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pubmed_35_8344 | Today, these exist worldwide organizations related with the practice of medicine that are interested in marking recommendations and in formulating guidelines for better performance of physicians and health professionals. These organizations are headed by universities, associations, colleges, research center, and work groups and are made up of well-known physicians with academic prestige from the private and public sectors. This report presents a brief overview concerning the development of three clinical guides related with illnesses frequently observed in the physician's office: rhinosinusitis gastroesophageal reflux diseases (GERD), and prostate benign hyperplasia. These guides are issued by one of the most important academic institutions in the country. In the above-mentioned works, the efforts of specialist who are opinion leaders in these topics form different states of the country converge. Likewise, critical points to consider for producing clinical guides are provided mechanisms of diffusion, consultation, feedback and updating of these documents, have already been provided and focus on national medical practice quality of services, and the manner in which to carry out diagnosis and therapy at the different levels of medical care, with emphasis on preventing complications. | pubmed_35_8344 |
pubmed_600_21233 | A novel therapeutic design of nanofibrous scaffolds, holding a capacity to load and deliver dual growth factors, that targets bone regeneration is proposed. Mesoporous bioactive glass nanospheres (MBNs) were used as bioactive nanocarriers for long-term delivery of the osteogenic enhancer fibroblast growth factor 18 (FGF18). Furthermore, a core-shell structure of a biopolymer fiber made of polyethylene oxide/polycaprolactone was introduced to load FGF2, another type of cell proliferative and angiogenic growth factor, safely within the core while releasing it more rapidly than FGF18. The prepared MBNs showed enlarged mesopores of about 7 nm, with a large surface area and pore volume. The protein-loading capacity of MBNs was as high as 13% when tested using cytochrome C, a model protein. The protein-loaded MBNs were smoothly incorporated within the core of the fiber by electrospinning, while preserving a fibrous morphology. The incorporation of MBNs significantly increased the apatite-forming ability and mechanical properties of the core-shell fibers. The possibility of sequential delivery of two experimental growth factors, FGF2 and FGF18, incorporated either within the core-shell fiber (FGF2) or within MBNs (FGF18), was demonstrated by the use of cytochrome C. In vitro studies using rat mesenchymal stem cells demonstrated the effects of the FGF2-FGF18 loadings: significant stimulation of cell proliferation as well as the induction of alkaline phosphate activity and cellular mineralization. An in vivo study performed on rat calvarium defects for 6 weeks demonstrated that FGF2-FGF18-loaded fiber scaffolds had significantly higher bone-forming ability, in terms of bone volume and density. The current design utilizing novel MBN nanocarriers with a core-shell structure aims to release two types of growth factors, FGF2 and FGF18, in a sequential manner, and is considered to provide a promising therapeutic scaffold platform that is effective for bone regeneration. | pubmed_600_21233 |
pubmed_702_21759 | BACKGROUND
Liver disease is commonly seen in the clinic and its pathological characteristic is combined hepatocellular death and apoptosis. Promoting hepatocyte regeneration is one of the main methods of treating liver disease. Serotonin (5-HT) is an important compound which participates in various life process, and 95% of it is carried by platelets in the blood. A recent finding showed that platelet-derived serotonin is the key factor in liver regeneration, which fails without serotonin. This study aimed to investigate the effects of quipazine, a selective 5-HT receptor agonist, on proliferation and apoptosis in the human hepatocyte strain L-02.
METHODS
L-02 cells were cultured in medium with 5-HT and quipazine, and samples were collected at 24, 48, and 72 hours. The methyl thiazolyl tetrazolium (MTT) method was used to test viability, flow cytometry to assess the cell cycle, the Annexin-V/PI method to evaluate apoptosis, and immunohistochemistry to detect proliferating cell nuclear antigen (PCNA).
RESULTS
Compared with the control group, the viability of L-02 cells was improved in the 10, 50, and 250 microg/ml quipazine groups (P<0.05); the percentage of S-phase and PCNA-positive cells were increased in the 2, 10, 50, and 250 microg/ml quipazine groups (P>0.05); and no difference in the percentage of apoptotic cells was found between the 50 microg/ml quipazine and control groups (P>0.05).
CONCLUSION
Quipazine improves proliferation of a human hepatocyte strain in vitro, and this is not based on the inhibition of apoptosis. | pubmed_702_21759 |
pubmed_430_8501 | Polymorphism at Hbb (haemoglobin beta-chain) is widespread in natural populations of the house mouse, Mus musculus, and appears to be maintained by natural selection. This report is an attempt to correlate genotypic fluctuations at Hbb with a most important physiological attribute of haemoglobin, its oxygen carrying capacity. Oxygen affinity has been studied and P50 values have been measured in 12 inbred strains as well as wild-caught mice from Skokholm island. The mean P50 of each inbred strain is a constant characteristic, although there is high within-strain variation and the oxygen affinity of the blood of an individual can fluctuate considerably from week to week. The causes of this variation remain obscure but neither within-strain nor between-strain differences are correlated with known modulators of oxygen binding. In general, the blood of mice of inbred strains as well as wild-caught mice that are homozygous for Hbbd tends to have a higher oxygen affinity than that from comparable animals homozygous for Hbbs, but it seems likely that the oxygen dissociation properties of haemoglobin are not the only ones important in determining differential survival of a particular Hbb type under varying environmental stress. | 10.1098/rspb.1983.0050 |
pubmed_590_13016 | Notions of core, support, and inversion of a soft set have been defined and studied. Soft approximations are soft sets developed through core and support and are used for granulating the soft space. Membership structure of a soft set has been probed in and many interesting properties are presented. We present a new conjecture to solve an optimum choice problem. Our Example 31 presents a case where the new conjecture solves the problem correctly. | 10.1155/2014/327408 |
pubmed_784_19355 | We report palilalia and acquired stuttering in a 60-year-old Japanese male with Parkinson's disease. At the age of 54, he presented with resting tremor in the hand and foot on the left, and gradual slowness in voluntary movements. Two years later, resting tremor involved the right foot, and an expressionless face and frozen gait occurred. A diagnosis of Parkinson's disease was made and treatment with L-dopa and carbidopa resulted in conspicuous improvement. At the age of 57, he developed compulsive repetitions of syllables, words and phrases, and sentences infrequently when he spoke. They have been persisting for four years. Repetitions increased in spontaneous speech while they decreased in oral reading and repetition of sentences. These repetitions in speech were symptomatologically diagnosed as palilalia and acquired stuttering. Brain CT showed slight brain atrophy, and brain MRI disclosed a few lesions indicating lacunae in the left substantia nigra, left putamen, and right internal capsule. SPECT showed a slight decrease in blood flow in the frontal lobes and basal ganglia bilaterally. Full IQ on WAIS was 105, and neither agnosia nor apraxia was detected. Palilalia and acquired stuttering, though the pathomechanism has not been clarified, have been reported to occur usually secondary to cerebral vascucular lesions and very rarely in Parkinson's disease. In the present case, they may have been produced by the parkinsonian nigro-striatal lesions. Alternatively, they may have been induced by the small vascular lesions demonstrated by MRI. | pubmed_784_19355 |
pubmed_1044_16496 | We investigate numerically and experimentally the concept of nonlinear dispersion relation (NDR) in the context of partially coherent waves propagating in a one-dimensional water tank. The nonlinear random waves have a narrow-bandwidth Fourier spectrum and are described at leading order by the one-dimensional nonlinear Schrödinger equation. The problem is considered in the framework of integrable turbulence in which solitons play a key role. By using a limited number of wave gauges, we accurately measure the NDR of the slowly varying envelope of the deep-water waves. This enables the precise characterization of the frequency shift and the broadening of the NDR while also revealing the presence of solitons. Moreover, our analysis shows that the shape and the broadening of the NDR provides signatures of the deviation from integrable turbulence that is induced by high order effects in experiments. We also compare our experimental observations with numerical simulations of Dysthe and of Euler equations. | 10.1038/s41598-022-14209-7 |
pubmed_916_11343 | This cross-sectional study evaluated lifetime prevalence of suicide attempts in 170 HIV/AIDS patients with substance use disorders and the impact of suicide attempt history on subjective indices of quality of life and objective indices of cognitive and physical functioning. All patients met the diagnostic criteria for past-year cocaine or opioid use disorders and 27% of patients also had co-occurring alcohol use disorders. Compared to their counterparts without a history of a suicide attempt, patients with a history of a suicide attempt (n = 60, 35.3%) had significantly poorer emotional and cognitive quality of life scores (ps < .05), but not physical, social, or functional/global quality-of-life scores. Lifetime suicide attempt status was unrelated to objective indices of cognitive functioning, but there was a non-significant trend (p = .07) toward lower viral loads in those with a lifetime suicide attempt relative to those without. The findings indicate that suicide attempt histories are prevalent among HIV/AIDS patients with substance use disorders and relate to poorer perceived emotional and cognitive quality of life, but not objective functioning. HIV/AIDS patients with substance use disorders should be screened for lifetime histories of suicide attempts and offered assistance to improve perceived emotional and cognitive functioning. | 10.1177/0956462415585668 |
pubmed_984_15348 | UNLABELLED
Sex differences in clinical and experimental pain experiences are well documented. However, there has been little work investigating men's and women's experiences with common painful events. This study examined sex differences in the nature and intensity of common pain experiences. Participants (102 women and 85 men) completed the Prior Pain Experience Questionnaire, which is a 79-item assessment of an individual's pain experience, recalled pain ratings, and imagined pain ratings. Analyses of variance were conducted to assess for sex differences in overall pain experience and pain ratings. Men and women did not have significant differences in the overall number of reported pain experiences or in the overall mean pain rating of those experiences. However, they differed in specific pain events experienced (eg, men experienced concussions more than women) and pain ratings (eg, women rated minor surgery as significantly more painful than men). Individuals who imagined pain events tended to rate them as equally or more painful than individuals who experienced those pain events.
PERSPECTIVE
Results of this study demonstrate that men and women have varying types of pain experiences without evidence that the overall pain experience differs between sexes. It was also found that imagined pain ratings are often worse than experienced pain ratings, lending support for the tendency of individuals to catastrophize. | 10.1016/j.jpain.2009.04.016 |
pubmed_1067_3785 | The objective of this study was to evaluate the possibility and describe the methodology of a computed tomography-guided anterior approach to superior hypogastric plexus block for noncancer pain. A computed tomography-guided anterior approach to the superior hypogastric plexus was used in 2 patients with pelvic pain and anatomic disturbance of the lumbar spine, which was a contraindication to the conventional dorsal approach. The first case was a 43-year-old patient suffering from burning pain of the urethra. Pain relief using analgesics and antidepressants was insufficient. The posterior approach was excluded due to coexisting irritation of the L5 nerve root. The second case was a 68-year-old man suffering from chronic burning and itching pain of the urethra and glans penis. Conservative therapy (anti-inflammatory drugs, tramadol, spasmolytics) failed to provide satisfactory pain relief. The posterior approach was contraindicated because of laterally prominent L5 vertebral body osteophytes. Both patients received a prognostic block to the superior hypogastric plexus via the anterior approach guided by computed tomography. Visual analog scale scores prior to the block were 6 to 7 and 5 to 6, respectively. The visual analog scale scores 24 hours after the block were 1 and 0, respectively. The second patient received a permanent neurolytic block via the anterior approach to provide long-term pain relief. In conclusion, the authors describe the computed tomography-guided anterior approach to the superior hypogastric plexus for chronic pelvic pain. The technique is simple to perform, and the analgesic effect is satisfactory. More extensive studies are necessary to evaluate the safety of this approach. | 10.1097/01.ajp.0000146214.08910.21 |
pubmed_192_10306 | OBJECTIVES
This study examines neuromuscular firing patterns in overhead athletes and non-athletes of the periscapular, prime-moving, and rotator cuff muscles during "clinical" cardinal plane physiological movements.
DESIGN
Cohort prospective study.
SETTING
EMG recordings were taken of the periscapular, prime-moving, and rotator cuff muscles during flexion, scaption, and abduction performed at fast, medium, and slow speeds with a loaded (3 kg) and unloaded arm.
PARTICIPANTS
14 Handball players and 20 non-athletes. Differences in firing patterns between groups were analyzed by fitting mixed linear models with random intercepts per subject, and fixed factors for group, muscle, movement type, speed, and load.
MAIN OUTCOME MEASURES
No difference in timing of activation was seen between the professional athletes and non-athletes.
RESULTS
Speed and load appear to independently vary muscle activation timing in a non-intuitive manner in both athletes and non-athletes. Onset timing of periscapular, prime movers and rotator cuff muscles are prior to movement in all scenarios studied, with rotator cuff muscles firing last.
CONCLUSIONS
Onset activation patterns in overhead athletes are not different to non-athletes during cardinal plane movements. | 10.1016/j.ptsp.2019.02.007 |
pubmed_1121_12737 | OBJECTIVE
Behavioral parent training (BPT) is the first line of treatment for preschool-aged children with attention-deficit hyperactivity disorder (ADHD); however, clinically significant improvements are not universal. In the current study, we employ a person-centered approach to create subgroups of families based on the intersection of multiple parent, child, and family pre-treatment factors. Further, we explore the utility of pre-treatment family profiles in predicting post-treatment differences in observed parenting behavior (i.e., behavioral control, parental warmth) and clinically significant change in child ADHD and oppositional symptoms.
METHOD
Longitudinal data were collected using observational and parent-, teacher- and clinician-reported assessments from 130 parent-child dyads (Mage= 3.57, range = 3.0- 4.11, 73.8% male, 69.2% White, 25.6% Hispanic) participating in BPT.
RESULTS
Findings from the current study suggest three distinct family profiles, which consisted of one profile with high family stress (HFS) as evidenced by elevated symptomatology across parent, child, and family-level domains, a second profile with elevated parental anxiety (PA), and a final profile with elevated parental depression (PD). These family-centered profiles were differentially associated with changes in observed parenting practices. Specifically, the PD profile (39%) demonstrated minimal improvements in behavioral control and warmth following treatment. In contrast, the HFS profile (30%) only improved in behavioral control and the PA profile (31%) improved in both parenting domains following treatment. In addition, marginally significant differences in child oppositional and ADHD symptoms were observed across profiles.
CONCLUSIONS
Family-centered approaches may be useful for selecting and implementing interventions. | 10.1080/15374416.2020.1867987 |
pubmed_425_9613 | Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features-(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4-6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children. | 10.1007/s00401-019-02088-8 |
pubmed_862_12844 | We present what to our knowledge is a new application of optical frequency upconversion of images in quadratic materials to dynamic UV microstereolithography. A 150 x 150 point visible image transmitted by a liquid-crystal display was upconverted in a lithium triborate crystal, and the UV image was successfully used to polymerize a commercial stereolithographic resin. | 10.1364/ao.40.004953 |
pubmed_1076_21558 | CD1d belongs to a group of nonclassical antigen-presenting molecules that present glycolipid antigens and thereby activate natural killer T (NKT) cells, a subset of bifunctional T cells. Little is known so far regarding the expression and physiologic regulation of CD1d. Here we show that all-trans-retinoic acid (RA), the active metabolite of vitamin A, rapidly (1 hr after treatment) increases CD1d mRNA in human and rodent monocytic cells at a physiologic dose (10 nM). The induction is RA specific and RA receptor (RAR) dependent-RA and an RARalpha agonist, Am580, both had a pronounced positive effect, whereas the addition of RARalpha antagonist partially blocked the increase in CD1d mRNA induced by RA and Am580. The induction was also completely blocked by the presence of actinomycin D. A putative RA-response element was identified in the distal 5' flanking region of the CD1d gene, which binds nuclear retinoid receptors and was responsive to RA in both gel mobility shift assay and transient transfection assay in THP-1 cells. These results further confirmed the transcriptional regulation of RA in CD1d gene expression. Moreover, RA significantly increased alpha-galactosylceramide-induced spleen cell proliferation. These studies together provide evidence for a previously unknown mechanism of CD1d gene expression regulation by RA and suggest that RA is a significant modulator of NKT cell activation. | pubmed_1076_21558 |
pubmed_51_18630 | Physicians often struggle with how to manage the task of breaking bad news with patients. Moreover, the arduous nature of the task can contribute to physician detachment from the patient or an avoidance of breaking the news in a timely manner. A plan of action can only improve physician confidence in breaking bad news, and also make the task more manageable. Over a decade ago, Rabow and McPhee offered a strategy; the ABCDE plan, which provided a patient centered framework from which to deliver troubling news to patients and families. At the heart of this plan was the creation of a safe environment, the demonstration of timely communication skills, and the display of empathy on the physician's part. Careful consideration of the doctor's own reactions to death and dying also played an important role. A close review of the five tenets of this plan indicates the relevance of Rabow and McPhee's strategy today. The patient base in our nation and state continues to be older, on average, and physicians are faced with numerous patients who have terminal illness. A constructive plan with specific ideas for breaking bad news can help physicians effectively navigate this difficult task. | pubmed_51_18630 |
pubmed_538_13291 | As early as 1550 B.C., Egyptians realized the benefits of garlic as a remedy for a variety of diseases. Many epidemiological studies support the protective role of garlic and related allium foods against the development of certain human cancers. Natural garlic and garlic cultivated with selenium fertilization have been shown in laboratory animals to have protective roles in cancer prevention. Certain organoselenium compounds and their sulfur analogs have been identified in plants. Organoselenium compounds synthesized in our laboratory were compared with their sulfur analogs for chemopreventive efficacy. Diallyl selenide was at least 300-fold more effective than diallyl sulfide in protecting against 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in rats. In addition, benzyl selenocyanate inhibited the development of DMBA-induced mammary adenocarcinomas and azoxymethane-induced colon cancer in rats and benzo[a]pyrene-induced forestomach tumors in mice. The sulfur analog, benzyl thiocyanate, had no effect under the same experimental conditions. Furthermore, we showed that 1,4-phenylenebis(methylene)selenocyanate, but not its sulfur analog, significantly inhibited DMBA-DNA adduct formation and suppressed DMBA-induced mammary carcinogenesis. Collectively, these results indicate that structurally distinctive organoselenium compounds are superior to their corresponding sulfur analogs in cancer chemoprevention. Additionally, synthetic aromatic selenocyanates are more effective cancer chemopreventive agents than the naturally occurring selenoamino acids. Because plants are capable of utilizing selenium in a manner similar to that in sulfur assimilation pathways, future studies should aim at determining whether, under appropriate conditions, these potent cancer chemopreventive synthetic selenium compounds can be synthesized by garlic and related allium foods. | 10.1093/jn/136.3.864S |
pubmed_332_5668 | WHAT IS KNOWN AND OBJECTIVE
Thrombolysis using intravenous tissue plasminogen activator (tPA) is the only available evidence-based treatment for acute ischaemic stroke; however, its current utilization is very low. Therefore, the aim of this article is to review the literature regarding the use of intravenous tPA for the treatment of acute ischaemic stroke. The review will also compare utilization rates of thrombolysis in different centres across the world and identify key reasons for the underutilization of thrombolysis in stroke.
METHODS
MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA) and Google Scholar were searched for relevant original articles, review papers and other publications over the publication period 1995-2012.
RESULTS AND DISCUSSION
The National Institute of Neurological Disorders and Stroke (NINDS) (1995, N = 624 patients) and ECASS III (2008, N = 821 patients) are two pivotal randomized controlled trials providing evidence for the use of intravenous tPA within 3 h or 3-4.5 h from stroke onset, respectively. Both trials have shown that tPA administration decreases disability at 90 days from stroke. Furthermore, a recent pooled analysis of randomized controlled trials (2010, N = 3670 patients) supports these results, highlighting that early stroke treatment is associated with better outcomes, especially when treatment is started within 90 min of stroke onset (but suggesting that the benefit could be afforded within a 4.5-h time window). Three major observational trials, STARS (2000, N = 389 patients), CASES (2005, N = 1135 patients) and SITS-MOST (2007, N = 6483 patients), have reported acceptable safety and efficacy in clinical practice. However, only a small proportion of acute ischaemic stroke patients receive tPA in clinical practice, because of the limited availability of tPA-utilizing sites and suboptimal use of tPA in sites where it is available.
WHAT IS NEW AND CONCLUSION
tPA reduces disability in stroke patients. Moreover, acceptable safety has been demonstrated in routine clinical practice. However, tPA is significantly underutilized, and specific efforts are needed to encourage appropriate implementation of the stroke treatment guidelines to optimize the use of this important therapy. | 10.1111/j.1365-2710.2012.01366.x |
pubmed_401_7752 | Stabilizing the quality of industrial product materials remains a challenge. This applies mainly to new or significantly modified materials. It also refers to special processes. The tests of product quality can stabilize the quality of industrial product materials. The popular method for this is using the non-destructive testing (NDT). The NDT identifies incompatibility but does not determine the cause of its occurrence. Hence, it was necessary to support the process of identifying causes of incompatibilities in products. The purpose of the article was to develop a model based on a new approach to determine the ranking of actions that are possible as part of the process of stabilizing the quality of industrial products. The model was developed to improve quality through sequential and systematic methods of identification (and reduce) and incompatibility. The quality management techniques and decision method were applied and combined in this model, i.e., SMART(-ER) the method, method of selecting a team of experts, brainstorming (BM), Ishikawa diagram with the 5M rule, Likert scale validation technique, arithmetic average, and Grey Relational Analysis (GRA). The test of this model was carried out to find cracks in the outer hull of 418 alloy four-point bearing (CPW-S 5616), which was identified by NDT (magnetic-powder method). As a result, a ranking of activities was obtained to stabilize the quality of the product and the main cause of incompatibility was indicated, i.e., the cause which can influence to the most degree influence on occurrence the incompatibility. The originality of the proposed model is an application in the right order of specially selected and combined qualitative methods and supporting decision methods. The finding of causes of incompatibility of products is the basis of product improvement in the area of stabilizing the quality of materials, mainly by the occurrence of special processes. The universality of the model refers to the possibility of its application for any material, processes of its formation, and processes of products, and any incompatibilities where the model can be integrated with quality control. | 10.3390/ma15134440 |
pubmed_1063_12392 | PURPOSE
The aim of this work is to describe the clinical implementation of respiratory-gated spot-scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery.
MATERIALS AND METHODS
A custom respiratory gating interface incorporating the Real-Time Position Management System (RPM, Varian Medical Systems, Inc., Palo Alto, CA, USA) was developed in-house for our synchrotron-based delivery system. To assess gating performance, a motion phantom and radiochromic films were used to compare gated vs nongated delivery. Site-specific treatment planning protocols and conservative motion cutoffs were developed, allowing for free-breathing (FB), breath-holding (BH), or phase-gating (Ph-G). Room usage efficiency of BH and Ph-G treatments was retrospectively evaluated using beam delivery data retrieved from our record and verify system and DICOM files from patient-specific quality assurance (QA) procedures.
RESULTS
More than 70 patients were treated using active motion management between the launch of our motion mitigation program in October 2015 and the end date of data collection of this study in January 2018. During acceptance procedures, we found that overall system latency is clinically-suitable for Ph-G. Regarding room usage efficiency, the average number of energy layers delivered per minute was <10 for Ph-G, 10-15 for BH and ≥15 for FB, making Ph-G the slowest treatment modality. When comparing to continuous delivery measured during pretreatment QA procedures, the median values of BH treatment time were extended from 6.6 to 9.3 min (+48%). Ph-G treatments were extended from 7.3 to 13.0 min (+82%).
CONCLUSIONS
Active motion management has been crucial to the overall success of our SSPT program. Nevertheless, our conservative approach has come with an efficiency cost that is more noticeable in Ph-G treatments and should be considered in decision-making. | 10.1002/acm2.12584 |
pubmed_713_11818 | BACKGROUND
Chitin and its derivative chitosan are readily exploited, especially in food, cosmetic, pharmaceutical, biomedical, chemical, and textile industries. The biopolymers are currently recovered from the crustacean shells after purification from the large amount of proteins and minerals. The key problems are centered around a lot of chemical waste and allergenic potential of the heat-stable remaining proteins. Fungi can be considered as an alternative eco-friendlier source of the chitin and chitosan due to the lower level of inorganic materials and absence of the allergenic proteins.
RESULTS
The work presents a new chemical assay to change the composition of the milled Fomes fomentarius fruiting bodies. A gradual 13-fold increase of the chitin amount accompanied by 14-fold decrease of the glucan content was obtained after repetitive alkali-acidic treatment. Raw material contained mainly chitin with 30% degree of deacetylation. After the first and second alkali treatment, the polymer was defined as chitosan with comparable amounts of N-acetyl-D-glucosamine and D-glucosamine units. The last treated samples showed an increase of the chitin amount to 80%, along with typical for the natural tinder fibers degree of deacetylation and three-dimensional fibrous hollow structure.
CONCLUSIONS
A new approach allowed a gradual enrichment of the pulverized Fomes fomentarius fruiting bodies with chitin or chitosan, depending on the extraction conditions. High stability and fibrous structure of the fungal cell walls with a drastically increased chitin ratio let us suggest a possibility of the targeted production of the chitin-enriched fungal material biotechnologically under eco-friendly conditions. | 10.1186/s40694-021-00112-9 |
pubmed_665_20583 | OBJECTIVE
To investigate the role of human transcription factor NF-E2-related factor 2 (Nrf2) in the induction of the gene expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A and its isoforms by epigallocatechin gallate (EGCG).
METHODS
(1) Human colon carcinoma cells Caco-2 and HT-29 were cultured. Immunocytochemistry, western blotting and confocal laser microscopy were used to detect the protein expression of Nrf2. Twenty samples of colon carcinoma with surrounding normal tissues were collected during endoscopic course. (2) RNA interference expression vector pSilencer 3.1-H1 was used to construct four Nrf2-trageting plasmids: pSilence-Nrf2-A, B, C, and D and a control pSilence-CON. Cells were transfected with pSilence-Nrf2 for 48 hours to observe the effects of transient transfection. Cells were stably transfected with pSilence-Nrf2-B for 4 weeks and re-named as Caco-2-siNrf2 and HT-29-siNrf2 (siNrf2 cells), and others stably transfected with blank plasmid pSilencer 3.1-H1 were used as controls. (3) EGCG was added into the culture fluid of cells before and after the stably transfection. RT-PCR was used to detect the mRNA expression of Nrf2, UGT1A, UGT1A8 and UGT1A10 in cells and the samples of human colon cancer tissue.
RESULTS
(1) The expressions of UGT1A8 and UGT1A10 mRNA were significantly lower than that in the surrounding healthy mucosa. (2) The mRNA expression of Nrf2, UGT1A8, and UGT1A10 increased by 1.8-9.2 times after the addition of EGCG (all P < 0.05). Immunocytochemistry, western blotting and immunofluorescence demonstrated a significant increase of Nrf2 protein expression in the nucleus after treatment with EGCG. (3) SalIenzyme digestion and DNA sequencing confirmed that pSilence-Nrf2-A, B, C, and D and pSilence-CON were all successfully constructed. The inhibition rate of Nrf2 gene expression was above 80% 48 h after transfection with pSilence-Nrf2-B, and that was no significant difference after transfection with pSilence-CON (P > 0.05). There was specific inhibition of Nrf2 in Caco-2-siNrf2, HT-29-siNrf2 cells (both P < 0.01). (4) The basal levels of UGT1A8 and UGT1A10 mRNA expression in the Caco-2-siNrf2 and HT-29-siNrf2 cells were lower by 15%-65% in comparison with those in control, and the induction of genes by EGCG was largely attenuated in them (all P > 0.05).
CONCLUSION
Nrf2 is localized in the cytoplasm of non-stimulated cells, and EGCG triggered its rapid nuclear accumulation. Suppression of Nrf2 gene expression results in down-regulation of the constructive expression of UGT genes and their induction by EGCG. EGCG induces the expression of UGT1A, UGT1A8 and UGT1A10 genes via a Nrf2-dependent mechanism. | pubmed_665_20583 |
pubmed_310_1607 | We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SBP in SHR. Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment. But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner. | 10.1016/s0024-3205(01)01071-2 |
pubmed_108_22090 | BACKGROUND AND AIMS
Minimally invasive esophagectomy is a favored alternative in high-volume centers. We evaluated the introduction of, and transition to, minimally invasive esophagectomy at a medium volume tertiary referral center (10-20 esophagectomies annually) with focus on surgical results.
MATERIAL AND METHODS
Patients who underwent minimally invasive esophagectomy or open transthoracic surgery for carcinoma of the esophagus or gastroesophageal junction (Siewert I and II) during 2007-2016 were retrospectively studied. Sorted on surgical approach, perioperative data, surgical outcomes, and postoperative complications were analyzed and multivariate regression models were used to adjust for possible confounders.
RESULTS
One hundred and sixteen patients were included, 51 minimally invasive esophagectomy (21 hybrid and 30 totally minimally invasive) and 65 open resections. The groups were well matched. However, higher body mass index, neoadjuvant chemoradiotherapy, and cervical anastomosis were more frequent in the minimally invasive esophagectomy group. Minimally invasive esophagectomy was associated with less peroperative bleeding (384 vs 607 mL, p = 0.036) and reduced length of stay (14 vs 15 days, p = 0.042). Duration of surgery, radical resection rate, and postoperative complications did not differ between groups. Lymph node yield was higher in the minimally invasive esophagectomy group, 18 (13-23) vs 12 (8-16), p < 0.001, confirmed in a multivariate regression model (adjusted odds ratio 3.15, 95% class interval 1.11-8.98, p = 0.032).
CONCLUSION
The introduction of minimally invasive esophagectomy at a medium volume tertiary referral center resulted in superior lymph node yield, less peroperative blood loss and shorter length of stay, without compromising the rate of radical resection, or increasing the complication rate. | 10.1177/1457496919826722 |
pubmed_739_7599 | A case of ulcerative colitis complicated with convulsive seizure is reported. Magnetic resonance imaging studies strongly suggested cerebral vasculitis was the main cause of this episode. | 10.1007/BF02936377 |
pubmed_433_24939 | Lunar surface temperature is one of the fundamental thermophysical parameters of the lunar regolith, which is of great significance to the interpretation of remote-sensing thermal data. In this study, a daytime surface temperature model is established focusing on the lunar superficial layer with high spatial-temporal resolution. The physical parameters at the time of interest are adopted, including effective solar irradiance, lunar libration, large-scale topographic shading, and surrounding diffuse reflection. Thereafter, the 1/64° temperature distributions at five local times are quantitatively generated and analyzed in Sinus Iridum. Also, combined with Chang'E-2 microwave radiometer (CELMS) data and Diviner thermal infrared (TIR) data, the spectral emissivity distributions are estimated as a potential geological application of the simulated surface temperature. The results are as follows: (1) daytime surface temperature in Sinus Iridum is significantly affected by the local topography and observation time, and the influence of diffuse reflection energy is obvious; (2) the emissivity distributions provide a new way to understand the thermophysical properties difference of lunar regolith at different depths; (3) the influence of lunar orbiting revolution and precession on surface temperature should be analyzed carefully, which shows the importance of using the parameters at the time of interest. | 10.3390/s19245545 |
pubmed_650_15213 | The propagation of health education is within the range of nurses' professional duties. It necessitates the use of specific methods and techniques of work. "Inasmuch as the doctor treats, it is the nurse who creates best possible conditions for recovering and keeping health conditions permitting treatment or prevention" (3, 12). The increased level of general education among people and changes in modern nursing make the nurse face new tasks in her work. Nurse must be qualified in the field of health education if she works in the out-patient medical service as well as in hospital. She must be able to convince people about the necessity of changing life style, harmful and improper habits. The fulfillment of this difficult, yet important task may change patient's and his family's health habits and behaviour. So, nowadays the nurse must combine two functions: health-nursing called health-missioner's work with sick-nursing (1, 4, 9). Work in the field of health education requires high level of professional knowledge, skills, methods, recognition of educational and sanitary needs of a social group, personal direct influence based on proper social attitude, which is very important (10, 11). Health education is best and most effectively propagated in situations of individual contact with the patient (7). Patients seeking help in medical service institutions are interested in their health and want to do something in the field (8). The analysis of nurse's and midwife's positions shows that work in out-patient health service and in hospital offers a close contact with the patient and his environment.(ABSTRACT TRUNCATED AT 250 WORDS) | pubmed_650_15213 |
pubmed_874_22727 | We report a 17-yr-old boy who developed a microangiopathic hemolytic anemia presumed secondary to tacrolimus shortly following a living-related donor renal transplant. This was initially managed by plasmapheresis. Reinstitution of calcineurin inhibition using cyclosporine led to recurrence of hemolysis, so an alternative agent was needed. He was commenced on monthly intravenous belatacept, with no further recurrence of the hemolysis, and subsequent stable graft function. Modulation via CTLA-4 offers an alternative immunosuppressive tactic if current regimens produce graft threatening adverse effects. The method of administration and frequency of dosage of belatacept also lends itself well to the high-risk period of adolescence and transition. We propose that belatacept may therefore also have utility in difficult cases complicated by poor concordance, common in the adolescent age group. | 10.1111/petr.12278 |
pubmed_41_8511 | We present a quantum fingerprinting protocol relying on two-photon interference which does not require a shared phase reference between the parties preparing optical signals carrying data fingerprints. We show that the scaling of the protocol, in terms of transmittable classical information, is analogous to the recently proposed and demonstrated scheme based on coherent pulses and first-order interference, offering comparable advantage over classical fingerprinting protocols without access to shared prior randomness. We analyze the protocol taking into account non-Poissonian photon statistics of optical signals and a variety of imperfections, such as transmission losses, dark counts, and residual distinguishability. The impact of these effects on the protocol performance is quantified with the help of Chernoff information. | 10.1364/OE.25.027475 |
pubmed_669_6933 | Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing. Here, we present a set of 30 reporting criteria as the basis for such a guideline for Developmental and Reproductive Toxicology (DART) testing in the nematode Caenorhabditis elegans. Small organisms like C. elegans are upcoming in new approach methodologies for hazard assessment; thus, reliable and robust test protocols are urgently needed. A literature assessment of the fulfilment of the reporting criteria demonstrates that although studies describe methodological details, essential information such as compound purity and lot/batch number or type of container is often not reported. The formulated set of reporting criteria for C. elegans testing can be used by (i) researchers to describe essential experimental details (ii) data scientists that aggregate information to assess data quality and include data in aggregated databases (iii) regulators to assess study data for inclusion in regulatory hazard assessment of chemicals. | 10.1093/toxres/tfab109 |
pubmed_335_10642 | During a soccer match, players are often required to control the ball velocity of a kick. However, little information is available for the fundamental qualities associated with kicking at various effort levels. We aimed to illustrate segmental dynamics of the kicking leg during soccer instep kicking at submaximal efforts. The instep kicking motion of eight experienced university soccer players (height: 172.4 ± 4.6 cm, mass: 63.3 ± 5.2 kg) at 50, 75 and 100% effort levels were recorded by a motion capture system (500 Hz), while resultant ball velocities were monitored using a pair of photocells. Between the three effort levels, kinetic adjustments were clearly identified in both proximal and distal segments with significantly different (large effect sizes) angular impulses due to resultant joint and interaction moments. Also, players tended to hit an off-centre point on the ball using a more medial contact point on the foot and with the foot in a less upright position in lower effort levels. These results suggested that players control their leg swing in a context of a proximal to distal segmental sequential system and add some fine-tuning of the resultant ball velocity by changing the manner of ball impact. | 10.1080/02640414.2018.1470216 |
pubmed_278_17460 | Migraine seriously affects the physical and mental health of patients because of its recurrence and the hypersensitivity to the environment that it causes. However, the pathogenesis and pathophysiology of migraine are not fully understood. We addressed this issue in the present study using an autodynamic functional connectome model (A-DFCM) with twice-clustering to compare dynamic functional connectome patterns (DFCPs) from resting-state functional magnetic resonance imaging data from migraine patients and normal control subjects. We used automatic localization of segment points to improve the efficiency of the model, and intergroup differences and network metrics were analyzed to identify the neural mechanisms of migraine. Using the A-DFCM model, we identified 17 DFCPs-including 1 that was specific and 16 that were general-based on intergroup differences. The specific DFCP was closely associated with neuronal dysfunction in migraine, whereas the general DFCPs showed that the 2 groups had similar functional topology as well as differences in the brain resting state. An analysis of network metrics revealed the critical brain regions in the specific DFCP; these were not only distributed in brain areas related to pain such as Brodmann area 1/2/3, basal ganglia, and thalamus but also located in regions that have been implicated in migraine symptoms such as the occipital lobe. An analysis of the dissimilarities in general DFCPs between the 2 groups identified 6 brain areas belonging to the so-called pain matrix. Our findings provide insight into the neural mechanisms of migraine while also identifying neuroimaging biomarkers that can aid in the diagnosis or monitoring of migraine patients. | 10.1155/2021/6614520 |
pubmed_330_23781 | Lu/BCAM, the unique erythroid receptor for laminin 511/521, interacts with the erythrocyte membrane skeleton through spectrin binding. It has been reported that Hereditary Spherocytosis red blood cells (HS RBC) exhibit increased adhesion to laminin. We investigated the role of Lu/BCAM-spectrin interaction in the RBC adhesion properties of 2 splenectomised HS patients characterized by 40% spectrin deficiency. Under physiological flow conditions, HS RBC exhibited an exaggerated adhesion to laminin that was completely abolished by soluble Lu/BCAM. Triton extraction experiments revealed that a greater fraction of Lu/BCAM was unlinked to the membrane skeleton of HS RBC, as compared to normal RBC. Disruption of the spectrin interaction site in Lu/BCAM expressed in the transfected K562 cell line resulted in a weakened interaction to the skeleton and an enhanced interaction to laminin. These results demonstrated that the adhesion of HS RBC to laminin was mediated by Lu/BCAM and that its interaction with the spectrin-based skeleton negatively regulated cell adhesion to laminin. Finally, the results of this study strongly suggest that the reinforced adhesiveness of spectrin-deficient HS RBC to laminin is partly brought about by an impaired interaction between Lu/BCAM and the membrane skeleton. | 10.1111/j.1365-2141.2009.07973.x |
pubmed_543_18453 | Platelet-activating factor (PAF), proposed as an important inflammatory mediator in asthma, reproduces several of the features of asthma, such as microvascular leakage, mucus secretion, bronchoconstriction, and possibly increased airway responsiveness. Modipafant (UK-80,067) is the (+)-enantiomer of UK-74,505, a potent and specific PAF antagonist. We have assessed the effect of modipafant over 28 d in adult subjects with moderately severe asthma in a placebo-controlled parallel group study. A total of 218 patients with asthma were enrolled into the single-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr) entered the double-blind treatment phase after demonstrating symptomatic asthma in the final week of the single-blind run-in phase. Patients could take up to 1600 micrograms inhaled corticosteroid and an inhaled beta 2 agonist as rescue medication. A total of 59 patients with asthma took modipafant (one 50 mg capsule twice daily), and 61 took matched placebo. There was no significant difference between placebo and modipafant in diurnal variation in PEF, morning and evening PEF, clinic FEV1, rescue bronchodilator usage, symptom score, or airway responsiveness. We previously showed that the racemate UK-74,505 had no effect on antigen challenge, and this study shows that the active (+)-enantiomer modipafant has no effect in chronic asthma. This suggests that PAF is not an important mediator in asthma. | 10.1164/ajrccm.151.5.7735582 |
pubmed_290_10577 | Vitamin D deficiency is recognized as a pandemic affecting all ages and strata of population. The endogenous cutaneous synthesis of vitamin D is insufficient to maintain normal body requirement which necessitates the need for vitamin D supplementation or food-fortification. Conventional fat-soluble preparations of vitamin D have been traditionally used for prevention and therapeutic purposes. Recent advances in technology have enabled delivery of vitamin D through nanoemulsion formulations which ensure higher absorption and drug delivery. The following review briefly discusses the issues of bioavailability of nanoemulsion preparation of vitamin D vis-a-vis conventional fat soluble preparations. | 10.1016/j.jcot.2019.07.014 |
pubmed_560_21917 | The effects of ipsapirone and cannabidiol (CBD) on healthy volunteers submitted to a simulated public speaking (SPS) test were compared with those of the anxiolytic benzodiazepine diazepam and placebo. Four independent groups of 10 subjects received, under a double-blind design, placebo or one of the following drugs: CBD (300 mg), diazepam (10 mg) or ipsapirone (5 mg). Subjective anxiety was evaluated through the Visual Analogue Mood Scale (VAMS) and the State-trait Anxiety Inventory (STAI). The VAMS anxiety factor showed that ipsapirone attenuated SPS-induced anxiety while CBD decreased anxiety after the SPS test. Diazepam, on the other hand, was anxiolytic before and after the SPS test, but had no effect on the increase in anxiety induced by the speech test. Only ipsapirone attenuated the increase in systolic blood pressure induced by the test. Significant sedative effects were only observed with diazepam. The results suggest that ipsapirone and CBD have anxiolytic properties in human volunteers submitted to a stressful situation. | 10.1177/026988119300700112 |
pubmed_767_10125 | Deciphering a complete landscape of protein-RNA interactions in the human proteome remains an elusive challenge. We computationally elucidate RNA binding proteins (RBPs) using an approach that complements previous efforts. We employ two modern complementary sequence-based methods that provide accurate predictions from the structured and the intrinsically disordered sequences, even in the absence of sequence similarity to the known RBPs. We generate and analyze putative RNA binding residues on the whole proteome scale. Using a conservative setting that ensures low, 5% false positive rate, we identify 1511 putative RBPs that include 281 known RBPs and 166 RBPs that were previously predicted. We empirically demonstrate that these overlaps are statistically significant. We also validate the putative RBPs based on two major hallmarks of their RNA binding residues: high levels of evolutionary conservation and enrichment in charged amino acids. Moreover, we show that the novel RBPs are significantly under-annotated functionally which coincides with the fact that they were not yet found to interact with RNAs. We provide two examples of our novel putative RBPs for which there is recent evidence of their interactions with RNAs. The dataset of novel putative RBPs and RNA binding residues for the future hypothesis generation is provided in the Supporting Information. | 10.1002/pmic.201800064 |
pubmed_422_18649 | Sixteen cases of granulomatous mastitis were seen in the Breast Clinic of the Rio Blanco Regional Hospital in Veracruz, México. The mean age was 41.7 years (range 22-62), mean previous pregnancies was 5. Lactancy in last 6 months was registered in 50% of the cases, but no cases of puerperal mastitis were seen. Seventy five percent of the patients presented with a breast mass (mean 6 cm), suspicious of cancer in 62.5%. In 2 of 16 cases (12.5) there was an associated breast carcinoma, and in one case tuberculosis was the etiology. Surgical treatment consisted in wide local excision in 100% and mastectomy in 2 cases. Steroids were not used. Recurrent disease was seen in 2 cases at a mean follow-up of 20 months. Awareness of this rare entity is important for the surgeon and the pathologist because the definitive diagnosis is made microscopically, through evaluation of a wide breast tissue sample. | pubmed_422_18649 |
pubmed_370_9299 | 1. The role of carbonic anhydrase near the medullary chemoreceptors has been investigated in the cat. Vertebral artery injections have been used to cause abrupt changes in respiration as a result of changes in the activity of medullary chemoreceptors. 2. Injections of 100% CO2-saline were used to stimulate respiration and of Tris or alkalinized albumin solution to cause a reduction in respiration. 3. The injections gave rapid effects. We studied the effect on these of benzolamide (1-4 mg/kg i.v.) a carbonic anhydrase inhibitor which does not easily cross the blood-brain barrier and acetazolamide (50 mg/kg i.v.) an inhibitor which crosses the barrier more easily. 4. The effects of Tris were much reduced after benzolamide. Even addition of benzolamide to the injected Tris or albumin was sufficient to reduce their effects. 5. The effects of CO2-saline were reduced only after acetazolamide i.v. Whereas addition of carbonic anhydrase to injected Tris potentiated the effects on respiration, after acetazolamide this potentiation was much less marked. 6. It is concluded that carbonic anhydrase acts in the region of the medullary chemoreceptors at two sites: (a) outside the blood-brain barrier, probably at the luminal surface of the capillary endothelium, where it may act on plasma buffers, and (b) inside the barrier, in association with the chemoreceptors, where it may accelerate CO2/pH equilibration. | 10.1113/jphysiol.1981.sp013938 |
pubmed_39_17512 | Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the CFTR gene. We have explored a more efficient genetic screening strategy based on next-generation sequencing (NGS) of the CFTR gene. We validated this approach in a cohort of 177 patients with previously known CFTR mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq™ CFTR panel. The DNA libraries were pooled, barcoded, and sequenced using an Ion Torrent PGM sequencer. The combination of different robust bioinformatics tools allowed us to detect previously known pathogenic mutations and polymorphisms in the 177 samples, without detecting spurious pathogenic calls. In summary, the assay achieves a sensitivity of 94.45% (95% CI: 92% to 96.9%), with a specificity of detecting nonvariant sites from the CFTR reference sequence of 100% (95% CI: 100% to 100%), a positive predictive value of 100% (95% CI: 100% to 100%), and a negative predictive value of 99.99% (95% CI: 99.99% to 100%). In addition, we describe the observed allelic frequencies of 94 unique definitely and likely pathogenic, uncertain, and neutral CFTR variants, some of them not previously annotated in the public databases. Strikingly, a seven exon spanning deletion as well as several more technically challenging variants such as pathogenic poly-thymidine-guanine and poly-thymidine (poly-TG-T) tracts were also detected. Targeted NGS is ready to substitute classical molecular methods to perform genetic testing on the CFTR gene. | 10.1002/mgg3.149 |
pubmed_583_278 | BACKGROUND
To date, there are estimates for the percentage of unknown cases of doping and illicit drug use in fitness sports, but not for elite sports. This can be attributed to the problem of implementing questionnaires and surveys to get reliable epidemiological estimates of deviant or illicit behaviour.
METHODS
All athletes questioned were subject to doping controls as members or junior members of the national teams. In order to estimate the prevalence of doping and illicit drug abuse, the athletes were either issued an anonymous standardized questionnaire (SQ; n=1394) or were interviewed using randomized response technique (RRT; n=480). We used a two-sided z-test to compare the SQ and RRT results with the respective official German NADA data on the prevalence of doping.
RESULTS
Official doping tests only reveal 0.81% (n=25,437; 95% CI: 0.70-0.92%) of positive test results, while according to RRT 6.8% (n=480; 95% CI: 2.7-10.9%) of our athletes confessed to having practiced doping (z=2.91, p=0.004). SQ and RRT both revealed a prevalence of about 7% for illicit drug use, but SQ failed to indicate a realistic prevalence of doping (0.20%; 95% CI: 0.02-0.74%).
CONCLUSIONS
We demonstrate for the first time that data from official doping tests underestimate the true prevalence of doping in elite sports by more than a factor of eight. Our results indicate that implementing RRT before and after anti-doping measures could be a promising method for evaluating the effectiveness of anti-doping programs. | 10.1016/j.drugalcdep.2009.07.026 |
pubmed_242_10210 | The concept of health-related quality of life has a long history in the field of oncology treatment and research. We present a brief history of how the concept has evolved in oncology and the sentinel events in that process. We then focus on advances in measurement science as applied to health-related quality of life measures and argue that a compelling new set of measurement tools is now available, including brief, generic measures with good psychometric qualities (exemplified by the new PROMIS measures and the possibility of a common metric spanning all diseases). The last section of the paper turns to emerging opportunities for these measures, including in clinical trials, healthcare reform, and regulatory deliberations. Our conclusion is that health-related quality of life is more important today than it has ever been, and that the time has come for an even wider adoption of the new measures. | 10.1037/a0037821 |
pubmed_554_19573 | In this paper, we propose a multiview 3D display calibration algorithm that compensates for misalignment between constituent layers. To minimize distortion of the 3D image due to misalignment, we employ an iterative algorithm using camera feedback. We first establish a mathematical model for the multiview display and predict distortion of a test image pattern due to misalignment. Then, we define two characteristic features of the feedback camera image that indicate the status of the alignment. Based on the mathematical model, we design a compensation algorithm that consists of cascaded one-dimensional root-finding blocks for two-dimensional optimization. Finally, we experimentally verify the image distortion model, convergence of the iterative algorithm, and image quality improvement. The accuracy of the proposed algorithm exceeds the required accuracy for linear extrinsic crosstalk compensation. | 10.1364/AO.57.004576 |
pubmed_203_10216 | Prodigiosin (PG) is a bacterial red pigment with interesting immunosuppressive and apoptotic properties that have been partly attributed to its ability to uncouple V-ATPase through the promotion of the H+/Cl- symporter. In the present study, we investigate the effect of non-apoptotic concentrations of PG on the lysosomal-pH and on cell cycle progression in colon cancer cells. Lysosomal-pH was tested in DLD-1 cells using acridine orange vital staining. Orange granules, indicative of acidified lysosomes, decreased significantly in cells treated with 25 nM of PG for 1/2 h, and disappeared completely at 100 nM. This suggests that PG can induce lysosomal alkalinization without any apparent cytotoxic effect. Cell cycle progression was analysed in HT29 cells and we found that PG induces a blockage in the G1 phase. This blockage correlates with p21(WAF1/CIP1) induction, and it can be triggered either dependently or independently of p53. In conclusion, the reversible increase in lysosomal-pH and cytosol acidification induced by non-apoptotic concentrations of PG in colon cancer cells, suggests that the apoptotic process induced by PG can not be solely explained by changes in intracellular pH. The effect of intracellular acidification on cell cycle arrest must be analysed more exactly. | 10.1016/j.lfs.2005.04.059 |
pubmed_782_6924 | BACKGROUND
Recent advancements in clinical dentistry have increased the possibilities of surgical procedures in the mental region. A detailed knowledge of mental foramen (MF) morphometry is significant to preserve integrity of the mental nerve trunk in surgical interventions such as orthognathic surgery, implant placement and anaesthetic block.
OBJECTIVE
The aim of this study was to determine the most accurate position of the mental foramen by using new assessment approach in a sample of dental patients presenting to the specialist dental clinic, College of Dentistry, Al Jouf University, Saudi Arabia.
STUDY DESIGN
A retrospective study was performed using cone beam computed tomography (CBCT) of 600 patients (40.1 ± 11.78 years old). Following inclusion and exclusion criteria, 395 CBCT were finally obtained and analyzed for the most accurate position of the mental foramen (MF) by OnDemand 3D software (Seoul, Korea). Prevalence of shape of MF and accessory MF were also assessed. Pearson chi-square test was employed to test significant differences between genders and races.
RESULTS
The most common horizontal and vertical position of the mental foramen was in line with the long axis of 2nd premolar (41.3%) and below the root apex level (93.2%), respectively. The most common shape of MF was round type (72.66%). The prevalence of accessory 2MF and 3MF was 2.28% and 0.25%, respectively.
CONCLUSION
New information about MF presented in this article can help anatomists, prosthodontists, orthodontists, surgeons, forensic odontologists and paleoanthropologists to predict the position of the MF and perform safer surgeries. | 10.1080/00016357.2017.1387813 |
pubmed_534_12099 | The recent identification of the interplay between metabolizing enzymes and BCRP has drawn more and more attention from people. BCRP, a transporter belonging to ATP-binding cassette (ABC) family, has been hypothesized to play roles in many aspects including protecting the human body against therapeutics because it is expressed in the tissues that function as barriers in vivo. Efficient coupling of BCRP and metabolizing enzymes enables rapid elimination of foreign compounds from the body because BCRP could facilitate the excretion of metabolites catalyzed by phase I and II enzymes into bile, urine and feces. Without BCRP coupling, pass through the cell membrane may be difficult for them by passive diffusion because of the increment of the molecular weight and water solubility. Thus the metabolism-efflux alliance has extraordinary importance to drug metabolism, distribution, pharmacological effect, toxicity and elimination. In this manuscript, a brief discussion about the interplays of BCRP and metabolizing enzymes in liver, intestine, kidney, lung and other organs were presented and summarized. Many endogenous and exogenous compounds belong to different chemical groups, for instance, the dietary flavonoids and the steroidal hormones were involved. Clarifying the cooperation mechanisms of BCRP and enzymes could lead to a better prediction of drug clearance in vitro. | 10.2174/138920021610151210184205 |
pubmed_947_20753 | BACKGROUND
To reduce the spread of COVID-19, several countries in Africa instituted countrywide lockdowns and other public health measures. Whereas lockdowns contributed to the control of the pandemic, there were concerns about the unintended consequences of these measures especially in the most vulnerable populations. We assessed unintended socio-economic and health consequences due to the COVID-19 pandemic and the mitigation measures among slum dwellers in Kampala to inform the on-going and future pandemic response strategies.
METHODS
This was a mixed methods cross-sectional study conducted in Bwaise I and Bwaise III slums of Kawempe division, Kampala Uganda from October to December 2020. We used systematic sampling to randomly select 425 household heads for the face-to-face quantitative interviews. We also conducted six focus group discussions (FGDs) with slum dwellers and used photovoice among eight Community Health Workers (CHWs) to document unintended socio-economic and health consequences. Quantitative data were imported into STATA version 14.0 for analysis, while qualitative data were analysed thematically using NVivo version 12. Modified Poisson regression analysis was conducted to establish factors associated with impact on access to food.
RESULTS
Most respondents reported limited access to food (71.1%; 302/425); disruption in education (77.1%; 270/350); drop in daily income and wages (86.1%; 329/382) and loss of employment (63.1; 125/198). Twenty five percent of the respondents (25.4%; 86/338) reported domestic violence as one of the challenges. Seven themes emerged from the qualitative findings on the impact of COVID-19 including: limited access to food; negative impact on children's rights (child labour and teenage pregnancies) and education; poor housing and lack of accommodation; negative social behaviours; negative impact on family and child care; reduced income and employment; and negative impact on health and access to health care services.
CONCLUSION
The slum dwellers of Bwaise I and Bwaise III experienced several negative socio-economic and health consequences of COVID-19 and its prevention measures that severely affected their wellbeing. Children experienced severe consequences such as child labour and teenage pregnancies among the girls. Response activities should be contextualised to different settings and protocols to protect the vulnerable groups in the community such as children and women should be developed and mainstreamed in response activities. | 10.1186/s12889-021-12453-6 |
pubmed_1071_11737 | Over the centuries architectural theory evolved several notions of embodiment, proposing in the nineteenth and twentieth century that architectonic experience is related to physiological responses of the observer. Recent advances in the cognitive neuroscience of embodiment (or bodily self-consciousness) enable empirical studies of architectonic embodiment. Here, we investigated how architecture modulates bodily self-consciousness by adapting a video-based virtual reality (VR) setup previously used to investigate visuo-tactile mechanisms of bodily self-consciousness. While standing in two different interiors, participants were filmed from behind and watched their own virtual body online on a head-mounted display (HMD). Visuo-tactile strokes were applied in synchronous or asynchronous mode to the participants and their virtual body. Two interiors were simulated in the laboratory by placing the sidewalls either far or near from the participants, generating a large and narrow room. We tested if bodily self-consciousness was differently modulated when participants were exposed to both rooms and whether these changes depend on visuo-tactile stimulation. We measured illusory touch, self-identification, and performed length estimations. Our data show that synchronous stroking of the physical and the virtual body induces illusory touch and self-identification with the virtual body, independent of room-size. Moreover, in the narrow room we observed weak feelings of illusory touch with the sidewalls and of approaching walls. These subjective changes were complemented by a stroking-dependent modulation of length estimation only in the narrow room with participants judging the room-size more accurately during conditions of illusory self-identification. We discuss our findings and previous notions of architectonic embodiment in the context of the cognitive neuroscience of bodily self-consciousness and propose an empirical framework grounded in architecture, cognitive neuroscience, and VR. | 10.3389/fpsyg.2013.00354 |
pubmed_314_7638 | High-valent vanadium complexes bearing a variety of chelating aryloxides including di- and linear tri-phenolates, C/N-capped tripods, phenoxyimines and calixarenes type ligands, when used in combination with dialkylaluminium halides as co-catalyst and a reactivator, are found to act as highly active catalytic systems for alpha-olefin polymerisation. Pro-catalyst structure-catalytic activity trends can be identified for the various ligand families employed. | 10.1039/b924088h |
pubmed_247_16852 | Hepatocellular carcinoma is not only the leading cause of male cancer death in Taiwan, but also one of the most common cancers in the world. The survival of hepatocellular carcinoma patients is very low, mainly due to the lack of effective treatments. Radiation and chemotherapies in general are not satisfactory: surgery itself is the most effective treatment for hepatocellular carcinoma but only on small resectable tumors. The overall prognosis is still poor. Previously, we have found that the level of glucocorticoid receptor and its mRNA in hepatocellular carcinoma was significantly higher than that of the adjacent liver tissue. This correlated well with the elevated serum alpha-fetoprotein levels in patients with hepatocellular carcinoma. Recently, a female hormone, progesterone, has been found to inhibit the expression of alpha-fetoprotein in hepatoma cells. In addition, progesterone has been used to treat a few hepatocellular carcinoma patients with promising responses. These results together with our hypothesis that the expression of alpha-fetoprotein is regulated by glucocorticoid receptor complex in proliferating hepatocellular carcinoma cells lead to the conclusion that steroid hormones and/or their antagonists may interfere with the function of glucocorticoid receptors in tumors, consequently regulate tumor growth. The potential of hormonal therapy for treatment of hepatocellular carcinoma is worthy of further investigation. | 10.1016/0306-9877(91)90262-w |
pubmed_463_19970 | Subtalar joint instability is hypothesized to occur after injuries to the calcaneofibular ligament (CFL) in isolation or in combination with the cervical and the talocalcaneal interosseous ligaments. A common treatment for hindfoot instability is the application of an ankle brace. However, the ability of an ankle brace to promote subtalar joint stability is not well established. We assessed the kinematics of the subtalar joint, ankle, and hindfoot in the presence of isolated subtalar instability, investigated the effect of bracing in a CFL deficient foot and with a total rupture of the intrinsic ligaments, and evaluated how maximum inversion range of motion is affected by the position of the ankle in the sagittal plane. Kinematics from nine cadaveric feet were collected with the foot placed in neutral, dorsiflexion, and plantar flexion. Motion was applied with and without a brace on an intact foot and after sequentially sectioning the CFL and the intrinsic ligaments. Isolated CFL sectioning increased ankle joint inversion, while sectioning the CFL and intrinsic ligaments affected subtalar joint stability. The brace limited inversion at the subtalar and ankle joints. Additionally, examining the foot in dorsiflexion reduced ankle and subtalar joint motion. | 10.1002/jor.22468 |
pubmed_849_8938 | Hepatitis B virus X protein (HBx) is involved in the pathogenesis of hepatocellular carcinoma (HCC). Overexpression of the transcripts from the P3 and P4 promoters of the insulin-like growth factor-II (IGF-II) gene is observed in HCC. The present study investigated the involvement of HBx in IGF-II overexpression and its epigenetic regulation. Firstly, the effects of HBx on P3 and P4 mRNA expression, the methylation status of the P3 and P4 promoters, and MBD2 expression were analyzed in human HCC cells and HCC samples. Next, interaction between HBx and MBD2 or CBP/p300 was assessed by co-immunoprecipitation, and HBx-mediated binding of MBD2 and CBP/p300 to the P3 and P4 promoters and the acetylation of the corresponding histones H3 and H4 were evaluated by quantitative chromatin immunoprecipitation. Finally, using siRNA knockdown, we investigated the roles of MBD2 and CBP/p300 in IGF-II overexpression and its epigenetic regulation. Our results showed that HBx promotes IGF-II expression via inducing the hypomethylation of the P3 and P4 promoters, and that HBx increases MBD2 expression, directly interacts with MBD2 and CBP/p300, and elevates their recruitment to the hypomethylated P3 and P4 promoters with increased acetylation levels of the corresponding histones H3 and H4. Further results showed that endogenous MBD2 and CBP/p300 are necessary for HBx-induced IGF-II overexpression and that CBP/p300 presence and CBP/p300-mediated acetylation of histones H3 and H4 are partially required for MBD2 binding and its demethylase activity. These data suggest that HBx induces MBD2-HBx-CBP/p300 complex formation via interaction with MBD2 and CBP/p300, which contributes to the hypomethylation and transcriptional activation of the IGF-II-P3 and P4 promoters and that CBP/p300-mediated acetylation of histones H3 and H4 may be a rate-limiting step for the hypomethylation and activation of these two promoters. This study provides an alternative mechanism for understanding the pathogenesis of HBx-mediated HCC. | pubmed_849_8938 |
pubmed_425_2902 | Ribozymes are functional RNA molecules that can catalyze biochemical reactions. Since the discovery of the first catalytic RNA, various functional ribozymes (e.g., self-cleaving ribozymes, splicing ribozymes, RNase P, etc.) have been uncovered, and their structures and mechanisms have been identified. Ribozymes have the advantage of possessing features of "RNA" molecules; hence, they are highly applicable for manipulating various biological systems. To fully employ ribozymes in a broad range of biological applications in synthetic biology, a variety of ribozymes have been developed and engineered. Here, we summarize the main features of ribozymes and the methods used for engineering their functions. We also describe the past and recent efforts towards exploiting ribozymes for effective and novel applications in synthetic biology. Based on studies on their significance in biological applications till date, ribozymes are expected to advance technologies in artificial biological systems. | 10.1016/j.biotechadv.2019.107452 |
pubmed_588_23750 | Several animal models have been developed to investigate the pathobiology of pancreatitis, but few studies have examined the effects that altered pancreatic gene expression have in these models. In this study, the sensitivity to secretagogue-induced pancreatitis was examined in a mouse line that has an altered acinar cell environment due to the targeted deletion of Mist1. Mist1 is an exocrine specific transcription factor important for the complete differentiation and function of pancreatic acinar cells. Mice lacking the Mist1 gene [Mist1 knockout (KO) mice] exhibit cellular disorganization and functional defects in the exocrine pancreas but no gross morphological defects. Following the induction of pancreatitis with caerulein, a CCK analog, we observed elevated serum amylase levels, necrosis, and tissue damage in Mist1 KO mice, indicating increased pancreatic damage. There was also a delay in the regeneration of acinar tissue in Mist1 KO animals. Molecular profiling revealed an altered activation of stress response genes in Mist1 KO pancreatic tissue compared with wild-type (WT) tissue following the induction of pancreatitis. In particular, Western blot analysis for activating transcription factor 3 and phosphorylated eukaryotic initiation factor 2alpha (eIF2alpha), mediators of endoplasmic reticulum (ER) stress, indicated limited activation of this pathway in Mist1 KO animals compared with WT controls. Conversely, Mist1 KO pancreatic tissue exhibits increased expression of growth arrest and DNA damage inducible 34 protein, an inhibitor of eIF2alpha phosphorylation, before and after the induction of pancreatitis. These finding suggest that activation of the ER stress pathway is a protective event in the progression of pancreatitis and highlight the Mist1 KO mouse line as an important new model for studying the molecular events that contribute to the sensitivity to pancreatic injury. | 10.1152/ajpgi.00512.2006 |
pubmed_585_10650 | Many serious liver diseases affecting millions of people world-wide cannot be treated despite many efforts which warrants a search for new therapeutic strategies. Potent drugs may not be effective enough in vivo or exhibit adverse effects and enhanced delivery into the target cells may improve this significantly. We aim to summarize the available options for drug delivery to the different intrahepatic cell-types. The most relevant target cells are identified for each liver disease and the strategies for drug delivery to these cells are subsequently reviewed. The review describes the use of proteins, viruses, polymers and liposomes for therapeutic purposes in various liver diseases. It is shown that to date, all resident intrahepatic cells can be reached with several different drug carriers. Much progress has been made in recent years to deliver small drug molecules, proteins and nucleic acids specifically to the key pathogenic cells in vivo. The knowledge of drug targeting gained in the past decades, combined with a proper preclinical evaluation, may bring new therapeutics to the clinic in the near future. | 10.1016/j.jconrel.2012.02.011 |
pubmed_518_1596 | OBJECTIVE
To determine the effect on a cohort of family physicians of health care system reforms in Ontario and the relationship of reforms to their career satisfaction.
DESIGN
Follow-up survey in 1999 of a cohort initially studied in 1993, posing many of the original questions along with some new ones. Four focus groups of other Ontario family physicians.
SETTING
Family practices in Ontario.
PARTICIPANTS
All family physicians who had received certification after completing a family medicine residency between 1989 and 1991 and were practising in Ontario in 1993. This report addresses only those members of the cohort who continued to practise family medicine in Ontario (N = 236). Four focus groups with a total of 27 family physicians.
MAIN OUTCOME MEASURES
Reaction to health care system reforms. Perceived effect of reforms on practice. Current perception of quality of health care system and level of career satisfaction and changes in these variables since 1993.
RESULTS
Response rate was 53% of original cohort. Only three of 13 selected health reforms were believed to have had a favourable effect. Physicians reported lower levels of satisfaction with their careers. Overall quality of the health care system was perceived by both respondents and focus group members to have declined. Several difficulties affected practice and personal life.
CONCLUSION
Family physicians viewed the effect of health care reforms negatively and were significantly less satisfied with their careers than they were in 1993. Better consultation with stakeholders before implementation of reforms is needed to ensure that these stakeholders understand the likely effects of these reforms. | pubmed_518_1596 |
pubmed_521_317 | Derivatives of the murine bone marrow-derived, IL-3-dependent cell line, BAF3, were isolated following recombinant retroviral infection which showed disregulated expression of human c-Myc oncoprotein. Such cells entered apoptosis and lost viability more rapidly than parental BAF3 cells when IL-3 was removed. c-Myc disregulation also resulted in an inability of BAF3 cells to survive in either sub-optimal concentrations of IL-3, or saturating concentrations of IL-4 and insulin-like growth factor-1. Furthermore, BAF3 cells with disregulated c-Myc expression were more sensitive to the induction of apoptosis by DNA-damaging agents. These effects of c-Myc disregulation could be inhibited by co-expression of the Bcl-2 oncoprotein. The implications of these data for the transformation of haematopoietic cells by disregulation of Myc expression are discussed. | 10.1093/intimm/6.8.1169 |
pubmed_445_729 | Pituitary function studies have been carried out in eight male and eight female patients with Down's syndrome who were suspected of having hypothyroidism secondary to pituitary deficiency. In all cases, the response of Human Growth Hormone to hypoglycaemia was adequate and the response of Lutenising Hormone and Follicle Stimulating Hormone to the injection of Lutenising Hormone and Follicle Stimulating Hormone was not signfiicantly greater than that in age and sex-matched institutionalised controls. Therefore there is no evidence that the relative hypothyroidism in these patients is due to pituitary hypofunction, nor do the results provide evidence of pituitary deficiency in Down's syndrome generally. | 10.1111/j.1365-2788.1978.tb00985.x |
pubmed_984_23172 | Bicaudal-D (Bic-D) and Egalitarian (Egl) are required for the dynein-dependent localization of many mRNAs in Drosophila, but the mRNAs show no obvious sequence similarities, and the RNA-binding proteins that recognize them and link them to dynein are not known. In this issue of Genes & Development, Dienstbier and colleagues (pp. 1546-1558) present evidence that the elusive RNA-binding protein is Egl itself. As well as linking mRNA to dynein, they show that Egl also activates dynein motility by binding Bic-D and the dynein light chain. | 10.1101/gad.1821509 |
pubmed_1102_4194 | BACKGROUND
The burden of diabetes is exceptionally high among American Indian and Alaska Native (AI/AN) peoples. The Indian Health Service (IHS) and Tribal health programs provide education, case management, and advanced practice pharmacy (ECP) services for AI/ANs with diabetes to improve their health outcomes.
OBJECTIVE
The objective of this study was to evaluate patient outcomes associated with ECP use by AI/AN adults with diabetes.
RESEARCH DESIGN
This observational study included the analysis of IHS data for fiscal years (FY) 2011-2013. Using propensity score models, we assessed FY2013 patient outcomes associated with FY2012 ECP use, controlling for FY2011 baseline characteristics.
SUBJECTS
AI/AN adults with diabetes who used IHS and Tribal health services (n=28,578).
MEASURES
We compared health status and hospital utilization outcomes for ECP users and nonusers.
RESULTS
Among adults with diabetes, ECP users, compared with nonusers, had lower odds of high systolic blood pressure [odds ratio (OR)=0.85, P<0.001] and high low-density lipoprotein cholesterol (OR=0.89, P<0.01). Among adults with diabetes absent cardiovascular disease (CVD) at baseline, 3 or more ECP visits, compared with no visits, was associated with lower odds of CVD onset (OR=0.79, P<0.05). Among adults with diabetes and CVD, any ECP use was associated with lower odds of end-stage renal disease onset (OR=0.60, P<0.05). ECP users had lower odds of 1 or more hospitalizations (OR=0.80, P<0.001).
CONCLUSIONS
Findings on positive patient outcomes associated with ECP use by adults with diabetes may inform IHS and Tribal policies, funding, and enhancements to ECP services to reduce disparities between AI/ANs and other populations in diabetes-related morbidity and mortality. | 10.1097/MLR.0000000000001521 |
pubmed_428_2019 | The 2525 amino acid SMRT corepressor is an intrinsically disordered hub protein responsible for binding and coordinating the activities of multiple transcription factors and chromatin modifying enzymes. Here we have studied its interaction with HDAC7, a class IIa deacetylase that interacts with the corepressor complex together with the highly active class I deacetylase HDAC3. The binding site of class IIa deacetylases was previously mapped to an approximate 500 amino acid region of SMRT, with recent implication of short glycine-serine-isoleucine (GSI) containing motifs. In order to characterize the interaction in detail, we applied a random library screening approach within this region and obtained a range of stable, soluble SMRT fragments. In agreement with an absence of predicted structural domains, these were characterized as intrinsically disordered by NMR spectroscopy. We identified one of them, comprising residues 1255-1452, as interacting with HDAC7 with micromolar affinity. The binding site was mapped in detail by NMR and confirmed by truncation and alanine mutagenesis. Complementing this with mutational analysis of HDAC7, we show that HDAC7, via its surface zinc ion binding site, binds to a 28 residue stretch in SMRT comprising a GSI motif followed by an alpha helix. | 10.1038/s41598-017-03718-5 |
pubmed_278_15741 | BACKGROUND
Data-driven methods such as independent component analysis (ICA) makes very few assumptions on the data and the relationships of multiple datasets, and hence, are attractive for the fusion of medical imaging data. Two important extensions of ICA for multiset fusion are the joint ICA (jICA) and the multiset canonical correlation analysis and joint ICA (MCCA-jICA) techniques. Both approaches assume identical mixing matrices, emphasizing components that are common across the multiple datasets. However, in general, one would expect to have components that are both common across the datasets and distinct to each dataset.
NEW METHOD
We propose a general framework, disjoint subspace analysis using ICA (DS-ICA), which identifies and extracts not only the common but also the distinct components across multiple datasets. A key component of the method is the identification of these subspaces and their separation before subsequent analyses, which helps establish better model match and provides flexibility in algorithm and order choice.
COMPARISON
We compare DS-ICA with jICA and MCCA-jICA through both simulations and application to multiset functional magnetic resonance imaging (fMRI) task data collected from healthy controls as well as patients with schizophrenia.
RESULTS
The results show DS-ICA estimates more components discriminative between healthy controls and patients than jICA and MCCA-jICA, and with higher discriminatory power showing activation differences in meaningful regions. When applied to a classification framework, components estimated by DS-ICA results in higher classification performance for different dataset combinations than the other two methods.
CONCLUSION
These results demonstrate that DS-ICA is an effective method for fusion of multiple datasets. | 10.1016/j.jneumeth.2021.109214 |
pubmed_799_26 | OBJECTIVE
To determine the content of amentoflavone in 11 species of Selaginella medicinal materials.
METHODS
HPLC was used with kromasil (250 x 4. 6 mm, 5 microm) column. The mobile phase consisted of methanol and phosphate buffer. The gradient condition was 0-->28 min with methanol 50%-->58%, and 30-->35 min with methanol 58%-->70%. The column temperature was 40 degrees C. The flow rate was 1. 0 ml/min and the detection wavelength at 330 nm.
RESULTS
Amentoflavone showed a good linearity in the range of 153 - 767 ng. The average recovery was 97.03% and RSD was 0. 80% (n = 5).
CONCLUSION
The method was rapid, accurate and can be used for quality control of Selaginella medicinal materials. | pubmed_799_26 |
pubmed_915_19674 | Cardiac disease can present in the training room through three portals: the preparticipation history and physical may identify concerns, the athlete may present with symptoms, or screening modalities may demonstrate abnormal findings. Training-related cardiovascular remodeling can mimic real disease, therefore providers must be able to separate the two. Sports medicine providers must be knowledgeable in how these present and how to care for these concerns to ensure proper care and avoid unnecessary restrictions of athletes. This article discusses 10 common cardiac concerns that can arise in the training room. | 10.1016/j.csm.2019.05.002 |
pubmed_422_19574 | Fucoid zygotes establish a rhizoid-thallus growth axis in response to environmental signals; however, these extrinsic cues are not necessary for polarization, suggesting that zygotes may have inherent polarity. The hypothesis that sperm entry provides a default pathway for polarization of zygotes cultured in the absence of environmental signals was tested, and was supported by several lines of evidence. First, an F-actin patch, a cortical marker of the rhizoid pole, formed at the sperm entry site within minutes of fertilization. Second, the sperm entry site predicted the site of polar adhesive secretion (the first morphological manifestation of the rhizoid pole) and the position of rhizoid outgrowth. Third, when fertilization was restricted to one hemisphere of the egg, rhizoid outgrowth always occurred from that hemisphere. Fourth, delivery of sperm to one location within a population of eggs resulted in polarization of both adhesive secretion and rhizoid outgrowth toward the sperm source. Finally, induction of polyspermy using low sodium seawater increased the frequency of formation of two rhizoids. Sperm entry therefore provides an immediate default axis that can later be overridden by environmental cues. | 10.1242/dev.127.3.493 |
pubmed_547_2958 | PURPOSE
To review and update techniques of posterior segment ophthalmic fundus imaging.
DESIGN
Literature review and collective experience of the authors.
METHODS
This perspective includes sections on digital imaging, fundus autofluorescence, ultrasonography, angiography, and optical coherence tomography (OCT) -ophthalmoscopy written by leading clinicians and researchers in these areas.
RESULTS
Digital angiography has become the new standard in the ophthalmic community based upon improved technology which has enhanced resolution, processing time, and ease of image duplication, manipulation, and transmission. A relatively new imaging technique, fundus autofluorescence, highlights lipofuscin deposits and improves our understanding of the metabolic status of the retinal pigment epithelium. Diagnostic ultrasonography continues to be a major adjunct to ocular evaluation where advances now allow for exceptional versatility and portability. High speed angiographic techniques provide detailed visualization of choroidal perfusion which improves our understanding of both normal and pathologic vascular phenomenon. Advances in high-resolution OCT currently under development promise an even more detailed fundus representation. The integration of the scanning laser ophthalmoscope and OCT has produced a dynamic new instrument, the OCT ophthalmoscope, which simultaneously images the fundus in numerous ways with point to point correlation.
CONCLUSIONS
Ophthalmic imaging technology has revolutionized fundus examination. Currently available systems have contributed significantly to our understanding of the pathophysiology and treatment of various retinal diseases. Future advances promise near histologic resolution of retinal structures as well as real-time image manipulation and instantaneous transmission world-wide. | 10.1016/j.ajo.2003.12.035 |
pubmed_20_8270 | This article employs meta-analysis procedures to evaluate whether children with cochlear implants demonstrate lower spoken-language vocabulary knowledge than peers with normal hearing. Of the 754 articles screened and 52 articles coded, 12 articles met predetermined inclusion criteria (with an additional 5 included for one analysis). Effect sizes were calculated for relevant studies and forest plots were used to compare differences between groups of children with normal hearing and children with cochlear implants. Weighted effect size averages for expressive vocabulary measures (g = -11.99; p < .001) and for receptive vocabulary measures (g = -20.33; p < .001) indicated that children with cochlear implants demonstrate lower vocabulary knowledge than children with normal hearing. Additional analyses confirmed the value of comparing vocabulary knowledge of children with hearing loss to a tightly matched (e.g., socioeconomic status-matched) sample. Age of implantation, duration of implantation, and chronological age at testing were not significantly related to magnitude of weighted effect size. Findings from this analysis represent a first step toward resolving discrepancies in the vocabulary knowledge literature. | 10.1093/deafed/env060 |
pubmed_377_21739 | The groundwater quality for drinking, domestic and irrigation in the village Lutfullapur Nawada, Loni, district Ghaziabad, U.P., India, has been assessed. Groundwater samples were collected, processed and analyzed for temperature, pH, conductivity, salinity, total alkalinity, carbonate alkalinity, bicarbonate alkalinity, total hardness, calcium hardness, magnesium hardness, total solids, total dissolved solids, total suspended solids, nitrate-nitrogen, chloride, fluoride, sulfate, phosphate, silica, sodium, potassium, calcium, magnesium, total chromium, cadmium, copper, iron, nickel, lead and zinc. A number of groundwater samples showed levels of electrical conductivity (EC), alkalinity, chloride, calcium, sodium, potassium and iron exceeding their permissible limits. Except iron, the other metals (Cr, Cd, Cu, Ni, Pb, and Zn) were analyzed below the permissible limits. The correlation matrices for 28 variables were performed. EC, salinity, TS and TDS had significant positive correlations among themselves and also with NO (3) (-) , Cl(-), alkalinity, Na(+), K(+), and Ca(2+). Fluoride was not significantly correlated with any of the parameters. NO (3) (-) was significantly positively correlated with Cl(-), alkalinity, Na(+), K(+) and Ca(2+). Chloride also correlated significantly with alkalinity, Na(+), K(+) and Ca(2+). Sodium showed a strong and positive correlation with K(+) and Ca(2+). pH was negatively correlated with most of the physicochemical parameters. This groundwater is classified as a normal sulfate and chloride type. Base-exchange indices classified 73% of the groundwater sources as the Na(+)-SO (4) (2-) type. The meteoric genesis indices demonstrated that 67% of groundwater sources belong to a deep meteoric water percolation type. Hydrochemical groundwater evaluations revealed that most of the groundwaters belong to the Na(+)-K(+)-Cl(-)-SO (4) (2-) type followed by Na(+)-K(+)-HCO (3) (-) type. Salinity, chlorinity and SAR indices indicated that majority of groundwater samples can be considered suitable for irrigation purposes. | 10.1007/s10661-011-2279-0 |
pubmed_1014_9090 | BACKGROUND
Handgrip is a ubiquitous human movement that was critical in our evolution. However, the differences in brain activity between grip type (i.e. power or precision) and pattern (i.e. dynamic or static) are not fully understood. In order to address this, we performed Activation Likelihood Estimation (ALE) analysis between grip type and grip pattern using functional magnetic resonance imaging (fMRI) data. ALE provides a probabilistic summary of the BOLD response in hundreds of subjects, which is often beyond the scope of a single fMRI experiment.
METHODS
We collected data from 28 functional magnetic resonance data sets, which included a total of 398 male and female subjects. Using ALE, we analyzed the BOLD response during power, precision, static and dynamic grip in a range of forces and age in right handed healthy individuals without physical impairment, cardiovascular or neurological dysfunction using a variety of grip tools, feedback and experimental training.
RESULTS
Power grip generates unique activation in the postcentral gyrus (areas 1 and 3b) and precision grip generates unique activation in the supplementary motor area (SMA, area 6) and precentral gyrus (area 4a). Dynamic handgrip generates unique activation in the precentral gyrus (area 4p) and SMA (area 6) and of particular interest, both dynamic and static grip share activation in the area 2 of the postcentral gyrus, an area implicated in the evolution of handgrip. According to effect size analysis, precision and dynamic grip generates stronger activity than power and static, respectively.
CONCLUSION
Our study demonstrates specific differences between grip type and pattern. However, there was a large degree of overlap in the pre and postcentral gyrus, SMA and areas of the frontal-parietal-cerebellar network, which indicates that other mechanisms are potentially involved in regulating handgrip. Further, our study provides empirically based regions of interest, which can be downloaded here within, that can be used to more effectively study power grip in a range of populations and conditions. | pubmed_1014_9090 |
pubmed_77_371 | The relationship between platelet surface negative charge and hyperfunction was examined by determining electrophoretic mobility (EPM), aggregability, and sialic acid of platelets in prostatic cancer, prostatic cancer with estrogen, prostatic cancer with estrogen and aspirin, prostatic hypertrophy, and healthy aged males. Estrogen treated prostatic cancer patients had significantly higher platelet EPM. A good linear correlation was found between sialic acid and EPM (r = 0.97, p less than 0.001). EPM was negatively correlated with primary aggregations by adrenaline and ADP but not with secondary or maximum aggregations, suggesting increased surface negative charge may inhibit primary aggregation. Estrogen and platelet population changes influenced surface negative charge. Neuraminidase removal of platelet surface sialic acid resulted in dose-dependent decreases of EPM which paralleled decreases in sialic acid. Aspirin treated patients and platelets incubated with aspirin in vitro both showed increased platelet EPM. These results suggest that platelet surface negative charge may directly affect platelet function. | pubmed_77_371 |
pubmed_815_5925 | Diabetes mellitus is a common metabolic disorder associated with chronic complications such as nephropathy, angiopathy, retinopathy and peripheral neuropathy. Diabetes is not often considered to have deleterious effects on the brain. However, long-term diabetes results in a variety of subtle cerebral disorders, which occur more frequently than is commonly believed. Diabetic cerebral disorders have been demonstrated at a neurochemical, electrophysiological, structural and cognitive level; however, the pathogenesis is still not clear. Probably alterations in cerebral blood supply and metabolic derangements play a role, as they do in the pathogenesis of diabetic neuropathy. Furthermore, the brain is also affected by recurrent episodes of hypoglycaemia and poor metabolic control. We describe herein the cerebral manifestations of diabetes and discuss the putative pathogenetic mechanisms. | 10.1007/BF00417687 |
pubmed_1057_6567 | OBJECTIVE
Cerebral revascularization using the superficial temporal artery diverts some of the blood supply from the scalp to the brain. This may compromise the blood supply to the scalp and could result in more wound complications.
OBJECTIVE
This retrospective chart review aimed to identify the incidence of, and independent risk factors for, wound complications after cerebral revascularization using the superficial temporal artery.
METHODS
Patients who underwent cerebral revascularization using the superficial temporal artery between January 2003 and February 2017 were studied. Minor wound complications included superficial skin necrosis, and mild wound dehiscence, while major wound complications included full-thickness skin necrosis, deep infection, and osteomyelitis that required additional surgical treatment.
RESULTS
A total of 482 cerebral revascularization procedures using the superficial temporal artery were included. Wound complications developed in 32 cases (6.6% of the total), including 7 classified as major in severity (1.5% of the total). The multivariate analysis revealed diabetes mellitus (odds ratio 4.058, p = 0.001), low body mass index (odds ratio 1.21, p = 0.009), and thin scalp (odds ratio 1.82, p < 0.001) as the main risk factors for wound complications. Every 1-mm increase in scalp thickness was associated with a protective effect on wound complications (odds ratio 0.549).
CONCLUSION
Cerebral revascularization using the superficial temporal artery was associated with a relatively high incidence of wound complications. Diabetes mellitus, low body mass index, and thin scalp were found to be independent risk factors for wound complications. The thickness of the scalp could be a useful predictor of wound complications. | 10.1007/s00701-020-04500-9 |
pubmed_804_21170 | PURPOSE
Comparative evaluation of morphological features of anterior capsules and apoptosis induction in epithelial cells after femtosecond laser-assisted cataract surgery (FLACS) and standard phacoemulsification surgery.
METHODS
Group 1: 30 FLACS anterior capsulotomies and Group 2: 30 manual anterior continuous curvilinear capsulorhexes. All patients were operated on by the same experienced surgeon. Morphological features of the anterior capsules and apoptosis induction in epithelial cells were evaluated.
RESULTS
All patients revealed a significant mean best-corrected visual acuity (BCVA) improvement 3 months after surgery, and no major intraoperative nor postoperative complications occurred. The capsular epithelium appeared to be preserved in both groups. Scanning electron microscopy analysis revealed irregular saw-tooth shaped edges in capsules from Group 1 whereas capsules from Group 2 showed regular and smooth edges. A statistically significant higher expression of the downstream apoptotic effector cleaved caspase 3 was observed in Group 1.
CONCLUSIONS
The saw-tooth appearance was likely due to the progressive sequence of laser pulses on the capsule. The low energy/high frequency properties of the laser pulse, combined with an overlapped pulse pattern, resulted in highly continuous morphology of capsule edges. The higher apoptosis induction in FLACS group might be due to photodisruption-dependent plasma generation and formation of cavitation bubbles. | 10.1155/2018/7242837 |
pubmed_707_11228 | Acute cholecystitis (AC) is a common condition and its incidence is rising. New technologies have advanced the imaging diagnosis of AC, providing more structural and functional information as well as allowing the radiologist to distinguish AC from mimics and identify complications from both the disease and its management. Dual energy CT aids in detecting gallstones and gallbladder wall enhancement, which helps to diagnose AC and identify its complications. Similarly, contrast-enhanced and non-contrast perfusion ultrasound techniques improve detection of abnormal gallbladder wall enhancement. Advances in MR imaging including hepatobiliary contrast agents aid in characterizing post-cholecystectomy complications such as bile leaks. Newer interventional techniques have also expanded the suite of options for minimally invasive management. Lumen apposing metal stents provide more options for conservative treatment in non-surgical candidates and are compared to a standard percutaneous cholecystostomy. Radiologists should be familiar with these advanced imaging methods and intervention techniques and the value they can bring to the diagnosis and management of AC. | 10.1007/s00261-022-03451-2 |
pubmed_256_20063 | The immunosuppressive agent FK-506 has received much attention due to its efficacy and potency in the areas of transplant rejection and autoimmune disease. Calcineurin, a Ca(2+)-calmodulin activated phosphatase, was recently implicated in the immunosuppressive mechanism of FK-506. In our ongoing search for superior immunosuppressive agents, we have synthesized several analogues of FK-506 and tested their mechanistic and immunosuppressive actions. It was found that C-18 hydroxyl analogues of ascomycin, an analogue of FK-506 also called FR900520, bound tightly to immunophilin FKBP-12, but do not show any immunosuppressive activity in vitro or in vivo despite good bioavailability. Further, they reverse the inhibition of calcineurin caused by FK-506/FKBP-12 complex. | 10.1016/0014-5793(93)81196-7 |
pubmed_65_20356 | Two cowpea varieties (Ife-brown and Kano-white varieties) were used for the study. The effects of insect infestation on the chemical composition and physicochemical properties of these cowpea seeds were studied. The proximate composition, mineral content, total starch, total soluble sugars, bulk density, fat and water absorption capacities, viscosity, gelation capacity and emulsion properties of infested cowpea varieties were compared with those of uninfested cowpeas. Effects of infestation on nitrogen solubility and on the protein fractions were also determined. Infestation depleted the protein, starch and soluble sugar contents of cowpeas. Oil and water absorption capacities were increased while emulsification, foam and viscosity properties were reduced. The nitrogen solubility pattern was altered. Uninfested Kano-white cowpeas (UKW) possessed better foam properties than uninfested Ife-brown cowpeas (UFB). On the other hand, UFB had better emulsification properties than UKW. | 10.1023/a:1008039411269 |
pubmed_634_13737 | The vitellogenesis-inhibiting hormone (VIH), also known as gonad-inhibiting hormone, is a neuropeptide hormone in crustaceans that belongs to the crustacean hyperglycemic hormone (CHH)-family peptide. There is regulation vitellogenesis by VIH during gonad maturation in crustaceans. A full-length Scylla olivacea VIH (Scyol-VIH) was identified through reverse transcription polymerase chain reaction and rapid amplification of cDNA ends. The open reading frame consists of 378 nucleotides, which encodes a 126-amino acid precursor protein, including a 22-residue signal peptide and a 103-amino acid mature peptide in which 6 highly conserved cysteine residues are present. There was expression of the Scyol-VIH gene in immature female Scylla olivacea in the eyestalk, brain and ventral nerve cord. The Scyol-VIH gene expression was localized to the eyestalk X-organ, brain neuronal clusters 6 and 11, and in multiple neuronal clusters of the ventral nerve cord. The relative abundance of Scyol-VIH mRNA transcript in the eyestalk was relatively greater in immature stage females, then decreased as ovarian maturation progressed. Furthermore, eyestalk Scyol-VIH increased after dopamine (5 μg/g BW) injection. The present research provides fundamental information about Scyol-VIH and its potential effect in controlling reproduction. | 10.1016/j.anireprosci.2019.106122 |
pubmed_1051_11890 | AIM
The aim is to add a pragmatic contribution to the discussion of an algorithm to discharge patients treated with Lu-177-PSMA under the aspect of radiation protection. This also may be applied to therapies with other radioactive tracers in the future.
MATERIAL AND METHODS
478 cycles of Lu-177-PSMA-617 (140 patients) were analyzed. The remaining activity in the patient and the dose rate were correlated. From frequent intratherapeutic measurements (biexponential fit) scenarios for discharging patients are deduced.
RESULTS
Thirty-four per cent of all patients treated with Lu-177-PSMA received 3 to 5 cycles per calendar year. The dose limit of 1 mSv per calendar year (German Law) at a distance of 2 m from the patient would be exceeded in 10 % and 15 % of the treated patients if discharged 72 hours after treatment given 3 and 4 cycles per calendar year, respectively. Mean specific dose rate was 0.00462µSv/(h MBq) at a distance of 1 m. A universal correlation between dose rate and the remaining activity in the patient could not be found.
CONCLUSION
The multi cycle concept of the therapies with Lu-177 PSMA has to be taken into account prospectively when discharging the patients. Given the physical half-life of Lu-177 an anticipation of 4 treatment cycles per calendar year leads to a clearly arranged, conservative rule. | 10.1055/a-1697-8126 |
pubmed_462_16243 | BACKGROUND
The collapse of the soft tissues of the upper airway during sleep is decisive in the pathogenesis of the obstructive sleep apnea syndrome. The administration of an air flow of adjustable pressure through the nose is efficient to overcome the obstruction and favor respiration without apnea.
METHODS
Twenty-two patients with obstructive sleep apnea syndrome were treated with continuous positive pressure of the upper airway with the aim of evaluating the effect of this treatment on sleep, respiration and cardiac rhythm following the first night of treatment.
RESULTS
Following the night of treatment an increase of the III, IV states and sleep REM with a shortening of REM latency was observed. The number of apneas diminished drastically thus improving cardiac arrhythmias detected in the basal study.
CONCLUSIONS
Treatment of the upper airway with continuous positive pressure is efficient not only for the correction of apneas and cardiac arrhythmia but also for the consolidation of a normal sleep cycle. | pubmed_462_16243 |
pubmed_671_210 | Gastric inhibitory polypeptide (GIP) is a candidate hormone for an incretin which stimulates or potentiates insulin secretion. We elucidated that, in five patients with hyperparathyroidism, GIP and insulin responded remarkably to glucose ingestion, and that hypercalcaemia appeared to have a stimulatory effect on glucose-induced GIP release as well as on insulin release. In nine healthy subjects a 2% calcium solution was continuously infused intravenously and a hypercalcaemic state was maintained. This caused GIP to respond significantly more to glucose ingestion. In spite of GIP being considered an incretin in the normoglycaemic state, GIP does not markedly stimulate insulin secretion. However, in the hypercalcaemic state in healthy subjects, glucose-induced GIP and insulin secretion is significantly greater than in the normocalcaemic state. The potentiated response of insulin to glucose may be caused, in part, by GIP. | 10.1016/0167-0115(82)90104-5 |
pubmed_894_20841 | Certain covalently linked insulin dimers have previously been found to have a greater ability to bind to the insulin receptor than to stimulate lipogenesis in adipocytes. The present report presents data indicating that the same insulin dimers also have a greater ability to bind to the receptor than to stimulate the kinase activity of the insulin receptor. In particular, one such covalently linked insulin dimer had less than 1% the potency of native insulin in stimulating the receptor kinase although it could bind to the solubilized receptor with 30% the potency of native insulin. In contrast, this dimer could down regulate the insulin receptor with approximately 30% the potency of native insulin. These results suggest that stimulation of the receptor kinase may require more than simple occupancy of the receptor binding site whereas down regulation of the receptor may require only the binding of ligand to the receptor. | 10.1016/0014-5793(84)81344-7 |
pubmed_545_9420 | Liriope platyphylla is used as an important medicinal plant for fatigue, cough, and inflammation in South Korea. Here, we report the complete chloroplast genome of L. platyphylla. The total genome size of the chloroplast is 157,076 bp with a large single-copy region (LSC: 85,374 bp), a small single-copy region (SSC: 18,748 bp), and inverted repeat regions (IRa and IRb: 26,477 bp). The GC content of the L. platyphylla chloroplast was 37.6%. The cp genome encoded a set of 129 genes, including 83 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic tree analysis indicated that L. platyphylla is closely related to L. spicata. | 10.1080/23802359.2020.1787898 |
pubmed_16_2067 | MOTIVATION
Heterochronous gene sequence data is important for characterizing the evolutionary processes of fast-evolving organisms such as RNA viruses. A limited set of algorithms exists for estimating the rate of nucleotide substitution and inferring phylogenetic trees from such data. The authors here present a new method, Tree and Rate Estimation by Local Evaluation (TREBLE) that robustly calculates the rate of nucleotide substitution and phylogeny with several orders of magnitude improvement in computational time.
METHODS
For the basis of its rate estimation TREBLE novelly utilizes a geometric interpretation of the molecular clock assumption to deduce a local estimate of the rate of nucleotide substitution for triplets of dated sequences. Averaging the triplet estimates via a variance weighting yields a global estimate of the rate. From this value, an iterative refinement procedure relying on statistical properties of the triplets then generates a final estimate of the global rate of nucleotide substitution. The estimated global rate is then utilized to find the tree from the pairwise distance matrix via an UPGMA-like algorithm.
RESULTS
Simulation studies show that TREBLE estimates the rate of nucleotide substitution with point estimates comparable with the best of available methods. Confidence intervals are comparable with that of BEAST. TREBLE's phylogenetic reconstruction is significantly improved over the other distance matrix method but not as accurate as the Bayesian algorithm. Compared with three other algorithms, TREBLE reduces computational time by a minimum factor of 3000. Relative to the algorithm with the most accurate estimates for the rate of nucleotide substitution (i.e. BEAST), TREBLE is over 10,000 times more computationally efficient.
AVAILABILITY
jdobrien.bol.ucla.edu/TREBLE.html | 10.1093/bioinformatics/btl577 |
pubmed_908_17378 | Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes. In contrary, JMJD3 silencing or its inhibitor GSK-J4 suppressed ISO-induced cardiac hypertrophy. Mechanistically, JMJD3 was recruited to demethylate H3K27me3 at the promoter of β-MHC to promote its expression and cardiac hypertrophy. Thus, our results reveal that JMJD3 may be a key epigenetic regulator of β-MHC expression in cardiomyocytes and a potential therapeutic target for cardiac hypertrophy. | 10.1016/j.mce.2018.05.009 |
pubmed_1135_19815 | Induction of mucus hypersecretion in the airway epithelium by Th2 cytokines is associated with the expression of TMEM16A, a Ca2+-activated Cl- channel. We asked whether exposure of airway epithelial cells to bacterial components, a condition that mimics the highly infected environment occurring in cystic fibrosis (CF), also results in a similar response. In cultured human bronchial epithelial cells, treatment with pyocyanin or with a P. aeruginosa culture supernatant caused a significant increase in TMEM16A function. The Ca2+-dependent Cl- secretion, triggered by stimulation with UTP, was particularly enhanced by pyocyanin in cells from CF patients. Increased expression of TMEM16A protein and of MUC5AC mucin by bacterial components was demonstrated by immunofluorescence in CF and non-CF cells. We also investigated TMEM16A expression in human bronchi by immunocytochemistry. We found increased TMEM16A staining in the airways of CF patients. The strongest signal was observed in CF submucosal glands. Our results suggest that TMEM16A expression/function is upregulated in CF lung disease, possibly as a response towards the presence of bacteria in the airways. | 10.1371/journal.pone.0131775 |
pubmed_31_12244 | Autism spectrum disorders (ASD) are a group of heterogeneous neurological disorders that are highly variable and are clinically characterized by deficits in social interactions, communication, and stereotypical behaviors. Prevalence has risen from 1 in 10,000 in 1972 to 1 in 59 children in the United States in 2014. This rise in prevalence could be due in part to better diagnoses and awareness, however, these together cannot solely account for such a significant rise. While causative connections have not been proven in the majority of cases, many current studies focus on the combined effects of genetics and environment. Strikingly, a distinct picture of immune dysfunction has emerged and been supported by many independent studies over the past decade. Many players in the immune-ASD puzzle may be mechanistically contributing to pathogenesis of these disorders, including skewed cytokine responses, differences in total numbers and frequencies of immune cells and their subsets, neuroinflammation, and adaptive and innate immune dysfunction, as well as altered levels of immunoglobulin and the presence of autoantibodies which have been found in a substantial number of individuals with ASD. This review summarizes the latest research linking ASD, autoimmunity and immune dysfunction, and discusses evidence of a potential autoimmune component of ASD. | 10.3389/fncel.2018.00405 |
pubmed_297_11019 | Oligoanilines with characteristic properties of the electrically conductive emeraldine salt form of polyaniline (PANI-ES) are promising molecules for various applications. A mixture of such oligoanilines can be obtained, for example, enzymatically under mild conditions from the linear aniline dimer p-aminodiphenylamine (PADPA) with hydrogen peroxide (H2O2) and low amounts of horseradish peroxidase (HRP) in an aqueous pH = 4.3 suspension of anionic vesicles formed from AOT, the sodium salt of bis(2-ethylhexyl)sulfosuccinate. However, the simultaneous formation of undesired side products containing phenazine-type units or oxygen atoms is unsatisfactory. We have found that this situation can be improved considerably by using a mixture of PADPA and aniline instead of PADPA only but otherwise nearly identical conditions. The PANI-ES-like oligoaniline products that are obtained from the PADPA and aniline mixture were not only found to have much lower contents of phenazine-type units and not contain oxygen atoms but also were shown to be more electroactive in cyclic voltammetry measurements than the PANI-ES-like products obtained from PADPA only. The AOT vesicle suspension remained stable without product precipitation during and after the entire reaction so that it could be analyzed by in situ UV/visible/near-infrared, in situ electron paramagnetic resonance, and in situ Raman spectroscopy measurements. These measurements were complemented with ex situ high-performance liquid chromatography analyses of the deprotonated and reduced products formed from mixtures of PADPA and either fully or partially deuterated aniline. On the basis of the results obtained, a reaction mechanism is proposed for explaining this improved HRP-triggered, vesicle-assisted synthesis of electroactive PANI-ES-like products. The oligomeric products obtained can be further used, without additional special workup, for example, to coat electrodes for their possible application in biosensor devices. | 10.1021/acs.langmuir.8b00953 |
pubmed_765_8901 | Fragile X associated tremor/ataxia syndrome (FXTAS) is a late adult-onset neurodegenerative disorder that affects movement and cognition in male and female carriers of a premutation allele of 55-200 CGG repeats in the Fragile X mental retardation (FMR1) gene. It is currently unknown if and when an individual carrier of a premutation allele will develop FXTAS, as clinical assessment fails to identify carriers at risk before significant neurological symptoms are evident. The primary objective of this study was to investigate the alternative splicing landscape at the FMR1 locus in conjunction with brain measures in male individuals with a premutation allele enrolled in a very first longitudinal study, compared to age-matched healthy male controls, with the purpose of identifying biomarkers for early diagnosis, disease prediction and, a progression of FXTAS. Our findings indicate that increased expression of FMR1 mRNA isoforms, including Iso4/4b, Iso10/10b, as well as of the ASFMR1 mRNAs Iso131bp, are present in premutation carriers as compared to non-carrier healthy controls. More specifically, we observed a higher expression of Iso4/4b and Iso10/10b, which encode for truncated proteins, only in those premutation carriers who developed symptoms of FXTAS over time as compared to non-carrier healthy controls, suggesting a potential role in the development of the disorder. In addition, we found a significant association of these molecular changes with various measurements of brain morphology, including the middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), pons, and midbrain, indicating their potential contribution to the pathogenesis of FXTAS. Interestingly, the high expression levels of Iso4/4b observed both at visit 1 and visit 2 and found to be associated with a decrease in mean MCP width only in those individuals who developed FXTAS over time, suggests their role as potential biomarkers for early diagnosis of FXTAS. | 10.1038/s41598-020-67946-y |
pubmed_720_724 | OBJECTIVE
Altered activity within reward-related neural regions, including the ventral striatum (VS) and medial prefrontal cortex (mPFC), is associated with concurrent problematic substance use. The aims of the present study were (a) to identify patterns of reward-related neural activity that prospectively predicted changes in alcohol use 2 years after magnetic resonance imaging in a sample of adolescents, and (b) to examine whether these patterns differed by sex. We also tested whether depression symptoms or impulsivity mediated associations between neural activity and future alcohol use.
METHOD
Participants were 262 adolescents (129 male and 133 female) of Mexican origin who completed the Monetary Incentive Delay task during a functional magnetic resonance imaging scan at age 16. Participants reported on their alcohol use at ages 16 and 18.
RESULTS
Results indicated that different patterns of reward-related neural activity predicted future increases in alcohol use for male and female adolescents. In boys, higher VS activity during reward anticipation and average ventral mPFC activity during reward feedback predicted increases in alcohol use from age 16 to 18 years; in girls, higher dorsal mPFC activity and blunted VS activity during reward anticipation predicted increases in alcohol use from age 16 to 18 years. Depression symptoms or impulsivity did not mediate these associations.
CONCLUSION
The results suggest that different pathways of risk may lead to problematic alcohol use for adolescent boys and girls. These sex differences in neural risk pathways have important implications for prevention and intervention approaches targeting Mexican-origin youth. | 10.1016/j.jaac.2019.05.022 |
pubmed_422_11609 | Vanilla claviculata, V. barbellata and V. dilloniana are distributed throughout the Caribbean islands and are all found in Puerto Rico. The vegetative parts of the species are similar; however, their conspicuous flowers easily distinguish them. Electrophoresis of seven polymorphic enzymes revealed that the genetic composition of the three species is also very similar: they deviate mainly from each other in allele frequencies rather than by specific alleles. A hierarchical analysis of genetic differentiation showed that the between-species component is slightly higher (FSG=0.237) than the component between populations within species (FPS=0.141). Nevertheless, they are efficiently recognized by their genotypic compositions. In V. barbellata and V. claviculata 97-99% of all individuals were assigned to the correct species. Assignment to a wrong species occurred only with individuals at localities where species coexist. This suggests that the species may hybridize. | 10.1038/sj.hdy.6885880 |
pubmed_1057_17360 | The BLM helicase protein plays a vital role in DNA replication and the maintenance of genomic integrity. Variation in the BLM helicase gene resulted in defects in the DNA repair mechanism and was reported to be associated with Bloom syndrome (BS) and cancer. Despite extensive investigation of helicase proteins in humans, no attempt has previously been made to comprehensively analyse the single nucleotide polymorphism (SNPs) of the BLM gene. In this study, a comprehensive analysis of SNPs on the BLM gene was performed to identify, characterize and validate the pathogenic SNPs using computational approaches. We obtained SNP data from the dbSNP database version 150 and mapped these data to the genomic coordinates of the "NM_000057.3" transcript expressing BLM helicase (P54132). There were 607 SNPs mapped to missense, 29 SNPs mapped to nonsense, and 19 SNPs mapped to 3'-UTR regions. Initially, we used many consensus tools of SIFT, PROVEAN, Condel, and PolyPhen-2, which together increased the accuracy of prediction and identified 18 highly pathogenic non-synonymous SNPs (nsSNPs) out of 607 SNPs. Subsequently, these 18 high-confidence pathogenic nsSNPs were analysed for BLM protein stability, structure-function relationships and disease associations using various bioinformatics tools. These 18 mutants of the BLM protein along with the native protein were further investigated using molecular dynamics simulations to examine the structural consequences of the mutations, which might reveal their malfunction and contribution to disease. In addition, 28 SNPs were predicted as "stop gained" nonsense SNPs and one SNP was predicted as "start lost". Two SNPs in the 3'UTR were found to abolish miRNA binding and thus may enhance the expression of BLM. Interestingly, we found that BLM mRNA overexpression is associated with different types of cancers. Further investigation showed that the dysregulation of BLM is associated with poor overall survival (OS) for lung and gastric cancer patients and hence led to the conclusion that BLM has the potential to be used as an important prognostic marker for the detection of lung and gastric cancer. | 10.1038/s41598-020-69033-8 |
pubmed_782_5548 | BACKGROUND
Prenatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs) or polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like compounds [DLCs]) through environmental chemicals may affect the neurodevelopment of children. In our previous study, an inverse association was observed between prenatal DLCs and neurodevelopment of infants aged 6months in both sexes. However, studies are yet to determine how long these adverse effects last.
OBJECTIVE
To examine whether the effects of DLCs on cognitive development remains at 42months.
METHODS
In this prospective cohort study conducted in Sapporo, Japan, pregnant mothers' blood was analyzed for the congener level of DLCs. The Kaufman Assessment of Battery for Children (K-ABC) was used to test their children's cognitive development at 42months. A total of 141 mother-child pairs were included in the final analysis. The multiple linear regression analysis was used to examine the association between the K-ABC scores and DLC levels in the maternal blood.
RESULTS
Seven isomers (1,2,3,6,7,8-HxCDD, 2,3,4,7,8-PeCDF, 33'44'55'-HxCB(#169), 2344'5- PenCB(#114), 233'44'5-HexCB(#156), 233'44'5'-HexCB(#157), 23'44'55'-HexCB(#167), total PCDF, and TEQ-PCDD, PCDF, PCDD/DFs levels were positively associated with the achievement score (AS) of K-ABC. However, total non-ortho PCBs were negatively associated with the Mental Processing Composite Score (MPCS) of K-ABC in males. In females, increased TEQ-dl PCB and TEQ-PCDD/F/dl-PCB were also associated with increasing AS score.
CONCLUSIONS
This study suggests that the negative effects of prenatal DLC exposure on children's cognitive development at 6months were not observed in children aged 42months. Regarding the sex-specific effects, AS and DLCs were positively correlated in females, whereas those of MPCS and DLCs were significantly negative in males. | 10.1016/j.scitotenv.2017.09.267 |
pubmed_705_10312 | Gastric M1 mucin and the MUC5AC gene show a similar oncofetal expression in the colon. Our aim was to determine whether M1 mucin is the product of the MUC5AC gene. A recombinant baculovirus encoding the C-terminal portion of the MUC5AC gene as a fusion protein was isolated and the immunoreactivity of the recombinant mucin (rM) toward M1 antibodies studied. Chicken antibodies also were raised against purified rM. Besides its reactivity with L56/C, a serum recognizing the bacterially expressed MUC5AC gene product, rM was endowed with M1 immunoreactivity: (i) rM-expressing cells were stained specifically with anti-M1 serum and with the monoclonal antibody (MAb) 21M1, defining the M1-f epitope; (ii) both L56/C and anti-M1 antibodies recognized the same bands in immunoblots of rM-containing cell extracts; (iii) the 21M1 antibody reacted with rM in an immunoradiometric assay. Among the 7 M1 epitopes, M1-f was the only one encoded by the 3' portion of the MUC5AC gene. It was the only epitope detected in a native mucin M1-derived 170 kDa bromelain proteolytic fragment. Furthermore, the staining patterns of human tissues obtained with either anti-rM chicken antibodies or anti-M1 antibodies were identical. We conclude that M1 immunoreactivity is encoded at least in part by the MUC5AC gene. | 10.1002/(sici)1097-0215(19980302)75:5<767::aid-ijc17>3.0.co;2-3 |
pubmed_800_13021 | Canine atopic dermatitis is commonly diagnosed in pruritic animals. Many studies have attempted to determine the inheritance pattern of both atopic dermatitis and of elevated allergen-specific IgE production. Despite many clinical, laboratory and breeding studies, the mode of inheritance and genetic mutations underlying this disease currently remain elusive. | 10.1016/s0165-2427(01)00297-5 |
pubmed_934_6048 | PURPOSE
The aim of this study was to examine the influence of age on cycling efficiency and sprint power output in well-trained endurance masters athletes.
METHODS
The investigation was conducted on 60 healthy well-trained triathletes separated into six separate groups (n = 10) depending on age: 20-29 years old; 30-39 years old; 40-49 years old; 50-59 years old; 60-69 years old; 70 years old. Each participant attended the laboratory on three separate occasions to perform (1) an incremental cycling test, (2) maximal peak sprint power test, involving three 5-s sprint efforts (3) and a 10-min sub-maximal cycling test for determination of cycling efficiency.
RESULTS
Cycling efficiency decreased beyond 50 years (50-59 years compared with 20-29 years: -7.3 ± 1.8%; p < 0.05) and continued to decrease beyond 60 years (60-69 years compared with 50-59 years: -10.7 ± 2.4%; p < 0.05), no further decrease was observed after 70 years. A continuous impairment in maximal sprint power output was observed after the age of 50 years leading to an overall decrease of 36% between 20-29 years and >70 years. Significant positive relationships were observed between maximal sprint power output and both cycling efficiency (r(2) = 0.64, p < 0.05) and maximal aerobic power (r(2) = 0.42 and p < 0.05).
CONCLUSION
The present data indicates a significant effect of ageing on cycling efficiency and maximal sprint power output after 50 years and a significant relationship was found between these two parameters. | 10.1007/s00421-014-2977-8 |
pubmed_857_22271 | The results of pyelonephritis treatment in 48 pregnant patients are analyzed. Twenty-three patients were administered routine antibacterial therapy, in 25 ones plasmapheresis was added to it. Immunity status of all the patients was examined. Antibiotic therapy was conducive to improvement of the patients' status, to a reduction of the renal inflammation severity, though it did not completely eliminate immunodeficiency signs. B lymphocyte and immunoglobulin levels persisted reduced. Plasmapheresis promoted a more swift elimination of clinical and laboratory signs of pyelonephritis and virtually completely liquidated immunodeficiency. | pubmed_857_22271 |
pubmed_760_20700 | INTRODUCTION
Health is an exclusive and subjective phenomenon, and one of the most important situations with regard to perception of health, arises when patients suffer from a chronic disease. This study was conducted within the qualitative research framework and aimed to explore the meanings of health as perceived by a group of Iranian diabetic patients.
METHODS
A descriptive qualitative analysis design was used. Data were collected through semi-structured interviews with 20 participants among diabetic patients, who were admitted to the diabetes care centre of Tohid Hospital of the Kurdistan University of Medical Sciences, Sanandaj, Iran during a ten-month period in 2014. Interviews were transcribed and analysed through conventional content analysis.
RESULTS
Based on the findings of the study, three major health-related themes emerged: 1) the syndrome of the healthy body and the happy heart (physical well-being vivacity, satisfaction, and calmness of the mind), 2) life without compulsory limitations (lack of dietary limitations, No activity limitations, lack of social limitations), and 3) exalted spirituality (satisfying self and others, trusting God, remembering God).
CONCLUSION
Health care providers should consider the meaning of health in special groups, chiefly in patients with chronic diseases. It facilitates the development of appropriate programmes to improve desirable health levels among diabetic patients. | 10.19082/2904 |
pubmed_564_6778 | Measles virus transcription generates multiple P/C gene-specific mRNAs by a process which has been termed editing. In one of these mRNAs, the cotranscriptional addition of a single nontemplated G residue allows translational access to the V protein reading frame. The protein translated from this mRNA has been called V and consists of 231 amino-terminal amino acid residues identical to those at the amino terminus of the P protein followed by a unique carboxy-terminal domain consisting of 68 amino acids from the V reading frame. The most striking feature of this unique domain is the presence within it of seven cysteine residues whose presence and position are highly conserved among different paramyxoviruses. The number and arrangement of these cysteine residues is suggestive of a zinc finger protein. We have used a zinc binding protocol to determine that V protein does indeed bind zinc, have further demonstrated that this metal binding activity is highly specific to zinc, and have shown that it is the unique carboxy-terminal domain of the V protein that is responsible for zinc binding. | 10.1006/viro.1994.1050 |
pubmed_810_1520 | The successful implementation of process and product changes for a therapeutic protein drug, both during clinical development and after commercialization, requires a detailed evaluation of their impact on the protein's structure and biological functionality. This analysis is called a comparability exercise and includes a data driven assessment of biochemical equivalence and biological characterization using a cadre of analytical methodologies. This review focuses on describing analytical results and lessons learned from selected published therapeutic protein comparability case studies both for bulk drug substance and final drug product. An overview of the currently available analytical methodologies typically used is presented as well as a discussion of new emerging analytical techniques. The potential utility of several novel analytical approaches to comparability studies is discussed including distribution and stability of protein drugs in vivo, and enhanced evaluation of higher-order protein structure in actual formulations using hydrogen/deuterium exchange mass spectrometry, two-dimensional nuclear magnetic resonance fingerprinting or empirical phase diagrams. In addition, new methods for detecting and characterizing protein aggregates and particles are presented as these degradants are of current industry-wide concern. The critical role that analytical methodologies play in elucidating the structure-function relationships for therapeutic protein products during the overall assessment of comparability is discussed. | pubmed_810_1520 |
pubmed_162_3574 | BACKGROUND
There are no previous studies dealing with paroxysmal atrial fibrillation (AF) and hypertension using electrocardiogram and tissue doppler imaging (TDI). The aim of this study was to investigate and identify the predictive indicators for paroxysmal AF in hypertensive patients using P wave dispersion (Pd) and TDI.
METHODS
Patients with hypertension were enrolled. Patients with paroxysmal AF were classified as the PAF group, and patients without a history of paroxysmal AF were classified as the NAF group. The clinical data, P wave indicators and TDI indicators were collected and compared between the two groups.
RESULTS
A total of 120 patients were enrolled into the study with 40 cases in the PAF group and 80 cases in the NAF group. Compared with NAF group, Pd, maximum P wave duration (Pmax), left ventricular end-diastolic dimension (LVEDd) and left atrial dimension (LAD) were significantly longer (P < .05) in the PAF group. PAL, PAI, PAR, LR, LI and IR were significantly longer (P < .05) in the PAF group than in the NAF group. As for ROC analysis, Pd and PAL had the greatest area under the curve. The best diagnostic value of Pd and PAL was 40ms and 78ms, respectively. The combination of Pd ≥40ms with Pmax ≥ 110ms showed higher specificity and positive predictive value but decreased sensitivity and negative predictive value for paroxysmal AF.
CONCLUSIONS
The PAF group had significantly longer atrial electromechanical time and higher Pd compared with NAF group. The combination of Pd and TDI may be helpful to predict the onset of paroxysmal AF in patients with hypertension. | 10.1532/hsf.1831 |
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