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pubmed_362_5896
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BACKGROUND
Non-infectious retinal disease, even in the HAART era, continues to be one of the most common diagnoses in patients with HIV, with prevalences of up to 27% of cases. This study aims to characterize the association between demographic variables and their role. As a risk factor for the development of non-opportunistic non-infectious retinal disease in patients with HIV/AIDS.
METHODS
An integrative review of the literature was carried out according to Arksey O'Malley's approach, based on the PICO methodology and following the PRISMA recommendations; An exhaustive search was carried out in databases of articles that were filtered using established criteria, with their extraction and analysis carried out qualitatively.
RESULTS
Ocular manifestations from any cause develop from 35 years of age in patients with HIV/AIDS, with the highest risk for age-related macular degeneration over the fourth decade of life and for the development of neuroretinal disorder on the fifth decade of life; some studies report a slight tendency to diagnose macular degeneration in women and those who acquired AIDS through sexual contact; data contrasted with increased risk for diagnosing neuroretinal disorder in homosexual men who also use intravenous drugs, possibly due to oversampling in studies; non-Hispanic whites and African Americans were the races most commonly affected by neuroretinal disease; the means between the 11.3-14.5 years elapsed since the HIV diagnosis were more frequently associated with cognitive impairment and both in those with high or low CD4 counts, and in patients with high or low viral loads, neuroretinal disease without Statistically significant differences. Adherence and early initiation of HAART had a modest impact on the development of neuroretinal disease.
DISCUSSION
Even in the HAART era, non-infectious neuroretinal disease and cytomegalovirus retinitis remain the most frequent ocular diagnoses, however, different studies argue an increase in age-related non-infectious retinal diseases in patients with HIV, theories that are may explain by the increase in life expectancy, the metabolic effects of HAART itself or the generalized pro-inflammatory state in this group of patients, it is essential to recognize this new diagnostic challenge in order to direct preventive efforts through the use of cost-effective sociodemographic risk predictors towards that technological tools for diagnosis and treatment can be targeted.
CONCLUSIONS
HIV/AIDS patients who present at the ophthalmological consultation with the suggested sociodemographic predictors have a high risk of visual impairment due to non-infectious retinopathy, therefore prevention, diagnosis and treatment efforts directed at these diseases should be increased.
|
10.1016/j.oftale.2020.11.019
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pubmed_72_10864
|
It is still not very clear what roles the various Ag species play in the toxicity of silver nanoparticles (AgNPs). In this study, we found that traditional exposure media result in uncontrollable but consistent physicochemical transformation of AgNPs, causing artifacts in determination of median lethal concentration (LC50) and hindering the identification of Ag species responsible for the acute toxicity of AgNPs to Daphnia magna. This obstacle was overcome by using 8 h exposure in 0.1 mmol L(-1) NaNO3 medium, in which we measured the 8-h LC50 of seven AgNPs with different sizes and coatings, and determined the concentrations of various Ag species. The LC50 as free Ag(+) of the seven AgNPs (0.37-0.44 μg L(-1)) agreed very well with that of AgNO3 (0.40 μg L(-1)), and showed the lowest value compared to that as total Ag, total Ag(+), and dissolved Ag, demonstrating free Ag(+) is exclusively responsible for the acute toxicity of AgNPs to D. magna, while other Ag species in AgNPs have no contribution to the acute toxicity. Our results demonstrated the great importance of developing appropriate exposure media for evaluating risk of nanomaterials.
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10.1038/srep09674
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pubmed_798_4496
|
Molecular investigations of the sulfate reducing bacteria that target the dissimilatory sulfite-reductase subunit A gene (dsr A) are plagued by the nonspecific performance of conventional PCR primers. Here we describe the incorporation of the FailSafe PCR System to optimize environmental analysis of dsr A by PCR amplification and denaturing gradient gel electrophoresis. PCR-DGGE analysis of dsr A composition revealed that SRB diversity was greater and more variable throughout the vertical profile of a marine sediment core obtained from a gas hydrate site (GC234) in the Gulf of Mexico than in a sediment core collected from a nearby site devoid of gas hydrates (NBP). Depth profiled dsr B abundance corresponded with sulfate reduction rates at both sites, though measurements were higher at GC234. This study exemplifies the numerical and functional importance of sulfate reducing bacteria in deep-sea sedimentary environments, and incremental methodological advancements, as described herein, will continue to streamline the analysis of sulfate reducer communities in situ.
|
10.1002/jobm.200800278
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pubmed_687_16960
|
STUDY DESIGN
Cross-sectional study.
PURPOSE
The purpose of this study was to elucidate the relevance among Schmorl's node (SN), chronic low back pain (CLBP), and intervertebral disc degeneration (IVDD) with the use of magnetic resonance imaging T2 mapping.
OVERVIEW OF LITERATURE
SN may be combined with CLBP and/or IVDD; however, their relationship has not been determined to date.
METHODS
A total of 105 subjects were included (48 men and 57 women; mean age, 63.2±2.7 years; range, 22-84 years). We analyzed five functional spinal unit levels (L1-S1) and evaluated the T2 values of the anterior annulus fibrosus (AF), nucleus pulposus, and posterior AF. We compared the low back pain (LBP) Visual Analog Scale (VAS) scores and the T2 values in each decade with or without SN.
RESULTS
There were no remarkable differences in SN prevalence rate regarding age decade or gender. SNs were more prevalent in the upper 2 levels (70.3%). LBP VAS scores with and without SN were 64.7±4.3 mm and 61.9±2.8 mm, respectively, with no significant differences between the groups (p=0.62). The T2 values of anterior AF with SN were significantly lower than those without SN in patients in their 50s, 60s, 70s, and 80s (p<0.01).
CONCLUSIONS
SN presence is not itself a risk factor for CLBP; however, it indicates IVDD of the anterior AF in subjects with SN who are ≥50 years old.
|
10.31616/asj.2019.0231
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pubmed_827_882
|
UNLABELLED
The aim of the present study was to evaluate the efficacy of the immunostimulating therapy with a new vaccine Ismigen in preventing recurrent infections of the upper respiratory tract in subjects belonging to a community of cloistered nuns. This product is a lysate obtained by mechanical lysis of bacteria (MLBL) usually responsible of respiratory tract infections. A randomized, double-blind, parallel groups, placebo controlled clinical trial was carried out in 47 nuns (age range 25-80 years) living in a cloistered religious community, suffering from recurrent infections of the upper respiratory tract. The 47 patients were allocated by randomization to two groups: Group A--The 24 patients (mean age SD: 48.12 +/- 14.25 years) of this group received one sublingual tablet of MLBL per day, for 10 consecutive days per month for 3 consecutive months (October, November and December 2001). Group B--The 23 patients (mean age +/- SD: 49.04 +/- 14.73 years) of this group received daily one sublingual tablet of taste masked placebo, for 10 consecutive days per month for 3 consecutive months (October, November and December 2001). At the end of the treatment period patients of both groups were followed up for further three months without any immunostimulating treatment.
RESULTS
During and at the end of the treatment phase the number of respiratory infections (primary end-point) and their duration were statistically significantly lower in the MLBL group than in the placebo group. Moreover the administration of MLBL induced a marked reduction in the number of patients showing symptoms of infection in comparison to baseline and approximately 79 % of the patients showed an improvement of one or more of the evaluated symptoms. In the MLBL group a statistically significant increase of serum immunoglobulins (IgG +35%; IgM +86%; IgA +80 %) and salivary IgA (+110%) was found, in comparison to baseline; on the contrary no significant differences were observed in the placebo group. The beneficial effects of MLBL found in the treatment period were maintained also in the three-month follow-up. No adverse events associated with the treatment were found in both group. The results of this study demonstrate that MLBL is an efficacious and safe therapeutic option for the treatment and prevention of recurrent upper respiratory tract infections and that its use is recommended in subjects with a possible immune deficit.
|
10.1055/s-0031-1296937
|
pubmed_410_23569
|
OBJECTIVE
In this review, we investigate the relationship between agent transparency, Situation Awareness, mental workload, and operator performance for safety critical domains.
BACKGROUND
The advancement of highly sophisticated automation across safety critical domains poses a challenge for effective human oversight. Automation transparency is a design principle that could support humans by making the automation's inner workings observable (i.e., "seeing-into"). However, experimental support for this has not been systematically documented to date.
METHOD
Based on the PRISMA method, a broad and systematic search of the literature was performed focusing on identifying empirical research investigating the effect of transparency on central Human Factors variables.
RESULTS
Our final sample consisted of 17 experimental studies that investigated transparency in a controlled setting. The studies typically employed three human-automation interaction types: responding to agent-generated proposals, supervisory control of agents, and monitoring only. There is an overall trend in the data pointing towards a beneficial effect of transparency. However, the data reveals variations in Situation Awareness, mental workload, and operator performance for specific tasks, agent-types, and level of integration of transparency information in primary task displays.
CONCLUSION
Our data suggests a promising effect of automation transparency on Situation Awareness and operator performance, without the cost of added mental workload, for instances where humans respond to agent-generated proposals and where humans have a supervisory role.
APPLICATION
Strategies to improve human performance when interacting with intelligent agents should focus on allowing humans to see into its information processing stages, considering the integration of information in existing Human Machine Interface solutions.
|
10.1177/00187208221077804
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pubmed_332_22214
|
Participation--defined as engagement in life situations, including leisure and recreational activities--is associated with the improvement of people with disabilities' quality of life. Several specific instruments assess leisure, but none of them has been adapted to the Spanish context. The goal of this study is to adapt and validate the Spanish version of the Leisure Assessment Inventory (LAI; B. A. Hawkins, P. Ardovino, N. B. Rogers, A. Foose, & N. Olsen, 2002 ). The adaptation of the original version of the LAI was carried out through translation and backward translation, and the validity of the instrument was analyzed. Descriptive analyses (means and standard deviations) were conducted for each LAI index. Construct validity was assessed through Pearson's product-moment correlation among the diverse LAI indexes, and convergent-discriminant validity through the correlation of the diverse indexes and the measures of quality of life. Results show that the LAI indexes are valid measures of the attributes of leisure behavior (participation, preference, interest, and barriers). This study provides a valid instrument to assess the participation profile of adults with disabilities in leisure activities.
|
10.1352/1934-9556-50.3.233
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pubmed_419_12718
|
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.
|
10.3390/cancers14215246
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pubmed_211_14460
|
Investigated the association between negative life events and protective factors in predicting the adaptive, emotional, and behavioral functioning of school-age children. Three possible models of this relation were tested using hierarchical analyses: the compensatory model, the challenge model, and the immunity/vulnerability model. Participants were 140 children between the ages of 8 to 13.6 years. Inconsistent with all 3 models, negative life events were not associated with adaptive or internalizing behavior. However, consistent with the compensatory model, both negative life events and protective factors contributed independently to the prediction of externalizing behavior. Also, a significant interaction was found in predicting internalizing behavior for the female-only sample showing girls with significant negative life events and social support demonstrating less internalizing behavior.
|
10.1207/s15374424jccp2704_1
|
pubmed_973_17728
|
The National Association of County and City Health Officials (NACCHO) is the national organization representing local health departments. It supports efforts that protect and improve the health of all people and all communities by promoting national policy, developing resources and programs, seeking health equity, and supporting effective local public health practice and systems.
|
10.1097/PHH.0b013e3181d0d057
|
pubmed_385_13063
|
Ultrasonic effects on the cathodic debromination of stilbenedibromides on a platinum cathode was examined. Current efficiency and stereoselectivity for trans-stilbene, which was formed along with cis-stilbene in the cathodic debromination of stilbenedibromides, were significantly increased under ultrasonication with an intensity over the ultrasonic cavitation threshold. This ultrasonic effect is rationalized as due to mass transport promotion in the electrode-electrolytic solution interface. A mechanism for the ultrasonic effect is discussed in detail on the basis of the reaction pathway of the debromination of stilbenedibromides.
|
10.1016/j.ultsonch.2004.03.006
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pubmed_495_9108
|
Two atypical serological markers of hepatitis B virus (HBV) infection were detected in 19 patients during a 18-month period study. Pattern 1 (10 patients) was consistent with HBV-2 infection. Reactivity of HbsAG was confirmed by neutralization tests; the absence of other markers was also verified, included anti-HBcIgM. Three of the patients were classified in high risk groups and seven in the low risk groups for hepatitis B; in none of them was co-infection with hepatitis A virus (HAV) detected. Pattern 2 (9 patients) was characterized by the detection of HBsAg and HBeAg and the absence of other hepatitis B markers. Six of these patients were HIV-positive patients and had increased and persistent levels (for longer than 12 weeks) of these markers. In the three remaining patients (with no underlying immunological disorders) there was a loss of these markers within a variable time (2 days to 16 weeks). Nevertheless, DNA-VHB was detected in one of these serum samples once all markers of virus B had disappeared.
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pubmed_495_9108
|
pubmed_1033_13336
|
The norA gene, which is located on the chromosome of Staphylococcus aureus, encodes the multidrug efflux protein with 12 transmembrane segments (TMS), and the overexpression of norA by the mutation of the transcriptional control region confers resistance to fluoroquinolones and antiseptics. In this study, the nucleotide sequence and transcriptional expression of norA genes were studied in six standard laboratory strains and 15 clinical isolates, which included 5 antiseptic-susceptible strains and 10 resistant strains. Seven mutations leading to up-regulation of norA transcription were identified. In addition, a novel allele of norA (norAII) was identified whose 3'-terminal region sequence and profile of antimicrobial susceptibility differs from those of original norA.
|
10.1089/mdr.2004.10.197
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pubmed_109_10737
|
Cerebrospinal fluid and serum immunoglobulins were studied in 76 patients with acute meningitis of various aetiologies. This comparative study showed that the increase of CSF immunoglobulin levels was related to important modifications of the permeability of the blood-brain barrier (especially in case of bacterial meningitis) or to a local in situ production (particularly in case of "viral" meningitis). Results obtained allow us to draw a different biochemical pattern in purulent meningitis and acute lymphocytic meningitis.
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pubmed_109_10737
|
pubmed_1040_11726
|
A two-year-old boy and his mother with the Tricho-Rhino-Phalangeal syndrome type I were studied. The mother showed the complete triad of the syndrome with fine, sparse, slow-growing hair, pear-shaped nose and abnormal fingers. Cone-shaped epiphyses of the phalanges of the hands and shortening of the mesophalanges and of the first and fifth metacarpals were observed radiographically. With the exception of the extreme shortening of several phalanges and metacarpals the above mentioned symptoms were also present in the son.
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pubmed_1040_11726
|
pubmed_1104_12025
|
STUDY OBJECTIVES
To examine the effects of hydroxyethyl starch (HES) on renal function.
DESIGN
Randomized, controlled trial.
SETTING
Operating theatre of a university hospital.
PATIENTS
60 ASA physical status I and II male patients undergoing middle ear surgery.
INTERVENTIONS
Patients received either lactated Ringer's solution (LRS) or one of three HES solutions. The HES solutions were administered in a dose of 15 mL/kg bodyweight (bw), the Ringer's solution in a dose of 60 mL/kg bw, after induction of anesthesia over a period of one hour.
MEASUREMENTS
Blood and urine samples for hormone and enzyme tests were obtained at defined times before, during, and after surgery. Urine excretion, glomerular filtration rate (GFR), renal plasma flow, and routine hemodynamic parameters were measured simultaneously.
MAIN RESULTS
There were no significant intergroup differences regarding GFR, renal plasma flow, or tubular and glomerular integrity as measured by specific proteins and enzymes (alpha-1-microglobulin, Tamm-Horsfall-protein, immunoglobulin G, and N-acetyl-beta-D-glucosaminidase). Arginine vasopressin decreased in all groups during and following anesthesia, aldosterone and plasma renin activity decreased only in the HES groups, and angiotensin II decreased only in the HES 200/0.5 group. Central venous pressure increased during fluid administration in the LRS group and returned to baseline sooner in the HES groups.
CONCLUSIONS
Hydroxyethyl starch administration appears to be risk-free with regard to renal function in patients without preexisting renal dysfunction who undergo general anesthesia. The relevance of the decrease in aldosterone following HES therapy needs further investigation.
|
10.1016/s0952-8180(01)00225-2
|
pubmed_422_9677
|
The retinal rod Na/Ca-K exchanger (NCKX) is a unique calcium extrusion protein utilizing both inward sodium gradient and outward potassium gradient. Three mammalian rod NCKX cDNAs have been cloned to date, but quantitative analysis of NCKX function in heterologous systems has proven difficult. Here, we describe a simple system for quantitative analysis of NCKX function; stable transformation of cultured insect cells with the novel pEA1/153A vector containing NCKX cDNAs was combined with measurements of potassium-dependent (45)Ca uptake in sodium-loaded cells. We carried out structure-function studies on NCKX with the following results: 1) two-thirds of the full-length sequence of bovine NCKX could be deleted without affecting potassium-dependent calcium transport and without affecting key properties of the potassium binding site; 2) the affinity of NCKX for potassium was about 10-fold greater in choline medium when compared with lithium medium; this shift was observed in rod outer segments or in cells expressing full-length rod NCKX, the above deletion mutant, or a distantly related NCKX paralog cloned from Caenorhabditis elegans. We conclude that the potassium binding site is highly conserved among members of the NCKX family and is formed by residues located within the two sets of transmembrane spanning segments in the NCKX sequence.
|
10.1074/jbc.275.1.669
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pubmed_189_23333
|
BACKGROUND
The development of Cone-beam X-ray luminescence computed tomography (CB-XLCT) has allowed the quantitative in-depth biological imaging, but with a greatly ill-posed and ill-conditioned inverse problem. Although the predefined permissible source region (PSR) is a widely used way to alleviate the problem for CB-XLCT imaging, how to obtain the accurate PSR is still a challenge for the process of inverse reconstruction.
METHODS
We proposed an optimized prior knowledge via a sparse non-convex approach (OPK_SNCA) for CB-XLCT imaging. Firstly, non-convex Lp-norm optimization model was employed for copying with the inverse problem, and an iteratively reweighted split augmented lagrangian shrinkage algorithm was developed to obtain a group of sparse solutions based on different non-convex p values. Secondly, a series of permissible regions (PRs) with different discretized mesh was further achieved, and the intersection operation was implemented on the group of PRs to get a reasonable PSR. After that, the final PSR was adopted as an optimized prior knowledge to enhance the reconstruction quality of inverse reconstruction.
RESULTS
Both simulation experiments and in vivo experiment were performed to evaluate the efficiency and robustness of the proposed method.
CONCLUSIONS
The experimental results demonstrated that our proposed method could significantly improve the imaging quality of the distribution of X-ray-excitable nanophosphors for CB-XLCT.
|
10.1016/j.cmpb.2022.106645
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pubmed_211_7838
|
Several proteins with significant identity to ubiquitin have been characterized recently. In contrast to ubiquitin's main role in targeting proteins for degradation, a described function of one family of ubiquitin-related proteins, the Rub family, is to serve as a stable post-translational modification of a complex involved in the G1-to-S cell cycle transition. Rub proteins have been found in animals, plants, and fungi and consist of 76 residues with 52-63% identity to ubiquitin. In this study three different RUB proteins within the plant Arabidopsis are identified; two differ by only 1 amino acid, while the third is only 77.6% identical to the other two. Genes encoding all three are expressed in multiple organs. In addition, we report the crystal structure of higher plant RUB1 at 1.7-A resolution to help elucidate the functional differences between Rub and ubiquitin. RUB1 contains a single globular domain with a flexible COOH-terminal extension. The overall RUB1 structure is very similar to ubiquitin. The majority of the amino acid differences between RUB1 and ubiquitin map to the surface. These changes alter the electrostatic surface potential in two regions and likely confer specificity between ubiquitin and RUB1 and their ubiquitin-activating enzyme (E1) or E1-like activating enzymes.
|
10.1074/jbc.273.52.34976
|
pubmed_297_7993
|
Chain pharmacies are expanding in many low and middle-income countries (LMICs). Historically practices of independent pharmacies in these settings have been poor, and there is a need to understand how these new organisational arrangements are affecting the functioning of pharmacies, and the implications for public health. Drawing on economics literature, we develop a set of hypotheses as to how chains could address the quality failures that typify LMIC retail pharmacy markets, and explore these hypotheses using a set of 38 in-depth interviews, conducted in Bengaluru, India between 2014 and 2015. We look specifically at how being organised in a chain affects several key behaviours: employment of qualified staff; the ability of government authorities to focus regulation on central management structures; the propensity for firms to self-regulate; and the impact of the potentially lower-powered incentives faced by chain employees compared to independent owners. In practice, few differences were identified between chain and independent organisations in these areas. Not all chains were operating with a qualified pharmacist (akin to independent shops). Drug control authorities did not take advantage of the existing chain architecture to enforce regulation. Chains did heavily self-regulate but their focus was on customer service, rather than aspects of quality relevant to health outcomes. Additionally, widespread bribery in the sector was a barrier to effective drug control. Finally, the incentives faced by chain employees were not low-powered due to rewarding sales targets and pressure to increase sales. We observed that chains exerted strong influence over their staff but the potential to exploit this to improve quality of care is not currently being realised. A shift in focus from customer satisfaction to outcomes of public health concern is unlikely without either financial incentives or strengthened external regulation.
|
10.1016/j.socscimed.2018.07.001
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pubmed_1111_14244
|
This study performed a bacteriological analysis of the liquid soap in dispensers that health professionals use for hand washing. This exploratory, cross-sectional study was developed at the hospitalization units of a medium-sized hospital in Fortaleza, Ceará, Brazil. Data were collected between May and July 2007. Fifty-nine liquid soap dispensers were analyzed, of which 33 contained the following microorganisms: Burkholderia cepacia (14), Pseudomonas putidas (9), Pseudomonas aeruginosa (3), Klebsiella pneumoniae (3), Enterobacter clocae (2), and Pseudomonas luteola (2). The units with the largest number of contaminated samples were the surgical (n=7) and the dermatological clinics (n=4). Contamination was also found in an original flask of the same lot of liquid soap used to fill up the dispensers. In conclusion, there is a need to regulate and control the quality of these products in the production lines as well as during use in hospital services, mainly because they are used to prevent hospital infection.
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pubmed_1111_14244
|
pubmed_155_7649
|
Despite the fact that mature SP10c DNA contains dTMP, the acid-soluble fraction of infected cells contained no dTTP during the interval of phage replication. However, infected cells contained normal cellular levels of dATP, dGTP, and dCTP. Upon infection of deoxythymidine-starved Bacillus subtilis M160 (a deoxythymidine-requiring mutant of B. subtilis W23), mature phage DNA with a normal dTMP content was made. SP10c codes for an enzyme that seems to catalyze the tetrahydrofolate-dependent transfer of 1-carbon fragments to the 5 position of dUMP. The transfer of 1-carbon fragments is not accompanied by oxidation of tetrahydrofolage to dihydrofolate, implying that the enzyme in question is not a dTMP synthetase. It is proposed that dTMP in mature SP10c DNA is derived by the postreplicational modification of some other nucleotide and not by the direct incorporation of dTTP into DNA.
|
10.1128/JVI.29.1.61-68.1979
|
pubmed_182_10836
|
PURPOSE
MRI has limited ability to detect multifocal disease or the full extent of prostate involvement with clinically significant prostate cancer (sPC). We compare the spatial co-localization at sextant resolution of MRI lesions and histopathological mapping by combined targeted and extended systematic biopsies.
MATERIALS AND METHODS
Sextants were mapped for sPC (ISUP group ≥ 2) by 24-core transperineal systematic biopsies in 316 patients with suspicion for sPC and by MR lesions of PI-RADS score of ≥ 3. The gold standard is combined systematic (median 23 cores) and targeted biopsies.
RESULTS
Of 316 men, 121 (38%) harbored sPC. Of these 121 patients, 4 (3%) had a negative MRI. MRI correctly identified 117/121 (97%) patients with sPC. In these patients, mpMRI missed no additional sPC in 96 (82%), while MRI-negative sPC lesions were present in 21 patients (18%). Of 1896 sextants, 379 (20%) harbored sPC. MR-positive sextants contained sPC in 26% (337/1275), compared to 7% (42/621) in MR-negative sextants. On a patient basis, sensitivity was 0.97, specificity 0.22, positive predictive value 0.43, and negative predictive value 0.91. On a sextant basis, sensitivity was 0.73, specificity 0.38, positive predictive value 0.26, and negative predictive value 0.93.
CONCLUSION
MpMRI mapping agreed well with histopathology with, at the observed sPC prevalence and on a patient basis, excellent sensitivity and negative predictive value, and acceptable specificity and positive predictive value for sPC. However, 18% of sPC was outside the mpMRI mapped region, quantifying limitations of MRI for complete localization of disease extent.
KEY POINTS
• Currently, exclusive MRI mapping of the prostate for focal treatment planning cannot be recommended, as significant prostate cancer may remain untreated in a substantial number of cases. • At the observed sPC prevalence and on a patient basis, mpMRI has excellent sensitivity and NPV, and acceptable specificity and PPV for detection of prostate cancer, supporting its use to detect suspicious lesions before biopsy. • Despite the excellent global performance, 18% of sPC was outside the mpMRI mapped region even when a security margin of 10 mm was considered, indicating that prostate MRI has limited ability to completely map all cancer foci within the prostate.
|
10.1007/s00330-018-5751-1
|
pubmed_839_10796
|
This paper describes an innovative sensing approach allowing capture, discrimination, and classification of transients automatically in gait. A walking platform is described, which offers an alternative design to that of standard force plates with advantages that include mechanical simplicity and less restriction on dimensions. The scope of the work is to investigate as an experiment the sensitivity of the distributive tactile sensing method with the potential to address flexibility on gait assessment, including patient targeting and the extension to a variety of ambulatory applications. Using infrared sensors to measure plate deflection, gait patterns are compared with stored templates using a pattern recognition algorithm. This information is input into a neural network to classify normal and affected walking events, with a classification accuracy of just under 90 per cent achieved. The system developed has potential applications in gait analysis and rehabilitation, whereby it can be used as a tool for early diagnosis of walking disorders or to determine changes between pre- and post-operative gait.
|
10.1243/09544119JEIM523
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pubmed_464_611
|
The sole member of the Piscihepevirus genus (family Hepeviridae) is cutthroat trout virus (CTV) but recent metatranscriptomic studies have identified numerous fish hepevirus sequences including CTV-2. In the current study, viruses with sequences resembling both CTV and CTV-2 were isolated from salmonids in eastern and western Canada. Phylogenetic analysis of eight full genomes delineated the Canadian CTV isolates into two genotypes (CTV-1 and CTV-2) within the Piscihepevirus genus. Hepevirus genomes typically have three open reading frames but an ORF3 counterpart was not predicted in the Canadian CTV isolates. In vitro replication of a CTV-2 isolate produced cytopathic effects in the CHSE-214 cell line with similar amplification efficiency as CTV. Likewise, the morphology of the CTV-2 isolate resembled CTV, yet viral replication caused dilation of the endoplasmic reticulum lumen which was not previously observed. Controlled laboratory studies exposing sockeye (Oncorhynchus nerka), pink (O. gorbuscha), and chinook salmon (O. tshawytscha) to CTV-2 resulted in persistent infections without disease and mortality. Infected Atlantic salmon (Salmo salar) and chinook salmon served as hosts and potential reservoirs of CTV-2. The data presented herein provides the first in vitro and in vivo characterization of CTV-2 and reveals greater diversity of piscihepeviruses extending the known host range and geographic distribution of CTV viruses.
|
10.3390/v13091730
|
pubmed_1080_2868
|
Restoration of damaged hepatocytes after ischemia was studied functionally and morphometrically in a rat model with partial hepatic vascular occlusion. In 30 min occlusion group (n = 35), ATP (mols/mg of protein) dropped down to nearly zero, but returned to the pre-ischemic level within 6 hours after reperfusion. The number of mitochondria (Mt)/unit area of cytoplasm (N/beta m2) increased to 1.41 times of the pre-ischemic value. Simultaneously, the area of single Mt decreased to 2/3 of the pre-ischemic value. Cellular necrosis and subsequent fibrosis were slight, not different from those of the controls. In 60 min occlusion group (n = 35), it took 14 days for ATP to return to the pre-ischemic level. An increase in the number of Mt and reduction in the Mt area, were slight compared with 30 min occlusion group. In contrast, necrosis and subsequent fibrosis markedly developed with a concomitant increase in lysosomes. In conclusion, it was suggested that, in 30 min of ischemia, active division of Mt, which is a compensatory mechanism of Mt reduced the degree in ischemic damage of hepatocytes, in contrast, in 60 min ischemia, division of mitochondria was limited, causing delayed recovery of ATP and severe necrotic change of hepatocytes.
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pubmed_1080_2868
|
pubmed_987_13662
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Type IV pili (T4P) are common bacterial surface appendages involved in different biological processes such as adherence, motility, competence, pathogenesis, and conjugation. In this work, we describe the T4P of TP114, an IncI2 enterobacterial conjugative plasmid recently shown to disseminate at high rates in the mouse intestinal tract. This pilus is composed of the major PilS and minor PilV pilins that are both important for conjugation in broth and in the gut microbiota but not on a solid support. The PilV-coding sequence is part of a shufflon and can bear different C-terminal domains. The shufflon is a multiple DNA inversion system containing many DNA cassettes flanked by recombination sites that are recognized by a shufflon-specific tyrosine recombinase (shufflase) promoting the recombination between DNA segments. The different PilV variants act as adhesins that can modify the affinity for different recipient bacteria. Eight PilV variants were identified in TP114, including one that has not been described in other shufflons. All PilV variants allowed conjugative transfer with different recipient Escherichia coli strains. We conclude that the T4P carried by TP114 plays a major role in mating pair stabilization in broth as well as in the gut microbiota and that the shufflon acts as a biological switch modifying the conjugative host range specificity. IMPORTANCE Conjugative plasmids are involved in horizontal gene transfer in the gut microbiota, which constitutes an important antibiotic resistance gene reservoir. However, the molecular mechanisms used by conjugative plasmids to select recipient bacteria and transfer at high rates in the mouse gut microbiota remain poorly characterized. We studied the type IV pilus carried by TP114 and demonstrated that the minor pilin PilV acts as an adhesin that can efficiently select target cells for conjugative transfer. Moreover, the pilV gene can be rapidly modified by a shufflon, hence modulating the nature of the recipient bacteria during conjugation. Our study highlights the role of mating pair stabilization for conjugation in broth as well as in the gut microbiome and explains how the host spectrum of a plasmid can be expanded simply by remodeling the PilV adhesin.
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10.1128/spectrum.02303-21
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pubmed_247_16773
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The relationship between mouse-protective activities against aerosol and intracerebral (i.c.) challenge with virulent B. pertussis organisms and pertussis toxin (PT)-neutralizing activities against ADP-ribosylation (ADPR), CHO cell-clustering (CC), leukocytosis-promoting (LP) and islet-activating (IA) activities of anti-PT antibody, was investigated using anti-PT mouse monoclonal antibodies (MAbs): ten anti-S1, four anti-S23, one anti-S2, two anti-S3, and three anti-S4 MAbs. All the anti-S1 MAbs neutralized ADPR activity of PT. Among them, six MAbs: 1B7, 1D7, 3F11, 10D6, 8G4 and E1E, showed mouse-protection in either an aerosol or i.c. challenge system. These protective MAbs neutralized both LP and IA activities but showed little or no neutralization against CC activity except for 1B7. All anti-S2 and/or S3 MAbs showed higher CC-neutralizing activity and protected the mice against the aerosol challenge, but very little against the i.c. challenge. The mouse-protection was not necessarily parallel to either PT-neutralizing activity or CC-neutralizing activity. The protective MAbs against S1, S2 and S3 decreased the number of bacteria and the amount of pertussis toxin in the lungs of mice challenged with the aerosol. These results suggest that the role of the anti-PT antibody in mouse-protection is not only neutralization of PT but also prevention of bacterial growth in the respiratory tract. Four anti-S1 and two anti-S4 MAbs showed neither neutralization nor protection. Competitive ELISA using the biotinylated MAbs suggested that four anti-S1 MAbs: 1B7, 1D7, 3F11 and 10D6, which showed the highest and almost complete mouse-protection, may recognize the same or closely related epitope(s) or areas on PT. The foregoing results suggested that prediction of the protection of MAbs only by the neutralizing activity against any one of the PT activities must be difficult and that competition ELISA may be helpful for such predictions.
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pubmed_247_16773
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pubmed_312_3485
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The activity of alveolitis in 25 patients with pulmonary sarcoidosis was determined by analysis of T-Lymphocytes and their subpopulations collected by broncho-alveolar lavage. The characterization of the lymphocytes was performed with monoclonal antibodies (BL-series). An amount of T-lymphocytes higher than 28% of all cells and a proportion of T4/T8-lymphocytes of 8:1 and over are signs of the activity of the alveolitis and an indication for corticoid therapy.
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pubmed_312_3485
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pubmed_589_10194
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Photonic bandgap fiber optic gyroscope (PBFOG) is a novel fiber optic gyroscope (FOG) with excellent environment adaptability performance compared to a conventional FOG. In this work we find and investigate the backward secondary-wave coherence (BSC) error, which is a bias error unique to the PBFOG and caused by the interference between back-reflection-induced and backscatter-induced secondary waves. Our theoretical and experimental results show a maximum BSC error of ~4.7°/h for a 300-m PBF coil with a diameter of 10 cm. The BSC error is an important error source contributing to bias instability in the PBFOG and has to be addressed before practical applications of the PBFOG can be implemented.
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pubmed_589_10194
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pubmed_192_8928
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INTRODUCTION
Patients with pre-existing autoimmune diseases have been excluded from clinical trials of immune checkpoint inhibitors (ICIs) for cancer. Real-world evidence is necessary to understand ICI safety in this population.
METHODS
Patients treated with ICIs from 2011 to 2017 were identified using data from a large health insurer. Outcomes included time to (1) any hospitalization; (2) any hospitalization with an irAE diagnosis; and (3) outpatient corticosteroid treatment. The key exposure was pre-existing autoimmune disease, ascertained within 12 months before starting ICI treatment, and defined either by strict criteria (one inpatient or two outpatient claims at least 30 days apart) or relaxed criteria only (any claim, without meeting strict criteria).
RESULTS
Of 4438 ICI-treated patients, pre-existing autoimmune disease was present among 179 (4%) by strict criteria, and another 283 (6%) by relaxed criteria only. In multivariable models, pre-existing autoimmune disease by strict criteria was not associated with all-cause hospitalization (HR 1.27, 95% CI 0.998-1.62), but it was associated with hospitalization with an irAE diagnosis (HR 1.81, 95% CI 1.21-2.71) and with corticosteroid treatment (HR 1.93, 95% CI 1.35-2.76). Similarly, pre-existing autoimmune disease by relaxed criteria only was not associated with all-cause hospitalization (HR 1.11, 95% CI 0.91-1.34), but was associated with hospitalization with an irAE diagnosis (HR 1.46, 95% CI 1.06-2.01) and corticosteroid treatment (HR 1.46, 95% CI 1.13-1.88).
CONCLUSION
Pre-existing autoimmune disease was not associated with time to any hospitalization after initiating ICI therapy, but it was associated with a modest increase in hospitalizations with irAE diagnoses and with corticosteroid treatment.
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10.1007/s00262-019-02321-z
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pubmed_937_12276
|
The aim of the study was establishing which parameters play a significant prognostic role in acute haemorrhagic stroke in its acute phases (during 30 days from stroke onset). The material included 110 patients with haemorrhagic stroke (HS) treated in the years 1997-1999 at the II Neurology Department, Institute of Psychiatry and Neurology in Warsaw or at the Neurology Department, Hospital in Piła. The analysis of risk factors, fitness before stroke and on the first day of the disease was based on history data. On the first day of the disease the assessment included state of consciousness, brain stem signs, vomiting, stroke type on the basis of clinical condition (according to Oxford classification, OCSP), blood pressure, body temperature measurements, intensity of neurological signs according to Scandinavian scale (SSS). In the blood glucose level, fibrinogen, leucocyte count and ESR were determined. In the first week consciousness state, blood pressure and miction were checked repeatedly. It was found that serious consciousness disturbances, stroke type TACS, POCS and severe not classified stroke, presence of brain stem involvement, low SSS score, high body temperature, high leucocyte count and glucose level were more frequent in patients who died within 30 days after stroke onset. Prognostically important were also instability of blood pressure and urinary incontinence in the first week. All clinical observation and laboratory analyses of prognostic importance in the acute phase of HS can be done in typical hospital settings.
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pubmed_937_12276
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pubmed_594_4738
|
OBJECTIVES
In recent years, glutathione S-transferase pi (GST-pi) has attracted much attention and has been studied as a mechanism of multidrug resistance of tumors to anticancer drugs. In the present study, we immunohistologically measured the expression of GST-pi in tumor tissues using surgical specimens obtained from patients with malignant ovarian tumors.
METHODS
Of 137 patients with malignant ovarian tumors treated and managed during a period of 20 years since the establishment of Tsukuba University Hospital, 117 patients were selected as subjects because of the presence of complete data on their clinical courses as well as paraffin blocks preserved in a good condition. GST-pi in these specimens was immunohistochemically stained to determine the correlation between GST-pi stainability and clinical outcomes. Stainability was graded as 0 when GST-pi was completely absent, 1 when less than 20% of tumor cells were stained, 2 when 20--60% were stained, and 3 when more than 60% were stained.
RESULTS
When the correlation between stainability and clinical outcomes was analyzed with Kaplan--Meier method, excluding stage Ia cases that did not receive adjuvant chemotherapy at our hospital, significantly better clinical outcomes were observed in the low stainable group, compared with the high stainable group (P<0.01--0.05, Cox--Mantel test, Wilcoxon's test).
CONCLUSION
Since the stainability for GST-pi was high in tumors of histological types with strong resistance to anticancer drugs, and better clinical outcomes were observed in cases having a lower stainability score, the expression of GST-pi was thought to play some role in the resistance of malignant ovarian tumors to anticancer drugs.
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10.1016/s0301-2115(00)00473-5
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pubmed_1025_20563
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Clinicians must frequently decide whether or not to treat patients with loss of posterior teeth, a condition called the shortened dental arch (SDA). Although many studies have been reported, there are no clear recommendations for the management of SDA cases. In this work, therefore, an innovative system, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, was used to grade the evidence and strength of recommendations for clinical intervention. An extensive literature search for longitudinal studies was conducted on 17 November 2010 in the PubMed and LILACS electronic databases using the term shortened dental arch. A 'snowballing' strategy, for example, manual searching of the reference lists of included papers, was also conducted. Unpublished and published studies were sought in ClinicalTrials.gov and in the search engine 'Google' (Scholar) in English, French, German, Italian, Portuguese and Spanish. Finally, grey literature was searched in OpenSIGLE (System for Information on Grey Literature in Europe). Titles and abstracts of 133 articles were initially assessed. Nine studies were finally included. Although there was no difference between the effectiveness of restorative and non-restorative approaches for SDA, fixed partial dentures seem better than removable prostheses. The overall body of evidence was, however, graded as low quality. Two different clinical scenarios are used to illustrate recommendations in the management of SDA cases by the use of the GRADE system. The GRADE approach may improve transparency in a shared decision-making process, mainly under conditions in which the quality of evidence is low or unclear.
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10.1111/j.1365-2842.2011.02230.x
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pubmed_0_22380
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The rymv1-3 allele of the eIF(iso)4G-mediated resistance to Rice yellow mottle virus (RYMV) is found in a few Oryza glaberrima cultivars. The same resistance-breaking (RB) mutations emerged in the central domain of the VPg after inoculation of isolates of different strains. The RB mutations were fixed, often sequentially, at codons 41 and 52 which paralleled an increase in virus accumulation. RB mutations also emerged after inoculation of an avirulent infectious clone, indicating that they were generated de novo in resistant plants. Only virus isolates with a threonine at codon 49 of the VPg broke rymv1-3 resistance, those with a glutamic acid did not. A small subset of these isolates overcame rymv1-2 resistance, but following a specific pathway. Comparison with the RB process of rymv1-2, a resistance allele found in a few Oryza sativa cultivars, showed similarities in the mode of adaptation but revealed converse virulence specificity of the isolates.
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10.1016/j.virol.2010.09.007
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pubmed_463_23379
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UNLABELLED
Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment (18)F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC.
METHODS
We retrospectively analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment (18)F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG.
RESULTS
Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG > 121.9 g and uniformity ≤ 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P < 0.001, < 0.001, and 0.002, respectively). Patients with TLG > 121.9 g or uniformity ≤ 0.138 were further divided according to age, and different PFS and DSS were observed.
CONCLUSION
Uniformity extracted from the normalized gray-level cooccurrence matrix represents an independent prognostic predictor in patients with advanced T-stage OPSCC. A scoring system was developed and may serve as a risk-stratification strategy for guiding therapy.
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10.2967/jnumed.112.119289
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pubmed_722_22339
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Despite the progress of the past two decades, the cause of Alzheimer's disease (AD) and effective treatments against it remain elusive. The hypothesis that amyloid-β (Aβ) peptides are the primary causative agents of AD retains significant support among researchers. Nonetheless, a growing body of evidence shows that Aβ peptides are unlikely to be the sole factor in AD etiology. Evidence that Aβ/amyloid-independent factors, including the actions of AD-related genes, also contribute significantly to AD pathogenesis was presented in a symposium at the 2010 Annual Meeting of the Society for Neuroscience. Here we summarize the studies showing how amyloid-independent mechanisms cause defective endo-lysosomal trafficking, altered intracellular signaling cascades, or impaired neurotransmitter release and contribute to synaptic dysfunction and/or neurodegeneration, leading to dementia in AD. A view of AD pathogenesis that encompasses both the amyloid-dependent and -independent mechanisms will help fill the gaps in our knowledge and reconcile the findings that cannot be explained solely by the amyloid hypothesis.
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10.1523/JNEUROSCI.4305-10.2010
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pubmed_122_13997
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The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1β and TNF-α in lipopolysaccharide (LPS)-activated microglial cells by suppressing NF-κB P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-κB signaling pathway, thus revealing a new mechanism of CNS demyelination.
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10.3389/fncel.2018.00392
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pubmed_904_5382
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OBJECTIVE
To explore the parent perspective on discharge home from the neonatal intensive care unit (NICU).
STUDY DESIGN
We interviewed parents of NICU graduates with a range of demographic characteristics and medical complexities to explore parent perspectives on readiness for discharge. Interviews were transcribed and coded by a 6-member team. We performed content analysis to identify themes and develop a family-centered conceptual framework around readiness for NICU discharge.
RESULTS
We interviewed a total of 15 parents who experienced NICU stays with 18 infants. Parents who have experienced NICU discharge have a spectrum of needs that evolve from the time the child is in the NICU, at time of discharge, and at home afterward. These needs consistently centered around 5 themes-communication, parent role clarity, emotional support, knowledge sources, and financial resources.
CONCLUSIONS
Parents described many ways the system could have better prepared them and connected them with essential resources. Summarizing the voices of the parents who participated in this study, we have compiled a series of practical recommendations for clinicians to use in daily practice to help parents feel prepared and confident for the transition home from the NICU.
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10.1016/j.jpeds.2018.08.086
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pubmed_460_10814
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The records of 335 patients admitted to the general medicine wards and to the medical intensive and coronary care unit (MICCU) at Brooke Army Medical Center were retrospectively reviewed to assess the frequency of advance directives and "do not resuscitate" (DNR) designations. Two hundred sixty-seven (79.7%) were admitted to the ward and 68 (20.3%) were admitted to the MICCU. Advance directives were executed in 14.9% of patients. DNR designations were made for 21 (7.9%) patients on the ward and 11 (16.2%) patients in the MICCU (p = 0.064). There were no statistical differences in mean length of stay, presence of advance directives, or documentation of advance directives in ward versus MICCU patients. However, there was a statistical difference in the number of deaths in the MICCU as compared with that on the ward (9.7 vs. 2.7%, p < 0.05). The frequency of advance directives and DNR designations did not differ between ward and MICCU patients in this population, although there was a trend for greater DNR designations in the MICCU environment.
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10.7205/milmed.169.6.433
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pubmed_349_18269
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BACKGROUND Increased expression of vimentin in tissue samples from patients with colorectal cancer (CRC) has been previously demonstrated, but its prognostic significance remains controversial, and the clinical significance for patients with stage II CRC is still unknown. The aim of this study was to evaluate the expression of vimentin in CRC and its potential prognostic significance. MATERIAL AND METHODS We analyzed vimentin expression in 203 CRC tissue samples from patients with stage II cancer using immunohistochemistry, and correlated the findings with clinicopathological patient features. CRC-specific survival (CSS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis was performed using the Cox proportional hazards method for survival. RESULTS Vimentin expression was significantly correlated only with tumor (T) stage (p=0.024). Kaplan-Meier survival analysis indicated that vimentin expression could stratify the CSS and DFS of patients with stage II CRC at high risk (p=0.029, p=0.042, respectively), but not those of low-risk stage II patients (p=0.208, p=0.361, respectively). Univariate and multivariate analysis further revealed that stromal vimentin expression is an independent prognostic factor for CSS and DFS of high-risk stage II patients (p=0.043, p=0.022, respectively). Moreover, high-risk stage II patients with low stromal vimentin expression benefitted more from standard adjuvant chemotherapy than those with high stromal vimentin expression (CSS: p=0.012 vs. p=0.407; DFS: p=0.017 vs. p=0.420). CONCLUSIONS Our study suggests that stromal vimentin expression is a promising indicator for survival prediction and adjuvant chemotherapy response in patients with stage II CRC with high-risk factors for recurrence.
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10.12659/msm.904486
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pubmed_33_19557
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Proactive interference (PI) has traditionally been understood as an adverse consequence of stimulus repetition during memory tasks. Herein, we present data that emphasize costs as well as benefits of PI for monkeys performing an auditory delayed matching-to-sample (DMTS) task. The animals made same/different judgments for a variety of simple and complex sounds separated by a 5-s memory delay. Each session used a stimulus set that included eight sounds; thus, each sound was repeated multiple times per session for match trials and for nonmatch trials as the sample (Cue 1) or test (Cue 2) stimulus. For nonmatch trials, performance was substantially diminished when the test stimulus had been previously presented on a recent trial. However, when the sample stimulus had been recently presented, performance was significantly improved. We also observed a marginal performance benefit when stimuli for match trials had been recently presented. The costs of PI for nonmatch test stimuli were greater than the combined benefits of PI for nonmatch sample stimuli and match trials, indicating that the net influence of PI is detrimental. For all three manifestations of PI, the effects are shown to extend beyond the immediately subsequent trial. Our data suggest that PI in auditory DMTS is best understood as an enduring influence that can be both detrimental and beneficial to memory-task performance.
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10.1002/ajp.22076
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pubmed_752_16595
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Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development.
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pubmed_752_16595
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pubmed_44_1910
|
INTRODUCTION
Identifying tumor infiltration or compression in patients with non-Hodgkin's malignant lymphoma presenting peripheral neuropathy can be a difficult task.
METHODS
We collected a series of patients with peripheral neuropathy with demonstrated lymphomatous infiltration or compression managed between October 1977 and October 2001 to search for clinico-pathological correlations.
RESULTS
Ten cases were reviewed. Neurological manifestations were the inaugural symptom of the disease in 7 patients. Clinical presentations included 5 focal (3 cranial nerve palsies, 2 brachial radiculopathies) and 5 diffuse neuropathies (3 polyradiculoneuropathies, 1 polyneuropathy and 1 mononeuritis multiplex). The mechanisms of peripheral nerve involvement were classified into lymphomatous meningoradiculitis (5 cases), involvement of cranial nerves or spinal roots in their extraneuraxial course (3 cases) and infiltration of distal peripheral nerves (2 cases). Four long lasting survivals after treatment were observed.
CONCLUSIONS
Prognosis depends much more on the haematological disease than on the neurological symptoms or tumor location.
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10.1016/s0035-3787(05)85141-0
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pubmed_1014_7569
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Neuroscience has become prevalent in recent years; nevertheless, its value in the examination of psychological and philosophical phenomena is still a matter of debate. The examples reviewed here suggest that neuroscientific tools can be significant in the investigation of such complex phenomena. In this article, we argue that it is important to study concepts that do not have a clear characterization and emphasize the role of neuroscience in this quest for knowledge. The data reviewed here suggest that neuroscience may (1) enrich our knowledge; (2) outline the nature of an explanation; and (3) lead to substantial empirical and theoretical discoveries. To that end, we review work on hedonia and eudaimonia in the fields of neuroscience, psychology, and philosophy. These studies demonstrate the importance of neuroscientific tools in the investigation of phenomena that are difficult to define using other methods.
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10.3389/fnhum.2014.00388
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pubmed_515_12402
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High colistin resistance rates in Acinetobacter spp. were recently reported in Korean hospitals (J. Antimicrob. Chemother 2007;60:1163). In this study, we investigated if colistin-resistant Acinetobacter spp. isolates from Korean hospitals disseminated clonally or emerged independently. Multilocus sequence typing (MLST) analysis was performed for 58 colistin-resistant Acinetobacter spp. isolates: 8 isolates of the Acinetobacter baumannii subgroup A, 16 isolates of the A. baumannii subgroup B, and 34 isolates of the genomic species 13TU. A phylogenetic tree inferred from concatenated sequences of 7 MLST loci showed a clear distinction among the 3 Acinetobacter groups. In the MLST analysis, most colistin-resistant Acinetobacter spp. isolates showed different allele profiles at the 7 loci; that is, they belonged to different clones. Despite the clear distinction between the 3 Acinetobacter groups, interrelationships among the 3 groups were not consistent within the gene trees. In addition, some isolates showed clustering incongruent with their species or group identities in some gene trees. MLST analysis indicated that most colistin-resistant Acinetobacter spp. isolates from Korean hospitals arose independently. Considering the increasing use of colistin and the high recombination rate of Acinetobacter spp., independent but frequent emergence of colistin resistance in Acinetobacter spp. isolates is of great concern.
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10.1016/j.diagmicrobio.2009.01.012
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pubmed_1103_139
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This study investigates the respiratory physiology of bioluminescent larvae of Pyrearinus termitilluminans in relation to their tolerance to hypoxia and hyperoxia and to the supply of oxygen for bioluminescence. The partial pressure of oxygen (P(O2)) was measured within the bioluminescent prothorax by in vivo electron paramagnetic resonance (EPR) oximetry following acclimation of larvae to hypoxic, normoxic and hyperoxic (normobaric) atmospheres and during periods of bioluminescence (during normoxia). The P(O2) in the prothorax during exposure to an external P(O2) of 15.2, 160 and 760 mmHg was 10.3+/-2.6, 134+/-0.9 and 725+/-73 mmHg respectively (mean +/- s.d., N=5; 1 mmHg=0.1333 kPa). Oxygen supply to the larvae via gas exchange through the spiracles, measured by determining the rate of water loss, was also studied in the above atmospheres and was found not to be dependent upon P(O2). The data indicated that there is little to no active control of extracellular tissue P(O2) within the prothorax of these larvae. The reduction in prothorax P(O2) observed during either attack-response-provoked bioluminescence or sustained feeding-related bioluminescence in a normoxic atmosphere was variable, but fell within the range 10-25 mmHg. The effect of hypoxic atmospheres on bioluminescence was measured to estimate the intracellular P(O2) within the photocytes of the prothorax. Above a threshold value of 50-80 mmHg, bioluminescence was unaffected by P(O2). Below this threshold, an approximately linear relationship between P(O2) and bioluminescence was observed. Taken together with the extracellular P(O2) measurements, this suggests that control of P(O2) within the photocyte may occur. This work establishes that EPR oximetry is a valuable technique for long-term measurement of tissue P(O2) in insects and can provide valuable insights into their respiratory physiology. It also raises questions regarding the hypothesis that bioluminescence can have a significant antioxidative effect by reduction of prothorax P(O2 )through oxygen consumption.
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10.1242/jeb.202.19.2631
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pubmed_399_10115
|
The clinical usefulness of a I-131 anti CEA F(ab')2 MoAB and CA 19-9 F(ab')2 MoAB cocktail(IMACIS-1) for the localization of a cancer has been studied in 35 patients (Lung Ca. 10, Pancreas Ca. 7, Gastric Ca. 6, Colon Ca. 5, Hepatoma 2, Cholangio Ca. 2, Esophageal Ca. 1, Uterus Ca. 1, and, Retroperitoneal tumor 1). Of these 28 patients (80%) had an abnormal accumulation of radioactivity in the tumor sites (Lung Ca. 5, Pancreas Ca. 7, Gastric Ca. 6, Colon Ca. 5, Hepatoma 2, Esophageal Ca. 1, Uterus Ca. 1, and, Retroperitoneal tumor 1). Eighteen cases (56.3%) in 32 cases in which the primary site was known showed an abnormal radioactive accumulation and, similarly, 20 metastatic sites (71.4%) in 16 cases with 28 metastatic sites also showed an abnormal accumulation of radioimmunoscintigraphy showed no correlation with the serum CEA or CA 19-9 concentration. Further, no side effect was observed.
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pubmed_399_10115
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pubmed_171_5988
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Chondroitin sulfate (CAS 24967-93-9, CS) is a natural polymer of a disaccharide consisting of glucuronic acid and N-acetyl glucosamine which is sulfated either in the 4 or 6 position. It is administered orally as a slow acting drug to treat osteoarthritis, though there is much debate about its effectiveness and its mode of action, given that macromolecules are not normally absorbed in the gastrointestinal (GI) tract. Initially using a spectrophotometric assay, the stability of CS was tested in the presence of both tissues and lumenal contents of stomach, small intestine, cecum and colon. There was no degradation by the contents of the stomach or small intestine or in any of the tissues. Degradation only took place in the contents of the colon and particularly the cecum. Using 14C-radiolabelled CS it was shown that the cecum contents degraded CS down to the component disaccharides. The 14C-radiolabelled CS was also used to investigate the transport of CS across the different parts of the GI tract in vitro. The CS was transported across the small intestine in low amounts in the intact form, probably by the mechanism of endocytosis. In the colon and the cecum, higher amounts of radioactivity were transported, but most of the radioactivity was in the form of the degradation products, the disaccharides. This study shows that small amounts of CS may cross the upper intestine intact, but in the distal GI tract the molecule is effectively degraded, presumably by the enzymes in the intestinal flora.
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10.1055/s-0031-1296972
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pubmed_358_731
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The pulmonary response of Wistar rats to a cumulative dose of 1 mg/kg body weight of a polymeric alpha,omega-diamine was examined using the intratracheal route of administration. Instillation of the test substance was on days 0 and 7 followed by a 3-month postobservation period. Static and dynamic pulmonary function tests, including arterial blood gas determinations, were performed during wk 5, 9, and 13. At all time points, significantly depressed flow-volume curves, reduced quasistatic compliance, and reduced vital capacity were observed. These were associated with increases of residual volume and functional residual capacity in the presence of unremarkable changes of total lung capacity (TLC). One of the most predominant dysfunctions of the lung was a severe maldistribution of ventilation, indicated by the single-breath nitrogen washout test. The carbon monoxide diffusing capacity (DL(CO)), in turn, was only mildly decreased, and differences between treatment and control groups did not reach statistical significance. Assessment of arterial blood gases demonstrated a statistically significantly increased venous admixture with subsequent slight hypoxemia. In summary, the predominant dysfunction appeared to be consistent with an obstructive rather than restrictive lung disease. The functional changes observed may account for the effect on arterial blood gases, suggesting a mismatch of the ventilation-perfusion relationship. Either measurement appear to demonstrate a relative stable dysfunction during the 3-mo postinstillation observation period. Collectively, this study supports the view held that polymeric alpha, omega-diamines appear to be potent pneumotoxicants.
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10.1080/08958370050030967
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pubmed_580_25227
|
After the implementation of the comprehensive schistosomiasis control measures centering on health education for 3 years, the awareness rate of schistosomiasis control increased by 96.56% in construction workers of Dechang highway construction engineering projects in Poyang Lake region, the number of workers adopting preventive measures increased significantly, and no schistosome infection occurred. It is suggested that the comprehensive measures focusing on health education, combined with environment depollution and public administration can prevent schistosome infection effectively among construction workers.
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pubmed_580_25227
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pubmed_228_13538
|
INTRODUCTION
Endodontic-related paresthesia is a potential complication despite the development of endodontic materials and techniques. We describe a case of periapical lesion-induced paresthesia that was successfully treated endodontically. The literature review of endodontic-related paresthesia is also presented.
METHODS
The patient sought treatment from a general practitioner for lower lip paresthesia as the only symptom. Paresthesia was present on the left side of the lower lip extending from the mandibular midline to the second premolar both extraorally and intraorally in the area of mental nerve stem. Apical lesion of an endodontically treated second premolar with short obturation was observed radiographically. Retreatment was unsuccessful at reaching the apex; instead, swelling, pain, and extension of numbness on the region resulted, and the patient was referred to an endodontist.
RESULTS
The root canal chemomechanical debridement was completed, and calcium hydroxide was placed for the follow-up. Two months later the symptoms had significantly improved, the radiograph indicated partial healing, and the tooth was obturated. The healing progressed so that the symptoms completely resolved within a year after the treatment.
CONCLUSIONS
Periapical pathosis might cause paresthesia with a good potential for healing after appropriate endodontic treatment. Complications might be prevented by careful preoperative examination, good quality radiographs, and good instrumentation, irrigation, and obturation techniques. However, according to the literature paresthesia might still occur. In case of treatment-related paresthesia in which apical extrusion of endodontic materials is observed, the need for surgical debridement (especially in cases of extrusion of obturation materials) should be considered within 48 hours.
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10.1016/j.joen.2011.06.016
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pubmed_134_6641
|
INTRODUCTION AND AIM
Sedation of patients is an important complement to endoscopic procedures. The aim of this study was to analyze tolerance, complications and cost-effectiveness in patients undergoing diagnostic upper gastrointestinal endoscopy.
PATIENTS AND METHOD
A total of 357 patients were prospectively studied: 138 non-sedated, 116 sedated with midazolam and 103 sedated with midazolam and meperidine. Subjective tolerance, tolerance perceived by the endoscopist, complications, and cost-effectiveness were evaluated. The Chi-square test was used for the statistical analysis. P-values of less than 0.05 were considered statistically significant.
RESULTS
Subjective tolerance was greater in patients sedated with midazolam and meperidine than in the other groups (p < 0.05). Tolerance perceived by the endoscopist was greater in the group sedated with both drugs than in the group sedated with midazolam (p < 0.05). Subjective tolerance was better in sedated men and women but there was no association between sedation and perceived tolerance according to sex. Subjective tolerance was better in sedated patients older than 70 years than in those younger than 40 years (p < 0.05). Complications were more frequent in sedated patients and the most frequent complication in all the groups studied was mild desaturation; there was a significant difference between the group sedated with midazolam and meperidine and the non-sedated group (p < 0.05). Non-sedation had the best cost-effectiveness ratio but sedation with midazolam and meperidine was the most effective alternative.
CONCLUSION
From the point of view of the endoscopist, endoscopy can be performed without sedation, although subjective tolerance is greater in patients sedated with midazolam and meperidine. Non-sedation is more cost-effectiveness than sedation but if sedation is required midazolam and meperidine achieve better results in terms of effectiveness than midazolam alone.
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10.1157/13070376
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pubmed_343_22048
|
BACKGROUND
Quality monitoring is increasingly important to support and assure sustainability of the orthopedic practice. Surgeons in nonacademic settings often lack resources to accurately monitor quality of care. Widespread use of electronic medical records (EMR) provides easier access to medical information, facilitating its analysis. However, manual review of EMRs is highly inefficient. Artificial intelligence (AI) software allows for the development of algorithms for extracting relevant complications from EMRs. We hypothesized that an AI-supported algorithm for complication data extraction would have an accuracy level equal to or higher than manual review after total hip arthroplasty (THA).
METHODS
A total of 532 consecutive patients underwent 613 THA between January 1 and December 31, 2017. A random derivation cohort (100 patients, 115 hips) was used to determine accuracy. After generation of a gold standard, the algorithm was compared to manual extraction to validate performance in raw data extraction. The full cohort (532 patients, 613 hips) was used to determine recall, precision, and F-value.
RESULTS
AI accuracy was 95.0%, compared to 94.5% for manual review (P = .69). Recall of 96.0% (84.0%-100%), precision of 88.0% (33%-100%) and F-measure of 0.85 (0.5-1) was achieved for all adverse events. No adverse events were recorded in 80.6%, 1.3% required reintervention and 18.1% had "transient" events.
CONCLUSION
The use of an automated, AI-supported search algorithm for EMRs provided continuous feedback on the quality of care with a performance level comparable to manual data extraction, but with greater speed. New clinical information surfaced, as 18.1% of patients can be expected to have "transient" problems.
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10.1016/j.arth.2019.07.039
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pubmed_888_1495
|
On anaesthetized dogs the role NO and mitochondrial permeability transition pore (MPTP) in the regulation of regional blood circulation, efficiency of oxygen using, and muscle contraction force was investigated. Under different frequency stimulation it was shown, that short-term (30") smoothly tetanic contraction (40 Hz) is more economic for a skeletal muscle than short-term (30") single contractions (8 Hz) with respect to the efficiency of oxygen using. Injection NOS inhibitor L-NMMA (2.7 mg/kg, i.a.) resulted in pronounced fall of a functional hyperemia magnitude (P < 0.01), significant reduction of the muscle contractions force (P < 0.01), and efficiency of oxygen using (P < 0.01), in m.gastrocnemicus, in comparison with control. Pretreatment with an exogenous activator of MPTP phenilarsine oxide (PAO, 0.2 mg/kg, i.a.) caused a marked inhibition of an endothelium-dependent vessels dilation on skin-muscle region of rear limb. At the same time the muscle contractions force was significantly decreased (P < 0.01) and efficiency of oxygen using was diminished too (P < 0.01). This was accompanied by an appearance in blood from v. femoralis mitochondrial factor (MF), indicating MPTP activation. Preliminary injection of the exogenous NO donor sodium nitroprusside (0.2 mg/kg, i.v.) prevented considerably an inhibition of a dilation vessels reserve, a fall of muscle contractions force (P < 0.01) and considerably reduced oxygen cost (P < 0.01) of a m.gastercnemicus work also. The concentration of MF in blood from v. femoralis also was considerably reduced (P < 0.001) that has been the evidence of MPTP inhibition. Thus, activation of MPTP and development of oxidative stress resulted in endothelium dysfunction, a force of muscle contraction diminishing and a significant decrease in efficiency of oxygen using. NO essentially reduced the negative effects of MPTP activation and was antagonist of oxidative damages development.
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pubmed_888_1495
|
pubmed_553_8152
|
Vectorcardiogram (VCG) was studied in four patients with hypertrophic cardiomyopathy (HCM) with RSR' pattern in right chest leads. In these patients there ws an anterior QRS loop with a slow inscription in the initial part of the QRS loop, the pathognomonic initial pig-tail curl pattern was also observed in two patients. Though mid-terminal conduction delay was also observed in two patients, the slowly inscribed terminal QRS vector oriented anteriorly and to the right, thus characteristic of right, thus characteristic of right bundle branch block (RBBB), was not observed. The initial conduction delay was attributed to the conduction disturbance as the result of hypertrophy and disarray of the muscle fiber, particularly in the septal area. The recognition of this VCG pattern provides a pertinent clue in the clinical detection of HCM.
|
10.1253/jcj.44.734
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pubmed_189_6502
|
Gene expression profiling studies have shown the pathogenetic role of oncogenic pathways in extranodal natural killer/T-cell lymphoma (ENKL). In this study, we aimed to identify the microRNAs (miRNAs) playing potential roles in ENKL, and to evaluate the genes and biological pathways associated to them. Gene expression profiles of ENKL patients were acquired from the gene expression omnibus (GEO) database. Most differentially expressed (DE)-miRNAs were identified in ENKL patients using limma package. Gene targets of the DE-miRNAs were collected from online databases (miRDB, miRWalk, miRDIP, and TargetScan), and used in Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses on Database for annotation, visualization, and integrated discovery database, and then used in protein-protein interaction (PPI) analysis on STRING database. Hub genes of the PPI network were identified in cytoHubba, and were evaluated in Biological networks gene ontology. According to the series GSE31377 and GSE43958 from GEO database, four DE-miRNAs were screened out: hsa-miR-363-3p, hsa-miR-296-5p, hsa-miR-155-5p, and hsa-miR-221-3p. Totally 164 gene targets were collected from the online databases, and used in the GO and KEGG pathway analyses and PPI network analysis. Ten hub genes of the PPI network were identified: AURKA, TP53, CDK1, CDK2, CCNB1, PLK1, CUL1, ESR1, CDC20, and PIK3CA. Those hub genes, as well as their correlative pathways, may be of diagnostic or therapeutic potential for ENKL, but further clinical evidence is still expected.
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10.1515/med-2021-0409
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pubmed_294_3747
|
One essential component of health system reform is to bring the number of physicians in line with the needs of the population. The physician supply policies of prepaid group practice health maintenance organizations have been cited as one model to achieve this goal. Planning for physician supply should be an explicit public-sector activity and should not be left to the private sector, because some areas are not sufficiently populated to support competing providers under a managed competition scheme. A new model for planning for physician supply should include the following strategies: (1) erecting barriers to entry into medical practice; (2) encouraging early retirement; (3) restructuring economic incentives; (4) reallocating physicians to underserved areas in the United States and abroad; and (5) creating new areas of professional responsibility for physicians.
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10.1377/hlthaff.12.2.89
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pubmed_908_4601
|
Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancer types, including colorectal cancer (CRC). However, the role of PlncRNA-1 in CRC remains unclear. The aim of our present study was to investigate the potential functions of PlncRNA-1 in CRC and to identify the underlying mechanisms of action. We demonstrated that up-regulated PlncRNA-1 in CRC tissues and cells promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis in vitro, enhanced tumor growth and matastasis in vivo and was associated with cell migration and invasion, EMT process of CRC cells. In addition, PlncRNA-1 was a target of miR-204 and enhanced the expression of an endogenous miR-204 target, MMP9 in CRC cells. Furthermore, we found that PlncRNA-1 activates Wnt/β-catenin pathway through the miR-204 in CRC cells. These results suggest that the PlncRNA-1/miR-204/ Wnt/β-catenin regulatory network may shed light on tumorigenesis in CRC.
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10.1002/jcb.27031
|
pubmed_499_5633
|
The stiffness of brain tissue changes during development and disease. These changes can affect neuronal morphology, specifically dendritic arborization. We previously reported that N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors regulate dendrite number and branching in a manner that is dependent on substrate stiffness. Since mitochondria affect the shape of dendrites, in this study, we determined whether the stiffness of substrates on which rat hippocampal neurons are grown affects mitochondrial characteristics and if glutamate receptors mediate the effects of substrate stiffness. Dendritic mitochondria are small, short, simple, and scarce in neurons cultured on substrates of 0.5 kPa stiffness. In contrast, dendritic mitochondria are large, long, complex, and low in number in neurons grown on substrates of 4 kPa stiffness. Dendritic mitochondria of neurons cultured on glass are high in number and small with complex shapes. Treatment of neurons grown on the stiffer gels or glass with the NMDA and AMPA receptor antagonists, 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively, results in mitochondrial characteristics of neurons grown on the softer substrate. These results suggest that glutamate receptors play important roles in regulating both mitochondrial morphology and dendritic arborization in response to substrate stiffness.
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10.1007/s10439-022-02987-0
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pubmed_300_13268
|
The psychiatric ward is a complex organization. It contains two main groups: the patients and the staff. The different needs of each group influence the encounters between patients, the consumers, and staff, the suppliers. We shall discuss those needs and analyze the ways they interfere with or complement the therapeutic group work. For example: staff members need specific therapeutic group work for their professional development, and the patients need the group in order to maintain some form of interpersonal contact and to keep themselves active. The staff holds therapeutic groups in order to monitor the activity on the ward, while the patients seek a space where they can express their concerns about their treatment. Some vignettes will be presented which demonstrate these different needs, of staff and patients, and the way they were explored in the staff's group supervision meetings.
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pubmed_300_13268
|
pubmed_642_11116
|
BACKGROUND
Community water fluoridation is known to play a significant role in enhancing oral health by reducing the incidence of dental caries. However, the level of fluoride in the supplied public water in the Eastern Province of Saudi Arabia is unknown.
OBJECTIVE
To determine water fluoride levels at the main sources supplying water to households and schools in two major cities (Dammam and Al-Khobar) of the Eastern Province of Saudi Arabia.
METHODS
From the Directorate of Water Agency and Directorate of Education, the following were identified as the main sources of public water supply in Dammam and Al-Khobar: the water agency, public water tanks and four contracted companies. Two samples were collected from each of these six identified water sources at two different time points (in January and July 2016; 2 samples/site/time point; N = 24) using 500 mL polythene bottles. Each sample was analyzed using an ion chromatography system at different detection limits (including the lowest detection limit of 0.065 ppm) to determine the fluoride level.
RESULTS
There was no fluoride detected in any sample even at the lowest detection limit, indicating that fluoride levels in the studied water samples were <0.065 ppm.
CONCLUSION
This study found that in the cities studied, fluoride levels, if any, are considerably below the optimum recommended level for the prevention of dental caries (i.e., 0.7 ppm).
|
10.4103/sjmms.sjmms_176_16
|
pubmed_826_3468
|
OBJECTIVE
The aim of the present study was to examine weight gain and its association with clinical and sociodemographic characteristics in patients using newer antidepressants.
METHODS
The study had a cross-sectional design. A total of 362 consecutive psychiatric patients taking antidepressant drugs for 6 to 36 months were included in the study.
RESULTS
The prevalence rate of weight gain was 55.2%; 40.6% of the patients had a weight gain of 7% or more compared to the baseline. Overall, antidepressant use was significantly related to increased body weight. Specifically, citalopram, escitalopram, sertraline, paroxetine, venlafaxine, duloxetine and mirtazapine, but not fluoxetine, were associated with significant weight gain. Multivariate logistic regression analysis indicated that lower education status, lower body mass index at the onset of antidepressant use and family history of obesity were independent predictors of weight gain ≥7% compared to the baseline.
CONCLUSIONS
The study results suggest that patients who take newer antidepressants might have significant problems related to body weight.
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pubmed_826_3468
|
pubmed_1141_11922
|
A revision of chigger mites species, being closely related to Neotrombicula vulgaris (Schluger, 1955), is given. 2 new species are described: N. aideriensis sp. n. from Western Kopetdagh and N. macrovulgaris sp. n. from Western Caucasus. N. aideriensis sp. n. differs from all other species of the vulgaris group by presence of single barb on the lateral seta of palpal tibia in most specimens. This species differs also from N. vulgaris by lesser width of scutum, shorter setae of scutum and idiosoma and by longer legs. N. macrovulgaris sp. n. differs from all other species of the vulgaris group by longer legs, more numerous idiosomal setae and by larger scutum. N. vulgaris is recorded for the first time in Bulgaria, Turkmenistan (western Kopet-Dag) and Krasnodar Territory, N. baschkirica Kudryashova, 1998--in Chuvashia, Kirov Province, Komi Republic and Tyumen' Province, N. kharadovi Kudryashova, 1998--in Russia (Altai Territory) and in Karaganda Province (Kazakhstan). The latter species is reported from several new hosts. Variation of morphometric parameters in the vulgaris group are investigated by the methods of multivariate analysis, the pattern of correlations between them is shown. A complex of diagnostic features in the group is revised. Discriminant functions produced by the computer program DIADIS (A. L. Lobanov, ZI RAS) allows to determine confidently representatives of the vulgaris group. Ecogeographical component of intraspecific variability and character variance at the specific level is revealed in vulgaris group. N. macrovulgaris characterized by the largest scutum, numerous setae and long legs was found in the most rigorous, cold and damp climate (alpine zone of western Caucasus). On the other hand, N. kharadovi, which have the most fine scutum and shortest setae, inhabits rather dry and warm Middle Asia and neighbouring territories. The sample of N. vulgaris collected in the steppe part of Stavropol' Territory differed from the material collected in mountain forests of Western Caucasus by low values of the most part of measurements. N. kharadovi samples from plains of Middle Asia differed from samples of this species collected in western Pamirs, central Kazakhstan and Altay Territory by more fine scutum and shorter setae.
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pubmed_1141_11922
|
pubmed_415_23483
|
Autophagy is one of the newest and fastest emerging research areas in biomedical life sciences. Autophagosomes, large double-membrane vesicles enclosing cytoplasmic components targeted for degradation, are the hallmark of this catabolic pathway. The origin of the lipid bilayers composing these transport carriers has been the central enigma of the field since the discovery of autophagy. A series of recent studies has implicated several cellular organelles as the possible source of the autophagosomal membranes, if anything further clouding our view. In this compendium, we will discuss these apparently contradictory results and briefly emphasize the relevance of determining the lipid source used for autophagy for future translational research, for example in drug discovery programs.
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10.3410/B3-25
|
pubmed_261_9667
|
BACKGROUND
The distribution of radiation oncologists across the United States varies significantly among geographic regions. Accompanying these variations exist geographic variations in prostate cancer mortality. Prostate cancer outcomes have been linked to variations in urologist density, however, the impact of geographic variation in the radiation oncologist workforce and prostate cancer mortality has yet to be investigated. The goal of this study was to determine the effect of increasing radiation oncologist density on regional prostate cancer mortality.
METHODS
Using county-level prostate cancer mortality data from the National Cancer Institute and Centers for Disease Control as well as physician workforce and health system data from the Area Resource File a regression model was built for prostate cancer mortality controlling for categorized radiation oncologist density, urologist density, county socioeconomic factors and pre-existing health system infrastructure.
RESULTS
There was statistically significant reduction in prostate cancer mortality (3.91-5.45% reduction in mortality) in counties with at least 1 radiation oncologist compared with counties lacking radiation oncologists. However, increasing the density of radiation oncologists beyond 1 per 100 000 residents did not yield statistically significant incremental reductions in prostate cancer mortality.
CONCLUSION
The presence of at least one radiation oncologist is associated with significant reductions in prostate cancer mortality within that county. However, the incremental benefit of increasing radiation oncologist density exhibits a plateau effect providing marginal benefit. In order to optimize outcomes a geographically aware policy, which addresses the size and distribution of the workforce, must be in place in order prevent geographic disparities in prostate cancer mortality.
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10.1038/pcan.2012.28
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pubmed_633_17906
|
BACKGROUND
In order to understand more about pain presentations in primary care, the authors undertook a descriptive study on musculoskeletal pain presentations to a general practice with a special interest in musculoskeletal medicine. The aim was to describe and categorise musculoskeletal pain presentations into pain subtypes.
METHODS
Over a 5 week period in 2009, 133 consecutive musculoskeletal pain patients consented to participate in a study on pain presentations. Patients were categorised into: somatic, somatic referred, neuropathic or a combination of these. Further information was collected on age, gender, length of attendance, mode of referral, and current pain history.
RESULTS
Patients were predominantly female with chronic pain problems. Somatic low back pain was the commonest pain presentation. Neuropathic pain was a feature of 25% of cases, with pure somatic referred pain presenting in 1 in 7 cases. Nearly half of the patients were referred by their usual general practitioner. DISCUSSION Differentiating pain types is important in pain management. Neuropathic and somatic referred pain are common presentations to primary practice but may be difficult to detect. Data on pain presentation subtypes in primary practice is important to inform medical educators and research organisations and instruct future planning for primary care.
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pubmed_633_17906
|
pubmed_618_5489
|
This paper presents a novel features mining approach from documents that could not be mined via optical character recognition (OCR). By identifying the intimate relationship between the text and graphical components, the proposed technique pulls out the Start, End, and Exact values for each bar. Furthermore, the word 2-gram and Euclidean distance methods are used to accurately detect and determine plagiarism in bar charts.
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10.1155/2014/612787
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pubmed_147_3774
|
The approach Clark labels "action-oriented predictive processing" treats all cognition as part of a system of on-line control. This ignores other important aspects of animal, human, and robot intelligence. He contrasts it with an alleged "mainstream" approach that also ignores the depth and variety of AI/Robotic research. I don't think the theory presented is worth taking seriously as a complete model, even if there is much that it explains.
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10.1017/S0140525X12002439
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pubmed_984_19525
|
This paper reports corrections and improvements of the previously reported direct force balance method (DFBM) developed for lateral calibration of atomic force microscopy. The DFBM method employs the lateral force signal obtained during a force-distance measurement on a sloped surface and relates this signal to the applied load and the slope of the surface to determine the lateral calibration factor. In the original publication [Rev. Sci. Instrum. 77, 043903 (2006)], the tip-substrate contact was assumed to be pinned at the point of contact, i.e., no slip along the slope. In control experiments, the tip was found to slide along the slope during force-distance curve measurement. This paper presents the correct force balance for lateral force calibration.
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10.1063/1.3142243
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pubmed_691_6986
|
In the absence of recognized pneumonitis, psittacosis is unlikely to be considered as a cause of infection in patients with febrile illnesses. To identify findings useful in the diagnosis of psittacosis, the clinical and roentgenographic characteristics of 46 cases that occurred in two outbreaks among workers in turkey processing plants were reviewed. Headache (96% of patients), chills (93% of patients), and fever (89% of patients) were the most common symptoms; a nonproductive cough occurred in 65% of patients. Rales or rhonchi were detected in only six (18%) of 33 patients examined, but 21 (72%) of 29 patients receiving a chest film had roentgenographic evidence of pneumonia. We conclude that few diagnostically useful symptoms or signs occur in patients with psittacosis but that roentgenographically confirmed pneumonitis may occur commonly in patients with little clinical evidence of pneumonitis. A history of exposure to birds, in an individual with a flu-like illness, appears to be the single best clue to the diagnosis of psittacosis.
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pubmed_691_6986
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pubmed_1110_25448
|
Enterovirus-71 (EV71) and coxsackievirus-A16 (CA16) frequently cause hand-foot-mouth disease (HFMD) epidemics among infants and young children. CA16 infections are usually mild, while EV71 disease may be fatal due to neurologic complications. As such, the ability to rapidly and specifically recognize EV71 is needed to facilitate proper case management and epidemic control. Accordingly, the aim of this study was to generate antibodies to EV71-virion protein-2 (VP2) by phage display technology for further use in specific detection of EV71. A recombinant peptide sequence of EV71-VP2, carrying a predicted conserved B cell epitope fused to glutathione-S-transferase (GST) (designated GST-EV71-VP2/131-160), was produced. The fusion protein was used as bait in in-solution biopanning to separate protein-bound phages from a murine scFv (MuscFv) phage display library constructed from an immunoglobulin gene repertoire from naïve ICR mice. Three phage-transformed E. coli clones (clones 63, 82, and 83) produced MuscFvs that bound to the GST-EV71-VP2/131-160 peptide. The MuscFv of clone 83 (MuscFv83), which produced the highest ELISA signal to the target antigen, was further tested. MuscFv83 also bound to full-length EV71-VP2 and EV71 particles, but did not bind to GST, full-length EV71-VP1, or the antigenically related CA16. MuscFv83 could be a suitable reagent for rapid antigen-based immunoassay, such as immunochromatography (ICT), for the specific detection and/or diagnosis of EV71 infection as well as epidemic surveillance.
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10.1007/s00705-018-3731-z
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pubmed_791_16521
|
Drug resistance and relapse after treatment of visceral leishmaniasis (VL) with the chemotherapeutic drugs has impeded the VL elimination programme especially, in the endemic region of Bihar, India. Currently, Antimonials (Sbv) have been rendered obsolete (Bihar) as frequent treatment failure and relapse in Sbv treated patient's warrants greater vigilance and attention to the limited drugs. A clinical isolate of L.donovani obtained from an Amphotericin B (AmB) relapse patient was evaluated for its susceptibility to AmB and a hyperlipidemic drug Guggul. The evaluation of susceptibility or resistance to any drug still relies on in vitro assay on promastigote and amastigote stages of Leishmania spp. as there are no validated markers which can ascertain drug resistance in Leishmania. The anti-promastigote effect of AmB and Guggul were demonstrated by significant cellular and morphological changes exhibiting apoptosis-mediated cell death. To further illustrate the molecular mechanism of the parasite's response upon exposure to either AmB and Guggul, sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for quantitative proteomics analysis was performed along with computational data analysis; revealing considerable differences in the proteome profiles which could be regarded as putative markers for resistance or drug targets for development of therapeutic antileishmanials.
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10.1016/j.jprot.2020.104017
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pubmed_674_18498
|
Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states.
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10.1101/gr.216309.116
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pubmed_436_6311
|
Alpha-synuclein (alpha-syn) is implicated in the pathogenesis of Parkinson's disease (PD). Mutations in alpha-syn gene or alpha-syn locus (SNCA) triplication are associated with mitochondrial abnormalities and early onset of familial PD. The goals of the present study were to examine whether alpha-syn is localized in the mitochondria of alpha-syn overexpressing cells (HEK-syn cells); and whether alpha-syn overexpression causes cells to be more vulnerable to mitochondrial toxin, rotenone. Western blotting and confocal microscopy techniques were employed to assess localization of alpha-syn in the mitochondria of HEK-293 cells that were stably transfected with human wild-type alpha-syn. The results demonstrated that the mitochondrial fractions that were isolated from HEK-syn cells showed the presence of alpha-syn, whereas, no alpha-syn was detected in the mitochondrial fractions of control HEK cells. The mitochondria of HEK-syn cells were found to be more susceptible to rotenone-induced toxicity when compared to control HEK cells. The intracellular ATP levels were significantly decreased in HEK-syn cells in response to sub toxic concentrations of rotenone. These results suggest that under overexpression conditions, alpha-syn may translocate to mitochondria and cause enhanced toxicity in response to sub toxic concentrations of mitochondrial toxins. This study has implications to the pathogenesis of familial PD where alpha-syn overexpression is mainly involved.
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10.1016/j.neulet.2008.05.005
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pubmed_787_6868
|
BACKGROUND
This study explores the premise that shame episodes can have the properties of traumatic memories, involving intrusions, flashbacks, strong emotional avoidance, hyper arousal, fragmented states of mind and dissociation.
METHOD
A battery of self-report questionnaires was used to assess shame, shame traumatic memory and depression in 811 participants from general population (481 undergraduate students and 330 subjects from normal population).
RESULTS
Results show that early shame experiences do indeed reveal traumatic memory characteristics. Moreover, these experiences are associated with current feelings of internal and external shame in adulthood. We also found that current shame and depression are significantly related. Key to our findings is that those individuals whose shame memories display more traumatic characteristics show more depressive symptoms. A moderator analysis suggested an effect of shame traumatic memory on the relationship between shame and depression.
LIMITATIONS
The transversal nature of our study design, the use of self-reports questionnaires, the possibility of selective memories in participants' retrospective reports and the use of a general community sample, are some methodological limitations that should be considered in our investigation.
CONCLUSION
Our study presents novel perspectives on the nature of shame and its relation to psychopathology, empirically supporting the proposal that shame memories have traumatic memory characteristics, that not only affect shame in adulthood but also seem to moderate the impact of shame on depression. Therefore, these considerations emphasize the importance of assessing and intervening on shame memories in a therapeutic context.
|
10.1002/cpp.659
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pubmed_976_5983
|
Cardiac contusion is usually caused by blunt chest trauma and therefore is frequently suspected in patients involved in car or motorcycle accidents. The diagnosis of a myocardial contusion is difficult because of non-specific symptoms and the lack of an ideal test to detect myocardial damage. Cardiac contusion can cause life threatening arrhythmias and cardiac failure. Many diagnostic methods, such as ECG, biochemical cardiac markers, transthoracic and transoesophageal echocardiography, and radionuclide imaging studies, have been investigated to determine their use in predicting such complications. Recently, cardiac troponin I and T were found to be highly sensitive for myocardial injury. Troponin I and T have also proved to be useful in the stratification of patients at risk for complications. Nevertheless, diagnosis of a cardiac contusion and identification of patients at risk remain a challenge. In this review the current diagnostic tests will be discussed. Also, based on these diagnostic tests, a screening strategy containing data from the latest studies is presented, with the intention of detecting patients at risk.
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10.1136/heart.89.5.485
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pubmed_826_17464
|
Currently, there is an increase in the number of patients with infections of the skin and soft tissue. There is a question of closing tissue defects after the elimination period of acute inflammation. Application auto skin grafting free split-skin graft does not always lead to a positive outcome of primary closure of the defect and to the appearance of one more wound skin. The technique that avoids these drawbacks is proposed.
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pubmed_826_17464
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pubmed_846_6752
|
Mechanism of uptake of inorganic phosphate (Pi) by the maternal border of the dually perfused guinea pig placenta was studied using the paired-tracer dilution technique with 32P-phosphate and 14C-sucrose being the tracers. Placental uptake of radioactive phosphate increased when the concentration of Pi in the perfusion fluid was reduced, and it decreased during anoxia, in presence of CN or during perfusion with low-Na or Na-free fluids. Iodoacetate was without effect. These observations are consistent with placental uptake of Pi being effected by a carrier mediated process dependent on external Na and, partly, on placental metabolism. Unidirectional flux of Pi from the maternal vascular space into the cell compartment of the placenta, estimated from the values of instantaneous extraction of 32P, correlated significantly with foetal weight. The flux per unit weight of the foetus was 17.0 +/- 1.0 nmol X min-1 g-1.
|
10.1007/BF00580797
|
pubmed_505_21914
|
Postoperative delirium (POD) is an acute change in cognitive status characterized by fluctuating consciousness and is associated with high incidences of morbidity, high complication rates, and long hospitalizations. This study was performed to determine the incidence of POD and the perioperative risk factors in order to predict which patients have an increased risk and thus to prevent POD after major head and neck surgery. The authors retrospectively evaluated 341 patients who underwent laryngectomy or the Commando (combined operation of mouth, mandible, and neck dissection) procedure at Pusan National University Hospital from January 1986 through July 2001. Postoperative delirium developed in 13.8% of the patients who underwent laryngectomy (42 of 304) and 13.5% of the patients who underwent the Commando procedure (5 of 37). A multivariate analysis showed that older age, hypertension, low postoperative O2 saturation, and decreased postoperative hemoglobin levels were risk factors for POD (p < .05). Postoperative delirium is preventable, and its incidence can be decreased by predicting these risk factors during the preoperative and postoperative periods.
|
10.1177/000348940411300111
|
pubmed_195_24500
|
A method was developed for the determination of (129)I in soil samples that uses an ICP-MS equipped with an octopole reaction system. Oxygen was used as the reaction gas for reducing the background intensity of m/z 129, principally by (129)Xe(+). The contribution of polyatomic ions, such as (127)IH(2)(+), could be effectively corrected for by assuming a production ratio ((127)IH(2)(+)/(127)I(+) = 3 × 10(-8)). The measured (129)I/(127)I ratios in a NIST standard solution and Fukushima soil samples are consistent with the expected value within the analytical error. This method provides a powerful tool for investigating radioiodine contamination in Fukushima and elsewhere.
|
10.2116/analsci.29.271
|
pubmed_277_2126
|
Over the last two decades, progress towards new drugs for the treatment of Chagas' disease has been disappointing. However, as a result of the parasite genome sequencing projects, the possibility of identifying novel drug targets through genomics, proteomics and bioinformatics has never been better. Progress towards the development of novel therapeutics, from target identification and validation by chemical and genetic means through to rational drug design, is illustrated with reference to the metabolism and functions of trypanothione, with particular emphasis on trypanothione reductase, one current drug target of choice.
|
pubmed_277_2126
|
pubmed_485_15591
|
Two groups of duodenal ulcer (DU) patients, responders and nonresponders, have been compared in order to verify if psychological factors are linked to relapse. Responders are defined as those patients who on endoscopy did not present proven relapse during treatment with maintenance doses of antisecretory drugs (cimetidine 400 mg/day, ranitidine 150 mg/day, pirenzepine 50 mg/day) for a period of 12 months after healing of the lesion. Nonresponders were all patients presenting with at least one relapse during treatment with antisecretory drugs. One hundred and twelve DU patients (81 responders, 31 nonresponders) were examined with the Cattell 16 Personality Factors Questionnaire (16PF) form C. There were no significant differences between the two groups for age, sex, duration of illness and type of drug treatment. The 16 PF scores of responders and nonresponders were not statistically different except in the case of factor E (dominance), in which the nonresponder subjects scored higher than responder subjects (p less than 0.01). However, when the significance level was corrected for the number of variables involved, the above finding is not considered to be meaningful.
|
10.1159/000199584
|
pubmed_551_17944
|
BACKGROUND/AIMS
In Jordan, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a significant health problem, and the incidence was reported to be about 3.6%. The aims of this study are to investigate the most common molecular mutations of the G6PD gene among Jordanians in northern Jordan and to examine the correlation between the genotype and phenotype of this enzyme deficiency.
METHODS
Seventy-five blood samples were collected from patients attending King Abdullah University Hospital and Princess Rahma Teaching Hospital. The G6PD gene was scanned for mutations using a DNA sequencing technique.
RESULTS
Our results showed 11 variations (7 exonic and 4 intronic) as follows: c.202 G>A (rs1050828), c.376 A>G (rs1050829), c.404 A>C (CM962574 single-nucleotide polymorphism), c.542 A>T (rs5030872), c.563 C>T (rs5030868), c.1003 G>A (rs5030869), c.1311 C>T (rs2230037), c.486-90 C>T, c.486-60 C>G (rs2515904), c.770+175 C>T (rs2515905) and c.1311 C>T (rs2230037). Among these, G6PD Mediterranean (c.563 C>T) was the most common in our patients, with a frequency of 76.2%, followed by G6PD A- (c.202 G>A + c.376 A>G) with 19%, and an equal frequency of 1.6% was found for G6PD Chatham (c.1003 G>A), G6PD Santamaria (c.542 A>T + c.376 A>G) and G6PD Cairo (c.404 A>C).
CONCLUSION
This is the first report of G6PD Santamaria and Cairo among our Jordanian population.
|
10.1159/000339505
|
pubmed_540_24815
|
BACKGROUND
The introduction in many countries of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to significant reductions in acute bacterial meningitis (ABM) in children. However, recent population-based data on ABM in sub-Saharan Africa are limited.
METHODS
Population-based surveillance for meningitis was carried out in a rural area of The Gambia under demographic surveillance from 2008 to 2017, using standardised criteria for referral, diagnosis and investigation. We calculated incidence using population denominators.
RESULTS
We diagnosed 1,666 patients with suspected meningitis and collected cerebrospinal fluid (n = 1,121) and/or blood (n = 1,070) from 1,427 (88%) of cases. We identified 169 cases of ABM, 209 cases of suspected non-bacterial meningitis (SNBM) and 1,049 cases of clinically suspected meningitis (CSM). The estimated average annual incidence of ABM was high at 145 per 100,000 population in the <2-month age group, 56 per 100,000 in the 2-23-month age group, but lower at 5 per 100,000 in the 5-14-year age group. The most common causes of ABM were Streptococcus pneumoniae (n = 44), Neisseria meningitidis (n = 42), and Gram-negative coliform bacteria (n = 26). Eighteen of 22 cases caused by pneumococcal serotypes included in PCV13 occurred prior to vaccine introduction and four afterwards. The overall case fatality ratio for ABM was 29% (49/169) and was highest in the <2-month age group 37% (10/27). The case fatality ratio was 8.6% (18/209) for suspected non-bacterial meningitis and 12.8% (134/1049) for clinically suspected meningitis cases.
CONCLUSIONS
Gambian children continue to experience substantial morbidity and mortality associated with suspected meningitis, especially acute bacterial meningitis. Such severely ill children in sub-Saharan Africa require improved diagnostics and clinical care.
|
10.1371/journal.pone.0265299
|
pubmed_897_22828
|
Currently available antiepileptic drugs aim to avoid recurrence of the epileptic seizures. They act by different mechanisms, at the level of the synaptic transmission and the membrane excitability. There is a large choice of antiepileptic drugs. The prescription of an antiepileptic drug relies on strict rules: it is first necessary to determine the epileptic syndrome, because some molecules may be inefficient or may worsen an epileptic syndrome, whereas they can be highly efficient in another epileptic syndrome. Among the antiepileptic drugs, known to be efficient in a specific epileptic syndrome, the choice of one molecule is done according to the suspected tolerance and therefore mainly depends on the characteristics of the patient. Rules for the initiation and adaptation of antiepileptic drugs are presented. Additional molecules, with new targets, must be developed in the future to take care of 25% of the patients with an epilepsy resistant to adapted and well-conducted treatments.
|
10.1016/j.lpm.2011.01.001
|
pubmed_603_1385
|
15-Hydroxyeicosatetraenoic acid, a predominant metabolic product of arachidonic acid (AA) catalyzed by 15-lipoxygenase (15-LO), plays an important role in hypoxic pulmonary arterial hypertension (PAH). Hypoxia-inducible factor-1α (HIF-1α) as a critical oxygen-sensitive transcriptional factor participates in many physiological and pathological processes including PAH. Therefore, it is possible that there may be some connections between HIF-1α and 15-LO/15-HETE in hypoxic pulmonary artery smooth muscle cells. Our results showed that HIF-1α inhibitor or siRNA reduced hypoxia-induced upregulation of 15-LO and endogenous 15-HETE, meanwhile HIF-1α expression and transcriptional activity were induced by 15-HETE under both normoxic and hypoxic conditions. It suggests there exists a potential positive feedback regulatory loop between HIF-1α and 15-LO/15-HETE. Furthermore, cell viability assay and several cell apoptosis assays, including TUNEL assay, Western blot, nuclear morphology determination, mitochondrial potential analysis, indicated that blocking HIF-1α induced apoptosis, decreased cell viability and suppressed the anti-apoptosis effects of 15-HETE. Taken together, our data indicate that upregulation of 15-LO/15-HETE in response to hypoxia may be partially mediated by HIF-1α which is also regulated by 15-HETE in a positive feedback manner, and HIF-1α can effectively inhibit pulmonary artery smooth muscle cells apoptosis which leads to vascular remodeling. The feedback loop between HIF-1α and 15-LO/15-HETE would obviously reinforce hypoxia-induced anti-apoptosis effect and may become a novel target of therapy in PAH.
|
pubmed_603_1385
|
pubmed_1060_73
|
Using the labeled DNA fragments containing the genes for cholera toxin the strains of cholera vibrios were studied for the presence of cholera toxin genes. Vibrio cholerae strains isolated from natural water reservoirs under the favourable epidemic situation do not contain the cholera toxin genes. The DNA hybridization method was compared with other methods used in research and practical work for estimation of epidemic importance of cholera vibrios.
|
pubmed_1060_73
|
pubmed_590_11397
|
In highly urbanized areas, surface water and groundwater are particularly vulnerable to sewer exfiltration. In this study, as an alternative to Microbial Source Tracking (MST) methods, we propose a new method combining microbial and chemical fecal indicators (Escherichia coli (E. coli)) and wastewater micropollutants (WWMPs) analysis both in water and sediment samples and under different meteorological conditions. To illustrate the use of this method, wastewater exfiltration and subsequent infiltration were identified and quantified by a three-year field study in an urban canal. The gradients of concentrations observed suggest that several sources of fecal contamination of varying intensity may be present along the canal, including feces from resident animal populations, contaminated surface run-off along the banks and under bridge crossings, release from contaminated banks, entrainment of contaminated sediments, and most importantly sewage exfiltration. Calculated exfiltration-infiltration volumes varied between 0.6 and 15.7 m(3)/d per kilometer during dry weather, and between 1.1 and 19.5 m(3)/d per kilometer during wet weather. WWMPs were mainly diluted and degraded below detection limits in water. E. coli remains the best exfiltration indicator given a large volume of dilution and a high abundance in the wastewater source. WWMPs are effective for detecting cumulated contamination in sediments from a small volume source and are particularly important because E. coli on its own does not allow source tracking.
|
pubmed_590_11397
|
pubmed_196_21698
|
Previously, we identified plasma microRNA (miR) profiles that associate with markers of microvascular injury in patients with diabetic nephropathy (DN). However, miRs circulate in extracellular vesicles (EVs) or in association with HDL or the RNA-binding protein argonaute-2 (Ago-2). Given that the EV- and HDL-mediated miR transfer toward endothelial cells (ECs) regulates cellular quiescence and inflammation, we hypothesized that the distribution of miRs among carriers affects microvascular homeostasis in DN. Therefore, we determined the miR expression in EV, HDL, and Ago-2 fractions isolated from EDTA plasma of healthy control subjects, patients with diabetes mellitus (DM) with or without early DN (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m2), and patients with DN (eGFR <30 mL/min/1.73 m2). Consistent with our hypothesis, we observed alterations in miR carrier distribution in plasma of patients with DM and DN compared with healthy control subjects. Both miR-21 and miR-126 increased in EVs of patients with DN, whereas miR-660 increased in the Ago-2 fraction and miR-132 decreased in the HDL fraction. Moreover, in vitro, differentially expressed miRs improved EC barrier formation (EV-miR-21) and rescued the angiogenic potential (HDL-miR-132) of ECs cultured in serum from patients with DM and DN. In conclusion, miR measurement in EVs, HDL, and Ago-2 may improve the biomarker sensitivity of these miRs for microvascular injury in DN, while carrier-specific miRs can improve endothelial barrier formation (EV-miR-21/126) or exert a proangiogenic response (HDL-miR-132).
|
10.2337/db18-1360
|
pubmed_223_16601
|
We examined the results of 1.3 million drug tests performed on patients being monitored for compliance with pain medications and substance abuse rehabilitation to determine if the 2016 CDC prescribing guidelines had any impact on opiate benzodiazepine use. We observed that the combination of the opiate drugs morphine, oxycodone, and hydrocodone with the benzodiazepine metabolites oxazepam, alphahydroxyalprazolam, and 7-aminoclonazepam showed many patients were on a combination of these drugs. This ranged from approximately 9 to 16%. There was considerable variability between opiate drug pairs, but there was a general trend to fewer patients on the combination of opiate-benzodiazepine over the 2016 to 2019 time frame.
|
pubmed_223_16601
|
pubmed_465_1413
|
A case of Dühring-Brocq with high titres of ANA is reported. It was not possible to demonstrate a SLE. The associations DH-SLE, blistering diseases-SLE, ANA-DH are reviewed.
|
pubmed_465_1413
|
pubmed_572_19678
|
Beige adipocytes can interconvert between white and brown-like states and switch between energy storage versus expenditure. Here we report that beige adipocyte plasticity is important for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons, repressed the browning of white fat and decreased energy expenditure. Conversely feeding reduced hypothalamic TCPTP, to increase AgRP/NPY neuronal insulin signaling, white adipose tissue browning and energy expenditure. The feeding-induced repression of hypothalamic TCPTP was defective in obesity. Mice lacking TCPTP in AgRP/NPY neurons were resistant to diet-induced obesity and had increased beige fat activity and energy expenditure. The deletion of hypothalamic TCPTP in obesity restored feeding-induced browning and increased energy expenditure to promote weight loss. Our studies define a hypothalamic switch that coordinates energy expenditure with feeding for the maintenance of energy balance.
|
10.1016/j.cmet.2017.07.013
|
pubmed_808_18525
|
Leishmaniasis are diverse group of diseases caused by numerous species of genus Leishmania. Herein we have contrived a systematic review and meta-analysis on the prevalence of Leishmania species in rodents of Iran. For this purpose, following the general methodology recommended for systematic reviews and meta-analysis, six English databases (PubMed, Science Direct, Scopus, Ovid, Web of Science and Google Scholar) and four Persian databases (Magiran, SID, Iran Doc and Iran Medex) were explored during January 1995 till June 2015. Papers were selected based on 8 pre-defined inclusion criteria. During the years, a total number of 4485 different rodents were captured; among which 1291 cases were Leishmania positive. The calculated weighted prevalence of Leishmania species in rodents was 23% (95% CI=18-28). Given geographical zones of Iran, the highest and lowest prevalence rate was belonged to North 50% (95% CI=40-61) and West 11% (95% CI=5-17), respectively. Rhombomys opimus (1766), Meriones lybicus (1258) and Tatera indica (488) were the three most abundant captured rodents, while the highest prevalence of Leishmania species was observed in Nesokia indica 48% (95% CI=42-54) and followed by R. opimus 39% (95% CI=30-47). Egger's regression test was performed to detect publication bias, which revealed it may not have a significant influence on overall weighted prevalence estimate (P=0.317). Meta-regression analysis demonstrated that there is no significant relationship between overall prevalence with sample size (P=0.1) and year of publication (P=0.7). The results showed remarkable prevalence of Leishmania species in rodent reservoirs. In future, adopting a suitable strategy for control and combat with rodents is necessary.
|
10.1016/j.actatropica.2017.04.022
|
pubmed_509_17209
|
The cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) has been considered a serious health threat because of its putative role in multiple neurodegenerative diseases. First reports on BMAA concentrations in cyanobacteria were alarming: nearly all cyanobacteria were assumed to contain high BMAA concentrations, implying ubiquitous exposure. Recent studies however question this presence of high BMAA concentrations in cyanobacteria. To assess the real risk of BMAA to human health, this discrepancy must be resolved. We therefore tested whether the differences found could be caused by the analytical methods used in different studies. Eight cyanobacterial samples and two control samples were analyzed by three commonly used methods: HPLC-FLD analysis and LC-MS/MS analysis of both derivatized and underivatized samples. In line with published results, HPLC-FLD detected relatively high BMAA concentrations in some cyanobacterial samples, while both LC-MS/MS methods only detected BMAA in the positive control (cycad seed sarcotesta). Because we could eliminate the use of different samples and treatments as causal factors, we demonstrate that the observed differences were caused by the analytical methods. We conclude that HPLC-FLD overestimated BMAA concentrations in some cyanobacterial samples due to its low selectivity and propose that BMAA might be present in (some) cyanobacteria, but in the low µg/g or ng/g range instead of the high µg/g range as sometimes reported before. We therefore recommend to use only selective and sensitive analytical methods like LC-MS/MS for BMAA analysis. Although possibly present in low concentrations in cyanobacteria, BMAA can still form a health risk. Recent evidence on BMAA accumulation in aquatic food chains suggests human exposure through consumption of fish and shellfish which expectedly exceeds exposure through cyanobacteria.
|
10.1371/journal.pone.0036667
|
pubmed_648_8975
|
Suppression of the immune system has been constantly reported in the last years as a classical side effect of opioid drugs. Most of the studies on the immunological properties of opioids refer to morphine. Although morphine remains the "reference molecule," other semisynthetic and synthetic opioids are frequently used in the clinical practice. The primary objective of this review is to analyze the available literature on the immunomodulating properties of opioid drugs different from morphine in preclinical models and in the human. A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "opioids," "Natural killer cells," "cytokines," and "lymphocytes." The results achieved concerning the effects of fentanyl, methadone, oxycodone, buprenorphine, remifentanil, tramadol, and tapentadol on immune responses in animal studies, in healthy volunteers and in patients are reported. With some limitations due to the different methods used to measure immune system parameters, the large range of opioid doses and the relatively scarce number of participants in the available studies, we conclude that it is not correct to generalize immunosuppression as a common side effect of all opioid molecules.
|
10.3389/fimmu.2019.02914
|
pubmed_810_4129
|
Beginning in 2005, the Centers for Disease Control and Prevention (CDC) expanded the overseas presumptive treatment of intestinal parasites with albendazole to include refugees from the Middle East. We surveyed the prevalence of helminths and protozoa in recent Middle Eastern refugees (2008-2010) in comparison with refugees from other geographical regions and from a previous survey (2001-2004) in Santa Clara County, California. Based on stool microscopy, helminth infections decreased, particularly in Middle Eastern refugees (0.1% versus 2.3% 2001-2004, P = 0.01). Among all refugees, Giardia intestinalis was the most common protozoan found. Protozoa infections also decreased somewhat in Middle Eastern refugees (7.2%, 2008-2010 versus 12.9%, 2001-2004, P = 0.08). Serology for Strongyloides stercoralis and Schistosoma spp. identified more infected individuals than stool exams. Helminth infections are increasingly rare in refugees to Northern California. Routine screening stool microscopy may be unnecessary in all refugees.
|
10.4269/ajtmh.2012.12-0349
|
pubmed_80_14925
|
BACKGROUND
Over 28 000 individuals were infected with Ebola virus during the West Africa (2013-2016) epidemic, yet there has been criticism of the lack of robust clinical descriptions of Ebola virus disease (EVD) illness from that outbreak.
OBJECTIVES
To perform a meta-analysis of published data from the epidemic to describe the clinical presentation, evolution of disease, and predictors of mortality in individuals with EVD. To assess the quality and utility of published data for clinical and public health decision-making.
DATA SOURCES
Primary articles available in PubMed and published between January 2014 and May 2017.
ELIGIBILITY
Studies that sequentially enrolled individuals hospitalized for EVD and that reported acute clinical outcomes.
METHODS
We performed meta-analyses using random-effect models and assessed heterogeneity using the I2 method. We assessed data representativeness by comparing meta-analysis estimates with WHO aggregate data. We examined data utility by examining the availability and compatibility of data sets.
RESULTS
In all, 3653 articles were screened and 34 articles were included, representing 16 independent cohorts of patients (18 overlapping cohorts) and at least 6168 individuals. The pooled estimate for case fatality rate was 51% (95% CI 46%-56%). However, pooling of estimates for clinical presentation, progression, and predictors of mortality in individuals with EVD were hampered by significant heterogeneity, and inadequate data on clinical progression. Our assessment of data quality found that heterogeneity was largely unexplained, and data availability and compatibility were poor.
CONCLUSIONS
We have quantified a missed opportunity to generate reliable estimates of the clinical manifestations of EVD during the West Africa epidemic. Clinical data standards and data capture platforms are urgently needed.
|
10.1016/j.cmi.2019.06.032
|
pubmed_410_246
|
Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions.
|
10.1016/S1473-3099(21)00808-2
|
pubmed_428_17618
|
OBJECTIVE
To Study the effect of C677T and MTHFR gene polymorphism on side effects of HD-MTX in ALL children.
METHODS
The gene polymorphism of C677T A303G and MTHFR C677T were detected by PCR in 98 ALL children from January 2014 to January 2016. The side effects during HD-MTX therapy were observed, and the relationship among GSTP1, MTHFR gene polymorphism and incidence of side effect of HD-MTX were analyzed.
RESULTS
Among 98 ALL children, the gene variation was observed in 61 ALL children (62.24%). Polymorphism study on C677T A303G showed that the gene frequency of A was 84.69%, while that of G was 15.31%; for polymorphism of MTHFR C677T, gene frequency of C was 66.33%, and that of T was 33.67%. Seven patients(7.14%) experienced with bone marrow supression, 23 patients(23.47%) with liver function damage, 15 patients(15.31%) with renal function damage, 48 patients(48.98%) with gastrointestinal reactions and 46 patients(46.94%) with mucosal lesions. After adjustment of sex, age, risk stratification and dosage of MTX, the gene polymorphism had no significant relationship with bone marrow suppression, gastrointestinal reactions and mucosal lesions(P>0.05). However, the number of the mutant genes had statistically significant relationship with liver and renal function damage(P<0.05).
CONCLUSION
The risk of side effects during HD-MTX therapy increases in ALL children with combined mutation of MTHFR and C677T.
|
10.7534/j.issn.1009-2137.2017.03.016
|
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