In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA A receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E GABA ) in MNCs. This E GABA shift was associated with increased expression of NaϪ cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA A receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl Ϫ gradients.

No abstract

BackgroundWe evaluated the outcomes of patients with papillary thyroid carcinoma (PTC) who underwent transoral robotic thyroidectomy (TORT).MethodsWe retrospectively analyzed the perioperative outcomes of 200 patients (170 women and 30 men) with PTC who underwent TORT at a single center between March 2016 and February 2018.ResultsThere were 182 and 13 cases of lobectomy and total thyroidectomy, respectively, with corresponding mean operative times of 200.6 ± 31.2 and 265.7 ± 63.0 minutes. On average, 5.6 ± 3.45 lymph nodes were retrieved per patient. There were 12 cases of perioperative morbidity. No conversion to endoscopic or conventional open surgery was noted. In a subgroup analysis for predictors of difficult TORT, patient sex was the only factor showing a significant operative time difference between a difficult and a nondifficult thyroidectomy.ConclusionTORT can be performed safely in patients with PTC without serious complications.

PurposeAn oxaliplatin-based regimen is the most common adjuvant chemotherapy for patients with stage II/III colorectal cancer, but many patients experience dose reduction or early termination of chemotherapy due to side effects. We conducted this study to verify the range of reduction with oncologic safety.MethodsPatients with stage II/III colorectal cancer who received adjuvant FOLFOX chemotherapy were enrolled in this study. The total amount of oxaliplatin administered per patient was calculated as a percentile based on 12 cycles of full-dose FOLFOX as a standard dose. The cutoff values showing significant differences in survival were calculated, and the clinicopathologic outcomes of patient groups classified by the value were compared.ResultsAmong a total of 611 patients, there were 107 stage II patients, and 504 stage III patients. At 60% of the standard dose of oxaliplatin, the patients in the dose reduction group were older (62 years vs. 58 years, P = 0.003), had lower body mass index (BMI) (23.1 kg/m2 vs. 24.0 kg/m2, P = 0.005), and were more exposed to neoadjuvant treatment (18.0% vs. 9.1%, P = 0.003) in comparison to the standard group. At 60% of the standard dose, there were no significant differences in 5-year disease-free survival (DFS) and overall survival (OS) between the 2 groups (5-year DFS: 73.5% vs. 74.2%, P = 0.519; 5-year OS: 71.9% vs. 81.5%, P = 0.256, respectively).ConclusionPatients with old age, low BMI, and more frequent exposure to neoadjuvant treatment tended to show lower compliance with chemotherapy. More than 60% dose should be administered to patients with stage II/III colorectal cancer as adjuvant chemotherapy to achieve acceptable oncologic outcomes.

Objectives/Hypothesis: Obesity is an increasing health concern worldwide. It has been associated with perioperative complications that could affect patient outcomes. Our aim was to compare surgical outcomes in obese and nonobese patients after transoral robotic thyroid (TORT) surgery.Study Design: Retrospective cohort study.Methods: A total of 304 consecutive patients who underwent TORT between January 2012 to December 2017 were included in the study. Patients were divided into two groups according to their body mass index (BMI): BMI < 30 kg/m 2 and BMI ≥ 30 kg/m 2 . Patient demographics, operative extent, pathological data, surgical outcomes, and postoperative complications were included and analyzed. A χ 2 test was used to compare categorical variables, and a Student t test was used to compare changes of continuous variables between groups. Statistical significance was conferred by a two-tailed P value of ≤.05.Results: There were 290 patients in the non-obese group and 14 patients in the obese group. There was no statistically significant difference between the two groups in terms of patient demographics, operative procedure, or pathological characteristics. The only statistically significant difference was for lymph node dissection (P = .012); however, for both groups, unilateral central node dissection was the most common procedure. There was also no statistically significant difference found for operative time, length of stay, pain score, or postoperative complications including TORT-specific complications such as oral commissure tear and general complications such as recurrent nerve injury.Conclusions: This initial experience shows that TORT appears to be a safe and feasible option for obese patients pursuing scarless thyroid surgery.

Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein ( 1 ), a major component of Scutellaria baicalensis , was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a , a biphenyl flavanone analog, as a novel human TSLP inhibitor for the discovery and development of new anti-allergic drugs.

Background Transoral vestibular approach endoscopic thyroidectomy has gained popularity worldwide because it avoids a cutaneous incision. Some surgeons have expressed reservations about operating with only 2 instruments in the endoscopic technique, and some therefore utilize an axillary incision as an adjunct to facilitate dissection. The Intuitive da Vinci single port robotic system offers the potential to overcome this limitation without an axillary incision. Methods In this study, the Intuitive da Vinci single port robotic surgical system was used to perform transoral thyroidectomy on 2 human cadavers. Results A total thyroidectomy was performed in 2 cadavers using the da Vinci single port (SP) robot via transoral vestibular technique. The dissections were performed with removal of the thyroid gland and preservation of the recurrent laryngeal nerves and parathyroid glands. Conclusion In our evaluation, transoral vestibular approach robotic thyroidectomy using the Intuitive da Vinci SP system facilitated dissection without the need for an axillary incision.

Emerging flexible optoelectronics requires a new type of protective material that is not only hard but also flexible. Organic–inorganic (O–I) hybrid materials have been used as a flexible cover window to increase wear resistance and polymer‐like flexibility. However, the hardness of O–I hybrid materials is much lower than that of metals and ceramics due to the low intrinsic hardness of the organic matrix and limited volume fraction of inorganic reinforcement. Herein, a new type of hybrid nanocomposite combining an O–I hybrid material with continuous and ordered 3D inorganic nanoshell as an additional reinforcement is proposed. The 3D alumina nanoshell uniformly embedded in the epoxy‐siloxane molecular hybrid (ESMH) enables a rule of mixture without a loss in flexibility. Two types of reinforcements comprising siloxane molecules and 3D alumina shell ensure a metal‐like hardness (1.3 GPa), which is significantly higher than that of the typical polymers and polymer nanocomposites. The 3D hybrid nanocomposite films show superb impact resistance due to the 3D alumina nanoshell that effectively suppresses crack propagation. Inch‐scale 3D hybrid nanocomposite films also endure 20 000 bending cycles without failure and maintain high transparency (>82.0% at 550 nm) in the visible regions.