Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Background: Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased. Cardiovascular events can occur during cancer treatment. This observational study aimed to report the incidence of major adverse cardiovascular events (MACE) after cancer treatment using real-world data. Objectives: Patients diagnosed with advanced-stage lung cancer between January 2011 and December 2017 were enrolled. Data were collected from the Chang Gung Research Database (CGRD). Design: Retrospective cohort study. Methods: Baseline characteristics, clinical stages, pathologies, and outcomes were retrieved from the CGRD. Results: We identified 4406 patients with advanced lung cancer, of whom 2197 received first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and 2209 received first-line platinum-based chemotherapy. Most patients in the first-line EGFR-TKI group were never-smokers (74.9%), whereas those in the first-line chemotherapy group were ever-smokers (66.0%). The incidence of MACE was not significantly different between the two groups (12.0% versus 11.9%, p = 0.910). However, the incidence of ischemic stroke was higher in the first-line EGFR-TKI group than in the first-line chemotherapy group (3.9% versus 1.9%, p < 0.001). Conclusion: MACEs are common in patients with advanced-stage lung cancer during treatment. The incidence of MACE was similar between the first-line EGFR-TKI therapy and first-line chemotherapy groups. Although more patients in the EGFR-TKI group were female and never-smokers, the risk of ischemic stroke was higher in patients who received first-line EGFR-TKI therapy than in those who received first-line chemotherapy.

Association of Nilotinib With Cardiovascular Diseases in Patients With Chronic Myelogenous Leukemia: A National Population-Based Cohort Study.

BACKGROUND: Tyrosine kinase inhibitor (TKI) treatment has been identified to be a risk factor for metabolic syndrome and cardiovascular diseases (CVDs) in patients diagnosed with chronic myeloid leukemia (CML). However, the specific contribution of post-TKI metabolic syndrome and the individual TKIs, including imatinib, nilotinib, and dasatinib, contribute to the development of CVDs remains unclear. METHODS: We conducted a nationwide database to investigate the incidence of post-TKI metabolic syndrome, including diabetes, hyperlipidemia, and hypertension, as well as their association with CVDs. To compare the risk of post-TKI comorbidities and CVDs among TKIs, we utilized the incidence rate ratio (IRR), and subdistribution hazard ratio (SHR) calculated from multiple Fine-Gray models. RESULTS: A total of 1211 patients without diabetes, 1235 patients without hyperlipidemia, and 1074 patients without hypertension were enrolled in the study. The incidence rate of post-TKI diabetes and hyperlipidemia was the highest in patients treated with nilotinib compared to imatinib and dasatinib (IRRs ≥ 3.15, Ps ≤ .047). After adjusting for confounders, nilotinib remained a significant risk factor for post-TKI diabetes and hyperlipidemia at an SHR of 3.83 (P < .001) and 5.15 (P < .001), respectively. Regarding the occurrence of CVDs, patients treated with nilotinib were more likely to develop CVDs than those treated with imatinib in non-hyperlipidemic group (IRR = 3.21, P = .020). Pre-existing and post-TKI hyperlipidemia were found to have a stronger association with CVDs, with SHR values of 5.81 (P = .034) and 13.21 (P = .001), respectively. CONCLUSION: The findings of this study indicate that nilotinib treatment is associated with increased risks of diabetes and hyperlipidemia, with hyperlipidemia being the most significant risk for CVDs. Therefore, we recommend that CML patients receiving nilotinib should undergo screening for diabetes and hyperlipidemia prior to initiating TKI treatment. Additionally, regular monitoring of lipid profiles during TKI therapy and implementing effective management strategies to control hyperlipidemia are crucial.

Real-world patient characteristics and treatment patterns of polycythemia vera in Taiwan between 2016 and 2017: a nationwide cross-sectional study.

Background: Polycythemia vera (PV) patients often experience constitutional symptoms and are at risk of thromboembolism as well as disease progression to myelofibrosis or acute myeloid leukemia. Not only is PV often overlooked but treatment options are also limited, however. Objectives: To explore the patient characteristics and treatment pattern of PV patients in Taiwan, and compare with other countries reported in the literature. Design: This is a nationwide cross-sectional study. Methods: The National Health Insurance Research Database in Taiwan, which covers 99% of the population, was utilized. Patients were identified during the cross-sectional period between 2016 and 2017, and their retrospective data were retrieved from 2001 to 2017. Results: A total of 2647 PV patients were identified between 1 January 2016 and 31 December 2017. This study described the demographic information of these patients, including number of patients by risk stratification and by sex, age at diagnosis, age at cross-sectional period, rate of bone marrow aspiration/biopsy at diagnosis, comorbidities, number of postdiagnosis thrombosis, number of disease progression, and death. The mortality rate of PV patients (4.1%) over 60 of age was higher than the general population of the same age group (2.8%). This study also compared the different treatment patterns between sexes and risk groups. Hydroxyurea was deferred to an older age, but conversely was prescribed at higher dose to younger patients. Alarmingly, a high proportion of patients did not receive phlebotomy or hydroxyurea for at least 2 years. Furthermore, discrepancies in prevalence, age at diagnosis, sex ratio, incidence of thrombosis and mortality were also found when compared with data reported in other countries. Conclusion: The clinical landscape of PV in Taiwan between 2016 and 2017 was examined. Distinctive patterns of phlebotomy and hydroxyurea were identified. Overall, these findings highlight the importance of understanding the patient characteristics and treatment patterns of PV in different regions to better inform clinical practice and improve patient outcomes.

Suramin ameliorates osteoarthritis by acting on the Nrf2/HO-1 and NF-κB signaling pathways in chondrocytes and promoting M2 polarization in macrophages.

Osteoarthritis (OA)-the most prevalent of arthritis diseases-is a complicated pathogenesis caused by cartilage degeneration and synovial inflammation. Suramin has been reported to enhance chondrogenic differentiation. However, the therapeutic effect of suramin on OA-induced cartilage destruction has remained unclear. Suramin is an anti-parasitic drug that has potent anti-purinergic properties. This study investigated the protective effects and underlying mechanisms of suramin on articular cartilage degradation using an in vitro study and mice model with post-traumatic OA. We found that suramin markedly suppressed the IL-1ß increased expression of matrix destruction proteases-such as ADAMT4, ADAMTS5, MMP3, MMP13, and inflammatory mediators-including the iNOS, COX2, TNFα, and IL-1ß; while greatly enhancing the synthesis of cartilage anabolic factors-such as COL2A1, Aggrecan and SOX9 in IL-1ß-induced porcine chondrocytes. In vivo experiments showed that intra-articular injection of suramin ameliorated cartilage degeneration and inhibited synovial inflammation in an anterior cruciate ligament transection (ACLT)-induced OA mouse model. In mechanistic studies, we found that exogenous supplementation of suramin can activate Nrf2, and accordingly inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and mitogen-activated protein kinase (MAPK) pathways, thereby alleviating the inflammation and ECM degeneration of chondrocytes stimulated by IL-1ß. In addition, suramin also repolarized M1 macrophages to the M2 phenotype, further reducing the apoptosis of chondrocytes. Collectively, the results of the study suggests that suramin is a potential drugs which could serve as a facilitating drug for the application of OA therapy toward clinical treatment.

Inference for the dimension of a regression relationship using pseudo-covariates.

In data analysis using dimension reduction methods, the main goal is to summarize how the response is related to the covariates through a few linear combinations. One key issue is to determine the number of independent, relevant covariate combinations, which is the dimension of the sufficient dimension reduction (SDR) subspace. In this work, we propose an easily-applied approach to conduct inference for the dimension of the SDR subspace, based on augmentation of the covariate set with simulated pseudo-covariates. Applying the partitioning principal to the possible dimensions, we use rigorous sequential testing to select the dimensionality, by comparing the strength of the signal arising from the actual covariates to that appearing to arise from the pseudo-covariates. We show that under a "uniform direction" condition, our approach can be used in conjunction with several popular SDR methods, including sliced inverse regression. In these settings, the test statistic asymptotically follows a beta distribution and therefore is easily calibrated. Moreover, the family-wise type I error rate of our sequential testing is rigorously controlled. Simulation studies and an analysis of newborn anthropometric data demonstrate the robustness of the proposed approach, and indicate that the power is comparable to or greater than the alternatives.

Non-missile penetrating brain injury-surgical techniques for removing a long penetrating foreign body: a case report.

PURPOSE: Penetrating brain injury (PBI), a relatively uncommon injury, is associated with remarkable secondary complications such as vascular injury, intracranial haemorrhage, infection, and mortality. Non-missile PBI (NMPBI) due to sharp or blunt objects is usually treated surgically by removing the penetrating object, evacuating the associated haemorrhage, identifying possible bleeders along with haemostasis, and performing debridement. Various approaches are used for different scenarios of non-missile PBI according to the object's characteristics, penetrating site, depth, associated intracerebral haemorrhage (ICH), and presence of vascular injury along the penetrating tract. NMPBI cases are rarely reported among civilians. We herein describe a patient who was successfully treated for NMPBI, as well as frontal ICH, by simultaneously removing the heavy, metallic penetrating foreign body. METHODS: We performed corticotomy through a shorter tract instead of a deep penetrating trajectory, which minimizes the extent of damage to the brain and enables immediate management of vascular injury under direct vision while removing the foreign body, and intraoperative sonography, which provides real-time information of the penetrating object and the surrounding brain structure. We did not perform computed tomography angiography and digital subtraction angiography (DSA) because the stab location was at the frontal region, with low risk of vascular injury. Moreover, DSA is time-consuming, which may delay decompressive surgery. RESULTS: The patient was successfully treated through an alternative approach removing the long, heavy, metallic penetrating foreign body and eliminating the accompanying frontal ICH simultaneously. Focal brain abscess developed 8 days after the injury and resolved completely after antibiotics treatment. Dysphasia gradually improved but right distal limbs weakness with spasticity is still present. CONCLUSIONS: Our findings suggest prompt diagnosis by preoperative imaging, screening of vascular injury, decompression with debridement, and antibiotics treatment are important. The alternative surgical approach we proposed is exceptional and should be considered while treating patients with deep NMPBI.

Arthroscopic Partial Trapeziectomy for Thumb Carpometacarpal Joint Osteoarthritis: 5-Year Follow-up.

Osteoarthritis of the thumb carpometacarpal (CMC) joint is the most common type of arthritis of the hand. The goal of the study was to evaluate clinical results and radiographic changes after arthroscopic partial trapeziectomy combined with ligament shrinkage and K-wire fixation to treat thumb CMC joint arthritis. From February 2013 to March 2014, 24 patients with thumb CMC joint arthritis received this arthroscopic procedure. We investigated the preoperative and postoperative Modified Mayo Wrist Score (MMWS); Disabilities of the Arm, Shoulder and Hand (DASH) score; radiographic changes; and associated complications. Sixteen patients completed 5 years of functional score and radiographic follow-up. Comparison of preoperative and postoperative MMWS and DASH scores showed significant improvement after the arthroscopic procedure. Pre-operative and postoperative evaluation of radiographic changes showed significant differences in the CMC joint distance, scaphoid-metacarpal distance, trapezium-metacarpal distance, and metacarpal prominence distance. This arthroscopic procedure is an effective and less invasive method for the treatment of CMC joint arthritis. This procedure can improve clinical function, preserve the mechanical height of the trapezium, and increase CMC joint space. We report our surgical technique and some pitfalls that required attention during the arthroscopic procedure. [Orthopedics. 2022;45(3):e140-e147.].

Different impacts of common risk factors associated with thrombocytopenia in patients with hepatitis B virus and hepatitis C virus infection.

BACKGROUND: Thrombocytopenia is a common extrahepatic manifestation in chronic liver disease. However, there have been rare studies of impacts of risk for hepatitis C virus-associated thrombocytopenia (HCV-TP) and hepatitis B virus-associated thrombocytopenia (HBV-TP). The aim of this study is to evaluate different impacts of risk factors for HCV-TP and HBV-TP. METHODS: We retrospectively collected 1803 HCV patients and 1652 HBV patients to examine the risk factors for time to moderate and severe thrombocytopenia (platelet counts <100 × 109/L and <50 × 109/L, respectively) by Cox proportional hazards models. Moreover, we prospectively enrolled 63 HCV-TP patients, 11 HBV-TP patients, and 27 HCV controls to detect specific antiplatelet antibodies by enzyme-linked immunosorbent assay and analyze their effects. RESULTS: Prevalence of platelet <100 × 109/L was 11.86% and 6.35% in HCV and HBV patients without cancer history, respectively. HCV-to-HBV incidence rate ratio for thrombocytopenia was 6.95. Initial thrombocytopenia was the most significant risk factor for HCV-TP and HBV-TP regardless of thrombocytopenia severity. Splenomegaly and cirrhosis were significant risk factors for moderate, but not severe HCV-TP. Hyperbilirubinemia was an important moderate and severe HBV-TP risk factor. Antiplatelet antibodies were correlated with HCV-TP severity, of which anti-glycoprotein IIb/IIIa antibody being associated with smaller spleen size. The antiplatelet autoantibody might contribute to thrombocytopenia either independently or with splenomegaly as the important risk in HCV-TP patients without advanced cirrhosis. CONCLUSION: HCV was associated with higher thrombocytopenia incidence than HBV. Thrombocytopenia risk factors varied with virus type and severity. Different management for HCV-TP and HBV-TP was suggested.

First report of an adult female patient with endobronchial inflammatory myofibroblastic tumor in Taiwan: A case report.

An inflammatory myofibroblastic tumor (IMT) of the respiratory system is an uncommon disease. In Taiwan, there is a lack of previous studies on tracheobronchial IMT. The tumor is characterized by overexpression of anaplastic lymphoma receptor tyrosine kinase (ALK)-1. Surgical resection is the standard treatment of choice nowadays.

Hemoglobin A1c Levels Associated with Age and Gender in Taiwanese Adults without Prior Diagnosis with Diabetes.

Several studies have reported that Hemoglobin A1c (HbA1c) levels increase with age for people without diabetes. However, HbA1c levels associated with age and gender have not been well investigated for Taiwanese adults. The objective of this study was to investigate the sex-specific association between HbA1c levels and age for Taiwanese adults without diabetes. The data were collected from the Taiwan Biobank database with inclusive criteria being participants without diabetes. The association between HbA1c values and age was conducted by linear regression analysis, HbA1c values between sexes were compared by two-sample t-test, and HbA1c levels among age groups were compared using one-way ANOVA. The results showed that HbA1c levels were positively correlated with age, and the levels for males were significantly higher than for females among all participants. However, there was no significantly positive correlation between HbA1c levels and age in males for age group of 50-70 years. The levels of males were significantly higher than females for age groups of 30-39 and 40-49 years. There were significant differences in HbA1c levels among age groups for all participants, males, and females except for the two age groups of 50-59 and 60-70 years in males. Age and gender were important factors affecting HbA1c levels. Our results suggested that the HbA1c cut-point levels for the diagnosis of diabetes should vary by age and gender.

Intra-Articular Injection of (-)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis.

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Resection of swollen temporal muscles in patients with intractable intracranial hypertension after decompressive craniectomy.

BACKGROUND: Decompressive craniectomy is employed as treatment for traumatic brain swelling in selected patients. We discussed the effect of temporal muscle resection in patients with intractable intracranial hypertension and temporal muscle swelling after craniectomy. METHODS: Records of 280 craniectomies performed on 258 patients who were admitted with severe head injury were retrospectively reviewed. Eight patients developed intractable increased intracranial pressure with temporal muscle swelling within 24 h after craniectomy and were treated by muscle resection. RESULTS: The initial Glasgow Coma Scale score was 7 ± 1. The mean intracranial pressure was 41.7 ± 8.59 mmHg before muscle resection and 14.81 ± 8.07 mmHg immediately after surgery. Five patients had skull fracture and epidural hematoma at the craniectomy site. The mean intensive care unit stay was 11.25 ± 5.99 days. Glasgow Outcome Scale-Extended scoring performed during the 12-month follow-up visit showed that 6 patients (75%) had a favorable outcome. CONCLUSIONS: Our study findings indicate that a direct impact on the temporal region during trauma may lead to subsequent temporal muscle swelling. Under certain circumstances, muscle resection can effectively control intracranial pressure.

A Miniature Intermittent-Flow Respirometry System with a 3D-Printed, Palm-Sized Zebrafish Treadmill for Measuring Rest and Activity Metabolic Rates.

Zebrafish are a preferred vertebrate model for evaluating metabolism during development, and for toxicity studies. However, commercially available intermittent-flow respirometry systems (IFRS) do not provide a suitable zebrafish-scaled swimming tunnel with a low water volume and proper flow velocities. We developed a miniature IFRS (mIFRS) with a 3D-printed, palm-sized zebrafish treadmill for measuring the swimming ability and metabolic rate of a single one- or three-month-old zebrafish with and without toxicity treatment. The 3D-printed zebrafish treadmill consists of discrete components assembled together which enables the provision of a temporary closed circulating water flow. The results showed that three-month-old zebrafish of normal physiological status had higher energetic efficiency and could swim at a higher critical swimming speed (Ucrit) of 16.79 cm/s with a lower cost of transport (COTopt) of 0.11 µmol g-1m-1. However, for a single three-month-old zebrafish treated with an antibacterial agent, Ucrit decreased to 45% of normal zebrafish and the COTopt increased to 0.24 µmol g-1m-1, due to the impairment of mitochondria. Our mIFRS provides a low-cost, portable, and readily adaptable tool for studying the swimming performance and energetic metabolism of zebrafish.

Front-line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control.

BACKGROUND: Approximately 3%-5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum-based chemotherapy as front-line treatment for patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the direct comparison between them in the front-line setting remains lacking. METHODS: A total of 48 patients with ALK-positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front-line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed. RESULTS: Patients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression-free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log-rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08-0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause-specific hazard ratio, 0.21; 95% CI 0.06-0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment. CONCLUSION: Ceritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front-line treatment of ALK-positive advanced NSCLCs.

Biomechanical behavior of cavity design on teeth restored using ceramic inlays: An approach based on three-dimensional finite element analysis and ultrahigh-speed camera.

Ceramic fracture and debonding are the primary failures that follow ceramic inlay and can lead to stress and tooth fracture. In this study, we examined two designs-concave and flat-of the gingival cavity bottom for tooth cavities restored using ceramic inlays. We investigated the biomechanical behavior of ceramic inlay-restored teeth (concave and flat) through three-dimensional finite element analysis (FEA) and experimentally validated the results using an ultrahigh-speed camera. We conducted in vitro real-time recording of the deformation of a restored tooth during loading using an ultrahigh-speed camera. This technique enables further image registration to observe deformation variation and vector fields. The deformation vector fields revealed that the concave design moved the deformation toward the buccal side of the cavity bottom, whereas the flat design moved it toward the palatal side. These findings correlated with the FEA results, which indicated that the concave design constrained stress in the dentin cavity and relieved palatal stress. Our results suggest that incorporating a concave design in cavity preparation can improve the fracture resistance of ceramic inlay-restored teeth, preventing unrestorable fractures. The current study is the first to utilize an ultrahigh-speed camera in dental biomechanics, and such cameras are useful for nondestructive and dynamic analysis. STATEMENT OF SIGNIFICANCE: First utilize ultrahigh-speed cameras in dental biomechanics analysis. Tooth fracture videos captured by ultrahigh-speed camera helps us learn fracture mechanics in between tooth cavity design and ceramic inlay. Concave design leads to stress in safer areas that causes a less damaging fracture. Minimal invasive preparation by concave design strengthens tooth fracture resistance. Non-destructive data from ultrahigh-speed cameras combined with FEA can get more insight into how the stress and strain derived in biomaterials.

Bioenergetic Health Assessment of a Single Caenorhabditis elegans from Postembryonic Development to Aging Stages via Monitoring Changes in the Oxygen Consumption Rate within a Microfluidic Device.

Monitoring dynamic changes in oxygen consumption rates (OCR) of a living organism in real time provide an indirect method of monitoring changes in mitochondrial function during development, aging, or malfunctioning processes. In this study, we developed a microfluidic device integrated with an optical detection system to measure the OCR of a single developing Caenorhabditis elegans (C. elegans) from postembryonic development to aging stages in real time via phase-based phosphorescence lifetime measurement. The device consists of two components: an acrylic microwell deposited with an oxygen-sensitive luminescent layer for oxygen (O2) measurement and a microfluidic module with a pneumatically driven acrylic lid to controllably seal the microwell. We successfully measured the basal respiration (basal OCR, in pmol O2/min/worm) of a single C. elegans inside a microwell from the stages of postembryonic development (larval stages) through adulthood to aged adult. Sequentially adding metabolic inhibitors to block bioenergetic pathways allowed us to measure the metabolic profiles of a single C. elegans at key growth and aging stages, determining the following fundamental parameters: basal OCR, adenosine triphosphate (ATP)-linked OCR, maximal OCR, reserve respiratory capacity, OCR due to proton leak, and non-mitochondrial OCR. The bioenergetic health index (BHI) was calculated from these fundamental parameters to assess the bioenergetic health of a single developing C. elegans from the postembryonic development to aging stages. The changes in BHI are correlated to C. elegans development stage, with the highest BHI = 27.5 for 4-day-old adults, which possess well-developed bioenergetic functionality. Our proposed platform demonstrates for the first time the feasibility of assessing the BHI of a single C. elegans from postembryonic development to aging stages inside a microfluidic device and provides the potential for a wide variety of biomedical applications that relate mitochondrial malfunction and diseases.

The bidirectional association among female hormone-related cancers: breast, ovary, and uterine corpus.

Breast, ovarian, and uterine corpus cancers are common female cancers and categorized as hormone-related diseases. Previous studies reported a unidirectional relationship for each cancer, but few studied the reciprocal association in the same cohort. A population-based study was carried out in Taiwan to test the hypothesis that there are pairwise bidirectional associations among these cancers. Using the same cohort of 110,112 cases with primary female cancers including uterine corpus cancer (11,146 cases), ovarian cancer (12,139 cases), or breast cancer (86,827 cases) from the Taiwan Cancer Registry from 1979 to 2008, the pairwise risks of second cancer among uterine corpus, ovary, and breast cancer cases were evaluated by standardized incidence ratios (SIRs) and the corresponding 95% confidence intervals (CIs) to quantify the excess of second malignancies. A reciprocal relationship was found for these three female cancers, particularly most prominent between uterine and ovarian cancers, followed by breast and uterine cancers as well as breast and ovarian cancers. The overall risk of second cancers was highest within the first 5 years after the diagnosis of primary cancer. The bidirectional relationships suggest common risk factors among these three female cancers. This is the largest cohort study to focus on the bidirectional associations among hormone-related cancers in Asian women, and these results could aid in the development of early prevention strategies and follow-up surveillance programs.

Optimal group testing designs for estimating prevalence with uncertain testing errors.

We construct optimal designs for group testing experiments where the goal is to estimate the prevalence of a trait using a test with uncertain sensitivity and specificity. Using optimal design theory for approximate designs, we show that the most efficient design for simultaneously estimating the prevalence, sensitivity, and specificity requires three different group sizes with equal frequencies. However, if estimating prevalence as accurately as possible is the only focus, the optimal strategy is to have three group sizes with unequal frequencies. Based on a Chlamydia study in the United States, we compare performances of competing designs and provide insights into how the unknown sensitivity and specificity of the test affect the performance of the prevalence estimator. We demonstrate that the proposed locally D- and Ds -optimal designs have high efficiencies even when the prespecified values of the parameters are moderately misspecified.

Capnography monitoring the hypoventilation during the induction of bronchoscopic sedation: A randomized controlled trial.

We hypothesize that capnography could detect hypoventilation during induction of bronchoscopic sedation and starting bronchoscopy following hypoventilation, may decrease hypoxemia. Patients were randomized to: starting bronchoscopy when hypoventilation (hypopnea, two successive breaths of at least 50% reduction of the peak wave compared to baseline or apnea, no wave for 10 seconds) (Study group, n = 55), or when the Observer Assessment of Alertness and Sedation scale (OAAS) was less than 4 (Control group, n = 59). Propofol infusion was titrated to maintain stable vital signs and sedative levels. The hypoventilation during induction in the control group and the sedative outcome were recorded. The patient characteristics and procedures performed were similar. Hypoventilation was observed in 74.6% of the patients before achieving OAAS < 4 in the control group. Apnea occurred more than hypopnea (p < 0.0001). Hypoventilation preceded OAAS < 4 by 96.5 ± 88.1 seconds. In the study group, the induction time was shorter (p = 0.03) and subjects with any two events of hypoxemia during sedation, maintenance or recovery were less than the control group (1.8 vs. 18.6%, p < 0.01). Patient tolerance, wakefulness during sedation, and cooperation were similar in both groups. Significant hypoventilation occurred during the induction and start bronchoscopy following hypoventilation may decrease hypoxemia without compromising patient tolerance.