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OBJECTIVE: To report on neurophysiological outcomes derived from transcranial magnetic stimulation (TMS) following autologous mesenchymal stem cells (aMSCs) therapy in patients with multiple sclerosis (MS). METHODS: 20 adults with confirmed MS were recruited to participate in a phase II randomized control trial to assess the safety and potential benefits of aMSCs infusion. At Week 0, patients were randomly assigned to receive either aMSCs (n = 9) or a placebo infusion (n = 11). At Week 24, the placebo group received the aMSCs infusion. Blind assessments were performed at Weeks 0, 24 and 48. Outcomes consisted of TMS measures of corticomotor excitability and motor conduction along with measures of motor impairments and disability. RESULTS: Post-infusion, no change was detected in measures of corticomotor excitability or measures of intra- or interhemispheric inhibition. The latency of motor evoked potentials and central motor conduction time were significantly prolonged. These changes in motor conduction were associated with declines in hand dexterity post-infusion. CONCLUSION: Clinical and neurophysiological measures showed no improvement following aMSCs therapy in this cohort of MS patients. SIGNIFICANCE: Although promising, stem cell therapy remains elusive regarding its benefits in influencing disease activity in MS patients. | Evoked Potentials, Motor |
OBJECTIVE: This study analysed all hospitalisations of persons over the age of 65 years for oral health-related conditions, over a decade, and projected future hospitalisation rates. BACKGROUND: The proportion of older Australians is increasing, and their oral health is improving. At the same time, there is concern about the increasing burden that hospitalisations place on government health budgets. METHODS: Hospitalisation data of all patients older than 65 years, admitted to hospital for an oral health-related condition in Western Australia over a decade, were analysed. RESULTS: Over a ten-year period, a total of 11608 people over the age of 65 were admitted to hospital, with 10% 85 years and older, 52% were men, and 0.1% were Aboriginal patients. The highest rates of hospitalisation were for those from the most disadvantaged areas. Over ten years, there was a significant annual increase in rates of hospitalisation (4.4%). Overall, most admissions were for 'Malignant neoplasms' (16.6%), 'Dental caries' (15.4%) and 'Other disorders of the teeth and supporting structures' (14.3%). These three conditions accounted for almost half of all admissions (46.4%). Projections indicate high future burdens of hospitalisation. CONCLUSIONS: It is of concern that hospitalisations for oral health-related reasons among the oldest patients include high numbers with potentially preventable conditions such as dental caries. Projections indicate that if current trends are set to continue, hospitalisations for oral health-related conditions among Western Australians older than 65 years will place a considerable burden on the health system. | National Health Programs |
The role of vertebrates as amplifying and maintenance hosts for vesicular stomatitis New Jersey virus (VSNJV) remains unclear. Livestock have been considered dead-end hosts because detectable viraemia is absent in VSNJV-infected animals. This study demonstrated two situations in which cattle can represent a source of VSNJV to Simulium vittatum Zetterstedt (Diptera: Simuliidae) by serving: (a) as a substrate for horizontal transmission among co-feeding black flies, and (b) as a source of infection to uninfected black flies feeding on sites where VSNJV-infected black flies have previously fed. Observed co-feeding transmission rates ranged from 0% to 67%. Uninfected flies physically separated from infected flies by a distance of up to 11 cm were able to acquire virus during feeding although the rate of transmission decreased as the distance between infected and uninfected flies increased. Acquisition of VSNJV by uninfected flies feeding on initial inoculation sites at 24 h, 48 h and 72 h post-infection, in both the presence and absence of vesicular lesions, was detected." | Vesicular stomatitis New Jersey virus |
This statement was written under the auspices of the World Gastroenterology Organization's Guidelines Committee. The authors are members of the Review Team of the WGO Endoscope Disinfection Guideline and have experience in endoscopy, endoscope reprocessing, and microbiology, including biofilms. During the preparation of the WGO Update on Endoscope Disinfection Guidelines, concerns about simethicone on endoscope channel surfaces compromising cleaning and disinfection were raised. Publications on simethicone, including modes of delivery, effectiveness, and risks, have been reviewed. The paper was written as a companion to the new guidelines with a focus on minimizing the risks of simethicone in endoscope reprocessing. | Simethicone |
The rapid transfer of electrons in the photosynthetic redox chain is achieved by the formation of short-lived complexes of cytochrome b6f with the electron transfer proteins plastocyanin and cytochrome c6. A balance must exist between fast intermolecular electron transfer and rapid dissociation, which requires the formation of a complex that has limited specificity. The interaction of the soluble fragment of cytochrome f and cytochrome c6 from the cyanobacterium Nostoc sp. PCC 7119 was studied using NMR spectroscopy and X-ray diffraction. The crystal structures of wild type, M58H and M58C cytochrome c6 were determined. The M58C variant is an excellent low potential mimic of the wild type protein and was used in chemical shift perturbation and paramagnetic relaxation NMR experiments to characterize the complex with cytochrome f. The interaction is highly dynamic and can be described as a pure encounter complex, with no dominant stereospecific complex. Ensemble docking calculations and Monte-Carlo simulations suggest a model in which charge-charge interactions pre-orient cytochrome c6 with its haem edge toward cytochrome f to form an ensemble of orientations with extensive contacts between the hydrophobic patches on both cytochromes, bringing the two haem groups sufficiently close to allow for rapid electron transfer. This model of complex formation allows for a gradual increase and decrease of the hydrophobic interactions during association and dissociation, thus avoiding a high transition state barrier that would slow down the dissociation process. | Cytochromes c6 |
Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina. | Eye Diseases, Hereditary |
Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus shown to cause human disease, such as adult T-cell leukemia and HTLV-1 associated myelopathy/tropic spastic paraparesis. HTLV-1 mainly infects CD4 T cells and deregulates their differentiation, function and homeostasis, which should contribute to the pathogenesis of HTLV-1, for example, inducing transformation of infected CD4 T cells and chronic inflammatory diseases. Therefore, not only virological approach but also immunological approach regarding CD4 T cells are required to understand how HTLV-1 causes related human diseases. This review focuses on recent advances in our understanding of the interaction between HTLV-1 and the main host cell, CD4 T cells, which should provide us some clue to the mechanisms of HTLV-1 mediated pathogenesis." | Primate T-lymphotropic virus 1 |
Sequential activation of DNA replication origins is precisely programmed and critical to maintaining genome stability. RecQL4, a member of the conserved RecQ family of helicases, plays an essential role in the initiation of DNA replication in mammalian cells. Here, we showed that RecQL4 protein tethered on the pre-replicative complex (pre-RC) induces early activation of late replicating origins during S phase. Tethering of RecQL4 or its N terminus on pre-RCs via fusion with Orc4 protein resulted in the recruitment of essential initiation factors, such as Mcm10, And-1, Cdc45, and GINS, increasing nascent DNA synthesis in late replicating origins during early S phase. In this origin activation process, tethered RecQL4 was able to recruit Cdc45 even in the absence of cyclin-dependent kinase (CDK) activity, whereas CDK phosphorylation of RecQL4 N terminus was required for interaction with and origin recruitment of And-1 and GINS. In addition, forced activation of replication origins by RecQL4 tethering resulted in increased replication stress and the accumulation of ssDNAs, which can be recovered by transcription inhibition. Collectively, these results suggest that recruitment of RecQL4 to replication origins is an important step for temporal activation of replication origins during S phase. Further, perturbation of replication timing control by unscheduled origin activation significantly induces replication stress, which is mostly caused by transcription-replication conflicts. | RecQ Helicases |
This paper reports the development of a staff training program at The Wesley Hospital in response to perceived needs. A training needs analysis identified priorities for training. Three courses have been run: decision making workshops, stress management workshops, and an assertion seminar. The design of these courses, and staff responses are discussed. Future developments in the training program are proposed." | Personnel Administration, Hospital |
Background and Objectives: Hypertension affects at least 80% of hemodialysis patients. Inappropriate control of blood pressure is mentioned as one of the essential cardiovascular risk factors associated with development of cardiovascular events in dialysis populations. The aim of the cross-sectional, retrospective study was the evaluation of the antihypertensive treatment schedule and control of blood pressure in relation to the guidelines in the group of hemodialysis patients. Additionally, we assessed the level of decrease in blood pressure by each group of hypotensive agents. Materials and Methods: 222 patients hemodialyzed in a single Dialysis Unit in three distinct periods of time-2006, 2011, and 2016-with a diagnosis of hypertension were enrolled in the study. The analysis of the antihypertensive treatment was based on the medical files and it consisted of a comparison of the mean blood pressure results reported during the six consecutive hemodialysis sessions. Results: The mean values of blood pressure before hemodialysis were as follows: 134/77, 130/74, and 140/76 mmHg, after hemodialysis 124/74, 126/73, and 139/77 mmHg in 2006, 2011, and 2016 respectively. The goal of predialysis blood pressure control (<140/90) was achieved by up to 64.3% of participants in 2006 as compared to 49.4% in 2016. Additionally, the postdialysis goal (<130/90) reached 57.1% of the study population in 2006 as compared to 27.1% of patients in 2016. The differences in percentage of patients using single, double, triple, and multidrug therapy during observation were not statistically significant. The most often used drugs were ss-blockers, diuretics, and calcium channel blockers in all points of the study. Blockades of the renin-angiotensin-aldosterone system in 2006 and calcium channel blockers in 2011 and 2016 were the drugs with highest impact on lowering blood pressure. Conclusions: The goal of predialysis or postdialysis blood pressure control was achieved in a lower percentage of patients during the period of the study. Blockade of renin-angiotensin-aldosterone system and calcium channel blockers decrease the blood pressure significantly. It is necessary to achieve better control of blood pressure in prevention of cardiovascular incidents. | Leprostatic Agents |
Congenital central nervous system (CNS) tumors are rare, accounting for <5% of childhood CNS tumors. Although the definition remains arbitrary, 'congenital' is often defined as CNS tumors diagnosed at birth or within a few months after birth. Congenital CNS tumors are now increasingly detected on prenatal ultrasound, with polyhydramnios as the most frequent finding. After delivery, most congenital CNS tumors are associated with macrocrania and hydrocephalus. Teratomas are the most common congenital CNS tumors; other common tumors include astrocytomas, embryonal tumors such as medulloblastomas, and choroid plexus tumors. Choroid plexus tumors (predominantly papillomas) have the best outcome, as aggressive surgical resection can be curative. Other congenital CNS tumors have a collectively poor prognosis, although some subtypes may benefit from complete resections and chemotherapy. Given the rare incidences and diverse pathology of congenital CNS tumors, multicenter studies are required to accurately assess treatment efficacy and outcome measures. | Neuroectodermal Tumors |
The distribution of cartilage in the bony section of the eustachian tube was studied by examining histological serial sections of 50 temporal bones of infants and adults. When cartilage was found to be present in the bony segments of the eustachian tube, its cross-sectional area was measured. Cartilage was seen in the isthmic region in all specimens. In the post-isthmic region it was present in all of the specimens taken from infants and in 92.3% of the adult specimens. In the pretympanic region cartilage was found in 34.6% of the infants' eustachian tubes and in 25% of the adults'. The results indicate that cartilage is also present in the bony part of the eustachian tube at all ages but diminishes in frequency the more the eustachian tube approaches the middle ear. | Cartilage |
A method of preparation a seed-less active insert of iodine-125 ophthalmic applicator is described. Internal electrolysis was applied for fixing iodine-125 on the concave surface of the silver shell which is afterwards hermetically sealed inside a spherically shaped acrylic insert. The current-voltage characteristics of the galvanic cell used for deposition of silver iodide were determined. The results of the measurements of the energy spectra of the radiation emitted by a seed-less and seed-containing applicator are presented. The iodine-125 surface distribution uniformity on a silver shell was measured. The depth dose rate measurements indicate that the total activity incorporated in a seed-less applicator can be lower than that in seed-containing, while simultaneously assuring the desired dose rate. | Iodine Radioisotopes |
TAF8 is part of the transcription factor II D complex, composed of the TATA-binding protein and 13 TATA-binding protein-associated factors (TAFs). Transcription factor II D is the first general transcription factor recruited at promoters to assemble the RNA polymerase II preinitiation complex. So far disorders related to variants in 5 of the 13 subunits of human transcription factor II D have been described. Recently, a child with a homozygous c.781-1G>A mutation in TAF8 has been reported. Here we describe seven further patients with mutations in TAF8 and thereby confirm the TAF8 related disorder. In two sibling patients, we identified two novel compound heterozygous TAF8 splice site mutations, c.45+4A > G and c.489G>A, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8. In five further patients, the previously described c.781-1G > A mutation was present on both alleles. The clinical phenotype associated with the different TAF8 mutations is characterized by severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Cerebral imaging showed hypomyelination, a thin corpus callosum and brain atrophy. Moreover, repeated imaging in the sibling pair demonstrated progressive cerebral and cerebellar atrophy. Consistently, reduced N-acetylaspartate, a marker of neuronal viability, was observed on magnetic resonance spectroscopy. Further review of the literature shows that mutations causing a reduced expression of transcription factor II D subunits have an overlapping phenotype of microcephaly, developmental delay and intellectual disability. Although transcription factor II D plays an important role in RNA polymerase II transcription in all cells and tissues, the symptoms associated with such defects are almost exclusively neurological. This might indicate a specific vulnerability of neuronal tissue to widespread deregulation of gene expression as also seen in Rett syndrome or Cornelia de Lange syndrome. | Transcription Factor TFIID |
Recent reports suggest that first-degree atrioventricular block is not benign. However, there is no evidence that shortening of the PR interval can improve outcome except for symptomatic patients with a very long PR interval >/=0.3 s. Because these patients require continual forced pacing, biventricular pacing should be used according to accepted guidelines for third-degree AV block. Functional atrial undersensing may occur in patients with conventional dual-chamber pacing and first-degree AV block because the sinus P-wave tends to be displaced into the post-ventricular atrial refractory period (PVARP) an arrangement that may cause a pacemaker syndrome. Prevention requires programming a shorter AV and PVARP that is feasible because retrograde conduction is rare in first-degree AV block patients. A relatively new pacing mode to minimize right ventricular stimulation has been designed by eliminating the traditional AV interval but with dual-chamber backup. This pacing mode permits the establishment of very long AV intervals that may cause pacemaker syndrome. About 50% of patients undergoing cardiac resynchronization therapy (CRT) have a PR interval >/=200 ms. The CRT patients with first-degree AV block are prone to develop electrical desynchronization more easily than those with a normal PR interval. The duration of desynchronization after exceeding the upper rate on exercise is also more pronounced. AV junctional ablation is rarely necessary in patients with first-degree AV block but should be considered for symptomatic functional atrial undersensing or when the disturbances caused by first-degree AV block during CRT cannot be managed by programming." | Cardiac Resynchronization Therapy Devices |
Capillary zone electrophoretic (CZE) separations and mass spectrometric analysis of salmon calcitonin and related analogues were performed to generate electrophoresis and mass fingerprints for quality control of the recombinant polypeptide pharmaceutical salmon calcitonin. The calcitonins and their corresponding tryptic digests were successfully separated by CZE at low pH in fused silica capillaries dynamically modified with poly-cationic polymers. The poly-cationic modified inner surface of the fused silica capillaries generated a strong anionic electroosmotic flow (EOF). Analytes of negative, neutral, and positive charge were all swept through the capillary toward the positive electrode. Compared to Polybrene-coated capillaries, capillaries coated with PEI showed a markedly slower but much more stable electroosmotic flow. The migration order of the analytes was predicted by comparing approximate values of the charge to (molecular mass)2/3 ratios. The predicted migration order was confirmed by off-line analysis of CZE fractions with matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). | Calcitonin |
A 73-year-old woman with no significant past medical history presents with a palpable lump in the midshaft of the left tibia and intermittent mild discomfort for the past 8 months. | Adamantinoma |
The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this ratio and has been identified as an important regulator of cancer cell survival and progression. SCD1 converts SFAs into MUFAs and is important for maintaining membrane fluidity, cellular signaling, and gene expression. Many malignancies, including cancer stem cells, have been reported to exhibit high expression of SCD1. Therefore, targeting SCD1 may provide a novel therapeutic strategy for cancer treatment. In addition, the involvement of SCD1 in cancer stem cells has been observed in various types of cancer. Some natural products have the potential to inhibit SCD1 expression/activity, thereby suppressing cancer cell survival and self-renewal activity. | Stearoyl-CoA Desaturase |
Cyclacillin, a new aminosalicylic semisynthetic penicillin, was compared with amoxicillin for the therapy of acute bacterial maxillary sinusitis in 80 patients (ages, 12 to 70 years) in a prospective, double-blind, randomized clinical trial. Direct sinus aspirations for quantitative culture were done for all patients before and after 10 days of therapy. Both drugs were administered at a dosage of 500 mg orally three times daily. Among culture-positive patients, clinical cure was achieved in 23 of 26 patients and 25 of 27 patients treated with cyclacillin and amoxicillin, respectively, for an overall cure rate of 91%. Bacteriologic failure occurred in 9% (4 of 44 patients); 3 of the 4 failures were in the cyclacillin group. There was no correlation between clinical or bacteriologic cure and the results of sinus transillumination (clear, dark) at follow-up. Initial direct sinus aspirates were positive in 57 of 80 cases (70%): 25 (44%) of these were the result of Streptococcus pneumoniae and 23 (40%) were the result of Haemophilus influenzae. All of these isolates were susceptible (MIC, less than or equal to 0.5 microgram/ml) to both study drugs; no ampicillin-resistant H. influenzae was recovered. On day 10 of therapy, mean concentrations of both drugs in serum were 2.5 to 2.7 micrograms/ml, but no antibiotic was detectable in 20 of 21 simultaneous sinus aspirates. Adverse effects (rash, diarrhea) were infrequent and similar in both groups. Cyclacillin appears equivalent to amoxicillin in the therapy of acute maxillary sinusitis. | Cyclacillin |
Optical magnification has broadened the horizons of dentistry in general and periodontics in particular. Improvement in visual acuity, made possible through optical magnification, is becoming an integral part of modern dental practices. Through the quiet trend toward microdentistry, the authors have used microsurgical principles to improve visual acuity and the precision of existing surgical techniques to broaden the scope and character of periodontics, with knowledge and technology borrowed from medicine. The effect of periodontal microsurgery may include more predictable therapeutic results, less invasive procedures with reduced patient discomfort, more rapid healing, improved cosmetic results, and greater patient acceptance. This article provides a brief overview of magnification in dentistry and how it is used in periodontal microsurgery as applied to reconstructive gingival surgery in the treatment of gingival recession. | Microsurgery |
The human genome codes for 12 annexins with highly homologous membrane-binding cores and unique amino termini, which endow each protein with its specific biological properties. Not unique to vertebrate biology, multiple annexin orthologs are present in almost all eukaryotes. Their ability to combine either dynamically or constitutively with membrane lipid bilayers is hypothetically the key property that has led to their retention and multiple adaptation in eukaryotic molecular cell biology. Annexin genes are differentially expressed in many cell types but their disparate functions are still being discovered after more than 40 years of international research. A picture is emerging from gene knock down and knock out studies of individual annexins that these are important supporters rather than critical players in organism development and normal cell and tissue function. However, they appear to be highly significant early responders" toward challenges arising from cell and tissue abiotic or biotic stress. In humans, recent focus has been on involvement of the annexin family for its involvement in diverse pathologies, especially cancer. From what has become an exceedingly broad field of investigation, we have selected four annexins in particular: AnxA1, 2, 5, and 6. Present both within and external to cells, these annexins are currently under intensive investigation in translational research as biomarkers of cellular dysfunction and as potential therapeutic targets for inflammatory conditions, neoplasia, and tissue repair. Annexin expression and release in response to biotic stress appears to be a balancing act. Under- or over-expression in different circumstances appears to damage rather than restore a healthy homeostasis. This review reflects briefly on what is already known of the structures and molecular cell biology of these selected annexins and considers their actual and potential roles in human health and disease." | Annexin A1 |
Haematoma after thyroid surgery can lead to airway obstruction and death. We therefore developed guidelines to improve the safety of peri-operative care of patients undergoing thyroid surgery. We conducted a systematic review to inform recommendations, with expert consensus used in the absence of high-quality evidence, and a Delphi study was used to ratify recommendations. We highlight the importance of multidisciplinary team management and make recommendations in key areas including: monitoring; recognition; post-thyroid surgery emergency box; management of suspected haematoma following thyroid surgery; cognitive aids; post-haematoma evacuation care; day-case thyroid surgery; training; consent and pre-operative communication; postoperative communication; and institutional policies. The guidelines support a multidisciplinary approach to the management of suspected haematoma following thyroid surgery through oxygenation and evaluation; haematoma evacuation; and tracheal intubation. They have been produced with materials to support implementation. While these guidelines are specific to thyroid surgery, the principles may apply to other forms of neck surgery. These guidelines and recommendations provided are the first in this area and it is hoped they will support multidisciplinary team working, improving care and outcomes for patients having thyroid surgery. | Hematoma |
Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA. | Hand Transplantation |
This review examines aspects of the phenomenon of biostimulation in swine, goats, sheep, cattle and deer, to improve the collective knowledge and exploitation of its relevant mechanisms and effects in animal production. The long-term goal is to implement biostimulation strategies that benefit livestock reproduction and production while being both cost-effective and socially acceptable. | Artiodactyla |
The pedigree information on bulls was collected from Frozen Semen Bank (FSB). Male reproductive data on seminal characters (semen volume (SV), sperm concentration (SC), initial progressive motility (IPM), post-thaw motility (PTM), and total spermatozoa (TS)) were analyzed to calculate their repeatability, heritability, genetic correlation, phenotypic correlation, and environmental correlation values. The principal component analysis revealed SV and SC were the two most important characters among the five seminal characters that can be further used. The repeatability value for seminal characters was very low (0.02-0.2). The sire component of heritability value varied from very low to low (0.0001 to - 0.24). The dam component of heritability value varied from very low to high (0.01 to 0.64). The genetic correlation value calculated from the sire component indicated a slightly antagonistic relationship between SV and SC (- 0.007) and SV and PTM (- 0.049). The environmental correlation value was found to be negative for all the traits except the value calculated from the dam component between SC and IPM (0.027). The phenotypic correlation values between the seminal traits were low and mostly negative except between SC and IPM (0.107) and PTM and TS (0.109). Statistically significant correlation was observed between PTM and SV (- 0.157), PTM and IPM (- 0.145), PTM and TS (0.109), and SC and IPM (0.107). Since the estimated heritability, repeatability, and the correlation values were found low, individual selection method cannot be applied on these bulls. | Sperm Count |
Fertilization of R. clamitans eggs in their native jelly occurred when inseminated with high concentrations of R. catesbeiana sperm. Contrary to previous evidence, the block to cross-fertilization of the R. clamitans egg is not complete. This raises the possibility that R. clamitans x R. catesbeiana hybrids may form in nature. | Ranidae |
Four cases of the Curtis-Fitz-Hugh syndrome diagnosed laparoscopically and with microbiological or serological evidence of chlamydial pelvic infection are reviewed. The case histories emphasize the part played by renal angle and left upper quadrant symptoms. In one patient the surface of the spleen was affected by the same classical inflammation normally seen on the surface of the liver. In 3 patients bilateral or left-sided renal angle pain and tenderness constituted the presenting features, or a major manifestation, and in all patients renal tract investigations were entirely normal. The patient with laparoscopic perisplenitis also had perihepatitis and pelvic inflammation, the latter being florid in all cases. Perisplenitis and perinephritis are proposed as possible additional manifestations of this syndrome. | Perinephritis |
Dichoptically viewed complex texture stereograms with correlated spatial frequency information can yield stable depth perception, implying cooperative interaction between the two eyes. Dichoptically viewed dissimilar texture pairs may yield competition in the form of binocular rivalry. To study whether stereopsis and rivalry can spatially coexist when stimulus conditions for both are present, we had observers dichoptically view spatial frequency filtered random-dot patterns. The left eye viewed one half-image of an RDS; the right eye viewed the superimposition of the other RDS half-image (which when paired alone with the left-eye RDS yielded stereoscopic depth) and a noise target (which on its own engaged in rivalry with the right eye target). Observers judged the quality of depth and the rate of rivalry for these stereo-pairs. When the contrast of the noise component was low, observers experienced stereopsis and stable single vision that included the noise. At intermediate noise contrasts, local regions were seen either in rivalry or in stereoscopic depth, but rivalry and depth were not experienced at the same spatial location simultaneously. At high noise contrasts, the right eye target dominated almost exclusively, with little hint of stereopsis. Essentially the same pattern of results was obtained in forced-choice experiments in which observers judged the direction of stereoscopic tilt from vertical cosine gratings differing slightly in spatial frequency. Considered together, these results are inconsistent with theories positing that rivalry and stereopsis coexist at the same spatial location because they occur within independent, parallel pathways. | Depth Perception |
BACKGROUND: Enterocytozoon bieneusi is a common species of microsporidia that not only influences human health but also threatens animal productive performance and value. However, there have been no systematic studies of the prevalence of E. bieneusi in sheep in China. RESULTS: A total of 953 fecal specimens were collected from sheep from 11 provinces across five regions of China and analyzed for E. bieneusi by nested PCR targeting the ribosomal internal transcribed spacer (ITS). Enterocytozoon bieneusi infections were detected in four regions, with an overall infection rate of 20.4% (194/953). The highest infection rate was detected in pre-weaned lambs (25.0%), followed by post-weaned lambs (22.2%) and adult sheep (14.6%). Enterocytozoon bieneusi was found in nine of the 11 tested provinces, with infection rates between 2.9-51.7%. Eleven genotypes were identified based on ITS analysis, including seven known genotypes (BEB6, CHG1, CHG3, CHS7, CHS8, COS-I and NESH5) and four novel genotypes (CHHLJS1, CHHLJS2, CHNXS1 and CHXJS1). All 11 genotypes were clustered into group 2, and the zoonotic genotype BEB6 was the dominant genotype (n = 129, 66.5%) in sheep. CONCLUSION: The prevalence of E. bieneusi was studied in five regions representing most areas where sheep are bred in China. This is the first report of E. bieneusi infection in sheep for seven Chinese provinces. Geographical differences were detected in the distribution of E. bieneusi genotypes, but no differences were found among sheep in different age groups. The zoonotic genotype BEB6 was the dominant genotype, indicating that sheep are a potential source of zoonotic microsporidiosis in China. These results improve our knowledge of the epidemiology of E. bieneusi in sheep in China. | Enterocytozoon |
PURPOSE: To describe the long-term management of bilateral limbal stem cell deficiency secondary to a severe chemical burn. METHODS: Descriptive case report. IMPORTANCE: This case highlights the importance of early intervention in ocular chemical burns for the preservation of tissue integrity and avoidance of perforation. We also review the use of proper ocular surface reconstructive techniques to restore the function of the limbal area, as well as the immunomodulatory strategies and follow-up needed for these interventions. | Burns, Chemical |
Cyclin-dependent kinases determine the timing of key events in the cell cycle, and may also regulate other important cellular functions. Although some of the effects of activating these kinases are clear, the mechanisms by which the effects are produced are not; several types of chemical probes that might be enlightening can be imagined. | Cyclin-Dependent Kinases |
The aim of the present study was to assess the persistence of clenbuterol residues in retinal tissue of pigs after repeated administration in a growth-promoting dose, using enzyme-linked immunosorbent assay (ELISA) as a screening method for quantitative determination. A growth-promoting dose of clenbuterol (20 mug/kg body mass per day) was administered orally to the experimental group (n = 6) for 21 days, whereas control animals (n = 3) were left untreated. Clenbuterol-treated pigs were randomly sacrificed (n = 3) on days 0 and 45 of treatment discontinuation, and clenbuterol residues were determined in retinal tissue dissected from the eye. ELISA was found to be acceptable for quantitative determination of clenbuterol in retinal samples because previous method validation yielded mean recovery values of 84.3-96.5% with variation coefficients < 14%. The mean (+/- SD) retinal clenbuterol concentration was 1874 +/- 114 ng/g immediately upon clenbuterol withdrawal (day 0) and 73 +/- 4 ng/g on the last day post-withdrawal (day 45). Study results pointed to a very high potential of clenbuterol accumulation in retinal tissue and marked persistence of clenbuterol residues upon anabolic dose administration, suggesting retinal tissue to be a very useful matrix for effective control of residual clenbuterol in food-producing pigs. | Clenbuterol |
Individual signalling events are processed in distinct, spatially segregated domains of the plasma membrane. In a smooth muscle, the sarcolemma is divided into domains of focal adhesions alternating with caveolae-rich zones, both harbouring a specific subset of membrane-associated proteins. Recently, we have demonstrated that the sarcolemmal lipids are similarly segregated into domains of cholesterol-rich lipid rafts and glycerophospholipid-rich non-raft regions. In the present study, we provide a detailed structural analysis of the relationship between these proteinaceous and lipid domains. We demonstrate that the segregation of plasmalemmal protein constituents is intimately linked to that of the membrane lipids. Our results imply that lipid segregation is critical for the preservation of membrane protein architecture and essential for directional translocation of proteins to the sarcolemma. We show that the membrane lipid segregation is supported by the annexin protein family in a Ca2+-dependent manner. Eukaryotic cells harbour numerous, tissue-specific subsets of annexins. By examining the significance of this variety in a smooth muscle, we demonstrate that four different annexins target membrane sites of distinct lipid composition and that each annexin requires a different [Ca2+] for its translocation to the sarcolemma. Our results suggest that the interactions of annexins with distinct plasma membrane regions promote membrane segregation and, in combination with their individual Ca2+ sensitivity, might allow a spatially confined, graded response to a multitude of extra- or intracellular stimuli. | Muscle, Smooth |
Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 +/- 15 and 34 +/- 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects. | Torsemide |
In view of all the reported evidence by electromyography in the 1970s, by histology in the 1980s, and by cerebral imagery since the 2000s, Duane retraction syndrome (DRS) has been described as the consequence of a congenital anomaly of the 6th cranial nerve nuclei with aberrant innervations by supply from the 3rd cranial nerve. Both genetic and environmental factors are likely to play a role when the cranial nerves and ocular muscles are developing between the 4th and the 8th week of gestation. New data from eye movement recordings contributed to better understanding the binocular control of saccades. Modeling of saccades in DRS seems promising for the quantification of the innervational deficit and the mechanical properties of the eye plant. The usual clinical classification of DRS needs to be updated in order to match more accurately the underlying dysinnervation of the extra ocular muscles and to illustrate the continuum that exists between the various forms. This review aims to summarize the major findings about DRS and to guide the clinician in the surgical management of this particular form of strabismus." | Congenital Cranial Dysinnervation Disorders |
OBJECTIVE: The genetic mutations causing the constitutive activation of MEK/ERK have been regarded as an initiating factor in papillary thyroid carcinoma (PTC). The ERK-specific dual specificity phosphatase 6 (DUSP6) is part of the ERK-dependent transcriptional output. Therefore, the coordinated regulation of the activities of ERK kinases and DUSP6 may need to be reestablished to make new balances in PTC. METHODS: To investigate the role of DUSP6 in the regulation of ERK1/2 (MAPK3/1)-dependent transcription, 42 benign neoplasms and 167 PTCs were retrospectively analyzed by immunohistochemistry with dideoxy sequencing to detect BRAF(V600E) mutation. RESULTS: The expressions of total ERK1/2, DUSP6, c-Fos (FOS), c-Myc (MYC), cyclin D1, and PCNA were markedly increased in PTC compared with those in benign neoplasms. However, phospho-ERK1/2 was detected in only eight (4.8%) cases out of 167 PTC samples. Unexpectedly, the staining intensity and nuclear localization of ERK1/2 were not affected by the presence or absence of the BRAF(V600E) mutation. However, the expressions of c-Fos and PCNA were elevated in BRAF(V600E)-positive PTC compared with those in BRAF(V600E)-negative PTC. Interestingly, the higher staining intensities of DUSP6 were associated with the level of total ERK1/2 expression (P=0.04) and with high-risk biological features such as age (P=0.05), tumor size (P=0.01), and extrathyroidal extension (linear by linear association, P=0.02). In addition, DUSP6 silencing significantly decreased the cell viability and migration rate of FRO cells. CONCLUSIONS: The coordinated upregulation of total ERK1/2 and its phosphatase, DUSP6, is related to bare detection of phospho-ERK1/2 in PTC regardless of BRAF(V)(600E) mutation status. A link between DUSP6 expression and high-risk features of PTC suggested that DUSP6 is an important independent factor affecting the signaling pathways in established PTC." | Dual Specificity Phosphatase 6 |
Platelets play a central role in hemostasis and wound healing. The latter is mediated by release of secretory proteins on platelet activation, which directly or indirectly influences virtually all aspects of the wound healing cascade. Studies in basic science have shown a dose-response relationship between the platelet concentration and levels of secretory proteins, as well as between platelet concentration and certain proliferative events of significance to the healing wound. Technologies to provide autologous platelet rich plasma to the repair site are now being used in a wide variety of clinical applications, with the majority of such studies suggesting a role in the surgeon's armamentarium. Little standardization in the field exists, which has made it difficult to fully evaluate the literature on the subject and unequivocally establish applications for which the technology truly has merit. This article presents fundamental background on platelet biology and the role of platelets in both hemostasis and wound healing, as well as methods of preparing, characterizing, and using platelet rich plasma, to provide the reader a foundation on which to critically evaluate prior studies and plan future work. | Plateletpheresis |
Tunicamycin, a new antibiotic, halts the formation of physical particles of Semliki forest and fowl plague virus, whereas avian oncornavirus particles which show a reduction in infectivity and do not contain detectable labeled glycoprotein are released in the presence of the drug. In Semliki forest virus-infected cells only the protein moieties of the glycoproteins could be labeled. In cells infected with fowl plague and avian sarcoma virus neither intact glycoproteins nor their protein moieties could be detected. By using a protease inhibitor (N-alpha-p-tosyl-L-lysin chloromethyl ketone, TLCK) it could be shown, however, that the carbohydrate-free hemagglutinin precursor of influenza virus is synthesized but is presumably degraded by intracellular proteases in the absence of TLCK as a consequence of the lack of carbohydrate." | Tosyllysine Chloromethyl Ketone |
A rapid large scale procedure was devised for the purification of desmosine and isodesmosine from ligamentum nuchae elastin. The method makes use of the hydrophilic nature of the desmosines which preferentially absorbs to cellulose fibers in mixtures of organic solvents. Resolution of the isomers was achieved on a polystyrene resin column. | Desmosine |
Formalin-fixed, paraffinembedded (FFPE) human brain tissues are very often stored in formalin for long time. Formalin fixation reduces immunostaining, and the DNA/RNA extraction from FFPE brain tissue becomes suboptimal. At present, there are different protocols of fixation and several procedures and kits to extract DNA/RNA from paraffin embedding tissue, but a gold standard protocol remains distant. In this study, we analyzed four types of fixation systems and compared histo and immuno-staining. Based on our results, we propose a modified method of combined fixation in formalin and formic acid for the autoptic adult brain to obtain easy, fast, safe and efficient immunolabelling of long-stored FFPE tissue. In particular, we have achieved an improved preservation of cellular morphology and obtained success in postmortem immunostaining for NeuN. This nuclear antigen is an important marker for mapping neurons, for example, to evaluate the histopathology of temporal lobe epilepsy or to draw the topography of cardiorespiratory brainstem nuclei in sudden infant death syndrome (SIDS). However, NeuN staining is frequently faint or lost in postmortem human brain tissues. In addition, we attained Fluoro Jade C staining, a marker of neurodegeneration, and immunofluorescent staining for stem cell antigens in the postnatal human brain, utilizing custom fit fixation procedures." | Histocytological Preparation Techniques |
This article starts from the DSM definition of psychic trauma. A central source in this field is the 1992 book by Judith Herman. One line of investigation is the sexual abuse of women and children. In an early phase, both Janet and Freud described dissociation as a reaction to trauma. In 1897, Freud disputed the reality of sexual trauma, a position countered later by Ferenczi. In a later phase, this subject was investigated by the American feminist movement. Studies of physical abuse are then described, followed by mental abuse and neglect. Another line of investigation is combat neurosis. The two lines converged in the definition of PTSD and its incorporation into the DSM in 1980. The views on trauma of John Bowlby and Alice Miller are also discussed. The integration of the relational model in psychoanalysis with the trauma literature is presented. The most recent advances are located in neurobiology. The discussion makes a preliminary investigation of the remote causes of war and sexual violence. | Abreaction |
The characteristics of social phobia and shyness were compared on six dimensions: somatic features, cognitive characteristics, behavioral responses, daily functioning, clinical course, and onset characteristics. The results revealed that shyness and social phobia have a number of similar features. However, as currently conceptualized, the two syndromes differ in a number of important aspects as well. Definitive distinctions are hampered by the lack of empirical studies directing comparing the two conditions and by the heterogeneity of the shy population. Recommendations for clarifying some of the ambiguities are made. | Shyness |
We screened and identified an endophytic bacterium that could efficiently degrade PAHs, which would expand the library of polycyclic aromatic hydrocarbons (PAHs) degrading microorganisms and reduce the pollution risk of crops. Its degradation mechanism and colonization performance were preliminarily examined. The results showed that strain PX1 belonged to Stenotrophomonas maltophilia. The strain had broad spectrum ability to remove PAHs. In PAH mineral salt (MS) media, almost 100% naphthalene was degraded by strain PX1 after 7-d incubation. In a cultivation system solely containing phenanthrene of 50.0 mg.L(-1), pyrene of 20.0 mg.L(-1), fluoranthene of 20.0 mg.L(-1) or benzo[a]pyrene of 10.0 mg.L(-1), the degradation efficiency of phenanthrene, pyrene, fluoranthene and benzo[a]pyrene by strain PX1 reached 72.6%, 50.7%, 31.9%, and 12.9%, respectively. Pyrene was selected as PAHs model to study the degradation characteristics of strain PX1. Enzyme activity tests showed that the activities of phthalate dioxygenase, catechol-1,2-dioxygenase, and catechol-2,3-dioxygenase in strain PX1 were induced by pyrene. Some metabolic intermediates such as 4,5-epoxypyrene, 4,5-dihydroxypyrene, gentilic acid/protocatechuic acid, salicylic acid, cis-hexadienedioic acid/2-hydroxymyxofuroic acid semialdehyde, cis-2'-carboxyphenylpyruvic acid, 1-hydroxy-2-naphthoic acid, and salicylaldehyde were detected during the degradation of pyrene by strain PX1. Results of the seed soaking experiment showed that strain PX1 could efficiently colonize in Ipomoea aquatic and Triticum aestivum. After inoculated with strain PX1, the growth of I. aquatic and T. aestivum was significantly increased, and the pyrene concentration in I. aquatic, T. aestivum and MS media was reduced by 29.8%-50.7%, 52.4%-67.1% and 8.0%-15.3%, respectively. Our results suggested that strain PX1 degraded pyrene mainly through 'salicylate pathway' and 'phthalate pathway', and could be colonized into plants and promote plant growth. | Catechol 2,3-Dioxygenase |
The morphology and histology of the cetacean adrenal gland are poorly understood. Therefore, this study examined 32 pairs of adrenal glands from 18 pan-tropical spotted dolphins (Stenella attenuata) and 14 spinner dolphins (Stenella longirostris). In both species, the cortex was pseudolobulated and contained a typical mammalian zonation. Medullary protrusions (0-3 per section) and a medullary band were identified in both species. For S. attenuata, no statistical differences were found in the cortex to medulla (CM) ratio or the percent cross-sectional area (PCA) of the adrenal glands compared with sex or sexual maturity. The mean CM ratio for S. attenuata was 2.34 and the PCA was 64.4% cortex, 29.4% medulla and 6.2%'other'. 'Other' indicates blood vessels, connective tissue and the gland capsule itself. For S. longirostris, there was no statistical difference in the CM ratio compared with sexual maturity. However, a statistical difference was found between the CM ratio and sex, suggesting sexual dimorphism (female CM ratio = 2.46 and males = 3.21). No statistical differences were found in the PCA of S. longirostris adrenal glands by sexual maturity. However, a statistical difference was found between the PCA by sex. Female S. longirostris adrenal glands consisted of 65.0% cortex, 27.3% medulla and 7.7% 'other', whereas male adrenal glands consisted of 71.7% cortex, 22.7% medulla and 5.6% 'other'. | Stenella |
We analyzed 88 unrelated subjects with Type 1 (insulin-dependent) diabetes and 64 sibling controls (maximum one per diabetic) for associations between immunoglobulin allotype antigens (GM and KM) and Type 1 diabetes. None were found. However, we did find interactions between GM, HLA-DR, and Type 1 diabetes (significant or of borderline significance after considering the effect of multiple tests): possession of Glm(2) appeared to increase susceptibility to diabetes in individuals who had HLA-DR3 but not HLA-DR4, while possession of G3m(5) appeared to increase susceptibility in individuals who had HLA-DR4 but not HLA-DR3. These results suggest that genetic predisposition to Type 1 diabetes is partially determined by alleles at the GM locus (or a locus in linkage disequilibrium with GM) interacting with alleles at the HLA-DR locus (or a locus in linkage disequilibrium with HLA-DR). | HLA-DR Serological Subtypes |
Western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses were detected in the Imperial Valley during the summers of 1991-1994 by isolation from the primary vector, Culex tarsalis Coquillett, and by the seroconversion of sentinel chickens. Enzootic transmission consistently was not detected first each year at sampling sites near specific landscape features such as a heron rookery and other riparian habitats along the New River, sites along the Mexican border, or saline and freshwater marshes along the southern shore of the Salton Sea. Despite mild winter temperatures and the elevated vernal abundance of Cx. tarsalis, WEE and SLE activity was not detected until June or July, indicating considerable amplification may be necessary before detection by testing mosquito pools for virus infection or sentinel chicken sera for antibodies. Results did not permit the spatial focusing of early season control efforts or research on mechanisms of virus interseasonal persistence." | Encephalitis Virus, Western Equine |
The symptoms of Iron Deficiency Anemia (IDA) and beta-thalassemia (beta-TT) disease are similar and the distinction between them is time consuming and costly. There are several indices used to differentiate IDA from beta-thalassemia disease. Complete Blood Count (CBC) is a rapid, inexpensive and accessible test for the diagnosis of anemia and is used as a primary test. However, since CBC cannot fully distinguish between IDA and beta-thalassemia, more advanced testing is required. These tests are not available in small centers and are performed on higher-cost devices. Moreover, it is important to differentiate between anemia and beta-thalassemia medically for two reasons (IDA). First, if a patient with beta-Thalassemia is diagnosed with IDA, the patient is given unnecessary iron supplementation as a result of the treatment, which is recommended by the doctor. Secondly, when the patient with beta-thalassemia is diagnosed with IDA, children will have beta-thalassemia patients in marriages. A decision support system to distinguish between beta-Thalassemia and IDA has been developed. Logistic Regression, K-Nearest Neighbours, Support Vector Machine, Extreme Learning Machine and Regularized Extreme Learning Machine classification algorithms were used in the proposed system. Classification performance was evaluated with Accuracy, sensitivity, f-measure, Specificty parameters using Hemoglobin, RBC, HCT, MCV, MCH, MCHC and RDW parameters obtained from 342 patients. 96.30% accuracy for female, 94.37% for male, and 95.59% in co-evaluation of male and female patients were obtained. | beta-Thalassemia |
Strain AUS118(T) was isolated from an Argas lagenoplastis tick collected from the nest of a Petrochelidon ariel (fairy martin) in Australia in 2013. Microscopic observation of infected cell cultures indicated this strain had a morphology and intracellular location typical of Rickettsiaspecies. Phylogenetic analysis of this strain based firstly on multi-locus sequence analysis and subsequently on whole genome analysis demonstrated that AUS118(T) was most closely related to, but divergent from Rickettsia japonica and Rickettsia heilongjiangensis. We therefore propose the creation of a novel species, Rickettsia fournieri sp. nov, with the type strain AUS118(T) (DSM 28985 and CSUR R501). | Argas |
PURPOSE: To identify the most effective interventions to treat nipple trauma in breastfeeding mothers. DESIGN AND METHODS: Systematic literature review using the PICO strategy. The search was conducted on the electronic information systems Medline-PubMed, Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), World Health Organization Library Information System (WHOLIS), Cochrane, ScienceDirect (Elsevier), Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL), using standardized and unstandardized descriptors. Studies were selected if they were controlled or uncontrolled randomized clinical trials written in English, Portuguese, or Spanish. Two reviewers evaluated the studies independently using a guide, and in case there were disagreements, a third reviewer was called on to reach a consensus. Of the 496 studies located, five were included. FINDINGS: The treatments investigated were lanolin, lanolin in association with breast protection shells, breast milk, hydrogel, adhesive polyethylene film dressings, a spray containing chlorhexidine with alcohol, and distilled water. All the groups in every study received breastfeeding education. The best outcomes for the treatment of nipple trauma used lanolin (recommendation B, evidence level 2) and breast milk (recommendation B, evidence level 2). Although one clinical study was found with positive outcomes resulting from treatment using a spray containing alcohol and chlorhexidine 0.2% (recommendation B, evidence level 2), this treatment modality should be further investigated since literature is not in favor of using antiseptic substances in skin wound treatment. CONCLUSIONS: Considering the treatments investigated, the most favorable evidence indicates the use of lanolin alone or in association with breast protection shells and breast milk expressed and rubbed into the nipple and areola after each feeding session. However, the results obtained in this review are inconclusive, indicating the need for further studies in order to clarify the action of breast milk and lanolin on the damaged tissues, as well as studies involving samples representative of the number needed to treat. CLINICAL RELEVANCE: This study provides evidence for nursing practice, thus contributing to the improvement of lactating mothers with nipple trauma care and, consequently, improving the rates of successful breastfeeding as well as the quality of life of breastfeeding mothers. | Lanolin |
Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output. | Epiregulin |
The structure of YaaE from Bacillus subtilis was determined at 2.5-A resolution. YaaE is a member of the triad glutamine aminotransferase family and functions in a recently identified alternate pathway for the biosynthesis of vitamin B(6). Proposed active residues include conserved Cys-79, His-170, and Glu-172. YaaE shows similarity to HisH, a glutaminase involved in histidine biosynthesis. YaaD associates with YaaE. A homology model of this protein was constructed. YaaD is predicted to be a (beta/alpha)(8) barrel on the basis of sequence comparisons. The predicted active site includes highly conserved residues 211-216 and 233-235. Finally, a homology model of a putative YaaD-YaaE complex was prepared using the structure of HisH-F as a model. This model predicts that the ammonia molecule generated by YaaE is channeled through the center of the YaaD barrel to the putative YaaD active site. | Glutaminase |
OBJECTIVE: Perfectionism has been described as a multidimensional core vulnerability factor in various forms of dysfunction and disorders. Recently, we described our empirically supported-dynamic-relational treatment for perfectionism. This treatment integrates psychodynamic and interpersonal principles to reduce perfectionism and symptoms and enhance relationships with others and self by focusing on underlying relational patterns. METHOD: We discuss this approach and present Azure, a 27-year-old woman who completed our group treatment and subsequent individual therapy as a follow-up. RESULTS: Azure underwent a comprehensive psychological pretreatment assessment, the results of which were used to develop a working formulation that guided the group and individual psychotherapy. A description of the formulation and her experience in therapy are discussed and pre- and post-treatment data illustrate changes in Azure's perfectionism and symptoms. CONCLUSIONS: We discuss changes that occurred over the course of treatment. | Perfectionism |
Sickle cell anemia is a genetic blood disorder arising from a point mutation in the beta-globin gene that leads to the replacement of glutamic acid residue by valine at the sixth position of the beta--chain of hemoglobin. At low oxygen tension, the mutant hemoglobin, sickle hemoglobin, polymerizes inside the red blood cells into a gel or further into fibers leading to a drastic decrease in the red cell deformability. As a result, micro-vascular occlusion arises which may lead to serious, sometimes fatal, crises. The present article reviews the historical, genetic, molecular, cellular, and clinical aspects of the disease. A review for the development and design of drugs to treat sickle cell anemia is presented. Anti-sickling agents are classified, based on the target to be modified, into three classes: the gene, the sickle hemoglobin molecule, and the red cell membrane modifiers. In spite of the full understanding of the pathology, physiology, and the molecular nature of the disease, and the development of large number of antisickling agents, a cure for sickle cell anemia still is unavailable. Strategies to treat sickle cell anemia since the early times of the disease state discovery in 1910, has focussed mainly on prophylactic measures to alleviate the painful crises. The article addresses clinical approaches used then and now to treat the disease, and the rationale of their use. Currently in clinical practice, hydroxyurea is the most commonly used agent to treat the disease, and it has been recently approved by the united states Food and Drug Administration as a drug for that purpose. | Antisickling Agents |
INTRODUCTION AND PURPOSE: Yersinia enterocolitica belongs to the family of Enterobacteriaceae and is a psychrophilic pathogen that is associated with foodborne infections. It usually causes gastroenteritis, mesenteric lymphadenitis, and septicemia. This study aimed to molecular detection, biotyping, and serotyping of Yersinia enterocolitica isolated from chicken livers in Tabriz. MATERIALS AND METHODS: One hundred chicken liver samples were collected randomly from poultry slaughterhouses in Tabriz for three months. After enrichment process, the presence of Yersinia enterocolitica in studied samples was determined through culture-based methods, biochemical and molecular tests. Then the biotype and serotype of the isolates were determined. RESULTS: 31 samples (31%) were positive for Yersinia enterocolitica by both phenotypic and molecular assays. Among positive samples, 25 (80.64%) had non-pathogenic biotype 1 A with serotype O: 5 (23 samples) and O: 8 (2 samples). 6 (19.36%) had biotype 1B and all of them had O: 3 serotype. The serotype Yersinia enterocolitica O: 9 was not found. CONCLUSION: the present study highlighted the significance of chicken liver as potential source of Yersinia enterocolitica infection in Tabriz city. | Serotyping |
Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed, but further investigations including in vivo studies are needed to clarify how important these more-than-additive effects are for risk assessment. | Maleic Hydrazide |
Chloroflexales (Chloroflexi) are typical members of the anoxygenic photosynthesizing component of microbial mats and have mostly been characterized from communities associated to hot springs. Here, we report the assembly of five metagenome-assembled genomes (MAGs) of a novel lineage of Chloroflexales found in mesophilic lithifying microbial mats (microbialites) in Lake Alchichica (Mexico). Genomic and phylogenetic analyses revealed that the bins shared 92% of their genes, and these genes were nearly identical despite being assembled from samples collected along a depth gradient (1-15 m depth). We tentatively name this lineage Candidatus Lithoflexus mexicanus. Metabolic predictions based on the MAGs suggest that these chlorosome-lacking mixotrophs share features in central carbon metabolism, electron transport, and adaptations to life under oxic and anoxic conditions, with members of two related lineages, Chloroflexineae and Roseiflexineae. Contrasting with the other diverse microbialite community members, which display much lower genomic conservation along the depth gradient, Ca. L. mexicanus MAGs exhibit remarkable similarity. This might reflect a particular flexibility to acclimate to varying light conditions with depth or the capacity to occupy a very specific spatial ecological niche in microbialites from different depths. Alternatively, Ca. L. mexicanus may also have the ability to modulate its gene expression as a function of the local environmental conditions during diel cycles in microbialites along the depth gradient. | Chloroflexi |
Neuronal connections are arranged topographically such that the spatial organization of neurons is preserved by their termini in the targets. During the development of topographic projections, axons initially explore areas much wider than the final targets, and mistargeted axons are pruned later. The molecules regulating these processes are not known. We report here that the ligands of the Eph family tyrosine kinase receptors may regulate both the initial outgrowth and the subsequent pruning of axons. In the presence of ephrins, the outgrowth and branching of the receptor-positive hippocampal axons are enhanced. However, these axons are induced later to degenerate. These observations suggest that the ephrins and their receptors may regulate topographic map formation by stimulating axonal arborization and by pruning mistargeted axons. | Ephrin-A3 |
Molecular techniques have allowed the identification of new viruses in a number of patients with cryptogenic hepatitis. Whether they are clinically inapparent or true hepatitis agents remains unknown for some of them. Latest described viruses include GBV, TTV and SENV. However, based on the limited data available, they do not seem to be contenders for the new hepatitis virus title. However, researchers are looking for a role of these viruses in other chronic and acute human diseases. Only a careful evaluation of the data and the scientific concordance of all the evidence will resolve the question of whether they are only commensal viruses or pose a real pathogenic potential. | Circoviridae |
Root-end cavities have traditionally been prepared by means of small round or inverted cone burs in a micro-handpiece. Since sonically or ultrasonically driven microsurgical retrotips became commercially available in the early 1990s, this new technique of retrograde root canal instrumentation has been established as an essential adjunct in periradicular surgery. At first glance, the most relevant clinical advantages are the enhanced access to root ends in limited working space and the smaller osteotomy required for surgical access because of the various angled designs and small size of the retrotips. However, a number of experimental studies comparing root-end preparations made with microsurgical tips to those made with burs have demonstrated other advantages of this new technique, such as deeper cavities that follow the original path of the root canal more closely. The more centered root-end preparation also lessens the risk of lateral perforation. In addition, the geometry of the retrotip design does not require a beveled root-end resection for surgical access thus decreasing the number of exposed dentinal tubules. A controversial issue of sonic or ultrasonic root-end preparation is the formation of cracks or microfractures, and its implication on healing success. The present paper reviews experimental and clinical studies about the use of microsurgical retrotips in periradicular surgery and discusses many issues raised in previous papers. | Apicoectomy |
Monoclonal antibodies specific for the adhesion molecules participating in lymphocyte homing, lymphocyte function associated antigen-1 (LFA-1) and very late antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), were used to characterize their expression pattern in human lymph nodes by immunohistochemical and immunoelectron microscopic techniques. The location of LFA-1-positive lymphocytes and selective expression of ICAM-1 on the luminal plasma membrane of high endothelial venule endothelium suggested that the LFA-1/ICAM-1 adhesion pathway participates only in the initial step of the lymphocyte migration process. Lymphocytes passing through endothelium appear not to be influenced by this pathway. VCAM-1 was detected occasionally on the endothelium of high endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in peripheral lymph nodes. VLA4-positive lymphocytes tended to be more frequently observed within high endothelial venules in mesenteric lymph nodes than in peripheral ones. Strong expression of both ligands, ICAM-1 and VCAM-1, was noted on the plasma membrane of follicular dendritic cells, and was especially prominent on their labyrinthine folding, and on the interdigitating cells in the paracortex. Furthermore, both LFA-1- and VLA4-positive lymphocytes localized around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways play an important role in the lymphocyte recognition of antigen-presenting cells." | Lymphocyte Function-Associated Antigen-1 |
The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues. | Amyloidosis, Familial |
PURPOSE: To evaluate the role of MR Sialography(MRS) in diagnosis of submandibular sialolithiasis. METHODS: Twenty-one patients with submandibular sialolithiasis were scanned by MRS, the results of MRS were compared with those after proper treatment. RESULTS: The results of MRS were consistent with those after proper treatment. CONCLUSION: MRS has high diagnostic accuracy in diagnosis of sialolithiasis including submandibular sialadenitis. | Sialography |
HIV-exposed seronegative KIR3DS1 homozygotes have a reduced risk of HIV infection. HLA-F is the ligand for the activating NK cell receptor (NKR) KIR3DS1. HLA-F is expressed on HIV-infected CD4 T cells. Coculture of sorted, HIV-infected CD4(-) (siCD4(-)) T cells with NK cells activated a higher frequency of KIR3DS1(+) than KIR3DS1(-) NK cells from KIR3DS1 homozygotes to elicit anti-HIV functions such as CCL4, gamma interferon (IFN-gamma), and CD107a expression. This was the case whether KIR3DS1(+/-) NK cells were analyzed inclusively or exclusively by gating out NK cells coexpressing the NKRs, KIR2DL1/L2/L3, 3DL2, KIR2DS1/S2/S3/S5, NKG2A, and ILT2. Blocking the interaction of HLA-F on siCD4(-) cells with KIR3DS1 on exclusively gated KIR3DS1(+) NK cells with KIR3DS1-Fc chimeric protein or an HLA-F-specific monoclonal antibody reduced the frequency of activated KIR3DS1(+) cells compared to that under control conditions. KIR3DS1(+) NK cell activation by HIV-infected CD4(+) cells may underlie the reduced risk of KIR3DS1 homozygotes to HIV infection.IMPORTANCE This study investigated a mechanism that may underly epidemiological studies showing that carriage of the KIR3DS1 homozygous genotype is more frequent among HIV-exposed seronegative subjects than among HIV-susceptible individuals. Carriage of this genotype is associated with a reduced risk of HIV infection. The protective mechanism involves the interaction of HLA-F on CD4(+) cells infected with replication-competent HIV with the activating NK receptor, KIR3DS1. This interaction leads to the activation of KIR3DS1(+) NK cells for secretion of cytokines and chemokines with anti-HIV activity. Among these is CCL4, which binds and blocks CCR5, the coreceptor for HIV entry of HIV into new target cells. In the setting of an exposure to HIV, incoming HIV-infected cells expressing HLA-F rapidly activate KIR3DS1(+) NK cells to elicit anti-HIV activity. Exclusive gating strategies and blocking experiments support the notion that the HLA-F/KIR3DS1 interaction is sufficient to activate NK cell functions. | Receptors, KIR3DS1 |
BACKGROUND: The transforming growth factor-beta (TGF-beta) pathway plays a vital role in driving cancer cell epithelial-mesenchymal transition (EMT). Zonula occludens-1 (ZO-1), which is downregulated in response to TGF-beta, is able to control endothelial cell-cell tension, cell migration, and barrier formation. However, the molecular mechanism of how TGF-beta regulates ZO-1 expression remains unclear. METHODS: Breast cancer cells were treated with TGF-beta to induce an EMT progress. Chromatin immunoprecipitation and dual-luciferase reporter assay were performed to investigate direct relationship between Snail and RNA binding motif protein 38 (RBM38). The RNA immunoprecipitation combined with RNA electrophoretic mobility shift assay and dual-luciferase reporter assay were conducted to testify direct relationship between RBM38 and ZO-1. The ZO-1 siRNA was transfected to breast cancer cells that overexpress RBM38 and the control, followed by transwell and Matrigel invasion assays to examine cell migratory and invasive ability. RESULTS: Transforming growth factor-beta induced a remarkable downregulation of RBM38 in breast cancer that was directly regulated by transcription repressor Snail targeting the E-box elements in promoter region of RBM38 gene. Additionally, RBM38 positively regulated ZO-1 transcript via directly binding to AU/U-rich elements in its mRNA 3'-UTR. Moreover, by magnifying RBM38 expression, cell migration and invasion mediated by knockdown of ZO-1 in breast cancer were reversed. CONCLUSIONS: All the results clarified a linear regulation relationship among Snail, RBM38, and ZO-1, implicating RBM38 as a pivotal mediator in TGF-beta-induced EMT in breast cancer. | Zonula Occludens Proteins |
Conventional magnetic resonance imaging (MRI) allows for a detailed noninvasive visualization/examination of posterior fossa structures and represents a fundamental step in the diagnostic workup of many cerebellar disorders. In the first part of this chapter methodologic issues, like the correct choice of hardware (magnets, coils), pro and cons of the different MRI sequences, and patient management during the examination are discussed. In the second part, the MRI anatomy of the cerebellum, as noted on the various conventional MRI sequences, as well as a detailed description of cerebellar maturational processes from birth to childhood and into adulthood, are reported. Volumetric studies on the cerebellar growth based on three-dimensional MRI sequences are also presented. Moreover, we briefly discuss two main topics regarding conventional MRI of the cerebellum that have generated some debate in recent years: the differentiation between cerebellar atrophy, hypoplasia, and pontocerebellar hypoplasia, and signal changes of dentate nuclei after repetitive gadolinium-based contrast injections. The advantages and benefits of advanced neuroimaging techniques, including (1)H magnetic resonance spectroscopy, diffusion-weighted imaging, diffusion tensor imaging, and perfusion-weighted imaging are discussed in the last section of the chapter. | Cerebellum |
The aim of this work was to synthesize and investigate properties of a novel dimethacrylic monomer based on bioderived alicyclic diol--isosorbide. Its potential as a possible substitute of 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (BISGMA), widely used in dental restorative materials and suspected for toxicity was assessed. The novel monomer was obtained in a three-step synthesis. First, isosorbide was etherified by a Williamson nucleophilic substitution and subsequently oxidized to isosorbide diglycidyl ether (ISDGE). A triphenyl phosphine catalyzed addition of methacrylic acid to ISDGE resulted in 2,5-bis(2-hydroxy-3-methacryloyloxypropoxy)- 1,4:3,6-dianhydro-sorbitol (ISDGMA). The monomer obtained was photopolymerized using camphorquinone/2-(dimethylamino)ethyl methacrylate initiating system. Next, compositions with triethylene glycol dimethacrylate (TEGDMA) were prepared and polymerized. Double bond conversion, polymerization shrinkage and water sorption of resulting polymers were determined. Selected mechanical (flexular strength and modulus, Brinell hardness) and thermomechanical (DMA analysis) properties were also investigated. BISGMA based materials were prepared as reference for comparison of particular properties." | Bisphenol A-Glycidyl Methacrylate |
BACKGROUND: Acute respiratory tract infections (ARTIs) are common in children and can involve both upper and lower airways. Many children experience frequent ARTI episodes or recurrent respiratory tract infections (RRTIs) in early life, which creates challenges for paediatricians, primary care physicians, parents and carers of children.In China, Astragalus (Huang qi), alone or in combination with other herbs, is used by Traditional Chinese Medicine (TCM) practitioners in the form of a water extract, to reduce the risk of ARTIs; it is believed to stimulate the immune system. Better understanding of the therapeutic mechanisms of Astragalus may provide insights into ARTI prevention, and consequently reduced antibiotic use. OBJECTIVES: To assess the effectiveness and safety of oral Astragalus for preventing frequent episodes of acute respiratory tract infections (ARTIs) in children in community settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 12, 2015), MEDLINE (Ovid) (1946 to 31 December 2015), Embase (Elsevier) (1974 to 31 December 2015), AMED (Ovid) (1985 to 31 December 2015), Chinese National Knowledge Infrastructure (CNKI) (1979 to 31 December 2015) and Chinese Scientific Journals full text database (CQVIP) (1989 to 31 December 2015), China Biology Medicine disc (CBM 1976 to 31 December 2015) and Wanfang Data Knowledge Service Platform (WanFang) (1998 to 31 December 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing oral Astragalus as a sole Chinese herbal preparation with placebo to prevent frequent episodes of ARTIs in children. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for this review. We assessed search results to identify relevant studies. We planned to extract data using standardised forms. Disagreements were to be resolved through discussion. Risk of bias was to be assessed using the Cochrane 'Risk of bias' tool. We planned to use mean difference (MD) or standardised mean difference (SMD) for continuous data and risk ratio (RR) or odds ratio (OR) to analyse dichotomous data, both with 95% confidence intervals (CIs). MAIN RESULTS: We identified 6080 records: 3352 from English language databases, 2724 from Chinese databases, and four from other sources. Following initial screening and deduplication, we obtained 120 full-text papers for assessment. Of these, 21 were not RCTs; 55 did not meet the inclusion criteria because: participants were aged over 14 years; definition was not included for recurrent or frequent episodes;Astragalus preparation was not an intervention; Astragalus preparation was in the formula but was not the sole agent; the Astragalus preparation was not administered orally; or Astragalus was used for treatment rather than prevention of ARTI. A further 44 studies were excluded because they were not placebo-controlled, although other inclusion criteria were fulfilled.No RCTs met our inclusion criteria. AUTHORS' CONCLUSIONS: We found insufficient evidence to enable assessment of the effectiveness and safety of oral Astragalus as a sole intervention to prevent frequent ARTIs in children aged up to 14 years. | Astragalus propinquus |
Benign gynecologic conditions constitute the majority of the general gynecologist's practice. Along with health maintenance examinations, contraceptive management, family planning issues, and concerns about incontinence, the gynecologic conditions for which patients commonly present include adnexal masses, leiomyomata, endometriosis, and pelvic inflammatory disease. This article addresses each of these last four entities and incorporates a discussion of their etiologies, clinical presentations, keys to diagnosis, and the various treatment options available. | Genital Diseases |
The significant physical and emotional effects of chemotherapy-induced nausea and vomiting (CINV) are experienced by cancer patients. Severe symptoms decrease the patient's quality of life and potentially deters further treatment. The five main forms of CINV (i.e., acute, delayed, anticipatory, breakthrough, and refractory) require different treatment regimens, which often include 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids. Despite a significant amount of research and development of antiemetic agents, management of CINV remains a great challenge with many needs waiting to be adequately addressed, such as controlling non-acute CINV, developing appropriate CINV treatment protocols for multiple-day chemotherapy patients, and providing options for those prone to CINV despite treatment. Further research is required to optimize CINV management for these patients." | Neurokinin-1 Receptor Antagonists |
Cognitive impairment is one of the most common comorbidities in temporal lobe epilepsy. To recapitulate epilepsy-associated cognitive decline in an animal model of epilepsy, we generated pilocarpine-treated chronic epileptic mice. We present a protocol for three different behavioral tests using these epileptic mice: novel object location (NL), novel object recognition (NO), and pattern separation (PS) tests to evaluate learning and memory for places, objects, and contexts, respectively. We explain how to set the behavioral apparatus and provide experimental procedures for the NL, NO, and PS tests following an open field test that measures the animals' basal locomotor activities. We also describe the technical advantages of the NL, NO, and PS tests with respect to other behavioral tests for assessing memory function in epileptic mice. Finally, we discuss possible causes and solutions for epileptic mice failing to make 30 s of good contact with the objects during the familiarization sessions, which is a critical step for successful memory tests. Thus, this protocol provides detailed information about how to assess epilepsy-associated memory impairments using mice. The NL, NO, and PS tests are simple, efficient assays that are appropriate for the evaluation of different kinds of memory in epileptic mice. | Muscarinic Agonists |
INTRODUCTION: Intradialytic hypotension remains the most common complication for outpatient hemodialysis, and relative blood volume monitoring was designed to reduce hypotension. Reports of the usefulness of this technology, however, have been variable. METHODS: We audited the usefulness of relative blood volume monitoring recorded throughout the mid-week dialysis in 72 stable adult outpatients who had multifrequency bioimpedance measurements. RESULTS: The blood volume measurement (BVM) at the end of the session was 91.6 +/- 0.6% and was not different from the nadir BVM recorded (90.7 +/- 0.5). The BVM was strongly correlated with change in hematocrit (r = -0.56, p < 0.001) and albumin (r = -0.69, p < 0.001), but had no relationship with pre-, intra- or postdialysis blood pressure recordings. The BVM was not associated with ultrafiltration volume, but did correlate with a postdialysis change in extracellular fluid volume (r = -0.39, p = 0.006). CONCLUSION: In this audit, although the BVM at the end of the dialysis session was correlated with changes in hematocrit, serum albumin and extracellular fluid volume, the change in the relative BVM did not mirror changes in intradialytic blood pressure. | Blood Volume Determination |
Seaweeds of the genera Laminaria, Gelidium, and Porphyra have been used in both food and non-food industries due to their unique properties and characteristic biological activity. This study assesses the antioxidant activity and immunomodulatory properties of the acidic polysaccharides extracted from Laminaria ochroleuca, Porphyra umbilicalis, and Gelidium corneum collected in the Atlantic coast of Tarifa (Cadiz, Spain). The proliferation of murine cell line RAW 264 decreased with increasing concentration of polysaccharides of the three algal species. The highest both antioxidant (25.69 mumol TE g(-1) DW) and immunomodulatory activities were observed in the sulfated polysaccharides of L. ochroleuca compared to that of P. umbilicalis and G. corneum. Sulfated polysaccharides of L. ochroleuca presented high potential anticancer activity in cell lines of human colon cancer HTC-116 (IC(50) = 0.44 mg mL(-1)), human malignant melanoma G-361 (IC(50) = 5.42 mg mL(-1)), breast adenocarcinoma human MCF-7 (IC(50) = 8.32 mg mL(-1)), and human leukemia U-937 (IC(50) = 3.72 mg mL(-1)). It is concluded that metabolites of L. ochroleuca can offer significant advantages for the pharmaceutical industry, particularly when macrophage activation is required. | Porphyra |
Retroperitoneal sarcomas are rare and aggressive tumors with a negative prognosis as there is currently no satisfactory treatment for them. The only proven factor that can significantly increase the otherwise poor survival of sarcoma patients is the radically of resection. However, the completeness of resection is hindered by the hypervascularized nature of sarcomas and the frequent involvement of major blood vessels. In this context, we propose to operate on retroperitoneal sarcomas only with the use of extracorporeal circulation, applying vascular clamps above and below the tumor, even with short periods of hypothermic circulatory arrest in complex cases. This technique would allow the surgeon to achieve complete tumor resections, approach large blood vessels easier and perform sofisticated vascular reconstructions with no fear of hemorrhage which is fundamental to achieve a bloodless surgical field. Also, we speculate on the etiology of retroperitoneal sarcomas that appear mostly during the period of menopause/andropause. Although both estrogens and androgens have been incriminated in inducing various cancer types, including sarcomas, an endogenous estradiol cathabolyte has been shown to have anti-tumor effects. Considering that during menopause/andropause sex steroid levels actually decrease, our second working hypothesis is that the increasing follicle-stimulating hormone (FSH) and especially luteinizing hormone (LH) levels, together with the relative estrogen/androgen imbalance, may be the triggering cause. Also, a certain level of estrogens (Methoxyestradiol) may be essential in limiting tumor development and dedifferentiation. Given that extragonadal sarcomas appear to behave as endocrine tumors, a targeted hormonal therapy, together with controlled radical resections in complex cases of tumor vascular involvement, would certainly provide a strong link to both prevention and treatment of retroperitoneal sarcomas and even of cancer in general. | Neoplasms, Hormone-Dependent |
A series of monoclonal antibodies reactive with normal myeloid cells at different stages of differentiation (anti-MY4, -MY7, -MY8, -Mo1, -Ia) were used to characterize the leukemic cells of 70 patients with acute myeloblastic leukemia (AML). Sixty-two of the leukemias expressed a phenotype corresponding to a recognizable immature normal myeloid cell. These 62 cases could be divided into 4 phenotype groups, corresponding approximately to the normal CFU-C (group I, 21%), myeloblast (group II, 26%), promyelocyte (group III, 8%), and promonocyte (group IV, 45%). Morphological subtyping of these leukemias tended to agree with the immunologic phenotype, particularly with more differentiated" morphological subtypes, such as acute monocytic leukemia or acute promyelocytic leukemia. However, each phenotype group contained more than one morphological type of AML, indicating that the level of differentiation of the surface membrane of AML cells may not always be concordant with morphology. The phenotype groups were also analyzed with respect to cytochemical staining patterns, age, the presence of Auer rods, and complete remission rates. Statistically significant differences among the groups were noted in the distribution of myeloperoxidase staining, nonspecific esterase staining, and Auer rods. The complete remission rates varied from 60% (groups III and IV) to 88% (group II). These results suggest that surface marker analysis in AML may be used as a highly reproducible classification system that will provide additional information about the leukemic cells in conjunction with morphological analysis." | Naphthol AS D Esterase |
BACKGROUND: It remains unclear whether a residual tumor mass following therapy influences the prognosis of neuroblastoma. METHODS: We retrospectively reviewed 20 patients with intermediate-risk tumors treated at our institution between 1993 and 2012 to elucidate whether additional treatment is required for residual tumors. RESULTS: The patient ages at diagnosis ranged from 0 days to 7 years. The 5-year overall survival rate was 94.4%. Thirteen patients had Stage 3 disease and seven patients had Stage 4 disease. Nine patients showed intraspinal extension. Twelve patients had a residual tumor mass at the completion of therapy, and eight showed intraspinal extension. Five of these 12 patients showed metaiodobenzylguanidine (MIBG) uptake at the end of treatment, but the uptake disappeared during the follow-up period. Except for one patient who died due to treatment complications, the rest are all alive, and nine are alive with a residual mass. We examined the residual mass in four patients and found that these tissues had differentiated into a ganglioneuroma or changed to a necrotic tissue. For the three patients with neurological symptoms at the end of treatment, some slight neurological symptoms still remained during the follow-up. Five patients with an intraspinal mass eventually presented with new symptoms. CONCLUSIONS: The presence of a residual mass at the end of treatment did not influence the patients' prognosis. Therefore, an invasive radical surgical resection and additional treatment may not be necessary. Cases with a residual intraspinal mass also require a long-term follow-up to assess the neurological prognosis.The presence of a residual mass in cases of intermediate-risk neuroblastoma at the end of treatment did not influence the patients' prognosis. | Neoplasm, Residual |
Two distinct human liver and one erythrocyte aldehyde dehydrogenase (ALDH) were reported earlier.. In this study we show evidence to support the existence of another aldehyde dehydrogenase in human stomach tissues. This enzyme does not utilize formaldehyde, acetaldehyde or pyruvic aldehyde as substrate. Furfuraldehyde is readily oxidized while propion-aldehyde is used to a lesser extent. One genetic variant was seen among 71 Chinese stomach specimens while another different variant was found among 33 Indian samples." | Oxidoreductases Acting on Aldehyde or Oxo Group Donors |
A virulent avian infectious bronchitis virus (IBV) was isolated from 30-day-old broiler chickens that exhibited respiratory symptoms, nephropathologic lesions, and a high proportion of deaths in the People's Republic of China during 2005. The strain, designated YN, was genetically and pathologically characterized. Phylogenetic analysis showed that YN and most of the previously characterized IBV isolates found in China were phylogenetically classified into 2 main genetic clusters. The YN isolate caused severe lesions and resulted in deaths of 65% in experimental infections of 30-day-old specific-pathogen-free chickens. Tracheal and severe kidney lesions developed in all infected birds, confirming the ability of YN strain to induce both respiratory and renal disease. IBV antigens were detected by immunohistochemical analysis in the trachea, lung, kidney, and bursa, consistent with histopathologic observations, virus isolation, and reverse transcription PCR detection. We showed that YN IBV exhibits severe pathogenicity in chickens, and that similar viruses are prevalent in China. | Infectious bronchitis virus |
Overproduction of sweat, sweaty skin and body odours are unpleasant for many social groups. Body cleansing products are designed to combat these undesirable features of skin. In addition, antiperspirant and deodorant products are more specifically used in the underarm site by a large part of the adult population. Antiperspirants are offered to control emotionally triggered sweating in the armpit. Deodorants are designed to combat malodour generated from bacteria-modified sweat. This review summarizes the physiology of eccrine, apocrine and apoeccrine sweat glands. The mechanisms of action of antiperspirants and deodorants are described as well as the factors influencing their efficacies. A series of tests using various measurement methods can be used to demonstrate the efficacy of antiperspirants. These include the gravimetric method, water evaporation quantification, electrodermal measurements, staining procedures, dye injections and cyanoacrylate skin surface strippings and casting replicas. Deodorant efficacy can be evaluated by sensory assessments performed by an expert panel. Indirect support is provided by visualization of apocrine gland excretion and collection of sweat and volatile compounds. Microbiological assessments and chromatographic analysis also provide indirect information. | Deodorants |
UDP-sugars are key precursors for biomass production in nature (synthesis of cellulose, hemicellulose, etc.). They are produced de novo by distinct UDP-sugar producing pyrophosphorylases. Studies on the roles of these enzymes using genetic knockouts were hampered by sterility of the mutants and by functional-complementation from related enzyme(s), hindering clear interpretation of the results. In an attempt to override these difficulties, we turned to the reverse chemical genetics approaches to identify compounds which interfere with the activity of those enzymes in vivo. Hit expansion on one of such compounds, a salicylimide derivative, allowed us to identify several inhibitors with a range of activities. The present study provides a structure-activity relationship for these compounds. | Uridine Diphosphate Sugars |
Tocopherols are considered to be powerful antioxidants, but prooxidative effects are discussed for higher concentrations. The aim of this in vitro study was to investigate the dose-dependent inhibition of oxidation product formation caused by alpha-tocopherol, and to estimate the range of maximum antioxidant activity of alpha-tocopherol at different stages of lipid oxidation. Alpha-tocopherol was added to rapeseed oil triglycerides (ROTG, purified rapeseed oil) in concentrations ranging from 25 to 1500 micromol/kg ROTG. The inhibitory activity of alpha-tocopherol increased up to a concentration of 100 micromol/kg ROTG. A concentration of 125 micromol alpha-tocopherol/ kg ROTG did not result in an improved antioxidant effect. The formation of volatile secondary oxidation products followed the same trend, and the maximum inhibitory effect was also found for 100 micromol alpha-tocopherol/kg. Further, concentrations between 250 and 1500 micromol alpha-tocopherol/kg ROTG clearly caused increased formation of hydroperoxides during the induction period. However, compared to the control, all tested alpha-tocopherol concentrations resulted in a reduction of hydroperoxide formation and no prooxidative effects were observed. | alpha-Tocopherol |
INTRODUCTION: COVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals' response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals. METHODS: HIV-positive individuals (n = 121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naive to SARS CoV-2 was used. The participants' Anti-RBD IgG responses were measured by ELISA at baseline and 3-4 weeks after receiving the first dose of an mRNA vaccine). RESULTS: Eleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between the HIV negative control group (n = 20) and the combined HIV+ group (n = 106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm(3). (p < 0.0001). Increasing age was independently associated with decreased immunogenicity. CONCLUSION: HIV-positive individuals with CD4 counts over 250 cells/mm(3) have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm(3)) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose. | Immunogenicity, Vaccine |
In hypertensive animals and humans, cardiac hypertrophy may occur as a consequence of an external load on the heart. Several studies have suggested that the non-pulsatile components of arterial haemodynamics, such as arterial pressure and vascular resistance, do not adequately represent the ventricular afterload and are not well correlated with the degree of cardiac hypertrophy (CH). The present study was undertaken to analyse the correlation between the degree of CH and various haemodynamic parameters in the spontaneously hypertensive rat (SHR) with established hypertension. A total of 36 SHRs (6-8 months) with a tail-cuff pressure above 190 mm Hg were used. Control data were obtained from 32 age-matched normotensive Wistar Kyoto rats (WKY). Animals were anaesthetized with pentobarbitone sodium (40 mg/kg i.p.) and artificially ventilated with a respirator. A Millar catheter with a high-fidelity pressure sensor was used to record the aortic pressure and an electromagnetic flow transducer to monitor the aortic flow. The pressure and flow signals were subjected to Fourier transformation for the analysis of the arterial impedance spectrum. The left ventricular weight-to-body weight ratio (LVW/BW) was taken as a measure of the degree of CH. The measured haemodynamic parameters in these anaesthetized, open-chest SHRs were systolic pressure (SP) (mean +/- SE) 172 +/- 4 mm Hg, diastolic pressure (DP), 120 +/- 3 mm Hg, pulse pressure (PP) 52 +/- 2 mm Hg, peripheral resistance (Rp) 344,032 +/- 8,012 dyne.s.cm-5, characteristic impedance (Zc) 6,442 +/- 313 dyne.s.cm-5, the impedance modulus at the first harmonic (Z1) 26,611 +/- 1,061 dyne.s.cm-5, mean arterial compliance (Cm) 0.87 +/- 0.04 microliter/mm Hg and LVW/BW 3.092 +/- 0.026 mg/g.(ABSTRACT TRUNCATED AT 250 WORDS) | Cardiomegaly |
The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology. Employing yeast two-hybrid screening of a mouse kidney cDNA library with the carboxyl-terminal cytoplasmic domain of the murine AT1a receptor as a bait, we have isolated a novel protein with a predicted molecular mass of 18 kDa, which we have named ATRAP (for AT1 receptor-associated protein). ATRAP interacts specifically with the carboxyl-terminal domain of the AT1a receptor but not with those of angiotensin II type 2 (AT2), m3 muscarinic acetylcholine, bradykinin B2, endothelin B, and beta2-adrenergic receptors. The mRNA of ATRAP was abundantly expressed in kidney, heart, and testis but was poorly expressed in lung, liver, spleen, and brain. The ATRAP-AT1a receptor association was confirmed by affinity chromatography, by specific co-immunoprecipitation of the two proteins, and by fluorescence microscopy, showing co-localization of these proteins in intact cells. Overexpression of ATRAP in COS-7 cells caused a marked inhibition of AT1a receptor-mediated activation of phospholipase C without affecting m3 receptor-mediated activation. In conclusion, we have isolated a novel protein that interacts specifically with the carboxyl-terminal cytoplasmic domain of the AT1a receptor and affects AT1a receptor signaling." | 1-Sarcosine-8-Isoleucine Angiotensin II |
OBJECTIVE: Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential proatherogenic effects of domain interaction in vivo. METHODS AND RESULTS: We studied atherosclerosis susceptibility of hypomorphic Apoe mice expressing either Thr-61 or Arg-61 apoE (ApoeT(h/h) or ApoeR(h/h)mice). On a chow diet, both mouse models were normolipidemic with similar levels of plasma apoE and lipoproteins. However, on a high-cholesterol diet, ApoeR(h/h) mice displayed increased levels of total plasma cholesterol and very-low-density lipoprotein as well as larger atherosclerotic plaques in the aortic root, arch, and descending aorta compared with ApoeT(h/h) mice. In addition, evidence of cellular dysfunction was identified in peritoneal ApoeR(h/h) macrophages which released lower amounts of apoE in culture medium and displayed increased expression of major histocompatibility complex class II molecules. CONCLUSIONS: These data indicate that domain interaction mediates proatherogenic effects of apoE4 in part by modulating lipoprotein metabolism and macrophage biology. Pharmaceutical targeting of domain interaction could lead to new treatments for atherosclerosis in apoE4 individuals. | Apolipoprotein E4 |
The obtained and published data on pharynx regeneration in planarians have been reviewed. Planarians can regenerate from a small body fragment and restore all missing organs including the pharynx. The pharynx is a relatively autonomous organ with a differentiated structure and specialized function. Pharynx regeneration has specific features, and its studies are of considerable theoretical interest. Pharynx regeneration can also be a convenient model to study the molecular mechanisms of regeneration that remain undisclosed. In addition, this model can be used to test biologically active compounds in order to elucidate their effect on morphogenesis. This subject of investigation benefits by a simpler and more adequate analysis as well as a possibility to use large numbers of animals and small quantities of analyzed substances. | Pharynx |
To establish the evaluation method for muscle power exerted by explosive gripping, this study aimed to examine the reliability of parameters and the muscle power output properties in both genders. Fifteen young men and 15 women participated in this study. Each subject carried out explosive grip tests twice using a simple muscle power measurement device (weight loading method), each time with 20, 30, 40, and 50% loads of maximum grip strength (MGS) by isometric contraction. Peak power was drawn from the product of the measured peak velocity and relative loads. The reliability of each parameter in all loads was good (interclass correlation coefficient >0.75) for both genders. The MGS showed insignificant correlation with all parameters. Peak power values were larger in men than in women for all loads, and the women's values were 44.5-52.2% of the men's. A large gender difference was found for 20% MGS. In conclusion, the reliability of muscle power parameters measured by the measurement device in this study is high. It was judged that the device used in this study can properly evaluate the gender difference in muscle power output properties by explosive gripping. | Muscle Strength Dynamometer |
With the current shift to include positive outcomes of trauma, this research was designed to explore factors that allow growth to occur. Structural equation modeling was used to test a model for understanding posttraumatic growth. A sample (N = 174) of bereaved HIV/AIDS caregivers completed questionnaires. Spirituality, social support, and stressors were found to have a positive relationship with growth. Facilitation of posttraumatic growth is crucial to all helping professions. | Orthopsychiatry |
Four cases of ear reduction for congenital macrotia and ear asymmetry are presented. To minimize the visible scarring the technique of helical advancement was used. The indications for this uncommon procedure are discussed with a review of the literature. This simple technique has been effective in achieving the desired reduction, leaving the scar hidden in the eaves of the helix, and we endorse its wider use. | Ear, External |
Rational: Senescence is a major aging process that contributes to the development of cardiovascular diseases, but the underlying molecular mechanisms remain largely unknown. One reason is due to the lack of suitable animal models. We aimed to generate a cardiomyocyte (CM)-specific senescent animal model, uncover the underlying mechanisms, and develop new therapies for aging associated cardiac dysfunction. Methods: The gain/loss of circHIPK3 approach was used to explore the role of circHIPK3 in cardiomyocyte (CM) senescence. To investigate the mechanisms of circHIPK3 function in cardiac senescence, we generated CM-specific tamoxifen-induced circHIPK3 knockout (CKO) mice. We also applied various analyses including PCR, Western blot, nuclear and cytoplasmic protein extraction, immunofluorescence, echocardiography, RNA immunoprecipitation assay, RNA-pulldown assay, and co-immunoprecipitation. Results: Our novel CKO mice exhibited worse cardiac function, decreased circHIPK3 expression and telomere length shortening in the heart. The level of the senescence-inducer p21 in the hearts of CKO mice was significantly increased and survival was poor compared with control mice. In vitro, the level of p21 in CMs was significantly decreased by circHIPK3 overexpression, but increased by circHIPK3 silencing. We showed that circHIPK3 was a scaffold for p21 mRNA-binding protein HuR and E3 ubiquitin ligase beta-TrCP. circHIPK3 silencing weakened the interaction between HuR and beta-TrCP, reduced HuR ubiquitination, and enhanced the interaction between HuR and p21 mRNA. Moreover, we found that mice injected with human umbilical cord mesenchymal stem cell-derived exosomes (UMSC-Exos) showed increased circHIPK3 levels, decreased levels of p21, longer telomere length, and good cardiac function. However, these beneficial effects exerted by UMSC-Exos were inhibited by silencing circHIPK3. Conclusions: We successfully generated CM-specific CKO mice for aging research. Our results showed that deletion of circHIPK3 led to exaggerated CM senescence and decreased cardiac function. As a scaffold, circHIPK3 enhanced the binding of E3 ubiquitin ligase beta-TrCP and HuR in the cytoplasm, leading to the ubiquitination and degradation of HuR and reduced p21 activity. In addition, UMSC-Exos exerted an anti-senescence and cardio-protective effect by delivering circHIPK3. These findings pave the way to the development of new therapies for aging associated cardiac dysfunction." | beta-Transducin Repeat-Containing Proteins |
Interleukin-11 (IL-11) is a polyfunctional cytokine whose biological actions require a specific IL-11 receptor (IL-11R) and the transmembrane transducer gp130. Here we report the production of a soluble form of the murine IL-11R and demonstrate that it interacts with IL-11 ligand with high affinity. The affinity of IL-11 alone for gp130 is below the level of detection, but a complex of IL-11 and soluble IL-11R interacts with gp130 with high affinity. The addition of soluble IL-11R potentiates the effects of exogenous IL-11 in cells that are normally responsive to IL-11. A biological response to IL-11 can be reconstituted in BAF cells transfected with gp130 by addition of IL-11 and soluble IL-11R. These findings show that the cytoplasmic domain of the IL-11R is not required for the biological effects of IL-11 and that a complex of IL-11 and IL-11R mediates signalling by association with gp130." | Interleukin-11 Receptor alpha Subunit |
In-tube solid-phase microextraction (IT-SPME) was developed about 24 years ago as an effective sample preparation technique using an open tubular capillary column as an extraction device. IT-SPME is useful for micro-concentration, automated sample cleanup, and rapid online analysis, and can be used to determine the analytes in complex matrices simple sample processing methods such as direct sample injection or filtration. IT-SPME is usually performed in combination with high-performance liquid chromatography using an online column switching technology, in which the entire process from sample preparation to separation to data analysis is automated using the autosampler. Furthermore, IT-SPME minimizes the use of harmful organic solvents and is simple and labor-saving, making it a sustainable and environmentally friendly green analytical technique. Various operating systems and new sorbent materials have been developed to improve its extraction efficiency by, for example, enhancing its sorption capacity and selectivity. In addition, IT-SPME methods have been widely applied in environmental analysis, food analysis and bioanalysis. This review describes the present state of IT-SPME technology and summarizes its current trends and future perspectives, including method development and strategies to improve extraction efficiency. | Solid Phase Microextraction |
Porous poly(butyl methacrylate-co-ethylene dimethacrylate), poly(benzyl methacrylate-co-ethylene dimethacrylate), and poly(styrene-co-divinylbenzene) monoliths have been prepared on the top of standard sample plates used for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and the modified plates were used for laser desorption/ionization mass spectrometry (LDI-MS). The hydrophobic porous surface of these monoliths enables the transfer of sufficient energy to the analyte to induce desorption and ionization prior to TOFMS analysis. Both UV and thermally initiated polymerization using a mask or circular openings in a thin gasket have been used to define spot locations matching those of the MALDI plates. The desorption/ionization ability of the monolithic materials depends on the applied laser power, the solvent used for sample preparation, and the pore size of the monoliths. The monolithic matrices are very stable and can be used even after long storage times in a typical laboratory environment without observing any deterioration of their properties. The performance of the monolithic material is demonstrated with the mass analysis of several small molecules including drugs, explosives, and acid labile compounds. The macroporous spots also enable the archiving of samples. | Nortriptyline |
Alexander disease is a neurological genetic disorder characterized by progressive white-matter degeneration, with astrocytes containing cytoplasmic aggregates, called Rosenthal fibers, including the intermediate filament glial fibrillary acidic protein (GFAP). The age of onset of the disease defines three different forms, infantile, juvenile and adult, all due to heterozygous GFAP mutations and characterized by a progressive less severe phenotype from infantile to adult forms. In an Italian family with a recurrent mild adult onset of Alexander disease, we have identified two GFAP mutations, coupled on a same allele, leading to p.[R330G; E332K]. Functional studies on this complex allele revealed less severe aggregation patterns compared to those observed with p.R239C GFAP mutant, associated with a severe Alexander disease phenotype. Moreover, in addition to confirming the involvement of the ubiquitin-proteasome system in cleaning cells from aggregates and a dominant effect of the novel mutant protein, in cells expressing the mild p.[R330G; E332K] mutant we have observed that indirect alphaB-crystallin overexpression, induced by high extracellular potassium concentration, could completely rescue the correct filament organization while, under the same experimental conditions, in cells expressing the severe p.R239C mutant only a partial rescue effect could be achieved. | Alexander Disease |
BACKGROUND: Although proven measures for reducing injury due to motor vehicle collision and residential fires exist, the number of families properly and consistently using child passenger restraints and smoke alarms remains low. This paper describes the design of the Safety In Seconds (SIS) 2.0 study, which aims to evaluate the impact of a smartphone app on parents' use of child restraints and smoke alarms. METHODS: SIS is a multisite randomised controlled trial. Participants are parents of children aged 4-7 years who are visiting the Pediatric Emergency Department or Pediatric Trauma Service. Parents are randomised to receive tailored education about child passenger safety or about fire safety via the SIS smartphone app. A baseline and two follow-up surveys at 3 months and 6 months are conducted. Primary outcomes are: (1) having the correct child restraint for the child's age and size; (2) restraining the child in the back seat of the car; (3) buckling the child up for every ride; (4) having the restraint inspected by a child passenger safety technician; (5) having a working smoke alarm on every level of the home; (6) having hard-wired or lithium battery smoke alarms; (7) having and (8) practising a fire escape plan. DISCUSSION: Finding ways to communicate with parents about child passenger and fire safety continues to be a research priority. This study will contribute to the evidence about how to promote benefits of proper and consistent child restraint and smoke alarm use. TRIAL REGISTRATION NUMBER: NCT02345941; Pre-results. | Child Restraint Systems |
The marine picocyanobacteria Synechococcus and Prochlorococcus numerically dominate open ocean phytoplankton. Although evolutionarily related they are ecologically distinct, with different strategies to harvest, manage and exploit light. We grew representative strains of Synechococcus and Prochlorococcus and tracked their susceptibility to photoinactivation of Photosystem II under a range of light levels. As expected blue light provoked more rapid photoinactivation than did an equivalent level of red light. The previous growth light level altered the susceptibility of Synechococcus, but not Prochlorococcus, to this photoinactivation. We resolved a simple linear pattern when we expressed the yield of photoinactivation on the basis of photons delivered to Photosystem II photochemistry, plotted versus excitation pressure upon Photosystem II, the balance between excitation and downstream metabolism. A high excitation pressure increases the generation of reactive oxygen species, and thus increases the yield of photoinactivation of Photosystem II. Blue photons, however, retained a higher baseline photoinactivation across a wide range of excitation pressures. Our experiments thus uncovered the relative influences of the direct photoinactivation of Photosystem II by blue photons which dominates under low to moderate blue light, and photoinactivation as a side effect of reactive oxygen species which dominates under higher excitation pressure. Synechococcus enjoyed a positive metabolic return upon the repair or the synthesis of a Photosystem II, across the range of light levels we tested. In contrast Prochlorococcus only enjoyed a positive return upon synthesis of a Photosystem II up to 400 mumol photons m-2 s-1. These differential cost-benefits probably underlie the distinct photoacclimation strategies of the species. | Prochlorophytes |
Selecting appropriate tools providing reliable quantitative measures of individual populations in biofilms is critical as we now recognize their true polymicrobial and heterogeneous nature. Here, plate count, quantitative real-time polymerase chain reaction (q-PCR) and peptide nucleic acid probe-fluorescence in situ hybridization (PNA-FISH) were employed to quantitate cystic fibrosis multispecies biofilms. Growth of Pseudomonas aeruginosa, Inquilinus limosus and Dolosigranulum pigrum was assessed in dual- and triple-species consortia under oxygen and antibiotic stress. Quantification methods, that were previously optimized and validated in planktonic consortia, were not always in agreement when applied in multispecies biofilms. Discrepancies in culture and molecular outcomes were observed, particularly for triple-species consortia and antibiotic-stressed biofilms. Some differences were observed, such as the higher bacterial counts obtained by q-PCR and/or PNA-FISH (</=4 log(10) cells/cm(2)) compared to culture. But the discrepancies between PNA-FISH and q-PCR data (eg D. pigrum limited assessment by q-PCR) demonstrate the effect of biofilm heterogeneity in method's reliability. As the heterogeneity in biofilms is a reflection of a myriad of variables, tailoring an accurate picture of communities changes is crucial. This work demonstrates that at least two, but preferentially three, quantification techniques are required to obtain reliable measures and take comprehensive analysis of polymicrobial biofilm-associated infections. | Carnobacteriaceae |
Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression." | ATP Binding Cassette Transporter, Subfamily A |
The binding characteristics of 3H-quinuclidinyl benzilate (QNB) to strips of intact tissue and to isolated plasma membrane fraction (PM) from rabbit urinary bladder were studied. QNB binding to both preparations was of high affinity and low capacity. The equilibrium dissociation constants (KD) for binding to tissue strips and PM were 2.2 and 0.045 nM respectively. Muscarinic antagonists inhibited QNB binding more effectively than agonists. Ca-antagonist D-600, but not nifedipine caused an inhibition of QNB binding to PM. Vanadate, ouabain or N-ethylmelaimide had no significant effect on QNB binding. In contrast to the binding in PM, binding in the intact tissue was reduced by K-depolarization. | Quinuclidinyl Benzilate |
BACKGROUND: Physical overload results in the development of pathological changes in the organs and systems and thereby causes their dysfunction. This leads to disadaptation, vegetative imbalance, and disturbances in the cardiovascular, nervous, endocrine and other systems. Taken together, these changes give rise to a syndrome of overtraining. In this context, the pathogenetically sound method of therapy appears to be the most suitable for the management of this condition based on the physiotherapeutic non-invasive interventions for the correction of physiological characteristics and the psycho-emotional status of the patients. One such method is bioresonance therapy (BRT). AIM: The objective of the present study was to evaluate the influence of bioresonance therapy (BRT) on the health status of the athletes presenting with the overtraining syndrome. MATERIAL AND METHODS: The study included 60 athletes presenting with the overtraining syndrome. They were divided into two groups each comprised of 30 subjects of comparable age, sex, sport, and sports qualification. Group I was composed of 30 athletes who were treated by means of bioresonance therapy. Group II (control) contained the athletes who received placebo procedures (i.e. the procedures with the use of a non-functioning device). All the athletes were examined before and after the treatment with the application of the clinical and instrumental methods. RESULTS: The study has demonstrated that the use of bioresonance therapy significantly increases the parasympathetic influence on the rhythm of the heart, reduces the stress on the central contour of its regulation, contributes to the 'economization' of the cardiac activity; has an antihypertensive effect (more pronounced with respect to systolic blood pressure (SBP)), has a normalizing effect on the variability of blood pressure (BP) in the patients with initial BP instability, and significantly decreases the time index in connection with monitoring blood pressure; moreover, BRT has a normalizing effect on the circadian rhythm of BP and corrects the rate of the morning rise in diastolic blood pressure (DBP). CONCLUSION: Bioresonance therapy can be considered as a method for the correction of the syndrome of overtraining in the athletes with the enhanced activity of the sympathetic nervous system. | Bioresonance Therapy |
We studied five unrelated Mexican carriers of the Spanish (deltabeta)(0)-thalassemia [(deltabeta)(0)-thal] mutation to characterize the size of the deletion, the 5' and 3' breakpoints and the 5' beta-globin haplotype. Sequence analysis revealed the presence of an 89,548 bp deletion. The delta- and beta-globin genes, two olfactory receptor genes (OR51V1 and OR52A1) and two pseudogenes (OR52Z1P and OR51A1P) were deleted. The 5' breakpoint was located at the same position as previously reported, and the 3' breakpoint was situated 7.0 kb downstream of OR52A1 and 11.7 kb upstream of OR52A5. The Spanish (deltabeta)(0)-thal allele was associated with the 5' haplotype 2 [- + + - +] in the studied patients. Because this mutation is relatively frequent in Spain, and the Mexican population contains a high level of Spanish genetic background, we propose that the mutation in both populations share a common ancestral origin. | delta-Globins |
Subsets and Splits