Opioidergic Regulation of Emotional Arousal: A Combined PET–fMRI Study

Abstract

Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify μ-opioid receptor and type 2 dopamine receptor (MOR and D₂R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D₂R availability—here reliably quantified only in striatum—was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.

https://ift.tt/2FyB3Kb

Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations

Abstract

Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.

https://ift.tt/2qY267v

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Abstract

Guselkumab (Tremfya^®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.

https://ift.tt/2OUYhJO

Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective

Abstract

Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.

https://ift.tt/2FyGhW4

Thyroid® High-Impact Articles

FREE ACCESS through December 5, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association^®

Read now:

Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration
Petter Strømme, Stefan Groeneweg, Elaine C. Lima de Souza, Chantal Zevenbergen, Anette Torgersbråten, Asbjørn Holmgren, Ebrar Gurcan, Marcel E. Meima, Robin P. Peeters, W. Edward Visser, Linda Høneren Johansson, Almira Babovic, Henrik Zetterberg, Heike Heuer, Eirik Frengen, Doriana Misceo, and Theo J. Visser

Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating Triiodothyronine Levels in Hypothyroid Rats
Rodrigo R. Da Conceição, Gustavo W. Fernandes, Tatiana L. Fonseca, Barbara M.L.C. Bocco, and Antonio C. Bianco 

Response to Lenvatinib in Children with Papillary Thyroid Carcinoma
Priya Mahajan, Jonathan Dawrant, Albert Kheradpour, Norma M. Quintanilla, Monica E. Lopez, Robert C. Orth, Ioanna Athanassaki, and Rajkumar Venkatramani 

Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma
Young Shin Song, Jae-Kyung Won, Seong-Keun Yoo, Kyeong Cheon Jung, Min Joo Kim, Su-Jin Kim, Sun Wook Cho, Kyu Eun Lee, Ka Hee Yi, Jeong-Sun Seo, and Young Joo Park 

Diagnostic Performance of Ultrasound-Based Risk-Stratification Systems for Thyroid Nodules: Comparison of the 2015 American Thyroid Association Guidelines with the 2016 Korean Thyroid Association/Korean Society of Thyroid Radiology and 2017 American Congress of Radiology Guidelines
Eun Ju Ha, Dong Gyu Na, Won-Jin Moon, Young Hen Lee, and Nami Choi 

The post <i>Thyroid^®</i> High-Impact Articles appeared first on American Thyroid Association.

https://ift.tt/2OW13P9

Combined Karapandzic-Abbé/Estlander/Stein Flap For Subtotal and Total Lower Lip Reconstruction

Background: Lower lip reconstruction remains a challenging task due to multi-functional and high aesthetic requirements that have to be achieved for successful outcome. This is particularly true to near-total lower lip defects, encompassing over 70% of lower lip loss due to cancer, trauma or burns. Despite the fact that numerous flaps and their modifications have been described over the past century, only a few valuable techniques and concepts withstood the test of time for sub-total lower lip defects, each having their own drawbacks.

https://ift.tt/2BqFv9H

“Radiological Morphometric Analysis of the Zygomatic Arch: Application of Osteosynthesis on the Upper Arch Border for Rigid Fixation”

This study was designed to introduce a novel method of applying osteosynthetic materials to the upper zygomatic arch border for fracture fixation through a temporal incision, and analyze the radiologic morphometric dimensions of the arch to verify its validity.

https://ift.tt/2Kpwy3s

Temporal Trends in Immediate Post-Mastectomy Breast Reconstruction

Breast reconstruction after mastectomy offers significant improvements in quality of life for breast cancer (BC) patients. To improve access to post-mastectomy breast reconstruction (PMBR) for BC patients in the U.S., the Women's Health and Cancer Rights Act (WHCRA) was implemented in 1999, mandating coverage of PMBR by all insurers. Prior to WHCRA, post mastectomy breast reconstruction (PMBR) was variably covered by insurers as it was primarily viewed as a cosmetic procedure. The objectives of this study were to explore whether the incidence of PMBR has changed over time and whether patient age, receipt of radiation therapy, or tumor grade has an effect on the incidence of reconstruction over time.

https://ift.tt/2BoYPUF

Cancer Stem Cells within Moderately Differentiated Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-angiotensin System

To investigate expression of components of the renin-angiotensin system (RAS): pro-renin receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) by the cancer stem cell (CSC) subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNCSCC).

https://ift.tt/2KoNZkA

Sub-muscular Plane for Augmentation Mammoplasty Patients Increases Silicone Gel Implant Rupture Rate

Breast augmentation is one of the most common aesthetic procedures performed worldwide. One of the worst associated complications is implant rupture, a topic that will be addressed in the present study. The risk of developing silicone gel breast implant rupture following breast augmentation is associated with multiple factors, including: older generation implant, increased implant age, implant type, specific manufacturer, severe capsular contracture (Baker grade III or IV), and the presence of local symptoms.

https://ift.tt/2BqMbVl

Functional outcomes of upper eyelid blepharoplasty: a systematic review.

Various functional outcomes after upper blepharoplasty are reported in the literature. We systematically reviewed the literature to assess the objective and subjective functional effects of upper blepharoplasty.

https://ift.tt/2Kt9jWc

Impact of Incidental Findings in Preoperative CTA imaging for Autologous Breast Reconstruction

CT angiography (CTA) can be performed pre-operatively for perforator mapping in autologous breast reconstruction. The full impact of incidental CTA findings on breast reconstruction remains unclear.

https://ift.tt/2BoX0az

A retrospective comparison of 3M™ Micropore™ with other common dressings in cosmetic breast surgery

Surgical site infection has considerable cost implications for healthcare providers. Evidence suggests that the use of Micropore™ tape as a dressing for surgical incisions may be associated with reduced/comparable rates of infection in surgical wounds. 3M™ Micropore™ tape is significantly cheaper than conventional wound dressings. The purpose of this study was to compare differences in the rate of wound healing problems including superficial incisional surgical site infection (SSI) and wound healing problems following cosmetic breast procedures between Micropore™ tape and other common wound dressings.

https://ift.tt/2Kp3Gbr

Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients

Abstract

Purpose

The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC).

Methods

The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance.

Results

Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC.

Conclusions

The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available.

https://ift.tt/2TuQ9Dv

Association of serum ghrelin with weight gain during pregnancy in overweight and normal women

Abstract

Purpose

Despite the fact that the ghrelin hormone plays pivotal role in the process of weight gain, its correlation with weighing during pregnancy has not been elucidated. Hence, the present study was conducted to evaluate the correlation between plasma ghrelin levels and gestational weight gain in overweight and normal women.

Methods

This prospective cohort study was conducted in 27 overweight and 18 normal body mass index (BMI) pregnant women referring to Tehran health care centers. Weight gain during all trimesters of pregnancy was measured and the blood samples were collected at 8–12 (first trimester) and 16–20 weeks (second trimester) of pregnancy. The plasma total ghrelin concentration was measured by ELISA method.

Results

The overweight pregnant women exhibited significantly lower weight gain at the second (p = 0.002), third trimesters (p = 0.005) as well as total weighing during pregnancy (p = 0.001) compared to the normal BMI pregnant women. There was no significant difference in plasma ghrelin levels between the groups from the first to the second trimesters of pregnancy (p > 0.05). Moreover, no correlation was found between ghrelin levels and gestational weight gain in the overweight and normal groups.

Conclusions

Our results indicate that the increased level of serum ghrelin could not be considered as a key mediator for weight gain difference during pregnancy of overweight women.

https://ift.tt/2Ae1jn2

Outcomes in Patients Treated With Carfilzomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

This 5-year follow-up of a phase 2 clinical trial assesses long-term durability of minimal residual disease–negative remission and time to disease progression among patients with newly diagnosed multiple myeloma who received triplet-based induction therapy with lenalidomide maintenance therapy.

https://ift.tt/2DNEefr

Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer

To the Editor Goodman et al recently described a consistent benefit from radiotherapy (RT) in terms of survival and distant disease control after breast-conserving surgery (BCS), but not mastectomy, in 2 cohorts of patients with breast cancer (BC) harboring any circulating tumor cells (CTCs). Speers and Rugo emphasize that the lack of benefit from RT in patients with CTC-negative status is probably owing to the study being underpowered to detect small benefits, and the findings should not be regarded as contradictory to abundant randomized evidence of the benefit of RT. We agree and value the identification of a predictive biomarker of RT benefit.

https://ift.tt/2S74hRL

Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients

This cohort study examines patient data in the European Society for Blood and Marrow Transplantation Registry for causes of death, risk factors, and overall survival rates among patients who received a second cancer diagnosis after being treated with stem cell transplant.

https://ift.tt/2DNEdbn

Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer

To the Editor Cann et al conducted an interesting study to evaluate the associations of 3 body composition measures with overall survival (OS) in patients with nonmetastatic breast cancer. Comparing patients with and without sarcopenia, the authors report a hazard ratio (HR) of 1.41 (95% CI, 1.18-1.69). Although a statistically significant association between sarcopenia and OS was established, a 40% increase in the HR for sarcopenia is difficult to interpret clinically. The hazard cannot be interpreted as a risk (ie, the chance or likelihood of an event occurring). Moreover, without the background hazard function as a benchmark in patients without sarcopenia, a 40% increase might not amount to a clinically meaningful difference. Furthermore, when the HR is not constant over time, it is unclear how to interpret the observed HR.

https://ift.tt/2S0IJGq

Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer—Reply

In Reply McCaw et al propose using restricted mean survival time (RMST) as an alternative to the Cox proportional hazards models we used to examine the influence of body composition on survival in patients with breast cancer. While we agree that RMST presents an alternative method of interpreting data with less restrictions about model fit, there are several reasons why we chose the approach used. First, our article is an epidemiological study examining body composition risk factors for survival, not a randomized clinical trial. Thus, it is unlikely that a clinician would ever inform a patient with low muscle or excess adiposity that she had 6 fewer months to live compared with a patient with normal weight or normal muscle, especially because it is unknown if losing adiposity or gaining muscle will change a patient's survival. Mean differences generated from RMST may be more appropriate for patients who need to make informed decisions about treatment. Our study is meant to generate new hypotheses for potential future clinical trials and to help clinicians understand the underlying mechanisms regarding the role of body composition to survival. Thus, presenting relative risks for this purpose is informative. Additionally, other studies on this topic have used statistical approaches similar to the approach we used so that results can easily be compared.

https://ift.tt/2DNEbAh