141 research outputs found

    IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

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    Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

    The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

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    Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations

    Poliserosite, artrite e doença respiratória em leitões: estudo de caso

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    O complexo da poliserosite em suínos é causado por múltiplos factores, em particular pelo agente Haemophilus parasuis (HPS), que tem vindo a causar vários problemas em suínos, quer ao nível respiratório, quer nas articulações. O agente HPS é o responsável pela Doença de Glässer (DG), caracterizada por uma inflamação generalizada da pleura, pericárdio, peritoneu, membranas sinoviais e meninges, acompanhada pela elevada presença de fibrina. HPS é normalmente um agente secundário causado por algum factor predisponente, como stress, pneumonias ou por algum vírus, em particular o Vírus do Síndrome Respiratório e Reprodutor Porcino (PRRSv).No caso das pneumonias verificou-se que o agente HPS é um invasor secundário oportunista e que causa doença em associação com outros agentes víricos ou bacterianos e está associado com maior prevalência de pneumonia por agentes respiratórios víricos, como o Síndrome Respiratório e Reprodutor Porcino (PRRS). Durante este estudo de caso acompanhou-se um lote de leitões desde o desmame até ao final da recria, em que foram feitas serologias e enviados leitões inteiros para laboratório de forma a isolar e identificar o agente. Foi feita a avaliação da morbilidade bem como o cálculo do índice de tosse e taxa de mortalidade nas primeiras quatro semanas de recria. Efectuaram-se necropsias dos leitões deste lote. Pretende-se, como objectivo deste estudo, definir o agente primário causador da patologia, neste caso o PRRSv, bem como a entrada da infecção bacteriana secundária causada pelo HPS. Procedeu-se à vacinação do efectivo frente ao PRRSv. Como profilaxia, devido à falha de protecção de imunidade maternal, fez-se a administração de tulatromicina a todos os leitões até todo o efectivo estar devidamente protegido frente ao PRRSv, conferindo assim uma boa imunidade maternal.The porcine polyserositis complex is caused by multiple factors, particularly by Haemophilus parasuis (HPS), which has been causing several problems in pigs, both at the respiratory and articular levels. HPS is the causative agent of Glässer's Disease (DG), characterized by a generalized inflammation of the pleura, pericardium, peritoneum, synovial membranes and meninges, toguether with an abundant presence of fibrin. HPS is usually a secondary agent enhanced by some predisposing factor, like stress, pneumonia or some viruses, such as Porcine Reproductive and Respiratory Syndrome virus (PRRSv). In pneumonia, it has been show that HPS is an opportunistic secondary invader causing disease in association with other viral or bacterial agents being PRRSv the most prevalent respiratory viral agent found together with HPS. During this study a batch of piglets was followed from weaning until the end of nursery season, when serologies were performed, samples were collected and whole piglets were sent to pathology in order to isolate and identify the agent. Health condition was evaluated as well as the calculation of cough index and mortality rate in the first four weeks of nursery. Necropsies of the piglets of this batch were also carried out.The objective of this study was to define the primary agent causing disease (in this case PRRSv), as well as the factors that predisposed to secondary bacterial infections caused by HPS. Following these findings all herd was vaccinated against PRRSv. Due to lack of protective maternal immunity, tulathromycin was administered in pigs, as prophylactic measure until all sows were adequately protected against PRRSv, thus conferring good maternal immunity to their offspring

    An Exome-Chip Association Analysis in Chinese Subjects Reveals a Functional Missense Variant of GCKR That Regulates FGF21 Levels

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    Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5,169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian exome-chip was used to detect genetic determinants influencing circulating FGF21 levels. Single-variant association analysis interrogating 70,444 single nucleotide polymorphisms identified a novel locus, GCKR, significantly associated with circulating FGF21 levels at genome-wide significance. In the combined analysis, the common missense variant of GCKR, rs1260326 (p.Pro446Leu), showed an association with FGF21 levels after adjustment for age and sex (P = 1.61 × 10−12; β [SE] = 0.14 [0.02]), which remained significant on further adjustment for BMI (P = 3.01 × 10−14; β [SE] = 0.15 [0.02]). GCKR Leu446 may influence FGF21 expression via its ability to increase glucokinase (GCK) activity. This can lead to enhanced FGF21 expression via elevated fatty acid synthesis, consequent to the inhibition of carnitine/palmitoyl-transferase by malonyl-CoA, and via increased glucose-6-phosphate–mediated activation of the carbohydrate response element binding protein, known to regulate FGF21 gene expression. Our findings shed new light on the genetic regulation of FGF21 levels. Further investigations to dissect the relationship between GCKR and FGF21, with respect to the risk of metabolic diseases, are warranted.postprin

    Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood

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    Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed

    Oral health of community dwelling elders in Hong Kong

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    Introduction: The world’s population is ageing and the elders are vulnerable to oral health problems. This project aimed to observe the oral health status of community dwelling elders in Hong Kong, investigate the oral health impact on their quality of life and nutritional status, and provide oral health education and preventive service. Methods: Community dwelling elders (65 or above) were recruited from five community centers. An interviewer-administered questionnaire was completed to collect information on their socio-demographic background and oral health perception/practice. Their oral health related quality of life (OHQoL) and nutritional status were measured by using the Geriatric Oral Health Assessment Index (GOHAI) and Mini-Nutritional Assessment (MNA), respectively. Their tooth and periodontal status, oral hygiene and soft tissues were examined. Individualized advice, oral health education and scaling were provided. Results: A total of 195 elders participated. Despite their sound knowledge on dental caries, their awareness of the causes and risk factors of periodontal diseases was low. Several misconceptions of oral health were common and their expectation towards oral health was low. Although 81% brush their teeth at least twice a day, over 75% did not perform interdental cleaning mainly due to unawareness of the necessity (32%) and lack of skills (42%). Their dental visits were treatment-driven and mainly for pain-relieving and emergency care. Only 19% were regular dental attendees. The mean (SD) DMFT was 8.9 (7.8). Over 60% had periodontal pockets; 6% were edentulous and 38% had fewer than 20 teeth. The mean (SD) total GOHAI score was 56.4 (8.0); 60% reported negative impact of oral health on their quality of life. The mean (SD) MNA score was 25.2 (2.9); 30% had malnutrition or were at risk. Multivariate analysis showed that tooth loss and untreated decayed teeth (DT) were significant determinants of poor OHQoL; older age, higher education level, and poorer OHQoL were significantly associated with higher risk of malnutrition (all p<0.05). Conclusions: Oral health problems are common among community dwelling elders in Hong Kong. Their oral health awareness and practice are yet to be improved. Tooth loss and unmet treatment need for dental caries significantly compromise elders’ quality of life, which in turn increases their risk for malnutrition. Outreach oral health education and service are well received by the community.published_or_final_versio

    PHIL and Squid Embolization of Cerebral Arteriovenous Malformation: A Retrospective Case Series of 23 Patients

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    Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Aliso Viejo, CA, USA) and Squid (Balt, Irvine, CA, USA) are 2 newer liquid embolic agents used in endovascular embolization of cerebral arteriovenous malformation (AVM). This study aims to investigate and compare the effectiveness and safety profile of the 2 newer liquid embolic agents in the embolization of cerebral AVM. This is a retrospective study on all patients diagnosed with cerebral AVM undergoing endovascular embolization with liquid embolic agents PHIL and Squid admitted to the Division of Neurosurgery, Department of Surgery in Prince of Wales Hospital from January 2014 to June 2021. Twenty-three patients with cerebral AVM were treated with 34 sessions of endovascular embolization with either PHIL or Squid (17 sessions each) liquid embolic agents with a male to female ratio of 2.3:1 (male 16; female 7) and mean age of 44.6 (range, 12 to 67). The mean total nidus obliteration rate per session was 57% (range, 5% to 100%). Twenty-one patients (91.3%) received further embolization, stereotactic radiosurgery, or surgical excision after initial endovascular embolization. There were 2 morbidities (1 neurological and 1 non-neurological, 6%) and no mortalities (0%). All patients had static or improvement in modified Rankin Scale at 3 to 6 months at discharge. PHIL and Squid are effective and safe liquid embolic agents for endovascular embolization of cerebral AVM, achieving satisfactory nidal obliteration rates and patient functional outcomes

    Oseltamivir-Resistant Influenza A Pandemic (H1N1) 2009 Virus, Hong Kong, China

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    Resistance to oseltamivir was observed in influenza A pandemic (H1N1) 2009 virus isolated from an untreated person in Hong Kong, China. Investigations showed a resistant virus with the neuraminidase (NA) 274Y genotype in quasi-species from a nasopharyngeal aspirate. Monitoring for the naturally occurring NA 274Y mutation in this virus is necessary
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