Immune landscape in children with X-linked retinoschisis.

Background: X-linked retinoschisis is a retinovitreal disorder primarily affecting males, starting in childhood. Over time, patients experience deterioration of vision due to the lack of retinoschisin-1 function. In clinical trials performing intravitreal gene delivery in those affected by this disorder, ocular inflammation was observed, which may have masked efficacy.

Sex-specific correlations between orbital volume and anthropometric characteristics in Taiwanese adults.

Background/purpose: There is no study available addressing the relationship between orbital volume (OV) and skeletal patterns. The purpose of this study was to investigate the correlations between the OV and patient's characteristics (sex, age, height, and skeletal patterns) of Taiwanese adults.

Materials And Methods: Cone-beam computed tomography images of 94 individuals (men: 47; women: 47) were analyzed to measure their OV and maxillary dimensions.

An osmolarity dependent mechanism partially ameliorates retinal cysts and rescues cone function in a mouse model of X-linked retinoschisis.

Introduction: X-linked retinoschisis (XLRS) is a vitreoretinal dystrophy caused by gene mutations which disrupt retinoschisin-1 (RS1) function. Vital for retinal architecture, the absence of functional RS1 leads to the development of intraretinal cysts. Intravitreal injection of a gene therapy for treating XLRS caused ocular inflammation in high dose groups in a phase I/II clinical trial.

Delivering large genes using adeno-associated virus and the CRE-lox DNA recombination system.

Adeno-associated virus (AAV) is a safe and efficient gene delivery vehicle for gene therapies. However, its relatively small packaging capacity limits its use as a gene transfer vector. Here, we describe a strategy to deliver large genes that exceed the AAV's packaging capacity using up to four AAV vectors and the CRE-lox DNA recombination system.

Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.

The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT).

Investigating the role of Caspase-1 in a mouse model of Juvenile X-linked Retinoschisis.

Purpose: Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease progression has been identified. We performed electroretinogram (ERG) and standardized optical coherence tomography (OCT) in mice deficient in the Retinoschisin-1 () and and Caspase-11 genes (-KO ) to test the hypothesis that may play a role in disease evolution and or severity of disease. Currently, no studies have ventured to investigate the longer-term effects of on phenotypic severity and disease progression over time in XLRS, and specifically the effect on electroretinogram.

Delivering large genes using adeno-associated virus and the CRE-lox DNA recombination system.

Adeno-associated virus (AAV) is a safe and efficient gene delivery vehicle for gene therapies. However, its relatively small packaging capacity limits its use as a gene transfer vector. Here, we describe a strategy to deliver large genes that exceed the AAV's packaging capacity using up to four AAV vectors and the CRE-lox DNA recombination system.

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-h in a mouse model of X-linked retinoschisis.

Purpose: X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin () gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-h utilizing the knockout (-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery.

A visually guided swim assay for mouse models of human retinal disease recapitulates the multi-luminance mobility test in humans.

Purpose: The purpose of this study was to develop a visually guided swim assay (VGSA) for measuring vision in mouse retinal disease models comparable to the multi-luminance mobility test (MLMT) utilized in human clinical trials.

Methods: Three mouse retinal disease models were studied: Bardet-Biedl syndrome type 1 (), = 5; Bardet-Biedl syndrome type 10 (), = 11; and X linked retinoschisis (retinoschisin knockout; KO), = 5. Controls were normally-sighted mice, = 10.

Subretinal gene therapy delays vision loss in a Bardet-Biedl Syndrome type 10 mouse model.

Blindness in Bardet-Biedl syndrome (BBS) is caused by dysfunction and loss of photoreceptor cells in the retina. , mutations of which account for approximately 21% of all BBS cases, encodes a chaperonin protein indispensable for the assembly of the BBSome, a cargo adaptor important for ciliary trafficking. The loss of BBSome function in the eye causes a reduced light sensitivity of photoreceptor cells, photoreceptor ciliary malformation, dysfunctional ciliary trafficking, and photoreceptor cell death.

The BBSome regulates mitochondria dynamics and function.

Objective: The essential role of mitochondria in regulation of metabolic function and other physiological processes has garnered enormous interest in understanding the mechanisms controlling the function of this organelle. We assessed the role of the BBSome, a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins, in the control of mitochondria dynamic and function.

Methods: We used a multidisciplinary approach that include CRISPR/Cas9 technology-mediated generation of a stable Bbs1 gene knockout hypothalamic N39 neuronal cell line.

Progressive retinal degeneration of rods and cones in a Bardet-Biedl syndrome type 10 mouse model.

Bardet-Biedl syndrome (BBS) is a multi-organ autosomal-recessive disorder caused by mutations in at least 22 different genes. A constant feature is early-onset retinal degeneration leading to blindness. Among the most common forms is BBS type 10 (BBS10), which is caused by mutations in a gene encoding a chaperonin-like protein.

Effect of socioeconomic status on survival in patients on the Diabetes Shared Care Program: Finding from a Taiwan nationwide cohort.

Background: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan to improve the care quality of patients with diabetes. Socioeconomic status (SES) is one of the important factors affecting health, and it is confirmed as a predictor of various diseases and deaths.This study aimed to determine the relationship between survival rate and SES among patients who participated in the DSCP.

Retinal ciliopathies through the lens of Bardet-Biedl Syndrome: Past, present and future.

The primary cilium is a highly specialized and evolutionary conserved organelle in eukaryotes that plays a significant role in cell signaling and trafficking. Over the past few decades tremendous progress has been made in understanding the physiology of cilia and the underlying pathomechanisms of various ciliopathies. Syndromic ciliopathies consist of a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis.

COVID-19 Vaccination Attitudes and Intention: Message Framing and the Moderating Role of Perceived Vaccine Benefits.

The United States is one of the hardest-hit countries by the COVID-19 pandemic and yet there is widespread hesitancy to take the vaccine. In order to address vaccine hesitancy and foster public understanding of the COVID-19 vaccine, it is necessary to strategize public health messages based on evidence. To this end, we use experimental data to examine the effects of four message frames on participants' attitudes toward the COVID-19 vaccine and their vaccine intention.

A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment.

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS).

Photoreceptor cilia, in contrast to primary cilia, grant entry to a partially assembled BBSome.

The BBSome is a protein complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBS18 that associates with intraflagellar transport complexes and specializes in ciliary trafficking. In primary cilia, ciliary entry requires the fully assembled BBSome as well as the small GTPase, ARL6 (BBS3). Retinal photoreceptors possess specialized cilia.

Barthel Index, but not Lawton and Brody instrumental activities of daily living scale associated with Sarcopenia among older men in a veterans' home in southern Taiwan.

Background: Older adults are more likely to experience the disorder of skeletal muscles.

Objective: This study aimed to examine the prevalence of sarcopenia using the diagnostic procedures of sarcopenia recommended by the Asian Working Group for Sarcopenia in 2019. The association of sarcopenia with physical activity and other factors was also explored.

The Trend of Aggressive Treatments in End-of-Life Care for Older People With Dementia After a Policy Change in Taiwan.

Objectives: We evaluated the trend of end-of-life healthcare utilization and life-sustaining interventions for older adults with dementia 3 to 4 years after the change in hospice policy.

Design: Population-based retrospective cohort study.

Setting And Participants: We used the National Health Insurance Research database of enrolled patients ≥65 years of age diagnosed with dementia who died in 2010-2013 (n = 2062).

The absence of BBSome function decreases synaptogenesis and causes ectopic synapse formation in the retina.

Photoreceptors possess ribbon synapses distinct from the conventional synapses in the brain. Little is known about the function of the BBSome, a complex integral in ciliary and intracellular trafficking, in ribbon synaptic formation. We performed immunohistochemistry using retinas from Bardet-Biedl Syndrome (BBS) mouse models and found that BBS mutant animals have significantly fewer ribbon synapses in the outer plexiform layer and increased ectopic synapses in the outer nuclear layer compared to controls.

BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment.

Genetic mutations disrupting the structure and function of primary cilia cause various inherited retinal diseases in humans. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic ciliopathy characterized by retinal degeneration, obesity, postaxial polydactyly, intellectual disability, and genital and renal abnormalities. To gain insight into the mechanisms of retinal degeneration in BBS, we developed a congenital knockout mouse of Bbs8, as well as conditional mouse models in which function of the BBSome (a protein complex that mediates ciliary trafficking) can be temporally inactivated or restored.

Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid.

Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system.

Dynamic regulation of aquaporin-4 water channels in neurological disorders.

Aquaporin-4 water channels play a central role in brain water regulation in neurological disorders. Aquaporin-4 is abundantly expressed at the astroglial endfeet facing the cerebral vasculature and the pial membrane, and both its expression level and subcellular localization significantly influence brain water transport. However, measurements of aquaporin-4 levels in animal models of brain injury often report opposite trends of change at the injury core and the penumbra.

CNS wide simulation of flow resistance and drug transport due to spinal microanatomy.

Spinal microstructures are known to substantially affect cerebrospinal fluid patterns, yet their actual impact on flow resistance has not been quantified. Because the length scale of microanatomical aspects is below medical image resolution, their effect on flow is difficult to observe experimentally. Using a computational fluid mechanics approach, we were able to quantify the contribution of micro-anatomical aspects on cerebrospinal fluid (CSF) flow patterns and flow resistance within the entire central nervous system (CNS).