A tennis lesson: sharp practice in the science behind the Sharapova case

Maria Sharapova (and hundreds of other elite athletes) took meldonium, a drug developed at the time of the USSR for the treatment of heart attack and stroke, though it has never been approved for use anywhere outside of the former Soviet Union. Meldonium is an inhibitor of -butyrobetaine hydroxylase, an enzyme involved in the carnitine biosynthetic pathway.1 Intake results in a reduction of tissue carnitine content, including the heart and skeletal muscles. Carnitine plays a critical role in transferring long-chain fatty acids across mitochondrial inner membrane into the mitochondrial matrix, to enable entry of the fatty acid moiety into the oxidation pathway, to synthesise ATP aerobically.2 In cases when intracellular carnitine availability is compromised, such as in neonatal primary carnitine deficiency,3 those affected experience hypoglycaemia, fatigue, seizures and cardiomyopathy.3 Carnitine-deficient individuals are sensitive to prodrugs containing the pivaloyl moiety, as pivalic acid...

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Evaluation of low-level laser therapy on skeletal muscle ischemia–reperfusion in streptozotocin-induced diabetic rats by assaying biochemical markers and histological changes

Abstract

The purpose of the present study was to assess the effects of low-level laser therapy (LLLT) on skeletal muscle ischemia–reperfusion (IR) injuries in streptozotocin-induced diabetic rats. Twenty male Wistar rats were randomly assigned into two experimental groups, as follows: the diabetic IR group (G1, n = 10) and the diabetic IR + LLLT group (G2, n = 10). Ischemia was induced in anesthetized rats from the right femoral artery clipping for 2 h, followed by a reperfusion for 24 h. Then, the laser irradiation (K30 handheld probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface area = 1 cm², energy density = 1.8 J/cm²) was carried out by irradiating the rats over a unique point on the skin over the middle region of the right gastrocnemius muscle belly three times (every 8 h), starting after initiating the reperfusion for 3 min. At the end of the reperfusion period, rats were anaesthetized and blood samples were collected and used for the estimation of pO₂, pCO₂, pH, HCO₃, serum creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Subsequently, the right gastrocnemius muscle samples were taken for wet/dry weight ratio assessment and histological/biochemical examination. The pO₂, pCO₂, HCO₃, and pH levels were similar for both groups (P > 0.05). The serum LDH and CPK levels were significantly lower (P < 0.05) for G2 compared to G1. In comparison to G1, tissue malondialdehyde level in G2 was significantly decreased (P < 0.05). In G2, superoxide dismutase activity was significantly increased compared to G1 (P < 0.05). Unlike G2, a significant decrease in the activity of catalase was observed in G1 (P < 0.05). The wet/dry ratio in G1 was significantly higher than that of G2 (P < 0.05). Histological examination confirmed that the extent of muscle changes in G1 was higher than G2 (P < 0.05). Finally, according to this study, LLLT has a beneficial effect on the IR muscle injury treatment in the diabetic rats. Therefore, we suggest that further research needs to be conducted using different laser parameters and examining response over a longer period of tissue recovery.

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Acute effects of low-level laser therapy irradiation on blood lactate and muscle fatigue perception in hospitalized patients with heart failure—a pilot study

Abstract

The objective of the present study is to evaluate the acute effects of low-level laser therapy (LLLT) on functional capacity, perceived exertion, and blood lactate in hospitalized patients with heart failure (HF). Patients diagnosed with systolic HF (left ventricular ejection fraction <45 %) were randomized and allocated prospectively into two groups: placebo LLLT group (n = 10)—subjects who were submitted to placebo laser and active LLLT group (n = 10)—subjects who were submitted to active laser. The 6-min walk test (6MWT) was performed, and blood lactate was determined at rest (before LLLT application and 6MWT), immediately after the exercise test (time 0) and recovery (3, 6, and 30 min). A multi-diode LLLT cluster probe (DMC, São Carlos, Brazil) was used. Both groups increased 6MWT distance after active or placebo LLLT application compared to baseline values (p = 0.03 and p = 0.01, respectively); however, no difference was observed during intergroup comparison. The active LLLT group showed a significant reduction in the perceived exertion Borg (PEB) scale compared to the placebo LLLT group (p = 0.006). In addition, the group that received active LLLT showed no statistically significant difference for the blood lactate level through the times analyzed. The placebo LLLT group demonstrated a significant increase in blood lactate between the rest and recovery phase (p < 0.05). Acute effects of LLLT irradiation on skeletal musculature were not able to improve the functional capacity of hospitalized patients with HF, although it may favorably modulate blood lactate metabolism and reduce perceived muscle fatigue.

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Low level laser therapy associated with a strength training program on muscle performance in elderly women: a randomized double blind control study

Abstract

The aging process leads to a gradual loss of muscle mass and muscle performance, leading to a higher functional dependence. Within this context, many studies have demonstrated the benefits of a combination of physical exercise and low level laser therapy (LLLT) as an intervention that enhances muscle performance in young people and athletes. The aim of this study was to evaluate the effects of combination of LLLT and strength training on muscle performance in elderly women. For this, a hundred elderly women were screened, and 48 met all inclusion criteria to participate in this double-blind placebo-controlled trial. Volunteers were divided in three groups: control (CG = 15), strength training associated with placebo LLLT (TG = 17), and strength training associated with active LLLT (808 nm, 100 mW, 7 J) (TLG = 16). The strength training consisted of knee flexion-extension performed with 80 % of 1-repetition maximum (1-RM) during 8 weeks. Several outcomes related to muscle performance were analyzed through the 6-min walk test (6-MWT), isokinetic dynamometry, surface electromyography (SEMG), lactate concentration, and 1-RM. The results revealed that a higher work (p = 0.0162), peak torque (p = 0.0309), and power (p = 0.0223) were observed in TLG compared to CG. Furthermore, both trained groups increased the 1-RM load (TG vs CG: p = 0.0067 and TLG vs CG: p < 0.0001) and decreased the lactate concentration in the third minute after isokinetic protocol (CG vs TLG: p = 0.0289 and CG vs TG: p = 0.0085). No difference in 6-MWT and in fatigue levels were observed among the groups. The present findings suggested that LLLT in combination with strength training was able to improve muscle performance in elderly people.

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Improved Butanol–Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples

Abstract

Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol–methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1 % acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh–Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples.

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Role of Environmental Factors on Resuming Valued Activities Poststroke: A Systematic Review of Qualitative and Quantitative Findings

Publication date: June 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 6
Author(s): Sandra Jellema, Rob van der Sande, Suzanne van Hees, Jana Zajec, Esther M. Steultjens, Maria W. Nijhuis-van der Sanden
ObjectiveTo investigate how reengagement in valued activities poststroke is influenced by environmental factors.Data SourcesPubMed, CINAHL, and PsycINFO were searched to June 2015 using multiple search terms for stroke, activities, disability, and home and community environments, with the following constraints: English, humans, and adults.Study SelectionStudies were included that contained data on how reengagement in valued activities of community-dwelling stroke survivors was influenced by the environment. Two reviewers independently selected the studies. The search yielded 3726 records; 39 studies were eventually included.Data ExtractionFindings were extracted from qualitative, quantitative, and mixed-design studies. Two reviewers independently assessed study quality using the Oxford Critical Appraisal Skills Programme lists and independently extracted results.Data SynthesisThematic analysis was conducted on qualitative data, revealing 9 themes related to the iterative nature of the process of reengagement and the associated environmental factors. During the process of reengagement, environmental factors interact with personal and disease-related factors in a gradual process of shaping or abandoning valued activities. The sociocultural context in this case determines what activities are valued and can be resumed by stroke survivors. Social support; activity opportunities and obligations; familiar and accessible environments; resources and reminders; and a step-by-step return facilitate stroke survivors to explore, adapt, resume, and maintain their activities. Social support is helpful at all stages of the process and particularly is important in case stroke survivors are fearful to explore their activity possibilities. The quantitative data identified largely endorsed these findings. No quantitative data were found in respect to the iterative nature of the process, familiar environments, or accessibility.ConclusionsReengagement in valued activities is a gradual process. In each stage of the process, several environmental factors play a role. During rehabilitation, professionals should pay attention to the role physical and social environmental factors have in reengagement poststroke and find ways to optimize stroke survivors' environments.



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Molecular Imaging of Small Animals

This article reviews Molecular Imaging of Small Animals by H. Zaidi

 

Instrumentation and Applications. Editor: . , Heidelberg, NY, 2014. 760 pp. Price: $239.00. ISBN: 978-1-4939-0893-6 (hardcover).

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Imaging in Nuclear Medicine

This article reviews Imaging in Nuclear Medicine

 

Editors. A. Giussani and C. Hoeschen , Heidelberg, NY, 2013. Hardcover 237 pp. Price: $139.00. ISBN: 978-3-642-31414-8 eBook Price: $109.00. ISBN: 978-3-642-31415-5.

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Erratum: “Coverage-based treatment planning to accommodate deformable organ variations in prostate cancer treatment” [Med. Phys. 41(10), 101705 (14pp.) (2014)]

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Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist's role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications and includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country's regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformité Européenne), and institutional review boards and radiation safety committees.

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A concept for classification of optimal breathing pattern for use in radiotherapy tracking, based on respiratory tumor kinematics and minimum jerk analysis

Purpose:

During radiotherapy, maintaining the patient in a relaxed and comfortable state helps ensure respiratory regularity and reproducibility, thereby supports accurate respiratory tracking/gating treatment. Criteria to evaluate respiratory naturalness, regularity, and phase robustness are therefore needed to aid for the treatment system numerically and medical observers visually. This study introduces a new concept of respiratory tumor kinematics that describes the trajectory of tumor motion with respiration, leading to the minimum jerk theory. Using this theory, this study proposes novel respiratory criteria for respiratory naturalness, regularity, and phase robustness.

Methods:

According to respiratory tumor kinematics, tumor motion follows the minimum curvature/jerk trajectory in 4D spacetime. Using this theory, the following three respiratory criteria are proposed: (1) respiratory naturalness , the residual sum of the squared difference between the normalized average free respiratory wave (single inhalation/exhalation averaged over each 10 phases) and the normalized minimum jerk theoretical respiratory wave; (2) respiratory regularity , the cumulative jerk squared cost function sampling every 0.2 s with a peak adjustment coefficient, 16; and (3) respiratory phase robustness (L Δ), a second-order partial differential in the respiratory position for regarded C j16 as the respiratory position function. To verify these respiratory criteria, values obtained from CyberKnife tracking marker log data for 15 patients were compared with regard to the correlation error between the correlation model and the imaged tumor position, as well as with the number of remodels. The C j16 growth curve was also compared between 15 patients and 15 healthy volunteers.

Results:

In the 15 patients, data with Us C j16(60 s) Us values (less respiratory naturalness) and higher C j16(60 s) values (less respiratory regularity) demonstrated more than 3 mm average/5 mm maximum correlation errors and an increased number of remodels. The data for the 15 patients and 15 volunteers demonstrated that the C j16 growth curve over 120 s from the start of sampling indicated patient-specific respiratory trends and that the distribution of L Δ clearly showed the respiratory phase shift. In 22 of 30 subjects, the degree of change in the Cj growth curve trends from 60 to 120 s was 22% ± 13% (average ± SD). In contrast, the residual data observed when C j16 > 1000 showed minimum and mean changes of 91% and 180%, respectively.

Conclusions:

The authors developed and verified novel respiratory criteria for respiratory naturalness, regularity, and phase robustness obtained using respiratory tumor kinematics and minimum jerk analysis. These criteria should be useful in monitoring respiratory trends on a real-time basis during treatment, as well as in selecting optimal breathing for tracking/gating radiation treatment and defining numerical goals for respiratory training/gating.

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Conformal image-guided microbeam radiation therapy at the ESRF biomedical beamline ID17

Purpose:

Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target.

Methods:

This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles.

Results:

Using four external fiducial markers of 1.7  mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2  mm can be achieved with an angular deviation of less than 2^∘. Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1  mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam.

Conclusions:

The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials.

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Quantitative IR microscopy and spectromics open the way to 3D digital pathology

Currently, only mass-spectrometry (MS) microscopy brings a quantitative analysis of chemical contents of tissue samples in 3D. Here, the reconstruction of a 3D quantitative chemical images of a biological tissue by FTIR spectro-microscopy is reported. An automated curve-fitting method is developed to extract all intense absorption bands constituting IR spectra. This innovation benefits from three critical features: (1) the correction of raw IR spectra to make them quantitatively comparable; (2) the automated and iterative data treatment allowing to transfer the IR-absorption spectrum into a IR-band spectrum; (3) the reconstruction of an 3D IR-band matrix (x, y, z for voxel position and a 4^th dimension with all IR-band parameters). Spectromics, which is a new method for exploiting spectral data for tissue metadata reconstruction, is proposed to further translate the related chemical information in 3D, as biochemical and anatomical tissue parameters. An example is given with oxidative stress distribution and the reconstruction of blood vessels in tissues. The requirements of IR microscopy instrumentation to propose 3D digital histology as a clinical routine technology is briefly discussed.

The reconstruction of a 3D quantitative chemical image of a biological tissue by FTIR spectro-microscopy is reported. An automated curve-fitting method is developed to extract all intense absorption bands constituting IR spectra. Spectromics, which is a new method for exploiting spectral data for tissue metadata reconstruction, is proposed to further translate the related chemical information in 3D, as biochemical and anatomical tissue parameters. The requirements of IR microscopy instrumentation to propose 3D digital histology as a clinical routine technology is briefly discussed.

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Effect of photodynamic therapy for the treatment of halitosis in adolescents – a controlled, microbiological, clinical trial

Halitosis can exert a negative influence on the social relations of adolescents and affect one's self-image. The aim of this study was to evaluate the clinical and microbiological effect of antimicrobial photodynamic therapy (aPDT) on halitosis in adolescents. Forty-six individuals aged 12 to 19 years were randomly allocated: Group 1 – treatment with photodynamic therapy; Group 2 – treatment with a tongue scraper and Group 3 – treatment with a tongue scraper and photodynamic therapy. The count of bacterial colony-forming units per milliliter was used for the microbiological analysis. Statistical analysis involved the Kruskal–Wallis test followed by the Student–Newman–Keuls test. ANOVA was used for the determination of colony-forming units after treatment. The level of significance for all statistical tests was 5% (p < 0.05). After treatment, a statistically significant reduction in total volatile sulfur compounds was found in all groups (p < 0.001), with the largest reduction (median: 0) found in Group 3 (tongue scraper and photodynamic therapy). Moreover, a statistically significant difference was found between treatment with aPDT and a tongue scraper alone (p < 0.001). The present findings demonstrate an option for the treatment of halitosis in adolescents, with an immediate effect and without the mechanical aggression to the toungue.

Halitosis can affect the social life and bring a lot of embarrassment to anyone who has this condition, especially by teenagers who are in a phase of social acceptance, it is mainly caused by degradation of organic substrates by anaerobic bacteria present in the dorsum of the tongue. This study aimed to propose a new approach to treatment for halitosis using antimicrobial photodynamic therapy, due to the high efficiency of this therapy when used in other dental treatments, and few studies submitted for this purpose. As a result it was possible to observe an immediate result in the reduction of halitosis.

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Front Cover: In situ non-destructive measurement of biofilm thickness and topology in an interferometric optical microscope (J. Biophotonics 6/2016)

The cover picture shows a biofilm imaged using a new technique that utilizes white light interferometry (WLI). WLI is an established surface metrology technique that has not been previously used to image biofilms and we present the first images of biofilm growth using this nondestructive method. WLI produces a 3D topographical map of the biofilm with nanometer vertical resolution that will enable detailed studies of biofilm features and growth rates.

Further details can be found in the article by Curtis Larimer et al. on pp. 656–666.

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Contents: J. Biophotonics 6/2016

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Issue Information: J. Biophotonics 6/2016

No abstract is available for this article.

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Back Cover: Observation of an improved healing process in superficial skin wounds after irradiation with a blue-LED haemostatic device (J. Biophotonics 6/2016)

Graphic composition representing thermographic images taken during EMOLED treatment of a superficial skin wound (middle), surrounded by multiphoton (top) and confocal fluorescence (bottom) images of a superficial skin wound treated with EMOLED (left) and untreated (right).

Further details can be found in the article by Riccardo Cicchi et al. on pp. 645–655.

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Effectiveness of Gotu Kola Extract 750 mg and 1000 mg Compared with Folic Acid 3 mg in Improving Vascular Cognitive Impairment after Stroke

This study aimed to determine the effectiveness of gotu kola (Centella asiatica) in improving cognitive function in patients with vascular cognitive impairment (VCI). This study uses a quasi-experimental design. Subjects in this study were patients with poststroke cognitive impairment who were treated at two hospitals in Yogyakarta, Indonesia. The number of subjects was 48: 17 subjects were treated with 1000 mg/day of gotu kola extract, 17 subjects treated with 750 mg/day of gotu kola extract, and 14 subjects treated with 3 mg/day of folic acid for 6 weeks. A Montreal Cognitive Assessment-Indonesian version (MoCA-Ina) was conducted at the beginning of treatment and after 6 weeks of therapy. It was found that all trials effectively improved poststroke VCI based on MoCA-Ina scores over the course of the study. There is no significant difference in ΔMoCA-Ina (score at the 6th week of treatment − score at the beginning) mean score among the three groups, indicating that gotu kola is as effective as folic acid in improving poststroke VCI. Gotu kola was shown to be more effective than folic acid in improving memory domain. This study suggested that gotu kola extract is effective in improving cognitive function after stroke.

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Looking for New Herbal Treatments for Metabolic Syndrome

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Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy

"Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics.

Antibiotic resistance is able to enhance bacterial fitness in vivo as well as bacterial virulence during infections. Cutting back on antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Alternative approaches that have the potential to by-pass the classic antibiotics have to be considered.

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Developmental Psychobiology: Volume 58, Number 5, July 2016

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Issue Information

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Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study

Digestive and Liver Diseases

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How to predict difficult laparoscopic cholecystectomy? Proposal for a simple preoperative scoring system

The American Journal of Surgery

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Changes in fat-soluble vitamin levels after gastrectomy for gastric cancer

Surgery Today

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Predicting individual survival after hepatectomy for hepatocellular carcinoma: A novel nomogram from the HCC east & west study group

Journal of Gastrointestinal Surgery

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Development of new fatty liver, or resolution of existing fatty liver, over 5 years of follow up: Effect of exercise

Journal of Hepatology

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Acute severe ulcerative colitis - Evidence-based consensus statements

Alimentary Pharmacology and Therapeutics

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Seroepidemiological survey of hepatitis B virus infection among 764,460 women of childbearing age in rural China: A cross-sectional study

Journal of Clinical Virology

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Outcomes of oesophageal atresia and tracheo-oesophageal fistula repair

Journal of Paediatrics and Child Health

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The effect of deworming on tests of tuberculosis infection in children with recent tuberculosis exposure: A randomized controlled trial

The Pediatric Infectious Disease Journal

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Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - A GIRCG study

European Journal of Surgical Oncology

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Evaluation of a Modified Italian European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire for Individuals with Celiac Disease

Journal of the Academy of Nutrition and Dietetics

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Systematic use of isolated pancreatic anastomosis after pancreatoduodenectomy: Five years of experience with zero mortality

European Journal of Surgical Oncology

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The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: a meta-analysis

European Journal of Surgical Oncology

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Chemogenetic approach to model hypofrontality

Publication date: August 2016
Source:Medical Hypotheses, Volume 93
Author(s): Ike dela Peña, Wei-Xing Shi
Clinical evidence suggests that the prefrontal cortex (PFC) is hypofunctional in disorders including schizophrenia, drug addiction, and attention-deficit/hyperactivity disorder (ADHD). In schizophrenia, hypofrontality has been further suggested to cause both the negative and cognitive symptoms, and overactivity of dopamine neurons that project to subcortical areas. The latter may contribute to the development of positive symptoms of the disorder. Nevertheless, what causes hypofrontality and how it alters dopamine transmission in subcortical structures remain unclear due, in part, to the difficulty in modeling hypofrontality using previous techniques (e.g. PFC lesioning, focal cooling, repeated treatment with psychotomimetic drugs). We propose that the use of designer receptors exclusively activated by designer drugs (DREADDs) chemogenetic technique will allow precise interrogations of PFC functions. Combined with electrophysiological recordings, we can investigate the effects of PFC hypofunction on activity of dopamine neurons. Importantly, from a drug target discovery perspective, the use of DREADDs will enable us to examine whether chemogenetically enhancing PFC activity will reverse the behavioral abnormalities associated with PFC hypofunction and dopamine neuron overactivity, and also explore druggable targets for the treatment of schizophrenia and other disorders associated with abnormalities via modulation of the G-protein coupled receptor signaling pathway. In conclusion, the use of the DREADDs technique has several advantages over other previously employed strategies to simulate PFC hypofunction not only in terms of disease modeling but also from the viewpoint of drug target discovery.



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Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: A vicious cycle

Publication date: August 2016
Source:Medical Hypotheses, Volume 93
Author(s): J.H. Kim, J.H. Park, M. Eisenhut, J.W. Yu, J.I. Shin
Inflammasomes are caspase-1-activating molecular platforms that produce active interleukin (IL)-1β and are implicated in various central nervous system (CNS) diseases. These multi-protein complexes can be activated by exposure of cells to low osmolality. The inflammasome nucleotide-binding and oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) is hereby the main sensor of cellular osmolality. IL-1β was found to stimulate the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland either by action of prostaglandins or indirectly by causing the release of IL-6.Based on these findings, we hypothesize that the hyponatremia caused by a wide range of CNS diseases is able to induce significant cell swelling with induction of a hyposmotic intracellular environment, which activates the NLRP3 inflammasome, causing the release of IL-1β and induced by IL-1β, IL-6, which increases the production of ADH that leads to more profound hyponatremia. Supportive evidence for this hypothesis is the finding that IL-1 injection can induce ADH release and hyposmotic effect of ADH induced hyponatremia can, via the mechanical effect of cell swelling, activate transient receptor potential channels, which via transforming growth factor β-activated kinase 1 activate NLRP3. Implications of this hypothesis, if confirmed, would include that hyponatremia can be exacerbated through this vicious cycle but also that the inflammasomes are key mediators of this process. Confirmation of this hypothesis would have implications for prevention and clinical management of changes in patients sodium levels related to syndrome of inappropriate antidiuretic hormone secretion (SIADH) with interventions targeting inflammatory mediator production and function of inflammasomes with the potential of prevention of permanent brain damage in a wide range of CNS diseases.



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Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

Publication date: August 2016
Source:Medical Hypotheses, Volume 93
Author(s): Alessandro Miani
Music is ubiquitous. Yet, its biological relevance is still an ongoing debate. Supporting the view that music had an ancestral role in courtship displays, a pilot study presented here provides preliminary evidence on the link between music and sexual selection. The underlying hypothesis is based on the fact that the sexually dimorphic neuropeptide vasopressin has its receptors in the part of the brain involved in music and dance performance (the basal ganglia), and its concentrations rise during sexual arousal in men. In addition, music, dance, and courtship phenotypes seem to be in part regulated by vasopressin and its genes. Hence, to test this hypothesis, a rhythmic synchronization task was employed here on one male subject during sexual arousal. Results revealed a significant effect of sexual arousal on rhythm synchronization. This is the first report that empirically supports the hypothesis on the role of music in sexual selection. Further studies are clearly required.



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Coatings, Vol. 6, Pages 22: Thermal Protection of Carbon Fiber-Reinforced Composites by Ceramic Particles

The thermal barrier efficiency of two types of ceramic particle, glass flakes and aluminum titanate, dispersed on the surface of carbon-fiber epoxy composites, has been evaluated using a cone calorimeter at 35 and 50 kW/m2, in addition to temperature gradients through the samples' thicknesses, measured by inserting thermocouples on the exposed and back surfaces during the cone tests. Two techniques of dispersing ceramic particles on the surface have been employed, one where particles were dispersed on semi-cured laminate and the other where their dispersion in a phenolic resin was applied on the laminate surface, using the same method as used previously for glass fiber composites. The morphology and durability of the coatings to water absorption, peeling, impact and flexural tension were also studied and compared with those previously reported for glass-fiber epoxy composites. With both methods, uniform coatings could be achieved, which were durable to peeling or water absorption with a minimal adverse effect on the mechanical properties of composites. While all these properties were comparable to those previously observed for glass fiber composites, the ceramic particles have seen to be more effective on this less flammable, carbon fiber composite substrate.

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Molecules, Vol. 21, Pages 715: Sorbicillinoids from Fungi and Their Bioactivities

Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids have been reported in the past few decades. This mini-review aims to briefly summarize their occurrence, structures, and biological activities.

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Nutrients, Vol. 8, Pages 326: The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children

Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations ≥75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50–74.9 nmol/L (OR = 2.21, 1.33–3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children.

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Nutrients, Vol. 8, Pages 320: Does Metabolically Healthy Obesity Exist?

The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of "more fat means more metabolic disease", and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated.

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Molecules, Vol. 21, Pages 717: Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract

A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 × 100 mm) with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI) interface using multiple reaction monitoring (MRM) in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE) method with ethyl acetate after being spiked with an internal standard (bifendate). The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of −14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax) were 70.10 ± 11.78 ng/mL for purpurin, 26.09 ± 6.6 ng/mL for munjistin, and 52.10 ± 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax) was 1.61 ± 0.24 h for purpurin, 2.58 ± 0.19 h for munjistin, and 1.99 ± 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to rats.

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Nanomaterials, Vol. 6, Pages 102: Fluorescent Nanocomposite of Embedded Ceria Nanoparticles in Crosslinked PVA Electrospun Nanofibers

This paper introduces a new fluorescent nanocomposite of electrospun biodegradable nanofibers embedded with optical nanoparticles. In detail, this work introduces the fluorescence properties of PVA nanofibers generated by the electrospinning technique with embedded cerium oxide (ceria) nanoparticles. Under near-ultra violet excitation, the synthesized nanocomposite generates a visible fluorescent emission at 520 nm, varying its intensity peak according to the concentration of in situ embedded ceria nanoparticles. This is due to the fact that the embedded ceria nanoparticles have optical tri-valiant cerium ions, associated with formed oxygen vacancies, with a direct allowed bandgap around 3.5 eV. In addition, the impact of chemical crosslinking of the PVA on the fluorescence emission is studied in both cases of adding ceria nanoparticles in situ or of a post-synthesis addition via a spin-coating mechanism. Other optical and structural characteristics such as absorbance dispersion, direct bandgap, FTIR spectroscopy, and SEM analysis are presented. The synthesized optical nanocomposite could be helpful in different applications such as environmental monitoring and bioimaging.

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JMSE, Vol. 4, Pages 39: Gene Transcript Profiling in Sea Otters Post-Exxon Valdez Oil Spill: A Tool for Marine Ecosystem Health Assessment

Using a panel of genes stimulated by oil exposure in a laboratory study, we evaluated gene transcription in blood leukocytes sampled from sea otters captured from 2006–2012 in western Prince William Sound (WPWS), Alaska, 17–23 years after the 1989 Exxon Valdez oil spill (EVOS). We compared WPWS sea otters to reference populations (not affected by the EVOS) from the Alaska Peninsula (2009), Katmai National Park and Preserve (2009), Clam Lagoon at Adak Island (2012), Kodiak Island (2005) and captive sea otters in aquaria. Statistically, sea otter gene transcript profiles separated into three distinct clusters: Cluster 1, Kodiak and WPWS 2006–2008 (higher relative transcription); Cluster 2, Clam Lagoon and WPWS 2010–2012 (lower relative transcription); and Cluster 3, Alaska Peninsula, Katmai and captive sea otters (intermediate relative transcription). The lower transcription of the aryl hydrocarbon receptor (AHR), an established biomarker for hydrocarbon exposure, in WPWS 2010–2012 compared to earlier samples from WPWS is consistent with declining hydrocarbon exposure, but the pattern of overall low levels of transcription seen in WPWS 2010–2012 could be related to other factors, such as food limitation, pathogens or injury, and may indicate an inability to mount effective responses to stressors. Decreased transcriptional response across the entire gene panel precludes the evaluation of whether or not individual sea otters show signs of exposure to lingering oil. However, related studies on sea otter demographics indicate that by 2012, the sea otter population in WPWS had recovered, which indicates diminishing oil exposure.

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Inorganics, Vol. 4, Pages 18: Tetrapropylammonium Occlusion in Nanoaggregates of Precursor of Silicalite-1 Zeolite Studied by 1H and 13C NMR

The dynamic behavior of tetrapropylammonium (TPA) cations in the clear precursor sols for silicalite synthesis has been investigated by 1H diffusion ordered spectroscopy (DOSY), T1, T2, and T1ρ 1H relaxation, as well as 1H→13C cross polarization (CP) nuclear magnetic resonance. The DOSY NMR experiments showed the presence of strong solute–solvent interactions in concentrated sols, which are decreasing upon dilution. Similarities in dependence of diffusion coefficients with fractional power of the viscosity constant observed for nanoparticles, TPA cations and water led to the conclusion that they aggregate as anisotropic silicate-TPA particles. Relaxation studies as well as 1H→13C CP experiments provide information on dynamic properties of ethanol, water and TPA cations, which are function of silicate aggregates. The general tendency showed that the presence of silicate as oligomers and particles decreases the relaxation times, in particular T2 and T1ρH, as a consequence of involvement of these latter in ion-pairing interactions with water-solvated TPA molecules slowing down their mobility. Furthermore, from the 1H→13C CP dynamics curve profiles a change in the CP transfer regime was observed from fast (TCH << T1ρH) for solutions without silicates to moderate (TCH~T1ρH) when silicates are interacting with the TPA cations that may reflect the occlusion of TPA into flexible silicate hydrate aggregates.

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Toxins, Vol. 8, Pages 169: Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed

Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences.

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Vaccines, Vol. 4, Pages 21: Aeromonas hydrophila OmpW PLGA Nanoparticle Oral Vaccine Shows a Dose-Dependent Protective Immunity in Rohu (Labeo rohita)

Aeromonas hydrophila is a Gram-negative bacterium that causes high mortality in different fish species and at different growth stages. Although vaccination has significantly contributed to the decline of disease outbreaks in aquaculture, the use of oral vaccines has lagged behind the injectable vaccines due to lack of proven efficacy, that being from primary immunization or by use of boost protocols. In this study, the outer membrane protein W (OmpW) of A. hydrophila was cloned, purified, and encapsulated in poly d,l-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) for oral vaccination of rohu (Labeo rohita Hamilton). The physical properties of PLGA NPs encapsulating the recombinant OmpW (rOmpW) was characterized as having a diameter of 370–375 nm, encapsulation efficiency of 53% and −19.3 mV zeta potential. In vitro release of rOmpW was estimated at 34% within 48 h of incubation in phosphate-buffered saline. To evaluate the efficacy of the NP-rOmpW oral vaccine, two antigen doses were orally administered in rohu with a high antigen (HiAg) dose that had twice the amount of antigens compared to the low antigen (LoAg) dose. Antibody levels obtained after vaccination showed an antigen dose dependency in which fish from the HiAg group had higher antibody levels than those from the LoAg group. The antibody levels corresponded with post challenge survival proportions (PCSPs) and relative percent survival (RPS) in which the HiAg group had a higher PCSP and RPS than the LoAg group. Likewise, the ability to inhibit A. hydrophila growth on trypticase soy agar (TSA) by sera obtained from the HiAg group was higher than that from the LoAg group. Overall, data presented here shows that OmpW orally administered using PLGA NPs is protective against A. hydrophila infection with the level of protective immunity induced by oral vaccination being antigen dose-dependent. Future studies should seek to optimize the antigen dose and duration of oral immunization in rohu in order to induce the highest protection in vaccinated fish.

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Water, Vol. 8, Pages 236: Evaluation of Water Efficiency in Green Building in Taiwan

Low carbon policies, including those aimed at increasing water efficiency, have been adopted as a crucial strategy for combating global warming and climate change. The green building evaluation system used in Taiwan was first applied in 1999 and initially utilized a building's water efficiency as the threshold index for determining the building's environmental impact. Since 1999, more than a thousand buildings have been certified as green buildings using this evaluation system. The quantitative effects of water conservation efforts should be provided to policy makers as a form of positive feedback. To that end, the present study offers a calculation process for estimating the quantitative volume of water saved by practical green buildings. The baseline water usage for all kinds of buildings was determined to serve as the criterion for determining the water-saving efficiency of individual buildings. An investigation of the average water-saving rate from 2000 to 2013 for 1320 buildings certified as green buildings was also conducted to validate the estimation results and found that these green buildings saved an average of approximately 37.6% compared to the baseline water usage rate for all buildings. Water savings will inevitably follow from the use of water-saving appliances or water-saving designs for buildings. The proposed calculation process can be used to clarify the relationships between specific water-saving concepts and the real water usage efficiency of green buildings.

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Toxins, Vol. 8, Pages 169: Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed

Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences.

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Molecules, Vol. 21, Pages 714: Hydrazino-methoxy-1,3,5-triazine Derivatives’ Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution

The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6-tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy-1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH3, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH3, DMeHT and DHMeT behaved as mixed type inhibitors.

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JFMK, Vol. 1, Pages 249-253: A Newborn with Arterial Tortuosity Syndrome: The Importance of Timely Diagnostic Work-Up in Patients Presenting with Cutis Laxa

Arterial tortuosity syndrome (ATS) is a rare, autosomal recessively inherited connective tissue disorder characterized by severe and widespread arterial tortuosity of the aorta and of middle-sized arteries with an increased risk of aneurysm, dissection, and stenosis involving either the aorta or the pulmonary arteries or both. In this article, we report the clinical findings and molecular characterization of a newborn with ATS presenting with cutis laxa, respiratory distress, and dislocation of the nasogastric tube due to a gastric volvulus and an open pleuroperitoneal channel. Based on this case report, we emphasize early diagnostic work-up in all patients presenting with cutis laxa in order to prevent adverse cardiovascular events. Data suggests that early diagnosis is life-saving in these patients.

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Molecules, Vol. 21, Pages 707: Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts

Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of 13C-CP/MAS and 15N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated.

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Factors associated with fetal shunt dislodgement in lower urinary tract obstruction

• What's already known about this topic?•Shunt dislodgement is the most common technical complication of intervention for fetal LUTO•Predictors of this event are not known

• What does this study add?•This study explores factors associated with shunt dislodgement in a cohort in which both major shunt types were used•Failure of shunts to remain in the orthotopic position was found to be associated with shunt type

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Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line

Horm Metab Res
DOI: 10.1055/s-0042-108196

Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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