Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

Objective: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development

A Neural Pre-Conditioning Active Learning Algorithm to Reduce Label Complexity

Deep learning (DL) algorithms rely on massive amounts of labeled data. Semi-supervised learning (SSL) and active learning (AL) aim to reduce this label complexity by leveraging unlabeled data or carefully acquiring labels, respectively. In this work, we primarily focus on designing an AL algorithm but first argue for a change in how AL algorithms should be evaluated. Although unlabeled data is readily available in pool-based AL, AL algorithms are usually evaluated by measuring the increase in supervised learning (SL) performance at consecutive acquisition steps. Because this measures performance gains from both newly acquired instances and newly acquired labels, we propose to instead evaluate the label efficiency of AL algorithms by measuring the increase in SSL performance at consecutive acquisition steps. After surveying tools that can be used to this end, we propose our neural pre-conditioning (NPC) algorithm inspired by a Neural Tangent Kernel (NTK) analysis. Our algorithm incorporates the classifier's uncertainty on unlabeled data and penalizes redundant samples within candidate batches to efficiently acquire a diverse set of informative labels. Furthermore, we prove that NPC improves downstream training in the large-width regime in a manner previously observed to correlate with generalization. Comparisons with other AL algorithms show that a state-of-the-art SSL algorithm coupled with NPC can achieve high performance using very few labeled data.Comment: NeurIPS 202

Pneumatization Pattern of the Frontal Recess: Relationship of the Anterior-to-Posterior Length of Frontal Isthmus and/or Frontal Recess with the Volume of Agger Nasi Cell

ObjectivesWe analyzed the pneumatization pattern of the frontal recess (FR) in a Korean population. We also determined the correlation between the volume of the agger nasi cell (ANC) and the anterior-to-posterior (A-P) length of the frontal isthmus (FI) and FR.MethodsMultiplanar paranasal sinus computed tomography (CT) images from 105 patients who underwent endoscopic sinus surgery were reviewed. The prevalence of frontal recess cells (FRCs), thickness of the frontal beak (FB), volume of the ANC, A-P length of the FI, and FR were evaluated.ResultsThe ANC was identified in 96% of the patients and frontal cells (FCs) in 32% (FC type 1, 24.2%; type 2, 4.2%; type 3, 3.1%; and type 4, 0%). The prevalences of frontal bullar, suprabullar, supraorbital ethmoidal, and interfrontal sinus septal cells were 10%, 7.8%, 3.6%, and 6.8%, respectively. The A-P lengths of the FR and FI were 10.1±3.1 and 8.4±2.9 mm, respectively. The thickness of the FB was 7.8±1.8 mm and the volume of the ANC averaged 394.1±240.5 mm3. The thickness of the FB did not correlate with the volume of the ANC. In contrast, the A-P length of the FI and FR were positively correlated with the volume of the ANC.ConclusionANCs and FCs were found in 96% and 32% of the cases in this series. FC type 4 was not seen. What appeared to be FC4 on conventional CT was identified as FBC from reconstructed parasagittal images. A large ANC increased the A-P length of the FI and FR, regardless of the thickness of the FB

Efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia: study protocol for a randomized controlled trial (SALSA trial)

Abstract Background Hyponatremia is the most common electrolyte imbalance encountered in clinical practice, associated with increased mortality and length of hospital stay. However, no high-quality evidence regarding whether hypertonic saline is best administered as a continuous infusion or a bolus injection has been found to date. Therefore, in the current study, we will evaluate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia. Methods/design This is a prospective, investigator-initiated, multicenter, open-label, randomized controlled study with two experimental therapy groups. A total of 178 patients with severe symptomatic hyponatremia will be enrolled and randomly assigned to receive either rapid intermittent bolus or slow continuous infusion management with hypertonic saline. The primary outcome is the incidence of overcorrection at any given period over 2 days. The secondary outcomes will include the efficacy and safety of two other approaches to the treatment of hyponatremia with 3% hypertonic saline. Discussion This is the first clinical trial to investigate the efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe hyponatremia. Trial registration ClinicalTrials.gov, identifier number: NCT02887469 . Registered on 1 August 2016

Eccrine Angiomatous Hamartoma Mimicking a Traumatic Hemorrhage

Eccrine angiomatous hamartoma (EAH) is a rare benign disease that is characterized by an abnormal proliferation of eccrine glands and vascular elements. It is generally congenital, but it can appear before puberty. It usually presents as a single plaque or nodule, but multiple patch-like lesions are also possible. EAH is mostly asymptomatic, but it is sometimes associated with pain or hyperhidrosis. It generally does not require aggressive treatment, but the lesion can be excised due to pain, enlargement and cosmetic reasons. A 3-week-old Korean female presented with a hemorrhagic skin lesion on the right foot since birth. There was no specific birth history. The lesion first appeared on the third toe of the right foot and quickly spread to almost half of the right foot. Histopathology examination revealed acanthosis in the epidermis and a proliferation of eccrine ducts, glands and capillaries. The eccrine glands were immunohistochemically-positive for carcinoembryonic antigen

Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Catecholaminergic Polymorphic Ventricular Tachycardia in a Patient With Recurrent Exertional Syncope

A 16-year-old male with a prior history of recurrent syncope was referred to our hospital after being resuscitated from cardiac arrest developed while playing volleyball. His electrocardiogram (ECG) demonstrated ventricular fibrillation at a local emergency department. After referral, an ECG showed bidirectional ventricular tachycardia (VT) and nonsustained Torsade de Pointes. Two days later, his heart rate became regular, and no additional episodes of VT were observed. His ECG showed sinus rhythm with a corrected QT interval of 423 msec, and two-dimensional echocardiography was unremarkable. We made the diagnosis of a catecholaminergic polymorphic VT. However, only premature ventricular complex bigeminy was induced on exercise ECG and epinephrine infusion tests, and the patient showed no episodes of syncope. His father and mother had different missense mutations in the cardiac ryanodine receptor on genetic testing. The proband had both mutations in different alleles and was symptomatic. It was recommended that the patient avoid competitive physical activities, and a β-blocker was prescribed

Diagnostic Benefit of Thyroglobulin Measurement in Fine-Needle Aspiration for Diagnosing Metastatic Cervical Lymph Nodes from Papillary Thyroid Cancer: Correlations with US Features

Objective: Our goals were to determine the added value of fine-needle aspiration biopsy (FNAB)-thyroglobulin (Tg) measurements over FNAB-cytology alone for diagnosing metastatic nodes, and to determine whether the ultrasound features of lymph nodes can be used to identify lymph nodes that may benefit from FNAB-Tg measurement in patients with papillary thyroid cancer. Materials and Methods: We retrospectively evaluated 76 surgically proven cervical lymph nodes. Twenty-nine patients were awaiting surgery and 18 patients had undergone thyroid surgery for papillary thyroid cancer. Ultrasound-guided FNAB and Tg measurements were performed and the ultrasound features were evaluated. Results: The accuracies, sensitivities, and specificities of FNAB-cytology, FNAB-Tg, and combined FNAB-Tg/cytology were 90%, 80%, and 100%; 92%, 95%, and 90%; and 93%, 96%, and 90%, respectively. The diagnostic sensitivity of FNAB-Tg for metastatic nodes was significantly higher than that of FNAB-cytology (p = 0.011). Furthermore, combined FNAB-Tg/cytology significantly increased sensitivity (p = 0.002) and accuracy (p = 0.03) as compared with FNAB-cytology. Conclusion: Combined FNAB-Tg/cytology is significantly more sensitive and accurate at detecting metastatic nodes than FNAB-cytology alone. FNAB-Tg was better at diagnosing metastases in small lymph nodes

Effects of Thiazide on the Expression of TRPV5, Calbindin-D28K, and Sodium Transporters in Hypercalciuric Rats

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D28K, and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2. To quantitate the expression of TRPV5, calbindin-D28K, and sodium transporters, western blotting was performed. In both experiments, HCTZ significantly decreased urinary calcium excretion. TRPV5 protein abundance decreased in all hypercalciuric rats, and restored by HCTZ in both high salt with HCTZ and high Ca with HCTZ group. Calbindin-D28K protein abundance increased in the high salt and high salt with HCTZ groups, but did not differ among groups in experiment 2. Protein abundance of NHE3 and NKCC2 decreased in all hypercalciuric rats, and were restored by HCTZ in only high Ca-induced hypercalciuric rats. In summary, protein abundance of TRPV5, NHE3, and NKCC2 decreased in all hypercalciuric rats. The hypocalciuric effect of HCTZ is associated with increased protein abundance of TRPV5 in high salt or calcium diet-induced hypercalciuric rats