A homozygous mutation of GNRHR in a familial case diagnosed with polycystic ovary syndrome

Context

PCOS is a heterogeneous condition characterized by hyperandrogenism and chronic anovulation and affects about 10% of women. Its etiology is poorly known, but a dysregulation of gonadotropin secretion is one of its hallmarks.

Objective

As the etiology of PCOS is unclear, we have performed a genome-wide analysis of a consanguineous family with three sisters diagnosed with PCOS.

Methods

Whole-exome sequencing and Sanger sequencing confirmation.

Results

Whole-exome sequencing allowed the detection of the missense variant rs104893836 located in the first coding exon of the GNRHR gene and leading to the p.Gln106Arg (p.Q106R) substitution. Sanger sequencing of all available individuals of the family confirmed that the variant was homozygous in the three affected sisters and heterozygous in both parents.

Conclusions

This is the first description of a GNRHR gene mutation in patients diagnosed with PCOS. Although we do not exclude a possible interaction of the identified variant with the genetic background and/or the environment, our result suggests that genetic alterations in the hypothalamo–pituitary axis may play role in the pathogenesis of PCOS.

http://ift.tt/2nF5W53

Associations between serum levels of calcium, parathyroid hormone and future risk of venous thromboembolism: the Tromso study

Objective

The relationship between serum levels of calcium, parathyroid hormone (PTH) and risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the associations between serum levels of calcium and PTH, with future risk of VTE in a general adult population.

Design

Population-based cohort.

Methods

A total of 27 712 subjects (25–87 years) who participated in Tromsø 4 (1994–1995) and Tromsø 5 (2001–2002) surveys were included in the study, and total calcium and PTH were measured in 27 685 and 8547 subjects respectively. Incident VTE was recorded through December 31, 2012. Cox-regression models with calcium and PTH as time-varying exposures were used to calculate hazard ratios (HR) of VTE by quartiles of calcium and PTH. Quartiles of calcium and PTH were also combined to assess the effect of discordants of both PTH and calcium (e.g. highest and lowest quartiles of both calcium and PTH) on VTE risk using the middle two quartiles as reference.

Results

There were 712 VTEs during 15.0 years of median follow-up. Serum levels of calcium and PTH were not associated with risk of VTE. However, subjects with discordant high serum levels of both calcium and PTH (calcium ≥2.45 mmol/L and PTH ≥4.0 pmol/L) had increased risk of VTE compared to those in subjects with normal calcium and PTH (multivariable HR: 1.78, 95% CI: 1.12–2.84).

Conclusions

Serum levels of calcium and PTH separately were not associated with future risk of VTE, but subjects with high levels of both calcium and PTH had increased risk of VTE compared to those in subjects with normal levels.

http://ift.tt/2o9Zr8g

Risk factors for post-thyroidectomy haemorrhage: a meta-analysis

Background

Post-thyroidectomy haemorrhage is a rare but potentially life-threatening and unpredictable complication of thyroid surgery. In this study, we analysed the potential risk factors for the occurrence of post-thyroidectomy haemorrhage.

Methods

The PubMed and SCIE databases were comprehensively searched for studies published before June 30, 2016. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included, and RevMan 5.3 software was used to analyse the data.

Results

Twenty-five studies and 424 563 patients were included in this meta-analysis, and post-thyroidectomy haemorrhage occurred in 6277 patients (incidence rate = 1.48%). The following variables were associated with an increased risk of post-thyroidectomy haemorrhage: older age (MD = 4.30, 95% CI = 3.09–5.52, P < 0.00001), male sex (OR = 1.73, 95% CI = 1.54–1.94, P < 0.00001), Graves' disease (OR = 1.76, 95% CI = 1.44–2.15, P < 0.00001), antithrombotic agents use (OR = 1.96, 95% CI 1.55–2.49, P < 0.00001), bilateral operation (OR = 1.71, 95% CI = 1.50–1.96, P < 0.00001), neck dissection (OR = 1.53, 95% CI = 1.11–2.11, P = 0.01) and previous thyroid surgery (OR = 1.62, 95% CI = 1.12–2.34, P = 0.01). Malignant tumours (OR = 1.07, 95% CI = 0.89–1.28, P = 0.46) and drainage device use (OR = 1.27, 95% CI = 0.74–2.18, P = 0.4) were not associated with post-thyroidectomy haemorrhage.

Conclusion

Our systematic review identified a number of risk factors for post-thyroidectomy haemorrhage, including older age, male sex, Graves' disease, antithrombotic agents use, bilateral operation, neck dissection and previous thyroid surgery. Early control of modifiable risk factors could improve patient outcomes and satisfaction.

http://ift.tt/2nFgpxs

Increase in thyroglobulin antibody and thyroid peroxidase antibody levels, but not preterm birth-rate, in pregnant Danish women upon iodine fortification

Objective

The presence of thyroid antibodies in pregnancy has been associated with preterm birth. In the non-pregnant population, the implementation of the Danish iodine fortification program has increased the prevalence of thyroid antibodies. This study investigated the prevalence of thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) in pregnant Danish women before, during and after implementation of the iodine fortification program and association with preterm birth.

Design

Comparative cohort study of 1368 pregnancies from three cohorts gathered before (1996–1998), during (2000–2003) and after (2008–2009) the iodine fortification program.

Methods

In cohort 1 (n = 297), TPOAbs were measured (DYNOtest (BRAHMS)). In cohorts 2 (n = 148) and 3 (n = 923), both TPOAbs and TgAbs were measured (Kryptor immunofluorescent assay (BRAHMS)). The prevalence and effect of antibody positivity were explored using three cut-offs: TPOAbs and/or TgAbs >100 kU/L, TPOAbs and/or TgAbs >60 kU/L and TPOAbs >30 and/or TgAbs >20 kU/L. National preterm birth data were extracted from the National Birth Registry.

Results

In the three cohorts, TPOAb levels >60 kU/L were found in 5.4, 8.1 and 12.0% ( ²(2, n = 1367) = 11.7, P = 0.003) respectively, and TPOAbs and/or TgAbs >60 kU/L in 8.1 and 16.2% in cohorts 2 and 3 respectively ( ²(2, n = 1070) = 6.5, P = 0.01). TgAb levels (>20 kU/L) had increased plenty-fold from cohort 2 to 3 ( ²(1, n = 1071) = 136.5, P < 0.001). Preterm birth occurred in 4.1% of all pregnancies with no effect from antibody positivity (TPOAbs and/or TgAbs >60 kU/L, ²(1, n = 1039) = 0.0, P = 0.98, aOR = 1.1, 95% CI (0.4–2.7)). The national preterm birth-rate showed no increase over the same period.

Conclusions

Thyroid antibody positivity in Danish pregnant women has more than doubled upon the implementation of the iodine fortification program without an increase in preterm birth-rate.

http://ift.tt/2o9R3FN

MANAGEMENT OF ENDOCRINE DISEASE: Neuroendocrine surveillance and management of neurosurgical patients

Advances in the management of traumatic brain injury, subarachnoid haemorrhage and intracranial tumours have led to improved survival rates and an increased focus on quality of life of survivors. Endocrine sequelae of the acute brain insult and subsequent neurosurgery, peri-operative fluid administration and/or cranial irradiation are now well described. Unrecognised acute hypopituitarism, particularly ACTH/cortisol deficiency and diabetes insipidus, can be life threatening. Although hypopituitarism may be transient, up to 30% of survivors of TBI have chronic hypopituitarism, which can diminish quality of life and hamper rehabilitation. Patients who survive SAH may also develop hypopituitarism, though it is less common than after TBI. The growth hormone axis is most frequently affected. There is also accumulating evidence that survivors of intracranial malignancy, who have required cranial irradiation, may develop hypopituitarism. The time course of the development of hormone deficits is varied, and predictors of pituitary dysfunction are unreliable. Furthermore, diagnosis of GH and ACTH deficiency require dynamic testing that can be resource intensive. Thus the surveillance and management of neuroendocrine dysfunction in neurosurgical patients poses significant logistic challenges to endocrine services. However, diagnosis and management of pituitary dysfunction can be rewarding. Appropriate hormone replacement can improve quality of life, prevent complications such as muscle atrophy, infection and osteoporosis and improve engagement with physiotherapy and rehabilitation.

http://ift.tt/2nFbPPQ

Contact system activation and high thrombin generation in hyperthyroidism

Background

Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity.

Subjects and methods

In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone–DNA complex, double-stranded DNA and neutrophil elastase) and contact system markers (activated factor XII (XIIa), high-molecular-weight kininogen (HMWK), prekallikrein and bradykinin) were measured.

Results

Patients with hyperthyroidism showed higher levels of fibrinogen (median (interquartile range), 315 (280–344) vs 262 (223–300), P = 0.001), D-dimer (103.8 (64.8–151.5) vs 50.7 (37.4–76.0), P < 0.001), peak thrombin (131.9 (102.2–159.4) vs 31.6 (14.8–83.7), P < 0.001) and endogenous thrombin potential (649 (538–736) vs 367 (197–1147), P = 0.021) in TGA with 1 pM tissue factor, neutrophil elastase (1.10 (0.39–2.18) vs 0.23 (0.20–0.35), P < 0.001), factor XIIa (66.9 (52.8–87.0) vs 73.0 (57.1–86.6), P < 0.001), HMWK (6.11 (4.95–7.98) vs 3.83 (2.60–5.68), P < 0.001), prekallikrein (2.15 (1.00–6.36) vs 1.41 (0.63–2.22), P = 0.026) and bradykinin (152.4 (137.6–180.4) vs 118.3 (97.1–137.9), P < 0.001) than did normal controls. In age- and sex-adjusted logistic regression analysis, fibrinogen, factor VIII, IX and XIIa, D-dimer, peak thrombin, neutrophil elastase, HMWK and bradykinin showed significant odds ratios representing hyperthyroidism's contribution to coagulation and contact system activation. Free T4 was significantly correlated with factors VIII and IX, D-dimer, double-stranded DNA and bradykinin.

Conclusion

This study demonstrated that contact system activation and abundant NET formation occurred in the high thrombin generation state in hyperthyroidism and were correlated with free T4 level.

http://ift.tt/2o9YSez

One-stop-shop radioiodine dosimetry in patients with Graves’ disease

http://ift.tt/2o9K9jA

Proteasome inhibitor MG132 induces thyroid cancer cell apoptosis by modulating the activity of transcription factor FOXO3a

Abstract

Proteasome inhibitors are promising antitumor drugs with preferable cytotoxicity in malignant cells and have exhibited clinical efficiency in several hematologic malignancies. P53-dependent apoptosis has been reported to be a major mechanism underlying. However, apoptosis can also be found in cancer cells with mutant-type p53, suggesting the involvement of p53-independent mechanism. Tumor suppressor forkhead Box O3 is another substrate of proteasomal degradation, which also functions partially through inducing apoptosis. The aim of this study was to explore the effect of proteasome inhibition on the expression and activity of forkhead Box O3 in thyroid cancer cells. Using flow cytometry, western blot, immunofluorescence staining and quantitative RT-PCR assays, we assessed proteasome inhibitor MG132-induced apoptosis in thyroid cancer cells and its effect on the expression and activity of forkhead Box O3. The resulted showed that MG132 induced significant apoptosis, and caused the accumulation of p53 protein in both p53 wild-type and mutant-type thyroid cancer cell lines, whereas the proapoptotic targets of p53 were transcriptionally upregulated only in the p53 wild-type cells. Strikingly, upon MG132 administration, the accumulation and nuclear translocation of transcription factor forkhead Box O3 as well as transcriptional upregulation of its proapoptotic target genes were found in thyroid cancer cells regardless of p53 status. Cell apoptosis was enhanced by ectopic overexpression while attenuated by silencing of forkhead Box O3. Altogether, we demonstrated that proteasome inhibitor MG132 induces thyroid cancer cell apoptosis at least partially through modulating forkhead Box O3 activity.

http://ift.tt/2nF73l3

How do etiological factors can explain the different clinical features of patients with differentiated thyroid cancer and their histopathological findings?

Abstract

The aim was to retrospectively analyse the clinical–histopathological characteristics of patients with newly diagnosis of differentiated thyroid cancer (DTC) referred to two Italian centres, one in Northern and the other in Southern Italy, between 2000 and 2013. 1081 patients were included and subdivided into two groups: group A (474 patients from Novara) and group B (607 patients from Naples). The group A came from the industrial area of Novara, while the Group B came from the areas around Vesuvius and Campi Flegrei. The two groups were comparable for iodine levels, body mass index, diagnostic timing and clinical procedures. For all patients, demographic and clinical data were collected. No difference was found in gender, whereas the age at diagnosis was later in the group A (group A 53.1 ± 15.16 years, group B 41.9 ± 14.25 years, p < 0.001). In both groups, the most frequent histotype was papillary thyroid cancer (PTC) with prevalence of follicular variant in group A (p < 0.0001) and classical variant in group B (p < 0.0001). Aggressive histological features were mainly seen in group A (bilaterality p < 0.0001, multifocality p < 0.0001 and thyroid capsular invasion p < 0.0001). Microcarcinomas were more frequent in group A (p < 0.0001) but mostly characterized by bilaterality (p < 0.001) and multifocality (p < 0.04). In both groups, tumour-associated thyroiditis showed a significant increase over the years (group A p < 0.05, group B p < 0.04). Environmental factors could justify the differences found in our study. These preliminary data should stimulate the need for an Italian Cancer Registry of DTC in order to allow an epidemiological characterization, allowing the identification of specific etiological factors and an improvement in the management of the disease.

http://ift.tt/2o9BjT3

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) in insulinomas: Indications and clinical relevance in a single investigator cohort of 47 patients

Abstract

Purpose

This study was aimed to investigate the role and relevance of endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of insulinomas.

Methods

We have analysed the frequency, clinical indications, success rate (obtaining diagnostic tissue), diagnostic accuracy (in comparison to the pathological diagnosis after surgery), complications, and tolerability of endoscopic ultrasound-guided fine-needle aspiration biopsy and the localization and size of the lesions in 47 consecutive patients (29 females, 18 males; 46 ± 15 years) who had surgery for insulinoma following fasting test and were explored by single investigator EUS 1994–2015.

Results

Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed in 21 % (10/47) of the patients. The clinical indications for endoscopic ultrasound-guided fine-needle aspiration biopsy were non-conclusive result of fasting test (n = 7), missing toxicology (n = 2), suspected malignancy at EUS (n = 1), suspicious extra-pancreatic localization of the lesion (n = 1). The diagnostic success rate of the procedure was 80 % (8/10 cases), the diagnostic accuracy of the fine-needle aspiration biopsy 70 % (7/10 cases). The lesions undergoing endoscopic ultrasound-guided fine-needle aspiration biopsy were localized in the cauda (n = 5), corpus (n = 2), caput/processus uncinatus (n = 3), the diameter of the tumors was 21 ± 18 (10–70) mm. Only one accidental vascular puncture without any clinical complication occurred and all patients tolerated the procedure well.

Conclusions

In the majority of cases, positive fasting test, negative toxicology, and detection of a typical pancreatic lesion at endoscopic ultrasound is sufficient for the diagnosis of insulinoma and the definition of the appropriate surgical strategy. Based on our data, we suggest including endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of organic hyperinsulinism in selected patients with inconclusive or uncertain diagnosis before surgery.

http://ift.tt/2nFfc9b

Do people trust dentists? Development of the Dentist Trust Scale

Abstract

Background

This study aimed to adapt a measure of trust in physicians generally to trust in dentists and to assess the reliability and validity of the measure.

Methods

Questionnaire data were collected from a simple random sample of 596 Australian adults. The 11-item General Trust in Physicians Scale (Hall et al., 2002) was modified to apply to dentists.

Results

The Dentist Trust Scale (DTS) had good internal consistency (Cronbach's alpha = 0.92) and exploratory factor analysis revealed a single factor solution. Lower DTS scores were associated with less trust in the dentist last visited, having previously changed dentists due to unhappiness with the care received, currently having dental pain, usual visiting frequency, dental avoidance, and with past experiences of discomfort, gagging, fainting, embarrassment and personal problems with the dentist.

Conclusions

The majority of people appear to exhibit trust in dentists generally. The DTS shows promising reliability and validity evidence.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nnFlHF

Optimization of surface electrodes location for H-reflex recordings in soleus muscle

Publication date: June 2017
Source:Journal of Electromyography and Kinesiology, Volume 34
Author(s): Alberto Botter, Taian M. Vieira
The Hoffmann reflex (H reflex) is extensively used to investigate the spinal motor neuron excitability in healthy and pathological subjects. Obtaining a representative and robust amplitude estimation of the H reflex is of marked relevance in clinical as well as in research applications. As for the motor responses, this issue is strictly related to the electrode positioning, especially for large, pinnate muscles such as the triceps surae. In this study we investigated the effect of electrode position on soleus H-reflex amplitude. A grid of 96 electrodes was used to identify maximal H reflexes (Hmax) across the whole soleus region available for surface recording. The spatial distribution of Hmax amplitude detected in monopolar and single-differential derivations was used to determine where greatest reflex responses were detected from soleus. For both derivations and for all participants, largest Hmax were detected consistently over the central soleus region, in correspondence of the muscle superficial aponeurosis. Indeed, the amplitude of Hmax provided by conventional electrodes (1cm² area, 2cm apart) located centrally was significantly greater (median: 35% for monopolar and 79% for single-differential derivations) than that obtained medially, where surface electromyograms are typically recorded from soleus. Computer simulations, used to assist in the interpretation of results, suggest the soleus pinnate architecture was the key determinant of the medio-lateral variability observed for the experimental Hmax. The presented results provide a clear indication for electrode positioning, of crucial relevance in applied studies aimed at eliciting H reflexes.



http://ift.tt/2nYB4gc

Standards for Reporting EMG Data

Publication date: April 2017
Source:Journal of Electromyography and Kinesiology, Volume 33





http://ift.tt/2nnJzyF

Interplay between body stabilisation and quadriceps muscle activation capacity

Publication date: Available online 22 March 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Theodoros M. Bampouras, Neil D. Reeves, Vasilios Baltzopoulos, Constantinos N. Maganaris
The study aimed to distinguish the effect of stabilisation and muscle activation on quadriceps maximal isometric voluntary contraction (MVC) torque generation. Nine subjects performed a) an MVC with restrained leg and pelvis (Typical MVC), b) a Typical MVC with handgrip (Handgrip MVC), c) an MVC focusing on contracting the knee extensors only (Isolated knee extension MVC), and d) an MVC with unrestrained leg and pelvis (Unrestrained MVC). Torque and activation capacity between conditions were compared with repeated measures ANOVA and dependent t-tests. EMG (from eleven remote muscles) was compared using Friedman's and Wilcoxon. Typical MVC (277.2±49.6 Nm) and Handgrip MVC (261.0±55.4 Nm) were higher than Isolated knee extension MVC (210.2±48.3 Nm, p<0.05) and Unrestrained MVC (195.2±49.7 Nm, p<0.05) torque. Typical MVC (83.1±15.9%) activation was higher than Isolated knee extension MVC (68.9±24.3%, p<0.05), and both Typical MVC and Handgrip MVC (81.8±17.4%) were higher than Unrestrained MVC (64.9±16.2%, p<0.05). Only flexor carpi radialis, biceps brachii, triceps brachii and external oblique muscles showed EMG differences, with Isolated knee extension MVC consistently lower than Typical MVC or Handgrip MVC. Stabilisation of the involved segments is the prime concern allowing fuller activation of the muscle, reinforcing the need for close attention to stabilisation during dynamometry-based knee joint functional assessment.



http://ift.tt/2nYmWDI

Carpal tunnel syndrome impairs index finger responses to unpredictable perturbations

Publication date: Available online 16 March 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Emily L. Grandy, Kaihua Xiu, Tamara L. Marquardt, Chengliu Li, Peter J. Evans, Zong-Ming Li
The fine-tuning of digit forces to object properties can be disrupted by carpal tunnel syndrome (CTS). CTS' effects on hand function have mainly been investigated using predictable manipulation tasks; however, unpredictable perturbations are commonly encountered during manual tasks, presenting situations which may be more challenging to CTS patients given their hand impairments. The purpose of this study was to investigate muscle and force responses of the index finger to unpredictable perturbations in patients with CTS. Nine CTS patients and nine asymptomatic controls were instructed to stop the movement of a sliding plate by increasing index finger force following an unexpected perturbation. The electrical activity of the first dorsal interosseous muscle and forces exerted by the index finger were recorded. CTS patients demonstrated 20.9% greater muscle response latency and 12.0% greater force response latency compared to controls (p<0.05). The duration of plate sliding was significantly different between groups (p<0.05); the CTS group's duration was 142.2±5.8ms compared to the control group's duration of 133.1±8.4ms. Although CTS patients had increased muscle and force response durations comparatively, these differences were not statistically significant. Findings from this study suggest CTS-induced sensorimotor deficits interfere with accurate detection, processing and response to unpredictable perturbations. These deficits could be accounted for at multiple levels of the peripheral and central nervous systems. Delayed and decreased responses may indicate inefficient object manipulation by CTS patients and may help to explain why CTS patients tend to drop objects.



http://ift.tt/2nnPG6q

One-stop-shop radioiodine dosimetry in patients with Graves’ disease

http://ift.tt/2o9K9jA

Proteasome inhibitor MG132 induces thyroid cancer cell apoptosis by modulating the activity of transcription factor FOXO3a

Abstract

Proteasome inhibitors are promising antitumor drugs with preferable cytotoxicity in malignant cells and have exhibited clinical efficiency in several hematologic malignancies. P53-dependent apoptosis has been reported to be a major mechanism underlying. However, apoptosis can also be found in cancer cells with mutant-type p53, suggesting the involvement of p53-independent mechanism. Tumor suppressor forkhead Box O3 is another substrate of proteasomal degradation, which also functions partially through inducing apoptosis. The aim of this study was to explore the effect of proteasome inhibition on the expression and activity of forkhead Box O3 in thyroid cancer cells. Using flow cytometry, western blot, immunofluorescence staining and quantitative RT-PCR assays, we assessed proteasome inhibitor MG132-induced apoptosis in thyroid cancer cells and its effect on the expression and activity of forkhead Box O3. The resulted showed that MG132 induced significant apoptosis, and caused the accumulation of p53 protein in both p53 wild-type and mutant-type thyroid cancer cell lines, whereas the proapoptotic targets of p53 were transcriptionally upregulated only in the p53 wild-type cells. Strikingly, upon MG132 administration, the accumulation and nuclear translocation of transcription factor forkhead Box O3 as well as transcriptional upregulation of its proapoptotic target genes were found in thyroid cancer cells regardless of p53 status. Cell apoptosis was enhanced by ectopic overexpression while attenuated by silencing of forkhead Box O3. Altogether, we demonstrated that proteasome inhibitor MG132 induces thyroid cancer cell apoptosis at least partially through modulating forkhead Box O3 activity.

http://ift.tt/2nF73l3

How do etiological factors can explain the different clinical features of patients with differentiated thyroid cancer and their histopathological findings?

Abstract

The aim was to retrospectively analyse the clinical–histopathological characteristics of patients with newly diagnosis of differentiated thyroid cancer (DTC) referred to two Italian centres, one in Northern and the other in Southern Italy, between 2000 and 2013. 1081 patients were included and subdivided into two groups: group A (474 patients from Novara) and group B (607 patients from Naples). The group A came from the industrial area of Novara, while the Group B came from the areas around Vesuvius and Campi Flegrei. The two groups were comparable for iodine levels, body mass index, diagnostic timing and clinical procedures. For all patients, demographic and clinical data were collected. No difference was found in gender, whereas the age at diagnosis was later in the group A (group A 53.1 ± 15.16 years, group B 41.9 ± 14.25 years, p < 0.001). In both groups, the most frequent histotype was papillary thyroid cancer (PTC) with prevalence of follicular variant in group A (p < 0.0001) and classical variant in group B (p < 0.0001). Aggressive histological features were mainly seen in group A (bilaterality p < 0.0001, multifocality p < 0.0001 and thyroid capsular invasion p < 0.0001). Microcarcinomas were more frequent in group A (p < 0.0001) but mostly characterized by bilaterality (p < 0.001) and multifocality (p < 0.04). In both groups, tumour-associated thyroiditis showed a significant increase over the years (group A p < 0.05, group B p < 0.04). Environmental factors could justify the differences found in our study. These preliminary data should stimulate the need for an Italian Cancer Registry of DTC in order to allow an epidemiological characterization, allowing the identification of specific etiological factors and an improvement in the management of the disease.

http://ift.tt/2o9BjT3

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) in insulinomas: Indications and clinical relevance in a single investigator cohort of 47 patients

Abstract

Purpose

This study was aimed to investigate the role and relevance of endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of insulinomas.

Methods

We have analysed the frequency, clinical indications, success rate (obtaining diagnostic tissue), diagnostic accuracy (in comparison to the pathological diagnosis after surgery), complications, and tolerability of endoscopic ultrasound-guided fine-needle aspiration biopsy and the localization and size of the lesions in 47 consecutive patients (29 females, 18 males; 46 ± 15 years) who had surgery for insulinoma following fasting test and were explored by single investigator EUS 1994–2015.

Results

Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed in 21 % (10/47) of the patients. The clinical indications for endoscopic ultrasound-guided fine-needle aspiration biopsy were non-conclusive result of fasting test (n = 7), missing toxicology (n = 2), suspected malignancy at EUS (n = 1), suspicious extra-pancreatic localization of the lesion (n = 1). The diagnostic success rate of the procedure was 80 % (8/10 cases), the diagnostic accuracy of the fine-needle aspiration biopsy 70 % (7/10 cases). The lesions undergoing endoscopic ultrasound-guided fine-needle aspiration biopsy were localized in the cauda (n = 5), corpus (n = 2), caput/processus uncinatus (n = 3), the diameter of the tumors was 21 ± 18 (10–70) mm. Only one accidental vascular puncture without any clinical complication occurred and all patients tolerated the procedure well.

Conclusions

In the majority of cases, positive fasting test, negative toxicology, and detection of a typical pancreatic lesion at endoscopic ultrasound is sufficient for the diagnosis of insulinoma and the definition of the appropriate surgical strategy. Based on our data, we suggest including endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of organic hyperinsulinism in selected patients with inconclusive or uncertain diagnosis before surgery.

http://ift.tt/2nFfc9b

Clinico-Dermoscopic Features of Spitz Naevi by Age and Anatomic Site: A Study of 378 Spitz Naevi

Abstract

Spitz naevi (SN) are benign melanocytic naevi characterized by spindled and epithelioid cells in histology seen in both children and adults. In the present study, we aimed to determine whether there is a difference in the dermoscopic features of SN by age and anatomic site. Previous studies have demonstrated this association in congenital and common naevi.

This article is protected by copyright. All rights reserved.

http://ift.tt/2o2rdXc

Intravenous immunoglobulin contributes to control anti-melanoma differentiation-associated protein 5 (MDA5) antibody-associated dermatomyositis with palmar violaceous macules/papules

Abstract

Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of dermatomyositis (DM) patients who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report 3 cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined modality therapy including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide, and immunoglobulins (IVIG). In all 3 cases, the serum ferritin levels, which are known to represent the disease activity of RP-ILD, were decreased after IVIG administration. IVIG might contribute to control of the disease activity of anti-MDA5 antibody-positive DM. Moreover, palmar violaceous macules/papules around the interphalangeal joints, which was observed in all 3 cases in the incipient stage, might be a useful sign to suggest a diagnosis of anti-MDA5 antibody-associated DM.

This article is protected by copyright. All rights reserved.

http://ift.tt/2na8oxi

Is Universal HLA-B*15:02 Screening a Cost-Effective Option in an Ethnically-Diverse Population? A Case Study of Malaysia

Abstract

Background

Strong association was documented between human leukocyte antigen (HLA)-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Beyond Asia, the HLA testing is potentially valuable in many countries with increasingly diverse communities of Asian ancestry, to facilitate an early recognition of patient susceptibility to SCARs.

Objective

To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/ toxic epidermal necrolysis in an ethnically-diverse Malaysian population.

Methods

A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly-diagnosed epilepsy among adults - (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. From a societal perspective, base-case analysis and sensitivity analyses were performed over lifetime time horizon. Incremental cost-effectiveness ratios were calculated.

Results

In the base-case analysis, both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared to current practice, universal HLA-B*15:02 screening resulted in 0.0255 quality-adjusted life years (QALYs) loss at an additional cost of USD707, while VPA prescribing resulted in 0.2622 QALYs loss at an additional cost of USD4,127, due to estimated differences in antiepileptic treatment efficacy.

Conclusions

This study suggests that universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia compared to current practice. However, with the emergence of an ethnically-diverse population in many other countries, this may render HLA-B*15:02 screening a potentially viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.

This article is protected by copyright. All rights reserved.

http://ift.tt/2o2gJHp

High prevalence of alcohol use disorders in patients with inflammatory skin diseases

Abstract

Background

There is a known association between psoriasis and heavy alcohol consumption. Causality remains unclear with evidence supporting both alcohol triggering psoriasis and psoriasis predisposing to heavy alcohol consumption. However, the association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined.

Objective

To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease.

Methods

We conducted an observational cross sectional study in a single hospital out-patient department. We recruited 609 patients in 5 groups; psoriasis, eczema, cutaneous lupus (lupus), other inflammatory disorders and a reference population with skin lesions. The primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD).

Results

Observed prevalence of AUD was: psoriasis (30.6%), eczema (33.3%), cutaneous lupus (12.3%), other inflammatory disease (21.8%) and non-inflammatory disease (14.3%). Odds ratios(OR) (95% CI) for AUDs in inflammatory groups compared with non-inflammatory, adjusted for age and gender were: psoriasis 1.65 (0.86-3.17), eczema 2.00 (1.03-3.85), lupus 1.03 (0.39-2.71), other inflammatory 1.32 (0.68-2.56). OR were reduced if also adjusted for DLQI. The prevalence of DLQI of ≥11 was: psoriasis 31.1%, eczema 43.7%, cutaneous lupus 17.5%, other inflammatory 17.2% and non-inflammatory 2.8%.

Conclusions

Patients with eczema attending a single site hospital clinic have been shown to have high levels of alcohol use disorders of a similar level to patients with psoriasis and higher than patients with non-inflammatory skin diseases. The role of alcohol in the exacerbation of eczema needs further investigation. Caution and a full alcohol history is recommended when treating eczema patients with potentially hepatotoxic medication. By identifying heavier drinking patients we may be able to support them with interventions to reduce alcohol intake and potentially improve their skin disease.

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Prognostic Importance of the site of Recurrence in Patients with Metastatic Recurrent Cervical Cancer

Publication date: Available online 27 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Tae Hun Kim, Moon-Hong Kim, Beob-Jong Kim, Sang-Il Park, Sang-Young Ryu, Chul-Koo Cho
PurposeThe clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of this study were to investigate survival outcome according to the site of recurrence in a large cohort of cervical cancer patients.Methods and MaterialsOf 1,322 patients with primary cervical cancer from 2000 to 2013, 205 patients with recurrence after primary or adjuvant post-operative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors via the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcome were evaluated retrospectively under approval from the institutional review board.ResultsRegarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump) (10.7%) and pelvic (pelvic lymph nodes or pelvic side wall) (8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as Type-A DO, whereas the other subgroups were labeled Type-B DO. Patients with type-A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The five-year overall survival rates were significantly higher in the Type-A DO group than in the other groups (44.8% in the Type-A DO group, 12.6% in the pelvic group, and 6.8% in the Type-B DO group).ConclusionsWe identified a patient subgroup with favorable outcome after salvage therapy, Type-A DO, which was defined as recurrence in distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.

Teaser

The prognosis of patients with metastatic recurrent cervical cancer is known to be poor despite of salvage therapy. However, this study showed that a subgroup of patients with distant lymph nodes only or lung parenchyma only showed remarkably longer overall survival than the other groups. While the role of active salvage therapy remains unknown, the site of recurrence may have a critical factor in prognosis of metastatic recurrent cervical cancer.


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Defining and Shattering The Glass Ceiling in Radiation Oncology

Publication date: Available online 27 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Miriam A. Knoll




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Late Cardiac Toxicity after Mediastinal Radiotherapy for Hodgkin Lymphoma: Contributions of Coronary Artery and Whole Heart Dose-Volume Variables to Risk Prediction

Publication date: Available online 27 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ezra Hahn, Haiyan Jiang, Angela Ng, Shaheena Bashir, Sameera Ahmed, Richard Tsang, Alexander Sun, Mary Gospodarowicz, David Hodgson
PurposeMediastinal radiotherapy (RT) for Hodgkin Lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry.Methodsand Materials; A random sample of 125 HL patients treated with mediastinal RT was selected and 3D cardiac dose-volume data was generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and three coronary arteries included: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries.ResultsThere were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: Whole heart Dmean (HR 1.09, p=0.0083), dose homogeneity (HR 0.94, p=0.0034), male gender (HR 2.31, p=0.014), and age (HR 1.03, p=0.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, p<0.001), volume of left anterior descending artery receiving 5Gy (HR 0.98, p=0.003), and volume of left circumflex artery receiving 20Gy(HR 1.03, p<0.001).ConclusionIn addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When evaluating all types of cardiotoxicity the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery based model was superior.

Teaser

There are limited data to indicate the potential value of dosimetric parameters other than mean heart dose in predicting late cardiotoxicity after radiation for Hodgkin Lymphoma. We explored the value of these other dosimetric variables. Increasing cardiotoxicity was associated with increasing whole-heart Dmean, increasing cardiac dose inhomogeneity, and also male sex and increasing age; coronary artery dose did not value to predicting all-cause cardiotoxicity. However, when evaluating ischemic cardiac events only, a coronary artery-based model was superior.


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A simple and sensitive aptasensor for colorimetric detection of adenosine triphosphate based on unmodified gold nanoparticles

Publication date: 1 June 2017
Source:Talanta, Volume 168
Author(s): Yu Mao, Tingting Fan, Rachel Gysbers, Yin Tan, Feng Liu, Shuo Lin, Yuyang Jiang
A simple and sensitive colorimetric aptasensor for rapid and facile detection of adenosine triphosphate (ATP) has been demonstrated here based on aptamer-based hairpin probes and unmodified gold nanoparticles (AuNPs). The hairpin probe is constructed by adding another five nucleotides to the 5′-end of an anti-ATP aptamer which can hybridize to nucleotides at the 3′-end of the aptamer, forming a hairpin-shaped structure. In the absence of ATP, the hairpin probes are rigid, and the AuNPs are susceptible to salt-induced aggregation. Conversely, upon binding with target ATP, the hairpin probes undergo conformational changes, forming aptamer-ATP complexes and exposing flexible ends which coat the surface of AuNPs to inhibit their aggregation in the high salt solution. Subsequently, a blue-to-red color change can be recognized by the naked eye. The aptasensor achieved selective responses toward ATP with a detection limit of 0.1μM, and exhibited high-quality detection performance in biological samples. In addition, this detection method is simple, rapid and cost-effective, holding great potential for further applications in point-of-care research.

Graphical abstract

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Antiplasmodial Activity of Targeted Zinc(II)-Dipicolylamine Complexes

Publication date: Available online 27 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Douglas R. Rice, María de Lourdes Betancourt Mendiola, Claribel Murillo-Solano, Lisa A. Checkley, Michael T. Ferdig, Juan C. Pizarro, Bradley D. Smith
This study measured the antiplasmodial activity of nine zinc-dipicolylamine (ZnDPA) complexes against three strains of Plasmodium falciparum, the causative parasite of malaria. Growth inhibition assays showed significant activity against all tested strains, with 50% inhibitory concentrations between 5 and 600 nM and almost no toxic effect against host cells including healthy red blood cells. Fluorescence microscopy studies with a green-fluorescent ZnDPA probe showed selective targeting of infected red blood cells. The results suggest that ZnDPA coordination complexes are promising antiplasmodial agents with potential for targeted malaria treatment.

Graphical abstract

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Mycobacterium tuberculosis lysine-ɛ-aminotransferase a potential target in dormancy: benzthiazole based inhibitors

Publication date: Available online 27 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Rudraraju Srilakshmi Reshma, Variam Ullas Jeankumar, Nidhi Kapoor, Shalini Saxena, Karyakulam Andrews Bobesh, Astakala Rishi Vachaspathy, Pappachan E Kolattukudy, Dharmarajan Sriram
MTB lysine-ɛ-aminotransferase (LAT) was found to play a crucial role in persistence and antibiotic tolerance. LAT serves as a potential target in the management of latent tuberculosis. In present work we attempted to derivatize the benzthiazole lead identified through high throughput virtual screening of Birla Institute of Technology and Science in house database. For Structure activity relationship purpose 22 derivatives were synthesized and characterized. Among synthesized compounds, eight compounds were found to be more efficacious in terms of LAT inhibition when compared to lead compound (IC50 10.38 ± 1.21 µM). Compound 22 exhibits bactericidal action against nutrient starved Mycobacterium tuberculosis (MTB). It also exhibits significant activity in nutrient starvation model (2.9 log folds) and biofilm model (2.3 log folds).

Graphical abstract

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Investigation of Aryl Isonitrile Compounds with Potent, Broad-spectrum Antifungal Activity

Publication date: Available online 27 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Haroon Mohammad, Kwaku Kyei-Baffour, Waleed Younis, Dexter C. Davis, Hassan Eldesouky, Mohamed N. Seleem, Mingji Dai
Invasive fungal infections present a formidable global public health challenge due to the limited number of approved antifungal agents and the emergence of resistance to the frontline treatment options, such as fluconazole. Three fungal pathogens of significant concern are Candida, Cryptococcus, and Aspergillus given their propensity to cause opportunistic infections in immunocompromised individuals. New antifungal agents composed of unique chemical scaffolds are needed to address this public health challenge. The present study examines the structure-activity relationship of a set of aryl isonitrile compounds that possess broad-spectrum antifungal activity primarily against species of Candida and Cryptococcus. The most potent derivatives are capable of inhibiting growth of these key pathogens at concentrations as low as 0.5 µM. Remarkably, the most active compounds exhibit an excellent safety profile and are non-toxic to mammalian cells even at concentrations up to 256 µM. The present study lays the foundation for further investigation of aryl isonitrile compounds as a new class of antifungal agents.

Graphical abstract

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Discovery of acylguanidine oseltamivir carboxylate derivatives as potent neuraminidase inhibitors

Publication date: Available online 27 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Zhaoliang Li, Yanchun Meng, Shengtao Xu, Wang Shen, Zhaoqing Meng, Zhenzhong Wang, Gang Ding, Wenzhe Huang, Wei Xiao, Jinyi Xu
In search of novel anti-influenza agents with higher potency, a series of acylguanidine oseltamivir carboxylate analogues were synthesized and evaluated against influenza viruses (H1N1 and H3N2) in vitro. The representative compounds with strong inhibitory activities (IC50<40nM) against neureminidase (NA) were further tested against the NA from oseltamivir-resistant strain (H259Y). Among them, compounds 9 and 17 were potent NA inhibitors that exhibited a 5 and 11-fold increase in activity comparing with oseltamivir carboxylate (2, OC) against the H259Y mutant, respectively. Furthermore, the effect against influenza virus H259Y mutant (H1N1) replication and cytotoxicity assays indicated that compounds 9 and 17 exhibited a 20 and 6-fold increase than the parent compound 2, and had no obvious cytotoxicity in vitro. Moreover, the molecular docking studies revealed that the docking modes of compounds 9 and 17 were different from that of oseltamivir, and the new hydrogen bonds and hydrophobic interaction were formed in this case. This work provided unique insights in the discovery of potent inhibitors against NAs from wild-type and oseltamivir-resistant strains.

Graphical abstract

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Maternal thyroid parameters in pregnant women with different ethnic backgrounds: do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

Abstract

Objective

Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a TSH upper reference limit (cutoff) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cutoffs (institutional, ethnicity-specific, 2.5 mIU/L (Endocrine Society) and 4.0 mIU/L (American Thyroid Association)).

Design

Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women.

Method

The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-ab), thyroid-stimulating hormone (TSH) and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with Sub-Saharan (SaBg; 28.6%), 754 North-African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded.

Results

The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; p<0.001 respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; p=0.006 and 0.014 respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cutoff, but when 4.0 mIU/L or the institutional cutoff (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1 vs 3.3%, p=0.008 and 0.013 respectively). The use of ethnicity-specific cutoffs did not change the prevalence of SCH as compared to the use of institutional cutoffs. However, when these cutoffs were used the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; p<0.001) relative to the 2.5 mIU/L cutoff,.

Conclusions

Pregnant women with a Sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cutoffs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cutoff.

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Cabergoline-related impulse control disorder in an adolescent with a giant prolactinoma

Giant prolactinomas, rare in children, can have devastating endocrine, neurological and visual sequelae. Dopamine agonists (DA) are effective first-line therapy with few side-effects at doses usually used for prolactinoma treatment¹, but higher-dose therapy for Parkinson's disease has well-recognized associations with impulse control disorders (ICD) including pathological gambling, impulsive eating, compulsive shopping and hypersexuality. Such associations are not well recognized with prolactinomas; to our knowledge this is the first reported case of hypersexuality in an adolescent receiving cabergoline for a giant prolactinoma.

This article is protected by copyright. All rights reserved.

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LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors

Conditions:   Diabetes;   Diabetes Mellitus, Type 2
Interventions:   Drug: liraglutide;   Drug: placebo
Sponsor:   Novo Nordisk A/S
Recruiting - verified March 2017

http://ift.tt/2mICNqp

Study of Oral PQR309 in Patients With Advanced Solid Tumors

Condition:   Cancer
Intervention:   Drug: PQR 309
Sponsors:   PIQUR Therapeutics AG;   Roswell Park Cancer Institute;   M.D. Anderson Cancer Center;   University Hospitals Cleveland Medical Center;   Mayo Clinic;   Hospital Clinic of Barcelona;   University College London Hospitals;   Churchill Hospital
Recruiting - verified March 2017

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IFC (editorial board)

Publication date: April 2017
Source:Peptides, Volume 90





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The International Neuropeptide society pages

Publication date: April 2017
Source:Peptides, Volume 90





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Gayle & Richard Olson prize pages

Publication date: April 2017
Source:Peptides, Volume 90





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Editorial Board/Aims and Scope

Publication date: 4 April 2017
Source:Vaccine, Volume 35, Issue 15





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Pneumococcal carriage and serotype variation before and after introduction of pneumococcal conjugate vaccines in patients with acute otitis media in Switzerland

Publication date: 4 April 2017
Source:Vaccine, Volume 35, Issue 15
Author(s): Aurélie Allemann, Pascal M. Frey, Silvio D. Brugger, Markus Hilty
BackgroundAcute otitis media (AOM) is an important cause for antibiotic prescription within the paediatric population and Streptococcus pneumoniae is a major pathogen associated with AOM episodes. This study aimed at analysing the influence of the heptavalent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) on pneumococcal carriage and serotype distribution in AOM.MethodsNasopharyngeal swabs (NPS) and middle ear fluid (MEF) were collected within a Swiss surveillance study of outpatients from all ages with AOM between 2004 and 2015, covering three vaccination eras (pre-PCV7, PCV7 and PCV13). Samples were cultured for pneumococcal identification, and the association of vaccine era with pneumococcal carriage was investigated by logistic regression analysis adjusting for sociodemographic factors.FindingsIn total, 3300 NPS and 620 MEF were included in this study. The number of samples from patients with AOM dropped over vaccination eras and S. pneumoniae was less frequently isolated in the PCV13 era as compared to the other two eras. The latest (PCV13) vaccination era was independently associated with a reduced pneumococcal carriage within NPS (adjusted odds ratio 0.65, 95%-CI 0.45–0.94). Investigating serotype epidemiology, vaccine serotypes decreased significantly after the conjugate vaccine introductions with the exception of serotype 3. Within the non-PCV13 serotypes, a particular increase of serogroups 11, 15 and 23 was observed in both NPS and MEF.ConclusionA substantial change in pneumococcal carriage and serotype epidemiology suggests an impact of the conjugate vaccines on pneumococcal AOM in Switzerland.



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A recombinant subunit vaccine for bovine RSV and Histophilus somni protects calves against dual pathogen challenge

Publication date: 4 April 2017
Source:Vaccine, Volume 35, Issue 15
Author(s): Laurel J. Gershwin, Nicole E. Behrens, Heather A. McEligot, Francisco R. Carvallo-Chaigneau, Lauren T. Crum, Brianna M. Gunnarson, Lynette B. Corbeil
Bovine respiratory syncytial virus (BRSV) and Histophilus somni synergize to cause respiratory disease in cattle. These pathogens cause enhanced disease during dual-infection and an IgE response to antigens of H. somni in dual-infected but not singly infected calves. Vaccines containing whole inactivated BRSV or H. somni have been associated with IgE responses A vaccine strategy that avoids stimulation of IgE antibodies would provide superior protection from dual infection. We hypothesized that a subunit vaccine consisting of the nucleoprotein (NP) from BRSV and the recombinant antigen IbpA DR2 (a surface antigen of H. somni with two toxic fic motifs) in Quil A adjuvant would elicit protection without disease enhancement. Three groups of calves were vaccinated twice with either: Formalin inactivated BRSV (FI) plus Somnivac®, NP & IbpA DR2 plus Quil A or Quil A alone, followed by BRSV and H. somni challenge. Clinical scores and antibody levels (to whole pathogens and to the subunits) were evaluated. Lungs were examined at necropsy on day 23 after infection. Clinical scores were significantly greatest for the FI & Somnivac® group and both clinical scores and lung pathology were lowest for the subunit group. All calves shed BRSV in nasal secretions. FI & Somnivac® induced IgE antibodies to H. somni and BRSV, but not to NP or DR2. The subunit vaccine did not induce an IgE antibody response to IbpA DR2 antigen and induced little IgE to H. somni. It did not induce an IgG antibody response to BRSV and H. somni, but stimulated production of IgG antibodies against the subunits. In summary, the subunit vaccine, consisting of the BRSV NP and H. somni IbpA DR2 in Quil A, protected against severe clinical signs and decreased lung pathology but did not prevent viral shedding. Importantly it prevented synergistic disease expression in response to dual infection.



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A small-molecule IRF3 agonist functions as an influenza vaccine adjuvant by modulating the antiviral immune response

Publication date: 4 April 2017
Source:Vaccine, Volume 35, Issue 15
Author(s): Peter Probst, John B. Grigg, Myra Wang, Ernesto Muñoz, Yueh-Ming Loo, Renee C. Ireton, Michael Gale, Shawn P. Iadonato, Kristin M. Bedard
Vaccine adjuvants are essential to drive a protective immune response in cases where vaccine antigens are weakly immunogenic, where vaccine antigen is limited, or where an increase in potency is needed for a specific population, such as the elderly. To discover novel vaccine adjuvants, we used a high-throughput screen (HTS) designed to identify small-molecule agonists of the RIG-I-like receptor (RLR) pathway leading to interferon regulatory factor 3 (IRF3) activation. RLRs are a group of cytosolic pattern-recognition receptors that are essential for the recognition of viral nucleic acids during infection. Upon binding of viral nucleic acid ligands, the RLRs become activated and signal to transcription factors, including IRF3, to initiate an innate immune transcriptional program to control virus infection. Among our HTS hits were a series of benzothiazole compounds from which we designed the lead analog, KIN1148. KIN1148 induced dose-dependent IRF3 nuclear translocation and specific activation of IRF3-responsive promoters. Prime-boost immunization of mice with a suboptimal dose of a monovalent pandemic influenza split virus H1N1 A/California/07/2009 vaccine plus KIN1148 protected against a lethal challenge with mouse-adapted influenza virus (A/California/04/2009) and induced an influenza virus-specific IL-10 and Th2 response by T cells derived from lung and lung-draining lymph nodes. Prime-boost immunization with vaccine plus KIN1148, but not prime immunization alone, induced antibodies capable of inhibiting influenza virus hemagglutinin and neutralizing viral infectivity. Nevertheless, a single immunization with vaccine plus KIN1148 provided increased protection over vaccine alone and reduced viral load in the lungs after challenge. These findings suggest that protection was at least partially mediated by a cellular immune component and that the induction of Th2 and immunoregulatory cytokines by a KIN1148-adjuvanted vaccine may be particularly beneficial for ameliorating the immunopathogenesis that is associated with influenza viruses.



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Modulation of regulatory T cells by intranasal allergen immunotherapy in an experimental rat model of airway allergy

Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Saibal Moitra, Ankur Datta, Somnath Mondal, Iman Hazra, Sk Md Omar Faruk, Prasanta K. Das, Anjan K. Basu, Santanu K. Tripathi, Swapna Chaudhuri
Allergic airway diseases such as asthma and allergic rhinitis are increasing in prevalence worldwide. The theory of an altered Th1/Th2 balance in allergic diathesis has recently been termed a "procrustean paradigm" as it failed to explain many preclinical findings. Regulatory T cells (Treg) have now been shown to be critical in T-cell homeostasis and in the maintenance of peripheral tolerance to allergens. Allergen specific immunotherapy (SIT) has been shown to induce regulatory T cells in allergic patients. Among various types of SIT, intranasal immunotherapy had not been studied in detail for the treatment of allergic airway diseases. So, there was a need to study the contribution of regulatory T cells and their mechanistic pathways following intranasal immunotherapy in-vivo. It had been previously shown that intranasal allergen immunotherapy using Alstonia scholaris pollen extract abrogates allergic airway inflammation with decline in IgE and Th2 cytokine levels. The present study for the first time offers a multi-targeted approach towards attenuation of airway allergy by the generation of CD4+CD25+Foxp3+T cells and other subsets of Treg cells like Tr1 cells, Th3 cells, CTLA4+Treg cells, and also modulation of various Treg cell surface molecules like GITR, OX40, CD39 and CD73 by intranasal immunotherapy in the same animal model. This animal experiment will thus help to chart out newer molecular targets for treating allergic asthma or rhinitis.

Graphical abstract

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Cordycepin negatively modulates lipopolysaccharide-induced cytokine production by up-regulation of heme oxygenase-1

Publication date: June 2017
Source:International Immunopharmacology, Volume 47
Author(s): Rui Qing, Zezhi Huang, Yufei Tang, Qingke Xiang, Fan Yang
AimsThe present study is to investigate the effect of cordycepin on the expression of heme oxygenase-1 (HO-1) in lipopolysaccharide (LPS)-activated microphages, as well as its mechanism of action.MethodsMouse RAW264.7 cells were treated with different concentrations of cordycepin for 0–16h. Western blotting was used to determine the expression of HO-1 and the phosphorylation of c-Src and the p47^phox subunit of NADPH oxidase. Intracellular reactive oxygen species (ROS) level was determined using H2DCFDA as fluorescent probe. Laser-scanning confocal microscopy was used to visualize the nuclear translocation of NF-E2-related factor 2 (Nrf2). Enzyme-linked immunosorbent assay was performed to measure the inhibitory effect of cordycepin on LPS-induced secretion of tumor necrosis factor-α and interleukin-6.ResultsCordycepin induced the phosphorylation of c-Src and p47^phox subunit of NADPH oxidase in RAW264.7 cells. Cordycepin increased the secretion of ROS by activating NADPH oxidase. In addition, cordycepin enhanced the expression of HO-1 in RAW264.7 cells in both dose- and time-dependent manners. Of note, elevated HO-1 expression induced by cordycepin treatment was regulated by c-Src/NADPH oxidase/ROS pathway. HO-1 expression induced by cordycepin was dependent on the activation of Nrf2, which was regulated by c-Src/NADPH oxidase/ROS. Cordycepin reduced LPS-induced secretion of proinflammatory cytokines through up-regulation of HO-1.ConclusionThe present study demonstrates that cordycepin induces the expression of HO-1 in RAW264.7 cells via c-Src/NADPH oxidase/ROS/Nrf2 pathway, and plays an anti-inflammatory role by inhibiting the secretion of cytokines from macrophages.



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A novel approach to segmentation and measurement of medical image using level set methods

Publication date: June 2017
Source:Magnetic Resonance Imaging, Volume 39
Author(s): Yao-Tien Chen
The study proposes a novel approach for segmentation and visualization plus value-added surface area and volume measurements for brain medical image analysis. The proposed method contains edge detection and Bayesian based level set segmentation, surface and volume rendering, and surface area and volume measurements for 3D objects of interest (i.e., brain tumor, brain tissue, or whole brain).Two extensions based on edge detection and Bayesian level set are first used to segment 3D objects. Ray casting and a modified marching cubes algorithm are then adopted to facilitate volume and surface visualization of medical-image dataset. To provide physicians with more useful information for diagnosis, the surface area and volume of an examined 3D object are calculated by the techniques of linear algebra and surface integration. Experiment results are finally reported in terms of 3D object extraction, surface and volume rendering, and surface area and volume measurements for medical image analysis.



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Efficient dibutyltin (DBT) elimination by the microscopic fungus Metarhizium robertsii under conditions of intensive aeration and ascorbic acid supplementation

Abstract

Dibutyltin (DBT) is an environmental pollutant characterized by immunotoxic, neurotoxic, and pro-oxidant properties. In this study, an attempt was made to enhance DBT elimination by the Metarhizium robertsii strain. We observed enhanced fungal growth in the bioreactor (pO₂ ≥ 20%) compared to flask cultures (μ _max increased from 0.061 to 0.086 h⁻¹). Moreover, under aerated conditions, M. robertsii mycelium with "hairy" morphology biodegraded DBT (20 mg l⁻¹) 10-fold faster in the bioreactor than in the flask cultures. Monobutyltin (MBT) and a hydroxylated derivative of MBT (OHBuSnH₂) were detected as by-products of dibutyltin debutylation. Simultaneous usage of glucose and butyltins indicates the comatabolic nature of monobutyltin and dibutyltin removal. In order to protect fungal cells from oxidative stress caused by DBT presence, vitamin C (20 mg l⁻¹) was applied. Supplementation with ascorbic acid (AA) resulted in a 3-fold acceleration of MBT removal during the first 7 h of incubation. Using the HPLC-MS/MS technique, a quantitative analysis of malondialdehyde (MDA), a marker of oxidative stress, was performed. In the AA presence, a decrease in the MDA amount (about 45%) was observed compared to the case with fungal cells exposed to DBT alone.

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Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

Kisspeptin and neurokinin B (NKB) are neuropeptides co-expressed in the mammalian hypothalamus and coordinately control GnRH signaling. We have found that Nkb and kisspeptin neurons are distinct in the teleost, striped bass (STB) and capitalized on this phenomenon to study the mode of action of Nkb and its related neuropeptide-F (Nkf), both of which are encoded by the tac3 gene. In vitro brain slices and in vivo administration studies revealed that Nkb/f consistently downregulated kiss2, whereas antagonist (AntD) administration restored this effect. Overall, a minor effect was noted on gnrh1 expression, whereas Gnrh1 content in the pituitaries was reduced after Nkb/f treatment and increased with AntD. Concomitantly, immunostaining demonstrated that hypothalamic Nkb neurons border and densely innervate the largest kiss2 neuronal population in the hypothalamus, which also coexpresses Nkb receptor. No expression of Nkb receptor or Nkb neuronal projections was detected near/in Gnrh1 soma in the preoptic area. At the level of the pituitary, however, the picture was more complex: both Nkb/f and AntD upregulated lhb and fshb expression and Lh secretion in vivo. Together with the stimulatory effect of Nkb/f on Lh/Fsh secretion from pituitary cells, in vitro, this may indicate an additional independent action of Nkb/f within the pituitary, in which the hypothalamic pathway is more dominant. The current study demonstrates that Nkb/f utilizes multiple pathways to regulate reproduction in the STB and that in the brain, Nkb mainly acts as a negative modulator of kiss2 to regulate the release of Gnrh1.

http://ift.tt/2mHTKkE

The influence of citrate and oxalate on 99TcVII, Cs, NpV and UVI sorption to a Savannah River Site soil

Publication date: June 2017
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): D. Montgomery, K. Barber, N. Edayilam, K. Oqujiuba, S. Young, T. Biotidara, A. Gathers, M. Danjaji, N. Tharayil, N. Martinez, B. Powell
Batch sorption experiments were conducted with 0.5–50 ppb ⁹⁹Tc, ¹³³Cs, ²³⁷Np and U in the presence and absence of citrate and/or oxalate in a 25 g/L Savannah River Site (SRS) soil suspension. Citrate and oxalate were the ligands of choice due to their relevancy to plant exudates, the nuclides were selected for their wide range of biogeochemical behavior, and the soil from SRS was selected as a model Department of Energy (DOE) site soil. Batch samples were continually mixed on a rotary shaker and maintained at a pH of approximately 5. Analysis via ICP-MS indicated that sorption of ²³⁷Np increased with ligand concentration compared to baseline studies, as did sorption of ⁹⁹Tc although to a lesser extent. The increased sorption of ²³⁷Np is proposed to be due to a combination of factors that are dependent on the ligand(s) present in the specific system including, ligand dissolution of the soil by citrate and formation of tertiary soil-oxalate-Np complexes. The increased ⁹⁹Tc sorption is attributed to the dissolution of the soil by the ligands, leading to an increase in the number of available sorption sites for ⁹⁹Tc. Uranium sorption decreased and dissolution of native uranium was also observed with increasing ligand concentration, thought to be a result of the formation of strong U-ligand complexes remaining in the aqueous phase. The majority of these effects were observed at the highest ligand concentrations of 50 mgC/L. No notable changes were observed for the ¹³³Cs system which is ascribed to the minimal interaction of Cs⁺ with these organic ligands.



http://ift.tt/2nZZ2IH

Role of germinal centers for the induction of broadly-reactive memory B cells

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Yoshimasa Takahashi, Garnett Kelsoe
Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continued survival/proliferation of B cells that bind with low affinity or react to cryptic epitopes, increasing their chance of memory recruitment. In this review, we discuss the adaptive strategies of B-cell memory to viral antigenic variations.



http://ift.tt/2nX37N5

Scholar : These new articles for AIDS Care are available online

The online platform for Taylor & Francis Online content New for AIDS Care and online now on Taylor & Francis Online: Original Articles Meaning in life, resilience, and psychological well-being among children affected by parental HIV Hongfei Du, Xiaoming Li, Peilian Chi, Junfeng Zhao & Guoxiang Zhao Pages: 1-7 | DOI: 10.1080/09540121.2017.1307923 Emerging from the database shadows: characterizing undocumented immigrants in a large cohort of HIV-infected persons Jonathan Ross, David B. Hanna, Uriel R. Felsen, Chinazo O. Cunningham & Viraj V. Patel Pages: 1-8 | DOI: 10.1080/09540121.2017.1307921 Now available - Human Service Organizations: Management, Leadership & Governance BEST ARTICLES – click here. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Hi

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Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Regulatory elements: A boost to RNA processing

Nature Reviews Genetics. doi:10.1038/nrg.2017.20

Author: Linda Koch

http://ift.tt/2nDKe1j

Genome organization: Zooming in on nuclear organization

Nature Reviews Genetics. doi:10.1038/nrg.2017.23

Author: Katharine H. Wrighton

http://ift.tt/2omldVl

Functional variomics and network perturbation: connecting genotype to phenotype in cancer

Nature Reviews Genetics. doi:10.1038/nrg.2017.8

Authors: Song Yi, Shengda Lin, Yongsheng Li, Wei Zhao, Gordon B. Mills & Nidhi Sahni

http://ift.tt/2nDRTNh

Disease genomics: Transitioning from association to causation with eQTLs

Nature Reviews Genetics. doi:10.1038/nrg.2017.22

Author: Dorothy Clyde

http://ift.tt/2omp6ts

Cimicifugamide from Cimicifuga rhizomes functions as a nonselective β-AR agonist for cardiac and sudorific effects

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): ZengYong Wang, Qian Wang, Man Zhang, XueYan Hu, GuoYu Ding, Min Jiang, Gang Bai
Cimicifuga rhizomes (CR) are used in the treatment of respiratory and cardiovascular diseases in traditional Chinese medicine, but their key effective components and mechanism of action have not yet been reported. In this study, the cardiac, antipyretic and sudorific effects of CR were evaluated using the toad heart failure in vitro model and mice fever and sweating in vivo models. Moreover, the UPLC/Q-TOF-MS-integrated β2-AR luciferase reporter gene assay system was used to screen the bioactive ingredients from CR extract, and the activity of this ingredient were verified using the above-mentioned in vitro and vivo models. Our results showed that CR had anti-heart failure, antipyretic and sweating effects, which could be antagonized by propranolol. On the other hand, cimicifugamide was screened as β2-AR agonist from CR and cimicifugamide could activate β1, 2-ARs more significantly than β3-AR in β-ARs selectivity assessment. The results not only revealed the key effective components and mechanism of CR in traditional use but also supplied a characteristic complementary ingredient for quality control of CR.

Graphical abstract

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Induction of apoptotic DNA fragmentation mediated by mitochondrial pathway with caspase-3-dependent BID cleavage in human gastric cancer cells by a new nitroxyl spin-labeled derivative of podophyllotoxin

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Yu-Jie Yang, She-Ning Qi, Rui-Yue Shi, Jun Yao, Li-Sheng Wang, Hu-Qin Yuan, Yuan-Xue Jing
Purpose4-[4′′-(2′′, 2′′, 6′′, 6′′-tetramethyl-l′′-piperidinyloxy) amino]–4′-demethyl-epipodophyllotoxin (GP7) is a new semi-synthesized nitroxyl spin-labeled derivative of podophyllotoxin with anti-leukemic and anti-osteosarcoma effects. The purpose of the present study is to investigate the anti-gastric cancer (GC) effects of GP7 and the possible involvement of caspase pathway in GP7-induced apoptotic DNA fragmentation in human GC cells.Materials and methodsEffects of GP7 on the proliferation of human GC cell lines MKN28, AGS, BGC-823 and HGC-27 in different degrees of differentiation and normal human gastric epithelial cell line GES-1 were studied by MTT assay and compared with the effects of etoposide. Effects of GP7 on cell viability and heat shock protein 90 expression of BGC-823 and HGC-27 cells were analyzed by trypan blue exclusion test and western blotting, respectively. Effects of GP7 on apoptotic DNA fragmentation and caspase pathway of BGC-823 and HGC-27 cells were detected by agarose gel electrophoresis, colorimetric assay and western blotting. Caspase-3 inhibitor was used to manipulate the activity of caspase-3.ResultsGP7 inhibited concentration- and time-dependently the proliferation of human GC cells, and the inhibitory effect of GP7 on the proliferation of BGC-823 or HGC-27 cells was 1.15- or 1.21-fold higher than that of etoposide. GP7 downregulated heat shock protein 90, improved the anti-GC effects of adriamycin, cisplatin, 5-fluorouracil and their combinations, induced apoptotic DNA fragmentation, activations of caspase-9 and -3 but not -8, cytochrome-c release and BID cleavage in BGC-823 and HGC-27 cells. Caspase-3 inhibitor abrogated GP7-induced BID cleavage, decreased cytochrome-c release, caspase-9 and -3 activities and apoptotic DNA fragmentation but increased cell viability in BGC-823 and HGC-27 cells.ConclusionOur findings indicate that GP7 is a promising anti-GC derivative of podophyllotoxin, and GP7-induced apoptosis in human GC cells may be mediated by mitochondrial pathway with caspase-3-dependent BID cleavage.



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Enhance the anti-renca carcinoma effect of a DNA vaccine targeting G250 gene by co-expression with cytotoxic T-lymphocyte associated antigen-4(CTLA-4)

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Youguang Zhao, Zhitao Wei, Hang Yang, Xiaowei Li, Qiwu Wang, Liang Wang, Shadan Li
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Co-expression specific antigens and extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for its enhancement on G250/MN/CA IX (G250)-specific immune responses and its anti-tumor effects in renal carcinoma mice model. Consequently, we constructed a DNA vaccine containing the G250 and the CTLA-4 gene. Vaccination with the co-expression DNA not only induced much higher level of anti-CTLA4 and anti-G250 antibody, but also increased G250-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with G250-expressing tumors were generated. After injection into the tumor-bearing mouse model, the plasmid carrying the co-expression gene of CTLA4 and G250 showed stronger inhibition of tumor growth than the plasmid expressing CTLA4 or G250 alone. These observations emphasize the potential of the CTLA4 and G250 co-expression DNA vaccine, which could represent a promising approach for tumor immunotherapy.



http://ift.tt/2nZk4qX

Fluorescence resonance energy transfer usage to track the sequence promoter changes in CGB5 gene in ovarian cancer patients

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Mirosław Andrusiewicz, Izabela Skibińska, Emilia Gąsiorowska, Piotr Białas, Małgorzata Kotwicka
PurposeThe survival rates for ovarian cancer patients remain very low, often as a result of late diagnosis due to the asymptomatic course of the early stage disease. Based on the important biological contribution of human chorionic gonadotropin to various key processes including; cell cycle control, DNA repair, cellular differentiation and developmental processes, we hypothesized that genetic polymorphisms in the genes promoter could be associated with ovarian cancer risk. Thus, the purpose of the study was to determine whether particular polymorphisms occur in the promoter region of the human chorionic gonadotropin polypeptide 5 encoding gene, and if so, are they associated with ovarian cancer outcome.Patients and methodsWe analyzed Central European females diagnosed with ovarian cancer (n=95) and controls (n=76) for the occurrence of at least one of three polymorphisms (rs7260002, rs7246045, rs540432391) and their impact on cancer risk. The fluorescence resonance energy transfer technique was used in order to conduct single nucleotide polymorphisms genotyping.ResultsThe occurrence of two studied polymorphisms, rs7260002 and rs540432391 present in the 5′ upstream region of the chorionic gonadotropin (CG) gene were associated with an increased risk of ovarian cancer. The former polymorphism had a minor impact on cancer risk (P=0.049; OR=1.95; 95% CI=0.97–3.92), while the latter had a much larger impact and may be of great importance in the evaluation of cancer development in the analyzed population (p<0.001; OR 8.5; 95% CI 3.59–20.23).ConclusionsThe fluorescence resonance energy transfer application used in tracking the sequence promoter variations of genes expressed during tumorigenesis may be an important factor in early prediction of ovarian cancer. Taking under consideration the elevated CG expression associated with several different cancer types it seems reasonable to estimate if the analyzed polymorphisms could affect cancer outcome.



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The effect of theophylline on acetic acid induced ulcerative colitis in rats

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Masoumeh Ghasemi-Pirbaluti, Ehsan Motaghi, Ali Najafi, Mohammad Javad Hosseini
BackgroundUlcerative colitis is a relapsing inflammatory disorder of the colon. There is a need to explore the new treatments for this disorder. Theophylline, a competitive inhibitor of phosphodiesterase, is shown to have anti-inflammatory properties. However, the effect of theophylline on ulcerative colitis has not yet been investigated. The present study evaluated the effect of theophylline on acetic acid induced ulcerative colitis in rats.Materials and methodsColitis was induced by instillation of 2ml of acetic acid solution (3%). Colon samples were evaluated grossly and microscopically and assayed for myeloperoxidase (MPO) activity and proinflammatory cytokine concentrations.ResultsTreatment with theophylline at the doses of 20 and 50mg/kg attenuated acetic acid induced ulcerative colitis as shown by improvement in body weight loss, macroscopic score, ulcer area, hematocrit and histopathological score. Theophylline treatment also reduced MPO activity and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1 β) and interleukin 6 (IL-6) concentrations in inflamed colon.ConclusionTheophylline has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities. Therefore, theophylline has the potential to be used for successful treatment of ulcerative colitis.



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Physicochemical characterization of the oolong tea polysaccharides with high molecular weight and their synergistic effects in combination with polyphenols on hepatocellular carcinoma

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Jingya Wang, Wei Liu, Zhongqin Chen, Haixia Chen
This study was to investigate the synergistic effects of polysaccharides with the molecular weight more than 80kDa (OTPS1) and polyphenols (OTP) isolated from oolong tea on hepatocellular carcinoma (HCC) in vitro and in vivo. The physicochemical properties of OTPS fractions were characterized. The synergistic effects of OTPS1 and OTP were evaluated based on the combination index (CI). Results showed that the highest uronic acid contents (32.96%) and viscosity (239.56mLg⁻¹), multicavity structure of OTPS1 were contributed to the synergistic effects with OTP (52.17% content of epigallocatechin-3-gallate (EGCG)). OTPS1 and OTP showed the strongest synergism ability on SMMC7721 cells (CI<0.2). Co-administrated with OTPS1 and OTP exhibited the synergistic effects on the tumor proliferation and growth with the CI values of 0.34 and 0.39, respectively. Antioxidative and immune levels of the mice were obviously increased after combination administration. These results suggested that OTPS1 in combination with OTP might be functional supplements for the treatment of HCC.

Graphical abstract

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Effect of aquo-alchoholic extract of Glycyrrhiza glabra against Pseudomonas aeruginosa in Mice Lung Infection Model

Publication date: June 2017
Source:Biomedicine & Pharmacotherapy, Volume 90
Author(s): Ankita Singh Chakotiya, Ankit Tanwar, Pranay Srivastava, Alka Narula, Rakesh Kumar Sharma
The prevalence of lung infection caused by Pseudomonas aeruginosa strains that are classified as multi-drug resistant has increased considerably and is mainly attributed to relative insufficiency of potent chemotherapeutic modalities. The present study was conducted to evaluate the antimicrobial activity of aquo-alcoholic extract of Glycyrrhiza glabra against the P. aeruginosa causing lung infection in Swiss albino mice. The study involves evaluation of lethal dose of P. aeruginosa in Swiss albino mice and analysis of disease manifestation that includes bacteremia, hypothermia, reduction in body weight and other parameters for 48h of infection. Physical manifestations of infected mice showed a significant decline in body temperature that is 29±0.57°C (at 48th h) from 38.81±0.33°C (0h) and 30% weight loss was observed at the end of the study. Further the efficacy of G. glabra extract against lung infection induced with the calculated lethal dose was evaluated by employing bacteremia, histopathology and radiological analysis. Bacterial burden showed that 2.30±0.02 Log10CFU/mL at day 7, a significant decline in the bacterial load as compared to day 1 when the bacterial burden was found to be 3.32±0.1 Log10CFU/mL. Histopathological results showed more diffuse and patchy accumulation of inflammatory cells within the alveolar space also the infiltrates were noted in all the lung section of infected mice. In treated animal group improved lung histology was seen with the exudates were less seen in D1 dose (20mg/kg) and disappeared in D2 dose (80mg/kg). The study clearly declares that the G. glabra extract is effective against lung infection caused by P. aeruginosa at dose of 80mg/kg. The LCMS results revealed that the extract contains Glycyrrhizin, Stigmasterol and Ergosterol, Licochalcone and Glabridin. The current study expected to further exploit the biomedical properties of this extract in the preparation of a potent regimen against such threatening pathogen.



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Report of the 13th Annual International Pachyonychia Congenita Consortium Symposium

Summary

The International Pachyonychia Congenita Consortium (IPCC) is a group of physicians and scientists from around the world dedicated to developing therapies for pachyonychia congenita, a rare autosomal dominant skin disorder. The research presented at the 13th Annual Research Symposium of the IPCC, held on 10–11 May 2016, in Scottsdale, AZ, U.S.A., is reported here.

http://ift.tt/2o8o1GA

Clinical characteristics and follow-up results of 12 cases of paradoxical embolism

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Hong-liang Zhang, Zhi-hong Liu, Qin Luo, Yong Wang, Zhi-hui Zhao, Chang-ming Xiong
This article contains the clinical characteristics of the paradoxical embolized patients and the following up results. Data included are related to the article "Paradoxical embolism: Experiences from a single center" (Zhang Hong-liang, Liu Zhi-hong, Luo Qin, Wang Yong, Zhao Zhi-hui, Xiong Chang-ming, in press) [1]. The data are obtained from the hospital records and telephone interview.



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Data on the effects of anti-cancer drug of resveratrol in breast cancer cells, MDA-MB-231 cells

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Eunmi Park
The data here is related to the article, "Curcumin enhances poly (ADP-ribose) polymerase inhibitor sensitivity to chemotherapy in breast cancer cells" (Y.E Choi, and E. Park, 2015) [1]. The article shows that curcumin, as a natural bioactive compound, enhanced DNA damage response and induced cell death in MDA-MB-231 cells [1]. This data includes that breast cancer cells, MDA-MB-231 respond to DNA damage after UV irradiation, post to resveratrol treatment. The data shows that resveratrol treatment results in reduction of S-phase cell cycle and induction of γ-H2AX, which is a hallmark of DNA damage after UV irradiation in breast cancer cells, MDA-MB-231. Moreover, resveratrol sensitizes breast cancer cells to respond to UV treatment as a natural bioactive compound.



http://ift.tt/2nVRDtz

Data on subgroup specific baseline characteristics and serum sphingosine-1-phosphate concentrations in the Study of Health in Pomerania

Publication date: June 2017
Source:Data in Brief, Volume 12
Author(s): Eileen Moritz, Danilo Wegner, Stefan Groß, Martin Bahls, Marcus Dörr, Stephan B. Felix, Till Ittermann, Stefan Oswald, Matthias Nauck, Nele Friedrich, Rainer H. Böger, Günter Daum, Edzard Schwedhelm, Bernhard H. Rauch
In this data article, we provide subgroup specific baseline characteristics and serum sphingosine-1-phosphate (S1P) concentrations for healthy individuals within the Study of Health in Pomerania (SHIP)-TREND cohort. After exclusion of subjects with cardiovascular disease, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes and/or chronic kidney disease stadium III or IV, four subgroups were defined according to different limits for body mass index (BMI), alterations in blood lipid levels and smoking status. Tables show respective clinical and laboratory parameters stratified by gender. Serum S1P concentrations are also stratified by age groups. The data presented herein is related to the research article entitled "Reference intervals for serum sphingosine-1-phosphate in the population-based Study of Health in Pomerania" (E. Moritz, D. Wegner, S. Groß, M. Bahls, M. Dörr, S.B. Felix, T. Ittermann, S. Oswald, M. Nauck, N. Friedrich, R.H. Böger, G. Daum, E. Schwedhelm, B.H. Rauch, Clin Chim Acta. 468 (2017) 25–31) [1].



http://ift.tt/2nm46DY

Genome organization: Zooming in on nuclear organization

Two studies report new methods for studying the 3D genome — one captures three-way contacts and the other calculates 3D structures of genomes in single cells.

http://ift.tt/2n7P7LY

Disease genomics: Transitioning from association to causation with eQTLs

http://ift.tt/2nDIZzh

Regulatory elements: A boost to RNA processing

http://ift.tt/2n7JXQh

Functional variomics and network perturbation: connecting genotype to phenotype in cancer

The abundance and heterogeneity of mutations in cancer create challenges for understanding their effects, but such functional characterization will be crucial for optimizing clinical care. In this Review, the authors discuss diverse computational tools and systems biology experimental strategies for elucidating the functional effects of cancer mutations, including consequences on gene regulation, protein structure and local and global perturbations of molecular interaction networks.

http://ift.tt/2nDRrOJ

Lichenoid folliculitis, a unifying concept

Abstract

Skin diseases presenting with keratotic papules, atrophy, cicatricial alopecia, and/or "lichenoid" histopathologic changes have been described under at least 30 names. This family of diseases contains two subgroups, largely based on clinical features: keratosis pilaris atrophicans (KPA; including keratosis pilaris atrophicans faciei/ulerythema ophryogenes, atrophoderma vermiculata , and keratosis follicularis spinulosa decalvans); and the lichen planopilaris (LPP) subgroup (including LPP, frontal fibrosing alopecia, Graham-Little-Piccardi-Lassueur Syndrome, and fibrosing alopecia in a pattern distribution). An interface dermatitis with lichenoid inflammation is characteristic of the LPP group of disorders, but the literature provides scant information about the histopathology of the KPA group. Our experience has been that the two subgroups show a unifying histologic similarity as well as considerable clinical overlap. Since these conditions overlap clinically and histologically, we propose that the term lichenoid folliculitis (LF) be used to refer to this group of diseases, thus simplifying cumbersome nomenclature and highlighting the possibility of shared pathogenesis and treatment options.

http://ift.tt/2nDni26

Clinical Thyroidology High-Impact Articles

FREE ACCESS through April 7, 2017.
Read Now:

Multimodality Treatment with Surgery, External-Beam Radiation, and Chemotherapy Improves Survival for Selected Patients with Anaplastic Thyroid Cancer
Masha J. Livhits, Michael W. Yeh

Active Surveillance of Small, Low-Risk Papillary Thyroid Cancers Can Be a Safe Alternative to Surgery in Selected Patients
Angela M. Leung

Pregnancy Has Little Effect on the Progression of Differentiated Thyroid Cancer in Women with an Excellent, Indeterminate, or Biochemically Incomplete Risk Classification Status
Charles H. Emerson

Large NIFTP Have a Very Low Risk of Recurrence
Jerome M. Hershman

The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.

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