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BACKGROUND: Medication adherence is an important factor in the management of chronic obstructive pulmonary disease (COPD). However, the rate of non-adherence to medications is high in COPD and is associated with worsened clinical outcomes and health-related quality of life for patients. OBJECTIVES: Our study aimed to evaluate the impact of a pharmaceutical care program led by pharmacists in the improvement of medication adherence and quality of life for COPD patients in Vietnam. METHODS: A pre- and post-intervention study was conducted over 12 months. Pharmacists provided brief counselling which focused on the role of COPD medications and the importance of adherence. Morisky Medication Adherence Scale was used to evaluate patients' adherence. Quality of life was assessed using the EQ-5D-5L questionnaire and clinical outcomes were evaluated by symptom scores. These outcomes were reassessed at baseline (T0), after 3 months (T1), 6 months (T2) and 12 months (T3). RESULTS: Study participants consisted of 211 COPD patients (mean age: 66.6â¯+/-â¯8.2 years). The percentage of patients with good adherence significantly increased from 37.4% to 53.2% (pâ¯<â¯0.001) after the program. Mean medication adherence scores improved from 6.7 (T0) to 7.4 (T2) and 7.4 (T3) (pâ¯<â¯0.001). EQ-5D-5L index values also increased from 0.47 (T0) to 0.59 (T3) (pâ¯<â¯0.001). There was no significant change in symptom scores across the duration of the study. CONCLUSIONS: Medication adherence and quality of life of COPD patients improved considerably after implementation of a pharmaceutical care program, thus supporting a vital role for pharmacists alongside physicians in the management of COPD." | Evidence-Based Pharmacy Practice |
Investigated the utility of subtests from the Wechsler-Bellevue Intelligence Scale and the Halstead-Reitan Neuropsychological Test Battery to differentiate between alcoholics and nonalcoholics (N = 76). Analyses of variance indicated that the alcoholics were more impaired than nonalcoholics. It was found that the Wechsler-Bellevue Performance subtests were more discriminative than were Verbal subtests, with performance on the Halstead-Reitan variables being intermediate. The nine measures that differentiated most significantly between groups were subjected to a stepwise multivariate discriminant analysis. The resulting function correctly classified Ss with an overall accuracy of 74.7%. It was found that the Block Design subtest was the best single discriminator. The findings were discussed in relationship to previous findings and with respect to general issues of clinical neuropsychological assessment. | Psychological Tests |
Three different types of contrast media, monomeric ionic, dimeric ionic and monomeric non-ionic, were tested and compared concerning their toxicity on three experimental models: I. Pulmonary artery and aortic pressure after contrast medium injection into the right atrium in rabbits: II. Ventricular contractile force and heart rate after perfusion of the coronary arteries on the isolated rabbit heart: III. Aortic endothelium of rats. Non-ionic contrast medium was, in all three experiments, less toxic than monomeric ionic; thus it caused less rise in pulmonary artery pressure (I) and caused less reduction in ventricular contractile force and heart rate (II) and caused less damage on aortic endothelium of rats (III). The non-ionic contrast medium also gave less toxic reaction in two (I and II) of the three models compared to the dimericionic contrast medium. In experimental model III there was no difference between these two agents. Also, the dimeric ionic contrast medium caused less toxic reactions in all three models than the monomeric ionic contrast medium. | Iothalamate Meglumine |
The paper describes the construction of a new type of ion-selective electrode sensitive to tetraphenylborate (TPB-) and its electric characteristics. The electrode responds to increasing concentrations of the TPB- anion in accordance with the Nernst equation and can be used down to 0.1 microM concentration. The applicability of the electrode for measuring the membrane potential (positive inside) was proved in inside-out oriented membrane vesicles derived from Paracoccus denitrificans. The calculated values were 175 +/- 12 mV with NADH and 180 +/- 6 mV with succinate. | Tetraphenylborate |
With the FDA approval of larotrectinib, NTRK fusion assessment has recently become a standard part of management for patients with locally advanced or metastatic cancers. Unlike somatic mutation assessment, the detection of NTRK fusions is not straightforward, and various assays exist at the DNA, RNA, and protein level. Here, we investigate the performance of immunohistochemistry and DNA-based next-generation sequencing to indirectly or directly detect NTRK fusions relative to an RNA-based next-generation sequencing approach in the largest cohort of NTRK fusion positive solid tumors to date. A retrospective analysis of 38,095 samples from 33,997 patients sequenced by a targeted DNA-based next-generation sequencing panel (MSK-IMPACT), 2189 of which were also examined by an RNA-based sequencing assay (MSK-Fusion), identified 87 patients with oncogenic NTRK1-3 fusions. All available institutional NTRK fusion positive cases were assessed by pan-Trk immunohistochemistry along with a cohort of control cases negative for NTRK fusions by next-generation sequencing. DNA-based sequencing showed an overall sensitivity and specificity of 81.1% and 99.9%, respectively, for the detection of NTRK fusions when compared to RNA-based sequencing. False negatives occurred when fusions involved breakpoints not covered by the assay. Immunohistochemistry showed overall sensitivity of 87.9% and specificity of 81.1%, with high sensitivity for NTRK1 (96%) and NTRK2 (100%) fusions and lower sensitivity for NTRK3 fusions (79%). Specificity was 100% for carcinomas of the colon, lung, thyroid, pancreas, and biliary tract. Decreased specificity was seen in breast and salivary gland carcinomas (82% and 52%, respectively), and positive staining was often seen in tumors with neural differentiation. Both sensitivity and specificity were poor in sarcomas. Selection of the appropriate assay for NTRK fusion detection therefore depends on tumor type and genes involved, as well as consideration of other factors such as available material, accessibility of various clinical assays, and whether comprehensive genomic testing is needed concurrently. | Oncogene Proteins, Fusion |
PURPOSE: To demonstrate the potential for visual recovery after surgery for early foveal involvement by progressive degenerative retinoschisis. METHODS: Surgical case report. RESULTS: A 79-year-old woman was monitored over 4 years for degenerative retinoschisis in the inferotemporal periphery of both eyes. Over the course of follow-up, visual acuity in the left eye decreased from 20/40 to 20/100, concurrent with extension of the schisis cavity into the macula. Macular involvement was confirmed on optical coherence tomography imaging, and there was no rhegmatogenous retinal detachment. The patient elected to undergo 25-gauge pars plana vitrectomy and drainage of the schisis cavity. Eleven weeks after surgery, the macula remained attached, and the uncorrected visual acuity was 20/30. Fundus examination and spectral domain optical coherence tomography confirmed ongoing resolution of the macula-involving retinoschisis. CONCLUSION: Bullous degenerative retinoschisis is believed to result in an absolute scotoma that is not surgically correctable. Our patient's excellent visual recovery suggests that the synaptic integrity of the macular outer plexiform layer can be preserved and a permanent scotoma avoided if early macular involvement by progressive degenerative retinoschisis is surgically repaired. | Macula Lutea |
BACKGROUND: Highly crosslinked polyethylene (HXLPE) was developed for its superior wear properties in comparison to conventional polyethylene (CPE). Concern over fatigue resistance has prevented widespread adoption of HXLPE for use in total ankle arthroplasty (TAA). The aim of this study was to determine whether HXLPE has sufficient fatigue strength for total ankle arthroplasty under simulated physiologically relevant motion profiles and loading in the ankle. METHODS: Physiologic load and motion profiles representative of walking gait were incorporated into a computational model of a semiconstrained, fixed-bearing TAA to determine the loading state with highest stresses in the HXLPE bearing. Subsequent fatigue testing to 10 million cycles (Mc) at 5600 N was performed to assess bearing strength. RESULTS: Peak stresses in the bearing were predicted at peak axial load and peak dorsiflexion during gait, occurring near heel off. All samples withstood 10 Mc of fatigue loading at that orientation without polyethylene bearing fracture. CONCLUSION: HXLPE had sufficient fatigue strength to withstand 10 Mc of loading at more than 5 times body weight at the point of peak stresses during simulated gait in total ankle arthroplasty. CLINICAL RELEVANCE: HXLPE may be mechanically strong enough to withstand the in vivo demands of the ankle. Improvements in wear afforded by HXLPE can be obtained without compromising sufficient polyethylene strength properties in total ankle arthroplasty." | Arthroplasty, Replacement, Ankle |
Establishment of molecular diagnostics offering quantitative technology is directly associated with real-time polymerase chain reaction (PCR). This rapid, accurate and sensitive method requires careful execution, including reliable calibration standards. The storage of such standards is crucial to prevent nucleic acid decay and to ensure stable results using real-time PCR. In this study, a broad investigation of possible causes of DNA degradation during storage was performed, including GC-content of the fragments, long-term storage, rapid freeze-and-thaw experiments, genomic DNA and short DNA fragments of different species, the influence of shear stress and the effect of nuclease remaining after DNA isolation. Several known chemical DNA degradation mechanisms have been matched with the experimental data through a process of elimination. Protocols for practical application, as well as a theoretical model describing the underlying mechanisms of deviation of real-time PCR results due to decay of standard DNA, have been developed. Primary amines in the buffer composition, which enhance depurination of the DNA helix, and shear stress due to ice crystal formation, could be identified as major sources of interaction. This results in degradation of the standard DNA, as well as in the probability of occurrence of mismatches affecting real-time PCR performance. | DNA, Bacterial |
To investigate the effect of acetylcholine on the formation and maintenance of the end plate, presynaptic (hemicholinium-3 and botulinum toxin) and postsynaptic (curare and alpha-bungarotoxin) blocking agents were injected into the amniotic sac or chorioallantoic circulation of chick embryos during different stages of their development (days 3 to 11, 3 to 18, and 12 to 18). Tntercostal or anterior and posterior latissimus dorsi muscles were examined by electron microscopy. Regardless of the duration of treatment, the type of agent, or the type of muscle, nerve ingrowth into muscle and end-plate formation were not arrested and the ultrastructure of nerve terminals and postsynaptic regions was normal. By contrast, muscle fiber ultrastructure was affected by acetylcholine blockade if continued beyond day 11. By day 11 both treated and control muscles were composed primarily of myotubes. Muscles treated beyond day 11 showed impaired fiber differentiation and persistence of many myotubes. In addition, many fiber regions contained unassembled fine filaments intermingled with other organelles. In hemicholinium-3 treated muscles ther were also mitochondrial abnormalities and an increased number of lipid droplets. The findings suggest that the altered structure of the neuromusclar junction in myasthenia gravis is not due to the lack of a trophic effect of acetylcholine. The impaired fiber maturation in the chick embryos may be related to the lack of acetylcholine mediated fiber activity. | Hemicholinium 3 |
Illusions of inappropriate familiarity with the current experience or hallucinatory recall of memories are reported in temporal lobe seizures. Pathophysiological hypotheses have been proposed, involving temporal limbic regions (Hughlings-Jackson), temporal neocortex (interpretive cortex", Penfield), or both (Bancaud). Recent data acquired from presurgical investigations using intracerebral electrode recordings, demonstrate a critical role for the sub- and para-hippocampal cortices. From this, a novel hypothesis of cortico-limbic networks emerged: deja-vu results from an abnormal synchronization between rhinal cortices and hippocampus, and reminiscences ("dreamy state") from activation of the associational function of the hippocampus in re-assembling elements of the past experience networks. "Experiential" phenomena are better scrutinized during direct cortical stimulation than during spontaneous occurrence, because it allows precise spatiotemporal correlations to be made between the illusion/hallucination and the electrical discharge features and localization. Therefore, we present a summary of the stimulation data published since Penfield's seminal studies, review the anatomical and physiological correlations of stimulation findings, and question their functional significance. We reappraise the distinct and coactive roles of the various regions involved in perception-memory processes including the hippocampus, rhinal cortices, temporal neocortex and constituent elements of the ventral stream. Additionally, we draw insights from what is known about the perception-cognition continuum underlying the construction of episodic memories. Finally, we compare the results from cortical stimulation in the epileptogenic zone with the use of stimulation for memory enhancement and explore what this reveals about the mechanisms of stimulation." | Deja Vu |
A d-f heterometallic MOF using the 2,2'-bipyridine-4,4'-dicarboxylic acid ligand (H(2)LZ) was obtained by solvothermal synthesis, namely [EuZn(LZ)(2)(HCOO)(H(2)O)(3)](n) (1). The structure analysis shows that compound 1 comprises heterometallic Zn(2+) and Eu(3+) ions, which are connected by LZ(2-) and HCOO(-) anions to form a three-dimensional framework. MOF 1 exhibited high stability of fluorescence intensity in the scope of pH 2-11 in an aqueous solution. Furthermore, MOF 1 served as an excellent selective sensing material for the detection of folic acid in the presence of some imitating materials of the human body and discerned sulfaquinoxaline in sulfonamide drugs with high sensitivity, selectivity, and reusability. Moreover, we designed and manufactured a sensor paper based on MOF 1 as a portable device for the visual detection of folic acid and sulfaquinoxaline. More crucially, this is the first example in which luminescent MOF is used to identify sulfaquinoxaline molecules in an aqueous solution. In addition, the luminescence sensing mechanisms of MOF 1 for the detection of the above analytes were explored in detail. | Sulfaquinoxaline |
BACKGROUND: This study was conducted to evaluate the effects of commonly used injection medication combinations on supraspinatus tenocyte cell viability and tissue metabolism. METHODS: Twenty adult dogs underwent ultrasound guided injection of the canine equivalent of the subacromial space, based on random assignment to one of four treatment groups (n=5/group): normal saline, 1.0% lidocaine/methylprednisolone, 1.0% lidocaine/triamcinolone or 0.0625% bupivacaine/triamcinolone. Full-thickness sections of supraspinatus tendon were harvested under aseptic conditions and evaluated on days 1 and 7 post-harvest for cell viability and tissue metabolism. Data were analyzed for significant differences among groups. RESULTS: Tendons exposed to 1% lidocaine/ methylprednisolone had significantly lower cell viability at day 1 as compared to all other groups and control. All local anesthetic/ corticosteroid combination groups had decreased cell viability at day 7 when compared to the control group. CONCLUSIONS: This study demonstrated significant in vivo supraspinatus tenotoxicity following a single injection of combination local anesthetic/ corticosteroid when compared to saline controls. LEVEL OF EVIDENCE: Level II. | Tenocytes |
Symphytum officinale (comfrey), Tussilago farfara (coltsfoot) and Borago officinalis (borage) have long histories of therapeutic use, but their safety has been questioned due to the presence of unsaturated pyrrolizidine alkaloids (PAs). The evidence base underlying these concerns relies in part on case reports. This systematic review assesses these case reports for their reliability to inform this debate. METHOD: Study selection was restricted to case reports describing possible pyrrolizidine alkaloid related harm and ingestion of comfrey, coltsfoot or borage. An extensive search of academic databases was conducted. Papers meeting the criteria were critically appraised. RESULTS: The search resulted in 11 appropriate case reports, none of which involved borage. Nine reports were assessed for causality and indicated some degree of association between the material ingested and the adverse event. Lack of unequivocal identification of the species ingested compromised attribution and was a significant source of uncertainty. Three levels of identity confusions were found; misidentification or substitution at the level of the whole herb; omission of appropriate botanical identification and attribution of a specific PA to either comfrey or coltsfoot when it is a constituent found in other plants of established toxicity. CONCLUSION: These cases are an unreliable body of evidence on which to draw conclusions about the safety of the oral consumption of Symphytum officinale and Tussilago farfara. Toxicological studies based on oral ingestion of phytochemically-complex preparations of these herbs may be the most accurate methodology for assessing clinical risk. | Tussilago |
Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major role in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease. | Osteoclasts |
Electrochemical impedance spectroscopy (EIS) is a powerful tool to measure and quantify the system impedance. However, EIS only provides an average result from the entire electrode surface. Here, we demonstrated a reflection impedance microscope (RIM) that allows us to image and quantify the localized impedance on conductive surfaces. The RIM is based on the sensitive dependence between the materials' optical properties, such as permittivity, and their local surface charge densities. The localized charge density variations introduced by the impedance measurements will lead to optical reflectivity changes on electrode surfaces. Our experiments demonstrated that reflectivity modulations are linearly proportional to the surface charge density on the electrode and the measurements show good agreement with the simple free electron gas model. The localized impedance distribution was successfully extracted from the reflectivity measurements together with the Randles equivalent circuit model. In addition, RIM is used to quantify the impedance on different conductive surfaces, such as indium tin oxide, gold film, and stainless steel electrodes. A polydimethylsiloxane-patterned electrode surface was used to demonstrate the impedance imaging capability of RIM. In the end, a single-cell impedance imaging was obtained by RIM. | Electric Conductivity |
Using Census-derived data for consistent spatial units, this paper explores how the population of Britain in 1991, 2001 and 2011 was spatially structured by self-reported health including exploring the trajectories of change. This paper uses consistent small area units to examine the changing spatial structure of census-derived Limiting, Long-Term Illness (LLTI) in Britain over the twenty year period and utilises the 2011 Office for National Statistics Output Area Classification (OAC) as a geodemographic indicator. The results allow the geography of change to be captured, highlighting how health is inextricably linked to geography, demonstrating quantitatively a complex, yet distinctive, spatial organisation of health inequalities within Britain. Overall decreasing unevenness values, coupled with increased positive spatial association suggests that neighbouring areas have become more similar over time - the distinction between areas characterised by poor health or by good health is decreasing. | Geography |
BACKGROUND: Dextromethorphan, a clinically available N-methyl-D-aspartic acid (NMDA) receptor antagonist, has an analgesic effect in patients with diabetic neuropathy. The aim of this study was to evaluate the analgesic and adverse effects of a single high dose of dextromethorphan on spontaneous pain in patients suffering long-term neuropathic pain of traumatic origin. METHODS: Fifteen patients with post-traumatic neuropathic pain participated in this placebo-controlled, double-blind, randomized crossover study. On two separate occasions, the participants received 270 mg of dextromethorphan hydrobromide or placebo. Pain intensity, adverse effects and serum concentrations of dextromethorphan and metabolites were registered. RESULTS: Dextromethorphan had a statistically significant analgesic effect compared with placebo, but the effect varied markedly among the patients. Light-headedness was the most important adverse effect reported. Extensive metabolizers of dextromethorphan had an apparently better analgesic effect than poor metabolizers. CONCLUSION: This report indicates that a single high dose of dextromethorphan has an analgesic effect in patients with neuropathic pain of traumatic origin. The main metabolite dextrorphan seems to be important for the analgesic effect. At the relatively high dose studied, the clinical usefulness of dextromethorphan is limited to that portion of the patient population experiencing analgesia without an unacceptable level of adverse effects. | Dextromethorphan |
BACKGROUND: The rising incidence of osteoporotic fractures requires novel treatment strategies. OBJECTIVE: Implant augmentation with bone cement is considered to be a promising approach but the benefits and risks need to be carefully evaluated. METHODS: Experimental investigation of the biomechanical potential and the associated risks with special reference to the osteoporotic proximal femur and proximal humerus. RESULTS: Even small amounts of bone cement (3 ml) applied to the proximal femur in combination with intramedullary nailing led to more than a 50% increase in the number of test cycles before failure. The heat and pressure generated in the bone did not exceed critical thresholds. Short to midterm effects of subchondral cement placement on the adjacent cartilage can be excluded. The risk for cement leakage needs to be considered. CONCLUSION: Implant augmentation offers high biomechanical potential to prevent mechanical complications after fracture fixation in osteoporotic bone. Early and confident mobilization of elderly patients therefore appears to be possible. With appropriate handling, associated risks seem controllable; however, implant augmentation cannot be applied as a routine concept for osteoporotic fracture management. The application requires careful evaluation on a case by case basis under comprehensive consideration of mechanical and biological factors. | Cementoplasty |
During chronic antigen exposure, a subset of exhausted CD8(+) T cells differentiate into stem cell-like or progenitor-like T cells expressing both transcription factor Tcf-1 (T cell factor-1) and co-inhibitory receptor PD-1. These Tcf-1(+) stem-like or progenitor exhausted T cells represent the key target for immunotherapies. Deeper understanding of the biology of Tcf-1(+)PD-1(+) CD8(+) T cells will lead to rational design of future immunotherapies. Here, we summarize recent findings about the migratory and resident behavior of Tcf-1(+) T cells. Specifically, we will focus on TGF-beta-dependent lymphoid tissue residency program of Tcf-1(+) T cells, which may represent a key to understanding the differentiation and maintenance of Tcf-1(+) stem-like CD8(+) T cells during persistent antigen stimulation." | Costimulatory and Inhibitory T-Cell Receptors |
Activation of G protein-gated inwardly rectifying potassium (GIRK) channels leads to a hyperpolarization of the neuron's membrane potential, providing an important component of inhibition in the brain. In addition to the canonical G protein-activation pathway, GIRK channels are activated by small molecules but less is known about the underlying gating mechanisms. One drawback to previous studies has been the inability to control intrinsic and extrinsic factors. Here we used a reconstitution strategy with highly purified mammalian GIRK2 channels incorporated into liposomes and demonstrate that cholesterol or intoxicating concentrations of ethanol, i.e., >20 mM, each activate GIRK2 channels directly, in the absence of G proteins. Notably, both activators require the membrane phospholipid PIP(2) but appear to interact independently with different regions of the channel. Elucidating the mechanisms underlying G protein-independent pathways of activating GIRK channels provides a unique strategy for developing new types of neuronal excitability modulators." | G Protein-Coupled Inwardly-Rectifying Potassium Channels |
This article reviews diagnosis of cerebral amyloid angiopathy (CAA) during life and possible approaches to prevention. A clinical diagnosis of probable CAA" can be made in patients aged 60 years or older with multiple hemorrhages confined to lobar brain regions and no other cause of hemorrhage. Gradient-echo MRI facilitates diagnosis by showing previous hemorrhages with high sensitivity. This technique can also mark the progression of CAA, as 50% of studied patients developed new petechial hemorrhages during 1.5 years of follow-up. The apolipoprotein E epsilon2 and epsilon4 alleles are associated with increased risk and earlier age of first hemorrhage, but are neither sensitive nor specific for CAA. The major remaining challenges are to develop new markers for the presence of CAA and treatments to block vascular amyloid deposition and vessel breakdown." | Cerebral Amyloid Angiopathy |
Management of flexor tendon injuries is one of the most demanding tasks in hand surgery. Despite substantial improvements in surgical technique and postoperative rehabilitation protocols, functional outcomes may still be somewhat unreliable. In the present article, the authors present complications encountered after flexor tendon repair and provide their preferred methods of prevention and treatment. | Trigger Finger Disorder |
The author analyses 5-year results of the treatment of 548 patients with breast cancer according to the type of the operative intervention: Halsted's radical mastectomy, Peity's modified radical mastectomy, and mastectomy with axillary lymphadenectomy. In stages T1-2, N0, M0 the results of all three types of operations were the same. No statistically significant difference was revealed between Halsted's mastectomy and modified radical mastectomy in stages T2-3, N1-3, M0 which allows it to be recommended for wider use. | Mastectomy, Radical |
The results of a hospital security survey using a random sampling of hospital organizations in the AHA Membership Directory. The survey covered staffing, security attire and equipment, training, use of physical security, and bicycle patrols. No serious security staffing cutbacks have taken place in the past two years, according to survey respondents. | Security Measures |
In kidney transplantation, the use of minimally invasive damage biomarkers that are more sensitive and specific than plasma creatinine will be crucial to enable early, actionable detection or exclusion of structural kidney damage due to acute or chronic rejection. Donor-derived cell-free DNA (dd-cfDNA), which can be quantified, for example, through next-generation sequencing, droplet digital PCR and quantitative PCR, is a candidate biomarker with great potential for enabling comprehensive monitoring of allograft injury. dd-cfDNA has a favourable overall diagnostic performance for the detection of rejection and its high negative predictive value might be especially useful for avoiding unnecessary biopsies. Elevated dd-cfDNA levels have been shown to be detectable before graft injury can be clinically identified using current diagnostic methods. Moreover, dd-cfDNA falls rapidly to baseline levels after successful treatment for rejection owing to its short half-life. dd-cfDNA can detect graft injury caused by immune activation owing to insufficient immunosuppression and might therefore also help guide immunosuppression dosing. The fractional abundance of dd-cfDNA can be affected by changes in the recipient cfDNA (for example, due to infection or physical exercise) but the use of absolute quantification of dd-cfDNA overcomes this limitation. Serial dd-cfDNA determinations might therefore facilitate cost-effective personalized clinical management of kidney transplant recipients to reduce premature graft loss. | Cell-Free Nucleic Acids |
Stone surgery is one of oldest surgical practices undertaken by man. Hippocrates refused to let his followers cut for the stone" and it was only in February 1980, when the first human trial of shock wave therapy on a renal stone was performed with success that a new era in minimally invasive treatment (surgery) for stones was opened up and this condemnation was finally resolved in the Hippocratic Oath. Endoscopy, using natural orifices, supported by anaesthesia, incremented by technology and with access to all points along the urinary tract, began by competing with ESWL, but is now the treatment of choice in most cases. As far as we know humans have always had stones. First, lithiasis was endemic bladder stones in children, now it is renal in general. Added to this a number of well-known risk factors, a rapid increase in obesity in the population, as well as bariatric surgery for its treatment, are causing an increase in the prevalence and recurrence of lithiasis everywhere. A short history of the advances made with the introduction and development of the ureteroscope, along with auxiliary devices, will show why this is the preferred technique at the moment for treating lithiasis in general and for treating stones in pregnant women, children and the obese in particular. Being a minimally invasive surgery, with a low morbidity and a very high efficiency and stonefree rate, has become established as a clear future technique for both adults and children. This development is not only due to technological advancements, but also to the routine use of the Holmium: YAG LASER for intracorporeal lithotripsy, capable of destroying any stone regardless of its composition or location, surpassing the ability of any other lithotripter. It is also due to the development of devices that allow access to the ureter and all parts of the kidney, as well as auxiliary aids to assist in the handling of stones during treatment. New LASERs, robotic control of the fdURS and digital imaging, as well as disposable devices, have had and, indeed, continue to have a unique impact on future development in this field. However, success will continue to depend on the careful choice of fURS, energy source and ancillary instruments obtained by the urologist during both real life and virtual training in human simulators." | Ureteroscopy |
The primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The rapid resetting of arterial baroreceptor afferents toward any sustained new level of blood pressure ensures that the reflex acts as an effective buffer of short-term blood pressure fluctuations that accompany daily life but also ensures that arterial baroreflexes play little role in setting the long-term level of blood pressure. Nevertheless, the minimization of blood pressure variability by baroreflex mechanisms is important as studies suggest that a diminished baroreflex is an independent risk factor or sudden death after myocardial infarction. In hypertensive humans and animals, the baroreflex control of heart rate is diminished. Using the steady-state method for assessment of the cardiac baroreflex in rats, we have shown that the change in baroreflex sensitivity is due to a reduction in the vagal range. Although the cardiac sympathetic component of the baroreflex is normal, the level of cardiac sympathetic activity is enhanced, particularly in young hypertensive rats. We have shown that there is a stronger inverse relationship between vagal heart rate range and levels of cardiac hypertrophy than with other variables, such as blood pressure, hypertension, or indexes of vascular hypertrophy. Treatments that reduce cardiac hypertrophy restore cardiac vagal function. Centrally acting antihypertensive agents increase the sensitivity of vagal baroreceptor heart rate reflexes, mainly through an action on central alpha 2-adrenoceptors. They also reduce cardiac sympathetic activity and diminish cardiac sympathetic baroreflexes through a non-alpha 2-adrenoceptor, possibly an imidazoline receptor mechanism. Both of these effects are beneficial in hypertension, where cardiac sympathetic function is enhanced and vagal activity is reduced. Thus, these actions would be expected to cause a desirable reduction in blood pressure variability. The effect of hypertension on baroreflex control of sympathetic vasomotor function is less clear. Studies have shown diminished, normal, and enhanced sympathetic vasomotor baroreflex control. Basal renal sympathetic drive, however, appears to be increased in human essential hypertension. Our studies in conscious rabbits have shown that rilmenidine reduces renal sympathetic baroreflex function. Rilmenidine acts principally at the level of the rostral ventrolateral medullary imidazoline receptors to markedly reduce the basal renal sympathetic nerve activity and the maximum response to transient fluctuations in blood pressure. Thus, in addition to their antihypertensive actions, centrally acting agents, such as rilmenidine, reduce cardiac and renal sympathetic baroreflex responses and increase cardiac vagal baroreflex sensitivity. This provides an ideal profile of action for the restoration of baroreflex function in addition to reversal of cardiac and vascular hypertrophy in hypertension. | Baroreflex |
We describe the red phosphorescence exhibited by a class of structurally simple benzo[2,1,3]thiadiazoles at room temperature. The photophysical properties of these molecules in deoxygenated cyclohexane, including their absorption spectra, steady-state photoluminescence and excitation spectra, and phosphorescence lifetimes, are presented. Time-dependent density functional theory calculations were carried out to better understand the electronic excited states of these benzo[2,1,3]thiadiazoles and why they are capable of phosphorescence. | Thiadiazoles |
The justification for performing surgery on patients most often rests on observational studies and rarely on correctly conducted randomised trials, which is the highest level of evidence. For methodological and ethical reasons, surgical trials can be problematic. However, the ethical problems are greater if trials are not performed, since it will then not be possible to find out which of the available interventions have no effect or are harmful. The problems can be overcome in many cases, and by intra- and international co-operation it would be possible to carry out many more trials, which would increase the level of evidence for surgery in daily practice. When randomised trials have not been performed, one is obliged to look for the evidence in prospective cohort studies, e.g. clinical databases, which, however, are more suitable for evaluating complications to surgery under routine circumstances than for evaluating useful effects." | Surgical Procedures, Operative |
The rapid development of artificial intelligence (AI) and digital health raise concerns about equitable access to innovative interventions, appropriate use of health data and privacy, inclusiveness, bias and discrimination, and even changes to the clinician-patient relationship. This article outlines a number of ethical and legal issues when examining the use of AI in gastroenterology. Substantive ethico-legal principles including respect for persons, privacy and confidentiality, integrity, conflict of interest, beneficence, nonmaleficence, and justice, are discussed. Much of what we articulated is relevant to the use of AI in other medical fields. Going forward, consorted efforts should be use to address more particular and concrete problems, but for now, a principle-based approach is best used in problem-solving. | Gastroenterology |
Dehydroepiandrosterone (DHEA) and 5-androstene-3 beta,17 beta-diol (ADIOL) were determined by radioimmunoassay in human primary mammary cancer cytosol preparations. The range and means +/- S.D. (ng/g, wet weight, of tissue) in individual tumors were: DHE, 12.3 +/- 14.4, n = 34; and ADIOL, 2.7 +/- 2.1, n = 43. In 23 tumors in which both steroids were measured in the same extract, they were significantly correlated, and in these tumors the ratio of ADIOL to DHEA was lower in estrogen receptor (ERC)-negative than in ERC-positive tumors, but this difference was not significant. The ratio of ADIOL to DHEA was 5-fold higher in purified nuclei obtained from pooled primary mammary cancer tissue compared to that in the cytosol. DHEA was present in the cytosol of tumors from premenopausal women in significantly higher concentrations than in cytosols of postmenopausal women [0.73 +/- 0.49 ng/mg cytosol protein (n = 14) versus 0.35 +/- 0.35 (n = 19); p < 0.02], whereas the concentrations of ADIOL were similar [0.12 +/- 0.09 ng/mg cytosol protein (n = 18) and 0.10 +/- 0.11 (n = 25), for pre- and postmenopausal women, respectively]. In ERC-positive tumors, there was a negative correlation between ERC concentration and cytosol ADIOL levels in both premenopausal (r = -0.46, n = 10) and postmenopausal (r = -0.24; n = 20) subjects and also DHEA levels in postmenopausal women only (r = -0.30; n = 12). However, none of these correlations reached statistical significance. In view of the known high affinity of ADIOL for ERC (Kd approximately 6 nM) and its estrogen-like activity in vivo, these data suggest that the concentration of ADIOL in the tumor cytosols is sufficiently high to translocate ERC and provoke an estrogen response. | Androstenediols |
Health care professionals are increasingly called upon to work collaboratively. This commentary discusses our experience at the Summer Institute on Interdisciplinary Health Research, which aimed to increase the capacity of future Canadian researchers to work with health professionals from other disciplines. We discuss, in particular, our small group experience--the challenges we faced, and how we were able to resolve the internal conflicts that occurred. We also discuss the conditions necessary to engage in interdisciplinary work and offer suggestions to improve future initiatives to build interdisciplinary research capacity. | Interprofessional Relations |
Protein phosphorylation on certain serine or threonine residues preceding proline (Ser/Thr-Pro) is a pivitol signaling mechanism in diverse cellular processes and its deregulation can lead to human disease. However, little is known about how these phosphorylation events actually control cell signaling. Pin1 is a highly conserved enzyme that isomerizes only the phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Recent results indicate that such conformational changes following phosphorylation are a novel signaling mechanism pivotal in regulating many cellular functions. This mechanism also offers new insights into the pathogenesis and treatment of human disease, most notably cancer and Alzheimer's disease. Thus, Pin1 plays a key role in linking signal transduction to the pathogenesis of cancer and Alzheimer's disease - two major age-related diseases. | Phosphoamino Acids |
Primary Progressive Aphasia (PPA) is a neurodegenerative disorder initially presenting with progressive language imapirment. This article provides a clinically oriented review of PPA. Different clinical presentations and imaging findings of 3 subtypes, agrammatic, semantic and logopenic, are presented. Underlying neuropathology, medical and social management aspects of these patients are reviewed. | Aphasia, Primary Progressive |
BACKGROUND: Maintenance of euvolemia and cerebral perfusion are recommended for the prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). We conducted a pilot randomized controlled study to assess the feasibility and efficacy of goal-directed therapy (GDT) to correct fluid and hemodynamic derangements during endovascular coiling in patients with aSAH. METHODS: This study was conducted between November 2015 and February 2019 at a single tertiary center in Canada. Adult patients with aSAH within 5 days of aneurysm rupture were randomly assigned to receive either GDT or standard therapy during endovascular coiling. The incidence of dehydration at presentation and the efficacy of GDT were evaluated. RESULTS: Forty patients were allocated to receive GDT (n=21) or standard therapy (n=19). Sixty percent of all patients were found to have dehydration before the coiling procedure commenced. Compared with standard therapy, GDT reduced the duration of intraoperative hypovolemia (mean difference 37.6 [95% confidence interval, 6.2-37.4] min, P=0.006) and low cardiac index (mean difference 30.7 [95% confidence interval, 9.5-56.9] min, P=0.035). There were no differences between the 2 treatment groups with respect to the incidence of vasospasm, stroke, death, and other complications up to postoperative day 90. CONCLUSIONS: A high proportion of aSAH patients presented at the coiling procedure with dehydration and a low cardiac output state; these derangements were more likely to be corrected if the GDT algorithm was used. Compared with standard therapy, use of the GDT algorithm resulted in earlier recognition and more consistent treatment of dehydration and hemodynamic derangement during endovascular coiling. | Early Goal-Directed Therapy |
Cadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC. Using single molecule force spectroscopy and applying Jarzynski's equality we determined the kinetics and thermodynamics of Dsg2 homophilic binding. Notably, the free energy landscape of Dsg2 dimerization exposes a high activation barrier which is in line with the proposed strand-swapping binding motif. Although the binding motif is not directly affected by the mutations the binding kinetics differ significantly from the wildtype. Furthermore, we applied a dispase based cell dissociation assay using HT1080 cell lines over expressing Dsg2 wildtype and mutants, respectively. Our molecular and cellular results consistently demonstrate that Dsg2 mutations can heavily affect homophilic Dsg2 interactions. Furthermore, the full thermodynamic and kinetic description of Dsg2 dimerization provides a consistent model of the so far discussed homophilic cadherin binding. | Desmogleins |
To obtained an accurate, rapid and efficient method for authenticate medicinal snakes listed in Chinese Pharmacopoeia (Zaocysd humnades, Bungarus multicinctus, Agkistrodon acutus), a rapid PCR method for authenticate snakes and its adulterants was established based on the classic molecular authentication methods. DNA was extracted by alkaline lysis and the specific primers were amplified by two-steps PCR amplification method. The denatured and annealing temperature and cycle numbers were optimized. When 100 x SYBR Green I was added in the PCR product, strong green fluorescence was visualized under 365 nm UV whereas adulterants without. The whole process can complete in 30-45 minutes. The established method provides the technical support for authentication of the snakes on field. | Snakes |
The study of the symbiotic interaction between rhizobia and legumes represents a major theme in plant biology. This interaction results in the formation of nodules, root organs in which the bacteria reduce atmospheric nitrogen into ammonia, which can subsequently be utilized by the plant. The execution of the different developmental stages observed during nodule ontogenesis involves many cellular processes with significant roles for the plant cytoskeleton. A challenging question in cell biology is how the cytoskeleton organizes itself into the dynamic arrays required for cell differentiation and functioning. Nodulation is, particularly, well qualified as an experimental system for cytoskeleton research because an early essential step of the plant/microbe interaction takes place in surface-exposed root hairs, well suited for cell biological in vivo experimentation. Moreover, the changes in the organization of the cytoskeleton can be elicited by a well-defined molecule, the Nod factor, or by bacterial inoculation, thus providing the researcher with the possibility of controlling the cytoskeletal changes in target cells. In addition, the well-known cytology of the symbiotic interaction facilitates the correlation between the changes in the organization of the plant cytoskeleton with both histological and cellular changes. In this review, the current knowledge on the role of the plant cytoskeleton during nodulation is summarized, with emphasis on the interaction between Medicago truncatula and Sinorhizobium meliloti. | Cytoskeleton |
Virulence factors responsible for bacterial pathogenicity are often encoded by plasmids. In Melissococcus plutonius, the causative agent of European foulbrood of honey bees, a putative virulence plasmid (pMP19) possessing mtxA, which encodes a putative insecticidal toxin, was found by comparative genome analyses. However, as the role of pMP19 in the pathogenesis of European foulbrood remains to be elucidated, we generated pMP19 cured-M. plutonius from representative strains of the three genetically distinct groups (CC3, CC12 and CC13) and compared their virulence against Apis mellifera larvae using our in vitro infection model. Under the conditions tested, the loss of pMP19 abrogated the pathogenicity in CC3 strains, and > 94% of pMP19-cured CC3 strain-infected larvae became adult bees, suggesting that pMP19 is a virulence determinant of CC3 strains. However, introduction of mtxA on its own did not increase the virulence of pMP19-cured strains. In contrast to CC3 strains, the representative CC12 strain remained virulent even in the absence of pMP19, whereas the representative CC13 strain was avirulent even in the presence of the plasmid. Thus, pMP19 plays a role in the virulence of M. plutonius; however, its impact on the virulence varies among strains with different genetic backgrounds. | Enterococcaceae |
We studied the effect of prostaglandins (PGs) A1, delta 7-A1, A2, D2, E1, E2, F2 alpha, J2 and delta 12-J2 on the replication of herpes simplex virus type 2 (HSV-2). Of nine PGs we tested, delta 7-PGA1 was found to have the most potent inhibitory effect; 50% inhibitory dose (ID50) was 0.35 microgram/ml in the plaque reduction assays and HSV-2 induced protein synthesis was strongly suppressed at 0.5 microgram/ml whereas at this dose, the protein synthesis of uninfected cells was not inhibited. Dot blot hybridization analysis revealed that delta 7-PGA1 and delta 12-PGJ2 inhibited the primary transcription of HSV-2. Thus we suggest that those PGs are primarily active at the level of mRNA synthesis. | Prostaglandins A, Synthetic |
Syntheses of various isomeric dihydropiperazines can be approached successfully by taking advantage of the regioselective monothionation of their respective diones. Preparation of the precursor unsymmetrical N-substituted piperazinediones from readily available diamines is key to this selectivity. The dihydropiperazine ring system, as exemplified in 1-[(6-chloropyridin-3-yl)methyl]-4-methyl-3-oxopiperazin-2-ylidenecyanamide (4) and 1-[(2-chloro-1,3-thiazol-5-yl)methyl]-4-methyl-3-oxopiperazin-2-ylidenecyanamide (25), has been shown to be a suitable bioisosteric replacement for the imidazolidine ring system contained in neonicotinoid compounds. However, placement of the cyanoimino electron-withdrawing group further removed from the pyridine ring, as in 4-[(6-chloropyridin-3-yl)methyl]-3-oxopiperazin-2-ylidenecyanamide (3a), or relocation of the carbonyl group, as in 1-[(6-chloropyridin-3-yl)methyl]-4-methyl-5-oxopiperazin-2-ylidenecyanamide (5), results in significantly decreased bioisosterism. The dihydropiperazine ring system of 4 and 25 also lends a degree of rigidity to the molecule that is not offered by the inactive acyclic counterpart 2-[(6-chloropyridin-3-yl)-methyl-(methyl)amino]-2-(cyanoimino)-N,N-dimethylacetamide (6). A pharmacophore model is proposed that qualitatively explains the results on the basis of good overlap of the key pharmacophore elements of 4 and imidacloprid (1); the less active regioisomers of 4 (3a, 5, and 6) feature a smaller degree of overlap. | Cyanamide |
Schistosomiasis continues to pose significant public health problems in many developing countries. Mass drug administration (MDA) is the most adopted control option but there is increasing evidence for the development of praziquantel-resistant Schistosoma strains. This shortcoming has necessitated the search for other effective methods for the control of schistosomiasis. The breaking of Schistosoma transmission cycles through the application of molluscicides into snail infested freshwater bodies has yielded positive outcomes when integrated with MDA in some countries. However, few of such effective molluscicides are currently available, and where available, their application is restricted due to toxicity concerns. Some nanotized particles with molluscicidal activities against the different stages of snail intermediate hosts of schistosomes have been reported. Importantly, the curcumin-nisin nanoparticle synthesized by our group was very effective and it showed no significant toxicity in a mouse model and brine shrimps. This, therefore, offers the possibility of developing a molluscicide that is not only safe for man but also is environmentally friendly. This paper reviews nanoparticles with molluscicidal potential. The methods of their formulation, activities, probable mechanisms of actions, and their toxicity profiles are discussed. More research should be made in this field as it offers great potential for the development of new molluscicides. | Molluscacides |
The age at which infants can demonstrate the ability to deduce abstract rules can be reduced by more than half, from 21 months to 9 months. The key is to introduce a physical connection between the items to be conceptually related. I argue here that making the same change in how items are presented might also help some preschoolers with learning delays, especially some children with autism. I also suggest that the roles of premotor and ventrolateral prefrontal cortices in deducing abstract rules might have been misinterpreted behaviorally and anatomically. The crucial brain region may be the periarcuate, which partially overlaps both premotor and lateral prefrontal cortex. The cognitive ability made possible by this region might be something far more elementary than previously considered: the ability to perceive conceptual connections in the absence of physical connection. | Frontal Lobe |
Golgins are large coiled-coil proteins that play a role in tethering of vesicles to Golgi membranes and in maintaining the overall structure of the Golgi apparatus. Six Arabidopsis proteins with the structural characteristics of golgins were isolated and shown to locate to Golgi stacks when fused to GFP. Two of these golgin candidates (GC1 and GC2) possess C-terminal transmembrane (TM) domains with similarity to the TM domain of human golgin-84. The C-termini of two others (GC3/GDAP1 and GC4) contain conserved GRAB and GA1 domains that are also found in yeast Rud3p and human GMAP210. GC5 shares similarity with yeast Sgm1p and human TMF and GC6 with yeast Uso1p and human p115. When fused to GFP, the C-terminal domains of AtCASP and GC1 to GC6 localized to the Golgi, showing that they contain Golgi localization motifs. The N-termini, on the other hand, label the cytosol or nucleus. Immuno-gold labelling and co-expression with the cis Golgi Q-SNARE Memb11 resulted in a more detailed picture of the sub-Golgi location of some of these putative golgins. Using two independent assays it is further demonstrated that the interaction between GC5, the TMF homologue, and the Rab6 homologues is conserved in plants. | Golgi Matrix Proteins |
This commentary considers the impact to date of Australia's Royal Commission into Institutional Responses to Child Sexual Abuse on child- and youth-serving organizations, particularly its influence on organizations' efforts to create and maintain 'child safe, child friendly' cultures, policies and practices. Opportunities and challenges for organizational leaders are outlined. The commentary calls for more involvement by researchers in empirical research that is relevant to the causes and prevention of abuse in organizations, and for findings to be disseminated in ways that are useful to organizations. | Advisory Committees |
Classical antidepressants elevate the monoamine levels in the brain by preventing re-uptake of monoamines after release. Treatment of depression with monoamine re-uptake inhibitors is associated with low clinical efficacy and remission rate due to the delayed onset of therapeutic responses. Therefore, the development of alternative antidepressants is essential for successful treatment of this disease. Recently, glutamate receptor antagonists including ketamine and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) have received wide attention as fast-acting therapeutic alternatives for treatment of depression. | Excitatory Amino Acid Agents |
Musculoskeletal models have proven to be a valuable tool in human orthopaedics research. Recently, veterinary research started taking an interest in the computer modelling approach to understand the forces acting upon the canine musculoskeletal system. While many of the methods employed in human musculoskeletal models can applied to canine musculoskeletal models, not all techniques are applicable. This review summarizes the important parameters necessary for modelling, as well as the techniques employed in human musculoskeletal models and the limitations in transferring techniques to canine modelling research. The major challenges in future canine modelling research are likely to centre around devising alternative techniques for obtaining maximal voluntary contractions, as well as finding scaling factors to adapt a generalized canine musculoskeletal model to represent specific breeds and subjects. | Dogs |
Two experiments using male rats evaluated the effects of a range of doses of the neurosteroid, pregnenolone sulfate (PS), or of the synthetic neurosteroid, ethylestrenol (E), on the retention of a passive avoidance task. The steroids either were given immediately after the training trial or 1 h before the first retention test. Retention tests were given both 24 h and 48 h after acquisition. In both experiments, separate groups of animals were trained under low or moderate footshock conditions. At all doses tested both PS and E improved retention under the low footshock conditions. In groups trained with the higher footshock, the steroid-treated groups performed no better than the vehicle controls. Indeed, there were suggestions that some doses impaired retention. These results seem best understood as an induction of bimodality or 'turbulence' in behavior as used in Chaos theory rather than a shift in an inverted U-shaped retention function. In the second experiment in which the steroids were given before retention testing, they were generally without effect. | Ethylestrenol |
Sulforaphane (SFN) is a potent anticancer agent which could protect the skin from ultraviolet (UV) radiation-induced insults. Currently, the metabolic rewiring and epigenetic reprograming induced by UVB and the role of SFN in UVB-mediated skin cell transformation remain largely unknown. Herein, we study the metabolome, epigenome, and transcriptome of human keratinocytes (HaCaT cells) exposed to UVB with or without SFN using liquid chromatography-mass spectroscopy, DNA methylation sequencing, and RNA sequencing. UVB increases intracellular reactive oxygen species (ROS) and SFN enhances ROS acutely in post-UVB-exposed HaCaT cells. UVB and SFN alter multiple metabolites and metabolism-related signaling pathways. Pathway analysis shows that UVB impacts numerous signaling pathways including STAT3, inhibition of matrix metalloproteases, and TGF-beta, among others. DNA/CpG methylation analysis shows that SFN could partially reverse some of the alterations of UVB-induced CpG methylome. Integrating RNA-seq and Methyl-seq data, starburst plots show the correlation of mRNA expression and CpG methylation status. The potential linkages between the metabolome, CpG methylome, and transcriptome suggest that metabolites produced during metabolism act as cofactors or substrates for catalytic epigenetic modification and transcriptional regulation. These results indicate that UVB drives metabolic rewiring, epigenetic reprograming, and phenotypic transcriptomic alterations and SFN would block or attenuate many of these aberrations, potentially contributing to the overall protective effect of SFN against UVB-induced skin damage. | Isothiocyanates |
Many older people have a bad oral health, with (root) caries a prevalent cause. Alarming results of research projects raise the question whether sufficient preventive measures are being taken to prevent the development and progress of (root) caries in frail older people. A review of the recent literature revealed that in frail older people and physically or cognitively impaired adults, daily use of a 5,000 ppm fluoride toothpaste and quarterly application of chlorhexidine or sodium fluoride can decrease by half the risk of root caries. In the Netherlands, toothpaste containing 5,000 ppm fluoride is not (yet) on the market. At the present time, only the advice brochure 'Prevention of root caries' is available. Another measure to prevent deterioration of oral health among frail older people is paying attention to frail older people who do not visit their dentist on a regular basis due to physical limitations and care dependency. When this is the case, it is necessary to intensify professional oral healthcare with instructions to personal caregivers and professional care providers in order to fight (root) caries. | Cariostatic Agents |
A previously reported visible spectrophotometric method for the analysis of aminacrine hydrochloride in creams, jellies, and suppositories was studied collaboratively by 8 laboratories. Aminacrine hydrochloride was extracted into acidic ethanol and its visible spectrum recorded. The amount present was calculated by determining the net absorbance between the absorbance maximum at about 402 nm and one-half the sum of the absorbance of the minima at about 389 and 412 nm. Each collaborator received 4 creams (0.2%), 1 jel (0.2%), 1 molded suppository (6 mg/3.198 g), and 2 gelatin-encapsulated suppository samples (12 mg/6.661 g and 14 mg/6.863 g). The cream samples included blind duplicates prepared to contain 0.212% aminacrine hydrochloride, 15% sulfanilamide, and 2% allantoin. Mean recovery for the authentic cream was 104.7% with a coefficient of variation (CV) of 9.22%. The commercial products contained these respective amounts (CVs): creams, 100.0% (2.48%) and 101.5% (2.16%); jel, 118.0% (9.58%); molded suppository, 102.7% (1.88%); and gelatin encapsulated suppositories, 93.1% (1.0%) and 94.3% (1.60%). Standard aminacrine hydrochloride provided for the study was 99.6% pure by nonaqueous titration. Thin layer chromatographic identification of aminacrine hydrochloride was also tested collaboratively. The method was not adopted by AOAC. | Aminacrine |
Galactorrhea is the production of breast milk that is not the result of physiologic lactation. Milky nipple discharge within one year of pregnancy and the cessation of breastfeeding is usually physiologic. Galactorrhea is more often the result of hyperprolactinemia caused by medication use or pituitary microadenomas, and less often hypothyroidism, chronic renal failure, cirrhosis, pituitary macroadenomas, hypothalamic lesions, or unidentifiable causes. A pregnancy test should be obtained for premenopausal women who present with galactorrhea. In addition to prolactin and thyroid-stimulating hormone levels, renal function should also be assessed. Medications contributing to hyperprolactinemia should be discontinued if possible. Treatment of galactorrhea is not needed if prolactin and thyroid-stimulating hormone levels are normal and the discharge is not troublesome to the patient. Magnetic resonance imaging of the pituitary gland should be performed if the cause of hyperprolactinemia is unclear after a medication review and laboratory evaluation. Cabergoline is the preferred medication for treatment of hyperprolactinemia. Transsphenoidal surgery may be necessary if prolactin levels do not improve and symptoms persist despite high doses of cabergoline and in patients who cannot tolerate dopamine agonist therapy. | Cabergoline |
Genome-wide association studies have identified hundreds of genetic loci that are associated with immune-mediated diseases. Most disease-associated variants are non-coding, and a large proportion of these variants lie within enhancers. As a result, there is a pressing need to understand how common genetic variation might affect enhancer function and thereby contribute to immune-mediated (and other) diseases. In this Review, we first describe statistical and experimental methods to identify causal genetic variants that modulate gene expression, including statistical fine-mapping and massively parallel reporter assays. We then discuss approaches to characterise the mechanisms by which these variants modulate immune function, such as clustered regularly interspaced short palindromic repeats (CRISPR)-based screens. We highlight examples of studies that, by elucidating the effects of disease variants within enhancers, have provided important insights into immune function and uncovered key pathways of disease. | Inverted Repeat Sequences |
A mycolic acid-containing actinobacterium designated strain MMS17-SY073(T) was isolated from island soil. The isolate showed best growth at 25 degrees C, pH 6, and 0 % (w/v) NaCl. The phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MMS17-SY073(T) belongs to the genus Gordonia, and is mostly related to the type strains of Gordonia soli (98.5 % sequence similarity), Gordonia polyisoprenivorans (98.1%), and Gordonia hankookensis (97.8%). The genome-based comparisons showed a clear distinction between the strain and the two neighbouring species, G. soli and G. polyisoprenivorans, with the average nucleotide identities (ANI) of 75.8 and 76.3 %, respectively. Notably, the genome of strain MMS17-SY073(T) was the largest in total stretch and gene counts among the complete genomes of Gordonia, and contained a number of biosynthetic gene clusters for secondary metabolites, in particular those for non-ribosomal peptide synthetases. The major polar lipids were diphosphatidyl glycerol (DPG), phosphatidyl glycerol (PG), phosphatidyl ethanolamine (PE), phosphatidyl inositol (PI) and phosphatidyl inositol mannoside (PIM). The isoprenoid quinone was MK-9(H(2)), and the main fatty acids were C(16 : 0) (30.2%) and 10-methyl-C(18 : 0) (33.7%). The whole cell hydrolysates contained galactose, arabinose, and meso-diaminopimelic acid. The DNA G+C content was 67.4 mol%. Based on phenotypic, chemotaxonomic and genetic analysis, strain MMS17-SY073(T) should be classified as a new species of the genus Gordonia, for which the name Gordonia insulae sp. nov. is proposed (type strain=MMS17-SY073(T)=KCTC 49257(T)=JCM 33277(T)). | Gordonia Bacterium |
Nerium indicum is an India-Pakistan-originated shrub belonging to the oleander family. The ingestion of leaves of N. indicum before a meal is known to effect the lowering of postprandial glucose levels in Type II diabetic patients and this plant is now used as a folk remedy for Type II diabetes in some regions of Pakistan. In the present study, the hot-water extract of N. indicum leaves was found to reduce the postprandial rise in the blood glucose when maltose or sucrose was loaded in rats. It was also found that the extract strongly inhibited alpha-glucosidase, suggesting that the suppression of the postprandial rise in the blood glucose is due to the occurrence of some inhibitors of alpha-glucosidase in the leaves. We, therefore, tried to isolate the active principles from the leaf extract, using alpha-glucosidase-inhibitory activity as the index. Employing Sephadex G-15, silica gel and reversed-phase HPLC, we isolated two active compounds. The UV, mass and NMR spectrometric analyses established that the chemical structures of these compounds are 3-O-caffeoylquinic acid (chlorogenic acid) and its structural isomer, 5-O-caffeoylquinic acid. Both compounds were shown to inhibit alpha-glucosidases in a non-competitive manner. The authentic chlorogenic acid was found to suppress the postprandial rise in the blood glucose in rats and also inhibited the absorption of the glucose moiety from maltose and glucose in the everted gut sac system prepared from rat intestine. These results demonstrate that chlorogenic acid is one of the major anti-hyperglycemic principles present in the leaves of N. indicum. Furthermore, among polyphenol compounds tested, quercetin and catechins were shown to have strong inhibitory activity against alpha-glucosidase. | Nerium |
The rabbitfish Siganus canaliculatus is the first marine teleost shown to be able to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors catalyzed by two fatty acyl desaturases (fad) including Delta4 Fad and Delta6/Delta5 Fad as well as two elongases (Elovl4 and Elovl5). Previously, hepatocyte nuclear factor 4alpha (Hnf4alpha) was demonstrated to be predominant in the transcriptional regulation of two fads. To clarify the regulatory mechanisms involved in rabbitfish lipogenesis, the present study focused on the regulatory role of Hnf4alpha to elovl5 expression and LC-PUFA biosynthesis. Bioinformatics analysis predicted two potential Hnf4alpha elements in elovl5 promoter, one binding site was confirmed to interact with Hnf4alpha by gel shift assays. Moreover, overexpression of hnf4alpha caused a remarkable increase both in elovl5 promoter activity and mRNA contents, while knock-down of hnf4alpha in S. canaliculatus hepatocyte line (SCHL) resulted in a significant decrease of elovl5 gene expression. Meanwhile, hnf4alpha overexpression enhanced LC-PUFA biosynthesis in SCHL cell, and intraperitoneal injection to rabbitfish juveniles with Hnf4alpha agonists (Alverine and Benfluorex) increased the expression of hnf4alpha, elvol5 and Delta4 fad, coupled with an increased proportion of total LC-PUFA in liver. The results demonstrated that Hnf4alpha is involved in LC-PUFA biosynthesis by up-regulating the transcription of the elovl5 gene in rabbitfish, which is the first report of Hnf4alpha as a transcription factor of the elovl5 gene in vertebrates. | Hepatocyte Nuclear Factor 4 |
Zinc oxide nanoparticles (ZnO NPs) are promising candidates as animal diet additive. However, several studies have reported that ZnO NPs cause adverse effects on organisms. Hen egg yolk proteins play vital roles during embryonic development. Although we found ZnO NPs altered the function of the ovary and liver, the effects of ZnO NPs on egg yolk proteins are not as yet understood. In this report, egg yolk proteome was investigated after ZnO NPs treatment. A total of 37 proteins were specifically regulated just by ZnO-NP-50 mg/kg, and 22 proteins were changed solely by ZnSO(4)-50 mg/kg. Seventeen proteins were regulated by both ZnO-NP-50 mg/kg and ZnSO(4)-50 mg/kg treatments. Furthermore, the proteins changed by ZnO NPs or ZnSO(4) were enriched into different functional groups, respectively, by GO analysis and KEGG pathway enrichment. For the first time, this investigation reports that intact NPs produce a different impact on the egg yolk proteome compared to that of Zn(2+). The changes in protein levels by ZnO NPs in egg yolk might influence the value of egg yolk as nutrient and the embryonic development. | Egg Yolk |
OBJECTIVE: To explore how a student-run clinic (SRC) in primary health care (PHC) was perceived by students, patients and supervisors. DESIGN: A mixed methods study. Clinical learning environment, supervision and nurse teacher evaluation scale (CLES + T) assessed student satisfaction. Client satisfaction questionnaire-8 (CSQ-8) assessed patient satisfaction. Semi-structured interviews were conducted with supervisors. SETTING: Gustavsberg PHC Center, Stockholm County, Sweden. SUBJECTS: Students in medicine, nursing, physiotherapy, occupational therapy and psychology and their patients filled in questionnaires. Supervisors in medicine, nursing and physiotherapy were interviewed. MAIN OUTCOME MEASURES: Mean values and medians of CLES + T and CSQ-8 were calculated. Interviews were analyzed using content analysis. RESULTS: A majority of 199 out of 227 student respondents reported satisfaction with the pedagogical atmosphere and the supervisory relationship. Most of the 938 patient respondents reported satisfaction with the care given. Interviews with 35 supervisors showed that the organization of the SRC provided time and support to focus on the tutorial assignment. Also, the pedagogical role became more visible and targeted toward the student's individual needs. However, balancing the student's level of autonomy and the own control over care was described as a challenge. Many expressed the need for further pedagogical education. CONCLUSIONS: High student and patient satisfaction reported from five disciplines indicate that a SRC in PHC can be adapted for heterogeneous student groups. Supervisors experienced that the SRC facilitated and clarified their pedagogical role. Simultaneously their need for continuous pedagogical education was highlighted. The SRC model has the potential to enhance student-centered tuition in PHC. Key Points Knowledge of student-run clinics (SRCs) as learning environments within standard primary health care (PHC) is limited. We report experiences from the perspectives of students, their patients and supervisors, representing five healthcare disciplines. Students particularly valued the pedagogical atmosphere and the supervisory relationship. Patients expressed high satisfaction with the care provided. Supervisors expressed that the structure of the SRC supported the pedagogical assignment and facilitated student-centered tuition - simultaneously the altered learning environment highlighted the need for further pedagogical education. Student-run clinics in primary health care have great potential for student-regulated learning. | Student Run Clinic |
By the end of 1997, only 121 communities (59 percent) of the population in Massachusetts were receiving fluoridated water serving 3,523,615 people. Eleven communities, three of which are naturally fluoridated, are partially fluoridated communities. According to the 1992 Fluoridation Census. Massachusetts was ranked 35th in the nation by percentage of its population living in fluoridated communities. From 1968 to 1997, there were 135 fluoridation orders by 112 communities, of which 67 (49.6 percent) had binding referenda, with 30 (45 percent) winning and 37 (55 percent) losing the vote (one community had one order and two referenda due to a court decision). Eventually, 78 (58 percent) of the 135 orders resulted in fluoridation being implemented. The average length of time from the order of fluoridation to its implementation was seven years, with a range of less than one year to 29 years. From 1968 to 1977, there were 91 fluoridation orders as compared to only eight from 1988 to 1997. Fluoridation is still the most cost-effective preventive measure for dental disease and needs to be promoted once again in Massachusetts. | Fluoridation |
Canine glaucoma is a common cause of vision loss associated with raised intraocular pressure, and leads to damage of the retina and optic nerve head. In most cases, medical treatment alone cannot provide long-term management of intraocular pressure control and preservation of vision. Surgical intervention is usually recommended to either decrease aqueous humor production, or increase its outflow. Among the current available procedures, filtering techniques are aimed at increasing aqueous humor outflow. Proper surgical timing and a combination of cyclodestructive and filtering procedures have been recently suggested to improve the long-term success of surgical treatment in dogs. Bleb fibrosis and surgical failure are still common occurrences in filtration surgery with relapse of glaucoma and vision loss. End stage procedures, such as enucleation, evisceration with intrascleral prosthesis, and chemical ablation of the ciliary bodies are then recommended to address chronic discomfort in buphthalmic and blind eyes. | Glaucoma Drainage Implants |
The increase in population growth rate warrants the development of additional contraceptive methods that are widely acceptable, free from side effects and less expensive. Immunocontraception, and in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilization, offers an attractive approach to control fertility. The development of a contraceptive vaccine based on sperm antigen represents a promising approach to contraception. In mammals, fertilization is completed by the direct interaction of sperm and egg, a process mediated primarily by sperm surface proteins. Sperm have proteins that are unique, cell specific, immunogenic and accessible to antibodies. A few of the sperm specific proteins have been isolated and characterized. The antibodies raised against the sperm specific antigens have proved to be extremely effective at reducing sperm-egg interaction in vitro; fertility trials in sub-human primates would eventually prove the effectiveness of the sperm antigens in terms of contraceptive efficacy. | Contraception, Immunologic |
OBJECTIVE To evaluate the mRNA expression of T helper (Th)1, Th2, and Th17 cell-associated inflammatory mediators in cells of bronchoalveolar lavage fluid samples collected from healthy horses exposed to hyperbaric oxygen (HBO) and to monitor blood oxygen concentration during and following HBO therapy. ANIMALS 8 healthy horses. PROCEDURES In a randomized controlled crossover design study, each horse was exposed (beginning day 1) to 100% oxygen at a maximum of 3 atmospheres absolute (304 kPa) daily for 10 days or ambient air at atmospheric pressure in the HBO chamber for an equivalent amount of time (control). Bronchoalveolar lavage fluid samples were collected on days 0 and 10. After validation of candidate reference genes, relative mRNA expressions of various innate inflammatory, Th1 cell-derived, Th2 cell-derived (including eotaxin-2), Th17 cell-derived, and regulatory cytokines were measured by quantitative PCR assays. For 3 horses, arterial blood samples were collected for blood gas analysis during a separate HBO session. RESULTS The optimal combination of reference genes was glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine ribosyltransferase, and ribosomal protein L32. Compared with day 0 findings, expression of eotaxin-2 mRNA was significantly lower (0.12-fold reduction) and the percentage of neutrophils in bronchoalveolar lavage fluid samples was significantly lower on day 10 when horses received HBO therapy. Values of Pao2 rapidly increased (> 800 mm Hg) but immediately decreased to pretreatment values when HBO sessions ended. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HBO therapy does not increase mRNA expression of inflammatory cytokines, but reduces eotaxin-2 mRNA transcription. The Pao2 increase was transient with no cumulative effects of HBO. | Chemokine CCL24 |
INTRODUCTION: Prodromal symptoms commonly precede hereditary angioedema (HAE) attacks. There is continuing interest in evaluating prodromes as treatment indicators, but a paucity of relevant data. This study was designed to prospectively identify prodomal characteristics in patients voluntarily reporting such information around the time of seeking treatment for an acute HAE attack. METHODS: Twenty-eight patients with HAE were enrolled in this survey, which was conducted in the context of an open-label study of treatment of HAE attacks with plasma-derived C1-inhibitor concentrate. At the time of treatment, patients were encouraged to answer survey questions about prodromal symptoms preceding that particular HAE attack. RESULTS: Twenty-one patients provided prodromal information for 253 treated HAE attacks. Seventy-one percent of patients (15/21) reported prodromes. Three patients accounted for approximately 80% of the attacks and 89% of the reported prodromal symptoms. Prodromes were experienced before 67.6% (171/253) of attacks, with a mean of 1.4 prodromes per attack. Fatigue was the most frequent prodrome (42% of attacks), followed by nausea (26%), and flu-like symptoms (22%). The median duration of a prodrome before an attack was 12 h (range, 0.33-24 h). CONCLUSIONS: Despite many limitations in the study design, these findings confirm that prodromes are frequently associated with HAE attacks in many patients and occur sufficiently early to allow time for treatment initiation. The frequency of "false positive" prodromal symptoms remains undetermined, and the authors captured data only on attacks severe enough to warrant treatment. Additional well-designed prospective studies are clearly needed to continue investigating the potential clinical relevance of prodromes." | Hereditary Angioedema Types I and II |
Azospirillum brasilense is a plant growth promoting bacteria used as an inoculant in diverse crops. Accurate analytical methods are required to enumerate viable cells in inoculant formulations or in planta. We developed a quantitative polymerase chain reaction (qPCR) assay associated to propidium monoazide (PMA) to evaluate the cell viability of A. brasilense in inoculant and in maize roots. A. brasilense was grown in culture medium and was exposed to 50 âÂÂ. Maize roots were grown in vitro and harvested 7 days after inoculation. Quantification was performed by qPCR, PMA-qPCR, and plate counting. Standard curves efficiency values ranged from 85 to 99%. The limit of detection was 10(4) CFU per gram of fresh root. Enumeration obtained in maize roots by qPCR where higher than enumeration by PMA-qPCR and by plate counting. PMA-qPCR assay was efficient in quantifying inoculant viable cells and provides reliable results in a quickly and accurately way compared to culture-dependent methods. | Azospirillum brasilense |
BACKGROUND: Although fear of negative evaluation (FNE) has long been recognized as a core cognitive bias in social anxiety, fear of positive evaluation (FPE) has received considerable attention over the past several years. The literature would benefit from a synthesis of the current state of the research in order to contribute to our understanding of FPE. METHODS: A systematic review of the literature was conducted in order to address several questions: (a) Is self-reported FPE distinct from self-reported FNE? (b) Is self-reported FPE related to social anxiety symptomatology? and (c) Is self-reported FPE uniquely related to social anxiety symptomatology when accounting for self-reported FNE? Inclusion criteria included studies published in English, testing FPE and FNE with trait-based measures, and testing social anxiety with either self-report or diagnostic interviews. RESULTS: There were 33 studies identified in this review that provided convincing empirical support for each of these questions across community and clinical samples of adolescents, undergraduates, and adults. LIMITATIONS: The systematic review did not have access to null results, present meta-analytic results, or include studies that evaluated FPE or social anxiety with experimental designs. CONCLUSIONS: The findings from the systematic review support updated theoritical models of social anxiety and highlight the importance of assessing and treating FPE in clinical interventions. | Diagnostic Self Evaluation |
OBJECTIVE: To analyze peritoneal spillage and displacement of indocyanine green (ICG)-stained tissues from uterine cervix to pelvis during intracorporeal/vaginal colpotomy in laparoscopic-assisted hysterectomy. MATERIALS AND METHODS: Eleven patients undergoing laparoscopic-assisted hysterectomy were included. One patient with an incidental diagnosis of endometrial cancer was excluded. Of the 10 patients, five underwent intracorporeal colpotomy (IC) and five received vaginal colpotomy (VC) during laparoscopic-assisted hysterectomy. Approximately 5 cm of resected round ligament from each patient was stained with ICG and cut to 1.0 x 1.0 cm in size. Four to five fragments of ICG-stained tissues were placed and sutured on the uterine cervix before colpotomy. During and after colpotomy, serial pictures under white and fluorescence light were taken to document peritoneal spillage and displacement of ICG-stained tissues to the pelvic peritoneum. RESULTS: Peritoneal spillage of ICG occurred in the entire IC group. Displacement of ICG-stained tissues from uterine cervix to pelvic peritoneum were visualized in three (60%) patients undergoing IC. In the five patients who received VC, peritoneal spillage of ICG and displacement of ICG-stained tissue to pelvic peritoneum did not occur. There were no perioperative complications. CONCLUSIONS: IC in minimally invasive radical hysterectomy should not be performed because peritoneal spillage of ICG and displacement of ICG-stained tissues from uterine cervix to pelvis frequently occurs during IC. Therefore, specific measures to prevent tumor exposure during colpotomy should be implemented in cervical cancer patients. | Colpotomy |
Laboratory-confirmed influenza is a nationally notifiable disease in Australia. According to notification data, Queensland has experienced more severe influenza seasons than other states and territories. However, this method ignores available denominator data: the number of laboratory tests performed. We propose that negative results of laboratory tests for influenza should be made notifiable, alongside laboratory-confirmed disease, and used to calculate the proportion of positive test results in real-time. Using data from the public health pathology services of three Australian states - Queensland Health laboratories, the Victorian Infectious Diseases Reference Laboratory and Western Australia's PathWest - for 2004 to 2008, we show that incorporating laboratory-negative test data into national surveillance data would add to and improve our understanding of influenza epidemiology. | Disease Notification |
Ligands such as enzyme inhibitors stabilize the native conformation of a protein upon binding to the native state, but some compounds destabilize the native conformation upon binding to the non-native state. The former ligands are termed "stabilizer chaperones" and the latter ones "destabilizer chaperones." Because the stabilization effects are essential for the medical chaperone (MC) hypothesis, here we have formulated a thermodynamic system consisting of a ligand and a protein in its native- and non-native state. Using the differential scanning fluorimetry and the circular dichroism varying the urea concentration and temperature, we found that when the coenzyme NADP(+) was absent, inhibitors such as isolithocholic acid stabilized the aldo-keto reductase AKR1A1 upon binding, which showed actually the three-state folding, but destabilized AKR1B10. In contrast, in the presence of NADP(+) , they destabilized AKR1A1 and stabilized AKR1B10. To explain these phenomena, we decomposed the free energy of stabilization (DeltaDeltaG) into its enthalpy (DeltaDeltaH) and entropy (DeltaDeltaS) components. Then we found that in a relatively unstable protein showing the three-state folding, native conformation was stabilized by the negative DeltaDeltaH in association with the negative DeltaDeltaS, suggesting that the stabilizer chaperon decreases the conformational fluctuation of the target protein or increase its hydration. However, in other cases, DeltaDeltaG was essentially determined by the delicate balance between DeltaDeltaH and DeltaDeltaS. The proposed thermodynamic formalism is applicable to the system including multiple ligands with allosteric interactions. These findings would promote the development of screening strategies for MCs to regulate the target conformations." | NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases |
This study assessed the test-retest reliability of air plethysmographic parameters for the evaluation of arterial and venous function of the lower extremity in normal, healthy adults. Fourteen voluntary subjects underwent air plethysmographic tests on two occasions, 1-2 weeks apart, with three tests being performed at each visit. Test-retest reliability was assessed via correlation coefficients and the intraclass correlations. Differences in the parameters of arterial inflow (AI), venous volume (VV), venous refilling time (VFT), venous refilling index (VFI), ejection volume (EV) and residual fraction (EF) obtained on the two separate occasions were small (r = 0.81 approximately 0.95; ICC = 0.94 approximately 0.99), whereas differences in ejection fraction (EF), residual volume (RV) and venous outflow (OF) measurements were much larger (r = 0.50 approximately 0.61; ICC = 0.58 approximately 0.95). The findings demonstrate that evaluation of blood flow in the lower limbs of healthy individuals using air plethysmography is reliable in test-retest measures, suggesting that this technique represents a sensitive method for quantifying changes in parameters of arterial and venous functions of the lower extremity. | Plethysmography |
AIM: To assess the effect of cerumen impaction and its removal on hearing ability and cognitive function in elderly patients with memory disorders in Japan. METHODS: Pure tone audiometry (PTA) and the Mini-Mental State Examination (MMSE) were administered to participants before and after cerumen removal. Participants who had cerumen impaction in the better-hearing ear comprised the case group; the control group consisted of participants who either did not have cerumen impaction or had it in the worse hearing ear. Hearing and cognition changes were compared between the groups after cerumen removal. RESULTS: A total of 55 patients who completed all examinations were assigned to the case group (29 patients) or the control group (26 patients). The average hearing change was 4.6 +/- 7.4 in the case group and 0.9 +/- 0.9 in the control group (P = 0.029). The average change in MMSE score was 0.7 +/- 2.5 in the case group and -1.0 +/- 4.1 in the control group (P = 0.068). The case group showed a significant improvement in MMSE scores after age adjustment compared with the control group (P = 0.049). CONCLUSION: Hearing improved significantly in the case group relative to controls after cerumen removal. A significant cognitive improvement in the case group relative to controls was additionally observed after cerumen removal with age adjustment. Thus, the present results suggest routine ear canal examinations might benefit elderly individuals with memory disorders. | Cerumenolytic Agents |
INTRODUCTION: We sought to determine the surgical outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) enrolled in the European Congenital Heart Surgeons Association (ECHSA) database. MATERIALS AND METHODS: From 1999 to 2019, 907 patients with ALCAPA underwent surgical repair and were included in the current study. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and results of concomitant mitral valve surgery and postoperative mechanical circulatory support (MCS). RESULTS: The overall in-hospital mortality was 6% (54/907) and was significantly higher in neonates (p = .01), patients with lower body surface area (BSA) (p = .01), and those requiring postoperative MCS (p = .001). Associated mitral valve surgery was performed in 144 patients (15.9%) and was associated with longer cardiopulmonary bypass (CPB) and aortic cross-clamp times (AOX) (p </= .0001) but was not significantly related to an increase in in-hospital mortality. Postoperative MCS was required in 66 patients (7.3%). These patients were younger (p </= .001), had a lower BSA (p </= .001), and required a longer CPB (p </= .001) and AOX time (p </= .001). CONCLUSIONS: ALCAPA repair can be achieved successfully, and with low surgical risk. Concomitant mitral valve procedures can be performed without increasing operative mortality. The use of MCS remains a valuable option, especially in younger patients." | Anomalous Left Coronary Artery |
Non-natural terpenoids offer potential as pharmaceuticals and agrochemicals. However, their chemical syntheses are often long, complex, and not easily amenable to large-scale production. Herein, we report a modular chemoenzymatic approach to synthesize terpene analogues from diphosphorylated precursors produced in quantitative yields. Through the addition of prenyl transferases, farnesyl diphosphates, (2E,6E)-FDP and (2Z,6Z)-FDP, were isolated in greater than 80 % yields. The synthesis of 14,15-dimethyl-FDP, 12-methyl-FDP, 12-hydroxy-FDP, homo-FDP, and 15-methyl-FDP was also achieved. These modified diphosphates were used with terpene synthases to produce the unnatural sesquiterpenoid semiochemicals (S)-14,15-dimethylgermacrene D and (S)-12-methylgermacrene D as well as dihydroartemisinic aldehyde. This approach is applicable to the synthesis of many non-natural terpenoids, offering a scalable route free from repeated chain extensions and capricious chemical phosphorylation reactions. | Dimethylallyltranstransferase |
This study evaluates the efficacy of autologous fat injection for medialization of the paralyzed vocal fold. In 21 patients with unilateral vocal fold paralysis, autologous abdominal fat was injected into the thyroarytenoid muscle to achieve medialization. All patients were followed up with serial videolaryngoscopy and voice evaluation. At 2 months' follow-up, the voice was judged to be excellent in 10 patients, slightly breathy but significantly better than the preoperative voice in 6 patients, and markedly breathy in 4 patients. At 3 to 4 months' follow-up, of the 10 patients with excellent results, 5 maintained an excellent voice, 3 had developed slight breathiness, and 1 had developed severe breathiness. Long-term (6 to 12 months) results were available in 11 patients, and all of them maintained the same voice quality that was noted during the 3 to 4 months' examination. Magnetic resonance imaging of the larynx was obtained in 7 patients at intervals ranging from 1 to 7 months and compared to the baseline scan obtained at 1 week postoperative to assess the amount of fat remaining in the muscle. The images showed fat volume to persist, but a decrease in the fat signal was observed over time. The results suggest that the duration of medialization with autologous fat is variable, but appears to last at least 2 to 3 months. This loss of volume after 3 months seems to be due to absorption of the fat and possibly muscle atrophy. Autologous fat injection is relatively safe and easy to perform, and is an ideal method of temporary vocal fold medialization in patients in whom return of vocal fold function is expected. | Vagus Nerve Diseases |
The aim of hemodynamic monitoring in intensive care is to recognize derangements in physiologic variables, which herald the progression toward organ failure. Traditionally the term vital signs" refers to heart rate, arterial pressure, respiratory rate and body temperature monitoring. Continuous monitoring of vital signs, is advocated, since trends are more significant than single measurements, and is still a cornerstone, in the hemodynamic evaluation of a critically ill patient. Nevertheless, the spectrum of hemodynamic derangements that can arise during intensive care unit stay is very large and often additional information, beside the vital signs, are needed to evaluate correctly the individual patient." | Central Venous Pressure |
BACKGROUND: There are no efficacious pharmacotherapies for cannabis dependence. The effects of quetiapine are well matched to the symptoms of cannabis withdrawal and could be useful in the treatment of cannabis dependence. OBJECTIVES: To evaluate quetiapine for the treatment of cannabis dependence and determine the optimal dosing. METHODS: In an eight-week open-label outpatient pilot trial, we evaluated the feasibility of quetiapine treatment for cannabis dependence in 15 outpatients. Quetiapine was gradually titrated to 600 mg or the maximum tolerated dose. RESULTS: The mean study retention was 6.5 weeks (+/-2.3), with 67% of participants completing all eight weeks of the trial. The mean maximum dose achieved was 197 mg/day (range: 25-600 mg/day). Only two of the 15 participants were able to achieve the target dose of 600 mg daily. There were no serious adverse events and no participants were discontinued from the trial due to adverse effects. The most common reported adverse effects were fatigue (80% of participants) and somnolence (47%). From baseline to week 8, the modeled overall decrease in daily dollar value of marijuana was 76.3% (CI: 63.4%, 84.7%). Over the eight weeks of the study, there was a 46.9% (CI: 11%, 68.3%) decrease in urine tetrahydrocannabinol-9-carboxylic acid (THCOOH) levels. CONCLUSIONS: These preliminary results are promising in that quetiapine treatment was tolerated by cannabis-dependent patients and associated with decreased cannabis use. The recommended maximum target dose for cannabis-dependent patients is 300 mg daily. These preliminary data support further evaluation of quetiapine as a treatment for cannabis dependence. | Thiepins |
BACKGROUND: Peripheral T-cell lymphomas (PTCL) account for about 10% of all lymphomas in Western countries. The aim of the present study is to analyze the initial characteristics and prognostic factors in a large series of PTCL patients. PATIENTS AND METHODS: 174 patients (105 male/69 female; median age 61 years) were diagnosed with PTCL according to the R.E.A.L. Classification in nine Spanish institutions between 1985 and 1996. Cutaneous lymphomas and T-cell chronic lymphocytic/prolymphocytic leukemia were excluded from the study. Univariate and multivariate analyses were used to assess the prognostic value of the main initial variables. RESULTS: The distribution according to histology subgroup was: PTCL unspecified, 95 cases (54.4%); anaplastic large-cell Ki-l-positive (ALCL), 30 cases (17%); angioimmunoblastic T cell, 22 cases (13%); angiocentric, 14 cases (8%); intestinal T cell, 12 cases (7%), and hepatosplenic gamma delta T cell, one case (0.6%). As compared to the other types, ALCL presented more frequently in ambulatory performance status, without extranodal involvement, in early stage, normal serum beta 2-microglobulin (B2M) level and low-risk international prognostic index (IPI). Most patients were treated with adriamycin-containing regimens. The overall CR rate was 49% (69% for ALCL vs. 45% for other PTCL; P < 0.02). The risk of relapse was 48% at four years. Median survival of the series was 22 months (65 months for ALCL vs. 20 months for other PTCL; P = 0.03), with a four-year probability of survival of 38% (95% confidence intervals (95% CI): 28-48). In the univariate analysis, in addition to the histology, older age, poor performance status, presence of B-symptoms, extranodal involvement, bone marrow infiltration, advanced Ann Arbor stage, high serum LDH, high serum B2M, and intermediate- or high-risk IPI were related to poor survival. In the multivariate analysis the histologic subgroup (ALCL vs. other PTCL) (P = 0.02; response rate (RR): 4.3), the presence of B-symptoms (P = 0.02, RR: 2.2), and the IPI (low vs. high) (P = 0.04, RR: 2) maintained independent predictive value. When the analysis was restricted to the unspecified subtype, only IPI had independent prognostic value (P = 0.003; RR: 3.5). CONCLUSIONS: PTCL have adverse prognostic features at diagnosis, respond poorly to therapy and have short survival, with no sustained remission. ALCL constitutes a subgroup which responds better to therapy and has a longer survival. | Lymphoma, T-Cell, Peripheral |
BACKGROUND: Idiopathic mast cell activation syndrome (MCAS) is one of the causes for recurrent complaints. The diagnosis is sometimes delayed but also often made incorrectly. CASE: Our patient presented with recurrent attacks of itching, redness of the skin, diarrhea and near collapse. During an attack his serum tryptase level rose significantly. We could not identify an underlying trigger. A diagnosis of idiopathic mast cell activation syndrome was made. He was successfully treated with a combination of H1 and H2 blockade. CONCLUSION: MCAS is characterized by recurrent complaints. To make the diagnosis a significant rise in mast cell mediators is required. Given the diversity of symptoms many patients with somatically unexplained symptoms wrongfully believe to be suffering from MCAS. | Mast Cell Activation Syndrome |
Most women experience changes surrounding the start of menstruation. These changes are influenced by sociocultural context. Consequently, certain changes are more pronounced in some cultures than in others. Girls enter menarche with a clear set of paramenstrual expectations that may alter their menstrual cycle-related experiences when they become postmenarcheal. This study explored expectations concerning the paramenstrual changes of 1,173 premenarcheal girls living in rural and urban areas of Mexico. In accordance with the findings of studies conducted in other countries, Mexican premenarcheal girls associate menstruation with a set of mostly negative expectations. A comparison of the results from urban and rural girls revealed that urban girls expected negative paramenstrual changes more, while rural ones expected positive changes more. These differences suggest that the cultures in which girls are brought up have an impact on their expectations. Urban girls are more exposed to media which present a picture of menses as a debilitating event, while rural girls link menses with health because it is associated with the ability to have children. | Menstruation |
The aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV. Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t(1/2ÃÂz) , Cl(T) , and V(dss) were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C(max(obs)) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 mug/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route. | Injections, Intramuscular |
The financing of long-term care is one of the largest and most vexing health care problems facing our society. The problem will be further exacerbated when the rate of growth in the number of persons needing long-term care is further accelerated by the graying of those in the baby boom" generation. The current financing mechanism, which relies almost entirely on concurrent funding through either a means tested welfare program (Medicaid) or self-pay, is inequitable and inadequate even for our present needs. Despite the magnitude of the problem, only recently has sufficient attention been focused on finding alternatives to the current means of financing long-term care. The search for a solution has been hampered by multiple, and sometimes conflicting, policy and political considerations. After reviewing the demographic and social roots of our current dilemma and listing the major alternatives for financing long-term care, a series of basic principles and definitions are reviewed. These elements are meant to serve as guidelines to compare and evaluate the growing number of proposals which seek to create a more effective and equitable system for financing long-term care. Future articles in this section will detail some of the more promising approaches to the dilemma of financing long-term care." | Long-Term Care |
Other authors have demonstrated earlier that cells of normal synovium contain metallothionein. The protein was also detected in several other normal cell types and in tumors derived from the cells. Metallothionein content is thought to reflect proliferative activity of neoplastic cells. Therefore, it was decided to demonstrate metallothionein expression in various types of synovial sarcoma. The present study aimed to determine metallothionein cellular expression by immunocytochemical techniques in nine cases of biphasic, six cases of monophasic (spindle cell), and five cases of poorly differentiated synovial sarcoma, and to compare the expression with those of vimentin and cytokeratin 19. Metallothionein expression was demonstrated in epithelioid cells in all cases of biphasic type sarcoma and in spindle cells in all cases of monophasic type tumors. In poorly differentiated tumors, metallothionein expression was detected in four of five cases (80%). Expression of cytokeratin 19 was typical for epithelioid cells and expression of vimentin for spindle cells of synovial sarcoma. A much less pronounced expression of the proteins was observed in poorly differentiated tumors. The results indicate that metallothionein expression may prove useful in differential diagnosis and for defining prognosis in cases of synovial sarcomas. | Sarcoma, Synovial |
Highly fluorescent rhodamine/rosamine analogues 2 were prepared from ketone 1. | Rhodamines |
Although very rare, red-cell immunization is a main factor of hemolytic fetal anemia and severe neonatal jaundice. We emphasize on the prevention of immunization in different situations of feto maternal bleeding by early intravenous injection of 200 at 300 IU or more depending on the term of pregnancy, the circumstances and results of the Kleihauer's test. Prophylaxis corresponds a systematic intramuscular injection of 300 IU immunoglobulin (Natead ) at 28 WA, is performed in many countries. This measure implies information and rigor from Perinatal's professional. If this systematic prophylaxis was conducted, it is not necessary to repeat the IAR until the birth. But if the patient has not received the injection of 28 WA, IAR of the 8th month must be maintained. | Rh Isoimmunization |
With the number of outpatient cardiac catheterizations increasing, much attention has recently been focused on the use of 5 French catheters for cardiac catheterization and selective coronary angiography. However, there are few reports in the literature regarding the technical aspects of their use or the quality of cineangiograms obtained. We reviewed our experience with these catheters in our first 100 consecutive cases. All cineangiograms were diagnostic, though 9% were deemed only of fair quality (incomplete luminal filling in some frames) by two experienced observers. Technical problems encountered with the use of these catheters included instability of the right Judkin's catheter in the right coronary ostium owing to high torquability, streaming of contrast during left coronary injections, and difficulty entering the left ventricle with a pig-tail catheter. | Cineangiography |
Butyric acid fermentation by Clostridium couples with the synthesis of acetic acid. But the presence of acetic acid reduces butyric acid yield and increases separation and purification costs of butyric acid. Hence, enhancing the butyrate/acetate ratio is important for economical butyric acid production. This study indicated that enhancing the acetyl-CoA to butyrate flux by overexpression of both the butyryl-CoA/acetate CoA transferase (cat1) and crotonase (crt) genes in C. tyrobutyricum could significantly reduce acetic acid concentration. Fed-batch fermentation of ATCC 25755/cat1 + crt resulted in increased butyrate/acetate ratio of 15.76 g/g, which was 2.24-fold higher than that of the wild-type strain. Furthermore, in order to simultaneously increase the butyrate/acetate ratio, butyric acid concentration and productivity, the recombinant strain ATCC 25755/ppcc (co-expression of 6-phosphofructokinase (pfkA) gene, pyruvate kinase (pykA) gene, cat1, and crt) was constructed. Consequently, ATCC 25755/ppcc produced more butyric acid (46.8 vs. 35.0 g/L) with a higher productivity (0.83 vs. 0.49 g/L.h) and butyrate/acetate ratio (13.22 vs. 7.22 g/g) as compared with the wild-type strain in batch fermentation using high glucose concentration (120 g/L). This study demonstrates that enhancing the acetyl-CoA to butyrate flux is an effective way to reduce acetic acid production and increase butyrate/acetate ratio. | Clostridium tyrobutyricum |
Four population dynamics models, namely Verhulst, Gompertz, Rosenzweig, and Svirezhev ones, have been used to approximate two well-known time-series of Paramecia aurelia and P. caudatum population size (Gause, 1934). The parameters are estimated for each of the models by the least-square method (with global fitting) in two different ways: with and without an additional upper bound for a parameter value. In the latter (traditional) case, when the deviations of theoretical (model) trajectories from experimental time-series have been tested for normality (Kolmogorov-Smirnov test, Shapiro-Wilk test) with zero average, and for the presence/absence of serial correlations (Durbin-Watson criteria), the best results are obtained for the Gompertz and Verhulst models. In the former, more realistic, case (when we impose an additional constraint that the parameter meaning the carrying capacity of the environment has to be greater than any element in the sample), the best results are observed for the Gompertz model. Under this constraint, the canonical technique for deviation analysis can be applied in a restricted version only. | Paramecium caudatum |
The mechanisms underlying preferential atrophy of the striatum in Huntington's disease (HD) are unknown. One hypothesis is that a set of gene products preferentially expressed in the striatum could determine the particular vulnerability of this brain region to mutant huntingtin (mHtt). Here, we studied the striatal protein micro-crystallin (Crym). Crym is the NADPH-dependent p38 cytosolic T3-binding protein (p38CTBP), a key regulator of thyroid hormone (TH) T3 (3,5,3'-triiodo-l-thyronine) transportation. It has been also recently identified as the enzyme that reduces the sulfur-containing cyclic ketimines, which are potential neurotransmitters. Here, we confirm the preferential expression of the Crym protein in the rodent and macaque striatum. Crym expression was found to be higher in the macaque caudate than in the putamen. Expression of Crym was reduced in the BACHD and Knock-in 140CAG mouse models of HD before onset of striatal atrophy. We show that overexpression of Crym in striatal medium-size spiny neurons using a lentiviral-based strategy in mice is neuroprotective against the neurotoxicity of an N-terminal fragment of mHtt in vivo. Thus, reduction of Crym expression in HD could render striatal neurons more susceptible to mHtt suggesting that Crym may be a key determinant of the vulnerability of the striatum. In addition our work points to Crym as a potential molecular link between striatal degeneration and the THs deregulation reported in HD patients. | mu-Crystallins |
Factors affecting the outcome of endodontic treatment are discussed from the theoretical viewpoint (microbes, foreign bodies and epithelium) and from a clinical aspect (preoperative factors, intraoperative factors and miscellaneous factors). The following conditions favour endodontic success significantly: the absence of a periapical infection, a well-condensed root filling, the root filling extending to 2 mm within the radiographic apex and not beyond, a satisfactory coronal restoration, use of a rubber dam during treatment and cases involving primary root canal treatment as opposed to retreatment. Other factors have the potential to affect success rates, but these have not yet been quantified. Although there is an array of potential factors that influence the outcome of endodontic treatment, success is most significantly dependent upon the elimination of root canal infection present when treatment starts and the prevention of contamination during treatment. | Treatment Failure |
The black-and-white traits on shells and mantle edges of the Pacific oyster, Crassostrea gigas, are inheritable and correlated, and black shells (melanin pigmentation) are usually found in the Pacific oysters. Based on differentially expressed genes from RNA-Seq and physiological characteristics, in this study, Black-shelled Pacific oysters (BSO) and White-shelled Pacific oysters (WSO) were selected to determine the molecular differences between oysters with obviously different melanin content. The differences in the process of immune recognition and modulation indicated that BSO may be more sensitive to the immune substances. There might have different modulation mode of apoptosis and phagocytosis between BSO and WSO, and caspase-3 might have played a key role in the apoptotic process of BSO. Different oxidation-related pathways were enriched in both BSO and WSO, suggesting the different response strategies of BSO and WSO to oxidative stress. The physiological evidences showed that, compared with WSO, in BSO, the tyrosinase content, the caspase-3 activity and the suppression of hydroxyl radical increased, and the reactive oxygen species concentration decreased. Therefore, immune-related molecular and physiological differences were found between BSO and WSO. | Crassostrea |
Gait analysis is necessary to diagnose movement disorders. In order to reduce the costs of three-dimensional motion capture systems, new low-cost methods of motion analysis have been developed. The purpose of this study was to evaluate the inter- and intra-rater reliability of Kinovea((R)) and the agreement with a three-dimensional motion system for detecting the joint angles of the hip, knee and ankle during the initial contact phase of walking. Fifty healthy subjects participated in this study. All participants were examined twice with a one-week interval between the two appointments. The motion data were recorded using the VICON Motion System((R)) and digital video cameras. The intra-rater reliability showed a good correlation for the hip, the knee and the ankle joints (Intraclass Correlation Coefficient, ICC > 0.85) for both observers. The ICC for the inter-rater reliability was >0.90 for the hip, the knee and the ankle joints. The Bland-Altman plots showed that the magnitude of disagreement was approximately +/-5 degrees for intra-rater reliability, +/-2.5 degrees for inter-rater reliability and around +/-2.5 degrees to +/-5 degrees for Kinovea((R)) versus Vicon((R)). The ICC was good for the hip, knee and ankle angles registered with Kinovea((R)) during the initial contact of walking for both observers (intra-rater reliability) and higher for the agreement between observers (inter-rater reliability). However, the Bland-Altman plots showed disagreement between observers, measurements and systems (Kinovea((R)) vs. three-dimensional motion system) that should be considered in the interpretation of clinical evaluations." | Physical Functional Performance |
Loss of the INK4a/ARF/INK4b locus on chromosome 9p21 is among the most frequent cytogenetic events in human cancer. The products of the locus--p15(INK4b), p16(INK4a), and ARF--play widespread and independent roles in tumor suppression. Recent data also suggest that expression of p16(INK4a) induces an age-dependent decrease in the proliferative capacity of certain tissue-specific stem cells and unipotent progenitors. Here, we discuss the regulation and role of p16(INK4a), ARF, and p15(INK4b) in cancer and aging." | Cyclin-Dependent Kinase Inhibitor Proteins |
This article discusses some issues related to Brazilian dental researches having the bioethics as the rationale for appraising the adequacy of the scientific production in relation to the social context, aiming to contribute to a shift of the professional health formation. From a search in journals database and CAPES ranking instrument (Qualis) it was observed that most journals are aimed to publish dental materials and techniques of limited social range. This result reflects a trend of the scientific knowledge in this field to focus the market rather than national and regional needs which should be the priority under the bioethical point of view. The lack of room available for publication of researches of Preventive and Social Dentistry and relative areas is an invitation to reflect about a scientific production capable to construct an ethical and socially compromised professional training. | Bioethical Issues |
The present study was done to determine the long-term success and survival of fixed partial dentures (FPDs) and to evaluate the risks for failures due to specific biological and technical complications. A MEDLINE search (PubMed) from 1966 up to March 2004 was conducted, as well as hand searching of bibliographies from relevant articles. Nineteen studies from an initial yield of 3658 titles were finally selected and data were extracted independently by three reviewers. Prospective and retrospective cohort studies with a mean follow-up time of at least 5 years in which patients had been examined clinically at the follow-up visits were included in the meta-analysis. Publications only based on patients records, questionnaires or interviews were excluded. Survival of the FPDs was analyzed according to in situ and intact failure risks. Specific biological and technical complications such as caries, loss of vitality and periodontal disease recurrence as well as loss of retention, loss of vitality, tooth and material fractures were also analyzed. The 10-year probability of survival for fixed partial dentures was 89.1% (95% confidence interval (CI): 81-93.8%) while the probability of success was 71.1% (95% CI: 47.7-85.2%). The 10-year risk for caries and periodontitis leading to FPD loss was 2.6% and 0.7%, respectively. The 10-year risk for loss of retention was 6.4%, for abutment fracture 2.1% and for material fractures 3.2%. | Denture, Partial, Fixed |
The development of a skilled research workforce in aging is fundamental to understanding conditions associated with growing older and extending healthy, active years of life. The National Institutes of Health (NIH) supports the training of health scientists, and its National Institute on Aging (NIA) prioritizes the professional development of investigators with an interest in aging. Since 1987, NIA's Summer Institute on Aging Research, renamed the Butler-Williams (B-W) Scholars Program in 2013, has offered an intensive one-week experience on issues, opportunities, and challenges of research on aging, with emphasis on disparities and health equity. The first 30 years of the Program are described in this report, including its history, selected curriculum highlights, Scholar outcomes, and qualitative data from faculty, and the program's impact on the training, growth, and development of scientists in aging research. Questions raised over a decade ago by the Committee on the Future Health Care Workforce for Older Americans Board on Health Care Services are revisited, and recommendations for the future are provided. This important Program remains an exemplar for the training and development of health scientists for careers that advance biomedical research and emphasize an equitable understanding of factors related to extending healthy years of life." | National Institute on Aging (U.S.) |
Dental anxiety can be a hindrance to treatment. It is prevalent, so helping patients to overcome it should not be regarded as the province of a specialist. Hypnosis can be effective but is underused. A comparison of the conscious, alert state and hypnosis/nitrous oxide sedation is shown by electroencephalogram examples. The benefits and drawbacks of the use of hypnosis are discussed and suggestions of ways of learning and using hypnosis outlined. CLINICAL RELEVANCE: This paper is an overview of the common problem of dental anxiety and a pragmatic approach to overcoming it using hypnotherapy. | Hypnosis, Anesthetic |
In order to evaluate the composition of active constituents in phytopharmaceutical preparations, valid analytical methods are required. For the determination of the active terpene constituents of Ginkgo biloba (the ginkgolides and bilobalide), a liquid chromatography-mass spectrometry (LC-MS) method has been developed using atmospheric pressure chemical ionisation (APCI) in the negative ion mode. This detection mode was found to be much more sensitive and selective compared to UV; indeed the ginkgo terpene trilactones lack strong UV chromophores and flavonoids interfere with their UV detection. LC-APCI/MS detection allowed a considerable reduction in analysis time when compared to LC-UV, because LC resolution was only needed between the pair of isomers ginkgolide B and ginkgolide J. All compounds were selectively detected by single ion monitoring of their specific deprotonated molecules [M-H]-. The samples were directly injected without pre-purification, and a fast gradient was applied, reducing the total time of analysis to 14 min. With this method, the ginkgo terpene trilactones were detected on-line in the picogram range. Several commercial ginkgo preparations on the Swiss market were analysed, and the ginkgolide and bilobalide contents were evaluated using the method described. | Ginkgolides |
MAGE (melibiose-derived advanced glycation end-product) is the glycation product generated in the reaction of a model protein with melibiose. The in vivo analog accumulates in several tissues; however, its origin still needs explanation. In vitro MAGE is efficiently generated under dry conditions in contrast to the reaction carried in an aqueous solvent. Using liquid chromatography coupled with mass spectrometry, we analyzed the physicochemical properties and structures of myoglobin glycated with melibiose under different conditions. The targeted peptide analysis identified structurally different AGEs, including crosslinking and non-crosslinking modifications associated with lysine, arginine, and histidine residues. Glycation in a dry state was more efficient in the formation of structures containing an intact melibiose moiety (21.9%) compared to glycation under aqueous conditions (15.6%). The difference was reflected in characteristic fluorescence that results from protein structural changes and impact on a heme group of the model myoglobin protein. Finally, our results suggest that the formation of in vitro MAGE adduct is initiated by coupling melibiose to a model myoglobin protein. It is confirmed by the identification of intact melibiose moieties. The intermediate glycation product can further rearrange towards more advanced structures, including cross-links. This process can contribute to a pool of AGEs accumulating locally in vivo and affecting tissue biology. | Melibiose |
OBJECTIVE: To evaluate the effects of intranasal benzodiazepines (midazolam and diazepam), alpha(2)-agonists (xylazine and detomidine) and their antagonists (flumazenil and yohimbine) in canaries. STUDY DESIGN: Prospective randomized study. ANIMALS: Twenty-six healthy adult domesticated canaries of both sexes, weighing 18.3 +/- 1.0 g. METHODS: In Study 1 an attempt was made to determine the dose of each drug that allowed treated canaries to be laid in dorsal recumbency for at least 5 minutes, i.e. its effective dose. This involved the evaluation of various doses, during which equal volumes of the tested drug were administered slowly into each nostril. In study 2 the onset of action, duration and quality of sedation induced by each drug at its effective dose were evaluated. The efficacy of flumazenil and yohimbine in antagonizing the effects of the sedative drugs was also studied. RESULTS: In study 1 administration of 25 microL per nostril diazepam (5 mg mL(-1) solution) or midazolam (5 mg mL(-1) solution) to each bird caused adequate sedation within 1-2 minutes; birds did not move when placed in dorsal recumbency. After administration of 12 microL per nostril of either xylazine (20 mg mL(-1)) or detomidine (10 mg mL(-1)), birds seemed heavily sedated and assumed sternal recumbency but could not be placed in dorsal recumbency. Higher doses of xylazine (0.5 mg per nostril) or detomidine (0.25 mg per nostril) prolonged sedation but did not produce dorsal recumbency. In study 2 in all treatment groups, onset of action was rapid. Duration of dorsal recumbency was significantly longer (p < 0.05) with diazepam (38.4 +/- 10.5 minutes) than midazolam (17.1 +/- 2.2 minutes). Intranasal flumazenil (2.5 microg per nostril) significantly reduced recumbency time. Duration of sedation was longer with alpha(2)-agonists compared with benzodiazepines. Detomidine had the longest duration of effect (257.5 +/- 1.5 minutes) and midazolam the shortest (36.9 +/- 2.4 minutes). Nasally administered flumazenil significantly reduced the duration of sedation with diazepam and midazolam while yohimbine (120 microg per nostril) effectively antagonized the effects of xylazine and detomidine. CONCLUSION: Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries. | Canaries |
Three novel 14-membered cyclopeptide alkaloids, justicianenes B-D (1-3), were isolated from the EtOH extract of the whole plant of Justicia procumbens L., and their structures were determined on the basis of detailed NMR spectroscopic data and the absolute stereochemistry of the ring-bonded alpha-amino acids in the cyclopeptide alkaloids were determined by ECD spectra. The isolated compounds were evaluated for their in vitro cytotoxicity against human cancer cell lines, including brest cancer MCF-7, cervix carcinoma HeLa, lung cancer A549 and H460, and diphyllin (14) showed moderate cytotoxicity against the HeLa, A549 and H460 cells with IC(50) of 9.13, 23.12, 42.34 microM, respectively, justicianene D showed weak cytotoxicity against the MCF-7 cell with inhibition rate of 50% at the concentration of 90 microM. | Justicia |
OBJECTIVES: To validate and compare four tools, the Fracture Risk Assessment Tool (FRAX) without bone mineral density (BMD), Beijing Friendship Hospital Osteoporosis Screening Tool (BFH-OST), Osteoporosis Self-Assessment Tool for Asians (OSTA), and BMD, to identify painful new osteoporotic vertebral fractures (PNOVFs). METHODS: A total of 2874 postmenopausal women treated from June 2013 to June 2022 were enrolled and divided into two groups: patients with PNOVFs who underwent percutaneous vertebroplasty (PNOVFs group, n = 644) and community-enrolled females (control group, n = 2230). Magnetic resonance and X-ray imaging were used to confirm the presence of PNOVFs. Dual-energy X-ray absorptiometry was performed to calculate the BMD T-scores. Osteoporosis was diagnosed according to WHO Health Organization criteria. Data on the clinical and demographic risk factors were self-reported using a questionnaire. The ability to identify PNOVFs using FRAX, BFH-OST, OSTA, and BMD scores was evaluated using receiver operating characteristic (ROC) curves. For this evaluation, we calculated the areas under the ROC curves (AUCs), sensitivity, specificity, and optimal cut-off points. RESULTS: There were significant differences in FRAX (without BMD), BFH-OST, OSTA, and BMD T-scores (total hip, femoral neck, and lumbar spine) between the PNOVFs and control groups. Compared with BFH-OST, OSTA, and BMD, the FRAX score had the best identifying value for PNOVFs; the AUC of the FRAX score (optimal cutoff =3.6%) was 0.825, while the sensitivity and specificity were 82.92% and 67.09%, respectively. CONCLUSION: FRAX may be the preferable tool for identifying PNOVFs in postmenopausal women, while BFH-OST and OSTA can be applied as more simple screening tools for PNOVFs. | Osteoporotic Fractures |
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