Irreversible Condition Research Articles

Prevalence Factors Associated With Vision Impairment and Blindness Among Individuals 85 Years and Older in Russia

Visual performance is important for quality of life. However, vision impairment among adults 85 years and older has not been intensively examined. To assess the prevalence of mild vision impairment (VI), moderate to severe vision impairment, and blindness and the factors associated with these conditions among a population 85 years and older. The Ural Very Old Study was a population-based cohort study conducted in rural and urban areas in Bashkortostan, Russia from 2017 to 2020. Among 1882 eligible individuals 85 years and older, 1526 participants (81.1%) were enrolled. Ophthalmologic, physical, and mental examinations. Prevalence of vision impairment and blindness based on best-corrected visual acuity (BCVA; measured using modified Early Treatment of Diabetic Retinopathy Study charts) in the better eye or both eyes. Mild vision impairment was defined as BCVA worse than 6/12 to 6/18, and moderate to severe VI was defined as BCVA worse than 6/18 but equal to or better than 3/60. Blindness was defined as BCVA worse than 3/60. Among 1526 participants, 1149 individuals (75.3%; 846 women [73.6%]; mean [SD] age, 88.2 [2.8 years]) had available BCVA measurements and were included in the present analysis. Mild vision impairment was present in 114 individuals (9.9%; 95% CI, 8.2%-11.7%), moderate to severe VI in 562 individuals (48.9%; 95% CI, 46.0%-51.8%), and blindness in 68 individuals (5.9%; 95% CI, 4.6%-7.3%). Factors associated with moderate to severe VI were cataracts (324 individuals [57.7% of those with moderate to severe VI and 28.2% of total population; 95% CI, 25.6%-30.8%]), secondary cataracts (4 individuals [0.7% of those with moderate to severe VI and 0.3% of total population; 95% CI, 0%-0.7%]), age-related macular degeneration (78 individuals [13.9% of those with moderate to severe VI and 6.8% of total population; 95% CI, 5.3%-8.3%]), glaucoma (45 individuals [8.0% of those with moderate to severe VI and 3.9% of total population; 95% CI, 2.8%-5.0%]), corneal opacifications (26 individuals [4.6% of those with moderate to severe VI and 2.3% of total population; 95% CI, 1.4%-3.1%]), myopic maculopathy (13 individuals [2.3% of those with moderate to severe VI and 1.1% of total population; 95% CI, 0.5%-1.7%]), and nonglaucomatous optic nerve damage (4 individuals [0.7% of those with moderate to severe VI and 0.3% of total population; 95% CI, 0%-0.7%]). Factors associated with blindness were cataracts (33 individuals [48.5% of those with blindness and 2.9% of total population; 95% CI, 1.9%-3.8%]), age-related macular degeneration (15 individuals [22.1% of those with blindness and 1.3% of total population; 95% CI, 0.7%-2.0%]), glaucoma (7 individuals [10.3% of those with blindness and 0.6% of total population; 95% CI, 0.2%-1.1%]), myopic maculopathy (3 individuals [4.4% of those with blindness and 0.3% of total population; 95% CI, 0%-0.6%]), and corneal opacifications (2 individuals [2.9% of those with blindness and 0.2% of total population; 95% CI, 0%-0.4%]). Higher moderate to severe VI prevalence was associated with older age (odds ratio [OR], 1.19; 95% CI, 1.11-1.28; P < .001), higher blood pressure (OR, 1.01; 95% CI, 1.00-1.02; P = .03), lower hand grip force (OR, 0.88; 95% CI, 0.83-0.95; P < .001), lower score on the Mini-Mental State Examination (OR, 0.95; 95% CI, 0.92-0.98; P < .001), lower prothrombin index (OR, 0.93; 95% CI, 0.89-0.97; P < .001), lower refractive error (OR, 0.91; 95% CI, 0.85-0.97; P = .006), and lower prevalence of previous cataract surgery (OR, 0.48; 95% CI, 0.33-0.68; P < .001). In this cohort study of individuals 85 years and older, the prevalence of moderate to severe VI and blindness was relatively high. Cataracts were the main reversible condition associated with vision loss, and age-related macular degeneration, glaucoma, and myopic maculopathy were the main irreversible conditions. Because a higher prevalence of moderate to severe VI was associated with lower cognitive function and physical strength, improvement of vision through increases in cataract surgery and measures to prevent and treat irreversible conditions may help to improve cognitive function and physical strength.

Fasu-Net: Fast Alzheimer’s Disease Screening with Undersampled MRI Using Convolutional Neural Networks

Alzheimer’s Disease (AD) is a progressive and irreversible neurodegenerative condition, which results in dementia. Mild Cognitive Impairment (MCI) is an intermediate state between normal aging and AD. Instead of traditional questionnaire method, magnetic resonance imaging (MRI) can be used by radiologists to diagnose and screening AD recently, but long acquisition time is not conducive to screening AD and MCI. To solve this problem, we develop a Fasu-Net (Fast Alzheimer’s disease Screening neural network with Undersampled MRI) for AD and MCI clinical classification. The network uses undersampled structural MRI with a shorter acquisition time to improve the screening and diagnosis efficiency of AD. For achieving the best classification result, three axial planes of brain MR images were feed into the Fasu-Net with transfer learning method. The experiment results on undersampled 3D T1-weighted images database (ADNI) show that in the AD versus MCI versus HC (Healthy Controls) classification, the Fasu-Net achieved the accuracy of 91.41%, thus can be a potential method for fast clinical screening of AD.

Periodontal Microbiome Part I: A Literature Review

Periodontal disease is one of the most chronic infectious diseases, it is initiated by a reversible inflammatory condition called gingivitis, if untreated, it progresses to an irreversible condition called periodontitis, if not resolved, it leads to tooth loss. Periodontitis is a multifactorial disease, one of these factors is the periodontal microbiome. Consequently, the microbiome is altered according to the host state i.e., health, gingivitis, periodontitis. The microbiome in health is comprised of a variety of microorganisms called health-associated species. They consist of gram-positive cocci and rod with gram-negative species. In this state, the microbiome participates in various physiological functions. While in gingivitis, the microbiome shifts in its composition and can now initiate an inflammatory condition. While in periodontitis, the microbiome is changed to a state where new microorganisms emerge which initiate a periodontal tissue destruction phenomenon. These microorganisms are referred to disease-associated species. Environmental factors are present in which they alter the microbiome composition. Smoking and diabetes were one of the strong extrinsic factors that negatively shape the microbiome into a more aggressive form. Individuals with poor glycemic control or consume tobacco products are more prone to periodontal diseases because their microbiome is rich in bacterial complexes which negatively affects the periodontium. The effect of antibiotic consumption on the microbiome was more or less advantageous, it was observed that not all antibiotics affect the microbiome composition.

Relationship between family functions with depression in palliative patients

Background: Diseases or health problems are a part of life that can occur at any time. Terminal disease represents a patient's irreversible health condition, so that this group of patients can be given a therapeutic approach known as palliative care. Patients who experience significant conflict in the family can increase the likelihood of depression. Patients and Methods: This is a descriptive cross-sectional study in 32 subjects chosen by consecutive sampling. Measuring instrument used was Beck’s Depression Inventory. The family function scale is derived from the McCaster’s Model of Family Functioning known as the Family Assessment Device (FAD). Results: In this study, the average age of the sample was 46 years, unmarried from high school education. In the description of family functions obtained with overall results with moderate function. Correlation between the two things was found to be a weak negative correlation between FAD score and BDI score. The smaller the value score of FAD then will the greater the value of BDI. The worse the function of the family will be more severe levels of depression experienced by the sample in this study. Conclusion: We found there was a significant weak negative correlation between family function and depression in palliative patients at Sanglah Hospital Denpasar.

Ecology, security and international action: beyond sanctions on North Korea

This article explores the international measures that can resolve ecological problems in a highly securitised zone, taking North Korea (DPRK) as an example. The main question posed is how effective the available international policy measures for ecological risk mitigation are in a highly securitised country. Irreversible ecological conditions and aggravating humanitarian crises co-influence each other and threaten society as a whole. The main purpose of the article is to suggest ways of mainstreaming the environmental aspect of security in international actions that engage with problematised countries like North Korea. A cross-cutting analysis is provided on the possible approaches – including environmental aid, extended or integral humanitarian exemption, and proactive ecological intervention – for the international community to be engaged in the field of environmental security under three different circumstances: peace, security alert and conflict. The current international measures employed in North Korea demonstrate that available tools are either overused or underused, thereby failing to address the interconnectivity of the triple perils for the economy, human welfare and ecosystem, and further aggravating political tensions.

CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics

BackgroundAlzheimer's disease (AD) is an insidious, irreversible, and progressive neurodegenerative health condition manifesting as cognitive deficits and amyloid beta (Aβ) plaques and neurofibrillary tangles. Approximately 50 million individuals are affected by AD, and the number is rapidly increasing globally. This review explores the role of CRISPR/Cas9 gene editing in the management of AD and its clinical manifestations. Aim of ReviewThis review aims to provide a deep insight into the recent progress in CRISPR/Cas9-mediated genome editing and its use against neurodegenerative disorders, specifically AD. However, we have referred to its use against parkinsons’s disease (PD), Huntington’s disease (HD), and other human diseases, as is one of the most promising and emerging technologies for disease treatment. Key Scientific Concepts of ReviewThe pathophysiology of AD is known to be linked with gene mutations, that is, presenilin (PSEN) and amyloid beta precursor protein (APP). However, clinical trials focused at the genetic level could not meet the desired efficiency. The CRISPR/Cas9 genome editing tool is one of the most powerful technologies for correcting inconsistent genetic signatures and now extensively used for AD management. It has significant potential for the correction of undesired gene mutations associated with AD. This technology has allowed the development of empirical AD models, therapeutic lines, and diagnostic approaches for better understanding the nervous system, from in vitro to in vivo models.

Mild Cognitive Impairment and its Lifestyle-Related Risk Factors in the Elderly

Context: Alzheimer's dementia (AD), an irreversible condition is an important cause of disability in old age. Mild cognitive impairment (MCI) is an intermediate state between normal cognition and dementia. Amnestic MCI (aMCI) is the precursor of AD. Identification of modifiable lifestyle risk factors help in the prevention of aMCI, and thereby in the prevention of AD. Aim: The purpose of this study was to determine the prevalence of aMCI and different lifestyle factors associated with types of MCI. Methods: This cross-sectional study was conducted amongst the elderly (≥60 years). A sample of 576 persons was selected using a multistage sampling technique. Vernacular adaptation of Hindi Mini-Mental State Examination tool was used to screen dementia and MCI. Geriatric Depression Scale-15 was used for screening depression. Data were collected using a pre-designed and pretested schedule and SPSS was used for data entry and analysis. Results: The prevalence of MCI was found to be 22.4% among the elderly. Out of all MCI cases, the prevalence of aMCI was 38.8% in this study. The lack of social and leisure engagement was found to be significantly associated with the type of MCI. Conclusion: The comparatively higher prevalence of aMCI is just the tip of the iceberg. Lack of social and leisure engagement is a highly predictive risk factor.

Retinal findings in chronic kidney disease patients on hemodialysis

Background Chronic kidney disease (CKD) is an irreversible condition that leads to progression to end-stage renal disease that requires hemodialysis or kidney transplantation for patient survival and these patients are at risk of developing many complications. In the present study, the retinal findings in CKD patients on hemodialysis are evaluated. Patients and methods This is a cross-sectional noninterventional study that was carried out on CKD patients on hemodialysis for at least 3 months in the Nephrology Unit, Tanta University, Egypt; 160 eyes of 80 patients were included over 6 months. A complete ophthalmic evaluation was performed. Color fundus and spectral domain optical coherence tomography were performed at presentation. Results The visual acuity ranged from 6/6 to 6/18 in 80 eyes, which represents 50%, from 6/24 to 6/60 in 62 eyes, which represents 38.75%, and from less than 6/60 to perception of light in 18 eyes, which represents 11.25%. Fundus examination revealed that eight eyes were normal (5%). Hypertensive retinal changes occurred in 82 eyes with variable degrees of retinopathy. Diabetic retinopathy was found in 30 (18.75%) eyes and macular degeneration was detected in 20 (12.5%) eyes. Retinal vasculitis occurred in two (1.25%) eyes, branch retinal vein occlusion was detected in six (3.75%) eyes, glaucomatous optic neuropathy was found in eight (5%) eyes and central retinal artery occlusion occurred in four (2.5%) eyes. Conclusion The most common visual problems in hemodialysis patients that lead to visual loss are hypertensive and diabetic retinopathy. Hence, it is mandatory to screen fundus changes in CKD to prevent loss of vision.

LED control of gene expression in a nanobiosystem composed of metallic nanoparticles and a genetically modified E. coli strain

BackgroundWithin the last decade, genetic engineering and synthetic biology have revolutionized society´s ability to mass-produce complex biological products within genetically-modified microorganisms containing elegantly designed genetic circuitry. However, many challenges still exist in developing bioproduction processes involving genetically modified microorganisms with complex or multiple gene circuits. These challenges include the development of external gene expression regulation methods with the following characteristics: spatial–temporal control and scalability, while inducing minimal permanent or irreversible system-wide conditions. Different stimuli have been used to control gene expression and mitigate these challenges, and they can be characterized by the effect they produce in the culture media conditions. Invasive stimuli that cause permanent, irreversible changes (pH and chemical inducers), non-invasive stimuli that cause partially reversible changes (temperature), and non-invasive stimuli that cause reversible changes in the media conditions (ultrasound, magnetic fields, and light).MethodsOpto-control of gene expression is a non-invasive external trigger that complies with most of the desired characteristics of an external control system. However, the disadvantage relies on the design of the biological photoreceptors and the necessity to design them to respond to a different wavelength for every bioprocess needed to be controlled or regulated in the microorganism. Therefore, this work proposes using biocompatible metallic nanoparticles as external controllers of gene expression, based on their ability to convert light into heat and the capacity of nanotechnology to easily design a wide array of nanostructures capable of absorbing light at different wavelengths and inducing plasmonic photothermal heating.ResultsHere, we designed a nanobiosystem that can be opto-thermally triggered using LED light. The nanobiosystem is composed of biocompatible gold nanoparticles and a genetically modified E. coli with a plasmid that allows mCherry fluorescent protein production at 37 °C in response to an RNA thermometer.ConclusionsThe LED-triggered photothermal protein production system here designed offers a new, cheaper, scalable switchable method, non-destructive for living organisms, and contribute toward the evolution of bioprocess production systems.

Prone Positioning Covid-19 Patients: A Double-Edged Sword-A Case Report of a Devastating Ocular Complication.

In the late 1970s, prone positioning was established as an efficient treatment for acute respiratory distress syndrome (ARDS). Currently, with the world facing a global health crisis due to the COVID-19 pandemic, it has become an accepted routine practice in intensive care units dealing with critically ill COVID-19 patients. Ophthalmic complications associated with the prone position are not a novelty in clinical practice. Indeed, it is estimated that in patients undergoing spine surgery, prone positioning carries a tenfold increased risk of eye injury when compared to supine and lateral positioning. The majority of these complications are treatable ocular surface disorders, but irreversible sight-threatening conditions also occur. We report a unique and dramatic case of a ruptured globe in a COVID-19 patient placed in prolonged prone position, emphasizing its difficult diagnosis and management while focusing on life-saving support.

Impact of Alzheimer's Dementia on Caregivers and Quality Improvement through Art and Music Therapy.

Dementia is a general term for a series of medical conditions that affect the brain and evolve progressively. According to the literature, there are over 200 subtypes and causes of dementia, with Alzheimer’s disease (AD) being the most common in elderly people. AD is an irreversible progressive neurodegenerative condition that leads to a decline in mental function, enough to disrupt daily life. Thinking skills slowly deteriorate, which, in advanced stages, makes it impossible to perform simple tasks. Besides the change in the quality of life of AD patients and their families, there is a considerable alteration in the quality of life of their caregivers, whose health can be negatively affected by the development of mental and somatic disorders. This article reviews the literature in order to reveal the benefits of applying non-pharmacological interventions such as music and art therapy to improve quality of life. This article also aims to shed light on the impact of this disease on the caregiver’s life. Music and art therapy have produced reliable results in the treatment of patients with AD, and the best effects are related to increased socialization and the maintenance of social status.

COVID-19 and Its Relation to Takotsubo Cardiomyopathy

Takotsubo Cardiomyopathy (TC) is a stress caused heart condition, it might be transient or complicatedwith other irreversible conditions. Recently, many case reports were released indicating of COVID-19 casescomplicated with TC. This paper aimd to review studies that examined the correlation between COVID-19and TC. An electronic search was carried out using PubMed and Google Scholar data base.The TC is oneof the major COVID-19 complications that must be taken into consideration. The exact mechanism is stillunknown. Further studies are needed in order to confirm this relationship in addition to investigating theunderlying mechanism.

Abstract IA-027: Dysregulated metabolic and immune pathways underlying radiation fibrosis and lymphedema

Abstract Introduction: Radiation fibrosis (RF) is a long-term complication affecting up to ~1/3 of all patients post treatment, characterized by excess extracellular matrix (ECM), decreased tissue elasticity, leading to potential loss of organ function. The regulation of ECM production and degradation is complex, mediated through a myriad of cytokines including TGFB, and environmental conditions such as hypoxia. Currently, this is an irreversible and untreatable condition, affecting up to 6M cancer survivors in the US. Lymphedema is another inflammatory condition, which also has no effective treatments and is irreversible. In the literature, there is a strong suggestion that metabolic dysregulation might be an underlying process affecting both RF and lymphedema; hence, this avenue of investigation was undertaken for both conditions. Materials &amp; Methods: Mouse models were established for both RF and lymphedema, using the C3H and C57/Bl6 mice; respectively. Genome-wide transcriptomic sequencing analyses were undertaken for both conditions, using human and mouse tissues. For the lymphedema experiments, single-cell RNA-sequencing (scRNA-seq) was performed, to identify the different cell types in the murine lymphedematous fluid. Finally, a pharmacogenomics strategy was undertaken using the CMAP and L1000 databases for the RF and lymphedema studies; respectively, to identify novel compounds or drugs, which can treat these conditions. Results: For both RF and lymphedema studies, metabolic dysregulation, and specifically, downregulation of PPAR signaling and fatty acid oxidation (FAO) were key pathways driving the production and reducing the degradation of collagen, the predominant component of the ECM. Conversely, upregulation of PPAR signaling reduced transcription of key ECM genes for both conditions. In the RF studies, CD36, a membrane transporter of long chain fatty acids, was discovered to play a critical role in regulating the trafficking of collagen and lysosomal degradation. ScRNA-seq of murine lymph fluid identified 8 cell clusters with T helper 17 (Th17) cells being the dominant population (24%). Furthermore, these immune cells also demonstrated downregulation of PPAR signaling, suggesting that this process was universal at both the bulk, and single cell level. Pharmacogenomics analyses identified caffeic acid or its derivate CAPE (caffeic acid phenethyl ester) to be compounds, which can be systemically administered, and reduced cellular proliferation and fibrosis in pre-clinical models for both conditions. Vorinostat however, was even more effective in reducing these processes in lymphedema conditions. Conclusion: For the first time, we have demonstrated that metabolic dysregulation with downregulation of PPAR signaling and FAO as major contributors to both RF and lymphedema. These processes can be mitigated pharmacologically, by using agents such as CAPE or Vorinostat, indicating that these heretofore-untreatable toxicities of radiation therapy can be reversed using such strategies. Citation Format: Fei-Fei Liu. Dysregulated metabolic and immune pathways underlying radiation fibrosis and lymphedema [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-027.

Targeting autophagy as a therapeutic strategy to prevent dopamine neuron loss in early stages of Alzheimer disease

ABSTRACT Alzheimer disease (AD) is a neurodegenerative disorder for which no approved medication exists. AD is characterized by worsening cognitive and non-cognitive symptoms, and research in the AD field strives to identify very precocious brain alterations leading to an irreversible condition. Recently it has been demonstrated that several early AD symptoms are paralleled with degeneration of neurons producing dopamine (DA), a neurotransmitter involved in the regulation of cognitive and non-cognitive functions. Actually, we found that ventral tegmental area (VTA) DA neurons degenerate early in a validated AD mouse model (Tg2576). Here, we summarize new data showing how macroautophagy/autophagy impairment – due to enhanced activity of the ABL/c-Abl kinase – might cause the DA neuron loss. We also proved that nilotinib, an ABL inhibitor, restores autophagy flux, thus preventing VTA neurodegeneration. Most notably, from a clinical point of view, nilotinib, by preventing DA neuronal loss, preserves DA outflow in VTA-projecting areas, improving Tg2576 behavioral phenotypes. Our findings shed light on the mechanism involved in DA neurodegeneration, revealing that autophagy represents a viable therapeutic target in early AD.

Abstract PS13-06: Lower rates of neuropathy with oral paclitaxel and encequidar (oPac+E) compared to IV paclitaxel (IVPac) in treatment of metastatic breast cancer (mBC): Study KX-ORAX-001

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity associated with IVPac. Primarily sensory, CIPN is an often irreversible condition primarily affecting the hands and feet associated with pain, numbness, tingling, and sensitivity to cold and has a significant impact on quality of life and treatment tolerance. Risk of CIPN increases with age, dose intensity, cumulative dose, and preexisting conditions including diabetes. Methods: Study KX-ORAX-001 was a phase III, randomized, international study in women with mBC for whom treatment with IVPac was recommended. Eligible patients were randomized 2:1 to receive oPac+E or IVPac. Patients continued treatment until discontinuation due to progressive disease or toxicity. oPac 205 mg/m2 was given once daily for 3 days weekly. E 12.9 mg was given 1 hour before each dose of oPac. IVPac 175 mg/m2 was infused over 3 hours every 3 weeks. The primary endpoint was efficacy defined as tumor response confirmed by BICR at two consecutive evaluations. Key secondary endpoints included PFS, OS. Safety was monitored throughout the study. Results: A total of 402 mBC patients were enrolled, 265 randomized to oPac+E and 137 to IVPac (ITT population). 399 patients were treated and comprise the safety population. The confirmed response rate was significantly greater in the oPac+E group vs IVPac (35% vs 23%) for the ITT population. Median overall survival was (27.7 vs 16.7 months, ITT) at the time of the analysis. Long-term follow up for final determination of PFS and OS is ongoing.Incidence of neuropathy-related TEAEs were lower in patients receiving oPac+E vs IVPac: Overall (21% vs 64%; all grades), grade ≥3 (2% vs 15%). Cumulative risk for neuropathy with IVPac was &amp;gt;50% by week 8 and was 83% at week 88. In contrast, the cumulative risk of neuropathy with oPac+E rose slowly and plateaued at 34% at week 88. Treatment discontinuations due to neuropathy occurred only in the IVPac arm (8%). Dose reductions due to neuropathy were reported in 8% of IVPac treated patients and in 2% of oPac+E treated patients. In agreement with the lower rates of peripheral neuropathy in patients treated with oPac+E, there was lower use of medications used for the treatment of neuropathic symptoms. Use of gabapentin or pregabalin was 12% for patients receiving oPac+E vs 40% for IVPac treated patients. Conclusions: oPac+E was associated with greater efficacy in the treatment of patients with mBC and a lower incidence of neuropathy, slower onset and lesser severity of neuropathic events compared to IVPac 175mg/m2 administered every three weeks. Fewer patients receiving oPac+E required dose reduction due to neuropathy and no patients receiving oPac+E discontinued treatment due to neuropathy. Reduction in neuropathy may improve quality of life and allow longer administration of effective therapy while maintaining dose intensity. Citation Format: H S Rugo, G Umanzor, F J Barrios, R H Vasallo, M A Chivalan, S Bejarano, J R Ramirez, L Fein, R D Kowalyszyn, D L Cutler, D Kramer, J Goldfinch, H Wang, T Moore, R MF Kwan. Lower rates of neuropathy with oral paclitaxel and encequidar (oPac+E) compared to IV paclitaxel (IVPac) in treatment of metastatic breast cancer (mBC): Study KX-ORAX-001 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-06.

Prevalence of Respiratory Symptoms among Quarry Workers in Brunei Darussalam

Background: The mining and quarrying industry is considered a hazardous work sector due to occupational exposure to quarry dust and particulate matter, resulting in workers' respiratory illnesses. These occupational respiratory illnesses tend to have a long latency before the diagnosis is made, and therefore early detection of respiratory symptoms is crucial to prevent the development of chronic irreversible respiratory conditions. This study aimed to assess quarry workers' self-reported respiratory symptoms and their health-related quality of life (HRQOL) in Brunei.&#x0D; Methods: A descriptive study using a convenient sampling method was involving 23 quarry workers from three quarry companies in Brunei. The data were collected using the adapted St. George's Respiratory Questionnaire (SGRQ), which was self-administered to all participants. Data were analyzed using descriptive statistics.&#x0D; Results: Cough was the most typical reported symptom (26.1%) among quarry workers, followed by cough with phlegm (8.6%), shortness of breath (4.3%), and chest discomfort (4.3%). The mean total SGRQ score was 7.51 (±11.70), while the sub-domain scores for symptoms, activity, and impact were 10.60 (±12.37), 6.30 (±11.43), and 7.35 (±15.87), respectively.&#x0D; Conclusion: The key findings revealed that there was a low prevalence of respiratory symptoms in quarry workers. Prevalence of respiratory symptoms was higher among workers who were smokers, those who were exposed to quarry materials, and those who had been employed longer. The study's findings can be utilized by health professionals to plan, implement and evaluate preventative measures for mining and quarrying work settings.

Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases.

Interstitial lung diseases (ILDs) are chronic irreversible pulmonary conditions with significant morbidity and mortality. Diagnostic approaches to ILDs are complex and multifactorial. Effective therapeutic interventions are continuously investigated and explored with substantial progress, thanks to advances in basic understanding and translational efforts. Extracellular vesicles (EVs) offer a new paradigm in diagnosis and treatment. This leads to two significant implications: new disease biomarker discovery that enables reliable diagnosis and disease assessment and the development of regenerative medicine therapeutics that target fibroproliferative processes in diseased lung tissue. In this review, we discuss the current understanding of the role of diseased tissue-derived EVs in the development of interstitial lung diseases, the utility of these EVs as diagnostic and prognostic tools, and the existing therapeutic utility of EVs. Furthermore, we review the potential therapeutic application of EVs derived from various cellular sources.

Presence of a mutation in PSEN1 or PSEN2 gene is associated with an impaired brain endothelial cell phenotype in vitro

BackgroundAlzheimer’s disease (AD) is the most common form of neurodegenerative disease. It is an irreversible condition marked by irreversible cognitive loss, commonly attributed to the loss of hippocampal neurons due to the formation of senile plaques and neurofibrillary tangles. Although the sporadic form is the most prevalent, the presence of familial form (involving several genes such as APP, PSEN1, and PSEN2) of the disease is commonly used as a model for understanding the pathophysiology of the disease. The aim of this study is to investigate the effect of a mutation on PSEN1 and PSEN2 genes on the BBB function using induced pluripotent stem cells (iPSCs).Methods iPSC lines from patients suffering from a familial form of Alzheimer’s disease and harboring mutations in PSEN1 or PSEN2 were used in this study and compared to a control iPSC line. Cells were differentiated into brain microvascular endothelial cells (BMECs) following established differentiation protocols. Barrier function was assessed by measuring TEER and fluorescein permeability, drug transporter activity was assessed by uptake assay, glucose uptake and metabolism assessed by cell flux analyzer, mitochondrial potential by JC-1, and lysosomal acidification by acridine orange.ResultsiPSC-derived BMECs from the FAD patient presenting a mutation in the PSEN1 gene showed impaired barrier function compared to the FAD patient harboring a mutation in PSEN2 and to the control group. Such impaired barrier function correlated with poor tight junction complexes and reduced drug efflux pump activity. In addition, both PSEN1 and PSEN2-BMECs displayed reduced bioenergetics, lysosomal acidification, autophagy, while showing an increase in radical oxygen species (ROS) production. Finally, PSEN1- and PSEN2-BMECs showed an elevated secretion of Aβ1–40 peptides compared to control-BMECs.ConclusionsOur study reports that iPSC-derived BMECs obtained from FAD patients showed impaired barrier properties and BMEC metabolism. In particular, mutation in the PSEN1 gene was associated with a more detrimental phenotype than mutation in PSEN2, as noted by a reduced barrier function, reduced drug efflux pump activity, and diminished glucose metabolism. Therefore, assessing the contribution of genetic mutations associated with Alzheimer’s disease will allow us to better understand the contribution of the BBB in dementia, but also other neurodegenerative diseases.

Comparative evaluation of periodontal inflammatory conditions among gutka-chewers with and without prediabetes.

The metabolic syndrome has become one of the major public-health challenges worldwide which include diabetes, prediabetes (raised blood glucose level), abdominal obesity, high cholesterol level, and high blood pressure. Periodontitis is described as a multi-factorial irreversible and cumulative condition and, is also the sixth complication of diabetes. Areca nut chewing has already been linked with the development of various cancers, and more recently with metabolic syndrome. Therefore, the purpose of the study is to investigate the association of periodontal inflammatory conditions among gutka chewing with and without prediabetes patients. There are about 50 pre-diabetic and 50 healthy patients, both males and females with the age range of 18 years to 45 years, were included in the study. They were then divided into 4 groups based upon gutka chewers and non-chewers i.e., pre-diabetic gutka chewers (PDC), pre-diabetic non-chewers (PDNC), healthy gutka chewers (HC), and healthy non-chewers (HNC). A complete demographic data was obtained along with clinical and radiographic parameters i.e. plaque index (PI), sulcus bleeding index (SBI), probing depth (PD), marginal bone loss (MBL) were recorded. A statistical analysis was performed and Bonferroni adjustment post hoc test was performed for multiple comparisons. The overall results suggested that the clinical periodontal parameters i.e., PD, PI, SBI and radiologic parameters i.e., MBL are significantly higher in prediabetes chewers compared with healthy chewers and healthy non chewers. The periodontal inflammatory conditions are worse in gutka chewers compared to non-chewers in healthy and pre-diabetic patients, concluding that the severity of periodontal inflammation is governed by hyperglycemia when compared to habitual gutka usage.

Crack path comparisons of a mixed phase‐field fracture model and experiments in punctured EPDM strips

AbstractWorking on quasi‐static phase‐field fracture modeling in nearly incompressible solids for crack propagation is a challenging task. To avoid arising locking effects therein, a mixed form for the solid displacement equation is developed, resulting in two unknowns: a displacement field and a hydro‐static pressure variable. In order to fulfil an inf‐sup condition, stable Taylor‐Hood elements are employed for the displacement‐pressure system. The irreversibility condition of the crack evolution is handled by help of a primal‐dual active set method. To get both a sharper crack and reasonable computational costs, adaptive meshes are used based on a predictor‐corrector scheme. The crack paths from the numerical simulations are compared on the experimentally observed crack paths in carbon black filled ethylene propylene diene monomer (EPDM) rubber strips. The punctured EPDM strips with a hole and a given notch at different heights are stretched till total failure.