Clinical Updates on Antiplatelet Therapy for Secondary Prevention in Acute Ischemic Stroke.

Antiplatelet therapy is the first-line management for noncardioembolic transient ischemic attack (TIA) and acute ischemic stroke (IS). Herein, we review the safety and efficacy of antiplatelet therapies in patients with IS and TIA, primarily focusing on the acute stage. We discuss current antiplatelet monotherapy and the factors influencing efficacy and continuation rate according to clinical trial data. Aspirin remains the most commonly used first-line antiplatelet agent for preventing noncardioembolic stroke recurrence, and clopidogrel, cilostazol, and ticagrelor are feasible alternatives. Various short-term dual antiplatelet therapies (including clopidogrel-aspirin and ticagrelor-aspirin combination therapy) for minor stroke and high-risk TIA are also reviewed. For selected patients with specific stroke etiologies, short-term dual antiplatelet therapy with aspirin combined with clopidogrel or ticagrelor can significantly reduce the risk of stroke. However, insufficient evidence supports the benefits of triple antiplatelet therapy for recurrent noncardioembolic stroke prevention, and this treatment substantially increases the rate of bleeding complications. Keyword: antiplatelet therapy, acute ischemic stroke, secondary prevention, transient ischemic attack.

The Association between Ankle-Brachial Index/Pulse Wave Velocity and Cerebral Large and Small Vessel Diseases in Stroke Patients.

(1) Background: The study investigated whether the ankle-brachial index (ABI) and pulse wave velocity (baPWV) could reflect the severity of small vessel disease (SVD) and large artery atherosclerosis (LAA). (2) Methods: A total of 956 consecutive patients diagnosed with ischemic stroke were prospectively enrolled from July 2016 to December 2017. SVD severity and LAA stenosis grades were evaluated via magnetic resonance imaging and carotid duplex ultrasonography. Correlation coefficients were calculated between the ABI/baPWV and measurement values. Multinomial logistic regression analysis was performed to determine predictive potential. (3) Results: Among the 820 patients included in the final analysis, the stenosis grade of extracranial and intracranial vessels was inversely correlated with the ABI (p < 0.001, respectively) and positively correlated with the baPWV (p < 0.001 and p = 0.004, respectively). Abnormal ABI, not baPWV, independently predicted the presence of moderate (adjusted odds ratio, aOR: 2.18, 95% CI: 1.31-3.63) to severe (aOR: 5.59, 95% CI: 2.21-14.13) extracranial vessel stenosis and intracranial vessel stenosis (aOR: 1.89, 95% CI: 1.15-3.11). Neither the ABI nor baPWV was independently associated with SVD severity. (4) Conclusions: ABI is better than baPWV in screening for and identifying the existence of cerebral large vessel disease, but neither test is a good predictor of cerebral SVD severity.

Assessment of circulating extracellular vesicles from calorie-restricted mice and humans in ischaemic injury models.

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration.

Investigating the interaction between neuropsychiatry features and daily activities on social function in patients with Parkinson's disease with mild cognitive impairment.

BACKGROUND: Social functioning is crucial for daily living and is an essential indicator of dementia in patients with Parkinson's disease. The pattern of social functioning in patients with Parkinson's disease without dementia (i.e. those who are cognitively intact or have mild cognitive impairment (PD-MCI)) and its determinants are unclear. AIMS: In exploring the heterogeneity of social functioning among patients with Parkinson's disease-associated dementia, we determined the optimal cut-off score of the Parkinson's Disease Social Functioning Scale (PDSFS) for patients with PD-MCI, and the variables influencing patients' social functioning. METHOD: A total of 302 participants underwent the Mini-Mental State Examination (MMSE) and PDSFS; 120 patients with Parkinson's disease completed the measurements (MMSE, Activities of Daily Living Scale and Neuropsychiatric Inventory). Group comparisons, receiver operating characteristic curves, Spearman correlation and multiple and hierarchical regression analyses were conducted. RESULTS: The PD-MCI group scored the lowest on the PDSFS (F = 10.10, P < 0.001). The PDSFS cut-off score was 53 (area under the curve 0.700, sensitivity 0.800, specificity 0.534). The MMSE (ß = 0.293, P = 0.002), Activities of Daily Living Scale (ß = 0.189, P = 0.028) and Neuropsychiatric Inventory (ß = -0.216, P = 0.005) scores predicted the PDSFS score. Further, there was an interaction effect between the Activities of Daily Living Scale and Neuropsychiatric Inventory scores on the PDSFS score (ß = 0.305, P < 0.001). CONCLUSIONS: We determined a PDSFS cut-off score for detecting PD-MCI and found that patients with PD-MCI have social dysfunction. Future research should focus on the effects of neuropsychiatry symptoms and activities of daily living on social functioning, and tailor the intervention programme for patients with Parkinson's disease.

The Association between Osteoporosis and Peripheral Artery Disease: A Population-Based Longitudinal Follow-Up Study in Taiwan.

Background: There are several possible links that have been used to claim that osteoporosis and peripheral artery disease (PAD) are associated; however, the solid evidence is not sufficient. This study aimed to use the Taiwan National Health Insurance Research Database (NHIRD) to determine if osteoporosis is associated with peripheral artery disease (PAD). Method: NHIRD records from 23 million patients were collected to recruit two matched cohort groups: 64,562 patients with and 64,562 patients without osteoporosis. To compare the crude hazard ratio (HR) and the incidence rate ratio between the two cohort groups for PAD, the Cox model was used. Result: With an adjusted HR of 1.18 (95% CI, 1.08-1.29), the osteoporosis cohort group had a significantly greater risk for PAD than the group without osteoporosis. The cumulative incidence of PAD in the cohort group was also statistically higher than it was in the group without osteoporosis (1.71% and 1.39%; p ≤ 0.0001, log-rank) over the 10-year follow-up period. In addition, the osteoporotic patients with ischemic stroke, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) had a significantly increased risk of PAD based on subgroup analysis. Conclusions: There was a positive association between osteoporosis and the development of PAD, as patients with osteoporosis had an increased incidence of PAD over time.

A New Instrument Combines Cognitive and Social Functioning Items for Detecting Mild Cognitive Impairment and Dementia in Parkinson's Disease.

Background: The commonly used screening tests for Parkinson's disease (PD) are the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which only focus on cognitive function. A composite assessment that considers both cognitive and social dysfunction in PD would be helpful in detecting mild cognitive impairment (MCI) and PD dementia (PDD). Objective: We aimed to simplify the commonly used tools and combine cognitive and social functioning tests to detect early MCI and PDD. Materials and Methods: A total of 166 participants (84 PD patients and 82 healthy) were recruited who completed the MMSE, MoCA, PD social functioning scale (PDSFS), clock drawing test, activities of daily living, comprehensive neuropsychological assessment (e.g., executive, attention, language, memory, and visuospatial functions), and movement disorder society (MDS)-unified PD rating scale. According to the MDS diagnostic criteria, the patients were grouped into PD-nonMCI, PD-MCI, or PDD. Results: To detect PD-MCI, the optimal cut-off scores for the simplified MoCA and the combined test were 9 and 35. The discrimination values measured by the area under the receiver operating characteristic curve (AUC) of the two tests were 0.767 (p < 0.001) and 0.790 (p < 0.001). When the simplified MoCA was 7 or the combined test 30, the patients would be classified as having PDD. The AUCs of the two tests were 0.846 (p < 0.001) and 0.794 (p = 0.003). Conclusion: We suggest considering both cognitive and social functions when detecting PD-MCI and PDD.

Factors associated with mortality in patients with super-refractory status epilepticus.

Super-refractory status epilepticus (SRSE) is a critical condition in which seizures persist despite anesthetic use for 24 h or longer. High mortality has been reported in patients with SRSE, but the cause of death remains unclear. We investigated the factors associated with mortality, including clinical characteristics, SE etiologies and severities, treatments, and responses in patients with SRSE in a 13-year tertiary hospital-based retrospective cohort study comparing these parameters between deceased and surviving patients. SRSE accounted for 14.2% of patients with status epilepticus, and 28.6% of SRSE patients died. Deceased patients were mostly young or middle-aged without known systemic diseases or epilepsy. All deceased patients experienced generalized convulsive status epilepticus and failure of anesthetic tapering-off, significantly higher than survivors. An increased number of second-line anesthetics besides midazolam was observed in the deceased (median, 3, interquartile range 2-3) compared to surviving (1, 1-1; p = 0.0006) patients with prolonged use durations (p = 0.047). For mortality, the cut-off number of second-line anesthetics was 1.5 (AUC = 0.906, p = 0.004). Deceased patients had significantly higher renal and cardiac complications and metabolic acidosis than survivors. In SRSE management, multi-anesthetic use should be carefully controlled to avoid systemic complications and mortality.

Ankle-Brachial Index Predicts Long-Term Renal Outcomes in Acute Stroke Patients.

Renal dysfunction is common after stroke. We aimed to investigate the clinical predictability of the ankle−brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) on poststroke renal deterioration. A total of 956 consecutive participants with acute ischemic stroke between 1 July 2016, and 31 December 2017 were enrolled and a final of 637 patients were recruited for final analysis. By using the group-based trajectory model (GBTM), the patients' renal function trajectories were grouped into the low, intermediate, and high categories (LC, IC, and HC). Significant deterioration in the slope was noted in the IC (p < 0.001) and LC (p = 0.002) groups but was nonsignificant in the HC (p = 0.998) group. Abnormal ABI (ABI ≤ 0.9) was independently related to LC (adjusted odds ratio: 2.40; 95% CI, 1.16−4.95; p = 0.019) and was also independently associated with increased risks of a ≥30% decline in eGFR (adjusted hazard ratio [aHR], 2.28; 95% CI, 1.29−4.05; p = 0.005), a doubling of serum creatinine (aHR, 3.60; 95% CI, 1.93−8.34; p < 0.001) and ESRD (HR, 3.28; 95% CI, 1.23−8.74; p = 0.018). However, baPWV did not have a significant relationship with any of the renal outcomes. Patients with a lower ABI during acute stroke should receive regular renal function tests and should be closely monitored to improve poststroke renal care.

Hypomimia May Influence the Facial Emotion Recognition Ability in Patients with Parkinson's Disease.

BACKGROUND: Hypomimia is a clinical feature of Parkinson's disease (PD). Based on the embodied simulation theory, the impairment of facial mimicry may worsen facial emotion recognition; however, the empirical results are inconclusive. OBJECTIVE: We aimed to explore the worsening of emotion recognition by hypomimia. We further explored the relationship between the hypomimia, emotion recognition, and social functioning. METHODS: A total of 114 participants were recruited. The patients with PD and normal controls (NCs) were matched for demographic characteristics. All the participants completed the Mini-Mental State Examination and the Chinese Multi-modalities Emotion Recognition Test. In addition to the above tests, the patients were assessed with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and Parkinson's Disease Social Functioning Scale (PDSFS). RESULTS: Patients with PD with hypomimia had worse recognition of disgust than NCs (p = 0.018). The severity of hypomimia was predictive of the recognition of disgust (ß= -0.275, p = 0.028). Facial emotion recognition was predictive of the PDSFS score of PD patients (ß= 0.433, p = 0.001). We also found that recognizing disgust could mediate the relationship between hypomimia and the PDSFS score (ß= 0.264, p = 0.045). CONCLUSION: Patients with hypomimia had the worst disgust facial recognition. Hypomimia may affect the social function of PD patients, which is related to recognizing the expression of disgust. Emotion recognition training may improve the social function of patients with PD.

Investigations of silane-MDP interaction in universal adhesives: A ToF-SIMS analysis.

OBJECTIVES: The purposes of this study were to investigate whether the presence of silane in universal adhesives affects the functions of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and adhesion to zirconia. METHODS: Two silane-containing universal adhesives (Scotchbond Universal (SBU) and Clearfil Universal-Bond (CUB)) and two silane-free adhesives (All-Bond Universal (ABU) and SE-Bond primer (SE)) were individually applied on zirconia disks. Time-of-flight secondary-ion-mass-spectrometry (ToF-SIMS) examined the distributions of MDP- and silane-related ions, as well as evidence of zirconium phosphate (ZrP) compounds, on the surface and interfacial regions using a depth profiling mode. The hydrophilicity and resin wettability of the treated zirconia were examined using a contact angle test. For the shear bond strength (SBS) test, the zirconia disks were air-blasted, treated with the assigned adhesives, and bonded with pre-cured composite cylinders using a resin cement. These resin-zirconia assemblies received a bond test after 24-h storage. RESULTS: Both SBU and CUB exhibited silane-related ions and ZrO2(OH)-, but fewer PO- ions in the interfacial regions. CUB had more siloxane-related ions. SE-treated zirconia had abundant PO- ions and particularly high PO3-- and ZrP- related ions in the interfacial regions. The silane-free adhesives exhibited a higher affinity to both water and adhesive liquids. SE showed significantly higher SBSs compared to ABU, while SBU and CUB were not statistically different. SIGNIFICANCE: The silane content may cause hydroxylation of zirconia and affect MDP adsorption. An acidic pH accelerated the condensation of silanol. The bond performance of the MDP-based adhesive could be influenced by the silane content and other components.

Novel Polymerization of Dental Composites Using Near-Infrared-Induced Internal Upconversion Blue Luminescence.

Blue light (BL) curing on dental resin composites results in gradient polymerization. By incorporating upconversion phosphors (UP) in resin composites, near-infrared (NIR) irradiation may activate internal blue emission and a polymerization reaction. This study was aimed to evaluate the competency of the NIR-to-BL upconversion luminance in polymerizing dental composites and to assess the appropriate UP content and curing protocol. NaYF4 (Yb3+/Tm3+ co-doped) powder exhibiting 476-nm blue emission under 980-nm NIR was adapted and ball-milled for 4-8 h to obtain different particles. The bare particles were assessed for their emission intensities, and also added into a base composite Z100 (3M EPSE) to evaluate their ability in enhancing polymerization under NIR irradiation. Experimental composites were prepared by dispensing the selected powder and Z100 at different ratios (0, 5, 10 wt% UP). These composites were irradiated under different protocols (BL, NIR, or their combinations), and the microhardness at the irradiated surface and different depths were determined. The results showed that unground UP (d50 = 1.9 µm) exhibited the highest luminescence, while the incorporation of 0.4-µm particles obtained the highest microhardness. The combined 20-s BL and 20-120-s NIR significantly increased the microhardness on the surface and internal depths compared to BL correspondents. The 5% UP effectively enhanced the microhardness under 80-s NIR irradiation but was surpassed by 10% UP with longer NIR irradiation. The combined BL-NIR curing could be an effective approach to polymerize dental composites, while the intensity of upconversion luminescence was related to specific UP particle size and content. Incorporation of 5-10% UP facilitates NIR upconversion polymerization on dental composites.

Carbazole- and thiophene-containing conjugated microporous polymers with different planarity for enhanced photocatalytic hydrogen evolution.

We report the synthesis of two carbazole-thiophene-based conjugated microporous polymers (Cz-3Th and Cz-4Th CMPs) with different degrees of planarity for photocatalytic hydrogen evolution from water. Depending upon the building linker's planarity, we found that the porous structure, hydrogen-evolution rate, and photocatalytic stability of the resultant CMPs varied.

The novel three-dimensional pulse images analyzed by dynamic L-cube polynomial model.

A dynamic L-cube polynomial is proposed to analyze dynamic three-dimensional pulse images (d3DPIs), as an extension of the previous static L-cube polynomial. In this paper, a weighted least squares (WLS) method is proposed to fit the amplitude C(t) of d3DPI at four physiological key points in addition to the best fit of L-cube polynomials to the measured normal and cold-pressor-test (CPT)-induced taut 3DPIs. Compared with other two fitting functions, C(t) of a dynamic L-cube polynomial can be well matched by the proposed WLS method with the least relative error at four physiological key points in one beat with statistical significance, in addition to the best fit of the measured 3DPIs. Therefore, a dynamic L-cube polynomial can reflect dynamic time characteristics of normal and CPT-induced hypertensive taut 3DPIs, which can be used as an evidence of hypertension diagnosis.

Using Artificial Neural Network to Discriminate Parkinson's Disease from Other Parkinsonisms by Focusing on Putamen of Dopamine Transporter SPECT Images.

BACKGROUND: The challenge of differentiating, at an early stage, Parkinson's disease from parkinsonism caused by other disorders remains unsolved. We proposed using an artificial neural network (ANN) to process images of dopamine transporter single-photon emission computed tomography (DAT-SPECT). METHODS: Abnormal DAT-SPECT images of subjects with Parkinson's disease and parkinsonism caused by other disorders were divided into training and test sets. Striatal regions of the images were segmented by using an active contour model and were used as the data to perform transfer learning on a pre-trained ANN to discriminate Parkinson's disease from parkinsonism caused by other disorders. A support vector machine trained using parameters of semi-quantitative measurements including specific binding ratio and asymmetry index was used for comparison. RESULTS: The predictive accuracy of the ANN classifier (86%) was higher than that of the support vector machine classifier (68%). The sensitivity and specificity of the ANN classifier in predicting Parkinson's disease were 81.8% and 88.6%, respectively. CONCLUSIONS: The ANN classifier outperformed classical biomarkers in differentiating Parkinson's disease from parkinsonism caused by other disorders. This classifier can be readily included into standalone computer software for clinical application.

Impairment of Membrane Lipid Homeostasis by Bichalcone Analog TSWU-BR4 Attenuates Function of GRP78 in Regulation of the Oxidative Balance and Invasion of Cancer Cells.

The specialized cholesterol/sphingolipid-rich membrane domains termed lipid rafts are highly dynamic in the cancer cells, which rapidly assemble effector molecules to form a sorting platform essential for oncogenic signaling transduction in response to extra- or intracellular stimuli. Density-based membrane flotation, subcellular fractionation, cell surface biotinylation, and co-immunoprecipitation analyses of bichalcone analog ((E)-1-(4-Hydroxy-3-((4-(4-((E)-3-(pyridin-3-yl)acryloyl)phenyl)piperazin-1-yl)methyl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (TSWU-BR4)-treated cancer cells showed dissociation between GRP78 and p85α conferring the recruitment of PTEN to lipid raft membranes associated with p85α. Ectopic expression of GRP78 could overcome induction of lipid raft membrane-associated p85α-unphosphorylated PTEN complex formation and suppression of GRP78PI3KAktGTP-Rac1-mediated and GRP78-regulated PERKNrf2 antioxidant pathway and cancer cell invasion by TSWU-BR4. Using specific inducer, inhibitor, or short hairpin RNA for ASM demonstrated that induction of the lipid raft membrane localization and activation of ASM by TSWU-BR4 is responsible for perturbing homeostasis of cholesterol and ceramide levels in the lipid raft and ER membranes, leading to alteration of GRP78 membrane trafficking and subsequently inducing p85α-unphosphorylated PTEN complex formation, causing disruption of GRP78PI3KAktGTP-Rac1-mediated signal and ER membrane-associated GRP78-regulated oxidative stress balance, thus inhibiting cancer cell invasion. The involvement of the enrichment of ceramide to lipid raft membranes in inhibition of NF-κB-mediated MMP-2 expression was confirmed through attenuation of NF-κB activation using C2-ceramide, NF-κB specific inhibitors, ectopic expression of NF-κB p65, MMP-2 promoter-driven luciferase, and NF-κB-dependent reporter genes. In conclusion, localization of ASM in the lipid raft membranes by TSWU-BR4 is a key event for initiating formation of ceramide-enriched lipid raft membrane platforms, which causes delocalization of GRP78 from the lipid raft and ER membranes to the cytosol and formation of p85α-unphosphorylated PTEN complexes to attenuate the GRP78-regulated oxidative stress balance and GRP78p85αAktGTP-Rac1NF-κBMMP-2-mediated cancer cell invasion.

The Impact of Antiplatelet Use on the Risk of Intracerebral Hemorrhage in Patients with Alzheimer's Disease: A Nationwide Cohort Study.

BACKGROUND: Antiplatelet use on the risk of intracerebral hemorrhage (ICH) in patients with Alzheimer's disease (AD) has not yet been completely elucidated. OBJECTIVE: This large epidemiologic study aims to estimate the risk of ICH in AD patients treated with antiplatelet therapy (APT). METHODS: Using data from Taiwan's National Health Insurance Research Database, ICH risk in APT-treated AD patients with a validated diagnosis (N = 824) was determined. AD without APT and non-AD with and without APT comparison cohorts were selected. To adjust for confounders and competing risk of death, inverse probability of treatment weighting using propensity scores and competing risks regression (CRR) were applied. Cox proportional hazards regression analysis estimated ICH risk in all cohorts comparing with non-AD without APT. RESULTS: Among the 824 AD patients with APT, 79.6% were prescribed aspirin. ICH incidence rates in the AD (with/without APT) and non-AD (with/without APT) cohorts were 2.88/2.70 and 2.24/1.20 per 1,000 person-years, respectively. Overall, AD with (adjusted hazards ratio (aHR), 2.29; 95% CI, 1.19-4.38) and without (aHR, 1.97; 95% CI, 1.08-3.61) APT and non-AD with APT (aHR, 1.80; 95% CI, 1.34-2.42) were at a higher risk and had elevated subdistribution HR obtained from CRR than non-AD without APT controls. However, the risk was comparable between the AD cohorts with and without APT (HR, 1.16; 95% CI, 0.51-2.66). CONCLUSIONS: Our study indicated both the APT and non-APT users in AD population yielded higher ICH risks. However, whether APT use potentiate the risk of ICH in AD patients may warrant further evaluation.

Clinical Outcome of Immediate Transurethral Surgery for Benign Prostate Obstruction Patients with Acute Urinary Retention: More Radical Resection Resulted in Better Voiding Function.

INTRODUCTION: Transurethral surgery of the prostate is currently the gold standard treatment modality for patients with benign prostatic hyperplasia (BPH) with recurrent acute urinary retention. This study aimed to evaluate the outcome and predictors of patients receiving immediate surgery after acute urinary retention (AUR) episodes. MATERIALS AND METHODS: From January 2016 to January 2017, we retrospectively included 714 patients who received transurethral surgery of prostate due to BPH. Among them, 158 patients received surgeries immediately after an AUR episode. General characteristics data including age, Body mass index (BMI), International prostate symptom score (IPSS score), prostate volume and Prostate-specific antigen (PSA) were reviewed. We also collected surgery-related parameters including surgical types, operation time, and specimen weight. Resection ratio was defined as (resected specimen weight)/(Transurethral ultrasound (TRUS) volume). The catheterization status on discharge, post-operative medication for BPH, and AUR within 3 months after operation were evaluated. Statistical analysis was performed with Statistical product and service solutions (SPSS). RESULTS: The mean age of the patients was 73.5 years, with a BMI of 24 kg/m2. IPSS total score was 25 with a Voiding symptom/Storage symptom score (V/S score) of 14.6 and 10.4, respectively. A total of 74 (46.8%) patients still took medication for BPH for over 1 month after the surgeries, 28 (17.7%) patients were not catheter-free at the time of discharge, and 14 (8.9%) patients had AUR within 3 months after the surgeries. Surgical type did not impact the outcome of surgeries. In patients who received Transurethral resection of the prostate (TURP), the resection ratio is the only predictor for the catheterization status on discharge and post-operative medication for BPH within 3 months after operation. CONCLUSIONS: In patients with BPH-related AUR followed by immediate transurethral surgeries, more radical resection is significantly correlated with short-term medication-free and catheter-free status.

Topical anesthesia for staple removal from surgical wounds on the knee: a prospective, double-blind, randomized trial.

BACKGROUND: Staple removal from surgical wounds is painful. Only a few articles have provided expert opinions using anesthetic cream for such a problem; however, direct application of the anesthetic cream to a wound may cause infection. A safe alternative can be an anesthetic patch without wound contact. MATERIALS AND METHODS: This was a prospective, double-blind, randomized clinical trial. Sixty patients who underwent primary total knee replacement were assigned to an experimental group or control group. One lidocaine patch was applied around the surgical wound for each patient in the experimental group. Alternatively, the adhesive sides of the lidocaine patches were shielded with waterproof films in the control group. A resident peeled off the patch before a single nursing practitioner removed the staples. Pain was assessed with the 10-cm visual analog scale, and a face pain scale-revised was performed. The patients and the nursing practitioner were blind to the management. RESULTS: Mean visual analog scale and face pain scale-revised scores were significantly lower in the experimental group. The mean pain score was significantly lower in the experimental group if the application time was >47 min; for patients with application time of 47 min or shorter, the score was comparable with the mean pain scores of the control group (P = 0.215). CONCLUSIONS: Removal of the metal skin staples after total knee arthroplasty is associated with moderate-to-severe pain. The lidocaine patch applied topically around the surgical wound could effectively reduce the pain during the procedure, without remarkable complications such as systemic adverse effects or wound contamination.

Development of an Economical DNA Delivery System by "Acufection" and its Application to Skin Research.

Dysregulation of immune response in skin is associated with numerous human skin disorders. Direct transfer of immune-related genes into skin tissue is a fascinating approach to investigate immune modulation of cutaneous inflammation in mouse models of human diseases. Here we present a cost-effective protocol that delivered naked DNA in mouse skin and leads to transgene expression. The method is coined "acufection", denoting acupuncture-mediated DNA transfection. To perform acufection, mouse skin was first infused with DNA in phosphate-buffered saline (PBS) and then pricked lightly with a bundle of acupuncture needles to facilitate the absorption of DNA and transfection into cells. The plasmid DNA is presumably taken up by the keratinocyte and dendritic cells (DCs) in the skin and expressed into protein. Mechanical prick with the needles per se did not cause skin damage or induce keratinocyte activation. The expression of the transfected genes was detected in the skin at both transcriptional and translational levels following acufection for 2 days and maintained up to 7 days. The primary goal for the development of this acufection method was to investigate a previously undefined isoform of IL-15. Using this method, an alternatively spliced IL-15 isoform with partially deleted exon 7 (IL-15ΔE7) was expressed in the skin and subsequently treated with a Toll-like receptor 7 (TLR7) agonist, imiquimod (IMQ), to induce inflammation. Acufection-delivered IL-15ΔE7 in skin suppressed keratinocyte proliferation, epidermal thickness and neutrophil recruitment in IMQ-induced cutaneous inflammation. With increasing interest in identifying the regulatory mechanisms of cutaneous inflammation, the protocol described here provides a cost effective and versatile alternative to the gene gun system or microseeding for DNA delivery in vivo. It may potentially allow discovery of the function of a novel gene in the skin or for investigating new treatment for cutaneous diseases.

Facility evaluation of resigned hospital physicians:managerial implications for hospital physician manpower.

INTRODUCTION: Turnover of physicians might be responsible for reducing patients' trust and affecting hospital performance. This study aimed to understand physicians' psychological status regarding their hospital work environment and the resources of independent practitioners. METHOD: This was a cross-sectional study with 774 physicians who had resigned from hospitals and were now practicing privately in clinics in Taichung City as its study population. A mail survey with a multidimensional questionnaire was sent to each subject. RESULTS: This study revealed that older physicians were less satisfied regarding the work environment in their respective former hospitals. Male physicians were found to be more satisfied with the tangible resources of their hospitals. Internal medicine physicians were found to be less satisfied overall with the intangible resources. Gynecologists and pediatricians were found to be more satisfied with their hospital environments. The physicians who worked long hours per week reported that they were less satisfied with their job content. The physicians who had opportunities to learn advanced skills and enhance their knowledge were more satisfied with their hospital environment, tangible resources, and intangible resources. In addition, physicians in private hospitals were found to be more satisfied with their job content, but they were less satisfied with work motivation and retention and intangible resources. In addition, physicians who worked in hospitals located in Taichung city reported that they were less satisfied with their tangible resources than the physicians working in hospitals outside of the city. CONCLUSION: This study focused on the satisfaction of physicians who had already left their respective hospitals instead of current retained physicians. From this study, it is our recommendation that hospital managers should pay closer attention to the real needs and expectations of the physicians they employ, and managers should consider adjusting their managerial perspectives when establishing new human resources policies or making decisions.