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Frailty, family, and church support among urban African American elderly.
A community-based survey of 507 African Americans aged 60 and older from South Central Los Angeles was conducted to estimate the prevalence of frailty and describe the correlation between frailty, social support from family and church, and use of community services. Persons were considered frail if they met criteria for any of four conditions: functional impairment, depression, urinary incontinence, falls. Sixty-seven percent met criteria for frailty. Analyses revealed that frail elderly were significantly less likely to report feeling very close to family. Family contact, feeling that church was important, and receiving church support were similar for the frail and nonfrail. Frail elderly were more likely to use community services. These findings suggest that frail elderly in this population may not receive more support from family and church than nonfrail elderly. There is a need for caution when assuming families and churches in urban African American communities are able to support the most vulnerable elderly. | {
"pile_set_name": "PubMed Abstracts"
} |
Evidence of overcharging in the complexation between oppositely charged polymers and surfactants.
We report on the complexation between charged-neutral block copolymers and oppositely charged surfactants studied by small-angle neutron scattering. Two block copolymers/surfactant systems are investigated, poly(acrylicacid)-b-poly(acrylamide) with dodecyltrimethylammonium bromide and poly(trimethylammonium ethylacrylate methylsulfate)-b-poly(acrylamide) with sodium dodecyl sulfate. Two two systems are similar in terms of structure and molecular weight but have different electrostatic charges. The neutron-scattering data have been interpreted in terms of a model that assumes the formation of mixed polymer-surfactant aggregates, also called colloidal complexes. These complexes exhibit a core-shell microstructure, where the core is a dense coacervate microphase of micelles surrounded by neutral blocks. Here, we are taking advantage of the fact that the complexation results in finite-size aggregates to shed some light on the complexation mechanisms. In order to analyze quantitatively the neutron data, we develop two different approaches to derive the number of surfactant micelles per polymer in the mixed aggregates and the distributions of aggregation numbers. With these results, we show that the formation of the colloidal complex is in agreement with overcharging predictions. In both systems, the amount of polyelectrolytes needed to build the core-shell colloids always exceeds the number that would be necessary to compensate the charge of the micelles. For the two polymer-surfactant systems investigated, the overcharging ratios are 0.66+/-0.06 and 0.38+/-0.02. | {
"pile_set_name": "PubMed Abstracts"
} |
Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump.
Two clinical Staphylococcus aureus isolates were investigated due to their unusual antimicrobial susceptibility pattern, i.e. erythromycin-susceptible but clindamycin-resistant. These isolates harboured identical copies of a plasmid-borne vga(A)(LC) gene not previously described in S. aureus. The native plasmids carrying vga(A)(LC) were transferable to a susceptible laboratory strain of S. aureus in vitro, in which they conferred resistance patterns similar to the parent isolates. | {
"pile_set_name": "PubMed Abstracts"
} |
Comprehensive noninvasive assessment of cardiac involvement in limited systemic sclerosis.
To assess cardiovascular abnormalities in patients with limited systemic sclerosis (SSc), using noninvasive cardiac techniques. Sixty-three patients with limited SSc were prospectively evaluated with Doppler echocardiography and thallium-201 perfusion scintigraphy after a cold-stress test and radionuclide ventriculography. In the patients with limited SSc, there was a significantly high prevalence of abnormal left- and right-diastolic function parameters (P = 0.001 and P = 0.0002, respectively), thickening of papillary muscles (46%; P = 0.003), and mild mitral regurgitation (49%; P < 0.0001), compared with controls. Systolic pulmonary arterial hypertension was detected in 9 patients (14%), and pericardial effusion in 11 patients (18%). In 64% of patients with limited SSc, an ischemic response was detected on the thallium cold-stress scan; similarly, an ischemic response was detected in 57% of patients with primary Raynaud's phenomenon (P < 0.0001 versus controls). Although the frequency of cardiovascular symptoms was low in patients with limited SSc, a significant rate of cardiovascular abnormalities was found by noninvasive cardiac techniques. | {
"pile_set_name": "PubMed Abstracts"
} |
[Medical support of the Armed Forces of the Russian Federation: results of activity and tasks for 2016].
The author gives an analysis of activity of the medical service of the Armed Forces in 2015 concerning development of normative legal basis for the military health care, improvement of the level of operational and mobilization readiness of subunits of army group, and military-medical institutions, improvement of effectiveness of treatment and evacuation measures, health resort treatment, medical stuff training optimization, sanitary-and-epidemiologic support, material and technical support improvement, adoption of advanced scientific achievements focusing on medical care delivery to army group, active development and increase in medical information systems, telehealth. system. The author gives data characterizing state and level of development of medical service of the Armed Forces and its dynamics. Main tasks and parameters of development of the service in 2016 and up to 2020 are formulated. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis of oximes under ultrasound irradiation.
The condensation of aldehydes and ketones with hydroxylamine hydrochloride results oximes in 50.7-98.7% yields in EtOH under ultrasound irradiation. Compared with conventional methods, the main advantages of the present procedure are milder conditions, shorter reaction time and higher yields. | {
"pile_set_name": "PubMed Abstracts"
} |
Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury.
Randomized experimental study. To investigate the molecular mechanisms of quercetin in spinal cord injury (SCI) rats. China. One hundred female Sprague-Dawley rats were randomly assigned into four groups: sham group, SCI group, SCI+Vehicle (Veh) group, and the SCI+Quercetin (Que) group. The influences of quercetin on proinflammatory cytokine levels, histological changes and locomotion scale were estimated. SCI significantly promoted nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation and increased proinflammatory cytokine productions in the SCI group as compared with the sham group. Quercetin administration significantly decreased reactive oxygen species production, inhibited NLRP3 inflammasome activation and reduced inflammatory cytokine levels. Moreover, quercetin administration attenuated histopathology and promoted locomotion recovery. Quercetin can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation. | {
"pile_set_name": "PubMed Abstracts"
} |
Impact of siRNA overhangs for dendrimer-mediated siRNA delivery and gene silencing.
Small interfering RNA (siRNA) have attracted considerable attention, as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing siRNA delivery vectors thanks to their unique, well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure. We have recently disclosed the structurally flexible fifth-generation TEA-core PAMAM dendrimer (G5) as an effective nanocarrier for delivery of sticky siRNA bearing long complementary sequence overhangs (dA)n/(dT)n (n = 5 or 7). Here, using combined experimental/computational approaches, we successfully clarified (i) the underlying mechanisms of interaction between the dendrimer nanovector G5 and siRNA molecules bearing either complementary or noncomplementary sequence overhangs of different length and chemistry and (ii) the impact of siRNA overhangs contributing toward the improved delivery potency. Using siRNA with complementary overhangs offer the best action in term of gene silencing through the formation of concatemers, that is, supramolecular structures resulting from synergistic and cooperative binding via (dA)n/(dT)n bridges (n = 5 or 7). On the other hand, although siRNA bearing long, noncomplementary overhangs (dA)n/(dA)n or (dT)n/(dT)n (n = 5 or 7) are endowed with considerably higher gene silencing potency than normal siRNA with (dT)2/(dT)2, they remain less effective than their sticky siRNA counterparts. The observed gene silencing potency depends on length, nature, and flexibility of the overhangs, which behave as a sort of clamps that hold and interact with the dendrimer nanovectors, thus impacting siRNA delivery performance and, ultimately, gene silencing. Our findings can be instrumental in designing siRNA entities with enhanced capability to achieve effective RNA interference for therapeutic applications. | {
"pile_set_name": "PubMed Abstracts"
} |
Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.
Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation. | {
"pile_set_name": "PubMed Abstracts"
} |
Beyond using composite measures to analyze the effect of unmet supportive care needs on caregivers' anxiety and depression.
Caregiver research has relied on composite measures (eg, count) of unmet supportive care needs to determine relationships with anxiety and depression. Such composite measures assume that all unmet needs have a similar impact on outcomes. The purpose of this study is to identify individual unmet needs most associated with caregivers' anxiety and depression. Two hundred nineteen caregivers completed the 44-item Supportive Care Needs Survey and the Hospital Anxiety and Depression Scale (minimal clinically important difference = 1.5) at 6 to 8 months and 1, 2, 3.5, and 5 years following the patients' cancer diagnosis. The list of needs was reduced using partial least square regression, and those with a variance importance in projection >1 were analyzed using Bayesian model averaging. Across time, 8 items remained in the top 10 based on prevalence and were labelled "core." Three additional ones were labelled "frequent," as they remained in the top 10 from 1 year onwards. Bayesian model averaging identified a maximum of 3 significant unmet needs per time point-all leading to a difference greater than the minimal clinically important difference. For depression, none of the core unmet needs were significant, rather significance was noted for frequent needs and needs that were not prevalent. For anxiety, 3/8 core and 3/3 frequent unmet needs were significant. Those unmet needs that are most prevalent are not necessarily the most significant ones, and findings provide an evidence-based framework to guide the development of caregiver interventions. A broader contribution is proposing a different approach to identify significant unmet needs. | {
"pile_set_name": "PubMed Abstracts"
} |
The mechanism of orotidine 5'-monophosphate decarboxylase: catalysis by destabilization of the substrate.
The mechanism of orotidine 5'-monophosphate decarboxylase (OMP decarboxylase, ODCase) was studied using the decarboxylation of orotic acid analogues as a model system. The rate of decarboxylation of 1,3-dimethylorotic acid and its analogues as well as the stability of their corresponding carbanion intermediates was determined. The results have shown that the stability of the carbanion intermediate is not a critical factor in the rate of decarboxylation. On the other hand, the reaction rate is largely dependent on the equilibrium constant for the formation of a zwitterion. Based on these results, we have proposed a new mechanism in which ODCase catalyzes the decarboxylation of OMP by binding the substrate in a zwitterionic form and providing a destabilizing environment for the carboxylate group of OMP. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation of Helicobacter pylori from vomitus in children and its implication in gastro-oral transmission.
The route of transmission of Helicobacter pylori (H. pylori) is unclear. Gastro-oral transmission via contaminated vomitus has been proposed as an important mode of transmitting H. pylori, especially in children. This pilot study attempted to isolate H. pylori from the vomitus of children. Children presenting for evaluation with gastroenteritis-associated vomiting were studied. Fresh vomitus samples were collected for detection of H. pylori by bacteriological culture and polymerase chain reaction, (PCR). A rapid, whole blood test was used to determine the H. pylori status of patients. A total of 18 children with mean age of 6 yr were studied; four had a positive serology test. Among these four children, H. pylori was isolated from vomitus by culture in one child and by PCR in two. An 18-month-old girl with negative serology had H. pylori detected in vomitus by PCR. Six months later, she had seroconversion confirmed, suggesting that she had an acute H. pylori infection on initial presentation. This is the first study reporting successful isolation of H. pylori from naturally produced vomitus. The result implies that transmission of H. pylori infection by vomitus, especially in children, is possible. | {
"pile_set_name": "PubMed Abstracts"
} |
ASHP therapeutic position statement on the use of statins in the prevention of atherosclerotic vascular disease in adults.
Elevated blood cholesterol levels contribute significantly to ASVD and are often undertreated or not treated at all. Evaluation and management of lipid disorders should be guided by current NCEP guidelines. For patients with elevated cholesterol levels after appropriate therapeutic lifestyle changes, statins are a safe and effective means of reducing cardiovascular events. Because of their proven safety and effectiveness, ASHP supports the use of statins as first-line therapy for the primary and secondary prevention of atherosclerotic events. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of antimycin, glucose deprivation, and serum on cultures of neurons, astrocytes, and neuroblastoma cells.
The resistance of cultured mouse neuroblastoma cells, primary cultures of rat cerebellar neurons, and rat brain astrocytes to a block of aerobic metabolism was studied. Parameters such as lactate production and ATP content were measured in the presence of antimycin A and under various conditions of glucose, oxygen, and serum supply. The following conclusions can be drawn: (1) All cell types studied were characterized by an active production of lactate; (2) Incubation of the various cell types in the absence of glucose at normal oxygen tension did not affect ATP levels; (3) Respiration blocked by antimycin led to a Pasteur effect; (4) Neuroblastoma cells, but not the other cell types, were fully resistant to inhibition of respiration provided that sufficient glucose was supplied; (5) In the absence of glucose no stores of energy or utilizable substrate were present in the cell types studied when respiration was blocked; (6) In the presence of fetal calf serum anoxic neurons showed irreversible signs of degeneration. | {
"pile_set_name": "PubMed Abstracts"
} |
Meiotic segregation patterns and ICSI pregnancy outcome of a rare (13;21) Robertsonian translocation carrier: a case report.
t(13;21) is an uncommon Robertsonian translocation (RT) with limited information in the literature. Hereby, we assessed the meiotic segregation and interchromosomal effect (ICE) in sperm nuclei from a t(13;21) carrier. The pregnancy outcome following ICSI was also included as reference for physicians and patients. Dual-colour fluorescent in situ hybridization (FISH) was carried out to analyse the segregation pattern of chromosomes 13 and 21, while triple-colour FISH was used to investigate the possible concurrence of ICE. With respect to chromosomal constitutions of 13 and 21, 88.39% of the spermatozoa were normal or balanced due to alternative segregations, and 11.08% showed nullisomy or disomy as a result of adjacent segregations. However, for chromosome 18 and sex chromosomes, the proportion of normal haploids was 98.79%. The rate of disomy was not significantly higher than the controls for either chromosome 18 or X/Y. The rare t(13;21) case exhibited a similar pattern of meiotic segregation as in the common RTs. ICEs were not observed in the current case. | {
"pile_set_name": "PubMed Abstracts"
} |
Different time courses of GTP[gamma-S]-induced exocytosis and current oscillations in isolated mouse pancreatic acinar cells.
Exocytosis in isolated mouse pancreatic acinar cells was investigated using the dual-frequency method for measuring membrane capacitance and ionic conductances. Under control conditions, single exo- and endocytotic events could be resolved. The total cell capacitance slightly decreased to 98.7 +/- 0.9% of the initial cell capacitance within 10 min after establishing the whole-cell configuration. When guanosine 5'-O-(3-thiophosphate) (GTP[gamma-S] was added to the patch pipette, stepwise elevations in membrane capacitance occurred and the cell capacitance increased to 106.7 +/- 1.6% within 10 min. Exocytosis was also stimulated by GTP[gamma-S] when a Ca2+-free pipette solution supplemented with 1 to 10 mM ethylenebis(oxonitrilo) tetraacetate (EGTA) was used. Measurement of the DC current component in parallel with AC current analysis was used to isolate components of the Ca2+-dependent Cl- and monovalent cation conductances from the whole-cell conductance. These experiments demonstrate that in GTP[gamma-S]-stimulated pancreatic acinar cells: (1) activation of Cl- currents precedes that of cation currents, and (2) fusion of the zymogen granule membrane with the plasma membrane does not lead to incorporation of active Cl- or nonselective cation channels (>/= 10 pS). | {
"pile_set_name": "PubMed Abstracts"
} |
The suspensory muscle of the duodenum.
The suspensory muscle of the duodenum continues the muscular layers of the duodenum, which is consequently surrounded on its mesenteric border only by the muscularis mucosae. Between the muscle bundles of the suspensor there is much loose connective and adipose tissue. Microganglions of no more than 90 cells may be found between the muscle bundles of the suspensor. In their superior part, the muscle bundles have connective sheaths, which are continuous with the adventitia of the aorta and celiac trunk. It is most probable that the suspensor acts like a sphincter and is innervated contrarily to the duodenum. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of administration route and length of exposure on pharmacokinetics and metabolism of diltiazem in dogs.
The objective of this study was to systematically determine the pharmacokinetics and metabolism of diltiazem (DTZ) after a single i.v. dose, and after single and multiple oral (p.o.) doses. Four mongrel dogs (3 M, 1 F), aged 1-3 years, body weight 19-25 kg, were each given a single 30 mg dose of DTZ as a solution by i.v injection, the same dose orally from an immediate release tablet (Cardizem, Aventis Pharma, Canada, QC), and also t.i.d. for 10 doses. A 3-4 week washout period was allowed between each treatment. Blood samples (4 ml each) were obtained after each treatment from each animal via a cephalic vein at 0 (just before dosing), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, and 12.0 h post dose. Urine samples were collected for 24 h. The plasma samples were immediately separated by centrifugation and stored at -20 degrees C until analysis. The results showed that the bioavailability after a single p.o. dose of DTZ was 26+/-24%. Following a single i.v. dose, DTZ declined bi-exponentially with a terminal half-life (t1/2) of 4.2+/-1.7 h. N-Monodesmethyl DTZ (M(A)), deacetyl DTZ (M1), and deacetyl N-monodesmethyl DTZ (M2) were the major metabolites. Contrary to the results observed in clinical studies, there were no increase of plasma concentrations of DTZ after repeated doses (accumulation factor R = 0.94+/-0.51). Plasma concentrations of M1 decreased following repeated oral doses, accompanying by an increase of plasma concentrations of M2, although these changes were not statistically significant (p >0.05). This study cautions the use of mongrel dogs for direct extrapolation to humans, particularly for chronic pharmacokinetics studies of DTZ. | {
"pile_set_name": "PubMed Abstracts"
} |
[Telemedicine in Germany. Status, Barriers, Perspectives].
Telemedicine as a subject has reached politics, doctors and patients, but it has still not been able to make the leap from research, development, and testing into real practice. This is generally because of the great barriers to implementation, mainly the lack of telematics infrastructure and of payment regulations in Germany. Telemedicine projects are mainly isolated applications and it has not been possible to integrate them in to nationwide regular health services. Other challenges along the path to standard care include that research-based small-medium enterprise (SME) companies usually face high barriers hindering access to this market, because it is imposible for them to finance all the required evidence-based studies to verify the medical benefits and the econimic efficiency. Additionally, a high market nontransparency is noted. However, the signs of progress are visible, e.g., the E-health initiative of the German government or recent legislative initiatives. However, long processes are observed that do not facilitate the use of telemedicine. Although some federal states, e.g., North Rhine Westphalia, Bavaria, Mecklenburg-Western Pomerania, and Saxony, show exemplary activities, there are still many white areas on the telemedicine map of Germany. The road to standard care will be long, but is not unattainable. The reasons for supporting telemedicine are still strong. The future development of telemedicine applications will contribute to sustainable and high-quality patient care in Germany. | {
"pile_set_name": "PubMed Abstracts"
} |
Transmission of IFN-induced activities by cell to cell communication.
In conclusion, many of the activities of IFN are transmissible between cells and may involve more than one transfer mechanism. These mechanisms probably involve secondary messenger molecules which are shared with hormones and act at the transcriptional level. The transfer system seems to be a major amplification process for IFN action. It will be interesting in the future to determine the spectra of IFN activities which are transferable as well as the processes involved. | {
"pile_set_name": "PubMed Abstracts"
} |
Update on nocturia: the best of rest is sleep.
Adequate sleep is a basic requirement for good health. Adults generally require 7 to 8 hours of sleep per night. Sleep deprivation is associated with a decreased ability to perform tasks controlled by the frontal lobe, such as planning, concentration, motor performance, and high-level intellectual skills. Constant poor-quality sleep can also cause excessive daytime sleepiness, depression, and immune function compromise. In addition, continued sleep disruption has been associated with an increased risk for mortality. | {
"pile_set_name": "PubMed Abstracts"
} |
[Amino acid composition of lactic acid bacteria].
The amino acid composition of summary proteins in the strains 17, 33, 35 of the lactic acid bacteria cultures was studied in a nutrient medium with an automatic amino acids analyzer manufactured by the firm "Hitachi". The qualitative amino acids composition of various strains in the lactic acid bacteria cultures is identical with a total of 18 amino acids definable therein. As concerns the content of leucine, treonine, phenylalanine, isoleucine, methionine, tryptophan, arginine, glutamic and asparagic acids, as well as proline--the strains 17, 33 and 35 of the lactic acid bacteria cultures practically do not differ from one another. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of beta adrenergic drugs on phospholipid synthesis in the human fetal lung].
Human fetal lungs originating from legal absortion (n:16) (8-12 weeks) were cultured for 3 weeks. The effects of beta-adrenergic and/or corticosteroid stimulation on the synthesis of osmiophilic lamellar bodies i.e. surfactant production in II type pneumocytes were studied. Fenoterol (10 ng/5 ml for 5 days) has no effect on the synthesis of lamellar bodies. Following dexamethasone treatment (10 ng/5 ml for 5 days) characteristic osmiophilic lamellar bodies appeared in the cytoplasm. If fenoterol and dexamethasone were applied together in the culture altered lamellar body structure could have been observed: the lamellar bodies had a large homogenous osmiophilic center and some parts of the osmiophilic material were found outside the lamellar bodies. It seems that the beta-adrenergic stimulation does not induce lamellar body synthesis, but it can play a role in the release of surfactant from the lamellar bodies into cytoplasm and alveolar space as well. | {
"pile_set_name": "PubMed Abstracts"
} |
Using electronic medical records to determine prevalence and treatment of mental disorders in primary care: a database study.
With prevention and treatment of mental disorders a challenge for primary care and increasing capability of electronic medical records (EMRs) to facilitate research in practice, we aim to determine the prevalence and treatment of mental disorders by using routinely collected clinical data contained in EMRs. We reviewed EMRs of patients randomly sampled from seven general practices, by piloting a study instrument and extracting data on mental disorders and their treatment. Data were collected on 690 patients (age range 18-95, 52% male, 52% GMS-eligible). A mental disorder (most commonly anxiety/stress, depression and problem alcohol use) was recorded in the clinical records of 139 (20%) during the 2-year study period. While most patients with the common disorders had been prescribed medication (i.e. antidepressants or benzodiazepines), a minority had been referred to other agencies or received psychological interventions. 'Free text' consultation notes and 'prescriptions' were how most patients with disorders were identified. Diagnostic coding alone would have failed to identify 92% of patients with a disorder. Although mental disorders are common in general practice, this study suggests their formal diagnosis, disease coding and access to psychological treatments are priorities for future research efforts. | {
"pile_set_name": "PubMed Abstracts"
} |
Challenges associated with current and future TB treatment.
Current tuberculosis (TB) treatment is based on a combination of drugs that were developed mostly in the central decades of the last century. Cure rates are high for drug sensitive strains of Mycobacterium tuberculosis (M. tb) when the recommended complex and lengthy treatment protocols are adhered to. However the difficulty in correctly prescribing and adhering to these protocols, the emergence of M tb strains resistant to multiple drugs, and drug-drug interactions that interfere with optimal treatment of HIV and TB coinfected patients have generated a pressing need for improved TB therapies. Together with the ominous global burden of TB, these shortcomings of current treatment have contributed to a renewed interest in the development of improved drugs and protocols for the treatment of tuberculosis. This article highlights hurdles related to the optimized use of existing drugs and challenges related to the development of novel, improved products, focusing in particular on aspects inherent in TB drug clinical development. Concluding comments propose processes for more efficient development of new TB therapies. | {
"pile_set_name": "PubMed Abstracts"
} |
[Low molecule and middle molecule metabolites with haemodynamic activity in the ultrafiltrate from uraemic patients (author's transl)].
Substances causing blood pressure changes and myocardial damage in rats were first detected in the ultrafiltrate obtained from patients on long-term haemodialysis by means of size separation, high-voltage electrophoresis and thin-layer chromatography. Of the 100 to 140 fractions produced by Sephadex G 15 chromatography at least 3 raised the blood pressure when administered in doses of 2 to 10 mg/0.1 to 0.2 ml 0.9% NaCl, that is the high molecular fraction 18 to 23 and the low molecular fractions 71 to 72 and 73 to 74. The fractions 96 to 98 and 97 to 106 showed high toxicity. Less than 1 mg/0.1 to 0.2 ccm 0.9% NaCl produced cardiac arrest. The fractions 35 to 55, which originate from the middle molecules and are retained in regularly uraemia, contain substances which caused a reduction in blood pressure at low dosage and cardiotoxic effects at a dosage of more than 10 mg. Thin-layer chromatography indicates that the substances most probably consist of peptides whose structure contains the amino acids leucine, isoleucine, valine, glutamic acid, aspartic acid, alanine and cystine. | {
"pile_set_name": "PubMed Abstracts"
} |
Lack of pathogenicity of immunodominant T and B cell determinants of the nicotinic acetylcholine receptor epsilon-chain.
The nicotinic acetylcholine receptor (nAChR) is the autoantigen in seropositive myasthenia gravis (MG) that is a T cell-dependent B cell-mediated autoimmune disorder. We tested the immunogenicity and myasthenogenicity of the extracellular and first transmembrane domain of the epsilon-chain(1-221) of the nAChR in inbred and MHC congenic rat strains. Immunodominant T and B cell determinants did not induce experimental autoimmune myasthenia gravis (EAMG), although immunization resulted in strong Th1 and B cell responses, which could be mapped with overlapping peptides of the nAChR epsilon-subunit in eight different rat strains. Our data underscores the concept that immunodominant autoantigen-specific T and B cell responses can lack pathogenicity in autoimmune disease and might be of relevance for the physiological integrity of the organism. | {
"pile_set_name": "PubMed Abstracts"
} |
Zonisamide ameliorates symptoms of secondary paroxysmal dystonia.
A number of medications have been used with varying success to treat the symptoms of generalized, focal, and paroxysmal dyskinesias; these agents include anticonvulsant, benzodiazepine, neuroleptic, dopaminergic, dopamine antagonist, and carbonic anhydrase inhibitor types. The carbonic anhydrase inhibitor drug group is best represented by acetazolamide, which has been widely applied in the treatment of paroxysmal dyskinesias. Zonisamide, which has several putative pharmacologic mechanisms of action, is a member of the carbonic anhydrase inhibitor drug group. Zonisamide was chosen for treatment of secondary paroxysmal dystonia in a patient with pyruvate dehydrogenase deficiency (case 1) and in two patients with neonatal hemochromatosis and family history of neonatal hemochromatosis (cases 2 and 3). Although zonisamide ameliorated the symptoms of secondary paroxysmal dystonia in these three patients, the precise biochemical mechanism remains unclear, and further studies are needed to substantiate and explain this finding. | {
"pile_set_name": "PubMed Abstracts"
} |
ENB members back chief executive.
English National Board Chief Executive Tony Smith has received messages of support from all ENB members in response to an anonymous letter calling for his resignation. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of myelinated nerve fibers in the sixth cranial nerve of the rat: a quantitative electron microscope study.
Myelination was studied quantitatively in the sixth cranial nerves of rats by counting and measuring all myelinated fibers during the first three postnatal weeks. In transverse semithin and thin sections cut serially at a well-defined anatomical site in the midsphenoid region, only a few axons (mean 12) were myelinated at birth. On days 2, 4, and 8, counts of myelinated fibers were respectively 5 times (mean 57), 20 times (mean 230), and 24 times (mean 273) the number seen at birth. During the second postnatal week, the number of myelinated fibers remained constant, whereas growth of axons and their myelin sheaths continued. By 15 days these fibers were large and relatively uniform in size; they had compact, circular myelin sheaths. During the third postnatal week, myelination of previously unmyelinated, smaller axons began. The number of myelinated fibers increased again and the size distribution of myelinated fibers became bimodal. Axon diameters, fiber diameters, and myelin sheath dimensions for all fibers were calculated from measurements made on electron micrographs. The transverse length of the myelin membrane increased exponentially with time. The growth increased rapidly during the formation of the first 20 spiral layers and remained relatively constant during the subsequent enlargement of the compact sheath. The association of axon diameter and myelin sheath thickness was poor at young ages, but it improved progressively with maturation of the sheath. The results show that myelination begins around axons that have a wide range of diameters. Also, the first axons to be myelinated become the large myelinated fibers of the sixth nerve. The small myelinated fibers originate from axons that do not become myelinated until the third postnatal week. Myelination, though differing in onset by 2 weeks, appeared to be similar in both populations as judged by similarity of sheath morphology and growth rates. It is of interest that at the level studied, the sixth nerve also contains a fascicle of unmyelinated cranial sympathetic fibers. | {
"pile_set_name": "PubMed Abstracts"
} |
Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection.
This retrospective study aimed to investigate the associations between the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and disease severity in patients with chronic HBV infection-related liver disease (CHB). Patients with CHB were retrospectively identified. Clinical data for 172 HBV-infected patients and 40 healthy controls were collected from the electronic patient medical record system database of our hospital. HBV-related-compensated-cirrhosis patients (HBV-CC patients) had a significantly lower mean PLR than did other patients (P<0.001). HBV-related-decompensated-cirrhosis patients (HBV-DC patients) had a significantly higher mean NLR than did any other patients (P<0.001). In the entire cohort of CHB patients, significant correlations were observed between the PLR and both serum HBV DNA (r=0.264, P<0.001) and serum HBeAg (r=0.240, P=0.002). The PLR was significantly correlated with serum HBV DNA in both HBV-CC patients (r=-0.116, P=0.044) and HBV-DC patients (r=0.456, P=0.008). In HBV-Active-Carriers patients (HBV-AC patients), the PLR was positively correlated with serum HBeAg level (r=0.321, P=0.023). In HBV-DC patients, the NLR was positively correlated with serum HBeAg level (r=0.372, P=0.033). In the logistic regression prediction model, a predictive probability cutoff of 0.392 had the highest sensitivity and specificity (sensitivity, 91.2%; specificity, 84.0%) in distinguishing between HBV-CC and HBV-AC patients. A NLR cutoff value of 2.94 had the highest sensitivity and specificity (sensitivity, 81.8%; specificity, 88.2%) in distinguishing between HBV-DC and HBV-CC patients. The PLR and NLR partially reflect the amounts of serum HBV DNA and serum HBeAg levels circulating in CHB patients. The logistic regression model including the PLR and age most accurately distinguished between HBV-CC and HBV-AC patients. The NLR may be useful for follow-up in HBV-CC patients to predict disease progression. In summary, the PLR and NLR provided a supplementary means for effectively managing chronic HBV infection and disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Shortened telomeres join to DNA breaks interfering with their correct repair.
Telomeres cap chromosome ends, avoiding end-to-end fusions and subsequent chromosome instability. Telomeric functions and DNA repair pathways are closely related. Telomere dysfunction has been shown to result in hypersensitivity to ionizing radiation. In this study, we have used the telomerase knockout model to investigate how telomere shortening influences the correct repair of broken chromosomes. We show that the correct repair of double-strand breaks is impaired in telomerase knockout mice. The chromosomes with shortened telomeres fuse to radiation-induced breaks, interfering with the correct rejoining of the broken ends. This type of fusion is responsible for the increased chromosome instability observed in this mouse model, after exposure to ionizing radiation. Our finding may be important for understanding the increased radiation sensitivity associated with age in humans, as well as for comprehending the interindividual differences to the cytotoxic effects of radiation therapy in cancer patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Tetra-arsenic tetra-sulfide ameliorates lupus syndromes by inhibiting IL-17 producing double negative T cells.
Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Tetra-arsenic tetra-sulfide (As4 S4 ), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects. In our previous study, BXSB lupus-prone mice treated with As4 S4 has showed improved monocytosis, decreased serum interleukin (IL)-6 and suppressed skin, liver and renal lesions with well-tolerance. In this study, we explored the effect and mechanism of As4 S4 on the MRL/lpr mice. MRL/lpr and wild MRL/MpJ mice were divided into control and As4 S4 treatment groups and dosed with As4 S4 or placebo for 8 weeks. We found that As4 S4 prevented the skin, renal and lung lesions of MRL/lpr mice. As4 S4 significantly decreased the double negative T (DN T) cells and reduced the serum levels of IL-17, IL-10, and antinuclear antibodies titer. Further results revealed that the FasL was decreased, and activated caspases elevated in DN T cells in As4 S4 treated MRL/lpr mice. Taken together, As4 S4 could selectively suppresses DN T cells by inducing apoptosis. It also reduced inflammatory cytokines IL-17, which may be produced by DN T cells. As4 S4 may represent a new therapy for SLE. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression and identification of mutated osteoprotegerin in culture cells and larvae of silkworm.
The mutated osteoprotegerin (OPG-372) gene was inserted into the baculovirus transfer vector pBacPAK8, and the recombinant plasmid was co-transfected with linearized Bm-BacPAK6 virus DNA into BmN cells, then homologous recombination occurred inside the cells. The recombinant virus BmNPV-OPG-372 was screened and identified by Southern blotting. The recombinant human OPG-372 was expressed in cultured cells and the larvae of silkworm by inoculation of recombinant virus. The expression products were run on the SDS-PAGE and their immunoreactivities were determined by Western blotting. It was found that a 42 kD recombinant protein was expressed in BmN cells and a 46 kD one in larvae respectively. The bioactivities of the recombinant proteins were determined by hypocalcemic effect assay in the mice. The results showed that the recombinant proteins had a significant hypocalcemic effect on mice sera. | {
"pile_set_name": "PubMed Abstracts"
} |
Reduced cell surface expression of a mutated dipeptidyl peptidase IV (DPP IV/CD26) correlates with the generation of a beta strand in its C-terminal domain.
Dipeptidyl peptidase IV (DPP IV/CD26) belongs to a non-classical subfamily of serine-proteases. Sequence comparisons have identified Asp599, Ser624, Asp657, Asp702, and His734 as highly conserved residues of mouse DPP IV. We previously reported the identification of Ser624, Asp702 and His734 as the catalytic triad of mouse DPP IV (David, F., Bernard, A. M., Pierres, M., and Marguet, D. (1993) J Biol. Chem. 268, 17247-17252). Using site-directed mutagenesis, we have shown here that substitution of Asp599 for Ala (D599A) specifically decreases the cell-surface expression of DPP IV in stably transfected mouse fibroblasts. The D599A mutant remained as a high mannose immature glycoprotein and was rapidly degraded. This retention/degradation process correlates with the generation of a beta strand in the C-terminal region of DPP IV as shown by three dimensional computer modeling. Our results suggest that conserved residue Asp599 is important for the proper folding, glycosylation and transport of mouse DPP IV. | {
"pile_set_name": "PubMed Abstracts"
} |
[The ancient clinical application of umbilical therapy for retention of urine].
By collecting relevant ancient literature, with retention of urine, umbilical therapy and Shenque (CV 8) as key words, various umbilical therapies for retention of urine from the Song dynasty to Qing dynasty were retrieved and summarized. The results indicated rich knowledge of umbilical therapy was recorded in ancient literature (the Song dynasty to the Qing dynasty), including 9 kinds of therapies e.g. sticking umbilical method, ironing umbilical method, pasting umbilical method, smearing umbilical method, filling umbilical method, sealing umbilical method, covering umbilical method, dripping umbilical method and bundling umbilical method. Moreover, the detailed methods were briefly explained. It is hoped to provide reference for modern application of umbilical therapy for retention of urine. | {
"pile_set_name": "PubMed Abstracts"
} |
Monitoring the fall of large atmospheric ice conglomerations: a multianalytical approach to the study of the Mejorada del Campo megacryometeor.
Certain local atmospheric anomalies, such as the formation of unusually large ice conglomerations (megacryometeors), have been proposed to be a potential natural hazard for people and aviation, as well as geoindicators for fingerprinting larger-scale atmospheric environmental changes. On March 13th 2007, at approximately 10:15 am, an ice chunk weighing about 10 kg fell from the clear-sky and crashed through the roof (around 15 m) of an industrial storage house in Mejorada del Campo, a town located 20 km east from Madrid. The megacryometeor monitoring follow-up and the original investigation presented here includes, for the first time, both logistic and scientific collaboration between the Laboratory of the Environment, Criminalistic Service (SECRIM, the Spanish "Guardia Civil") and academic and scientific institutions (universities and the Spanish National Research Council). We propose that the management procedure of the incident, along with the detailed scientific research and combination of analytical methodologies in different laboratories, can serve as a protocol model for other similar events. | {
"pile_set_name": "PubMed Abstracts"
} |
An optimized method for establishing high purity murine CD8+ T cell cultures.
Establishing CD8(+) T cell cultures has been empirical and the published methods have been largely individual laboratory based. In this study, we optimized culturing conditions and show that IL-2 concentration is the most critical factor for the success of establishing CD8(+) T cell cultures. High IL-2 concentration encouraged T cells to non-specifically proliferate, express a B cell marker, B220, and undergo apoptosis. These cells also lose typical irregular T cell morphology and are incapable of sustaining long-term cultures. Using tetramer and intracellular cytokine assessments, we further demonstrated that many antigen-specific T cells have been rendered nonfunctional when expanded under high IL-2 concentration. When IL-2 is used in the correct range, B220-mediated cell depletion greatly enhanced the success rate of such T cell cultures. | {
"pile_set_name": "PubMed Abstracts"
} |
Bipolar disorder and attention-deficit/hyperactivity disorder in children and adolescents.
The relationship between bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents has been one of the most hotly debated topics in recent child psychiatry literature. At the heart of the matter is whether large numbers of children with bipolar disorder are being unrecognized or misdiagnosed. The differential diagnoses of juvenile-onset bipolar disorder can be complicated by many factors, but the most common clinical dilemmas seem to arise from overlapping symptomatology with ADHD and the differing treatment strategies these diagnoses imply. This article discusses the similarities and differences between these disorders with respect to phenomenology, epidemiology, family history, brain imaging, and treatment response. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical considerations in the design of protocols for somatic gene therapy.
Despite two decades of investigating the potential for somatic gene therapy in curing human disease, few clinical trials are being proposed. This delay is due in part to limitations of existing methods for gene transfer and to the recognized need to proceed judiciously into this controversial arena. Delay is also caused by a disjunction between the traditional precedents and principles of clinical investigation and the procedures instituted to regulate somatic gene therapy. The premise of this report is twofold: first, that more extensive clinical investigation of gene transfer technologies would be beneficial to patients, medicine, and basic science and second, that clinical investigations could be expedited by appealing to the established experience in clinical investigation without compromising the scientific excellence and discipline essential for this highly public process. This report develops a clinical perspective on potential applications of existing gene transfer technologies and the issues involved in developing experimental protocols. The initiation of clinical trials should be a primary goal of gene therapy research programs. | {
"pile_set_name": "PubMed Abstracts"
} |
First-order type II quasi-phase-matched UV generation in periodically poled KTP.
Type II quasi-phase matching was employed for first-order frequency doubling of a single-longitudinal-mode Ti:sapphire laser in periodically poled KTP with a domain-inverted period of 9.01 mum . In a single-pass configuration, 0.44 mW of UV power at 398.8 nm was generated for an input of 780 mW, corresponding to a normalized conversion efficiency of 0.09%W(-1) cm(-1) . The nonlinear coefficient d(24) = 2.82 pm/V was deduced from the measurements. The larger grating period for the type II quasi-phase-matched second-harmonic-generation process than for type I quasi-phase matching, lowers the fabrication constrains in the short-wavelength region and increases the acceptance bandwidth. | {
"pile_set_name": "PubMed Abstracts"
} |
Serum levels of iron and proteins in oral submucous fibrosis (OSMF).
Serum proteins, serum iron and total iron binding capacity were estimated in 50 patients with oral submucous fibrosis and 50 patients with oral leukoplakia. The values were compared with that of 50 age- and sex-matched controls. A significant depression in hemoglobin and serum iron was observed in both groups of patients, whereas total iron binding capacity showed significant change only in the oral submucous fibrosis patients. Serum protein values were significantly lower in all the patients. The role of iron deficiency anemia in the causation of this premalignant lesion is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Ego ideal and ideal ego.
A genetic and functional differentiation between the ego ideal and the ideal ego is proposed. This differentiation allows for a more precise characterization and interpretation of ego libido in symptoms and transference. These genetic and functional differentiations of ego ideal and ideal ego can be used to clarify the differing severities of the types of narcissistic disorder: psychosis, borderline personality disorder, narcissistic personality disorder, from normal maturity. It can also be put to work in refining one's formulation of the narcissistic complications of the classical transference neurosis. This usefulness has been demonstrated in relation to clinical material. In neurosis the ideal ego is a source of symptoms and inappropriate transference demands; in culture it finds embodiment in aggrandized concepts of human nature; in mature adults it is the comforting memory of a vanished splendour. | {
"pile_set_name": "PubMed Abstracts"
} |
The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21.
The intron-containing gene encoding human ribosomal protein S6 (rpS6), the major phosphoprotein in the mammalian ribosome, has been cloned. Using a PCR based cloning strategy we have isolated the rpS6 intron-containing gene in the presence of its many processed pseudogenes and determined the DNA sequence of the entire gene and its upstream and downstream flanking regions. The human rpS6 gene is 3979 bp in length and comprises six exons. Despite lacking a consensus TATA box, primer extension analysis indicates that the start of transcription is located at a single C residue within an 11 bp oligopyrimidine tract. The first exon, which contains the ATG start codon, is 48 bp in length. The DNA sequence in the 5' region of the gene has features of a CpG-rich island. Using fluorescence in situ hybridization (FISH) analysis the position of the rpS6 gene has been sublocalized to human chromosome 9p21. The similarities and differences between rpS6 and other previously characterized ribosomal protein genes are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Induction of rat liver microsomal drug-metabolizing enzymes by a new sleep inducer 450191-S and plasma levels of 450191-S-metabolites.
Liver microsomal 7-alkoxycoumarin O-dealkylase activities in rats were stimulated by the administration of large doses of 5-[(2-aminoacetamide)methyl]-1-[4-chloro-2-(o-chlorobenzoyl)phenyl ]-N, N-dimethyl-1 H-s-triazole-3-carboxamide hydrochloride dihydrate (450191-S), a new sleep inducer which is a 1H-1,2,4-triazolyl benzophenone derivative. To obtain the correlation between the stimulation or induction of hepatic enzymes and the plasma level of the metabolites of 450191-S, various amounts of 450191-S were administered orally to rats and the metabolites in plasma were determined by high performance liquid chromatography. Plasma concentration-time profiles for metabolites in rats showed the appearance of metabolites in plasma followed by their rapid disappearance from blood when the animals received non-inducing amounts of 450191-S. On the other hand, the profiles of metabolites in rats administered higher amounts of the drug showed very high plasma concentrations of metabolites, especially 8-chloro-6-(2-chlorophenyl)-N-methyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-2) and 8-chloro-6-(2- chlorophenyl)-N-hydroxymethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-A), which were maintained for a long time with slow elimination. These results led to the conclusion that the induction of hepatic drug-metabolizing enzymes is closely correlated with the high plasma concentrations of metabolites and their prolonged existence in plasma. | {
"pile_set_name": "PubMed Abstracts"
} |
Deciphering carbon sources of mussel shell carbonate under experimental ocean acidification and warming.
Ocean acidification and warming is widely reported to affect the ability of marine bivalves to calcify, but little is known about the underlying mechanisms. In particular, the response of their calcifying fluid carbonate chemistry to changing seawater carbonate chemistry remains poorly understood. The present study deciphers sources of the dissolved inorganic carbon (DIC) in the calcifying fluid of the blue mussel (Mytilus edulis) reared at two pH (8.1 and 7.7) and temperature (16 and 22 °C) levels for five weeks. Stable carbon isotopic ratios of seawater DIC, mussel soft tissues and shells were measured to determine the relative contribution of seawater DIC and metabolically generated carbon to the internal calcifying DIC pool. At pH 8.1, the percentage of seawater DIC synthesized into shell carbonate decreases slightly from 83.8% to 80.3% as temperature increases from 16 to 22 °C. Under acidified conditions, estimates of percent seawater DIC incorporation decreases clearly to 65.6% at 16 °C and to 62.3% at 22 °C, respectively. These findings indicate that ongoing ocean acidification and warming may interfere with the calcification physiology of M. edulis through interfering with its ability to efficiently extract seawater DIC to the calcifying front. | {
"pile_set_name": "PubMed Abstracts"
} |
Lipschütz ulcer and group A streptococcal tonsillitis.
Lipschütz ulcers (LU) are non-sexually related genital ulcers, rarely reported. We describe a healthy 11-year-old girl, who presented with fever and a painful vulvar ulcer associated with erythematous tonsillitis. Throat swab test for Group A Streptococcus (GAS) was positive. She was treated with amoxicillin. Further investigation was negative, including Herpes Simplex virus DNA from ulcer swab and serology for Epstein-Barr virus, cytomegalovirus and Mycoplasma pneumoniae Antistreptolysin O titre was high. The ulcer healed in 2 weeks, with no recurrence in a 1 year follow-up period. The association of LU with GAS tonsillitis is very rare. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional expression of recombinant anti-BNP scFv in methylotrophic yeast Pichia pastoris and application as a recognition molecule in electrochemical sensors.
Recent studies have revealed the potential of B-type natriuretic peptide (BNP) as a good prognostic marker for patients with heart failure. Antibodies against BNP are expected to be usefully employed in the diagnosis of heart failures. We established a more efficient method to produce functional anti-BNP, single chain variable fragment (scFv) using a eukaryotic expression system of Pichia pastoris. Although analysis of the N-terminal (NT) sequence of the expressed anti-BNP scFv indicated that the two Ste13 sites of the secreted anti-BNP scFv were not cleaved, the specificity of anti-BNP scFv was not affected significantly. The binding activity of anti-BNP scFv against other antigens, against four other antigens, NT probrain peptide (NT-pro BNP), atrial natriuretic peptide (ANP), carcinoembryonic antigen (CEA) and human serum albumin (HSA), was only one thousandth that of the original BNP antigen, which clearly demonstrated the specific binding of recombinant scFv toward BNP. The anti-BNP, scFv-based, electrochemical immunoassay exhibited excellent analytical performance with a detection limit of 1 fg/ml and a wide linear detection range from 1 to 10,000 fg/ml. The optimum culture conditions to obtain the maximum concentration of recombinant scFv were a pH range of 5.0-7.0 and an incubation temperature of 20°C. This anti-BNP scFv expressed in P. pastoris has the potential for promising applications in the diagnosis of heart failure. | {
"pile_set_name": "PubMed Abstracts"
} |
The peacock's train (Pavo cristatus and Pavo cristatus mut. alba) II. The molecular parameters of feather keratin plasticity.
Thermal activation analysis of plastic deformation of peacock tail feathers, by temperature changes and stress relaxation, gave for the keratin cortex an activation enthalpy of 1.78 ± 0.89 eV and an activation volume of 0.83 ± 0.13 nm³, for both the blue and the white subspecies. These values suggest that breaking of electrostatic bonds is responsible for plasticity in feather keratin. These might be bonds between keratin and nonkeratinous matrix or keratin-keratin cross-links. The mechanical properties of the rachis cortex are surprisingly uniform along the length of the feathers. | {
"pile_set_name": "PubMed Abstracts"
} |
Integrated diagnostic and data analysis system of the C-2W advanced beam-driven field-reversed configuration plasma experiment.
The new C-2W experiment (also called Norman) at TAE Technologies, Inc. studies the evolution of field-reversed configuration (FRC) plasmas sustained by neutral beam injection. Data on the FRC plasma performance are provided by a comprehensive suite of diagnostics that includes over 700 magnetic sensors, four interferometer systems, multi-chord far-infrared polarimetry, two Thomson scattering systems, ten types of spectroscopic measurements, multiple fast imaging cameras with selectable atomic line filters, bolometry, reflectometry, neutral particle analyzers, and fusion product detectors. Most of these diagnostic systems are newly built using experience and data from the preceding C-2U experiment to guide the design process. A variety of commercial and custom acquisition electronics collect over 4000 raw signals from the C-2W diagnostics. These data are processed into physics results using a large-scale database of diagnostics metadata and analysis software, both built using open-source software tools. | {
"pile_set_name": "PubMed Abstracts"
} |
Minimising biases in full configuration interaction quantum Monte Carlo.
We show that Full Configuration Interaction Quantum Monte Carlo (FCIQMC) is a Markov chain in its present form. We construct the Markov matrix of FCIQMC for a two determinant system and hence compute the stationary distribution. These solutions are used to quantify the dependence of the population dynamics on the parameters defining the Markov chain. Despite the simplicity of a system with only two determinants, it still reveals a population control bias inherent to the FCIQMC algorithm. We investigate the effect of simulation parameters on the population control bias for the neon atom and suggest simulation setups to, in general, minimise the bias. We show a reweight ing scheme to remove the bias caused by population control commonly used in diffusion Monte Carlo [Umrigar et al., J. Chem. Phys. 99, 2865 (1993)] is effective and recommend its use as a post processing step. | {
"pile_set_name": "PubMed Abstracts"
} |
[Use of cycloferon in a combined treatment of chlamydial conjunctivitis].
A high therapeutic efficiency of cycloferon, an interferon inductor, was demonstrated when it is combined with antibiotics in the treatment of chlamidial conjuctivitis. The use of the mentioned drug for acute chlamidial conjuctivitis prevents relapses. | {
"pile_set_name": "PubMed Abstracts"
} |
High incidence of precipitins in sera of heroin addicts.
We analyzed sera of 50 consecutively hospitalized heroin-abuse patients for precipitins against several antigens. Forty-seven addicts had precipitins against extracts from moldy hay, and 34 against extracts from bagasse. Thirty-six showed precipitin bands against extracts from one or more of the following: Aspergillus, Micropolyspora faeni, and Thermoactinomyces vulgaris. These findings were significantly different from those of a control population (P less than .0001 for all antigens tested). The recent culture identification of bacteria and fungi from street heroin suggests that the addicted population may be injecting antigenic material intravenously, with subsequent antibody formation. | {
"pile_set_name": "PubMed Abstracts"
} |
[Tuberculosis in hospital department health care workers].
Tuberculosis (TB) is considered an occupational disease in health care workers (HCW) and its transmission in health care facilities is an important concern. Some hospital departments are at higher risk of infection. To describe TB cases detected after TB screening in HCW from a hospital department (Ear, Nose and Throat - ENT) who had had contact with active TB cases. All HCW (73) from Hospital São João's ENT Unit who had been in contact with two in-patients with active TB underwent TB screening. Those who had symptoms underwent chest X-ray and mycobacteriological sputum exam. Of 73 HCW who underwent TB screening, TB diagnosis was established in 9 (8 female; median age: 30 years; 1 doctor, 6 nurses, 2 nursing auxiliaries). Pulmonary TB was found in 8 and extra- -pulmonary TB in 1. Microbiology diagnosis was obtained in 7 cases by sputum smear, n=2; culture exam in bronchial lavage, n=4 and histological exam of pleural tissue, n=1. In 4 cases, Mycobacterium tuberculosis genomic DNA was extracted from cultures and molecular typing was done. All cases had identical MIRU types, which allowed identification of the epidemiological link. Nosocomial TB is prominent and efforts should be made to implement successful infection control measures in health care facilities and an effective TB screening program in HCW. Molecular typing of Mycobacterium tuberculosis facilitates cluster identification. | {
"pile_set_name": "PubMed Abstracts"
} |
Dravet syndrome with an exceptionally good seizure outcome in two adolescents.
We present two children who exhibited the characteristics of Dravet syndrome during infancy and young childhood, with SCN1A mutation, but nevertheless achieved seizure freedom for at least four years during adolescence. These patients had no episodes of convulsive status epilepticus with a duration of more than 30 minutes and their overall favourable seizure outcome may be related to the prevention of convulsive status epilepticus. | {
"pile_set_name": "PubMed Abstracts"
} |
Endothelial cell transduction in primary cultures from regressing mesonephros.
Loss of renal function during normal aging is associated with vascular alterations. Consequently, new therapeutic approaches, including gene therapy, to protect renal endothelial cells are expected to be greatly beneficial. Quail mesonephros is a transitory embryonic kidney that has been used for the study of vascular development and involution. Vascular alterations in regressing mesonephros are similar to those observed in aging kidney. In the present study, we examined adenovirus-mediated gene transfer to endothelial cells in primary cultures from developing and regressing quail mesonephros. Quail embryos with developing and regressing mesonephros were examined on day 6 (30HH) and day 11 (40HH) of incubation, respectively. The senescence markers, associated beta-galactosidase activity and p16(INK4a), were examined in whole mesonephros. Quail embryos were injected intracardiacally with adenoviral vectors (rAd-CMV-LacZ) and endothelial cell transduction examined. In addition, primary cell cultures from mesonephros were exposed to adenoviral vectors. Endothelial cells in primary cultures were identified as QH1(+), LEP100(-) and acidic phosphatase(-) cells and adenovirus-transduced cells were those positive for bacterial-associated beta-galactosidase activity. We report that endothelial cells in the whole regressing mesonephros and primary cell cultures expressed senescence markers. In addition, we observed that adenoviral vectors were able to transduce endothelial cells in the whole regressing mesonephros, and that cultured endothelial and macrophagic cells from the regressing mesonephros were more efficiently transduced than those derived from the developing mesonephros. Our results suggest that quail mesonephros provides a practical model to assay gene transfer to endothelial cells in regressing/senescent vessels. | {
"pile_set_name": "PubMed Abstracts"
} |
Further observations on the phagocytosis of Candida albicans by hamster and human oocytes.
Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes for up to 21 hours in order to determine the nature and time course of phagocytosis of these organisms. Aliquotes of the interacting cells were taken at various time intervals for electron microscopic examination. Some specimens had their zona pellucidae enzymatically removed prior to incubation with yeast, and these specimens showed the most extensive interaction and phagocytosis of Candida. The zona pullucida appears to be an effective barrier to yeast, at least over the time span studied. The observations are consistent with the hypothesis of an initial attachment of yeast via a surface component to oocyte microvilli followed by phagocytic uptake into an endosome. There is no compelling evidence of lysosomal degradation of the yeast over the time course of this study; however, the oocytes appear to undergo some degenerative changes at long incubation times. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of acid-base status on the kinetics of the ventilatory response to moderate exercise.
To determine the influence of altered carotid body drive on exercise ventilatory kinetics, five subjects performed four repetitions of constant-load cycle ergometer exercise during air and O2 breathing under each of the following conditions: 1) metabolic acidosis, (NH4Cl, 0.3 g . kg-1 . day-1); 2) metabolic alkalosis (NaHCO3, 0.7 g . kg-1 . day-1); and 3) control (CaCO3, 0.1 g . kg-1 . day-1). Ventilatory and gas exchange variables were computed, breath-by-breath, and the time constant of the ventilatory response in each condition was determined by a least-squares technique. While breathing air, metabolic acidosis caused the magnitude of the ventilatory response to increase and the time constant of the ventilatory kinetics to decrease. With metabolic alkalosis the increase in ventilation caused by exercise tended to be smaller and time constant larger although these changes were not statistically significant. Hyperoxia slowed the ventilatory response in the three acid-base conditions to a similar value. Thus hyperoxia slowed the ventilatory kinetics to a greater degree during acidosis than during control or alkalosis. We conclude that ventilatory dynamics during moderate exercise can be appreciably influenced by the acid-base status with acidosis significantly speeding the response dynamics. And, as these effects are abolished by hyperoxia, they appear to be mediated via the carotid bodies, in the human. | {
"pile_set_name": "PubMed Abstracts"
} |
[Clinical effectiveness of home treatment as compared to inpatient treatment at the Alexianer Hospital Krefeld, Germany].
Although all relevant guidelines recommend "home treatment" (HT) as part of psychiatric care, this strategy is very rarely applied in the German mental health system. For the first time HT was introduced in Germany as "integrative psychiatric treatment" (IPT) at the Alexianer Hospital in Krefeld. In the present study IPT was compared for the first time with inpatient treatment considering patient characteristics, drop-out rates, effects on symptoms and rehopitalisation after treatment. 106 patients who had been treated by IPT in 2001 (or subgroups) were compared to patients who were treated as inpatients in the same year (or subgroups). Regarding sample characteristics IPT patients were significantly older and more often female than inpatients. Inpatients were more frequently diagnosed with organic, schizophrenia or personality disorders. The drop-out rate from IPT (inpatient stay during IPT treatment) was 17.9 % (n = 19). The pre-post effect sizes on symptoms in 14 randomly selected patients with schizophrenia were very large (d = 1.7 - 2.6). At two-year follow-up there were no differences between IPT and a matched inpatient sample with respect to days spent in inpatient treatment (25.4 vs.27.9 days). In the German mental health system, at least in a subgroup of severely mentally ill patients, treatment effects of HT are comparable to the effects of inpatient treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of outreach in the development of the nurse consultant role in critical care: cause or effect?
Critical care nurse consultant roles have evolved against a background of service innovation that has resulted in the development of critical care outreach services. Despite compelling evidence that there was a serious problem with the management of critically ill patients in the ward environment, there is little evidence to support outreach as a concept or as a role for nurse consultants. The aims for this part of the study were to: A national postal survey of all 72 critical care nurse consultants in post in England by August 2003; response rate 72% (n = 52). All data was entered on to a computer anonymously and analysed using SPSS version 11.5. A factor analysis revealed a sub-set of nurse consultants who had a significantly greater involvement in outreach activity. Critical care nurse consultants have a high involvement in the development of care for critically ill patients outside the traditional boundaries of critical care. A sub-set emerged that has a significantly greater involvement in outreach activity. This includes roles such as working with an individual or team to develop their practice (whole group mean involvement score M = 4.45, outreach M = 4.88, p < 0.001); developing education outside the ICU/HDU (whole group M = 4.13, outreach M = 4.88, p < 0.001) and receiving nurse led referrals from the wards (whole group M = 3.92, outreach M = 4.81, p < 0.001). Given the lack of evidence for outreach, organisations should consider the high level of involvement of the nurse consultant outside the traditional boundaries of the ICU/HDU. | {
"pile_set_name": "PubMed Abstracts"
} |
The photophase light intensity does not affect the scotophase melatonin response in the domestic pig.
This study investigated the effects of the photophase light intensity on the scotophase melatonin response. Twelve, 8-month-old crossbred gilts were allocated to three groups of four and housed in temperature- and lighting-controlled climate rooms. The rooms had a light intensity of 40, 200 or 10,000 lx and a light-dark cycle of 12 L:12 D. The gilts were allowed to acclimatize to a new lighting regimen for 1 week before being sampled at 2h intervals for 24h. Following the sampling, pigs were transferred under a different light intensity, allowed to adjust for 1 week and sampled again. The procedure was repeated three times so that all the groups went through all three lighting regimens (light intensities). All the gilts exhibited a clear circadian serum melatonin rhythm under each lighting regimen with high melatonin concentrations occurring during the scotophase. There was no difference in the scotophase melatonin response in terms of mean concentrations or duration of increased melatonin levels within or between the groups under different lighting regimens. There was considerable inter-individual variation in the dark phase melatonin response but the individual profiles were consistent under the different lighting regimens. It is concluded that when a certain threshold light intensity (<40lx) is exceeded, the photophase light intensity has no effect on the scotophase melatonin response. These results imply that extremely high light intensities during the photophase would provide no additional benefits compared with normal comfortable light intensity, if artificial lighting programs were introduced to commercial piggeries in order to reduce seasonal effects on reproduction. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of minimization of psychopathology on the Rorschach in cleric and noncleric alleged sex offenders.
The assessment of response-bias is critical in forensic psychological evaluations of alleged sex offenders because sex offenders frequently minimize psychopathology or personal limitations. This study tested predictions based on prior research that minimization on the Rorschach would be reflected by higher P, D, A, Lambda, and PER, and lower R, Blends, and Zf. We divided a sample of cleric and noncleric alleged sex offenders according to (a) whether they showed minimization on the MMPI, and (b) whether they admitted to their charges. We then compared these groups on the purported Rorschach validity indices. Our results do not support the use of any of these Rorschach scores in the assessment of minimization. We recommend that in forensic psychological evaluations, the Rorschach should not be used to assess defensiveness and is best used in combination with other psychometric instruments more sensitive to response-bias. | {
"pile_set_name": "PubMed Abstracts"
} |
[The role of gut instinct is an important subject].
The role of gut instinct in general practice is an important topic. The reliance on gut instinct by experienced doctors is thought to be a form of intuitive decision-making which fits in with System 1 processes in the dual process model in higher cognition. Special mention is made of the theories on intuitive decision-making by the famous Dutch psychologist De Groot, who, when investigating thought processes of chess masters more than half a century ago, developed a fundamental theory on intuitive heuristics. Further studies on the determinants and conditions under which heuristics, such as the reliance on gut instinct, are applied in clinical practice are very welcome. | {
"pile_set_name": "PubMed Abstracts"
} |
Protein synthesis inhibitors, like growth factors, may render resting 3T3 cells competent for DNA synthesis: a radioautographic and cell fusion study.
Serum-deprived (0.1-0.2%) resting NIH 3T3 mouse fibroblasts pre-incubated with cycloheximide (7.5 micrograms/ml), or puromycin (10 micrograms/ml), were fused with stimulated cells taken 10 h after changing the medium to one containing 10% serum, and DNA synthesis was investigated in the nuclei of monokaryons, homodikaryons and heterodikaryons using radioautography with the double-labelling technique. Pre-incubation of resting cells with inhibitors of protein synthesis for 1-4 h abolished their ability to suppress DNA synthesis in stimulated nuclei in heterokaryons. Three hours after the removal of cycloheximide from the medium, the resting cells acquired once again the inhibitory capacity for entry of stimulated nuclei into the S period. This inhibitory influence disappeared also in the case of post-fusion cycloheximide application as well as following an 8-12 h pre-treatment of resting cells with actinomycin D (1 microgram/ml) prior to fusion. Pre-incubation of resting cells for 12 h with PDGF (1 u/ml-1) followed by an 8-48 h incubation in serum-free medium stimulated the onset of DNA synthesis. A brief exposure (45 min) of resting cells to cycloheximide (7.5 micrograms/ml), or puromycin (7.5 micrograms/ml), exerted a similar effect, inducing by itself the entry of cells into the S period. The results support the assumption that acquirement, by resting cells, of competence for DNA replication includes as a necessary step the down-regulation of intracellular growth inhibitors whose formation depends on protein synthesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Health psychology's contribution to addressing the cancer problem: update on accomplishments.
Each year approximately 1.5 million Americans are stricken with or die from cancer. In recent years, more psychologists have begun study of the psychological and behavioral aspects of cancer, and the rate, quality, and integration of findings are accelerating. This article provides an update on the major areas of accomplishment, with the findings grouped into disease-relevant time points. | {
"pile_set_name": "PubMed Abstracts"
} |
The addition of nano-sized hydroxyapatite to a sports drink to inhibit dental erosion: in vitro study using bovine enamel.
This study examined the dental erosion and demineralization potential of a sports drink containing nano-sized hydroxyapatite (nano-HA) as an additive. The experimental solutions were Powerade (PA) alone and PA with 0.05%, 0.10%, and 0.25% nano-HA. The pH, titratable acidity, and calcium and phosphate content of each solution were analysed, and the degree of saturation with respect to the dental enamel (DS(En)) was obtained. Twelve sound bovine enamel specimens for each group were treated in accordance with the pH-cycling schedule which had 60min treatment with experimental solution per day for 7 days. The erosion potential was determined from the changes in surface micro hardness (SMH), the depths of erosion and demineralized layer using confocal laser scanning microscopy (CLSM), and the morphological changes to the tooth surface were examined with scanning electron microscopy (SEM) after pH-cycling. pH and DS(En) increased with increasing nano-HA concentration in the drinks, whereas the titratable acidity decreased. There were significant differences in the SMH between the PA alone and >0.10% nano-HA groups (p<0.001). Although the PA alone group showed a pronounced erosion depth, CLSM showed no erosion depth in 0.25% nano-HA group. SEM showed an intact surface with increasing nano-HA concentration in the drinks. In conclusion, dental erosion was effectively prevented with increase of adding concentration of nano-HA, and a sports drink containing 0.25% nano-HA might prevent dental erosion. | {
"pile_set_name": "PubMed Abstracts"
} |
Distribution of intramuscularly administered erythromycin into subcutaneous tissue chambers before and after inoculation with Pasteurella haemolytica.
Distribution of erythromycin into subcutaneous tissue chambers was characterised pharmacokinetically and the effect of Pasteurella haemolytica infection on the extent of penetration was studied. Thermoplastic tissue chambers were implanted subcutaneously in the paralumbar fossae of six calves. Thirty-five days after implantation, the tissue chamber distribution of intramuscularly administered erythromycin (30 mg kg-1) was studied. Chambers were then inoculated with P haemolytica and the tissue chamber pharmacokinetics of erythromycin were again studied. Diffusion of erythromycin into tissue chambers was best described using a two-compartment model with tissue chambers representing a relatively inaccessible compartment. Despite changes in chamber fluid pH, the extent of erythromycin penetration into chambers was not affected by P haemolytica inoculation. Comparison of computer simulated concentration-time curves resulting from different routes of administration revealed that penetration of erythromycin into less accessible sites was more likely to be higher after intravenous administration than after intramuscular administration. | {
"pile_set_name": "PubMed Abstracts"
} |
The thioredoxin system and not the Michaelis-Menten equation should be fitted to substrate saturation datasets from the thioredoxin insulin assay.
The thioredoxin system, consisting of thioredoxin reductase, thioredoxin and NADPH, is present in most living organisms and reduces a large array of target protein disulfides. The insulin reduction assay is commonly used to characterise thioredoxin activity in vitro, but it is not clear whether substrate saturation datasets from this assay should be fitted and modeled with the Michaelis-Menten equation (thioredoxin enzyme model), or fitted to the thioredoxin system with insulin reduction described by mass-action kinetics (redox couple model). We utilized computational modeling and in vitro assays to determine which of these approaches yield consistent and accurate kinetic parameter sets for insulin reduction. Using computational modeling, we found that fitting to the redox couple model, rather than to the thioredoxin enzyme model, resulted in consistent parameter sets over a range of thioredoxin reductase concentrations. Furthermore, we established that substrate saturation in this assay was due to the progressive redistribution of the thioredoxin moiety into its oxidised form. We then confirmed these results in vitro using the yeast thioredoxin system. This study shows how consistent parameter sets for thioredoxin activity can be obtained regardless of the thioredoxin reductase concentration used in the insulin reduction assay, and validates computational systems biology modeling studies that have described the thioredoxin system with the redox couple modeling approach. | {
"pile_set_name": "PubMed Abstracts"
} |
Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies.
Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional "pyramid" approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with > or = 1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)-positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0-3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0-4, 5-9, 10-14, 15-19, and 20+ years). "Control" correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30 percent reduction in long term disability with consistent DMARD use, are most likely conservative. An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data. | {
"pile_set_name": "PubMed Abstracts"
} |
Ureteral endoscopy with passively deflectable, irrigating flexible ureteroscopes.
Flexible, passively deflectable fiberoptic ureteroscopes were used in 18 selected patients. The flexible endoscope must be stabilized with a cystoscope, flexible introducer sheath, or guide wire for placement through the urethra and bladder into the ureter. Irrigation through the instrument is beneficial in clearing the visual field and distending the lumen. These instruments can visualize the lumen of the ureter, and the medial and superior portion of the renal pelvis and intrarenal collecting systems. Their diagnostic value is limited to selected clinical situations. | {
"pile_set_name": "PubMed Abstracts"
} |
Beneficial actions of S-nitroso-N-acetylpenicillamine, a nitric oxide donor, in murine traumatic shock.
We studied the effects of the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), in rat traumatic shock characterized by hypotension, increases in plasma free amino-nitrogen (5.3 +/- 0.5 U/ml vs. 2.5 +/- 0.3 U/ml controls) and intestinal myeloperoxidase activities (2.7 +/- 1.0 U/100 mg vs. 0.2 +/- 0.1 U/100 mg controls), and a survival time of 143 +/- 20 min. Moreover, superior mesenteric artery rings isolated from rats in traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine only 21 +/- 6% of U-46619 induced contraction. Administration of 100 micrograms/kg SNAP 10 min post-trauma followed by 10 micrograms/kg/h infusion prolonged survival time to 273 +/- 18 min (p < .05), attenuated the increases in plasma free amino-nitrogen (3.1 +/- 0.4 U/ml, p < .05) and tissue myeloperoxidase activities (0.6 +/- 0.3 U/100 mg, p < .05). Moreover, SNAP significantly preserved superior mesenteric artery endothelial function; the vasorelaxation to acetylcholine was 54 +/- 4% (p < .01). Protective effects were not seen in traumatic shock rats treated with the non-NO-donating parent compound N-acetylpenicillamine. These results indicate that SNAP affords significant protection in murine traumatic shock which may be achieved through maintenance of systemic blood pressure, preservation of vascular endothelial integrity, and inhibition of neutrophil-endothelial interaction and the resultant reduced microvascular leakiness. | {
"pile_set_name": "PubMed Abstracts"
} |
Chemotherapy for trophoblastic neoplasms in the Philippines.
This paper presents a protocol currently used in the diagnosis and management of trophoblastic disease, amongst participating hospitals within the Greater Manila Area, Philippines. Using the protocol as a general guide, the results of the study of several authors were presented. The commonly used chemotherapeutic agent are methotrexate and actinomycin D depending upon local availability and price affordability. Prophylactic chemotherapy is resorted to, in view of the inconsistent monitoring of the HCG and patients either in danger of being lost to follow-up or actually fail to report for follow up. The results of the studies generally point to the facts that: trophoblastic neoplasms is indeed a problem amongst Filipino women; the success of chemotherapy is dependent upon early diagnosis, availability of a more sensitive HCG monitoring system; a wide selection of available and affordable chemotherapeutic agents and above all faithful patient compliance. | {
"pile_set_name": "PubMed Abstracts"
} |
Rational Design of Advanced Photosensitizers Based on Orthogonal BODIPY Dimers to Finely Modulate Singlet Oxygen Generation.
The synthesis, photophysical characterization, and modeling of a new library of halogen-free photosensitizers (PS) based on orthogonal boron dipyrromethene (BODIPY) dimers are reported. Herein we establish key structural factors in order to enhance singlet oxygen generation by judiciously choosing the substitution patterns according to key electronic effects and synthetic accessibility factors. The photosensitization mechanism of orthogonal BODIPY dimers is demonstrated to be strongly related to their intrinsic intramolecular charge transfer (ICT) character through the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism. Thus, singlet oxygen generation can be effectively modulated through the solvent polarity and the presence of electron-donating or withdrawing groups in one of the BODIPY units. The photodynamic therapy (PDT) activity is demonstrated by in vitro experiments, showing that selected photosensitizers are efficiently internalized into HeLa cells, exhibiting low dark toxicity and high phototoxicity, even at low PS concentration (0.05-5×10-6 m). | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of cyclosporin A on the anti-CD3 antibody- and concanavalin A-induced activation and membrane potential of human T lymphocytes.
The immunosuppressive effect of cyclosporin A (CsA) was studied on the anti-CD3 antibody (anti-CD3)- and concanavalin A (Con A)-induced activation of human T lymphocytes. A similar suppressive effect was observed in the Con A- and anti-CD3-induced proliferation as measured by the amount of [3H]thymidine incorporated on the third day of culture. When the cells were washed 30 min after activation with anti-CD3, the response was diminished and the CsA sensitivity was increased. In contrast, addition of interleukin-2 (IL-2) resulted in a significantly increased response and a decreased sensitivity. In cultures activated with anti-CD3, CsA treatment resulted in suppression of proliferation after 3 days and an enhancement after 5 days. This latter phenomenon was not seen in cultures treated with Con A. Removal of macrophages (MPH) abolished the proliferative response to anti-CD3. The addition of 10% MPH restored the response, while pretreatment of MPH with CsA diminished this ability. There were differences in the activation kinetics elicited by these two agents as reflected by the changes in membrane potential and the rate of IL-2 receptor (Tac) expression. The changes in the membrane potential (in the absence of CsA) seemed to be parallel with Tac expression and thymidine incorporation. CsA caused a hyperpolarization of the cell membrane. Both Con A and anti-CD3 brought about a strong depolarization which was blocked by the presence of CsA. | {
"pile_set_name": "PubMed Abstracts"
} |
Psychological behaviorism's reading therapy program: parents as reading therapists for their children's reading disability.
The study presents data on the effectiveness of a parent-administered behavioral reading therapy program. Ten parents administered the therapy program to their second- to fourth-grade children with reading disability. All 10 children received 70 therapy sessions (30 minutes per session), with 5 of the 10 children receiving approximately 51 additional sessions, for a total of 121 sessions. Parents were able to administer the program effectively, and the children participated in an enthusiastic manner. Detailed records from the therapy sessions showed a high degree of mastery of the reading materials, and the children also showed significant and clinically meaningful improvements on standardized reading measures. Although the results must be viewed cautiously given the absence of a control group, the potential of the parent-administered reading therapy program for the remediation of reading disability seems good. | {
"pile_set_name": "PubMed Abstracts"
} |
Assessment of functional outcomes of temporalis muscle transfers for patients with longstanding facial paralysis.
Usually, clinical evaluation of facial reanimation provides accurate information about contraction of the mimetic muscles and phonation but fails to identify smile recovery and to quantify the motility of the lower third of the face during a smile. The purpose of this study was to verify that, in longstanding facial palsy, the modified temporalis muscle transfer (MTMT) can result in the ability to smile, not only voluntarily with chewing, but also spontaneously with a sudden emotional stimulus, and to confirm that a symmetric smile can be obtained. Ten patients of the treated group (group T; 4 women and 6 men) were randomly selected from a population of 24 patients with longstanding facial palsy treated by MTMT. Five normal subjects of the control group (group C; 3 women and 2 men) were enrolled as the control population. Functional outcomes after transposed temporalis muscle were examined and measured through clinical assessment by using a scored smile symmetry grading system, video recording, and surface electromyography (sEMG). In addition, the voluntary smile test (VST) and the not-voluntary smile test (NVST) were performed to study voluntary and spontaneous smiling. Subjects in the VST group (group T) were able to smile voluntarily and the expression was characterized by symmetry. In the NVST group, they were able to smile spontaneously and the symmetry of the smile was maintained for 8 subjects and only partially for 2 subjects. During both tests, the temporalis muscle of the treated side and the orbicularis oris muscle of the not-treated side were activated during smiling, indicating spontaneous activity of the transposed temporalis muscle with an emotional stimulus. For the control group, smiles during VST and NVST were symmetric and the temporalis muscles were not activated during smiling, whereas the orbicularis oris muscles were. Our study shows that the Morrison MTMT is able to restore the voluntary smile ability. Particularly, this technique allows for recovery of the spontaneous smile with symmetry. This assessment would seem to suggest that the transposed temporalis muscle might adapt from a chewing to a mimetic muscle. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1535-E1543, 2016. | {
"pile_set_name": "PubMed Abstracts"
} |
Dopaminergic neuron development in rats: biochemical study from prenatal life to adulthood.
Dopaminergic cell development has been studied mainly using morphological techniques and especially histofluorescence. However, the biochemical characteristics of dopamine (DA) neuron development and its physiological role during ontogeny are much less known. In the present article, the biochemical development of DA neurons, from day 13 of prenatal life to adulthood, is evaluated in Sprague-Dawley rats. DA was first detected on day 14 of gestation. The brain increase in this neurotransmitter begins on day 17 in the proencephalon and on day 18 in the mesencephalon, reaching on day 20 a level similar to that found during adulthood in the latter but not in the former. DA levels in the proencephalon rise slowly to adulthood level when compared to DA in the mesencephalon. The modifications observed in tyrosine levels are also largely similar to those reported for DA. Finally, the study of the first 48 h of life shows an increase in tyrosine levels and a decrease in dihydroxyphenylacetic acid levels (with a reduction of DA turnover) during the first 4-5 h of postnatal life. Since the serotonergic modification was completely different from DA modification, we conclude that the biochemical alteration of DA neurons during early postnatal development is specific. The present data suggest that DA neurons play different roles before and after reaching adult development. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasmacytic hyperplasia--the early form of posttransplant lymphoproliferative disorder--with atypical morphology and clinical course in patient after liver transplantation: a case report.
This case report describes an early lesion of posttransplant lymphoproliferative disorder (PLTD)--plasmacytic hyperplasia with atypical morphology. The 54-year-old patient was 4 months after liver transplantation due to alcoholic cirrhosis. The postoperative course had been uneventful without graft rejection episodes. Primary immunosuppressive therapy included tacrolimus and prednisone. On admission to the hospital the patient showed rapidly increasing jaundice, hepatomegaly, anemia, thrombocytopenia, and significant leukocytosis. A biopsy suggested generalized infection. Acute Epstein-Barr virus (EBV) infection was confirmed using serological methods. Despite treatment the patient died. On autopsy we found features of generalized infection. Histological examination of the enlarged lymph nodes showed plasmacytic hyperplasia despite lymph node atrophy. Plasmacytic hyperplasia, an early lesion of PTLD despite usually a good prognosis with multifactor therapy may display a rapid course that leads to death through intensified immunosuppression. In accordance with other reports we confirmed reactivation of EBV infection as the probable cause of plasmacytic hyperplasia. The lymph node morphology of plasmacytic hyperplasia may be atypical with atrophy of lymphoid components accompanying plasma cell proliferation. | {
"pile_set_name": "PubMed Abstracts"
} |
Vanadium polyoxoanion-bridged macrocyclic metal complexes: from one-dimensional to three-dimensional structures.
The reactions of four-coordinated transition metal macrocyclic complexes [ML](ClO(4))(2) (L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane, M = Ni, Cu) with NH4VO3 under different conditions gave four coordination polymers of {[(CuL)(0.5)(H2L)(1.5)][H2V10O2)] x 6H(2)O}(n) (1x6H(2)O), {[NiL](3)[V16O38(H2O)] x 6H(2)O}(n) (2 x 6H(2)O), {[NiL][VO(3)](2) x 0.33H2O}(n) (3.0.33H(2)O), and {[CuL][VO(3)](2) x 0.33H(2)O}(n) (4 x 0.33H2O). Single crystal X-ray diffraction analyses reveal that four diverse vanadium polyoxoanions, [H2V1oO28)(4-) cluster, [V16O38(H2O)](6-) cage, [V6O18](6-) ring, and [VO(3)](n)(n-) chain, were obtained from the same reactant NH(4)VO(3) under different conditions. In 1, the cluster anion [H2V10O28](4-) alternately bridges [CuL]2+/[H2L]2+ to form a one-dimensional chain, and the [V16O38(H2O)](6-) cage in 2 links three [NiL]2+ into a two-dimensional sheet. Compounds 3 and 4 show three-dimensional structures, which are constructed by the connections of hexanuclear [V6O18](6-) rings with [NiL]2+ in 3 and [VO3](n)(n-) chains with [CuL]2+ in 4, respectively, generating one-dimensional channels occupied by guest water molecules. | {
"pile_set_name": "PubMed Abstracts"
} |
Magnetization transfer ratio as a predictor of malignancy in breast lesions: preliminary results.
MRI is an important tool for investigating breast cancer. Although recognized as the method of choice for screening high-risk patients, and for other indications the role of MRI for lesion characterization remains controversial. Recently some authors have advocated the use of morphologic and postcontrast features for this purpose. Quantitative breast MRI techniques have not been applied extensively in breast diseases. Magnetization transfer (MT) is a quantitative MR technique commonly used to investigate neurological diseases. In breast diseases the use of MT has been limited to improving visualization of areas of enhancement in postcontrast images. The purpose of this study was to evaluate the feasibility and utility of MT in discriminating benign from malignant breast lesions. Fifty-two lesions, BIRADS 4 and 5, from 49 patients, were prospectively evaluated using the MT ratio (MTR). Patients were divided into two groups: benign and malignant lesions. The MTR of fat, pectoralis major muscle, fibroglandular tissue, and breast lesions were calculated. A statistically significant difference was found between MTR from benign and malignant lesions (P < 0.001). Preliminary results suggest that MT can be used to evaluate breast lesions. Further studies are necessary to better define the utility and applicability of this technique. | {
"pile_set_name": "PubMed Abstracts"
} |
WITHDRAWN: Epigenetic silence of HOTAIR contributes to the metastasis of pancreatic cancer via targeting miR-138.
Ahead of Print article withdrawn by publisher. | {
"pile_set_name": "PubMed Abstracts"
} |
Profile of the prehospital system in Madagascar.
To delineate the present characteristics of emergency medical services (EMS) on the island of Madagascar. This was a retrospective study of ambulance runs over a five-year period. The island covers 587,041 square kilometers with a population of 15 million, of whom 78% live in rural areas. Madagascar has 0.13 EMS workers per 1,000 people in urban areas, compared with 0.001 EMS workers per 1,000 people in rural areas. The urban physician/population ratio is 1 per 8,160, while in rural areas the ratio is 1/30,000. There is no "911" dispatching system. The EMS system offers transport services in 90% of ambulance runs. Ambulance calls are dispatched by police and fire departments in 80% of cases and by private calls in the remaining 20%. Madagascar has a telephone/population ratio of 1 per 239. Each vehicle is staffed by two emergency medical technicians (EMTs) who are paid by local hospitals and clinics that operate under a medical director. Urban EMS covers an average radius of 100 km, in contrast to the community-based rural EMS that serves a radius of only 25 km. The EMS system receives critically ill patients in 35% of its runs, obstetrical emergencies in 30%, surgical emergencies in 25%, and pediatric emergencies in the remaining 10%. This study shows that urban EMS is more organized, has a better-developed infrastructure, and has more personnel than its counterparts in rural areas. Future work will determine the impact of a rising population shift from rural to urban areas on this evolving EMS system. | {
"pile_set_name": "PubMed Abstracts"
} |
[Epidemiology and Public Health: tendencies of the Brazilian epidemiology production regarding volume, indexation and investigation areas - 2001 to 2006].
This article examines and interprets the trends of epidemiological production in Brazil in the Public Health context. CAPES indicators from 2001 to 2006 were used as database. We analyzed 26 programs and select the 10 major ones to analyze their bibliographic production in indexed journals. It was observed that the total production of epidemiological articles accounted for 40% of production in Public Health and 55% of the production was published in international journals, especially Cadernos de Saúde Pública, Revista de Saúde Pública and Ciência & Saúde Coletiva. The most prevalent themes were public health nutrition, maternal and infant health and, infectious diseases, particularly AIDS. Environmental e worker's heath, oral health, violence and health of the elderly have been ratified as objects of study for the discipline, while meta-analysis and geoprocessing appear as a useful tool for health services. We conclude that the epidemiological production tends to increase in indexed publications, covering various topics and a wide spectrum of relevant issues to Brazilian health policy. | {
"pile_set_name": "PubMed Abstracts"
} |
A semi-automated software tool to study treadmill locomotion in the rat: from experiment videos to statistical gait analysis.
A computer-aided method for the tracking of morphological markers in fluoroscopic images of a rat walking on a treadmill is presented and validated. The markers correspond to bone articulations in a hind leg and are used to define the hip, knee, ankle and metatarsophalangeal joints. The method allows a user to identify, using a computer mouse, about 20% of the marker positions in a video and interpolate their trajectories from frame-to-frame. This results in a seven-fold speed improvement in detecting markers. This also eliminates confusion problems due to legs crossing and blurred images. The video images are corrected for geometric distortions from the X-ray camera, wavelet denoised, to preserve the sharpness of minute bone structures, and contrast enhanced. From those images, the marker positions across video frames are extracted, corrected for rat "solid body" motions on the treadmill, and used to compute the positional and angular gait patterns. Robust Bootstrap estimates of those gait patterns and their prediction and confidence bands are finally generated. The gait patterns are invaluable tools to study the locomotion of healthy animals or the complex process of locomotion recovery in animals with injuries. The method could, in principle, be adapted to analyze the locomotion of other animals as long as a fluoroscopic imager and a treadmill are available. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional salutogenic mechanisms of the brain.
Neuroscientists are typically interested in the brain in relation to disease, but much could also be learned by studying the brain in relation to health. The brain has processes, functional salutogenic mechanisms, that contribute to health by enabling one's outlook on life to benefit one's health. For example, the belief that things will work out as well as can reasonably be expected is a key aspect of the outlook of people who tend to stay well even when in potentially stressful situations. Believing in God, feeling happy, being mutually in love, and expecting things to change for the better are also outlooks that can be salutogenic. Beliefs need not even be rational or realistic in order for them to be salutogenic, as shown by phenomena such as faith healing and the placebo effect. Thus, the brain responds to stimuli and interprets them, mainly without one's awareness, in ways that can enhance one's well-being. Although little is presently known concerning neuropathways of functional salutogenic mechanisms, further research on relations between salutogenesis and brain function can be expected to provide new strategies for improving health worldwide. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of demographic variables on cytomegalovirus antibody seropositivity among prospective blood donors in Jos, Nigeria.
Cytomegalovirus, otherwise called human herpes virus type 5, is a transfusion transmissible pathogen responsible for significant morbidity and mortality among various groups of individuals with damaged or impaired host immunity. Although it has a worldwide distribution, the infection is thought to be more widespread in developing countries where certain demographic factors and living conditions are thought to be responsible for the observed increased prevalence of this infection. The aim of this study is to evaluate the effect of living conditions, using certain selected demographic parameters, on CMV seropositivity, among blood donors in Jos. A total of 200 prospective blood donors who presented for bleeding were recruited consecutively into the study. Questionnaire was used to obtain the personal, educational, social and demographic data of donors. Screening for CMV antibodies was performed on each serum sample using ELISA kit ("DIALAB", Austria) (www.dialab.at). The relationship between the extent of crowding and CMV status of donors was statistically significant, p<0.05. Other studied donor demographic parameters (source of drinking water, place of abode and type of toilet facility) did not statistically influence donor CMV status, p>0.05. Our study showed that overcrowding was the most significant factor that statistically influenced donor CMV status in Jos, Nigeria. There is, therefore, an urgent need for concerted effort to handle the problem of overcrowding in developing countries and Nigeria in particular. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunoblot analysis of humoral immune responses to Leucocytozoon caulleryi in chickens.
The humoral antibody responses of chickens infected or immunized with Leucocytozoon caulleryi were analyzed by immunoblot comparing with protection against challenge infection, agar-gel precipitation (AGP) test, enzyme-linked immunosorbent assay (ELISA), and parasitemia. IgG antibodies in the sera from chickens infected with L. caulleryi were found to react with 20-35 bands of approximate molecular weights 25-300 kDa, such as 33, 44, 58, 79, 94, and 141 kDa from 3 to 50 wk after infection. In chickens immunized with schizont antigens from L. caulleryi, several bands were reacted with sera 2 wk after the second immunization, e.g., 36, 58, 71, 81, 97, 112, and 123 kDa. Chickens that recovered from the primary infection showed complete protection against reinfection, whereas immunized chickens showed partial protection against challenge infection. These results suggest that the difference in antibody response to schizont antigen might cause the difference in protection between immunized and infected chickens. | {
"pile_set_name": "PubMed Abstracts"
} |
Defining a reference range for cold agglutinin titers.
The cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively. Prospective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences. Titers from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors. Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts. | {
"pile_set_name": "PubMed Abstracts"
} |
Isoniazid and rifampin drug susceptibility testing: application of 2,3,5-triphenyl tetrazolium chloride assay and microscopic-observation drug-susceptibility assay directly on Ziehl-Neelsen smear positive sputum specimens.
The current study was aimed to evaluate the performance of direct 2,3,5-triphenyl tetrazolium chloride assay and direct microscopic observation drug susceptibility assay with indirect Löwenstein-Jensen proportion method directly on Ziehl-Neelsen smear positive sputum specimens. Direct acid fast bacilli smear positive sputum specimens (n=264) were subjected to isoniazid and rifampicin drug susceptibility testing by direct 2,3,5-triphenyl tetrazolium chloride assay, direct microscopic observation drug susceptibility assay, and the performances were compared with indirect Löwenstein-Jensen proportion method. The direct 2,3,5-triphenyl tetrazolium chloride assay demonstrated an overall sensitivity, specificity, positive predictive value, and negative predictive value of 99.2%, 82.4%, 99.2%, and 88.5%, respectively, for the detection of isoniazid and rifampicin resistant Mycobacterium tuberculosis isolates when compared to indirect Löwenstein-Jensen proportion method. Likewise, the overall sensitivity, specificity, positive predictive value and negative predictive value of direct microscopic observation drug susceptibility assay were 98.8%, 82.4%, 99.2%, and 78.2%, respectively. The direct 2,3,5-triphenyl tetrazolium chloride assay was found to be an economical alternative method for the rapid and accurate detection of isoniazid and rifampicin resistance from direct acid fast bacilli smear positive sputum specimens. | {
"pile_set_name": "PubMed Abstracts"
} |
[Famotidine does not modify the plasma levels of lidocaine for spinal anesthesia. A comparative study of famotidine and cimetidine].
H2 receptor antagonists are often used to reduce gastric acidity prior to general or regional anaesthesias. However cimetidine and ranitidine have been found to increase plasma levels of local anaesthetics such as lidocaine. This study aimed to compare famotidine--another H2 receptor antagonist--with cimetidine in this respect. 33 male patients 70 years old or more, scheduled for surgery under spinal anaesthesia and randomized into 3 groups, received either diazepam 0.15 mg.kg-1 and famotidine 20 mg (group A) or diazepam and cimetidine 200 mg (group B) or diazepam only (group C) on the previous night and 90 minutes before spinal anaesthesia by hyperbaric lidocaine 5%, 3 ml. Arterial blood samples were taken 3 minutes after spinal injection then every 15 minutes unto 90 minutes after the first sampling. Lidocaine plasma levels were measured by fluorescence polarization immunoassay and the results were statistically analyzed. In famotidine group lidocaine levels were intermediate between B and C groups levels, and the increase was of lesser duration than in B group. Elimination mechanism of lidocaine with and without H2 inhibitor is briefly discussed. Therefore famotidine would appear to be more convenient than other H2 receptor inhibitors whenever antacid protective effects are sought after prior to regional anaesthesia. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of sublingual nitroglycerin on resting pulmonary gas exchange and hemodynamics in man.
Simultaneous hemodynamic, ventilation and blood gas measurements were performed in 19 males during cardiac catheterization for evaluation of chest pain syndrome before and 3 to 5 min after 0.4 mg sublingual nitroglycerin. Pulmonary arterial pressures and total pulmonary vascular resistance fell (P less than 0.001 for both), and mean systemic arterial pressure decreased (P less than 0.05). However, peripheral vascular resistance, cardiac output, and mixed venous PO2 did not change. Total and tidal ventilation, PCO2, pH, and base excess remained unchanged. However, the arterial PO2 decreased from a mean of 80 +/- 3 (SEM) to 72 +/- 2 mm Hg (P less than 0.001) and mean venous admixture increased from 8.8 +/- 1% to 12.6 +/- 1.5% (P less than 0.001). The alveolar arterial PO2 difference increased (P less than 0.001) and the dead space tidal volume ratio rose (P less than 0.05). We conclude that the decrease in arterial PO2 following sublingual nitroglycerin is caused by redistribution of pulmonary blood flow with imbalance in ventilation-perfusion relationships or shunting. | {
"pile_set_name": "PubMed Abstracts"
} |
Perinatal assessment of cerebral flow velocity wave forms in the human fetus and neonate.
The temporal relationship between changes in cerebral Doppler flow velocity wave forms, ductal patency, blood gases, and blood pressure during the transition from intrauterine to newborn life was assessed longitudinally in 16 healthy term fetuses and newborns. Doppler flow velocity wave forms were obtained from fetal cerebral arteries (anterior cerebral, internal carotid, and basilar) before birth, within 8 h after birth, and again at 24 and 48 h after birth. The resistance index was used as a measure of vascular resistance. The resistance index of the cerebral arteries studied increased significantly between the antenatal and 8-h study periods. This was followed by a significant decrease below fetal levels by the 24-h study period, with little change thereafter. We conclude that in the newborn human, as in the newborn lamb, the transition from fetal to immediate newborn life is associated with an increase in cerebral vascular resistance and thus a decrease in cerebral blood flow in response to the increase in arterial oxygenation. The subsequent decrease in the cerebral resistance index between 8 and 24 h of life cannot be explained by a loss of ductal shunting nor by associated changes in newborn blood gases or blood pressure, but may rather reflect a remodeling of the circulation due to impedance matching. | {
"pile_set_name": "PubMed Abstracts"
} |
Standardised detoxification in cases of polydrug use.
In recent decades the pattern of substance use among patients admitted for detoxification has changed from predominantly single-substance use to simultaneous multi-substance use. The evidence base for pharmacological treatment of polydrug users remains inadequate. A non-experimental cohort study was conducted with 284 polydrug users in the Detoxification Unit of Sørlandet Hospital in 2013. The therapeutic approach was standardised, and was based on social therapy and symptomatic treatment of withdrawal symptoms with valproate and clonidine as key medications. Three quarters of the patients were male and they had used more than three different substances on average. The average age was 39 years. In total, 75 % of patients completed the detoxification programme, and for 95 % detoxification occurred without complications. In 89 % of cases, the standard treatment protocol was followed. There was a weak but significant correlation between treatment discontinuation and the number of substances used (OR = 1.42, p < 0.05). In terms of complications, 1.1 % experienced delirium tremens, 1.1 % epileptic seizures and 1.4 % substance-induced psychosis. Transfer to a somatic ward was necessary for 2.1 % of patients, and to a psychiatric ward for 1.4 %. The completion rate in this study was considerably higher than in previous detoxification studies, and the complication rate was lower. In view of the good results observed and the high degree of standardised treatment, the regimen can be considered a safe treatment option for other detoxification units. | {
"pile_set_name": "PubMed Abstracts"
} |
Rational manipulation of amyloidogenesis using an atomic level map of peptide-fibril interactions.
Amyloidogenic aggregation has been the subject of intense research over the past few decades, but the mechanisms underlying the early stages of amyloidogenesis remain elusive. Here we demonstrate for the first time manipulation of amyloidogenesis based on an atomic level map of peptide-fibril interactions in early- and late-stage ordered aggregation. Several point mutants with specific amyloidogenic properties are introduced, including one that "stalls" early in the aggregation process, forming early-stage fibrillar aggregates, but not mature fibrils. | {
"pile_set_name": "PubMed Abstracts"
} |
Selective attenuation of the extrinsic limb of the tissue factor-driven coagulation protease cascade by occupancy of a novel peptidyl docking site on tissue factor.
Tissue factor (TF), the receptor and cofactor for factor VIIa (VIIa) for cellular initiation of the coagulation protease cascade, drives thrombogenesis, inflammation, tumor cell metastasis, and the lethality of severe sepsis. To identify TF surface loci that can selectively inhibit substrate zymogen association and activation, TF(1-218), the extracellular domain, was used as the target for the phage display search. This resulted in selection of 59 clones from a phage gpVIII surface protein-expressed library of constrained combinatorial peptides. Of these, one encoding the peptide Glu-Cys-Leu-Arg-Ser-Val-Val-Thr-Cys on gpVIII most avidly bound TF(1-218), as did the synthetic peptide. Inhibition of binding was selective with an IC(50) of 30 nM for proteolytic activation of factor X by the TF(1-218)-VIIa complex. In contrast, there was no inhibition of factor IX activation. The selective inhibition of only factor X association with TF(1-218) will spare the intrinsic hemostatic pathway while attenuating the extrinsic thrombogenic pathway. This and related peptidyl structures provide the potential for the more precise identification of TF surface loci that mediate selective functional properties of the protein as well as a structural basis for the design of novel molecules for selectively attenuating initiation of the extrinsic limb of the coagulation protease cascade and other functions of TF. | {
"pile_set_name": "PubMed Abstracts"
} |
The effects of growth hormone therapy in children with radiation-induced growth hormone deficiency.
The effects of growth hormone (GH) therapy were studied in 6 children, previously treated for brain tumours which did not directly involve the hypothalamic-pituitary axis, and who had received cranial irradiation between 2.1 and 10 years earlier. All 6 were short with a standing height standard deviation score (SDS) from -1.7 to -3.3. Impaired growth hormone responses to an insulin tolerance test (ITT) were observed in all 6 and to a Bovril stimulation test in 5 children. The remainder of pituitary function was essentially normal. All 6 were prepubertal and 5 had a retarded bone age. During the pre-treatment year the 6 children's growth rates varied fom 2.0 to 5.1 cm. Subsequently all received human GH in a dose of 5 units 3 times weekly for 1 year. The growth rate in each was at least 2 cm greater during the treatment year than the pre-treatment year. Growth during the treatment year ranged from 6.0 to 10.1 cm. In 5 of the 6 the improvement in growth rate could be totally ascribed to the GH therapy. In the sixth there was significant pubertal maturation during the treatment year and only in this subject did the bone age advance at a significantly greater rate than the chronological age. | {
"pile_set_name": "PubMed Abstracts"
} |
Ciclosporin-induced immunosuppression in vitro. II. Variation in sensitivity and binding capacity.
The purpose of the present study was to analyse and correlate variations in lymphocyte sensitivity to, and binding of, ciclosporin (CsA) in vitro. Peripheral blood lymphocytes from healthy individuals were harvested over a 5-week period and activated with purified protein derivative (PPD) or alloantigens in the presence or absence of CsA (1 microgram/ml). Sensitivity to CsA was expressed as the ability of the drug to suppress cell proliferation ([3H]thymidine incorporation) and high-affinity interleukin-2 receptor (IL-2R) expression. Binding capacity was tested in a [3H]CsA binding assay. A significant variability in both sensitivity and binding capacity was recorded between individuals (P less than 0.001). There was no correlation between high sensitivity and high binding capacity. The intraindividual day-to-day variability did not differ significantly from the experimental (intra- and interassay) variability. The CsA-induced suppression of high-affinity IL-2R expression varied between 57.1 and 98.9%, while suppression of [3H]thymidine incorporation varied between 81.0 and 97.4%. Specific binding of 10 nM [3H]CsA at 37 degrees C varied between 5.4 and 10.7%. | {
"pile_set_name": "PubMed Abstracts"
} |
[Synthesis and pharmacologic evaluation of some dihydropyran carboxylic acids].
The synthesis of three new dihydropyran carboxylic acids has been performed by uncommon procedures: cyanosilylation, cyclisation of oxime. Their chemical structure was confirmed by I.R. and N.M.R. data. In a pharmacological evaluation they were found to possess significant effects on the passive cutaneous anaphylaxis test and on the central nervous system; one of them showed an interesting antiallergic effect whilst another showed an interesting sedative effect. | {
"pile_set_name": "PubMed Abstracts"
} |
Replication protein a 32 kDa subunit (RPA p32) binds the SH2 domain of STAT3 and regulates its transcriptional activity.
STATs (signal transducers and activators of transcription) are transcription factors that contain SH2 domains and are activated by tyrosine phosphorylation in response to cytokines and growth factors. Replication protein A (RPA) is a heterotrimeric complex that consists of three subunits, p70, p32 and p11, and has important functions in DNA replication and metabolism. Here, we present evidence that the RPA p32 subunit binds specifically to the SH2 domain of STAT3 in a phosphotyrosine-independent manner. We confirm their protein-protein interactions by yeast 2-hybrid analyses and in vitro binding assays using recombinant proteins generated from bacteria and in vitro translation. We also show that STAT3 binds to RPA p32 in vivo by conducting co-precipitation experiments. As the SH2 domain is highly involved in the tyrosine phosphorylation and the transcriptional activity of STAT3, over-expression of RPA p32 correspondingly augmented growth factor-stimulated tyrosine phosphorylation and transcription activities of STAT3. | {
"pile_set_name": "PubMed Abstracts"
} |
Structure-function relationship of estrogen receptors in cardiovascular pathophysiological models.
The ancestral status of estrogen receptor (ER) in the family of the steroid receptors has probably contributed to the pleiotropic actions of estrogens, and in particular of 17β-estradiol (E2). Indeed, in addition to their well described role in sexual development and reproduction, they influence most of the physiological processes. The pathophysiological counterpart of these actions includes several highly beneficial effects such as prevention of osteoporosis, atheroma and type 2 diabetes,… However, estrogens also promotes two deleterious actions : the stimulation of the proliferation of the epithelium of two sex targets : uterus and breast, favoring an increase in risk of epithelial cancer in these two tissues. These actions are mediated by the activation of ER alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions AF-1 and AF-2, but can also elicit rapid membrane initiated steroid signals. Although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. One major challenge consists in uncoupling some beneficial actions from other deleterious ones, i.e. selective ER modulation. Tamoxifen and raloxifen are beneficial to prevent the recurrence of breast cancer, and mimic estrogen action mainly on bone, but their effets on atheroma and on type 2 diabetes are if any marginal. These last years, several labs, and in particular our lab, have attempted: 1) To perform an in vivo molecular "dissection" of ER alpha, allowing the uncoupling of some of its actions, and potentially paving the way to optimized selective ER modulators. (reviewed in Arnal JF, et al. Br J Pharmacol. 2012;165:57-66). 2) To describe an unexpected action of E2 treatment at the level of platelet responses in mice, that protects the animals from thromboembolism through the haematopoietic ER alpha. (Valéra MC et al. Blood. 2012, in press). | {
"pile_set_name": "PubMed Abstracts"
} |
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