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1.
SN Compr Clin Med ; : 1-5, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33948534

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an unprecedented upheaval in our health-care systems. Amongst the many challenges posed by the disease, increased risk of thromboembolism has presented a distinct new front for increased mortality and morbidity. While there are multiple documented evidences for the same, the exact mechanism, knowledge of groups at-risk, and mitigation strategies are evolving. We present a case of a young individual who was diagnosed with acute lymphoblastic leukemia (ALL), was started on appropriate chemotherapy, and subsequently developed severe COVID-19 pneumonia. He was treated for COVID-19 pneumonia and recovered from the illness. However, his recovery from COVID-19 was further complicated by cortical venous sinus thrombosis (CVT). Contrast enhanced magnetic resonance imaging (CEMRI) brain and magnetic resonance venography (MRV) revealed the diagnosis of CVT with hemorrhagic parenchymal changes. He was managed with therapeutic anticoagulation and cerebral decongestants and was subsequently shifted to oral anticoagulant therapy. While the case was managed at a tertiary care setting, it opened up the question of identifying the high-risk groups and to formulate guidelines for extended thromboprophylaxis in these patients.

2.
Adv Protein Chem Struct Biol ; 124: 47-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33632470

RESUMO

Diabetes mellitus has emerged as a severe burden on the medical health system across the globe. Presently, around 422 million people are suffering from diabetes which is speculated to be expanded to about 600 million by 2035. Patients with type 2 diabetes are at increased risk of developing detrimental metabolic and cardiovascular complications. The scientific understanding of this chronic disease and its underlying root cause is not yet fully unraveled. Protein kinases are well known to regulate almost every cellular process through phosphorylation of target protein in diverse signaling pathways. The important role of several protein kinases including AMP-activated protein kinase, IκB kinase and protein kinase C have been well demonstrated in various animal models. They modulate glucose tolerance, inflammation and insulin resistance in the cells via acting on diverse downstream targets and signaling pathways. Thus, modulating the activity of potential human kinases which are significantly involved in diabetes by targeting with small molecule inhibitors could be an attractive therapeutic strategy to tackle diabetes. In this chapter, we have discussed the potential role of protein kinases in glucose metabolism and insulin sensitivity, and in the pathogenesis of diabetes mellitus. Furthermore, the small molecules reported in the literature that can be potentially used for the treatment of diabetes have been discussed in detail.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/enzimologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases/metabolismo , Animais , Glucose , Intolerância à Glucose , Humanos , Resistência à Insulina , Transdução de Sinais
3.
Br J Ophthalmol ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468492

RESUMO

PURPOSE: We described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes. METHODS: We included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system. RESULTS: Over the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression. CONCLUSION: Risk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy.

4.
Age Ageing ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33480974

RESUMO

BACKGROUND: The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. OBJECTIVE: To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. DESIGN: Cross-sectional. SETTING: Population-based. SUBJECTS: Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. METHODS: VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. RESULTS: Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14-1.82, and OR: 1.52, 95%CI 1.19-1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11-1.81, and OR: 1.50, 95%CI 1.15-1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19-2.22), moderate CIND (OR: 1.93, 95%CI 1.45-2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62-3.11) increased significantly with every SD worsening of VA. CONCLUSIONS: Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.

5.
Ophthalmology ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33333104

RESUMO

TOPIC: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional association of VI and CIM remains equivocal. Hence, we conducted a systematic review and meta-analysis to examine this bidirectional relationship. CLINICAL RELEVANCE: Sixty percent risk of CIM has not been well elucidated in the literature. A bidirectional relationship between VI and CIM may support the development of strategies for early detection and management of risk factors for both conditions in older people. METHODS: PubMed, Embase, and Cochrane Central registers were searched systematically for observational studies, published from inception until April 6, 2020, in adults 40 years of age or older reporting objectively measured VI and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We also examined study quality, publication bias, and heterogeneity. RESULTS: Forty studies were included (n = 47 913 570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds of: (1) any CIM (cross-sectional: OR, 2.38 [95% CI, 1.84-3.07]; longitudinal: OR, 1.66 [95% CI, 1.46-1.89]) and (2) clinically diagnosed dementia (cross-sectional: OR, 2.43 [95% CI, 1.48-4.01]; longitudinal: OR, 2.09 [95% CI, 1.37-3.21]) compared with persons without VI. Significant heterogeneity was explained partially by differences in age, sex, and follow-up duration. Also, some evidence suggested that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most articles (8/9 [89%]) reporting significantly positive associations; however, meta-analyses on this association could not be conducted because of insufficient data. DISCUSSION: Overall, our work suggests that VI is a risk factor of CIM, although further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both conditions in older people may minimize individual clinical and public health consequences.

6.
Biochem Biophys Rep ; 24: 100856, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33294634

RESUMO

Background: Proteins have tendency to form inactive aggregates at higher temperatures due to thermal instability. Maintenance of thermal stability is essential to gain the protein in sufficient quantity and biologically active form during their commercial production. Methods: BL21-DE3 Rosetta E. coli cells which contains plasmid pET43.1a vector was used for producing zDHFR protein commercially. The purification of N-terminal Histidine tagged zDHFR was performed by Immobilized Metal Ion chromatography (IMAC). Investigations were performed in existence and non existence of Silver nanoparticles (AgNPs). The inactivation kinetics of zDHFR in existence and non existence of AgNPs were monitored over a range of 40-80 °C as monitored by UV-Visible absorption spectroscopy. Results: The protein completely lost its activity at 55 °C. Kinetics of inactivated zDHFR follows first order model in presence and absence of AgNPs. Decrease in rate constant (k) values at respective temperatures depicts that AgNPs contribute in the thermostability of the protein. AgNPs also assists in regaining the activity of zDHFR protein. Conclusions: AgNPs helps in maintaining thermostability and reducing the aggregation propensity of zDHFR protein. General significance: Result explains that AgNPs are recommended as a valuable system in enhancing the industrial production of biologically active zDHFR protein which is an important component in folate cycle and essential for survival of cells and prevents the protein from being aggregated.

7.
Aging Dis ; 11(6): 1444-1458, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269099

RESUMO

To describe the rationale, design and methodology of a geographically-representative and population-based study investigating the epidemiology, impact, personal and economic burden of age-related eye diseases, declining visual and other sensory systems in Asians aged >60 years in Singapore.PIONEER (The PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans Study) is currently a cross-sectional study targeting 3152 Chinese, Malay and Indian adults who are Singapore citizens or permanent residents aged 60 years and older living across Singapore. The study is intended to be longitudinal, with several waves of data planned to be collected in the future. The sampling frame consisted of 7000 names derived from age, gender and ethnicity-stratified random sampling of individuals >60 years. Selected individuals were invited via letters, home visits, and telephone calls for a clinical assessment at the Singapore Eye Research Institute. Individuals with limited mobility were examined in a custom-designed mobile eye clinic. Questionnaires were subsequently administered at participants' homes by trained interviewers in their preferred language. A total of 3,299 participants (from East, West, North and South Singapore) were approached from December 2017 to November 2019. Of these, 953 (28.5%) were deemed ineligible. Out of 2,346 eligible participants, 904 (38.5%) refused, and 1,442 (61.5%) attended our clinical testing protocol, giving an initial response rate of 61.5%. Of these, 1,170 (81%) were cognitively able to complete the questionnaire assessment. The mean age±SD of our participants was 73.8±8.6 years; n=798 (55.3%) were female; and 828 (57.4%) were of Chinese ethnicity. The findings from this study will allow a deeper understanding of the risk factors and impact of aging in Asian populations, particularly in relation to the visual function and other functional system.

8.
J Invasive Cardiol ; 32(12): E378, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33257590

RESUMO

During inflation of the Inoue balloon during a balloon mitral valvotomy, indentation and compression of the Inoue balloon was seen. This is indirect evidence of severe subvalvular disease.

9.
BMJ Case Rep ; 13(12)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323421

RESUMO

Long QT syndrome with Torsades de Pointes (TdP) is a life-threatening polymorphic ventricular arrhythmia. The corrected QT (QTc) prolongation >500 milliseconds (ms) has been associated with TdP. Hypocalcaemia due to severe vitamin D deficiency is an uncommon cause of acquired long QT. We hereby present a case of a 40-year-old woman with sensorineural deafness and having symptoms of palpitations and presyncope. She had a QTc interval of 556 ms (reference range, QTc 451-470 ms in adult healthy woman) on 24-hour Holter analysis. Genetic analysis for congenital long QT syndrome was negative. She was diagnosed with severe hypocalcaemia secondary to severe vitamin D deficiency. After treatment with intravenous calcium gluconate, followed by oral vitamin D and calcium supplementation, the QTc became normalised and no further episode of palpitations or presyncope occurred. The causes of vitamin D deficiency was due to inadequate exposure to sunlight and a strict vegan diet.


Assuntos
Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/etiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Adulto , Cálcio/uso terapêutico , Gluconato de Cálcio/uso terapêutico , Eletrocardiografia Ambulatorial/métodos , Feminino , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Síndrome do QT Longo/tratamento farmacológico , Metoprolol/uso terapêutico , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
10.
Commun Biol ; 3(1): 755, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311586

RESUMO

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10-16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10-19), TMPRSS5 (rs4936279, P = 2.5 × 10-10), LINC01412 (rs16823886, P = 1.3 × 10-9), GLTSCR1 (rs1005911, P = 9.8 × 10-9), and COMMD1 (rs62149908, P = 1.2 × 10-8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

11.
J Family Med Prim Care ; 9(9): 4769-4773, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33209798

RESUMO

Background: First case of COVID-19 was reported in December 2019 and within a timespan of few months, it has become a pandemic. It has created havoc globally and India is no exception. Globally, it is emphasized that preventive measures play an important role in controlling the rapid spread of COVID-19. In India, 68% of population is rural and this population is going to play a crucial role in the containment of the pandemic. Realizing the key position of rural population in COVID control, this study was conducted to assess the knowledge, attitude, and practices of rural population about the disease. Method and Material: A cross-sectional questionnaire-based study was conducted on patients and their relatives from 1st April, 2020 to 31st May, 2020. A total of 372 participants hailing from rural areas were enrolled. Results: Most common source of information for the participants was through television (54.8%) and radio (49.2%). Only 77% claimed that they were using face mask and 72% claimed to be following social distancing. A large (60%) proportion of the participants did not know that COVID-19 could spread from asymptomatic patients. Education of participants was a key determinant for use of social distancing and face mask as a preventive tool. With increasing age, the practice of social distancing and the use of face mask were decreasing in our study. Conclusion: Television/Radio channels form an important source of information and need to be used more effectively to educate the people about the disease and create awareness about effective preventive measures. People need to be educated about the role of asymptomatic carriers in spreading the disease.

12.
J Invasive Cardiol ; 32(11): E299, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33130598

RESUMO

Iatrogenic pneumopericardium after pericardiocentesis due to accidental leakage from the side port of the sheath has been reported in the literature. In the present case, it occurred during passage of the guidewire. Every step needs to be done meticulously. The patient should be advised not to take a deep breath during the puncture.

13.
Drug Res (Stuttg) ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33137836

RESUMO

Fungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.

14.
J Obstet Gynaecol ; : 1-7, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073639

RESUMO

Preeclampsia (PE) remains a leading cause of maternal morbidity and mortality all over the world. However, its aetiology and pathophysiology remain elusive. Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) inactivates PAF and is seen to decrease in normotensive women. The role of PAF-AH in preeclampsia has been in investigational literature, so far. The few studies done have shown a positive association of elevated levels of PAF-AH with preeclampsia. However, this marker has not been studied in the Indian population to-date and such studies are needed to elucidate the pathogenesis of this condition. Our study aimed to determine the PAF-AH activity by spectrophotometric assay in maternal plasma of 73 PE patients versus 73 normotensive controls and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the genetic level. Relative mRNA expression was calculated by Δ DCT method and a fold change was calculated by 2-ΔDCT. We found that the mean plasma PAF-AH activity levels among cases was significantly higher than the normotensive controls. However, the mRNA expression of the PAF-AH gene was similar between the cases and controls, as well as between severe and non-severe preeclampsia (true fold change =1). To conclude, PAF-AH appears to be increased in women with preeclampsia and hence may contribute to pathophysiology and severity. However, a larger sample size will be required to reiterate this association. Recently, PAF-AH inhibitors such as Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE. IMPACT STATEMENT What is already known on this subject? Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) hydrolyses and inactivates PAF and is seen to decrease in normotensive women. The role of platelet activating factor-acetylhydrolase (PAF-AH) in preeclampsia has been investigational so far. Few studies done have shown a positive association of elevated levels of PAF-AH in preeclamptic women. What do the results of this study add? Our study aimed to determine the activity of PAF-AH in maternal plasma of PE patients versus normal pregnancy and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the level of the gene. We found that plasma PAF-AH activity among preeclamptics was significantly higher than in the controls with a possible role in early-onset preeclampsia (<32 weeks), in the Indian population. This marker has never been studied in this population earlier. The results of our study re-emphasised its role in the pathogenesis of preeclampsia. What are the implications of these findings for clinical practice and/or further research? Such studies are important to not only give us a greater understanding of the various pathways involved in this multifactorial dreaded condition, but can also offer us a marker for early identification of women at risk. Recently, PAF-AH inhibitors like Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.

15.
ACS Omega ; 5(34): 21550-21560, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32905276

RESUMO

The sphingosine kinase-1/sphingosine-1-phosphate pathway is linked with the cancer progression and survival of the chemotherapy-challenged cells. Sphingosine kinase-1 (SphK1) has emerged as an attractive drug target, but their inhibitors from natural sources are limited. In this study, we have chosen harmaline, one of the ß-carboline alkaloids, and report its mechanism of binding to SphK1 and subsequent inhibition. Molecular docking combined with fluorescence binding studies revealed that harmaline binds to the substrate-binding pocket of SphK1 with an appreciable binding affinity and significantly inhibits the kinase activity of SphK1 with an IC50 value in the micromolar range. The cytotoxic effect of harmaline on non-small-cell lung cancer cells by MTT assay was found to be higher for H1299 compared to A549. Harmaline induces apoptosis in non-small-cell lung carcinoma cells (H1299 and A549), possibly via the intrinsic pathway. Our findings suggest that harmaline could be implicated as a scaffold for designing potent anticancer molecules with SphK1 inhibitory potential.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32912848

RESUMO

INTRODUCTION: The study aimed to evaluate Choroidal Vascularity Index (CVI) of Haller's and Sattler's layers and their relationships with choroidal and retinal thickness, volumes measured on enhanced depth imaging-optical coherence tomography (OCT) scans in the eyes of patients without diabetes, patients with diabetes with no diabetic retinopathy (DR) and patients with diabetes and DR. RESEARCH DESIGN AND METHODS: Retrospective analysis of 165 eyes from 84 Singapore Indian Eye Study-2 study participants (group 1: no diabetes, group 2: diabetes with no DR and group 3: with DR). Groups 1 and 2 were matched by age and gender from group 3. RESULTS: In the eyes of patients with diabetes without DR, the macular CVI of Haller's but not Sattler's layer was significantly reduced compared with eyes of patients without diabetes. Eyes with >5 years of diabetes have significantly decreased CVI of Sattler's layers (mean difference=0.06 ± 0.10, p=0.04) and also decreased subfoveal choroidal volume (mean difference=0.89 ± 0.16 mm3, p=0.02), compared with those with ≤5 years of diabetes. CONCLUSION: Diabetic eyes without DR had significantly lower CVI of macular Haller's layer than those of healthy controls. With a longer duration of diabetes, CVI of subfoveal Sattler's layer and choroidal volume continue to decrease, irrespective of diabetic control, suggesting that early diabetic choroidopathy mainly affects larger choroidal veins initially before medium-sized arterioles. The CVI of macular Haller's layer could potentially be used as a marker on spectral domain OCT imaging in newly diagnosed patients with diabetes for the onset of DR and as a possible prognostication tool in diabetic eyes. Future prospective longitudinal studies in diabetic eyes would be useful in establishing the relationship between CVIs of Haller's and Sattler's layer with visual acuity as a marker of photoreceptor health and visual prognosis.

17.
J Gerontol A Biol Sci Med Sci ; 75(12): 2461-2470, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32735331

RESUMO

BACKGROUND: Age-related sensory loss and frailty are common conditions among older adults, but epidemiologic research on their possible links has been inconclusive. Clarifying this relationship is important because sensory loss may be a clinically relevant risk factor for frailty. METHODS: In this systematic review and meta-analysis, we searched 3 databases for observational studies investigating 4 sensory impairments-vision (VI), hearing (HI), smell (SI), and taste (TI)-and their relationships with frailty. We meta-analyzed the cross-sectional associations of VI/HI each with pre-frailty and frailty, investigated sources of heterogeneity using meta-regression and subgroup analyses, and assessed publication bias using Egger's test. RESULTS: We included 17 cross-sectional and 7 longitudinal studies in our review (N = 34,085) from 766 records. Our cross-sectional meta-analyses found that HI and VI were, respectively, associated with 1.5- to 2-fold greater odds of pre-frailty and 2.5- to 3-fold greater odds of frailty. Our results remained largely unchanged after subgroup analyses and meta-regression, though the association between HI and pre-frailty was no longer significant in 2 subgroups which lacked sufficient studies. We did not detect publication bias. Longitudinal studies largely found positive associations between VI/HI and frailty progression from baseline robustness, though they were inconclusive about frailty progression from baseline pre-frailty. Sparse literature and heterogenous methods precluded meta-analyses and conclusions on the SI/TI-frailty relationships. CONCLUSIONS: Our meta-analyses demonstrate significant cross-sectional associations between VI/HI with pre-frailty and frailty. Our review also highlights knowledge gaps on the directionality and modifiability of these relationships and the impact of SI/TI and multiple sensory impairments on frailty.

18.
Transl Vis Sci Technol ; 9(5): 11, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32821483

RESUMO

Purpose: The purpose of this study was to determine the rates of, and factors associated with, eyecare utilization and spectacle affordability among Singaporeans with vision impairment (VI). Methods: We included adults with VI from their second visit of the Singapore Epidemiology of Eye Disease Study. Data on eyecare utilization and spectacle affordability were collected. Low eyecare utilization was defined as no eye check ever or eye checks not even once per year in reference to at least once per year. Difficulty affording glasses was defined as glasses being rated as expensive in reference to not expensive. Results: There were 985 adults (14.5%; 415 Malays, 260 Indian, and 310 Chinese; mean age [SD]: 69.5 [10.2] years; 55.4% women) with VI who answered the above questions, were included. Of these, 624 (63.4%) wore glasses. The rates of low eyecare utilization and difficulty affording eyeglasses were 31% and 63%, respectively. Compared to Chinese (23.8%) and Indians (18.8%), Malays (57.4%) had the highest rates of low eyecare utilization (P < 0.001), and most difficulty affording eyeglasses (47.2% vs. 26.1% and 26.6% in Chinese and Indians, respectively; P < 0.001). Younger age, low socioeconomic status, absence of diabetes, absence of self-reported eye conditions, and poor vision were independently associated with low eyecare utilization, whereas older age and female sex was associated with difficulty affording glasses. Conclusions: In this multi-ethnic population with VI, almost one-third had low eyecare utilization and nearly two-thirds reported difficulty affording eyeglasses. Translational Relevance: This will inform strategies, such as tailored eyecare utilization awareness campaigns and awareness of available subsidy schemes for at-risk Singaporeans, such as Malays.

19.
Int J Biol Macromol ; 161: 1496-1505, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32771517

RESUMO

Sphingosine kinase 1 (SphK1) plays a significant role in various cellular processes, including cell proliferation, apoptosis, and angiogenesis. SphK1 is considered as an attractive target for drug development owing to its connection with several diseases, including cancer. In the current work, the urea-induced unfolding of SphK1 was performed at pH 8.0 and 25 °C using CD and fluorescence spectroscopy. SphK1 follows a biphasic unfolding transition (N â‡Œ I â‡Œ D) with an intermediate (I) state populated around 4.0 M urea concentration. The circular dichroism ([θ]222) and fluorescence emission spectra (λmax) of SphK1 with increasing concentrations of urea were analyzed to calculate Gibbs free energy (ΔG0) for both the transitions (N â‡Œ I and I â‡Œ D). A significant overlap of both the transitions obtained by two spectroscopic properties ([θ]222 and λmax) was observed, indicating that both N â‡Œ I and I â‡Œ D transition follow two-step equilibrium unfolding pattern. Also, we performed 100 ns molecular dynamics (MD) simulations to get atomistic insights into the structural changes in SphK1 with increasing urea concentrations. Our results showed a consistent pattern of the SphK1 unfolding with increasing urea concentrations. Together, spectroscopic and MD simulation findings provide deep insights into the unfolding mechanism and conformational features of SphK1.

20.
Ophthalmology ; 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32738259

RESUMO

PURPOSE: Visual impairment (VI) can have a detrimental impact on vision-related quality of life (VRQoL), but it is still unclear how this relationship varies with age across the VI spectrum. We determined the age-stratified, cross-sectional, and longitudinal associations between VI severity and VRQoL. DESIGN: The baseline and follow-up Singapore Chinese Eye Studies (SCES-1/-2; 2009-2011 and 2015-2017). PARTICIPANTS: A total of 3068 SCES-1 participants (mean age [standard deviation {SD}]: 59.5 [9.8] years; 50.2% female) and 1919 SCES-2 participants (mean age [SD]: 56.8 [8.3] years; 49.9% female). METHODS: Visual impairment was defined as visual acuity (VA) of > 0.3 logarithm of the minimum angle of resolution (logMAR) units; VI severity as mild-moderate (logMAR scores less than the median of all individuals with VI) and severe (logMAR scores median or greater); and VI incidence as VI absence at baseline, but evident at follow-up. Age was stratified into 40 to 49 years, 50 to 64 years, and ≥65 years. MAIN OUTCOME MEASURES: Rasch-transformed scores from the 32-item Impact of Visual Impairment (IVI) questionnaire were used to measure the "Reading," "Mobility," and "Emotional" domains of VRQoL. Multiple linear regression models determined the age-stratified associations of prevalent and incident VI with all 3 VRQoL outcomes, adjusted for potential confounders. RESULTS: Of the 807 persons with prevalent VI, 55.9% had mild-moderate and 44.1% had severe VI. Compared with no VI, age-stratified analyses showed that VRQoL decrements were significant only in the older age groups (mild-moderate VI: 6.2% and 8.1% reduction in Mobility and Reading scores in those aged ≥ 65 years; severe VI: 8.5% to 13.4% reductions in the 3 VRQoL scores in those aged ≥ 50 years). This interaction with older age became more pronounced with incident VI (N = 168), where decrements in all 3 VRQoL domains were evident only in those aged ≥65 years compared with persons without incident VI. CONCLUSIONS: Our results suggest that the VI-VRQoL associations are driven mainly by older individuals aged ≥65 years, highlighting the need for effective regular screening and early intervention modalities to prevent the presence and onset of VI, and subsequent VRQoL declines, in these individuals.

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