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5,081 result(s) for "Li, Patrick"
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Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong
Purpose We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre. Methods A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD). Results Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) ( p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases ( p = 0.01). Conclusion We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.
Strategies for combating antibiotic resistance in bacterial biofilms
Biofilms, which are complexes of microorganisms that adhere to surfaces and secrete protective extracellular matrices, wield substantial influence across diverse domains such as medicine, industry, and environmental science. Despite ongoing challenges posed by biofilms in clinical medicine, research in this field remains dynamic and indeterminate. This article provides a contemporary assessment of biofilms and their treatment, with a focus on recent advances, to chronicle the evolving landscape of biofilm research.
Diversifying the structure of zinc finger nucleases for high-precision genome editing
Genome editing for therapeutic applications often requires cleavage within a narrow sequence window. Here, to enable such high-precision targeting with zinc-finger nucleases (ZFNs), we have developed an expanded set of architectures that collectively increase the configurational options available for design by a factor of 64. These new architectures feature the functional attachment of the FokI cleavage domain to the amino terminus of one or both zinc-finger proteins (ZFPs) in the ZFN dimer, as well as the option to skip bases between the target triplets of otherwise adjacent fingers in each zinc-finger array. Using our new architectures, we demonstrate targeting of an arbitrarily chosen 28 bp genomic locus at a density that approaches 1.0 (i.e., efficient ZFNs available for targeting almost every base step). We show that these new architectures may be used for targeting three loci of therapeutic significance with a high degree of precision, efficiency, and specificity. Genome editing often requires cleavage within a narrow sequence window. Here the authors develop an expanded set of zinc finger nuclease architectures that increase the available configurations by a factor of 64 and can target almost every base at loci of therapeutic significance.
RiboTag translatomic profiling of Drosophila oenocytes under aging and induced oxidative stress
Background Aging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, liver shows age-related dysregulation of lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In the fruit fly, Drosophila melanogaster , liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Compared to fat body, little is known about how oenocytes age and what are their roles in aging regulation. To characterize age- and stress-regulated gene expression in oenocytes, we performed cell-type-specific ribosome profiling (RiboTag) to examine the impacts of aging and oxidative stress on oenocyte translatome in Drosophila . Results We show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila , and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, oxidative phosphorylation, ribosome, proteasome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and immune response pathways were up-regulated. In addition, most of the peroxisomal genes were down-regulated in aged oenocytes, including genes involved in peroxisomal biogenesis factors and fatty acid beta-oxidation. Many age-related mRNA translational changes in oenocytes are similar to aged mammalian liver, such as up-regulation of innate immune response and Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism. Furthermore, oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). Conclusions Our oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes were altered in both oenocytes and liver during aging. Thus, our translatome analysis provide important genomic resource for future dissection of oenocyte function and its role in lipid metabolism, stress response and aging regulation.
Pathophysiology of Pulmonary Fibrosis in the Context of COVID-19 and Implications for Treatment: A Narrative Review
Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies’ integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.
Total hip arthroplasty in osteonecrosis secondary to sickle cell disease
Background Sickle cell disease (SCD) is a multisystem disease, and the predominant articular manifestation is osteonecrosis (ON). Total hip arthroplasty (THA) is technically challenging, and the complication rates are high. In this retrospective study, we have analysed the outcome of THA in a cohort of patients with SCD at our institution. Materials and methods We identified 34 THAs between 1999 and 2016 in 30 patients (mean age 37 years) from our SCD database. Co-morbidities, both sickle and non-sickle-related, were documented. Complications and indications for revision surgery were analysed. Results An uncemented prosthesis was predominantly used. The mean follow-up was 10.5 years (range 1–18). Six patients had revision surgery (17.6%), 2 (5.8%) for Prosthetic Joint Infection (PJI), and 4 (11.7%) for osteolysis of the acetabular component. Conclusion Our revision rates were comparable to the published literature. Our combined sickle cell clinic and the coordinated multidisciplinary management have been successful in reducing morbidity.
Epidemiology and clinical outcome of intraocular foreign bodies in Hong Kong: a 13-year review
The purpose of this study was to describe the epidemiology, visual outcome and prognostic factors of intraocular foreign body (IOFB) injuries in a tertiary centre in Hong Kong. A retrospective review of 21 eyes in 21 patients with IOFB that presented to United Christian Hospital from January 2001 to July 2014 was performed. IOFB represented 16 % of all open-globe traumas. There was a high male predominance (90 %). The mean age was 42. Work-related injuries (86 %) were the main cause, where only 10.5 % had eye protection. Hammering was the commonest mechanism of injury (43 %). Most IOFBs were metallic (67 %). The IOFB was found in the anterior segment in 31 % and posterior segment in 69 %. 57 % presented with an initial visual acuity of ≥0.1, and up to 24 % of patients had an initial visual acuity of better than or equal to 0.5. Most cases (76 %) received prompt surgical intervention within 24 h, and there was a low (0 %) endophthalmitis rate. Forty-eight percent had an improvement in visual acuity, defined as final visual acuity more than or equal to 2 lines of improvement from initial visual acuity, and 48 % attained a final visual acuity of better than or equal to 0.5. One case underwent evisceration. A smaller IOFB size (<5 mm) was associated with a good final visual acuity of better than or equal to 0.5 ( p  = 0.048). It was also found that a posterior segment IOFB was more likely to give a final VA of less than 0.5 ( p  = 0.035). IOFB remains a significant complication of work-related injuries in Hong Kong. This is the first local study that explores the epidemiology of IOFB injuries in Hong Kong. The favourable visual outcome and low endophthalmitis rate may be related to early removal of IOFB. Despite legal ordinances for mandatory eye protection, the uptake of eye protection was low.
Peptidylarginine Deiminase 2 in Host Immunity: Current Insights and Perspectives
Peptidylarginine deiminases (PADs) are a group of enzymes that catalyze post-translational modifications of proteins by converting arginine residues into citrullines. Among the five members of the PAD family, PAD2 and PAD4 are the most frequently studied because of their abundant expression in immune cells. An increasing number of studies have identified PAD2 as an essential factor in the pathogenesis of many diseases. The successes of preclinical research targeting PAD2 highlights the therapeutic potential of PAD2 inhibition, particularly in sepsis and autoimmune diseases. However, the underlying mechanisms by which PAD2 mediates host immunity remain largely unknown. In this review, we will discuss the role of PAD2 in different types of cell death signaling pathways and the related immune disorders contrasted with functions of PAD4, providing novel therapeutic strategies for PAD2-associated pathology.
Does Choice of Combination Antiretroviral Therapy (cART) Alter Changes in Cerebral Function Testing after 48 Weeks in Treatment-Naive, HIV-1–Infected Individuals Commencing cART? A Randomized, Controlled Study
Background. Neurocognitive impairment remains prevalent, despite combination antiretroviral therapy (cART). Differences between changes in cerebral function and alternative cARTs have not been prospectively assessed. Methods. Treatment-naive, HIV-1–infected individuals randomly allocated to commence cART (tenofovir-emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir [arm 2], or zidovudine-abacavir [arm 3]) were eligible. Cerebral function tests included neurocognitive testing and assessment of cerebral metabolites using proton magnetic resonance spectroscopy in several anatomical voxels, including right frontal white matter and right basal ganglia, at baseline and after 48 weeks. N-acetylaspartate–to–creatine (NAA/Cr) ratios were calculated. Both the differences between changes in neurocognitive function and NAA/Cr ratios over 48 weeks and the study arms (arm 1 vs arm 2; arm 1 vs arm 3) were assessed. Results. Thirty subjects completed study procedures (9, 9, and 12 subjects in arms 1, 2, and 3, respectively). Mean CD4+ cell counts ( lusmn; standard deviation) were 218 lusmn;87 cells/ µL at baseline and 342 lusmn;145 cells/ µL at week 48. The mean plasma HIV-1 RNA level was µ50 copies/mL for 28 of the 30 subjects at week 48. Over 48 weeks, greater improvements in identification reaction time (P=.04) and executive function (P=.02) were observed in arm 3, compared with arm 1 (0.03, inus;0.30, inus;0.50 log10 ms change in identification reaction time, in arms 1, 2, and 3, respectively). Increases in the NAA/Cr ratio were observed in all voxels (maximum 38% in right basal ganglia), with greater increases observed in arm 1 than in arm 2 (P=.03) in frontal white matter (30%, inus;7%, and 0% change in the NAA/Cr ratio, in arms 1, 2, and 3, respectively). Conclusions. To our knowledge, this is the first study to prospectively describe different changes in cerebral function testing parameters between different cARTs. Greater improvements in neuronal recovery (NAA/Cr ratio) were observed for recipients of tenofovir-emtricitabine plus efavirenz (arm 1), and greater improvements in neurocognitive function testing were observed for recipients of tenofovir-emtricitabine plus zidovudine-abacavir (arm 3).
Intercellular trafficking via plasmodesmata: molecular layers of complexity
Plasmodesmata are intercellular pores connecting together most plant cells. These structures consist of a central constricted form of the endoplasmic reticulum, encircled by some cytoplasmic space, in turn delimited by the plasma membrane, itself ultimately surrounded by the cell wall. The presence and structure of plasmodesmata create multiple routes for intercellular trafficking of a large spectrum of molecules (encompassing RNAs, proteins, hormones and metabolites) and also enable local signalling events. Movement across plasmodesmata is finely controlled in order to balance processes requiring communication with those necessitating symplastic isolation. Here, we describe the identities and roles of the molecular components (specific sets of lipids, proteins and wall polysaccharides) that shape and define plasmodesmata structural and functional domains. We highlight the extensive and dynamic interactions that exist between the plasma/endoplasmic reticulum membranes, cytoplasm and cell wall domains, binding them together to effectively define plasmodesmata shapes and purposes.