Virtual reality skateboarding training for balance and functional performance in degenerative lumbar spine disease.

BACKGROUND: Degenerative lumbar spine disease (DLD) is a prevalent condition in middle-aged and elderly individuals. DLD frequently results in pain, muscle weakness, and motor impairment, which affect postural stability and functional performance in daily activities. Simulated skateboarding training could enable patients with DLD to engage in exercise with less pain and focus on single-leg weight-bearing. The purpose of this study was to investigate the effects of virtual reality (VR) skateboarding training on balance and functional performance in patients with DLD. METHODS: Fourteen patients with DLD and 21 age-matched healthy individuals completed a 6-week program of VR skateboarding training. The motion capture and force platform systems were synchronized to collect data during a single-leg stance test (SLST). Musculoskeletal simulation was utilized to calculate muscle force based on the data. Four functional performance tests were conducted to evaluate the improvement after the training. A Visual Analogue Scale (VAS) was also employed for pain assessment. RESULTS: After the training, pain intensity significantly decreased in patients with DLD (p = 0.024). Before the training, patients with DLD took longer than healthy individuals on the five times sit-to-stand test (p = 0.024). After the training, no significant between-group differences were observed in any of the functional performance tests (p > 0.05). In balance, patients with DLD were similar to healthy individuals after the training, except that the mean frequency (p = 0.014) was higher. Patients with DLD initially had higher biceps femoris force demands (p = 0.028) but shifted to increased gluteus maximus demand after the training (p = 0.037). Gluteus medius strength significantly improved in patients with DLD (p = 0.039), while healthy individuals showed consistent muscle force (p > 0.05). CONCLUSION: This is the first study to apply the novel VR skateboarding training to patients with DLD. VR skateboarding training enabled patients with DLD to achieve the training effects in a posture that relieves lumbar spine pressure. The results also emphasized the significant benefits to patients with DLD, such as reduced pain, enhanced balance, and improved muscle performance.

Impact of a targeted temperature management quality improvement project on survival and neurologic outcomes in cardiac arrest patients.

BACKGROUND: Targeted temperature management (TTM) is recommended for postresuscitation care of patients with sudden cardiac arrest (SCA) and its implementation remains challenging. This study aimed to evaluate the newly designed Quality Improvement Project (QIP) to improve the quality of TTM and outcomes of patients with SCA. METHODS: Patients who experienced out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) with return of spontaneous circulation (ROSC) and were treated in our hospital between January 2017 and December 2019 were enrolled retrospectively. All included patients received QIP intervention initiated as follows: (1) Protocols and standard operating procedures were created for TTM; (2) shared decision-making was documented; (3) job training instruction was created; and 4) lean medical management was implemented. RESULTS: Among 248 included patients, the postintervention group (n = 104) had shorter duration of ROSC to TTM than the preintervention group (n = 144) (356 vs 540 minutes, p = 0.042); better survival rate (39.4% vs 27.1%, p = 0.04), and neurologic performance (25.0% vs 17.4%, p < 0.001). After propensity score matching (PSM), patients who received TTM (n = 48 ) had better neurologic performance than those without TTM (n = 48) (25.1% vs 18.8%, p < 0.001). OHCA (odds ratio [OR] = 2.705, 95% CI: 1.657-4.416), age >60 (OR = 2.154, 95% CI: 1.428-3.244), female (OR = 1.404, 95% CI: 1.005-1.962), and diabetes mellitus (OR = 1.429, 95% CI: 1.019-2.005) were negative predictors of survival; while TTM (OR = 0.431, 95% CI: 0.266-0.699) and bystander cardiopulmonary resuscitation (CPR) (OR=0.589, 95% CI: 0.35-0.99) were positive predictors. Age >60 (OR= 2.292, 95% CI: 1.58-3.323) and OHCA (OR= 2.928, 95% CI: 1.858-4.616) were negative predictors of favorable neurologic outcomes; while bystander CPR (OR=0.572, 95% CI: 0.355-0.922) and TTM (OR=0.457, 95% CI: 0.296-0.705) were positive predictors. CONCLUSION: A new QIP with defined protocols, documented shared decision-making, and medical management guidelines improves TTM execution, duration from ROSC to TTM , survival, and neurologic outcomes of cardiac arrest patients.

The pathological mechanisms and novel therapeutics for Leber's hereditary optic neuropathy.

Optic neuropathies were estimated to affect 115 in 100,000 population in 2018. Leber's Hereditary Optic Neuropathy (LHON) as one of such optic neuropathy diseases that was first identified in 1871 and can be defined as a hereditary mitochondrial disease. LHON is associated with three mtDNA point mutations which are G11778A, T14484, and G3460A that affect the NADH dehydrogenase subunits of 4, 6, and 1, respectively. However, in most cases, only one point mutation is involved. Generally, in manifestation of the disease, there are no symptoms until the terminal dysfunction in the optic nerve is observed. Due to the mutations, nicotinamide adenine dinucleotide (NADH) dehydrogenase or complex I is absent and thus ATP production is stopped. This further causes the generation of reactive oxygen species and retina ganglion cells apoptosis. Aside from the mutations, there are several environmental factors such as smoking and alcohol consumption that can be pointed out as the risk factors of LHON. Nowadays, gene therapy has been intensively studied for LHON treatment. Disease models using human induced pluripotent stem cells (hiPSCs) have been utilized for LHON research.

Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood. METHODS: The transcriptome profiles of aged or young human retinal tissues from the GEO database were analyzed for MT-related gene expression. The pathological changes in the retina in the NaIO3-induced mouse model were quantitatively determined by staining with hematoxylin and eosin. Retinal whole-mounting immunofluorescence staining was conducted to determine the expression of the Treg-specific marker FOXP3. The phenotypes of M1/M2 macrophages were representing related gene markers in the retina. The GEO database includes biopsies from patients with retinal detachment for ENPTD1, NT5E, and TET2 gene expression. A pyrosequencing assay was performed for NT5E DNA methylation on human primary Tregs, and siTET2 transfection engineering was used. RESULTS: MT synthesis-related genes in retinal tissue may be affected by age. Our study shows that MT can effectively restore NaIO3-induced retinopathy and maintain retinal structural integrity. Importantly, MT may assist the conversion of M1 to M2 macrophages to promote tissue repair, which may be caused by the increased infiltration of Tregs. Moreover, MT treatment may upregulate TET2, and further NT5E demethylation is associated with Treg recruitment in the retinal microenvironment. CONCLUSIONS: Our findings suggest that MT can effectively ameliorate retinal degeneration and regulate immune homeostasis via Tregs. Modulation of the immune response may provide a key therapeutic strategy.

A novel balance training approach: Biomechanical study of virtual reality-based skateboarding.

Introduction: The use of virtual reality (VR) technology in training and rehabilitation gained increasing attention in recent years due to its potential to provide immersive and interactive experiences. We developed a novel VR-based balance training, VR-skateboarding, for improving balance. It is important to investigate the biomechanical aspects of this training, as it would have benefited both health professionals and software engineers. Aims: This study aimed to compare the biomechanical characteristics of VR-skateboarding with those of walking. Materials and Methods: Twenty young participants (10 males and 10 females) were recruited. Participants underwent VR-skateboarding and walking at the comfortable walking speed, with the treadmill set at the same speed for both tasks. The motion capture system and electromyography were used to determine joint kinematics and muscle activity of the trunk and legs, respectively. The force platform was also used to collect the ground reaction force. Results: Participants demonstrated increased trunk flexion angles and muscle activity of trunk extensor during VR-skateboarding than during walking (p < 0.01). For the supporting leg, participants' joint angles of hip flexion and ankle dorsiflexion, as well as muscle activity of knee extensor, were higher during VR-skateboarding than during walking (p < 0.01). For the moving leg, only hip flexion increased in VR-skateboarding when compared to walking (p < 0.01). Furthermore, participants increased weight distribution in the supporting leg during VR-skateboarding (p < 0.01). Conclusion: VR-skateboarding is a novel VR-based balance training that has been found to improve balance through increased trunk and hip flexion, facilitated knee extensor muscles, and increased weight distribution on the supporting leg compared to walking. These differences in biomechanical characteristics have potential clinical implications for both health professionals and software engineers. Health professionals may consider incorporating VR-skateboarding into training protocols to improve balance, while software engineers may use this information to design new features in VR systems. Our study suggests that the impact of VR-skateboarding particularly manifest when focusing on the supporting leg.

AHR/TET2/NT5E axis downregulation is associated with the risk of systemic lupus erythematosus and its progression.

The prognosis of systemic lupus erythematosus (SLE) is unpredictable. This study aimed to examine the regulatory mechanism of the AHR/TET2/NT5E pathway during SLE progression. The AHR, TET2 and NT5E expression levels were examined in T regulatory cells (Tregs) of patients with SLE. The correlation of AHR, TET2 or NT5E expression levels with the immunosuppressive functions of Tregs was analysed. In patients with SLE, the number of CD4+ IL2RA- FOXP3+ T cell subset was positively correlated with the SLE disease activity index value and negatively correlated with the AHR and TET2 expression levels in CD4+ IL2RA+ FOXP3+ Tregs. Transcriptional profiles of 79 patients with SLE obtained from the Gene Expression Omnibus database (GSE61635 dataset) revealed a significant positive correlation between the mRNA expression levels of AHR and TET2. In silico analysis predicted that the TET2 promoter comprises an AHR-binding site. Kynurenine (KYN) promoted the binding of AHR to the TET2 promoter in Tregs of patients with SLE and Jurkat T cell lines. Furthermore, NT5E expression was significantly downregulated in Tregs of patients with SLE, which can be attributed to the dysregulation of NT5E promoter methylation status induced by downregulated TET2 activity. Furthermore, the Treg immunosuppressive activity, which is mediated through the TET2 and A2AR-adenosine pathways, in the KYN-treated group was approximately two-fold higher than that in the control group. The AHR/TET2/NT5E axis mediates the Treg immunosuppressive activity. These findings provide novel insights for the development of therapeutic approaches for SLE and related autoimmune diseases.

Pluripotent Stem Cells in Clinical Cell Transplantation: Focusing on Induced Pluripotent Stem Cell-Derived RPE Cell Therapy in Age-Related Macular Degeneration.

Human pluripotent stem cells (PSCs), including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent valuable cell sources to replace diseased or injured tissues in regenerative medicine. iPSCs exhibit the potential for indefinite self-renewal and differentiation into various cell types and can be reprogrammed from somatic tissue that can be easily obtained, paving the way for cell therapy, regenerative medicine, and personalized medicine. Cell therapies using various iPSC-derived cell types are now evolving rapidly for the treatment of clinical diseases, including Parkinson's disease, hematological diseases, cardiomyopathy, osteoarthritis, and retinal diseases. Since the first interventional clinical trial with autologous iPSC-derived retinal pigment epithelial cells (RPEs) for the treatment of age-related macular degeneration (AMD) was accomplished in Japan, several preclinical trials using iPSC suspensions or monolayers have been launched, or are ongoing or completed. The evolution and generation of human leukocyte antigen (HLA)-universal iPSCs may facilitate the clinical application of iPSC-based therapies. Thus, iPSCs hold great promise in the treatment of multiple retinal diseases. The efficacy and adverse effects of iPSC-based retinal therapies should be carefully assessed in ongoing and further clinical trials.

Effectiveness of salt substitute on cardiovascular outcomes: A systematic review and meta-analysis.

Hypertension-related death is the leading cause of mortality worldwide, making blood pressure (BP) control an important issue. Salt substitute is a non-pharmaceutical strategy to improve hypertension control. The goal of this study was to evaluate the effect of salt substitute on BP and cardiovascular disease. The authors searched the Cochrane Library and PubMed databases through March 2022, and assessed the risk-of-bias for included studies by the Cochrane risk-of-bias tool. Twenty-three randomized controlled trials with 32073 patients were included in our systematic review. A meta-analysis with random effects was performed to analyze the effects of salt substitute on systolic and diastolic BP, 24-h urinary sodium and potassium, and cardiovascular and all-cause mortality. In the random-effects model, participants consuming salt substitute showed significant reduction in systolic BP (mean difference (MD) -4.80 mmHg, 95% confidence interval (CI) -6.12 to -3.48, P < 0.0001) and diastolic BP (MD -1.48 mmHg, 95% CI -2.06 to -0.90, P < 0.0001) compared with participants consuming normal salt. In the urine electrolyte analysis, the salt substitute group had significant reduction in 24-h urine sodium (MD -22.96 mmol/24-h, P = 0.0001) and significant elevation in 24-h urine potassium (MD 14.41 mmol/24-h, P < 0.0001). Of the five studies with mortality outcome data, salt substitute significantly reduced all-cause mortality (hazard ratio 0.88, P = 0.0003). In conclusion, our analyses showed that salt substitute has a strong effect on lowering BP and reducing all-cause mortality. By modifying the daily diet with salt substitute, the authors can improve BP control by using this non-pharmaceutical management.

Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model.

Hot compress modalities are used to ameliorate pain despite prevalent confusion about which modality should be used and when. Most recommendations for hot compresses are based on empirical experience, with limited evidence to support its efficacy. To obtain insight into the nerve transmission mechanism of hot compresses and to identify the nerve injury marker proteins specifically associated with sciatic nerve pain, we established a rat model of chronic constriction injury (CCI) and performed mechanical allodynia, electrophysiology, and histopathological analysis. All CCI rats exhibited geometric representation of the affected hind paw, which indicated a hyper-impact on both mechanical gait and asymmetry of gait on day 28. The CCI model after 28 days of surgery significantly reduced compound muscle action potential (CMAP) amplitude, but also significantly reduced latency. Administration of hot compress for 3 weeks (heated at 40-42°C, cycle of 40 min, and rest for 20 min, three cycles each time, three times per week) significantly increased the paw withdrawal thresholds in response to stimulation by Von Frey fibers and reversed the CCI-induced reduced sciatic functional index (SFI) scores. Hot compress treatment in the CCI model improved CMAP amplitude and latency. The S100 protein expression level in the CCI+Hot compression group was 1.5-fold higher than in the CCI group; it dramatically reduced inflammation, such as tumor necrosis factor alpha and CD68 expression in nerve injury sites. Synaptophysin (Syn) expression in the CCI+Hot compression group was less than threefold in the CCI group at both nerve injury sites and brain (somatosensory cortex and hippocampus). This finding indicates that local nerve damage and inflammation cause significant alterations in the sensorimotor strip, and hot compress treatment could significantly ameliorate sciatic nerve pain by attenuating Syn and inflammatory factors from local pathological nerves to the brain. This study determines the potential efficacy and safety of hot compress, and may have important implications for its widespread use in sciatic nerve pain treatment.

Autophagy reprogramming stem cell pluripotency and multiple-lineage differentiation.

The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.

Quality care in ST-segment elevation myocardial infarction.

Over the past decades, the treatment of ST-segment elevation myocardial infarction (STEMI) has been redefined with the incorporation of evidence from multiple clinical trials. Recommendations from guidelines are updated regularly to reduce morbidity and mortality. However, heterogeneous care systems, physician perspectives, and patient behavior still lead to a disparity between evidence and clinical practice. The quality of care has been established and become an integral part of modern healthcare in order to increase the likelihood of desired health outcomes and adhere to professional knowledge. For patients with STEMI, measuring the quality of care is a multifactorial and multidimensional process that cannot be estimated solely based on patients' clinical outcomes. The care of STEMI is similar to the concept of "the chain of survival" that emphasizes the importance of seamless integration of five links: early recognition and diagnosis, timely reperfusion, evidence-based medications, control of cholesterol, and cardiac rehabilitation. Serial quality indicators, reflecting the full spectrum of care, have become a widely used tool for assessing performance. Comprehension of every aspect of quality assessment and indicators might be too demanding for a physician. However, it is worthwhile to understand the concepts involved in quality improvement since every physician wants to provide better care for their patients. This article reviews a fundamental approach to quality care in STEMI.

Attenuation of in vitro and in vivo melanin synthesis using a Chinese herbal medicine through the inhibition of tyrosinase activity.

BACKGROUND: In traditional Chinese medicine, the skin reflects the health of body organs. A skin whitening agent, named seven whitening creams (also called Chi-Bai-San), has been used since ancient times in China. Chi-Bai-San reduces melanin and helps to reduce wrinkles. PURPOSE: We aimed to determine the skin-whitening ability and safe dose of the seven compounds in Chi-Bai-San. STUDY DESIGN: A common use for Chinese medicine is decocted in water. To mimic the function of Chi-Bai-San apply in clinical, we boiled all seven compound in water, respectively. These single recipe extractions and a mixture of these seven items were used in zebrafish embryo and B16F10 melanoma cell to identify the anti-melanogenesis function. METHODS: Chi-Bai-San comprises Bai-Lian (Ampelopsis japonica), Bai-Ji (Bletilla striata), Bai-Zhi (Angelica dahurica), Bai-Zhu (Atractylodes macrocephala), Bai-Shau (Paeonia lactiflora), Fu-Ling (Wolfiporia cocos), and Jen-Ju-Fen (Pearl powder). All components were extracted by heating in distilled water. The supernatant was collected after centrifugation. The extracted components were introduced into zebrafish embryos at different doses to determine the safe dose. B16F10 melanoma cells were treated with the final dose of each component and the component mixture. Melanin content and tyrosinase activity were assessed in zebrafish and B16F10 cells. Chi-Bai-San and its components were exposed to α MSH-induced B16F10 cells, and detected for mechanism of anti-melanogenesis pathway. RESULTS: Most compounds were not toxic at a low dose (0.1 mg/ml), except A. macrocephala, which resulted in a survival rate of only 30% at 72 hpf. The final dose of A. dahurica, P. lactiflora, W. cocos, and pearl was 1 mg/ml; that of A. japonica was 0.5 mg/ml; and that of A. macrocephala and B. striata was 0.1 mg/ml. Chi-Bai-San markedly decreased melanin content 37.47% in zebrafish embryos. Further, Chi-Bai-San abolished tyrosinase activity and MITF-mediated tyrosinase expression by down regulating the upstream transcription factors ZEB2, ß-catenin, and CREB2 in α MSH-induced B16F10 cells. Additionally, Chi-Bai-San might reduce melanosome secretion from melanocytes. CONCLUSION: Our findings indicate that safety and efficacy of heat-extracted Chi-Bai-San, which can reduce αMSH-induced melanin production by inhibiting the key role of melogenic-related transcription factor and promote the synergic effect of seven types of traditional Chinese herbal medicines.

Single pulley double-strand anchor suture fixation of the coronoid process in terrible triad of the elbow injury.

BACKGROUND: Terrible triad of the elbow injury is difficult to manage, and the role of the coronoid process in instability is very important. We describe a simple, modified suture technique to fix a coronoid process fragment using suture anchor fixation. METHODS: Eight patients (three female and five male) with coronoid process injuries with the fragment involving <50% of the total height (Regan-Morrey type I/II) in terrible triad of elbow injury were included. Patients were treated operatively via a lateral Kocher's approach, and coronoid process fractures were repaired with a single pulley double-strand suture technique. Structures were addressed in a sequential fashion-the coronoid process, radial head, lateral ulnar collateral ligament. RESULTS: All patients were treated with the single pulley double-strand anchor suture technique and the coronoid process fragment was found to be in good contact with the original avulsion site using the method. The final Mayo Elbow Performance Score was excellent (> 90) in six patients and good (between 85 and 89) in two patients after operation 6 months. CONCLUSION: The single pulley double-strand suture tie method using a suture anchor is a less invasive and simpler fixation method for the repair of coronoid process fractures in patients with terrible triad of the elbow injuries and results in good outcomes.

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Pandemic aspect of dexamethasone: Molecular mechanisms and clinical application.

The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.

[Using Healthcare Failure Mode and Effects Analysis to Reduce Intra-Arterial Thrombectomy Preoperative Preparation Error Rates in the Emergency Room].

BACKGROUND & PROBLEMS: Intra-arterial thrombectomy (IAT) is a novel surgery that may restore cerebral blood flow in patients with ischemic stroke and lower the risks of permanent brain damage and disability. Because the process of preoperative preparation for IAT is complicated, error rates for this process have been reported in previous studies to be as high as 100%. Although these errors did not result in serious damage to patients, the risk to patient safety remains. Therefore, reducing the error rate for IAT preoperative preparation is necessary to improve patient safety. PURPOSE: To reduce the rate of IAT preoperative preparation error in an emergency room. RESOLUTION: This project applied healthcare failure mode and effect analysis (HFMEA) to evaluate the potential risks of IAT preoperative preparation in an emergency room. Based on the resultant hazard score, critical preventive measures were adopted, including creating a quick response code consent form, designing order packages, developing a checklist form, modifying stroke operating procedures and policies, planning suitable education content for staffs, developing criteria for evaluating preoperative preparation procedures, and installing vital signs equipment. RESULTS: After implementation of these measures, the hazard scores of 13 out of the 16 potential failure causes decreased to < 8, and the progress rate was 81.3%. The follow-up error rate for preoperative preparation was 0% in October 2019, which fulfilled the goal of this project. CONCLUSIONS: Preoperative preparation for IAT is complicated and time-consuming. In this project, HFMEA was introduced to ensure that preoperative preparation was accomplished in a complete and timely manner. Based on the results, after implementation, preparation work was effectively completed and operations were performed on schedule. Other hospitals may consider using this tool to evaluate potential risks to patient safety and to develop solutions to improve the quality of healthcare processes.

Establishment of an induced pluripotent stem cell (iPSC) line from a 7-year-old male patient with profound hearing loss carrying c.235delC in GJB2 gene.

Gap junction protein beta 2 gene (GJB2) mutations are the most frequent cause of hereditary hearing impairment. The recessive c.235delC mutation in the GJB2 gene is the most common mutation causing severe to profound sensorineural hearing loss in the Asian population. The induced pluripotent stem cell (iPSC) line was generated using the integration-free Sendai virus method from peripheral blood mononuclear cells (PBMCs) of a hearing-impaired patient with homozygous GJB2 c.235delC mutation. This cell line may serve as a cellular model for studying the pathogenic mechanisms of deafness caused by GJB2 mutations.

Generation of induced pluripotent stem cells from a patient with Best Dystrophy carrying 11q12.3 (BEST1 (VMD2)) mutation.

Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and central visual loss. In this report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012-04, from the peripheral blood mononuclear cells of a female patient with BD by using the Sendai virus delivery system. The resulting iPSCs retained the disease-causing DNA mutation, expressed pluripotent markers and could differentiate into three germ layers. We believe that BD patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

Aryl Hydrocarbon Receptor Deficiency Attenuates Oxidative Stress-Related Mesangial Cell Activation and Macrophage Infiltration and Extracellular Matrix Accumulation in Diabetic Nephropathy.

AIMS: Activation of glomerular mesangial cells (MCs) and functional changes of renal tubular cells are due to metabolic abnormalities, oxidative stress, and matrix accumulation in the diabetic nephropathy (DN). Aryl hydrocarbon receptor (AhR) activation has been implicated in DN. In this study, we investigated the role of AhR in the pathophysiological processes of DN using AhR knockout (AhRKO) and pharmacological inhibitor α-naphthoflavone mouse models. RESULTS: The increased blood glucose, glucose intolerance, MC activation, macrophage infiltration, and extracellular matrix (ECM) accumulation were significantly attenuated in AhRKO mice with diabetic inducer streptozotocin (STZ) treatment. AhR deficiency by genetic knockout or pharmacological inhibition also decreased the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), lipid peroxidation, oxidative stress, NADPH oxidase activity, and N-ɛ-carboxymethyllysine (CML, a major advanced glycation end product) in STZ-induced diabetic mice. CML showed remarkably increased AhR/COX-2 DNA-binding activity, protein-DNA interactions, gene regulation, and ECM formation in MCs and renal proximal tubular cells, which could be reversed by siRNA-AhR transfection. CML-increased AhR nuclear translocation and biological activity in MCs and renal proximal tubular cells could also be effectively attenuated by antioxidants. INNOVATION: We elucidate for the first time that AhR plays an important role in MC activation, macrophage infiltration, and ECM accumulation in DN conferred by oxidative stress. CONCLUSIONS: AhR-regulated COX-2/PGE2 expression and ECM deposition through oxidative stress cascade is involved in the CML-triggered MC activation and macrophage infiltration. These findings suggest new insights into the development of therapeutic approaches to reduce diabetic microvascular complications. Antioxid. Redox Signal. 24, 217-231.

Water pollutant monitoring by a whole cell array through lens-free detection on CCD.

Environmental contamination has become a serious problem to human and environmental health, as exposure to a wide range of possible contaminants continuously increases due to industrial and agricultural activities. Whole cell sensors have been proposed as a powerful tool to detect class-specific toxicants based upon their biological activity and bioavailability. We demonstrated a robust toxicant detection platform based on a bioluminescence whole cell sensor array biochip (LumiChip). LumiChip harbors an integrated temperature control and a 16-member sensor array, as well as a simple but highly efficient luminescence collection setup. On LumiChip, samples were infused in an oxygen-permeable microfluidic flow channel to reach the sensor array. Time-lapse changes in bioluminescence emitted by the array members were measured on a single window-removed linear charge-coupled device (CCD) commonly used in commercial industrial process control or in barcode readers. Removal of the protective window on the linear CCD allowed lens-free direct interfacing of LumiChip to the CCD surface for measurement with high light collection efficiency. Bioluminescence induced by simulated contamination events was detected within 15 to 45 minutes. The portable LumiSense system utilizing the linear CCD in combination with the miniaturized LumiChip is a promising potential platform for on-site environmental monitoring of toxicant contamination.