Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.

OBJECTIVE: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. METHODS: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. RESULTS: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. CONCLUSION: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Synergistic Effects of Silicate-Platelet Supporting Ag and ZnO, Offering High Antibacterial Activity and Low Cytotoxicity.

Silver nanoparticles (AgNPs) are remarkably able to eliminate microorganisms, but induce cytotoxicity in mammalian cells, and zinc oxide nanoparticles (ZnONPs) are considered to have a wide bactericidal effect with weak cytotoxicity. In this study, both zinc oxide nanoparticles and silver nanoparticles were co-synthesized on a nano-silicate platelet (NSP) to prepare a hybrid of AgNP/ZnONP/NSP. Ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction (XRD), and transmission electron microscopy (TEM) were used to characterize the formation of nanoparticles on the NSP. Synthesized ZnONP/NSP (ZnONP on NSP) was confirmed by the absorption peaks on UV-Vis and XRD. AgNP synthesized on ZnONP/NSP was also characterized by UV-Vis, and ZnONP/NSP showed no interference with synthesis. The images of TEM demonstrated that NSP provides physical support for the growth of nanoparticles and could prevent the inherent aggregation of ZnONP. In antibacterial tests, AgNP/ZnONP/NSP exhibited more efficacy against Staphylococcus aureus (S. aureus) than ZnONP/NSP (ZnONP was synthesized on NSP) and AgNP/NSP (AgNP was synthesized on NSP). In cell culture tests, 1/10/99 (weight ratio) of AgNP/ZnONP/NSP exhibited low cytotoxicity for mammalian cells (>100 ppm). Therefore, AgNP/ZnONP/NSP, containing both AgNP and ZnONP, with both strong antibacterial qualities and low cytotoxicity, showed potentially advantageous medical utilizations due to its antibacterial properties.

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. METHODS: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. RESULTS: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38). CONCLUSIONS: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study.

BACKGROUND: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database. METHODS: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000-2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed. RESULTS: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000-2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis. CONCLUSIONS: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.

Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study.

BACKGROUND: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. "This study investigated the risk of incident CFS among patients with IBD". METHODS: We conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS. RESULTS: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment. CONCLUSION: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS.

Increased risk of chronic fatigue syndrome following pneumonia: A population-based Cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan. METHODS: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders. RESULTS: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person-years among the non-pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32-1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p < 0.05). Additionally, patients with pneumonia had a significantly increased risk of thromboembolism compare with control group (p < 0.05).

Primary endodermal sinus tumor in the posterior cranial fossa: clinical analysis of 7 cases.

OBJECTIVE: To clarify the clinical features, therapeutic method and outcomes of the primary endodermal sinus tumors (ESTs) in the posterior cranial fossa. METHODS: The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed. And a 4-year-old boy diagnosed with EST in our hospital was reported. The clinical manifestations, therapy, pathologic features, and prognosis of these cases were analyzed. RESULTS: Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review, including six cases searched from the PubMed and one case from our hospital. Six patients were boy and one patient's gender was not available from the report. Ages ranged from 1 to 5 years (mean 3.14 years). The mean tumor size in our cohort was 4.4 cm. Six cases came from East Asia. Schiller-Duval bodies were found in all seven neoplasms. All tumors were positive for alpha-fetoprotein. The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy. The mean follow-up time was 24.4 months (range 5-52 months). Six tumors were totally removed, and four of them recurred. Three cases died including one whose tumor was partially removed. CONCLUSIONS: The serum alpha-fetoprotein level is well correlated with the severity of the tumor. A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa. The prognosis of extragonadal intracranial EST is poor.

Intratumoral thermo-chemotherapeutic alginate hydrogel containing doxorubicin loaded PLGA nanoparticle and heating agent.

Chemotherapy has been widely used to treat cancer; however, the non-specific systemic toxicity of chemotherapeutic agents has always been an issue. Local injection treatment is a strategy used to reduce the undesired adverse effects of chemotherapeutic drugs. In addition, chemotherapeutic agents combined with thermotherapy are effective in further enhancing therapeutic potency. In the present study, we prepared an injectable hydrogel, namely, doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle (DPN) and magnetite nanoparticle (MNP) embedded in alginate hydrogel (DPN/MNP-HG), where DPN and MNP were the chemotherapeutic and heating agents, respectively, for intratumoral thermo-chemotherapy. Injectable DPN/MNP-HG, which possesses solid-like elastic properties, was conveniently prepared via ionic cross-linking at room-temperature. When exposed to an alternating magnetic field (AMF), DPN/MNP-HG exhibited controllable heat generation with a reversible temperature-rise profile. Regarding the kinetics of DOX release, both with and without AMF, DPN/MNP-HG exhibited a slow initial burst and sustained release profile. In cytotoxicity studies and subcutaneous mouse cancer models, successful thermo-chemotherapy with DPN/MNP-HG resulted in significantly lower cell viability and increased tumor-growth suppression; mice also exhibited good tolerance to injected DPN/MNP-HG both with(+) and without AMF application. In conclusion, the proposed thermo-chemotherapeutic DPN/MNP-HG for local intratumoral injection is a promising formulation for cancer treatment.

The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) often experience a high accumulation of protein-bound uremic toxins (PBUTs), specifically indoxyl sulfate (IS) and p-cresyl sulfate (pCS). In the early stages of CKD, the buildup of PBUTs inhibits bone and muscle function. As CKD progresses, elevated PBUT levels further hinder bone turnover and exacerbate muscle wasting. In the late stage of CKD, hyperparathyroidism worsens PBUT-induced muscle damage but can improve low bone turnover. PBUTs play a significant role in reducing both the quantity and quality of bone by affecting osteoblast and osteoclast lineage. IS, in particular, interferes with osteoblastogenesis by activating aryl hydrocarbon receptor (AhR) signaling, which reduces the expression of Runx2 and impedes osteoblast differentiation. High PBUT levels can also reduce calcitriol production, increase the expression of Wnt antagonists (SOST, DKK1), and decrease klotho expression, all of which contribute to low bone turnover disorders. Furthermore, PBUT accumulation leads to continuous muscle protein breakdown through the excessive production of reactive oxygen species (ROS) and inflammatory cytokines. Interactions between muscles and bones, mediated by various factors released from individual tissues, play a crucial role in the mutual modulation of bone and muscle in CKD. Exercise and nutritional therapy have the potential to yield favorable outcomes. Understanding the underlying mechanisms of bone and muscle loss in CKD can aid in developing new therapies for musculoskeletal diseases, particularly those related to bone loss and muscle wasting.

Quaternized Amphiphilic Block Copolymers as Antimicrobial Agents.

In this study, a novel polystyrene-block-quaternized polyisoprene amphipathic block copolymer (PS-b-PIN) is derived from anionic polymerization. Quaternized polymers are prepared through post-quaternization on a functionalized polymer side chain. Moreover, the antibacterial activity of quaternized polymers without red blood cell (RBCs) hemolysis can be controlled by block composition, side chain length, and polymer morphology. The solvent environment is highly related to the polymer morphology, forming micelles or other structures. The polymersome formation would decrease the hemolysis and increase the electron density or quaternized groups density as previous research and our experiment revealed. Herein, the PS-b-PIN with N,N-dimethyldodecylamine as side chain would form a polymersome structure in the aqueous solution to display the best inhibiting bacterial growth efficiency without hemolytic effect. Therefore, the different single-chain quaternized groups play an important role in the antibacterial action, and act as a controllable factor.

Developing and Validating Risk Scores for Predicting Major Cardiovascular Events Using Population Surveys Linked with Electronic Health Insurance Records.

A risk prediction model for major cardiovascular events was developed using population survey data linked to National Health Insurance (NHI) claim data and the death registry. Another set of population survey data were used to validate the model. The model was built using the Nutrition and Health Survey in Taiwan (NAHSIT) collected from 1993-1996 and linked with 10 years of events from NHI data. Major adverse cardiovascular events (MACEs) were identified based on hospital admission or death from coronary heart disease or stroke. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), conducted in 2002 was used for external validation. The NAHSIT data consisted of 1658 men and 1652 women aged 35-70 years. The incidence rates for MACE per 1000 person-years were 13.77 for men and 7.76 for women. These incidence rates for the TwSHHH were 7.27 for men and 3.58 for women. The model had reasonable discrimination (C-indexes: 0.76 for men; 0.75 for women), thus can be used to predict MACE risks in the general population. NHI data can be used to identify disease statuses if the definition and algorithm are clearly defined. Precise preventive health services in Taiwan can be based on this model.

The risk of fibromyalgia in patients with iron deficiency anemia: a nationwide population-based cohort study.

Since iron is essential for neurotransmitter synthesis, decreased iron stores might lead to reduced production of biogenic amines which phenomenon was shown in Fibromyalgia (FM) patients. The aims are to investigate the association of iron deficiency anemia (IDA) and FM and to find the effects of different interventions. We conducted a study using the Taiwan National Health Insurance Research Database. The IDA cohort consisted of 13,381 patients with newly diagnosed IDA between 2000 and 2008. Each patient with IDA was frequency-matched with one people without IDA, by sex, age and index year. The Cox proportional hazards regression analysis was conducted to estimate the association between IDA and FM risk. The event was the occurrence of FM. The overall incidence density rate of FM in the IDA cohort was higher than in the non-IDA cohort with a multivariable Cox proportional hazards model measured adjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.13-1.25). When using non-IDA group as reference, we compared with different therapies for IDA. The adjusted HRs of FM were 1.38 (95% CI = 1.30-1.47), 1.10 (95% CI = 1.03-1.16), 1.18 (95% CI = 0.98-1.43) and 0.73 (95% CI = 0.58-0.90) for IDA patient without therapy, iron supplement alone, blood transfusion alone and both iron supplement and blood transfusion respectively. Our results suggest IDA is associated with an increased risk of FM. All patients should have iron supplementation both to correct anemia and replenish body stores.

How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight.

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

Neuregulin 1 enhances cell adhesion molecule L1 like expression levels and promotes malignancy in human glioma.

Neural cell adhesion molecular L1-like protein (CHL1) is a member of the cell adhesion molecule L1 family and serves an important role in the development and progression of tumors. The cytokine neuregulin 1 (NRG1) has been indicated in the tumorigenesis and promotion of metastasis through the modulation of L1. However, the roles of NRG1 in regulating CHL1 in glioma have not been elucidated. The present study investigated the protein expression levels and roles of CHL1 and the possible correlation between NRG1 and CHL1 protein expression levels in human gliomas, both in vivo and in vitro. Using immunohistochemistry coupled with a human glioma tissue microarray, it was demonstrated that the percentage of CHL1-positive areas was the highest in grade II glioma tissues. Using immunofluorescence staining, a positive correlation was identified between the expression levels of CHL1 and proliferating cell nuclear antigen. In addition, CHL1 downregulation also resulted in increased senescence of U-87 MG human glioblastoma cells. In vitro, administration of NRG1α induced a significant increase in CHL1 protein expression levels in human glioma SHG-44 and U251 cells and in human glioblastoma U-87 MG cells, whereas NRG1ß failed to increase CHL1 expression levels in U251 cells. These findings were further confirmed by the downregulation of NRG1 expression levels using small interfering RNA treatment, which resulted in the reduction of CHL1 protein expression levels in U-87 MG cells. These data indicate that NRG1 can regulate CHL1 protein expression levels in gliomas, that it is correlated with malignancy, and that NRG1 may contribute to malignancy by upregulating CHL1 protein expression levels in glioma/glioblastoma cells.

Cost-drivers of medical expenses in burn care management.

BACKGROUND: Profound differences exist in the cost of burn care globally, thus we aim to investigate the affected factors and to delineate a strategy to improve the cost-effectiveness of burn management. METHODS: A retrospective analysis of 66 patients suffering from acute burns was conducted from 2013 to 2015. The average age was 26.7 years old and TBSA was 42.1% (±25.9%). We compared the relationship between cost and clinical characteristics. RESULTS: The estimated cost of acute burn care with the following formula (10,000 TWD) = -19.80 + (2.67 × percentage of TBSA) + (124.29 × status of inhalation injury) + (147.63 × status of bacteremia) + (130.32 × status of respiratory tract infection). CONCLUSION: The majority of the cost were associated with the use of antibiotics and burns care. Consequently, it is crucial to prevent nosocomial infection in order to promote healthcare quality and reduce in-hospital costs.

[Recombinant AAV1 mediated vascular endothelial growth factor gene expression promotes angiogenesis and improves neural function: experiment with rats].

OBJECTIVE: To investigate the therapeutic effect of vascular endothelial growth factor (VEGF) gene expression mediated by recombinant AAV1 (rAAV1) vector in brain ischemia and the mechanism thereof. METHODS: Sixty-four SD rats were randomly divided into 2 equal groups and received intra-ventricular injection with rAAV1-VEGF or rAAV1-lacZ as controls. 21 days later the rats underwent transient middle cerebral artery occlusion (MCAO). Neurological severity score (NSS) was recorded 1, 2, 3, 7, 14, and 21 days after MCAO. 48 rats were sacrificed 21 days after MCAO and brains were taken out from 48 rats. Immune quantitative analysis was used to identify the quantity of VEGF expression. Immunohistochemistry was used to identify the site of VEGF expression. Immunofluorescence double labeling of von Willebrand factor (vWF) and 5-bromodeoxy-uridine (BrdU) was performed to detect the proliferation of endothelial cells. Fluorescein isothiocyanate (FITC)-dextran was infused into the caudal vein of 8 rats from each group and then the rats were killed with their brains taken out to evaluate the cerebral microvessel perfusion and microvessel density. RESULTS: The NSSs of the VEGF group 7, 14, and 21 days after MCAO were all significantly lower than those of the control group (all P < 0.05), and the VEGF165 protein expression quantity was 27 times as that of the control group (P < 0.05). Immunohistochemistry demonstrated that VEGF expression was distributed mainly in the caudate putamen, corpus callosum, choroid plexus, and hippocampus in the VEGF group, while no expression was detected in the control group. The microvessel density of the VEGF group was 157 +/- 13, significantly higher than that of the control group [(89 +/- 9), P < 0.05]. BrdU +/vWF + endothelial cells were detected in the area adjacent to the MCAO. The density of microvessel infused with FITC-dextran was (152,617 +/- 13,076) microm2/mm2 in the VEGF group, significantly higher than that of the control group [(91,658 +/- 6577) microm2/mm2 P < 0.05]. CONCLUSION: rAAV1 mediates the VEGF gene expression in multiple structures in the brain and attenuates the neurological deficit of MCAO. VEGF gene transfer may stimulate angiogenesis and improves blood supply in brain. Neovascularization may be a therapeutic strategy for brain ischemia.

Development of Benzimidazole Derivatives as Novel Anti-platelet Drugs.

BACKGROUND: Benzimidazoles are privileged biomolecules which form an integral part of vitamin B12 and have been attracting numerous researchers all over the world to assess their potential therapeutic significance. OBJECTIVES: The comparative in vitro antiplatelet activity of newly synthesized benzimidazole derivatives, M3BIM, C2BIM, and L2BIM in thrombin, adenosine diphosphate (ADP) and epinephrineinduced washed human platelets was investigated. METHOD: Reversed-phase silica gel column chromatography, Aggregometry, Flow cytometry and Immunoblotting were used in this study. RESULTS: M3BIM exhibited a concentration (25-100 µM) dependent inhibitory effect on platelet aggregation induced by thrombin (0.01 U/mL) in washed human platelets and by epinephrine (10 µM) only at a maximum concentration of 500 µM in platelet-rich plasma (PRP); however, C2BIM and L2BIM had no response even at 500 µM against thrombin and 1mM against epinephrine-induced platelet aggregation. Moreover, all these three compounds were not inhibited platelet aggregation induced by ADP (20 µM). Additionally, these compounds showed no effects in thrombin-induced P-selectin expression and αIIbß3 activation, as evidenced by flow cytometry and clot reaction assays, respectively. Besides, M3BIM (100 µM) significantly abolished thrombin-induced Akt and mitogen-activated protein kinases (MAPKs) phosphorylation; whereas 200 µM C2BIM and L2BIM were not effective on these proteins. CONCLUSION: This study affords confirmation for the inhibitory effect of M3BIM in a low dose thrombin and epinephrine-induced platelet aggregation in vitro compared to other imidazole derivatives, C2BIM and L2BIM. These outcomes may recommend that M3BIM can be appraised as a prospective benzeimidazole compound for the treatment of thrombin -induced platelet defect and its related diseases.

Damping effects on the response of maxillary incisor subjected to a traumatic impact force: a nonlinear finite element analysis.

OBJECTIVES: The aim of this study was to evaluate the effects of damping on stress concentration in an impacted incisor. METHODS: Damping ratios of maxillary incisors were tested using an in vivo modal testing method. A finite element model of the upper central incisor was established for dental trauma analysis. To assess the effect of damping properties on induced stresses in the traumatized incisors, equivalent stresses in the finite element model with various damping ratios were calculated for comparison. The mechanisms of cushioning properties of the upper incisors on traumatic injuries were assessed by profiling the stress distributions in the incisor model sequentially with time. RESULTS: The measured damping ratio of maxillary incisors was 0.146+/-0.037. When the incisor was subjected to an impact force, high stresses were concentrated at the labial and lingual incisor edges, cervical ridge, and the area around root apex. When the damping ratios of the incisor model were set at 10- and 50-fold of the measured values, the peak stresses induced near the impact site of the incisor model were reduced from 24.0 to 23.2 and 15.9 MPa, respectively. On the other hand, the peak stress lagged and the stress existence period increased when the damping properties were taken into consideration. CONCLUSIONS: Damping properties of teeth provide protection to the tooth during traumatic injury by decreasing the peak stress magnitude due to release of strain energy over a longer period.

Bariatric versus diabetes surgery after five years of follow up.

BACKGROUND: Bariatric surgery (BS) is totally different from diabetes surgery (DS) in the patient characters, goals of surgery, and management although similar in surgical procedure. Comparison of BS and DS with long-term data is lacking. MATERIALS AND METHODS: A retrospective review of patients who received BS and patients who received DS at Min-Sheng General Hospital from 2007 to 2013 was designed. All inpatient and outpatient follow-up data were analyzed. Patients undergoing BS for the treatment of morbid obesity were compared with patients undergoing metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM). Patients who received revision surgeries were excluded. The main outcome measures were: (1) operation risk; (2) weight loss; and (3) diabetes remission. RESULTS: Between 2007 and 2013, 2073 patients who received BS and 741 patients who received DS were recruited from both centers. DS patients were older (41.1 ± 10.9 years vs. 33.1 ± 9.3 years, p < 0.05) and were more likely to be male (40.2% vs. 28.2%, p < 0.05) and to have diabetes (100% vs. 6.0%, p < 0.05), however, they had similar body mass index (BMI) (37.9 ± 8.0 vs. 38.5 ± 9.7, p = 0.78) compared to the BS patients. Surgical procedures are significantly different between the two groups (73.3% of the DS surgeries were gastric bypass procedure, whereas this procedure made up only 47.1% of BS surgeries). Although the major complication rates were similar (2.0% vs. 2.4%), the DS program had a significant higher mortality rate than the BS program (0.54% vs. 0.1%; p < 0.05). At the 5-year follow-up time point, 58.0% of the BS patients had achieved successful results (weight loss > 30%) and 80% of the DS patients had complete remission of their diabetes [hemoglobin A1c (HbA1c) < 6.0%]. Both the DS and the BS group had good results in up to 85% of the patients at the 5-year follow-up time point. CONCLUSION: The clinical profiles were very different between the BS and the DS programs. Both programs achieved the desired outcomes equally well, however, the DS program had a higher risk than the BS program.