index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_614_5145
|
Little is known about how total testosterone and estradiol-17β influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17β, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17β and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17β was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17β versus those with higher baseline estradiol-17β. Lower baseline estradiol-17β was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17β levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17β levels when responsiveness was measured using total IPSS and IPSS-V.
|
10.1111/andr.12114
|
pubmed_875_4732
|
Correction for 'The anti-inflammatory effect of a glycosylation product derived from the high hydrostatic pressure enzymatic hydrolysate of a flatfish byproduct' by In-Hu Choe, et al., Food Funct., 2016, 7, 2557-2565.
|
10.1039/c6fo90026g
|
pubmed_461_498
|
Left ventricular function was measured by echocardiography in 22 patients with pure mitral stenosis. Thirteen patients underwent closed transventricular mitral valvulotomy and nine underwent open mitral valvulotomy using cardiopulmonary bypass. Preoperative left ventricular function was normal in most patients but was depressed in older subjects (P less than 0.05) and in those undergoing a second operation on the mitral valve (P less than 0.001). The decrease in left ventricular function was probably related to the duration of mitral valve disease, with fibrosis and rigidity of the subvalvar apparatus and posterobasal left ventricular wall. There was no change in ventricular dimensions or in left ventricular function as measured by percentage shortening of the left ventricular diameter and ejection fraction 7 to 12 days after open or closed mitral valvulotomy.
|
pubmed_461_498
|
pubmed_267_814
|
The vapour pressures of 30 N-nitrosamines between 0 and 40 degrees C are calculated by means of well-known and experimentally proven formulae. The saturation concentration of the nitrosamines in air is presented as mmHg, ppm and mg/m3. For N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosopyrrolidine (NPYR) the calculated values are compared with actual measurements in the same temperature range and are found to coincide very closely. Furthermore the partial pressures of NDMA, NDEA and NPYR over an aqueous solution were experimentally determined and are tabulated in mmHg and mg/m3, for practical purposes. The calculations have been programmed in BASIC on a scientific computer, however, commercial programmable pocket calculators would also have been sufficient.
|
10.1016/0300-483x(82)90093-2
|
pubmed_126_12065
|
OBJECTIVE
The objective of this work was to examine osteoblast-like cell attachment and morphology in vitro to osteoceramic materials with three different surface morphologies.
METHODS
Osteoceramic composite disks were fabricated from tricalcium phosphate and magnesium-aluminate spinel (MgAl2O4) in a 50 vol% ratio. The disks were prepared with three different surface morphologies, including as-fired (irregular), etched (rough), or polished through 1 mm diamond paste (smooth). Osteoblast-like cell cultures were plated onto the prepared disks for 2 h, and the number of attached cells was determined. ANOVA and Student Newman-Kuels tests were used to test for significant differences in cell attachment (p < 0.05). SEM was used to visually evaluate the nature of the cellular adaptation on the osteoceramic surfaces.
RESULTS
Some additional surface roughening resulted from the interaction between the osteoceramic disks and the biological culture media during the attachment assay. A statistically larger number of cells was found to be attached to the etched osteoceramic surfaces compared to the as-fired and polished osteoceramic surfaces or the tissue culture plastic control. Cellular adaptation was extensive on all three osteoceramic surfaces at 2 h.
SIGNIFICANCE
These results are consistent with previous in vivo work and continue to support the hypothesis that osteoceramic materials have potential for implants and bone substitute materials.
|
10.1016/s0109-5641(97)80010-3
|
pubmed_592_445
|
BACKGROUND
Data on health or health service use are invariably used to test the validity of proxy measures of need, for use in resource allocation formulae. Perceived health state is a good measure to use in this respect, as it is closely linked to perceived need and the decision to consult health services. This being the case, a large community based study was undertaken which collected data on perceived health, using the Nottingham Health Profile (NHP), with the aim of testing the validity of a variety of Census based measures as proxy measures of the need for health care.
METHOD
A postal questionnaire survey of 9565 people living in the former South East Thames Regional Health Authority was conducted and the relationship between their perceived health state and the socio-economic characteristics of their electoral ward of residence analysed.
RESULTS
A relatively low response rate (59 per cent) weakened any conclusions to be drawn from the results. However, significant correlations between perceived health and a variety of the Census based indicators were found. The highly skewed distribution of responses to the NHP statements made the results difficult to analyse and interpret.
CONCLUSIONS
Although the study gave an indication of those variables that might be incorporated into resource allocation formulae, the NHP is not a particularly efficient instrument to use in a community setting. It is argued that the appropriateness of an approach to determining appropriate needs weights in allocation formulae, which attempts to find one indicator of all health care needs at the District Health Authority level, must be questioned.
|
10.1093/oxfordjournals.pubmed.a024512
|
pubmed_809_10330
|
OBJECTIVES
To describe HSV-1 seroprevalence in children in the United States and to examine factors associated with herpes simplex virus type 1 (HSV-1) infection in children.
STUDY DESIGN
Sera samples available from 2989 children age 6 to 13 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 1999-2002 were tested for HSV-1 antibodies using a type-specific immunodot assay. HSV-1 seroprevalence in children age 12 to 13 years was compared with that reported in an earlier survey (NHANES 1988-1994).
RESULTS
Overall, HSV-1 seroprevalence in children age 6 to 13 years was 31.1% (95% confidence interval [CI], 28.6% to 33.9%). Seroprevalence increased with age, from 26.3% in 6- to 7-year-olds to 36.1% in 12-to 13-year-olds, and varied by race/ethnicity, birthplace, and poverty level. Among US-born children age 12 to 13 years, the point estimate of HSV-1 seroprevalence was lower in NHANES 1999-2002 than in NHANES 1988-1994 (34.3% vs 38.1%), but the differences were not statistically significant.
CONCLUSIONS
HSV-1 is a common infection in US children, with more than 25% infected by age 7. Race/ethnicity, birthplace, and poverty level are predictors for HSV-1 infection in children.
|
10.1016/j.jpeds.2007.04.065
|
pubmed_702_7425
|
We present the derivation of an analytical model for the self-shading error of an oceanographic upwelling radiometer. The radiometer is assumed to be cylindrical and can either be a profiling instrument or include a wider cylindrical buoy for floating at the sea surface. The model treats both optically shallow and optically deep water conditions and can be applied any distance off the seafloor. We evaluate the model by comparing its results to those from Monte Carlo simulations. The analytical model performs well over a large range of environmental conditions and provides a significant improvement to previous analytical models. The model is intended for investigators who need to apply self-shading corrections to radiometer data but who do not have the ability to compute shading corrections with Monte Carlo simulations. The model also can provide guidance for instrument design and cruise planning.
|
10.1364/opex.12.004709
|
pubmed_936_14293
|
Background
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis and represents an important global public health issue. Single-nucleotide polymorphisms and INDELs are common genetic variations that can be located in genes associated with immune response and, therefore, they may have direct implications over the phenotype of susceptibility to infections like tuberculosis. This study aimed to investigate the association between the 17 genetic polymorphisms and susceptibility to tuberculosis in a Brazilian population.
Methods
This case-control study enrolled 283 individuals with active tuberculosis and 145 health care workers. Four INDELs and 13 single nucleotide polymorphisms and were genotyped using Multiplex PCR method and TaqMan SNP Genotyping Assays. Group comparisons for categorical variables were performed using the chi-squared test, whilst the t-Student test was used to analyze the continuous variables. Multiple logistic regression analyses were performed to estimate the odds ratio (OR) with 95% confidence intervals (CI). Deviation from Hardy-Weinberg equilibrium was assessed using chi-squared tests with Bonferroni correction. The results were analyzed comparing the genotypic distributions adopting the dominant model and the estimated values of p corrected for multiple tests through FDR (False Discovery Rate) test.
Results
The HWE test confirmed that the genotypic frequencies for polymorphisms were balanced. The frequency of Del allele was 73 and 75%, in cases and controls respectively. Frequency of Del allele was significantly higher in the control group than TB group. The homozygous Del/Del genotype was present in 51.6% of cases and 58.6% of controls. The rare Ins/Ins genotype was present in only 7.6% of controls and 6% of cases. The ACE Del/Del genotype was significantly higher in the cases than in controls revealing significant protection for TB in the domain model (OR = 0.465; p < 0.005).
Conclusions
The Del/Del genotype of the rs4646994 in ACE gene was associated with susceptibility to tuberculosis. The identification of genetic variants responsible for susceptibility to tuberculosis will allow the development of new diagnostic tools for tuberculosis infection. These studies will help improve control and the future eradication of this disease.
|
10.1186/s41231-022-00116-6
|
pubmed_269_5945
|
Background: Although there are several ways to transmit HIV, condomless sex remains the primary mode in sub-Saharan Africa, including South Africa, with KwaZulu-Natal Province being one of the epicentres of HIV infection. This study explored the use of condoms in serodiscordant couples who were exposed to an HIV-risk reduction intervention that aimed to improve condom use and reduce the spread of HIV.Methods: A Total of 30 couples completed a paper-based questionnaire on their demographics and general health at baseline and 3 months, plus a semi-structured questionnaire with four domains. An analysis of HIV knowledge, condom use, condom use attitudes and protection perceptions about how other serodiscordant couples behave was conducted following a 12-week HIV risk reduction intervention. Participants were randomised 2:1 into intervention and control groups.Results: Condom use increased from 55% at baseline to 73.7% (p = .0047) at 3 months for the intervention group and condom use in the last 7 days increased from 53% to 86% (p = .0117). For the control group, condom use remained low at the 3 months follow up period (p = .625). HIV knowledge improved significantly from baseline to 3 months for the intervention group (p < .0001), as well as the control group (p = .0005). Negative HIV condom use attitude scores in both groups decreased significantly from baseline to 3 months; intervention group (p = .0059) and control group (p = .0007).Conclusion: HIV knowledge and condom use improved significantly, while negative condom use attitudes and HIV protection perceptions decreased significantly following exposure to a risk-reduction intervention, suggesting that HIV preventive interventions should focus on partnership interventions.
|
10.1177/09564624221076617
|
pubmed_483_9738
|
A nitrocellulose colony-blot assay was developed to detect enterotoxigenic strains of Clostridium perfringens on an agar medium. To enhance sporulation and enterotoxin production, a number of modifications of the Duncan-Strong (D-S) medium were tested, including the substitution of raffinose for starch and the addition of theobromine, papaverine and various combinations of soil and fecal extracts. Colonies of enterotoxigenic strains were most consistently positive and produced the most intense color reactions on a modified D-S medium containing raffinose, theobromine and 50% (vol/vol) bovine fecal extract. This modified medium stimulated production of detectable enterotoxin by colonies in more than 90% of the enterotoxigenic strains tested. No false-positive reactions were observed. This enzyme-linked, immunosorbent assay (ELISA) was not as effective in the analysis of broth cultures or fecal samples. Our results indicate that the nitrocellulose colony-blot assay will be useful for screening enterotoxigenic strains in epidemiologic studies.
|
10.4315/0362-028X-48.3.227
|
pubmed_187_1880
|
Insulin and catecholamines are known to exert effects on hepatocyte growth and metabolism. The binding of insulin, the plasma levels of insulin (INS), and the plasma catecholamine levels of epinephrine (EPI) and norepinephrine (NE) were measured during liver regeneration after partial hepatectomy (PH). A significant decrease (p < 0.05) of INS receptor binding capacity was found at 1, 2, and 3 days after operation. A single insulin injection (2.5 IU/kg body weight) at 24 h after sham operation or partial hepatectomy did not affect these changes of INS binding to hepatocytes. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. Within 20 min after liver resection or sham operation, plasma NE and EPI concentrations increased rapidly. Then, a significant decrease was observed in plasma catecholamine levels at 1 h after laparotomy and PH. In both groups, laparotomized and partially hepatectomized plasma levels of NE at 4 h reached control values and remained unchanged at the 4- and 24-h periods. After PH, the levels of EPI remained elevated at 4 h in comparison with laparotomy. Adrenal tyrosine hydroxylase mRNA levels were significantly elevated at 4 h in both PH and sham-operated groups. These results suggest that signals that are initiated by catecholamines and transduced through second messengers presumably participate in the trigger mechanism of liver regeneration, while insulin (considered as a secondary mitogen) enhances a stimulus for liver regeneration.
|
10.1111/j.1749-6632.1997.tb51859.x
|
pubmed_569_20101
|
The use of injectable local anesthetic solutions to facilitate pain-free surgery is an integral component of many procedures performed by the plastic surgeon. In many instances, a solution that has both rapid onset and prolonged duration of analgesia is optimal. A combination of lidocaine and bupivacaine, plain or with epinephrine, is readily available in most Canadian health care settings where such procedures are performed, and fulfills these criteria. However, commercially available solutions of both medications are acidic and cause a burning sensation on injection. Buffering to neutral pH with sodium bicarbonate is a practical method to mitigate the burning sensation, and has the added benefit of increasing the fraction of nonionized lipid soluble drug available. The authors report on the proportions of the three drugs to yield a neutral pH, and the results of an initial survey regarding the use of the combined solution with epinephrine in hand surgery.
|
10.4172/plastic-surgery.1000913
|
pubmed_528_8630
|
Single-molecule optical experiments carried out in conjunction with externally applied electric fields show deliberate spatial and intensity control over CdSe nanowire (NW) emission. In particular, by applying external fields to electrically isolated (single) NWs, their emission can be localized in areas of the wire closest to the positive electrode. In a few cases, the resulting emission intensity increases over the corresponding zero-field value by nearly an order of magnitude. More often than not, factors of 2-3 are seen. Reversing the field polarity causes the emission to localize in opposite regions of the wire. Emission from individual NWs can therefore be modulated. Complementary ac electric field measurements show that the effect persists up to 500 kHz. To explain the phenomenon, the effective passivation of surface trap states by mobile carriers is speculated. This, in turn, causes local changes in the NW emission quantum yield (QY). To verify the presence of such mobile charges, both ensemble and single NW bundle electrophoresis experiments are conducted. By investigating subsequent NW rotational and translational dynamics, an estimate for the number of mobile carriers is determined. A lower limit (best case) linear charge density of approximately 0.45-1.2 mobile electrons per micrometer of the wire is obtained. Apart from self-consistently explaining the field-induced NW emission modulation, the resulting data and subsequent analysis also suggests that the same mobile carriers may be the root cause of NW emission intermittency. Furthermore, given the ubiquity of stray charges, the resulting hypothesis may have additional applicability toward explaining blinking in other systems, a problem of current interest especially within the context of colloidal QDs.
|
10.1021/ja073642w
|
pubmed_1110_17437
|
Living beings on the Earth are subjected to and entrained (synchronized) to the natural 24-h light-dark cycle. Interestingly, they can also be entrained to an external artificial cycle of non-24-h periods. The range of these periods is called the entrainment range and it differs among species. In mammals, the entrainment range is regulated by a main clock located in the suprachiasmatic nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works have found that the entrainment range depends on the cellular coupling strength in the SCN. In particular, the entrainment range decreases with the increase of the cellular coupling strength, provided that all the neuronal oscillators are identical. However, the SCN neurons differ in the intrinsic periods that follow a normal distribution in a range from 22 to 28 h. In the present study, taking the dispersion of the intrinsic neuronal periods into account, we examined the relationship between the entrainment range and the coupling strength. Results from numerical simulations and theoretical analyses both show that the relationship is altered to be paraboliclike if the intrinsic neuronal periods are nonidentical, and the maximal entrainment range is obtained with a suitable coupling strength. Our results shed light on the role of the cellular coupling in the entrainment ability of the SCN network.
|
10.1103/PhysRevE.96.052207
|
pubmed_550_16199
|
The purpose of this study was to assess the effects of music therapy on pain and anxiety in pediatric burn patients during nursing procedures. Nine subjects were randomly selected to participate in this study. Qualitative and quantitative data was collected on the patients' pain, anxiety, heart rate, blood oxygenation, and engagement level through measurement tools and interviews. The results from the qualitative and quantitative data indicated that music therapy reduced pain, anxiety, and behavioral distress. The quantitative data were analyzed and an inverse relationship between engagement in music therapy and lower behavioral distress scores was noted. Additionally, a linear relationship between engagement and behavioral distress was noted; significance was found but was moderated by the age of the child. However, no significant relationship was found between heart rate and behavioral distress. The results from the qualitative data from the interviews with the patients, parents, nurses and music therapist indicated that music therapy reduced pain and anxiety, and that engagement in music therapy enhanced relaxation. In addition, music therapy positively affected patients' mood, compliance, and the relaxation level. Finally, parents/guardians and nurses involved in the study reported that music therapy helped them to feel more relaxed as well.
|
10.1093/jmt/44.3.217
|
pubmed_1075_24793
|
PURPOSE
One of the main challenges related to electromagnetic tracking in the clinical setting is a placement of the field generator (FG) that optimizes the reliability and accuracy of sensor localization. Recently, a new mobile FG for the NDI Aurora(®) tracking system has been presented. This Compact FG is the first FG that can be attached directly to an ultrasound (US) probe. The purpose of this study was to assess the precision and accuracy of the Compact FG in the presence of nearby mounted US probes.
MATERIALS AND METHODS
Six different US probes were mounted onto the Compact FG by means of a custom-designed mounting adapter. To assess precision and accuracy of the Compact FG, we employed a standardized assessment protocol. Utilizing a specifically manufactured plate, we measured positional data on three levels of distances from the FG as well as rotational data.
RESULTS
While some probes had negligible influence on tracking accuracy two probes increased the mean distance error up to 1.5 mm compared with a reference measurement of 0.5 mm. The jitter error consistently stayed below 0.2 mm in all cases. The mean relative error in orientation was found to be smaller than 3°.
CONCLUSION
Attachment of an US probe to the Compact FG does not have a critical influence on tracking accuracy in most cases. Clinical benefit of this promising mobile FG must be shown in future studies.
|
10.1007/s11548-012-0740-3
|
pubmed_697_17032
|
Single nucleotide polymorphisms (SNPs) are genetic variations that contribute to human phenotypes associated with various diseases. SNPs are involved in the regulation of a broad range of physiological and pathological processes, such as cellular senescence, apoptosis, inflammation, and immune response, by upregulating the expression of classical inflammation markers. Recent studies have suggested that SNPs located in gene-encoding microRNAs (miRNAs) affect various aspects of diseases by regulating the expression or activity of miRNAs. In the last few years, miRNA polymorphisms that increase and/or reduce the risk of developing many diseases, such as cancers, autoimmune diseases, and cardiovascular diseases, have attracted increasing attention not only because of their involvement in the pathophysiology of diseases but also because they can be used as prognostic biomarkers for a variety of diseases. In this review, we summarize the relationships between miRNA SNPs and the pathophysiology and risk of diseases.
|
10.1111/cge.12950
|
pubmed_701_13423
|
Because of concern that steady sexual partners of patients infected with human immunodeficiency virus (HIV) may be infected despite negative results in tests for antibody to HIV, we studied 50 sexually active couples with discordant antibody results, assessing the agreement between these serological results and those obtained by p24 antigen testing, the polymerase chain reaction (PCR), and culture. Forty-nine of 50 seropositive sexual partners were also positive for HIV by PCR; the remaining seropositive partner was positive by culture. All seronegative partners also had negative results in the other three tests. Moreover, seronegative partners continued to have negative results in all tests for a mean follow-up period of 17 months despite ongoing sexual relations with their seropositive partners. Seronegative infection was not documented in these partners at risk for sexual transmission of HIV. HIV-negative individuals in stable, monogamous sexual relationships with HIV-infected partners apparently do not have a high incidence of infection despite continued sexual exposure.
|
10.1093/clinids/21.1.122
|
pubmed_834_2545
|
Hepatocyte nuclear factor (HNF)-3 alpha, -3 beta, and -3 gamma are liver transcription factors that mediate the coordinate expression of a number of hepatocyte-specific genes. The HNF-3 proteins share DNA-binding-domain homology among themselves and with the Drosophila homeotic protein forkhead (fkh). The HNF-3/fkh DNA-binding domain constitutes an uncharacterized protein motif that recognizes its cognate DNA binding site as a monomer. Additional HNF-3/fkh-related proteins are known to be required for determination events during embryogenesis in Drosophila and Xenopus. In this report, we describe the isolation of nine additional HNF-3/fkh homologue (HFH) clones from rodent tissue cDNAs by using both low-stringency hybridization and a polymerase chain reaction protocol. Many of the HFH genes exhibit a tissue-restricted expression pattern and are transcribed in tissues other than liver, including brain, kidney, lung, and intestine. The HNF-3/fkh motif therefore comprises a large gene family of transcription factors that play a role in tissue-specific gene regulation and development.
|
10.1073/pnas.90.9.3948
|
pubmed_393_4226
|
In the main wind direction of a coal-fired power plant dust and soil samples have been collected to analyse the content of fly-ash coming from the power plant. The fly-ash particles are spherical and contain the natural radionuclides mainly Ra-226, Pb-210, Po-210 and K-40 in a higher concentration when compared with the original coal. The investigation of soil samples results in increased Pb-210 and Po-210 concentrations when compared with the natural environment. By presence of spherical particles in dust and soil samples the power plant can be identified as the emitter.
|
10.1016/0048-9697(85)90204-9
|
pubmed_417_13713
|
Adaptation of eight kinds of resin restorations on Class V enamel cavity, cement-enamel-junction (CEJ) cavity and root surface cavity were compared. Extracted human premolars were used as experimental specimens. Restored specimens were divided into two groups; short storage group of 2 week duration and long storage group of 6 month duration. The specimens were thermal cycled during storage. After that replicas of the vertical sections were made for examination by SEM and the gaps measured from photographs. The appearance and width of gaps between resin and cavity walls were characterised by the type of cavity and the filling materials. In Class V enamel cavity, gaps were observed on the cavity floor, whilst almost none was observed in other areas showing good adaptation. In the CEJ cavity, gaps appeared only at the cavity floor and gingival wall. In the root surface cavity, gaps were observed on all cavity walls with smaller widths on the occlusal wall and greater width on the cavity floor. Clearfil-F and Clearfil-F II showed fine adaptation on all cavities in general, especially on the dentinal cavity wall. Almost all the materials showed a tendency to form gaps which was found to increase with time. The difference in width, however, varied with the materials used.
|
pubmed_417_13713
|
pubmed_769_1106
|
OBJECTIVE
To evaluate the efficacy and safety of programmed cell death receptor-1 (PD-1)/programmed cell death-ligand protein-1 (PD-L1) inhibitors in triple-negative breast cancer (TNBC) to provide a treatment basis for TNBC.
METHODS
Published case-control studies on PD-1/PD-L1 inhibitors in the treatment of TNBC were retrieved from PubMed, Embase, and Cochrane Library databases, and collected data were processed by RevMan 5.4.
RESULTS
A total of 7 studies with 4340 study subjects were obtained, including 2092 PD-L1-negative cases, 1375 PD-L1-positive cases, and 847 PD-L1 unidentified cases. The use of PD-1/PD-L1 inhibitors showed no significant impact on patients' progression-free survival (PFS) and overall survival (OS). The use of PD-1/PD-L1 inhibitors in the PD-L1-positive subgroup significantly improved patients' PFS and OS. Treatment with PD-1/PD-L1 inhibitors presented no significant effect on the incidence of adverse events (AEs) but increased the risk of AE grade ≥3 and severe AEs (SAEs).
CONCLUSION
PD-1/PD-L1 inhibitors are effective in the treatment of TNBC, which is strongly correlated with the expression of PD-L1; patient selection and clinical application require further investigation and verification.
|
10.1155/2022/2407211
|
pubmed_137_6513
|
Biohybrid odorant sensors (BOSs) composed of biological materials and artificial detectors have recently attracted much attention due to their high degree of sensitivity and selectivity. Although portability is crucial for the practical use of BOSs on site, the currently used artificial detectors for biological signals are unportable. In this study, we propose a portable cell-based odorant sensor, which uses cell-laden collagen micropillars to compensate the low optical abilities of portable artificial detectors. The micropillars were composed of HEK293T cells expressing olfactory receptors, which emit a fluorescence signal based on the extent of odorant stimulation using a calcium fluorescent indicator. By stacking cells vertically in the micropillars, we achieved different levels of amplification of the fluorescence signals by varying the height of the micropillars. As a working demonstration of the portable BOS, we successfully detected different concentrations of odorants using an inexpensive web camera. The BOS was also able to distinguish the slight differences between an agonist and an antagonist. We believe that the portability of our BOS would facilitate its applications in point-of-care testing and on-site detection of hazardous materials.
|
10.1039/c9lc00131j
|
pubmed_156_19723
|
Filamin-A (filamin-1) is an actin-binding protein involved in the organization of actin networks. Our previous study shows that filamin-A interacts with BRCA2, and lack of filamin-A expression results in increased cellular sensitivity to several DNA damaging agents in melanoma cells (Yuan, Y., and Shen, Z. (2001) J. Biol. Chem. 276, 48318-48324), suggesting a role of filamin-A in DNA damage response. In this report, we demonstrated that deficiency of filamin-A results in an 8-h delay in the recovery from G2 arrest in response to ionizing radiation. However, filamin-A deficiency does not affect the initial activation of the G2/M checkpoint. We also found that filamin-A deficiency results in sustained activation of Chk1 and Chk2 after irradiation. This in turn causes a delay in the dephosphorylation of phospho-Cdc2, which is inhibitory to the G2/M transition. In addition, filamin-A-deficient M2 cells undergo mitotic catastrophe-related nuclear fragmentation after they are released from the G2 arrest. Together, these data suggest a functional role of filamin-A in the recovery from G2 arrest and subsequent mitotic cell death after DNA damage.
|
10.1074/jbc.M306794200
|
pubmed_590_12888
|
Avenir d’Enfants [Future of Children] emerged from a partnership between the government of Quebec and the Lucie and André Chagnon Foundation. The organization aims to provide local communities with resources, in order to support synergy between the principal early childhood organizations: childcare services, healthcare services, schools, family community organizations and municipalities. This article presents the context in which Avenir d’Enfants came into being, explains how the organization helps create the right conditions for local and regional initiatives to have an impact on the development of children living in a situation of poverty, and presents the challenges and success factors of this approach.
|
10.1177/1757975914520787
|
pubmed_862_4675
|
The Earth's mantle beneath ocean ridges is widely thought to be depleted by previous melt extraction, but well homogenized by convective stirring. This inference of homogeneity has been complicated by the occurrence of portions enriched in incompatible elements. Here we show that some refractory abyssal peridotites from the ultraslow-spreading Gakkel ridge (Arctic Ocean) have very depleted 187Os/188Os ratios with model ages up to 2 billion years, implying the long-term preservation of refractory domains in the asthenospheric mantle rather than their erasure by mantle convection. The refractory domains would not be sampled by mid-ocean-ridge basalts because they contribute little to the genesis of magmas. We thus suggest that the upwelling mantle beneath mid-ocean ridges is highly heterogeneous, which makes it difficult to constrain its composition by mid-ocean-ridge basalts alone. Furthermore, the existence of ancient domains in oceanic mantle suggests that using osmium model ages to constrain the evolution of continental lithosphere should be approached with caution.
|
10.1038/nature06688
|
pubmed_972_19705
|
We studied the mechanisms of induction of recombinase activity in peripheral T cells of patients with autoimmune type 1 diabetes mellitus. It was shown that the presence of CD40 on T cell membrane (not typical of these cells) is crucial for this process: expression of recombinase RAG-1 in diabetic patients was detected primarily in αβTCR(+)CD40(+) lymphocytes; targeted CD40-dependent activation of intact T cells in vitro increases, while blockade of CD40 signal in the culture of stimulated T cells abolishes recombinase expression.
|
10.1007/s10517-012-1522-1
|
pubmed_639_16295
|
Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study. We recruited 316 community dwellers, including 76 patients with sarcopenia and 240 controls, and obtained their body measurements associated with sarcopenia. We collected three-dimensional anthropometric body-surface measurements from 11,158 participants during 2000-2008 and followed up this cohort for 15 years to examine the association of these measurements with the risk of chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), heart disease, and nephrotic syndrome. Univariate analysis, canonical correlation, and Cox regression analysis were performed to explore the associations. Decreased waist width, upper left arm circumference, and left thigh circumference were significantly associated with sarcopenia. The adverse body measure score (ABMS) was derived by combining significant measurements, namely left upper arm circumference, waist width, and left thigh circumference, and used to predict the risk of hypertension, T2DM, heart diseases, and nephrotic syndrome. A positive association was observed between the ABMS and chronic diseases. Considering the first quartile of the ABMS as a reference, we determined hazard ratios of 2.259, 2.495, 1.332, and 1.595 for hypertension, T2DM, heart disease, and nephrotic syndrome, respectively, in the fourth quartile. Chronic diseases were more strongly associated with the ABMS than with sarcopenia-related body measurements alone. A high ABMS, which includes higher upper arm circumference, higher waist width, and lower thigh circumference, can significantly predict chronic diseases.
|
10.1038/s41598-021-85316-0
|
pubmed_622_14453
|
AIMS
To investigate platelet-derived growth factor receptor (PDGFR)alpha and PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS). Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors, which act through an inhibitory effect on class 3 receptor tyrosine kinase members such as PDGFRalpha, PDGFRbeta and c-kit.
METHODS AND RESULTS
The immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37 archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour cells) and positive (weakly positive 11-50% positive cells; strongly positive > 50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by 19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for PDGFRbeta, but endothelial cells stained positive. A mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen metastatic ESS from three patients detected no mutations leading to amino acid changes in the mature protein.
CONCLUSIONS
Patients with PDGFRalpha+ ESS may benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and paracrine stimulation loops, blocking neovascularization and enhancing the effects of chemotherapy.
|
10.1111/j.1365-2559.2007.02634.x
|
pubmed_550_23181
|
4 OSW-1 analogues featuring modified carbohydrate moieties were prepared. The purpose of these modifications was to assess the importance of certain chemical functions with respect to biological activity. The synthesis and biological activity of the target molecules are shown.
|
10.1016/j.bmcl.2007.07.017
|
pubmed_261_3587
|
BACKGROUND
Based on spatiotemporal clustering of human dengue virus (DENV) infections, transmission is thought to occur at fine spatiotemporal scales by horizontal transfer of virus between humans and mosquito vectors. To define the dimensions of local transmission and quantify the factors that support it, we examined relationships between infected humans and Aedes aegypti in Thai villages.
METHODOLOGY/PRINCIPAL FINDINGS
Geographic cluster investigations of 100-meter radius were conducted around DENV-positive and DENV-negative febrile "index" cases (positive and negative clusters, respectively) from a longitudinal cohort study in rural Thailand. Child contacts and Ae. aegypti from cluster houses were assessed for DENV infection. Spatiotemporal, demographic, and entomological parameters were evaluated. In positive clusters, the DENV infection rate among child contacts was 35.3% in index houses, 29.9% in houses within 20 meters, and decreased with distance from the index house to 6.2% in houses 80-100 meters away (p<0.001). Significantly more Ae. aegypti were DENV-infectious (i.e., DENV-positive in head/thorax) in positive clusters (23/1755; 1.3%) than negative clusters (1/1548; 0.1%). In positive clusters, 8.2% of mosquitoes were DENV-infectious in index houses, 4.2% in other houses with DENV-infected children, and 0.4% in houses without infected children (p<0.001). The DENV infection rate in contacts was 47.4% in houses with infectious mosquitoes, 28.7% in other houses in the same cluster, and 10.8% in positive clusters without infectious mosquitoes (p<0.001). Ae. aegypti pupae and adult females were more numerous only in houses containing infectious mosquitoes.
CONCLUSIONS/SIGNIFICANCE
Human and mosquito infections are positively associated at the level of individual houses and neighboring residences. Certain houses with high transmission risk contribute disproportionately to DENV spread to neighboring houses. Small groups of houses with elevated transmission risk are consistent with over-dispersion of transmission (i.e., at a given point in time, people/mosquitoes from a small portion of houses are responsible for the majority of transmission).
|
10.1371/journal.pntd.0001730
|
pubmed_339_77
|
MR imaging, with its unique soft-tissue contrast resolution, noninvasiveness, and multiplanar capabilities, has been applied to the assessment of tendon abnormalities of the foot and the ankle.
|
pubmed_339_77
|
pubmed_57_24926
|
The role of specific antiviral treatment in severe acute hepatitis B has been subject to debate during the past few years. We present clinical findings in a series of three cases of severe acute hepatitis B and one case of acute hepatitis B treated with entecavir during 2007-2009, with interesting evolution. Entecavir appeared to improve the clinical evolution in the reported cases. Two of the patients displayed HBsAg to HBsAb seroconversion while another patient went into an inactive HBsAg carrier state. In the case of mild acute hepatitis B, the liver enzymes had returned to normal, symptomatology had receded but HBsAg had remained positive. Without data on viral load, we were unable to determine whether the patient had entered an inactive HBsAg carrier state or had continued into the services of another medical unit, for treatment of chronic HBV infection. We also discuss into detail a case which displayed transient initial HBe seroconversion at 1 week, followed by seroreversion to positive HBeAg and negative HBeAb at week 3, and a new seroconversion at week 7. We assess the possible roles of precore mutations, antibody-dependent cellular cytotoxicity, coinfection with Epstein Barr virus and the function of Kupffer cells.
|
10.11599/germs.2012.1009
|
pubmed_733_21253
|
Chondroitin AC lyase from Flavobacterium heparinum degrades chondroitin sulfate glycosaminoglycans via an elimination mechanism resulting in disaccharides or oligosaccharides with delta4,5-unsaturated uronic acid residues at their nonreducing end. Mechanistic details concerning the ordering of the bond-breaking and -forming steps of this enzymatic reaction are nonexistent, mainly due to the inhomogeneous nature of the polymeric substrates. The creation of a new class of synthetic substrates for this enzyme has allowed the measurement of defined and reproducible k(cat) and K(m) values and has expanded the range of mechanistic studies that can be performed. The primary deuterium kinetic isotope effect upon k(cat)/K(m) for the abstraction of the proton alpha to the carboxylic acid was measured to be 1.67 +/- 0.07, showing that deprotonation occurs in a rate-limiting step. Using substrates with leaving groups of differing reactivity, a flat linear free energy relationship was produced, indicating that the C4-O4 bond is not broken in a rate-determining step. Taken together, these results strongly suggest a stepwise mechanism. Consistent with this was the measurement of a secondary deuterium kinetic isotope effect upon k(cat)/K(m) of 1.01 +/- 0.03 on a 4-[(2)H]-substrate, indicating that no sp2 character is developed at C4 during the rate-limiting step, thereby ruling out a concerted syn-elimination.
|
10.1021/ja020627c
|
pubmed_594_9739
|
BACKGROUND
The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocytes in HD and its relations to clinical presentation and to EBV expression have not been characterized fully. Grade II HD is a more aggressive form of the disease. The authors studied cases of HD by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph nodes and to characterize the phenotype of these lymphocytes in relation to EBV expression, tumor grade, and clinical presentation. MATERIALS AND METHODS The authors prospectively studied lymph nodes from 48 patients with the diagnosis of HD by FCM for T (CD3, CD4, and CD8) and B (CD19) lymphocytes. Ratios of helper to suppressor (CD4 to CD8) and ratios of T to B (CD3 to CD19) lymphocytes were calculated. In situ hybridization for EBV also was performed. The tumors were graded. Clinical data related to age and stage of the disease were retrospectively analyzed.
RESULTS
There were 30 male and 18 female patients with an age range of 7 to 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Eleven (23%) cases were classified as Grade II disease. All Grade II cases showed EBV expression, whereas only 13 (39%) cases of Grade I disease were positive (P = 0.03). EBV-positive cases had a median CD4 to CD8 ratio of 1.62, whereas EBV-negative cases had a ratio of 3.86 (P = 0.01). Grade I cases had a median CD4 to CD8 ratio of 4.58, whereas Grade II cases had a ratio of 1.62 (P = 0.007). EBV-positive cases had a median T-lymphocyte to B-lymphocyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.77). Grade I cases had a median T-lymphocyte to B-lymphocyte ratio of 3.51, whereas Grade II cases had a ratio of 1.71 (P = 0.001). A higher percentage of children was seen in the EBV-positive cases than in the negative ones (58% vs. 29%). Cases with low (< 1.5) CD4 to CD8 ratios showed more incidence of high-stage disease (Stages III and IV) than patients with higher ratios (81% vs. 51%). High-stage disease also was seen more frequently in patients with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%).
CONCLUSION
The authors found that the local immune response in HD may vary from one case to another. The findings also suggest that EBV may play a role in the pathogenesis of the disease in relation to T- and B-lymphocyte response. A more profound immune suppression and decrease in overall T and helper lymphocytes may be seen in aggressive EBV-positive variants of the disease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior.
|
10.1002/1097-0142(20010601)91:11<1957::aid-cncr1220>3.0.co;2-6
|
pubmed_347_4411
|
BACKGROUND
Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system.
METHODS
The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed.
DISCUSSION
The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting.
TRIAL REGISTRATION
Clinical Trials NCT01611818.
|
10.1186/1471-244X-13-21
|
pubmed_649_15889
|
Vitamin D-dependent Ca2+-binding protein from pig duodenum was hydrolysed with trypsin in the presence of Ca2+ and two products were obtained: T1, which differed from the native protein by loss of Ac-Ser-Ala-Gln-Lys from the N-terminus and Ile-Ser-Gln-OH from the C-terminus, and T2, which differed from T1 by loss of a C-terminal lysine. The hydrolysis inactivated one of the two high-affinity Ca2+-binding sites on the native protein, and the remaining site was stable in T1 but labile in T2 when the proteins were Ca2+-free. Binding studies showed that T1 had Kd values of 2.8 +/- 0.1 nM, 57 +/- 13 microM and 0.8 +/- 0.3 microM for Ca2+, Mg2+ and Mn2+ respectively, and T2 had Kd 2.2 +/- 0.3 nM for Ca2+. The affinity for Mn2+, together with the other Kd values, identified the site on T1 as the site on the native protein previously found to have Kd 0.6 microM for Mn2+, rather than one with Kd 50 microM for Mn2+. In contrast with both the native protein and another form of the protein with a single Ca2+-binding site, the intrinsic fluorescence of T1 and T2 was little affected by the addition of Ca2+. It was concluded that the active binding site in T1 and T2, and also the site in the native protein with the higher affinity for Mn2+, was probably in the C-terminal half of the molecule.
|
10.1042/bj2370781
|
pubmed_452_16895
|
Ruminant livestock systems in the (Sub-)Tropics differ from those in temperate areas. Yet, simulation models used to study resource use and productive performance in (sub-)tropical cattle production systems were mostly developed using data that quantify and characterize biological processes and their outcomes in cattle kept in temperate regions. Ergo, we selected the LIVestock SIMulator (LIVSIM) model, modified its cattle growth and lactation modules, adjusted the estimation of the animals' metabolizable energy and protein requirements, and adopted a semi-mechanistic feed intake prediction model developed for (sub-)tropical stall-fed cattle. The original and modified LIVSIM were evaluated using a meta-dataset from stall-fed dairy cattle in Ethiopia, and the mean bias error (MBE), the root mean squared error of prediction (RMSEP), and the relative prediction error (RPE) were used to assess their accuracy. The modified LIVSIM provided more accurate predictions of voluntary dry matter intake, final body weights 140 days postpartum, and daily milk yields than the original LIVSIM, as shown by a lower MBE, RMSEP, and RPE. Therefore, using data that quantify and characterize biological processes from (sub-)tropical cattle production systems in simulation models used in the (Sub-)Tropics can considerably improve their accuracy.
|
10.3390/ani10050816
|
pubmed_117_20552
|
BACKGROUND AND AIMS
Opioid associated death and overdose is a growing burden in societies all over the world. In recent years, legislative changes have increased access to naloxone in the take-home setting for use by patients with a substance use disorder and bystanders, to prevent opioid overdose deaths. However, few studies have explored the factors influencing the uptake by its multiple stakeholders. The aim of this scoping review was to explore the factors influencing the use of take-home naloxone from the perspectives of different stakeholders.
METHODS
A scoping review methodology was adopted with a systematic search of databases EMBASE, MEDLINE and PubMed. A variation of the search words "naloxone", "opioid" and "overdose" were used in each database. The articles were screened according to the predetermined inclusion/exclusion criteria and categorized based on their key perspective or target population.
RESULTS
The initial database search yielded a total of 1483 articles. After a series of screening processes, 51 articles were included for analysis. Two key stakeholder perspectives emerged: patients and bystanders (n = 36), and healthcare professionals (n = 15). Within the patient and bystander group, a strong consensus arose that there were positive outcomes from increased access to take-home naloxone and relevant training programs. Despite these positive outcomes, some healthcare professionals were concerned that take-home naloxone would encourage high-risk opioid use.
CONCLUSION
Take-home naloxone is slowly being introduced into community practice, with a sense of enthusiasm from patients and bystanders. There are still a number of barriers that need to be addressed from healthcare professionals' perspective. Future research should be aimed at emergency care professionals outside of the US, who are most experienced with naloxone and its potential impact on the community.
|
10.3390/pharmacy8040232
|
pubmed_211_21215
|
The functional role of the dopamine transporter (DAT) in central dopaminergic neurotransmission was assessed further by investigating the consequences on dopamine (DA) turn-over of up- and down-regulation of this protein induced by a non-viral gene transfer approach. For this purpose, expression plasmids containing the sense or antisense coding sequence of DAT complexed with the cationic polymer, polyethylenimine (PEI), were injected into the rat substantia nigra, the brain region containing the majority of DA cell bodies. Before in vivo injection, the efficacies of the different DNA constructs were assessed by transfection studies into LLC-PK1 cells. Stereotaxic administration of the sense plasmid complexed to PEI induced, 3 days later, a significant increase in the immunoautoradiographic labelling by anti-DAT antibodies of the substantia nigra and various DA projection areas. These effects were associated with a significantly enhanced capacity of striatal synaptosomes to take up [3H]-DA and lasted up to 14 days postinjection. In contrast, 7 days after intranigral administration of the antisense plasmid complexed to PEI, we observed a significant decrease of DAT immunolabelling in the substantia nigra and [3H]-DA uptake by striatal synaptosomes. Whereas DA turnover in the striatum was unaltered 3 days after intranigral administration of the sense plasmid, it was increased 7 days after intranigral administration of the antisense construct. These data indicate that non-viral transfer of the sense or antisense coding sequence of DAT can be used as a novel approach to induce long-term changes in central DA neurotransmission.
|
10.1046/j.1460-9568.1998.00366.x
|
pubmed_482_9614
|
Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5',8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3-6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.
|
10.3390/cells9071671
|
pubmed_115_764
|
NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1(-/-) hematopoietic stem cells to osteoclast-deficient Fos(-/-) mice, and by Fos(-/-) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1(-/-) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.
|
10.1084/jem.20051150
|
pubmed_1102_20704
|
CD26/Dipeptidyl peptidase IV (DPPIV) is a cell surface glycoprotein with numerous roles including glucose metabolism, immunomodulation, and tumorigenesis. CD26/DPPIV is well recognized in diabetes, with DPPIV inhibitors being a class of oral hypoglycemic drugs called gliptins that are commonly used to treat type two diabetes mellitus. Recent work also indicated a potential role for CD26 in infectious diseases, including COVID-19, and immune-mediated disorders such as rheumatoid arthritis, inflammatory bowel disease, and graft-versus-host disease. In cancer, CD26/DPPIV expression has been characterized in numerous tumors such as hematologic malignancies, malignant pleural mesothelioma (MPM), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastrointestinal stromal tumor (GIST), and prostate, lung, colorectal, and ovarian (PLCO) cancer. Hence, CD26 has been frequently studied as a tumor biomarker and therapeutic target. CD26/DPPIV-targeted therapies have been evaluated in various cancers, including the use of anti-CD26 monoclonal antibodies as anticancer treatment in selected neoplasms. This review highlights our current understanding of the role of CD26 in cancer, diabetes, immune-mediated diseases, and infectious diseases. Enhanced understanding of CD26 biology and function may lead to novel therapeutic approaches in multiple human diseases.
|
10.7759/cureus.13495
|
pubmed_311_13938
|
AIMS
Hypotension can be a symptom of paraneoplastic autonomic neuropathy (PAN). Onconeural antibodies (OA) provide strong evidence for the paraneoplastic origin of neurological syndromes. Our goal was to assess the frequency of PAN among patients with advanced malignancies and hypotension using OA.
METHODS
Patients with advanced malignancies and hypotension were screened and enrolled as per protocol. Plasma levels of six classical OAs were assessed in these patients. We prospectively evaluated other symptoms of PAN in these patients.
RESULTS
31 patients out of 740 screened met the criteria of this cross-sectional study. OAs were present in 4 patients (12.9%). Anti-amphiphysin was found in 1 patient (3.23%), anti- CV2 (anti-CRPM5, anti- collapsin- response mediator protein) was present in 1 patient (3.23%), 1 patient (3.23%) was positive for anti-Hu and anti-Ma2 was present in 1 patient (3.23%). No patient was positive for 2 or more OAs. Normalization of blood pressure in concordance with partial remission occurred in 5 patients. The most used criteria for PAN were fulfilled in 9 patients.
CONCLUSION
The frequency of PAN may be underestimated in a busy oncology clinic. Assessing OAs may aid in the differential diagnosis of hypotension of unknown origin.
|
10.5507/bp.2018.073
|
pubmed_292_18699
|
Changes to the work environment prompted by the movement toward patient-centered care have the potential to improve occupational stress among health care workers by improving team-based work activities, collaboration, and employee-driven quality improvement. This study was conducted to examine professional quality of life among providers at patient-centered care pilot facilities. Surveys were conducted with 76 Veterans Affairs employees/providers at facilities piloting patient-centered care interventions, to assess demographics, workplace practices and views (team-based environment, employee voice, quality of communication, and turnover intention), and professional quality of life (compassion satisfaction, burnout, and secondary traumatic stress).Professional quality-of-life subscales were not related to employee position type, age, or gender. Employee voice measures were related to lower burnout and higher compassion satisfaction. In addition, employees who were considering leaving their position showed higher burnout and lower compassion satisfaction scores. None of the work practices showed relationships with secondary traumatic stress.
|
10.1097/HCM.0000000000000070
|
pubmed_322_17099
|
BACKGROUND
Aconitum heterophyllum Wall. ex Royle and Aconitum balfourii Stapf, are two highly important, threatened medicinal plants of the Indian Himalayan Region. Root-tubers of Aconites have occupied an important place in Indian pharmacopoeia from very ancient times. India is a hub of the wild-collected medicinal herbs industry in Asia and these two aconites are known to have been heavily traded from the region in illicit manner. Prosecution of these illegal trading crimes is hampered by lack of pharma-forensic expertise and tools.
METHODS AND RESULTS
Present study was conducted to evaluate the discriminatory potential of rbcL, a Chloroplast based DNA barcode marker for the authentication of these two Himalayan Aconites. Fresh plant samples were collected from their natural distributional range as well as raw materials were procured from herbal market and a total of 32 sequences were generated for the rbcL region. Analysis demonstrated that rbcL region can successfully be used for authentication and importantly, both the aconites, were successfully discriminated by rbcL locus with high bootstrap support (> 50%).
CONCLUSION
Molecular markers could certainly be relied upon morphological and chemical markers being tissue specific, having a higher discriminatory power and not age dependent. Phylogenetic analysis using Maximum Likelihood Method revealed that the rbcL gene could successfully discriminate Himalayan Aconites to species level and have potential to be used in pharma-forensic applications as well as to curb illicit trade of these invaluable medicinal plants.
|
10.1007/s11033-021-06675-5
|
pubmed_707_9932
|
Multiple primary malignant neoplasms (MPMNs) or multiple primary malignancies are defined as two or more histologically distinct malignancies present in the same individual. While second or higher-order malignancies account for approximately 18% of all cancers in the United States, it is reasonable to presume that MPMNs are now occurring more frequently than previously reported. Underserved groups such as blacks and Hispanics may represent a high proportion of these underreported cases due to well-established health disparities. Although the role of health disparities has been well established in single primary malignancies, less is known on racial differences in patients with multiple primaries. In comparing MPMNs by race, blacks have lower survival rates compared to white patients. Moreover, despite the lower overall incidence of MPMNs in blacks compared to white patients, when broken down by the specific types of cancers and gender, there are significant racial disparities in the incidence of prostate cancer and possibly other cancers. Further research and case reports are required to explore the risk factors of developing MPMNs in these groups. Our case series explores three African American patients with MPMNs that are rarely described in the literature and outlines the management challenges of treating multiple malignancies.
|
10.7759/cureus.21585
|
pubmed_343_10237
|
Esophageal adenocarcinoma (EAC) is an aggressive and challenging disease to treat, with an overall five‑year survival rate of <20%. Early malignant cell dissemination contributes to this poor prognosis. Epithelial‑mesenchymal transition (EMT) induces the invasion and metastasis of carcinoma cells. Empty spiracles homeobox 2 (EMX2) is a homeodomain‑containing transcription factor, which is associated with numerous cancer types, and has been demonstrated to regulate EMT. In the present study, 48 pairs of EAC and adjacent normal tissues were analyzed. The results revealed that EMX2 was downregulated in EAC tissues, and its expression was negatively correlated with the DNA hypermethylation of its promoter. Additionally, the OE19 and OE33 EAC cell lines were treated with the DNA methyltransferase inhibitor 5‑aza‑2'‑deoxycytidine, and the results indicated that EMX2 expression was increased. Overexpressing EMX2 in EAC cell lines enhanced the expression of apoptotic markers, inhibited cell migration and invasion, led to the upregulation of E‑cadherin and the downregulation of mesenchymal markers, and suppressed AKT, mTOR and S6K phosphorylation. Furthermore, EMX2 overexpression sensitized EAC cells to cisplatin. These results demonstrated that EMX2 inhibited the AKT/mTOR/S6K signaling pathway and decreased EMT. However, the downregulation of EMX2 was revealed to be associated with EMT in EAC, indicating that EMX2 may be a potential target for the management of EAC.
|
10.3892/or.2019.7284
|
pubmed_608_22840
|
BACKGROUND
Expression patterns of many laticifer-specific gens are closely correlative with rubber yield of Hevea brasiliensis (para rubber tree). To unveil the mechanisms underlying the rubber yield, transcript levels of nine major latex metabolism-related genes, i.e., HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), diphosphomevalonate decarboxylase (PMD), farnesyl diphosphate synthase (FPS), cis-prenyltransferase (CPT), rubber elongation factor (REF), small rubber particle protein (SRPP), dihydroxyacid dehydratase (DHAD) and actin depolymerizing factor (ADF), were dertermined, and the relationship between rubber yield with their expression levels was analysed.
RESULTS
Except HbHMGR1, HbPMD and HbDHAD, most of these genes were predominantly expressed in latex, and bark tapping markedly elevated the transcript abundance of the analyzed genes, with the 7th tapping producing the greatest expression levels. Both ethephon (ETH) and methyl jasmonate (MeJA) stimulation greatly induced the expression levels of the examined genes, at least at one time point, except HbDHAD, which was unresponsive to MeJA. The genes' expression levels, as well as the rubber yields and two yield characteristics differed significantly among the different genotypes examined. Additionally, the latex and dry rubber yields increased gradually but the dry rubber content did not. Rubber yields and/or yield characteristics were significantly positively correlated with HbCPT, HbFPS, HbHMGS, HbHMGR1 and HbDHAD expression levels, negatively correlated with that of HbREF, but not significantly correlated with HbPMD, HbSRPP and HbADF expression levels. In addition, during rubber production, significantly positive correlations existed between the expression level of HbPMD and the levels of HbREF and HbHMGR1, between HbSRPP and the levels of HbHMGS and HbHMGR1, and between HbADF and HbFPS.
CONCLUSIONS
The up-regulation of these genes might be related to the latex production of rubber trees under the stress of bark tapping and latex metabolism. The various correlations among the genes implied that there are differences in their synergic interactions. Thus, these nine genes might be related to rubber yield and yield-related traits in H. brasiliensis, and this work increases our understanding of their complex functions and how they are expressed in both high-and medium-yield rubber tree varieties and low-yield wild rubber tree germplasm.
|
10.1186/s12864-018-5242-4
|
pubmed_757_13580
|
Heart failure remains a health challenge in Africa, associated with significant rates of hospitalization, morbidity and mortality. The current review aims to summarize the most recent data on the epidemiology, aetiology, risk factors and management of heart failure, comparing countries in North Africa and sub-Saharan Africa. There is a paucity of data on heart failure epidemiology, aetiology and management, and on the sociodemographic characteristics of African patients with heart failure. Heart failure prevalence has been evaluated among all medical admissions or admissions to cardiac units or emergency departments in a few hospital-based studies conducted in countries in North Africa and sub-Saharan Africa. Common causes of heart failure in Africa include ischaemic heart disease, hypertensive heart disease, dilated cardiomyopathy and valvular heart disease. The aetiology of heart failure differs between countries in North Africa and sub-Saharan Africa. Diagnosing heart failure proves challenging in Africa because of a lack of basic tools and the necessary human resources. The principal drugs used frequently for heart failure therapy are lacking in sub-Saharan Africa. The clinical profile of heart failure in sub-Saharan Africa differs from that in North African countries; this is related to aetiological factors, socioeconomic status and availability of diagnostic tools. There is an evident need to establish a large multicentre registry to evaluate the heart failure burden in almost all African countries, and to highlight the major cardiovascular risk factors and co-morbidities. The present review highlights the importance of this syndrome in Africa, and calls for improvements in its early diagnosis, treatment and, possibly, prevention.
|
10.1016/j.acvd.2021.07.001
|
pubmed_105_19587
|
INTRODUCTION
Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive tryptophan-depleting enzyme expressed in nasopharyngeal carcinoma (NPC) tissue. However, IDO has not been reported in the peripheral blood of NPC patients. The aim of this study was to analyze, IDO1 and IDO2 messenger RNA (mRNA) expression, the kynurenine (Kyn) and tryptophan (Trp) plasma levels, their clinical values and their relationship with cytokine levels in NPC.
METHODS
We evaluated IDO1 and IDO2 mRNA expression in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR, plasma Trp and Kyn levels by HPLC, and cytokine levels by ELISA in 75 NPC patients and 51 healthy controls.
RESULTS
Compared to controls, IDO1 mRNA expression was significantly upregulated and IDO2 mRNA expression was significantly downregulated in PBMC of patients. Also compared to controls, plasma Kyn levels and Kyn/Trp ratio were significantly higher in patients. At the time of diagnosis, the plasma Kyn/Trp ratio was associated with advanced cancer status and was an independent prognostic factor for worse disease-specific survival. According to cancer stages, IDO1 mRNA expression was positively correlated with plasma Kyn/Trp ratio in patients with earlier stages (I-II-III) but negatively correlated in patients with the late-stage cancer (IV). Tumor necrosis factor-α, interleukin (IL)-6 and IL-10 levels were significantly higher in patients compared to controls. Moreover, and despite treatment, patients simultaneously carrying high plasma Kyn/Trp ratio and high plasma IL-6 and IL-10 levels at diagnosis died approximately 1 year after first diagnosis.
CONCLUSION
Measuring blood IDO mRNA expression and Kyn/Trp ratio at diagnosis could be a potential marker to evaluate NPC progression and predict survival outcome.
|
10.1002/iid3.690
|
pubmed_1027_12682
|
From an obscure frontier surgeon George Crawford Gorgas became internationally acclaimed as a preventive medicine genius. By his initiative in translating the known scientific facts made possible during the blossoming of bacteriology, he performed service not only in the United States but in Cuba, Central and South America, South Africa, and Eastern Europe. He fought for 10 years successfully against yellow fever, malaria, and other diseases during the construction of the Panama Canal, and continued triumphs against disease in other world situations. This is a rather concise account emphasizing his continued devotion and dedication as a humanitarian. He fashioned the Army Medical Department into an efficient machine as Surgeon General, and following his amazing military career of over 38 years, made further contributions in preventive medicine with the Rockefeller Foundation.
|
pubmed_1027_12682
|
pubmed_178_14880
|
No practical methods are presently available for measurement of alveolar bone activity at one instant of time. However, roentgenological methods making measurements at 2 different times can be used to assess alveolar bone activity. The most sensitive, specific and accurate method for this purpose presently in use is 125I absorptiometry. This method has the further advantage of giving the patient minimal radiation exposure. New methodology is under development which obviates the need for fixed geometry and could provide a 3-dimensional image of alveolar bone.
|
10.1111/j.1600-051x.1983.tb02178.x
|
pubmed_229_6770
|
Hexane extracts of epicuticular wax from cv. Gala apples were noted to have an unusual, broad absorbance maximum at approximately 258 nm, which led us to isolate and identify the primary UV-absorbing compounds. Column and thin-layer chromatography yielded a fraction that gave a series of paired, 260-nm-absorbing peaks on C(18) HPLC. These were shown to be a family of phenolic fatty acid esters, for which retention times increased with increasing fatty acid chain length, and paired peaks were esters of two related phenolics with the same fatty acid moiety. Alkaline hydrolysis of the esters released two water-soluble phenolics separable by C(18) HPLC. Electrospray ionization mass spectrometry gave a molecular mass of 150 for both, and (1)H NMR plus UV absorbance spectra identified them as E and Z isomers of p-coumaryl alcohol. Alkaline cleavage of the fatty acid esters in the presence of methanol or ethanol resulted in partial derivatization of E-p-coumaryl alcohol to the corresponding gamma-O-methyl or O-ethyl ether. Gradient HMQC NMR of the HPLC-purified stearate ester of E-p-coumaryl alcohol indicated that fatty acid esterification occurs at the gamma-OH rather than at the 4-OH on the phenyl ring. This is the first report of fatty acid esters of monolignols as a natural plant product.
|
10.1021/jf010409n
|
pubmed_1057_8525
|
In this study, custom-tailored graphene oxide quantum dots (GOQD) were synthesized as functional nanofillers to be embedded into the polyamide (PA) membrane for reverse osmosis (RO) via interfacial polymerization (IP). The heterostructured interface-functionalization of amine/sulfonic decoration on GOQD (N/S-d-GOQD) takes place via the tuning of the molecular design. The embedded N/S-d-GOQD inside the PA matrix contributes to facilitating water molecules quick transport due to the more accessible capturing sites with higher internal polarity, achieving a nearly 3-fold increase in water permeance when compared to the pristine thin-film composite (TFC) membrane. Covalent bonding between the terminal amine groups and the acyl chloride of trimesoyl chloride (TMC) enables the formation of an amplified selective layer, while the sulfonic part assists in maintaining a robust membrane surface negative charge, thus remarkably improving the membrane selectivity toward NaCl. As a result, the newly developed TFN membrane performed remarkably high water permeance up to 5.89 L m-2 h-1 bar-1 without the compromising of its favorable salt (NaCl) rejection ratio of 97.1%, revealing a comparably high separation property when comparing to the state-of-the-art RO membranes, and surpassing the permeability-selectivity trade-off limits. Furthermore, we systematically investigated the GOQDs with different surface decorations but similar configurations (including 3 different nanofillers of pristine GOQD, amine decorated GOQD (N-d-GOQD), and N/S-d-GOQD) to unveil the underlying mechanisms of the swing effects of internal geometry and polarity of the embedded nanofillers on contributing to the uptake, and/or release of aqueous molecules within TFN membranes, providing a fundamental perspective to investigate the impact of embedded nanofillers on the formation of an IP layer and the overall transporting behavior of the RO process.
|
10.1021/acsami.0c10301
|
pubmed_197_21129
|
Blindness caused by severe vasculitis or uveitis is rare in juvenile systemic lupus erythematosus (JSLE) patients. In a 27-year period, 5367 patients were followed at our Paediatric Rheumatology Division and 263 (4.9%) patients had JSLE (American College of Rheumatology criteria). Of note, two (0.8%) of them had irreversible blindness. One of them presented with cutaneous vasculitis and malar rash, associated with pain and redness in both eyes, impairment of visual acuity due to iridocyclitis and severe retinal vasculitis with haemorrhage. Another patient had peripheral polyneuropathy of the four limbs and received immunosuppressive drugs. Three weeks later, she developed diffuse herpes zoster associated with acute blindness due to bilateral retinal necrotizing vasculitis compatible with varicella zoster virus ocular infection. Despite prompt treatment, both patients suffered rapid irreversible blindness. In conclusion, irreversible blindness due to retinal vasculitis and/or uveitis is a rare and severe lupus manifestation, particularly associated with disease activity and viral infection.
|
10.1177/0961203310378412
|
pubmed_217_12722
|
Prostate cancer (CaP) is a common reproductive cancer among men. This study was conducted to correlate the cancer incidence with Gangetic zone and to correlate the tumor marker prostate specific antigen (PSA) level in serum with different age groups and stage of malignancy. Patients suffering from CaP in the pathology unit of Mahavir Cancer Sansthan (Hospital and Research Centre), Patna, Bihar, India were studied from June 2009 to May 2010. PSA level in the serum of CaP patients was estimated by ELISA method. CaP incidence was highly recorded in Gangetic zone than the non-Gangetic zone. Maximum patients were in the 56 - 75 years age group with a marked predominance. Results of PSA examination showed that serum PSA level was not correlating with the age of patient and stage of malignancy. Significantly, elevated level of more than 10 ng/ml of PSA was recorded among the studied cancer patients. In this study, it is concluded that Gangetic zone habitat have high risk of CaP and elevated level of PSA was marked in Bihar, India.
|
10.7314/apjcp.2012.13.1.221
|
pubmed_155_9298
|
The histopathology of 145 malignant lymphomas of the small intestine in Iraq have been studied and results compared with the clinical and immunological findings. The most common pathology was an intense mucosal lymphoplasmacytic proliferation effacing the villi and crypts partially or completely. This was either 'pure', usually of mature plasma cells limited to the lamina propria or associated with a fullblown lymphoplasmacytic lymphoma, almost always of the upper small intestine. The syndrome presented as abdominal pain, chronic diarrhoea, clubbing and, sometimes, the serological demonstration of alpha heavy chains. Other types of lymphomas were associated with 'non-specific' mucosal inflammation or follicular lymphoid hyperplasia. They were either lymphocytic, plasmacytic or lymphoblastic with 'starry sky' histiocytic reaction, representing distinct clinicopathological entities unrelated to 'alpha heavy chain disease'. Hodgkin's disease was extremely rare in this series.
|
10.1111/j.1365-2559.1979.tb02986.x
|
pubmed_432_11171
|
Collagen and thrombin challenged platelets from vitamin E-deficient rabbits generated significantly more 12-HETE when compared to the platelets from vitamin E-supplemented rabbits. Similarly, conversion of arachidonic acid to 12-HETE was increased in platelets from vitamin E-deficient rabbits. These data show that vitamin E plays a role not only in deacylation of platelet phospholipids but also in the lipoxygenase mediated reactions.
|
pubmed_432_11171
|
pubmed_1110_14428
|
OBJECTIVE: To determine frequency of use and safety of epinephrine containing local anesthesia among dermatologists in the United Kingdom and venereologists undertaking penile biopsy. DESIGN: A survey was distributed nationally to members of the British Association of Dermatologists and the British Association for Sexual Health and Human Immunodeficiency Virus in December 2016. RESULTS: Sixty-six responses were received: 36.4 percent of respondents used epinephrine routinely, 16.7 percent sometimes used it, and 47 percent did not use it at all. Epinephrine use was more commonly by dermatologists in either some or all cases (56.8%) compared with venereologists (40%). Only two complications were reported to epinephrine use. Both were temporary without report of necrosis. CONCLUSION: Use of epinephrine-containing local anesthesia is common among physicians in the United Kingdom undertaking penile biopsies. Despite this, no episodes of necrosis were observed. While further investigation is still required, it is likely that use of epinephrine-containing local anesthesia is safe for local penile injection.
|
pubmed_1110_14428
|
pubmed_933_15212
|
Quantum chemical based investigation is presented on the Abraham solvation parameters for 23 molecular (non-polymeric) GLC stationary phases. PM6 semiempirical calculations combined with conductor-like screening model (COSMO) have been utilized. Comprehensive search for an optimal model was carried out, based on best subset selection from 86 variables considered. A unified quantitative structure-property relationship model has been developed for all five Abraham parameters reported. The selected set of five structure-driven descriptors was subjected to statistical analyses, and was shown to be useful for stationary phase classification.
|
10.1016/j.chroma.2009.09.074
|
pubmed_772_596
|
Obesity bias is the tendency to negatively judge an overweight or obese individual based on assumed and/or false character traits, such as being physically unattractive, incompetent, lazy and lacking self-discipline. Obesity biases, such as teasing or weight criticism during physical activity (PA), can be psychologically or emotionally damaging for overweight children and adolescents. Ultimately, the effects students experience over time may create a psychological barrier and students can become resistant to schools' health and PA interventions that promote lifestyle changes. Fortunately, the psychological effects of obesity bias are mediated by social buffers and coping mechanisms. Several PA-related researchers have proposed strategic intervention components, but no studies have been completed in PA settings. The purpose of this review was to discuss the nature and different types of obesity bias in PA settings. Major theoretical frameworks of the aetiology and change mechanisms of obesity biases from the psychological literature were reviewed and direct applications for strategic component interventions were made for PA settings. Because of the pervasiveness and entrenchment of obesity bias, it is obvious that multiple theoretical frameworks need to be considered and even combined to create safe and caring school PA environments for students.
|
10.1111/j.1467-789X.2007.00403.x
|
pubmed_543_392
|
DNA polymerase delta requires proliferating cell nuclear antigen and replication factor C to form a holoenzyme efficient in DNA synthesis. We have analyzed three different aspects of calf thymus DNA polymerase delta holoenzyme: (i) analysis of pausing during DNA synthesis, (ii) replication of double-stranded DNA in the absence of additional factors, and (iii) replication of double-stranded DNA in the presence of the two known replicative DNA helicases from simian virus 40 and bovine papilloma virus. DNA polymerase delta holoenzyme replicated primed single-stranded DNA at a rate of 100-300 nucleotides/min, partially overcoming multiple pause sites on DNA. While Escherichia coli single-strand DNA binding protein helped DNA polymerase delta pass through pause sites, the DNA polymerase delta itself appeared to dissociate from the template in the absence of synthesis or when encountering pause sites. Proliferating cell nuclear antigen likely remained on the template. DNA polymerase delta holoenzyme could perform limited strand displacement synthesis on double-stranded gapped circular DNA, and this reaction was not stimulated either by replication protein A or by E. coli single-strand DNA binding protein. DNA polymerase delta holoenzyme could efficiently cooperate with replicative DNA helicases from simian virus 40 (large T antigen) and bovine papilloma virus 1 (protein E1) in replication through double-stranded DNA in a reaction that required replication protein A or E. coli single-strand DNA binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1021/bi00015a011
|
pubmed_734_8179
|
Over the last 50 years, there have been shifts in the incidence of gastric and esophageal cancers in the United States, including a decline in noncardia gastric adenocarcinoma (NCGC), and increases in cardia gastric adenocarcinoma (CGC) and esophageal adenocarcinoma (EAC).1,2 Hypotheses for the changing incidences include eradication of Helicobacter pylori, the main causative agent of NCGC, and rising rates of reflux, obesity, and diet, which are risk factors associated with EAC and CGC.1,3.
|
10.1016/j.cgh.2022.03.034
|
pubmed_1041_15811
|
The stability of a formulated heparin was examined during its sterilization by autoclaving. A new method to follow loss in heparin binding to the serine protease inhibitor, antithrombin III, and the serine protease, thrombin, was developed using a surface plasmon resonance competitive binding assay. This loss in binding affinity correlated well with loss in antifactor IIa (thrombin) activity as well as antifactor Xa activity as measured using conventional amidolytic assays. Autoclaving also resulted in a modest breakdown of the heparin backbone as confirmed by a slight reduction in number-averaged and weight-averaged molecular weight and an increase in polydispersity. Although no clear changes were observed by nuclear magnetic resonance spectroscopy, disaccharide composition analysis using high-performance liquid chromatography-electrospray ionization-mass spectrometry suggested that loss of selected sulfo groups had taken place. It is this sulfo group loss that probably accounts for a decrease in the binding of autoclaved heparin to antithrombin III and thrombin as well as the observed decrease in its amidolytic activity.
|
10.1002/jps.22527
|
pubmed_781_5812
|
AIM
The aims of this study were to investigate the phenotypic and genotypic of extended-spectrum β-lactamase (ESBL) and metallo-β-lactamases (MBLs) and determine phylogenetic background E. coli isolates from fecal samples of patients with diarrhea in Kerman, southeast of Iran.
BACKGROUND
The emergence of ESBLs and MBLs-producing E. coli caused problems in antibiotic treatments. E. coli strains can be assigned to four main phylog-groups, including: A, B1, B2 and D.
PATIENTS AND METHODS
E. coli isolates (n=216) were obtained from fecal samples of patients with diarrhea between June and December 2013. ESBLs and MBLs were confirmed by disk-diffusion and broth micro-dilution methods. Using PCR, the ESBL-positive isolates were screened to determine the phylo-groups and the presence of bla CTX-M-15, bla OXA-1, bla PER-1, bla VIM and bla IMP genes.
RESULTS
ESBL-positive isolates (n= 56) were detected. Among ESBL-positive isolates, 51 isolates were positive for bla CTX-M15 and one isolate was positive for both bla CTX-M-15 and bla OXA-1 genes. None of the isolates were positive for bla PER-1, bla VIM and bla IMP genes. PCR assay for phylotyping of isolates indicated that the isolates were belonged to groups A (54.16%), B1 (11.11%), B2 (12.96%) and D (21.75%). The isolates possessed bla CTX-M-15 gene were belonged to A (35 isolates), B1 (5), B2 (3) and D (8) phylo-groups.
CONCLUSION
Our results indicate that bla CTX-M-15 gene is widespread among diarrheagenic E. coli isolates. ESBL-producing E. coli isolates were disseminated among a diversity of phylo-groups. Further studies are necessary to identify the ESBL genes in relation to phylogenetic groups.
|
pubmed_781_5812
|
pubmed_568_9599
|
BACKGROUND
Previous meta-analyses have examined the clinical efficacy and acceptability of deep brain stimulation (DBS) compared with sham therapy or paired active therapy. However, the absence of head-to-head clinical trials with some treatment comparisons creates uncertainty for decision makers. Thus, to provide new evidence-based medical evidence for clinical treatment, we undertook a meta-analysis to assess the efficacy and safety of DBS in patients with depression based on high-quality randomized controlled studies.
METHODS
The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. PubMed/Medline and EMBASE will be searched before May 2021 for all studies, using various combinations of the following free text and key terms: deep brain stimulation; depression; random. No language restrictions will be applied. The method of data extraction will follow the approach outlined by the Cochrane Handbook for Systematic Reviews of Interventions. Review Manager software 5.3 is used for the meta-analysis. The quality of randomized trials will be assessed by Cochrane risk of bias tool for randomized controlled trials.
RESULTS
The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.
OSF REGISTRATION NUMBER
10.17605/OSF.IO/Q5B3S.
|
10.1097/MD.0000000000026044
|
pubmed_456_18798
|
OBJECTIVE
To assess the inpatient hospitalization burden and costs of patients with autoimmune encephalitis (AE) at a tertiary care institution.
METHODS
Adult inpatients with AE were identified retrospectively from July 1, 2005, to June 30, 2015. Demographic and clinical data were collected and analyzed. Billing data were compared to those of patients with herpes simplex encephalitis (HSE). Charges were adjusted for inflation.
RESULTS
Of 244 admissions for encephalitis reviewed, 63 patients met criteria for probable or definite AE. Thirty-one (49%) patients were antibody positive, and 27 (43%) were admitted to the intensive care unit (ICU). Median hospital charges per patient with AE were more than $70,000; median length of stay (LOS) was 15 days; and in-hospital mortality was 6%. Patients admitted to the ICU had substantially higher median hospital charges (ICU $173,000 per admission vs non-ICU $50,000 per admission, p < 0.001). LOS was strongly associated with charges and was driven by delay in diagnosis of AE, prolonged treatment courses, and lack of response to therapy. Compared with HSE, median hospital charges per patient with AE were nearly 4 times higher, median AE LOS was 3 times higher, and total charges over the study period were nearly twice as high.
CONCLUSIONS
Patients with AE used more inpatient health care resources per patient during a 10-year period than patients with HSE at our institution. ICU-admitted patients with AE were responsible for a substantially higher financial burden than non-ICU-admitted patients with AE. Our data underscore the need for the development of novel diagnostic and therapeutic modalities to improve patient outcomes and to decrease hospital burden in AE.
|
10.1212/WNL.0000000000006990
|
pubmed_212_12641
|
Over a period of 10 years, 233 adult patients were treated for severe tetanus in this ICU. Criteria of severity, clinical patterns, and a detailed plan of treatment are outlined. The authors emphasize that such treatment implicates the permanent availability of trained personel in handling cardiorespiratory emergencies as well as prolonged mechanical ventilatory assistance in a specially designed environment (ICU). The form of therapy described herein seems to be the best currently available management regime, inasmuch as it can be expected to reduce significantly the notoriously high mortality associated with severe tetanus. Although this therapy is very expensive and time consuming, this is the price to be paid when the life of one of these patients is endangered. Complications are usually bizarre and unexpected. The authors found a high incidence of infectious respiratory complications, probably related to a change in the tracheal flora secondary to antibiotic therapy and a less than ideal care of tracheostomies. Unexpected cardiac arrest was the most common cardiovascular complication and also the most common cause of death; in the majority of these cases, a satisfactory explanation for this complication was not found, but it could have been related to overactivity of the autonomic nervous system.
|
pubmed_212_12641
|
pubmed_933_10092
|
BACKGROUND
There is evidence of the association between the apolipoprotein E (APOE) and coronary disease; however, there are controversies.
OBJECTIVE
To evaluate the association between the number of coronary vessels with significant obstruction defined by angiography, the APOE polymorphism and clinical variables.
METHODS
This was a cross-sectional, multicenter study with 207 patients (138 men), with acute coronary syndrome (ACS), in the city of Niteroi, state of Rio de Janeiro, Brazil, who underwent coronary angiography and genotype determination for the APOE *2*3*4 polymorphism by the Restriction Fragment Length Polymorphism (RFLP) method.
RESULTS
The frequency of the alleles was APOE *2 - 6.8%, *3 - 82.5%, *4 - 10.7%. Regarding the number of affected vessels, 27% of patients presented monoarterial obstruction, 33.8% biarterial and 39.1% triarterial and/or left coronary trunk. The degree of multivascular lesion did not correlate with the presence of the *4 allele (p= 0.78), but with age > 55 years (p=0.025), being an ex-smoker (p=0.004) and dyslipidemia (p=0.05) at the multivariate analysis and also with previous coronary artery disease (CAD) (p=0.05), diabetes (p=0.038) and metabolic syndrome (p=0.021) at the univariate analysis. The prevalence of dyslipidemia, diabetes and systemic arterial hypertension (SAH) was elevated regarding similar studies, with progressive increases in the prevalence of SAH (p=0.59) and diabetes (p=0.06), according to the number of affected vessels.
CONCLUSION
The APOE polymorphism was not associated with the number of coronary vessels with significant obstruction at any age range. On the other hand, age > 55 years, being an ex-smoker and dyslipidemia associated with the multivascular lesion.
|
pubmed_933_10092
|
pubmed_343_7668
|
Adolescents are highly motivated to engage in social interactions, and researchers have hypothesized that positive social relationships during adolescence can have long term, beneficial effects on stress reactivity and mental well-being. Studies of laboratory rodents provide the opportunity to investigate the relationship between early social experiences and later behavioral and physiological responses to stressors. In this study, female Lister-hooded rats (N = 12 per group) were either (a) provided with short, daily encounters (10 min/day) with a novel partner during mid-adolescence (postnatal day 34-45; "social experience," SE, subjects) or (b) underwent the same protocol with a familiar cagemate during mid-adolescence ("control experience," CE, subjects), or (c) were left undisturbed in the home cage (non-handled "control," C, subjects). When tested in adulthood, the groups did not differ in behavioral responses to novel environments (elevated plus maze, open field, and light-dark box) or in behavioral and physiological (urinary corticosterone) responses to novel social partners. However, SE females emitted significantly more 50 kHz ultrasonic vocalizations than control subjects both before and after social separation from a familiar social partner, which is consistent with previous findings in male rats. Thus, enhanced adolescent social experience appears to have long-term effects on vocal communication and could potentially modulate adult social relationships.
|
10.1002/dev.21906
|
pubmed_147_3989
|
The synthesis and structure-activity relationships of a novel aryl uracil series which contains a fused 5,6-bicyclic ring unit for HCV NS5B inhibition is described. Several analogs display replicon cell culture potencies in the low nanomolar range along with excellent rat pharmacokinetic values.
|
pubmed_147_3989
|
pubmed_719_11107
|
INTRODUCTION
As a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non-factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed.
AIM
The Future of Immunotolerance Treatment (FIT) group was established to contemplate, determine and recommend the best management options for patients with haemophilia A and inhibitors.
DISCUSSION AND CONCLUSIONS
Despite the considerable success of emicizumab in the management of inhibitor patients, the FIT group still sees the importance of eradicating inhibitors. However, the availability of emicizumab and other non-factor therapies in the future might impact greatly on how ITI is undertaken. Theoretically, concomitant use of emicizumab and FVIII might allow emicizumab to effectively prevent bleeding with lower dose ITI regimens. This might allow for the greater adoption of low-dose/low-frequency FVIII ITI regimens, which may result in a reduced need for central venous access devices while still maintaining a reasonable likelihood of ITI success. The FIT group proposes a new management algorithm for current ITI (without emicizumab) and a hypothetical new approach with the availability of emicizumab. As there are no published data regarding the concomitant use of emicizumab and FVIII for ITI, the FIT Expert group encourages the undertaking of properly conducted prospective studies to explore these approaches further.
|
10.1111/hae.13762
|
pubmed_1110_21610
|
We characterized the C9orf72 hexanucleotide repeat expansion (RE) mutation in amyotrophic lateral sclerosis (ALS) patients of 2 distinct origins, Ashkenazi and North Africa Jews (AJ, NAJ), its frequency, and genotype-phenotype correlations. In AJ, 80% of familial ALS (fALS) and 11% of sporadic ALS carried the RE, a total of 12.9% of all AJ-ALS compared to 0.3% in AJ controls (odds ratio [OR] = 44.3, p < 0.0001). In NAJ, 10% of fALS and 9% of sporadic ALS carried the RE, a total of 9.1% of all NAJ-ALS compared to 1% in controls (OR = 9.9, p = 0.0006). We identified a risk haplotype shared among all ALS patients, although an association with age at disease onset, fALS, and dementia were observed only in AJ. Variations were identified downstream the repeats. The risk haplotype and these polymorphisms were at high frequencies in alleles with 8 repeats or more, suggesting sequence instability. The different genotype-phenotype correlations and OR, together with the large range in age at onset, suggest that other modifiers and risk factors may affect penetrance and phenotype in ALS.
|
10.1016/j.neurobiolaging.2017.12.015
|
pubmed_927_1497
|
The clinical and secretory status of sixty patients nine-fourty-four months after highly selective vagotomy for duodenal ulcer is exposed. Mortality and morbidity are very low. The long-term clinical results are Visick I and II in more than 85 p. cent of cases. The results of basal and peak acid output after insulin and pentagastrin are presented. The question: "is highly selective vagotomy sufficient for hypersecretors?" is discussed.
|
pubmed_927_1497
|
pubmed_3_19144
|
OBJECTIVE
To investigate the relationship between the expression of hypoxia inducible factor la (HIF-1alpha) and the neuron apoptosis during a hypoxia ischemia brain damage and explore the role of HIF-1alpha in regulating the neuron apoptosis and repairing the brain damaged by hypoxia and ischemia.
METHODS
Forty SD rats aged 10 days were randomly divided into the experiment group and the control group, with 20 rats in each group. In the experimental group, the rats were anesthetized with ethylether. The right common carotid artery was exposed and ligated. Then, they were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2.5 hours. In the control group, the right common carotid artery was exposed but was not ligated or exposed to hypoxia. The brain tissues were harvested from the rats in the both groups at 4, 8, 24, 48 and 72 hours after the hypoxia and ischemia, and from the rats in the control group at the same time points. The HIF-1alpha protein expression and the cleaved caspase 3 (CC3) protein expression were detected with the immunohistochemistry method. The apoptosis cells were detected with the TUNEL staining method.
RESULTS
In the experimental group, the HIF-1alpha expression was significantly increased at 4 hours after operation, at the peak level at 8 hours, and began to decrease at 24 hours. The CC3 protein was expressed at 4 hours after operation, and was slightly expressed at 8 hours, but was significantly increased at 24 hours; the higher levels were maintained at 48 and 72 hours. However, in the control group, both the expression levels of HIF-1alpha and the CC3 protein were extremely low. So, the expression levels of HIF-1alpha and the CC3 protein were significantly higher in the experimental group than in the control group (P < 0.01). The TUNEL staining showed that in the experimental group the positive cells were significantly increased after the hypoxia and ischemia, with a peak level at 72 hours after the hypoxia and ischemia; however, in the control group there were few positive cells. TUNEL positive cells in the experimental group were significantly more than that in the control group (P < 0.01).
CONCLUSION
The expression tendency of HIF-1alpha is completely different from that of CC3. HIF-1alpha may have a protective role in regulating the neuron apoptosis in the neonatal hypoxia-ischemia brain damage and may promote the repairing and rebuilding process in the brain that was damaged by hypoxia and ischemia.
|
pubmed_3_19144
|
pubmed_117_17479
|
Anatomical-based approaches, targeting either pulmonary vein isolation (PVI) or additional extra PV regions, represent the most commonly used ablation treatments in symptomatic patients with atrial fibrillation (AF) recurrences despite antiarrhythmic drug therapy. PVI remains the main anatomical target during catheter-based AF ablation, with the aid of new technological advances as contact force monitoring to increase safety and effective radiofrequency (RF) lesions. Nowadays, cryoballoon ablation has also achieved the same level of scientific evidence in patients with paroxysmal AF undergoing PVI. In parallel, electrical isolation of extra PV targets has progressively increased, which is associated with a steady increase in complex cases undergoing ablation. Several atrial regions as the left atrial posterior wall, the vein of Marshall, the left atrial appendage, or the coronary sinus have been described in different series as locations potentially involved in AF initiation and maintenance. Targeting these regions may be challenging using conventional point-by-point RF delivery, which has opened new opportunities for coadjuvant alternatives as balloon ablation or selective ethanol injection. Although more extensive ablation may increase intraprocedural AF termination and freedom from arrhythmias during the follow-up, some of the targets to achieve such outcomes are not exempt of potential severe complications. Here, we review and discuss current anatomical approaches and the main ablation technologies to target atrial regions associated with AF initiation and maintenance.
|
10.1111/pace.14140
|
pubmed_829_15293
|
The first postulated structure of the N(3) moiety appeared in a scientific journal in 1890 and was reported as a cyclic triangle with one N,N double bond and two N,N single bonds. Only in the last several years has our understanding of azides advanced to the point that we can now claim to know how to synthesize this prototypical bonding motif. This article examines the experiments and theory that were essential in reaching this point and suggests future directions of research on cyclic-N(3).
|
10.1039/b704782g
|
pubmed_567_9368
|
The development of a stability-indicating capillary zone electrophoresis (CZE) method for the determination of the drug azathioprine (AZA) and its related substances in bulk and dosage forms is described. Theophylline was used as an internal standard to improve quantitative results. The method was fully validated in terms of repeatability (n = 10, RSD for migration time and peak area ratio were 0.15% and 0.60%, respectively), reproducibility (n = 5, RSD of peak area ratio was 0.84%), linearity at two ranges of the azathioprine concentration, limits of detection (LOD) and quantitation (LOQ), and robustness. The method was applied for determination of the drug in bulk and a commercial tablet dosage form (recovery 98.3-101.3%) and in powder for injection (recovery 98.7-100.6%). The method was fast and reliable for the analysis of AZA and its related substances in bulk and dosage forms.
|
10.1081/ddc-100100355
|
pubmed_186_4474
|
OBJECTIVE
To compare 48-week changes in bone mineral density (BMD) and body fat distribution between patients continuing lopinavir/ritonavir and two NRTIs and those switching to lopinavir/ritonavir and lamivudine.
METHODS
Substudy of a randomized, open-label, multicenter OLE study was carried out. Adult HIV-infected patients with <50 copies/mL for ≥6 months were randomized (1:1) to continue lopinavir/ritonavir and two NRTIs or switching to lopinavir/ritonavir and lamivudine. Dual-energy X-ray absorptiometry (DXA) was performed at baseline and after 48 weeks to measure bone composition and body fat distribution in both the groups.
RESULTS
Forty-one patients (dual-therapy, n = 23; triple-therapy, n = 18) of 239, who received at least one dose of study medication, completed the study: median age, 42 years, 71% male, 73% Caucasian. At week 48, total BMD increased by 1.04% (95% CI, 0.06 to 2.01%) among patients switching to dual-therapy, whereas no significant changes occurred in patients maintaining triple-therapy. Dual-therapy and older age were independently associated with total BMD increase. Among patients discontinuing tenofovir-DF, a significant increase was seen in total BMD (1.43; 95% CI, -0.04 to 2.91) and total hip (1.33%; 95% CI, 0.44 to 2.22%). A non-statistically significant decrease in femoral and spinal BMD was observed in patients who discontinued abacavir and in those continuing triple-therapy. Regarding fat distribution, no significant changes were seen in both the treatment groups.
DISCUSSION
BMD increased following switching to lopinavir/ritonavir plus lamivudine in HIV-infected patients on suppressive triple-therapy with lopinavir/ritonavir and two NRTIs including tenofovir-DF.
|
10.1080/15284336.2016.1149929
|
pubmed_1119_1790
|
Lung preservation and its attendant ischemia-reperfusion injury is a complex phenomenon that begins with lung injury that may be present in the donor before any preservation intervention. Acute preservation interventions in common use include single-flush perfusion and donor core-cooling on cardiopulmonary bypass. From this moment forward the ischemia injury begins, and increases during the phase of organ storage. The lung continues to metabolize glucose even at these low temperatures, and future improvements may well lie in recognizing this requirement. With reperfusion, another phase of lung injury begins as the ischemic lung is overloaded with oxygen and oxygen free radicals are generated. Research efforts have focused on minimizing the effect of free-radicals at various steps along their formation and diminishing their interaction with cell membranes.
|
pubmed_1119_1790
|
pubmed_75_13966
|
The presence of 23,25-dihydroxyvitamin D3 has been demonstrated in vivo and in vitro by a number of laboratories. In order to evaluate the significance of 23-hydroxylation, renal 23-hydroxylase activity was compared to renal 24-hydroxylase activity in several species before and after treatment with 1,25-dihydroxyvitamin D3. The maximum activity of 23-hydroxylase varied widely among species. Treatment of animals with 1,25-dihydroxyvitamin D3 24 h and again 2 h prior to assay of renal tissue resulted in a 1.7- to 5.2-fold increase in 23-hydroxylase activity and a 3.8- to 20.6-fold increase in 24-hydroxylase activity compared to untreated controls. Maximum activity for both 23- and 24-hydroxylase required the enzyme substrate, 25-hydroxyvitamin D3, and an optimum concentration (30 mM) of an oxidizable substrate such as L-malate to supply the reducing equivalents of NADPH needed. Addition of 10 mumol of magnesium chloride resulted in 19 and 24% increases in activity for 23- and 24-hydroxylase, respectively. L-Malate supported the hydroxylation reactions better than succinate, alpha-ketoglutarate, or pyruvate. The apparent Km of calf renal 23-hydroxylase was 5.7 +/- 1.0 microM and of 24-hydroxylase, 2.0 +/- 0.2 microM. Apparent Km's for 23-hydroxylase varied from a low of 2.7 +/- 0.3 microM in the sheep to a high of 19.1 +/- 0.5 microM in the chick, and for 24-hydroxylase from 0.5 +/- 0.1 microM for the chick to 2.0 +/- 0.2 microM for the calf. Maximum velocity values (Vmax) ranged from 40 +/- 9 pmol/min/g for 23-hydroxylase in the chick to 396 +/- 92 in the calf, and for 24-hydroxylase from 108 +/- 89 pmol/min/g in the chick to 851 +/- 88 in the pig. These results help explain the in vivo metabolite concentrations and the predominance of the C(24)- over C(23)-oxidation pathways. Renal 23-hydroxylase was similar to 24-hydroxylase in that it was inhibited by carbon monoxide (63%), cyanide (51%), and antimycin (67%), required molecular oxygen, and functioned best at physiological pH 7.4. It was also inhibited by p-chloromercuribenzoate (39%), but not by dinitrophenol. The relatively large amount of 23-hydroxylase activity present in renal tissue of the calf and young chicks, dogs, goats, pigs, rats, mice, and sheep suggests a prominent role for this enzyme in vitamin D metabolism.
|
10.1016/0003-9861(86)90704-6
|
pubmed_31_9596
|
Improving people's life satisfaction has become an important goal for many individuals and societies. In this study we investigate how grit influences life satisfaction. We propose that individuals' self-esteem mediates the relationship between grit and life satisfaction. Study 1, with a sample of 243 employees enrolled in a business training course, found that an individual's grit was positively related to life satisfaction and that self-esteem fully mediated this relationship. In Study 2, with 218 full-time employees, self-efficacy, self-control, and self-consciousness were included as mediators, but they did not exceed the power of self-esteem in explaining the relationship between grit and life satisfaction. Implications, limitations and future research directions are discussed.
|
10.5334/pb.400
|
pubmed_262_14188
|
The Herald of Free Enterprise Disaster on the 6th of March 1987 just outside Zeebrugge harbour was without any doubt a disaster of major proportions. The ferry disaster highlighted different approaches in major incident procedures in both countries involved but nevertheless the identification team which was composed of both British and Belgian specialists did perform good work. The identification of the victims had to be done in three phases each of them with its own specific work and problems. As the process of identification of bodies is an exacting science, and forensic odontology is known to be among the most reliable scientific methods in mass disasters, it is easily understood that forensic odontology took an active part in all three phases of the identification process.
|
pubmed_262_14188
|
pubmed_872_16917
|
Free radicals are now well known to damage cellular components. To investigate whether age and thyroid level affect peroxidation speed, we examined the levels of malondialdehyde and antioxidant enzyme activities in different age groups of hypothyroid rats. Hypothyroidism was induced in 30- and 60-day-old Wistar Albino rats by the i.p. administration of propylthiouracil (10 mg kg(-1) body weight) for 15 days. While malondialdehyde levels of 30- or 60-day-old hypothyroid rats were increased in liver, they were decreased in the tissues of the heart and thyroid. While glucose-6-phosphate dehydrogenase activity levels did not change in heart, brain and liver tissues of 30-day-old rats, they increased in brain and heart tissues of 60-day-old experimental groups, but decreased in the liver. Catalase activities decreased in the liver and heart of rats with hypothyroidism, but increased in erythrocytes. In control groups while malondialdehyde levels increased in brain, heart and thymus with regard to age, they decreased in plasma. Glucose-6-phosphate dehydrogenase and catalase activities were not affected by age in tissues of the thymus, thyroid and brain, but they were decreased in the heart tissue. The changes in the levels of lipid peroxidation and antioxidant enzyme activities which were determined in different tissues of hypothyroid rats indicate a cause for functional disorder of these tissues. Moreover, there may be changes depending on age at lipid peroxidation and antioxidant enzyme activity levels.
|
10.1002/cbf.1031
|
pubmed_765_17312
|
BACKGROUND
Because of symptom overlap, there is uncertainty about the validity of depression rating scales in neurologic populations. The objectives of this study were to evaluate the validity of the Patient Health Questionnaire-9 (PHQ-9) for detecting Diagnostic and Statistical Manual-defined major depressive episodes in people with neurologic conditions.
METHODS
Participants were recruited from outpatient clinics for multiple sclerosis, epilepsy, migraine, Parkinson disease, and stroke for this cross-sectional study. Participants were administered a questionnaire (this included the PHQ-9), chart review, and a follow-up telephone interview. The Structured Clinical Interview for Depression was used as the reference standard for psychiatric diagnoses. The performance of PHQ-9 was analyzed using sensitivity, specificity, diagnostic odds ratios (DORs), and receiver operator curve analysis.
RESULTS
All neurologic subpopulations had a specificity greater than 78% and sensitivity greater than 79% at a cut-point of 10. Using a random-effects model, the I-squared value was 13.7%, and Tau2 was 0.05, showing homogeneity across the neurologic subpopulations. The pooled DOR was 25.3 (95% confidence interval [CI] 14.9-42.8). Meta-analytic analysis found that for sensitivity, the pooled estimate was 90% (95% CI 81-97), and for specificity, it was 85% (95% CI 79-90).
CONCLUSIONS
Despite theoretical concerns about its validity, the PHQ-9 performed well at its standard cut-point of 10. Consistent with the literature, being able to use a validated, brief tool that is available publicly should improve case finding of depression in neurologic populations. When considering clinical practicality along with the findings of this analyzed, this study confirmed that the PHQ-9 is valid in a general outpatient neurologic population.
|
10.1212/CPJ.0000000000000748
|
pubmed_788_895
|
BACKGROUND
The ongoing phase IIb POWER 1 (TMC114-C213) trial is designed to assess efficacy and safety of the protease inhibitor (PI) TMC114 (darunavir) in treatment-experienced HIV-1-infected patients.
DESIGN
This randomized, partially blinded, 24-week dose-finding study compared efficacy and safety of four doses of TMC114 plus low-dose ritonavir (TMC114/r) with investigator-selected control PI(s) (CPI[s]).
METHODS
Patients with one or more primary PI mutation and HIV RNA > 1000 copies/ml received optimized background therapy, plus TMC114/r 400/100 mg once daily, 800/100 mg once daily, 400/100 mg twice daily or 600/100 mg twice daily, or CPI(s). The primary endpoint (intent-to-treat) compared proportions of patients achieving viral load reduction >or= 1.0 log10 copies/ml from baseline.
RESULTS
In total, 318 patients were treated. Baseline mean viral load was 4.48 log10 copies/ml; median CD4 cell count was 179 cells/microl. In the CPI arm 62% of patients discontinued (virological failure: 54%); 10% of TMC114/r patients discontinued. More TMC114/r (69-77%) than CPI patients (25%) reached the primary endpoint (P < 0.001); 43-53% of TMC114/r patients and 18% of the CPI arm achieved viral load < 50 copies/ml (P < 0.001). TMC114/r demonstrated greater mean CD4 cell count increases versus CPI(s) (68-124 versus 20 cells/microl; P < 0.05). TMC114/r 600/100 mg twice daily demonstrated the highest virological and immunological responses. Adverse event incidence was similar between treatments; headache and diarrhoea were more common with CPI(s).
CONCLUSIONS
TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s). TMC114/r 600/100 mg twice daily has received regulatory approval in treatment-experienced patients.
|
10.1097/QAD.0b013e328013d9d7
|
pubmed_581_13767
|
Photoanodes comprising Au nanoparticles (GNPs) and thin TiO2 layers with a stacked structure were fabricated by repeating the application of TiO2 paste and GNP solutions on conductive glass to vary the distribution of GNPs in the TiO2 layer. The plasmon-enhanced characteristics of dye-sensitized solar cells (DSSCs) with such photoanodes were investigated. Both the absorption of the TiO2 layer and the performance of the DSSC are found to be most increased by plasmonic enhancement when GNPs are concentrated near the position in the TiO2 layer, which is the penetration depth of the incident light of wavelength corresponding to the maximum absorption of the N719 dye (~ 520 nm). When a GNP layer with a relatively high density of 1.3 μg/cm2 density was formed at its position, and two GNP layers with a relatively low density of 0.65 μg/cm2 were formed near the front side of the incident light, the short-circuit current density (Jsc) and energy conversion efficiency (η) of the DSSC were found to be 10.8 mA/cm2 and 5.0%, increases of 15 and 11%, respectively, compared with those of the DSSC without GNPs. Our work suggests that optimization of the distribution of GNPs in the TiO2 layer is very important for improving the performance of DSSCs fabricated by utilizing GNPs.
|
10.1186/s11671-017-2285-4
|
pubmed_222_2165
|
The endogenous cannabinoid receptor agonist anandamide is present in central and peripheral tissues. As the kidney contains both the amidase that degrades anandamide and transcripts for anandamide receptors, we characterized the molecular components of the anandamide signaling system and the vascular effects of exogenous anandamide in the kidney. We show that anandamide is present in kidney homogenates, cultured renal endothelial cells (EC), and mesangial cells; these cells also contain anandamide amidase. Reverse-transcriptase PCR shows that EC contain transcripts for cannabinoid type 1 (CB1) receptors, while mesangial cells have mRNA for both CB1 and CB2 receptors. EC exhibit specific, high-affinity binding of anandamide (Kd = 27.4 nM). Anandamide (1 microM) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 microM), but not by indomethacin (10 microM). Anandamide (10 nM) stimulates CB1-receptor-mediated NO release from perfused renal arterial segments; a similar effect was seen in EC. Finally, anandamide (1 microM) produces a NO-mediated inhibition of KCl-stimulated [3H]norepinephrine release from sympathetic nerves on isolated renal arterial segments. Hence, an anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects.
|
10.1172/JCI119677
|
pubmed_664_3931
|
Less than 5% of vulvar, vaginal and ovarian malignant diseases are sarcomas. Adequate knowledge of these particular malignant diseases is essential for accurate diagnosis and for choice of surgical treatment, adjuvant therapy and efficient medical treatment in relapse. A crucial aspect in the management of women with these diseases is a multidisciplinary approach. Globally, presenting signs and symptoms of these sarcomas are non-specific of histological type but linked to initial location. In view of this, management should be undertaken by clinicians experienced in these particular malignancies. Long-term side-effects, particularly in children with sarcoma, adversely affect quality of life. New treatment strategies require special attention.
|
10.1016/j.bpobgyn.2011.07.001
|
pubmed_48_25093
|
BACKGROUND
Validity of European Scleroderma Study Group (EScSG) activity indexes currently used to assess disease activity in systemic sclerosis (SSc) has been criticised.
METHODS
Three investigators assigned an activity score on a 0-10 scale for 97 clinical charts. The median score served as gold standard. Two other investigators labelled the disease as inactive/moderately active or active/very active. Univariate-multivariate linear regression analyses were used to define variables predicting the 'gold standard', their weight and derive an activity index. The cut-off point of the index best separating active/very active from inactive/moderately active disease was identified by a receiver-operating curve analysis. The index was validated on a second set of 60 charts assessed by three different investigators on a 0-10 scale and defined as inactive/moderately active or active/very active by other two investigators. One hundred and twenty-three were investigated for changes over time in the index and their relationships with those in the summed Medsger severity score (MSS).
RESULTS
A weighted 10-point activity index was identified and validated: Δ-skin=1.5 (Δ=patient assessed worsening during the previous month), modified Rodnan skin score (mRss) >18=1.5, digital ulcers=1.5, tendon friction rubs=2.25, C-reactive protein >1 mg/dL=2.25 and diffusing capacity of the lung for CO (DLCO) % predicted <70%=1.0. A cut-off ≥2.5 was found to identify patients with active disease. Changes in the index paralleled those of MSS (p=0.0001).
CONCLUSIONS
A preliminarily revised SSc activity index has been developed and validated, providing a valuable tool for clinical practice and observational studies.
|
10.1136/annrheumdis-2016-209768
|
pubmed_374_15190
|
We analyze the process of infection rate growth and decline for the recent global pandemic, applying a new method to the available global data. We describe and utilize an original approach based on statistical physics to predict the societal transmission timescale and the universal recovery trajectory resulting from the countermeasures implemented in entire societies. We compare the whole-society infection growth rates for many countries and local regions, to illustrate the common physical and mathematical basis for the viral spread and infection rate reduction, and validate the theory and resulting correlations. We show that methods traditionally considered for the numerical analysis and the control of individual virus transmission (e.g. ℜ0 scaling) represent one special case of the theory, and also compare our results to the available IHME computer model outcomes. We proceed to illustrate several interesting features of the different approaches to the mitigation of the pandemic, related to social isolation and "lockdown" tactics. Finally, we use presently available data from many countries to make actual predictions of the time needed for securing minimum infection rates in the future, highlighting the differences that emerge between isolated "islands" and mobile cities, and identifying the desired overall recovery trajectory.
|
10.1016/j.ssci.2020.104854
|
pubmed_21_4363
|
INTRODUCTION
We investigated the changing trend of various toxigenic Clostridium difficile isolates at a 3 500-bed hospital in Taiwan. Genetic relatedness and antimicrobial susceptibility of toxigenic C. difficile isolates were also examined.
METHODS
A total of 110 non-repeat toxigenic C. difficile isolates from different patients were collected between 2002 and 2007. Characterization of the 110 toxigenic isolates was performed using agar dilution method, multilocus variable-number tandem-repeat analysis (MLVA) genotyping, tcdC genotyping, and toxinotyping.
RESULTS
Among the 110 toxigenic isolates studied, 70 isolates harbored tcdA and tcdB (A⁺B⁺) and 40 isolates harbored tcdB only (A⁻B⁺). The annual number of A⁺B⁺ isolates considerably increased over the 6-year study (P = 0.055). A total of 109 different MLVA genotypes were identified, in which A⁺B⁺ isolates and A⁻B⁺ isolates were differentiated into two genetic clusters with similarity of 17.6%. Twenty-four (60%) of the 40 A⁻B⁺ isolates formed a major cluster, MLVA-group 1, with a similarity of 85%. Seven (6.4%) resistant isolates were identified, including two metronidazole-resistant and five vancomycin-resistant isolates.
CONCLUSIONS
This study indicated a persistence of a MLVA group 1 A⁻B⁺ isolates and an increase of A⁺B⁺ isolates with diverse MLVA types. Moreover, C. difficile isolates with antimicrobial resistance to metronidazole or vancomycin were found to have emerged. Continuous surveillance is warranted to understand the recent situation and control the further spread of the toxigenic C. difficile isolates, especially among hospitalized patients.
|
10.1371/journal.pone.0075471
|
pubmed_133_21895
|
Proper regulation of the human CD34 gene requires a combinatorial action of multiple proximal and long-range, cis elements. This report shows that, like the murine CD34 5' untranslated region (UTR), the corresponding region of the human CD34 gene is necessary for optimal promoter activity. We localized the most critical element of this region to base pairs +48/+75. Through oligonucleotide competition and antibody supershift experiments in electrophoretic mobility shift assays, we found that this sequence contains a binding site (CCAAT box) for the transcription factor NFY (nuclear factor Y), a factor mediating cell type-specific and cell-cycle regulated expression of genes. Mutating this site led to a 5-fold decrease in CD34 promoter activity in transient transfection experiments. Interestingly, NFY binds adjacently to the earlier identified c-myb binding site. Here we show that both binding sites are important for CD34 promoter function: mutating either site alone decreased CD34 promoter-driven reporter gene activity 4-fold. We also show that the integrity of the c-myb binding site is necessary for stabilization of NFY binding to its site. Such cooperation between c-myb, which is expressed in early hematopoietic cells, and NFY, which is expressed in many cell types, might contribute to specific activation of CD34 in stem cells. The CCAAT box motif was also noted in the 5' UTR of the murine CD34 gene, however, NFY did not bind to this region. Thus, our results indicate that the functional similarities between the human and murine CD34 5' UTRs are achieved through different molecular mechanism(s).
|
pubmed_133_21895
|
pubmed_773_12847
|
Synovectomies of the knee joint that were performed during the years 1960-65 at the Rheumatism Foundation Hospital because of rheumatoid arthritis have been re-examined after the lapse of 9.5 years in 156 patients and 202 knee joints and 110 non-operated knee joints of the same patients. Track of motion was helped both in synovectomized and in control knees. Deficiency of extension decreased only in the synovectomized knees; track of motion of the knee was improved by the operation. Swelling and pain appeared less often in operated than in control knees. The patient's own assessment of the operating results was good in 71% and poor in 12% of the cases. Radiological deterioration continued during the follow-up period both in the operated and in the control knees, though it was more severe in the latter. There is a distinct negative correlation between severity of disease and the patients's ability to work. Within the limits of this survey it is not possible to prove that synovectomy halts the radiological destruction of the knee joint; it is mainly a question of a measure that retards the rate of deterioration. One of the chief advantages of synovectomy of the knee is that it helps the patient to live a normal life and makes it possible for him to participate in working life.
|
10.3109/03009747609165457
|
pubmed_540_16547
|
Background: Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy globally with high recurrence and mortality rates. Cuproptosis is a new type of programmed cell death involved in tumor cell proliferation and growth, angiogenesis, and metastasis. Methods: The difference in cuproptosis-related genes (CRGs) between UCEC tissues and normal tissues deposited in The Cancer Genome Atlas database was calculated using the "limma" R package. LASSO Cox regression analysis was conducted to construct a prognostic cuproptosis-related signature. Kaplan-Meier analysis was conducted to compare the survival of UCEC patients. A ceRNA network was constructed to identify the lncRNA-miRNA-mRNA regulatory axis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to verify CRG expression in UCEC. Results: The expression of FDX1, LIAS, DLAT, and CDKN2A were upregulated, whereas the expression of LIPT1, DLD, PDHB, MTF1, and GLS were downregulated in UCEC versus normal tissues. The genetic mutation landscape of CRGs in UCEC was also summarized. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these CRGs were enriched in the tricarboxylic acid (TCA) cycle, glycolysis, and HIF-1 signaling pathway. LASSO Cox regression analysis was performed and identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1). UCEC patients with high risk scores had a poor prognosis with an area under the curve of 0.782 and 0.764 on 3- and 5-year receiver operating characteristic curves. Further analysis demonstrated a significant correlation between CDKN2A and pTNM stage, tumor grade, immune cell infiltration, drug sensitivity, tumor mutational burden (TMB) score, and microsatellite instable (MSI) score. The data validation of qRT-PCR further demonstrated the upregulation of CDKN2A and the downregulation of LIPT1 and GLS in UCEC versus normal tissues. The ceRNA network also identified lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis for UCEC. Conclusion: The current study identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1) for UCEC. The ceRNA network also identified that lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis may be involved in the progression of UCEC. Further in vivo and in vitro studies should be conducted to verify these results.
|
10.3389/fgene.2022.912037
|
pubmed_214_2420
|
Spatial transcriptomics (ST) can catalyze discoveries linking tissue function with spatial organization of cell types. However, technical variations and subtle differences between cell subtypes make this a challenging goal. Recent algorithms that carefully incorporate the details of the ST data generation process show the promise to overcome these challenges.
|
10.1016/j.cels.2022.04.004
|
pubmed_3_20504
|
Interleukin (IL)-7 and its receptor (IL-7Ralpha) play important roles in regulating lymphopoiesis. Previous studies have reported that human immunodeficiency virus-1 (HIV-1) viraemia affects the expression of IL-7Ralpha, but its effects on CD4+ and CD8+ T cell memory subsets have not been studied. Using eight-colour flow cytometry, we compared the immunophenotypic patterns of CD4+ and CD8+ T cell subsets expressing IL-7Ralpha and activation markers, as well as circulating IL-7 levels, in three well-defined groups of HIV-1-infected subjects: successfully treated, viraemic and long-term non-progressor (LTNP). Compared with successfully treated and LTNP subjects, viraemic patients had reduced expression of IL-7Ralpha on both CD4+ and CD8+ T cells, particularly on central and effector memory T cell compartments, and substantially elevated expression of activation markers on CD8+ T cell subsets. Circulating IL-7 levels were correlated negatively with the number of CD4+ and CD8+ T cell subsets expressing IL-7Ralpha; these associations were stronger with CD4+ T cell subsets and mainly with central and effector memory cells. The expression of activation markers on CD4+ and CD8+ cell T subsets was not related to circulating IL-7 levels. A strong negative correlation was observed between central memory CD4+ or CD8+ T cells expressing IL-7Ralpha and those expressing activation markers, independently of IL-7 levels. Collectively, these results provide further insight on the role of unsuppressed viral load in disrupting the IL-7/IL-7Ralpha system and contributing to HIV-1 disease progression.
|
10.1111/j.1365-2249.2008.03610.x
|
pubmed_618_23149
|
Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and an empty bone marrow. Standard treatments for AA include immunosuppressive therapy and bone marrow transplantation (BMT). BMT is the preferred option for young AA patients with a sibling donor, whereas in older patients or in those to be grafted from an unrelated donor BMT is exploited as second-line treatment. Current results of BMT for AA demonstrate cure rates up to 80 and 70% in BMT from HLA-matched siblings and unrelated donor, respectively, with age and stem cell source largely affecting the outcome. BMT is also a potential treatment option for paroxysmal nocturnal hemoglobinuria, a rare hematological disorder characterized by complement-mediated intravascular hemolytic anemia, thrombophilia and bone marrow failure.
|
10.1586/17474086.2014.967678
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.