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pubmed_416_19118 | BACKGROUND
The uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed.
METHODS
Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100.
RESULTS
Structures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP 9.5 and S-100. They were observed in specimens of the non-pregnant corpus and cervix and also in specimens of the pregnant cervix before onset of labor. However, they were absent in all specimens during labor.
CONCLUSION
Sensory corpuscles have here for the first time been detected in the human corpus and cervix uteri. Studies on the importance of the corpuscles in relation to the protective reflex actions that occur in the uterus during pregnancy should be performed in the future. | 10.1186/1477-7827-4-45 |
pubmed_705_12377 | The British Geriatrics Society has described 16 training objectives for senior house officers (SHOs) in geriatric medicine. We have developed these into an audit standard, and in a controlled trial we consider the effectiveness of audit as a means of monitoring and improving SHO training. SHOs from three hospitals were sent a questionnaire asking about the adequacy of formal and informal training for each objective; there was a response rate of 87%. Results were presented at an audit meeting in one hospital, inadequacies of training identified and the hospital's programme of teaching modified appropriately. Two control hospitals remained unaware of the audit findings and were therefore unable to modify their training programmes. Re-audit at six months completed the audit cycle; the control hospitals showing no change between the two audits. In the intervention hospital the adequacy of training over the 16 objectives improved from 59% at first audit to 73% at re-audit. The initial audit had highlighted three target objectives as needing special attention; here the improvement from 38% to 69% was even more impressive, and statistically significant at p < 0.05 on chi 2 test. Thus, although a questionnaire approach is inevitably subjective and affected by SHO satisfaction, the discipline of audit appeared effective in identifying and correcting deficiencies in an SHO training programme. | 10.1136/pgmj.73.866.798 |
pubmed_663_18725 | BACKGROUND & AIMS
Chronic infection with hepatitis Delta virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC); predictors of disease outcome are, however, poorly defined. We tracked the course of HDV infection in 299 patients over a mean period of 233 months.
METHODS
We analyzed data from patients who had been HDV positive for at least 6 months (230 males; mean age, 30 years) admitted from 1978 to 2006 to Maggiore Hospital, Milan. HDV infection was defined by the presence of HDV antigen in liver tissue or serum HDV RNA in anti-HDV/hepatitis B surface antigen seropositive patients. At enrollment, 7 patients had acute hepatitis, 101 had mild-moderate chronic hepatitis, 76 had severe chronic hepatitis, and 104 had histologic or clinical cirrhosis. Ninety patients were treated with interferon, 62 with corticosteroids, and 12 with nucleoside analogues; 135 received no therapy.
RESULTS
Over a mean period of 233 months, 82 patients developed cirrhosis. Among the 186 total patients with cirrhosis, 46 developed HCC, 43 ascites, 44 jaundice, and 1 encephalopathy. Female sex, alcohol abuse, and HDV replication were associated with liver decompensation; HBV replication and interferon were associated with HCC development. By the end of the study, 186 patients were still alive, 63 had died, and 29 had received liver transplants. The main cause of death was liver failure (n = 37, 59%); HDV replication was the only independent predictor of mortality.
CONCLUSIONS
Persistent HDV replication leads to cirrhosis and HCC at annual rates of 4% and 2.8%, respectively, and is the only predictor of liver-related mortality. | 10.1053/j.gastro.2009.01.052 |
pubmed_98_12506 | The performance of lithium batteries is largely dependent on the ionic conductivity within robust solid electrolytes. Poly(ethylene oxide) (PEO)-based electrolytes, however, have a low lithium ionic conductivity, which limits the hop of Li+. Herein, a novel PEO-based composite electrolyte is prepared that contains nonstoichiometric transition molybdenum trioxide (MoO3-) nanosheets as fillers to improve the ionic conductivity. The MoO3- nanosheets containing many oxygen vacancies can cross-link with PEO chains to reduce the energy barrier of Li+ migration and the matrix crystallinity, leading to an increase in the lithium-ion transference number (up to 0.56) and a high ionic conductivity (up to 6 × 10-4 S cm-1) at 60 °C. Meanwhile, the incorporation of MoO3- nanosheets alleviates the decomposition of the electrolyte, enhancing the tensile strength by ∼4 times compared to PEO. As a result, a LiFePO4/Li cell with PEO/LiTFSI/MoO3- (PLM3-x) delivers an excellent rate capability, high capacity, and lifespan during high rates (2 C, ≥10 000 cycles), which demonstrates a facile yet effective strategy toward high-performance lithium batteries. | 10.1021/acsami.1c19422 |
pubmed_1119_21363 | Differentiated human neuroblastoma LA-N1 cells that were exposed to dibutyryl adenosine 3',5'-cyclic monophosphate for 5 days (primed cells) showed increased adhesion to laminin-, fibronectin-, and collagen type I-coated plates as compared to unprimed cells. Moreover, primed cells seemed to adhere best to laminin. The binding site in laminin, mediating cell attachment, was identified as containing the YIGSR sequence, a known cell binding motif, located in the short arm of the B1 chain of laminin. The synthetic peptide amide, C(YIGSR)3-NH2, containing a repeat of this binding motif, inhibited the attachment of neuroblastoma cells to laminin in a competitive manner, and its inhibitory activity was inversely dependent on laminin concentrations. Affinity chromatography of membrane-extracted proteins over an Affi-Gel 10 column conjugated to C(YIGSR)3-NH2, revealed a major YIGSR-binding protein with an apparent molecular mass of 67 kDa. The 67-kDa surface membrane protein was specifically eluted from the column with the soluble C(YIGSR)3-NH2 peptide, but not with an unrelated peptide. Furthermore, no 67-kDa laminin-binding protein was recovered from an unrelated peptide matrix with the free C(YIGSR)3-NH2 peptide. Ligand blot overlay assays with biotin-labeled C(YIGSR)3-NH2 peptide demonstrated that the 67-kDa receptor is indeed a YIGSR-binding protein. This 67-kDa laminin-binding protein appeared to be down-regulated upon differentiation of LA-N1 cells, as indicated by the level of this protein and its mRNA. | 10.1074/jbc.270.22.13422 |
pubmed_651_4994 | The paper deals with the routine work of the statistical staff of a cancer control department. Problems of organization and planning of cancer control measures, such as handling of cancer patient registration cards, inspection visits of the Dispensary medical staff to different areas of the region, mass screening, establishment and supervision over out-patient examination posts, advanced training of doctors, doctors' assistants and nurses at the Dispensary, etc. are discussed. The experience reported in the article may be useful to the staff of local oncological dispensaries with a low- or medium-size population in their catchment areas. | pubmed_651_4994 |
pubmed_785_12612 | The well-documented human bias toward agency as a cause and therefore an explanation of observed events is typically attributed to evolutionary selection for a "social brain". Based on a review of developmental and adult behavioral and neurocognitive data, it is argued that the bias toward agency is a result of the default human solution, developed during infancy, to the computational requirements of object re-identification over gaps in observation of more than a few seconds. If this model is correct, overriding the bias toward agency to construct mechanistic explanations of observed events requires structure-mapping inferences, implemented by the pre-motor action planning system, that replace agents with mechanisms as causes of unobserved changes in contextual or featural properties of objects. Experiments that would test this model are discussed. | 10.3389/fnhum.2014.00597 |
pubmed_490_11078 | INTRODUCTION
More than one-fourth adolescents are exposed to unexpected frightening experiences and traumas until adulthood. In this study, we aimed to determine the potential role of serotonin transporter (5-HTT) gene polymorphism regarding resilience factors in the symptom variability of individuals exposed to sexual abuse.
METHODS
Adolescents aged 11-17 years, who were admitted to the Marmara University Child Psychiatry Outpatient Clinic Forensic division with sexual abuse experience history, were informed about the research, and volunteers were included in the study. Turkish versions of "Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL)" was used to assess the psychopathology and functionality. The evaluation of participants also included self-reports based on "Eysenck Personality Inventory" and "Ways of Coping Inventory" for reflecting the resilience domain.
RESULTS
The sample included 16 girls (88.9%) and 2 boys (11.1%), and the mean (±standard deviation) age was 14.58±1.97 years. Genotyping of the insertion/deletion polymorphism (5-HTTLPR) in the 5-HTT gene's transcriptional control zone was established, and 8 participants (44.4%) were determined to be of the LL genotype, while 7 (38.8%) were LS and 3 (16.6%) were SS carriers. Considering the relationship between coping styles regarding resilience and genetic variants, 87.5% of participants (n=7) exhibiting problem-focused coping style were determined found to carry the LL allele, while 90% (n=9) who exhibited emotion-focused coping styles were the SS-LS allele carriers (p=0.003).
CONCLUSION
Our findings suggest that 5-HTTLPR gene polymorphism has a significant impact on the formation of coping styles. More studies are needed to determine other factors involved in the complex relationship between 5-HTTLPR gene polymorphism and development of psychopathology. | 10.5152/npa.2016.12528 |
pubmed_434_11396 | Standardized criteria of response to treatment and a unified definition of resistance/intolerance to hydroxycarbamide (HC) in essential thrombocythaemia (ET) have been proposed by the European LeukaemiaNet (ELN). We have retrospectively evaluated such criteria in 166 ET patients treated with HC for a median of 4·5 years. Overall, 134 patients achieved a complete clinicohaematological response (CR) and 25 a partial response. Thirty-three patients met at least one of the ELN criteria defining resistance (n = 15) or intolerance (n = 21) to HC. Fifteen cases developed anaemia with thrombocytosis, which was associated with a high incidence of myelofibrosis and death from any cause. Other definitions of resistance were less useful. Factors determining the thrombotic risk were a history of prior thrombosis and a baseline leucocyte count >10 × 10⁹/ l. Of note, patients achieving a CR, even if sustained during the entire follow-up, did not benefit from a lower incidence of thrombosis or an improved survival. In conclusion, most ET patients respond to HC, but the achievement of response, as defined by the ELN, does not correlate with the patients' outcome. The best discriminating ELN criterion of resistance to HC was the detection of anaemia, which also identified a subgroup of patients with poor prognosis. | 10.1111/j.1365-2141.2010.08430.x |
pubmed_1111_3592 | Electron tomography (ET) is the leading imaging technique for visualizing the molecular architecture of complex biological specimens. Real-time ET systems allow scientists to acquire experimental datasets and obtain a preliminary version of three-dimensional structure of the specimen. This rough structure allows assessment of the quality of the sample and can also be used as a guide to collect more datasets. However, the low signal-to-noise ratio of the ET datasets precludes detailed interpretation and makes their assessment difficult. Therefore, noise reduction methods should be integrated in these real-time ET systems for their full exploitation. However, feature-preserving noise reduction methods are typically computationally intensive, which hinders real-time response. This work proposes and evaluates fast implementations of a sophisticated noise reduction method with capabilities of preservation of biologically relevant features. These implementations are designed to exploit the high performance computing (HPC) capabilities of modern multicore platforms and of graphics processing units. It is shown that the use of HPC on modern platforms makes this noise reduction method able to provide datasets appropriate for assessment in a matter of seconds, thereby making it suitable for integration in current real-time ET systems. | 10.1007/978-1-4419-7046-6_23 |
pubmed_955_6497 | PURPOSE
To determine the effect of disability glare (DG) upon luminance and color contrast sensitivity for young and elderly subjects.
METHODS
DG was defined as the difference in contrast sensitivity with and without the presence of a glare source. Isoluminant color gratings were modulated either along a red-green (R-G) or blue-yellow (B-Y) axis.
RESULTS
Without glare the effect of age on sensitivity to both luminance and R-G color-modulated gratings was small and did not reach statistical significance (P > 0.1). However, the reduction in sensitivity for B-Y color modulation was highly significant (P < 0.01). For both age groups, DG was greatest for the R-G stimulus and least for the B-Y. DG in the elderly increased relative to the young observers for both R-G and luminance-modulated gratings (P < 0.01) but not for B-Y (P > 0.01).
CONCLUSIONS
The precise effect of a glare source on color discrimination depends upon a complex interaction between the chromaticity of the glare source and that of the stimulus. In certain circumstances, such as in our R-G stimulus, glare can dramatically reduce chromatic discrimination ability by desaturating the component colors. | 10.1097/00006324-199412000-00010 |
pubmed_353_11061 | OBJECTIVE
Develop a patient education program that provides accurate and easy-to-understand information for newly diagnosed breast cancer patients.
METHODS
To inform development of the patient education program, we conducted a longitudinal series of semi-structured interviews with 30 breast cancer patients as well as one-time interviews with 22 healthcare providers. Responses guided the study team's decisions regarding both form and content.
RESULTS
We created a website (www.cancercarelinks.org) that reflects the needs expressed by patients and providers. The website is structured to answer six key questions that emerged in the interviews: What does my diagnosis mean? What will my treatment be like? Who will be involved with my treatment? What has treatment been like for others? How can I share my story with my family and friends? Where can I find more information and support? In a beta-test, 12 breast cancer patients rated the website as very clear, informative, trustworthy, useful, easy-to-understand, and easy to use.
CONCLUSION
The emotional weight of a breast cancer diagnosis, coupled with the amount of disparate information available, can be overwhelming for patients. Providing clear, accurate, and tailored information is a way to meet information needs and allay fears that patients will receive "bad" information.
PRACTICE IMPLICATIONS
Combining patient and provider input with the perspectives of a multidisciplinary team resulted in a promising patient education program for women diagnosed with breast cancer. The logic of this approach has implications for developing patient education programs for a variety of clinical contexts. | 10.1016/j.pec.2008.05.032 |
pubmed_1135_576 | Colorectal cancers are the third most common in both sexes and they are the second most common cause of cancer-related death. 12-15% of colorectal cancers develop through microsatellite instability (the hereditary mutation in at least one of DNA mismatch repair genes) pathway and they are 2-5% hereditary. In this study, we investigated the correlation between the clinicopathological features themselves and also the correlation between them and the immunohistochemical MLH-1, MSH-2, PMS-2, MSH-6 expressions in a total of 186 resection materials with colorectal adenocarcinoma between 2008 and 2012. All the cases were retrospectively evaluated in terms of age, sex, localization, size, accompanying polyp, multiple tumor, arising from polyp, differentiation, mucinous differentiation, pathological tumor stage, lymphovascular and perineural invasion, lymphocyte amount in the tumor microenvironment, surgical border and lymph node metastasis. We prepared multiple tissue blocks which had 4-millimeter tumor. Immunohistochemically, MLH-1, MSH-2, PMS-2, MSH-6 primary antibodies were studied. Statistically, "Kruskal-Wallis" ve "Pearson's chi-squared" tests were used. We found a positive correlation between loss of MLH-1 and PMS-2 expressions and the right-colon location, poor and mucinous differentiation and dense lymphocytic infiltration. In addition, loss of MSH-2 and MSH-6 expressions was correlated with the right-colon location, poor and mucinous differentiation. We found a meaningful relationship between immunohistochemical markers and clinicopathological features usually observed in tumors with microsatellite instability. This finding may arouse suspicion for MSI. However, the findings in our study must be supported with studies conducted in large series including molecular methods. | pubmed_1135_576 |
pubmed_877_4240 | The old novae V533 Her (Nova Her 1963), DI Lac (Nova Lac 1910), and RR Pic (Nova Pic 1891) are in (or near) their quiescent stage, following their nova explosions, and continue to accrete at a high rate in the aftermath of their explosions. They exhibit continua that are steeply rising into the FUV, as well as absorption lines and emission lines of uncertain origin. All three have Far Ultraviolet Spectroscopic Explorer (FUSE) spectra that offer not only higher spectral resolution but also wavelength coverage extending down to the Lyman Limit. For DI Lac, we have matched these FUSE spectra with existing archival International Ultraviolet Explorer spectral coverage to broaden the FUV wavelength coverage. We adopted the newly determined interstellar reddening corrections of Selvelli & Gilmozzi. The dereddened FUV spectra have been modeled with our grids of optically thick accretion disks and hot, NLTE white dwarf (WD) photospheres. The results of our modeling analysis indicate that the hot components in RR Pic and V533 Her are likely to be accretion disks with mass accretion rates of 10-8M⊙ yr-1 and 10-9M⊙ yr-1 respectively. However, the disk cannot produce the observed absorption lines. For the WD to be the source of the absorption lines in these two systems, it must be very hot, with a radius several times its expected size (because the WD in these systems is massive, it has a smaller radius). For DI Lac, we find the best fit to be a disk with Ṁ = 10-10M⊙ yr-1 with a 30,000 K WD. | 10.3847/1538-3881/153/3/109 |
pubmed_1082_5774 | The proliferating cell nuclear antigen (PCNA) is an adenovirus E1A-inducible factor that is intimately linked to the processes of DNA replication and cell cycle regulation. Previously, we defined a novel cis-acting element, the PCNA E1A-responsive element (PERE), that confers induction by the E1A 243R oncoprotein upon the human PCNA promoter. To better understand the regulation of PCNA expression by E1A 243R, we have identified cellular transcription factors that associate with the PERE. In electrophoretic mobility shift assays, the PERE formed three major complexes (P1, P2 and P3) with proteins in nuclear extracts from HeLa or 293 cells. Formation of complexes P2 and P3, which correlates with PCNA promoter activity in vivo, requires the activating transcription factor (ATF) binding site found within the PERE [Labrie et al. (1993) Mol. Cell. Biol., 13, 1697-1707]. Antibody interference experiments and mobility shift assays performed with in vitro-synthesized protein indicated that the transcription factor ATF-1 is a major component of these complexes. Similar assays demonstrated that the hepatitis B virus enhancer-associated protein RFX1 constitutes a major component of the P1 complex. In addition, we examined the binding of proteins to the minimal E1A-responsive promoter to identify other factors important for transcription from the PCNA promoter. Mobility shift assays revealed that a fragment encompassing the region from -87 to +62 relative to the transcription initiation site forms at least five complexes, EH1-EH5, with HeLa cell nuclear extracts. The transcription factor YY1 associates with the initiator element of the PCNA promoter. The identification of these transcription factors will allow their roles in the activation of PCNA by E1A to be evaluated. | 10.1093/nar/23.18.3732 |
pubmed_807_12010 | Despite evidence supporting improved incorporation of beneficial polyunsaturated fatty acids (PUFA) into ruminant products, such as meat and milk, following red clover and fish oil (FO) inclusion in the ruminant diet, little is known regarding the concomitant bacterial diversity. We evaluated the effects of feeding grass vs. red clover silage with incremental FO inclusion on known lipolytic, biohydrogenating, cellulolytic and proteolytic rumen bacterial communities of steers. Following 14 days of dietary adaptation, liquid-associated (LAB) and solid-associated (SAB) bacterial communities were harvested, DNA extracted and bacterial denaturing gradient gel electrophoresis (DGGE) and specific-bacterial quantitative PCR (QPCR) were undertaken. DGGE-derived dendrograms showed that diet caused the greatest change in LAB and SAB bacterial diversity, with FO inclusion at the 2% and 3% dry matter intake also causing some changes. QPCR revealed that diet resulted in changes in the DNA concentration of Anaerovibrio lipolytica, the Butyrivibrio proteoclasticus group, Fibrobacter succinogenes, Ruminococcus albus and Ruminococcus flavefaciens. FO inclusion caused changes in A. lipolytica, F. succinogenes and R. flavefaciens DNA concentration only. In the B. proteoclasticus group, which are the only known bacteria with the capacity to biohydrogenate PUFA to 18:0, DNA concentration did not correlate to 18:0 flow to the duodenum, however, suggesting that other bacteria may play a role in biohydrogenation. A greater understanding of microbial changes that accompany beneficial dietary changes will lead to novel strategies to improve ruminant product quality. | 10.1111/j.1574-6941.2010.00892.x |
pubmed_24_10448 | Gods and heroes of Greek myths have been of interest to psychoanalysts, who find them as symbols of human intrapsychic life, evolution, and conflicts. Many of these gods and heroes, like Oedipus, Electra, Eros, and Narcissus, have had their names given to psychological situations, conflicts, and diseases. Freud picked the myth of Narcissus as a symbol of a self-absorbed person whose libido is invested in the ego itself, rather than in other people. The term narcissistic personality disorder, also taken from the myth, describes a self-loving character with grandiose feelings of uniqueness. In this article, I reevaluate the myth of Narcissus and present a different psychoanalytic concept for this story. I view Narcissus as a symbol of a youth who seeks the image of anima or a feminine mental image in interpersonal love relationships, an image that can never be found in the real external world. This misguided quest for an imaginary love object only results in solitude. | 10.1007/s11231-005-9003-1 |
pubmed_730_7425 | AIMS
To study the absorption kinetics of sotalol following administration of different formulations. A formulation which results in fast absorption might be useful in the episodic treatment of paroxysmal supraventricular tachycardia (SVT), atrial fibrillation (Afib) or atrial flutter (Afl).
METHODS
In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually.
RESULTS
The addition of cisapride decreased the time at which maximum serum concentrations were reached (tmax) from 2.79 (1.85-4.34) h to 1.16 (0.68-2.30) h (P=0.009) [95% CI: -2.59, -0.55] and increased the absorption rate constant (ka) from 0.49 (0.31-0.69) h(-1) to 1.26 (0.52-5.61) h(-1) (P=0.017). The absolute bioavailability of sotalol was reduced by cisapride from 1.00+/-0.15 to 0.70+/-0.26 (P=0.006), while maximum serum concentrations of both oral solutions were not significantly different. Compared with the sublingually administered tablet with a median tmax of 2.12 (0.89-3.28) h, the sotalol/cisapride oral solution gave a smaller tmax (p=0.009) [95% CI: -1.64, -0.36]. The ka of the sotalol/cisapride solution was significantly (P=0.010) larger than the ka of 0.56 (0.33-0.75) h(-1) found after sublingual administration of the tablet.
CONCLUSIONS
The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl. | 10.1046/j.1365-2125.1998.00706.x |
pubmed_764_21179 | Grading of the cribriform pattern of prostate cancer is controversial, and the genetic changes are largely unknown. Furthermore, the pathogenetic relationship between the cribriform pattern of high-grade prostatic intraepithelial neoplasia (PIN) and cribriform carcinoma is poorly understood. We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y and a region-specific probe for c-myc to evaluate genetic changes in matched foci of high-grade PIN (48 foci) and prostatic carcinoma (71 foci) in 25 whole-mount radical prostatectomy specimens from patients with metastatic cancer. These cases included 10 foci of cribriform PIN and 10 foci of cribriform cancer. Numeric chromosomal anomalies were found in 67 and 68% of the high-grade PIN and carcinoma foci, respectively. Extra copies of the c-myc gene were identified in 52 and 44% of the high-grade PIN and carcinoma foci, respectively. The cribriform pattern of cancer had a higher percentage of foci with gain of chromosomes 7, 12, and Y, loss of chromosome 8, and extra copies of c-myc gene than other Gleason Primary Patterns 3 and 4; there was no difference, however, for all paired comparisons of genetic changes between the cribriform pattern of cancer and Gleason Primary Pattern 5 cancer. Cribriform PIN and cribriform cancer generally exhibited similar anomalies, although the percentage of foci with gain of chromosomes 10 and 12 was higher in cribriform cancer. Our results indicate that the cribriform pattern of prostate cancer shares genetic changes with Gleason Primary Pattern 5 and that both contain more genetic changes than the cribriform pattern of PIN. These findings suggest that the cribriform pattern of prostate cancer has biologic similarity with Gleason Pattern 5 carcinoma and that the cribriform pattern of PIN is closely associated with the cribriform pattern of prostatic carcinoma. | pubmed_764_21179 |
pubmed_489_3105 | Enterotoxigenic Escherichia coli (ETEC) causes child and travelers' diarrhea and is presumed to be water- and food-borne. Sporadic outbreaks were traced to consumption of contaminated fresh produce, particularly salad leaves as lettuce and parsley. Importantly, the mechanism by which ETEC binds salad leaves is not known. In this study we investigated the ability of clinical ETEC isolates to adhere to Eruca vesicaria (commonly known as rocket). Towards this end we inoculated pieces of cut E. vesicaria leaves with clinical ETEC isolates grown in Luria broth at 20°C, conditions that are not permissive for expression of the plasmid-encoded colonization factors and hence mimic the actual transmission pathways of ETEC through intake of contaminated food. We found that ETEC strains bind E. vesicaria at various efficiencies. Examination of representative strains by scanning electron microscopy revealed that they adhere to the E. vesicaria surface in a diffuse pattern by extended filaments resembling flagella. Using the prototype ETEC strain H10407 we found that it also binds to lettuce, basil and spinach leaves. Binding of H10407 was dependent on flagella as a fliC mutant attached to leaves at a much lower efficiency. Interestingly, under the employed environmental conditions EtpA, which forms a flagellar tip structure, and colonization factor I are dispensable for leaf attachment. The results show that ETEC can bind specifically to salad leaves, which might represent an important, yet less recognized, source of infection. | 10.1111/j.1758-2229.2010.00195.x |
pubmed_970_25244 | Flexible inorganic electronic devices (FIEDs) consisting of functional inorganic components on a soft polymer substrate have enabled many novel applications such as epidermal electronics and wearable electronics, which cannot be realized through conventional rigid electronics. The low thermal dissipation capacity of the soft polymer substrate of FIEDs demands proper thermal management to reduce the undesired thermal influences. The biointegrated applications of FIEDs pose even more stringent requirements on thermal management due to the sensitive nature of biological tissues to temperature. In this review, we take microscale inorganic light-emitting diodes (μ-ILEDs) as an example of functional components to summarize the recent advances on thermal management of FIEDs including thermal analysis, thermo-mechanical analysis and thermal designs of FIEDs with and without biological tissues. These results are very helpful to understand the underlying heat transfer mechanism and provide design guidelines to optimize FIEDs in practical applications. | 10.3390/mi11040390 |
pubmed_364_2095 | The unparalleled ability of DNA to recognize its complementary strand through Watson and Crick base pairing is one of the most reliable molecular recognition events found in natural systems. This highly specific sequence information encoded in DNA enables it to be a versatile building block for bottom-up self-assembly. Hence, the decoration of functional nanostructures with information-rich DNA is extremely important as this allows the integration of other functional molecules onto the surface of the nanostructures through DNA hybridization in a highly predictable manner. DNA amphiphiles are a class of molecular hybrids where a short hydrophilic DNA is conjugated to a hydrophobic moiety. Since DNA amphiphiles comprise DNA as the hydrophilic segment, their self-assembly in aqueous medium always results in the formation of nanostructures with shell made of DNA. This clearly suggests that self-assembly of DNA amphiphiles is a straightforward strategy for the ultradense decoration of a nanostructure with DNA. However, initial attempts toward the design of DNA amphiphiles were primarily focused on long flexible hydrocarbon chains as the hydrophobic moiety, and it has been demonstrated in several examples that they typically self-assemble into DNA-decorated micelles (spherical or cylindrical). Hence, molecular level control over the self-assembly of DNA amphiphiles and achieving diverse morphologies was extremely challenging and unrealized until recently.In this Account, we summarize our recent efforts in the area of self-assembly of DNA amphiphiles and narrate the remarkable effect of the incorporation of a large π-surface as the hydrophobic domain in the self-assembly of DNA amphiphiles. Self-assembly of DNA amphiphiles with flexible hydrocarbon chains as the hydrophobic moiety is primarily driven by the hydrophobic effect. The morphology of such nanostructures is typically predicted based on the volume ratio of hydrophobic to hydrophilic segments. However, control over the self-assembly and prediction of the morphology become increasingly challenging when the hydrophobic moieties can interact with each other through other noncovalent interactions. In this Account, the unique self-assembly behaviors of DNA-π amphiphiles, where a large π-surface acts as the hydrophobe, are described. Due to the extremely strong π-π stacking in aqueous medium, the assembly of the amphiphile is found to preferably proceed in a lamellar fashion (bilayer) and hence the morphology of the nanostructures can easily be tuned by the structural modification of the π-surface. Design principles for crafting various DNA-decorated lamellar nanostructures including unilamellar vesicles, two-dimensional (2D) nanosheets, and helically twisted nanoribbons by selecting suitable π-surfaces are discussed. Unilamellar vesicular nanostructures were achieved by using linear oligo(phenylene ethynylene) (OPE) as the hydrophobic segment, where lamellar assembly undergoes folding to form unilamellar vesicles. The replacement of OPE with a strongly π-stacking hydrophobe such as hexabenzocoronene (HBC) or tetraphenylethylene (TPE) provides extremely strong π-stacking compared to OPE, which efficiently directed the 2D growth for the lamellar assembly and led to the formation of 2D nanosheets. A helical twist in the lamella was achieved by the replacement of HBC with hexaphenylbenzene (HPB), which is the twisted analogue of HBC, directing the assembly into helically twisted nanoribbons. The most beneficial structural feature of this kind of nanostructure is the extremely dense decoration of their surface with ssDNA, which can further be used for DNA-directed organization of other functional nanomaterials. By exploring this, their potential as a nanoscaffold for predefined assembly of plasmonic nanomaterials into various plasmonic 1D, 2D, and 3D nanostructures through DNA hybridization is discussed. Moreover, the design of pH-responsive DNA-based vesicles and their application as a nanocarrier for payload delivery is also demonstrated. | 10.1021/acs.accounts.0c00492 |
pubmed_148_6848 | A study was made of the dependence of errors in recognizing visual and discriminating acoustic stimuli and of the reaction time (RT), on the duration of intersignal intervals (ISI) (10, 20, 50, 100, 200, 400, 600 and 1000 msec). With longer ISI a decrease in RT has been found, particularly pronounced in responses to the second stimuli of the pair. RT to the visual (acoustic) stimulus increases not only when an acoustic (photic) signal is present in the complex, but also in the case of its anticipation. The level of errors in recognizing visual and discriminating acoustic stimuli does not depend on ISI duration. The results so obtained are discussed as related to psychological refractory period and to interaction of sensorimotor channels of the human brain. | pubmed_148_6848 |
pubmed_618_20999 | PURPOSE/BACKGROUND
No evidence exits regarding the magnitude of the change in foot posture following the "modified reverse-6" (MR6) taping procedure, either alone or in combination with the "low-dye" (LD) taping technique. The purpose of this study was to investigate the change in the height and width of the midfoot after application of the MR6 and the MR6 plus the LD (MR6+LD) taping technique and determine how long those changes last.
METHODS
Eleven individuals (2 female and 9 male) were recruited for this study and were tested under each of two experimental conditions, the MR6 and the MR6+LD taping technique. The order of testing for the two conditions was randomly determined. For each condition, the height and width of the midfoot at 50% of each subject's foot length was initially measured and then again immediately following the application of the tape. These measurements were repeated four hours later immediately prior to running two miles on a treadmill, again immediately after running, and finally after another four hours.
RESULTS
The dorsal arch height increased significantly with both the MR6 and MR6+LD taping, but only the MR6+LD remained statistically greater after four hours, a bout of exercise and again at the end of the day. The mean width of the midfoot significantly decreased with both taping procedures. The change in the width of the midfoot remained significantly decreased in both taping conditions after exercise and throughout the day.
CONCLUSIONS
Both taping procedures are able to significantly change the height and width of the medial longitudinal arch of the foot, but the change lasted longer when the two taping procedures were combined.
LEVELS OF EVIDENCE
Level 3, Prospective Cohort Study. | pubmed_618_20999 |
pubmed_861_18011 | A novel microfluidic chip employing power-free polydimethylsiloxane (PDMS) femtoliter-sized arrays was developed for the detection of low concentrations of protein biomakers by isolating individual paramagnetic beads in single wells. Arrays of femtoliter-sized wells were fabricated with PDMS using well-developed molding techniques. Paramagnetic beads were functionalized with specific antibodies to capture the antigens. These antigens were labeled with enzymes via conventional multistep immunosandwich approach. After suspending in aqueous solutions of enzyme substrate, the solutions were delivered to the arrays using a conventional micropipette. The aqueous solutions were introduced into the microwells by capillarity and the beads were loaded into microwells by gravity. A fluorocarbon oil was then flowed into the chip to remove excess beads from the surface of the array and meanwhile isolated the femtoliter-sized wells. All processes were achieved by conventional micropipette, without external pumping systems and valves. Finally, the arrays were imaged using standard fluorescence imaging after incubation 30 min for digital counting enzyme molecules. It was demonstrated that the chip platform possessed the performance of digital counting with a linear dynamic range from 1 aM to 1 fM for the detection of biotinylated β-galactosidase (BβG), achieving a limit of detection (LOD) of 930 zM. Using this chip, a digital immunoassay to detect Tumor Necrosis Factor α (TNF- α) was developed. Since the chip fabrication is low-cost and circumvents the surface modification, we expect it can become a new chip-based digital immunoassay platform for ultrasensitive diagnostic of biomarkers. | 10.1016/j.bios.2019.111339 |
pubmed_163_13297 | We investigate multiplexing of four highly sensitive Fabry-Perot (FP) microresonators at the tip of a single-mode optical fiber for refractive index (RI) measurements with simultaneous temperature compensation. The individual sensing elements for RI or temperature consist of either open-cavity FP resonators or solid fiber core regions fabricated by diamond-blade dicing of single-mode optical fibers, respectively. The reflectivity of the open resonators is further enhanced by matched dielectric coatings. At the same time, the solid core resonators formed by the fiber pieces between the open cavities are used as thermometers. This allows immediate compensation for temperature cross-sensitivity during RI measurements. The general performance of the sensor is demonstrated by measuring the RI of sucrose solutions, where we use phase tracking of the characteristic Fourier transform components of the backreflected optical spectrum for evaluation. The temperature sensitivity is on average 20±/∘C with an accuracy of 0.01°C, fully sufficient for biomedical applications. Meanwhile, the four RI sensing (open) cavities show high sensitivity of approximately 1160 nm/RIU. Due to the compact size of the sensor, small spatial inhomogeneities of RI can be accurately detected. If the cavities are additionally filled with molecularly imprinted polymers or coated with thin functional layers, they could also be used for the detection of trace substances in biomedical laboratory-on-a-fiber applications. | 10.1364/AO.438565 |
pubmed_525_10802 | The authors give an account of an uncommon cause of haemoperitoneum--spontaneous rupture of an angiosarcoma-afflicted liver. During the urgent operation haemostatic stitches, partial devascularisation of the liver and tamponade were used. The patient died during the postoperative period due to prolonged haemorrhagic shock and developing multiorgan failure. The authors discuss possible methods of haemostasis of hepatic origin, and emphasize perihepatic tamponade (packing). Failure of the surgery of this case-history is discussed. | pubmed_525_10802 |
pubmed_39_19064 | BACKGROUND
The aim of this study was to determine the evolution of HIV infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their epidemiological characteristics in Barcelona city.
METHODS
Population-based incidence study of all newly occurring diagnoses of HIV infection, syphilis, gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A descriptive analysis was performed. The annual incidence rates per 100,000 inhabitants were calculated by sex, sexual conduct and educational level. To estimate global sex-specific rates we used the Barcelona city census; for the calculation of rates by sexual conduct and educational level we used estimates of the Barcelona Health Interview Survey. Trends were analysed using the chi-squared test for linear trend.
RESULTS
HIV. 66.8 % of the HIV cases were men who had sex with men (MSM). The incidence rates in MSM over the study period were from 692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh. and the MSM with a university education ranged from 196.3/100,000 to 1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with university education ranged from 176.7/100,000 to 530.1/100,000 inh.. Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with university education ranged from 9.3/100,000 to 265/100,000 inh.
CONCLUSION
An increase in cases of STI was observed. These STI mainly affected MSM with a university education. Continuing to monitor changes in the epidemiology of STI, and identifying the most affected groups should permit redesigning preventive programs, with the goal of finding the most efficient way to reach these population groups. | 10.1186/s12889-015-2344-7 |
pubmed_722_20087 | The SUPERFAMILY resource provides protein domain assignments at the structural classification of protein (SCOP) superfamily level for over 1400 completely sequenced genomes, over 120 metagenomes and other gene collections such as UniProt. All models and assignments are available to browse and download at http://supfam.org. A new hidden Markov model library based on SCOP 1.75 has been created and a previously ignored class of SCOP, coiled coils, is now included. Our scoring component now uses HMMER3, which is in orders of magnitude faster and produces superior results. A cloud-based pipeline was implemented and is publicly available at Amazon web services elastic computer cloud. The SUPERFAMILY reference tree of life has been improved allowing the user to highlight a chosen superfamily, family or domain architecture on the tree of life. The most significant advance in SUPERFAMILY is that now it contains a domain-based gene ontology (GO) at the superfamily and family levels. A new methodology was developed to ensure a high quality GO annotation. The new methodology is general purpose and has been used to produce domain-based phenotypic ontologies in addition to GO. | 10.1093/nar/gkq1130 |
pubmed_464_17840 | The phenomena of intermittent and complete synchronization between two out of three identical, magnetically coupled Superconducting QUantum Interference Devices (SQUIDs) are investigated numerically. SQUIDs are highly nonlinear superconducting oscillators/devices that exhibit strong resonant and tunable response to applied magnetic field(s). Single SQUIDs and SQUID arrays are technologically important solid-state devices, and they also serve as a testbed for exploring numerous complex dynamical phenomena. In SQUID oligomers, the dynamic complexity increases considerably with the number of SQUIDs. The SQUID trimer, considered here in a linear geometrical configuration using a realistic model with experimentally accessible control parameters, exhibits chaotic and hyperchaotic behavior in wide parameter regions. Complete chaos synchronization as well as intermittent chaos synchronization between two SQUIDs of the trimer is identified and characterized using the complete Lyapunov spectrum of the system and appropriate measures. The passage from complete to intermittent synchronization seems to be related to chaos-hyperchaos transitions as has been conjectured in the early days of chaos synchronization. | 10.1063/5.0058249 |
pubmed_271_24718 | Hygrophila spinosa T Ander, belonging to the family Acanthaceae, is a promising medicinal plant with great economic potential. The medicinal value of H. spinosa has been appreciated in the ancient medical literature. The plant contains terpenoids, alkaloids, flavonoids, and is traditionally known as an aphrodisiac, renal tonic, and for its health-promoting properties. The plant is cultivated throughout India. However, systematic information on the different aspects of this species is not available. In this review, an attempt has been made to present this information. | 10.4103/0973-7847.70912 |
pubmed_332_54 | Familial hypercholesterolemia (FH) is an autosomal-dominant inherited disease with a prevalence of one in 500 (heterozygous) to one in 1,000,000 (homozygous). Mutations of the low-density lipoprotein (LDL) receptor gene, the apolipoprotein B100 gene, or the PCSK9 gene may be responsible for the disease. The resulting LDL hypercholesterolemia results in premature atherosclerosis as early as childhood (homozygous FH) or in adulthood (heterozygous FH). Current treatment modalities include lifestyle modification, combination drug therapy (statin-based), and apheresis. Mipomersen is an antisense oligonucleotide which inhibits apolipoprotein B production independent of LDL receptor function and thus works in homozygous FH, heterozygous FH, and other forms of hypercholesterolemia. Mipomersen is given 200 mg/week subcutaneously. Phase III studies indicate that the LDL cholesterol concentration can be reduced by 25%-47%, lipoprotein(a) levels by 20%-40%, and triglyceride concentrations by approximately 10%. In general, mipomersen has no effect on high-density lipoprotein cholesterol concentrations. Although there is considerable interindividual variability, the observed lipid effects are largely independent of age, gender, concomitant statin therapy, and underlying dyslipoproteinemia. The most common side effects are injection site reactions (70%-100%), flu-like symptoms (29%-46%), and elevated transaminases associated with an increased liver fat content (6%-15%). Mipomersen may be an interesting addon drug in patients with heterozygous or homozygous FH not reaching treatment goals, either because baseline values are very high or because high-dose statins are not tolerated. | 10.2147/CE.S25239 |
pubmed_254_15499 | Despite having a focus on sustainability policy planning, failures occur during the implementation process. The gap between policy and its implementation causes failures of the sustainability policy. Against this backdrop, the primary objective of the present study is to explore the factors that create hurdles in the implementation of corporate sustainability policy in letters and spirits. The study adopts a systematic literature review (SLR) approach and reviews all the possible studies from 1950 to 2019 published by six major publishing houses. These studies were found using selected keywords. The findings of SLR reveal governance, education, and SMEs as frequently appearing words while exploring corporate sustainability. The stakeholder theory and the institutional theory appear as the most cited theories in the sustainability literature. The grassroots approach, environmental impact assessment, integrated sustainability assessment, evidence-based practice approach, systematic approach, economical instrument policy approach, and consultant services approach appear as the most relevant approaches used for policymaking in corporate sustainability. The SLR findings reveal five significant factors that influence corporate sustainability policy implementation and can cause the gap between policy and its implementation. These factors are government institutions (including macro and meso-institutions), internal and external stakeholders, management, organizational barriers, and normative references. | 10.1007/s11356-020-12143-7 |
pubmed_148_1528 | Seventy-one patients with acute pancreatitis are reviewed. Biliary disease was incriminated as an aetiological factor in 17 of these patients. During the period under review, 141 patients with acute cholecystitis were treated. The age and sex incidence in these 3 groups are compared, and some diagnostic problems are discussed. | pubmed_148_1528 |
pubmed_1084_23690 | The ADP-ribosyl cyclase CD38 whose catalytic domain resides in outside of the cell surface produces the second messenger cyclic ADP-ribose (cADPR) from NAD(+). cADPR increases intracellular Ca(2+) through the intracellular ryanodine receptor/Ca(2+) release channel (RyR). It has been known that intracellular NAD(+) approaches ecto-CD38 via its export by connexin (Cx43) hemichannels, a component of gap junctions. However, it is unclear how cADPR extracellularly generated by ecto-CD38 approaches intracellular RyR although CD38 itself or nucleoside transporter has been proposed to import cADPR. Moreover, it has been unknown what physiological stimulation can trigger Cx43-mediated export of NAD(+). Here we demonstrate that Cx43 hemichannels, but not CD38, import cADPR to increase intracellular calcium through RyR. We also demonstrate that physiological stimulation such as Fcγ receptor (FcγR) ligation induces calcium mobilization through three sequential steps, Cx43-mediated NAD(+) export, CD38-mediated generation of cADPR and Cx43-mediated cADPR import in J774 cells. Protein kinase A (PKA) activation also induced calcium mobilization in the same way as FcγR stimulation. FcγR stimulation-induced calcium mobilization was blocked by PKA inhibition, indicating that PKA is a linker between FcγR stimulation and NAD(+)/cADPR transport. Cx43 knockdown blocked extracellular cADPR import and extracellular cADPR-induced calcium mobilization in J774 cells. Cx43 overexpression in Cx43-negative cells conferred extracellular cADPR-induced calcium mobilization by the mediation of cADPR import. Our data suggest that Cx43 has a dual function exporting NAD(+) and importing cADPR into the cell to activate intracellular calcium mobilization. | 10.1074/jbc.M111.307645 |
pubmed_401_20922 | Textile industries are one of the leading environmental pollutants by releasing harmful dye effluents. In many textile distrts, the amount of excess color in treated textile effluent that exceeds regulatory limitations is still being a major concern. The combining usage of nanomaterials and polymer material to solve these issues using various techniques. In this research, graphene oxide-copper oxide (GO-CuO) nanomaterial have been incorporated into cellulose-acetate (CA), poly-ether sulfone (PES) blend polymer by using phase inversion process to fabricate thin film nanocomposite (TFN) membrane for removal of dye pollutant. The physiochemical properties of prepared TFN materials were studied by Fourier transform infra-red spectroscopy (FT-IR), X-ray diffractometer (XRD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), thermo gravimetric analysis (TGA), and mechanical strength analysis. Dye adsorption experiments were performed with four typical water-soluble organic dyes methylene blue (MB), rhodamine blue (Rh. B), methyl orange (MO) and Congo red (CR). After reaching adsorption equilibrium, the composite membrane final removal effectiveness for MB 92.42%, Rh. B 89.39%, CR 68.39%, and MO 58.82% respectively. As a result, the fabricated TFN material proves to be an effective adsorbent material for cationic dye molecules. Also, when the fabricated material was tested with textile industry effluent sample, all physio-chemical properties exhibited a considerable decrease in concentrations when compared to the real textile effluent concentration. The treated effluents permitted for a relatively greater growth and germination index of Tropical amaranth roots than the textile effluent, this demonstrates that phytotoxicity testing was also successful. The most effective temperature, concentration and pH were found to be 273 K, 1 × 10-5 M and pH 9. The fabricated TFN membrane material (GO-CuO @ CA-PES) can be recommended for water treatment applications. | 10.1007/s11356-022-21821-7 |
pubmed_469_19347 | In this study, sugarcane bagasse was pretreated with acid-catalyzed alcohols, i.e., ethanol (AE), ethylene glycol (AEG) and glycerol (AG) to prepare pulps for producing lignin-containing cellulose nanofibrils (LCNF) with tailored properties, such as hydrophilicity/hydrophobicity and dispersion stability. The results showed that AG-LCNF had the highest lignin content of 16% but relatively low hydrophobicity while AE-LCNF had a low lignin content of 11% but the highest hydrophobicity. LCNF diameter distribution, crystallinity, zeta potentials and thermal stability were also determined to understand the effects of pretreatment solvent. NMR analyses revealed that alcohols modified lignin at α-position by etherification and γ-position by esterification of aliphatic chains, subsequently affecting lignin oxidation by TEMPO in the LCNF production processes, LCNF properties and LCNF dispersion in different solvents. This study provided fundamental information in the design and tailored production of LCNF for various applications, such as manufacturing polymer composites and Pickering emulsions. | 10.1016/j.carbpol.2022.119602 |
pubmed_49_14412 | Three-dimensional reconstruction techniques including bull's-eye polar-coordinate maps, surface rendering, and surface modeling have been developed that help interpreting physicians assimilate complex 3-D tomographic data. Comparison of patient data with normal files highlights myocardial perfusion abnormalities, thus facilitating their recognition. In addition, AI systems that use heuristically defined rules derived from an expert knowledge base assist inexperienced observers in drawing conclusions regarding scan abnormalities. | 10.2214/ajr.152.6.1161 |
pubmed_590_18111 | The aims of this study were to evaluate pain, depression level, fatigue, sleep, and quality of life (QoL) among patients with benign joint hypermobility syndrome (BJHS) and to compare their results with those of healthy controls. The study involved 115 patients and 114 healthy volunteers. Pain level was rated using visual analogue scale (VAS) for all patients. Depression level, fatigue, sleep quality, and QoL of all the participants were evaluated by the Beck Depression Inventory (BDI), the Checklist Individual Strength (CIS), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form-36 (SF-36), respectively. VAS value was 6.29 ± 0.94 in the patient group. Comparison of two groups showed that there were statistically significant differences between the patient group and the control group with respect to BDI, total CIS, PSQI scores, SF-36 subscales (physical function, role physical, bodily pain, general health, role emotional, and mental health), and mental component summary (p < 0.001). While pain is the predominant symptom among BJHS patients, depression, fatigue, impaired sleep, and QoL also commonly occur. Thus, all of these components should be taken into account when assessing patients with BJHS. | 10.1007/s10067-014-2610-6 |
pubmed_171_15797 | Functional genetic polymorphisms of DNA repair genes are good candidates for cancer susceptibility markers. We studied two genes coding for proteins removing small DNA adducts by direct repair (MGMT), or mispaired DNA bases by base excision repair (TDG). The non-silent polymorphisms of MGMT (84:Phe, 143:Val, 178:Arg) and TDG (199:Ser, 367:Met), and the functional MGMT enhancer polymorphism, did not show any statistically significant association with lung cancer risk in our case-control analysis, but due to the relatively small number of individuals, strong conclusions on cancer risk association or lack thereof cannot be made. Sequencing of the TDG cDNA has not revealed any novel polymorphism, but did find an alternatively spliced mRNA missing exon 2. Our search for polymorphisms within the promoter-enhancer region of MGMT revealed three novel sequence variants. The functional significance of the previously published MGMT enhancer polymorphism (1099C->T) was assessed. The less frequent sequence variant of the enhancer was associated with a modest (16-64%), but statistically significant, increase of MGMT promoter-enhancer activity in the studied cell lines. This work points to the importance of studying the expression-regulating elements of genes, as they may contain functional polymorphisms with the potential for modulating risk of various diseases, including cancer. | 10.1046/j.1529-8817.2004.00079.x |
pubmed_750_13067 | Prediction of postoperative cerebral infarction after cardiovascular surgery is difficult. The present study investigated whether quantitative evaluation of preoperative cerebral blood flow used in the Japanese EC-IC Bypass Trial (JET) study is useful for the prediction of postoperative cerebral infarction after cardiovascular surgery. First, patients were divided into two groups based on preoperative cerebral blood flow. In an evaluation using preoperative imaging, patients with good or mildly decreased preoperative cerebral blood flow, divided into clinical stage I or II by quantitative evaluation showed no postoperative cerebral infarction. However, 24% of patients with poor cerebral blood flow who were categorized as clinical stage II, experienced postoperative cerebral infarction. The incidence rate was not statistically significantly different when the groups were compared. Second, patients were divided into two groups based on the anatomical area of the brain affected corresponding to clinical stage II. Patients with a 10% and greater brain involvement had a significantly higher incidence of postoperative cerebral infarction (38%) compared to others (0%, p<0.01). This method may be useful for the prediction of postoperative cerebral infarction after cardiovascular surgery, but a further prospective study is needed. (This is a translation of J Jpn Coll Angiol 2017; 57: 125-133.). | 10.3400/avd.oa.18-00116 |
pubmed_1105_14349 | A 66-year-old woman started oral prednisone for temporal artery biopsy (TAB) proven GCA and developed central haziness OD > OS. Visual acuity worsened to 20/100 OD and 20/25 OS. Clinical exam, optical coherence tomography (OCT) and fluorescein angiography (FA) revealed central serous chorioretinopathy (CSCR). The patient was treated with focal laser therapy for CSCR and steroid taper. Patients with giant cell arteritis on high dose steroids may present with significant loss of visual acuity and field. CSCR (precipitated by steroids) should be considered in the differential diagnosis as increasing the steroid dose for presumed visual loss secondary to GCA might worsen rather than improve the visual outcome. | 10.1080/08820530500511396 |
pubmed_922_4615 | Cocaine addiction is a chronic relapsing brain disorder characterized by compulsive drug seeking. Preliminary study suggested that bromodomain-containing protein 4 (BRD4), an epigenetic reader protein, participates in cocaine-induced reward and neuroplasticity. However, the exact role of BRD4 in cocaine addiction, particularly cocaine relapse, remains elusive. In this study, we found that BRD4 phosphorylation in the nucleus accumbens (NAc) was closely related to the maintenance of cocaine reinforcement and relapse in different cocaine exposure paradigms. Cocaine significantly increased the binding of phosphorylated BRD4 (pBRD4) at the promoter of Gria2 and Bdnf genes in the NAc. (+)JQ1, a selective BRD4 inhibitor, markedly reduced the reinforcement and reinstatement of cocaine-seeking behaviors, which was accompanied by the decreased expressions of GRIA2 and BDNF. Furthermore, chromatin immunoprecipitation assay showed that (+)JQ1 clearly attenuated cocaine-enhanced binding of pBRD4 at the promotor of Gria2 and Bdnf genes. Blockade of casein kinase II significantly attenuated BRD4 phosphorylation and cocaine relapse-like behaviors, suggesting the important role of pBRD4 in modulating cocaine effect. Together, our findings suggest that BRD4 phosphorylation in the NAc modulates multiple addiction-related behaviors of cocaine and particularly relapse to cocaine-seeking behaviors. Inhibition of BRD4 activity may be a novel target against cocaine addiction and relapse. | 10.1111/adb.12808 |
pubmed_1133_1444 | OBJECTIVE
The aim of the study was to examine the relationship between role stress, emotional exhaustion, and a supportive coworker climate among health care workers, by adopting a multilevel perspective.
METHODS
Aggregated data of 738 health care workers nested within 67 teams of three Italian hospitals were collected. Multilevel regression analysis with a random intercept model was used.
RESULTS
Hierarchical linear modeling showed that a lack of role clarity was significantly linked to emotional exhaustion at the individual level. At the unit level, the cross-level interaction revealed that a supportive coworker climate moderated the relationship between lack of role clarity and emotional exhaustion.
CONCLUSION
This study supports previous results of single-level burnout studies, extending the existing literature with evidence on the multidimensional and cross-level interaction associations of a supportive coworker climate as a key aspect of job resources on burnout. | 10.1097/JOM.0000000000001122 |
pubmed_989_15765 | An aberrant right subclavian artery (ARSA) can be overlooked by the conventional method as described by Chaoui et al., due to acoustic shadowing. The aim of this study was to evaluate the feasibility and accuracy of a novel screening method for ARSA by demonstrating the brachiocephalic artery bifurcation, referred to as the "No ARSA" sign. A prospective study conducted at a tertiary care center between 2018 and 2019 included unselected pregnant patients at a median gestational age of 15.1 (14.2-22.1; IQR (inter-quartile range)) weeks, who had been referred for a routine or targeted anomaly scan. All participants were scanned for the presence or absence of ARSA using both the conventional and the novel "No ARSA" methods for validation purposes. A total of 226 unselected patients were enrolled in the study. The "No ARSA" sign was visualized in 218 fetuses (96.5%). In the remaining 8 cases (3.5%), the "No ARSA" sign was not demonstrated. In these fetuses, an ARSA was visualized by the conventional method. The new method exhibited 100% feasibility and was in complete agreement with the conventional method. Intra- and inter-observer agreement was excellent (κ = 1). The results of the study suggest that the "No ARSA" sign is an efficient and reliable screening tool for ARSA. | 10.3390/jcm9082658 |
pubmed_488_496 | Absolute kidney length and the ratio of right to left kidney lengths were estimated by the method of Eklöf & Ringertz in a series of 142 patients with unilateral renal duplication. The anomalous kidney was frequently found to be larger than the contralateral one, particularly when associated with ectopic ureterocele, which was present in 34 patients. Nevertheless, a substantial number of reduplicated kidneys had a length below mean, some of them actually below -2SD. | 10.1177/028418517601705a11 |
pubmed_920_22164 | At present, GNSS (Global Navigation Satellite System) positioning technology is widely used for outdoor positioning services because of its high-precision positioning characteristics. However, in indoor environments, effective position information cannot be provided, because of the signals being obscured. In order to improve the accuracy and continuity of indoor positioning systems, in this paper, we propose a PDR/UWB (Pedestrian Dead Reckoning and Ultra Wide Band) integrated navigation algorithm based on an adaptively robust EKF (Extended Kalman Filter) to address the problem of error accumulation in the PDR algorithm and gross errors in the location results of the UWB in non-line-of-sight scenarios. First, the basic principles of UWB and PDR location algorithms are given. Then, we propose a loose combination of the PDR and UWB algorithms by using the adaptively robust EKF. By using the robust factor to adjust the weight of the observation value to resist the influence of the gross error, and by adjusting the variance of the system adaptively according to the positioning scene, the algorithm can improve the robustness and heading factor of the PDR algorithm, which is constrained by indoor maps. Finally, the effectiveness of the algorithm is verified by the measured data. The experimental results showed that the algorithm can not only reduce the accumulation of PDR errors, but can also resist the influence of gross location errors under non-line-of-sight UWB scenarios. | 10.3390/s21134390 |
pubmed_269_8026 | By fall 2020, students returning to U.S. university campuses were mandated to engage in COVID-19 mitigation behaviors, including masking, which was a relatively novel prevention behavior in the U.S. Masking became a target of university mandates and campaigns, and it became politicized. Critical questions are whether the influences of injunctive norms and response efficacy on one behavior (i.e. masking) spill over to other mitigation behaviors (e.g. hand-washing), and how patterns of mitigation behaviors are associated with clinical outcomes. We conducted a cross-sectional survey of college students who returned to campus (N = 837) to explore these questions, and conducted COVID-19 antibody testing on a subset of participants to identify correlations between behaviors and disease burden. The results showed that college students were more likely to intend to wear face masks as they experienced more positive injunctive norms, liberal political views, stronger response efficacy for masks, and less pessimism. Latent class analysis revealed four mitigation classes: Adherents who intended to wear face masks and engage in the other COVID-19 mitigation behaviors; Hygiene Stewards and Masked Symptom Managers who intended to wear masks but only some other behaviors, and Refusers who intended to engage in no mitigation behaviors. Importantly, the Hygiene Stewards and Refusers had the highest likelihood of positive antibodies; these two classes differed in their masking intentions, but shared very low likelihoods of physical distancing from others and avoiding crowds or mass gatherings. The implications for theories of normative influences on novel behaviors, spillover effects, and future messaging are discussed. | 10.1080/10410236.2022.2049047 |
pubmed_1105_2342 | Topoisomerase II-alpha (TOP2A) has been investigated as a potential predictor for the response to doxorubicin-based chemotherapy which is a representative TOP2A inhibitor and one of the most effective chemotherapeutics for the breast cancer treatment. We performed the assay for the TOP2A gene amplification and deletion on a tissue microarray (TMA) of 284 breast tumor samples from the patients treated by doxorubicin-based adjuvant chemotherapy. TOP2A gene was deleted in six patients (2.1%), whereas TOP2A gene was amplified in 20 (7.1%) of 284 tumors. Twenty-four of 26 TOP2A amplifications and deletions were associated with HER2 co-amplification. TOP2A amplification or deletion was not associated with poor clinical outcome. Nine (34.6%) of 26 patients with TOP2A amplification or deletion had recurrent disease. Thirty percent of the patients with TOP2A amplification had systemic recurrence whereas 50% of the patients with TOP2A deletion had systemic recurrence. On multivariate analysis, histologic grade and tumor size were the significant predictors for the disease-free survival and histologic grade was an only significant predictor for the overall survival. Our study indicates that response to the doxorubicin-based chemotherapy might be stratified by TOP2A amplification and deletion. However, relative low frequency of TOP2A genetic changes seems to hamper its clinical utility. | 10.1007/s10549-006-9170-7 |
pubmed_173_13786 | Epigenetic processes that regulate histone acetylation play an essential role in behavioral and molecular responses to cocaine. To date, however, only a small fraction of the mechanisms involved in the addiction-associated acetylome have been investigated. Members of the bromodomain and extraterminal (BET) family of epigenetic "reader" proteins (BRD2, BRD3, BRD4, and BRDT) bind acetylated histones and serve as a scaffold for the recruitment of macromolecular complexes to modify chromatin accessibility and transcriptional activity. The role of BET proteins in cocaine-induced plasticity, however, remains elusive. Here, we used behavioral, pharmacological, and molecular techniques to examine the involvement of BET bromodomains in cocaine reward. Of the BET proteins, BRD4, but not BRD2 or BRD3, was significantly elevated in the nucleus accumbens (NAc) of mice and rats following repeated cocaine injections and self-administration. Systemic and intra-accumbal inhibition of BRD4 with the BET inhibitor, JQ1, attenuated the rewarding effects of cocaine in a conditioned place preference procedure but did not affect conditioned place aversion, nor did JQ1 alone induce conditioned aversion or preference. Investigating the underlying mechanisms, we found that repeated cocaine injections enhanced the binding of BRD4, but not BRD3, to the promoter region of Bdnf in the NAc, whereas systemic injection of JQ1 attenuated cocaine-induced expression of Bdnf in the NAc. JQ1 and siRNA-mediated knockdown of BRD4 in vitro also reduced expression of Bdnf. These findings indicate that disrupting the interaction between BET proteins and their acetylated lysine substrates may provide a new therapeutic avenue for the treatment of drug addiction.
SIGNIFICANCE STATEMENT
Proteins involved in the "readout" of lysine acetylation marks, referred to as BET bromodomain proteins (including BRD2, BRD3, BRD4, and BRDT), have been shown to be key regulators of chromatin dynamics and disease, and BET inhibitors are currently being studied in several clinical trials. However, their role in addiction-related phenomena remains unknown. In the current studies, we revealed that BRD4 is elevated in the nucleus accumbens and recruited to promoter regions of addiction-related genes following repeated cocaine administration, and that inhibition of BRD4 attenuates transcriptional and behavioral responses to cocaine. Together, these studies reveal that BET inhibitors may have therapeutic utility in the treatment of cocaine addiction. | 10.1523/JNEUROSCI.0826-15.2015 |
pubmed_635_16144 | The nutrition transition with associated lifestyle-related non-communicable diseases has rapidly reached many developing countries, including Saudi Arabia. Therefore, the objective of this study was to examine the prevalence of overweight, obesity, and abdominal obesity among Saudi adolescents. This school-based multicentre cross-sectional study was conducted during 2009-2010 in three major cities in Saudi Arabia: Al-Khobar, Jeddah, and Riyadh. Participants included 2,908 students of secondary schools (1,401 males and 1,507 females) aged 14 to 19 years, randomly selected using a multistage stratified cluster-sampling technique. Weight, height, and waist-circumference were measured; prevalence of overweight and obes- ity was determined using age- and sex-specific BMI cutoff reference standards of the International Obesity Task Force (IOTF). Abdominal obesity was determined using waist-to-height ratio (WHtR) cutoffs (above 0.5). The prevalence of overweight was 19.5% in males and 20.8% in females while that of obesity was 24.1% in males and 14% in females. The prevalence of abdominal obesity in males and females was 35.9% and 30.3% respectively. Higher prevalence of obesity was observed among adolescents in private schools. Across all ages, overweight and obesity ranged from 39.9% to 45.6% in males and from 30.4% to 38.7% in females. ANCOVA, controlling for age, showed significant interaction effects (city by gender). It is concluded that the proportions of overweight, obesity, and abdominal obesity, observed among Saudi adolescents were remarkably high. Such high prevalence of overweight and obesity is a major public-health concern. | pubmed_635_16144 |
pubmed_324_18014 | Enhancers, silencer and insulators are DNA elements that play central roles in regulation of the genome that are crucial for development and differentiation. In metazoans, these elements are often separated from target genes by distances that can reach 100 Kb. How regulation can be accomplished over long distances has long been intriguing. Current data indicate that although the mechanisms by which these diverse regulatory elements affect gene transcription may vary, an underlying feature is the establishment of close contacts or chromatin loops. With the generalization of this principle, new questions emerge, such as how the close contacts are formed and stabilized and, importantly, how they contribute to the regulation of transcriptional output at target genes. This review will concentrate on examples where a functional role and a mechanistic understanding has been explored for loops formed between genes and their regulatory elements or among the elements themselves. | 10.1093/bfgp/elq033 |
pubmed_336_11865 | OBJECTIVE
Impaired pulmonary gas exchange after cardiac surgeries with cardiopulmonary bypass (CPB) often occurs, and the selection of mechanical ventilation mode, pressure-controlled ventilation (PCV) or volume-controlled ventilation (VCV), may be important for preventing hypoxia and improving oxygenation. The authors hypothesized that patients with PCV would show better oxygenation, compared with VCV, during one-lung ventilation (OLV) for mitral valve repair surgery (MVP) via thoracotomy.
DESIGN
Randomized controlled trial.
SETTING
University teaching hospital.
PARTICIPANTS
Sixty patients in each group.
INTERVENTIONS
MVP was performed using thoracotomy with OLV by PCV or VCV.
MEASUREMENTS AND MAIN RESULTS
Arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FIO2) were measured before anesthesia induction (T0), at skin incision (T1), after administration of heparin (T2), at 30 minutes after CPB weaning (T3), just before departure from the operating room to the intensive care unit (ICU) (T4), and 1 hour after ICU admission (T5), and PaO2/FIO2 ratio was calculated. Peak inspiratory pressure (PIP) and mean inspiratory pressure (Pmean) were recorded at T1, T2, T3, and T4. No significant difference was noted in the PaO2/FIO2 ratio between the groups at any measured point. PIP in the PCV group at all measured points was lower than that in the VCV group (T1, p<0.001; T2, p<0.001; T3, p<0.001; T4, p=0.025, respectively). Pmean was not different between the two groups at any measured point.
CONCLUSIONS
PCV during OLV in patients undergoing MVP via a thoracotomy with OLV showed lower PIP compared with VCV, but this did not improve pulmonary gas exchange. | pubmed_336_11865 |
pubmed_763_13990 | This study evaluated a new tool, "The Audit of Physical Activity Resources for Seniors" (APARS), which assesses the physical activity environment in Senior Living Residences (SLRs). Audits were conducted in 29 SLRs and inter-rater reliability was assessed. Pearson correlations were examined between APARS items and objectively measured physical activity and sedentary time, and self-rated health, collected from residents at a subset of 12 SLRs (N=147). Eighty-nine of the 90 items (98.9%) demonstrated Kappa or ICC values above .70 and/or percent agreement above 80%. The 90 items were summarized into nine scales. Two scales (outside supportive physical activity features/functionality and outside exercise facilities) were related to greater physical activity and less sedentary time. Four scales (inside social facilities, onsite services, exercise programs, and social activities) were related to greater sedentary time and better self-rated health. APARS items demonstrated adequate inter-rater reliability and some evidence for construct validity to assess health-related environments in retirement facilities. Social activities in SLRs could benefit residents by incorporating more physical activity. Use of APARS could inform more health-promoting designs of senior living facilities. | 10.1016/j.jaging.2011.03.004 |
pubmed_80_10205 | BACKGROUND
CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been significantly associated with Alzheimer's disease (AD). To ascertain whether CYP19A1 gene polymorphisms are correlated with the susceptibility to AD, we performed this systematic review and meta-analysis of currently available studies.
MATERIALS AND METHODS
A comprehensive literature search was conducted by using PubMed, Embase, and Web of Science databases and the Cochrane Library. The association was evaluated by using odds ratios (ORs) and 95% confidence intervals (CIs) through Stata software (version 12.0).
RESULTS
A total of eight articles including 39 case-control studies with 11,051 subjects including 3215 AD cases and 7836 controls were involved in this meta-analysis. By pooling all eligible studies, we detected that rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene were significantly associated with AD risk. A significant association between rs10046 polymorphism and AD risk was found under allele contrast, homozygous (TT vs CC: OR = 1.17, 95%CI = 1.02-1.34, I2 = 0.0%, P = 0.026), and dominant genetic models. In addition, we observed an association between with rs1143704 polymorphism under heterozygous and dominant genetic models (TT+TA vs AA: OR = 1.36, 95%CI = 1.03-1.79, I2 = 0.0%, P = 0.033). Similar results were found in rs767199 and rs727479 polymorphisms, while null results were found for other polymorphisms.
CONCLUSIONS
This systematic review and meta-analysis suggested that the rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene significantly increase AD susceptibility. In addition, our results demonstrated that homozygous TT genotype in rs10046, dominant AA and AG genotypes in rs767199, homozygous TT genotype in rs727479, and dominant TT and TA genotypes in rs1143704 might be the susceptibility genotypes for AD, while no associations were observed between rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms and AD susceptibility. | 10.1007/s10072-019-04003-1 |
pubmed_707_11633 | BACKGROUND
Tetanus, a vaccine-preventable disease, is still occurring in the elderly population of low- and middle-income countries with a high case-fatality rate. The objective of the study was to elucidate the factors associated with in-hospital mortality of tetanus in Bangladesh.
METHODS
This prospective observational study, conducted in two specialized infectious disease hospitals, conveniently selected adult tetanus patients (≥18 years) for inclusion. Data were collected through a preformed structured questionnaire. Kaplan Meier survival analysis and univariate and multivariable Cox regression analysis were carried out to assess factors associated with in-hospital mortality among patients. All analysis was done using Stata (version 16) and SPSS (version 26).
RESULTS
A total of 61 tetanus cases were included, and the overall in-hospital mortality rate was 34.4% (n = 21). Patients had an average age of 46.49 ±15.65 years (SD), and the majority were male (96.7%), farmers (57.4%), and came from rural areas (93.4%). Survival analysis revealed that the probability of death was significantly higher among patients having an age of ≥ 40 years, incubation time of ≤12 days, onset time of ≤ 4 days, and having complication(s). However, on multivariable Cox regression analysis, age (adjusted hazard ratio [aHR] 4.03, 95% Confidence Interval [CI] 1.07-15.17, p = 0.039) and onset time (≤4 days) (aHR 3.33; 95% CI 1.05-10.57, p = 0.041) came as significant predictors of in-hospital mortality after adjusting for incubation period and complications.
CONCLUSION
Older age and short onset time are the two most important determinants of in-hospital mortality of tetanus patients. Hence, these patients require enhanced emphasis and care. | 10.1371/journal.pntd.0010235 |
pubmed_625_22597 | Estrogen receptor α (ERα) is expressed in ~67% of breast cancers and is critical to their proliferation and progression. The expression of ERα is regarded as a major prognostic marker, making it a meaningful target to treat breast cancer (BCa). However, hormone receptor-positive BCa was sometimes irresponsive or even resistant to classic anti-hormonal therapies (e.g., fulvestrant and tamoxifen). Hence, novel anti-endocrine therapies are urgent for ERα+ BCa. A phase II study suggested that bortezomib, an inhibitor blocking the activity of 20 S proteasomes, intervenes in cancer progression for anti-endocrine therapy in BCa. Here we report that proteasome-associated deubiquitinases (USP14 and UCHL5) inhibitors b-AP15 and platinum pyrithione (PtPT) induce growth inhibition in ERα+ BCa cells. Further studies show that these inhibitors induce cell cycle arrest and apoptosis associated with caspase activation, endoplasmic reticulum (ER) stress and the downregulation of ERα. Moreover, we suggest that b-AP15 and PtPT block ERα signaling via enhancing the ubiquitin-mediated degradation of ERα and inhibiting the transcription of ERα. Collectively, these findings demonstrate that proteasome-associated deubiquitinases inhibitors b-AP15 and PtPT may have the potential to treat BCa resistant to anti-hormonal therapy. | 10.1038/s41389-018-0086-y |
pubmed_1049_2215 | JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a central nervous system infection that mainly affects AIDS patients. The extensive application of highly active antiretroviral therapy (HAART) is leading to the appearance of "long-term" survival PML patients. A reliable and feasible qualitative-quantitative test for both the detection of JCV and follow-up of its viral burden in this emerging group of patients is clearly required. With this aim, a dual qualitative-quantitative nested PCR is presented in this study for the analysis of JCV DNA in cerebrospinal fluid (CSF). Two newly designed internal controls, one competitive and the other noncompetitive, have been constructed to adapt this PCR to either measure the JCV burden or to allow a highly confident determination of JCV presence or clearance. The analytical sensitivity of the technique allows the detection of 0.01 fg (three genomes) of JCV DNA. Its qualitative application has been evaluated by analyzing single CSF samples from a group of 17 patients with PML and a control group of 20 patients with diverse neurological conditions other than PML, yielding sensitivity and specificity values of 100 and 90%, respectively. The quantitative application has been evaluated in vitro in blind tests with samples including serial dilutions of JCV, and in all cases the samples were successfully ordered considering the JCV titer. The dual quantitative-qualitative application offered by this nested PCR may provide an answer to the new requirements for evaluating and finely monitoring PML in AIDS patients receiving HAART. | 10.1128/JCM.37.3.724-728.1999 |
pubmed_898_12693 | Proper function of many physiological processes requires a robust circadian clock. Disruptions of the circadian clock can result in metabolic diseases, mood disorders, and accelerated aging. Therefore, identifying small molecules that specifically modulate regulatory core clock proteins may potentially enable better management of these disorders. In this study, we applied a structure-based molecular-docking approach to find small molecules that specifically bind to the core circadian regulator, the transcription factor circadian locomotor output cycles kaput (CLOCK). We identified 100 candidate molecules by virtual screening of ∼2 million small molecules for those predicted to bind closely to the interface in CLOCK that interacts with its transcriptional co-regulator, Brain and muscle Arnt-like protein-1 (BMAL1). Using a mammalian two-hybrid system, real-time monitoring of circadian rhythm in U2OS cells, and various biochemical assays, we tested these compounds experimentally and found one, named CLK8, that specifically bound to and interfered with CLOCK activity. We show that CLK8 disrupts the interaction between CLOCK and BMAL1 and interferes with nuclear translocation of CLOCK both in vivo and in vitro Results from further experiments indicated that CLK8 enhances the amplitude of the cellular circadian rhythm by stabilizing the negative arm of the transcription/translation feedback loop without affecting period length. Our results reveal CLK8 as a tool for further studies of CLOCK's role in circadian rhythm amplitude regulation and as a potential candidate for therapeutic development to manage disorders associated with dampened circadian rhythms. | 10.1074/jbc.RA119.011332 |
pubmed_54_3986 | Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. The post-transcriptional regulation is influenced by these lncRNAs by interfering with the microRNA pathways, involving in diverse cellular processes. The regulation of gene expression by lncRNAs at the epigenetic level, transcriptional and post-transcriptional level have been well known and widely studied. Recent recognition that lncRNAs make effects in many biological and pathological processes such as stem cell pluripotency, neurogenesis, oncogenesis and etc. This review will focus on the functional roles of lncRNAs in epigenetics and related research progress will be summarized. | 10.1186/1480-9222-16-11 |
pubmed_133_1533 | In all organisms, type II DNA topoisomerases are essential for untangling chromosomal DNA. We have determined the structure of the DNA-binding core of the Methanococcus jannaschii DNA topoisomerase VI A subunit at 2.0 A resolution. The overall structure of this subunit is unique, demonstrating that archaeal type II enzymes are distinct from other type II topoisomerases. However, the core structure contains a pair of domains that are also found in type IA and classic type II topoisomerases. Together, these regions may form the basis of a DNA cleavage mechanism shared among these enzymes. The core A subunit is a dimer that contains a deep groove that spans both protomers. The dimer architecture suggests that DNA is bound in the groove, across the A subunit interface, and that the two monomers separate during DNA transport. The A subunit of topoisomerase VI is homologous to the meiotic recombination factor, Spo11, and this structure can serve as a template for probing Spo11 function in eukaryotes. | 10.1093/emboj/18.21.6177 |
pubmed_552_9141 | Alzheimer's Disease (AD) is a very complex and devastating disorder of the brain that affects over 2 million people in the United States, mostly over age 65. Approximately one-half are taken care of at home by family members; the remainder are in institutions. Nearly 120,000 deaths are attributed to AD annually. While biomedical research continues to make headway in uncovering factors related to the disease, the causes, and therefore, the treatment remain just beyond our reach. In the meantime, persons with AD, their family members, and professional caregivers must learn to cope with this disabling disease on a day-to-day basis while waiting for a breakthrough. AD is characterized by a gradual decline in mental status and functional abilities over an extended period of time, from as short as 1 year to as long as 10 years or more. Eventually, all components of cerebral functioning are altered, with the neuronal losses exhibited at the cognitive and behavioral level. The nature and degree of decline depends on the extent of the progression of neuronal deterioration and, therefore, varies widely from patient to patient. The complex interactional patterns of pathophysiological brain changes and the concomitant cognitive/behavioral manifestations present careplanning and caregiving dilemmas. On the one hand, it is our responsibility as nurses to treat patients and teach others to care for patients in the least restrictive environment possible, while maintaining a choice of options, promoting optimal functioning, and fostering independence in the patient.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1016/s0883-9417(05)80009-3 |
pubmed_385_6698 | Electrical stimulation of the frog glossopharyngeal (GP) nerve evoked slow hyperpolarizing potentials (HPs) in taste cells. This study aimed to clarify whether slow HPs were postsynaptically induced in taste cells. The slow HPs were recorded intracellularly with a microelectrode. When Ca2+ concentration in the blood plasma was decreased to approximately 0.5 mM, the amplitude of slow HPs reduced and their latency lengthened. When the Ca2+ concentration was increased to approximately 20 mM, the amplitude of slow HPs increased and their latency shortened. Addition of Cd2+ to the plasma greatly reduced the amplitude of slow HPs and lengthened their latency. These data suggest that the slow HPs are dependent on presynaptic activities in the GP nerve terminals in the taste disk. Of various antagonists injected intravenously for blocking receptors of neurotransmitter biogenic amines and peptides, only antagonists for substance P blocked the slow HPs at 2-4 mg/kg body wt. Application of substance P of 2 mg/kg to the plasma induced hyperpolarizing responses in taste cells, whose amplitude was the same as that of the slow HPs induced by GP nerve stimulation. Application of a nonselective cation channel antagonist, flufenamic acid, to the plasma blocked the slow HPs. These results suggest that the slow HPs are generated by closing the nonselective cation channels in the postsynaptic membrane of taste cells following possible release of substance P from the GP nerve terminals in the taste disk. | 10.1093/chemse/bjh072 |
pubmed_283_23784 | Fabry disease is a rare, X-linked inborn error of glycosphingolipid metabolism caused by a deficiency of the lysosomal enzyme α-galactosidase A. Progressive deposition of GL-3 starts early in life, presumably as early as in fetal life. Chronic burning or provoked attacks of excruciating pain in hands and feet in Fabry disease are common in most children as well as GI-symptoms.We describe a case of pediatric Fabry disease with gastrointestinal dysmotility symptoms as primary and most severe complaints. Colonic pseudoobstruction and necrosis developed by the age of 15 years. We hypothesize that this patient developed a gastrointestinal phenotype of pediatric Fabry disease that has not been described before. | 10.1007/8904_2011_63 |
pubmed_983_14132 | Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines. | 10.1007/s11239-011-0667-5 |
pubmed_916_10301 | This study compares diagnostic imaging tools in detecting the parasitic swimbladder nematode Anguillicoloides crassus in Anguilla anguilla (L.) and focuses on ultrasound in an attempt to develop a non-destructive, field diagnostic test. Ultrasound use could allow the parasite to be diagnosed without decreasing the number of critically endangered European eels through post-mortem. In the preliminary study, eels were examined with computed radiography, computed tomography, magnetic resonance imaging, 14 MHz high-end ultrasound and 5 MHz low-end portable ultrasound, and the results were compared with post-mortem findings. This ultrasound scanning technique did not produce any promising results. A second batch of eels was examined using the same high-end and low-end ultrasounds, but employing a different scanning technique and comparing the results with post-mortem. This second study, scanning along the midline from below, allowed for the detection of anomalies associated with moderately infected animals. None of the eels used in this study were severely infected; thus, no conclusions can be made regarding the use of ultrasound in those animals. Overall, it was found that none of the techniques were useful in diagnosing mildly infected individuals; therefore, no single diagnostic imaging tool is sensitive enough to replace post-mortem for definite diagnosis. | 10.1111/jfd.12383 |
pubmed_676_5457 | Male sexual behavior is determined by the interaction of endocrine and environmental stimuli originating from the female, yet it is unknown how and where these stimuli are integrated within the brain. Activation of copulatory behavior by testosterone is limited by its central aromatization into an estrogen in the preoptic area. We investigated whether mating-induced neuronal activation as identified by the expression of the immediate early gene Fos occurs in aromatase-immunoreactive (ARO-ir) cells of the male quail preoptic area. Fos-immunoreactive (ir) cells were observed within and lateral to these ARO-ir cells groups but few ARO-ir cells contained Fos-ir indicating that mating-related stimuli do not directly affect estrogen-synthesizing cells. | 10.1097/00001756-199904060-00003 |
pubmed_1091_14208 | BACKGROUND
Echocardiography plays a central role in diagnosing infective endocarditis (IE). Accordingly, the European Society of Cardiology (ESC) has proposed a diagnostic echocardiographic algorithm. However, new studies are still needed to evaluate the degree of implementation of these guidelines in clinical practice and their consequences on incidence and prognosis of IE.
AIM
This study aims to investigate the diagnostic yield of the ESC proposed echocardiographic algorithm in patients with suspected IE. We also examined the association among IE diagnosis and clinical outcomes.
METHODS
Retrospective analysis of a series of patients undergoing the ESC algorithm for clinical suspicion of IE at our institution.
RESULTS
Between 2009 and 2013, 323 cases were managed by a multidisciplinary team for clinical suspicion of IE. Following ESC algorithm, 26 (8%) patients were diagnosed with IE and 297 (92%) had IE excluded. In 92% of patients with a good-quality negative transthoracic echocardiography (TTE) and low level of clinical suspicion, the first TTE was considered sufficient to rule out IE. During a mean follow-up of 2.3 ± 1.4 years, patients who had a final diagnosis of IE showed similar mortality (P = 0.2) and rates of combined endpoint (all-cause death, stroke/transient ischemic attack, advanced atrioventricular block, and heart failure) compared to patients without echocardiographic diagnosis of IE (P = 0.5). Only 1% of the patients who had IE excluded experienced IE in the following 3 months, none of them in the subgroup of patients, in which a first negative TTE was considered sufficient to rule out IE.
CONCLUSIONS
In spite of the current ESC recommendation TTE is used as part of a routine fever screen. Consequently, only a minority of patients had a final echocardiographic diagnosis of IE. Although in patients with low clinical suspicion a first negative TTE is sufficient to rule out IE, the incidence of clinical events is similar regardless the final diagnosis of IE. | 10.4103/jcecho.jcecho_49_17 |
pubmed_950_3111 | Sesame is an important oil-crop worldwide. Complex tradeoffs between various yield components significantly affect the outcome yield. Our aims were to characterize the effect of genotype, environment and management, and their interactions, on yield components. Wild-type line, bearing a bicarpellate-capsule and three capsules per leaf axil, and its derived mutant-line, featuring one tetracarpellate-capsule per leaf axil, were analyzed under two irrigation regimes and three sowing-stands. Dissection of flower meristems and capsules showed larger placenta size and final capsule diameter in the mutant-line. Allelic segregation of F2 population revealed that the number of carpels per capsule demonstrates monogenic inheritance, whereas the number of capsules per leaf axil is a polygenic trait. A significant effect of genotype, irrigation and stand was observed on most yield components. While wild-type had more capsules per plant, the mutant-line compensated by increased seed number per capsule and consequently accumulated the same number of seeds per plant. Under either high intra-row or inter-row density, the branches number was reduced; however, the outcome yield was compensated by number of plants per area. While some yield components showed phenotypic-plasticity (branching), other traits were genetically stable (number of capsules per leaf axil and number of carpels per capsule). Our result shed-light on tradeoffs between yield components and on their underlying mechanisms. | 10.1016/j.plantsci.2019.03.018 |
pubmed_620_9315 | The study of enolase in man-mouse somatic hybrids confirms synteny between ENO1 and the markers on human chromosome 1 (AK2, PGM1, Pep-C) and synteny between ENO2 and the markers on human chromosome 12 (LDHB, Pep-B). The study also shows that the different enolase bands observed in mouse cell strains (Cl1D, R4, A9, 3T3), in hamster cell strains (CH, V79/4, A3), and in 3 of the different bands observed in human fibroblasts have a dimeric structure. The formation of these enolase bands depends on genes at two different loci alpha and beta. The hamster cell line CH (HGPRT) showed a rare enolase phenotype with a two-banded pattern in the intermediate region, a triple-banded pattern in the slow region, and one single isozyme in the fast region. This hamster strain is heterozygous for the first locus and homozygous for the second one. The relationship between these different enolase bands is as follow: in the slow "a" zone, alpha1alpha1,alpha1 alpha2,alpha2alpha2; in the intermediate "i" zone, alpha1beta1, alpha2beta1; and, in the fast "b" zone, beta1beta1. It appears that the frequency of heterozygotes for the alpha or beta loci in man is very low. Of 32 unrelated fibroblast strains investigated, none was found to be heterozygous for the alpha or beta locus. | pubmed_620_9315 |
pubmed_648_7404 | An amendment to this paper has been published and can be accessed via a link at the top of the paper. | 10.1038/s41393-020-0413-y |
pubmed_953_23834 | PURPOSE
To evaluate a new computerized segmentation technique for the quantification of intraretinal and subretinal fluid in spectral-domain optical coherence tomography (SD OCT) images of the retina.
DESIGN
Prospective, cross-sectional study.
METHODS
Thirty-seven B-scan images of 37 patients with exudative age-related macular degeneration were chosen randomly from SD OCT volume scans (1 per volume scan). All hyporeflective areas in the image first were segmented automatically as candidate regions by the program. Researchers who were masked to the candidate region information selected each fluid region from the original image using a single mouse click. The program then delineated the boundary of each region selected and calculated quantitative parameters, including total area of fluid regions if multiple regions were selected. The performance of our technique was validated by comparing the results with the measurements obtained from boundaries manually delineated by 2 masked observers. Time efficiency, agreement with manual delineation, and intraobserver and interobserver agreement of using the program were evaluated.
RESULTS
The proposed technique reduced the average processing time per image approximately 6-fold (15 seconds for computerized segmentation vs 90 seconds for manual delineation). There was good agreement between computerized segmentation and manual delineation measured by intraclass correlation coefficient (range, 0.897 to 0.979) and the Dice coefficient (range, 0.721 to 0.785). The proposed technique has excellent intraobserver and interobserver agreement (intraclass correlation coefficient range, 0.998 to 0.999; Dice coefficient range. 0.959 to 0.981).
CONCLUSIONS
This computerized segmentation method allows for accurate and fast quantification of fluid in retinal SD OCT images and could assist in monitoring disease progression and evaluating therapeutic intervention. | pubmed_953_23834 |
pubmed_399_12607 | A retrospective study involving 78 cases of oral carcinoma was conducted to investigate their association with the habit of taking snuff orally known as 'snuff-dipping' and locally termed 'saffa'. It was found that 50 (81%) of the 62 questioned patients used snuff in the form of saffa. It was also found that carcinomatous changes usually developed in the area of the mouth where the snuff was habitually placed. It was concluded that the association between saffa and development of oral carcinoma is likely to be causal. | 10.1016/0266-4356(89)90152-6 |
pubmed_625_23026 | Radiotherapy (RT) may result in platelet activation and thrombosis development. To the best of our knowledge, the potential effect of volumetric-modulated arc therapy (VMAT), a novel radiotherapy technique, on platelet function and microRNA (miRNA/miR) expression has not been previously investigated. The present study aimed to determine the effect of VMAT on the alterations in platelet function parameters and miRNA expression levels. A total of 25 patients with prostate cancer and 25 healthy subjects were included in the present study. Blood samples were collected from the patient group on the day prior to RT (pre-RT), the day RT was completed (post-RT day 0), and 40 days following the end of therapy (post-RT day 40). Platelet count, mean platelet volume (MPV) value, platelet aggregation, plasma P-selectin, thrombospondin-1, platelet factor 4, plasma miR-223 and miR-126 expression levels were measured. A significant decrease in platelet count in the post-RT day 0 group was measured in comparison with the pre-RT and the post-RT day 40 groups. Pre-RT MPV values were higher than those of the post-RT day 0 and the post-RT day 40 groups. No significant differences were observed in the levels of platelet activation markers or miR-223 and miR-126 expression levels between the RT groups. Although RT may result in a reduction in platelet and MPV counts, the results of the present study indicate that platelet activation markers are not affected by VMAT. Therefore, it is possible that no platelet activation occurs during VMAT, owing to the conformal dose distributions, improved target volume coverage and the sparing of normal tissues from undesired radiation. | 10.3892/ol.2018.9167 |
pubmed_63_9896 | PURPOSE
To use the BI-RADS ultrasound classification in an intraobserver retrospective study of the interpretation of breast images.
MATERIALS AND METHODS
The study used 40 breast ultrasound images recorded in orthogonal planes, obtained from patients with an indication for surgery. Eight professionals experienced in breast imaging analysis retrospectively reviewed these lesions, in three rounds of image interpretation (with a 3-6 months interval between rounds). Observers had no access to information from medical records or histopathological results, and, without their knowledge, in each new round were assigned the same images previously interpreted by them. Fleiss-modified Kappa measures were the study main concordance index. Besides the BI-RADS, a scale grouping its categories 2-3 and 4-5 was also used. The statistical analysis concerned the intraobserver agreement.
RESULTS
Kappa values ranged from 0.37 to 0.75 (original categories) and from 0.73 to 0.87 (grouped categories). Overall, out of the 8 observers, 7 presented moderate to substantial concordance (Kappa values 0.51 to 0.74).
CONCLUSION
The BI-RADS is a reporting tool that provides a standardized terminology for US exams. In this study, moderate to substantial concordance in Kappa values was found, in agreement with other studies of the literature. | 10.1016/j.ejrad.2009.04.015 |
pubmed_1082_5440 | Loss of heterozygosity (LOH) at loci on chromosome 9p and/or 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder. However, localisation of the tumour suppressor locus or loci on 9q has been hampered by the relative infrequency of tumours with subchromosomal deletions. We have used 24 microsatellite markers to examine LOH in 70 new cases of TCC of the bladder and upper urinary tract. Forty tumours (57%) showed LOH at one or more loci on 9q and partial deletions were detected in five tumours (7%). Combined data from the five cases with partial deletions place one tumour suppressor locus at 9q34 between D9S61 and D9S66 (an estimated distance of 13-14 cM). This region is frequently deleted in other sporadic tumours and encompasses one of the loci for tuberous sclerosis (TSC1). One tumour contained a distinct deletion between D9S153 and D9S109 (9q13-q31), which encompasses the locus for the familial nevoid basal cell carcinoma syndrome (Gorlin syndrome). This may indicate the presence of another tumour suppressor locus on 9q for TCC. Our findings significantly reduce the regions of 9q within which suppressor genes for TCC may reside. The possible involvement of two deletion targets on 9q in addition to the locus at 9p21 implicated in TCC may explain why LOH at all loci on chromosome 9 is frequent in TCC. | pubmed_1082_5440 |
pubmed_1067_4090 | The United Kingdom Department of Health initiative on "The Expert Patient" (2001) reflects recent trends in political philosophy, ethics and health services research. The overall objective of the initiative is to encourage patients, particularly those suffering from chronic conditions to become more actively involved in decisions concerning their treatment. In doing so there would be (perhaps) an expectation of better patient compliance and (arguably) a resultant improvement in quality of life. Despite these anticipated beneficial influences on health outcomes, there may be a danger that such initiatives are being carried along by the general swell of enthusiasm for recognising and facilitating the claims of disadvantaged or discriminated against groups. What more attractive than that patients should be "liberated" from what might be seen as the oppression of medical paternalism? To a great extent the potential for success of the Expert Patient venture turns on:(a) whether and to what extent a patient can be considered truly to be an expert and (b) full acceptance by the medical and heath care professions of allowing patients a more equitable and positive role. Whilst clearly the patient is an expert in the hermeneutic sense - it is they and they alone who experience their illness - there is nevertheless a risk of confusing experience with expertise. Experience limited to an individual does not of itself give rise to the generalisations that underlie reliable clinical treatment. Neither do the vast majority of patients possess the physiological and pharmacological knowledge to fully appreciate the biological nature of their illness nor the basis, risks or limitations of therapeutic measures. Might the notion of "The Expert Patient" as informed co-decision maker become a well-meaning but rather vacuous aspiration similar to that of informed consent? Even worse, could patient "empowerment" have a deleterious effect? The paper reviews some of the major issues and concludes that the expert patient initiative could have benefits for both patients and health professionals if operated on the basis of concordance: an informed collaborative alliance that optimises the potential benefits of medical care. | 10.1007/s11019-005-2275-7 |
pubmed_67_17183 | BACKGROUND
Sarcopenia is a common skeletal muscle disorder in the elderly population. The patients with sarcopenia increased the cost of care and the risk for hospitalization. Magnesium deficiency might increase reactive oxygen species and protein damage. The purpose of our study was to demonstrate the relation between oral intake magnesium and sarcopenia by European Working Group on Sarcopenia in Older People (EWGSOP) 2 definition.
METHODS
Our study included 2532 participants with 1310 males and 1222 females. The multiple logistic regression model was designed to test the cross-sectional protective outcome of oral intake magnesium for sarcopenia.
RESULTS
Oral intake magnesium had a protective outcome with sarcopenia (odd ratio (OR) = 0.997, 95% CI = 0.996, 0.998, P < 0.001). After fully adjusted, the significance persisted with OR = 0.998 (95% CI = 0.996, 0.999, P < 0.001).
CONCLUSION
Results of the present study showed the dose dependent relationship between oral intake magnesium and sarcopenia. Sufficient oral intake magnesium might prevent patient from sarcopenia. | 10.1186/s12877-022-03522-5 |
pubmed_832_15966 | The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) altered the logistics of ongoing randomized controlled trials (RCTs). The need to reduce in-person research and clinical activities, however, presented an additional level of complexity in order to continue conducting RCTs that focused on the development of medications for Alcohol Use Disorder (AUD). The visits required a systematic objective evaluation from the physician and mental health professional and clinical staff, as many of the safety and efficacy assessments are self-reported. The following commentary addresses the successes and limitations our RCTs encountered during the coronavirus (COVID-19) pandemic. | 10.1016/j.alcohol.2021.01.001 |
pubmed_637_4145 | Computer simulations of clines (Brues, 1972; Endler, 1977) as well as theoretical arguments (Nagylaki, 1975), have shown that steps in gene frequencies will be pulled to partial barriers (areas of reduced gene flow) if they form within approximately a cline width of the partial barrier. The behavior of a hybrid zone between two chromosomal taxa ("Moreton" and "Torresian") of the acridine grasshopper Caledia captiva in southeast Queensland has been analyzed and found to comform qualitatively with a model of altered gene flow patterns. Clines in four enzyme systems were analyzed for 1983 and 1986 along a transect across the hybrid zone. The clines have shifted towards an area of regenerating forest, while homozygote frequencies have increased at this point. This forest barrier has broken the continuity of the spatial distribution of C. captiva, forming population islands in part of the hybrid zone, and thus reducing the amount of gene flow. The distance between the barrier and the original cline is approximately of the order of a cline width, so that they would be expected to interact. Historical information suggests that the secondary contact between the "Moreton" and "Torresian" taxa occurred very recently (1844-1940), due to the intensive land-clearing activities during the European settlement. | 10.1111/j.1558-5646.1991.tb02666.x |
pubmed_182_10932 | BACKGROUND
Traditionally in Asia, hepatitis B (HBV) accounts for the majority of hepatocellular carcinoma (HCC), but increasingly, non-viral or nonalcoholic steatohepatitis (NASH) etiology may play a more prominent role with current socioeconomic changes. There remains a paucity in data comparing NASH-HCC to HBV-related HCC. In this study, we explored the differences in clinical characteristics between HBV- and cryptogenic-related HCC.
METHODS
Patients with HCC seen in the Department of Gastroenterology and Hepatology, Singapore General Hospital were enrolled in an ongoing database since 1980. Patients with HCC attributed to HBV or cryptogenic etiology were identified. Comparison of clinical characteristics was performed between the two groups.
RESULTS
There were 916 HBV-HCC patients and 163 cryptogenic HCC patients, accounting for 70.9% and 12.6% of the total HCC cases (1292 patients), respectively. Out of the total cohort enrolled from 1980 to 2005, the ratio of cryptogenic to HBV patients was 1:6.7, while from 2006 to the current year, the ratio of cryptogenic to HBV patients has increased significantly to 1:3.9. Relative to patients with HBV, cryptogenic HCC patients were older (67.6 vs. 59.4 years old; p < 0.001), had lower proportion of male patients (69.9% vs. 83.8%; p < 0.001), and had higher incidence of smoking (32.2% vs. 25.8%; p = 0.008). HBV group had higher alanine transaminase (60.9 ± 85.7 U/L vs. 48.0 ± 52.1 U/L; p = 0.003), hemoglobin (12.7 ± 2.28 g/dL vs. 12.0 ± 2.46 g/dL, p < 0.001), albumin (32.9 ± 6.8 g/L vs. 31.3 ± 7.7 g/L; p = 0.007), and prothrombin time (13.2 ± 2.95 s vs. 12.7 ± 2.01 s, p = 0.023), as compared to the cryptogenic group. Cryptogenic HCC patients presented more frequently with unifocal HCC (55.2% vs. 46.5%; p = 0.002). There was no difference in the proportions of patients receiving surgical resection in both groups (23.5% in HBV group vs. 17.9% in cryptogenic group; p = 0.202). Cox regression analysis revealed no survival difference between cryptogenic-related HCC and HBV-related HCC (p = 0.367).
CONCLUSION
Temporal trends suggest that HCC attributed to HBV is on the decline, while cryptogenic- or NASH-related HCC is an emerging clinical entity. A paradigm shift in approach to screening, surveillance, and management of HCC may be required in view of the changing landscape of HCC epidemiology into an increasing non-viral etiology. | 10.1007/s10620-018-5331-x |
pubmed_512_11695 | The increasing demand for environmentally friendly production processes of green chemicals and fuels has stimulated research in microbial metabolic engineering. CRISPR-Cas-based tools for genome editing and expression control have enabled fast, easy, and accurate strain development for established production platform organisms, such as Escherichia coli and Saccharomyces cerevisiae. However, the growing interest in alternative production hosts, for which genome editing options are generally limited, requires further developing such engineering tools. In this review, we discuss established and emerging CRISPR-Cas-based tools for genome editing and transcription control of model and non-model prokaryotes, and we analyse the possibilities for further improvement and expansion of these tools for next generation prokaryotic engineering. | 10.1016/j.tibtech.2016.02.004 |
pubmed_290_14270 | Hinge craniotomy (HC) is a technique that allows for a degree of decompression whilst retaining the bone flap in situ, in a 'floating' or 'hinged' fashion. This provides expansion potential for ensuing cerebral oedema whilst obviating the need for cranioplasty in the future. The exact indications, technique and outcomes of this procedure have yet to be determined, but it is likely that HC provides an alternative technique to decompressive craniectomy (DC) in certain contexts. The primary objective was to collate and describe the current evidence base for HC, including perioperative parameters, functional outcomes and complications. The secondary objective was to identify current nomenclature, operative technique and operative decision-making. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Fifteen studies totalling 283 patients (mean age 45.1 and M:F 199:46) were included. There were 12 different terms for HC. The survival rate of the cohort was 74.6% (n = 211). Nine patients (3.2%) required subsequent formal DC. Six studies compared HC to DC following traumatic brain injury (TBI) and stroke, finding at least equivalent control of intracranial pressure (ICP). These studies also reported reduced rates of complications, including infection, in HC compared to DC. We have described the current evidence base of HC. There is no evidence of substantially worse outcomes compared to DC, although no randomised trials were identified. Eventually, a randomised trial will be useful to determine if HC should be offered as first-line treatment when indicated. | 10.1007/s10143-019-01180-7 |
pubmed_592_2049 | Estimates of calf blood flow with venous occlusion plethysmography vary widely between studies, perhaps due to the use of different plethysmographs. Consequently, we compared calf blood flow estimates at rest and during reactive hyperemia in eight healthy subjects (four men and four women) with two commonly used plethysmographs: the mercury-in-silastic (Whitney) strain gauge and Dohn air-filled cuff. To minimize technical variability, flow estimates were compared with a Whitney gauge and a Dohn cuff on opposite calves before and after 10 min of bilateral femoral arterial occlusion. To account for any differences between limbs, a second trial was conducted in which the plethysmographs were switched. Resting flows did not differ between the plethysmographs (P = 0.096), but a trend toward lower values with the Whitney was apparent. Peak flows averaged 37% lower with the Whitney (27.8 +/- 2.8 ml.dl-1.min-1) than with the Dohn plethysmograph (44.4 +/- 2.8 ml.dl-1.min-1; P < 0.05). Peak flow expressed as a multiple above baseline was also lower with the Whitney (10-fold) than with the Dohn plethysmograph (14.5-fold; P = 0.02). Across all flows at rest and during reactive hyperemia, estimates were highly correlated between the plethysmographs in all subjects (r2 = 0.96-0.99). However, the mean slope for the Whitney-Dohn relationship was only 60 +/- 2%, indicating that over a wide range of flows the Whitney gauge estimate was 40% lower than that for the Dohn cuff. These results demonstrate that the same qualitative results can be obtained with either plethysmograph but that absolute flow values will generally be lower with Whitney gauges. | 10.1152/jappl.1996.81.3.1418 |
pubmed_875_9062 | We examined the effect of acute exercise compared to a cognitive task on implicit approach/avoidance motivation to dessert food images using the Dessert-Approach-Avoidance Task. Participants randomized to exercise had a greater increase in approach motivation to dessert images compared to those completing cognitive tasks ( p=0.046), adjusting for disordered eating, task difficulty, and changes in negative affect. This study provides the first evidence for the use of the Dessert-Approach-Avoidance Task to evaluate the effects of acute exercise on implicit motivations for dessert images. Future studies should examine implicit response to food images using the Dessert-Approach-Avoidance Task in response to chronic exercise. | 10.1177/1359105316657404 |
pubmed_598_6662 | BACKGROUND
Despite common mechanisms of actions, glucagon-like peptide-1 receptor agonists differ in structure, pharmacokinetic profile, and clinical effects. This head-to-head trial compared semaglutide with dulaglutide in patients with inadequately controlled type 2 diabetes.
METHODS
This was an open-label, parallel-group, phase 3b trial done at 194 hospitals, clinical institutions or private practices in 16 countries. Eligible patients were aged 18 years or older and had type 2 diabetes with HbA1c 7·0-10·5% (53·0-91·0 mmol/mol) on metformin monotherapy. Patients were randomly assigned (1:1:1:1) by use of an interactive web-response system to once a week treatment with either semaglutide 0·5 mg, dulaglutide 0·75 mg, semaglutide 1·0 mg, or dulaglutide 1·5 mg subcutaneously. The primary endpoint was change from baseline in percentage HbA1c; the confirmatory secondary endpoint was change in bodyweight, both at week 40. The primary analysis population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment and before the onset of rescue medication. The safety population included all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment. The trial was powered for HbA1c non-inferiority (margin 0·4%) and bodyweight superiority. This trial is registered with ClinicalTrials.gov, number NCT02648204.
FINDINGS
Between Jan 6, 2016, and June 22, 2016, 1201 patients were randomly assigned to treatment; of these, 301 were exposed to semaglutide 0·5 mg, 299 to dulaglutide 0·75 mg, 300 to semaglutide 1·0 mg, and 299 to dulaglutide 1·5 mg. 72 (6%) patients withdrew from the trial (22 receiving semaglutide 0·5 mg, 13 receiving dulaglutide 0·75 mg, 21 receiving semaglutide 1·0 mg, and 16 receiving dulaglutide 1·5 mg). From overall baseline mean, mean percentage HbA1c was reduced by 1·5 (SE 0·06) percentage points with semaglutide 0·5 mg versus 1·1 (0·05) percentage points with dulaglutide 0·75 mg (estimated treatment difference [ETD] -0·40 percentage points [95% CI -0·55 to -0·25]; p<0·0001) and by 1·8 (0·06) percentage points with semaglutide 1·0 mg versus 1·4 (0·06) percentage points with dulaglutide 1·5 mg (ETD -0·41 percentage points [-0·57 to -0·25]; p<0·0001). From overall baseline mean, mean bodyweight was reduced by 4·6 kg (SE 0·28) with semaglutide 0·5 mg compared with 2·3 kg (0·27) with dulaglutide 0·75 mg (ETD -2·26 kg [-3·02 to -1·51]; p<0·0001) and by 6·5 kg (0·28) with semaglutide 1·0 mg compared with 3·0 kg (0·27) with dulaglutide 1·5 mg (ETD -3·55 kg [-4·32 to -2·78]; p<0·0001). Gastrointestinal disorders were the most frequently reported adverse event, occurring in 129 (43%) of 301 patients receiving semaglutide 0·5 mg, 133 (44%) of 300 patients receiving semaglutide 1·0 mg, 100 (33%) of 299 patients receiving dulaglutide 0·75 mg, and in 143 (48%) of 299 patients receiving dulaglutide 1·5 mg. Gastrointestinal disorders were also the most common reason for discontinuing treatment with semaglutide and dulaglutide. There were six fatalities: one in each semaglutide group and two in each dulaglutide group.
INTERPRETATION
At low and high doses, semaglutide was superior to dulaglutide in improving glycaemic control and reducing bodyweight, enabling a significantly greater number of patients with type 2 diabetes to achieve clinically meaningful glycaemic targets and weight loss, with a similar safety profile.
FUNDING
Novo Nordisk. | 10.1016/S2213-8587(18)30024-X |
pubmed_244_4063 | In the present study, a sequence of experiments was performed to assess the influence of the key process parameters on the formation of a carbon nanofiber-coated monolith (CNFCM), using a four-level factorial design in response surface methodology (RSM). The effect of reaction temperature, hydrocarbon flow rate, catalyst and catalyst promoter were examined using RSM to enhance the formation yield of CNFs on a monolith substrate. To calculate carbon yield, a quadratic polynomial model was modified through multiple regression analysis and the best possible reaction conditions were found as follows: a reaction temperature of 800 °C, furfuryl alcohol flow of 0.08525 mL/min, ferrocene catalyst concentration of 2.21 g. According to the characterization study, the synthesized CNFs showed a high graphitization which were uniformly distributed on a monolith substrate. Besides this, the feasibility of carbon dioxide (CO2) adsorption from the gaseous mixture (N2/CO2) under a range of experimental conditions was investigated at monolithic column. To get the most out of the CO2 capture, an as-prepared sample was post-modified using ammonia. Furthermore, a deactivation model (DM) was introduced for the purpose of studying the breakthrough curves. The CO2 adsorption onto CNFCM was experimentally examined under following operating conditions: a temperature of 30-50 °C, pressure of 1-2 bar, flow rate of 50-90 mL/min, and CO2 feed amount of 10-40 vol.%. A lower adsorption capacity and shorter breakthrough time were detected by escalating the temperature. On the other hand, the capacity for CO2 adsorption increased by raising the CO2 feed amount, feed flow rate, and operating pressure. The comparative evaluation of CO2 uptake over unmodified and modified CNFCM adsorbents confirmed that the introduced modification procedure caused a substantial improvement in CO2 adsorption. | 10.3390/ma13071775 |
pubmed_718_21037 | The type II and type III collagen alpha-1 chain C-telopeptides are a 27 mer with the sequence NAc-GPGIDMSAFAGLGPREKGPDPLQYMRA and a 22mer,NAc-GGGVASLGAGEKGPVGYGYEYR, respectively. Their conformations have been studied in CD3OH/H2O (80/20) solution by means of two-dimensional proton NMR and CD spectroscopy. Based on TOCSY and NOESY experiments, all resonances were assigned and the conformational properties were analyzed in terms of vicinal NH-H alpha coupling constants, sequential and medium range NOEs and amide proton temperature coefficients. The conformation of the type II C-telopeptide is essentially extended. Evidence from CD spectroscopy suggests that a very minor proportion of the peptide might be helical (ca.8%), but the NMR data show no evidence for a non-linear structure. The observation of reduced amide proton temperature dependence coefficients in certain sections of the molecule can, in view of the absence of any other supporting evidence, only be interpreted in terms of local shielding from solvent for sterical reasons (large hydrophobic side-chains). The conformation of the type III C-telopeptide is mostly extended except for a beta-turn ranging from Gly8 to Glu11, which is stabilized by a hydrogen-bond between NH of Glu11 and the carbonyl group of Gly8. The low temperature coefficient of NH(Glu11) and, in particular, the observation of a medium range NOE between H alpha (A9) and NH(E11) corroborate the existence of a beta-turn in this region. Although spectral overlap prevents a precise conclusion with regard to the type of beta-turn present, there is some evidence that it might be type II. | 10.1080/07391102.1993.10508014 |
pubmed_494_23307 | The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure, <140/90 or <130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C), <4.1 to <2.6 mmol l(-1) (<160 to <100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) had >or=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds. | 10.1038/jhh.2008.114 |
pubmed_44_1978 | BACKGROUND
Substance abuse in pain management can undermine treatment compliance, the effectiveness of therapies, and social support and functioning.
MATERIAL
An overview is given regarding pain management for patients on chronic use of opioids and for patients with drug dependence and substance abuse.
RESULTS
Clinical experience as well as relevant documentation demonstrates that management of these patients remains one of the most challenging problems in clinical medicine.
CONCLUSION
Assessment and treatment plans for this patient group require an understanding of tolerance, physical dependence and drug abuse. It is imperative that the patient's ongoing treatment is planned in a multidisciplinary setting, so as to assure a consistent, structured and shared approach by all caregivers. | pubmed_44_1978 |
pubmed_499_9063 | Necrotizing fasciitis (NF) is an aggressive, necrotic, life-threatening infection of the soft tissues. The delay on treatment is generally accompanied by almost 90 % lethality according to the development of septic shock and its associated complications. Primary Necrotizing Fasciitis of the Breast (PNFB) is seen extremely rare. To date, breast necrotizing fasciitis have been reported only as a limited number of case reports in the literature. PNFB is commonly misdiagnosed as cellulitis, mastitis, abscess or inflammatory breast cancer. Although PNFB is a very rapid and aggressive disease, which can be fatal. Delayed cases were unfortunately resulted in mortality due to several consequential reasons. Therefore, careful and detailed evaluation of all cases irrespective of age, especially those with risk factors and comorbidities, could be life saving in respect of early diagnosis and timely treatment. Our aim is to to present the analysis and treatment modalities of five primarily seen PFNB, in this case series. | 10.3855/jidc.14914 |
pubmed_968_19881 | This report intends to summarize the underlying pathophysiology, relevant symptoms, appropriate diagnostic workup, necessary imaging, and medical and surgical treatments of occipital neuralgia (ON). This was done through a comprehensive literature review of peer-reviewed literature throughout the most relevant databases. The current understanding of ON is that it causes neuropathic pain in the distribution of the greater occipital nerve, the lesser occipital nerve, the third occipital nerve or a combination of the 3. It is currently a subset of headaches although there is some debate if ON should be its own condition. Occipital neuralgia causes chronic, sharp, stabbing pain in the upper neck, back of the head, and behind the ears that can radiate to the front of the head. Diagnosis is typically clinical and patients present with intermittent, painful episodes associated with the occipital region and the nerves described above. Most cases are unilateral pain, however bilateral pain can be present and the pain can radiate to the frontal region and face. Physical examination is the first step in management of this disease and patients may demonstrate tenderness over the greater occipital and lesser occipital nerves. Anesthetics like 1% to 2% lidocaine or 0.25% to 0.5% bupivacaine can be used to block these nerves and antiinflammatory drugs like corticosteroids can be used in combination to prevent compressive symptoms. Other treatments like botulinum toxin and radiofrequency ablation have shown promise and require more research. Surgical decompression through resection of the obliquus capitis inferior is the definitive treatment however there are significant risks associated with this procedure. | 10.1097/SCS.0000000000008360 |
pubmed_73_8574 | The vertebrate Xlink domain is found in two types of genes: lecticans and their associated hyaluronan-and-proteoglycan-binding-link-proteins (HAPLNs), which are components of the extracellular matrix, and those represented by CD44 and stabilins, which are expressed on the surface of lymphocytes. In both types of genes, Xlink functions as a hyaluronan binding domain. We have already reported that protochordate ascidians possess only the latter type of gene. The present analysis of the expression of ascidian Xlink domain genes revealed that these genes function in blood cell migration and apoptosis. While the Xlink domain is found in various metazoans, including ascidians and nematodes, hyaluronan is believed to be specific for vertebrates. In comprehensive genome surveys for hyaluronan synthase (HAS), we found no HAS gene in ascidians. We also established that hyaluronan is absent from the ascidian body biochemically. Therefore, ascidians possess the Xlink domain, but they lack HA. We recovered one ascidian Xlink domain gene that encoded a heparin-binding protein, although it shows no affinity for hyaluronan. Based on these findings, we conclude that in invertebrates, the Xlink domain serves as heparin-binding protein domain and functions in blood cell migration and apoptosis. Its binding affinity for HA might have been acquired in the vertebrate lineage. | 10.1007/s00239-010-9363-x |
pubmed_1052_13388 | Unraveling the mechanisms underlying self and agency has been a difficult scientific problem. We argue for an event-control approach for naturalizing the sense of agency by focusing on the role of perception-action regularities present at different hierarchical levels and contributing to the sense of self as an agent. The amount of control at different levels of the control hierarchy determines the sense of agency. The current study investigates this approach in a set of two experiments using a scenario containing multiple agents sharing a common goal where one of the agents is partially controlled by the participant. The participant competed with other agents for achieving the goal and subsequently answered questions on identification (which agent was controlled by the participant), the degree to which they are confident about their identification (sense of identification) and the degree to which the participant believed he/she had control over his/her actions (sense of authorship). Results indicate a hierarchical relationship between goal-level control (higher level) and perceptual-motor control (lower level) for sense of agency. Sense of identification ratings increased with perceptual-motor control when the goal was not completed but did not vary with perceptual-motor control when the goal was completed. Sense of authorship showed a similar interaction effect only in experiment 2 that had only one competing agent unlike the larger number of competing agents in experiment 1. The effect of hierarchical control can also be seen in the misidentification pattern and misidentification was greater with the agent affording greater control. Results from the two studies support the event-control approach in understanding sense of agency as grounded in control. The study also offers a novel paradigm for empirically studying sense of agency and self. | 10.1371/journal.pone.0092431 |
pubmed_55_23525 | The efficiency of afala in the therapy of chronic abacterial prostatitis was demonstrated. The preparation considerably improved urodynamics, reduced pain syndrome and inflammation, decreased prostate volume, improved patient's quality of life, and restored microcirculation in the prostate. No changes in blood, urine, and ECG parameters were noted. No side effects requiring afala withdrawal were recorded. | 10.1007/s10517-009-0692-y |
pubmed_517_24502 | BACKGROUND
Various models and questionnaires have been developed for screening specific populations for obstructive sleep apnea (OSA) as defined by the apnea/hypopnea index (AHI); however, almost every method is based upon dichotomizing a population, and none function ideally. We evaluated the possibility of using the STOP-Bang model (SBM) to classify severity of OSA into 4 categories ranging from none to severe.
METHODS
Anthropomorphic data and the presence of snoring, tiredness/sleepiness, observed apneas, and hypertension were collected from 1426 patients who underwent diagnostic polysomnography. Questionnaire data for each patient was converted to the STOP-Bang equivalent with an ordinal rating of 0 to 8. Proportional odds logistic regression analysis was conducted to predict severity of sleep apnea based upon the AHI: none (AHI < 5/h), mild (AHI ≥ 5 to < 15/h), moderate (≥ 15 to < 30/h), and severe (AHI ≥ 30/h).
RESULTS
Linear, curvilinear, and weighted models (R(2) = 0.245, 0.251, and 0.269, respectively) were developed that predicted AHI severity. The linear model showed a progressive increase in the probability of severe (4.4% to 81.9%) and progressive decrease in the probability of none (52.5% to 1.1%). The probability of mild or moderate OSA initially increased from 32.9% and 10.3% respectively (SBM score 0) to 39.3% (SBM score 2) and 31.8% (SBM score 4), after which there was a progressive decrease in probabilities as more patients fell into the severe category.
CONCLUSIONS
The STOP-Bang model may be useful to categorize OSA severity, triage patients for diagnostic evaluation or exclude from harm. | 10.5664/JCSM.1306 |
pubmed_643_7535 | The aim of our study was to assess risk factors associated with vitamin D deficiency among HIV-1-infected patients on combination antiretroviral therapy (cART). A retrospective, case-control study was conducted to assess risk factors associated with vitamin D deficiency among HIV-1-infected adults on stable cART. Vitamin D deficiency was defined as 25-OH vitamin D concentration <30 ng/mL. A total of 195 patients (77% males, mean age 49.2 years) were enrolled into the study: 98 subjects with vitamin D deficiency (cases) and 97 with normal vitamin D serum concentration (controls). The mean serum concentration + standard deviation (SD) of vitamin D was 18.2+6.7 ng/mL among cases and 39.6+13.4 ng/ mL among controls. Current cART including tenofovir disoproxil fumarate (TDF) (OR 1.65; 95% CI, 1.31 to 1.94), osteoporosis (OR 1.78; 95% CI, 1.25 to 2.09), males who have sex with males (MSM) risk category (OR 1.59; 95% CI, 1.19 to 2.21), chronic hepatitis C (OR 1.44; 95% CI, 1.17 to 1.86), previous or current cancer (OR 1.47; 95% CI, 1.13 to 1.79), metabolic syndrome (OR 2.57; 95% CI, 1.96 to 2.98), and hepatic steatosis (OR 1.59; 95% CI, 1.17 to 2.05) were significant associated with an increased risk of vitamin D deficiency. On the other hand, current CD4+ lymphocyte count >600 cells/mm3 and current HIV RNA <20 copies/mL were significantly associated with a lower risk of vitamin D deficiency. In our case-control study, vitamin D deficiency is associated with TDF exposure, osteoporosis, and metabolic disturbances. | pubmed_643_7535 |
pubmed_200_14920 | BACKGROUND AND PURPOSE
Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters.
METHODS
Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes.
RESULTS
Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030).
CONCLUSIONS
Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth. | 10.1161/STROKEAHA.115.009828 |
pubmed_333_671 | Serologic studies were performed on 25 patients with systemic lupus erythematosus (SLE) during 29 acute episodes of central nervous system (CNS) disease. Increased anti-DNA antibody and decreased total serum hemolytic complement activity were observed only in those patients with associated extra-CNS disease manifestations. Patients with isolated CNS disease were otherwise in apparent clinical and serological remission regarding these two indices. No special association of cold-reactive IgM antilymphocyte antibodies was demonstrable in patients with ongoing CNS injury. Of special interest was an increased incidence of anti-Sm antibodies in the patients with CNS dysfunction relative to that in a large group of patients without neuropsychiatric disease. The incidence of anti-RNP was not increased. The data do not support direct involvement in SLE brain injury of either DNA/anti-DNA complexes or of lymphocytotoxic antibodies cross-reactive with brain cells, but do suggest an association of anti-Sm with CNS disease in this disorder. | 10.1002/art.1780210301 |
pubmed_170_23562 | It is widely accepted that redox status, along with the partial pressure of oxygen (pO(2)), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO(2) in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO(2) and the reduction rate at the region of pO(2) measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology. | 10.1158/0008-5472.CAN-09-4369 |
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