Interactions between Amyloid-β and Hemoglobin: Implications for Amyloid Plaque Formation in Alzheimer's Disease

Accumulation of amyloid-β (Aβ) peptides in the brain is one of the central pathogenic events in Alzheimer's disease (AD). However, why and how Aβ aggregates within the brain of AD patients remains elusive. Previously, we demonstrated hemoglobin (Hb) binds to Aβ and co-localizes with the plaque and vascular amyloid deposits in post-mortem AD brains. In this study, we further characterize the interactions between Hb and Aβ in vitro and in vivo and report the following observations: 1) the binding of Hb to Aβ required iron-containing heme; 2) other heme-containing proteins, such as myoglobin and cytochrome C, also bound to Aβ; 3) hemin-induced cytotoxicity was reduced in neuroblastoma cells by low levels of Aβ; 4) Hb was detected in neurons and glial cells of post-mortem AD brains and was up-regulated in aging and APP/PS1 transgenic mice; 5) microinjection of human Hb into the dorsal hippocampi of the APP/PS1 transgenic mice induced the formation of an envelope-like structure composed of Aβ surrounding the Hb droplets. Our results reveal an enhanced endogenous expression of Hb in aging brain cells, probably serving as a compensatory mechanism against hypoxia. In addition, Aβ binds to Hb and other hemoproteins via the iron-containing heme moiety, thereby reducing Hb/heme/iron-induced cytotoxicity. As some of the brain Hb could be derived from the peripheral circulation due to a compromised blood-brain barrier frequently observed in aged and AD brains, our work also suggests the genesis of some plaques may be a consequence of sustained amyloid accretion at sites of vascular injury

Treatment selection for tonsillar squamous cell carcinoma

AbstractBackgroundThe optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection.MethodsWe conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group.ResultsNo significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3–4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3–4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745).ConclusionBoth primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I–II diseases. Although RT/CRT organ preservation is used more frequently for stage III–IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated

Low-Cost and Easily Fabricated Ultrasound-Guided Breast Phantom for Breast Biopsy Training

We aimed to develop an inexpensive and easy-to-fabricate gelatin-based training phantom for improving the breast biopsy skill and confidence level of residents. Young’s modulus and acoustic properties of the gelatin tissue phantom and simulated tumors were investigated. Six residents were requested to evaluate the effectiveness of the breast phantom. The results showed that 83% (n = 5) of the participants agreed that the ultrasound image quality produced by the breast phantom was excellent or good. Only 17% (n = 1) of the participants claimed that there was room for improvement for the haptic feedback they received during the placement of the core needle into the breast phantom. The mean pre-instructional score was 17% (SD 17%) for all participants. The mean post-instructional score was 83% (SD 17%), giving an overall improvement of 67%. In conclusion, the mean needle biopsy skill and confidence levels of the participants substantially increased through simulation training on our breast phantom. The participants’ feedback showed the phantom is sufficiently realistic in terms of ultrasound imaging and haptic feedback during needle insertion; thus, the training outcome can be linked to the performance of residents when they perform a live biopsy

Long-Term Effectiveness of a Decision Support App (Pink Journey) for Women Considering Breast Reconstruction Surgery: Pilot Randomized Controlled Trial

BackgroundVarious kinds of breast reconstruction (BR) options, including implants and autologous, and surgery techniques, including traditional and endoscope assisted, can be used to perform surgery. All options have their own advantages and disadvantages. Women decide on an option depending on the values and preferences they emphasize. Lacking knowledge about BR or having decision difficulties during the treatment decision process makes women experience more decision regret, psychological distress, and poor body image. Delivering decision support with a values clarification exercise using eHealth approaches would be beneficial for patient outcomes. ObjectiveThis study aims to examine the effects of a decision support app on decision-making quality and psychological morbidity for women considering BR surgery. MethodsThis randomized controlled trial included women who were over 20 years of age and were newly diagnosed with breast cancer and candidates for mastectomy. Women having an option for breast conservation were excluded. After being referred from the outpatient physician, the women provided consent and completed the baseline assessment. Women allocated to the control group (CG) received usual care and were provided with a pamphlet with information about types of surgery and the advantages and disadvantages of different surgery types. Women allocated to the intervention group (IG) were given the same pamphlet and guided to use the Pink Journey app to support their decision. Then they were also prompted to discuss the opinions with their significant others. Finally, the decision-making process of using the app was printed out for women that they could take home. Decision conflict, anxiety, and depression were measured at baseline. At 1 week after the intervention (T1) and at 1 month (T2), 8 months (T3), and 12 months (T4) after surgery, the women completed decision conflict, decision regret, anxiety, depression, and body image scales. An intention-to-treat analysis was performed. ResultsFrom February 2018 to July 2019, 96 women were randomly assigned to the CG (n=48) or the IG (n=48). Results revealed that body image distress declined significantly for the IG but increased for the CG. The interaction of time and group also reached significance, indicating a significant decrease in body image distress from baseline in the IG compared with the CG after the 12th month (T4) follow-up (β=–2.25, standard error=1.01, P=.027). However, there was no significant difference in decision conflict (P=.21-.87), decision regret (P=.44-.55), anxiety (P=.26-.33), and depression (P=.20-.75), indicating that the decrease in these outcomes in the IG was not greater than those in the CG. ConclusionsAlthough we found no effect on decision conflict, decision regret, anxiety, and depression, a decision aid that combines surgery information and values clarification can help women reduce their body image distress. Trial RegistrationClinicalTrials.gov NCT04190992; https://clinicaltrials.gov/ct2/show/NCT0419099

Investigation of Geological Structures Using UAV Lidar and Its Effects on the Failure Mechanism of Deep-Seated Landslide in Lantai Area, Taiwan

The deep-seated landslide in the Lantai area, Taiwan, has a long history of landslide activity and often damages the sole access road to the Tai-Ping Mountain National Forest Recreation Area. This study adopted the high-resolution digital terrain model (DTMH) derived from UAV mounted LiDAR point cloud data for mapping geological structures and verified through field investigation. A slope model was proposed with mapped geological structures and shear zone, and numerical analysis was conducted using finite difference analysis. The failure mechanism was found to be significantly affected by the shear zone bounded by geological structures, which would not have been uncovered without the high-resolution DTM (DTMH). The resulting landslide behavior consisted well with mapped scarp, borehole data, and conformed with the event records. These results provided vital information supporting hazard mitigation strategy

A multiplex PCR assay for detection of Vibrio vulnificus, Aeromonas hydrophila, methicillin-resistant Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae from the isolates of patients with necrotizing fasciitis

Background: Vibrio vulnificus, Aeromonas hydrophila, methicillin-resistant Staphylococcus aureus (MRSA), group A Streptococcus, and group B Streptococcus are commonly detected causative agents of necrotizing fasciitis (NF) in Chia-Yi Chang Gung Memorial Hospital. The aim of this study was to develop and evaluate a multiplex PCR method for the simultaneous detection of five of the most important human pathogens involved in NF by using a novel combination of species-specific genes. Methods: The samples used were collected from 99 patients with surgically confirmed NF of the extremities who were hospitalized consecutively between June 2015 and November 2017. Two sets of blood and tissue samples were collected from all patients; one set was sent to a microbiology laboratory for bacterial identification and the other set was sent to an immunohistochemistry laboratory for PCR amplification. Results: The multiplex PCR results for the blood samples showed negative findings. The multiplex PCR results for the tissue specimens showed 28 positive findings. Fourteen (87.5%) of the 16 V. vulnificus culture-positive tissue specimens, six (75%) of the eight A. hydrophila culture-positive tissue specimens, and four (100%) of the four MRSA culture-positive tissue specimens were positive by PCR. Similarly, two (100%) of the group A Streptococcus and two (100%) of the group B Streptococcus were PCR-positive. Conclusions: The accuracy rate of the multiplex PCR presenting positive results in these culture-positive tissue samples was 87.5% (28/32). This suggests that multiplex PCR of tissue specimens may be a useful and rapid diagnostic tool for the detection of these lethal microorganisms in patients with NF. Keywords: Necrotizing fasciitis, Multiplex PCR, Diagnostics, Assa

Learning multiplication through computer-assisted learning activities

[[abstract]]This study develops and implements a computer-assisted learning (CAL) program with both multiplicative facts practices and the instruction of meaning behind these facts. The effectiveness of CAL on the development of multiplication abilities is also explored. Eight CAL activities are developed to teach multiplication to second grade elementary school students. The CAL program is comprised of three stages of instruction that addressed in succession the basic concept of multiplication, the meaning and properties of multiplication and multiplication-related computation skills. Evaluation of the effects of the learning activities reveals that CAL activities are effective in improving comprehension of the concept of multiplication and the meaning and properties of multiplication for students who have lower prior knowledge of multiplication, but it does not significantly improve the development of multiplication-related computation skills. Nevertheless, CAL activities facilitate overall learning of multiplication.