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pubmed_259_6606 | Studies in healthy individuals and split-brain patients have shown that the representation of facial information from the left visual field (LVF) is better than the representation of facial information from the right visual field (RVF). To investigate the neurophysiological basis of this LVF superiority in face perception, we recorded event-related potentials (ERPs) to centrally presented face stimuli in which relevant facial information is present bilaterally (B faces) or only in the left (L faces) or the right (R faces) visual field. Behavioral findings showed best performance for B faces and, in line with the LVF superiority, better performance for L than R faces. Evoked potentials to B, L, and R faces at 100- to 150-msec poststimulus showed no evidence of asymmetric transfer of information between the hemispheres at early stages of visual processing, suggesting that this factor is not responsible for the LVF superiority. Neural correlates of the LVF superiority, however, were manifested in a shorter latency of the face-specific N170 component to L than R faces and in a larger amplitude to L than R faces at 220-280 and 400-600 msec over both hemispheres. These ERP amplitude differences between L and R faces covaried across subjects with the extent to which the face-specific N170 component was larger over the right than the left hemisphere. We conclude that the two hemispheres exchange information symmetrically at early stages of face processing and together generate a shared facial representation, which is better when facial information is directly presented to the right hemisphere (RH; L faces) than to the left hemisphere (LH; R faces) and best when both hemispheres receive facial information (B faces). | 10.1162/089892903321593162 |
others_333_19103 | These studies present an efficient and sensitive method for detection of T cell growth factor (TCGF) activity in human lymphocyte cultures and illustrate that T cell growth factors are associated with T lymphocyte-mediated anti-HSV-1 responses. Secretion of TCGF is induced after stimulation of human peripheral blood mononuclear cells (PBMNC) with herpes simplex virus type 1 (HSV-1). Lymphokine activity is detected in a simple, sensitive method by studying [3H]thymidine incorporation after the addition of murine CTLL-20 cells to cultures of γ-irradiated (4000 R), virus-stimulated PBMNC. By using this assay, we find that PBMNC from seropositive but not seronegative individuals produce detectable TCGF activity in a dose-dependent manner after incubation with HSV-1. Maximum activity is detected between 24 to 48 hr of incubation and correlates with in vitro proliferation of nonirradiated PBMNC in response to the virus. In addition, γ-irradiated (1000 to 3000 R) PBMNC, which are frequently used as a source of antigen-presenting cells (APC), can secrete TCGF after contact with HSV-1. Lymphokine production by the APC-containing population is eliminated by γ-irradiation (5000 R); such APC can still present UV-inactivated HSV-1 to HSV-1-responsive lymphoblasts, indicating that lymphokine production by T cells residing in the APC population is not essential for antigen presenta | others_333_19103 |
pubmed_540_9482 | PURPOSE
To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS).
METHODS
The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to ≥ 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI.
RESULTS
The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations.
CONCLUSION
Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome. | 10.1007/s00586-022-07317-5 |
pubmed_697_6018 | We report experimental measurements of the axial plasma flow and the parallel ion temperature in a magnetized linear plasma device. We used laser induced fluorescence to measure Doppler resolved ion velocity distribution functions in argon plasma to obtain spatially resolved axial velocities and parallel ion temperatures. We also show changes in the parallel velocity profiles during the transition from resistive drift wave dominated plasma to a state of weak turbulence driven by multiple plasma instabilities. | 10.1063/1.4959275 |
pubmed_935_13356 | Myeloid and erythroid colony growth of the bone marrow and peripheral blood cells from one anaemic and four non-anaemic patients with Fanconi's anaemia were studied. Markedly decreased myeloid and erythroid colony growth was found in all five patients regardless of their haematological status. The decreased colony formation in non-anaemic patients with Fanconi's anaemia is thought to be due to an intrinsic cellular defect. | 10.1111/j.1365-2141.1980.tb01181.x |
pubmed_1098_7076 | Auranofin (Ridaura®, AUF) is a gold complex originally approved as an antirheumatic agent that has emerged as a potential candidate for multiple repurposed therapies. The best-studied anticancer mechanism of AUF is the inhibition of thioredoxin reductase (TrxR). However, a number of reports indicate a more complex and multifaceted mode of action for AUF that could be cancer cell type- and dose-dependent. In this study, we observed that AUF displayed variable cytotoxicity in five triple-negative breast cancer cell lines. Using representative MDA-MB-231 cells treated with moderate and cytotoxic doses of AUF, we evidenced that an AUF-mediated TrxR inhibition alone may not be sufficient to induce cell death. Cytotoxic doses of AUF elicited rapid and drastic intracellular oxidative stress affecting the mitochondria, cytoplasm and nucleus. A "redoxome" proteomics investigation revealed that a short treatment with a cytotoxic dose AUF altered the redox state of a number of cysteines-containing proteins, pointing out that the cell proliferation/cell division/cell cycle and cell-cell adhesion/cytoskeleton structure were the mostly affected pathways. Experimentally, AUF treatment triggered a dose-dependent S-phase arrest and a rapid disintegration of the actin cytoskeleton structure. Our study shows a new spectrum of AUF-induced early effects and should provide novel insights into the complex redox-based mechanisms of this promising anticancer molecule. | 10.3390/cancers14194864 |
pubmed_583_16625 | RATIONALE
Aldosterone has been shown to induce vascular damage, endothelial dysfunction, and myocardial fibrosis, which depend in part on activation of angiotensin II (Ang II)-mediated pathways. However, mechanisms underlying crosstalk between Ang II type 1 receptor (AT(1)R) and mineralocorticoid receptor (MR) are mostly unknown.
OBJECTIVES
We tested whether the lack of Ang II type 1a receptor (AT(1a)R) or Ang II type 1b receptor (AT(1b)R) would decrease cellular effects induced by aldosterone.
METHODS AND RESULTS
We examined the effect of Ang II or aldosterone after transfection of mesenteric vascular smooth muscle cells (VSMCs) from C57Bl/6 mice with small interference RNA for AT(1a)R, AT(1b)R, or MR for 48 hours. Ang II and aldosterone separately induced ERK1/2, c-Jun NH2-terminal protein kinase (JNK), and nuclear factor (NF)-kappaB phosphorylation after a 20-minute stimulation. Small interference RNA for AT(1a)R downregulated phosphorylation of ERK1/2, JNK, and NF-kappaB after aldosterone stimulation compared to controls. Downregulation of AT(1b)R or MR only abolished the activation of NF-kappaB. In VSMCs from C57Bl/6 mice, aldosterone and Ang II induced the activation of the c-fos promoter from 30 minutes to 1 hour. This effect was blocked when using VSMCs from AT(1a)R knockout mice.
CONCLUSION
We show for the first time that nongenomic and genomic effects of aldosterone are differentially dependent on activity of both AT(1a)R and AT(1b)R. Our data suggest that aldosterone augments AT(1)R-dependent activation of ERK1/2, JNK, and NF-kappaB in VSMCs. We provide mechanistic understanding and experimental in vitro support for the benefit of combination therapy with dual blockade of AT(1)R and MR to treat hypertension and progression of heart failure as reported in clinical studies and animal models. | 10.1161/CIRCRESAHA.109.196576 |
pubmed_982_7529 | Insect herbivory leads to induced resistance to subsequent infestations in plants. This is due in part to feeding-induced expression of genes that can lead to reduced palatability and/or digestibility of the plant material. We identified 57 distinct differentially expressed genes from poplars that were either infested by gypsy moth (Lymantria dispar) or mechanically wounded. Eleven highly insect-inducible genes were also found to be wound-inducible. Time course analysis revealed diverse timing of peak transcript accumulation. Sequence analysis of promoters suggested that the wound responsive elements, W and DRE, and the jasmonic acid responsive H motif, are over-represented in wound-induced poplar promoters and should be investigated further. | 10.1007/s10529-006-9119-2 |
others_137_4140 | Aims: Low gas diffusivity of the litter layer is held responsible for high seasonal nitrous oxide (N2O) and low nitric oxide (NO) emissions from acid beech forest soils with moder type humus. The objectives were (i) to evaluate whether these beech forest soils generally exhibit high seasonal N2O emissions and (ii) to assess the influence of gas diffusivity and nitrogen (N) mineralisation on N oxide fluxes. Methods: We measured N2O and NOx (NO + NO2) fluxes in six German beech stands and determined net N turnover rates and gas diffusivity of soil samples taken at each chamber. Results: High N2O emissions (up to 113 μg N m-2 h-1) were only observed at one beech stand. Net nitrification of the organic layer and soil gas diffusivity explained 77 % of the variation in N2O fluxes (P = 0.001). Fluxes of NOx were low (-6.3 to 12.3 μg N m-2 h-1) and appeared to be controlled by NOx concentrations in the forest air. Conclusions: Low soil gas diffusivity and high N turnover rates promoted high N2O losses in times of high soil respiration but were not necessarily associated with moder type humus. High seasonal emissions are probably less common in German beech forests than previously assumed. © 2013 The Author(s) | 10.1007/s11104-013-1602-7 |
pubmed_905_21122 | BACKGROUND
Consciousness, the medium of sentient thought, requires integrity of functional networks and their connectivity. In health, they function as a co-operative but mutually exclusive paradigm of introspection versus external awareness subserved via the Default Mode Network and Task Positive State, respectively. Higher thinking in the conscious state is then segregated according to need. There is research evidence to suggest that functional networks may be impacted in disorders of consciousness and conceptual support for a mechanistic role in delirium. This potentially central aspect of delirium manifestation is relatively unexplored.
OBJECTIVE
This article describes the role of disrupted functional networks in delirium. How this relates to current understanding of delirium neurobiology and the ramifications for clinical diagnosis is discussed.
METHOD
A review of the role of functional networks, particularly DMN and TPN, has been undertaken with respect to health and delirium. An exploration of how symptoms of delirium may be related to functional network aberrancy has been undertaken. Implications for research and clinical practice in delirium have been presented.
RESULTS
In delirium, a disturbance of consciousness, the DMN is pathologically co-activated and functional cortical connectivity is compromised. The clinical correlate is of an experiential singularity where internal and external drivers become indistinguishable, reality and delusion merge and the notion of self is effaced. Our group propose that functional network disruption in conjunction with cortical disconnectivity is central to the mechanism of delirium. Clinical tools may exploit the neurobiology of delirium to improve its diagnosis and an example of such a simple screening instrument (SQeeC) is provided.
CONCLUSION
Functional networks are critically disrupted in delirium and may be central to clinical features. A better understanding of the neurobiology of delirium will generate research opportunities with potential for therapeutic gains in detection, diagnosis, and management. | 10.2174/1874609809666161004142027 |
pubmed_608_11084 | Clubfoot. The clubfoot is secondary to an early trouble of foot development at the end of the first trimester of pregnancy. This explains the structural disorders which concern all the tissues of mid-hindfoot and the leg and the tendency to relapse during growth. The diagnostic is triple: positive, etiological and scoring classification. A clinical and radiological checking is mandatory until the end of growth. The treatment is conservative combining casts, splints and physiotherapy. The indication of Achilles tenotomy, not systematic, is evaluated on clinical and radiological criteria. Nocturnal orthosis until at least 5 years old is one of the most important therapeutic aspects. A soft tissue release is indicated in case of a significant deformity. Minor « enhancement procedures » as tibialis anterior tendon lenghtening or transfer, may be indicated for punctual flaw. The results in adults are good in 80% of cases, and inversely proportional to heavy treatments during childhood including surgeries. | pubmed_608_11084 |
pubmed_641_16693 | Lactoferrin (LTF), which is the major iron-binding protein in milk and physiological fluids, belongs to the transferrin family. We report here the sequence of a caprine LTF cDNA, 2411 bp in length, encoding the pre-protein (709 amino acid residues). Sequence comparisons reveal that structural features, including iron-binding sites, cysteine residues involved in disulphide bonds are remarkably conserved between LTF proteins from various species. Of the 5 potential glycosylation sites identified, only one site appears to be conserved between artiodactyls, rodents and humans. Using a somatic cell hybrid panel, the LTF locus was assigned to the bovine U12 syntenic group. This assignment and the localization of the LTF gene on bovine chromosome 22 (BTA 22) by Schwerin et al. (1) using fluorescent in situ hybridization achieves an additional analogy between a synteny group and a chromosome in cattle. Since serum transferrin (STF) had been previously mapped on BTA 1, in cattle LTF and STF loci are not localized on the same chromosome, conversely to the situation observed in humans (HSA 3) and mice (MMU 9). | 10.1006/bbrc.1994.2327 |
pubmed_106_12519 | Pressure-induced tensions in the xylem, the water conducting tissue of vascular plants, can lead to embolism in the water-conducting cells. The details and mechanisms of embolism repair in vascular plants are still not well understood. In particular, experimental results which indicate that embolism repair may occur during xylem tension cause great problems with respect to current paradigms of plant water transport. The present paper deals with a theoretical analysis of interfacial effects at the pits (pores in the conduit walls), because it was suggested that gas-water interfaces at the pit pores may be involved in the repair process by hydraulically isolating the embolized conduit. The temporal behaviour of bubbles at the pit pores was especially studied since the question of whether these pit bubbles are able to persist is of crucial importance for the suggested mechanism to work. The results indicate that (1) the physical preconditions which are necessary for the suggested mechanism appear to be satisfied, (2) pit bubbles can achieve temporal stability and therefore persist and (3) dissolving of bubbles in the conduit lumen may lead to the final breakdown of the hydraulic isolation. The whole process is, however, complex and strongly dependent on the detailed anatomy of the pit and the contact angle. | 10.1016/s0022-5193(03)00138-3 |
pubmed_710_4032 | Coxartrosis is a common cause of hip pain among the elderly population. Avascular necrosis (AVN), also known as osteonecrosis, is a disease that most commonly affects the femoral head as a result of decreased blood supply to the bone. The etiology and pathogenesis is still unclear, but there are various traumatic and atraumatic factors that have been suggested as risk factors for AVN. However, almost half of the patients present none of these risk factors. Compared to coxartrosis, AVN typically occurs in a younger population. Initially it can be difficult to differ between these conditions. Plain film radiographic findings are absent in early stages of AVN, but magnetic resonance imaging (MRI) can provide early diagnosis. Thereby, MRI is the golden standard of noninvasive diagnostic evaluation. We present a patient with bilateral AVN that initially was diagnosed with coxartrosis. | pubmed_710_4032 |
pubmed_270_18526 | BACKGROUND
Chemotherapy is effective against a wide variety of tumor cells, although its use is limited by side effects. In vitro experiments and phase I and II trials have shown that phytochemicals such as perillyl alcohol (P-OH) have antitumor effects. Pentoxifylline (PTX), a synthetic methylxanthine used mainly to treat pathologies associated with hematological diseases, sensitizes tumor cells to chemotherapy. The aim of this study was to determine whether PTX amplifies the antitumor effects of P-OH in U937 human myelomonocytic leukemia cells.
METHODS
Apoptosis was measured by the loss of mitochondrial membrane potential determined by flow cytometry using dihexyloxacarbocyanine iodide (DiOC6) and propidium iodide. Bcl-2 and Bax protein expression was also assessed by Western blot analysis.
RESULTS
P-OH and PTX induced loss of the mitochondrial membrane potential in U937 cells in vitro. Culturing the cells in the presence of both compounds caused a significant increase (p < 0.001) in apoptosis and expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins. However, despite their coexistence, Bax expression prevailed in our experiments. These data suggest that the effects of PTX might be attributable to changes in the mitochondrial membrane potential.
CONCLUSION
PTX sensitizes tumor cells to the anti-neoplastic action of P-OH. These observations may have clinical relevance in the treatment of cancer patients. | 10.1159/000096003 |
pubmed_58_15130 | Although many reports have revealed the importance of defective microglia-mediated amyloid β phagocytosis in Alzheimer's disease (AD), the underlying mechanism remains to be explored. Here we demonstrate that neurons in the brains of patients with AD and AD mice show reduction of sphingosine kinase1 (SphK1), leading to defective microglial phagocytosis and dysfunction of inflammation resolution due to decreased secretion of specialized proresolving mediators (SPMs). Elevation of SphK1 increased SPMs secretion, especially 15-R-Lipoxin A4, by promoting acetylation of serine residue 565 (S565) of cyclooxygenase2 (COX2) using acetyl-CoA, resulting in improvement of AD-like pathology in APP/PS1 mice. In contrast, conditional SphK1 deficiency in neurons reduced SPMs secretion and abnormal phagocytosis similar to AD. Together, these results uncover a novel mechanism of SphK1 pathogenesis in AD, in which impaired SPMs secretion leads to defective microglial phagocytosis, and suggests that SphK1 in neurons has acetyl-CoA-dependent cytoplasmic acetyltransferase activity towards COX2. | 10.1038/s41467-018-03674-2 |
pubmed_923_15393 | A survey of the current practice of general paediatric surgery in South Africa and Namibia was conducted by means of a postal questionnaire. One hundred and eighty-one replies were obtained (52%). Analysis showed that although surgeons are located predominantly in the major cities, 18% practised in the larger towns or rural areas. Although paediatric surgery represents a small volume of their work, most surgeons do attend to the surgical needs of children. The majority of surgeons have received some paediatric surgical training but this was considered inadequate by nearly half of all surgeons and by 60% of those who qualified in the last 10 years. Current postgraduate training at most of our universities involves a 3-6-month rotation, but from our survey this is considered insufficient in practice and there appears to have been some deterioration in paediatric surgical training in recent years. Steps needed to maintain paediatric surgical standards are discussed. | pubmed_923_15393 |
pubmed_1136_20628 | A word's frequency of occurrence and its predictability from a prior context are key factors determining how long the eyes remain on that word in normal reading. Past reaction-time and eye movement research can be distinguished by whether these variables, when combined, produce interactive or additive results, respectively. Our study addressed possible methodological limitations of prior experiments. Initial results showed additive effects of frequency and predictability. However, we additionally examined launch site (the distance from the pretarget fixation to the target) to index the extent of parafoveal target processing. Analyses revealed both additive and interactive effects on target fixations, with the nature of the interaction depending on the quality of the parafoveal preview. Target landing position and pretarget fixation time were also considered. Results were interpreted in terms of models of language processing and eye movement control. Our findings with respect to parafoveal preview and fixation time constraints aim to help parameterize eye movement behavior. | 10.1037/a0020363 |
pubmed_560_17179 | We determined the effects of emulsifier concentration and temperature on the distribution of gallic acid (GA) in a food-grade emulsion composed of 1:9 vol:vol stripped corn oil, acidic water and Tween 20. The distribution of GA can be defined by the partition constant between the aqueous and the interfacial regions, P(W)(I), which was determined by using a kinetic method and the pseudophase kinetic model. Once P(W)(I) is known, determining the distribution of GA is straightforward. Our results show that at least 40% of the total GA is located in the interfacial region of the emulsion at 0.005 volume fraction of Tween 20, and this percentage increases to ca. 85% of the total GA at 0.04 volume fraction of Tween 20. The variation of P(W)(I) with the temperature was used to estimate the thermodynamic parameters for the GA transfer from the aqueous to the interfacial region of the emulsion and the activation parameters for the reaction between 16-ArN(2)(+) and GA in the interfacial region. The free energy of transfer from the aqueous to the interfacial region, ΔG(T)(0,W→I), is negative, the enthalpy of transfer is small and negative, but the entropy of transfer is large and positive. Our results demonstrate that the partitioning of GA in acidic emulsions between aqueous and interfacial regions depends primarily on droplet concentration and is only slightly dependent on temperature. | 10.1016/j.jcis.2011.12.057 |
pubmed_568_15164 | BACKGROUND
Proclined teeth has been one of the main reasons for compromised esthetics. In a patient with proclined anteriors, retraction is done after 1st premolar extraction. Absolute/maximum anchorage is required to achieve the best esthetics.
OBJECTIVE
We conducted this study with the aim of retracting the proclined maxillary anterior teeth and to check for efficient retraction, type of tooth movement during retraction, and amount of anchorage loss.
METHODS
Patients with proclined anterior teeth where therapeutic extraction of first premolars is required were included in the study, where anchorage was taken with mini-implants in one group, and in the second group, conventional anchorage method of 1st and 2nd molar banding with TPA was chosen. Each group consisted of 8 subjects. Lateral cephalogram was taken both preretraction and 4 months after starting retraction to compare anchor loss, rate of retraction, and type of tooth movement of retracted anteriors, in both groups.
RESULTS
The retraction in the implant group was more than in the conventional group and the difference was statistically significant (P < 0.05). Anchorage loss was seen to be greater in conventional group than in the implant group and was also significant statistically. The type of tooth movement of the anterior teeth on retraction was also compared, with the implant group showing predominantly controlled tipping and the conventional group showing uncontrolled tipping movement. | 10.4103/jfmpc.jfmpc_841_20 |
pubmed_656_16019 | Smoking cigarettes with substantially lower nicotine than conventional cigarettes prior to a quit attempt may reduce the reinforcing effects of smoking, which could facilitate smoking cessation through extinction learning. This paper describes the development of a smoking cessation intervention designed to optimize extinction processes using reduced nicotine cigarettes, as well as the design and methods for an ongoing randomized controlled trial (RCT) to evaluate this intervention. Qualitative methods and pilot testing were conducted to develop the novel facilitated extinction (FE) intervention, with a key focus on maximizing opportunities for extinction learning during a five-week pre-quit period. The primary aims of the RCT are to test the effects of the FE intervention versus a standard (cognitive-behavioral) intervention, while also comparing two nicotine reduction schedules for providing very low nicotine content (VLNC) cigarettes. The efficacy of the intervention is currently being evaluated with treatment-seeking smokers (n = 208) randomly assigned to one of four conditions crossing FE versus standard intervention with immediate versus gradual transition to VLNC cigarettes. | 10.1016/j.cct.2020.106172 |
others_206_1460 | Cerebral infarcts can be overlooked or grossly underestimated in the second and third week after an ischemic stroke. We report a patient who presented with a vanishing stroke on a follow-up brain computed tomography scan, a condition known as the "fogging effect" phenomenon. © 2013 Elsevier B.V. All rights reser | 10.1016/j.jstrokecerebrovasdis.2012.08.009 |
pubmed_845_23510 | BACKGROUND
Randomized clinical trials (RCTs) in Parkinson's disease (PD) have historically enrolled a low number of underrepresented minorities, lessening the generalizability of therapeutic developments. Although there are racial disparities in PD, little is known regarding neuropsychiatric symptoms and other nonmotor manifestations across all races/ethnicities.
OBJECTIVE
To assess minority participation in PD trials evaluating the treatment of neuropsychiatric symptoms and explore underlying reasons.
METHODS
We systematically searched PubMed and Embase for RCTs with a primary goal of treating neuropsychiatric symptoms in PD patients from 2000-2019. The pooled prevalence and 95% confidence interval (CI) of being white and enrolled in a clinical trial was calculated using the inverse variance method. I-square was calculated as a measure of heterogeneity and meta-regression was used to evaluate temporal trends.
RESULTS
We included 63 RCTs with a total of 7,973 patients. In pooled analysis, 11 (17.5%) RCTs reported race/ethnicity. Of studies reporting this data, 5 African American (0.2%), 16 Hispanics (0.64%), and 539 Asians (21.44%) were enrolled. The pooled prevalence of being white in clinical trials was 98% (CI 0.97-0.98, p < 0.001), with 1,908 patients (75.8%). NIH-funded studies were most likely to report racial data when compared to non-NIH trials (p = 0.032).
CONCLUSION
This large pooled analysis found a small percentage of RCTs reporting race/ethnicity when evaluating treatment of neuropsychiatric symptoms in PD. There was a disproportionally high number of white patients when compared to African Americans and Hispanics. More studies are needed to investigate this discrepancy and improve rates of & minority enrollment in PD trials. | 10.3233/JPD-202045 |
pubmed_655_13249 | A simple and rapid method using an ammonia ion-selective electrode (ISE) to measure volatile bases in fish is proposed. Accuracy and precision were determined with 5, 10, 20, and 30 ppm NH3 standard solutions. Ammonia values obtained with the method correlate strongly with total volatile basic nitrogen (r2 = 0.88). Recoveries of added ammonia to homogenized fish samples ranged from 83.7 to 96.0%. Responses of the probe to trimethylamine (TMA), calculated as NH3 (mg/100 mL), ranged from 74.9 to 91.7%. These findings indicate that the probe measured TMA as well as ammonia. Storage trials on 8 fish species illustrated that the results obtained with the ISE method reflected nitrogen concentrations based on total volatile base (TVB) analysis. This procedure may be used in lieu of the traditional TVB method for on-site rapid screening of fish. | pubmed_655_13249 |
others_171_11529 | The present investigation was carried out to study the semen characteristics of Punganur bulls. The overall mean ejaculate volume (ml), mass activity (0-4 scale), individual motility (%), sperm concentration (millions/ml), live sperms (%), sperm head abnormalities (%), acrosomal damage (%), mid piece abnormalities (%), tail abnormalities (%) and total sperm abnormalities in neat semen of Punganur bulls were 3.25 ± 0.15, 3.26 ± 0.06, 72.85 ± 0.71, 1427.25 ± 3.77, 79.34 ± 0.33, 4.25 ± 0.07, 4.75 ± 0.07, 1.97 ± 0.27, 4.25 ± 0.08 and 10.46 ± 0.12, respectively espectively. Significant differencesences in ejaculate volume, mass activity, individual motility and live sperms were observed among the bulls | others_171_11529 |
pubmed_396_1964 | AIM
To evaluate a computed strain-gauge plethysmograph (CSGP) as a screening tool to exclude above knee deep venous thrombosis (DVT).
METHODS
The first phase took place in the Radiology department. One hundred and forty-nine patients had both Doppler ultrasound and CSGP performed. Discordant results were resolved by venography where possible. The second phase took place in an acute medical admissions ward using a modified protocol. A further 173 patients had both studies performed. The results were collated and analysed.
RESULTS
Phase 1. The predictive value of a negative CSGP study was 98%. There were two false-negative CSGP results (false-negative rate 5%), including one equivocal CSGP study which had deep venous thrombosis on ultrasound examination. Two patients thought to have thrombus on ultrasound proved not to have acute thrombus on venography. Phase 2. The negative predictive value of CSGP using a modified protocol was 97%. There were two definite and one possible false-negative studies (false-negative rate 4-7%).
CONCLUSION
Computer strain-gauge plethysmograph can provide a simple, cheap and effective method of excluding lower limb DVT. However, its use should be rigorously assessed in each hospital in which it is used. Goddard, A. J. P., Chakraverty, S. & Wright, J. (2001). Clinical Radiology56, 30-34. | 10.1053/crad.2000.0604 |
pubmed_1077_6919 | Three gold(iii) complexes with terminal amido ligands were prepared by the reaction of [Au(III)(trpy)(OH)](ClO4)2 and primary amines having electron-withdrawing groups such as 2-amino-4-chloropyrimidine, 2-amino-5-chloro-pyridine, and 2-aminopyrimidine. Conversion of the amido ligands into the imido or amine ligands resulted in the decomposition of the complexes by intramolecular redox reaction or the release of amine ligands, respectively. | 10.1039/c4dt02279c |
pubmed_381_19469 | The frequency of overweight and obesity is rising globally. These disorders are prevalent health problems. It has a substantial correlation with a number of health issues, including cardiovascular, metabolic, and diabetes mellitus disorders. Lycopene (Lyc) is an acyclic structural isomer of β-carotene and has powerful antioxidant properties with various promising therapeutic effects. In this study, rats fed a high-fat diet were examined to determine how lycopene affected metabolic syndrome and kidney damage. After being acclimated, rats were divided into 5 groups (n = 8/group) as follows: the first group served as the control and was fed on a normal pelleted diet (4.25% fat) until the end of the experiment. The second group (high-fat diet; HFD) was fed on a high-fat diet (45.5 kcal% fat) composed of 24% fat, 24% protein, and 41% carbohydrate. The third and fourth groups were fed on HFD and administered lycopene at 25 and 50 mg/kg bodyweight orally every day. The fifth group (standard drug group) received HFD and simvastatin (SVS; 10 mg/kg bodyweight orally daily) for 3 months. Tissue samples from the kidney were taken for determination of the biochemical parameters, lipid peroxidation (LPO), protein carbonyl (PC), reduced glutathione (GSH), total thiol group, antioxidant enzymes, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), in addition to renal mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2), renal levels of inflammatory markers [tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)], and apoptotic markers (BCL2 Associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Bax/Bcl-2 ratio). When compared to the control group, the HFD group's food consumption, body weight, serum levels of glucose, uric acid, creatinine, LPO, PC, TNF-α, IL-1β, Bax, and the Bax/Bcl-2 ratio all increased significantly. In the kidney sample of HFD-fed rats, there was a downregulation of Nrf2 mRNA expression along with a significant reduction in the enzymatic activity of SOD, CAT, GR, and GPx. Lyc treatment was able to successfully reverse HFD-mediated changes as compared to the HFD group. Consuming lyc helps to prevent fat and renal damage in a positive way. | 10.1021/acsomega.2c02796 |
pubmed_659_4434 | Background
Since its outbreak, the COVID-19-pandemic has had a tremendous impact on healthcare systems worldwide. We conducted a comparative study to analyze the pandemic's consequence on microsurgical reconstructions at a reconstructive plastic surgery center in Sweden.
Method
All free flaps performed at a single center between March 2019 and 2021 were analyzed. The patient cohort was divided into two groups, with a period of 1 year in each group: non-COVID-19 year and COVID-19 year. The periods were compared regarding the number and type of surgeries and patient characteristics.
Results
In the year prior to the pandemic, 123 free flap surgeries were performed, compared with 103 surgeries during the COVID-19 year. There was a significant shift in the most common site for free flap reconstruction: from the breast [which decreased by 42% (66-38)] to head and neck [which increased by 22% (41-50); OR 0.53 (P = 0.02)]. This was also reflected by a significant increase in hospital stay for free flap patients during the COVID-19 year (P = 0.02).
Conclusions
During the COVID-19 pandemic, a shift was seen from breast reconstructions toward head and neck reconstructions as the most common free flap procedure performed. An increasing backlog of elective breast reconstructions demands increased resources and tougher priorities, which challenge the healthcare system in the post-COVID-19 era. | 10.1097/GOX.0000000000004309 |
pubmed_204_2484 | Understanding and controlling the individual behavior of nanoscopic matter in liquids, the environment in which many such entities are functioning, is both inherently challenging and important to many natural and man-made applications. Here, we transport individual nano-objects, from an assembly in a biological ionic solution, through a nanochannel network and confine them in electrokinetic nanovalves, created by the collaborative effect of an applied ac electric field and a rationally engineered nanotopography, locally amplifying this field. The motion of so-confined fluorescent nano-objects is tracked, and its kinetics provides important information, enabling the determination of their particle diffusion coefficient, hydrodynamic radius, and electrical conductivity, which are elucidated for artificial polystyrene nanospheres and subsequently for sub-100-nm conjugated polymer nanoparticles and adenoviruses. The on-chip, individual nano-object resolution method presented here is a powerful approach to aid research and development in broad application areas such as medicine, chemistry, and biology. | 10.1126/sciadv.abd8758 |
others_195_328 | : The SARS-CoV-2 virus elicited a major public concern worldwide since December 2019 due to the high number of infections and deaths caused by COVID-19. The Omicron variant was detected in October 2021 which evolved from the wild-type SARS-CoV-2 and was found to possess many mutations. Omicron exhibited high transmissibility and immune evasion as well as reduced severity when compared to the earlier variants. Although vaccinated individuals were largely protected against infections in previous waves, the high prevalence of both reinfections and breakthrough infections with Omicron was observed. The aim of this review is to understand the effectiveness of previous infection on subsequent reinfection, given its significance in driving public health policy, including vaccination prioritization and lockdown requirements. Methods: A comprehensive literature search was conducted using several databases to target studies reporting data related to the effectiveness of the previous infection with SARS-CoV-2 in protecting against the Omicron variant. Screening of the studies, quality assessment and data extraction were conducted by two reviewers for each study. Results: Only 27 studies met our inclusion criteria. It was observed that previous infection was less effective in preventing reinfections with the Omicron variant compared to the Delta variant irrespective of vaccination status. Furthermore, being fully vaccinated with a booster dose provided additional protection from the Omicron variant. Additionally, most infections caused by Omicron were asymptomatic or mild and rarely resulted in hospitalizations or death in comparison to the Delta wave. Conclusion: A majority of the studies reached a consensus that although previous infection provides some degree of immunity against Omicron reinfection, it is much lower in comparison to Delta. Full vaccination with two doses was more protective against Delta than Omicron. Receiving a booster dose provided additional protection against Omicron. It is therefore clear that neither vaccination nor previous infection alone provide optimal protection; hybrid immunity has shown the best results in terms of protecting against either Omicron or Delta variants. However, additional research is needed to quantify how long immunity from vaccination versus previous infection lasts and whether individuals will benefit from variant-specific vaccinations to enhance protection from infection. © 2023, The Author(s) | 10.1186/s12879-023-08328-3 |
pubmed_828_6318 | Cell segmentation and tracking in time-lapse fluorescence microscopy images is a task of fundamental importance in many biological studies on cell migration and proliferation. In recent years, level sets have been shown to provide a very appropriate framework for this purpose, as they are well suited to capture topological changes occurring during mitosis, and they easily extend to higher dimensional image data. This model evolution approach has also been extended to deal with many cells concurrently. Notwithstanding its high potential, the multiple-level-set method suffers from a number of shortcomings, which limit its applicability to a larger variety of cell biological imaging studies. In this paper, we propose several modifications and extensions to the coupled-active-surfaces algorithm, which considerably improve its robustness and applicability. Our algorithm was validated by comparing it to the original algorithm and two other cell segmentation algorithms. For the evaluation, four real fluorescence microscopy image datasets were used, involving different cell types and labelings that are representative of a large range of biological experiments. Improved tracking performance in terms of precision (up to 11%), recall (up to 8%), ability to correctly capture all cell division events, and computation time (up to nine times reduction) is achieved. | 10.1109/TMI.2009.2038693 |
pubmed_298_16726 | Findings from research that has assessed the influence of dietary factors on child obesity have been equivocal. In the present study, we aimed to test the hypothesis that a positive change in diet quality is associated with favourable changes in BMI z-scores (zBMI) in schoolchildren from low socio-economic backgrounds and to examine whether this effect is modified by BMI category at baseline. The present study utilised data from a subsample (n 216) of the Resilience for Eating and Activity Despite Inequality study, a longitudinal cohort study with data collected in 2007-8 (T1) and 2010-11 (T2) in socio-economically disadvantaged women and children (5-12 years at T1). Dietary data were collected using a FFQ and diet quality index (DQI) scores derived at both time points. The objective measures of weight, height and physical activity (accelerometers) were included. The other variables were reported in the questionnaires. We examined the association between change in DQI and change in zBMI, using linear regression analyses adjusted for physical activity, screen sedentary behaviour and maternal education level both in the whole sample and in the sample stratified by overweight status at baseline. After accounting for potential covariates, change in diet quality was found to be inversely associated with change in zBMI only in children who were overweight at baseline (P= 0.035), thus supporting the hypothesis that improvement in diet quality is associated with a concurrent improvement in zBMI among already overweight children, but not among those with a normal BMI status. The identification of modifiable behaviours such as diet quality that affect zBMI longitudinally is valuable to inform future weight gain prevention interventions in vulnerable groups. | 10.1017/S0007114514000749 |
pubmed_835_13155 | OBJECTIVES
Robotic systems are moving toward more interaction with the environment, which requires improving environmental perception methods. The concept of primitive objects simplified the perception of the environment and is frequently used in various fields of robotics, significantly in the grasping challenge. After reviewing the related resources and datasets, we could not find a suitable dataset for our purpose, so we decided to create a dataset to train deep neural networks to classify a primitive object and estimate its position, orientation, and dimensions described in this report.
DATA DESCRIPTION
This dataset contains 8000 virtual data for four primitive objects, including sphere, cylinder, cube, and rectangular sheet with dimensions between 10 to 150 mm, and 200 real data of these four types of objects. Real data are provided by Intel Realsense SR300 3D camera, and virtual data are generated using the Gazebo simulator. Raw data are generated in.pcd format in both virtual and real types. Data labels include values of the object type and its position, orientation, and dimensions. | 10.1186/s13104-022-06155-4 |
pubmed_862_13699 | INTRODUCTION
Since the most decisive factor related to the cost of stroke is disability, any acute phase intervention to reduce disability will probably be cost-effective. The present acute stroke phase analysis is the first cost-benefit study on intraarterial procedures in acute stroke phase.
METHOD
Case-control study focusing on the cost of stroke including acute stroke patients subjected to interventionism in Hospital Virgen del Rocío in 2003-2004 was conducted. The data obtained was subsequently extrapolated to the number of patients who would have been treated if intraarterial procedures could be performed on a 24 hour-day basis.
RESULTS
32 patients were treated in 2003-2004. Direct cost (devices and human resources) of each treated patient was 10,502 euros and global saving in hospital stay and rehabilitation was 11,069 euros, resulting in 567 euros net saving per patient. Nevertheless, 92 patients would have been treated if intraarterial procedures could have been performed on a 24 hour-day basis, resulting in better financial results with 5,792 saving for each treated patient.
CONCLUSIONS
Intracraneal procedures in acute stroke has been shown to be cost-effective since cost of material and human resources is greatly exceeded by the saving in hospitalization and rehabilitation as a result of reduction in patient disability. | pubmed_862_13699 |
pubmed_272_19901 | To the uninitiated researcher, bioethics can be a confusing and sometimes bureaucratic process. The recent debates in international research ethics have both increased understanding of contentious issues while extending confusion to the international arena. Here, we attempt to demystify bioethics, or more specifically international research ethics, by defining ethics in the context of morality, reviewing core Western ethical principles, and highlighting challenges in international research ethics. | 10.1016/s1471-4914(02)02277-3 |
others_22_8970 | This study describes the natural history of dengue virus (DENV) infection in rhesus monkeys exposed to the bites of DENV-infected Aedes aegypti mosquitoes. Dengue virus-infected mosquitoes were generated by either intrathoracic inoculation or by oral feeding on viremic blood meals. Each of the six rhesus monkeys that were fed upon by intrathoracically infected mosquitoes developed non-structural protein 1 (NS1) antigenemia and an IgM response; viremia was detected in 4/6 individuals. No virological or immunological evidence of DENV infection was detected in the three monkeys exposed to mosquitoes that had been orally infected with DENV. These results demonstrate the utility of mosquito-borne challenge of rhesus monkeys with DENV. © 2020 American Society of Tropical Medicine and Hygiene. All rights reser | 10.4269/ajtmh.19-0633 |
pubmed_1021_3351 | Laparoscopic gallbladder drainage was performed as an alternative intervention to an emergency operation in 97 patients with acute cholecystitis whose ages ranged from 60 to 89 years. One patient died from thromboembolism of the pulmonary artery. After acute inflammation was arrested, 37 patients underwent cholecystectomy. The risk of a radical operation was ascertained to be very high in 58 cases. In 19 of these cases endoscopic cleansing of the cystic cavity was performed through cholecystostomy formed during laparoscopic drainage of the gallbladder. In 39 cases the therapeutic process was completed by a sparing operation--sanative cholecystostomy which was carried out under local anesthesia. There were no fatal outcomes in these groups. Endoscopic papillosphincterotomy was conducted in 17 patients, with stones in the gallbladder and choledocholithiasis, after which the stones were removed. The performance of endoscopic and surgical interventions which cause minimal injury provides for adequate sanative treatment of the gallbladder in cases in which cholecystectomy is an extremely high risk. | pubmed_1021_3351 |
pubmed_994_13014 | With the legalization of recreational marijuana in many states, we anticipate more women will be using and self-reporting marijuana use in pregnancy. Marijuana is the most common illicit drug used in pregnancy, with a prevalence of use ranging from 3% to 30% in various populations. Marijuana freely crosses the placenta and is found in breast milk. It may have adverse effects on both perinatal outcomes and fetal neurodevelopment. Specifically, marijuana may be associated with fetal growth restriction, stillbirth, and preterm birth. However, data are far from uniform regarding adverse perinatal outcomes. Existing studies are plagued by confounding by tobacco and other drug exposures as well as sociodemographic factors. In addition, there is a lack of quantification of marijuana exposure by the trimester of use and a lack of corroboration of maternal self-report with biological sampling, which contributes to the heterogeneity of study results. There is an emerging body of evidence indicating that marijuana may cause problems with neurological development, resulting in hyperactivity, poor cognitive function, and changes in dopaminergic receptors. In addition, contemporary marijuana products have higher quantities of delta-9-tetrahydrocannabinol than in the 1980s when much of the marijuana research was completed. The effects on the pregnancy and fetus may therefore be different than those previously seen. Further research is needed to provide evidence-based counseling of women regarding the anticipated outcomes of marijuana use in pregnancy. In the meantime, women should be advised not to use marijuana in pregnancy or while lactating. | pubmed_994_13014 |
pubmed_582_6693 | Generic preparedness education and training for the public health workforce has increased in availability over the past 5 years. Registered Nurses also have more opportunities available for participation in emergency and disaster preparedness curricula. Discipline- and specialty-specific training and education for public health nurses (PHNs) incorporating their population-based practice, however, remains a largely unexplored area that is not accessible except for sporadic local venues. The Public Health Nursing Surge Curriculum provides 50 hr of nursing continuing education and activity-based aggregate focused learning experiences that are completed within a 12-month period, including an in-classroom seminar. The Public Health Nursing Surge Curriculum was developed on a foundation of 25 competencies linking PHNs and their population-based practice to surge capability. The curriculum was built in partnership with statewide public health directors of nursing over a 12-month period and is evaluated by a 3-level process to include self-rated confidence in performance. The curriculum's use of a blended learning methodology enables staff-level PHNs to master individual competencies toward surge capability within the public health response system. | 10.1111/j.1525-1446.2008.00693.x |
pubmed_649_1261 | Statistical observations on inpatients and operations in our department from 1982 to 1985 were reviewed in comparison with the statistics for the preceeding three years. More elderly persons comprised the inpatients at our hospital than at other facilities. Urogenital tumors and urolithiasis were the predominant disease of the inpatients, as they were in the preceeding three years. Number of prostatic cancer has remarkably increased. Transurethral operations, TUR-P and TUR-Bt, were the most representative. Operations for the malignant disease, especially for prostatic cancer, were more frequent in this period than in the preceeding three years. As to urinary diversion, ileal conduit was the main procedure used during this four years. Kock continent ileal reservoir was adopted in 1985. In July 1985, open operations for urolithiasis were dramatically replaced by percutaneous and transurethral procedures. | pubmed_649_1261 |
pubmed_1124_12324 | When modulated through the harmonic motion of one mirror, the counterpropagating waves in a ring laser oscillate out of phase. A solution to the wave equation is presented that satisfies both the time-dependent boundary condition and the resonance condition. This theoretical prediction is confirmed experimentally to leading order in terms that are inversely proportional to the speed of light. The method of solution is applicable to arbitrary phase modulation at more than one spatial location in the cavity. Potential uses include the reduction of the locking problem in ring lasers and the testing of higher-order kinematic effects in the theory of relativity. | 10.1364/ao.41.001098 |
pubmed_347_13481 | PURPOSE
To describe a case of spontaneous dissociation of a fluocinolone acetonide implant (Retisert) 5 years following implantation.
DESIGN
Case report.
METHODS
A patient with chronic uveitis underwent placement of a fluocinolone acetonide implant in the right eye in 2006. The patient's inflammation was well controlled and did not recur, so the device was not replaced.
RESULTS
Five years after implantation, the patient presented with a new complaint of a shadow in his vision. The drug pellet was found to have separated spontaneously from the anchoring strut and was floating in the vitreous. Pars plana vitrectomy was performed with removal of the drug pellet, and the anchoring strut was left in place.
CONCLUSIONS
Spontaneous intraocular dissociation of a fluocinolone acetonide implant (Retisert) can occur years after placement, in the absence of trauma or other risk factors. Surgeons and patients must be aware of this potential complication as the implants age. | 10.3109/09273948.2012.736588 |
pubmed_1090_7413 | Prostaglandin F2 alpha (PGF2 alpha) and sex hormones (progesterone, androgens, and estradiol-17 beta) have been determined in the plasma of female water frog, Rana esculenta, utilizing radioimmunoassay methods (RIA). Plasma PGF2 alpha level increases in autumn-winter when recovery processes interest both gonad and oviduct. The PGF2 alpha plasma highest value has been recorded in October (4.52 +/- 0.58 ng/ml) and the lowest in May (1.43 +/- 0.12). The PGF2 alpha annual pattern is positively correlated to that of estradiol (but not to those of progesterone and androgens). Exogenous PGF2 alpha, injected into intact females during the various phases of the annual cycle, induces an increase of ovarian weight in frogs treated in December and February and an increase of plasma estradiol in postreproductive animals (June). Although preliminary, such results propose a putative implication of PGF2 alpha in ovarian recovery processes and in the interruption of reproductive processes in late summer. | 10.1016/0016-6480(90)90162-f |
pubmed_989_7122 | Cardiorenal syndrome type 1 (CRS-1) is an acute kidney injury (AKI) due to acute worsening of cardiac function. More than 20% of patients with acute heart failure develop AKI, and AKI predicts poor outcome. Although a number of potential pathways have been suggested as heart-kidney connectors which might drive the syndrome, there are significant barriers to investigation, such as a paucity of animal models, a lack of specific biomarkers, and an inconsistent temporal and causal relationship between changes in cardiac flow and development of renal dysfunction. Thus, mechanisms of heart-kidney interaction are still unclear, and there is no specific or effective therapy for CRS-1. This review, therefore, focuses on mitigating these challenges in the investigation of CRS-1. We review the available models and focus on mechanistic insights gained from those models. In particular, we focus on non-flow and endocrine mediators of CRS-1 such as heart-derived messengers which alter renal function and which may represent targetable pathways in this syndrome. As precise connectors of heart-kidney interaction remain unclear, the establishment of animal and relevant cell-culture models and further investigation are required. | 10.1159/000509353 |
pubmed_783_1501 | Despite the growing interest in circulating cell-free DNA (ccfDNA) analysis in various clinical fields, especially oncology and prenatal diagnosis, few studies on sample handling have been reported and no analytical consensus is available. The lack of consistency between the various protocols for sample handling and the techniques used for ccfDNA analysis is one of the major obstacles in translating ccfDNA analysis to clinical practice. Although this point is highlighted regularly in the published reviews on ccfDNA analysis, no standard operating procedure currently exists despite several ongoing clinical studies on ccfDNA analysis. This review examines the preanalytical parameters potentially affecting ccfDNA concentration and fragmentation at each preanalytical step from blood drawing to the storage of ccfDNA extracts. Analysis of data in the literature and our own observations revealed the influence of preanalytical factors on ccfDNA analysis. Based on these data, we determined the optimal preanalytical protocols for ccfDNA analysis and ultimately, a guideline for the translation of ccfDNA analysis in routine clinical practice. | pubmed_783_1501 |
pubmed_167_1619 | From 2005 to 2017, a total of 334 fresh fecal samples was obtained from 236 captive and free-ranging Grand Cayman iguanas ( Cyclura lewisi) in a captive breeding and release program. One-hundred-sixteen samples were obtained from individual captive iguanas living in enclosures with natural substrate, 161 samples from captive iguanas living in elevated wire-bottom enclosures, and 57 samples from free-ranging wild iguanas. These samples were cultured to isolate subspecies of Salmonella enterica. as part of prerelease health evaluations, and to determine baseline health assessments of captive and wild populations of these iguanas. There was a 5.45% (95% confidence interval [CI]: 1.14-15.12) prevalence of S. enterica in iguanas housed on natural substrate ( n = 51), 3.85% (CI: 1.42-8.19) in iguanas housed in elevated wire-bottom enclosures ( n = 157), and 6.06% (CI: 0.74-20.23) in wild free-ranging iguanas ( n = 38). These results demonstrate no significant difference ( P = 0.73) in S. enterica prevalence among these housing conditions. The incidence of S. enterica from 2005 to 2017 in the population sampled was 4.19% (CI 3.10-5.29). Ten different serotypes of S. enterica were isolated from 14 iguanas. Salmonella enterica ser. Saintpaul was the most frequent isolate. Annual S. enterica prevalence was calculated for iguanas housed in different enclosure types, for free-roaming wild iguanas, and for all cultured iguanas. The highest yearly prevalence was 23.08% (CI: 5.04-53.81) in iguanas tested in 2007 ( n = 21). No Salmonella enterica were cultured in 2005, 2008, 2009, 2010, 2011, 2012, and 2015. These results suggest that the shedding of S. enterica was not significantly different between housing types or between captive versus wild iguanas and therefore that release of captive iguanas did not significantly affect the health of the wild population or their exposure to S. enterica. | 10.1638/2017-0234.1 |
pubmed_288_15337 | We acquire information from the outside world through our eyes which contain the retina, the photosensitive component of the central nervous system. Once the adult mammalian retina is damaged, the retinal neuronal death causes a severe loss of visual function. It has been believed that the adult mammalian retina had no regenerative capacity. However, the identification of neuronal progenitor cells in the retina sheds some light on cellular therapies for damaged retinal regeneration. In this review, we highlight three potential stem/progenitor cells in the eye, the ciliary body epithelium cells, the iris pigmented epithelium cells, and Müller glia. In order to make them prime candidates for the possible treatment of retinal diseases, it is important to understand their basic characters. In addition, we discuss the key signaling molecules that function extracellularly and determine whether neuronal progenitors remain quiescent, proliferate, or differentiate. Finally, we introduce a secreted protein, Tsukushi, which is a possible candidate as a niche molecule for retinal stem/progenitor cells. | 10.1111/j.1440-169X.2008.01006.x |
pubmed_765_16102 | BACKGROUND
Enhancing detection of unrecognized atrial fibrillation among acute ischemic stroke patients is crucial for secondary stroke prevention.
AIM
To evaluate whether the detection rate of new atrial fibrillation in acute ischemic stroke patients without known atrial fibrillation could be improved by doing serial 12-lead electrocardiograms once daily for five days, compared with conventional 24-h Holter monitoring (24-h Holter).
METHODS
We conducted a randomized clinical trial to compare the detection rates of paroxysmal atrial fibrillation between serial electrocardiograms versus 24-h Holter from October 2015 to October 2018 at six hospitals. Eligible participants were acute ischemic stroke patients with aged ≥65 years, with neither atrial fibrillation history nor any presence of atrial fibrillation on baseline electrocardiogram at admission. The primary outcome was newly detected electrocardiogram in the serial electrocardiograms and 24-h Holter group.
RESULTS
Among 826 patients, baseline characteristics were similar between both groups. In the intention-to-treat analysis, there was no statistical difference between serial electrocardiograms versus 24-Holter to detect atrial fibrillation (8.4% vs. 6.9%; adjusted odds ratio 1.17, 95% confidence interval 0.69-2.01). Stepwise multivariate logistic regression revealed age ≥80 years and history of heart failure were associated with detection of paroxysmal atrial fibrillation whereas patients with lacunar infarction had lower odds for detection of paroxysmal atrial fibrillation.
CONCLUSIONS
Serial electrocardiograms had comparable detection rate of paroxysmal atrial fibrillation compared with 24-h Holter and might be a viable alternative to 24-h Holter as a first-line approach to survey for potential paroxysmal atrial fibrillation among elderly patients with acute ischemic stroke.Clinical Trial Registration: URL https://clinicaltrials.gov/ct2/show/NCT02578979Unique Identifiers: NCT02578979. | 10.1177/1747493020938297 |
pubmed_107_1811 | In previous work we have demonstrated that platelets depleted from secretory phospholipase A2 (sPLA2) produced similar amounts of thromboxane (Tx)B2 as control platelets upon stimulation by thrombin. However, since depletion of sPLA2 was not total, this sole finding only suggested the non-involvement of sPLA2 in arachidonic acid release. In the present study we provide further evidence for the non-involvement of sPLA2 in arachidonic acid liberation during platelet activation. Thus, rabbit platelets exposed to thrombin secreted sPLA2, released free arachidonic acid and formed TxB2 and inositol phosphates. In contrast, U46619, a stable prostaglandin (PG)H2 analogue, activates phospholipase C (PLC) and induces release of sPLA2 without TXB2 generation nor arachidonic acid liberation. At each concentration tested of both agonists, stimulation of sPLA2 activity paralleled the production of inositol phosphates. These data suggest that sPLA2 is dependent on phosphoinositide hydrolysis and on the release reaction and that it is not involved in the liberation of arachidonic acid from stimulated platelets. In addition, a dissociation was observed between sPLA2 and the enzyme involved in the arachidonic acid mobilization, suggesting that the liberation of this fatty acid from membrane phospholipids was mediated by cytosolic phospholipase A2 (cPLA2). Finally, PLC does not play a major role in arachidonic acid liberation, since U46619, which induced the breakdown of inositol phospholipids, failed to release arachidonic acid. In confirmation, neomycin, which inhibits PLC activity, failed to inhibit ATP, sPLA2 and arachidonic acid release upon stimulation of platelets by fluoroaluminate. These data demonstrate that sPLA2 is not involved in the arachidonic acid release by stimulated platelets and indicate that the activations of PLC, sPLA2 and cPLA2 are independent events. | 10.1111/j.1365-2141.1994.tb04990.x |
pubmed_962_2427 | BACKGROUND
Reports of pregnancy in acromegalic women are uncommon, numbering less than 100, in which a case of acromegaly first diagnosed in pregnancy is rare.
CASE
A 40-year-old woman in 19-week gestation was presented with a 10-week history of photophobia and visual disturbance. Elevated growth hormone (GH) levels in the serum, an inadequate suppression of GH secretion with glucose administration and a mass image in the pituitary fossa confirmed the diagnosis of acromegaly. We initiated dopamine agonist treatment, bromocriptine at a weekly dose of 1 mg at 27-week gestation. Ten weeks after the start of the bromocriptine treatment, the GH levels gradually decreased to a normal range, and visual symptoms were improved. Enlargement of the tumor was not observed throughout the pregnancy and the patient delivered a healthy infant following an eventful pregnancy. At 3 weeks after delivery, she underwent a transsphenoidal resection of a pituitary adenoma.
CONCLUSION
Pregnancy may lead to pituitary tumor growth and increase the risk of developing loss of vision. It is important to take pituitary tumors into consideration when encountering gravida with visual disturbance. | 10.1007/s00404-005-0114-y |
pubmed_815_1019 | This report describes a simple gas chromatographic-mass spectrometric (GC-MS) assay for the simultaneous analysis of alfentanil and its major metabolite, noralfentanil, in human plasma. The method facilitates the processing of numerous samples for pharmacokinetic analysis. Alfentanil and noralfentanil are extracted from plasma under basic conditions and noralfentanil is converted to the pentafluoropropionyl derivative. The extraction efficiencies for noralfentanil and alfentanil were > 99% and 70%, respectively. Standard curves were linear (r2 = 0.99) over the ranges of 5-500 ng/ml for alfentanil and 0.4-10 ng/ml for noralfentanil. Inter-day coefficients significant improvement over existing HPLC assays which require radiolabelled significant improvement over existing HPLC assays which require radiolabelled alfentanil. The simultaneous disposition of alfentanil and noralfentanil in plasma after intravenous administration in humans is described. | 10.1016/0378-4347(94)00201-0 |
pubmed_289_6008 | BACKGROUND
Data on sexually transmitted infections (STI) prevalence among HIV-infected women in Thailand are limited. We studied, among HIV-infected women, prevalence of STI symptoms and signs; prevalence and correlates of having any STI; prevalence and correlates of Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) among women without CT and/or GC symptoms or signs; and number of women without CT and/or GC symptoms or signs needed to screen (NNS) to detect one woman with CT and/or GC overall, among pregnant women, and among women ≤25 years.
METHODS
During October 2004-September 2006, HIV-infected women at 3 obstetrics and gynecology clinics were asked about sexual behaviors and STI symptoms, physically examined, and screened for chlamydia, gonorrhea, trichomoniasis, and syphilis. Multivariate logistic regression was used to identify correlates of infections. NNS was calculated using standard methods.
RESULTS
Among 1,124 women, 526 (47.0%) had STI symptoms or signs, 469 (41.7%) had CT and/or GC symptoms or signs, and 133 (11.8%) had an STI. Correlates of having an STI included pregnancy and having STI signs. Among 469 women and 655 women with vs. without CT and/or GC symptoms or signs, respectively, 43 (9.2%) vs. 31 (4.7%), 2 (0.4%) vs. 9 (1.4%), and 45 (9.6%) vs. 38 (5.8%) had CT, GC, or "CT or GC", respectively; correlates included receiving care at university hospitals and having sex with a casual partner within 3 months. NNS for women overall and women ≤25 years old were 18 (95% CI, 13-25) and 11 (95% CI, 6-23), respectively; and for pregnant and non-pregnant women, 8 (95% CI, 4-24) and 19 (95% CI, 14-27), respectively.
CONCLUSIONS
STI prevalence among HIV-infected women, including CT and GC among those without symptoms or signs, was substantial. Screening for CT and GC, particularly for pregnant women, should be considered. | 10.1186/1471-2458-13-373 |
others_196_5279 | Traumatic brain injury (TBI) is a devastating neurological disorder, although the underlying pathophysiology is poorly understood. TBI causes blood–brain barrier (BBB) disruption, immune cell trafficking, neuroinflammation and neurodegeneration. CCL20 is an important chemokine mediating neuroinflammation. Human mesenchymal stem cell (hMSC) therapy is a promising regenerative approach but the inflammatory microenvironment in the brain tends to decrease the efficacy of the hMSC transplantation. Reducing the inflammation prior to hMSC therapy improves the outcome. We developed a combined nano-cell therapy by using dendrimers complexed with plasmids (dendriplexes) targeting CCL20 and its sole receptor CCR6 to reduce inflammation followed by hMSC transplantation. Treatment of TBI mice with shRNA conjugated dendriplexes followed by hMSC administration downregulated the inflammatory markers and significantly increased brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex indicating future possible neurogenesis and improved behavioral deficits. Taken together, this nano-cell therapy ameliorates neuroinflammation and promotes brain tissue repair after TBI. © 2020 | 10.1016/j.nano.2020.102247 |
pubmed_1129_10276 | Introduction
While combat readiness is a top priority for the U.S. Army, there is concern that behavioral health (BH) return to duty (RTD) practices may under-represent the number of soldiers available for deployment. Profiling, the official administrative process by which medical duty limitations are communicated to commanders, was recently found to be significantly under-reporting BH readiness levels in one Army Division. This is a safety issue in addition to a readiness problem, and underscores the importance of better understanding RTD practices in order to offer solutions. This study sought to categorize the information and tools used by Army BH providers in garrison to make decisions about duty limitations that can affect BH readiness.
Materials and Methods
A qualitative approach was used for this study. Fourteen semi-structured interviews and three focus groups were conducted with a diverse convenience sample of Army BH providers in October 2015, resulting in input from 29 practitioners.
Results
Through thematic analysis, it was discovered that profile decisions are driven first by safety of the soldier and secondarily by the needs of the unit. To facilitate their clinical decision-making, providers consider an array of data including standardized scales, unit mission, consultation with unit leadership, meetings with other providers, and, when appropriate, discussion with the friends and family of the soldier.
Conclusions
If the military is to address the concern of under-reporting behavioral health readiness levels in garrison, it is critical to develop more predictability in treatment planning and reporting, as well as access to necessary data to make these clinical decisions. The interviews and focus groups revealed that while the technical process for initiating a profile does not vary, there is great disparity about the amount and type of information that is taken into consideration when making profile decisions. Categorization of the information that supports RTD decisions can lead to a better understanding of the process and inform leadership about ways to improve the accuracy of BH readiness reporting. | 10.1093/milmed/usy103 |
others_375_9125 | The effects of two temperatures (thermoneutral, 22°C v. fluctuating high temperature, 35·22°C), four food levels (ad libitum and three levels of food restriction) on growth and energy retention of growing pigs (male and female) was investigated in a 2 × 2 × 4 factorial experiment involving 48 individually penned pigs from 20 to 50 kg live weight. A second experiment was conducted over the 50 to 80 kg liveweight range using a 2 × 2 × 3 design. Mean daily digestible energy (DE) intake, daily gain, P2 backfat thickness, carcass fat proportion, total body energy retained and body energy retained as protein did not differ significantly between the temperature treatments in either experiment. Mean carcass protein proportion was greater at 35·22°C than at a constant 22°C. With pigs given food ad libitum during the 50 to 80 kg phase, an increase in temperature from 22°C to 35·22° reduced daily DE intake by 4·1 MJ (38·9 v. 34·8 MJ or 300 g food per day), reduced energy retention by 2·3 MJ/day (15·6 v. 13·3 MJ/day), and increased carcass protein proportion by 11 g/kg (142 v. 153 g/kg). There was a significant interaction between the effects of sex and temperature on P2 backfat thickness over both live-weight ranges. Female pigs housed at 35·22°C had 2·6 mm less P2 backfat at 50 kg (13 v. 15·6 mm) and 2 mm less at 80 kg (20 v. 22 mm) compared with females housed at 22°C. The P2 backfat thickness of male pigs did not vary at 50 kg (13·2 v. 13·5 mm) but when housed at 35·22°C males had 1·4 mm more P2 backfat at 80 kg (18·2 v. 19·6 mm). © 1988, British Society of Animal Science. All rights reser | 10.1017/S0003356100003615 |
others_267_4762 | Synergic effects among endo-xylanase, β-xylosidase, and acetyl xylan esterase of Bacillus stearothermophilus in the hydrolysis of xylan were studied by using birchwood, oat spelt, and acetylated xylan as substrates. Synergism between endo-xylanase and β-xylosidase was observed on all three substrates tested, indicating that β-xylosidase enhanced the production of xylose by relieving the end-product inhibition upon endo-xylanase conferred by xylooligomers. Endo-xylanase and β-xylosidase also showed synergism with acetyl xylan esterase in the hydrolysis of birchwood and acetylated xylan, while no synergic effect was detected in oat spelt xylan hydrolysis. Thus, the hydrolysis of xylan containing acetic acid side chains required the action of acetyl xylan esterase, which eliminated the steric hindrance of the side chains, leading to the better hydrolysis by endo-xylanase and β-xylosidase, and the acetyl xylan esterase activity was also enhanced by endo-xylanase and β-xylosidase for the latter enzymes provided acetyl xylan esterase with shorter xylan oligomers, the better substrate for the enzym | others_267_4762 |
pubmed_175_23153 | INTRODUCTION
Cutaneous squamous cell carcinoma (cSCC) is an invasive and malignant tumour that is common in the orbital region. However, adenocarcinoma of the lacrimal gland has an incidence of less than one case per million per year. We present a patient who experienced a cSCC and adenocarcinoma of the lacrimal gland, which is unusual for both these cancers to present in the same patient in such close proximity.
PRESENTATION OF CASE
A 47-year old male patient was referred for management of a cSCC of the right upper eyelid. This was treated surgically by means of wide local excision and orbital exenteration. Histological analysis of the resection specimen found an incidental synchronous lacrimal gland adenocarcinoma. To our knowledge this is the first case report to describe this phenomenon.
DISCUSSION
Although SCC is the most common secondary epithelial neoplasms of the orbit region, adenocarcinomas are rare in this same region. Currently, when performing a literature search, there has been no cases found that documents a poorly differentiated cSCC with a synchronous adenocarcinoma of the lacrimal gland. This is mainly because there are improved facilities and accessible healthcare. This report will mainly focus on the presentation and management of this patient case.
CONCLUSION
To our knowledge this is the first case report documenting a poorly differentiated cSCC and a synchronous adenocarcinoma of the lacrimal gland. Our case report raises the awareness of the possibility of patients with synchronous tumours and is a valuable addition to the literature. | 10.1016/j.ijscr.2020.02.006 |
pubmed_154_28 | The paper presents a short historical outline and contemporary use of scintigraphic studies of thyroid gland. Appropriate recommendations and correct interpretations of the results of routine thyroid scans and the usefulness of other scintigraphic studies with 111In-octreoscan, 99mTc-MIBI, 99mTc-DMSA, 18FDG and radiolabeled monoclonal anti-carcinoembryonic antigen antibodies were discussed in the light of the present thyroid diagnostic studies. Particular attention was paid to the dependence of the scintigraphic thyroid images upon the thyroid-stimulating hormone (TSH) level in the patient's serum. The chosen examples of scintigraphic studies show the advantages of scintigraphic evaluation of efficacy of radioiodine therapy. The most often mistakes of the scintigraphy interpretations were showed. | pubmed_154_28 |
others_157_5765 | and purpose: Prediction models may be reliable decision-support tools to reduce the workload associated with the measurement-based patient-specific quality assurance (PSQA) of radiotherapy plans. This study compared the effectiveness of three different models based on delivery parameters, complexity metrics and sinogram radiomics features as tools for virtual-PSQA (vPSQA) of helical tomotherapy (HT) plans. Materials and methods: A dataset including 881 RT plans created with two different treatment planning systems (TPSs) was collected. Sixty-five indicators including 12 delivery parameters (DP) and 53 complexity metrics (CM) were extracted using a dedicated software library. Additionally, 174 radiomics features (RF) were extracted from the plans’ sinograms. Three groups of variables were formed: A (DP), B (DP + CM) and C (DP + CM + RF). Regression models were trained to predict the gamma index passing rate PRγ(3%G, 2mm) and the impact of each group of variables was investigated. ROC-AUC analysis measured the ability of the models to accurately discriminate between 'deliverable' and 'non-deliverable' plans. Results: The best performance was achieved by model C which allowed detecting around 16% and 63% of the 'deliverable' plans with 100% sensitivity for the two TPSs, respectively. In a real clinical scenario, this would have decreased the whole PSQA workload by approximately 35%. Conclusions: The combination of delivery parameters, complexity metrics and sinogram radiomics features allows for robust and reliable PSQA gamma passing rate predictions and high-sensitivity detection of a fraction of deliverable plans for one of the two TPSs. Promising yet improvable results were obtained for the other one. The results foster a future adoption of vPSQA programs for HT. © 2023 The Author(s) | 10.1016/j.phro.2023.100435 |
pubmed_574_9808 | The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values. | 10.2165/00003088-199325010-00005 |
pubmed_1094_9291 | Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR. Our results further demonstrate that inhibition of PDK1 using small molecule inhibitors dichloroacetic acid (DCA) and dichloroacetophenone (DAP) resulted in reduced cell growth and increased apoptosis. We also confirm that combination treatment of DCA with chemotherapeutic agent carboplatin further enhanced the therapeutic efficacy compared to single drug treatment. In addition, we observed changes in glucose uptake, lactate and reactive oxygen species (ROS) levels as well as decreased cell migration in response to PDK1 inhibition. Additionally, we show that DCA treatment led to inhibition of PI3K/Akt pathway and reduction in PDK1 protein levels. Overall, our data suggest that targeting PDK1 could be a novel therapeutic strategy for RB. | 10.1371/journal.pone.0177744 |
pubmed_839_15236 | Two Citrus tristeza virus (CTV) isolates from New Zealand that display distinct phenotypes were isolated, examined and sequenced in full. The first isolate, NZ-M16, is largely asymptomatic and non-transmissible by the aphid vector Toxoptera citricida, while the second, NZ-B18, is highly transmissible and induces very severe symptoms on C. sinensis and C. aurantii. Phylogenetic analysis of the genome sequences showed that both isolates were approximately 90-93% similar to the VT and T318 isolates but possessed only 89% identity to one another. Based on sequence identity, both isolates are VT subtypes, with NZ-M16 being T3-like, while NZ-B18 is a member of a novel subtype with B165 from India. | 10.1007/s00705-009-0456-z |
pubmed_306_17579 | High-level lead exposure can have serious effects on the intellectual and behavioural development of young children. There has been much controversy in the last decade concerning the possible impact of low-level lead exposure upon the neurobehavioural and psychomotor development of children. Five longitudinal studies (Boston, Cincinnati, Cleveland, Port Pirie and Sydney) examining lead effects on child development were initiated in the early 1980s. These studies share multiple design features and include data on blood lead and neurobehavioural measurements from birth, six months, or annual intervals to seven years. All the studies use multivariate analysis to take into account possible confounding covariates with outcome measures.The studies tend to have varying results based on the covariates used and type of subject population. An analysis of the results of the five studies with regard to effects associated with prenatal and postnatal lead exposure and pregnancy outcome has been carried out and reveals inconsistencies in the onset, stability, and nature of neurobehavioural effects correlated with different indices of lead exposure. it is possible that the variation in reported results may be due to the use of different covariates and analyses among studies. A common analysis should be carried out among ail studies to further determine consistency of results. Although individual studies may show some effects, taken as a whole, the current published data from the five studies in this review are inconsistent and do not lend support to the concept that low level lead exposure resulting in blood lead levels below 25 μg dL(-1) is associated with neurobehavioural deficits in children. | 10.1007/BF01783488 |
pubmed_249_13004 | OBJECTIVE
To report the results of a 3-year follow-up evaluation of a trial comparing goserelin acetate depot injections with sham injections before endometrial ablation for the treatment of dysfunctional uterine bleeding (DUB).
DESIGN
Prospective, randomized, double-blind, parallel-group study.
SETTING
Thirty-seven centers in 12 countries.
PATIENT(S)
Three-hundred and fifty-eight premenopausal women aged over 30 years with DUB.
INTERVENTION(S)
Goserelin acetate (3.6 mg depot) every 28 days for 8 weeks, or sham depot every 28 days for 8 weeks, with endometrial ablation 6 weeks +/- 3 days after the first depot injection (i.e., when the endometrium is at its thinnest). The follow-up continued for 3 years.
MAIN OUTCOME MEASURE(S)
At the 3-year follow-up, bleeding in the previous 3 months and need for surgical intervention were recorded.
RESULT(S)
At 3 years, amenorrhea rates were 21% in the goserelin acetate group and 14% in the control group (estimated odds ratio, 1.8; 95% CI, 0.98-3.25; P=.0571). The surgical intervention rate (since the original procedure) was low and did not differ significantly between groups. For hysterectomy, it was 21% for the goserelin acetate group and 15% for the control group. For repeat ablations, it was 5.6% for the goserelin acetate group and 2.1% for the control group.
CONCLUSION(S)
Prethinning with goserelin acetate before endometrial ablation resulted in higher long-term amenorrhea rates than ablation without prethinning. | 10.1016/s0015-0282(00)01767-2 |
pubmed_348_24961 | BACKGROUND AND PURPOSE
Previous studies have examined volumetric abnormalities in Rett syndrome (RTT), using MR imaging and focusing on selective changes. However, these studies preceded the identification of MECP2 as the gene mutated in most RTT cases. We studied regional brain volume changes as noted by MR imaging in girls with RTT who had mutations in the MECP2 gene and more or less severe clinical outcomes to further characterize the neuroanatomy of RTT and its correlations with clinical severity.
MATERIALS AND METHODS
Complementary semiautomated Talairach- and voxel-based approaches were used to study spoiled gradient-recalled acquisition sequence MR imaging scans from 23 girls with MECP2 mutations/RTT, including a pair of discordant monozygotic twins and 25 age-matched control girls. Both absolute and relative volumetric changes were examined to account for the well-documented global reduction in brain volume seen in RTT.
RESULTS
Absolute volumetric reductions were observed throughout the brain in RTT. Selective/relative decreases in parietal lobe gray matter, particularly in the dorsal parietal region, and mild, diffuse reductions in cortical white matter were observed in the RTT group compared with control subjects. In girls with RTT and a more severe phenotype, anterior frontal lobe volumes were relatively more reduced. Twin comparisons revealed selective preservation of the occipital cortex.
CONCLUSION
Selective reductions of dorsal parietal gray matter and preservation of the occipital cortex seem to be basic neuroanatomic features of RTT, whereas preferential reduction of the anterior frontal lobe appears to be a correlate of clinical severity in this disorder. The most affected brain regions include those that may underlie key functional deficits observed in RTT. | 10.3174/ajnr.A0857 |
pubmed_1000_7255 | Our previous studies implicated that oxidized low-density lipoprotein (oxLDL), a putative atherogenic agent, impairs endothelium-dependent, nitric oxide (NO)-mediated dilation of isolated coronary arterioles to pharmacological agonists. However, it is not known whether oxLDL specifically affects NO-mediated dilation or generally impairs endothelium-dependent function, including the release of hyperpolarizing factors. In this regard, we investigated the dilation of isolated porcine coronary arterioles (50- to 100-microm luminal diameter) in response to the activation of various endothelium-dependent pathways before and after intraluminal incubation of the vessels with oxLDL (0.5 mg protein/ml for 60 min). In the absence of oxLDL, all vessels developed basal tone and dilated in response to the activation of NO synthase (by flow and adenosine), cyclooxygenase (by arachidonic acid), cytochrome P-450 monooxygenase (by bradykinin), and endothelial membrane hyperpolarization (by sucrose-induced hyperosmolarity). Incubation of the vessels with oxLDL for 60 min did not alter basal tone but did inhibit the vasodilatory responses to increased flow and adenosine in a manner similar to that of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. Vasodilations in response to flow and adenosine were not affected by intraluminal incubation of the vessels with either a vehicle solution or the native LDL (0.5 mg protein/ml, 60 min). In contrast with the NO-mediated response, hyperosmotic vasodilation mediated by endothelial hyperpolarization was not affected by oxLDL. Endothelium-dependent dilations to the cyclooxygenase activator arachidonic acid and to the cytochrome P-450 monooxygenase activator bradykinin and endothelium-independent vasodilation to sodium nitroprusside were also not altered by oxLDL. Collectively, these results indicate that oxLDL has a selective effect on endothelium-dependent dilation with specific impairment of the NO-mediated response, whereas cyclooxygenase and cytochrome P-450 monooxygenase-mediated dilations are spared from this inhibitory effect. In addition, oxLDL does not appear to affect vasodilation mediated by hyperpolarization of the endothelium. | 10.1152/ajpheart.2000.278.1.H175 |
pubmed_48_10463 | The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C. | 10.1073/pnas.1607147113 |
pubmed_770_9978 | A significant number of patients with non-Hodgkin's lymphoma have peripheral blood involvement during the course of their disease. Because the expression of receptor for the lectin peanut agglutinin PNA by normal lymphocytes is associated with noncirculating (stationary phase) cells, we studied the relationship between PNA binding by lymphoma cells and the presence of clonal B cells in the blood of 38 patients with B-cell lymphoma. The binding of PNA by cells in tissues was determined by the immunoperoxidase method and by two-color flow cytometry. Circulating lymphoma cells (clonal B cells) were identified by a sensitive flow-cytometric technique (kappa-lambda analysis) and were also studied for PNA binding in some cases. In all, 16 of 38 (42%) of lymphomas were PNA+, including a spectrum of histologic types. Circulating lymphoma cells were demonstrated in 17 of 22 PNA-lymphomas, whereas only 3 of 16 of PNA+ lymphomas had such circulating cells. Thus, there is a significant association between PNA binding and peripheral blood involvement by lymphoma (P less than .005 by chi-square analysis). In 12 cases, the circulating and tissue lymphoma cells had similar expression of PNA receptor (2 PNA+ and 10 PNA- cases), indicating that modulation of the PNA binding sites did not occur. In three patients who presented with lymphosarcoma cell leukemia, the circulating malignant cells were PNA-. These findings suggest that for both normal and malignant lymphocytes the absence of binding sites for PNA is associated with the capacity of these cells to circulate freely. | pubmed_770_9978 |
pubmed_149_24158 | INTRODUCTION
For some time, our faculty have expressed concerns regarding an apparent decrease in pharmacy students' academic productivity and performance. This study aimed to elucidate present conditions and suggest suitable interventions to improve the pharmacy program.
METHODS
Student cohorts starting the pharmacy program from 2009 to 2014 were followed with respect to performance in two courses (earlier and later). The students were segmented by entry qualifications, age, gender, etc. Eight students were further interviewed about their attitudes regarding their education.
RESULTS AND CONCLUSIONS
Achievement in the earlier course fell sharply over time, despite basically unchanged entry grade levels, increasing the workload for both teachers and students. This decrease was greater for male students. In the later course, the overall achievement level was higher, possibly due to less successful students dropping out. Subgrouping of students revealed differences in study achievement depending on age, gender, study program entrance qualifications, and admission "ranking". In the interviews, students frequently stressed that connections to their future profession should be clearer and appear earlier in the program. Furthermore, students claimed that lectures with many attendees prevent peer learning and suggested that smaller groups be formed to foster cooperation and unity within the program. Remaining within their original cohort was viewed as very important by most students. | 10.1016/j.cptl.2019.02.001 |
pubmed_912_153 | Haemocyanin (Hc) is a copper-containing respiratory protein, floating freely dissolved in the hemolymph of many arthropod species. A typical haemocyanin is a hexamer or oligohexamer of six identical or similar subunits, with a molecular mass around 75 kDa each. In the crustaceans, the haemocyanins appear to be restricted to the remipedes and the malacostracans. We have investigated the haemocyanins of two freshwater shrimps, the Amano shrimp Caridina multidentata and the bamboo shrimp Atyopsis moluccensis. We obtained three full-length and one partial cDNA sequences of haemocyanin subunits from the Amano shrimp, which were assigned to the α- and γ-types of decapod haemocyanin subunits. Three complete and two partial haemocyanin cDNA sequences were obtained from the bamboo shrimp, which represent subunit types α, β and γ. This is the first time that sequences of all three subunit types of the decapod haemocyanins were obtained from a single species. However, mass spectrometry analyses identified only α- and γ-type subunits, suggesting that a β-subunit is not a major component of the native haemocyanin of the bamboo shrimp. Phylogenetic and molecular clock analyses showed that malacostracan haemocyanins commenced to diversify into distinct subunit types already ~515 million years ago. β-subunits diverged first, followed by α- and γ-type subunits ~396 million years ago. The haemocyanins of phyllocarids and peracarids form distinct clades within the α/γ-cluster. Within the Caridea, an early divergence of distinct α-type subunits occurred ~200 MYA. The tree of the γ-subunits suggests a common clade of the Caridea (shrimps) and Penaeidae (prawns). | 10.1007/s00360-013-0740-9 |
pubmed_93_13396 | Single walled carbon nanotubes (SWNTs) suspended above the substrate can be fabricated simply and rapidly by chemical vapour deposition growth over pre-grown multi-walled carbon nanotubes (MWNTs). SWNTs are suspended either on a randomly organized carbon nanotube network on an unpatterned substrate, or between organized pillars made from vertically aligned nanotube forests on a patterned substrate. All nanotubes are produced during a single growth run using a two step growth technique. This approach enables the fabrication of laterally suspended SWNT networks which are well suited for optical applications. | 10.1088/0957-4484/18/13/135603 |
pubmed_665_14783 | The purpose of the study was to evaluate the influence of low-intensive laser therapy (LILT) on the aggregation properties of thrombocytes in patients with exacerbation of peptic ulcer (PU). The subjects, 111 patients aged 18 to 63, were divided into two groups: the main group (n = 81), and the control group (n = 30). In addition there were 15 healthy people who also underwent examination. Patients in the main group received complex treatment with untiulcer drugs and different methods of laser therapy: intravenous laser irradiation of blood, cutaneous irradiation, and a combination of both. The control group was treated with drugs only. The study found various changes in the aggregation properties of thrombocytes in patients with PU exacerbation, which consisted mostly in hyperaggregation. LILT had a normalizing effect on the aggregation properties of thrombocytes in patients of the main group. | pubmed_665_14783 |
pubmed_1034_18247 | OBJECTIVES
Heart transplantation is the standard treatment in end-stage heart failure and at shortage of cardiac allografts is its major limiting factor. Striving to optimize the use of this limited resource, the aspect that long distance procurement may increase the available donor pool must be taken into consideration. As poly(ADP-ribose)polymerase (PARP)-activation has been identified as a key pathway of reperfusion injury, we assessed the hypothesis that its inhibition would allow an extension of cold preservation time and protect the graft against ischaemia/reperfusion injury.
METHODS
Hearts from donor rats were explanted, stored in a preservation solution (Custodiol) at 4 °C for 4 h or 8 h, and heterotopically transplanted. A vehicle or the PARP-inhibitor, INO-1001 (5 mg/kg), was administered during the reperfusion period. We evaluated post-transplant graft function with a Millar micromanometer at different left-ventricular volumes. Additionally, in organ bath experiments the effect of PARP-inhibition on endothelium-dependent and -independent vasorelaxation was evaluated after long-term cold ischaemic storage/warm reperfusion.
RESULTS
PARP-inhibition resulted in a better systolic functional recovery of grafts submitted to 4 h and 8 h ischaemia. Furthermore, INO-1001 decreased the left-ventricular end-diastolic pressure after 8 h of ischaemia. Coronary blood flow was significantly higher after PARP-inhibition in comparison to controls. Endothelium-dependent vasorelaxation was significantly better in the INO-1001-groups than in the vehicle-treated transplant groups. After 24-h hypothermic storage, treatment of aortic ring with INO-1001 during reoxygenation significantly improved endothelial dysfunction.
CONCLUSIONS
By inhibiting the PARP activation, INO-1001 can protect the graft and endothelium from the injury that is caused by prolonged cold myocardial ischaemia/reperfusion, thereby improving post-transplant graft function. | 10.1093/ejcts/ezw426 |
pubmed_681_19609 | During preoperative assessment, risk factors of upper airway obstruction should be evaluated: respiratory insufficiency, low O(2) reserve, preoxygenation failure or difficult face mask ventilation. In healthy subjects, spontaneous breathing O(2) for 3 min is the reference method. Apnoea duration is longer after preoxygenation than after denitrogenation, even if FEO(2) and SpO(2) do not change during the two last minutes of preoxygenation. The apnea time is longer after 3 min spontaneous breathing than after four deep breaths for 1 min in most of the literature. Maximal breathing during 2 min can produce values comparable to those obtained with tidal volume breathing for 3 min. FEO(2) monitoring is helpful in the assessment of preoxygenation quality: In case of oxygenation impairment during anaesthesia induction, algorithm use is helpful. Because desperate emergencies will occur in association with anaesthesia, every location should have the immediate availability of Fastrach and trans tracheal ventilation. Every anaesthesiologist should be familiar with and well practised in a variety of airway management techniques. Teaching programs are organised in order to develop anaesthesiologist sensitisation and skill. | 10.1016/s0750-7658(03)00125-4 |
pubmed_633_7906 | National Institutes of Health (NIH) funding has contributed to improvements in the health of the nation, but the pace of progress, particularly in the war on cancer, has been frustratingly slow. Departments of family medicine receive less NIH funding than all other specialties. Although numerous factors contribute to low family medicine funding levels, persistent undervaluing of primary care plays a paramount role. Fueled by the harsh reality that our nation's health is unconscionably poor, we are entering a new era in our nation's research enterprise, a virtual research revolution. The 3 components of this revolution are the NIH roadmap, personalized medicine, and the Clinical and Translational Science Awards. Each of these elements will contribute to a growing emphasis on translational research. Translational research demands formation of innovative structures in academic health centers (AHCs) to enable them to address questions of vital relevance to improving public health. Service research, funded by the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and foundations, defines a new approach to research with high potential to improve the health of communities. To be a part of the research revolution, departments must rely on senior researchers to secure funding and provide mentorship for junior investigators. Junior investigators must relentlessly pursue answers to questions of direct relevance to improving health. Finally, department chairs have the obligation to identify research mentors, find ways to fund research gaps, and create a culture of scholarship and investigation. Advocating for AHCs to commit to improving the health of the regions they serve can have a substantial impact on the types of questions that centers choose to study and, ultimately, on the health of the communities they serve. | 10.3122/jabfm.2010.04.100111 |
others_356_15262 | New combinations for three species of Polypleurum have been proposed. The Apinagia type of embryo sac is recorded for the first time in a species of Polypleurum, P. filifolium. The Dicraea type of embryo sac found in P. dichotomum and P. munnarensis has been reinterpreted and renamed as the Polypleurum type. The embryo sac types met with in the family are discussed. The nucellar plasmodium organizes before the embryo sac attains maturity in all the three investigated species. © 1977 Springer-Verl | 10.1007/BF00984558 |
pubmed_905_1468 | There is a great interest in developing biomarkers to enable precision medicine and improve health outcomes of patients with COPD. However, biomarker development is extremely challenging and expensive, and translation of research endeavors to date has been largely unsuccessful. In most cases, biomarkers fail because of poor replication of initial promising results in independent cohorts and/or inability to transfer the biomarker from a discovery platform to a clinical assay. Ultimately, new biomarker assays must address 5 questions for optimal clinical translation. They include the following: is the biomarker likely to be (1) superior (will the test outperform current standards?); (2) actionable (will the test change patient management?); (3) valuable (will the test improve patient outcomes?); (4) economical (will the implementation of the biomarker in the target population be cost-saving or cost-effective?); and (5) clinically deployable (is there a pathway for the biomarker and analytical technology to be implemented in a clinical laboratory?)? In this article we review some of the major barriers to biomarker development in COPD and provide possible solutions to overcome these limitations, enabling translation of promising biomarkers from discovery experiments to clinical implementation. | 10.1016/j.chest.2016.09.012 |
pubmed_400_13097 | With increasing interest in the role of fetal programming in child and adulthood diseases, and therefore interest in the measurement of various factors at birth, it is essential to ascertain whether the factors of interest show any gestation- or parturition-associated changes. We have investigated whether mode of delivery influenced T-cell phenotype and function (CD4+) as has been described for monocytes and neutrophils. Interferon-gamma production in response to either the mitogen phytohemagglutinin or anti-CD2/CD3/CD28 F(ab')3 was significantly reduced by neonatal mononuclear cells compared with adult cells but did not differ with mode of delivery at term (normal vaginal delivery versus elective lower-segment cesarean section). Likewise, anti-CD2/CD3/CD28-stimulated IL-2 production by the neonate was lower than adult levels but did not differ with mode of delivery. The expression of common T-cell activation markers (CD25, MHC class II, CD69, CD62L, CD11a, CD44, and CD49d) was examined. Only CD62L (L-selectin) expression was significantly different, with fewer adult T cells expressing this surface antigen compared with neonatal T cells (p < 0.0003), and significantly more T cells from lower-segment cesarean section than normal vaginal delivery were positive for CD62L (p = 0.012). sCD62L levels were significantly lower in cord plasma compared with adult plasma but did not differ with mode of delivery. Thus the phenotype and function of cord blood T cells did not differ greatly with mode of delivery, but possible differences for the marker of interest should always be assessed. Furthermore, although there was no significant difference with mode of delivery for all markers, except CD62L, the variation in the normal vaginal delivery samples, as for the adults, was greater than in the lower-segment cesarean section samples, indicating that the effects of length of labor and stress at delivery may well be relevant. | 10.1203/01.PDR.0000069704.25043.BA |
pubmed_849_9401 | The aim of this study was to determine the variability of TD in children undergoing HSCT. Cases were identified as consecutively enrolled children in the period January 2011-January 2013 among patients attending the Paediatric Department of Spedali Civili of Brescia and all candidates to HSCT. The TST was conducted in two phases: identification of threshold values and identification of perceived stimulus intensity. Sixteen sapid solutions with four flavors (sucrose, sodium chloride, citric acid, and quinine hydrochloride) at four different concentrations were administered in a random sequence. The same protocol was administered at different time intervals: before starting the conditioning therapy (T0), during the conditioning therapy (T1) (two times), and every three months (two times) after engraftment post-HSCT (T2). A p-value < 0.05 was considered statistically significant. Fifty-one children (29 female and 22 male, mean age 5.2 ± 0.7 yr) were enrolled. Threshold value means for the four flavors increased during HSCT conditioning therapy (T1) (p < 0.01); intensity of perceived stimulus decreased during HSCT conditioning therapy (p < 0.01). At six months after engraftment (T2), both parameters had returned to starting values (T0). Changes in taste perception in children undergoing HSCT seem to occur especially during the conditioning therapy and resolve in about six months after engraftment post-HSCT. | 10.1111/petr.12535 |
pubmed_851_10963 | Myocardial infarction with normal coronary arteries is a well known pathology. It may or may not be associated with left ventricle wall motion abnormalities. Data was reviewed retrospectively for patients with ST elevation myocardial infarction who underwent cardiac catheterization. From the total number of patients evaluated 10.3% (17) patients had Myocardial Infarction with normal coronary arteries. Females were more likely to present with MINCA then males. Coronary flow was normal in 11 from 17 patients with MINCA. In 6 cases slow coronary flow was detected. Myocardial segments with slow coronary flow did not correlate with wall motion abnormalities detected by echocardiography and ventriculography. In 8 females, Takotsubo cardiomyopathy was suspected. Data were analyzed retrospectively and we were not able to obtain full coagulation panel for all evaluated patients. Myocardial biopsy was not performed in either of patients under observation. Spontaneous thrombolysis was suspected in number of cases. Most angiography investigations were done within three hours after symptoms start. Prognosis of patients with ST-elevation Myocardial Infarction (STEMI) and normal coronary arteries was good. No fatal or non-fatal complications during hospitalization. During 6 month, follow up one male patient was re-hospitalized due to Acute Coronary Syndrome (ACS) in 5.5 month after initial event. Repeated coronary angiography did not reveal the abnormalities. Our study is first attempt for collecting retrospectively different data for patients with STEMI and NCA. Important is that no correlation was found between wall motion abnormalities and coronary flow limitations (if present). Compared to other studies we found higher incidences of wall motion abnormalities detected by echocardiography and/or ventriculography. Future prospective design studies in STEMI and NCA are warranted to understand the pathophysiology and define right treatment approaches. Stress may be considered as prominent factor, but future studies are needed with psychological evaluation; autonomous nerves system testing and catecholamine levels determination to verify its role in this pathology. | pubmed_851_10963 |
pubmed_616_12265 | BACKGROUND
Results of small-scale studies have suggested that stem-cell therapy is safe and effective in patients with liver cirrhosis, but no adequately powered randomised controlled trials have been done. We assessed the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) and haemopoietic stem-cell infusions in patients with liver cirrhosis.
METHODS
This multicentre, open-label, randomised, controlled phase 2 trial was done in three UK hospitals and recruited patients with compensated liver cirrhosis and MELD scores of 11·0-15·5. Patients were randomly assigned (1:1:1) to receive standard care (control), treatment with subcutaneous G-CSF (lenograstim) 15 μg/kg for 5 days, or treatment with G-CSF for 5 days followed by leukapheresis and intravenous infusion of three doses of CD133-positive haemopoietic stem cells (0·2 × 106 cells per kg per infusion). Randomisation was done by Cancer Research UK Clinical Trials Unit staff with a minimisation algorithm that stratified by trial site and cause of liver disease. The coprimary outcomes were improvement in severity of liver disease (change in MELD) at 3 months and the trend of change in MELD score over time. Analyses were done in the modified intention-to-treat population, which included all patients who received at least one day of treatment. Safety was assessed on the basis of the treatment received. This trial was registered at Current Controlled Trials on Nov 18, 2009; ISRCTN, number 91288089; and the European Clinical Trials Database, number 2009-010335-41.
FINDINGS
Between May 18, 2010, and Feb 26, 2015, 27 patients were randomly assigned to the standard care, 26 to the G-CSF group, and 28 to the G-CSF plus stem-cell infusion group. Median change in MELD from day 0 to 90 was -0·5 (IQR -1·5 to 1·1) in the standard care group, -0·5 (-1·7 to 0·5) in the G-CSF group, and -0·5 (-1·3 to 1·0) in the G-CSF plus stem-cell infusion group. We found no evidence of differences between the treatment groups and control group in the trends of MELD change over time (p=0·55 for the G-CSF group vs standard care and p=0·75 for the G-CSF plus stem-cell infusion group vs standard care). Serious adverse events were more frequent the in G-CSF and stem-cell infusion group (12 [43%] patients) than in the G-CSF (three [11%] patients) and standard care (three [12%] patients) groups. The most common serious adverse events were ascites (two patients in the G-CSF group and two patients in the G-CSF plus stem-cell infusion group, one of whom was admitted to hospital with ascites twice), sepsis (four patients in the G-CSF plus stem-cell infusion group), and encephalopathy (three patients in the G-CSF plus stem-cell infusion group, one of whom was admitted to hospital with encephalopathy twice). Three patients died, including one in the standard care group (variceal bleed) and two in the G-CSF and stem-cell infusion group (one myocardial infarction and one progressive liver disease).
INTERPRETATION
G-CSF with or without haemopoietic stem-cell infusion did not improve liver dysfunction or fibrosis and might be associated with increased frequency of adverse events compared with standard care.
FUNDING
National Institute of Health Research, The Sir Jules Thorn Charitable Trust. | 10.1016/S2468-1253(17)30326-6 |
others_314_168738 | Antipsychotics share the common pharmacological feature of antagonizing the dopamine 2 receptor (D2R) which is abundant in the striatum and involved in both the therapeutic and side effects of this drugs class. Pharmacological blockade of striatal D2R, by disinhibiting the D2R-containing medium-size spiny neurons (MSNs), leads to a plethora of molecular, cellular and behavioral adaptations which are central in the action of antipsychotics. Here, we focused on the cell type-specific (D2R-MSNs) regulation of some striatal immediate early genes (IEGs), such as cFos, Arc and Zif268. Taking advantage of transgenic mouse models, pharmacological approaches and immunofluorescence analyses, we found that haloperidol-induced IEGs in the striatum required the synergistic activation of A2a (adenosine) and NMDA (glutamate) receptors. At the intracellular signaling level, we found that the PKA/DARPP-32 and mTOR pathways synergistically cooperate to control the induction of IEGs by haloperidol. By confirming and further expanding previous observations, our results provide novel insights into the regulatory mechanisms underlying the molecular/cellular action of antipsychotics in the striatum | 10.1101/2022.09.10.507436 |
pubmed_226_23880 | Maneuvering the architecture and composition of semiconductors is essential to optimizing their performance in photocatalytic solar-to-fuel conversion. Here, we show that ion exchange, having a disparate mechanism with direct nucleation and growth of semiconductor crystals, can provide a new platform for rational control over the geometry and electronic structures of chalcogenide semiconductor photocatalysts. As a demonstration, the ZnSe nanocubes possessing a hollowed architecture and doped with a controllable amount of Ag+ ions are accessed via sequential ion exchange. The kinetics of the exchange reaction offers a knob for regulating the electronic structures of the Ag-doped ZnSe hollow cubes and, hence, their functions in light harvesting and photogenerated charge separation. Such synergistically geometric and optoelectronic modulation of ZnSe brings an order of magnitude enhancement in photocatalytic H2 evolution activity relative to commercial ZnSe powders. Our study corroborates that ion exchange may open up new horizons for judicious fabrication and engineering of semiconductor-based photocatalyst materials. | 10.1021/acs.jpclett.1c04232 |
pubmed_785_8630 | INTRODUCTION
Iron is a key element in the transport and utilization of oxygen and a variety of metabolic pathways. Iron deficiency is a major cause of anemia and can be associated with fatigue, impaired physical function and reduced quality of life. Administration of oral or intravenous (i.v.) iron is the recommended treatment for iron-deficiency anemia (IDA) in different therapeutic areas.
AREAS COVERED
This article provides an overview of studies that evaluated i.v. iron sucrose for anemia and iron status management, either alone or in combination with erythropoiesis-stimulating agents, across various diseases and conditions.
EXPERT OPINION
Iron sucrose is an established, effective and well-tolerated treatment of IDA in patients with acute or chronic conditions such as chronic kidney disease, inflammatory bowel disease, pregnancy (second and third trimester), postpartum period, heavy menstrual bleeding and cancer who need rapid iron supply and in whom oral iron preparations are ineffective or not tolerated. Available data on patient blood management warrant further studies on preoperative iron treatment. First experience with iron sucrose follow-on products raises questions about their therapeutic equivalence without comparative clinical data in newly diagnosed patients or patients on existing chronic treatment. | 10.1517/14656566.2014.953928 |
pubmed_241_5245 | In Saccharomyces cerevisiae, the PUT1 and PUT2 genes are required for the conversion of proline to glutamate. The PUT1 gene encodes Put1p, a proline dehydrogenase (PRODH) enzyme localized in the mitochondrion. Put1p was expressed and purified from Escherichia coli and shown to have a UV-visible absorption spectrum that is typical of a bound flavin cofactor. A K(m) value of 36 mM proline and a k(cat)=27 s(-1) were determined for Put1p using an artificial electron acceptor. Put1p also exhibited high activity using ubiquinone-1 (CoQ(1)) as an electron acceptor with a k(cat)=9.6 s(-1) and a K(m) of 33 microM for CoQ(1). In addition, knockout strains of the electron transfer flavoprotein (ETF) homolog in S. cerevisiae were able to grow on proline as the sole nitrogen source demonstrating that ETF is not required for proline utilization in yeast. | 10.1016/j.abb.2010.04.020 |
pubmed_1070_15526 | Attachment theory is focused upon the development of the attachment process organized jointly by the child and the environmental factors which contribute to the development of the feeling of security. The authors focus on the mother-baby relationships and describe the normative process of attachment relationships during the first year of life. The ethologic perspective of this development is also summarized. The steps of the developing attachment relationship are described. The description of motherhood is focused on the bonding process, which is a more immediate and biologically based process and on caregiving which is a symmetrical motivational system as complex as the attachment one. The main factors known as having an impact on the two processes are described. | 10.1016/S0929-693X(08)73942-3 |
pubmed_1104_9290 | Amphotericin B was given to 19 dogs with leishmaniasis. The drug was diluted in an emulsion prepared by mixing 50 mg of amphotericin B desoxycholate with 40 ml of sterile water and 10 ml of soya bean oil solution. The dogs were infused over nearly one hour with 50 ml/kg of normal saline followed by 10 ml/kg of mannitol 20 per cent. The mixture was then loaded over 30 to 60 minutes using a syringe pump. The emulsion was given twice weekly, at an increasing dosage (from 1 to 2.5 mg/kg bodyweight), for a minimum of eight injections. All 17 dogs receiving a total dosage of more than 10 mg/kg were clinically cured by the end of the treatment, and 14 of these had a negative polymerase chain reaction test on bone marrow. | 10.1111/j.1748-5827.2001.tb01797.x |
pubmed_468_11189 | BACKGROUND
Cardiac dysfunction occurs commonly in sepsis. Impaired mitochondrial function is a potential cause of sepsis-associated myocardial depression. Cytochrome oxidase (COX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Glutamine (GLN) increases Krebs cycle intermediates and supports oxidative phosphorylation. Exogenous GLN has been shown to restore myocardial adenosine triphosphate levels and cardiac function following ischemia-reperfusion injury. The authors hypothesize that exogenous GLN will abrogate sepsis-induced myocardial COX inhibition and improve sepsis-associated myocardial depression.
METHODS
Under general anesthesia, male Sprague-Dawley rats underwent cecal ligation and double puncture (CLP) or sham operation. At the time of operation, rats underwent intraperitoneal injection of either GLN (0.75 g/kg) or an equal volume of saline. Twenty-four hours after the procedure, animals were killed, cardiac ventricles harvested, and mitochondria isolated. Steady-state COX kinetic activity was measured and normalized to citrate synthase activity. Steady-state levels of COX subunit I protein were determined with immunoblot analysis. Cardiac function was assessed using an isolated rat heart preparation. Five animals per group were evaluated. Significance was determined with analysis of variance and post hoc Tukey test.
RESULTS
CLP significantly decreased myocardial COX activity, oxygen consumption, left ventricular pressure (LVP), and pressure developed during isovolumic contraction (+dP/dt) and relaxation (-dP/dt). GLN restored COX activity to sham levels, significantly increased myocardial oxygen extraction and consumption, increased LVP toward sham values, and increased ±dP/dt by >30% following CLP.
CONCLUSION
The beneficial effects of GLN therapy during sepsis may be in part due to restoration of oxidative phosphorylation and abrogation of sepsis-associated myocardial depression. | 10.1177/0148607110383040 |
pubmed_26_13057 | Chlamydomonas raudensis Ettl UWO241, a natural variant of C. raudensis, is deficient in state transitions. Its habitat, the deepest layer of Lake Bonney in Antarctica, features low irradiance, low temperature, and high salinity. Although psychrophily and low-light acclimation of this green alga has been described, very little information is available on the effect of salinity. Here, we demonstrate that this psychrophile is halotolerant, not halophilic, and it shows energy redistribution between photosystem I and II based on energy spillover under low-salt conditions. Furthermore, we revealed that C. raudensis exhibits higher non-photochemical quenching in comparison with the mesophile Chlamydomonas reinhardtii, when grown with low-salt, which is due to the lower proton conductivity across the thylakoid membrane. Significance of the C. raudensis UWO241 traits found in the low salinity culture are implicated with their natural habitats, including the high salinity and extremely stable light environments. | 10.1007/s11120-008-9397-8 |
others_175_5973 | Although it is well known that fluctuations in soil moisture affect the decomposition of organic matter, few studies have provided direct evidence of the underlying biophysical mechanisms. Cycles of wetting and drying (W/D) may not only alter soil pore structure, but also stimulate a proliferation of fungi, since these organisms are typically less affected by drought stress than bacteria, and hence the development of fungal-induced soil water repellency. The biophysical interaction between these processes is likely to influence the decomposition of organic matter amendments to soil and carbon sequestration. By using soil cores amended with rice straw, the objectives of this study were to determine the effects of drying intensity and frequency of W/D cycles on decomposition rate after rewetting, soil pore-size distribution, soil microbial biomass (SMB) and soil water repellency, and to assess their biophysical interaction. One W/D cycle consisted of wetting a soil core from the bottom for 1.5-days at -0.03 kPa followed by 1.5, 3.5 or 6.5 days of drying in open air at 25 ± 2.5 °C. This resulted in different intensities of drying and frequencies of W/D cycles over a 120-d incubation period. The decomposition rate decreased with repeated W/D cycles and increasing drying intensity, particularly between the 3rd and 9th W/D cycles. The SMB-C concentration and soil water repellency peaked at the 3rd W/D cycle. The peak size of the SMB-C concentration was larger in the drier soils and soil water repellency was significantly related to SMB-C concentration (R = 0.57, P = 0.025). The soil with the strongest drying treatment had a greater concentration of particulate organic carbon (POC) and the lowest C:N ratio in POC. Although the decomposition rate was significantly correlated to the concentration of soil organic carbon (SOC) (P < 0.01), POC (P < 0.01) and SMB-C (P < 0.05), stepwise regression analysis further identified that it was largely correlated to soil pore characteristics. The decrease in the decomposition rate in the drier soil was largely explained by the increase in macropores >300 μm in diameter (R = 0.98). The results suggest that an increased drying intensity or a longer duration of drying after rainfall or irrigation may favour SOC sequestration through inhibiting decomposition of amended residue. This may be due to the formation of macropores and their subsequent stabilization via fungal growth and fungal-induced soil water repellency. © 2010 Elsevier L | 10.1016/j.soilbio.2010.11.027 |
pubmed_611_10574 | The metabolism of benzo[a]pyrene (BP) is known to lead to a large number of oxygenated compounds, some of which can bind covalently to DNA. We have studied the integrated metabolism of BP in vivo in germ-free rats given (14)C-labeled BP. Urinary metabolites were separated into groups according to acidity using lipophilic ion exchangers. The groups were analyzed by mass spectrometry and were further fractionated by high-performance liquid chromatography. The fraction of urinary metabolites previously shown to contain N-acetylcysteine and glucuronic acid conjugates was found to contain derivatives of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid as major components. These compounds, which were identified by mass spectrometry and NMR, accounted for about 30% of the total metabolites in urine, demonstrating that, surprisingly, ring opening is a major pathway for metabolism of BP in the germ-free rat. The dicarboxylic acid may be excreted in urine as an ester glucuronide. By using the single cell gel electrophoresis or COMET assay, we were able to demonstrate that the anhydride of 7-oxo-benz[d]anthracene-3, 4-dicarboxylic acid was an efficient inducer of DNA damage. Taken together, these results indicate that the novel ring opening metabolic pathway may provide alternative mechanisms for the toxicity of BP. | 10.1021/bi001148y |
pubmed_1030_9679 | Background
There is a lack of consensus regarding the optimal technique for revision posterior cruciate ligament (PCL) reconstruction.
Purpose
To evaluate midterm outcomes after revision PCL reconstruction using a single-bundle transtibial autograft.
Study Design
Case series; Level of evidence, 4.
Methods
We reviewed 17 patients who underwent revision PCL reconstruction performed in our medical center by a single surgeon from 2003 to 2016. The cohort included 12 male and 5 female patients with a mean age of 31.3 years (range, 17-48 years). All of the patients underwent single-bundle transtibial reconstruction using the same surgical technique and were reviewed at a minimum of 4 years postoperatively. Preoperative and postoperative posterior stress radiography was performed. The preoperative tibial slope and tibiofemoral angle were also measured. Preoperative and postoperative functional outcomes were evaluated using the International Knee Documentation Committee (IKDC) subjective and objective scores as well as the Lysholm score.
Results
The most common factor that contributed to the failure of primary surgery was misplaced tunnels, especially on the femoral side. There were 2 patients who had grade 2 laxity preoperatively, and 15 patients had grade 3 laxity preoperatively. At the latest follow-up, all 17 patients had grade 1 laxity. On posterior stress radiography, posterior displacement improved from 10.8 ± 2.1 mm preoperatively to 2.9 ± 1.1 mm at the latest follow-up (P < .001). The IKDC subjective score improved from 34.9 ± 6.8 preoperatively to 75.3 ± 15.7 postoperatively (P < .001), and the Lysholm score improved from 38.1 ± 10.0 preoperatively to 88.5 ± 7.6 postoperatively (P < .001). All patients reached the minimal clinically important difference (MCID) for the Lysholm score, and 94% reached the MCID for the IKDC subjective score, with 65% reaching the Patient Acceptable Symptom State.
Conclusion
According to the findings of this study, arthroscopic revision PCL reconstruction with a single-bundle transtibial autograft offered satisfactory outcomes at midterm follow-up. | 10.1177/23259671221115423 |
pubmed_551_6137 | We report infrared multiple photon dissociation (IRMPD) spectra for a series of crown-adducted, protonated amino acids, generated by electrospray ionization. The tight chelation of 18-crown-6 on the protonated NH(3)(+) moiety results in a considerable red shift of the NH(3)(+) stretch modes, notably the antisymmetric NH(3)(+) stretch. This is rationalized by a distortion of the NH(3)(+) normal mode potential energy surface, as verified by quantum chemical calculations. On the other hand, the local oscillator modes, such as the carboxylic acid OH stretch, indole NH stretch, and phenol OH stretches, remain well-resolved and are subject to minor and predictable blue shifts of 5-15 cm(-1). Other chemically diagnostic modes, such as the guanidine NH stretch and alcohol OH stretches, also have discernible band positions. Crucially, some of these diagnostic band positions have little to no overlap with one another and can hence be readily distinguished. In addition, the complexes are often found to efficiently photodissociate by neutral loss of 18-crown-6, particularly for higher-basicity amino acids. This in principle opens the door on multiplexing the IRMPD experiment, where the IR spectra of multiple precursors are recorded simultaneously. | 10.1021/jp305263b |
pubmed_5_2628 | Cardiac output, blood flow to the coeliac and mesenteric arteries, dorsal aortic blood pressure and heart rate were recorded simultaneously at rest and postprandial for 6 days in a teleost, the red Irish lord (Hemilepidotus hemilepidotus). We anticipated that gastrointestinal blood flow would increase postprandially, supported by an increase in cardiac output. However, we had no predictions for either the exact time-course of this response, or for the regional distribution of blood flow between to the two major arteries comprising the splanchnic circulation. In resting, unfed animals, blood flow to the coeliac artery and mesenteric artery was 4.1 +/- 0.6 ml min(-1) kg(-1) and 4.9 +/-1.3 ml min(-1) kg(-1), respectively (mean +/- SEM, n = 7), which together represented 34% of cardiac output. Feeding increased blood flow to the coeliac and mesenteric arteries in a time-dependent manner. The increase in coeliac artery blood flow preceded that in the mesenteric artery, a finding that is consistent with the coeliac artery supplying blood to the liver and stomach, while the mesenteric artery supplies blood to the stomach and intestine. Coeliac blood flow had increased by 84 +/- 18% after 1 day and had a peak increase of 112 +/- 40% at day 4 postprandial. Mesenteric blood flow was not significantly elevated at day 1, but had increased by 94 +/- 19% at day 4 postprandial. Cardiac output also increased progressively, increasing by a maximum of 90 +/- 30% at day 4. Because the increase in cardiac output was adequate to meet the postprandial increase in gut blood flow, the postprandial decreases in vascular resistance for the coeliac and mesenteric circulations mirrored the increases in blood flow. Intra-arterial injections of adrenaline and noradrenaline into resting fish more than doubled coeliac and mesenteric vascular resistances, and blood flow decreased proportionately. This adrenergic vasoconstriction was totally abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, which in itself approximately halved coeliac and mesenteric vascular resistances. These observations indicate a significant alpha-adrenergic tone in the gastrointestinal circulation of the red Irish lord, the loss of which could not entirely account for the post-prandial increase in gastrointestinal blood flow. Other control mechanisms are suggested. | 10.1007/s003600050269 |
pubmed_443_173 | The use of hematopoietic growth factors, although well established for the management of chemotherapy-induced neutropenia, remains controversial for the treatment of aplastic anemia and inherited bone marrow failure syndromes. The most commonly used factors are granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and erythropoietin. Newer growth factors such as stem cell factor, thrombopoietin, Flt3 ligand, and interleukins have shown promising results in the laboratory, and some have been used in clinical trials. This article reviews the clinical use of old and new hematopoietic growth factors in acquired and inherited bone marrow failure, and discusses emerging concerns about long term toxicity of these factors. | 10.1097/00062752-199805000-00014 |
pubmed_363_15136 | A case of primary intracerebral haemorrhage complicated by cerebral abscess is presented with a review of the literature. | 10.4314/eamj.v79i3.8898 |
pubmed_1119_16955 | Potential scavenging properties of cephalosporins (i.e. cefamandole, cefotaxime and ceftriaxone) towards hypochlorous acid (HOCl) as well as the antibacterial activity of control and HOCl-reacted antibiotics were investigated. We found that these drugs, at therapeutically relevant concentrations, are indeed scavengers of HOCl, with ceftriaxone showing the highest anti-HOCl capacity. However, the efficiency of cephalosporins in protecting biological molecules is also related to the chemical identity of such molecules. Indeed, the polyenoic compound beta-carotene is much better protected that the thiol compound GSH against HOCl attack. Moreover, the drugs do not appear to form chloramine derivatives as a result of their reaction with HOCl, and they inhibit taurine-chloramine formation. After HOCl challenge, the antibacterial activity of cefamandole, cefotaxime and ceftriaxone (tested against the standard strain Escherichia coli ATCC 25922) is approx. 8-, 5- and 4-fold lower, respectively, than that of the HOCl-unreacted antibiotics. The depression of the antibacterial activity of cephalosporins appears inversely related to their HOCl scavenging capacity, suggesting that the drug antioxidant groups may protect the beta-lactam ring against HOCl attack. In conclusion, physiological biomolecules are protected by cephalosporins against HOCl-driven oxidative injury with varying efficiency, this antioxidant defence being a consequence of a direct drug scavenging capacity towards HOCl. The interaction of cephalosporins with HOCl, however, results in a depression of their antibacterial activity. | 10.1016/0006-2952(95)00044-z |
pubmed_862_20848 | BACKGROUND
As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents.
METHODS
In the 44-week, parallel, open study that was undertaken in 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same time every day or to insulin lispro administered three times per day. The primary objective was to compare the change in haemoglobin A(1c) from baseline to endpoint (week 44) between the two regimens. Randomisation was done with a central randomisation service. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00311818.
FINDINGS
205 patients were randomly assigned to insulin glargine and 210 to insulin lispro. Mean haemoglobin A(1c) decrease in the insulin glargine group was -1.7% (from 8.7% [SD 1.0] to 7.0% [0.7]) and -1.9% in the insulin lispro group (from 8.7% [1.0] to 6.8% [0.9]), which was within the predefined limit of 0.4% for non-inferiority (difference=0.157; 95% Cl -0.008 to 0.322). 106 (57%) patients reached haemoglobin A(1c) of 7% or less in the glargine group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4.3 [SD 2.3] mmol/L vs -1.8 [2.3] mmol/L; p<0.0001) and nocturnal blood glucose (-3.3 [2.8] mmol/L vs -2.6 [2.9] mmol/L; p=0.0041) was better than it was in the insulin lispro group, whereas insulin lispro better controlled postprandial blood glucose throughout the day (p<0.0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5.2 [95% CI 1.9-8.9] vs 24.0 [21-28] events per patient per year; p<0.0001). Respective mean weight gains were 3.01 (SD 4.33) kg and 3.54 (4.48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3.13; 95% CI 2.04-4.22).
INTERPRETATION
A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A(1c). We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro.
FUNDING
Sanofi-Aventis. | 10.1016/S0140-6736(08)60485-7 |
pubmed_537_5792 | To determine when the calcium-binding protein parvalbumin appears during development, neurons in the chick Edinger Westphal nucleus were examined for parvalbumin immunoreactivity at a variety of embryonic stages. Parvalbumin immunoreactivity appeared on embryonic day 14 (E14, Hamburger and Hamilton stage 40) in predominantly lateral Edinger Westphal neurons. Cytochrome oxidase activity within the nucleus was examined throughout development, as an indicator of physiological activity, and expression of cytochrome oxidase was compared with that of parvalbumin. Cytochrome oxidase activity was found to be uniformly high in all parts of the Edinger Westphal nucleus throughout development. Either the Edinger Westphal nucleus in physiologically active quite early in its development or other energy demands mask the correlation of cytochrome oxidase with electrical activity. Cytochrome oxidase was expressed well before parvalbumin immunoreactivity appeared. Voltage-activated calcium currents were characterized in E12 Edinger Westphal neurons. In both amplitude and composition, E12 calcium currents resemble those of E16 neurons, excluding the possibility that calcium currents appear de novo during or just prior to the appearance of parvalbumin. Both cytochrome oxidase activity and calcium currents are observed in Edinger Westphal neurons well before the appearance of parvalbumin during development. These findings do not exclude the possibility that physiological activity affects the expression of parvalbumin since other factors such as changing patterns of synaptic activity or the appearance of calcium conducting NMDA receptors have yet to be examined. However, they raise the possibility that additional factors such as an intrinsic developmental program or a change in the neuron's basal intracellular calcium requirements may also be involved. | 10.1002/cne.903600406 |
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