Do pediatricians manage influenza differently than internists?

<p>Abstract</p> <p>Background</p> <p>Little is known about how pediatricians or internists manage influenza symptoms. Recent guidelines on antiviral prescribing by the Centers for Disease Control and Prevention (CDC) make almost no distinction between adults and children. Our objective was to describe how pediatricians in two large academic medical institutions manage influenza and compare them to internists.</p> <p>Methods</p> <p>At the end of the 2003–4 influenza season, we conducted a cross sectional on-line survey of physician knowledge, attitudes and practices regarding rapid diagnostic testing and use of antiviral therapy for influenza at two large academic medical centers, one in Massachusetts and the other in Texas. We collected data on self-reported demographics, test use, prescribing practices, and beliefs about influenza and anti-influenza drugs.</p> <p>Results</p> <p>A total of 107 pediatricians and 103 internists completed the survey (response rate of 53%). Compared to internists, pediatricians were more likely to perform rapid testing (74% vs. 47%, p < 0.0001), to use amantadine (88% vs. 48%, p < 0.0001), to restrict their prescribing to high-risk patients (86% vs. 53%, p < 0.0001), and to believe that antiviral therapy could decrease mortality (38% vs. 22%, p = 0.01). Other beliefs about antiviral therapy did not differ statistically between the specialties. Internists were more likely to be unfamiliar with rapid testing or not to have it available.</p> <p>Conclusion</p> <p>Pediatricians and internists manage influenza differently. Evidence-based guidelines addressing the specific concerns of each group would be helpful.</p

Fatal Cardiac Arrhythmia and Long-QT Syndrome in a New Form of Congenital Generalized Lipodystrophy with Muscle Rippling (CGL4) Due to PTRF-CAVIN Mutations

We investigated eight families with a novel subtype of congenital generalized lipodystrophy (CGL4) of whom five members had died from sudden cardiac death during their teenage years. ECG studies revealed features of long-QT syndrome, bradycardia, as well as supraventricular and ventricular tachycardias. Further symptoms comprised myopathy with muscle rippling, skeletal as well as smooth-muscle hypertrophy, leading to impaired gastrointestinal motility and hypertrophic pyloric stenosis in some children. Additionally, we found impaired bone formation with osteopenia, osteoporosis, and atlanto-axial instability. Homozygosity mapping located the gene within 2 Mbp on chromosome 17. Prioritization of 74 candidate genes with GeneDistiller for high expression in muscle and adipocytes suggested PTRF-CAVIN (Polymerase I and transcript release factor/Cavin) as the most probable candidate leading to the detection of homozygous mutations (c.160delG, c.362dupT). PTRF-CAVIN is essential for caveolae biogenesis. These cholesterol-rich plasmalemmal vesicles are involved in signal-transduction and vesicular trafficking and reside primarily on adipocytes, myocytes, and osteoblasts. Absence of PTRF-CAVIN did not influence abundance of its binding partner caveolin-1 and caveolin-3. In patient fibroblasts, however, caveolin-1 failed to localize toward the cell surface and electron microscopy revealed reduction of caveolae to less than 3%. Transfection of full-length PTRF-CAVIN reestablished the presence of caveolae. The loss of caveolae was confirmed by Atomic Force Microscopy (AFM) in combination with fluorescent imaging. PTRF-CAVIN deficiency thus presents the phenotypic spectrum caused by a quintessential lack of functional caveolae

Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling

Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy

On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Assessment of vitamin D levels in newly diagnosed children with type 1 diabetes mellitus comparing two methods of measurement: a facility&#39;s experience in the Middle Eastern country of Bahrain

Fatima Ahmed Al-Haddad,1 Mansoor H Rajab,2 S Mahmood Al-Qallaf,3 Abdulrahman O Musaiger,4 Kathryn H Hart5 1Dietetic Unit for Hospitals, 2Pediatric Endocrine and Diabetes Team, Pediatric Department, Salmaniya Medical Complex, 3Pharmacy Program, College of Health Sciences, University of Bahrain, Manama, 4Nutrition and Health Studies Unit Deanship of Scientific Research, University of Bahrain, Sakheer, Kingdom of Bahrain; 5School of Biosciences and Medicine, Department of Nutritional Sciences, University of Surrey, Guildford, UK Background: The number of children being diagnosed with type 1 diabetes mellitus (T1DM) is on the rise and has more than doubled in the past 10 years in Bahrain. Some studies have linked low vitamin D levels with an increased risk of diabetes. There are concerns regarding the variations in circulating 25(OH)D levels measured by different laboratories and by using different analytical techniques. Objective: The aim of this study was to evaluate the vitamin D levels of newly diagnosed children with T1DM using the &ldquo;gold standard method&rdquo; with high-pressure liquid chromatography&ndash;tandem mass spectrometry methods compared to the chemiluminescence micro-particle immunoassay (CMIA) used in a hospital laboratory. Subjects: Eighteen children, aged 6&ndash;12 years, who received a confirmed diagnosis of T1DM in 2014 were chosen as subjects. Methods: Serum vitamin D levels were assessed in a hospital, while an extra aliquot of blood collected during routine blood collection after acquiring informed written consents from the subjects, and sent to Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders to be analyzed by ultra-performance liquid chromatography&ndash;tandem mass spectrometry (UPLC-MS/MS). Results: The mean age of the study group was 9&plusmn;2 years. The mean total of 25(OH)D levels (D3 and D2) assessed by UPLC-MS/MS was 49.7&plusmn;18.8, whereas the mean total of 25(OH)D levels obtained from the CMIA assay was 44.60&plusmn;13.20. The difference in classification between the two methods was found to be statistically significant (P=0.004). A Bland&ndash;Altman plot showed a poor level of agreement between the two assay methods. The CMIA overestimated insufficient values and underestimated deficiency, when compared to UPLC-MS/MS. Conclusion: There was a statistically significant difference between the two assay methods with CMIA overestimating vitamin D insufficiency. Clinicians should be prudent in their assessment of a single vitamin D reading, when the gold standard method is not available or feasible. Keywords: type 1 diabetes, children, vitamin D, Middle Eas

Assessment of vitamin D levels in newly diagnosed children with type 1 diabetes mellitus comparing two methods of measurement: a facility's experience in the Middle Eastern country of Bahrain.

BACKGROUND: The number of children being diagnosed with type 1 diabetes mellitus (T1DM) is on the rise and has more than doubled in the past 10 years in Bahrain. Some studies have linked low vitamin D levels with an increased risk of diabetes. There are concerns regarding the variations in circulating 25(OH)D levels measured by different laboratories and by using different analytical techniques. OBJECTIVE: The aim of this study was to evaluate the vitamin D levels of newly diagnosed children with T1DM using the "gold standard method" with high-pressure liquid chromatography-tandem mass spectrometry methods compared to the chemiluminescence micro-particle immunoassay (CMIA) used in a hospital laboratory. SUBJECTS: Eighteen children, aged 6-12 years, who received a confirmed diagnosis of T1DM in 2014 were chosen as subjects. METHODS: Serum vitamin D levels were assessed in a hospital, while an extra aliquot of blood collected during routine blood collection after acquiring informed written consents from the subjects, and sent to Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders to be analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The mean age of the study group was 9±2 years. The mean total of 25(OH)D levels (D3 and D2) assessed by UPLC-MS/MS was 49.7±18.8, whereas the mean total of 25(OH)D levels obtained from the CMIA assay was 44.60±13.20. The difference in classification between the two methods was found to be statistically significant (P=0.004). A Bland-Altman plot showed a poor level of agreement between the two assay methods. The CMIA overestimated insufficient values and underestimated deficiency, when compared to UPLC-MS/MS. CONCLUSION: There was a statistically significant difference between the two assay methods with CMIA overestimating vitamin D insufficiency. Clinicians should be prudent in their assessment of a single vitamin D reading, when the gold standard method is not available or feasible

Characterization and Cytocompatibility of Collagen&ndash;Gelatin&ndash;Elastin (CollaGee) Acellular Skin Substitute towards Human Dermal Fibroblasts: In Vitro Assessment

Full-thickness skin wounds have become a serious burden to patients, medical care, and the socio-economic environment. The development of a safe and effective acellular skin substitute that can rapidly restore intact physiological skin is required. Natural bioactive materials including collagen, gelatin, and elastin possess significant advantages over synthetic biomaterials regarding biodegradability and biocompatibility. However, low mechanical strength, a faster biodegradation rate, and thermally unstable biomaterials lead to slow-healing and a high rate of post-implantation failure. To overcome these concerns, naturally occurring genipin (GNP) flavonoids were added to improve the mechanical strength, degradation rate, and thermal properties. Therefore, this study aimed to fabricate and characterize collagen&ndash;gelatin&ndash;elastin (CollaGee) biomaterials cross-linked with GNP as an acellular skin substitute potentially used in full-thickness wound healing. CollaGee at different ratios was divided into non-cross-linked and cross-linked with 0.1% GNP (w/v). The physicochemical, mechanical, and biocompatibility properties of CollaGee were further investigated. The results demonstrated that GNP-cross-linked CollaGee has better physicochemical (&gt;50% porosity, pore size range of 100&ndash;200 &micro;m, swelling ratio of &gt;1000%) and mechanical properties (resilience and cross-linking degree of &gt;60%, modulus of &gt;1.0 GPa) compared to non-cross-linked CollaGee groups. Furthermore, both cross-linked and non-cross-linked CollaGee demonstrated pivotal cellular compatibility with no toxicity and sustained cell viability until day 7 towards human dermal fibroblasts. These findings suggest that GNP-cross-linked CollaGee could be a promising ready-to-use product for the rapid treatment of full-thickness skin loss