The Accuracy of Readily Available Consumer-Grade Oxygen Saturation Monitors in Pediatric Patients.

BACKGROUND: Pulse oximetry measurement is ubiquitous in acute health care settings in high-income countries and is familiar to any parent whose child has been treated in such a setting. Oximeters for home use are readily available online and are incorporated in several smartphones and smartwatches. METHODS: We wished to determine how accurate are oximeters available online that are designated for adult and pediatric use, and the saturation monitor integrated in a smartphone, when used in children, compared to reference, hospital-grade oximeters. We evaluated a fingertip oximeter marketed for children purchased online; an adult fingertip oximeter purchased online; the oximeter integrated in a smartphone; and reference, hospital-grade oximeters. Participants were < 18 y of age. Bland-Altman charts were generated, and the estimated root mean square error (EARMS) was calculated. Rates of failure to obtain a measurement, relationship between device and time to successful measurement, relationship between age and time to successful measurement, and relationship between error (vs the reference device) and age were evaluated for each consumer-grade device. RESULTS: We measured SpO2 in 74 children between 0.1-17.0 y of age. Subjects weighing < 30 kg had a median (interquartile range [IQR]) age of 2 (1.0 month-1.4 y) months, and subjects weighing ≥ 30 kg had a median (IQR) age of 14.3 (11.9-16.2) y. Readings could not be obtained in 7.5, 0, and 38.8% of subjects using the pediatric, adult, and smartphone oximeters, respectively. The time to successful reading had a modest negative correlation with age with the inexpensive adult and pediatric oximeters. The inexpensive pediatric oximeter had an overall negative bias, with a mean difference from the reference device of -4.5% (SD 7.9%) and an error that ranged from > 8% to < 33% the reference device. The EARMS was 7.92%. The inexpensive adult oximeter demonstrated no obvious trend in error in the limited saturation range evaluated of 87-99%. The overall mean difference was -0.7% (SD 2.5%). EARMS was 2.5%. The smartphone oximeter underestimated SpO2 at saturations < 94% and overestimated SpO2 for saturations > 94%. Saturations could read as much as > 4%, or < 17%, than the reference oximeter. The mean difference was -2.9% (SD 5.2%). EARMS was 5.1%. CONCLUSIONS: Our findings suggest that the performance of consumer-grade devices varies considerably by both subject age and device. The pediatric fingertip device and smartphone application we tested are poorly suited for use in infants. The adult fingertip device we tested performed quite well in larger children with relatively normal oxygen saturations, and the pediatric fingertip device performed moderately well in subjects > 1 y of age who weighed < 30 kg. Given the vast number of devices available online and ever-changing technology, research to evaluate nonclinical oximeters will continue to be required.

Comparing Adherence with Best Practices in End-of-Life Care After Implementing the End-of-Life Order Set: A Quality Improvement Project in an Ottawa Academic Hospital.

Background: Physicians in acute care require tools to assist them in transitioning patients from a "life prolonging" approach to "end-of-life care," and standardized order sets can be a useful strategy. The end-of-life order set (EOLOS) was developed and implemented in the medical wards of a community academic hospital. Objective: To compare adherence with best practices in end-of-life care after implementing the EOLOS. Methods: We conducted a retrospective chart review of admitted patients with expected deaths in the year preceding EOLOS implementation ("before EOLOS" group), and in the 12 to 24 months following EOLOS implementation ("after EOLOS" group). Results: A total of 295 charts were included: 139 (47%) in the "before EOLOS" group and 156 (53%) in the "after EOLOS" group, of which 117/156 charts (75%) had a completed EOLOS. The "after EOLOS" group demonstrated more "do not resuscitate" orders and more written communication to team members about comfort goals of care. There was a decrease in nonbeneficial interventions in the last 24 hours of life in the "after EOLOS" group: high-flow oxygen, intravenous antibiotics, and deep vein thrombosis/venous thromboembolism prophylaxis. The "after EOLOS" group demonstrated increased prescription of all common end-of-life medications, except for opioids, which had a high preexisting rate of prescription. Patients in the "after EOLOS" group showed a higher rate of spiritual care and palliative care consult team consultation. Conclusion: Findings support standardized order sets as a good framework allowing generalist hospital staff to improve adherence to established palliative care principles and improve end-of-life care of hospital inpatients.

Structural Analysis of the Ash2L/Dpy-30 Complex Reveals a Heterogeneity in H3K4 Methylation.

Dpy-30 is a regulatory subunit controlling the histone methyltransferase activity of the KMT2 enzymes in vivo. Paradoxically, in vitro methyltransferase assays revealed that Dpy-30 only modestly participates in the positive heterotypic allosteric regulation of these methyltransferases. Detailed genome-wide, molecular and structural studies reveal that an extensive network of interactions taking place at the interface between Dpy-30 and Ash2L are critical for the correct placement, genome-wide, of H3K4me2 and H3K4me3 but marginally contribute to the methyltransferase activity of KMT2 enzymes in vitro. Moreover, we show that H3K4me2 peaks persisting following the loss of Dpy-30 are found in regions of highly transcribed genes, highlighting an interplay between Complex of Proteins Associated with SET1 (COMPASS) kinetics and the cycling of RNA polymerase to control H3K4 methylation. Overall, our data suggest that Dpy-30 couples its modest positive heterotypic allosteric regulation of KMT2 methyltransferase activity with its ability to help the positioning of SET1/COMPASS to control epigenetic signaling.

Recognizing asymmetry in pseudo-symmetry; structural insights into the interaction between amphipathic α-helices and X-bundle proteins.

An α-helix bundle is a small and compact protein fold always composed of more than 2 α-helices that typically run nearly parallel or antiparallel to each other. The repertoire of arrangements of α-helix bundle is such that these domains bind to a myriad of molecular entities including DNA, RNA, proteins and small molecules. A special instance of α-helical bundle is the X-type in which the arrangement of two α-helices interact at 45° to form an X. Among those, some X-helix bundle proteins bind to the hydrophobic section of an amphipathic α-helix in a seemingly orientation and sequence specific manner. In this review, we will compare the binding mode of amphipathic α-helices to X-helix bundle and α-helical bundle proteins. From these structures, we will highlight potential regulatory paradigms that may control the specific interactions of X-helix bundle proteins to amphipathic α-helices. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman.

Hypoxia upregulates MAPK(p38)/MAPK(ERK) phosphorylation in vitro: neuroimmunological differential time-dependent expression of MAPKs.

In mammalian cells, responses to hypoxia at the molecular transduction level are hallmarks of adaptation and survival under oxygen deprivation conditions. In this study, the protein expression patterns of mitogen-activated protein kinases (MAPKs) are investigated under hypoxia in primary cortical neurons and in a model of organotypic hippocampal slices in neonatal Sprague-Dawley rats. Abrupt fluctuations in MAPK expression can occur during anoxia, hypoxia, and relative hyperoxic shifts (e.g., reoxygenation); therefore, phosphorylation and dephosphorylation states could be crucial factors in metabolic reorganization for withstanding anaerobiosis. Whole cellular protein extracts were analyzed for the phosphorylation of MAPKp(p38) and MAPK(ERK-1/2 (p44/p42)) at threonine and tyrosine residues (Thr(180)/Tyr(182)) at different time periods of hypoxic exposure relative to a fixed normoxia control. The phospho-MAPK(p38) (p-MAPK(p38)) to MAPK(p38) relative unit ratio revealed that MAPK(p38) expression increased in cortical neurons after 5 and 10 min, but decreased abruptly afterwards (20 - 120 min). The expression of phospho-MAPK(ERK-1) (p-MAPK(ERK-1/p44)), however, decreased whereas that of p-MAPK(ERK-2/p42) increased compared to normoxia. In rat hippocampal slices (RHS), the expression of p-MAPK(p38) was slightly but significantly higher in hypoxia, whereas the expression of p-MAPK(ERK-2/p42) increased and that of p-MAPK(ERK-1/p44) was intangible. This indicates that in cortical neurons hypoxia differentially upregulated the phosphorylation activation states of MAPK(p38) and MAPK(ERK-1/2 (p44/p42)), whereas in the RHS model MAPK(p38) and MAPK(ERK-2/p42), but not MAPK(ERK-1/p44), phosphorylation states were upregulated in response to hypoxia. The neuroimmunological molecular patterns of the differential MAPK phosphorylation in vitro and ex vivo in response to hypoxic shift indicated a significant role for these kinases in cellular adaptation to oxygen deprivation, and thereby may identify physiologic and neuroprotective responsive signaling cofactors and pathways in cortical and hippocampal neurons during hypoxia.

The bioanalytical molecular pharmacology of the N-methyl-D-aspartate (NMDA) receptor nexus and the oxygen-responsive transcription factor HIF-1α: putative mechanisms and regulatory pathways unravel the intimate hypoxia connection.

Hypoxia-mediated regulation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) is phenomenal. NMDAR is no doubt an intriguing paradoxical glutamate receptor (GluR) with versatile actions. GluRs play a pivotal role in brain physiology and pathophysiology under ischemia and oxygen deprivation, where NMDARs are major contributors. Activation of NMDARs is closely associated with the kinetics of intracellular calcium (Ca(2+)) release, a main player in neuronal cell death in the central nervous system (CNS). However, CNS exposure to hypoxia modulates NMDAR/Ca(2+) physiology in such a way that there is a small window of operating neuroprotection, rather than the classical neuroinjurious effects manifested upon Ca(2+) release. The NMDAR connection with hypoxia-inducible factor-1α (HIF-1α), a transcription factor considered master regulator of oxygen sensing mechanisms, is not well established in the CNS. However, scanning the literature yielded a wealth of NMDAR/hypoxia connection but that with HIF-1α is not prominent. It is worth mentioning that this is not a comprehensive review on the effect of hypoxia on NMDAR physiology, rather this synopsis sheds light on the putative mechanisms involving HIF-1α and NMDAR regulation. Understanding the evidence of this intimate connection and its ramifications may bear potential applications in unraveling hypoxia-mediated injury, neuronal cell death and, most importantly, adaptive, neuroprotective mechanisms to oxygen deprivation.

Current opinion on 3-[2-[(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]- 4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid, an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti-inflammatory advances.

Caspases, or cysteinyl-aspartate specific proteases, are major contributing enzymes in inflammation. Caspases are highly specific cysteine proteases closely involved in inflammatory responses that are associated with programmed cell death, or apoptosis. Inappropriate regulation of cell death, therefore, substantially results in a wide array of diseases including, but not limiting to, neurodegenerative disorders, ischemic disorders, and cancer. The key molecular genes that control cell death are those cell death effectors (pro-apoptosis) of the caspase family, on one hand, and the cell death inhibitors (anti-apoptosis) of the Bcl-2 family, on the other hand. This unequivocal and unprecedented equilibrium between caspases and Bcl-2-related molecules essentially controls cells' final demise. Caspases and related proteases are potential therapeutic targets in a variety of acute and chronic diseases. Current design of biologically active molecules in recent technology is dependent on DNA-based scanning of the genome to engineer a variety of molecules such as apoptosis inhibitors, caspase regulators and caspase activators, and cytokines involved in caspase signaling. This synopsis aims to review relevant patents and to unravel the discovery of small-molecule caspase protease inhibitors and their clinical ramifications, and further sheds light on recent experimental and clinical trials, emphasizing a small molecule dubbed 3-[2-[(2- tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid (IDN- 6556/PF-03491390). Current opinion on investigational drugs targeting caspases and caspase-like proteases bears the significance of understanding the mechanisms of alleviating inflammatory-related acute and chronic conditions and their biomedical applications and repercussions.

Measurement of antioxidant activity and antioxidant compounds under versatile extraction conditions: II. The immuno-biochemical antioxidant properties of black sour cherry (Prunus cerasus) extracts.

Retrospectively, we have measured the antioxidant activity and a variety of antioxidant compounds under versatile extraction conditions of sweet cherry (Prunus avium) extracts. Further in this study, in order to understand the biochemical constituents and antioxidant activities of a variety of extracts of black sour cherries (P. cerasus), a related species, antioxidant compounds, including L-ascorbic acid (vitamin C), phenols, flavonoids, and anthocyanins, and the total antioxidant activity were simultaneously measured under varying extraction conditions (mild heating and brief microwave exposure) for: i) whole juice extracts (WJE), ii) methanol-extracted juice (MEJ), iii) ddH2O-extracted pomace (dPOM), and iv) methanol-extracted pomace (mPOM). The antioxidant activity for WJE was substantially increased with mild and prolonged exposure to either heating or microwave, such that the % inhibition against 2,2-diphenyl-1-bspicrylhydrazyl (DPPH) followed a positive correlation (heating, 5-20 min.; microwave, 1-2 min.), insignificant with MEJ and dPOM, whereas with mPOM there was sharp downregulation. L-Ascorbic acid content was not affected with mild to prolonged heating or microwave exposure (WEJ and mPOM), except a mild increase with MEJ and dPOM. Similarly, total phenols assessed showed no significant variations, as compared with control extracts, except a mild decrease with exposure for mPOM. In a manner similar to L-ascorbic acid, total flavonoid content was increased under varying conditions for WEJ and MEJ, and slightly decreased for dPOM and mPOM. On the other hand, anthocyanins showed differential variations with exposure (up- and downregulation). Assessment of extraction means as compared with WJE revealed sharp increase in the antioxidant activity for MEJ, dPOM and mPOM, significant increase in L-ascorbic acid, total phenol, and flavonoid contents for MEJ, dPOM and mPOM, and mild decrease in anthocyanin contents for MEJ, dPOM, and mPOM. These results substantiate the measurable antioxidant activities and contents of P. cerasus extracts under versatile conditions of mild exposure, an effect bearing significant fluctuation with biochemical properties. Since many of those molecules are known to have immuno-biochemical constituencies, antioxidant compounds in sour cherries may have putative antiinflammatory potential and applications in medicinal chemistry, corroborating the observation of regulating and attenuating the growth of microorganisms of medical importance in vitro.

Measurement of antioxidant activity and antioxidant compounds under versatile extraction conditions: I. the immuno-biochemical antioxidant properties of sweet cherry (Prunus avium) extracts.

Previously, we have meticulously examined the efficacy of the measurable antimicrobial activity of sweet cherry (Prunus avium) extracts on a wide spectrum of gram-positive and gram-negative bacteria, in addition to the fungus, Candida albicans, a priori. In order to further understand the biochemical constituents and antioxidant activities of a variety of extracts of sweet cherries, antioxidant compounds of immunological significance, including L-ascorbic acid (vitamin C), phenols, flavonoids, and anthocyanins, and the total antioxidant (free radical scavenging) activity were simultaneously measured under varying and versatile extraction conditions (mild heating [5, 10 and 20 min.], and brief microwave exposure [1, 2 and 5 min.]) for a variety of extracts: i) whole juice extracts (WJE), ii) methanol-extracted juice (MEJ), iii) ddH2O-extracted pomace (dPOM), and iv) methanol-extracted pomace (mPOM). The antioxidant activity under the versatile extraction conditions adopted in this study was conspicuously reduced, such that the % inhibition against 2,2- diphenyl-1-picrylhydrazyl (DPPH) followed an inverse, negative correlational trendline. Moreover, ascorbic acid content was not affected with mild to prolonged heating or microwave exposure, except tangibly with dPOM and mPOM. The total phenols content assessed showed no significant variations, as compared with control extracts. In a manner similar to ascorbic acid, total flavonoids were mildly reduced under varying conditions, an effect mimicked to a certain extent with anthocyanins. Assessment of extraction means as compared with WJE revealed sharp decrease in the antioxidant activity for dPOM and mPOM, significant increase in L-ascorbic acid, total phenol, and flavonoid contents for MEJ, dPOM, and mPOM, and mild decrease in anthocyanin contents for dPOM and mPOM. These results confirm the measurable antioxidant activities and contents of P. avium extracts under versatile conditions of mild exposure, an effect bearing significant biochemical properties of a variety of extraction methods. Further studies are currently investigating the effect of specific antioxidants of P. avium on microbial growth in vitro per se. Since many of the aforementioned molecules hold immunobiochemical constituencies, antioxidant compounds in sweet cherries may have putative anti-inflammatory potential in medicinal chemistry, corroborating the observation of regulating/attenuating the growth of microorganisms of medical importance in vitro.

On the cellular and molecular regulatory transcriptional mechanisms and responsive putative pathways to inflammatory oxidative stress revisited: current immunological breakthroughs and views at a glance.

Responses to oxidative stress are generally regulated by redox-responsive transcription factors (TFs). The abrupt variation in the partial pressure of oxygen (pO2) constitutes a regulatory mechanism. Such TFs forming an integral part of those putative pathways are hypoxia-inducible factor-1α(HIF)-1αand nuclear factor-κB (NF-κB), both are sufficiently tuned to govern such a specific response. Reactive species are produced during this transition and the antioxidant defense system controls their production. Oxidative stress occurs when there is imbalance between the production and removal of reactive species. Evidence exists showing that enhancement of the antioxidant defense system can reduce markers of oxidative stress. Recognition of reactive species and redox-mediated modifications as signals may open up a field of cell regulation via targeted control of TFs and hence can providea novel way of controlling diseases. This synopsis summates the major cutting-edge research work in the field of oxidative stress, and surgically identifies common and unique pathways involved with oxidative stress as means of regulatory elements governing TFs.

The immunopharmacologic potential of Semaxanib and new generation directed therapeutic drugs: Receptor tyrosine kinase regulation with anti-tumorigenensis/angiogenesis properties.

Molecular signaling of messages emanating from cellular membranes through receptor tyrosine kinases (RTKs) is a major mechanism for intercellular communication and transduction during development and metabolism, as well as in disease-associated processes. The phosphorylation status and signaling activity of RTKs are determined by a dynamic equilibrium of the activity of both RTKs and protein tyrosine phosphatases (PTPs). RTKs are essentially a class of cell-surface receptors for growth factors and other extracellular ligands, the most conspicuous perhaps are members of the vascular endothelial growth factor (VEGF) gene family, which plays a fundamental role in the growth and differentiation of vascular, as well as lymphatic endothelial cells. In particular, VEGF is a major regulator of normal (physiologic) and abnormal (cancerous) angiogenesis, including that associated with tumors and cancer. Blockers/inhibitors and regulators of RTKs are indeed promising cancer interventions, their specific mechanisms are yet to be unraveled. In this cutting-edge synopsis, I elaborate on breakthroughs/advances and current concepts of RTK regulation, further shedding light on exploring the role of potential regulators, particularly the RTK inhibitor Semaxanib, and the mechanisms associated with tumorigenesis in an effort to understand a potentially alleviating pharmacologic therapeutic intervention. This survey also tackles the loopholes and shortcomings of the aforementioned inhibitory role of Semaxanib, especially its inefficacy and ultimate discontinuation of relevant clinical trials.

NF-κB cellular and molecular regulatory mechanisms and pathways: therapeutic pattern or pseudoregulation?

As fascinating a molecule as it can potentially get, nuclear factor-κB (NF-κB), a regulatory transcription factor, is as intriguing. NF-κB is a dimeric complex that controls the transcription of essential genes. NF-κB is involved in a variety of responses that play a pivotal role in regulating the immune response to inflammation, infection, and nociception. Aberrant regulation of NF-κB has been linked to certain conditions such as cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune responses. Cellular and molecular regulatory mechanisms and pathways involving the regulation of this transcription factor are being unraveled. Therapeutic approaches have emerged underlying the regulatory impact of oligonucleotides/decoys and other non-decoy inhibitors on NF-κB modulation. In this synopsis, we emphasize the role of decoy therapy in understanding the crucial influence of this transcription factor, and further weigh not only the efficacy of this therapeutic approach but also its necessity and contraindications.

Clinical applications of magnets on cardiac rhythm management devices.

The growing indications for permanent pacemaker and implantable cardioverter defibrillator (ICD) implantation have increased the number of patients with these cardiac rhythm management devices (CRMDs). Cardiac rhythm management devices occasionally perform inappropriately in response to electromagnetic interference (e.g. surgical electrocautery) or lead noise over-sensing (e.g. lead fracture). Temporary reprogramming of the CRMDs using device programmers can prevent these untoward device responses. However, these programmers are device manufacturer specific and require technically qualified personnel to operate. This could cause delayed patient care and increased use of resources in certain clinical situations. Alternatively, clinical magnets, when appropriately positioned over the device site, can change the pacing to an asynchronous mode in pacemakers and suspend tachycardia therapies in ICDs. Although readily available, clinical magnets have not been widely used for this purpose, perhaps due to the unfamiliarity with the variable responses of CRMDs to magnet application. This article provides a comprehensive overview of the current literature on the mechanism of action and the specific responses of various CRMDs to clinical magnets.

A redox microenvironment is essential for MAPK-dependent secretion of pro-inflammatory cytokines: modulation by glutathione (GSH/GSSG) biosynthesis and equilibrium in the alveolar epithelium.

The characterization of oxidant (glutathione)-dependent regulation of MAPK(p38/RK)-mediated TNF-α secretion was undertaken in vitro, and the ramifications of the influence of a redox microenvironment were unraveled. Intermittent exposure of alveolar epithelial cells (FATEII) to LPS (endotoxin) transiently and temporally induced the expression of MAPK(p38/RK). This upregulation was associated with the activation of MAPKAP-K(2), manifested by the specific phosphorylation of the downstream heat-shock protein (Hsp)-27. Selective blockading of the MAPK(p38/RK) pathway using the pyridinyl imidazole SB-203580 abrogated the LPS-dependent release of TNF-α. N-acetyl-l-cysteine (NAC), a precursor of glutathione, reduced TNF-α secretion and increased [GSH]. Conversely, l-buthionine-(S,R)-sulfoximine (BSO), an irreversible inhibitor of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme in the pathway mediating GSH biosynthesis, augmented the secretion of TNF-α and [GSSG] accumulation. Whereas NAC abrogated the phosphorylation of MAPK(p38/RK), BSO reversibly amplified this effect. Furthermore, intermittent exposure of FATEII cells to the exogenous oxidants X/XO and H(2)O(2) upregulated the secretion of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α; this upregulation was correlated with increasing activity of key glutathione-related enzymes, closely involved with maintaining the cyclic GSH/GSSG equilibrium. These results indicate that a redox microenvironment plays a major role in regulating MAPK-dependent production of cytokines in the alveolar epithelium.

WITHDRAWN: A novel in vivo anti-inflammatory, immunomodulatory potential of a peptide analogue of thymulin (PAT) in the hippocampus: Evidence for the involvement of a NF-kappaB-dependent mechanism and mediation through the downregulation of the IkappaB-alpha/pIkappaB-alphapathway.

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Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced production of proinflammatory cytokines and NF-kappaB nuclear translocation and activation in the alveolar epithelium: unraveling the molecular immunomodulatory, anti-inflammatory effect of thymulin/Zn2+ in vitro.

The immunomodulatory potential of thymulin and zinc (Zn(2+)) in the perinatal alveolar epithelium is not well characterized. In an in vitro model of fetal alveolar type II epithelial cells (FATEII), we have investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin (ET/LPS [lipopolysaccharide])-induced release of IL-1beta, but not IL-6 or TNF-alpha. Furthermore, Zn(2+), an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, independently reduced the secretion of IL-1beta, TNF-alpha and, to a lesser extent, at a supraphysiologic dose (1 mM), IL-6. The underlying cellular and molecular pathways associated with the anti-inflammatory effect of thymulin and Zn(2+) in the alveolar epithelium are not well established. Further in this study, the role of cyclic AMP (cAMP) in the anti-inflammatory effect of thymulin was investigated, in addition to unraveling the possible involvement of the NF-kappaB pathway. Interestingly, thymulin upregulated, in a dose- and time-dependent manner, the release of the nucleotide cAMP. To understand whether the inhibitory effect of thymulin on cytokine release is cAMP-dependent, Forskolin, a labdane diterpene known to elevate intracellular cAMP, was shown to reduce the secretion of IL-1beta and TNF-alpha, but not IL-6, an effect mimicked by dibutyryl-cAMP (dbcAMP), an analog of cAMP. Alveolar epithelial cells treated with thymulin markedly showed a downregulation of the nuclear translocation of RelA (p65), the major transactivating member of the NF-kappaB family, in addition to NF-kappaB(1) (p50) and c-Rel (p75), an effect mildly substantiated with Zn(2+). Furthermore, thymulin/Zn(2+) reduced, in a dose-dependent manner, the DNA-binding activity of NF-kappaB (RelA/p65). These results indicate that the anti-inflammatory effect of thymulin, which is mediated by cAMP, is NF-kappaB-dependent and involves the downregulation of the release of proinflammatory cytokines, particularly IL-1beta, an effect synergistically amplified, at least in part, by Zn(2+). The molecular regulation of thymulin via a NF-kappaB-dependent pathway is critical to understanding the anti-inflammatory alleviating role of this nonapeptide in regulating proinflammatory signals.

The role of inflammatory cytokines and NF-kappaB/MAPK signaling pathways in the evolution of familial Mediterranean fever: current clinical perspectives and potential therapeutic approaches.

Familial Mediterranean fever (FMF) is one of the social and health care problems for several populations that is known as a historically endemic disease of inflammatory nature. FMF, albeit a rare disorder, is characterized by recurrent fevers and painful inflammation of various body parts, especially the abdomen, lungs, and joints. FMF is typically characterized by inflammation of the abdominal lining (peritonitis), inflammation of the lining surrounding the lungs (pleurisy), painful, swollen joints (arthralgia and occasionally arthritis), and a characteristic ankle rash, a condition that is referred to as recurrent polyserositis, or familial paroxysmal polyserositis. Moreover, FMF is an inherited inflammatory disorder usually occurring in people of Mediterranean origin - including Sephardic Jews, Arabs, Armenians, and Turks; but it may ostensibly affect any other ethnic group, however, rarely. While there's no cure for this disorder, FMF is typically diagnosed during childhood, and signs and symptoms are treatable - or even preventable - by specialized medical attrition. The inflammatory signaling pathways associated with the evolution of FMF are currently being unraveled has that has therapeutic repercussions. In this review, I recap major concepts associated with the cellular and molecular immunology of FMF, especially shedding light on the likely roles of inflammatory cytokines, the transcription factor nuclear factor (NF)-kappaB, and the superfamily of mitogen-activated protein kinases (MAPKs). Furthermore, I summarize current advances for the clinical treatments available for FMF.

Multi-organ damage induced by anabolic steroid supplements: a case report and literature review.

INTRODUCTION: The use of anabolic supplements and other related drugs for body building and to enhance athletic performance is nowadays widespread and acutely pervasive all around the world. This alarming increase in the use of anabolic and amino acid supplements has been linked to a diverse array of pathologies. As previously reported, the abuse of androgenic steroids is not without severe physiological, psychiatric and physical costs. The case we report here describes multi-organ damage resulting from the abuse and uncontrolled use of anabolic steroid supplements, mainly testosterone. CASE PRESENTATION: A 24-year-old white man presented with abdominal pain concomitant with nausea and vomiting. Laboratory analysis revealed hypercalcemia, elevated liver enzymes and high levels of amylase, lipase and creatine protein kinase. CONCLUSION: Amino acid as well as anabolic supplements may lead to abnormal functioning of many organs, which could be fatal in some instances. This mandates worldwide and concerted efforts to educate the public, especially the youth, about the dangers of these increasingly abused drugs.

MRI study of the capitate, lunate, and lunate fossa with relevance to proximal row carpectomy.

PURPOSE: To study the articular morphology (radius of curvature), (diameter, depth, circularity, and percent of circle) of the capitate, proximal lunate, and the lunate fossa of the distal radius using both magnetic resonance imaging (MRI) scans and plain radiographs. The correlation between plain radiographs and MRI scans for these measurements will also be assessed. METHODS: Twenty MRI scans and 17 sets of radiographs of asymptomatic volunteers were evaluated. Standardized surface landmarks were digitized and measured in both the sagittal and coronal planes. The parameters of interest were calculated from the digitized data using specialized software. RESULTS: Using MRI data, we determined the radius of curvature of the capitate to be only 37% +/- 10 of the lunate fossa of the distal radius on the coronal (anteroposterior) view and to be 57% +/- 10 on the sagittal (lateral) view. In both planes, the proximal lunate had a significantly larger diameter and radius of curvature than did the capitate. The ratio of the radius of curvature of the proximal capitate to the proximal lunate on the coronal projection ranged from .366 to .811, and on the sagittal projection the values ranged from .46 to .71. Plain radiographs were not sufficiently accurate to determine the radius of curvature ratio of the capitate to the lunate or to the lunate fossa of the distal radius on the coronal view based on a comparison with MRI data. Plain radiography did not correlate with MRI for most clinically relevant parameters. CONCLUSIONS: The articular morphology of the capitate does not closely correspond with that of the lunate fossa when compared with the proximal lunate articular surface. Based on observed variations in capitate morphology and the potential for associated alterations in joint contact forces after proximal row carpectomy, preoperative MRI may facilitate the selection of patients with more favorable capitate morphology.

How does electromagnetic navigation stack up against infrared navigation in minimally invasive total knee arthroplasties?

Forty-six primary total knee arthroplasties were performed using either an electromagnetic (EM) or infrared (IR) navigation system. In this IRB-approved study, patients were evaluated clinically and for accuracy using spiral computed tomographic imaging and 36-in standing radiographs. Although EM navigation was subject to metal interference, it was not as drastic as line-of-sight interference with IR navigation. Mechanical alignment was ideal in 92.9% of EM and 90.0% of IR cases based on spiral computed tomographic imaging and 100% of EM and 95% of IR cases based on x-ray. Individual measurements of component varus/valgus and sagittal measurements showed EM to be equivalent to IR, with both systems producing subdegree accuracy in 95% of the readings.