BackgroundEndoscopy-assisted breast surgery (EABS) performed through minimal axillary and/or periareolar incisions is a possible alternative to open surgery for certain patients with breast cancer. In this study, we report the early results of an EABS program in Taiwan.MethodsThe medical records of patients who underwent EABS for breast cancer during the period May 2009 to December 2014 were collected from the Taiwan Endoscopic Breast Surgery Cooperative Group database. Data on clinicopathologic characteristics, type of surgery, method of breast reconstruction, complications and recurrence were analyzed to determine the effectiveness and oncologic safety of EABS in Taiwan.ResultsA total of 315 EABS procedures were performed in 292 patients with breast cancer, including 23 (7.8%) patients with bilateral disease. The number of breast cancer patients who underwent EABS increased initially from 2009 to 2012 and then stabilized during the period 2012–2014. The most commonly performed EABS was endoscopy-assisted total mastectomy (EATM) (85.4%) followed by endoscopy-assisted partial mastectomy (EAPM) (14.6%). Approximately 74% of the EATM procedures involved breast reconstruction, with the most common types of reconstruction being implant insertion and autologous pedicled TRAM flap surgery. During the six-year study period, there was an increasing trend in the performance of EABS for the management of breast cancer when total mastectomy was indicated. The positive surgical margin rate was 1.9%. Overall, the rate of complications associated with EABS was 15.2% and all were minor and wound-related. During a median follow-up of 26.8 (3.3–68.6) months, there were 3 (1%) cases of local recurrence, 1 (0.3%) case of distant metastasis and 1 (0.3%) death.ConclusionThe preliminary results from the EABS program in Taiwan show that EABS is a safe procedure and results in acceptable cosmetic outcome. These findings could help to promote this under-used surgical technique in the field of breast cancer.

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SUMMARYBackground: Neurofibrillary tangles formed from tau misfolding have long been considered one of the pathological hallmarks of Alzheimer's disease (AD). The misfolding of tau in AD correlates with the clinical progression of AD and inhibition or reversal of tau misfolding may protect the affected neurons. Methods: We generated 293 and SH-SY5Y cells expressing DsRed-tagged pro-aggregation mutant of repeat domain of tau (DK280 tau RD ) to test indole/indolylquinoline derivatives for reducing tau misfolding and neuroprotection. Results: Four of the 10 derivatives tested displayed good misfolding-inhibitory effects on Tet-On 293 cells. Among them, NC009-1 and NC009-7 enhanced heat-shock 27 kDa protein 1 (HSPB1) expression to increase ΔK280 tau RD -DsRed solubility and promoted neurite outgrowth in Tet-On SH-SY5Y cells. Knockdown of HSPB1 resulted in decreased ΔK280 tau RD -DsRed solubility and reduced neurite outgrowth, which were rescued by addition of NC009-1/NC009-7. Treatment with indole/indolylquinoline derivatives also improved neuronal cell viability and neurite outgrowth in mouse hippocampal primary culture under tau cytotoxicity. Conclusion: Our results demonstrate how indole/indolylquinoline derivatives are likely to work in tau misfolding reduction, providing insight into the possible working mechanism of indole and indolylquinoline derivatives in AD treatment.

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that Hydrogen Sulfide (H2S) may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H2S donor, in a triple transgenic AD mouse model (3×Tg-AD) under footshock with situational reminders (SRs). Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H2S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1) levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β) (pSer9) was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB) and noradrenergic neurons in the locus coeruleus (LC) were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca2+]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca2+]i. Here we show that fluoxetine significantly reduces glucose stimulated insulin secretion (GSIS). MIN6 cells, an established murine immortalized β cell line, form smaller colonies of loosely packed cells with reduced cell-cell contact after fluoxetine treatment. Immunofluorescence staining reveals that fluoxetine increases cytoplasmic accumulation of E-cadherin and reduces the membrane-localized E-cadherin probably due to increase of its endocytosis. Fluoxetine inhibits spreading of β cells on E-cad/Fc coated slides and also disrupts E-cadherin-mediated actin filaments. Additionally, fluoxetine significantly suppresses endoplasmic reticulum (ER) calcium release and store-operated calcium entry (SOCE) activation, probably through reduction of ER calcium storage and inhibition of stromal interaction molecule 1 (STIM1) trafficking. These data suggest that exposure to fluoxetine results in impaired β cell functions, occurring in concert with reduction of E-cadherin-dependent cell adhesion and alterations of calcium homeostasis.