Metabolic Syndrome and Subclinical Hypothyroidism: A Type 2 Diabetes-Dependent Association

Introduction. Subclinical hypothyroidism (ScH) is an endocrine alteration that is related to cardiovascular risk factors, including those categorized as components of the Metabolic Syndrome (MS). However, findings in prior reports regarding an association between these alterations are inconsistent. The purpose of this study was to determine the relationship between both entities in adult subjects from Maracaibo City, Venezuela. Materials and Methods. The Maracaibo City Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with random and multistage sampling. In this substudy, 391 individuals of both genders were selected and TSH, free T3, and free T4 tests were performed as well as a complete lipid profile, fasting glycaemia, and insulin blood values. ScH was defined according to the National Health and Nutrition Examination Survey (NHANES) criteria: high TSH (≥4.12mUI/L) and normal free T4 (0.9-1,9 ng/dL) in subjects without personal history of thyroid disease. MS components were defined according to IDF/AHA/NHLBI/WHF/IAS/IASO-2009 criteria. A multiple logistic regression analysis was used to assess the relationship between MS components and ScH diagnosis. Results. Of the evaluated population, 10.5% (n=41) was diagnosed with ScH, with a higher prevalence in women (female: 13.6% versus male: 7.7%; χ2=3.56, p=0.05). Likewise, 56.1% (n=23) of the subjects with ScH were diagnosed with MS (χ2=4.85; p=0.03), being hyperglycemia the main associated criterion (χ2=11.7; p=0.001). In multivariable analysis, it was observed that the relationship was exclusive with the presence of type 2 diabetes mellitus (T2DM) OR: 3.22 (1.14-9.14); p=0.03. Conclusion. The relationship between ScH and MS in our population is dependent on the presence of hyperglycemia, specifically T2DM diagnosis, findings that vary from those previously reported in Latin American subjects.

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Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells

Abstract

Cholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrence rate is high and chemotherapy often cannot satisfactorily prolong survival. Cellular immunotherapy based on adoptive T-cell transfer is a potential treatment for CCA; however, the development of this technology and the search for an appropriate tumor-associated antigen are still ongoing. To enhance the cytotoxic activity of effector T cells against CCA, we developed self-differentiated monocyte-derived dendritic cells (SD-DC) presenting cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A), which is an overexpressed protein that plays a role in the regulation of tumor growth to activate T cells for CCA cell killing. Dendritic cells (DCs) transduced with lentivirus harboring tri-cistronic cDNA sequences (SD-DC-PR) could produce granulocyte–macrophage colony-stimulating factor, interleukin-4, and PRKAR1A. SD-DC showed similar phenotypes to those of DCs derived by conventional method. Autologous effector T cells (CD3+, CD8+) activated by SD-DC-PR exhibited greater cytotoxic activity against CCA than those activated by conventionally-derived DCs. Effector T cells activated by SD-DC-PR killed 60% of CCA cells at an effector-to-target ratio of 15:1, which is approximately twofold greater than the cell killing performance of those stimulated with control DC. The cytotoxic activities of effector T cells activated by SD-DC-PR against CCA cells were significantly associated with the expression levels of PRKR1A in CCA cells. This finding that SD-DC-PR effectively stimulated autologous effector T cells to kill CCA cells may help to accelerate the development of novel therapies for treating CCA.

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HER2 status in patients with residual rectal cancer after preoperative chemoradiotherapy: the relationship with molecular results and clinicopathologic features

Abstract

The specific role of human epidermal growth factor receptor-2 (HER2) status in rectal cancers remains unclear. This study therefore aimed to explore clinicopathologic and molecular characteristics, and prognostic value of HER2-positivity in residual mid- and/or low-rectal cancers after preoperative chemoradiotherapy (CRT). Surgical specimens from 145 patients with residual rectal cancer after preoperative CRT between January 2006 and January 2011 were used to evaluate HER2 status. HER2 protein expression and gene amplification were determined using immunohistochemistry (IHC) and silver in situ hybridization (SISH) on whole tissue sections, respectively. Polymerase chain reaction was used to analyze molecular characteristics, including microsatellite instability (MSI) and mutations in KRAS exon 2 (codon 12 and 13) and BRAF V600E mutation. Of 139 eligible patients, 8 (5.8%) had HER2 overexpression (IHC 2+ and 3+) that was not associated with clinicopathologic characteristics and patient survival, except positive circumferential resection margin (CRM) (P = 0.012). SISH was performed on 24 patient samples with IHC 1+ (n = 16), 2+ (n = 6), and 3+ (n = 2). HER2 amplification was identified in 3 patients (2.2%); however, this was also associated with positive CRM (P = 0.009) but not survival (all P > 0.05). Moreover, HER2 overexpression and amplification had no relationship with KRAS or BRAF mutations, and MSI status (all P > 0.05). HER2 positivity was found in a minority of rectal cancer patients and was not significantly associated with clinicopathologic and molecular characteristics. Our findings can be helpful in understanding the clinicopathologic bases of HER2 status in rectal cancers.

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Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study

Abstract

Introduction

The utility of immunotherapy in elderly melanoma patients is debated. We aimed in this study to evaluate the efficacy and tolerability of immunotherapy among elderly patients.

Method

This is a retrospective single-institution cohort study. Patients aged 75 years and above who had been treated with nivolumab, pembrolizumab or ipilimumab for advanced or metastatic melanoma, were included. Patients and disease characteristics were collected using electronic medical records. Objective response was determined according to the immune-related response criteria. Drug-related toxicities (DRT) were graded according to the CTCAE v4.03.

Results

99 patients were included with a mean age of 80 years (SD = 4). One patient received nivolumab and ipilimumab combination, but died because of drug-related diverticulitis. Median PFS on pembrolizumab, nivolumab or ipilimumab were equal to 11.9 (95% CI 5.4–18.4), 1.4 (95% CI 0.01–2.8), and 2.8 months (95% CI 2.6-3), respectively, while objective response rates were equal to 51.6, 12.5, and 17.3%, respectively. Median OS was not reached in patients who received only pembrolizumab, 8.7 months in the ipilimumab only group, and 23 months in patients receiving several immune therapies sequentially. Pembrolizumab, nivolumab, and ipilimumab grade 3–4 DRT rates were equal to 24.2, 62.5, and 32.7% respectively, while discontinuation rates were equal to 43.5, 62.5, and 28.8%, respectively.

Conclusions

Our study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further.

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An Unusual and Neglected Foreign Body in the Ethmoid Sinus

Abstract

We report a case of 7 years old male who was referred from Eye OPD with chronic discharge from right periorbita near inner canthus with suspected foreign body after 3 months of injury.

https://ift.tt/2ve20KH

An Unusual and Neglected Foreign Body in the Ethmoid Sinus

Abstract

We report a case of 7 years old male who was referred from Eye OPD with chronic discharge from right periorbita near inner canthus with suspected foreign body after 3 months of injury.

https://ift.tt/2ve20KH

Gastric Ultrasound for the Regional Anesthesiologist and Pain Specialist

This article in our series on point-of-care ultrasound (US) for the regional anesthesiologist and pain management specialist describes the emerging role of gastric ultrasonography. Although gastric US is a relatively new point-of-care US application in the perioperative setting, its relevance for the regional anesthesiologist and pain specialist is significant as our clinical practice often involves providing deep sedation without a secured airway. Given that pulmonary aspiration is a well-known cause of perioperative morbidity and mortality, the ability to evaluate for NPO (nil per os) status and risk stratify patients scheduled for anesthesia is a powerful skill set. Gastric US can provide valuable insight into the nature and volume of gastric content before performing a block with sedation or inducing anesthesia for an urgent or emergent procedure where NPO status is unknown. Patients with comorbidities that delay gastric emptying, such as diabetic gastroparesis, neuromuscular disorders, morbid obesity, and advanced hepatic or renal disease, may potentially benefit from additional assessment via gastric US before an elective procedure. Although gastric US should not replace strict adherence to current fasting guidelines or be used routinely in situations when clinical risk is clearly high or low, it can be a useful tool to guide clinical decision making when there is uncertainty about gastric contents. In this review, we will cover the relevant scanning technique and the desired views for gastric US. We provide a methodology for interpretation of findings and for guiding medical management for adult patients. We also summarize the current literature on specific patient populations including obstetrics, pediatrics, and severely obese subjects. Accepted for publication April 14, 2018. Address correspondence to: Stephen C. Haskins, MD, Department of Anesthesiology, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021 (e-mail: haskinss@hss.edu). The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Spectral and 3D cultural heritage documentation using a modified camera

Webb, EK; Robson, S; MacDonald, L; Garside, D; Evans, R; (2018) Spectral and 3D cultural heritage documentation using a modified camera. In: The International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XLII-2, 2018. (pp. pp. 1183-1190). Spatial Inf. Sci.: Riva del Garda, Italy. Green open access

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Deep Learning for Predicting Refractive Error From Retinal Fundus Images

Varadarajan, AV; Poplin, R; Blumer, K; Angermueller, C; Ledsam, J; Chopra, R; Keane, PA; ... Webster, DR; + view all Varadarajan, AV; Poplin, R; Blumer, K; Angermueller, C; Ledsam, J; Chopra, R; Keane, PA; Corrado, GS; Peng, L; Webster, DR; - view fewer (2018) Deep Learning for Predicting Refractive Error From Retinal Fundus Images. Investigative Ophthalmology & Visual Science , 59 (7) pp. 2861-2868. 10.1167/iovs.18-23887 . Green open access

https://ift.tt/2Akk1wI

What a dog transmissible tumor can teach us about cancer regression

Fassati, A; (2018) What a dog transmissible tumor can teach us about cancer regression. [Editorial comment]. Presented at: UNSPECIFIED. (In press).

https://ift.tt/2mNO8D6

The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers

Burgess, K; Li, H; Abo-zeid, Y; Fatimah, and; Williams, GR; (2018) The Effect of Molecular Properties on Active Ingredient Release from Electrospun Eudragit Fibers. Pharmaceutics , 10 (3) , Article 103. 10.3390/pharmaceutics10030103 . Green open access

https://ift.tt/2AfcqiR

HMeta-d: hierarchical Bayesian estimation of metacognitive efficiency from confidence ratings

Fleming, SM; (2017) HMeta-d: hierarchical Bayesian estimation of metacognitive efficiency from confidence ratings. Neuroscience of Consciousness , 2017 (1) , Article nix007. 10.1093/nc/nix007 . Green open access

https://ift.tt/2mQFXWM

Authoritarian amendments: Legislative institutions as intra-executive constraints in post-Soviet Russia

Noble, BH; (2018) Authoritarian amendments: Legislative institutions as intra-executive constraints in post-Soviet Russia. Comparative Political Studies (In press).

https://ift.tt/2AdCZoJ

Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

Li, C; Lev, S; Saiardi, A; Desmarini, D; Sorrell, TC; Djordjevic, JT; (2016) Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery. Journal of Fungi , 2 (3) , Article 24. 10.3390/jof2030024 . Green open access

https://ift.tt/2On2KWA

Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel

Schmidt, JM; Battlay, P; Gledhill-Smith, RS; Good, RT; Lumb, C; Fournier-Level, A; Robin, C; (2017) Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel. Genetics , 207 (3) pp. 1181-1193. 10.1534/genetics.117.300310 .

https://ift.tt/2AfcizT

Insight into Two ABC Transporter Families Involved in Lantibiotic Resistance

Clemens, R; Zaschke-Kriesche, J; Khosa, S; Smits, SHJ; (2017) Insight into Two ABC Transporter Families Involved in Lantibiotic Resistance. Frontiers in Molecular Biosciences , 4 , Article 91. 10.3389/fmolb.2017.00091 . Green open access

https://ift.tt/2mNl7az

Jwalk and MNXL Web Server: Model Validation using Restraints from Crosslinking Mass Spectrometry

Bullock, JMA; Thalassinos, K; Topf, M; (2018) Jwalk and MNXL Web Server: Model Validation using Restraints from Crosslinking Mass Spectrometry. Bioinformatics 10.1093/bioinformatics/bty366 . (In press). Green open access

https://ift.tt/2AfcfEd

MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas

Bongaarts, A; Prabowo, AS; Arena, A; Anink, JJ; Reinten, RJ; Jansen, FE; Spliet, WGM; ... Aronica, E; + view all Bongaarts, A; Prabowo, AS; Arena, A; Anink, JJ; Reinten, RJ; Jansen, FE; Spliet, WGM; Thom, M; Coras, R; Blümcke, I; Kotulska, K; Jozwiak, S; Grajkowska, W; Söylemezoğlu, F; Pimentel, J; Schouten-van Meeteren, AYN; Mills, JD; Iyer, AM; van Vliet, EA; Mühlebner, A; Aronica, E; - view fewer (2018) MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas. Oncotarget , 9 (46) pp. 28103-28115. 10.18632/oncotarget.25563 . Green open access

https://ift.tt/2OlCCeV

Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer

Sztupinszki, Z; Diossy, M; Krzystanek, M; Reiniger, L; Csabai, I; Favero, F; Birkbak, NJ; ... Szallasi, Z; + view all Sztupinszki, Z; Diossy, M; Krzystanek, M; Reiniger, L; Csabai, I; Favero, F; Birkbak, NJ; Eklund, AC; Syed, A; Szallasi, Z; - view fewer (2018) Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer. NPJ Breast Cancer , 4 , Article 16. 10.1038/s41523-018-0066-6 . Green open access

https://ift.tt/2AfcdMB

Why Are Single-Sex Schools Successful?

Dustmann, C; Ku, H; Kwak, DW; (2019) Why Are Single-Sex Schools Successful? Labour Economics (In press).

https://ift.tt/2mNl1jd

Skin cancer has a large impact on our public hospitals but prevention programs continue to demonstrate strong economic credentials.

Shih, STF; Carter, R; Heward, S; Sinclair, C; (2017) Skin cancer has a large impact on our public hospitals but prevention programs continue to demonstrate strong economic credentials. Aust N Z J Public Health , 41 (4) pp. 371-376. 10.1111/1753-6405.12679 . Green open access

https://ift.tt/2Afc9fP

Constraints on the diffuse high-energy neutrino flux from the third flight of ANITA

Gorham, PW; Allison, P; Banerjee, O; Batten, L; Beatty, JJ; Bechtol, K; Belov, K; ... Wissel, SA; + view all Gorham, PW; Allison, P; Banerjee, O; Batten, L; Beatty, JJ; Bechtol, K; Belov, K; Besson, DZ; Binns, WR; Bugaev, V; Cao, P; Chen, CC; Chen, CH; Chen, P; Clem, JM; Connolly, A; Cremonesi, L; Dailey, B; Deaconu, C; Dowkontt, PF; Fox, BD; Gordon, JWH; Hast, C; Hill, B; Hsu, SY; Huang, JJ; Hughes, K; Hupe, R; Israel, MH; Liewer, KM; Liu, TC; Ludwig, AB; Macchiarulo, L; Matsuno, S; Miki, C; Mulrey, K; Nam, J; Naudet, C; Nichol, RJ; Novikov, A; Oberla, E; Prohira, S; Rauch, BF; Roberts, JM; Romero-Wolf, A; Rotter, B; Russell, JW; Saltzberg, D; Seckel, D; Schoorlemmer, H; Shiao, J; Stafford, S; Stockham, J; Stockham, M; Strutt, B; Sutherland, MS; Varner, GS; Vieregg, AG; Wang, SH; Wissel, SA; - view fewer (2018) Constraints on the diffuse high-energy neutrino flux from the third flight of ANITA. Physical Review D , 98 (2) , Article 022001. 10.1103/PhysRevD.98.022001 . Green open access

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Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents

Jin, QQ; Wu, GQ; Peng, WW; Xia, XL; Hu, L; Iannetti, GD; (2018) Somatotopic Representation of Second Pain in the Primary Somatosensory Cortex of Humans and Rodents. Journal of Neuroscience , 38 (24) pp. 5538-5550. 10.1523/JNEUROSCI.3654-17.2018 . Green open access

https://ift.tt/2Afc4c1

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy

Imms, C; Wallen, M; Elliott, C; Hoare, B; Randall, M; Greaves, S; Adair, B; ... Reddihough, D; + view all Imms, C; Wallen, M; Elliott, C; Hoare, B; Randall, M; Greaves, S; Adair, B; Bradshaw, E; Carter, R; Orsini, F; Shih, STF; Reddihough, D; - view fewer (2016) Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy. BMC Pediatrics , 16 , Article 70. 10.1186/s12887-016-0608-8 . Green open access

https://ift.tt/2Oo43of

Modeling Protein Complexes Using Restraints from Crosslinking Mass Spectrometry

Bullock, JMA; Sen, N; Thalassinos, K; Topf, M; (2018) Modeling Protein Complexes Using Restraints from Crosslinking Mass Spectrometry. Structure , 26 (7) pp. 1015-1024. 10.1016/j.str.2018.04.016 . Green open access

https://ift.tt/2AfbYkF

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

Chandler, N; Best, S; Hayward, J; Faravelli, F; Mansour, S; Kivuva, E; Tapon, D; ... Chitty, LS; + view all Chandler, N; Best, S; Hayward, J; Faravelli, F; Mansour, S; Kivuva, E; Tapon, D; Male, A; DeVile, C; Chitty, LS; - view fewer (2018) Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management. Genet Med 10.1038/gim.2018.30 . (In press). Green open access

https://ift.tt/2OlT0vM

Modelled health benefits of a sugar-sweetened beverage tax across different socioeconomic groups in Australia: A cost-effectiveness and equity analysis

Lal, A; Mantilla-Herrera, AM; Veerman, L; Backholer, K; Sacks, G; Moodie, M; Siahpush, M; ... Peeters, A; + view all Lal, A; Mantilla-Herrera, AM; Veerman, L; Backholer, K; Sacks, G; Moodie, M; Siahpush, M; Carter, R; Peeters, A; - view fewer (2017) Modelled health benefits of a sugar-sweetened beverage tax across different socioeconomic groups in Australia: A cost-effectiveness and equity analysis. PLoS Medicine , 14 (6) , Article e1002326. 10.1371/journal.pmed.1002326 . Green open access

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