Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide and bevacizumab or placebo

Abstract

Background

In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed GBM patients treated with chemoradiation with or without bevacizumab (BV).

Methods

798 patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had >4 MRI scans for response evaluation. The volume of contrast enhancing tumor was quantified and used for subsequent analyses.

Results

A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (HR=1.578,P<0.0001) but not BV-treated group (HR=1.135,P=0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR=1.692,P=0.0005) and a trend toward longer OS was seen in BV-treated patients (HR=1.264,P=0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR=0.7509, P=0.0127) when accounting for age (P=0.0002), KPS (P=0.1516), post-surgical tumor volume (P<0.0001), MGMT status (P<0.0001), and treatment type (P=0.7637) using the post-chemoradiation baseline.

Conclusions

The post-chemoradiation time point is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

The TNF Receptor Family Member Fn14 is Highly Expressed in Recurrent Glioblastoma (GBM) and in GBM Patient-Derived Xenografts With Acquired Temozolomide Resistance

Abstract

Background

Glioblastoma (GBM) is a difficult-to-treat brain cancer that nearly uniformly recurs, and recurrent tumors are largely therapy-resistant. Our prior work has demonstrated an important role for the TWEAK receptor Fn14 in GBM patho-biology. In this study, we investigated Fn14 expression in recurrent GBM and in the setting of temozolomide (TMZ) resistance.

Methods

Fn14 mRNA expression levels in the non-neoplastic brain, primary (newly diagnosed) GBM, and recurrent GBM (post-chemotherapy and radiation) specimens were obtained from the TCGA data portal. Immunohistochemistry was performed using non-neoplastic brain, patient-matched primary and recurrent GBM, and gliosarcoma (GSM) specimens to examine Fn14 protein levels. Western blot analysis was used to compare Fn14 expression in parental TMZ-sensitive or matched TMZ-resistant patient-derived xenografts (PDXs) established from primary or recurrent tumor samples. The migratory capacity of control and Fn14-depleted TMZ-resistant GBM cells was assessed using the transwell migration assay.

Results

We found that Fn14 is more highly expressed in recurrent GBM tumors than their matched primary GBM counterparts. Fn14 expression is also significantly elevated in GSM tumors. GBM PDX cells with acquired TMZ resistance have higher Fn14 levels and greater migratory capacity than their corresponding parental TMZ-sensitive cells, and the migratory difference is due, at least in part, to Fn14 expression in the TMZ-resistant cells.

Conclusions

This study demonstrates that the Fn14 gene is highly expressed in recurrent GBM, GSM, and TMZ-resistant GBM PDX tumors. These findings suggest that Fn14 may be a valuable therapeutic target or drug delivery portal for treatment of recurrent GBM and GSM patients.

Meningioma transcription factors link cell lineage with systemic metabolic cues

Abstract

Background

Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability.

Methods

Here, we used the most common brain tumor, meningioma, which is strongly associated with female gender and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues. Meningioma patient-derived cell lines (PDCLs) were used for further validation and characterization.

Results

We identified eight TFs highly-enriched in meningioma. Expression of these TFs, which included SIX1, readily distinguished meningiomas from other primary brain tumors and was maintained in PDCLs and even in pulmonary meningothelial nodules. In meningioma PDCL, SIX1 and its co-activator EYA2, supported the expression of the leptin receptor (LEPR), the cell-surface receptor for leptin (LEP), the adipose-specific hormone that is high in women and in individuals with high BMI. Notably, these transcriptional regulatory factors, LEPR and LEP all contributed to support meningioma PDCL proliferation and survival, elucidating a survival dependency on both a core transcriptional program and a metabolic cell-surface receptor.

Conclusions

These findings provide one rationale for why lineage TF expression is maintained in meningioma and for the epidemiological association of female gender and obesity with meningioma risk.

Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development

Abstract

Background

Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear.

Methods

We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism.

Results

PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR.

Conclusions

Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

Radio-pharmaceuticals for cancer treatment – are they ready for prime time yet?

Functional immune characterization of HIV-associated non-small cell lung cancer

It’s time to rethink weight loss in cancer

Letter to the editor on “Body mass index and 20-specific cancers - re-analyses of dose-response meta-analyses of observational studies”

Representation of Obese Participants in Obesity-Related Cancer Randomized Trials

Abstract

Background

Obesity is a risk factor for numerous cancer types, and may influence cancer treatment outcomes. Underrepresentation of obese patients in obesity-related cancer randomized controlled trials (RCTs) may affect generalizability of results. We aimed to assess the reporting of information about eligibility and enrollment of obese participants in obesity-related cancer RCTs.

Methods

We conducted a systematic review of RCTs of 10 obesity-related cancer types (esophagus, colon/rectum, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovary, kidney, and thyroid cancer). We selected RCTs published between 2013 and 2016 in 5 major journals. For each trial, we examined the article, the protocol, and the registration record. We assessed if eligibility criteria limiting the enrollment of obese participants were reported, the proportion of obese participants that were enrolled, and if a subgroup analysis according to obesity status was reported. We systematically contacted corresponding authors and asked for information about eligibility of obese participants and the proportion of obese participants.

Results

We included 76 RCTs. Colon/rectum (n = 20), postmenopausal breast (n = 11), and kidney (n = 11) cancers were the most frequent types. Based on publicly available sources, information on the eligibility of obese participants was available in 5 (7%) trials. The proportion of obese participants could be estimated in 9 (12%) trials only. We found a subgroup analysis in only one RCT. When considering unpublished information, the eligibility of obese participants was explicitly stated in 31 (41%) trials but it was unclear if the remaining 59% trials considered obese participants as eligible and what proportion of obese participants was included. Across 22 trials, the median proportion of obese participants included was 18% [Q1-Q3 11-23].

Conclusion

Information on the eligibility and enrollment of obese participants in cancer RCTs is dramatically underreported. More transparency is needed to understand the applicability of obesity-related cancer RCT results to obese patients with cancer.

“ARTE and Craft of Bevacizumab in Elderly Patients with Glioblastoma”

Tailoring treatment of salivary duct carcinoma (SDC) by liquid biopsy:ARv7 expression in circulating tumor cells

Primary Tumor Sidedness and Benefit from FOLFOXIRI plus Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer

Abstract

Background

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.

Patients and methods

Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status.

Results

Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS (23.7 vs 31.0 months, HR = 1.42 [95%CI, 1.09-1.84], P=0.010) and a trend toward shorter PFS (10.2 vs 11.5 months, HR = 1.24 [95%CI:0.98-1.56], P=0.083) than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 vs. 0.89, P-for-interaction=0.099) and OS (HR = 0.56 vs. 0.99, P-for-interaction=0.030) and this advantage was independent of their RAS and BRAF status.

Conclusions

FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.

Hatchet Flap With Transposed Nasal Inset for Midfacial Reconstruction

Purpose: The purpose of this study is to report the surgical technique and functional outcomes of the hatchet flap with transposed nasal inset for midfacial defect repairs. Methods: An Institutional Review Board–approved, retrospective review was performed to identify patients treated using the hatchet flap with transposed nasal inset. Patient demographics, disease etiology, defect characteristics, and postoperative complications were collected from preoperative and follow-up visits. Results: The hatchet flap with transposed nasal inset was performed in 5 patients between March 2016 and April 2017. Two patients developed mild transient ischemia of the nasal inset flap tip without necrosis. A suture granuloma was removed in 1 patient. No additional surgical procedures were required after the nasal inset cheek flap. Conclusions: The hatchet flap with transposed nasal inset is an effective procedure to address defects involving the upper cheek, lower eyelid, and medial canthus. Incorporation of the nasal inset helps prevent distortion of the ala and facilitates closure of the flap donor site. This technique may be employed in certain patients as an acceptable alternative to more extensive Mustardé or paramedian forehead flaps. Accepted for publication February 14, 2018. The authors have no financial or conflicts of interest to disclose. Presented at the American Society of Ophthalmic Plastic and Reconstructive Surgery Fall Scientific Symposium on November 10, 2017 in New Orleans, LA; and at the European Society of Ophthalmic Plastic and Reconstructive Surgery on September 16, 2017 in Stockholm, Sweden. Address correspondence and reprint requests to Philip L. Custer, M.D., F.A.C.S., Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8096, St. Louis, MO 63110. E-mail: Custer@wustl.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Transconjunctival Triamcinolone Injection for Upper Lid Retraction in Thyroid Eye Disease—A New Injection Method

Purpose: To evaluate the role of transconjunctival triamcinolone acetonide (TA) injection in the management of upper eyelid retraction in thyroid eye disease. Methods: Retrospective interventional review of all patients who underwent transconjunctival TA injection (40 mg/mL) for thyroid eye disease–related upper eyelid retraction from January 2010 to December 2016 in a single tertiary institution. The present study comprised 2 groups: Patients receiving only TA injection (group 1), and patients receiving both TA injection and other immunosuppressive therapy (group 2). Results: There were a total of 99 patients and 135 eyes. Group 1 comprised of 36 eyes (26.7%), while group 2 comprised 99 (73.3%). Normalization or improvement of margin reflex distance 1 was seen in 77.4% and 97.2% of group 1 patients at early and late review, respectively, and 77.6% and 87.8% of group 2, respectively. Absence or improvement in International Thyroid Eye Disease Society inflammatory index was seen in 83.9% and 86.1% of group 1 at early and late review, respectively, and 71.9% and 76.8% of group 2, respectively. Both active (73.7%) and inactive (79.3%) groups showed good early success for improvement in margin reflex distance 1, with increased late success and no significant difference between the groups. For International Thyroid Eye Disease Society inflammatory index, the active group had better early and late success than the inactive group, with the difference being significant (P = 0.002) for late success. Conclusions: Transconjunctival TA injection is an effective treatment option for thyroid eye disease–related upper eyelid retraction, as a primary and adjunctive treatment, in both active and inactive thyroid eye disease patients. Accepted for publication February 26, 2018. The authors have no financial or conflicts of interest to disclose. The material in this article has been presented as a poster at the American Society of Ophthalmic Plastic and Reconstructive Surgery Annual Meeting, 2017. Address correspondence and reprint requests to Kyung In Woo, M.D., Ph.D., Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. E-mail: eyeminded@hanmail.net © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento

Publication date: Available online 19 April 2018
Source:Actas Dermo-Sifiliográficas
Author(s): Y. Peñate, O. Servitje, S. Machan, R. Fernández-de-Misa, M.T. Estrach, E. Acebo, J. Mitxelena, M.D. Ramón, A. Flórez, M. Blanes, M. Morillo, S. Medina, J. Bassas, A. Zayas, P. Espinosa, A. Pérez, N. Gónzalez-Romero, J.D. Domínguez, C. Muniesa, J. López Robles, A. Combalia, I. Yanguas, H. Suh, I. Polo-Rodríguez, I. Bielsa, A. Mateu, B. Ferrer, M.A. Descalzo, I. García-Doval, P.L. Ortiz-Romero
Antecedentes y objetivoLos linfomas primarios cutáneos son enfermedades poco frecuentes. Este artículo describe el Registro de linfomas cutáneos primarios de la AEDV y sus primeros resultados.Pacientes y métodosRegistro de enfermedad de pacientes con linfomas cutáneos primarios. Los centros participantes recogieron datos prospectivamente de todos los pacientes, incluyendo datos del diagnóstico, de los tratamientos, de las pruebas realizadas y del estado actual del paciente. Se realizó un análisis descriptivo.ResultadosEn diciembre del 2017 el registro tenía datos de 639 pacientes pertenecientes a 16 hospitales universitarios. Un 60% eran hombres y los diagnósticos, por orden de frecuencia, fueron: micosis fungoide/síndrome de Sézary (MF/SS) (348 casos; 55%), linfoma cutáneo primario de células B (LCCB) (184; 29%), trastorno linfoproliferativo de células T CD30+ (LTCD30+) (70; 11%) y otro tipo de linfoma T (OLT) (37; 5%). El número de casos incidentes recogidos durante el primer año fue de 105 (16,5%). En los pacientes con MF/SS, el diagnóstico más frecuente fue MF clásica (77,3%). La mitad de estos casos se diagnosticaron en estadio IA. La mayoría de los pacientes estaban en remisión parcial (32,5%) o enfermedad estable (33,1%). Los tratamientos más usados fueron los corticoides tópicos (90,8%) seguidos de fototerapia. En los pacientes con LCCB el diagnóstico más frecuente fue el linfoma de la zona marginal (50%). Casi todos los pacientes tuvieron afectación exclusivamente cutánea y casi la mitad fue T1a. La mayoría (76,1%) estaba en remisión completa. Los tratamientos más utilizados fueron la cirugía (55,4%) y la radioterapia (41,9%). En los pacientes con LTCD30+, el diagnóstico más frecuente fue la papulosis linfomatoide (68,6%). La mayoría fueron clasificados T3b (31,4%). La mitad de los casos estaban en remisión completa. Los tratamientos más frecuentes fueron los esteroides tópicos (68,6%), seguidos de la quimioterapia sistémica (32,9%).ConclusiónLas características del paciente con linfoma cutáneo primario en España no difieren de otras series descritas en la literatura. El registro facilitará al grupo de linfomas de la AEDV realizar investigación clínica.Background and objectivePrimary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year.Patients and methodsDisease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed.ResultsIn December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30⁺ T-cell lymphoproliferative disorder (CD30⁺ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30⁺ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%).ConclusionThe characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Graphical abstract

REPLY: [LETTERS]

Altered White Matter Microstructure in the Corpus Callosum and Its Cerebral Interhemispheric Tracts in Adolescent Idiopathic Scoliosis: Diffusion Tensor Imaging Analysis [PEDIATRICS]

BACKGROUND AND PURPOSE:

Neural system was one of the important contributors to the etiopathogenesis of adolescent idiopathic scoliosis; additionally, the morphology of corpus callosum interconnecting both hemispheres of the brain was found to be altered morphologically. Our aim was to evaluate and compare the microstructural changes of the corpus callosum and its interhemispheric white matter fiber tracts interconnecting both cerebral hemispheres in patients with adolescent idiopathic scoliosis and matched controls using diffusion tensor imaging.

MATERIALS AND METHODS:

Brain DTI was performed in 69 patients with adolescent idiopathic scoliosis (female, right thoracic/thoracolumbar curve) and 40 age-matched controls without adolescent idiopathic scoliosis (female). 2D and 3D segmentation of the corpus callosum were performed using a region-growing method, and the corpus callosum was further divided into 6 regions, including the rostrum, genu, anterior and posterior midbodies, isthmus, and splenium. The laterality index was calculated to quantify the asymmetry of the corpus callosum. Interhemispheric fiber tractography were performed using the Brodmann atlas.

RESULTS:

2D ROI analysis revealed reduced fractional anisotropy in the genu and splenium (P = .075 and P = .024, respectively). Consistently reduced fractional anisotropy on the left sides of the genu and splenium was also found in 3D ROI analysis (P = .03 and P = .012, respectively). The laterality index analysis revealed a pseudo-right lateralization of the corpus callosum in adolescent idiopathic scoliosis. Interhemispheric fibers via the splenium interconnecting Brodmann 3, 1, and 2; Brodmann 17; and Brodmann 18 (corresponding to the primary somatosensory cortex and primary and secondary visual cortices) were also found to have reduced fractional anisotropy (P ≤ .05).

CONCLUSIONS:

Reduced fractional anisotropy was found in the genu and splenium of the corpus callosum and corresponding interhemispheric fiber tracts interconnecting the somatosensory and visual cortices via the splenium. Our results are suggestive of altered white matter microstructure within the brain of those with adolescent idiopathic scoliosis, which could be related to abnormal brain maturation during adolescence in adolescent idiopathic scoliosis and could possibly explain the previously documented somatosensory function impairment and visuo-oculomotor dysfunction in this condition.

Value of Quantitative Collateral Scoring on CT Angiography in Patients with Acute Ischemic Stroke [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Many studies have emphasized the relevance of collateral flow in patients presenting with acute ischemic stroke. Our aim was to evaluate the relationship of the quantitative collateral score on baseline CTA with the outcome of patients with acute ischemic stroke and test whether the timing of the CTA acquisition influences this relationship.

MATERIALS AND METHODS:

From the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) data base, all baseline thin-slice CTA images of patients with acute ischemic stroke with intracranial large-vessel occlusion were retrospectively collected. The quantitative collateral score was calculated as the ratio of the vascular appearance of both hemispheres and was compared with the visual collateral score. Primary outcomes were 90-day mRS score and follow-up infarct volume. The relation with outcome and the association with treatment effect were estimated. The influence of the CTA acquisition phase on the relation of collateral scores with outcome was determined.

RESULTS:

A total of 442 patients were included. The quantitative collateral score strongly correlated with the visual collateral score ( = 0.75) and was an independent predictor of mRS (adjusted odds ratio = 0.81; 95% CI, .77–.86) and follow-up infarct volume (exponent β = 0.88; P < .001) per 10% increase. The quantitative collateral score showed areas under the curve of 0.71 and 0.69 for predicting functional independence (mRS 0–2) and follow-up infarct volume of >90 mL, respectively. We found significant interaction of the quantitative collateral score with the endovascular therapy effect in unadjusted analysis on the full ordinal mRS scale (P = .048) and on functional independence (P = .049). Modification of the quantitative collateral score by acquisition phase on outcome was significant (mRS: P = .004; follow-up infarct volume: P < .001) in adjusted analysis.

CONCLUSIONS:

Automated quantitative collateral scoring in patients with acute ischemic stroke is a reliable and user-independent measure of the collateral capacity on baseline CTA and has the potential to augment the triage of patients with acute stroke for endovascular therapy.

Volumetric Brain MRI Study in Fetuses with Congenital Heart Disease [PEDIATRICS]

BACKGROUND AND PURPOSE:

It is well-established that a high prevalence of infants with congenital heart defects surviving to childhood have neurodevelopmental abnormalities. The etiology is not clear. In this study, we aimed to find prenatal neuroanatomic changes in fetuses with congenital heart disease to better understand the pathophysiology behind these sequelae.

MATERIALS AND METHODS:

A retrospective study of 46 fetal brain MR imaging scans was performed at a tertiary medical center during a 4-year period. Clinical data were collected from electronic medical charts. Volumes of the supratentorial brain, right hemisphere, left hemisphere, and cerebellum were measured using a semiautomated method and were compared with the normal growth percentiles.

RESULTS:

We found that cerebellar volume and the cerebellar-supratentorial volume ratio were significantly lower among fetuses with congenital heart disease. Supratentorial and hemisphere volumes showed no difference between groups. This difference was not observed in fetuses with septation defects.

CONCLUSIONS:

Fetuses with congenital heart disease have smaller cerebellar volumes than healthy fetuses. Additional research is needed to assess this finding as a radiologic marker for long-term outcome.

Sequential Apparent Diffusion Coefficient for Assessment of Tumor Progression in Patients with Low-Grade Glioma [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Early and accurate identification of tumor progression in patients with low-grade gliomas is challenging. We aimed to assess the role of quantitative ADC analysis in the sequential follow-up of patients with low-grade gliomas as a potential imaging marker of tumor stability or progression.

MATERIALS AND METHODS:

In this retrospective study, patients with a diagnosis of low-grade glioma with at least 12 months of imaging follow-up were retrospectively reviewed. Two neuroradiologists independently reviewed sequential MR imaging in each patient to determine tumor progression using the Response Assessment in Neuro-Oncology criteria. Normalized mean ADC (ADC_mean) and 10th percentile ADC (ADC₁₀) values from FLAIR hyperintense tumor volume were calculated for each MR image and compared between patients with stable disease versus tumor progression using univariate analysis. The interval change of ADC values between sequential scans was used to differentiate stable disease from progression using the Fisher exact test.

RESULTS:

Twenty-eight of 69 patients who were evaluated met our inclusion criteria. Fifteen patients were classified as stable versus 13 patients as having progression based on consensus reads of MRIs and the Response Assessment in Neuro-Oncology criteria. The interval change of ADC values showed greater concordance with ultimate lesion disposition than quantitative ADC values at a single time point. The interval change in ADC₁₀ matched the expected pattern in 12/13 patients with tumor progression (overall diagnostic accuracy of 86%, P <.001). On average, the ADC₁₀ interval change predicted progression 8 months before conventional MR imaging.

CONCLUSIONS:

The interval change of ADC₁₀ values can be used to identify progression versus stability of low-grade gliomas with a diagnostic accuracy of 86% and before apparent radiologic progression on conventional MR imaging.

Neuroimaging in Dengue Seropositive Cases [LETTERS]

Noninvasive Assessment of Hemodynamic Stress Distribution after Indirect Revascularization for Pediatric Moyamoya Vasculopathy [PEDIATRICS]

BACKGROUND AND PURPOSE:

Indirect revascularization surgery is an effective treatment in children with Moyamoya vasculopathy. In the present study, we hypothesized that DSC-PWI may reliably assess the evolution of CBF-related parameters after revascularization surgery, monitoring the outcome of surgical pediatric patients with Moyamoya vasculopathy. Thus, we aimed to evaluate differences in DSC-PWI parameters, including the hemodynamic stress distribution, in surgical and nonsurgical children with Moyamoya vasculopathy and to correlate them with long-term postoperative outcome.

MATERIALS AND METHODS:

Pre- and postoperative DSC parameters of 28 patients (16 females; mean age, 5.5 ± 4.8 years) treated with indirect revascularization were compared with those obtained at 2 time points in 10 nonsurgical patients (6 females; mean age, 6.9 ± 4.7 years). We calculated 4 normalized CBF-related parameters and their percentage variance: mean normalized CBF of the MCA territory, mean normalized CBF of the proximal MCA territory, mean normalized CBF of cortical the MCA territory, and hemodynamic stress distribution. The relationship between perfusion parameters and postoperative outcomes (poor, fair, good, excellent) was explored using 1-way analysis of covariance (P < .05).

RESULTS:

A significant decrease of the mean normalized CBF of the proximal MCA territory and hemodynamic stress distribution and an increase of the mean normalized CBF of the cortical MCA territory were observed after revascularization surgery (P < .001). No variations were observed in nonsurgical children. Postoperative hemodynamic stress distribution and its percentage change were significantly different in outcome groups (P < .001).

CONCLUSIONS:

DSC-PWI indices show postoperative hemodynamic changes that correlate with clinical outcome after revascularization surgery in children with Moyamoya disease.

Comparison of 3T Intracranial Vessel Wall MRI Sequences [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Intracranial vessel wall MR imaging plays an increasing role in diagnosing intracranial vascular diseases. For a complete assessment, pre- and postcontrast sequences are required, and including other sequences, these result in a long scan duration. Ideally, the scan time of the vessel wall sequence should be reduced. The purpose of this study was to evaluate different intracranial vessel wall sequence variants to reduce scan duration, provided an acceptable image quality can be maintained.

MATERIALS AND METHODS:

Starting from the vessel wall sequence that we use clinically (6:42 minutes), 6 scan variants were tested (scan duration ranging between 4:39 and 8:24 minutes), creating various trade-offs among spatial resolution, SNR, and contrast-to-noise ratio. In total, 15 subjects were scanned on a 3T MR imaging scanner: In 5 subjects, all 7 variants were performed precontrast-only, and in 10 other subjects, the fastest variant (4:39 minutes) and our clinically used variant (6:42 minutes) were performed pre- and postcontrast.

RESULTS:

The fastest variant (4:39 minutes) had higher or comparable SNRs/contrast-to-noise ratios of the intracranial vessel walls compared with the reference sequence (6:42 minutes). Qualitative assessment showed that the contrast-to-noise ratio was most suppressed in the fastest variant of 4:39 minutes and the variant of 6:42 minutes pre- and postcontrast. SNRs/contrast-to-noise ratios of the fastest variant were all, except one, higher compared with the variant of 6:42 minutes (P < .008). Furthermore, the fastest variant (4:39 minutes) detected all vessel wall lesions identified on the 6:42-minute variant.

CONCLUSIONS:

A 30% faster vessel wall sequence was developed with high SNRs/contrast-to-noise ratios that resulted in good visibility of the intracranial vessel wall.

Immediate effects of yoga breathing with intermittent breath holding on response inhibition among healthy volunteers

Apar Avinash Saoji, BR Raghavendra, SK Rajesh, NK Manjunath

International Journal of Yoga 2018 11(2):99-104

Background: There is very little evidence available on the effects of yoga-based breathing practices on response inhibition. The current study used stop-signal paradigm to assess the effects of yoga breathing with intermittent breath holding (YBH) on response inhibition among healthy volunteers. Materials and Methods: Thirty-six healthy volunteers (17 males + 19 females), with mean age of 20.31 ± 3.48 years from a university, were recruited in a within-subject repeated measures (RM) design. The recordings for stop signal task were performed on three different days for baseline, post-YBH, and post yogic breath awareness (YBA) sessions. Stop-signal reaction time (SSRT), mean reaction time to go stimuli (go RT), and the probability of responding on-stop signal trials (p [r/s]) were analyzed for 36 volunteers using RM analysis of variance. Results: SSRT reduced significantly in both YBH (218.33 ± 38.38) and YBA (213.15 ± 37.29) groups when compared to baseline (231.98 ± 29.54). No significant changes were observed in go RT and p (r/s). Further, the changes in SSRT were not significantly different among YBH and YBA groups. Conclusion: Both YBH and YBA groups were found to enhance response inhibition in the stop-signal paradigm. YBH could be further evaluated in clinical settings for conditions where response inhibition is altered.

Resonance signaling and yoga

TM Srinivasan

International Journal of Yoga 2018 11(2):89-90

Classification of electrophotonic images of yogic practice of mudra through neural networks

Kotikalapudi Shiva Kumar, TM Srinivasan, Judu Ilavarasu, Biplob Mondal, HR Nagendra

International Journal of Yoga 2018 11(2):152-156

Background: Mudras signify a gesture with hands, eyes, and the body. Different configurations of the joining of fingertips are also termed mudra and are used by yoga practitioners for energy manipulation and for therapeutic applications. Electrophotonic imaging (EPI) captures the coronal discharge around the fingers as a result of electron capture from the ten fingers. The coronal discharge around each fingertip is studied to understand the effect of mudra on EPI parameters. Methods: The participants were from Swami Vivekananda Yoga Anusandhana Samsthana and Sushrutha Ayurvedic Medical College, in Bengaluru, India. There were 29 volunteers in the mudra group and 32 in the control group. There were two designs: one was a pre-post design with control the other was pre-post with repeated measures with 18 individuals practicing mudra for 3 days. The duration of intervention for the pre-post design was 10 min on the 1st day, 15 min on the 2nd day, and 20 min on the 3rd day. A neural network classifier was used for classifying mudra and control samples. Results: The EPI parameters, normalized area and average intensity, passed the test of normality Shapiro–Wilk. The Cohen's d, effect size was 0.988 and 0.974 for the mudra and control groups, respectively. Neural network-based analysis showed the classification accuracy of the post-intervention samples for mudra and control varied from 85% to 100% while the classification accuracy varied from 55% to 70% for the pre-intervention samples. The result of the mudra intervention showed statistically significant changes in the mean values on the 3rd day compared to the 1st day. Conclusions: The effect size of the variations in mudra was more than that of the control group. Mudra practice of a longer duration showed statistically significant change in the EPI parameter, average intensity in comparison to the practice on the 1st day.

Yoga for heart failure: A review and future research

Paula R Pullen, William S Seffens, Walter R Thompson

International Journal of Yoga 2018 11(2):91-98

Background: Complementary and alternative medicine is a rapidly growing area of biomedical inquiry. Yoga has emerged in the forefront of holistic medical care due to its long history of linking physical, mental, and spiritual well-being. Research in yoga therapy (YT) has associated improved cardiovascular and quality of life (QoL) outcomes for the special needs of heart failure (HF) patients. Aim: The aim of this study is to review yoga intervention studies on HF patients, discuss proposed mechanisms, and examine yoga's effect on physiological systems that have potential benefits for HF patients. Second, to recommend future research directions to find the most effective delivery methods of yoga to medically stable HF patients. Methods: The authors conducted a systematic review of the medical literature for RCTs involving HF patients as participants in yoga interventions and for studies utilizing mechanistic theories of stretch and new technologies. We examined physical intensity, mechanistic theories, and the use of the latest technologies. Conclusions: Based on the review, there is a need to further explore yoga mechanisms and research options for the delivery of YT. Software apps as exergames developed for use at home and community activity centers may minimize health disparities and increase QoL for HF patients.

Study to evaluate the changes in polycystic ovarian morphology after naturopathic and yogic interventions

M Ezhil Ratnakumari, N Manavalan, D Sathyanath, Y Rosy Ayda, K Reka

International Journal of Yoga 2018 11(2):139-147

Background: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders in women, with a prevalence ranging from 2.2% to 26% in India. Patients with PCOS face challenges including irregular menstrual cycles, hirsutism, acne, acanthosis nigricans, obesity and infertility. 9.13% of South Indian adolescent girls are estimated to suffer from PCOS. The efficacy of Yoga & Naturopathy (Y&N) in the management of polycystic ovarian syndrome requires to be investigated. Aims: The aim of the present study is to observe the morphological changes in polycystic ovaries of patients following 12 weeks of Y&N intervention. Settings and Design: The study was conducted at the Government Yoga and Naturopathy Medical College and Hospital, Chennai, India. The study was a single blinded prospective, pre-post clinical trial. Methods and Material: Fifty PCOS patients of age between 18 and 35 years who satisfied the Rotterdam criteria were recruited for the study. According to their immediate participation in the study they were either allocated to the intervention group (n=25) or in the wait listed control group (n=25). The intervention group underwent Y&N therapy for 12 weeks. Change in polycystic ovarian morphology, anthropometric measurements and frequency of menstrual cycle were studied before and after the intervention. Results: Significant improvement was observed in the ovarian morphology (P<0.001) and the anthropometric measurements (P<0.001) between the two groups. Conclusions: The findings of the study indicate that Y&N interventions are efficient in bringing about beneficial changes in polycystic ovarian morphology. We speculate that a longer intervention might be required to regulate the frequency of menstrual cycle.

Effect of yoga in the treatment of eating disorders: A single-blinded randomized controlled trial with 6-months follow-up

Kari Ebbesen Karlsen, Karianne Vrabel, Solfrid Bratland-Sanda, Pål Ulleberg, Kirsten Benum

International Journal of Yoga 2018 11(2):166-169

Aim of the Study: The aim of this study is to examine the effect of yoga treatment of eating disorders (EDs). Methods: Adult females meeting the Diagnostic and Statistical Manual-IV criteria for bulimia nervosa or ED not otherwise specified (n = 30) were randomized to 11-week yoga intervention group (2 × 90 min/week) or a control group. Outcome measures, the Eating Disorder Examination (EDE)-Interview and Eating Disorders Inventory-2 (EDI-2) scores, were administered at baseline, posttest, and at 6-month follow-up. There was a dropout rate of 30% (posttest) and 37% (6-month follow-up). Results: The intervention group showed reductions in EDE global score (P < 0.01), the EDE subscale restraint (P < 0.05), and eating concern (P < 0.01) compared to the control group. The differences between the groups increased at 6-month follow-up. There were no differences between the groups in the EDI-2 score. Conclusion: The results indicate that yoga could be effective in the treatment of ED.

Effects of yoga training on body composition and oxidant-antioxidant status among healthy male

Indranil Manna

International Journal of Yoga 2018 11(2):105-110

Background: The stressful condition may cause oxidative stress, which is responsible for various diseases. Aims: The present study was designed to find out whether yoga has impact on the reduction of oxidative stress. Methods: For the present study, 95 (n = 95) healthy male volunteers within the age group of 18–24 years were included, 35 (n = 35) volunteers were excluded. The remaining 60 (n = 60) volunteers were randomly divided into two groups: (a) Yoga Group (n = 30) and (b) Control Group (n = 30). Yoga training was given for 60 min per day, 6 days per week for 12 weeks in the yoga group, with no yoga training in control group. Assessment of body composition and oxidant-antioxidant status were performed in both the groups at baseline, before yoga training (0 week) and after (12 weeks) of the training. Results: Significant reduction (P < 0.001) in the percentage of body fat and malondialdehyde; significant elevation (P < 0.001) in superoxide dismutase, catalase, reduced glutathione and ascorbic acid levels were noted in the yoga group after 12 weeks when compared to baseline data (0 week). However, there was no significant difference in height, weight, body mass index, body surface area and lean body mass among the yoga group after 12 weeks when compared to baseline data. These changes might be due to yoga training. Conclusions: Regular yoga practice reduces body fat and oxidative stress. Yoga training may be helpful to reduce the chance of occurrence of various diseases and helps to maintain normal healthy lifestyle.

Yoga as a therapeutic intervention for the management of type 2 diabetes mellitus

Santwana Mondal, Brajanath Kundu, Sukanta Saha

International Journal of Yoga 2018 11(2):129-138

Purpose: This study aimed to investigate the effects of 12 weeks yogic intervention on blood sugar and lipid profile in elder women with Type 2 diabetes mellitus (T2DM). Subjects and Methods: Twenty elderly (age range 55–70 years) T2DM women were divided into two groups, namely, yogic intervention group (YIG: n = 10, age 64.70 ± 4.03, body mass index [BMI] 24.26 ± 3.40) and control group (CG: n = 10, age 64.40 ± 4.79, BMI 24.28 ± 2.36). YIG underwent yoga practice (Asanas, Kriyas, Pranayamas) for 12 weeks (3 sessions/week), while the CG continued their usual routine activities. Standing height, body weight, BMI, blood sugar, and lipid profile were measured before commencement and after 6 and 12 weeks of yogic intervention in both groups. Results: There was a significant (P < 0.01) decrease in fasting plasma glucose, postprandial blood sugar, total cholesterol, triglycerides, low-density lipoprotein, and very low density lipoprotein, with a significant (P < 0.01) increase in high-density lipoprotein level from its initial value in YIG, while showing insignificant result in CG. Conclusion: It can be said that yogic intervention may have the beneficial effects on blood sugar and lipid profile in elderly women with T2DM.

Effect of yogic breathing on accommodate braille version of six-letter cancellation test in students with visual impairment

Balaram Pradhan, Soubhagyalaxmi Mohanty, Alex Hankey

International Journal of Yoga 2018 11(2):111-115

Context: Attentional processes tend to be less well developed in the visually impaired, who require special training to develop them fully. Yogic breathing which alters the patterns of respiration has been shown to enhance attention skills. Letter cancellation tests are well-established tools to measure attention and attention span. Here, a modified Braille version of the six-letter cancellation test (SLCT) was used for students with visual impairment (VI). Aim: This study aimed to assess the immediate effects of Bhramari Pranayama (BhPr) and breath awareness (BA) on students with VI. Methods: This study was a self-as-control study held on 2 consecutive days, on 19 participants (8 males, 11 females), with a mean age of 15.89 ± 1.59 years, randomized into two groups. On the 1st day, Group 1 performed 10 min breath awareness and Group 2 performed Bhramari; on the 2nd day, practices were reversed. Assessments used a SLCT specially adapted for the visually impaired before and after each session. Results: The Braille letter cancellation test was successfully taken by 19 students. Scores significantly improved after both techniques for each student following practices on both days (P < 0.001). BhPr may have more effect on attention performance than BA as wrong scores significantly increased following BA (P < 0.05), but the increase in the score after Bhramari was not significant. Conclusions: Despite the small sample size improvement in attentional processes by both yoga breathing techniques was robust. Attentional skills were definitely enhanced. Long-term practice should be studied.

No differences in energy cost of a predetermined exercise among young overweight/obese and undernourished individuals

DV Muralidhara, Mohd Nasir Mat Nor, Ahmad L Zubaidi

International Journal of Yoga 2018 11(2):148-151

Background: Physical activity is an integral part of one's daily life. Obese (Ob) and undernourished (UN) persons are known to underperform physically as compared to normal weight (N) individuals. In this study, we have measured the energy spent to perform a prefixed exercise on treadmill walking and basal heart rate and blood pressure. Body mass index (BMI) and body fat of participating individuals were assessed. Fasting blood sugar and lipid profile were also evaluated. Materials and Methods: Eighty-three young individuals (male: 41; female: 42) of medical faculty, Universiti Sultan Zainal Abidin, who volunteered for the study, were recruited. The mean age of the individuals was 19.8 ± 0 years (P < 1.08). The individuals were grouped as N, UN/underweight, and overweight (Ow)/Ob based on BMI. Results: The results of the study revealed that there were no differences in the energy spent on performing the predetermined treadmill walking of 20 min duration among the three groups (a mean of 78 and 70 calories in all male and female subgroups, respectively). The distance covered by the males was 1.6 km while the females covered 1.4 km on treadmill walking in 20 min time. Basal blood pressure and heart rate and fasting blood sugar did not reveal any significant difference among the groups. However, total cholesterol and triglyceride levels were marginally higher in the Ow/Ob groups of male and female individuals as compared to other groups. Conclusion: Since the study individuals were very young and competitive by nature and possibly had no major metabolic disturbances, the differences in physical activity performances were not obvious. Possibly, such differences would become apparent only at later stages of life as age advances or when the intensity and duration of exercise are set at higher levels.

Effect of mula bandha yoga in mild grade pelvic organ prolapse: A randomized controlled trial

KM Sweta, Amrit Godbole, HH Awasthi, Uma Pandey

International Journal of Yoga 2018 11(2):116-121

Background: Pelvic organ prolapse is the growing health issue related to women of the reproductive and postmenopausal age group in India and across the globe. Treatment option for pelvic organ prolapse includes both surgical and non-surgical intervention. The development of pelvic organ prolapse is an indication for major surgery among 20% of all women. Nevertheless, the recurrence of pelvic organ prolapse is detected among 58% of the patient after surgery. This highlights the need for preventive measures for reducing the impact of pelvic organ prolapse. Aims and Objective: To study the effect of 3 months yoga therapy in female patients suffering from mild pelvic organ prolapse. Material and Methods: 50 Participants were allocated into two groups (25 in each group) by generating Random allocation sequence. Women aged 20-60 with symptomatic mild pelvic organ prolapse in the yoga group were offered Mulabandha yoga therapy along with other conventional treatment modalities, while the control group was only on conventional treatment. All participants gave written informed consent. An assessment was done by improvement in chief complaints and Pelvic Floor Distress Inventory-20 (PFDI-20) & Pelvic floor impact Questionnaire-7 (PFIQ-7) at baseline and at the end of 4, 8 & 12 weeks. Results At the end of 12 weeks, Post-study comparison between the two groups showed a significant improvement in chief complaints like perennial pain, P/V discharge, Perineal muscle laxity and Feeling of something coming out P/V (P < 0.001). Participants in the yoga group improved by (on average) 5.7 (95% confidence interval 3.1 to 14.7) points more on the PFDI-20 than did participants in the control group (P = 0.1) and a mean score of PFIQ-7 was also improved significantly. Conclusions: Although Mulabandha (Root Lock) yoga therapy led to a significantly greater improvement in PFDI-20 & PFIQ-7 scores the difference between the groups was below the presumed level of clinical relevance (15 points). More studies are needed to identify factors related to the success of Mulabandha (Root Lock) yoga therapy and to investigate long-term effects.

Bioenergy and its implication for yoga therapy

Chathapuram Rajan Narayanan, Konstantin Korotkov, Thaiyar Madabusi Srinivasan

International Journal of Yoga 2018 11(2):157-165

Electro photonic imaging (EPI) is being researched relative to its application for yoga therapy. Three parameters of interest in EPI measurements are as follows: Communication energy (C), integral or normalized area (IA), and Entropy (E). It is important to note that C indicates the total energy of communication for the organ system; IA is an indication of total amount of energy that is available for the organ system while entropy is an indication of the amount of coherence of the energy. Coherence and entropy are inversely related; this means less the entropy, more the coherence and vice versa. Illustrative cases of successful therapy with yoga practices in a wide variety of abnormal conditions are examined, and in every case, entropy is shown to decrease for the affected organ system while communication energy stays within stable range. Relative to the electromagnetic (Rubik) and living matrix (Oschman) models, it is suggested that the regulation of energy, its coherence in the biological system and interaction with life processes provide the basis for model building and design of health-promoting procedures. Further, this approach is examined relative to yoga theory, traditional medicine systems, and scientific developments in the field of gene expression and neuroplasticity and a generalized model that we call Unified System of Medicine is proposed. This model has direct implications on methods used to control the environmental factors to get robust results from EPI application for therapeutic purposes. Implications for furthering research in yoga therapy using EPI and implications of EPI as a translational technology between traditional medicine systems and modern medicine is discussed.

Effect of 6 months of meditation on blood sugar, glycosylated hemoglobin, and insulin levels in patients of coronary artery disease

Shashank Shekhar Sinha, Ajay Kumar Jain, Sanjay Tyagi, SK Gupta, Aarti Sood Mahajan

International Journal of Yoga 2018 11(2):122-128

Background and Objectives: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. It has been recognized that stress, diabetes, and hypertension are important in etiology and progression of CAD. This study is to evaluate the role of meditation in improving biochemical parameters such as blood glucose, glycosylated hemoglobin, and serum insulin levels in known CAD patients. Material and Methods: Sixty CAD patients are divided into two groups of which one group did meditation and other did not. Blood glucose, glycosylated hemoglobin, and fasting serum insulin levels were measured before and at the end of 6 months of study in both the groups. Results: At the end of the study, significant decrease was seen in patients who practiced meditation as compared to other group. Conclusion: Meditation may modulate the physiological response to stress through neurohumoral activation, which may be a novel therapeutic target for the treatment of CAD.

Effect of 1-week yoga-based residential program on cardiovascular variables of hypertensive patients: A Comparative Study

Kashinath G Metri, Balaram Pradhan, Amit Singh, HR Nagendra

International Journal of Yoga 2018 11(2):170-174

Introduction: Hypertension (HTN) is an important public health concern and a leading cause of morbidity and mortality worldwide. Yoga is a form of mind–body medicine shown to be effective in controlling blood pressure (BP) and reduces cardiac risk factors in HTN. Integrated approach of Yoga therapy (IAYT) is a residential yoga-based lifestyle intervention proven to be beneficial in several health conditions. Aim: To study the efficacy of 1 week of residential IAYT intervention on cardiovascular parameters in hypertensive patients. Methodology: Twenty hypertensive individuals (7 females) within age range between 30 and 60 years (average; 46.62 ± 9.9 years), who underwent 1 week of IAYT treatment for HTN, were compared with age- gender-matched non-IAYT group (5 females; average age; 47.08 ± 9.69 years) in terms of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), baroreflex sensitivity (BRS), and total peripheral vascular resistance (TPVR), IAYT program consisted of sessions of asanas, breathing practices, meditation and relaxation techniques, low salt, low-calorie diet, devotional session, and counseling. Individuals in non-IAYT group followed their normal routine. All the variables were assessed before and after one week. Data were analyzed using SPSS version 16. RM-ANOVA was applied to assess within group and between group changes after intervention. Results: There was a significant improvement in SBP (P = 0.004), DBP (P = 0.008), MAP (0.03), BRS (P < 0.001), and TPVR (P = 0.007) in IAYT, group whereas in control group, we did not find significant difference in any of the variables. Between-group comparison showed a significant improvement in SBP (P = 0.038), BRS (P = 0.034), and TPVR (P = 0.015) in IAYT group as compared to non-IAYT group. Conclusion: One-week IAYT intervention showed an improvement in baroreflex sensitivity, systolic BP, and total peripheral vascular resistance in hypertensive patients. However, further randomized control trials need to be performed to confirm the present findings.

High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands

Clinical Otolaryngology, EarlyView.

C‐reactive protein is an independent prognostic marker in patients with tongue carcinoma ‐ A retrospective study

Clinical Otolaryngology, EarlyView.

Endoscopic treatment of post‐supraglottoplasty stenosis

Clinical Otolaryngology, EarlyView.

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial

Mycoses, EarlyView.

Metabolic Syndrome Diagnosis: The Sooner the Better

Metabolic Syndrome and Related Disorders, Ahead of Print.

Is it worthy to treat hidradenitis suppurativa with adalimumab in patients with melanoma and other debilitating systemic diseases? A series of clinical dilemmas

Australasian Journal of Dermatology, EarlyView.

Clinicopathological, immunohistochemical and embryological aspects of cutaneous ciliated Müllerian cyst

Australasian Journal of Dermatology, EarlyView.

In vitro anti-inflammatory activity of terpenes via suppression of superoxide and nitric oxide generation and the NF-κB signalling pathway

Abstract

Background and Aims

Terpenes are considered the main components of essential oils and an important source for the identification of novel lead molecules. This study aimed to investigate the in vitro anti-inflammatory activity of l-carveol, l-carvone, and m-cimene (monoterpenes) and of valencene and guaiene (sesquiterpenes).

Methods

The influence on intracellular nitric oxide (NO) and pro- and anti-inflammatory cytokine (TNF-α, IL-1α and IL-10) production and on nuclear factor kappa B (NF-κB) activity was determined using Griess reagent, immunoenzymatic assay kits (ELISA) and chemiluminescence measurements in cell-based assays, respectively. Antioxidant activity was assayed through the protective effect against cellular oxidative damage produced by superoxide anion production (O ₂^·−) and hydrogen peroxide on macrophages and by the quenching activity of the NO radical.

Results and Discussion

Terpenes reduced the pro-inflammatory cytokines TNF-α and IL-1α and increased the production of IL-10. In addition, the terpenes, especially guaiene (53.3 ± 2.4%) and m-cymene (38.1 ± 0.6%), significantly inhibited NO production in a macrophage cell culture-based assay, whereas no effect was observed in the scavenging activity of this radical. l-carveol and m-cymene significantly inhibited O ₂^·− production with reductions of approximately 68.6 ± 2.2% and 48.2 ± 4.2%, respectively, at a concentration of 10 μM. Moreover, these terpenes were verified to suppress NF-κB activity. The results indicate that these terpenes have therapeutic potential and may be used to suppress inflammatory diseases or as a leading compounds.

Wedge‐shaped polydioxanone threads in a folded configuration (“Solid fillers”): A treatment option for deep static wrinkles on the upper face

Journal of Cosmetic Dermatology, EarlyView.

SNAI1, an endothelial–mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization

Abstract

Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial–mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.

Precis of Objective Becoming

Replies to Deasy and Maudlin

Lateral Wall Insufficiency Severity and Patient-Reported Nasal Obstruction Measures

This cohort study examines differences in lateral wall insufficiency severity in patients seen in consultation for functional, cosmetic, and combined rhinoplasty.

Temporal Hollowing Augmentation by Targeted Fat-Grafting Technique in Chinese Adults

This cohort study evaluates the safety and efficacy of the targeted fat-grafting technique for temporal hollowing augmentation of the face in Chinese adults.

β 2 -adrenoceptor signaling reduction is involved in the inflammatory response of fibroblast-like synoviocytes from adjuvant-induced arthritic rats

Abstract

Objective

To investigate the effects of β-AR signaling on fibroblast-like synoviocytes (FLS) from adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on β-AR desensitization mediated by GRK2 and β-arrestin2.

Methods

Animals were divided into a control group and an AA model group, and FLSs were cultured. Arthritis index, histopathology of joints, epinephrine (Epi) and norepinephrine (NE) were detected in vivo. The effect of the β-AR agonist isoprenaline (ISO) and the β₂-AR agonist salbutamol on FLS cell viability were detected by CCK8. Cytokines TNF-α, IL-1β, OPG and RANKL were examined by ELISA. The expression of β₂-AR was detected by immunofluorescence and flow cytometry. The cytomembrane expression and desensitization of β2-AR, GRK2, and β-arrestin2 were measured by flow cytometry and western blot.

Results

The concentration of NE increased to a peak on day 21, which was consistent with the arthritis index. The levels of Epi and NE in synovial tissues were decreased. ISO inhibited FLS cell viability and TNF-α, IL-1β, and RANKL secretion, and promoted OPG secretion. β₂-AR mediated the effects of ISO on FLS cell viability. β₂-AR signaling was weaker in AA rats compared to the controls. Elevated GRK2 and β-arrestin2 in cytomembranes promoted β₂-AR desensitization and may decrease the anti-inflammatory effect of β₂-AR signaling.

Conclusion

The activation of β₂-AR signaling exerts its anti-inflammatory activities on FLS. β₂-AR signaling decreased in the AA model, which might be related to the increased membrane expression of GRK2 and β-arrestin2, and promoted the excessive desensitization of β₂-AR. Decreased β₂-AR signaling may be relevant to the exacerbation of arthritis inflammation.

How to Work a Career fair

Navigating career fairsResearch CompaniesDevelop your communicationPrepareResume/CVDress professionally

The Presence of Colisitn resistance gene mcr-1 and -3 in ESBL producing Escherichia coli isolated from food in Ho Chi Minh City, Vietnam

Abstract

Colistin is indicated for the treatment of multidrug-resistant gram-negative bacterial infections. However, the spread of colistin-resistant bacteria harboring a mcr gene has become a serious concern. This study investigated local foods in Vietnam for contamination with colistin-resistant bacteria. A total of 261 extended-spectrum β-lactamase (ESBL)- and AmpC-producing Escherichia coli isolates from 330 meat and seafood products were analyzed for colistin susceptibility and the presence of mcr genes. Approximately 24% (62/261) of ESBL- or AmpC-producing E. coli isolates showed colistin resistance; 97% (60/62) of colistin-resistant isolates harbored mcr-1, whereas 3% (2/62) harbored mcr-3. As the result of plasmid analysis of two strains, both plasmid harboring mcr-3 was revealed that plasmid replicon type was IncFII. Sequencing analysis indicated that an insertion sequence was present near mcr-3, suggesting that IncFII plasmids harboring mcr-3 could be transferred to other bacterial species by horizontal transfer of the plasmid or transfer with some insertion sequence. In conclusion, ESBL-producing E. coli and AmpC-producing E. coli have acquired colistin resistance because 24% of such isolates show colistin resistance and 3% of the colistin-resistant strains harbor mcr-3. We reported the present of the mcr-3-carrying ESBL-producing E. coli isolated from pork in Vietnam.

Variation in accumulation, transport, and distribution of phthalic acid esters (PAEs) in soil columns grown with low- and high-PAE accumulating rice cultivars

Abstract

The extensive use of plasticizers containing di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) results in high residual concentrations in agricultural soils and poses potential risks to human health through the food chain. Here, two rice cultivars with low (Fengyousimiao) and high (Peizataifeng) phthalic acid ester (PAE) accumulation were grown in leaching columns packed with DBP- and DEHP-contaminated soils to investigate their transport, fraction distribution, and accumulation in soil-rice-water system. Significant differences in soil vertical distribution of DBP and DEHP were observed among the two cultivars, sterilization and non-sterilization treatments. Both DBP and DEHP could leach to the bottom layer even though their concentrations in both soil and pore water decreased along with soil depth. DBP and DEHP concentrations in pore water were significantly correlated with those in corresponding soil layer at ripening stage. The available fractions including desorbing and non-desorbing fractions were predominant in the total concentrations of DBP and DEHP of soils. DBP and DEHP storages in coarse soil fractions (i.e., coarse and fine sands) with higher bioavailability displayed higher bioconcentration factors compared to finer soil fractions (i.e., silt and clay), and bioconcentration factors of Peizataifeng were higher than those of Fengyousimiao. The variations in vertical migration and accumulation of DBP and DEHP by the two cultivars implied different adverse effects on the security of groundwater and food.

Recurrent candidal intertrigo: challenges and solutions