Search

PurposeTo compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among 4 glaucomatous optic disc phenotypes in early glaucoma.DesignClinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into 4 types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed effects model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes.ResultsAfter adjusting for confounders, the SS group (mean [95% CI]: -1.01 [-1.30, -0.73] µm/y) had the fastest mean rate of global cpRNFL thinning followed by FI (-0.77 [-0.97, -0.57] µm/y), MY (0.59 [-0.81, -0.36] µm/y), and GE (-0.58 [-0.75, -0.40] µm/y) at P < .001. The inferior temporal sector had the fastest rate of cpRNFL thinning among the regional measurements except for the MY group (-0.68 [-1.10, -0.26] µm/y, P = .002). In the multivariable analysis, GE (P = .002) and MY (P = .010) phenotypes were associated with significantly slower global rates of cpRNFL thinning compared with the SS phenotype.ConclusionsRates of cpRNFL thinning were different among the 4 glaucomatous optic disc phenotypes. Those patients with early glaucoma with SS phenotype have the fastest cpRNFL thinning. These patients may benefit from more frequent monitoring and the need to advance therapy if cpRNFL thinning is detected.

PurposeTo investigate central visual field (VF) defects among 4 phenotypes of glaucomatous optic discs.DesignCross-sectional study.MethodsOptic disc phenotypes were determined in eyes with definite or suspected glaucoma that had a 24-2 VF with mean deviation (MD) better than -12 dB and a 10-2 VF. 10-2 VFs were classified as abnormal based on a cluster criterion. Additionally, the average of the total deviation values at each 10-2 test point was compared by optic disc phenotype.ResultsThe following 4 glaucomatous optic disc phenotypes were identified in 448 eyes of 309 patients: focal ischemic (FI) (n = 121); generalized cup enlargement (GE) (n = 109); myopic glaucoma (MY) (n = 66); and senile sclerotic (SS) (n = 152). Although 24-2 VF MD values were similar among optic disc phenotypes, GE eyes had higher 10-2 VF MD (P = .004), as well as lower 24-2 VF pattern standard deviations (PSD) (P < .001) and VF 10-2 PSD (P < .001) than the other phenotypes. The prevalence of an abnormal VF 10-2 was highest in FI eyes (78.5%) and lowest in GE eyes (50.5%) (P < .001). In glaucoma suspects, the prevalence of an abnormal 10-2 VF was highest in the MY eyes (31.2%) and FI eyes (23.5%) and lowest in GE eyes (8.6%). In mild glaucoma, the prevalence of abnormal 10-2 VF test results was highest in FI eyes (79.2%) and lowest in GE eyes (44.4%) (P = .013).ConclusionsThe severity and prevalence of central VF loss varied among different glaucomatous optic disc phenotypes. Glaucomatous eyes with FI and MY optic disc phenotypes are more likely to have 10-2 VF loss, particularly in early disease, and especially may benefit from testing with both 10-2 and 24-2 VF tests.

Most studies aiming at unraveling the molecular events associated with cardiac congenital heart disease (CHD) have focused on the effect of mutations occurring in the nuclear genome. In recent years, a significant role has been attributed to mitochondria for correct heart development and maturation of cardiomyocytes. Moreover, numerous heart defects have been associated with nucleotide variations occurring in the mitochondrial genome, affecting mitochondrial functions and cardiac energy metabolism, including genes encoding for subunits of respiratory chain complexes. Therefore, mutations in the mitochondrial genome may be a major cause of heart disease, including CHD, and their identification and characterization can shed light on pathological mechanisms occurring during heart development. Here, we have analyzed mitochondrial genetic variants in previously reported mutational genome hotspots and the flanking regions of mt-ND1, mt-ND2, mt-COXI, mt-COXII, mt-ATPase8, mt-ATPase6, mt-COXIII, and mt-tRNAs (Ile, Gln, Met, Trp, Ala, Asn, Cys, Tyr, Ser, Asp, and Lys) encoding genes by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) in 200 patients with CHD, undergoing cardiac surgery. A total of 23 mitochondrial variations (5 missense mutations, 8 synonymous variations, and 10 nucleotide changes in tRNA encoding genes) were identified and included 16 novel variants. Additionally, we showed that intracellular ATP was significantly reduced (P=0.002) in CHD patients compared with healthy controls, suggesting that the mutations have an impact on mitochondrial energy production. Functional and structural alterations caused by the mitochondrial nucleotide variations in the gene products were studied in-silico and predicted to convey a predisposing risk factor for CHD. Further studies are necessary to better understand the mechanisms by which the alterations identified in the present study contribute to the development of CHD in patients.

Abstract Background Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. Method We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. Results Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57–4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07–2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00–1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30–1.53), high physical activity (PR: 0.66; 95% CI 0.45–0.95), use of opiate ever (PR: 0.46; 95% CI 0.26–0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12–0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. Conclusion Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Objective: According to the mounting data, microRNAs (miRNAs) may play a key role in reprogramming. miR-106bis considered as an enhancer in reprogramming efficiency. Based on induced pluripotent stem cells (iPSCs), cell treatments have a huge amount of potential. One of the main concerns about using iPSCs in therapeutic settings is the possibility of tumor formation. It is hypothesized that a procedure that can reprogram cells with less genetic manipulation reduces the possibility of tumorigenicity.Materials and Methods: In this experimental study, miR-106b-5p transduced by pLV-miRNA vector into mice isolated spermatogonial stem cells (SSCs) to achieve iPS-like cells. Then the transduced cells were cultured in specific conditions to study the formation of three germ layers. The tumorigenicity of these iPS-like cells was investigated by transplantation into male BALB/C mice.Results: We show that SSCs can be successfully reprogrammed into induced iPS-like cells by pLV-miRNA vector to transduce the hsa-mir-106b-5p into SSCs and generating osteogenic, neural and hepatoblast lineage cells in vitro as a result of pluripotency. Although these iPS-like cells are pluripotent, they cannot form palpable tumors in vivo.Conclusion: These results demonstrate that infection of hsa-mir-106b-5p into SSCs can reprogram them into iPSCsand advanced germ cell lineages without tumorigenicity. Also, a novel approach for studying the generation of iPSCsand the application of iPS or iPS-like cells in regenerative medicine is presented.

Purpose: To examine the epidemiology and factors of cannabis use among open-angle glaucoma (OAG) patients. Methods: In this cross-sectional study, OAG participants in the All of Us database were included. Cannabis ever-users were defined based on record of cannabis use. Demographic and socioeconomic data were collected and compared between cannabis ever-users and never-users using Chi-Square tests and logistic regression. Odds ratios (OR) of potential factors associated with cannabis use were examined in univariable and multivariable models. Results: Among 3723 OAG participants, 1436 (39%) were cannabis ever-users. The mean (SD) age of never-users and ever-users was 72.9 (10.4) and 69.2 (9.6) years, respectively (P

Introduction: Increasing levels of free radicals in the ova reduce the quality of their fertilization. Investigations have revealed the elevated production of tissue and serum-free radicals in women with polycystic ovary syndrome. Sirtuin-3 is located in mitochondria and plays an important role in the deactivation of free radicals. This study aimed to investigate the expression of the Sirtuin-3 gene in the ova of polycystic ovary syndrome affected mice. Material & Methods: Polycystic ovary syndrome was induced by the injection of estradiol valerate (40 mg/kg) in six NMRI mice (age: six weeks old; weight: 25±5); moreover, six mice were selected as a control group. Following the induction, the structure of the ovaries was examined using the histotechnique, and the serum levels of sex hormones were determined using ELISA. The ova were collected from the ovaries, and their RNA was extracted by a special kit and converted to cDNA. Real-Time PCR was performed to analyze the expression of Sirtuin-3, and the Gapdh gene was selected as an internal control. (Ethic code: 97/6505) Findings: In the mice with polycystic ovary syndrome, hydatid cysts were formed in the ovaries. Furthermore, serum FSH hormone levels decreased in the affected mice, while LH and testosterone levels elevated, compared to those in the control mice (P

Abstract The advent of spectral-domain optical coherence tomography has played a transformative role in posterior segment imaging of the eye. Traditionally, images of the optic nerve head and the peripapillary area have been used to evaluate the structural changes associated with glaucoma. Recently, there is growing evidence in the literature supporting the use of macular spectral-domain optical coherence tomography as a complementary tool for clinical evaluation and research purposes in glaucoma. Containing more than 50% of retinal ganglion cells in a multilayered pattern, macula is shown to be affected even at the earliest stages of glaucomatous structural damage. Risk assessment for glaucoma progression, earlier detection of glaucomatous structural damage, monitoring of glaucoma especially in advanced cases, and glaucoma evaluation in certain ocular conditions including eyes with high myopia, positive history of disc hemorrhage, and certain optic disc phenotypes are specific domains where macular imaging yields complementary information compared to optic nerve head and peripapillary evaluation using optical coherence tomography. Moreover, the development of artificial intelligence models in data analysis has enabled a tremendous opportunity to create an integrated representation of structural and functional alterations observed in glaucoma. In this study, we aimed at providing a brief review of the main clinical applications and future potential utility of macular spectral-domain optical coherence tomography in glaucoma.

Epoxy resins are widely used as encapsulating materials in the electronic and electrical industries, transportation, coatings, adhesives, and advanced composite matrices owing to their excellent heat, moisture and chemical resistance, high tensile strength, low shrinkage on curing, and excellent dimensional stability. Epoxy resins are very flammable; this nature seriously restricts their widespread applications, especially in the areas requiring high flame retardancy. To address this challenging problem, several approaches, such as use of halogen-based flame retardant, organophosphorus compounds (e.g., ammonium polyphosphate and melamine polyphosphate), inorganic flame retardants (most widely used alumina trihydrate and magnesium hydroxide known as ATH and MDH, respectively), nitrogen-based flame retardants, silicon-based flame retardants, intumescent flame retardants, and nanomaterials have been proposed. Phosphorus-containing compounds are mostly used as substitutes for the halogenated compounds in flame-retardant epoxy resins. Various phosphorus compounds are used as additive or reactive flame retardants. Comparing the additive flame retardants, reactive organophosphorus compounds present excellent flame retardant efficiency in the case of epoxy resins and it can be chemically linked to the backbone of the network either through being part of the curing agent or through the structure of epoxy resins itself and giving intrinsic flame retardancy. In this review, classification of flame retardants (halogen-based flame retardants, organophosphorus compounds, inorganic flame retardants, nitrogen- and silicon-based flame retardants, intumescent flame retardants and nanocomposites), the combustion cycle of polymers and application of flame retardants, especially phosphorus-based flame retardants for epoxy resins are introduced and classified. Experimental test methods for evaluation of flame retardancy like UL-94, limiting oxygen index and cone calorimeter are also discussed.

Background/aims To investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma. Methods A longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics. Results Faster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively). Conclusions Significant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) causes progressive age-related defects in memory and cognitive function and has emerged as a major health and socio-economic concern in the US and worldwide. To develop effective therapeutic treatments for AD, we need to better understand the neural mechanisms by which AD causes memory loss and cognitive deficits. Here we examine large-scale hippocampal neural population calcium activities imaged at single cell resolution in a triple-transgenic Alzheimer's disease mouse model (3xTg-AD) that presents both amyloid plaque and neurofibrillary pathological features along with age-related behavioral defects. To measure encoding of environmental location in hippocampal neural ensembles in the 3xTg-AD mice in vivo, we performed GCaMP6-based calcium imaging using head-mounted, miniature fluorescent microscopes (“miniscopes”) on freely moving animals. We compared hippocampal CA1 excitatory neural ensemble activities during open-field exploration and track-based route-running behaviors in age-matched AD and control mice at young (3–6.5 months old) and old (18–21 months old) ages. During open-field exploration, 3xTg-AD CA1 excitatory cells display significantly higher calcium activity rates compared with Non-Tg controls for both the young and old age groups, suggesting that in vivo enhanced neuronal calcium ensemble activity is a disease feature. CA1 neuronal populations of 3xTg-AD mice show lower spatial information scores compared with control mice. The spatial firing of CA1 neurons of old 3xTg-AD mice also displays higher sparsity and spatial coherence, indicating less place specificity for spatial representation. We find locomotor speed significantly modulates the amplitude of hippocampal neural calcium ensemble activities to a greater extent in 3xTg-AD mice during open field exploration. Our data offer new and comprehensive information about age-dependent neural circuit activity changes in this important AD mouse model and provide strong evidence that spatial coding defects in the neuronal population activities are associated with AD pathology and AD-related memory behavioral deficits.

Studio-based pedagogy has been central to urban design programmes as it can enable future urban designers to more effectively acquire an understanding of how cities work and critically engage with the role of design intervention. This paper aims to explore the capacities and challenges of learning and teaching urban design through studio pedagogy by drawing on empirical research from a blended urban design studio experiment during the COVID-19 pandemic in the UK. This is part of a broader exploratory project using a case study research design and mixed methods approach. This paper explains the process of designing and delivering two constructively aligned postgraduate urban design studios as part of the MA Urban Design programme at Cardiff University in the 2021–2022 academic year. It further discusses the findings of an online survey on the perceptions and experiences of students regarding blended design studio pedagogy. Designing two consecutive and constructively aligned design studios is argued to work better in comparison with designing two entirely separate stand-alone design studios engaging with different topics and sites. The paper highlights the importance of learning from cities as real urban design laboratories rather than merely analysing abstract secondary datasets. The value of policy review, small group reading discussions, and formative feedback opportunities is also highlighted as integral parts of the urban design studio pedagogy. The paper concludes by discussing a range of key issues concerning field site visit, policy review, community engagement, precedent review, student diversity, design studio topic, reading discussion, group size, formative feedback, engagement, educational background, and English language skills. The outcomes of this paper can inform future practices of developing pedagogical frameworks for blended urban design studios.

Forms of informal urbanism, ranging from informal settlement to street vending and informal transport, have become integral to how places work across different contexts and scales. In this article, we reflect on the ethics of researching forms of urban informality, with a focus on the capacities and challenges associated with exploring informal urbanism, particularly in the context of what is considered the global South. By drawing on our experiences of investigating various forms of informality in different contexts, this article engages with ethical considerations that arise when researching informal urbanism. We argue that designing, conducting and disseminating research on forms of urban informality can pose critical ethical questions for researchers who not only strive to bring about positive change but must also exercise caution to avoid causing more harm than good by exposing individuals at risk of exploitation, eviction or displacement. [ABSTRACT FROM AUTHOR]

Within the past decade, there has been a surge of interest in investigating the dynamics of informal street vending, motivated by the need to address economic, social, and political inequalities. We take stock of this literature, bringing together the various streams of research in which informal street vending is integral to how cities work, particularly in the context of what is considered as the global South. The review of the related literature in this paper is structured into eight key themes, including (1) gender, (2) typology/types, (3) spatiality of street vending and public space design, (4) health and well-being, (5) individual/collective agency, (6) policy environment, (7) use of technology, and (8) links to other forms of informality. The paper concludes by outlining certain research themes that are in the process of development, identifying some understudied areas, reflecting on existing gaps, and pointing to future research directions to enable further engagement with those aspects of informal street vending research that have remained underexplored.

Background and Objectives: Researchers all around the world are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the efficacy and safety of treatment with Remdesivir in hospitalized patients with COVID-19. Materials and Methods: We performed a systematic search in Pubmed, Embase, Web of Science, Google scholar and MedRxiv for relevant observational and interventional studies. The outcomes measures were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: Three randomized controlled trials and 2 cohort studies were included in our study. In the 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day efficacy of treatment with Remdesivir versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that the efficacy of Remdesivir was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowered 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have a significant difference; however, severe adverse event rate was lower in the 5-day Remdesivir group compared to the 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe, and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.

The imperative to address the challenge of transforming car-dependent cities and promoting sustainable mobilities requires that we engage with the relationships between urban morphology and forms of urbanity in public spaces surrounding transit nodes. While there has been a surge of interest in investigating the agency of urban planning and design in mitigating urban sprawl and its environmental impacts by creating mixed-use, dense, and walkable places, the extent to which the public space can enable streetlife intensity in proximity to transit remains underexplored. Through extensive urban mapping and comparison of two transit nodes in Tehran, this paper articulates the key morphological elements of building density, functional mix, and access networks, how they work in relation to forms of urbanity and informality in public space around stations, and what inferences can be made on how public space within station areas work in the context of rapidly urbanising cities compared to those in Western contexts. The nexus between functional mix, retail edges, and forms of urbanity has been found critical to the spatial configuration, performance, and transformation of transit station areas. Forms of informality have also been found integral to how public space works in the context of transit urban design. This paper contributes to the newfound accent on urban design dimensions concerning TODs in the context of less formal and more congested cities of the global South.