Commentary on Some Recent Theses Relevant to Combating Aging: October 2018

Rejuvenation Research, Ahead of Print.


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Heart toxicity from breast cancer radiotherapy

Abstract

Background

Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures.

Methods

A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed.

Results

Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; D_meanLV (mean dose left ventricle) < 3 Gy; V5_LV (volume of LV receiving ≥5 Gy) < 17%; V23_LV (volume of LV receiving ≥23 Gy) < 5%; D_meanLAD (mean dose left descending artery) < 10 Gy; V30_LAD (volume of LAD receiving ≥30 Gy) < 2%; V40_LAD (volume of LAD receiving ≥40 Gy) < 1%.

Conclusion

In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.

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Validation of classic and expanded criteria for endoscopic submucosal dissection of early gastric cancer: 7 years of experience in a Western tertiary cancer center

OBJECTIVE: Our aim was to evaluate the Japan Gastroenterological Endoscopy Society criteria for endoscopic submucosal resection of early gastric cancer (EGC) based on the experience in a Brazilian cancer center. METHODS: We included all patients who underwent endoscopic submucosal resection for gastric lesions between February 2009 and October 2016. Demographic data and information regarding the endoscopic resection, pathological report and follow-up were obtained. Statistical calculations were performed with Fisher's exact test and chi-square tests, with 95% confidence intervals. RESULTS: In total, 76% of the 51 lesions were adenocarcinomas, 16% were adenomas, and 8% had other diagnoses. The average size was 19.9 mm (±11.7). The average procedure length was 113.9 minutes (±71.4). The complication rate was 21.3%, with only one patient who needed surgical treatment (transmural perforation). Among the adenocarcinomas, 39.5% met the classic criteria for curability, 31.6% met the expanded criteria and 28.9% met the criteria for noncurative resection. Analysis of the indication criteria and curability revealed differences among cases with "only-by-size" expanded criteria (64.28%), other expanded criteria (40%) and classic criteria (89.47%), with a p-value of 0.049. During follow-up (15.8 months; ±14.3), 86.1% of the EGC patients had no recurrence. When well-differentiated and poorly differentiated lesions or lesions included in the classic and expanded criteria were compared, there were no differences in recurrence. The noncurative group presented a higher recurrence rate than the classic group (p=0.014). CONCLUSION: These results suggest that the Japanese endoscopic submucosal resection criteria might be useful for endoscopic treatment of EGC in Western countries.

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Regulation of HPV transcription

Human papillomavirus infection is associated with the development of malignant and benign neoplasms. Approximately 40 viral types can infect the anogenital mucosa and are categorized into high- and low-risk oncogenic human papillomavirus, depending on their association with the development of cervical carcinoma. High-risk human papillomavirus 16 and 18 are detected in 55% and 15% of all invasive cervical squamous cell carcinomas worldwide, respectively. Low-risk human papillomavirus 6 and 11 are responsible for 90% of genital warts and are also associated with the development of recurrent respiratory papillomatosis. Human papillomavirus preferentially infects mitotic active cells of the basal layer from both mucosal and cutaneous epithelium through microabrasions. The viral life cycle synchronizes with the epithelial differentiation program, which may be due, in part, to the binding of differentially expressed cellular transcription factors to the long control region throughout the various epithelial layers. This review aimed to summarize the current knowledge regarding the mechanisms by which viral gene expression is regulated and the influence of human papillomavirus heterogeneity upon this phenomenon. A better understanding of the regulatory mechanisms may elucidate the particularities of human papillomavirus-associated pathogenesis and may provide new tools for antiviral therapy.

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Innate immunity and HPV: friends or foes

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.

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Human polyomaviruses and cancer: an overview

The name of the family Polyomaviridae, derives from the early observation that cells infected with murine polyomavirus induced multiple (poly) tumors (omas) in immunocompromised mice. Subsequent studies showed that many members of this family exhibit the capacity of mediating cell transformation and tumorigenesis in different experimental models. The transformation process mediated by these viruses is driven by viral pleiotropic regulatory proteins called T (tumor) antigens. Similar to other viral oncoproteins T antigens target cellular regulatory factors to favor cell proliferation, immune evasion and downregulation of apoptosis. The first two human polyomaviruses were isolated over 45 years ago. However, recent advances in the DNA sequencing technologies led to the rapid identification of additional twelve new polyomaviruses in different human samples. Many of these viruses establish chronic infections and have been associated with conditions in immunosuppressed individuals, particularly in organ transplant recipients. This has been associated to viral reactivation due to the immunosuppressant therapy applied to these patients. Four polyomaviruses namely, Merkel cell polyomavirus (MCPyV), Trichodysplasia spinulosa polyomavirus (TSPyV), John Cunningham Polyomavirus (JCPyV) and BK polyomavirus (BKPyV) have been associated with the development of specific malignant tumors. However, present evidence only supports the role of MCPyV as a carcinogen to humans. In the present review we present a summarized discussion on the current knowledge concerning the role of MCPyV, TSPyV, JCPyV and BKPyV in human cancers.

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Pharmacogenetic testing in oncology: a Brazilian perspective

Pharmacogenetics, a major component of individualized or precision medicine, relies on human genetic diversity. The remarkable developments in sequencing technologies have revealed that the number of genetic variants modulating drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to rare mutations (minor allele frequency, MAF<1%) in addition to polymorphisms (MAF>1%) in pharmacogenes. This has major implications for the conceptual development and clinical implementation of pharmacogenetics. Drugs used in cancer treatment have been major targets of pharmacogenetics studies, encompassing both germline polymorphisms and somatic variants in the tumor genome. The present overview, however, has a narrower scope and is focused on germline cancer pharmacogenetics, more specifically, on drug/gene pairs for which pharmacogenetics-informed prescription guidelines have been published by the Clinical Pharmacogenetics Implementation Consortium and/or the Dutch Pharmacogenetic Working Group, namely, thiopurines/TPMT, fluoropyrimidines/UGT1A1, irinotecan/UGT1A1 and tamoxifen/CYP2D6. I begin by reviewing the general principles of pharmacogenetics-informed prescription, pharmacogenetics testing and the perceived barriers to the adoption of routine pharmacogenetics testing in clinical practice. Then, I highlight aspects of the pharmacogenetics testing of the selected drug-gene pairs and finally present pharmacogenetics data from Brazilian studies pertinent to these drug-gene pairs. I conclude with the notion that pharmacogenetics testing has the potential to greatly benefit patients by enabling precision medicine applied to drug therapy, ensuring better efficacy and reducing the risk of adverse effects.

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Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.

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Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

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Cosmetics, Vol. 5, Pages 60: Anti-Aging Efficacy of Melatonin-Based Cream: Clinical and Instrumental Skin Evaluation

Cosmetics, Vol. 5, Pages 60: Anti-Aging Efficacy of Melatonin-Based Cream: Clinical and Instrumental Skin Evaluation

Cosmetics doi: 10.3390/cosmetics5040060

Authors: Massimo Milani Mario Puviani

Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has been shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild to moderate skin aging. In an open prospective, evaluator-blinded trial, we evaluate the effects on skin texture of two months of treatment with a Melatosphere™-based cream. Fifteen women aged &gt;45 years with mild to moderate facial skin aging (Glogau score 2–4) participated in the trial, after providing their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global Assessment (IGA) of skin elastosis, roughness, level of dyschromia, skin dryness and the presence of actinic damage was also performed at the same time points using a four-grade score from 0 (no sign) to 3 (severe sign). At baseline, the mean (SD) IGA score was 8.2 (1.0). After two months, the IGA score significantly decreased to 4.2 (1.4) (49% reduction) (p = 0.0007). ANTERA 3D evaluations showed a significant reduction in the coarse and fine wrinkle volume in the target area of −31% and −18%, respectively. Melanin content was reduced significantly by −17%. Topical melatonin carried in Melatosphere™ improves, in the short term, signs of skin aging evaluated clinically and using the ANTERA 3D device in women with mild to moderate skin aging.

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The clinical value of assays detecting antibodies against domain I of β2-glycoprotein I in the antiphospholipid syndrome

Publication date: Available online 11 October 2018

Source: Autoimmunity Reviews

Author(s): Dongmei Yin, Bas de Laat, Katrien M.J. Devreese, Hilde Kelchtermans

Abstract

As the clinical symptoms of the antiphospholipid syndrome (APS) frequently occur irrespective of the syndrome, diagnosis predominantly depends on the laboratory assays measuring the level or function of antiphospholipid antibodies (aPLs). β2-glycoprotein I (β2GPI) is increasingly accepted as the most important target of aPLs. Anti-β2GPI antibodies constitute a heterogeneous population, but current in vivo and in vitro evidence show that especially the first domain (DI) of β2GPI contains an important pathogenic epitope. This epitope containing Glycine40-Arginine43 (G40-R43) has proven to be cryptic and only exposed when β2GPI is in its open conformation. A previous study demonstrated a highly variable exposure of the cryptic epitope in commercial anti-β2GPI assays, with implications on correct patient classification. Unexpectedly, recent unpublished data revealed impaired exposure of the pathogenic epitope in the commercially available anti-DI chemiluminescence immunoassay (CIA) assay detecting specific antibodies directed to DI.

In this review we summarize the laboratory and clinical performance characteristics of the different anti-DI assays in published data and conclude with inconsistent results for both the correlation of anti-DI antibodies with clinical symptoms and the added value of anti-DI antibodies in the classification criteria of APS. Additionally, we hypothesize on possible explanations for the observed discrepancies. Finally, we highly advise manufacturers to use normal pooled plasma spiked with the monoclonal anti-DI antibodies to verify correct exposure of the cryptic epitope.

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Accounting for All Costs in the Total Cost of Chimeric Antigen Receptor T-Cell Immunotherapy—Reply

In Reply We appreciate the opportunity to respond to comments from Whittington and colleagues on our research letter, which estimated costs associated with the chimeric antigen receptor T-cell (CAR-T) immunotherapies tisagenlecleucel (Kymriah; Novartis) and axicabtagene ciloleucel (Yescarta; Kite Pharma). Using publicly available data sources and results from the clinical trials evaluating these agents, we estimated the costs directly related to the administration and adverse effects of CAR-T immunotherapies, including manufacturing costs, physician and facility costs for leukapheresis, administration of lymphodepletion therapy, administration of CAR-T therapy, and hospitalizations for cytokine-release syndrome. We estimated the average expected cost of treating a patient with tisagenlecleucel and axicabtagene ciloleucel at $510 963 and $402 647, respectively.

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Androgen Deprivation Therapy and Dementia in Men With Prostate Cancer Receiving RT

This cohort study examines the association of androgen deprivation therapy with dementia in male veterans with prostate cancer who receive definitive radiotherapy.

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Reassessment of 4-Cycle Etoposide and Cisplatin in Good-Risk Metastatic Germ Cell Tumors

This Viewpoint assesses the current recommendation of treatment regimens with and without bleomycin for patients with metastatic germ cell tumors of the testis.

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Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women

This prospective cohort study evaluates the 5-year risk of cervical precancer following p16/ki-67 dual-stain triage of HPV-positive women.

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Plasma vs Tissue Next-Generation Sequencing in Non–Small Cell Lung Cancer

Although randomized clinical trial evidence of superior outcomes from using next-generation sequencing (NGS) in oncology clinical practice is still lacking, NGS has earned a place in the routine management of non–small cell lung cancer (NSCLC) for practical reasons. Non–small cell lung cancer is distinctive in that the portfolio of biomarker-driven targets with matched drugs approved by the US Food and Drug Administration or at least potentially available drugs is increasing so rapidly that performing a panel test has become more efficient and probably more cost-effective than testing for each mutation individually. Furthermore, tissue samples are not always available, and additional procedures to retrieve needed tissue entail potential risk and discomfort. A solution to this dilemma has been to perform a "liquid biopsy," in which the NGS is conducted on plasma rather than on tissue, obviating the need for invasive tissue biopsy. This more readily performed technique is already routinely used by many institutions, particularly when tissue biopsy specimens are unavailable. Like many other interventions in medicine, however, plasma-based NGS has been integrated into clinical practice without being evaluated in well-conducted prospective trials.

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Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women

This cohort study of women in the Nurses' Health Study II assesses the association of obesity and weight gain since early adulthood with early-onset colorectal cancer.

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Accounting for All Costs in the Total Cost of Chimeric Antigen Receptor T-Cell Immunotherapy

To the Editor Hernandez and colleagues estimated the total cost of chimeric antigen receptor T-cell (CAR-T) immunotherapy by presenting 11 patient-treatment pathways based on receipt of CAR-T infusion, development of cytokine release syndrome, and response to treatment. We agree that the treatment acquisition costs of tisagenlecleucel (Kymriah; Novartis) ($475 000 for pediatric leukemia) and axicabtagene ciloleucel (Yescarta; Kite Pharma) ($373 000 for adult lymphoma) are not an accurate representation of the total cost of CAR-T immunotherapy.

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Plasma-Based Genotyping for Personalized Therapy in Metastatic Non–Small Cell Lung Cancer

This study assesses whether plasma-based next-generation sequencing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting of patients with non–small cell lung cancer.

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Incorrect Surnames in Byline

In the article titled "Erythematous Velvety Plaque of the Scrotum and Penis," the surnames of 2 authors who appear in the byline have been tagged for correct display. Kae Jack Tay now displays as Tay KJ, and Valerie Huei Li Gan now displays as Gan VHL. The article was corrected online.

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Error In Figure 1

In the Original Investigation titled "Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis," published online September 3, 2018, there was an error in Figure 1C. The fatality rate percentage for adrenal fatalities was not correctly presented. This article was corrected online.

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Impairments of auditory-verbal short-term memory: do selective deficits of the input phonological buffer exist?

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Tim Shallice, Costanza Papagno

Abstract

The existence of the functional syndrome of auditory-verbal short-term storage impairment was used as strong supporting evidence for the presence of a phonological buffer in the first version of the Baddeley-Hitch working memory model. In later versions the syndrome corresponded to the selective impairment of the phonological input buffer. The present paper considers whether the correspondence between the functional syndrome, represented by 20 published cases, and a Baddeley-Hitch model component is still of value to memory theory. The following potential problems for the theoretical utility of the correspondence are considered:

1The apparent rarity of examples of the syndrome: are they outliers?

2Is short-term memory not merely the activation of long-term memory traces?

3Could the syndrome be due to failed interaction between perceptual and motor speech processing?

4Do some aspects of the syndrome not fit the Baddeley-Hitch model predictions?

5Has the Baddeley-Hitch model not been replaced by more powerful connectionist models?

6Could the syndrome arise from weakened speech perception processes?

It is argued that there are difficulties for each of these possibilities. It is held that the correspondence retains its value.

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Vision of the upper limb fails to compensate for kinesthetic impairments in subacute stroke

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Jennifer A. Semrau, Troy M. Herter, Stephen H. Scott, Sean P. Dukelow

Abstract

Kinesthesia is an essential component of proprioception allowing for perception of movement. Due to neural injury, such as stroke, kinesthesia can be significantly impaired. Throughout neurorehabilitation, clinicians may encourage use of vision to guide limb movement to retrain impaired kinesthesia. However, little evidence exists that vision improves kinesthetic performance after stroke. We examined behavioral and neuroanatomical characteristics of kinesthesia post-stroke to determine if these impairments improve with vision.

Stroke subjects (N=281) performed a robotic kinesthetic matching task (KIN) without and with vision at ∼10 days post-stroke. A robotic exoskeleton moved the stroke-affected arm while subjects mirror-matched the movement with the opposite arm. Performance was compared to 160 controls. Spatial and temporal parameters were used to quantify kinesthetic performance. A Kinesthetic Task Score was calculated to determine overall performance on KIN without and with vision. Acute stroke imaging (N=236) was collected to determine commonalities in lesion characteristics amongst kinesthetic impairment groups.

Forty-eight percent (N=135) of subjects had post-stroke impairment in kinesthesia both without and with vision. Only 19% (N=52) improved to control-level performance with vision. Of the 48% of subjects that failed to improve with vision, many (N=77, 57%) had neglect and/or field deficits. Notably 58 subjects (43%) did not have these deficits and still failed to improve with vision. Subjects who failed to improve with vision often had lesions affecting corticospinal tracts, insula, and parietal cortex, specifically the supramarginal gyrus and inferior parietal lobule.

Many individuals could not use vision of the limb to correct for impaired kinesthesia after stroke. Subjects that failed to improve kinesthesia with vision had lesions affecting known sensorimotor integration areas. Our results suggest that integration of spatial information is impaired in many individuals post-stroke, particularly after parietal cortex damage. The result is a disconnect between kinesthetic and visuomotor processing necessary for visual limb guidance.

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Stereotypic behaviours in frontotemporal dementia and progressive supranuclear palsy

Publication date: Available online 11 October 2018

Source: Cortex

Author(s): Sara Prioni, Veronica Redaelli, Paola Soliveri, Vincenza Fetoni, Federica Barocco, Paolo Caffarra, Augusto Scaglioni, Irene Tramacere, Floriano Girotti

Abstract

Introduction

The behavioural variant of frontotemporal dementia (bvFTD), and the Richardson variant of progressive supranuclear palsy (PSP-RS) share several clinical signs and symptoms. Since stereotypic behaviours are fairly common in bvFTD, and are also described in other degenerative dementias including Alzheimer's disease, and parkinsonisms with dementia, we aimed to examine the extent to which stereotypies also characterise PSP-RS.

Methods

We compared 53 bvFTD patients with 40 demented PSP-RS patients, seen consecutively as outpatients at four Italian Hospitals. Patients were assessed by the Neuropsychiatric Inventory (NPI); Mini Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) for cognitive functions; Stereotypy Rating Inventory (SRI) for stereotypies; Unified Parkinson's Disease Rating Scale (UPDRS) for motor function; and Activities of Daily Living (ADL) to assess autonomy in daily life.

Results

The groups did not differ for age, illness duration, cognitive functions or total NPI score; PSP-RS had significantly more depressive symptoms and greater motor and autonomy compromise than bvFTD. The groups did not differ significantly on total SRI score, but bvFTD had significantly more cooking and eating stereotypies. Twenty-three (57.5%) PSP-RS and 43 (81%) bvFTD patients had at least one stereotypy; 16/23 (69.5%) PSP-RS and 9/43 (20.9%) bvFTD patients appeared aware of their stereotypies.

Conclusion

Stereotypies were common in our demented PSP-RS patients. Further studies on earlier stage non-demented PSP patients are required to ascertain whether stereotypies are characteristic of PSP in general or are confined to PSP-RS, and whether they may be used to suggest a PSP diagnosis early in disease course.

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Pachyonychia congenita: A case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


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Deficiency of sun protection advertising exists in consumer magazines across demographic groups and varies by target demographic

Publication date: Available online 11 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): L.E. Wiznia, J. Wang, A.B. Steuer, N. Elbuluk

https://ift.tt/2Ca2tTh

Re-evaluating the Need for Routine Laboratory Monitoring in Isotretinoin Patients: A Retrospective Analysis

Publication date: Available online 11 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Radhika Shah, Daniela Kroshinsky

https://ift.tt/2CBOh6t

Galeatomy: A Useful Technique Aiding High-Tension Scalp Closures

Publication date: Available online 10 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Marjon Vatanchi, Roy C. Grekin

https://ift.tt/2C9CZFG

Use of the index of ideality of correlation to improve models of eco-toxicity

Abstract

Persistent organic pollutants are compounds used for various everyday purposes, such as personal care products, food, pesticides, and pharmaceuticals. Decomposition of considerable part of the above pollutants is a long-time process. Under such circumstances, estimation of toxicity for large arrays of organic substances corresponding to the above category of pollutants is a necessary component of theoretical chemistry. The CORAL software is a tool to establish quantitative structure—activity relationships (QSARs). The index of ideality of correlation (IIC) was suggested as a criterion of predictive potential of QSAR. The statistical quality of models for eco-toxicity of organic pollutants, which are built up, with use of the IIC is better than statistical quality of models, which are built up without use of data on the IIC.

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Pooled Analysis of Clinical Data From Six GSK Studies to Investigate the Efficacy of a Dentifrice Containing 67% Weight by Weight (w/w) Sodium Bicarbonate on Gingivitis and Plaque Accumulation

Conditions:   Gingivitis;   Plaque Accumulation
Interventions:   Other: Sodium bicarbonate;   Other: Control Dentifrice
Sponsor:   GlaxoSmithKline
Not yet recruiting

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Liquid Biopsy Evaluation and Repository Development at Princess Margaret

Conditions:   Cancer;   Breast Cancer;   Lung Cancer;   Colon Cancer;   Ovarian Cancer;   Melanoma;   Lymphoma;   Leukemia;   Mutation;   Lynch Syndrome;   Cowden Syndrome;   BRCA1 Mutation;   BRCA2 Mutation;   Uterine Cancer;   Myeloma;   Kidney Cancer;   Head and Neck Cancer;   Meningioma
Intervention:  
Sponsor:   University Health Network, Toronto
Recruiting

https://ift.tt/2OQW71S

Scholar : These new articles for The American Journal of Family Therapy are available online

The online platform for Taylor & Francis Online content New for The American Journal of Family Therapy and online now on Taylor & Francis Online: Original Article The Phenomenological Experience of Parents Who Live with a Boomerang Child D. Robert Casares Jr. & Carolyn C. White Pages: 1-17 | DOI: 10.1080/01926187.2018.1495133 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) 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.

Evaluation of corrosion control products on a distribution system through crowdsourcing

Abstract

Crowdsourcing of citizens was used to determine the effectiveness of corrosion control in a water distribution system. This study examines the frequency and severity of "Red Water" complaints over a period of 4 years, and two different corrosion control chemicals, polyphosphate and zinc orthophosphate. The data revealed that the frequency of Red Water complaints was higher when using zinc orthophosphate while the severity (higher iron) was higher when using polyphosphates. Varying the dose of zinc orthophosphate to account for cold months induced a greater number of customer complaints. Moreover, corrosion coupons studies suggest similar performance of both corrosion inhibitor products. The corrosion and complaints might be driven by microbial-induced processes in which diatoms might play a significant role.

https://ift.tt/2A4ohhB

Multi-wavelength laser treatments of spider nevi

Abstract

Spider nevi (SN) are one of common vascular diseases. Different treatment techniques have been described for SN previously, including electrocoagulation, argon laser, pulsed dye lasers (PDL), pulsed potassium titanylphosphate laser (KTP), and 1064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser. These methods are effective but may require good technical management, multiple treatments, and often result in scarring or pigmentation. Multi-wavelength laser combined with 595-nm PDL followed by 1064-nm Nd:YAG and can be selectively absorbed by hemoglobin in vessels. The 595-nm laser can target shallow vessels whereas the 1064-nm laser may target deeper vessels due to the different penetration capacities of these wavelengths. Moreover, Nd:YAG absorption is remarkable increased following by PDL treatment. Multi-wavelength laser treatments have been successfully used for vascular diseases but there is little experience in SN therapy. Consequently, these treatment parameters have not been established for SN, particularly in Asian patients with Fitzpatrick skin type (FST) IV. Report experience with using multi-wavelength laser for SN treatment in Asian patients with FST IV. Forty-three SN lesions received multi-wavelength laser treatments via a PDL followed by an Nd:YAG laser. The treatment was performed at 7 mm spot size at 9.5–11 J/cm², 10 ms with PDL, followed by Nd:YAG at 40–50 J/cm², 15 ms. The laser treatments were performed with a single pass without overlap. Complete resolution was observed in 40 lesions and an 80–90% improvement in the other three lesions after one treatment session. One patient had superficial scarring. Four patients had hyperpigmentation that resolved within 3 months. Multi-wavelength laser treatments are fast and effective interventions for SN treatment in Asian patients with minimal adverse effects when appropriate parameters are set.

https://ift.tt/2C8iw40

Effects of dehydroepiandrosterone (DHEA) supplementation on sexual function in premenopausal infertile women

Abstract

Purpose

To investigate the effects of dehydroepiandrosterone (DHEA) supplementation on female sexual function in premenopausal infertile women of advanced ages.

Methods

This observational study was conducted in an academically affiliated private fertility center. Patients included 87 premenopausal infertile women, 50 of whom completed the study including the Female Sexual Function Index (FSFI) questionnaires and comprehensive endocrine evaluation before and 4–8 weeks after initiating 25 mg of oral micronized DHEA TID.

Results

Age of patients was 41.1 ± 4.2 years, BMI 24.4 ± 6.1 kg/m², 86% were married, and 42% were parous. Following supplementation with DHEA, all serum androgen levels increased (each P < 0.0001), while FSH levels decreased by 2.6 ± 4.4 from a baseline of 10.3 ± 5.4 mIU/mL (P = 0.009). The FSFI score for the whole study group increased by 7% (from 27.2 ± 6.9 to 29.2 ± 5.6; P = 0.0166). Domain scores for desire increased by 17% (P = 0.0004) and by 12% for arousal (P = 0.0122); lubrication demonstrated an 8% trend towards improvement (P = 0.0551), while no changes in domain scores for orgasm, satisfaction, or pain were observed. Women in the lowest starting FSFI score quartile (<25.7), experienced a 6.1 ± 8.0 (34%) increase in total FSFI score following DHEA supplementation. Among these women, improvements in domain categories were noted for desire (40%), arousal (46%), lubrication (33%), orgasm (54%), satisfaction (24%), and pain (25%).

Conclusions

This uncontrolled observational study implies that supplementation with DHEA improves sexual function in older premenopausal women with low baseline FSFI scores.

https://ift.tt/2A4ji0s

Prevalence of degenerative joint disease of the temporomandibular joint: a systematic review

Abstract

Objectives

The purpose of this systematic review was to evaluate evidence about the prevalence of degenerative joint disease (DJD) of the temporomandibular joints (TMJ).

Materials and methods

We performed search on electronic databases and gray literature from their inception to January 2018. Studies reporting prevalence data of DJD on TMJ were included. DJD was assessed through clinical and imaging diagnosis. Studies risk of bias was evaluated using the Critical Appraisal Checklist for Studies Reporting Prevalence Data.

Results

From 1082 studies, 32 were identified, and the sample size included 3435 subjects. They were clustered into two groups: the first comprised studies that reported prevalence of DJD in TMJ secondary to rheumatic systemic diseases like juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) and the second group comprised studies that reported prevalence of DJD on temporomandibular disorder patients. The prevalence of DJD on JIA patients ranged from 40.42% (n = 47) to 93.33% (n = 15) and on RA patients from 45.00% (n = 20) to 92.85% (n = 56). Among TMD patients, the prevalence of DJD reported according to patients ranged from 18.01% (n = 1038) to 84.74% (n = 118) and reported according to joints ranged from 17.97% (n = 178) to 77.23% (n = 224).

Conclusion

This review attempts to high prevalence of DJD in patients with systemic rheumatic disease and a less prevalent, but still high, occurrence in patients with TMD without systemic involvement.

Clinical relevance

Specialist doctors and dentists should be alert to not underestimate and to correctly diagnose DJD of the TMJ early in patients with rheumatic disease and TMD.

https://ift.tt/2A4iTes

Response to the letter sent by Dr. Viroj Wiwanitkit entitled “Coffee waste, vector control and dengue”

https://ift.tt/2CCPoDc

Severe hyperchylomicronemia in two infants with novel APOC2 gene mutation

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2EfGbSJ

Prevalence of overweight and obesity and anthropometric reference centiles for Albanian children and adolescents living in four Balkan nation-states

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


https://ift.tt/2RIlBgj

Effects of dehydroepiandrosterone (DHEA) supplementation on sexual function in premenopausal infertile women

Abstract

Purpose

To investigate the effects of dehydroepiandrosterone (DHEA) supplementation on female sexual function in premenopausal infertile women of advanced ages.

Methods

This observational study was conducted in an academically affiliated private fertility center. Patients included 87 premenopausal infertile women, 50 of whom completed the study including the Female Sexual Function Index (FSFI) questionnaires and comprehensive endocrine evaluation before and 4–8 weeks after initiating 25 mg of oral micronized DHEA TID.

Results

Age of patients was 41.1 ± 4.2 years, BMI 24.4 ± 6.1 kg/m², 86% were married, and 42% were parous. Following supplementation with DHEA, all serum androgen levels increased (each P < 0.0001), while FSH levels decreased by 2.6 ± 4.4 from a baseline of 10.3 ± 5.4 mIU/mL (P = 0.009). The FSFI score for the whole study group increased by 7% (from 27.2 ± 6.9 to 29.2 ± 5.6; P = 0.0166). Domain scores for desire increased by 17% (P = 0.0004) and by 12% for arousal (P = 0.0122); lubrication demonstrated an 8% trend towards improvement (P = 0.0551), while no changes in domain scores for orgasm, satisfaction, or pain were observed. Women in the lowest starting FSFI score quartile (<25.7), experienced a 6.1 ± 8.0 (34%) increase in total FSFI score following DHEA supplementation. Among these women, improvements in domain categories were noted for desire (40%), arousal (46%), lubrication (33%), orgasm (54%), satisfaction (24%), and pain (25%).

Conclusions

This uncontrolled observational study implies that supplementation with DHEA improves sexual function in older premenopausal women with low baseline FSFI scores.

https://ift.tt/2A4ji0s

Bilateral suprazygomatic maxillary nerve blocks vs. infraorbital and palatine nerve blocks in cleft lip and palate repair: A double-blind prospective, randomised study

BACKGROUND Cleft defects are common craniofacial malformations which require early surgical repair. These patients are at high risk of postoperative airway obstruction and respiratory failure. Cleft surgery may require high doses of opioids which may contribute to these complications. OBJECTIVES To compare the effectiveness of proximal and distal approaches to blocking the maxillary nerve in patients undergoing cleft lip or cleft palate surgery. DESIGN Randomised, controlled and double-blind study. SETTING The current study was carried out in Guwahati (Assam, India) between April 2014 and June 2014. PATIENTS A total of 114 patients older than 6 months who underwent cleft lip or cleft palate surgery were included. Exclusion criteria included coagulation disorders, peripheral neuropathy or chronic pain syndrome, infection in the puncture site, allergy to local anaesthetics, lack of consent and language problems or other barriers that could impede the assessment of postoperative pain. INTERVENTIONS Patients were randomly assigned to one of two groups: proximal group (bilateral suprazygomatic maxillary nerve blocks) and distal group (bilateral infraorbital nerve blocks for cleft lip repair and bilateral greater and lesser palatine nerve blocks and nasopalatine nerve block for cleft palate surgery). MAIN OUTCOME MEASURE The primary endpoint was the percentage of patients requiring extra doses of opioids. Secondary endpoints included pain scores, respiratory and nerve block-related complications during the first 24 h. RESULTS In the intra-operative period, there was a significant reduction of nalbuphine consumption in the proximal group (9.1 vs. 25.4%, P = 0.02). The percentage of patients requiring intra-operative fentanyl was lower in the proximal group (16.4 vs. 30.5%, P = 0.07). There were no differences in either postoperative pain scores or in postoperative complications. No technical failure or block-related complications were reported. CONCLUSION Bilateral suprazygomatic maxillary nerve block is an effective and safe alternative to the traditional peripheral nerve blocks for cleft lip and cleft palate surgery, in a mixed paediatric and adult population. Correspondence to Gaston Echaniz, Department of Anesthesiology, Vall d'Hebron Hospital, Department of Surgery, Universitat Autònoma de Barcelona, Passeig de Vall d'Hebron, 119-129, Barcelona 08035, Spain. E-mail: grcechaniz@vhebron.net Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

https://ift.tt/2QHkxZ6

Measurement of forces applied using a Macintosh direct laryngoscope compared with a Glidescope video laryngoscope in patients with predictors of difficult laryngoscopy: A randomised controlled trial

BACKGROUND In patients with predictive features associated with easy direct laryngoscopy, videolaryngoscoy with the GlideScope has been shown to require less force when compared with Macintosh direct laryngoscopy. OBJECTIVE The aim of this study was to compare forces applied with Glidescope vs. Macintosh laryngoscopes in patients with predictive features associated with difficult direct laryngoscopy. DESIGN A prospective randomised study. SETTING Toronto General Hospital, a university tertiary centre in Canada. PATIENTS Forty-four patients aged over 18 years, with one or more features of difficult intubation, undergoing elective surgery requiring single-lumen tracheal intubation. INTERVENTION We measured the force applied to oropharyngeal tissues by attaching three FlexiForce Sensors (A201-25) to the concave surface of Macintosh and GlideScope laryngoscope blades. Anaesthetists or experienced anaesthesia residents performed laryngoscopies with both devices in a randomised sequence. MAIN OUTCOME MEASURES The primary outcome was peak force. The secondary outcomes were average force and impulse force. The latter is the integral of the force over the time during which the force acted. RESULTS Complete data were available for 40 individuals. Peak and average forces decreased with GlideScope (17 vs. 21 N, P = 0.03, and 6 vs. 11 N, P 

https://ift.tt/2A4QCoh

Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood

BACKGROUND Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. OBJECTIVE The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, an second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. DESIGN Diagnostic test study. SETTINGS A university research laboratory. From November 2014 to April 2016. PATIENTS Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. INTERVENTION ROTEM was triggered with 2.5 pmol l−1 of tissue factor and 10 μmol l−1 of phospholipid vesicles. MAIN OUTCOME MEASURES Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. RESULTS Modified ROTEM allowed detection of as little as 25 ng ml−1 FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml−1 in whole blood with 90% sensitivity and 85% specificity. CONCLUSION Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood. Correspondence to Charles M. Samama, MD, PhD, FCCP, Department of Anaesthesia and Intensive Care Medicine, Cochin University Hospital, 27 rue du Faubourg St Jacques, 75014 Paris, France Tel: +33 1 42 34 85 51/+33 6 62 14 86 64; fax: +33 1 58 41 14 15; e-mail: marc.samama@aphp.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

https://ift.tt/2QHkoF2

Spectroscopic study of breath ethylene via the mouth and nose

Abstract

The development of new techniques for breath analysis searching for objective biomarkers of oxidative stress showed promise in non-invasive disclosing health information of the well-being of a person. Although numerous biomarkers have been identified so far using breath analysis, very little is known about their origin if they are metabolic or providing from mouth contamination. For the introduction of breath tests into clinical practice, standardization of sample collection needs to be taken into account. Breath analysis has been performed using laser photoacoustic spectroscopy to evaluate exhaled breath by mouth and nose before and after brushing with toothpaste/baking soda in order to identify the important endogenous biomarkers without contaminant sources. As a known biomarker of oxidative stress in the human body, it is important to accurately assess ethylene from exhaled air. Differences in the concentrations of exhaled ethylene are observed after using toothpaste and baking soda. The levels of ethylene are lower for nose breathing compared with mouth breathing. However, the differences are not significant proving that ethylene is generally endogenous but may still exist some contamination, depending of the oral hygiene of each person. These results may lead to a procedure, whereby subjects should be instructed to use toothpaste before each breath test sampling, to avoid the possibility of contamination of endogenous biomarkers.

https://ift.tt/2pMTwrz

CAPON Is a Critical Protein in Synaptic Molecular Networks in the Prefrontal Cortex of Mood Disorder Patients and Contributes to Depression-Like Behavior in a Mouse Model

Abstract

Aberrant regulation and activity of synaptic proteins may cause synaptic pathology in the prefrontal cortex (PFC) of mood disorder patients. Carboxy-terminal PDZ ligand of NOS1 (CAPON) is a critical scaffold protein linked to synaptic proteins like nitric oxide synthase 1, synapsins. We hypothesized that CAPON is altered together with its interacting synaptic proteins in the PFC in mood disorder patients and may contribute to depression-like behaviors in mice subjected to chronic unpredictable mild stress (CUMS). Here, we found that CAPON-immunoreactivity (ir) was significantly increased in the dorsolateral PFC (DLPFC) and anterior cingulate cortex in major depressive disorder (MDD), which was accompanied by an upregulation of spinophilin-ir and a downregulation of synapsin-ir. The increases in CAPON and spinophilin and the decrease in synapsin in the DLPFC of MDD patients were also seen in the PFC of CUMS mice. CAPON-ir positively correlated with spinophilin-ir (but not with synapsin-ir) in mood disorder patients. CAPON colocalized with spinophilin in the DLPFC of MDD patients and interacted with spinophilin in human brain. Viral-mediated CAPON downregulation in the medial PFC notably reversed the depression-like behaviors in the CUMS mice. These data suggest that CAPON may contribute to aspects of depressive behavior, possibly as an interacting protein for spinophilin in the PFC.

https://ift.tt/2QNT8or

Functional Parcellation of the Cerebral Cortex Across the Human Adult Lifespan

Abstract

Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20–93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.

https://ift.tt/2A3uI4G

Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood

Abstract

With increasing attention on the developmental causes of neuropsychiatric disorders, appropriate animal models are crucial to identifying causes and assessing potential interventions. The common marmoset is an ideal model as it has sophisticated social/emotional behavior, reaching adulthood within 2 years of birth. Magnetic resonance imaging was used in an accelerated longitudinal cohort (n = 41; aged 3–27 months; scanned 2–7 times over 2 years). Splines were used to model nonlinear trajectories of grey matter volume development in 53 cortical areas and 16 subcortical nuclei. Generally, volumes increased before puberty, peaked, and declined into adulthood. We identified 3 milestones of grey matter development: I) age at peak volume; II) age at onset of volume decline; and III) age at maximum rate of volume decline. These milestones differentiated growth trajectories of primary sensory/motor cortical areas from those of association cortex but also revealed distinct trajectories between association cortices. Cluster analysis of trajectories showed that prefrontal cortex was the most heterogenous of association regions, comprising areas with distinct milestones and developmental trajectories. These results highlight the potential of high-field structural MRI to define the dynamics of primate brain development and importantly to identify when specific prefrontal circuits may be most vulnerable to environmental impact.

https://ift.tt/2QH7HK2

Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain

Abstract

Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans.Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual's brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.

https://ift.tt/2A4ajMH

Morphological and Physiological Characteristics of Ebf2-EGFP-Expressing Cajal-Retzius Cells in Developing Mouse Neocortex

Abstract

Cajal-Retzius (CR) cells are one of the earliest populations of neurons in the cerebral cortex of rodents and primates, and they play a critical role in corticogenesis and cortical lamination during neocortical development. However, a comprehensive morphological and physiological profile of CR cells in the mouse neocortex has not yet been established. Here, we systematically investigated the dynamic development of CR cells in Tg(Ebf2-EGFP)58Gsat/Mmcd mice. The morphological complexity, membrane activities and presynaptic inputs of CR cells coordinately increase and reach a plateau at P5–P9 before regressing. Using 3D reconstruction, we delineated a parallel-stratification pattern of the axonal extension of CR cells. Furthermore, we found that the morphological structure and presynaptic inputs of CR cells were disturbed in Reelin-deficient mice. These findings confirm that CR cells undergo a transient maturation process in layer 1 before disappearing. Importantly, Reelin deficiency impairs the formation of synaptic connections onto CR cells. In conclusion, our results provide insights into the rapid maturation and axonal stratification of CR cells in layer 1. These findings suggest that both the electrophysiological activities and the morphology of CR cells provide vital guidance for the modulation of early circuits, in a Reelin-dependent manner.

https://ift.tt/2QKV2Gh

The Pace of Neurogenesis Is Regulated by the Transient Retention of the Apical Endfeet of Differentiating Cells

Abstract

The development of the mammalian cerebral cortex involves a variety of temporally organized events such as successive waves of neuronal production and the transition of progenitor competence for each neuronal subtype generated. The number of neurons generated in a certain time period, that is, the rate of neuron production, varies across the regions of the brain and the specific developmental stage; however, the underlying mechanism of this process is poorly understood. We have recently found that nascent neurons communicate with undifferentiated progenitors and thereby regulate neurogenesis, through a transiently retained apical endfoot that signals via the Notch pathway. Here, we report that the retention time length of the neuronal apical endfoot correlates with the rate of neuronal production in the developing mouse cerebral cortex. We further demonstrate that a forced reduction or extension of the retention period through the disruption or stabilization of adherens junction, respectively, resulted in the acceleration or deceleration of neurogenesis, respectively. Our results suggest that the apical endfeet of differentiating cells serve as a pace controller for neurogenesis, thereby assuring the well-proportioned laminar organization of the neocortex.

https://ift.tt/2A4oq4J

Heritability of Gray Matter Structural Covariation and Tool Use Skills in Chimpanzees (Pan troglodytes): A Source-Based Morphometry and Quantitative Genetic Analysis

Abstract

Nonhuman primates, and great apes in particular, possess a variety of cognitive abilities thought to underlie human brain and cognitive evolution, most notably, the manufacture and use of tools. In a relatively large sample (N = 226) of captive chimpanzees (Pan troglodytes) for whom pedigrees are well known, the overarching aim of the current study was to investigate the source of heritable variation in brain structure underlying tool use skills. Specifically, using source-based morphometry (SBM), a multivariate analysis of naturally occurring patterns of covariation in gray matter across the brain, we investigated (1) the genetic contributions to variation in SBM components, (2) sex and age effects for each component, and (3) phenotypic and genetic associations between SBM components and tool use skill. Results revealed important sex- and age-related differences across largely heritable SBM components and associations between structural covariation and tool use skill. Further, shared genetic mechanisms appear to account for a heritable link between variation in both the capacity to use tools and variation in morphology of the superior limb of the superior temporal sulcus and adjacent parietal cortex. Findings represent the first evidence of heritability of structural covariation in gray matter among nonhuman primates.

https://ift.tt/2QDqTIE

Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus

Abstract

Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.

https://ift.tt/2A3uHxE

Sparse Representation in Awake Auditory Cortex: Cell-type Dependence, Synaptic Mechanisms, Developmental Emergence, and Modulation

Abstract

Sparse representation is considered an important coding strategy for cortical processing in various sensory modalities. It remains unclear how cortical sparseness arises and is being regulated. Here, unbiased recordings from primary auditory cortex of awake adult mice revealed salient sparseness in layer (L)2/3, with a majority of excitatory neurons exhibiting no increased spiking in response to each of sound types tested. Sparse representation was not observed in parvalbumin (PV) inhibitory neurons. The nonresponding neurons did receive auditory-evoked synaptic inputs, marked by weaker excitation and lower excitation/inhibition (E/I) ratios than responding cells. Sparse representation arises during development in an experience-dependent manner, accompanied by differential changes of excitatory input strength and a transition from unimodal to bimodal distribution of E/I ratios. Sparseness level could be reduced by suppressing PV or L1 inhibitory neurons. Thus, sparse representation may be dynamically regulated via modulating E/I balance, optimizing cortical representation of the external sensory world.

https://ift.tt/2QGKoA8

Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex

Abstract

SAD kinases regulate presynaptic vesicle clustering and neuronal polarization. A previous report demonstrated that Sada^−/− and Sadb^−/− double-mutant mice showed perinatal lethality with a severe defect in axon/dendrite differentiation, but their single mutants did not. These results indicated that they were functionally redundant. Surprisingly, we show that on a C57BL/6N background, SAD-A is essential for cortical development whereas SAD-B is dispensable. Sada^−/− mice died within a few days after birth. Their cortical lamination pattern was disorganized and radial migration of cortical neurons was perturbed. Birth date analyses with BrdU and in utero electroporation using pCAG-EGFP vector showed a delayed migration of cortical neurons to the pial surface in Sada^−/− mice. Time-lapse imaging of these mice confirmed slow migration velocity in the cortical plate. While the neurites of hippocampal neurons in Sada^−/− mice could ultimately differentiate in culture to form axons and dendrites, the average length of their axons was shorter than that of the wild type. Thus, analysis on a different genetic background than that used initially revealed a nonredundant role for SAD-A in neuronal migration and differentiation.

https://ift.tt/2A4aibB

Comparative effects of arsenite (As(III)) and arsenate (As(V)) on whole plants and cell lines of the arsenic-resistant halophyte plant species Atriplex atacamensis

Abstract

Whole plants and hypocotyl-derived calli of the halophyte plant species Atriplex atacamensis were exposed to 50 μM arsenate (As(V)) or 50 μM arsenite (As(III)). At the whole plant level, As(III) was more toxic than As(V): it reduced plant growth, stomatal conductance, photosystem II efficiency while As(V) did not. In roots, As accumulated to higher level in response to As(III) than in response to As(V). Within root tissues, both arsenate and arsenite were identified in response to each treatment suggesting that oxidation of As(III) may occur. More than 40% of As was bound to the cell wall in the roots of As(V)-treated plants while this proportion strongly decreased in As(III)-treated ones. In leaves, total As and the proportion of As bound to the cell wall were similar in response to As(V) and As(III). Non-protein thiol increased to higher extent in response to As(V) than in response to As(III) while ethylene synthesis was increased in As(III)-treated plants only. Polyamine profile was modified in a contrasting way in response to As(V) and As(III). At the callus level, As(V) and As(III) 50 μM did not reduce growth despite an important As accumulation within tissues. Calli exposed to 50 μM As did not increase the endogenous non-protein thiol. In contrast to the whole plants, arsenite was not more toxic than arsenate at the cell line level and As(V)-treated calli produced higher amounts of ethylene and malondialdehyde. A very high dose of As(V) (1000 μM) strongly reduced callus growth and lead to non-protein thiols accumulation. It is concluded that As(III) was more toxic than As(V) at the plant level but not at the cellular level and that differential toxicity was not fully explained by speciation of accumulated As. Arsenic resistance in A. atacamensis exhibited a cellular component which however did not reflect the behavior of whole plant when exposed to As(V) or As(III).

https://ift.tt/2RJJlB5

The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing's disease

Abstract

Purpose

Bilateral inferior petrosal sinus sampling (BIPSS) is useful for differential diagnosis of adult Cushing's disease (CD) but may not be so reliable in pediatric cases. The purpose of this study was to evaluate the sensitivity of BIPSS before and after desmopressin stimulation in pediatric CD, and to explore related factors of false-negative results and meanings of sampling lateralization.

Methods

We retrospectively analyzed 16 pediatric CD patients who underwent 17 BIPSS procedures from 2006 to 2017. CD was diagnosed if inferior petrosal sinus (IPS) to peripheral adrenocorticotropic hormone (ACTH) ratio was >2 at baseline or >3 after desmopressin stimulation. Sampling lateralization was yielded if interpetrosal sinus gradient was >1.4. Magnetic resonance imaging (MRI) was conducted. All the patients underwent surgery and the diagnosis was confirmed.

Results

The sensitivity was 64.7% (11/17) at baseline and 83.3% (10/12) after desmopressin stimulation. After stimulation, BIPSS reached its best sensitivity at 3 min. Sampling lateralization rate was 62.5% and 63.6% before and after stimulation, and the accordant rate with actual tumor lateralization was 50.0% and 42.9%, respectively. The accuracy of MRI in predicting the tumor lateralization was 80.0%. Sampling lateralization rate (81.8% in true-positive, 20.0% in false-negative, p = 0.036) and ACTH at dominant IPS (p = 0.001) was lower among false-negative patients.

Conclusions

The sensitivity of BIPSS in pediatric CD was low at baseline, but increased after desmopressin stimulation. Sampling lateralization cannot accurately indicate the tumor lateralization, but the absence of sampling lateralization with low ACTH at IPS is a hint of false-negative cases in BIPSS.

https://ift.tt/2CGDIz8

Hooked on Hooks? A Study in the Utilization of Skin Hooks

BACKGROUND The skin hook is a valuable instrument used in the practice of dermatologic surgery. However, because of numerous factors, the degree of its use varies extensively. OBJECTIVE The purpose of this study was to examine practice trends among dermatologic surgeons regarding the use of skin hooks, as well as analyze factors influencing their use. METHODS A survey comprising 14 questions was distributed to members of the American College of Mohs Surgery and the American Society for Dermatologic Surgery. Results were recorded, and statistical analysis was conducted using the 2-sample z-test to compare 2 population proportions. RESULTS Five hundred seventy-one responses were received, with comments. 85.1% of respondents reported using skin hooks. Their use was further characterized as minimal (20.7%), moderate (29.0%), and extensive (35.4%). The utilization of skin hooks was additionally categorized based on age, gender, fellowship training, number of years in practice, practice setting, and history of experience/observance of a sharps exposure. Only the presence or absence of fellowship training demonstrated a statistically significant difference in the use of skin hooks. CONCLUSION Skin hooks are highly used tools among dermatologic surgeons. Their use requires appropriate training and experience, and care must be taken to minimize risk of exposure. Address correspondence and reprint requests to: Summer Clark, MD, 619 NE 13th Street, Oklahoma City, OK, 73104, or e-mail: summerjamesclark@gmail.com The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2QJAEoH

Commentary on Patients' Body Image Improves After Mohs Micrographic Surgery for Nonmelanoma Head and Neck Skin Cancer

No abstract available

https://ift.tt/2A3nTQC

Efficacy of photobiomodulation on accelerating bone healing after tooth extraction: a systematic review

Abstract

Post-extraction healing of the socket may take up to 24 weeks to complete. This systematic review aims to evaluate whether photobiomodulation accelerates bone healing in those sockets. A search strategy was developed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Cochrane Library, and Scopus electronic databases were searched for in vivo studies with restrictions on the year (< 50 years old) and language (English). After applying the inclusion criteria, ten studies were selected for review. Test subjects included humans (3), rats (5), and rabbits (2), either healthy or with specified systemic condition(s). Laser parameters applied varied between studies significantly. Six studies measured bone density or bone trabeculae percentage, while remaining studies measured secondary outcome measures such as osteogenesis markers, patient's self-reported pain scores, and clinical epithelial regeneration. No side effects of photobiomodulation have been reported. Higher concentration of osteogenesis markers Ocn and Runx2 were consistently reported across studies, as well as higher percentage of bony trabeculae and bone density. Within the limitations of this review, improvement in bone repair can be found when using photobiomodulation in extraction sockets.

https://ift.tt/2NBeZgF

Types of advanced optical microscopy techniques for breast cancer research: a review

Abstract

A cancerous cell is characterized by morphological and metabolic changes which are the key features of carcinogenesis. Adenosine triphosphate (ATP) in cancer cells is primarily produced by aerobic glycolysis rather than oxidative phosphorylation. In normal cellular metabolism, nicotinamide adenine dinucleotide (NADH) is considered as a principle electron donor and flavin adenine dinucleotide (FAD) as an electron acceptor. During metabolism in a cancerous cell, a net increase in NADH is found as the pathway switched from oxidative phosphorylation to aerobic glycolysis. Often during initiation and progression of cancer, the developmental regulation of extracellular matrix (ECM) is restricted and becomes disorganized. Tumor cell behavior is regulated by the ECM in the tumor micro environment. Collagen, which forms the scaffold of tumor micro-environment also influences its behavior. Advanced optical microscopy techniques are useful for determining the metabolic characteristics of cancerous, normal cells and tissues. They can be used to identify the collagen microstructure and the function of NADH, FAD, and lipids in living system. In this review article, various optical microscopy techniques applied for breast cancer research are discussed including fluorescence, confocal, second harmonic generation (SHG), coherent anti-Stokes Raman scattering (CARS), and fluorescence lifetime imaging (FLIM).

https://ift.tt/2OSn6Kv

Effects of antibacterial photodynamic therapy on salivary mutans streptococci in 5- to 6-year-olds with severe early childhood caries

Abstract

Antibacterial photodynamic therapy (A-PDT) has been shown to kill oral bacteria in the planktonic culture, dental plaque, and biofilm. This study sought to assess the antimicrobial effect of A-PDT with toluidine blue O (TBO) and diode laser on salivary mutans streptococci in 5–6-year-olds with severe early childhood caries (SECC). This case-control study was conducted on 56 children with SECC divided into four groups, namely 0.1 mg/mL TBO, diode laser (633 nm, 20 mW, 6 J/cm²), combination of the two, and no intervention control group. A-PDT was performed on days 1 and 3. Salivary samples were collected before and after A-PDT on days 1 and 3, and 1 and 2 weeks after the second intervention (day 3). Samples were cultured on mitis salivarius agar, and after incubation, the colonies were counted. Data were subjected to repeated measures ANOVA, ANCOVA, and paired comparisons with least square difference and Tukey's test. Bacterial count significantly decreased on days 1 and 3, and 1 and 2 weeks after the second intervention. Bacterial count also decreased following the use of TBO and laser separately, but these reductions were not significant (P > 0.05). Within the limitations of this study, antimicrobial efficacy of TBO + laser was higher than that of diode laser or TBO alone. Durability of treatment increased with double-dose therapy. This modality may be used to decrease the colony count of salivary mutans streptococci in children with SECC.

https://ift.tt/2NB41HV

The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing's disease

Abstract

Purpose

Bilateral inferior petrosal sinus sampling (BIPSS) is useful for differential diagnosis of adult Cushing's disease (CD) but may not be so reliable in pediatric cases. The purpose of this study was to evaluate the sensitivity of BIPSS before and after desmopressin stimulation in pediatric CD, and to explore related factors of false-negative results and meanings of sampling lateralization.

Methods

We retrospectively analyzed 16 pediatric CD patients who underwent 17 BIPSS procedures from 2006 to 2017. CD was diagnosed if inferior petrosal sinus (IPS) to peripheral adrenocorticotropic hormone (ACTH) ratio was >2 at baseline or >3 after desmopressin stimulation. Sampling lateralization was yielded if interpetrosal sinus gradient was >1.4. Magnetic resonance imaging (MRI) was conducted. All the patients underwent surgery and the diagnosis was confirmed.

Results

The sensitivity was 64.7% (11/17) at baseline and 83.3% (10/12) after desmopressin stimulation. After stimulation, BIPSS reached its best sensitivity at 3 min. Sampling lateralization rate was 62.5% and 63.6% before and after stimulation, and the accordant rate with actual tumor lateralization was 50.0% and 42.9%, respectively. The accuracy of MRI in predicting the tumor lateralization was 80.0%. Sampling lateralization rate (81.8% in true-positive, 20.0% in false-negative, p = 0.036) and ACTH at dominant IPS (p = 0.001) was lower among false-negative patients.

Conclusions

The sensitivity of BIPSS in pediatric CD was low at baseline, but increased after desmopressin stimulation. Sampling lateralization cannot accurately indicate the tumor lateralization, but the absence of sampling lateralization with low ACTH at IPS is a hint of false-negative cases in BIPSS.

https://ift.tt/2CGDIz8

Efficacy of a drug composed of herbal extracts on postoperative discomfort after surgical removal of impacted mandibular third molar: a randomized, triple-blind, controlled clinical trial

Abstract

Objectives

This study investigated and compared the effectiveness of a phytotherapeutic drug composed of herbal extracts on postsurgical discomfort after mandibular third molar surgery.

Materials and methods

Eighty-two patients requiring the surgical removal of a mandibular third molar were randomly assigned to receive placebo (group 1), ibuprofen (group 2), and a phytotherapeutic drug (composed of baicalin, 190 mg; bromelain, 50 mg; escin, 30 mg) (group 3). Drugs were administered after tooth extraction twice a day for 5 days. The primary outcome, pain, was evaluated using a visual analogue scale at 2 h, 6 h, 12 h, 24 h, 48 h, and 7 and 10 days after surgery. The secondary outcomes were the changes in maximum mouth opening and facial contours (mm) between baseline and at 24 h, 72 h, and 7 and 10 days after surgery.

Results

Compared to the baseline, all treatments demonstrated an improvement in the primary and secondary outcomes. Moreover, compared to groups 1 and 2, patients in group 3 yielded a significant reduction of the postoperative pain score at 12 h (p < 0.001), 24 h (p = 0.010), and 48 h (p = 0.048) after surgery. The mean reduction of the swelling and trismus was similar between groups.

Conclusions

The results of this study suggest that a postoperative administration of a phytotherapeutic drug was found to be effective in postoperative pain management after the surgical removal of impacted mandibular third molars.

Clinical relevance

The phytotherapeutic drug composed of herbal extract determined a decrease in the severity of postoperative pain compared to ibuprofen and placebo.

https://ift.tt/2OTj5W5

Comparative effect of platelet-rich plasma, platelet-poor plasma, and fetal bovine serum on the proliferative response of periodontal ligament cell subpopulations

Abstract

Objectives

Cell-based therapies involve the need to expand cell cultures ex vivo for their subsequent implantation in an autologous manner. An important limitation regarding this technology is the use of fetal bovine serum (FBS) that has critical safety limitations. Platelet-derived fractions represent an autologous source of growth factors that may be used for the expansion of these cell cultures. Periodontal ligament (PDL) cells comprise a heterogeneous cell population that may not necessarily respond in a uniform manner to proliferative stimuli. The aim of this study was to evaluate the ability of two platelet-derived fractions, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) and FBS on the proliferative response of different subpopulations of PDL cell cultures.

Materials and methods

PDL cells were characterized and then exposed to PRP, PPP, or FBS during 2, 5, or 14 days to analyze cell proliferation and clonogenic capability. Cell proliferation was evaluated through immunofluorescence for Ki67 and by tracing carboxyfluorescein diacetate succinimidyl ester (CFSE) dye in combination with mesenchymal stem cell markers using flow cytometry.

Results

Both PRP and PPP stimulated PDL cell proliferation and their clonogenic ability. We found a significant increase of CD73- and CD90-positive cells after PRP or PPP treatment, compared to FBS. Otherwise, no differences were found regarding the response of CD146-or CD105-positive cells when stimulated with PRP, PPP, or FBS.

Conclusion

PRP and PPP can stimulate the proliferation and clonogenicity of PDL cell populations including cells positive for CD90 and CD73 markers.

Clinical relevance

These findings may have implications for future therapies aiming to stimulate periodontal regeneration using autologous growth factors.

https://ift.tt/2NA7EOw

Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity

Abstract

Because of the potential regenerative and cytoprotective effects of its content of numerous bioactive growth factors and cytokines, platelet-rich plasma (PRP) became an attractive biomaterial for therapeutic purposes. Therefore, the current study was designed to investigate the potential therapeutic effect of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity. To do so, hepatotoxicity was induced in rats by intraperitoneal administration of lead nitrate (7.5 mg/kg) thrice weekly for two consecutive weeks and/or a whole-body γ-irradiation at a single dose of 6 Gy. Activated PRP (0.5 ml/kg) was injected subcutaneously 24 h after the last dose of lead nitrate and/or γ-irradiation and continued twice weekly for three successive weeks. Lead nitrate intoxication and/or γ-irradiation resulted in a significant elevation of serum alanine transaminase and aspartate transaminase activities accompanied with a significant decrease in serum levels of total protein and albumin. Further, a significant increase in malondialdehyde level and nitric oxide content accompanied with a significant decrease in the reduced glutathione content and the enzyme activities of glutathione-S-transferase, superoxide dismutase, and catalase were observed. Additionally, hepatic extracellular signal-regulated kinase (ERK) and Akt signaling pathways were stimulated. PRP treatment notably ameliorated the induced cell injury, reduced the intracellular oxidative and interestingly increased the upregulation of phosphorylated ERK1/2 and Akt. Moreover, PRP treatment relieved lead nitrate and/or γ-radiation-induced hepatic histological damages. In conclusion, this study sheds the light on a probable therapeutic role of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity which might attribute to its ability to activate ERK and Akt signaling pathways.

https://ift.tt/2OTzMkf

Scholar : ΓΛΩΣΣΙΤΙΣ - νέα αποτελέσματα

[HTML] Pathologic findings and causes of death of stranded cetaceans in the Canary Islands (2006-2012)

J Díaz-Delgado, A Fernández, E Sierra, S Sacchini… - PloS one, 2018

This study describes the pathologic findings and most probable causes of
death (CD) of 224 cetaceans stranded along the coastline of the Canary
Islands (Spain) over a 7-year period, 2006–2012. Most probable CD, grouped …

Self-Assessment in Dermatopathology

M Mahalingam - 2018

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R. Anjali Kumbla, MD, Jeffrey M. Miller, MD, and

TG Hayes - Medical Secrets E-Book, 2018

Page 413. ONCOLOGY R. Anjali Kumbla, MD, Jeffrey M. Miller, MD, and Teresa G. Hayes,
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