Quality of Life and its associated factors among caregivers of patients with dementia – A cross-sectional study in Kuching, Sarawak, Malaysia

This study aimed to determine the quality of life and its associated factors among caregivers of patients with dementia in Kuching, Sarawak, Malaysia. Methods: This cross-sectional study was carried out among caregivers for dementia patients who visited three main hospitals in Kuching, Sarawak. Using a validated questionnaire, data was obtained based on socio-demographic profile, patient and caregiving characteristics, supports needs by caregivers, and quality of life (QoL) of caregivers modified from Zarit Burden Interview (ZBI), Hospital Anxiety and Depression Scale (HADS) and Evaluation’s Scale of the Caregiver’s QoL. Results: A total of 217 caregivers participated with response rate of 99.6%, with 67.3% female and 63.1% Chinese. Most respondent provide care for their parents (62.7%), and stay with patients (67.3%). Average duration of care was 4.2 years (SD±3.72). Resource referral (M=3.52, SD±1.334) and education support (M=3.67, SD±1.054) was highest need. Majority respondents experienced little to no burden (59%). Most respondents were not depressed (98.1%). The QoL of respondents was satisfactory (M=41.36, SD±25.840). Gender of caregivers, patients with behavioural and psychological symptoms of dementia, duration of caregiving, respite care need, caregiver disability or illness, belonging support need, education support need were significantly associated with QoL of caregivers (p<0.05). Conclusion: This study on QoL of caregivers of dementia patients in Sarawak, Malaysia shows that it can be influenced by many factors, both at the caregivers’ level as well as the patients themselves. Therefore, intervention should aim at patients and their caregivers, and within community and healthcare settings

Mental Health Status and Its Associated Factors Among Caregivers of Psychiatric Patients in Kuching, Sarawak

Introduction: Caregivers have a high risk of mental health disorders. The quality of patient care is inseparable from the mental health status of caregivers. The objective of this research was to study the mental health status among caregivers of psychiatric patients and its associated factors. Method: A cross-sectional study was conducted among 198 caregivers in Kuching from January till July 2014. The respondents were recruited using systematic sampling and were required to provide information on sociodemographic and environmental factors as well as complete the Hospital Anxiety and Depression Scale (HADS) questionnaire. The data was analysed using the IBM SPSS Statistical Software Version 20.0. Results: The prevalence rates of anxiety and depression among caregivers were 32.8% and 27.8%, respectively. The caregiver’s age (OR=0.97, 95% CI = 0.953 - 0.996), the perception of caregiving as an economic burden (OR= 2.70, 95% CI= 1.256 - 5.803) and the dependence of the patient (OR= 2.27, 95% CI= 1.087 - 4.719) were associated with anxiety. A caregiver who was male (OR= 2.21, 95% CI= 1.143 - 4.262), a caretaker who held the perception that a patient was dependent on them (OR=2.53, 95% CI= 1.203 - 5.337) , and a caretaker who lacked stress-coping skills (OR=2.48, 95% CI= 1.030 - 5.973) were found to be significant factors in depression. Conclusion: A high prevalence of probable anxiety and depression among caregivers points to the need to screen caregivers. There is a vital need to train healthcare workers to be able to detect early anxiety and depression. Culturally sensitive research should be carried out for different ethnicity, and improving the support system for caregivers is necessary

An asymmetric junctional mechanoresponse coordinates mitotic rounding with epithelial integrity

Epithelia are continuously self-renewed, but how epithelial integrity is maintained during the morphological changes that cells undergo in mitosis is not well understood. Here, we show that as epithelial cells round up when they enter mitosis, they exert tensile forces on neighboring cells. We find that mitotic cell–cell junctions withstand these tensile forces through the mechanosensitive recruitment of the actin-binding protein vinculin to cadherin-based adhesions. Surprisingly, vinculin that is recruited to mitotic junctions originates selectively from the neighbors of mitotic cells, resulting in an asymmetric composition of cadherin junctions. Inhibition of junctional vinculin recruitment in neighbors of mitotic cells results in junctional breakage and weakened epithelial barrier. Conversely, the absence of vinculin from the cadherin complex in mitotic cells is necessary to successfully undergo mitotic rounding. Our data thus identify an asymmetric mechanoresponse at cadherin adhesions during mitosis, which is essential to maintain epithelial integrity while at the same time enable the shape changes of mitotic cells

Platelet Reactive Oxygen Species, Oxidised Lipid Stress, Current Perspectives, and an Update on Future Directions

Blood platelets are anucleate cells that play a vital role in haemostasis, innate immunity, angiogenesis, and wound healing. However, the inappropriate activation of platelets also contributes to vascular inflammation, atherogenesis, and thrombosis. Platelet activation is a highly complex receptor-mediated process that involves a multitude of signalling intermediates in which Reactive Oxygen Species (ROS) are proposed to play an important role. However, like for many cells, changes in the balance of ROS generation and/or scavenging in disease states may lead to the adoption of maladaptive platelet phenotypes. Here, we review the diverse roles of ROS in platelet function and how ROS are linked to specific platelet activation pathways. We also examine how changes in disease, particularly the plasma oxidised low-density lipoprotein (oxLDL), affect platelet ROS generation and platelet function

Regenerative Potential Nanomedicine of Adipocyte Stem Cell-Derived Exosomes in Senescent Skin Tissue [Response to Letter]

An-Na Li,1,&amp;ast; Jing-Hua Sun,1,2,&amp;ast; Syafiqah Saidin,3,4 Jee Syuen Cheah,4,5 Chia-Hung Kuo,6 Ling Li,1 Jia-Shen Li,1 Ru-Yu Bai,1 Yong Diao,1 Hui-Min David Wang5,7&amp;ndash;9 1School of Medicine, Huaqiao University, Quanzhou, Fujian, 362021, People&amp;rsquo;s Republic of China; 2Hebei Key Laboratory of Basic Medicine for Diabetes, Shijiazhuang Second Hospital, Shijiazhuang, Hebei, 050000, People&amp;rsquo;s Republic of China; 3IJN-UTM Cardiovascular Engineering Centre, Institute of Human Centered Engineering, Universiti Teknologi Malaysia, Johor Bahru, Johor, 81310, Malaysia; 4Department of Biomedical Engineering &amp;amp; Health Sciences, Faculty of Electrical Engineering, Universiti Teknologi Malaysia, Johor Bahru, Johor, 81310, Malaysia; 5Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan, Republic of China; 6Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan, Republic of China; 7Regenerative Medicine and Cell Therapy Research Center; and Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 8Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, Republic of China; 9Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan, Republic of China&amp;ast;These authors contributed equally to this workCorrespondence: Hui-Min David Wang, Graduate Institute of Biomedical Engineering, National Chung Hsing University, No. 145, Xingda Road, South District, Taichung City, 402, Taiwan, Republic of China, Tel +886 4 22840733 &amp;num;651 ; +886 935753718, Email [email protected] Yong Diao, School of Medicine, Huaqiao University, Quanzhou, Fujian, 362021, People&amp;rsquo;s Republic of China, Email [email protected]

Application of wood waste ash in concrete making: revisited

Portland cement production is a carbon dioxide trigger responsible for almost 5% of the worlds CO2 emissions. Pozzolanic inclusions could contribute to sustainability particularly if they are derived from waste. Managing solid waste is increasingly becoming a global challenge as a result of increasing volume of accumulated waste from industrial and agricultural by-products. Environmental concerns as well as economic implications related with disposal of these wastes have prompted many researches in order to provide viable solutions. Recycling of these waste materials into the construction industry seems to be a more promising and viable alternative most especially in the manufacturing of greener and sustainable concrete material. Wood ash (WA) is a by-product derived from incineration of wood as well as its products such as sawdust, wood bark and chips. This paper presents an overview on investigations performed on the applicability of this material in mortar and concrete making. Specifics on physical, chemical, mineralogical and elemental characteristics of the waste material are discussed. It highpoints the impact of wood ash on workability, compressive and flexure strengths, water absorption, drying shrinkage, carbonation, alkali–silica reaction (ASR) and chloride permeability of concrete

Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner

Platelet activation is critical for haemostasis, but if unregulated can lead to pathological thrombosis. Endogenous platelet inhibitory mechanisms are mediated by prostacyclin (PGI2)-stimulated cAMP signalling, which is regulated by phosphodiesterase 3A (PDE3A). However, spatiotemporal regulation of PDE3A activity in platelets is unknown. Here, we report that platelets possess multiple PDE3A isoforms with seemingly identical molecular weights (100 kDa). One isoform contained a unique N-terminal sequence that corresponded to PDE3A1 in nucleated cells but with negligible contribution to overall PDE3A activity. The predominant cytosolic PDE3A isoform did not possess the unique N-terminal sequence and accounted for &gt;99% of basal PDE3A activity. PGI2 treatment induced a dose and time-dependent increase in PDE3A phosphorylation which was PKA-dependent and associated with an increase in phosphodiesterase enzymatic activity. The effects of PGI2 on PDE3A were modulated by A-kinase anchoring protein (AKAP) disruptor peptides, suggesting an AKAP-mediated PDE3A signalosome. We identified AKAP7, AKAP9, AKAP12, AKAP13, and moesin expressed in platelets but focussed on AKAP7 as a potential PDE3A binding partner. Using a combination of immunoprecipitation, proximity ligation techniques, and activity assays, we identified a novel PDE3A/PKA RII/AKAP7 signalosome in platelets that integrates propagation and termination of cAMP signalling through coupling of PKA and PDE3A

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

The critical role of platelet adenylyl cyclase 6 in haemostasis and thrombosis

Background Platelet activation is constrained by endothelial-derived prostacyclin (PGI2) through cyclic adenosine-5’-monophosphate (cAMP) signalling involving multiple isoforms of adenylyl cyclase (AC). The roles of specific AC isoforms in controlling haemostasis remain unclear and require clarification. Objectives To understand the specific contribution of AC6 in platelet haemostatic and thrombotic function. Methods A platelet-specific AC6 knockout (AC6-KO) mouse was generated. Biochemical approaches were used to determine intracellular signalling, with flow cytometry, tail bleeding time assays and in vivo thrombosis by ferric chloride were used to measure the haemostatic and thrombotic importance of platelet AC6. Results Loss of AC6 resulted in diminished accumulation of platelet cAMP in response to PGI2, while basal cAMP was unaffected. We found no differences in phosphodiesterase 3A (PDE3A) activity, suggesting the defect was in generation rather than hydrolysis of cAMP. Consistent with this, phosphorylation of PKA substrates, vasodilator-stimulated phosphoprotein and glycogen synthase kinase were diminished but not ablated. Functional studies demonstrated that the inhibition of thrombin-induced fibrinogen binding and P-selectin expression by PGI2 was severely compromised, while inhibition of GPVI-mediated platelet activation was largely unaffected. Under conditions of flow formed stable thrombi, but in the absence of AC6, thrombi were insensitive to PGI2. In vivo diminished sensitivity to PGI2 manifested as significantly reduced tail bleeding and accelerated occlusive arterial thrombus formation in response to vascular injury that were highly unstable and prone to embolisation in AC6-KO mice. Conclusions These data demonstrate that AC6 is linked directly to PGI2-mediated platelet inhibition and regulation of haemostasis and thrombosis in vivo

Efficient Algorithms for Probing the RNA Mutation Landscape

The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In particular, we show qualitative agreement between published Hepatitis C and HIV experimental mutagenesis studies and our analysis of deleterious mutations using RNAmutants. Our work also predicts other deleterious mutations, which could be verified experimentally. Finally, we provide evidence that the 3′ UTR of the GB RNA virus C has been optimized to preserve evolutionarily conserved stem regions from a deleterious effect of pointwise mutations. We hope that there will be long-term potential applications of RNAmutants in de novo RNA design and drug design against RNA viruses. This work also suggests potential applications for large-scale exploration of the RNA sequence-structure network. Binary distributions are available at http://RNAmutants.csail.mit.edu/