index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_303_3860
|
The influence of noradrenergic mechanisms on the effects of D- and L-amphetamine on lordosis behavior and stereotype activity was studied in ovariectomized estrogen + progesterone treated rats. Phenoxybenzamine, phentolamine and prazosin, which all block alpha-adrenergic receptors potentiated the inhibitory effect of D-amphetamine on lordosis behavior. Phenoxybenzamine and prazosin also potentiated the effect of L-amphetamine, while phentolamine did not increase the effect. No augmented effect of D- or L-amphetamine was obtained on stereotype activity after pretreatment with phenoxybenzamine or phentolamine. L-propranolol, which blocks beta-adrenergic receptors and pimozide, a dopamine receptor blocker did not influence the effect of D- or L-amphetamine on lordosis behavior. Clonidine an alpha-receptor stimulant drug inhibited lordosis response in estrogen treated rats. This is probably due to a presynaptic effect, decreasing the release of NA from nerve terminals. The possibility that D- and L-amphetamine activates a NA system which influences lordosis behavior either by a direct facilitation or by decreasing the activity of an inhibitory serotonergic system is discussed.
|
pubmed_303_3860
|
pubmed_1080_18271
|
In a regional study of the effect of the 1979 French seat-belt law, the nature and severity of car occupants' injuries were recorded for all car crashes during the same 3-month period in 1976, 1977, 1978 (before the law), and in 1979 (after the law). A trend analysis of data from all 4 years showed a slight decrease in the total injury rate, and significant decreases in the frequency of hospital admissions, and of head, face, arm, and leg injuries. Moderate pelvic and leg injuries, and serious head injuries were also less than expected in 1979. There was also a significant increase in the frequency of thoraco-lumbar spine injuries and of serious cervical spine injuries, but the absolute increase in these injuries was less than the absolute decrease in other injuries. These changes are compatible with the biomechanical effects of increased seat belt use, and thus suggest a beneficial effect of the law.
|
10.1016/0001-4575(89)90073-0
|
pubmed_754_12388
|
Apolipoprotein expression was examined in the postimplantation mouse embryo. Antibodies directed against murine Apolipoprotein AI and human low-density lipoprotein (LDL) particles specifically immunoprecipitated metabolically labelled radioactive apolipoproteins from the culture supernatant of 10.5 days post coitum (days p.c.) yolk sac visceral endoderm cultured in vitro. No evidence for apolipoprotein expression by other embryonic or extraembryonic tissues at this stage was obtained. Immunohistochemical staining at sectioned 10.5 days p.c. embryos with anti-Apolipoprotein AI antibodies revealed specific localization of immunoreactive material in the yolk sac visceral endoderm. We conclude that the yolk sac visceral endoderm is a source of lipoproteins during postimplantation embryonic development.
|
pubmed_754_12388
|
pubmed_212_10461
|
A sample of adolescents with cystic fibrosis was compared with a matched control group in a number of psychological dimensions. It was found that there were no significant differences between the groups in the aspects measured, and the reasons for this were explored.
|
pubmed_212_10461
|
pubmed_298_18579
|
Transglutaminase 2 (TG2) is the most widely distributed and most abundantly expressed member of the transglutaminase family of enzymes, a group of intracellular and extracellular proteins that catalyze the Ca²⁺-dependent posttranslational modification of proteins. It is a unique member of the transglutaminase family owing to its specialized biochemical, structural and functional elements, ubiquitous tissue distribution and subcellular localization, and substrate specificity. The broad substrate specificity of TG2 and its flexible interaction with numerous other gene products may account for its multiple biological functions. In addition to the classic Ca²⁺-dependent transamidation of proteins, which is a hallmark of transglutaminase enzymes, additional Ca²⁺-independent enzymatic and nonenzymatic activities of TG2 have been identified. Many such activities have been directly or indirectly implicated in diverse cellular physiological events, including cell growth and differentiation, cell adhesion and morphology, extracellular matrix stabilization, wound healing, cellular development, receptor-mediated endocytosis, apoptosis, and disease pathology. Given the wide range of activities of the transglutaminase gene family it has been suggested that, in the absence of active versions of TG2, its function could be compensated for by other members of the transglutaminase family. It is in the light of this assertion that we review, herein, TG2 activities and the possibilities and premises for compensation for its absence.
|
10.1155/2014/714561
|
pubmed_601_3922
|
The effects of an intravenous hyperimmune cytomegalovirus globulin after bone marrow transplantation are reported. From day -1 22 patients received 2 ml/kg body weight every two weeks during the first four months after BMT. Infusions were tolerated without any side effects. In three patients a CMV-infection could be documented which was symptomatic in two of them. A further patient experienced a CMV infection during the pretransplant phase before hyperimmune globulin had been administered. The most severe case presented as a nonlethal interstitial pneumonia.
|
pubmed_601_3922
|
pubmed_161_10427
|
In anaesthetized rats, neurones were found in the ventrolateral medulla that responded to antidromic stimulation of their axons in the thoracic spinal cord. These neurones were identified as being antidromic, according to various established electrophysiological criteria. A total of 44 antidromically identified neurones were found, 23 had conduction velocities below 2.0 m/s. Many (70%) had ongoing activity with a slow firing rate (0.2-5.0 Hz). Catecholamine-containing cells were visualized in this ventrolateral region using a modified Mg+-catalyzed glyoxylic acid technique and revealed multipolar, small diameter cells (17-20 microns) which were diffusely scattered (as demonstrated in previous histofluorescence studies). The Pontamine sky blue-marked recording sites of 7 units (0.3-1.1 m/s) showed close apposition to a CA-fluorescent cell whilst a further 4 (2.0-2.7 m/s) could not be correlated with the presence of a fluorescent cell. The results are discussed in the light of recent data in the rat, suggesting that the spinal cord catecholamine innervation arises from brainstem cell groups other than A1.
|
10.1016/0006-8993(83)91090-9
|
pubmed_904_12617
|
To investigate risk factors for extrahepatic cholangiocarcinoma (ECC) in China. A total of 200 ECC cases and 200 matched control were included in the study. The presence of cigarette smoking, alcohol drinking, choledocholithiasis, primary sclerosing cholangitis, liver fluke infection (Clonorchis sinensis), diabetes mellitus, was investigated through clinical records. Blood from all cases was tested for hepatitis B surface antigen. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Compared with controls, ECC patients had a higher prevalence of cigarette smoking (61.0 vs. 47.0%, P=0.007), alcohol drinking (17.5 vs. 3.5%, P<0.000), and choledocholithiasis (6.0 vs. 1.0%, P=0.011). By multivariate analysis, the significant risk factors for the development of ECC were current smoking (OR=1.90, 95% CI=1.08-3.34), heavy alcohol drinking (OR=2.08, 95% CI=1.39-3.13), and choledocholithiasis (OR=6.68, 95% CI=1.48-30.27). The prevalence of hepatitis B virus infection, diabetes mellitus were not significantly different between cases and controls. These findings suggest that smoking, alcohol drinking, and choledocholithiasis are positive risk factors for the development of ECC in China.
|
10.1097/CEJ.0000000000000468
|
pubmed_357_25265
|
It is unclear whether the current average use of personal music players (PMPs) including mobile phones has affected hearing in the general population. The association between the use of PMPs and hearing loss was assessed in a large population cross-sectional and follow-up study with the following distribution: cross-sectional (2018): n = 26,606, 56% women, mean age 54 years and 20-year follow-up (baseline 1998): n = 12,115, 57% women, mean age at baseline 43 years. Hearing threshold was determined as pure-tone average over the frequencies 3, 4, and 6 kHz. We used linear regression to assess relationships between hearing threshold and PMP use (yes), duration (1-2/2-6/>6 h per week), or sound volume (low/medium/high), with nonuse as reference. The PMP use increased from 8% in 1998 to 30% in 2018. Compared with nonusers, neither use nor duration was related to hearing threshold. As to sound volume, listening at low levels was associated with better thresholds (-2.5 dB [-4.1 to -0.8]), while listening at high levels was associated with worse thresholds (1.4 dB [0.1 to 2.8]). We adjusted for age, sex, baseline hearing threshold, education, noise exposure, ear infections, head injury, and daily smoking. The association with sound volume was nearly twice as strong when adjusting for hearing threshold at baseline. Accordingly, the possibility of reverse causality was reduced although not eliminated by the follow-up design. This large population study showed no association between normal PMP use and 20-year progression in hearing; however users listening to high levels increased their hearing threshold.
|
10.1177/23312165211015881
|
pubmed_140_8634
|
OBJECTIVE
To examine the associations between breastfeeding intensity and underexplored features of maternal-child interaction quality over and above the influence of breastfeeding initiation.
METHODS
The current study leveraged an on-going, multisite randomized controlled trial of a tiered parenting program for 462 Medicaid-eligible mothers and their infants in the United States. We examined whether breastfeeding intensity and exclusivity was associated with observed maternal sensitivity, intrusiveness, and detachment, as well as self-reported maternal verbal responsiveness, 6 months infant age. Analyses controlled for breastfeeding initiation, demographics, and early parenting experiences.
RESULTS
Higher intensity breastfeeding at 6 months was significantly related to higher maternal sensitivity (β = 0.12, p = 0.004) and lower maternal intrusiveness (β = -0.10, p = 0.045). There was no significant association between breastfeeding intensity at 6 months and detachment (β = -0.02, no significant [ns]) or self-reported verbal responsiveness (β = 0.11, ns). Results were the same when intensity was measured as a dichotomous indicator for exclusive breastfeeding. Effect sizes were small-to-moderate, ranging from Cohen's d = 0.26 to 0.31. Associations did not vary by site, race/ethnicity, infant difficultness, or household poverty.
CONCLUSION
The finding that breastfeeding intensity was significantly and independently associated with maternal sensitivity and intrusiveness is novel in the literature on low-income families from the United States. These findings have implications for breastfeeding promotion strategies and indicate that future research should explore synergistic or spillover effects of interventions aimed at maternal-child interaction quality into the infant feeding domain, particularly in the primary care setting.
|
10.1097/DBP.0000000000000743
|
pubmed_486_18346
|
In this study, Fe2+ addition was employed to overcome the negative effects of humic acid (HA) on contaminant removal by zerovalent iron (ZVI), and its feasibility to improve electron efficiency of ZVI was also tested. HA at high concentrations suppressed the removal of 4-nitrophenol (4-NP) by ZVI, while the addition of 0.25-1.0 mM Fe2+ could greatly mitigate this inhibitory effect and enhance 4-NP reduction. Specifically, with a mixed-order model, global fitting results showed that the addition of Fe2+ increased the rate constant from 0.124 × 10-2-0.219 × 10-2 mM/min to 0.227 × 10-2-0.417 × 10-2 mM/min and shortened lag period from 19.7-47.9 min to 8.0-15.2 min for 4-NP removal. The mechanistic investigation revealed this trend could be explained by the following aspects: i) Fe2+ can facilitate the generation of Fe(II)-containing oxides, which can act as an electron mediator or direct electron donor for 4-NP reduction; ii) the presence of Fe2+ could lead to aggregation of HA particles and accordingly reduced its coverage on ZVI surface. But the results of respike experiments indicate that Fe2+ addition did not show remarkable effect on the electron efficiency of 4-NP by ZVI, which should be associated with that Fe2+ was not able to favor the enrichment of 4-NP on ZVI surface.
|
10.1016/j.jhazmat.2019.121218
|
pubmed_1129_18593
|
Biomass fast pyrolysis oils contain molecules having a large variety of chemical functions and a wide range of molecular weights (from several tens to several thousand grams per mole). The good knowledge of their complex composition is essential for optimizing the conversion of bio-oils to biofuels, thereby requiring powerful separation techniques. In this work, we investigate the interest of centrifugal partition chromatography (CPC) as a first dimension for the analysis of a bio-oil. A CPC method is proposed to separate oxygen containing compounds according to their partition coefficients in the solvent system. This approach is a powerful and easy-to-use technique that enables fractionation of a bio-oil at a semi-preparative scale, without any sample loss related to adsorption on the stationary phase. Collected fractions are then injected in liquid chromatography as a second dimension of separation. Contour plot representations of the CPC × LC separation are established to discuss the potential of this approach. These representations can be used as a veritable fingerprint in the comparison of different samples or samples at different steps of a conversion process but also as a powerful tool to identify new compounds and describe the entire composition of the bio-oil.
|
10.1016/j.aca.2018.04.040
|
pubmed_794_4938
|
Recent advances in depth measurement and its utilization have made point cloud processing more critical. Additionally, the human head is essential for communication, and its three-dimensional data are expected to be utilized in this regard. However, a single RGB-Depth (RGBD) camera is prone to occlusion and depth measurement failure for dark hair colors such as black hair. Recently, point cloud completion, where an entire point cloud is estimated and generated from a partial point cloud, has been studied, but only the shape is learned, rather than the completion of colored point clouds. Thus, this paper proposes a machine learning-based completion method for colored point clouds with XYZ location information and the International Commission on Illumination (CIE) LAB (L*a*b*) color information. The proposed method uses the color difference between point clouds based on the Chamfer Distance (CD) or Earth Mover's Distance (EMD) of point cloud shape evaluation as a color loss. In addition, an adversarial loss to L*a*b*-Depth images rendered from the output point cloud can improve the visual quality. The experiments examined networks trained using a colored point cloud dataset created by combining two 3D datasets: hairstyles and faces. Experimental results show that using the adversarial loss with the colored point cloud renderer in the proposed method improves the image domain's evaluation.
|
10.3390/jimaging8050125
|
pubmed_214_5227
|
OBJECTIVE
In this rapidly digitizing world, it is becoming ever more important to understand people's online behaviors in both scientific and consumer research settings. The current work tests the feasibility of inferring personality traits from mouse movement patterns as a cost-effective means of measuring individual characteristics.
METHOD
Mouse movement features (i.e., pauses, fixations, speed, and clicks) were collected while participants (N = 791) completed an online image choice task. We compare the results of standard univariate and three forms of multivariate partial least squares (PLS) analyses predicting Big Five traits from mouse movements. We also examine whether mouse movements can predict a proposed measure of task attentiveness (atypical responding), and how these might be related to personality traits.
RESULTS
Each of the PLS analyses showed significant associations between a linear combination of personality traits (high Conscientiousness, Agreeableness, Openness, and low Neuroticism) and several mouse movements associated with slower, more deliberate responding (less unnecessary clicks and more fixations). Additionally, several click-related mouse features were associated with atypical responding on the task.
CONCLUSIONS
As the image choice task itself is not intended to assess personality in any way, our results validate the feasibility of using mouse movements to infer internal traits across experimental contexts.
|
10.1111/jopy.12736
|
pubmed_1037_23375
|
BACKGROUND
For decades, the food industry has sought to deflect criticisms of its products and block public health legislation through a range of offensive and defensive strategies. More recently, food corporations have moved on to present themselves as "part of the solution" to the health problems their products cause. This strategic approach is characterised by appeasement, co-option and partnership, and involves incremental concessions and attempts to partner with health actors. This paper details how corporate practices have evolved and changed over the past two decades and gives some definition to what this new political economy signifies for the wider behaviours of corporations producing and selling harmful commodities.
METHODS
This paper draws on public health and political science literature to classify the food industry's "part of the solution" strategy into three broad components: regulatory responses and capture; relationship building; and market strategies. We detail the key characteristics and consequences of each component.
RESULTS
The three components of the food industry's "part of the solution" strategy all involve elements of appeasement and co-option. They also improve the political environment and resources of the food industry. Regulatory responses offer incremental concessions that seek to maintain corporate influence over governance processes and minimise the threat of regulations; relationship building fosters access to health and government stakeholders, and opportunities to acquire and maintain channels of direct influence; and market strategies to make products and portfolios healthier bolster the market share and revenue of food corporations while improving their public image.
CONCLUSION
Rather being a signal of lost position and power, the food industry's repositioning as "part of the solution" has created a highly profitable political economy of 'healthy' food production, alongside continued production of unhealthy commodities, a strategy in which it is also less burdensome and conflictual for corporations to exercise political power and influence.
|
10.34172/ijhpm.2021.111
|
pubmed_219_20288
|
Neutral sphingomyelinase (nSMase) activation in response to environmental stress or inflammatory cytokine stimuli generates the second messenger ceramide, which mediates the stress-induced apoptosis. However, the signaling pathways and activation mechanism underlying this process have yet to be elucidated. Here we show that the phosphorylation of nSMase1 (sphingomyelin phosphodiesterase 2, SMPD2) by c-Jun N-terminal kinase (JNK) signaling stimulates ceramide generation and apoptosis and provide evidence for a signaling mechanism that integrates stress- and cytokine-activated apoptosis in vertebrate cells. An nSMase1 was identified as a JNK substrate, and the phosphorylation site responsible for its effects on stress and cytokine induction was Ser-270. In zebrafish cells, the substitution of Ser-270 for alanine blocked the phosphorylation and activation of nSMase1, whereas the substitution of Ser-270 for negatively charged glutamic acid mimicked the effect of phosphorylation. The JNK inhibitor SP600125 blocked the phosphorylation and activation of nSMase1, which in turn blocked ceramide signaling and apoptosis. A variety of stress conditions, including heat shock, UV exposure, hydrogen peroxide treatment, and anti-Fas antibody stimulation, led to the phosphorylation of nSMase1, activated nSMase1, and induced ceramide generation and apoptosis in zebrafish embryonic ZE and human Jurkat T cells. In addition, the depletion of MAPK8/9 or SMPD2 by RNAi knockdown decreased ceramide generation and stress- and cytokine-induced apoptosis in Jurkat cells. Therefore the phosphorylation of nSMase1 is a pivotal step in JNK signaling, which leads to ceramide generation and apoptosis under stress conditions and in response to cytokine stimulation. nSMase1 has a common central role in ceramide signaling during the stress and cytokine responses and apoptosis.
|
10.1038/cdd.2014.128
|
pubmed_669_4504
|
The sensitization of scintillation was investigated in crosslinked polymeric composite materials loaded with luminescent gold clusters aggregates acting as sensitizers, and with organic dye rhodamine 6G as the emitting species. The evolution in time of the excited states population in the systems is described by a set of coupled rate equations, in which steady state solution allowed obtainment of an expression of the sensitization efficacy as a function of the characteristic parameters of the employed luminescent systems. The results obtained indicate that the realization of sensitizer/emitter scintillating complexes is the strategy that must be pursued to maximize the sensitization effect in composite materials.
|
10.3390/nano11123387
|
pubmed_369_23516
|
PURPOSE
To determine concordance of promoter hypermethylation of ERβ (estrogen receptor β) and RARβ2 (retinoic acid receptor β2) in tumor and circulating DNA of Indian breast cancer patients and their association with clinicopathologic parameters and disease prognosis.
METHODS
ERβ and RARβ2 methylation was analyzed by methylation-specific PCR in the tumors and circulating DNA of 100 patients with invasive ductal breast carcinoma. Promoter hypermethylation was associated with the expression of the encoded protein in tumors by immunohistochemistry, and their prognostic utility was explored in a follow-up study.
RESULTS
Significant correlation was observed between promoter hypermethylation of ERβ (r = + 0.77; p ≤ 0.001) and RARβ2 (r = + 0.85; p ≤ 0.001) in tumors and paired sera. No association was found between ERβ and RARβ2 promoter hypermethylation and loss of protein expression. Kaplan-Meier survival curve showed loss of ERβ expression, and RARβ2 promoter hypermethylation was associated with poor overall survival (OS) (p = 0.03, p = 0.001). Breast cancer patients showing concurrent hypermethylation of ERβ and RARβ2 had a significantly shorter median OS (p = 0.02), underscoring that hypermethylation of these two genes may serve as an adverse prognosticator for breast carcinoma.
CONCLUSIONS
Methylation status of ERβ and RARβ2 in serum could potentially be used to predict invasive ductal breast carcinoma. Furthermore, concurrent ERβ and RARβ2 methylation as well as loss of ERβ expression may serve as a good prognostic marker.
|
10.1245/s10434-012-2323-5
|
pubmed_547_9235
|
A trisaccharide, the O-antigenic repeating unit of C. jejuni serotype O:23 and O:36, was synthesized as a 2'-azidoethyl glycoside by block addition of perbenzylated thiogalactoside donors to alpha-altroHepp-(1-->3)-GlcNPhth disaccharide acceptor in presence of IDCP promoter. The alpha-linked altroheptopyranoside moiety in the glycosyl acceptor was effectively prepared by Swern oxidation of alpha-mannohepp-(1-->3)-GlcNPhth disaccharide followed by mild reduction with NaCNBH3.
|
10.1007/BF02980097
|
pubmed_65_6002
|
OBJECTIVE
The purpose of this study was to compare the gastric acid inhibitory ability of increasing doses of intravenous (i.i.) pantoprazole with that of i.v. famotidine and placebo. Pentagastrin was infused continuously in healthy subjects as a model for patients with Zollinger-Ellison syndrome.
METHODS
Pentagastrin (1 microg/kg/h) was infused to stimulate maximum acid output in 39 subjects over a 25-h period. After 60 min of pentagastrin infusion, subjects received a single dose of i.v. pantoprazole (20, 40, 80, or 120 mg), i.v. famotidine (20 mg), or saline placebo. The variables measured were onset of response (time until acid output fell to < 10 mEq/h), duration of response (time acid output remained < 10 mEq/h), and cumulative acid output over 24 h.
RESULTS
All doses of i.v. pantoprazole produced a dose-dependent suppression of acid output to < 10 mEq/h. Single i.v. doses of pantoprazole, 80 and 120 mg, suppressed acid output by > 90% in all subjects for < or = 21 h and had an onset of action of < 1 h.
CONCLUSIONS
Intravenous pantoprazole has a rapid onset and a clear dose-related effect, with a significantly longer duration of action than that of i.v. famotidine.
|
10.1111/j.1572-0241.1999.01430.x
|
pubmed_769_23867
|
BACKGROUND
Poor sleep quality has a negative effect on pain among older adults. During the coronavirus disease 2019 (COVID-19) state of emergency, lifestyle changes can cause psychologic stressors and lead to poor sleep quality.
AIM
This study examined whether sleep quality status was associated with low back or knee pain changes during the COVID-19 state of emergency among community-dwelling Japanese old-old adults.
DESIGN
Cross-sectional investigation.
METHODS
In July 2020, during the COVID-19 epidemic, we conducted a postal survey for old-old adults aged ≥77 years and collected data on 597 participants. For those who had low back or knee pain at the time of the survey (in July), characteristics such as low back pain, knee pain, changes in pain status, and sleep quality status during the COVID-19 state of emergency (in March) were assessed.
RESULTS
Data from 597 participants showed the prevalence of low back pain (50.6%) and knee pain (40.7%) in July. Of those with low back or knee pain, 374 had pain changes during the state of emergency, with 12.3% worsening. Of these, 23.9% had poor sleep quality in March compared to non-change (p = .008). In a multivariate logistic regression model adjusted for potential confounders, poor sleep quality was significantly associated with pain worsening (odds ratio 2.80, 95% confidence interval 1.26-6.22).
CONCLUSIONS
During the COVID-19 state of emergency, poor sleep quality was associated with worsening low back or knee pain. This may indicate the need to pay attention to poor sleep quality to prevent the exacerbation of pain among old-old adults.
|
10.1016/j.pmn.2022.01.001
|
pubmed_760_20056
|
Invadopodia formation and extracellular matrix degradation are key events during cancer cell invasion, yet little is known about mechanisms mediating these processes. Here, we report that Rab40b plays a key role in mediating invadopodia function during breast cancer cell invasion. We also identify Tks5 (also known as SH3PXD2A), a known Src kinase substrate, as a new Rab40b effector protein and show that Tks5 functions as a tether that mediates Rab40b-dependent targeting of transport vesicles containing MMP2 and MMP9 to the extending invadopodia. Importantly, we also demonstrate that Rab40b and Tks5 levels are regulated by known tumor suppressor microRNA miR-204. This is the first study that identifies a new Rab40b-Tks5- and miR-204-dependent invadopodia transport pathway that regulates MMP2 and MMP9 secretion, and extracellular matrix remodeling during cancer progression.
|
10.1242/jcs.193904
|
pubmed_76_96
|
A full-length clone of pig kidney fructose 1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) was isolated by screening a cDNA library for complementation of an Escherichia coli fbp deletion mutation. The open reading frame of 1011 bases corresponds to 337 amino acids, two more than have been previously reported [Marcus, F., Edelstein, I., Reardon, I. & Heinrikson, R. L. (1982) Proc. Natl. Acad. Sci. USA 79, 7161-7165]. The extra two amino acids (Ala-Lys) are located at the C-terminal end of the protein as an extension. Comparison of the deduced amino acid sequence with the reported (see above) and revised amino acid sequence [Harrsch, P. B., Kim, Y., Fox, J. L. & Marcus, F. (1985) Biochem. Biophys. Res. Commun. 133, 520-526] indicates three differences in addition to the C-terminal extension. Gln-20, Thr-96, and Asn-199 in the amino acid sequence are found to be Glu, Ser, and Asp, respectively. Since the x-ray structure of the pig kidney enzyme has been reported, the cDNA clone will allow the construction of site-specific mutants to help test possible structure-function relationships in this important metabolic enzyme.
|
10.1073/pnas.89.7.3080
|
pubmed_999_22573
|
BACKGROUND
P. aeruginosa is the primary source of hospital-acquired infections. Unfortunately, antibiotic resistance is growing to precariously high levels, making the infections by this pathogen life-threatening and hard to cure. One possible alternative to antibiotics is to use phages. However, the isolation of phages suitable for phage therapy- be lytic, be efficient, and have a broad host range -against some target bacteria has proven difficult. To identify the best places to look for these phages against P. aeruginosa we screened hospital sewages, soils, and rivers in two cities.
RESULTS
We isolated eighteen different phages, determined their host range, infection property, and plaque morphology. We found that the sewage and sewage-contaminated environments are the most reliable sources for the isolation of Pseudomonas phages. In addition, phages isolated from hospital sewage showed the highest efficiency in lysing the bacteria used for host range determination. In contrast, phages from the river had larger plaque size and lysed bacteria with higher levels of antibiotic resistance.
CONCLUSIONS
Our findings provided additional support for the importance of sewage as the source of phage isolation.
|
10.1186/s12866-021-02197-z
|
pubmed_1135_12144
|
OBJECTIVES
To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care.
DESIGN
Systematic review of current evidence and economic modelling.
DATA SOURCES
Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts.
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered.
RESULTS
26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p ≤ 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were £7324 with standard care and £7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have ∼ 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of £20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not.
CONCLUSIONS
Self-monitoring appears to be a safe and cost-effective option.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42013004944.
|
10.1136/bmjopen-2015-007758
|
pubmed_597_16725
|
Mammals are unable to synthesize cobalamin or vitamin B12 and rely on the uptake of dietary cobalamin. The cubam receptor expressed on the intestinal endothelium is required for the uptake of cobalamin from the gut. Cubam is composed of two protein subunits, amnionless and cubilin, which are encoded by the AMN and CUBN genes respectively. Loss-of-function mutations in either the AMN or the CUBN gene lead to hereditary selective cobalamin malabsorption or Imerslund-Gräsbeck syndrome (IGS). We investigated Beagles with IGS and resequenced the whole genome of one affected Beagle at 15× coverage. The analysis of the AMN and CUBN candidate genes revealed a homozygous deletion of a single cytosine in exon 8 of the CUBN gene (c.786delC). This deletion leads to a frameshift and early premature stop codon (p.Asp262Glufs*47) and is, thus, predicted to represent a complete loss-of-function allele. We tested three IGS-affected and 89 control Beagles and found perfect association between the IGS phenotype and the CUBN:c.786delC variant. Given the known role of cubilin in cobalamin transport, which has been firmly established in humans and dogs, our data strongly suggest that the CUBN:c.786delC variant is causing IGS in the investigated Beagles.
|
10.1111/age.12094
|
pubmed_1050_20057
|
Latin American scientific production related to the COVID-19 epidemic means that only 6% represent publications by Latin American authors, led by countries such as Brazil and Mexico; however, this production is still scarce, so efforts must be doubled to make a substantial contribution to the search for alternatives to address the global health crisis that is now in place.
|
10.17235/reed.2020.7432/2020
|
pubmed_959_20686
|
AIM
To report a protocol for a qualitative study to better understand the key factors that influence decision making about pregnancy from women's perspectives and to use these data to develop a theoretical model for shared decision-making tools for the multiple stakeholders.
DESIGN
Mixed-method design using online surveys (with validated components) and purposively sampled follow-up semi structured interviews.
METHODS
Funded from September 2020 for 12 months. Online surveys of adult women (aged 18-50) identified via all Wales kidney database (n ≥ 500), additional recruitment through multidisciplinary healthcare professionals, relevant third sector organizations and social media. Follow-up in-depth qualitative interviews with n = 30 women. Linear regression models to identify associations between shared decision-making preferences and clinical and psychosocial variables. Qualitative interviews will use a visual timeline task to empower women in taking control over their narratives. Qualitative data will be fully transcribed and analysed thematically, based around a chronological and theoretical (theoretical domains framework) structure that maps out key challenges and opportunities for improved decision support in the care pathway. Visual timelines will be used during stakeholder consultation activities, to enable us to co-create a map of current support, gaps in provision, and opportunities for interventions. Quantitative data will be analysed descriptively to characterize our cohort. We will assemble a multidisciplinary shared decision-making intervention development group and provide ongoing stakeholder consultation activities with patient and public representatives.
DISCUSSION
Outcomes will support new learning into; the ways women's knowledge of kidney disease may affect family planning and pregnancy, their needs in terms of psychological and social support, and how they weigh up the pros and cons of starting a family.
IMPACT
Evidence will inform the design of new shared decision-making tools to better support women with the complex and often emotional decisions about having children while living with kidney disease.
|
10.1111/jan.14803
|
pubmed_704_3704
|
Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.
|
10.1039/d0an00813c
|
pubmed_994_11994
|
Frequent shift work causes disruption of the circadian rhythm and might on the long-term result in increased health risk. Current biomarkers evaluating the presence of circadian rhythm disturbance (CRD), including melatonin, cortisol and body temperature, require 24-hr ("around the clock") measurements, which is tedious. Therefore, these markers are not eligible to be used in large-scale (human) studies. The aim of the present study was to identify universal biomarkers for CRD independent of time of day using a transcriptomics approach. Female FVB mice were exposed to six shifts in a clockwise (CW) and counterclockwise (CCW) CRD protocol and sacrificed at baseline and after 1 shift, 6 shifts, 5 days recovery and 14 days recovery, respectively. At six time-points during the day, livers were collected for mRNA microarray analysis. Using a classification approach, we identified a set of biomarkers able to classify samples into either CRD or non-disrupted based on the hepatic gene expression. Furthermore, we identified differentially expressed genes 14 days after the last shift compared to baseline for both CRD protocols. Non-circadian genes differentially expressed upon both CW and CCW protocol were considered useful, universal markers for CRD. One candidate marker i.e. CD36 was evaluated in serum samples of the CRD animals versus controls. These biomarkers might be useful to measure CRD and can be used later on for monitoring the effectiveness of intervention strategies aiming to prevent or minimize chronic adverse health effects.
|
10.1371/journal.pone.0127075
|
pubmed_43_9059
|
BACKGROUND
Sedative-hypnotic (SH) medications are often used to treat chronic insomnia, with potentially serious long-term side effects. The objective of this study is to evaluate an interprofessional SH deprescribing program within a community team-based, primary care practice, with or without cognitive behavioural therapy for insomnia (CBT-I).
METHODS
Retrospective chart review for patients referred to the team pharmacist for SH deprescribing from February 2016 to June 2019.
RESULTS
A total of 121 patients were referred for SH deprescribing, with 111 (92%) patients who attempted deprescribing (average age 69, range 29-97 years) and 22 patients who also received CBT-I. Overall, 36 patients (32%) achieved complete abstinence, and another 36 patients (32%) reduced their dosage by ≥50%. For the 36 patients who achieved complete abstinence, 26 (72%) patients remained abstinent at 6 months (9 patients resumed using SH and 1 patient was lost to follow-up). The proportion of patients achieving complete abstinence or reduced dosage of ≥50% (successful tapering) was higher with CBT-I than without CBT-I but did not reach statistical significance (77% vs 62%, p = 0.22). There were also no statistically significant differences detected in the success between those who took a benzodiazepine and those who took a Z-drug (67% vs 61%, p = 0.55) or for those who took SH daily and those who took them intermittently (67% vs 44%, p = 0.09).
CONCLUSION
Almost two-thirds of patients participating in our pharmacist-led program were able to stop or taper their SH medications by ≥50%. The role of CBT-I in SH deprescribing remains to be further elucidated. Can Pharm J (Ott) 2021;154:xx-xx.
|
10.1177/17151635211014918
|
pubmed_394_13581
|
OBJECTIVE
The management of antenatally diagnosed ureteropelvic junction obstruction (PUJO) is controversial. Here, we present our experience over a period of 13 years and discuss our management protocol.
MATERIALS AND METHODS
We reviewed the files of 234 patients with antenatally diagnosed congenital hydronephrosis due to PUJO. Management was tailored to each patient, based on a combination of diethylenetetraminepentacetic acid renogram outcome, pelvic diameter, as well as the patient's symptoms.
RESULTS
Pyeloplasty was carried out early in 52 kidneys. Of the total, 182 patients were managed expectantly. Out of these, 45 underwent delayed pyeloplasty. The remaining 137 patients (189 units) were managed non-operatively. In patients who underwent early pyeloplasty, the mean split differential renal function was 37% before and 40.05% after surgery. In those with delayed intervention, the mean renal function was 37.8% before and 42.2% after surgery. In patients who did not have surgery, the mean differential renal function was 45.7% initially and 48.2% at the last accepted follow up. The overall operative success rate was 97.9%.
CONCLUSION
We believe that pyeloplasty is the proper treatment for babies with congenital PUJO and <40% split differential function and/or pelvic diameter >35 mm at the initial visit. In other patients a period of observation is warranted, and pyeloplasty should be carried out only if their kidney function deteriorates or the renogram curve does not show improvement. With the excellent results of pyeloplasty we believe that a safer approach is to operate on more kidneys rather than risk of losing valuable kidney function.
|
10.1016/j.jpurol.2005.07.005
|
pubmed_707_8193
|
Acute kidney injury contributes significantly to morbidity and mortality in hospitalized patients and is a common complication in the intensive care unit. Identification of patients at risk, elimination of modifiable risk factors and initiation of recommended preventive measures are the main cornerstones to prevent the onset and progression of acute kidney injury. Clinical and biomarker-based risk scores can help assess AKI-risk in specific patient populations. To date, there is no approved clinically effective drug to prevent AKI. Current guidelines suggest preventive care bundles that include optimizing volume status and renal perfusion by improving mean arterial pressure and using vasopressors, mainly norepinephrine. In addition, avoidance of volume overload and the targeted use of diuretics to achieve euvolemia are recommended. Nephrotoxic drugs require a critical risk-benefit assessment and therapeutic drug monitoring when appropriate. Contrast imaging should not be withheld from patients at risk of AKI when indicated but contrast medium should be limited to the smallest possible volume. Finally, recommendations include maintenance of normoglycemia and other measures to optimize organ function in specific patient populations.
|
10.1055/a-1609-0722
|
pubmed_796_6433
|
Neuropeptide Y (NPY) administration increases both hypothalamic corticotropin-releasing factor-like immunoreactivity (CRF-ir) and plasma adrenocorticotropin (ACTH). The dependence of these effects on noradrenaline and adrenaline was investigated by selectively depleting these neurotransmitters with 6-hydroxydopamine (6-OHDA) prior to administration of NPY. This combined treatment decreased hypothalamic CRF-ir (P less than 0.025), an effect isolated to the median eminence (P less than 0.025), whereas plasma ACTH increased greatly compared to 6-OHDA treatment alone (P less than 0.0005). In order to further investigate the potential mechanism of this NPY effect, the alpha 2-adrenergic agonist clonidine was administered to normal rats. This treatment increased plasma ACTH (P less than 0.005) and decreased hypothalamic CRF-ir (P less than 0.025), an effect localized to the median eminence (P less than 0.01). The results from both of these treatments are consistent with increased release of hypothalamic CRF. These data imply that the NPY-induced effects are dependent on normal noradrenergic/adrenergic neurotransmission. Depletion of these neurotransmitters allowed NPY to profoundly stimulate CRF release with no evidence for alteration in synthesis, a result common to alpha 2 stimulation.
|
10.1016/0006-8993(89)91112-8
|
pubmed_1073_9470
|
BACKGROUND
Despite the unprecedented and increasing amount of data, relatively little progress has been made in molecular characterization of mechanisms underlying Parkinson's disease. In the area of Parkinson's research, there is a pressing need to integrate various pieces of information into a meaningful context of presumed disease mechanism(s). Disease ontologies provide a novel means for organizing, integrating, and standardizing the knowledge domains specific to disease in a compact, formalized and computer-readable form and serve as a reference for knowledge exchange or systems modeling of disease mechanism.
METHODS
The Parkinson's disease ontology was built according to the life cycle of ontology building. Structural, functional, and expert evaluation of the ontology was performed to ensure the quality and usability of the ontology. A novelty metric has been introduced to measure the gain of new knowledge using the ontology. Finally, a cause-and-effect model was built around PINK1 and two gene expression studies from the Gene Expression Omnibus database were re-annotated to demonstrate the usability of the ontology.
RESULTS
The Parkinson's disease ontology with a subclass-based taxonomic hierarchy covers the broad spectrum of major biomedical concepts from molecular to clinical features of the disease, and also reflects different views on disease features held by molecular biologists, clinicians and drug developers. The current version of the ontology contains 632 concepts, which are organized under nine views. The structural evaluation showed the balanced dispersion of concept classes throughout the ontology. The functional evaluation demonstrated that the ontology-driven literature search could gain novel knowledge not present in the reference Parkinson's knowledge map. The ontology was able to answer specific questions related to Parkinson's when evaluated by experts. Finally, the added value of the Parkinson's disease ontology is demonstrated by ontology-driven modeling of PINK1 and re-annotation of gene expression datasets relevant to Parkinson's disease.
CONCLUSIONS
Parkinson's disease ontology delivers the knowledge domain of Parkinson's disease in a compact, computer-readable form, which can be further edited and enriched by the scientific community and also to be used to construct, represent and automatically extend Parkinson's-related computable models. A practical version of the Parkinson's disease ontology for browsing and editing can be publicly accessed at http://bioportal.bioontology.org/ontologies/PDON .
|
10.1186/s12976-015-0017-y
|
pubmed_855_20074
|
Protein kinase Cdelta (PKCdelta) is a widely expressed calcium-independent PKC isozyme that is induced at mRNA and protein levels upon stimulation of different cellular pathways. We found the rat PKCdelta gene to consist of 19 exons and to span approximately 29 kb. The exon-intron junctions follow the GT/AG rule. The 5' untranslated region is nearly 12 kb in length, and the transcription initiation site is surrounded by CG-rich sequences. The 5' flanking region contains putative binding sites for activator protein 1 (AP-1), nuclear factor kappa B (NFkappaB), stimulatory protein-1 (Sp-1) and nerve growth factor induced-C (NGFI-C) transcription factors. The PKCdelta gene is localized at the rat chromosome 19p14. The cloned gene will help to elucidate the role of PKCdelta in growth, differentiation and death of mammalian cells.
|
10.1016/s0378-1119(99)00539-9
|
pubmed_1112_4170
|
Published series suggest that, in carefully selected patients, long-term survival can be obtained when a complete resection of the primary site and metastasis is achieved. It comprises resection of additional malignant nodules in the contralateral lung (at present classified as M1a, but the additional nodule may be a second primary lung cancer), complete resection of the primary associated with limited metastatic pleural involvement (M1a), and resection of the primary with an isolated extrathoracic metastasis (mostly a single brain or adrenal). All these topics are discussed.
|
pubmed_1112_4170
|
pubmed_598_13076
|
Oral health is an essential component of children's general health. The aim of this study is to evaluate the training, knowledge, attitudes and practices of primary care paediatricians in oral health in Europe. Paediatricians were invited to complete a survey on the web. There was a 54.3% response rate. The oral health education of the responders was received mainly through continuing medical education and practical experience (51%) rather than in medical school or during paediatric residency training (33%). Twenty-four percent of the responders did not know that the first signs of caries were white spots on the surfaces of teeth. Although 98.8% of paediatricians check the oral health status of children, only 52% feel confident enough to identify dental caries. A large proportion of the paediatricians (43%) recommended a first dental visit for children above the age of 3 years and only 7% under 1 year of age.
CONCLUSIONS
Paediatricians are familiar with some aspects of the oral health but are not confident in identifying the risk factors. The current postgraduate curriculum in Paediatrics should incorporate training on basic oral healthcare. In addition, continuous educational programmes are needed to keep the knowledge of the paediatrician up to date. What is Known: • Oral health is an essential component of general health that influences the functional, psychological and social dimensions of a child's well-being. • Paediatricians are the leading providers of primary healthcare for children. What is New: • Paediatricians are familiar with some aspects of the oral health of children but are not confident in identifying the risk factors responsible for oral disease. • The current postgraduate curriculum in Paediatrics should incorporate training on basic oral healthcare in children.
|
10.1007/s00431-018-3108-z
|
pubmed_708_8912
|
We examined whether pretreatment with depot testosterone produces a functional alteration in benzodiazepine receptor sensitivity. This was accomplished by testing the ability of flurazepam to increase the threshold voltage for seizure production in groups of mice given vehicle or testosterone cypionate (1 or 5 mg/kg) 21 days prior to testing in an electroconvulsive shock paradigm. Depot testosterone treatment reduced flurazepam's antiseizure potency in this paradigm. That testosterone altered the ability of flurazepam to protect mice from seizures is consistent with previous reports suggesting a complex interaction between steroids and the BDZ/GABAA system.
|
10.1016/0306-4530(90)90050-j
|
pubmed_1084_19568
|
HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3'-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3'-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3'-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4), and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3'-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3'-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3'-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3'-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3'-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes.
|
10.1371/journal.pone.0025794
|
pubmed_518_13447
|
Low levels of lead, but not high levels, produce hypertension. This mystery has not yet been resolved. In this study we compared the in vitro vasoresponsiveness in rat thoracic aorta to low dose (10(-8) mol/L) and high dose (10(-5) mol/L and 10(-4) mol/L) lead acetate. In addition to the direct response to lead, we examined reactivity to norepinephrine, acetylcholine, isoproterenol, phorbol ester, and calcium in the presence and absence of lead. Neither low-dose nor high-dose lead directly affected aortic contractile or relaxant responses. However, lead, only at the highest concentration (10(-4) mol/L), increased the contractions to calcium at all submaximal calcium concentrations. We conclude that low-dose lead must increase blood pressure indirectly through a humoral effect. The reasons for the failure of high-dose lead to influence blood pressure remain to be explored.
|
10.1016/s0895-7061(01)02149-5
|
pubmed_1077_21463
|
Renal dendritic cells (DCs) and macrophages represent a constitutive, extensive and contiguous network of innate immune cells that provide sentinel and immune-intelligence activity; they induce and regulate inflammatory responses to freely filtered antigenic material and protect the kidney from infection. Tissue-resident or infiltrating DCs and macrophages are key factors in the initiation and propagation of renal disease, as well as essential contributors to subsequent tissue regeneration, regardless of the aetiological and pathogenetic mechanisms. The identification, and functional and phenotypic distinction of these cell types is complex and incompletely understood, and the same is true of their interplay and relationships with effector and regulatory cells of the adaptive immune system. In this Review, we discuss the common and distinct characteristics of DCs and macrophages, as well as key advances that have identified the renal-specific functions of these important phagocytic, antigen-presenting cells, and their roles in potentiating or mitigating intrinsic kidney disease. We also identify remaining issues that are of priority for further investigation, and highlight the prospects for translational and therapeutic application of the knowledge acquired.
|
10.1038/nrneph.2014.170
|
pubmed_304_19715
|
Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.
|
10.1016/j.psyneuen.2006.11.003
|
pubmed_718_4359
|
Dihydropteroate synthase is the target enzyme for the sulfonamide compounds, which are the mainstay of therapy for Pneumocystis carinii pneumonia, a common infection in patients with impaired immunity. The stability of this enzyme, its kinetic constants with respect to substrates, and the 50% inhibitory concentration (IC50) of several sulfonamides and the sulfone dapsone have been characterized using both cell-free and intact organism assay systems. Stability of the enzyme is dependent on storage temperature, reducing reagents, and to a lesser extent, protease inhibitors. The sulfonamides sulfadiazine and sulfamethoxazole were found to be highly potent inhibitors of P. carinii dihydropteroate synthase with IC50s of 0.42 and 0.71 microM, respectively. Dapsone had equivalent potency when compared with the most potent sulfonamides tested in both assay systems. Data suggest that sulfamethoxazole, sulfadiazine and dapsone may represent equivalent choices as P. carinii dihydropteroate synthase inhibitors, assuming an equivalent in vivo drug exposure can be achieved.
|
10.1093/infdis/169.2.456
|
pubmed_386_20338
|
Common beans are a staple food and the major source of iron for populations in Eastern Africa and Latin America. Bean iron concentration is high and can be further increased by biofortification. A major constraint to bean iron biofortification is low iron absorption, attributed to inhibitory compounds such as phytic acid (PA) and polyphenol(s) (PP). We have evaluated the usefulness of the common bean as a vehicle for iron biofortification. High iron concentrations and wide genetic variability have enabled plant breeders to develop high iron bean varieties (up to 10 mg/100 g). PA concentrations in beans are high and tend to increase with iron biofortification. Short-term human isotope studies indicate that iron absorption from beans is low, PA is the major inhibitor, and bean PP play a minor role. Multiple composite meal studies indicate that decreasing the PA level in the biofortified varieties substantially increases iron absorption. Fractional iron absorption from composite meals was 4%-7% in iron deficient women; thus the consumption of 100 g biofortified beans/day would provide about 30%-50% of their daily iron requirement. Beans are a good vehicle for iron biofortification, and regular high consumption would be expected to help combat iron deficiency (ID).
|
10.3390/nu7021144
|
pubmed_1125_9121
|
The proteolytic processing of bovine fibrinogen by MMP-2 (gelatinase A), which brings about the formation of a product unable to form fibrin clots, has been studied at 37 degrees C. Catalytic parameters, although showing a somewhat lower catalytic efficiency with respect to thrombin and plasmin, indeed display values indicating a pathophysiological significance of this process. A parallel molecular modelling study predicts preferential binding of MMP-2 to the beta-chain of fibrinogen through its haemopexin-like domain, which has been directly demonstrated by the inhibitory effect in the presence of the exogenous haemopexin-like domain. However, the removal of this domain does not impair the interaction between MMP-2 and fibrinogen, but it dramatically alters the proteolytic mechanism, producing different fragmentation intermediates. The investigation at various pH values between 6.0 and 9.3 indicates a proton-linked behaviour, which is relevant for interpreting the influence on the process by environmental conditions occurring at the site of an injury. Furthermore, the action of MMP-2 on peroxynitrite-treated fibrinogen has been investigated, a situation possibly occurring under oxidative stress. The chemical alteration of fibrinogen, which has been shown to abolish its clotting activity, brings about only limited modifications of the catalytic parameters without altering the main enzymatic mechanism.
|
10.1042/BJ20061064
|
pubmed_142_11467
|
BACKGROUND
To optimize autologous breast augmentation, a simple and reproducible surgical approach that maximizes the volume of fat transferred to the breast while minimizing the number of sessions and the operating time is needed.
OBJECTIVES
The authors describe a novel approach for large-volume fat grafting to the expanded skin and subcutaneous tissue of the breast immediately after explantation, exchanging the volume provided by the implants with transplanted fat in a single session.
METHODS
Eighty patients (160 breasts) undergoing explantation and autologous fat transfer were evaluated in a prospective study. Fat was harvested with the lipomatic power-assisted liposuction machine (Lipomatic Eva SP, Euromi SA, Verviers, Belgium) and was injected with simultaneous vibration and tunnelization of the recipient site by means of the same machine with suction disabled. Changes in breast volume were measured in terms of bra cup size, and patients were monitored by mammography and ultrasonography. Patient satisfaction was assessed with a questionnaire administered 6 months postoperatively.
RESULTS
Injected fat volumes ranged from 300 to 600 mL per breast. Operating times ranged from 45 to 90 minutes. For all patients, one injection session was sufficient to replace the volume of the previous implant. Patients were monitored for an average of 2 years, and complications included cyst formation in 9 of 160 breasts (5.6%) and infection in 2 breasts (1.25%).
CONCLUSIONS
Power-assisted transfer of autologous fat to the breast improves the ability of the recipient site to receive the graft and allows for explantation and fat transplantation in a single session. This approach is suitable for patients who desire a natural-appearing breast that is similar in volume to their previous implant.
|
10.1093/asj/sjv073
|
pubmed_52_2453
|
Spreading depression (SD) is a pathological wave of transient neuronal inactivation. We recently reported that the characteristic sustained complete depolarization is restricted to specific cell domains where the input resistance (R(in)) first becomes negligible before achieving partial recovery, whereas in adjacent, more polarized membranes it drops by much less. The experimental study of the participating membrane channels is hindered by their mixed contribution and heterogeneous distribution. Therefore, we derived a biophysical model to analyze the conductances that replicate the subcellular profile of R(in) during SD. Systematic variation of conductance densities far beyond the ranges reported failed to fit the experimental values. Besides standard potassium, sodium, and Glu-mediated conductances, the initial opening and gradual closing of an as yet undetermined large conductance is required to account for the evolution of R(in). Potassium conductances follow in the relative contribution and their closing during the late phase is also predicted. Large intracellular potential gradients from zero to rest are readily sustained between shunted and adjacent SD-spared membranes, which remain electroregenerative. The gradients are achieved by a combination of high-conductance subcellular domains and transmembrane ion redistribution in extended but discrete dendritic domains. We conclude that the heterogeneous subcellular behavior is due to local membrane properties, some of which may be specifically activated under extreme SD conditions.
|
10.1529/biophysj.106.090332
|
pubmed_214_17544
|
BACKGROUND
Quantification of mitral regurgitation (MR) by echocardiography is integral to assessing lesion severity and entails the integration of multiple Doppler-based parameters. These methods are founded primarily upon the principle of proximal isovelocity surface area (PISA), a two-dimensional (2D) method known to involve several assumptions regarding MR jet characteristics. The authors analyzed the results of a semiautomated method of three-dimensional (3D)-based regurgitant volume (RVol) estimation that accounts for jet behavior throughout the cardiac cycle and compared it with conventional 2D PISA methods for MR quantification.
METHODS
A total of 50 patients referred for transesophageal echocardiography for evaluation of primary (n = 25) and secondary (n = 25) MR were included for analysis. Three-dimensional full-volume color data sets were acquired, along with standard 2D methods for PISA calculation. A 3D semiautomated MR flow quantification algorithm was applied offline to calculate 3D RVol, with simultaneous temporal curves generated from the 3D data set. Three-dimensional RVol was compared with 2D RVol. Three-dimensional vena contracta area was also performed in all cases.
RESULTS
There was a modest correlation between 2D RVol and 3D RVol (r = 0.60). The semiautomated 3D approach resulted in significantly lower values of RVol compared with 2D PISA. Real-time and dynamic flow curve patterns were used for integral estimates of 3D RVol over the cardiac cycle, with a distinct bimodal pattern in functional MR and a brief and solitary peak in primary MR.
CONCLUSIONS
Using a semiautomated 3D software for the quantification of MR allows the simultaneous calculation of 3D RVol with an automated generation of dynamic flow curves characteristic of the underlying MR mechanism. The present flow curve pattern results highlight well-known differences between MR flow dynamics in degenerative MR compared with functional MR.
|
10.1016/j.echo.2022.05.005
|
pubmed_246_9898
|
Three of five siblings developed a progressive neurological disorder during infancy or early childhood characterized by cerebellar ataxia, choreoathetosis and peripheral neuropathy. Immunological studies revealed a marked selective deficiency of serum IgE in all three affected siblings. There was evidence of chromosomal instability in the three affected siblings and in one of the parents. One of the affected siblings also developed acute lymphoblastic leukaemia. In spite of many resemblances, this syndrome differs from classical or complete ataxia telangiectasia in that oculocutaneous telangiectases were lacking, the serum IgA and alpha-fetoprotein levels in this family were normal, there was no gonadal dysgenesis, and the cytogenetic findings were atypical.
|
10.1016/0022-510x(84)90019-4
|
pubmed_933_11677
|
A skin graft is the simplest way to reconstruct an area of skin loss. To improve the chance of successful take, shearing forces and haematoma formation between the bed and the graft must be reduced. To achieve this, many surgeons use a tie-over dressing to secure the graft. However, 'quilting' the graft to the wound bed is an alternative method for securing grafts which may be superior to tie-over dressings. The purpose of this study was to compare the outcome of securing a full thickness graft by tie-over dressing versus quilting in the hand. To do this, we performed a retrospective review of graft-take in a consecutive series of 40 patients undergoing dermofasciectomy for Dupuytren's disease over a five year period. Our results demonstrate no significant difference in graft-take comparing grafts secured with a tie-over dressing or by quilting. Importantly, there were no cases of injury to the tendons or neurovascular structures in those cases where the graft was secured by quilting. Our technique for securing the graft by quilting is less time-consuming compared with a tie-over dressing. Therefore, we no longer use tie-over dressings to secure full-thickness grafts in the hand.
|
10.1016/j.bjps.2009.09.008
|
pubmed_749_15868
|
Insulin receptor substrates (IRSs) are phosphorylated by IGF-I receptor tyrosine kinase in a ligand-dependent manner. In turn, they bind to and activate effector proteins such as PI3K, leading to various cell responses including cell proliferation. We had reported that ubiquitin ligase Nedd4 induces mono-ubiquitination of IRS-2, thereby enhancing IRS-2 tyrosine phosphorylation, leading to increased IGF signaling and mitogenic activity. Here we show that ubiquitin-specific protease 15 (USP15) antagonizes the effect of Nedd4 on IRS-2. We identified USP15 as a protein that preferentially bound to IRS-2 when IRS-2 was conjugated with ubiquitin. In HEK293 cells, Nedd4 overexpression induced IRS-2 ubiquitination, which was decreased by USP15 co-expression while increased by USP15 knockdown. Nedd4 overexpression enhanced IGF-I-dependent IRS-2 tyrosine phosphorylation, and USP15 co-expression suppressed it. Conversely, USP15 knockdown increased IRS-2 tyrosine phosphorylation and downstream signaling in prostate cancer PC-3 cells. We concluded that USP15 attenuates IGF-I signaling by antagonizing Nedd4-induced IRS-2 ubiquitination.
|
10.1016/j.bbrc.2017.01.101
|
pubmed_359_11393
|
In a sample of 503 American college students, the correlational matrix (18 x 18) of the Thalbourne, et al. Manic-Depressiveness Scale (1994) was subjected to exploratory factor analysis with a varimax rotation, which showed 13 items had the correct assignment to one of the scales (six for depression and seven for mania).
|
10.2466/pr0.96.3.603-604
|
pubmed_430_6182
|
1. We determined standard metabolic rates (SMR) of wild-caught adults of the Adelie penguin, southern giant fulmar, blue-eyed shag, and South Polar skua at Palmer Station, Antarctica, during January and February 1981. Oxygen consumption was measured volumetrically in a closed system at temperatures between 2 and 12 degrees C. 2. Mean SMR varied between 0.82 l O2/kg per hr for male fulmars and 1.30 l O2/kg per hr for unsexed adult skuas. Values were 174-198% of those predicted by the Lasiewski-Dawson equation for nonpasserines. 3. The SMR of the Adelie penguin was considerably higher than that reported in other studies and higher than most values for other species of penguins. 4. Our measurements of oxygen consumption agree with some estimates of metabolism based upon loss of mass by fasting birds during incubation.
|
10.1016/0300-9629(83)90363-8
|
pubmed_538_1943
|
Directed evolution is a powerful means in academic study and industrial application to modified and functionally improved proteins. There have been significant and impressive advances using the artificial method. Rational Evolutionary Design utilizes structural and sequence alignment information to create new genes and proteins. Rational Evolutionary Design has recently emerged as an attractive approach for studying function of proteins. The review mainly introduced four aspects: preferred codon usage, structural and sequence alignment, key domain analysis, site-directed recombination.
|
pubmed_538_1943
|
pubmed_125_9443
|
Photonics, the manipulation of light at nanoscale, is a key enabling technology with impact in health and energy applications, among others. In most cases photonics still relies on materials and fabrication methods inherited from other disciplines, usually requiring expensive, time-consuming and environmentally-unfriendly processes. Recent experiments demonstrated that advanced photonic materials, as complex as those known as 2.5 dimensional slab photonic crystals, also occur naturally in diatoms. These microscopic algae precipitate silicic acid from water to produce silicon dioxide membranes, relying on intracellular biomineralization mechanisms. Addressing some important aspects for the potential industrial utilization of these structures, we here propose that optical materials produced by the diatoms could serve as cost-effective and environmentally friendly alternatives to cleanroom nanofabrication. We demonstrate that photonic materials grown by the diatom species Coscinodiscus granii can be separated based on its hydrokinetic characteristics. We further show that the photonic membranes present low defect rates of ca. 1/100 unit cells and that variation in pore diameter, as observed between individual membranes, can affect the photonic properties at large, but only marginally at low refractive index contrast. Finally, we list algal culture collections operating worldwide, thus providing a global network for live diatoms and diatom materials. We discuss the feasibility and bottlenecks related to scaled-up growth for direct utilization of photonic materials from diatoms.
|
10.1039/d0fd00031k
|
pubmed_734_11314
|
Importance
Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived.
Objective
To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement.
Design, Setting, and Participants
This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021.
Exposures
SAVR or TAVR.
Main Outcomes and Measures
All-cause and cardiovascular (CV) mortality after aortic valve intervention.
Results
Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume).
Conclusions and Relevance
In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.
|
10.1001/jamacardio.2022.0340
|
pubmed_731_10150
|
OBJECTIVE
Analyzing and described the beverage consumption among Chinese adults.
METHODS
Using the data from nutrition and health monitoring of Chinese residents in 2010-2012. Multi-stage stratified proportion to the population cluster random sampling method was conducted to determine residents in 150 sites in 31 provinces. The food frequency questionnaire was used to collect the consumption frequency and amount of the carbonated beverage, fresh fruit and vegetable juice, fruit and vegetable juice beverage, lactobacillus beverage, dairy drink mix, coffee and tea beverage. The indicators of beverage consumption were calculated through weighted complex sampling processing by population data released by the National Bureau of Statistics in 2009.
RESULTS
In 2010-2012 the proportion of drinking beverages ≥ 1 times/day, 1-6 times/week, 1-3 times/month, < 1 times/month and none was 5. 7%( 95% CI 4. 4%-7. 0%), 24. 1%( 95% CI 21. 3%-26. 9%), 19. 5%( 95% CI 17. 0%-22. 1%), 9. 3%( 95% CI 7. 6%-10. 9%), 41. 4%( 95% CI 36. 4%-46. 5%), respectively. The proportion of drinking beverages ≥1 times/week among urban residents, men and18-44 age group was significantly higher than their counter part. The top consumption rate among the surveyed beverages was carbonated beverage with 41. 5%( 95% CI36. 8%-46. 2%). The average annual beverage consumption was 30. 6 L, with the highest consumption on tea beverage( 26. 2 L).
CONCLUSION
The beverage consumption rate was high among Chinese adults.
|
pubmed_731_10150
|
pubmed_0_13558
|
A 64-year old woman patient with dry pruritic rash, oral ulcers, persistent cough and significant weight loss was investigated and proved to be a case of hypereosinophilic syndrome.
|
pubmed_0_13558
|
pubmed_882_25311
|
RATIONALE
This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation.
OBJECTIVES
To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD.
METHODS
Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV1] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV1<60% predicted or history of acute exacerbation) versus all others.
RESULTS
From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health.
CONCLUSIONS
Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD.
|
10.15326/jcopdf.3.1.2015.0144
|
pubmed_377_24973
|
MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene regulation that have crucial roles in several types of tumors, including papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is regarded as a relevant diagnostic marker for this type of cancer. A computational search revealed that miR-146b-5p putatively binds to the 3' untranslated region (UTR) of SMAD4, an important member of the transforming growth factor β (TGF-β) signaling pathway. The TGF-β pathway is a negative regulator of thyroid follicular cell growth, and the mechanism by which thyroid cancer cells evade its inhibitory signal remains unclear. We questioned whether the modulation of the TGF-β pathway by miR-146b-5p can contribute to thyroid tumorigenesis. Luciferase reporter assay confirmed the direct binding of miR-146b-5p on the SMAD4 3'UTR. Specific inhibition of miR-146b-5p with a locked nucleic acid-modified anti-miR-146b oligonucleotide significantly increased SMAD4 levels in the human papillary carcinoma cell lines, TPC-1 and BCPAP. Moreover, suppression of miR-146b-5p increased the cellular response to the TGF-β anti-proliferative signal, significantly decreasing the proliferation rate. The overexpression of miR-146b-5p in normal rat follicular PCCL3 cells decreased SMAD4 levels and disrupted TGF-β signal transduction. MiR-146b-5p overexpression in PCCL3 cells also significantly increased cell proliferation in the absence of thyroid-stimulating hormone and conferred resistance to TGF-β-mediated cell-cycle arrest. Additionally, the activation of thyroid most common oncogenes RET/PTC3 and BRAF in PCCL3 cells upregulated miR-146b-5p expression. Our results confirm the oncogenic role of miR-146b-5p in thyroid follicular cells and contribute to knowledge regarding the modulation of TGF-β signal transduction by miRNAs in PTCs.
|
10.1038/onc.2011.381
|
pubmed_558_8724
|
In this report, we elaborate on a letter that Spallanzani wrote to Bonnet reporting his findings on regeneration in worms, snails, tadpoles, and salamanders. The letter (original in French and translated in English; see Supplementary Material, which is available online) was written to discuss whether or not regeneration in these animals supports Bonnet's theory on germs. The letter includes several drawings by Spallanzani, which were not published in the Prodromo, his book on Animal Reproduction. Spallanzani made important observations, which he described with considerable detail, but overall he was unable to confidently support Bonnet's theory. This letter reflects the way of thinking in the 18(th) century that shaped the important scientific fields of regeneration and reproduction.
|
10.1002/dvdy.22057
|
pubmed_508_9904
|
Sally Clark, Angela Cannings and Trupti Patel not only suffered the tragic sudden deaths of two or more babies. They were then accused, and in the first two cases convicted, of their murder. The misuse of statistics at Sally Clark's trial had profound consequences, especially for her, but also for the subsequent cases. Ray Hill reflects on the statistical issues involved.
|
10.1258/rsmmsl.47.1.2
|
pubmed_661_16710
|
We have investigated the influence on the excitability of lumbar motoneurons of 5-hydroxytryptamine (5-HT), substance P and thyrotropin releasing hormone (TRH), three substances which coexist in the same bulbospinal descending pathway and end in large part around motoneurons. We have also studied the effect of clonidine, an alpha 2 noradrenergic agonist. This was done in spinalized rats (T5) treated three weeks before with 5-7-dihydroxytryptamine. Under those circumstances 5-HTP (I.P.), 5-HT (intrathecally) TRH (I.P. or I.T.) and substance P (I.T.) all elicited a strong excitation of motoneurons as measured by integrated EMG of the hindlimb muscles. Substance P reduced by almost half the subsequent response to 5-HTP, 1 hour and 24 hours later. TRH given acutely did not modify the response to 5-HTP but given chronically for twenty one days by means of Alzet minipump, markedly increased the response to 5-HTP. Clonidine by itself decreased the excitability of motoneurons and antagonized the excitatory effect of 5-HTP and TRH. In a pilot trial, cyproheptadine, a 5-HT antagonist was shown to decrease the manifestations of spasticity in patients with a partial spinal lesion. Clonidine also appears to be of potential use in the treatment of spasticity.
|
10.1017/s0317167100038002
|
pubmed_166_12134
|
A high-yielding, cost-effective, modular and environmentally benign approach to [5,5]- or [6,5]-2-azabicyclic architectures bearing vicinal stereocenters, by Fe-catalyzed intramolecular dehydrative coupling of readily affordable alcohol-bearing allylic lactams is presented.
|
10.1039/c6ob02652d
|
pubmed_703_8436
|
BACKGROUND
Multiple myeloma remains an incurable malignancy despite of the recent approval of new molecular-targeted agents. The complex molecular mechanism, composed of various signal networks, including nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/AKT, Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), and interferon regulatory factor 4 (IRF4) pathways, is a major reason for treatment failure. Curcumin can regulate these molecules, but its low bioavailability prevents its clinical application.
MATERIALS AND METHODS
Growth-suppressive abilities of newly synthesized analogs, GO-Y030 and GO-Y078 were analyzed. Molecular-targeted abilities of the analogs for NF-κB, PI3K/AKT, JAK/STAT3, IRF4 pathways, as well as inhibition of interleukin-6 (IL-6) production, were also examined.
RESULTS
GO-Y030 and GO-Y078 were 7 to 12-fold more potent growth suppressors for myeloma cells, and 6- to 15-fold stronger inhibitors of NF-κB, PI3K/AKT, JAK/STAT3, and IRF4 pathways than curcumin. GO-Y78 also 14-fold more potently inhibited IL-6 production.
CONCLUSION
GO-Y030 and GO-Y078 are potential therapeutic candidates with enhanced abilities for multiple myeloma.
|
pubmed_703_8436
|
pubmed_374_12375
|
Liver diseases, a wide spectrum of pathologies from inflammation to neoplasm, have become an increasingly significant health problem worldwide. Noninvasive imaging plays a critical role in the clinical workflow of liver diseases, but conventional imaging assessment may provide limited information. Accurate detection, characterization and monitoring remain challenging. With progress in quantitative imaging analysis techniques, radiomics emerged as an efficient tool that shows promise to aid in personalized diagnosis and treatment decision-making. Radiomics could reflect the heterogeneity of liver lesions via extracting high-throughput and high-dimensional features from multi-modality imaging. Machine learning algorithms are then used to construct clinical target-oriented imaging biomarkers to assist disease management. Here, we review the methodological process in liver disease radiomics studies in a stepwise fashion from data acquisition and curation, region of interest segmentation, liver-specific feature extraction, to task-oriented modelling. Furthermore, the applications of radiomics in liver diseases are outlined in aspects of diagnosis and staging, evaluation of liver tumour biological behaviours, and prognosis according to different disease type. Finally, we discuss the current limitations of radiomics in liver disease studies and explore its future opportunities.
|
10.1111/liv.14555
|
pubmed_568_20166
|
Dual inhibition of the enzymatic pathways of cyclooxygenases (COX-1/COX-2) and lipoxygenase (LOX) is a rational approach for developing more efficient and safe anti-inflammatory agents. Herein, dual inhibitors of COX and LOX for the management of inflammation are reported. The structural modifications of starting pyrrolidine-2,5-dione aldehyde derivatives resulted in two structurally diverse families (Family A & B). Synthesized derivatives from both Families displayed preferential COX-2 affinity in submicromolar to nanomolar ranges. Disubstitution pattern of the most active series of compounds having N-(benzyl(4-methoxyphenyl)amino moiety presents a new template that is mimic to the diaryl pattern of traditional COX-2 inhibitors. Compound 78 with IC50 value of 0.051 ± 0.001 μM emerged as the most active compound. Highly potent COX-2/5-LOX inhibitors have also demonstrated appreciable in-vivo anti-inflammatory activity through carrageenan induced paw edema test. Moreover, the involvement of histamine, bradykinin, prostaglandin, and leukotriene mediators to adjust the inflammatory response were also studied. Apart from COX inhibition, sulfonamide is considered an important template for carbonic anhydrase inhibition. Hence, we also evaluated six sulfonamide derivatives for off-target in-vitro bovine carbonic anhydrase-II inhibition. Biological results were finally rationalized by docking simulations. Typically, most active COX-2 inhibitors interact with the amino acid residues responsible for the COX-2 selectivity.
|
10.1016/j.bioorg.2021.104969
|
pubmed_540_23554
|
OBJECTIVES
This study determined the efficacy of alcohol-free 0.05% cetylpyridinium chloride (CPC) mouthwash as an adjunct to twice-daily toothbrushing in comparison with 0.12% chlorhexidine gluconate (CHX) mouthwash and a placebo in reducing plaque accumulation and gingival inflammation. The side effects of the mouthwashes were also determined.
MATERIALS AND METHODS
A double-blind, parallel, randomized control trial was conducted with 219 university students who were divided into three trial groups using block randomization: CPC, CHX and placebo groups. Clinical oral examinations to assess dental plaque accumulation (modified Quigley-Hein Plaque Index), gingival health (Löe and Silness Gingival Index) and tooth staining (modified Lobene Stain Index) were performed at baseline and at 6 weeks.
RESULTS
Plaque and gingivitis scores were not significantly different among participants at baseline. After 6 weeks, plaque and gingivitis scores between the CPC and placebo groups and between the CHX and placebo groups were found to be significantly different. However, there was no significant difference between the CPC and CHX groups. The staining scores of participants in the CPC group were lower than those in the CHX group, but the difference was not significant. Taste alteration and numbness were more common among participants in the CHX group than in the CPC group. No significant difference in the perception of a burning sensation was observed.
CONCLUSIONS
The 0.05% CPC mouthwash was as efficient as 0.12% CHX mouthwash in reducing dental plaque accumulation and gingival inflammation with fewer side effects, supporting its use as an adjunct to toothbrushing.
|
10.1111/idh.12614
|
pubmed_369_25138
|
Visualization of DNA-protein interactions by atomic force microscopy (AFM) has deepened our understanding of molecular processes such as DNA transcription. Interpretation of systems where more than one protein acts on a single template, however, is complicated by protein molecules migrating along the DNA. Single-molecule AFM imaging experiments can reveal more information if the polarity of the template can be determined. A nucleic acid-based approach to end-labelling is desirable because it does not compromise the sample preparation procedures for biomolecular AFM. Here, we report a method involving oligonucleotide loop-primed synthesis for the end labelling of double-stranded DNA to discriminate the polarity of linear templates at the single-molecule level. Single-stranded oligonucleotide primers were designed to allow loop formation while retaining 3'-single-strand extensions to facilitate primer annealing to the template. Following a DNA polymerase extension, the labelled templates were shown to have the ability to form open promoter complexes on a model nested gene template using two Escherichia coli RNA polymerases in a convergent transcription arrangement. Analysis of the AFM images indicates that the added loops have no effect on the ability of the promoters to recruit RNA polymerase. This labelling strategy is proposed as a generic methodology for end-labelling linear DNA for studying DNA-protein interactions by AFM.
|
10.1093/nar/gks276
|
pubmed_1109_13848
|
BACKGROUND
Reduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.
METHODS
We measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.
RESULTS
Serum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p<0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p=0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p=0.006 and p<0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.
CONCLUSIONS
Our findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.
|
pubmed_1109_13848
|
pubmed_457_6507
|
Disasters are unpredictable and often result in mass casualties. Limited medical resources often affect the response to mass casualty incidents, undermining the ability of responders to adequately protect all of the casualties. Thus, the injuries of casualties are classified in hopes of fully utilizing medical resources efficiently in order to save the maximum possible number of people. However, as opinions on casualty prioritization are subjective, disagreements and disputes often arise regarding allocating medical resources. The present article focused on the 2015 explosion at Formosa Fun Coast, a recreational water park in Bali, New Taipei City, Taiwan as a way to explore the dilemma over the triage and resource allocation for casualties with burns over 90% and 50-60% of their bodies. The principles of utilitarianism and deontology in Western medicine were used to discuss the reasons and rationale behind the allocation of medical resources during this incident. Confucianism, a philosophical mindset that significantly influences Taiwanese society today, was then discussed to describe the "miracles" that happened during the incident, including the acquisition of assistance from the public and medical professionals. External supplies and professional help (social resources) were provided voluntarily after this incident, which had a profound impact on both the immediate response and the longer-term recovery efforts.
|
10.6224/JN.64.1.105
|
pubmed_485_5589
|
The influence of external factors, such as storage temperature and time on the content of free formaldehyde (FA) in fishery products is described. On the basis of the examination of several methods for the determination of free and bound FA, the following procedures are recommended: (1) for measuring free FA, the samples are extracted using 6% perchloric acid at room temperature and the FA content of the extracts is measured by the formation of 3,5-diacetyl-1,4-dihydrolutidine; (2) bound, acid-labile FA is released by steam distillation using 1% sulphuric acid, giving a pH value of about 1. The FA content of the distillates may be determined either by chromotropic acid assay or by the method described for the extracts.
|
10.1007/BF01123034
|
pubmed_517_22072
|
AIM
Management of fluid homeostasis remains a major challenge in hemodialysis patients. We aimed to establish whether the cardiac strain marker B-type natriuretic peptide (BNP) could help to identify hypervolemic patients at increased risk of death.
METHODS
BNP levels were determined before dialysis in the entire HD population at our institution (n = 57). IDWG and BNP were stratified above or below 1.5 kg or the median value, respectively. All patients were prospectively followed for 35 months. The influence of IDWG and BNP on mortality was assessed with a Cox proportional hazards model, adjusted for each other, as well as for demographics, comorbidities, cardiac function, residual diuresis, dialysis duration and efficiency and complications of renal failure.
RESULTS
Median BNP was 303 (135 - 692) and 21 (36%) patients displayed an average IDWG below 1.5 kg. During follow up a total of 25 (44%) patients died, 5 (26%) in the low IDWG group and 20 (53%) in the high IDWG group (adjusted hazard ratio (adjusted HR) 5.31 95% CI (1.47 - 19.1), p = 0.011). In the low BNP group 7 (25%) patients died and in the high BNP Group 18 (62%) patients died (adjusted HR 3.53 95 CI (1.37 - 9.09), p = 0.009). When both factors were considered simultaneously, patients with low BNP and low IDWG had an 11 times lower risk of death compared to patients with high BNP and high IDWG (HR. 0.08 95% CI (0.01 - 0.6129, p = 0.015).
CONCLUSIONS
BNP and IDWG are independent and incremental predictors of mortality in HD patients. These findings suggest that BNP guided fluid management could improve survival in these patients.
|
10.5414/cn106858
|
pubmed_1077_4480
|
Much of the evidence supporting a focus on end-of-life care for persons with kidney disease is in the form of expert opinion and professional practice guidelines based on multi-disciplinary input and an exploration of the known illness trajectory for renal disease. Limited intervention studies or randomized control trials related to palliative or hospice care for patients in the U.S. with ESRD remain, providing rich opportunities for nephrology researchers. Nephrology nurses should remain vigilant and open to opportunities to participate in research related to improving end-of-life care for persons with ESRD and should be at the forefront of designing evidence-based practice projects for end-of-life care options for this population.
|
pubmed_1077_4480
|
pubmed_203_11380
|
Molecular mobility is known to be a key parameter in controlling the physical properties of materials and thus their quality and performance. Beyond glass transition related changes, attention should be called to the impact of local motions remaining in the glassy state. Gelatinized waxy maize starch at different sucrose contents (0-20% solids) was equilibrated between 0 and 14% water and sorption isotherms determined at 25 degrees C. The effect of water and sucrose content on the molecular mobility of glassy starch was investigated by differential scanning calorimetry through enthalpy relaxation studies and dynamical mechanical thermal analysis. The existence of sucrose-starch interactions was suggested by the sorption isotherms not following the expected additivity of the single component sorption curves. Contrary to the glass transition or associated alpha relaxation, water and sucrose affected differently the secondary relaxations. Indeed, the beta relaxation observed around -15 degrees C was shifted to lower temperature upon increasing hydration, and to higher temperature when sucrose content increased, suggesting a hindering of these local motions. Enthalpy relaxation of the ternary mixtures was studied following aging up to 668 h at Tg -15 degrees C. Ternary mixtures exhibited an enthalpy relaxation upon aging lower than starch alone as a sign of lower polymer mobility in the presence of small molecules, contrary to the free volume theory. Relaxation kinetics were characterized with the Cowie-Ferguson model and compared to literature data. The extent of the enthalpy relaxation appeared to be controlled by the distance between the aging temperature and the beta relaxation temperature.
|
10.1002/bip.20358
|
pubmed_444_6253
|
BACKGROUND
Australian Cervical Screening Program guidelines no longer recommend colposcopy and cytology at six months following treatment of cervical intraepithelial neoplasia (CIN2/3) and a co-test of cure can be performed at 12 months without colposcopy.
AIMS
To determine the usefulness of six-month colposcopy and cytology and routine colposcopy with co-testing at 12 months in detecting persistent or recurrent disease in patients treated for CIN2/3.
MATERIALS AND METHODS
We conducted a review of all patients with histologically proven CIN2/3 who underwent a cervical excisional procedure between March 2012 and March 2017 in one specialised centre.
RESULTS
We examined 1215 cases and 750 remained after exclusions for analysis. At six months (722 cases, 96.2%) seven of 42 (16.7%) patients with high-grade cytology had a high-grade colposcopy and 24 of 42 (57.1%) had a normal colposcopy. Persistent CIN2/3 was diagnosed in 12 cases (1.7%) and only 1/3 had a high-grade colposcopy. Cytology was more useful than colposcopy in detecting persistent disease. At 12 months (638 cases, 85%) routine colposcopy at the time of co-testing had a high false positive rate with all high-grade changes negative on biopsy and co-test. Recurrent CIN2/3 was diagnosed in five cases, and four had normal colposcopy at co-testing.
CONCLUSIONS
There may be a delay in detection of persistent/recurrent CIN2/3 in a small number of cases without six-month colposcopy and cytology; however, it is not likely to negatively impact overall clinical outcome. Co-testing at 12 months following treatment of CIN2/3 without colposcopy is safe and routine colposcopy at collection of the co-test can be omitted.
|
10.1111/ajo.13248
|
pubmed_511_1923
|
BACKGROUND
Crocus sativus L. (saffron) is a scarce plant that has been used as food flavoring agent, coloring agent, and traditional herbal medicine.
METHODS
The bioactivity of exopolysaccharide (EPS) extracted from an endophytic fungus of C. sativus was examined for the first time by antioxidative, antitumor, and antibacterial assays. The extraction conditions for EPS were optimized by combining the response surface methodology with Box-Behnken design.
RESULTS
EPS exhibited excellent scavenging activities against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals, and moderate cytotoxicities against K562, A549, HL-60, and HeLa cells. The optimum extraction conditions for EPS were as follows: precipitation time of 16 h, precipitation temperature of 3.7°C, pH 7.2, and ratio of ethanol to fermented broth of 5:1 (L/L). Under the optimized conditions, the yield of EPS reached 162 ± 6 μg/L which was close to the predicted one (165 μg/L). Moreover, high-performance liquid chromatography of monosaccharide composition showed that EPS comprised mannose, glucose, galactose xylose, and arabinose in a molar ratio of 25.6:16.5:1.0:3.8:5.4.
CONCLUSION
EPS may be an eligible substitute for C. sativus and a potential bioactive source applicable to pharmaceutical and food industries.
SUMMARY
Exopolysaccharide (EPS) from endophytic fungus of Crocus sativus was studied for the first timeEPS extraction was optimized by combining response surface methodology with Box-Behnken designMonosaccharide composition and EPS structure were identified by high-performance liquid chromatography and Fourier-transform infrared spectroscopy. Abbreviations used: EPS: Exopolysaccharide, RSM: Response surface methodology, BBD: Box-Behnken design, DPPH: 1,1-diphenyl-2-picrylhydrazyl, VC: Ascorbic acid, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, LB: Luria Bertani, DMSO: dimethyl sulfoxide, PMP: 1-phenyl-3-methyl-5-pyrazolone, FT-IR: Fourier transform-infrared, HPLC: High-performance liquid chromatography, 3D: Three-dimensional, 2D: Two-Dimensional.
|
10.4103/pm.pm_96_17
|
pubmed_418_19446
|
To enable Saccharomyces cerevisiae to produce renewable fuels from lignocellulose in a consolidated bioprocess, a heterologous cellulase system must be engineered into this yeast. In addition, inherently low secretion titers and sensitivity to adverse environmental conditions must be overcome. Here, two native S. cerevisiae genes related to yeast stress tolerance, YHB1 and SET5, were overexpressed under transcriptional control of the constitutive PGK1 promoter and their effects on heterologous secretion of Talaromyces emersonii cel7A cellobiohydrolase was investigated. Transformants showed increased secreted enzyme activity that ranged from 22% to 55% higher compared to the parental strains and this did not lead to deleterious growth effects. The recombinant strains overexpressing either YHB1 or SET5 also demonstrated multi-tolerant characteristics desirable in bioethanol production, i.e. improved tolerance to osmotic and heat stress. Quantitative reverse transcriptase PCR analysis in these strains showed decreased transcription of secretion pathway genes. However, decreased unfolded protein response was also observed, suggesting novel mechanisms for enhancing enzyme production through stress modulation. Overexpression of YHB1 in an unrelated diploid strain also enhanced stress tolerance and improved ethanol productivity in medium containing acetic acid. To our knowledge, this is the first demonstration that improved heterologous secretion and environmental stress tolerance could be engineered into yeast simultaneously.
|
10.1093/femsyr/foz035
|
pubmed_708_21497
|
Distal radial fractures are common, and many methods of treatment have been reported but there are no studies that compare the different treatment methods. This randomized prospective study demonstrated no advantage in using an external fixator to immobilize reduced distal radial fractures over closed reduction and plaster cast immobilization in patients less than 60 years of age. The external fixator group had a significant complication rate.
|
10.1097/00005131-199003000-00005
|
pubmed_808_17327
|
Leucine (Leu), one of the three branch chain amino acids, acts as a signaling molecule in the regulation of overall amino acid (AA) and protein metabolism. Leucine is also considered to be a potent stimulus for the secretion of insulin from pancreatice β-cells. Our objective was to study the effects of a duodenal bolus infusion of Leu on insulin and glucagon secretion, on plasma AA concentrations, and to do a metabolomic profiling of dairy cows as compared to infusions with either glucose or saline. Six duodenum-fistulated Holstein cows were studied in a replicated 3 × 3 Latin square design with 3 periods of 7 days, in which the treatments were applied at the end of each period. The treatments were duodenal bolus infusions of Leu (DIL; 0.15 g/kg body weight), glucose (DIG; at Leu equimolar dosage) or saline (SAL). On the day of infusion, the treatments were duodenally infused after 5 h of fasting. Blood samples were collected at -15, 0, 10, 20, 30, 40, 50, 60, 75, 90, 120, 180, 210, 240 and 300 min relative to the start of infusion. Blood plasma was assayed for concentrations of insulin, glucagon, glucose and AA. The metabolome was also characterized in selected plasma samples (i.e. from 0, 50, and 120 min relative to the infusion). Body weight, feed intake, milk yield and milk composition were recorded throughout the experiment. The Leu infusion resulted in significant increases of Leu in plasma reaching 20 and 15-fold greater values than that in DIG and SAL, respectively. The elevation of plasma Leu concentrations after the infusion led to a significant decrease (P<0.05) in the plasma concentrations of isoleucine, valine, glycine, and alanine. In addition, the mean concentrations of lysine, methionine, phenylalanine, proline, serine, taurine, threonine, and asparagine across all time-points in plasma of DIL cows were reduced (P<0.05) compared with the other groups. In contrast to the working hypothesis about an insulinotropic effect of Leu, the circulating concentrations of insulin were not affected by Leu. In DIG, insulin and glucose concentrations peaked at 30-40 and 40-50 min after the infusion, respectively. Insulin concentrations were greater (P<0.05) from 30-40 min in DIG than DIL and SAL, and glucose was elevated in DIG over DIL and SAL from 30-75 min and 40-50 min, respectively. Multivariate metabolomics data analysis (principal component analysis and partial least squares discriminant analysis) revealed a clear separation when the DIL cows were compared with the DIG and SAL cows at 50 and 120 min after the infusion. By using this analysis, several metabolites, mainly acylcarnitines, methionine sulfoxide and components from the kynurenine pathway were identified as the most relevant for separating the treatment groups. These results suggest that Leu regulates the plasma concentrations of branched-chain AA, and other AA, apparently by stimulating their influx into the cells from the circulation. A single-dose duodenal infusion of Leu did not elicit an apparent insulin response, but affected multiple intermediary metabolic pathways including AA and energy metabolism by mechanisms yet to be elucidated.
|
10.1371/journal.pone.0176647
|
pubmed_1097_8300
|
Localized molecular orbitals (LMOs) are much more compact representations of electronic degrees of freedom than canonical molecular orbitals (CMOs). The most compact representation is provided by nonorthogonal localized molecular orbitals (NOLMOs), which are linearly independent but are not orthogonal. Both LMOs and NOLMOs are thus useful for linear-scaling calculations of electronic structures for large systems. Recently, NOLMOs have been successfully applied to linear-scaling calculations with density functional theory (DFT) and to reformulating time-dependent density functional theory (TDDFT) for calculations of excited states and spectroscopy. However, a challenge remains as NOLMO construction from CMOs is still inefficient for large systems. In this work, we develop an efficient method to accelerate the NOLMO construction by using predefined centroids of the NOLMO and thereby removing the nonlinear equality constraints in the original method ( J. Chem. Phys. 2004 , 120 , 9458 and J. Chem. Phys. 2000 , 112 , 4 ). Thus, NOLMO construction becomes an unconstrained optimization. Its efficiency is demonstrated for the selected saturated and conjugated molecules. Our method for fast NOLMO construction should lead to efficient DFT and NOLMO-TDDFT applications to large systems.
|
10.1021/jp1027838
|
pubmed_923_20598
|
The DNA sequencing and preliminary functional analysis of a 32 kb section of yeast chromosome I has been completed. This region lies on the left arm of the chromosome between the LTE1 and SPO7 genes and contains 14 open reading frames (ORFs) positioned closely together, with an average spacing of approximately 350 nucleotides between coding regions. Three of these ORFs correspond to previously identified genes, a further three show significant homology with other proteins, while the remaining eight ORFs share no significant homology to genes in the databases.
|
10.1139/g93-005
|
pubmed_573_13300
|
OBJECTIVE
This study compares pre- and posttest Leadership Practices Inventory (LPI-Self) scores for public health leaders who completed the Regional Institute for Health and Environmental Leadership (RIHEL) training program at least 2 years earlier; it seeks to identify factors contributing to changes in practices and overall leadership development for public health and environment leaders.
PARTICIPANTS/SETTING
Sixty-seven alumni who completed the yearlong RIHEL program between 1999 and 2002 participated through mailed surveys and phone interviews.
MAIN OUTCOME MEASURES
The Leadership Practices Inventory, an alumni leadership development survey, and interviews provided evidence for positive change in leadership practices.
RESULTS
Alumni experienced significant increases in pre- to post-LPI scores, collaborative leadership practices, and communication skills consistent with those taught in the RIHEL program. Women presented higher Encourage the Heart scores than men. Years of public health service negatively correlated with Total Change scores of LPI. The RIHEL program as a training intervention was credited significantly with changes in leadership practices for alumni studied. Nine influencing factors were identified for leadership development and are embedded in a Leadership Development Influence Model. These include self-awareness, a leadership development framework, and skills important in multiple leadership situations. Confidence was both an encouraging factor and a resulting factor to the increased exemplary leadership practices.
CONCLUSION
Leadership development in public health must include multiple factors to create consistent increases in exemplary leadership practices. While the study focused on the leadership development process itself, RIHEL training was reported as having a positive, significant impact overall in participant leadership development. This study adds research data as a foundation for training content areas of focus. Studies to further test the Leadership Development Influence Model will allow public health training programs to pinpoint training where it can make a difference to improve leadership development in the public health sector.
|
10.1097/PHH.0b013e3182703de2
|
pubmed_417_10993
|
We examined the rhythm of weight velocity in eight patients with Crohn's disease. In this paper we used the spline smoothing technique to study the cycle in the weight increment velocity curves derived from individual data during nutritional therapy. As a result of the weight measurement at four-day intervals, an infradian rhythm with the average cycle of 9.6 +/- 0.7 was recognized in all of the subjects in terms of the weight increment velocity. This rhythm was especially conspicuous in three adolescent patients with serious nutritional lesion. The cycle of the rhythm was unaffected by any of the following factors: energy intake, contents of nutritional therapy, medical examination during the period. Our findings of a common cycle in the process of convalescence from a low nutritious stage in patients with Crohn's disease suggest that, in others as well, the weight increment velocity might have an infradian rhythm with a kind of inherent periodicity.
|
pubmed_417_10993
|
pubmed_616_16429
|
Correlated binary data arise in a large variety of biomedical research. In order to evaluate methods for their analysis, computer simulations of such data are often required. Existing methods can often not cover the full range of possible correlations between the variables or are not available as implemented software. We propose a genetic algorithm that approaches the desired correlation structure under a given marginal distribution. The procedure generates a large representative matrix from which the probabilities of individual observations can be derived or from which samples can be drawn directly. Our genetic algorithm is evaluated under different specified marginal frequencies and correlation structures, and is compared against two existing approaches. The evaluation checks the speed and precision of the approach as well as its suitability for generating also high-dimensional data. In an example of high-throughput glycan array data, we demonstrate the usability of our approach to simulate the power of global test procedures. An implementation of our own and two other methods were added to the R-package 'RepeatedHighDim'. The presented algorithm is not restricted to certain correlation structures. In contrast to existing methods it is also evaluated for high-dimensional data.
|
10.1016/j.compbiomed.2017.10.023
|
pubmed_723_2539
|
The involvement of the interleukin (IL)-17 axis in many inflammatory and autoimmune diseases is now well established, and this has led to the development of successful targeted therapies. Its role in systemic lupus erythematosus (SLE) is less described, since SLE is characterized by the impairment of many other immune actors. However, results from animal models and patients strongly suggest that IL-17 and its producing cells are involved in SLE pathogenesis. Circulating levels of IL-17 are increased in lupus, and tissue staining shows the presence of IL-17-producing cells in organ lesions. Through different mechanisms, the IL-17 axis promotes autoantibody production, immune complex deposition, complement activation and then tissue damage. There are also many interactions with other immune and non-immune actors, which account for the broad spectrum of clinical manifestations and disease heterogeneity. SLE treatment faces challenges with many disappointing trials and persistent unmet needs. The identification of subsets of SLE patients with an IL-17-driven disease now constitutes the key priority before starting trials. More preclinical studies are needed to improve the selection of the right patients able to respond and tolerate the many inhibitors that are already available.
|
10.1177/0961203319891243
|
pubmed_900_23548
|
PURPOSE
We examined the preventability of adverse warfarin-related events and potential adverse warfarin-related events ("near misses") in the nursing home setting.
METHODS
We performed a cohort study of all long-term care residents of 25 nursing homes (bed size range, 90-360) in Connecticut during a 12-month observation period. The total number of residents in these facilities ranged from 2946 to 3212 per quarter. There were 490 residents who received warfarin therapy. Possible warfarin-related incidents were detected by quarterly retrospective review of nursing home records by trained nurse abstractors. Each incident was independently classified by 2 physician-reviewers to determine whether it constituted a warfarin-related event, its severity, and its preventability. The primary outcome was an adverse warfarin-related event, defined as an injury associated with the use of warfarin. Potential adverse warfarin-related events were defined as situations in which the international normalized ratio (INR) was noted to be 4.5 or greater, an error in management was noted, but no injury occurred. We also assessed time in specified INR ranges per nursing home resident day on warfarin.
RESULTS
Over the 12-month observation period, 720 adverse warfarin-related events and 253 potential adverse warfarin-related events were identified. Of the adverse warfarin-related events, 625 (87%) were characterized as minor, 82 (11%) were deemed serious, and 13 (2%) were life-threatening or fatal. Overall, 29% of the adverse warfarin-related events were judged to be preventable. Serious, life-threatening, or fatal events occurred at a rate of 2.49 per 100 resident-months; 57% of these more severe events were considered preventable. Errors resulting in preventable events occurred most often at the prescribing and monitoring stages of warfarin management. The percentages of time in the less than 2, 2 to 3, and more than 3 INR ranges were 36.5%, 49.6%, and 13.9%, respectively.
CONCLUSIONS
The use of warfarin in the nursing home setting presents substantial safety concerns for patients. Adverse events associated with warfarin therapy are common and often preventable in the nursing home setting. Prevention strategies should target the prescribing and monitoring stages of warfarin management.
|
10.1016/j.amjmed.2006.07.045
|
pubmed_317_24430
|
BACKGROUND
Currently, there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterize allergic reactions to non-pre-packed foods and to investigate whether staff in bakery shops were able to give advice regarding a safe product choice.
METHODS
Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 bakery shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as 'cow's milk-free' were bought, and cow's milk protein levels were measured using ELISA.
RESULTS
A total of 104 of 200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from bakery shops and 20% from ice cream parlours. Sixty percent of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. Eighty four percent of the staff felt able to advise food-allergic consumers regarding a safe product choice. Seventy three 'cow's milk-free' products were sold in 44 bakery shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving.
CONCLUSION
Staff in bakery shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as 'cow's milk-free'. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk-allergic children will show clinical relevant symptoms.
|
10.1111/all.12588
|
pubmed_44_9582
|
OBJECTIVE
To determine the prevalence of experiencing intra-familial violence among Mexican and Egyptian youth and to describe its associated risk factors.
METHODS
Data from questionnaires applied to 12,862 Mexican and 5,662 Egyptian youth, aged 10 to 19, who attended public schools were analyzed. Biviarate and logistic regression analysis were used to determine the relationship between socio-demographics, the experience of intra-familial violence and violence perpetration.
RESULTS
The prevalence of having experienced intra-familial violence was comparable across the Mexican and Egyptian populations (14% and 17%, respectively). In Mexico, young men were more likely to have experienced such violence (OR=2.36) than women, whereas in Egypt, young women were at slightly greater risk than young men (OR=1.25). Older age, male gender and urban residence were independent correlates of experiencing intra-familial violence among Mexican youth. For Egyptian adolescents, in contrast, younger age, female gender and having non-married parents were independent correlates of victimization. Intra-familial violence victims were also more likely than non-victims to perpetrate violence (Mexico: OR=13.13; Egypt: OR=6.58).
CONCLUSIONS
Mexican and Egyptian youth experienced intra-familial violence at a relatively low prevalence when compared with youth of other countries. A strong association was found between experiencing intra-familial violence and perpetrating violence.
|
10.1590/s0034-89102005000500003
|
pubmed_747_11662
|
The functional state of the hypothalamo-pituitary-thyroid axis was assessed in 14 women and girls with anorexia nervosa when at low body weight and again in 12 cases after they had gained weight. Mean serum thyroxine concentrations were low before and after weight gain. Mean serum triiodothyronine (T3) concentrations were substantially reduced at low weight and doubled after weight gain, the absolute values being linearly correlated with body weight expressed as a percentage of the ideal. Concentrations of reverse T3 were greatly increased in some patients initially and fell with weight gain. Basal concentrations of thyroid-stimulating hormone (TSH) were unchanged after weight gain but the TSH response to thyrotrophin-releasing hormone was significantly augmented; delayed patterns of response were found in seven out of 12 patients tested before and three out of 12 patients tested after weight gain. Changes in the hypothalamo-pituitary-thyroid axis are common in anorexia nervosa and probably represent both peripheral and central adaptations to the altered nutritional state.
|
10.1136/bmj.2.6136.526
|
pubmed_67_12883
|
Background
Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration.
Methods
Cochrane, Embase, MEDLINE, and Open-Gray were searched. Parameters such as changes in oxygen saturation, cavo-pulmonary pressure, maximum heart rate during exercise, exercise duration, and oxygen saturation after fenestration closure were pooled and statistical analysis performed.
Results
Among 922 publications, 12 retrospective observational studies were included. The included studies involved 610 patients, of which 552 patients (90.5%) had a fenestration. Of those patients, 505 patients (91.5%) underwent attempt at trans-catheter closure. When it could be estimated, the pooled overall mean age at trans-catheter fenestration closure was 6.6 ± 7.4 years, and the mean follow-up time was 34.4 ± 10.7 months. There were 32 minor (6.3%) and 20 major (4.0%) complications during or after trans-catheter Fontan fenestration closure. The forest plots demonstrate that following fenestration closure, there was a significant increase in the mean arterial oxygen saturation of 7.9% (95% CI 6.4-9.4%, p < 0.01). There was also a significant increase in the mean cavo-pulmonary pressure of 1.4 mmHg (95% CI 1.0-1.8 mmHg, p < 0.01) following fenestration closure. The exercise parameters reported in 3 studies also favored closing the fenestration as well, yet the exercise duration increase of 1.7 min (95% CI 0.7-2.8 min, p < 0.01) after fenestration closure is probably clinically insignificant.
Conclusion
Late closure of a Fontan fenestration has the impact of improving resting oxygen saturation, exercise oxygen saturation, and a modest improvement of exercise duration. These clinical benefits, however, may be at the expense of tolerating slightly higher cavo-pulmonary mean pressures.
|
10.3389/fped.2022.915045
|
pubmed_2_8776
|
ETHNOPHARMACOLOGICAL RELEVANCE
The use of African chewing sticks in maintaining oral health is widely practiced in African countries. It has been reported that chewing stick users have a lower rate of dental caries and a better general oral health than non-users. It is generally thought that the beneficial effect of chewing stick is attributed to the mechanical cleansing effect and antimicrobial substances present in the stick. However, the active antimicrobial substances remain uncharacterized.
AIM OF THE STUDY
To provide a scientific basis for the anti-caries effect of African chewing sticks, the authors purify an active antibacterial compound from Garcinia kola Heckel, a Nigerian chewing stick and examined the antibacterial activity of this compound against the cariogenic bacterium Streptococcus mutans.
MATERIALS AND METHODS
Methanol extract was prepared from Garcinia kola and was further fractionated by solvent extractions. Silica gel chromatography was used to purify the antibacterial compound from the active fraction. The identity of the purified compound was determined by NMR analysis. The antibacterial activity of the purified compound was examined by standard microbiological assays.
RESULTS
The antibacterial activity was found in the ether fraction and the active compound was isolated and determined to be a biflavonoid named GB1. GB1 was active against Streptococcus mutans and other oral bacteria with minimum inhibitory concentration (MIC) values of 32-64μg/ml. The basis for the antibacterial effect of GB1 was investigated using Streptococcus mutans as the target. At 256μg/ml, GB1 exhibited some bacteriocidal activity against Streptococcus mutans and induced the aggregation of Streptococcus mutans. GB1 has no apparent effects on protein synthesis and DNA synthesis but inhibited glucose uptake and utilization by Streptococcus mutans suggesting that GB1 exerts its antibacterial effect by inhibiting metabolism. GB1 also inhibited the formation of water-insoluble glucan by the extracellular glucosyltransferases from Streptococcus mutans in a dose-dependent manner. Streptococcus mutans did not develop resistance to GB1 upon subculturing in the presence of sub-MIC level of the biflavonoid.
CONCLUSION
The antibacterial effect and glucan synthesis-inhibition property of this biflavonoid may account for some of the beneficial effects reported in the chewing stick users.
|
pubmed_2_8776
|
pubmed_806_8397
|
We here present and characterize a programmable nanoliter scale droplet-on-demand device that can be used separately or readily integrated into low cost single layer rapid prototyping microfluidic systems for a wide range of user applications. The passive microfluidic device allows external (off-the-shelf) electronically controlled pinch valves to program the delivery of nanoliter scale aqueous droplets from up to 9 different inputs to a central outlet channel. The inputs can be either continuous aqueous fluid streams or microliter scale aqueous plugs embedded in a carrier fluid, in which case the number of effective input solutions that can be employed in an experiment is no longer strongly constrained (100 s-1000 s). Both nanoliter droplet sequencing output and nanoliter-scale droplet mixing are reported with this device. Optimization of the geometry and pressure relationships in the device was achieved in several hardware iterations with the support of open source microfluidic simulation software and equivalent circuit models. The requisite modular control of pressure relationships within the device is accomplished using hydrodynamic barriers and matched resistance channels with three different channel heights, custom parallel reversible microfluidic I/O connections, low dead-volume pinch valves, and a simply adjustable array of external screw valves. Programmable sequences of droplet mixes or chains of droplets can be achieved with the device at low Hz frequencies, limited by device elasticity, and could be further enhanced by valve integration. The chip has already found use in the characterization of droplet bunching during export and the synthesis of a DNA library.
|
10.1063/1.4907895
|
pubmed_1102_10231
|
BACKGROUND
One of the challenges to surgical reconstruction following oncologic proximal femur resection is reliable re-establishment of the abductor mechanism. Surgical and functional outcomes following re-approximation of the abductor mechanism to a metallic endoprosthetic after tumor resection of the proximal femur have not been well established in the literature.
METHODS
A retrospective review was performed, inclusive of patients who received a proximal femur replacement with a metallic endoprosthesis following tumor resection. Patients were divided into two groups: (1) those that received an abductor repair involving a trochanteric osteotomy and osseous fixation of the greater trochanter/abductor mechanism to the endoprosthesis, and (2) those that did not have a trochanteric osteotomy and therefore had an abductor repair consisting of only soft tissue reattachment to the endoprosthesis. The two groups were assessed for demographic characteristics, diagnosis, surgical outcomes including rates of complication and failure, radiographic evidence of trochanteric failure, and functional outcomes. Descriptive statistics, comparative statistics, and logistic regression analyses were performed to discern differences between the two study groups.
RESULTS
Fifty-three patients were included in the analysis, 29 had abductor reconstructions involving reattachment of the greater trochanter to the metallic endoprosthesis and 24 had soft tissue reconstruction of the abductor mechanism without bony fixation. There were no differences between the two groups for demographic data, cancer diagnosis, follow up, or survivorship. Radiographic evidence of trochanteric dissociation from the endoprosthesis was observed in 45% of osteotomy cases. Only 10% of patients in the trochanter osteotomy group and 38% of the soft tissue only group were able to resume a normal, non-Trendelenburg gait at final postoperative visit (p = .024). Need for an assistive ambulatory device was seen in 83% and 67% of the osteotomy and soft-tissue-only patients, respectively (p = .21).
CONCLUSION
Re-establishing the abductor mechanism following proximal femur oncologic resection remains a challenge to orthopedic oncologists. Even when possible, salvage of the greater trochanter for reattachment to the endoprosthesis did not lead to improved function in this series, when compared to a similar cohort that received a soft-tissue-only abductor repair. Abductor mechanism reconstruction with a greater trochanteric osteotomy and subsequent fixation to the proximal femur endoprosthesis had a high rate of radiographic failure. Additionally, reattachment of the greater trochanter to the proximal femur endoprosthesis demonstrated no improvement in Trendelenburg gait or reliance on an assistive ambulatory device when compared to a soft-tissue-only abductor repair.
|
10.1002/jso.26477
|
pubmed_241_4363
|
PURPOSE
The aim of the study was to examine the role of neuroticism and mastery in predicting the quality of life (QOL) among Chinese gynecologic cancer survivors.
METHODS
A total of 184 women participated in this prospective longitudinal study. Participants were to rate their quality of life at baseline (T1) and one year later (T2). Neuroticism as a predictor of QOL was examined by controlling for baseline QOL, sociodemographic, and disease variables using hierarchical linear regression modeling. Mastery as a mediator between the relationship of neuroticism and QOL was also examined.
RESULTS
Bivariate correlations showed that the cancer site, time since diagnosis, neuroticism, and mastery at T1 were related to various aspects of QOL at T1 and T2. After controlling for cancer site, time since diagnosis, QOL at T1, high levels of neuroticism at T1 predicted poor physical and emotional QOL at T2, but mastery at T1 did not mediate the relationship between neuroticism at T1 and QOL at T2.
CONCLUSIONS
Neuroticism is a salient personality variable that predicts poor emotional and physical well-being over time. Gynecologic cancer survivors high on neuroticism should be the target for intervention to reduce negative effects during the course of recovery.
|
10.1007/s11136-010-9657-x
|
pubmed_760_18486
|
In this report, we demonstrate that Brachypodium distachyon could serve as a relatively high throughput in planta functional assay system for Triticeae anther-specific gene promoters. There remains a vast gap in our knowledge of the promoter cis-acting elements responsible for the transcriptional regulation of Triticeae anther-specific genes. In an attempt to identify conserved cis-elements, 14 pollen-specific and 8 tapetum-specific Triticeae putative promoter sequences were analyzed using different promoter sequence analysis tools. Several cis-elements were found to be enriched in these sequences and their possible role in gene expression regulation in the anther is discussed. Despite the fact that potential cis-acting elements can be identified within putative promoter sequence datasets, determining whether particular promoter sequences can in fact direct proper tissue-specific and developmental gene expression still needs to be confirmed via functional assays preferably performed in closely related plants. Transgenic functional assays with Triticeae species remain challenging and Brachypodium distachyon may represent a suitable alternative. The promoters of the triticale pollen-specific genes group 3 pollen allergen (PAL3) and group 4 pollen allergen (PAL4), as well as the tapetum-specific genes chalcone synthase-like 1 (CHSL1), from wheat and cysteine-rich protein 1 (CRP1) from triticale were fused to the green fluorescent protein gene (GFP) and analyzed in transgenic Brachypodium. This report demonstrates that this model species could serve to accelerate the functional analysis of Triticeae anther-specific gene promoters.
|
10.1007/s00425-016-2612-5
|
pubmed_44_3290
|
The aim of the present work is to link the bioprotective effectiveness to the dynamic properties of a class of homologous disaccharides, that is, trehalose, maltose and sucrose, and their mixtures in water. The findings obtained by elastic neutron scattering point out a harmonic-anharmonic transition for all the three disaccharide mixtures. Using a new operative definition of 'fragility', the different degrees of 'strength' of the investigated systems are determined. The links existing between the degree of fragility and the cryptoprotective action are also discussed.
|
10.1016/j.carres.2005.09.026
|
pubmed_916_19799
|
miR-122 is the predominant liver miRNA that regulates hepatic lipid metabolism and inflammation. Hepatitis C virus (HCV) modulates host intracellular lipid metabolism. HCV stability and propagation also depend on an interaction between virus and miR-122. Our aims were to examine the associations between miR-122, apolipoproteins, and serum makers of fibrosis in chronic hepatitis C (CHC) patients. We evaluated baseline sera from 36 CHC genotype 1 patients who completed the Phase IIa study of miravirsen (LNA oligonucleotide targeting miR-122). Samples were assessed for liver transaminases, IL 28B genotype, IP-10, and lipid profiles. The noninvasive markers of liver fibrosis, APRI, and FIB-4, were calculated using standard formulae. miR-122 levels were measured using RT-PCR and expressed as fold-change compared to normal healthy controls. CHC patients were mostly male (61%) with mean age 47.5 ± 11.6 years. Patients with higher ApoB (ApoB/ULN ≥ 0.5) has significantly lower miR-122 levels in compared to patients with lower ApoB (ApoB/ULN < 0.5). (8.28 ± 6.23 vs. 16.28 ± 13.71; P = 0.02). There were no similar associations between miR-122 and ApoA-1 or between HCV RNA and lipoproteins. There were no differences in miR-122 levels between patients with different stages of fibrosis determined by APRI or FIB-4. Patients with lower ApoB had higher serum miR-122 levels. However, we cannot identify significant association between miR-122, ApoA-1, or fibrosis markers in this small cohort of CHC genotype 1 patients. The mechanism of HCV dyslipidemia is complex and could partly relate to the effect of miR-122 on lipid metabolism which requires further evaluation in a larger study.
|
10.1002/jmv.24230
|
pubmed_191_3739
|
2-Hydroxymethyl-1,4-dioxane 3 was resolved via salt formation between its hydrogen phthalate and (R)- or (S)-1-phenylethylamine, selective crystallization of the resultant diastereomeric mixtures and subsequent recovery of its enantiomers by saponification. The progress of the resolution was followed by chiral HPLC and the absolute stereochemistry of the two enantiomers determined by comparison of their specific rotations with that of (R)-3 synthesized from enantiomerically pure (R)-1-O-benzylglycerol. The results of the synthesis of 3 and of its resolution are discussed and compared with those previously obtained for 1,2-isopropylidene glycerol evaluating the consequences of replacement of ispropylidene with an ethylene bridge.
|
pubmed_191_3739
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.