protection and modulation of anti-and pro-apoptotic proteins are related to the neuroprotective effects of baicalein against rotenone induced cell death in SH-SY5Y cells.</p

The Strengths Model in Hong Kong

Mental health practice involves the continuous process of learning and refinement, especially when practitioners focus on the strengths and aspirations of individuals who are coping with serious mental illnesses (Tse et al., 2016). Cross-cultural considerations include beliefs, language, the role of social support, and the distinctive characteristics of specific communities that require localization in designing and offering mental health services. In this chapter, we describe the experience of adopting the Strengths Model in Hong Kong, starting with an introduction to the mental health system in the city. We then illustrate the development and implementation of the Strengths Model for the Chinese population in Hong Kong. We also briefly review research studies focusing on the Strengths Model in mental health practice in this cultural context (Tsoi et al., 2018; Tsoi, Tse, Canda, & Lo, 2019; Tse et al., 2019). The process of localization described in this chapter required the building of complex relationships among Strengths Model founders, scholars, organizations, caseworkers, and people facing mental health challenges

A targeted gene panel that covers coding, non-coding and short tandem repeat regions improves the diagnosis of patients with neurodegenerative diseases

Genetic testing for neurodegenerative diseases (NDs) is highly challenging because of genetic heterogeneity and overlapping manifestations. Targeted-gene panels (TGPs), coupled with next-generation sequencing (NGS), can facilitate the profiling of a large repertoire of ND-related genes. Due to the technical limitations inherent in NGS and TGPs, short tandem repeat (STR) variations are often ignored. However, STR expansions are known to cause such NDs as Huntington\u27s disease and spinocerebellar ataxias type 3 (SCA3). Here, we studied the clinical utility of a custom-made TGP that targets 199 NDs and 311 ND-associated genes on 118 undiagnosed patients. At least one known or likely pathogenic variation was found in 54 patients; 27 patients demonstrated clinical profiles that matched the variants; and 16 patients whose original diagnosis were refined. A high concordance of variant calling were observed when comparing the results from TGP and whole-exome sequencing of four patients. Our in-house STR detection algorithm has reached a specificity of 0.88 and a sensitivity of 0.82 in our SCA3 cohort. This study also uncovered a trove of novel and recurrent variants that may enrich the repertoire of ND-related genetic markers. We propose that a combined comprehensive TGPs-bioinformatics pipeline can improve the clinical diagnosis of NDs

In-vitro Strain and Modulus Measurements in Porcine Cervical Lymph Nodes

Cervical lymph nodes are common sites of metastatic involvement in head and neck cancers. These lymph nodes are superficially located and palpation is a common practice for assessing nodal hardness and staging cancer which is, however, too subjective and with limited accuracy. In this study, the mechanical properties of pig lymph node tissues were investigated using ultrasound elastography and indentation test. Lymph nodes were excised from fresh pork pieces and embedded in an agar-gelatin phantom for strain imaging by elastography. A strain ratio reflecting the strain contrast of lymph node over agar-gelatin phantom was used to assess the elasticity of the lymph node. A cutting device was then custom-designed to slice the phantom into uniform slices for indentation test. The measurements revealed that there were significant differences in both the strain ratio and Young’s modulus between the peripheral and middle regions of the lymph nodes (both p < 0.05); however, the results appeared contradictory. Correlation between the results of the two measurements (modulus ratio vs. inversed strain ratio) showed their association was moderate for both the peripheral and middle regions (R2 = 0.437 and 0.424 respectively). As the tests were only performed on normal lymph nodes, comparison in stiffness between healthy and abnormal lymph nodes could not be made. Future studies should be conducted to quantify the stiffness change in abnormal lymph nodes