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Hormone-sensitive lipase is one of the rate-determining enzymes in the hydrolysis of triglyceride, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1 treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The thin layer chromatography results also showed that the dysfunction of Hsl changed the whole body lipid profile, including increasing the content of TG and decreasing the proportion of PL. In addition, the systemic metabolic pattern was remodeled in hsla-/- and HSL-IN-1 treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle, enhanced the utilization of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1 treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.
The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.
Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04–0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94–2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.
This study aims for a greater understanding of how older adults (age 65 and older) in Jackson County, Florida, are prepared for and cope with the effects of a natural disaster.
A multidisciplinary, international research team developed a survey examining: (1) resources available to individuals aged 65+ in rural communities for preparing for a disaster; (2) challenges they face when experiencing a disaster; and (3) their physical, social, emotional, and financial needs when it strikes. The survey was administered with older adults (65+) in Jackson County, Florida, following Hurricane Michael in 2018. The descriptive, multivariate logistic, and linear regression analyses were performed to examine the relationship between respondents’ demographic information and needs, concerns, and consequences of disaster.
Results indicated (n = 139) rural community-dwelling older adults rely on social support, community organizations, and trusted disaster relief agencies to prepare for and recover from disaster-related events.
Such findings can be used to inform the development of new interventions, programs, policies, practices, and tools for emergency management and social service agencies to improve disaster preparedness and resiliency among older populations in rural communities.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.
Calcification within breast cancer is a diagnostically significant radiological feature that generally consists of hydroxylapatite. Samples from 30 cases of breast carcinoma with calcification were investigated using optical microscopy, energy-dispersive X-ray analysis, transmission-electron microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, synchrotron radiation X-ray diffraction and X-ray fluorescence. Under optical microscopy, the calcifications were found to consist of either irregular aggregates with widths > 200 μm or spherical aggregates similar to psammoma bodies with an average diameter of 30 μm. Transmission-electron microscopy showed that short columnar or dumbbell-shaped crystals with widths of 10–15 nm and lengths of 20–50 nm were the most common morphology; spherical aggregates (~1 μm in diameter) with amorphous coatings of fibrous nanocrystals were also observed. Results indicated that hydroxylapatite was the dominant mineral phase in the calcifications, and both CO32– and cation substitutions (Na, Mg, Zn, Fe, Sr, Cu and Mn) were present in the hydroxylapatite structure. Fourier-transform infrared spectra show peaks at 872 and 880 cm–1 indicating that CO32– substituted both the OH– (A type) and PO43– (B type) sites of hydroxylapatite, making it an A and B mixed type. The ratio of B- to A-type substitution was estimated in the range of 1.1–18.7 from the ratio of peak intensities (I872/I880), accompanied with CO32– contents from 1.1% to 14.5%. Trace arsenic, detected in situ by synchrotron radiation X-ray fluorescence was found to be distributed uniformly in the calcifications in the form of AsO43– substituting for PO43–. It is therefore proposed that identifying these trace elements in breast cancer calcifications may be promising for future clinical diagnostics.
A high-carbohydrate diet could achieve a protein-sparing effect, but it may cause negative impacts on the growth condition of fish due to their poor utilisation ability of carbohydrate. How to reduce the adverse effects caused by a high-carbohydrate diet is important for the development of aquaculture. In the present study, we aimed to identify whether inulin could attenuate the metabolic syndrome caused by a high-carbohydrate diet in fish. Nile tilapia (Oreochromis niloticus) (1·19 (sd 0·01) g) were supplied with 35 % carbohydrate (CON), 45 % carbohydrate (HC) and 45 % carbohydrate + 5 g/kg inulin (HCI) diets for 10 weeks. The results showed that addition of inulin improved the survival rate when fish were challenged with Aeromonas hydrophila, indicating that inulin had an immunostimulatory effect. Compared with the HC group, the HCI group had lower lipid accumulation in liver and the gene expression analyses indicated that addition of inulin down-regulated genes related to lipogenesis and up-regulated genes relevant to β-oxidation significantly (P < 0·05). Higher liver glycogen and glucose tolerance were found in the HCI group compared with the HC group (P < 0·05). These results indicated that inulin could alleviate the metabolic syndrome induced by a high-carbohydrate diet. Furthermore, addition of inulin to a high-carbohydrate diet changed the intestinal bacterial composition and significantly increased the concentration of acetic acid and propionic acid in fish gut which have the potential to increase pathogen resistance and regulate metabolic characteristics in fish. Collectively, our results demonstrated a possible causal role for the gut microbiome in metabolic improvements induced by inulin in fish.
Supported by (1) medical research grants CMRPG3C0041/42 from Chang Gung Memorial Hospital and NRRPG2H0031 from Ministry of Science and Technology, Taiwan to Chemin Lin (2) NMRPG3G6031/32 from Ministry of Science and Technology, Taiwan to Shwu-Hua, Lee (3) the KKHo International Charitable Foundation to Tatia Lee.
Suicide rate tends to peak in old age, and major depression is the most salient risk factor for late-life suicide. However, few studies have focused on the neuroscientific facet of suicide in the context of late-life depression (LLD).
We recruited 114 participants of LLD (28 with history of suicide attempt and 86 without) and 47 elderly controls. They received MRI scanning and behavioral assessment. White matter hyperintensity (WMH) was quantified by an automated segmentation algorithm and graph theoretical analysis was applied to resting-state fMRI. We used ANCOVA to compare group difference in WMH loading and multivariate generalized linear model to compare global and local topological parameters in fMRI signals, controlling for demographics. Partial correlation was conducted between imaging parameters and behavioral data in group of suicide attempters.
We found significant higher WMH in suicide attempters than those of LLD without suicide attempts and elderly controls (F =7.091; p = 0.001). Suicide attempters also had increased betweenness centrality (BC) in right superior occipital gyrus (SOG) (Bonferroni corrected), right precuneus (False positive corrected) and right superior temporal gyrus (uncorrected) and decreased BC in left hippocampus (uncorrected). In suicide attempters, higher BC in right SOG correlated with higher WMH, higher depression severity, higher illness awareness and insight, and lower cognitive function (digit backward), while higher BC in right precuneus correlated with higher decrease awareness and insight and higher cognitive function (digit backward).
Resonating with the vascular hypothesis in LLD, higher WMH was found in those having history of suicide attempts. However, the re-organized brain topology changes are related with divergent cognitive function and convergent heightened disease insight.
Women experience both physical and psychological changes during different phases of the menstrual cycle (MC), which can affect their decision making. The present study aims to investigate the impact of the MC on women’s preferences for conspicuous consumption. In three studies, women in the low-fertility phase were found to be more inclined toward conspicuous consumption, with the MC effect on conspicuous consumption being mediated by the extent of pride. We assumed that women in the low-fertility phase would feel less proud due to an evolutionary drive and that they would consume conspicuous products as a means of compensation. Meanwhile, women who were only children did not manifest such behavior. We infer that women from one-child families may have a greater sense of security and confidence, which buffers the mediating effect. This research contributes to both evolutionary psychology and marketing research and provides new insights for future studies.
l-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.
Although moving from institutional to home-like long-term care (LTC) settings can promote and sustain the health and wellbeing of older adults, there has been little research examining how home is perceived by older adults when moving between care settings. A qualitative study was conducted over a two-year period during the relocation of residents and staff from an institutional LTC home to a purpose-built LTC home in Western Canada. The study explored perceptions of home amongst residents, family members and staff. Accordingly, 210 semi-structured interviews were conducted at five time-points with 35 residents, 23 family members and 81 staff. Thematic analyses generated four superordinate themes that are suggestive of how to create and enhance a sense of home in LTC settings: (a) physical environment features; (b) privacy and personalisation; (c) autonomy, choice and flexibility; and (d) connectedness and togetherness. The findings reveal that the physical environment features are foundational for the emergence of social and personal meanings associated with a sense of home, and highlight the impact of care practices on the sense of home when the workplace becomes a home. In addition, tension that arises between providing care and creating a home-like environment in LTC settings is discussed.
Fatigue properties of Mo/W multilayers with individual layer thickness (λ) of 5, 20, 50 and 100 nm on flexible polyimide substrates were investigated. The experimental results show that the fatigue resistance increases with decreasing λ from 100 nm to 20 nm, and reaches the maximum at λ=20 nm, and then decreases when further decreasing λ. Fatigue cracks of Mo/W multilayers with different λ were found to propagate along columnar grain boundary in the out-of-plane direction and along the boundary of cluster structures. The enhanced fatigue resistance is attributed to the larger cluster inclination angles and the more tortuous in-plane cracking paths.
This chapter presents work from a Canadian project exploring the potential of community-based participatory research for drawing out how communities play a role in resilient ageing. The project used creative approaches as part of the research method rather than as the subject of the study. The chapter focuses on the importance of place and the authors helpfully explore the nuances of ‘place’. This common interest in community resilience, ageing and place is one of the features that draw Chapters Five, Six and Seven together. Another is the action-oriented nature of the research. The research discussed here, much like Chapter Seven, was intended both to explore the views of older people in the community and, through that, to give those people a voice in local processes of housing development.
This chapter critically explores the potential of an action-oriented, community-based participatory research (CBPR) approach to reveal ways in which communities can be resilient to the opportunities and challenges of ageing-in-place. In particular, the chapter considers the potential for using qualitative and creative methods to bring distinct viewpoints of local community stakeholders to the fore in terms of embedding aspects of place into the development of affordable housing for older adults. Community resilience refers here to the ‘existence, development and engagement of community resources by community members to thrive in an environment characterized by change, uncertainty, unpredictability and surprise’ (Magis, 2010, p 401). This is particularly important in the context of supporting ageing-in-place, where living in resilient communities can provide opportunities for civic participation, remaining active and sustaining community identity (Woolrych, 2017). Within the field of urban studies, there has been a shift towards a more transdisciplinary appreciation for community resilience, which combines the physical and psychosocial aspects of urban resilience (Coaffee, 2008). As such, the affordances of physical space play a role in supporting or constraining community resilience, particularly for older adults who may rely on the immediate neighbourhood for service supports and maintaining social roles (Hildon et al, 2009). This is important both in terms of the everyday life of the community and in responding to the challenges and opportunities of old age.
Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).
Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.
Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).
Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.
The present study aimed to investigate the effect of maternal malnutrition on offspring glucose tolerance and the epigenetic mechanisms involved. In total, twelve primiparous Landrace×Yorkshire gilts were fed rations providing either 100 % (control (CON)) or 75 % (undernutrition (UN)) nutritional requirements according to the National Research Council recommendations, throughout gestation. Muscle samples of offspring were collected at birth (dpn1), weaning (dpn28) and adulthood (dpn189). Compared with CON pigs, UN pigs showed lower serum glucose concentrations at birth, but showed higher serum glucose and insulin concentrations as well as increased area under the blood glucose curve during intravenous glucose tolerance test at dpn189 (P<0·05). Compared with CON pigs, GLUT-4 gene and protein expressions were decreased at dpn1 and dpn189 in the muscle of UN pigs, which was accompanied by increased methylation at the GLUT4 promoter (P<0·05). These alterations in methylation concurred with increased mRNA levels of DNA methyltransferase (DNMT) 1 at dpn1 and dpn28, DNMT3a at dpn189 and DNMT3b at dpn1 in UN pigs compared with CON pigs (P<0·05). Interestingly, although the average methylation levels at the muscle GLUT4 promoter were decreased at dpn189 compared with dpn1 in pigs exposed to a poor maternal diet (P<0·05), the methylation differences in individual CpG sites were more pronounced with age. Our results indicate that in utero undernutrition persists to silence muscle GLUT4 likely through DNA methylation during the ageing process, which may lead to the amplification of age-associated glucose intolerance.
This study explores the end-of-life (EoL) beliefs, values, practices, and expectations of a select group of harder-to-reach Chinese women living in England.
A cultural safety approach was undertaken to interpret 11 in-depth, semistructured interviews. Interviews were conducted in Mandarin and Cantonese. Transcripts were translated and back-translated by two researchers. Findings were analyzed using the technical analytical principles of grounded theory.
The key themes generated from our analysis include: acculturation; differential beliefs and norms in providing care: family versus health services; language and communication; Eastern versus Western spiritual practices and beliefs; and dying, death, and the hereafter.
Significance of Results:
End-of-life discussions can be part of an arduous, painful, and uncomfortable process, particularly for migrants living on the margins of society in a new cultural setting. For some Chinese people living in the United Kingdom, end-of-life care requires attention to acculturation, particularly Western versus Eastern beliefs on religion, spirituality, burial practices, and provision of care, and the availability of culturally specific care, all of which encompass issues related to gender. Stories of a purposive sample of Chinese women were viewed through a cultural safety lens to gain a deeper understanding of how social and cultural norms and expectations, in addition to the pressures of acculturation, impact gendered roles and responsibilities. The analysis revealed variations between/within Eastern and Western culture that resulted in pronounced, and oftentimes gendered, differences in EoL care expectations.
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n = 27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
Total variation (TV) and wavelet L1 norms have often been used as regularization terms in image restoration and reconstruction problems. However, TV regularization can introduce staircase effects and wavelet regularization some ringing artifacts, but hybrid TV and wavelet regularization can reduce or remove these drawbacks in the reconstructed images. We need to compute the proximal operator of hybrid regularizations, which is generally a sub-problem in the optimization procedure. Both TV and wavelet L1 regularisers are nonlinear and non-smooth, causing numerical difficulty. We propose a dual iterative approach to solve the minimization problem for hybrid regularizations and also prove the convergence of our proposed method, which we then apply to the problem of MR image reconstruction from highly random under-sampled k-space data. Numerical results show the efficiency and effectiveness of this proposed method.