High-Intensity Post-Stroke Rehabilitation Is Associated with Lower Risk of Pressure Ulcer Development in Patients with Stroke: Real-World Evidence from a Nationwide, Population-Based Cohort Study.

Background and Objectives: Multiple factors are associated with pressure ulcer (PU) development, including limited mobility following stroke. We performed a nationwide cohort study to investigate the impact of rehabilitation intensity on the incidence of post-stroke PU. Materials and Methods: Data of patients diagnosed with stroke between 2000 and 2012 were collected from the 2000 Longitudinal Health Insurance Database (Taiwan). Based on the number of rehabilitation sessions attended within 90 days of discharge, the rehabilitation intensity was classified as low, medium, or high. After adjusting for sociodemographic factors and comorbidities, the Cox proportional hazards model evaluated the risk of PU development during the 12-year follow-up period. Kaplan−Meier curves were used to estimate the cumulative incidence of PUs. Results: Our study included 18,971 patients who had their first episode of stroke. Of these, 9829 (51.8%) underwent rehabilitation therapy after discharge. Female patients and patients with a National Institutes of Health Stroke Scale (NIHSS) score >13 points, who commenced high-intensity post-stroke rehabilitation after discharge had a significantly lower risk of PU development than those who underwent low-intensity post-stroke rehabilitation after discharge. Cumulative survival analysis showed a significantly lower cumulative incidence of PU during the 12-year follow-up period in the high-intensity rehabilitation group. Conclusion: Compared with low-intensity post-stroke rehabilitation, high-intensity post-stroke rehabilitation after discharge from hospital is associated with a lower risk of post-stroke PU development, especially in female stroke patients and patients with a NIHSS score >13 points. High-intensity rehabilitation is also associated with a significantly lower cumulative incidence of PU events during the 12-year follow-up period.

The incidence of mental disorder increases after hip fracture in older people: a nationwide cohort study.

BACKGROUND: People living with dementia seem to be more likely to experience delirium following hip fracture. The association between mental disorders (MD) and hip fracture remains controversial. We conducted a nationwide study to examine the prevalence of MD in geriatric patients with hip fractures undergoing surgery and conducted a related risk factor analysis. MATERIAL AND METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance Research Database between 2000 and 2012 and focused on people who were older than 60 years. Patients with hip fracture undergoing surgical intervention and without hip fracture were matched at a ratio of 1:1 for age, sex, comorbidities, and index year. The incidence and hazard ratios of age, sex, and multiple comorbidities related to MD and its subgroups were calculated using Cox proportional hazards regression models. RESULTS: A total of 1408 patients in the hip fracture group and a total of 1408 patients in the control group (no fracture) were included. The overall incidence of MD for the hip fracture and control groups per 100 person-years were 0.8 and 0.5, respectively. Among MD, the incidences of transient MD, depression, and dementia were significantly higher in the hip fracture group than in the control group. CONCLUSIONS: The prevalence of newly developed MD, especially transient MD, depression, and dementia, was higher in the geriatric patients with hip fracture undergoing surgery than that in the control group. Prompt and aggressive prevention protocols and persistent follow-up of MD development is highly necessary in this aged society.

Factors Impacting Survival in Patients With Major Burn-Induced Acute Kidney Injury Postrenal Replacement Therapy: A Nationwide Study With 15 Years Follow-Up in Taiwan.

BACKGROUND: Major burn-induced acute kidney injury (AKI) causes extremely high mortality, even though renal replacement therapy (RRT) was thought of as the most efficient treatment. There was scanty research for investigating the characteristic of burn-AKI-RRT patients during intensive care. This study aims to investigate the factors impacting the survival outcomes in those burn-AKI-RRT cases. METHODS: Using the Taiwan National Health Insurance Research Database and its affiliated database, the Registry for Catastrophic Illness Patients, we defined a cohort composed of 171 patients encountering major burn-induced AKI and receiving RRT during burn care for a 15-year observation period. Demographic characteristic, comorbidities, total body surface area (TBSA), major procedures, and complications were analyzed to explore the factors affecting the survival outcomes during acute burn care and 1 year after discharge. RESULTS: Patients who underwent tracheostomy and skin grafting had higher survival rates during acute burn care (tracheostomy: mortality vs survival, 15.7% vs 30.2%; P = 0.0257; skin grafting: mortality vs survival, 57.4% vs 76.2%; P = 0.0134). Multivariate regression analysis showed that tracheostomy group significantly presented with lower mortality risk by 65% (odds ratio [OR], 0.35; P = 0.0372), and subgroup analysis of delaminating follow-up duration showed that patients with tracheostomy had higher overall survival by 22% (90-day postburn mortality: nontracheostomy vs tracheostomy, 58.3% vs 36.3%; adjusted hazards ratio, 0.39; 95% confidence interval, 0.22-0.69; P = 0.0011), especially during postburn first 30 days (adjusted hazards ratio, 0.15; 95% confidence interval, 0.05-0.49; P = 0.0016). Total body surface area did not significantly affect survival; however, mortality risk was significantly higher in those with a larger TBSA (TBSA, ≥80%; OR, 6.48; P = 0.0022; TBSA, 60-79%; OR, 3.12; P = 0.0518; TBSA, 40-59%; OR, 1.88; P = 0.2402; TBSA, 30-39% as reference). CONCLUSIONS: For patients with major burn-induced AKI receiving RRT, tracheostomy and skin grafting may improve survival in the cases living through acute burn stage.

Hepatic encephalopathy increases the risk of hip fracture: a nationwide cohort study.

BACKGROUND: Osteoporotic hip fracture is a common general health problem with a significant impact on human life because it debilitates the patients and largely decreases their quality of life. Early prevention of fractures has become essential in recent decades. This can be achieved by evaluating the related risk factors, as a reference for further intervention. This is especially useful for the vulnerable patient group with comorbidities. Hepatic encephalopathy (HE), a major complication of liver cirrhosis, may increase the rate of falls and weaken the bone. This study evaluated the correlation between hepatic encephalopathy and osteoporotic hip fracture in the aged population using a national database. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance Research Database between 2000 and 2012. We included people who were older than 50 years with hepatic encephalopathy or other common chronic illnesses. Patients with and without hepatic encephalopathy were matched at a ratio of 1:4 for age, sex, and index year. The incidence and hazard ratios of osteoporotic hip fracture between the both cohorts were calculated using Cox proportional hazard regression models. RESULTS: The mean age of the enrolled patients was 66.5 years. The incidence ratio of osteoporotic hip fracture in the HE group was significantly higher than that in the non-HE group (68/2496 [2.7%] vs 98/9984 [0.98%]). Patients with HE were 2.15-times more likely to develop osteoporotic hip fractures than patients without HE in the whole group. The risk ratio was also significantly higher in female and older individuals. The results were also similar in the comorbidity subgroups of hypertension, diabetes mellitus, hyperlipidemia, senile cataract, gastric ulcer, and depression. Alcohol-related illnesses seemed to not confound the results of this study. CONCLUSIONS: HE is significantly associated with an increased risk of osteoporotic hip fractures, and the significance is not affected by the comorbidities in people aged more than 50 years. The cumulative risk of fracture increases with age.

Age-related hearing loss and dementia: a 10-year national population-based study.

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.

Ecology and genomic features of infection with Mycobacterium avium subspecies paratuberculosis in Egypt.

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of paratuberculosis, or Johne's disease, in cattle, with potential involvement in cases of Crohn's disease in humans. Johne's disease is found worldwide and is economically important for both beef and dairy industries. In an effort to characterize this important infection in Egypt, we analysed the ecological and genomic features of recent isolates of M. paratuberculosis. In this report, we examined 26 Holstein dairy herds distributed throughout Egypt, from 2010 to 2013. Using PCR analysis of faecal samples, we estimated a mean herd-level prevalence of 65.4 %, with animal-level infection that reached a mean of 13.6 % among animals suffering from diarrhoea. Whole genome sequencing of field isolates identified numerous single nucleotide polymorphisms among field isolates relative to the standard M. paratuberculosis K10 genome. Interestingly, the virulence of M. paratuberculosis isolates from Egypt revealed diverse virulence phenotypes in the murine model of paratuberculosis, with significant differences in tissue colonization, particularly during the chronic stage of infection. Overall, our analysis confirmed that Johne's disease is a newly identified problem in Egypt and indicated that M. paratuberculosis has potentially diverse genotypes that impact its virulence. Further ecological mapping and genomic analysis of M. paratuberculosis will enhance our understanding of the transmission and evolutionary dynamics of this pathogen under natural field conditions.

Optical sensing of phenylalanine in urine via extraction with magnetic molecularly imprinted poly(ethylene-co-vinyl alcohol) nanoparticles.

Incorporation of superparamagnetic nanoparticles into molecularly imprinted polymers (MIPs) is useful for both bioseparations and for concentration and sensing of biomedically relevant target molecules in physiological fluids, through the application of a magnetic field. In this study, we combined the separation and concentration of a target (phenylalanine) in urine, using magnetic molecularly imprinted polymeric composite nanoparticles, with optical sensing, to improve assay sensitivity. This target is important as a catecholamine precursor, and as an important amino acid constituent of proteins. Poly(ethylene-co-vinyl alcohol)s were imprinted with target molecules, and showed a high imprinting effectiveness (target binding compared with binding to non-imprinted polymer particles.) Fluorescence spectrophotometry was used to measure binding of the target, and also binding of possible interfering compounds. These measurements suggest that functional groups on phenylalanine dominate the selectivity of the synthesized MIPs. Finally, the composite nanoparticles were used to separate and sense the target molecule in urine by Raman scattering microscopy.

Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway.

The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H(2)O(2) as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5'-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H(2)O(2) activates IRES-dependent translation. Thus, H(2)O(2) or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H(2)O(2) as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage.

The Risk of Venous Thromboembolism after Thoracolumbar Spine Surgery: A Population-Based Cohort Study.

Background: Although venous thromboembolism (VTE) is rare, including deep vein thrombosis (DVT) and pulmonary embolism (PE), it is a catastrophic complication after spinal surgery. This study was aimed to investigate the risk factors and incidence of VTE after thoracolumbar spine surgery (TLSS). Methods: We retrieved the data of 8697 patients >20 years old who underwent TLSS between 2000 and 2013 from Taiwan's Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with four individuals who did not undergo TLSS by age, sex, and index year (the control group). Results: The incidence rates of VTE in the TLSS and control groups were 1.84 and 0.69 per 1000 person-years, respectively. The TLSS group had a higher VTE risk (adjusted HR (aHR): 2.13, 95% confidence interval [95%CI]: 1.41−3.21), DVT (aHR: 2.20, 95%CI: 1.40−3.46), and PE (aHR: 1.60, 95%CI: 0.68−3.78) than the control group. The correlated risk factors of VTE included older age (50−64 years: aHR: 2.16, 95%CI: 1.14−4.09; ≥65 years: aHR: 3.18, 95%CI: 1.65−6.13), a history of cancer (aHR: 2.96, 95%CI: 1.58−5.54), heart failure (aHR: 2.19, 95%CI: 1.27−3.78), and chronic kidney disease (aHR: 1.83, 95%CI: 1.18−2.83). Conclusions: The overall VTE risk following TLSS was less than 2% but correlated with certain risk factors. This information could help the spine surgeon help the patient prevent this fatal complication.

Epidural Steroid Injections and the Risk of Osteoporosis in Lumbar Spondylosis Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: Epidural steroid injections (ESIs) involve the administration of steroids and local anesthetics into the spinal epidural space, and they are performed by inserting a needle between the ligamentum flavum and dura. This procedure is suitable for patients with lumbosacral radiculopathy secondary to disc herniation or postsurgical radicular pain. The relief period of the analgesic medications may be prolonged by > 6 weeks, resulting in nonsurgical management becoming a suitable option. However, the negative effect of ESIs on bone mineral density has been reported. OBJECTIVES: We aimed to clarify the association between ESIs and osteoporosis risk by analyzing a nationwide population database. STUDY DESIGN: This study is a nationwide retrospective cohort study. SETTING: Data on 1 million cases randomly selected from the 2000 Registry for Beneficiaries of the National Health Insurance Research Database (NHIRD) were collected. METHODS: In total, 4,957 patients who were diagnosed with lumbar spondylosis and received ESIs between 2000 and 2013 were identified from the NHIRD. Subsequently, another 4,957 patients with lumbar spondylosis were randomly selected from the same database and frequency matched by age, gender, and index year with the patients who received ESIs. RESULTS: The mean age of the patients were 50.3 ± 17.1 years. The incident rates of osteoporosis in the ESI and non-ESI groups were 7.95 and 7.01 per 1,000 person-years, respectively. Osteoporosis risk was significantly higher in the ESI cohort than in the non-ESI cohort (absolute standardized hazard ratio = 1.23, 95% confidence interval = 1.05-1.45, P = 0.01). The risk factors for osteoporosis were old age, being female, and undergoing ESIs. Osteoporosis risk was significantly higher in the ESI cohort than in the non-ESI cohort in the male, lowest-urbanization-level (fourth level), other-occupations, and comorbidity-free subgroups. LIMITATIONS: The NHIRD did not provide information on osteoporosis-related scales, renal function, blood pressure, smoking habit, pulmonary function, daily activities, and dosage of injected steroids. CONCLUSIONS: For patients diagnosed with lumbar spondylosis, ESIs are associated with a high osteoporosis risk. Thus, this therapy should be recommended with caution, especially for patients with correlated risk factors (e.g., high risk of osteoporotic fracture, low socioeconomic status, and retired or unemployed status).

Sodium-glucose co-transporter 2 inhibitor add-on therapy for metformin delays diabetic retinopathy progression in diabetes patients: a population-based cohort study.

To investigate how sodium-glucose co-transporter 2 inhibitors (SGLT2is) add-on therapy for metformin affects diabetic retinopathy (DR) progression in patients with type 2 diabetes mellitus (T2DM). This nationwide population-based study conducted from January 1, 2016, to December 31, 2018 involved 3,432,911 adults with T2DM in Taiwan. To adjust for potential confounders, data on sex, age, income, comorbidities, diabetes complication severity index score, staging of kidney disease, anti-diabetic medications, and index year were included. The outcome was DR progression, determined by procedure codes or the addition of ICD-9-CM or ICD-10-CM codes to the medical records of the patients during the study. Sensitivity analyses were performed to validate the findings. The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group [95% confidence interval (CI) 0.81-0.99, P = 0.026]. The Kaplan-Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort (log-rank P = 0.0261). The use of SGLT2is for less than 1 year and 1-2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41, 95% Cl 0.35-0.48; P < 0.001). The serial sensitivity analysis showed consistent findings. The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within 1 year before the outcome date (95% Cl 0.71-0.95; P = 0.009). Co-administration of metformin and SGLT2is may reduce the risk of DR progression. Short-term use of SGLT2is may markedly increase the risk of DR, whereas prolonged use SGLT2is may significantly decrease it.

The risk for chronic kidney disease in patients with heart diseases: a 7-year follow-up in a cohort study in Taiwan.

BACKGROUND: The worldwide increasing trend of chronic kidney disease (CKD) is of great concern and the role of heart disease deserves longitudinal studies. This study investigated the risk of developing CKD among patients with heart diseases. METHODS: From universal insurance claims data in Taiwan, we retrospectively identified a cohort of 26005 patients with newly diagnosed heart diseases and 52010 people without such disease from the 2000-2001 claims. We observed prospectively both cohorts until the end of 2007 to measure CKD incidence rates in both cohorts and hazard ratios (HR) of CKD. RESULTS: The incidence of CKD in the cohort with heart disease was 4.1 times greater than that in the comparison cohort (39.5 vs. 9.65 per 10,000 person-years). However, the HR changed into 2.37 (95% confidence interval (CI)=2.05-2.74) in the multivariate Cox proportional hazard model after controlling for sociodemographic characteristics and comorbidity. Compared with individuals aged<40 years, the HRs for CKD ranged from 2.70 to 4.99 in older age groups. Significant estimated relative risks of CKD observed in our patients were also independently associated with hypertension (HR=2.26, 95% CI=1.94-2.63) and diabetes mellitus (HR=2.44, 95% CI=2.13-2.80), but not with hyperlipidemia (HR=1.13, 95% CI=0.99-1.30). CONCLUSIONS: This population study provides evidence that patients with heart disease are at an elevated risk of developing CKD. Hypertension and diabetes mellitus are also comorbidity associated with increasing the CKD risk independently.

Lower risk of ischemic stroke among patients with chronic kidney disease using chinese herbal medicine as add-on therapy: A real-world nationwide cohort study.

Background: The incidence of ischemic stroke (IS) is much higher among patients with chronic kidney disease (CKD) compared to the general population. Few studies have evaluated the association between the risk of IS and the use of Chinese herbal medicine (CHM) in patients with CKD. We aimed to investigate the risk of IS among patients with CKD using CHM as add-on therapy. Methods: We conducted a retrospective cohort study based on Taiwan's National Health Insurance Research Database to assess 21,641 patients with newly diagnosed CKD between 2003 and 2012. Patients were classified as either the CHM (n = 3,149) or the non-CHM group (n = 3,149) based on whether they used CHM after first diagnosis of CKD. We used the proportional subdistribution hazards model of Fine and Gray to examine the hazard ratio (HR) of IS in propensity-score matched samples at a ratio of 1:1 for two groups. Results: The risk of IS was significantly reduced in the CHM group (adjusted HR [aHR]: 0.58, 95% confidence interval [CI]: 0.48-0.70) compared with the non-CHM group. Those who used CHM for >180 days had an even lower risk of IS than those in the non-CHM group (aHR: 0.51, 95% CI: 0.41-0.63). Additionally, frequently prescribed formulae, such as Ji-Sheng-Shen-Qi-Wan, Liu-Wei-Di-Huang-Wan, and Zhen-Wu-Tang were associated with a 30%-50% reduced risk of IS. Conclusion: Our results suggest that patients with CKD who used CHM as add-on therapy had a lower hazard of IS than those in the non-CHM group, especially for patients taking CHM for >180 days. Further experimental studies are required to clarify the causal relationship.

The incidence of severe urinary tract infection increases after hip fracture in the elderly: a nationwide cohort study.

Although urinary tract infection (UTI) is a common perioperative complication among elderly patients with hip fracture, its incidence and effects are often underestimated. This study investigated the effects of severe UTI (S-UTI) on elderly patients with hip fracture and the risk factors for this condition. In this retrospective nationwide cohort study, we searched Taiwan's National Health Insurance Research Database from 2000 to 2012 for data on patients aged ≥ 50 years with hip fracture who underwent open reduction and internal fixation or hemiarthroplasty for comparison with healthy controls (i.e. individuals without hip fracture). The study and comparison cohorts were matched for age, sex, and index year at a 1:4 ratio. The incidence and hazard ratios of age, sex, and multiple comorbidities associated with S-UTI were calculated using Cox proportional hazard regression models. Among the 5774 and 23,096 patients in the study and comparison cohorts, the overall incidence of S-UTI per 100 person-years was 8.5 and 5.3, respectively. The risk of S-UTI was cumulative over time and higher in the study cohort than in the comparison cohort, particularly in those who were older, were female, or had comorbidities of cerebrovascular accident or chronic renal failure.

Risk factors for carpal tunnel syndrome or trigger finger following distal radius fracture: a nationwide study.

New-onset carpal tunnel syndrome (CTS) and trigger finger after distal radius fractures (DRFs) with or without open reduction and internal fixation (ORIF) have been reported inconsistently across different studies. This study assessed the incidence of CTS and trigger finger after DRFs using Taiwan National Health Insurance Research Database. In total, 1454 patients in the case (ORIF) cohort and 1454 patients in the control (non-ORIF) cohort were included in this retrospective study. The mean age was approximately 55 years old, and the female to male ratio was approximately 3/2. Nine patients underwent carpal tunnel release (CTR) surgery after diagnosis of CTS in the case group, and no patients did in the control group; whereas 19 cases of CTS were diagnosed without CTR in the case group, and 4 such cases were observed in the control group. Five cases of trigger finger were diagnosed in the case group, and 3 cases were diagnosed in the control group. CTS were significantly associated with ORIF for DRFs within 9 months after the fracture, whereas trigger finger was not significantly different between groups. Diabetes mellitus was a significant risk factor for CTS and trigger finger within 9 months after the incidence of DRFs.

Fabrication and Performance of MEMS-Based Pressure Sensor Packages Using Patterned Ultra-Thick Photoresists.

A novel plastic packaging of a piezoresistive pressure sensor using a patterned ultra-thick photoresist is experimentally and theoretically investigated. Two pressure sensor packages of the sacrifice-replacement and dam-ring type were used in this study. The characteristics of the packaged pressure sensors were investigated by using a finite-element (FE) model and experimental measurements. The results show that the thermal signal drift of the packaged pressure sensor with a small sensing-channel opening or with a thin silicon membrane for the dam-ring approach had a high packaging induced thermal stress, leading to a high temperature coefficient of span (TCO) response of -0.19% span/°C. The results also show that the thermal signal drift of the packaged pressure sensors with a large sensing-channel opening for sacrifice-replacement approach significantly reduced packaging induced thermal stress, and hence a low TCO response of -0.065% span/°C. However, the packaged pressure sensors of both the sacrifice-replacement and dam-ring type still met the specification -0.2% span/°C of the unpackaged pressure sensor. In addition, the size of proposed packages was 4 × 4 × 1.5 mm(3) which was about seven times less than the commercialized packages. With the same packaging requirement, the proposed packaging approaches may provide an adequate solution for use in other open-cavity sensors, such as gas sensors, image sensors, and humidity sensors.

Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes.

Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti-inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA-treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG expression.

Microbial metabolism of steviol and steviol-16alpha,17-epoxide.

Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7alpha,11beta,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7alpha,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-alpha-d-glucopyranosyl ester (4), ent-13,16beta,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16alpha,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (10), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16beta-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11beta,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (12), and ent-11beta,13,16beta,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

Increased risk of stroke in contact dermatitis patients: A nationwide population-based retrospective cohort study.

Dermatologic diseases are not traditional risk factors of stroke, but recent studies show atopic dermatitis, psoriasis, and bullous skin disease may increase the risk of stroke and other cardiovascular diseases. No previous studies have focused on the association between contact dermatitis and stroke.We established a cohort comprised of 48,169 contact dermatitis patients newly diagnosed in 2000-2003 and 96,338 randomly selected subjects without the disorder, frequency matched by sex, age, and diagnosis year, as the comparison cohort. None of them had a history of stroke. Stroke incidence was assessed by the end of 2011 for both cohorts.The incidence stroke was 1.1-fold higher in the contact dermatitis cohort than in the comparison cohort (5.93 vs 5.37 per 1000 person-years, P < 0.01). The multivariable Cox method analyzed adjusted hazard ratios (aHRs) were 1.12 (95% confidence interval [CI], 1.05-1.19) for all stroke types and 1.12 (95% CI, 1.05-1.20) for ischemic stroke and 1.11 (95% CI, 0.94-1.30) for hemorrhagic stroke. The age-specific aHR of stroke for contact dermatitis cohort increased with age, from 1.14 (95% CI, 1.03-1.27) for 65 to 74 years; to 1.27 (95% CI, 1.15-1.42) for 75 years and older. The aHR of stroke were 1.16 (95% CI, 1.07-1.27) and 1.09 (95% CI, 1.00-1.18) for men and women, respectively.This study suggests that patients with contact dermatitis were at a modestly increased risk of stroke, significant for ischemic stroke but not for hemorrhagic stroke. Comorbidity, particularly hypertension, increased the hazard of stroke further.

Incorporation of styrene enhances recognition of ribonuclease A by molecularly imprinted polymers.

Ribonuclease A (RNase A) is an RNA-cleaving enzyme characterized by its high conformational stability and strong catalytic activity. This enzyme is ubiquitous in living organisms and is difficult to inactivate. In polymerase chain reaction (PCR) RNase activity is removed by adding inhibitors. Molecularly imprinted polymers (MIPs) with high selectivity, high stability, low cost and facile synthesis could prove useful in extraction of target molecules, such as RNase A, from reaction mixtures. In this investigation, MIPs were synthesized from the monomers styrene and polyethyleneglycol 400 dimethacrylate (PEG400DMA) in several different ratios. Styrene as a functional monomer gave MIPs with a higher affinity for RNase A than other functional monomers tested, according to both enzyme-linked immnuosorbent assay (ELISA) and isothermal titration calorimetry (ITC). The optimum volume ratio of styrene/PEG400DMA was 20/100 at 25 degrees C, and this ratio maximized the rebinding efficiency of RNase A to MIPs. Isothermal titration calorimetry was also used, and could be useful to design the composition of molecularly imprinted polymers for various target molecules.