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pubmed_298_16436 | BACKGROUND
Depression and diabetes cause significant burden for patients and the healthcare system and, when co-occurring, result in poorer self-care behaviors and worse glycemic control than for either condition alone. However, the clinical management of these comorbid conditions is complicated by a host of patient, provider, and system-level barriers that are especially problematic for patients in rural locations. Patient-centered medical homes provide an opportunity to integrate mental and physical health care to address the multifaceted needs of complex comorbid conditions. Presently, there is a need to not only develop robust clinical interventions for complex medically ill patients but also to find feasible ways to embed these interventions into the frontlines of existing primary care practices.
METHODS/DESIGN
This randomized controlled trial uses a hybrid effectiveness-implementation design to evaluate the Healthy Outcomes through Patient Empowerment (HOPE) intervention, which seeks to simultaneously address diabetes and depression for rural veterans in Southeast Texas. A total of 242 Veterans with uncontrolled diabetes and comorbid symptoms of depression will be recruited and randomized to either the HOPE intervention or to a usual-care arm. Participants will be evaluated on a host of diabetes and depression-related measures at baseline and 6- and 12-month follow-up. The trial has two primary goals: 1) to examine the effectiveness of the intervention on both physical (diabetes) and emotional health (depression) outcomes and 2) to simultaneously pilot test a multifaceted implementation strategy designed to increase fidelity and utilization of the intervention by coaches interfacing within the primary care setting.
DISCUSSION
This ongoing blended effectiveness-implementation design holds the potential to advance the science and practice of caring for complex medically ill patients within the constraints of a busy patient-centered medical home.
TRIAL REGISTRATION
Behavioral Activation Therapy for Rural Veterans with Diabetes and Depression: NCT01572389. | 10.1186/1472-6963-14-191 |
pubmed_499_1616 | 2,3,5,4'-Tetrahydrostilbene-2-o-β-d-glucoside (TSG) is the main active component of Polygonum multiflorum Thunb. It has effects on hypertension. However, the mechanism is unclear. Current research is devoted to exploring the mechanism of TSG improving HHcy-induced hypertension. The mice received a subcutaneous injection of Hcy in the presence or absence of TSG for 4 weeks. Blood pressure (BP) was measured using a noninvasive tail-cuff plethysmography method. Levels of plasma Hcy and endothelin-1 were measured using ELISA. Rat SMA without endothelium was cultured in a serum-free medium in the presence or absence of TSG with or without Hcy. The contractile response to sarafotoxin 6c or endothein-1 was studied using a sensitive myography. The levels of protein were detected using Western blotting. The results showed that TSG lowered HHcy-elevated BP and decreased levels of plasma Hcy and endothelin-1 in mice. Furthermore, the results showed that TSG inhibited Hcy-upregulated ET receptor expression and ET receptor-mediated contractile responses as well as the levels of p-ERK1/2 and p-p65 in SMA. In vivo results further validate the in vitro results. In conclusion, TSG can decrease the levels of plasma Hcy and ET-1 and downregulate Hcy-upregulated ET receptors in VSMCs by inhibiting the ERK1/2 /NF-κB/ETB2 pathway to lower the BP. | 10.1002/ptr.7519 |
pubmed_1055_10991 | Cervicovaginal fluid (CVF) samples may be a feasible alternative to amniotic fluid (AF) sampling in women with preterm premature rupture of the membranes (PPROMs), because PPROM causes AF to spill into the CVF. We aimed to assess the correlation and limits of agreement of interleukin 8 (IL-8) levels between CVF and AF in women with PPROM and to compare the clinical value of CVF IL-8 to AF IL-8 for the prediction of microbial invasion of amniotic cavity (MIAC). A retrospective cohort observational study was conducted on 85 women with singleton pregnancies (24-34 weeks) presenting with PPROM. The CVF samples were obtained simultaneously with AF samples retrieved by transabdominal amniocentesis. The levels of IL-8 in paired CVF and AF samples were measured with enzyme-linked immunosorbent assay in the same plate in duplicate using the same dilutions. The prevalence of a positive AF culture was 40% (34 of 85). The CVF IL-8 levels were significantly and positively correlated with AF IL-8 levels ( r = 0.778). However, the level of agreement between CVF and AF IL-8 levels yielded a Cohen κ statistic of 0.276. Paired Student t test revealed that the difference between CVF and AF IL-8 levels was statistically significant. The area under the curve for AF IL-8 was significantly higher than that for CVF IL-8 ( P = .013). In women with PPROM, IL-8 levels in CVF were significantly correlated with, but were significantly different from, those in AF samples. The CVF IL-8 has moderate predictive capability for the risk of MIAC, but this is inferior to AF IL-8. | 10.1177/1933719116651149 |
pubmed_304_13819 | NADH dehydrogenase subunit 2, encoded by the mtDNA, has been associated with resistance to autoimmune type I diabetes (T1D) in a case control study. Recently, we confirmed a role for the mouse ortholog of the protective allele (mt-Nd2(a)) in resistance to T1D using genetic analysis of outcrosses between T1D-resistant ALR and T1D-susceptible NOD mice. We sought to determine the mechanism of disease protection by elucidating whether mt-Nd2(a) affects basal mitochondrial function or mitochondrial function in the presence of oxidative stress. Two lines of reciprocal conplastic mouse strains were generated: one with ALR nuclear DNA and NOD mtDNA (ALR.mt(NOD)) and the reciprocal with NOD nuclear DNA and ALR mtDNA (NOD.mt(ALR)). Basal mitochondrial respiration, transmembrane potential, and electron transport system enzymatic activities showed no difference among the strains. However, ALR.mt(NOD) mitochondria supported by either complex I or complex II substrates produced significantly more reactive oxygen species when compared with both parental strains, NOD.mt(ALR) or C57BL/6 controls. Nitric oxide inhibited respiration to a similar extent for mitochondria from the five strains due to competitive antagonism with molecular oxygen at complex IV. Superoxide and hydrogen peroxide generated by xanthine oxidase did not significantly decrease complex I function. The protein nitrating agents peroxynitrite or nitrogen dioxide radicals significantly decreased complex I function but with no significant difference among the five strains. In summary, mt-Nd2(a) does not confer elevated resistance to oxidative stress; however, it plays a critical role in the control of the mitochondrial reactive oxygen species production. | 10.1074/jbc.M609367200 |
pubmed_1052_22637 | BACKGROUND
Although many children with Down syndrome experience hearing loss, there has been little research to investigate its impact on speech and language development. Studies that have investigated the association give inconsistent results. These have often been based on samples where children with the most severe hearing impairments have been excluded and so results do not generalize to the wider population with Down syndrome. Also, measuring children's hearing at the time of a language assessment does not take into account the fluctuating nature of hearing loss in children with Down syndrome or possible effects of losses in their early years.
AIMS
To investigate the impact of early hearing loss on language outcomes for children with Down syndrome.
METHODS & PROCEDURES
Retrospective audiology clinic records and parent report for 41 children were used to categorize them as either having had hearing difficulties from 2 to 4 years or more normal hearing. Differences between the groups on measures of language expression and comprehension, receptive vocabulary, a narrative task and speech accuracy were investigated.
OUTCOMES & RESULTS
After accounting for the contributions of chronological age and nonverbal mental age to children's scores, there were significant differences between the groups on all measures.
CONCLUSIONS & IMPLICATIONS
Early hearing loss has a significant impact on the speech and language development of children with Down syndrome. Results suggest that speech and language therapy should be provided when children are found to have ongoing hearing difficulties and that joint audiology and speech and language therapy clinics could be considered for preschool children. | 10.1111/1460-6984.12077 |
pubmed_230_19145 | The main transmission pathway of Helicobacter pylori has not been determined, but several reports have described detection of H. pylori DNA in drinking and environmental water, suggesting that H. pylori may be waterborne. To address this possibility, we developed, tested, and optimized two complementary H. pylori-specific real-time PCR assays for quantification of H. pylori DNA in water. The minimum detection level of the assays including collection procedures and DNA extraction was shown to be approximately 250 H. pylori genomes per water sample. Using our assays, we then analyzed samples of drinking and environmental water (n = 75) and natural water biofilms (n = 21) from a high-endemicity area in Bangladesh. We could not identify H. pylori DNA in any of the samples, even though other pathogenic bacteria have been found previously in the same water samples by using the same methodology. A series of control experiments were performed to ensure that the negative results were not falsely caused by PCR inhibition, nonspecific assays, degradation of template DNA, or low detection sensitivity. Our results suggest that it is unlikely that the predominant transmission route of H. pylori in this area is waterborne. | 10.1128/AEM.02779-08 |
pubmed_992_18172 | Comparative sequence analysis methods, such as phylogenetic footprinting, represent one of the most effective ways to decode regulatory sequence functions based upon DNA sequence information alone. The laborious task of assembling orthologous sequences to perform these comparisons is a hurdle to these analyses, which is further aggravated by the relative paucity of tools for visualization of sequence comparisons in large genic regions. Here, we describe a second-generation implementation of the GenePalette DNA sequence analysis software to facilitate comparative studies of gene function and regulation. We have developed an automated module called OrthologGrabber (OG) that performs BLAT searches against the UC Santa Cruz genome database to identify and retrieve segments homologous to a region of interest. Upon acquisition, sequences are compared to identify high-confidence anchor-points, which are graphically displayed. The visualization of anchor-points alongside other DNA features, such as transcription factor binding sites, allows users to precisely examine whether a binding site of interest is conserved, even if the surrounding region exhibits poor sequence identity. This approach also aids in identifying orthologous segments of regulatory DNA, facilitating studies of regulatory sequence evolution. As with previous versions of the software, GenePalette 2.1 takes the form of a platform-independent, single-windowed interface that is simple to use. | 10.1016/j.ydbio.2017.06.033 |
pubmed_34_24697 | OBJECTIVE
The objective of the study was the estimation of the influence of oral supplementation with low-dose l-arginine on feto-placental circulation in women with threatened preterm labor.
STUDY DESIGN
Oral administration of 3g of L-arginine daily or placebo as a supplement to standard tocolytic therapy was tried in 70 women with threatened preterm delivery, randomly assigned to the L-arginine (n=37) or placebo (n=33) groups. Twenty-five and 20 completed the study, respectively. Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as pregnancy outcome and biochemical markers of nitric oxide synthesis (plasma amino acid and nitrite/nitrate levels, as well as 24 h nitrite/nitrate excretion with urine) were estimated.
RESULTS
Starting from the second week of therapy, the UA PI values were significantly lower in the L-arginine group than in the placebo group. Moreover, treatment with L-arginine caused a significant increase in MCA PI and cerebro-placental ratio (CPR) values. The changes in feto-placental circulation in the L-arginine group were not associated with any signs of increased nitric oxide synthesis.
CONCLUSION
Oral supplementation with low doses of L-arginine changed feto-placental blood flow distribution in patients with threatened preterm labor. The exact mechanism of L-arginine action on feto-placental circulation requires further investigation. | 10.1016/j.ejogrb.2007.06.024 |
pubmed_672_1125 | The hypothesis that a transcutaneous monitor electrode can heat skin beyond the electrode edge was tested. This heating would cause a skin thermistor probe, if placed too close to the transcutaneous electrode, to transduce an artifactually high skin temperature. In a skin servo control system, this might result in a cooler environment than desired. Eight premature newborns in humidified incubators were tested once each between one and five days of age. Mean skin temperatures at 0.5 cm, 1.5 cm, and 2.5 cm from the electrode edge were significantly higher after electrode placement, although there were virtually no temperature changes in two of the subjects. Transcutaneous monitor electrodes can heat the surrounding skin. This may affect environment temperature in a skin servo control system if the skin probe is placed too close to the transcutaneous electrode. | pubmed_672_1125 |
pubmed_671_3044 | Na+ has been implicated as a requirement for the inhibition of adenylate cyclase by hormones and neurotransmitters. This study examines effects of salt concentration on neuroblastoma plasma membranes that occur in the absence of an inhibitory hormone. The adenylate cyclase response to stimulatory agonists (GTP plus PGE1 (3), PGI2 or PGE2) was influenced by NaCl. As the [NaCl] increased to 150 mM, an increase in maximal activity and a decrease in apparent affinity was observed. At concentrations above 150 mM, NaCl decreased prostaglandin affinity and progressively decreased maximal activation. The GTP requirement was not altered by 30 or 150 mM NaCl in the presence of PGE1 or PGI2. The rate of Gpp(NH)p stimulated activity increased as the [NaCl] was increased in the assay. This increased rate was conserved when membranes activated in the presence of Gpp(NH)p and NaCl were reassayed in the absence of guanine nucleotide or salt. The salt evoked rate increase was proportionally greater at submaximal MgCl2 concentrations. The concentration requirement for Mg2+ was reduced by salt for adenylate cyclase in the presence of GTP or Gpp(NH)p. However, the enzyme stimulated by hormone exhibited a Mg2+ requirement that was low in the absence of salt and could not be further reduced by increased [NaCl]. Alternative monovalent cations (150 mM Li+, K+, Cs+, but not choline or tetramethylammonium) and anions (SO4=) substituted for NaCl. The observed effects were reversible upon washing the membranes and neither ouabain nor tetrodotoxin altered the response. These effects may result from a conformational alteration of a protein particularly sensitive to neutral salts in the assay. | pubmed_671_3044 |
pubmed_753_4526 | Since the European funded project VREPAR--Virtual Reality in Neuro-Psycho-Physiology (1995)--different European research activities have been using virtual reality and advanced information and communication technologies to improve the quality of care in the treatment of many different mental health disorders including anxiety disorders, eating disorders and obesity. Now the European Commission funding is shifting from the traditional hospital-centred and reactive healthcare delivery model toward a person-centred and preventive one. The main outcome of this shift is the "Personal Health Systems" (PHS) paradigm that aims at offering continuous, quality controlled, and personalized health services to empowered individuals regardless of location. The paper introduces four recently funded projects--Interstress, Monarca, Optimi and Psyche--that aim at using PHS based on virtual reality, biosensors and/or mobile technologies to improve the treatment of bipolar disorders, depression and psychological stress. | pubmed_753_4526 |
pubmed_440_4006 | PURPOSE
Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients' physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients.
METHODS
Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses.
RESULTS
The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased.
CONCLUSIONS
Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support. | 10.1007/s00134-018-5342-2 |
pubmed_310_16089 | Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-II (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19. Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF. We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT. | pubmed_310_16089 |
pubmed_271_4117 | micoRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of a large number of human genes. Gliomas are the most common and deadly primary human brain tumors and are thought to originate from transformed stem-like cells (GSCs). microRNAs are frequently deregulated in cancer and gliomas and their deregulation has been associated with various aspects of glioma pathobiology. The present review summarizes the published literature on the role of miRNAs in gliomas with a focus on their role in GSCs. | 10.2741/3952 |
pubmed_1010_14455 | Hydroxy-safflor yellow A (HSYA) can exert a variety of effects upon the vascular system. However, the underlying mechanisms are not clear. The present study is to investigate its vasodilating effect and the mechanisms. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were enrolled for studying effects of HSYA on blood pressure, vasodilation, intracellular Ca2+ transient and membrane ion channels. Vasodilation and intracellular Ca2+ transient were measured by using vasomotor assay and fluorescence imaging system, respectively. The effect of HSYA on the large conductance Ca2+ activated and voltage-gated potassium channel (BKCa channel) currents in rat mesentery artery and on L-type calcium channel (Ca-L) currents in HEK293cells expressed with Ca-L were investigated using patch clamp techniques. Blood pressure of SHR and WKY rats were concentration dependently reduced by HSYA with a larger effect of HSYA in SHR than that in WKY rats. The tension of mesenteric arteries induced by 3 μM phenylephrine was attenuated by HSYA (IC50 = 90.8 μΜ). Patch clamp study showed that HSYA could activate BKCa channels and suppress Ca-L channels in a concentration dependent manner. The results of calcium signaling assays indicated that HSYA could reduce the intracellular free Ca2+ level. These findings demonstrate that HSYA could activate BKCa channels and inhibit Ca-L channels and reduce intracellular free Ca2+ level, which are probably important for its vasodilatory effect. | 10.1016/j.ejphar.2019.172873 |
pubmed_129_747 | The syndromes I have described are unfortunately not rare in Saudi and so the role of genetic counselling is an important, if difficult, one. Consanguinous marriages are a key cause of these diseases, but not one easily avoided. Marriage rituals in this part of the world are vastly different from those in the west. Many Saudis regard consanguinous unions, for example between cousins, as a further strengthening of family bonds. The role of genetics is not fully appreciated by parents and genetic disease is often attributed to other, extraneous causes: God's will; an illness suffered by the mother during pregnancy; or to the 'evil eye.' Even when genetic counsellors actively discourage parents who are at risk from having future children, this advice goes unheeded. Parents prefer to rely on: 'Insh'allah' or God's will' to safeguard them. Abortion is strictly prohibited by religious law and any affected offspring are cared for by a dedicated and loving family under the guidance of the Holy Qu'ran. They are rarely institutionalized. | pubmed_129_747 |
pubmed_767_1008 | OBJECTIVE
To examine the effect of hemodynamic assessment of the left gastric vein (LGV) as a noninvasive test to diagnose esophageal varices (EV) in cirrhosis patients.
METHODS
This cross-sectional study consisted of 229 cirrhosis patients (62.7 ± 11.8 years; Child-Pugh score 5-14). One hundred fifty-four patients had EV (67.2%; small, 53; medium, 71; large, 30). All patients underwent a blood test and Doppler ultrasound followed by upper gastrointestinal endoscopy on the same day. The diagnostic ability for EV was compared between LGV-related findings and the platelet count/spleen diameter ratio (Plt/Spl).
RESULTS
The detectability of the LGV was higher in patients with EV (129/144, 89.6%) than in those without (35/75, 46.7%; p < 0.0001), and was higher in those with large EV (30/30, 100%) than in those without (134/199, 67.3%; p = 0.0002). The positive detection of the LGV showed 100% sensitivity and negative predictive value (NPV) to identify large EV in the whole cohort and compensated group (n = 127). The best cutoff value in the LGV diameter was 5.35 mm to identify large EV, showing 0.753 area under the receiver operating characteristic curve (AUROC) with 90% sensitivity and 96.5% NPV. The Plt/Spl showed 62.1% sensitivity and 87.1% NPV, and the best cutoff value was 442.9 to identify large EV with 0.658 AUROC, which was comparable to LGV-based assessment (p = 0.162).
CONCLUSIONS
This same-day comparison study demonstrated the value of LGV-based noninvasive test to identify large EV with high sensitivity and NPV in cirrhosis patients at a lower cost. | 10.1038/s41424-018-0021-8 |
pubmed_690_21751 | The presence of clinically palpable finger joint nodules (Heberden's and Bouchard's nodes) was documented in 123 consecutive cases with diffuse idiopathic skeletal hyperostosis (DISH) of the thoracic spine and 191 matched DISH negative controls. The prevalence of palpable finger joint nodules was almost twice as frequent in cases with spinal DISH compared to controls (46% versus 31%, chi 2 = 7.67, P less than 0.01; multivariate adjusted odds ratio OR = 1.84; 95% CI: 1.14-2.98). This increase was most marked at the proximal interphalangeal joint, in males and in patients up to the age of 65 years. In addition and independent of other variables such as hyperostotic features, age and sex, the prevalence of palpable finger joint nodules was about twice as high in probands with a history of physically heavy work compared to those without (43% versus 26%, chi = 9.18, P less than 0.005; multivariate adjusted odds ratio OR = 2.10; 95% CI: 1.26-3.52). From these results we conclude that DISH should be considered as an independent risk factor in the development of finger joint nodules. | 10.1093/rheumatology/31.8.531 |
pubmed_3_821 | The hypoglycemic and hypocholesterolemic effects of high and low molecular weight chitosan were evaluated in streptozotocin (STZ)-induced diabetic rats. Rats were divided into three groups of normal rats (Experiment I) and three groups of diabetic rats (Experiment II). The first group received a cellulose (control) diet, the second group received a low MW (1.4 x 10(4)Da) chitosan diet and the third group received a high MW (1.0 x 10(6)Da) chitosan diet. All three diets were containing 0.5% cholesterol. Experiment I: rats fed with high MW or low MW chitosan diet had increased high density lipoprotein (HDL) cholesterol. However, chitosan did not affect plasma glucose in normal rats. Experiment II: significantly decreased plasma glucose and total cholesterol and increased HDL cholesterol and fecal cholesterol excretion were observed in diabetic rats fed with high MW chitosan diet than animals fed with cellulose diet. However, no statistical significant difference in plasma glucose and total cholesterol was observed in diabetic rats fed with low MW chitosan. The total content of SCFAs in cecum was significantly increased and the ratio of acetate to propionate was slight but significantly decreased in diabetic rats after consuming high MW chitosan diet. The activities of hepatic hexokinase were significantly increased and the intestinal disaccharidases including sucrase and maltase were significantly decreased in normal and diabetic rats fed with high MW chitosan diet. Results obtained from the present study demonstrated the potential of high MW chitosan in reducing hyperglycemia and hypercholesterolemia in STZ-induced diabetic rats. | 10.1016/j.fct.2007.12.012 |
pubmed_709_6971 | A new approach to the classification of disorders of urinary concentration and dilution is recommended based on recent studies of how the kidney elaborates a urine of widely varying osmolality. The capacity to concentrate urine depends on ft, the fractional reabsorption of solute delivered to the loop of Henle; fu, the excretion of solute relative to the sum of solute excretion and solute delivery to Henle's loop; fw, the fraction of solute loss by vascular outflow from the medulla relative to that reabsorbed by the loop; and finally, collecting duct response to antidiuretic hormone (ADH). A decrease in ft or in increased fu or fw will diminish urinary concentrating ability, as will resistance of the tubule to ADH. Conversely, urinary dilution depends on the delivery of sodium and water to the ascending limb; NaCl reabsorption by the ascending limb; and the absence of ADH. A decrease in sodium and water delivery to the ascending limb or in NaCl reabsorption by the ascending limb will impair urinary diluting ability, as will the presence of ADH. The consequences of disorders in urinary concentrating and diluting ability vary widely. In an alert patient with an intact thirst center, there may be no consequence; in a patient unable to communicate thirst or whose thirst center is deranged, the results may be catastrophic. Keeping in mind the kidney's few basic requirements for formation of concentrated or dilute urine may help the physician avoid these potentially serious dislocations of water balance. | 10.1016/0002-9343(82)90823-3 |
pubmed_847_12900 | Aberrant left hepatic artery (ALHA) can exist in up to 25% of the population. The presence of ALHA during lymph node (LN) dissection in gastric cancer may complicate the process. In this study, we aimed to evaluate the existence rate, management, and consequences of ALHA in our laparoscopic gastrectomy series. Demographical and clinical data of laparoscopically operated 158 consecutive gastric cancer patients were collected retrospectively. Study patients were divided into three groups according to absence, existence and preservation, and existence and sacrification of ALHA. Harvested LN numbers, operation time, and postoperative alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase values on consecutive days were analyzed using Kruskal-Wallis and Mann-Whitney U tests. P < .05 is accepted as significant. The median AST and ALT values of the ALHA-sacrificed group were higher than those of the group without ALHA and the ALHA-preserved group on the 1st, 3rd, and 5th postoperative days (P < .05). On the 10th day, liver enzymes returned to normal values. Adequate and appropriate dissection of LNs while preserving ALHA can be performed without prolonging the operation time. Sacrification of ALHA causes an increase in liver enzymes, with spontaneous recovery in most cases. | 10.1089/lap.2022.0005 |
pubmed_269_8960 | Iron is not only essential but also a toxic trace element. Under iron repletion, ferritin maintains cellular iron homeostasis by storing iron to avoid iron toxicity. Under iron depletion, the ferritin-specific autophagy adaptor NCOA4 delivers ferritin to lysosomes via macroautophagy to enable cells to use stored iron. Here, we show that NCOA4 also plays crucial roles in the regulation of ferritin fate under iron repletion. NCOA4 forms insoluble condensates via multivalent interactions generated by the binding of iron to its intrinsically disordered region. This sequesters NCOA4 away from ferritin and allows ferritin accumulation in the early phase of iron repletion. Under prolonged iron repletion, NCOA4 condensates can deliver ferritin to lysosomes via a TAX1BP1-dependent non-canonical autophagy pathway, thereby preventing relative iron deficiency due to excessive iron storage and reduced iron uptake. Together, these observations suggest that the NCOA4-ferritin axis modulates intracellular iron homeostasis in accordance with cellular iron availability. | 10.15252/embr.202154278 |
pubmed_885_17872 | A vast majority of the world buffalo resource is concentrated in tropical and subtropical countries. Apart from heat stress and poor nutritional availability, endometritis is one of the most commonly encountered reproductive problems limiting fertility and consequently productive potential of the species. As demonstrated recently, endometritis impairs growth and follicular fluid composition of the largest follicle in buffalo. In the present study, the effect of endometritis on luteal development, function, nitric oxide (NO), and ascorbic acid was investigated. Reproductive tracts were collected from 90 cyclic buffaloes at an abattoir and grouped into endometritic (n = 36) or non-endometritic (n = 54) buffaloes based on physical examination of uterine mucus, white side test, and uterine cytology. Samples with pus-containing mucus, positive reaction on white side test, and/or >5 % neutrophils were considered to be positive for endometritis. Corpora lutea were enucleated, weighed, classified into stages I to IV, and assayed for progesterone (P(4)), NO, and ascorbic acid concentrations. Endometritic buffaloes had lesser (P < 0.0001) luteal weight and P(4), NO, and ascorbic acid concentrations than non-endometritic buffaloes. The findings indicated that endometritis impairs corpus luteum development and function in buffalo. Reduced luteal NO and ascorbic acid concentrations during endometritis are novel findings. | 10.1007/s11250-012-0292-0 |
pubmed_269_7741 | Despite advanced therapies, the mortality of patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) remains around 50%. Mechanical complications of MI are rare nowadays but associated with high mortality in patients who present with CS. Different treatment strategies and mechanical circulatory support (MCS) devices have been increasingly used to improve the grim prognosis of refractory CS. This article discusses current evidence regarding the use of MCS in MI complicated by CS, ventricular septal rupture, free wall rupture and acute mitral regurgitation. Device selection should be tailored according to the cause and severity of CS. Early MCS initiation and multidisciplinary team cooperation is mandatory for good results. MCS associated bleeding remains a major complication and an obstacle to better outcomes. Ongoing prospective randomized trials will improve current knowledge regarding MCS indications, timing, and patient selection in the coming years. | 10.11909/j.issn.1671-5411.2022.02.004 |
pubmed_422_20998 | During pregnancy, the endometrium of the ewe secretes large amounts of a progesterone-induced protein of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS). This protein inhibits lymphocyte proliferation in response to concanavalin A (ConA), phytohemagglutinin (PHA), or mixed lymphocyte reaction. The purpose of these experiments was to characterize the mechanism by which OvUS inhibits lymphocyte proliferation. Ovine US caused dose-dependent inhibition of lymphocyte proliferation induced by phorbol myristol acetate (PMA), an activator of protein kinase C. The PHA-induced increase in CD25 expression was inhibited in peripheral blood mononuclear leukocytes (PBML) by OvUS. However, no effect of OvUS on Con A-induced expression of CD25 was observed. Further analysis using two-color flow cytometry revealed that OvUS inhibited ConA-induced expression of CD25 in gammadelta-TCR- cells but not gammadelta-TCR+ cells. Stimulation of PBML for 14 hr with ConA resulted in an increase in steady state amounts of interleukin-2 (IL-2) mRNA that was not inhibited by OvUS. Ovine US was also inhibitory to lymphocyte proliferation induced by human IL-2. Results suggest that OvUS acts to inhibit lymphocyte proliferation by blocking the upregulation of the IL-2 receptor and inhibiting IL-2-mediated events. Lack of an effect of OvUS on ConA-stimulated CD25 expression in gammadelta-TCR+ cells may reflect a different mechanism of activation of these cells or insensitivity to inhibition by OvUS. | 10.1046/j.1525-1373.2000.22310.x |
pubmed_822_25137 | INTRODUCTION
Cardiac patients are more prone to develop hemodynamic instability on induction of anesthesia and endotracheal intubation. The Airtraq(®) optical laryngoscope is a single-use rigid video laryngoscope that has been developed to facilitate tracheal intubation. There are limited studies comparing differences in the circulatory responses to Airtraq(®) and direct Macintosh larynngoscopy in cardiac patients.
AIM
The purpose of our study was to evaluate whether there was clinically significant difference between the hemodynamic response to orotracheal intubation guided by either of the two devices (Airtraq(®) and Macintosh laryngoscopes) in patients who underwent coronary artery bypass grafting surgery.
MATERIAL AND METHODS
In this clinical study we analyzed the hemodynamic response to endotracheal intubation performed with Airtraq(®) or Macintosh laryngoscopes in patients who underwent elective coronary artery bypass graft surgery under general anesthesia.
RESULTS
We analyzed: blood pressure (systolic, diastolic, mean), heart rate and peripheral oxygen saturation (all notified before induction in anesthesia, immediately after induction, at the time of intubation and thereafter one and five minutes after intubation). We also recorded the maximal values of blood pressure and heart rate, as well as calculated the product of heart rate and systolic blood pressure. There were statistically significant differences in the hemodynamic response between the groups. At the time of intubation, there was significant inter-group difference in heart rate, systolic, diastolic and mean blood pressure. Endotracheal intubation with Macintosh laryngoscope was accompanied by significant increase in blood pressure and heart rate compared to Airtraq(®) group.
CONCLUSION
The Airtraq(®) laryngoscope performed better than the Macintosh laryngoscope in terms of hemodynamic to the patient undergoing routine coronary artery bypass graft surgery. | 10.5455/aim.2015.23.280-284 |
pubmed_247_14348 | Lymph node-derived endothelial cells were immortalized by infection with SV40 virus and subclones expressing the marker MECA 325 specific for high-endothelial venules (HEV) were selected. These transformed mouse endothelial (TME-) cell lines grow permanently without requirement for special growth factors. Staining of the selected clones with endothelium-specific antibodies and with anti-von Willebrand factor antiserum and uptake of acetylated low-density lipoprotein provide evidence for their endothelial origin. The vascular addressins identified by mAbs MECA 79 and MECA 367 on HEV are not detectable, indicating that the phenotype of the cells differs from that of HEV-type endothelium. The TME cells display a constitutive capacity to bind lymphocytes. An additional binding component is induced by treatment of the TME cells with TNF alpha. Antibodies against the homing receptor LECAM-1 (lectin-related leucocyte-endothelial cell adhesion molecule 1), alpha 4-integrins, vascular addressins, LFA-1, or ICAM-1 known to block lymphocyte interaction with particular types of HEV were unable to inhibit the basal adhesion to TME cells, indicating that a further binding mechanism in mice is displayed by this cell type. The adhesion component induced by TNF alpha is mediated by alpha 4-integrins since enhanced binding could be blocked by an antibody against mouse alpha 4 (lymphocyte-Peyer's patch adhesion molecule 1/2). TME cell lines therefore seem to be a useful model for the dissection and analysis of hitherto poorly characterized murine lymphocyte/endothelial cell interaction mechanisms. | 10.1016/0014-4827(91)90431-s |
pubmed_896_16230 | Tea is one of the most popular beverages worldwide, and its quality is often affected by the excessive pesticide residues during production. During the detection of pesticide residues in tea by chromatography-mass spectrometry and other methods, a strong matrix effect attributed to tea polyphenols and pigments is observed, which seriously impacts the analysis results. In this study, Fe3O4 magnetic nanoparticles and boric acid-functionalized metal organic framework (BA-MOF) materials were combined to prepare a highly efficient adsorbent Fe3O4@BA-MOF for capturing tea polyphenols and pigments. An effective analysis method for pesticide residues in tea samples in combination with gas chromatography-mass spectrometry was established. The introduction of boronic acid ligands into the metal organic framework, as the recognition site of cis-diols, enhanced the polyphenol capture ability. Adsorption of the pigment in the matrix was achieved through π-π interactions between the MOF ligand and the pigment. This new material has significant advantages such as rapid magnetic separation, large surface area, and abundant functional sites. Fe3O4@BA-MOF was prepared by employing simple conditions and characterized by Fouriertransform infrared spectroscopy, scanning electron microscopy, and X-ray diffractometry to identify its functional groups and morphology. After investigating the adsorption effect of different doses of Fe3O4@BA-MOF adsorbents (5, 10, 30, 50, and 80 mg) on tea polyphenols, 50 mg of the adsorbent was added to the tea matrix and shaken thoroughly. The tea polyphenol content in the matrix solution was determined using an ultraviolet spectrophotometer. The polyphenols were reduced by 74.58% within 5 min. The effect of solution pH (2.0, 4.0, 6.0, and 7.0) on the adsorption efficiency was investigated, and pH 7.0 was chosen as the optimal condition. By adjusting the pH of the solution, Fe3O4@BA-MOF could be recycled, and it maintained the excellent adsorption performance after four cycles of use. The introduction of Fe3O4 magnetic nanoparticles led to rapid magnetic response characteristics during sample pretreatment and improved the pretreatment efficiency. In the actual application of tea pesticide detection, after Fe3O4@BA-MOF pretreatment, the average recovery rates of the ten pesticides were in the range of 75.8%-138.6%, and the RSD was in the range of 0.5%-18.7% (n=3). The Fe3O4@BA-MOF nanocomposite prepared by introducing the boric acid ligand into the MOF structure and incorporating Fe3O4 magnetic nanoparticles could specifically adsorb the tea polyphenol matrix. When applied to the detection of pesticide residues in tea, it purifies the matrix and improves the detection efficiency, thus being suitable for the detection and analysis of pesticides in tea. | 10.3724/SP.J.1123.2021.06003 |
pubmed_249_17195 | OBJECTIVE
To investigate the short-term effects of chemotherapy-surgery-chemotherapy regimen on clinically inoperable advanced ovarian cancer.
METHODS
Retrospective analysis was made on 16 cases of stage III and 2 cases of stage IV epithelial ovarian cancer with fixed pelvic mass. Neoadjuvant chemotherapy with CP (cisplatin + cyclophosphamide) or CAP (CP + adriamycin) regimen was given by intraarterial, intraperitoneal, or systemic routes accordingly for an average of 2.8 courses. Sixteen of the 18 cases were assessed to be operable after preoperative chemotherapy. The uterus, adnexa, omentum, pelvic lymph nodes (14/18), and implants were included in the cytoreductive surgery. Pelvic masses were found to have almost disappeared in 9, and macroscopic residuals were found in 11 (residuals < 2 cm in 2, and > 2 cm in 5) of the 18 cases. Postoperative chemotherapy (CP, CAP, or CEP, E = VP16) was given for an average of 5.9 courses.
RESULTS
Five out of 7 patients followed up for over 3 years have been surviving for 46, 44, 40, 38 and 36 months, respectively.
CONCLUSION
Chemotherapy-surgery-chemotherapy regimen has beneficial effects on clinically inoperable advanced ovarian carcinoma. | pubmed_249_17195 |
pubmed_72_11923 | Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers. | 10.2174/156802661511150408110453 |
pubmed_313_17307 | Temporal transcriptions of genes are achieved by different mechanisms such as dynamic interaction of activator and repressor proteins with promoters, and accumulation and/or degradation of key regulators as a function of cell cycle. We find that the TorR protein localizes to the old poles of the Escherichia coli cells, forming a functional focus. The TorR focus co-localizes with the nucleoid in a cell-cycle-dependent manner, and consequently regulates transcription of a number of genes. Formation of one TorR focus at the old poles of cells requires interaction with the MreB and DnaK proteins, and ATP, suggesting that TorR delivery requires cytoskeleton organization and ATP. Further, absence of the protein-protein interactions and ATP leads to loss in function of TorR as a transcription factor. We propose a mechanism for timing of cell-cycle-dependent gene transcription, where a transcription factor interacts with its target genes during a specific period of the cell cycle by limiting its own spatial distribution. | 10.3390/genes8010001 |
pubmed_155_9961 | Araneus cornutus spiderling activities recorded from hatching to scattering show a particular distribution of the general motor activity over a 24-hour period. More motor activity is first observed during the light sequence, while at a nocturnal activity distribution appears after the 2nd nymphean ecdysis. | pubmed_155_9961 |
pubmed_270_21101 | PURPOSE
This study was conducted to assess the efficacy of antibiotic-loaded polymethylmethacrylate (PMMA) beads in the management of lower extremity extracavitary prosthetic arterial graft infection.
METHODS
This was a retrospective review of 34 patients treated for vascular surgical site (VSS) infections involving 36 prosthetic lower extremity arterial bypasses using antibiotic-loaded PMMA beads and culture-specific parenteral antibiotics for 4 to 6 weeks. Sites of graft infection were explored, debrided, and cultured. As determined from the results of Gram's stains of VSS purulence, PMMA powder was polymerized with an antibiotic (vancomycin, daptomycin, or tobramycin/gentamicin, or a combination), molded into a chain of beads, and implanted adjacent to the infected graft after debridement and pulsed-spray antibacterial lavage. All wounds were closed primarily with planned exploration to verify sterilization before a graft preservation or in situ replacement procedure. Treatment outcomes, including wound sterilization, were analyzed based on tissue culture isolates, procedures for persistent infection, and freedom from graft infection.
RESULTS
Cultures isolated 42 pathogens, (32 gram-positive, 9 gram-negative, 1 Candida albicans) with methicillin-resistant Staphylococcus aureus (MRSA) cultured from 16 (44%) of 36 surgical site infections. As determined from the initial operative Gram's stain or a prior culture result, vancomycin PMMA beads were implanted in 29 of 36 VSS infections at the first procedure; daptomycin (n = 4) or tobramycin (n = 3) beads were implanted in the rest. Repeat VSS exploration and culture results led to an average of 2.5 antibiotic bead replacements before definitive treatment. A sterile (no growth on tissue culture) VSS was achieved in 87% of cases before a graft preservation (n = 16) or in-situ replacement of an infected graft (n = 20) procedure. No patient deaths occurred. Early and late limb salvage was 100%. Infection recurred in 4 (11%) VSSs during a mean 23-month follow-up period, one within 3 months owing to unrecognized bowel injury associated with in situ replacement of an aortofemoral graft limb.
CONCLUSION
Antibiotic-loaded PMMA beads may be a useful adjunct in the contemporary surgical management of VSS infection involving a prosthetic graft. Wound sterilization was achieved in most VSSs before graft preservation or an in-situ replacement procedure, including infections caused by MRSA, a pathogen isolated in half of the extracavitary prosthetic graft infections. This preliminary trial shows the potential benefit of this new technique, but further study is required to prove efficacy. | 10.1016/j.jvs.2006.05.056 |
pubmed_484_16938 | We share our experience about the operative treatment of 8 patients with strictures of esophagus in this summary. The new esophagus at 5 of them was made of colon, and at 3 of them of stomach. Only one patient died. | pubmed_484_16938 |
pubmed_267_8595 | A multicentre randomized clinical trial of the TCu220C, Lippes Loop D and Copper 7 was undertaken in nine WHO Collaborating centres for Clinical Research in Human Reproduction. A total of 984, 992 and 994 devices, respectively, were inserted between 1976 and 1978. The subjects were followed for two years. At this time 18,743, 17,013 and 17,927 woman-months experience had been accumulated with each device, respectively. The Lippes Loop consistently failed to perform as well as the TCu220C regardless of age or parity. The TCu220C had statistically significantly lower pregnancy rates at one and two years of use than either of the other two devices as well as lower expulsion rates. The TCu220C had lower removal rates at one and two years than the Lippes Loop and Copper 7. At one and two years the TCu220C had significantly higher continuation rates than the other two devices. It is concluded that the TCu220C is the device of choice amongst the three devices studied. | 10.1016/0010-7824(82)90167-6 |
pubmed_835_18910 | Pneumonia is a common lung disease that is the leading cause of death worldwide. It primarily affects children, accounting for 18% of all deaths in children under the age of five, the elderly, and patients with other diseases. There is a variety of imaging diagnosis techniques available today. While many of them are becoming more accurate, chest radiographs are still the most common method for detecting pulmonary infections due to cost and speed. A convolutional neural network (CNN) model has been developed to classify chest X-rays in JPEG format into normal, bacterial pneumonia, and viral pneumonia. The model was trained using data from an open Kaggle database. The data augmentation technique was used to improve the model's performance. A web application built with NextJS and hosted on AWS has also been designed. The model that was optimized using the data augmentation technique had slightly better precision than the original model. This model was used to create a web application that can process an image and provide a prediction to the user. A classification model was developed that generates a prediction with 78 percent accuracy. The precision of this calculation could be improved by increasing the epoch, among other subjects. With the help of artificial intelligence, this research study was aimed at demonstrating to the general public that deep-learning models can be created to assist health professionals in the early detection of pneumonia. | 10.1155/2022/5260231 |
pubmed_670_752 | In 1988 an epidemic of Q fever was detected in Leszno district. During 1973-1985 all 28,066 cattle tested for C. burnetii antibodies were found to be negative. The first seroconversions were found in cows which produced stillborn young. In the following years the number of seropositive cattle increased from 8.4% in 1987 to 21.6% in 1989. In 1988 all animal workers in the district were tested for C. burnetii antibodies. Of 4,264 persons tested, 1,451 (34%) were seropositive. A detailed study of workers and animals on one farm were performed. A herd of animals was found to be seropositive (32.1%), 68% of workers in direct contact with infected animals were seropositive and 29% of persons drinking raw milk. C. burnetii strains have been isolated from ticks, wild animals and birds hunted in close proximity of the farm. The dynamics of C. burnetii infection among animals and humans in this district and the fact that there is no importation of animal herds suggests that the possible route of introduction of Q fever in this area may be with imported semen or breeding bulls. The presence of C. burnetii in ticks and wild animals indicates the transfer of Q fever to the natural environment and its maintenance in this territory. | 10.1007/BF00145684 |
pubmed_234_17796 | The pattern of faecal excretion of Vibrio cholerae was studied over a duration of eight months among 13 cholera convalescents by two-weekly surveillance cultures. Stools and rectal swabs were cultured on Thiosulphate citrate bile salts sucrose (TCBS) agar for the recovery of vibrio pathogens. Clinical phase and convalescent phase V. cholerae strains were compared for antibiogram profiles. The population of vibrios recovered from faecal inocula was usually scanty (<10(3) vibrios/g). All clinical isolates except three were concordant with convalescent phase strains. Sensitivity to tetracycline was uniform for concordant V. cholerae strains, with minimum inhibitory concentration (MIC) ranging from 0.54-4.0 microg/ml. Nine (69.2%) of the convalescents had positive faecal cultures for periods ranging from two weeks to more than seven months. Two adults whose excretions lasted several months also tested positive for human immuno-deficiency virus (HIV) infections. The significance of stool surveillance cultures for identifying asymptomatic infections among convalescents who may need chemotherapy to abolish excretion is emphasised. However, it could not be established with certainty if vibrios excreted during convalescence were from enteric colonization by the causative strains, or re-infections with the common strains in circulation. | 10.1023/a:1007541317104 |
pubmed_695_17447 | Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load-bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair. | 10.1002/dvdy.278 |
pubmed_454_4282 | BACKGROUND
Docetaxel and oxaliplatin are active agents for advanced gastric cancer (GC). The combination of these two drugs in a triweekly schedule is an active and attractive regimen for gastric cancer but with significant hematological toxicities. A multicenter phase II study was designed to establish an active regimen with good tolerability by using a weekly docetaxel-oxaliplatin (DO) combination in GC patients.
METHODS
Eligible patients had histologically confirmed stage IV gastric cancer without previous palliative chemotherapy; age ≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2; at least one measurable lesion; and adequate hematological, renal, and liver functions. All patients received premedications with dexamethasone and 5-HT3 antagonist before the chemotherapy. Docetaxel (Taxotere®; Sanofi-Aventis) 30 mg/m(2) followed by oxaliplatin (Eloxatin®; Sanofi-Aventis) 65 mg/m(2) were administered on days 1 and 8 of each 21-day cycle. Treatment continued until disease progression, intolerable toxicity, or consent withdrawal. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Tumor responses were evaluated every 2 cycles by the Response Evaluation Criteria in Solid Tumors Guidelines.
RESULTS
From May 2007 to December 2008, a total of 47 patients were enrolled. There were 8 females and 39 males with a median age of 57 years (range 26-76). Forty-three patients were evaluable for response. Two patients obtained a complete response (4.7%) and 12 patients had a partial response (27.9%), with an overall response rate of 32.6% (95% confidence interval [CI] 19.1-48.5); 20 patients experienced stable disease (46.5%), and the disease progressed in 9 patients (20.9%). Median time to disease progression was 4.2 months and median overall survival was 8.3 months. All 47 patients were assessable for toxicity. Major grade 3/4 hematological toxicities were anemia (5 patients, 10.6%), neutropenia (2 patients, 4.3%), and leukopenia (1 patient, 2.1%). The most common grade 3/4 non-hematological toxicities were fatigue (3 patients, 6.4%) and aspartate aminotransferase (AST) elevation in 3 patients (6.4%).
CONCLUSIONS
The combination of weekly DO demonstrated a well-tolerated profile with moderate activity in the treatment of advanced gastric cancer. Further studies of the combination together with a fluoropyrimidine are warranted. | 10.1007/s10120-011-0060-2 |
pubmed_101_9639 | STUDY OBJECTIVES
Research has documented that adverse childhood experiences (ACEs) are associated with increased adult sleep disturbances, little is known about whether positive childhood experiences (PCEs) influence sleep health in adulthood. This study aimed to examine the associations of ACEs and PCEs with adulthood insomnia, as well as the extent to which PTSD and depressive symptoms mediated these associations.
METHODS
A sample of 7245 adults in China (male 32.7%; mean age 38.09 years, SD = 7.84, range from 18 to 81) completed self-report questionnaires to assess ACEs, PCEs, PTSD and depressive symptoms. Multiple linear regressions were used to examine the independent and interaction effects of ACEs and PCEs on insomnia. Path analyses were performed to examine the direct and indirect effects of ACEs and PCEs on insomnia.
RESULTS
After adjustment of demographics, ACEs (β = 0.11, p < 0.001) and PCEs (β = -0.09, p < 0.001) were both independently associated with adulthood insomnia, while the relationship between PCEs and insomnia was weakened but still significant among participants with high levels of ACEs. After controlling for demographics, PTSD and depressive symptoms partially mediated the overall effect of PCEs on insomnia, and fully mediated the relationship between ACEs and insomnia.
CONCLUSIONS
These data demonstrate that both positive and adverse childhood experiences influence adulthood insomnia. The findings highlight the importance of joint assessment of PCEs and ACEs to prevent and intervene insomnia. Optimizing the early childhood environment may help to foster healthy sleep throughout the life course. | 10.1016/j.sleep.2021.01.022 |
pubmed_265_6362 | The American Board of Emergency Medicine gathers extensive background information on emergency medicine residents and the programs in which they train. Before the compilation of this report, this information has not been widely available. | 10.1016/s0196-0644(98)70208-2 |
pubmed_677_5658 | Recently, novel applications of the nitroxide radicals have been proposed as antioxidant and anti-cancer agents. In view of the significance of nitroxide radical as a potential pharmaceutical agent for various applications in biological systems, it will be important to investigate further whether nitroxide radicals have a neurotoxicity or not. Blood-brain barrier permeable nitroxide radical, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM; five-membered ring nitroxide radical) would provide us more important information to explore the neuronal excitotoxicity of nitroxide radicals on the central nervous system. Every rat injected with PCAM showed limbic seizure with secondary generalization. PCAM administration resulted in neuronal cell loss in CA1 area, which is closely associated with the neurotoxicity of endogenous glutamate and nitroxide itself. More detailed studies on their possible toxicity of nitroxide radicals will be needed before the prospect of moving nitroxide from the experimental to the clinical arena when nitroxide radicals would be used for CNS disease in future. | 10.1023/b:nere.0000035804.80383.a1 |
pubmed_439_18689 | PURPOSE
Post-operative pain in the palm and scar area is the most common complication after carpal tunnel release and injury to the terminal branches of the palmar cutaneous nerve is generally considered one of the causes for this complication. The Authors performed an intraoperative study preserving the terminal branches of the palmar cutaneous branch of the median nerve and verifying the frequency, location and direction of the branches that cross an interthenar incision.
METHOD AND MATERIAL
Eighty-five consecutive patients (57 F - 28 M, mean age 66 y) underwent carpal tunnel release between February and June 2021. The cutaneous branches crossing the incision were identified and preserved by careful dissection. Subsequently they were counted and classified by their direction and distance from the proximal border of the transverse carpal ligament.
RESULTS
Sensory branches were found in 40 % of cases (34/85) and their origin was observed at an average of 1.05 cm (0-1.8 cm) distal from the proximal border of the carpal tunnel. A total of 44 branches were observed of which 23 branches crossed the incision with a transverse course and 21 with an oblique, generally proximal-distal radio-ulnar course. The subcutaneous layer overlying the distal third of the transverse carpal ligament was found to be devoid of sensory branches, therefore it can be considered a relatively safe area.
CONCLUSION
Isolation and protection of palmar sensory branches is important for improving carpal tunnel release results. This goal can be more easily achieved by locating the skin incision on the distal third of the transverse carpal ligament, where the sensory branches have a lower frequency, possibly associated with a second proximal incision (biportal technique) to better visualize the proximal portion of the ligament and antebrachial fascia. | 10.1055/a-1777-6694 |
pubmed_880_20950 | The title compound, C(11)H(16)O(3), was obtained by reaction of dimedone, 5,5-dimethylcyclohexane-1,3-dione, and α-chloro-acetone. The cyclo-hexenone ring exhibits an envelope conformation with puckering amplitudes Q = 0.433 (2) and Φ = -109.0 (3)°. The 2-oxopropyl fragment is almost perpendicular to the cyclo-hexa-none ring [dihedral angle = 77.72 (8)°]. In the crystal, the mol-ecules are linked to each other through O-H⋯O hydrogen bonding, building a chain parallel to the b axis. | 10.1107/S1600536809049046 |
pubmed_300_3787 | Closures of care homes have received considerable public attention. Fee levels and the cost of upgrading homes to meet the national minimum standards have been identified as the main factors influencing closures. The present paper compares private residential homes, dual-registered homes and nursing homes for older people which have closed between 1996 and 2001 with homes which have remained open. Homes which closed tended to be: smaller; to have had lower occupancy levels in 1996; to be the only home run by the organisation; to occupy converted buildings; to occupy multi-storey buildings, and if so, to have no lift; to have more shared bedrooms; and to have en suite facilities in none or only some of the bedrooms. These factors were interrelated and the effect of these variables in combination was examined using multivariate (logistic regression) analysis. Among the homes which remained open, only 34% provided at least 80% of places in single rooms, which was to have become the national minimum standard for existing homes until the standards were amended in March 2003. A separate analysis of data on social climate found that the homes with a more positive social environment were those most likely to have closed. The findings support the view that there is likely to be an increase in the importance of homes run by corporate providers relative to homes run as single, owner-managed homes, with a consequent reduction in choice for potential residents. At the same time, projections of future demand in a range of countries indicate that a considerable increase in provision will be required to meet the expected growth in the population of dependent older people, while developments in alternative forms of accommodation are unlikely to meet the growth in demand in the foreseeable future. | 10.1111/j.1365-2524.2004.00495.x |
pubmed_368_14472 | BACKGROUND
Lung cancer is the most common solid tumor in critically ill cancer patients who are admitted to intensive care units (ICUs). An ICU trial consists of unlimited ICU support for a limited time period.
CASE REPORT
We present the case of a 60-year-old woman with newly diagnosed metastatic lung adenocarcinoma who required mechanical ventilation due to respiratory failure. Empirical erlotinib treatment was administered through a nasogastric feeding tube as part of an ICU trial, which led to a dramatic and durable response.
CONCLUSION
Empirical erlotinib should be considered when epidermal growth factor receptor (EGFR) mutations are suspected in ICU newly diagnosed patients with lung adenocarcinoma. | pubmed_368_14472 |
pubmed_735_11322 | Stem cell therapy (SCT) has shown very promising preclinical results in a variety of regenerative medicine applications. Nevertheless, the complete utility of this technology remains unrealized. Imaging is a potent tool used in multiple stages of SCT and this review describes the role that imaging plays in cell harvest, cell purification, and cell implantation, as well as a discussion of how imaging can be used to assess outcome in SCT. We close with some perspective on potential growth in the field. | 10.1155/2016/9240652 |
pubmed_64_27117 | OBJECTIVES
To demonstrate the efficacy, safety, and pharmacokinetics of dexmedetomidine as a potential sedative for pediatric surgery patients in the ICU.
DESIGN
Phase 3, multicenter, open-label study.
SETTING
This study included 61 patients at 13 tertiary hospitals in Japan.
PATIENTS
Pediatric patients (≥ 45 wk corrected gestational age to < 17 yr) undergoing intensive care treatment with mechanical ventilation requiring greater than 6 hours estimated duration of sedation following elective cardiac surgery.
INTERVENTIONS
Dexmedetomidine was IV administered without a loading dose at age-specific dose regimens 0.2-1.4 (< 6 yr) and 0.2-1.0 µg/kg/hr (≥ 6 yr). The primary endpoint was the percentage of patients who did not require a rescue sedative (midazolam) infusion during mechanical ventilation or for the first 24 hours of a greater than 24 hours ventilation following the commencement of dexmedetomidine administration.
MEASUREMENTS AND MAIN RESULTS
Overall, 47 of the 61 patients (77.0%) did not require rescue midazolam. Adverse events were reported in 53 patients (86.9%). Frequently observed adverse events were hypotension (47.5%), bradycardia (31.1%), and respiratory depression (26.2%). Most of these adverse events were mild, a few moderate, and none severe. Although serious adverse events occurred in four patients, including one cardiac tamponade resulting in the withdrawal of dexmedetomidine, none of the adverse events resulted in mortality or were directly related to dexmedetomidine. The plasma dexmedetomidine concentration generally reached the target concentration of 0.3-1.25 ng/mL at 1-2 hours prior to completion of administration or immediately prior to the commencement of tapering.
CONCLUSIONS
The age-specific dose regimens of dexmedetomidine without an initial loading dose achieved an adequate sedation level during mechanical ventilation and caused no clinically significant adverse events in the intensive care pediatric patients. These effects were achieved within the therapeutic range of dexmedetomidine plasma concentration and were accompanied by minimal effects on hemodynamics and respiration. | 10.1097/PCC.0000000000002730 |
pubmed_254_3854 | OBJECTIVE
Concerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA).
METHODS
This prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made.
RESULTS
The study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment.
CONCLUSION
Shared decision making did not take significantly longer time and led to slightly more conservative decisions.
PRACTICE IMPLICATIONS
SDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation. | 10.1016/j.pec.2020.12.014 |
pubmed_1021_4785 | The therapeutic, preventive and curative, habits concerning malaria of expatriates living in Brazzaville, Congo, were investigated on two occasions. In March 1989 and April 1990, a questionnaire was handed out to the pupils of the French school to be filled in by their parents. Three quarters of the expatriates are Europeans, and 85 percent of these are French. In this country where the chemoresistance of Plasmodium falciparum has been established since 1985, chemoprophylaxis was regularly performed by expatriates during their first years of residence to diminish later on; in 1989 it was still practised by more than 50 percent of adults who had been living in the tropics for more than 10 years, but in 1990 this proportion had fallen to 35 percent. Chemoprophylaxis is provided by chloroquine in 3 out of 4 persons and by amodiaquine in 1 out of 5. Mefloquine and the chloroquine-proguanil combination are still rarely prescribed as preventive treatments. About 50 percent of the expatriates have had at least on attack of malaria in the previous 2 years, with or without chemoprophylaxis and irrespective of the measures taken to avoid mosquito bites. Mosquito nets, never sprayed with insecticides, are little used, but air-conditioning at night is favoured by 80 percent of the population studied. Curative treatment was distinctly altered between 1989 and 1990, with a rapidly increasing use of mefloquine or halofantrine after confirmation of the diagnosis or as presumptive therapy. | pubmed_1021_4785 |
pubmed_558_18087 | As a naturally wide distributed flavone, chrysin exhibits numerous biological activities including anticancer, anti-inflammatory, and antimicrobials activities. Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of antibacterial agents. We first used a structure-based approach to develop 18 novel chrysin analogues that target FabH for the development of new antibiotics. Structure-based design methods were used for the expansion of the chrysin derivatives including molecular docking and SAR research. Based on the results, 5-hydroxy-2-phenyl-7-(2-(piperazin-1-yl)ethoxy)-4H-chromen-4-one (3g) showed the most potent antibacterial activity with MIC of 1.56-6.25 microg/mL against the test bacterial stains, and docking simulation was performed to position compound 3g into the Escherichia coli FabH active site to determine the probable binding conformation. The biological assays indicated that compound 3g is a potent inhibitor of E.coli FabH as antibiotics. | 10.1016/j.bmc.2009.07.046 |
pubmed_756_13000 | UNLABELLED
PREMISE OF THE STUDY
Dispersal is a major feature of plant evolution that has many advantages but is not always favored. Wide dispersal, for example, leads to greater seed loss in oceanic-island endemics, and evolution has favored morphologies that limit dispersal. I tested the hypothesis that selection favored limited dispersal on gypsum islands in western North America, where edaphic communities are sparsely vegetated except for a specialized flora that competes poorly with the surrounding flora. •
METHODS
I applied a series of comparative phylogenetic approaches to gypsophilic species of Mentzelia section Bartonia (Loasaceae) to investigate the evolution of limited dispersal function in seed wings, which increase primary dispersal by wind. Through these tests, I determined whether narrowed wings were selected for in gypsophilic species. •
KEY RESULTS
Gypsophily was derived four to seven times. Seed area was not significantly correlated with gypsophily or wing area. Wing area was significantly smaller in the derived gypsum endemics, supporting the hypothesis in favor of limited dispersal function. A model-fitting approach identified two trait optima in wing area, with gypsum endemics having a lower optimum. •
CONCLUSIONS
Evolution into novel ecologies influences morphological evolution. Morphological characters have been selected for limited dispersal following evolution onto gypsum islands. Selection for limited dispersal ability has occurred across animals and plants, both in oceanic and terrestrial systems, which suggests that reduced dispersal ability may be a general process: selection favors limited dispersal if the difference in survival between the habitat of the parent and the surrounding area is great enough. | 10.3732/ajb.1300075 |
pubmed_1142_4386 | BACKGROUND
Management of cancer-related pain relies on the access to opioids. When regular opioids as morphine are not tolerated or are insufficient, adjuvant opioids as methadone are an affordable and effective analgesic.
AIM
The aim of the project was to describe the pattern of use and clinical experiences of methadone in patients with cancer-related pain at a low-resource hospital in Hyderabad, one of few Indian cancer centers with permission to prescribe methadone.
METHODS
Medical records of all patients who had been prescribed methadone, September 9, 2017 and November 19, 2019 were studied retrospectively. Data on analgesic treatment and opioid side effects were analyzed.
RESULTS
A total of 93 adult cancer patients were included in the study. A majority of patients (79%) were prescribed opioid analgesic, mainly morphine, before methadone introduction. The initial daily dose of methadone ranged between 5 and 22.5 years and in the vast majority of the patients 5 mg, divided in two daily administrations. A good analgesic effect, with decreased pain, was reported in 60% of the patients. No severe side effects were reported.
CONCLUSIONS
In this study, methadone as a primary opioid was used with a good analgesic effect for cancer pain in a low-resource setting. Indication for methadone was mainly uncontrolled pain with a regular opioid treatment. No severe adverse effects were reported. Further research and prospective studies are needed on methadone treatment in low-resource settings to establish the robust guidelines to support prescribing physicians. | 10.4103/IJPC.IJPC_275_20 |
pubmed_194_10187 | Two patients who had had no previous psychiatric symptoms became psychotic after their antiparkinsonism medication was changed from levodopa alone to a combination of levodopa and carbidopa, despite adherence to the appropriate and recommended dosage. Psychiatric symptoms disappeared after treatment with levodopa alone was resumed. | 10.1212/wnl.26.7.699 |
pubmed_452_15506 | This article provides the dataset for the use of power Doppler ultrasound to assess the equine uterus from the recent research article titled "Power Doppler can detect the presence of 7-8 days conceptuses prior to flushing in an equine embryo transfer program"(1). The vascularization of the endometrium was objectively assessed in mares by quantification of pixels in bitmap format (BMP) using computer assisted analysis of images. Fifty-two mares were examined on days 7 (26 mares) and 8 (26 mares) post-ovulation prior to performing flushing procedures for embryo recovery. Receiver operating characteristic (ROC) curves and Youden's J statistics were used to evaluate the value of the suggested variable in terms of its diagnostic value for identification of early pregnancy and to establish cut-off values allowing differentiation between pregnant and non-pregnant mares on days 7 and 8 post-ovulation. | 10.1016/j.dib.2020.105616 |
pubmed_98_24342 | The coronavirus disease-2019 (COVID-19) pandemic has not only changed the lives of people around the world but also affected all areas of the healthcare system, including sleep medicine. However, no studies in Korea have investigated the status of domestic sleep centers and their challenges during the pandemic.An online survey was performed from December 2020 to January 2021. Hospitals that belonged to sleep-related academic societies and were considered well managed were included in this survey. The questionnaire focused on changes in sleep center operations, infection control policies, and patient treatment since the start of the COVID-19 pandemic. Telemedicine and future directions for sleep medicine services were also investigated.Of the 20 sleep centers that responded, 80% were at university hospitals with more than 500 inpatient beds. During the third wave of the COVID-19 pandemic in Korea (November-December 2020), the routine operating schedule of the sleep study room was reduced in 30% of the sleep centers compared to November-December 2019 (before COVID-19). The number of type 1 polysomnographies performed decreased in 85% of the sleep centers. In contrast, in-lab positive airway pressure (PAP) titrations decreased in 40%, remained unchanged in 35%, and increased in 25%. With respect to prescriptions, 30% of the sleep centers increased the number of prescriptions for auto-titrating continuous PAP. However, 60% of the sleep centers reported no change in the rate of fixed continuous PAP and auto-titrating continuous PAP prescriptions. All sleep centers that participated in this survey agreed that the need for documented infection control regulations will continue after the COVID-19 pandemic. Since the beginning of the pandemic, 30% of the centers have tried telemedicine. However, respondents expressed concern about telemedicine, citing a number of practical issues.Compared to countries where the COVID-19 pandemic was severe, Korea had less impact of COVID-19 on the sleep center operations and sleep apnea treatment. Infection and quality control in the sleep study room are important and inevitable issues, and regulation within each institution is necessary. Further research and discussion are needed regarding telemedicine and home sleep apnea test in Korea. | 10.1097/MD.0000000000028461 |
pubmed_996_2495 | The present study was carried out to investigate whether there was any modulation of the spinal monosynaptic reflexes during mastication in the healthy humans and urethane-anesthetized rabbits and to elucidate the central neural mechanisms responsible for the modulation in the urethane-anesthetized rabbits. 1. Human soleus H-reflex was significantly facilitated during the rhythmical jaw movements and rhythmical gum chewing. 2. There was no significant difference in the magnitude of the facilitation between the jaw-opening and -closing phases. 3. In the rabbits, monosynaptic reflex (MSR) volleys recorded from the tibial nerve (TIB) innervating the crural extensors and the common peroneal nerve (CP) innervating the crural flexors tonically increased in amplitude during the masticatory movements induced by either intraoral stimulation or repetitive stimulation of the cortical masticatory area (CMA). 4. Antidromic field potentials in the anterior horn of the lumbar cord evoked by the stimulation of TIB and CP increased during the CMA-induced actual and fictive mastication. 5. There was no significant change in the amplitude of the directly evoked antidromic potential in the primary afferents by intraspinal stimulation during the CMA-induced mastication compared with the resting state. It was concluded that (1) the MSR of the crural muscles undergoes a tonic non-reciprocal facilitation during mastication, (2) the stomatognathic afferents induced during mastication are not essential for the facilitation, and (3) an increase in the excitability of motoneurons is mainly involved in the facilitation of the MSR during mastication. | 10.5357/koubyou.61.21 |
pubmed_1004_24848 | Anterior choroidal artery infarction (AChAI) can be the source of aphasia and spatial neglect, but we have no idea of the other possible cognitive disorders. Here, we investigated these disorders in a relatively large cohort of AChAI patients. Twenty patients with relatively recent infarction (left side: 13; mean delay = 47.4 days; 10 men; mean age = 59.6; mean education level, EL = 10.3) were included. We assessed nonspatial attention (alertness, Go Nogo, divided attention and visual vigilance from the computerized test TEA), spatial attention (bell test), language (BDAE) orientation (time, place), short-term memory (forward and backward digit spans, spatial span), executive functioning (WCST, TMT A and B, categorial evocation), delayed memory (Buschke verbal test, Rey figure test), and retrograde memory (questionnaire on famous events). The performance level was compared with that of 20 control subjects matched in age and EL. AChAI patients were impaired in several tests of attention (slowness, increase in omission and error rate), executive functioning (TMT B; categorical evocation) and delayed memory. Conversely, we found preservation of spatial attention, language, orientation, short-term memory, WCST, and retrograde memory. In conclusion, at the secondary phase post-stroke, these patients can present with moderate disorders of attention, memory and executive functioning, which are clearly less severe than what is usually observed following thalamic or cortical lesions. | 10.1007/s00415-008-0931-6 |
pubmed_419_14873 | The high demand for keratinolytic enzymes and the modest presentation of fungal keratinase diversity studies in scientific sources cause a significant interest in identifying new fungal strains of keratinase producers, isolating new enzymes and studying their properties. Four out of the 32 cultures showed a promising target activity on protein-containing agar plates-Aspergillus amstelodami A6, A. clavatus VKPM F-1593, A. ochraceus 247, and Cladosporium sphaerospermum 1779. The highest values of keratinolytic activity were demonstrated by extracellular proteins synthesized by Aspergillus clavatus VKPM F-1593 cultivated under submerged conditions on a medium containing milled chicken feathers. The enzyme complex preparation was obtained by protein precipitation from the culture liquid with ammonium sulfate, subsequent dialysis, and lyophilization. The fraction of a pure enzyme with keratinolytic activity (pI 9.3) was isolated by separating the extracellular proteins of A. clavatus VKPM F-1593 via isoelectric focusing. The studied keratinase was an alkaline subtilisin-like non-glycosylated protease active over a wide pH range with optimum keratinolysis at pH 8 and 50 °C. | 10.3390/ijerph192113939 |
pubmed_714_14752 | Mucor endocarditis after cardiovascular surgery is rare and usually fatal. We report the first known case of prosthetic aortic valve mucormycosis in a patient without predisposing risk factors who was successfully treated using a combination of early antifungal drug therapy and surgical removal of infected material. | 10.1378/chest.116.6.1818 |
pubmed_1000_20545 | Capitation contracting has created new challenges in the world of health care. The payment emphasis in a capitated environment concentrates on prepayment of services. Opportunities are created to control health care dollars by the physician or hospital group, but the potential downside must also be recognized. This article introduces the Provider Excess Loss (or "stop loss") insurance product and some of the main features of coverage. This insurance is specifically designed to protect providers in a capitated environment and is purchased by Physician Hospital Organizations (PHO), Independent Physician Associations (IPA), and physician-owned HMOs, among others. The emphasis is on collective purchasing. Focus on the main policy features-deductible options, allowable charges, and premium factors-should ensure a basic understanding of how coverage works and how to design coverage to make it fit the unique needs of each provider's risk. | pubmed_1000_20545 |
pubmed_43_19431 | Understanding the clinical significance of variants associated with hereditary cancer risk requires access to a pooled data resource or network of resources-a "cancer gene variant commons"-incorporating representative, well-characterized genetic data, metadata, and, for some purposes, pathways to case-level data. Several initiatives have invested significant resources into collecting and sharing cancer gene variant data, but further progress hinges on identifying and addressing unresolved policy issues. This commentary provides insights from a modified policy Delphi process involving experts from a range of stakeholder groups involved in the data-sharing ecosystem. In particular, we describe policy issues and options generated by Delphi participants in five domains critical to the development of an effective cancer gene variant commons: incentives, financial sustainability, privacy and security, equity, and data quality. Our intention is to stimulate wider discussion and lay a foundation for further work evaluating policy options more in-depth and mapping them to those who have the power to bring about change. Addressing issues in these five domains will contribute to a cancer gene variant commons that supports better care for at-risk and affected patients, empowers patient communities, and advances research on hereditary cancers. | 10.3390/jpm11070646 |
pubmed_641_13715 | RATIONALE AND OBJECTIVES
This study was devised to develop a method of measuring the acute effects of radiocontrast media on renal function and assessing the relationship of the dose of radiocontrast media infused with the incidence of radiocontrast-induced renal failure. In addition, the drug adenosine phosphate-magnesium chloride (ATP-MgCl2) was evaluated as a renoprotective agent.
METHODS
Eighteen patients with pre-existing renal impairment, (serum creatinine greater than 133 mumol/L) were randomized to receive a continuous infusion of ATP-MgCl2 or placebo before and during a radiocontrast procedure. Subjects were monitored with daily serum creatinine and with radionuclide renal clearance studies at baseline, during, and 24 hours after the radiocontrast procedure.
RESULTS
There was an initial deterioration in renal clearance in the entire study group (from 44.2 +/- 4.6 to 32.6 +/- 3.9 mL/min, P = .001) which was independent of the dose of radiocontrast infused. There was a persistent deterioration in renal clearance only in those who received greater than 135 mL of contrast media (from 48.6 +/- 7.8 to 37.1 +/- 3.9 mL/min, P = .05). There also was an increase in serum creatinine that persisted only in those subjects who received greater than 135 mL of contrast media (230 +/- 27 to 283 +/- 44 mumol/L, P = .01).
CONCLUSION
Persistent deterioration in renal function after radiocontrast administration appears to be dose-dependent and is not prevented by the use of ATP-MgCl2. Radionuclide techniques are useful in monitoring acute changes in renal function during radiocontrast procedures and may be of value in assessing renal impairment in future intervention studies. | 10.1097/00004424-199406000-00004 |
pubmed_524_4472 | Post-operative hemorrhage is a potentially life-threatening complication of tonsillectomy. While standard surgical maneuvers including the use of electrocautery, application of topical hemostatic agents, direct pressure, and suturing of the tonsillar pillars have traditionally been used for the treatment of severe bleeding, endovascular approaches are an important adjunct when other techniques are unsuccessful. Here, we describe the case of a 10-year-old female who presented with severe bleeding four days after tonsillectomy and adenoidectomy for chronic tonsillitis. She was taken emergently to the operating room where pulsatile bleeding was noted from the right inferior tonsillar pole. Hemostasis could not be achieved using electrocautery despite multiple attempts. The patient was taken for emergent angiography, which demonstrated an irregularity of the right tonsillar artery consistent with arterial vasospasm, and which corresponded to the intraoral site of bleeding localized by the surgeon. Coil embolization of the tonsillar artery was successfully performed, and the patient experienced no further bleeding. We conclude that endovascular embolization of branches of the external carotid artery is an effective treatment for severe post-tonsillectomy hemorrhage in children and should be considered when attempts at surgical control are ineffective. This procedure requires exceptional collaboration between the surgical, radiology, and anesthesia teams. | 10.7759/cureus.13217 |
pubmed_1123_1672 | Germ cell development requires timely transition from primordial germ cell (PGC) self-renewal to meiotic differentiation. This is associated with widespread changes in gene expression, including downregulation of stem cell-associated genes, such as OCT4 and KIT, and upregulation of markers of germ cell differentiation and meiosis, such as VASA, STRA8, and SYCP3. The stem cell-expressed RNA-binding protein Lin28 has recently been demonstrated to be essential for PGC specification in mice, and LIN28 is expressed in human germ cell tumors with phenotypic similarities to human fetal germ cells. We have therefore examined the expression of LIN28 during normal germ cell development in the human fetal ovary, from the PGC stage, through meiosis to the initiation of follicle formation. LIN28 transcript levels were highest when the gonad contained only PGCs, and decreased significantly with increasing gestation, coincident with the onset of germ cell differentiation. Immunohistochemistry revealed LIN28 protein expression to be germ cell-specific at all stages examined. All PGCs expressed LIN28, but at later gestations expression was restricted to a subpopulation of germ cells, which we demonstrate to be primordial and premeiotic germ cells based on immunofluorescent colocalization of LIN28 and OCT4, and absence of overlap with the meiosis marker SYCP3. We also demonstrate the expression of the LIN28 target precursor pri-microRNA transcripts pri-LET7a/f/d and pri-LET-7g in the human fetal ovary, and that expression of these is highest at the PGC stage, mirroring that of LIN28. The spatial and temporal restriction of LIN28 expression and coincident peaks of expression of LIN28 and target pri-microRNAs suggest important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary. | 10.1089/scd.2011.0730 |
pubmed_3_3382 | Recombinant-DNA (transgenic) animals intended for food production are approaching the market. Among them, recombinant-DNA fishes constitute the most advanced case. As a result, intergovernmental organizations are working on guidelines which would eventually become international standards for national food safety assessments of these products. This article reviews the emerging elements for the food safety assessment of products derived from recombinant-DNA animals. These elements will become highly relevant both for researchers and regulators interested in developing or analyzing recombinant-DNA animals intended to be used in the commercial elaboration of food products. It also provides references to science-based tools that can be used to support food safety assessments. Finally, it proposes recommendations for the further development of biosafety assessment methodologies in this area. | 10.1016/j.cimid.2007.11.007 |
pubmed_751_5814 | A single oral administration of a mixture of polychlorinated diphenyls (50 and mg/kg) leads to a dose-dependent increase in the cytochrome P-450 content in rat liver. The synthetic antioxidant ionol administered singly and repeatedly (30 mg/kg) does not exert any substantial influence on the hemoprotein content in the liver. Preliminary administration of ionol potentiates the action of the mixture of polychlorinated diphenyls on cytochrome P-450 induction in the liver of experimental animals. | pubmed_751_5814 |
pubmed_105_4687 | For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the overall dose and limit toxicities commonly seen with systemic administration. Effectiveness of non-ablative thermal therapy (hyperthermia) depends on the achieved thermal dose, defined as time-at-temperature, and leads to molecular dysfunction, cellular disruption, and eventual tissue destruction with vascular collapse. Hyperthermia therapy requires controlled heat transfer to the target either by in situ generation of the energy or its on-target conversion from an external radiative source. Magnetic hyperthermia (MHT) is a nanotechnology-based thermal therapy that exploits energy dissipation (heat) from the forced magnetic hysteresis of a magnetic colloid. MHT with magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs) requires the targeted deposition of MNPs into the tumor, followed by exposure of the region to an AMF. Emerging modalities such as magnetic particle imaging (MPI) offer additional prospects to develop fully integrated (theranostic) systems that are capable of providing diagnostic imaging, treatment planning, therapy execution, and post-treatment follow-up on a single platform. In this review, we focus on recent advances in image-guided MHT applications specific to liver cancer. | 10.3390/nano12162768 |
pubmed_256_17616 | This study evaluated the effect of surgical sympathectomy on pain-related behaviours in a well established model of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve in the rat. Behavioural abnormalities include spontaneous abnormal position of the hindpaw after the nerve constriction, indicative of "spontaneous pain", and changes in responses to mechanical or thermal stimuli applied to this paw. These changes are usually maximal at week 2 after the surgery, stable until weeks 3-4, and disappear between weeks 8 and 12. To assess the role of the sympathetic nervous system in the development and persistence of these abnormalities, four groups of rats were behaviourally tested: (i) rats receiving a complete sham surgery, (ii) rats with a sciatic nerve constriction produced by loose ligatures around the common nerve trunk plus a sham sympathectomy, (iii) rats receiving a lumbar sympathectomy with a sham nerve ligature, and (iv) rats receiving a simultaneous surgical lumbar sympathectomy and a sciatic nerve constriction. The efficacy of the sympathectomy was assessed by the measure of the noradrenaline level in the sciatic nerve. Sympathectomy reduced selectively or even prevented the abnormal reaction to cold temperature and to heat (45 degrees C) in rats with a peripheral mononeuropathy. In contrast, the abnormal reaction to mechanical pressure was not influenced, and the behavioural abnormalities indicating spontaneous pain were still present. Sympathectomy alone resulted in a reduction of the vocalization threshold to pressure on both hindpaws, but also a short-lasting increased tolerance to cold immersion. This study confirms the selective role of the sympathetic nervous system in affecting the development and maintenance of some abnormal pain-related behaviours to thermal stimuli in rats with a moderate, but persistent, constriction of one sciatic nerve. | 10.1016/0306-4522(95)00098-4 |
pubmed_247_12678 | We present a homology scanning microcomputer program to predict functional T-cell epitopes within proteins. By taking into account particular human or mouse restriction elements the predictions are made haplotype-specific. The generality of this approach is confirmed by (i) identification of well-characterized immunogenic T-cell determinants in lysozyme (ii) search for potential T epitopes on unanalysed proteins like the human beta 2-adrenoreceptor (iii) modification of non-immunogenic peptide sequences in order to generate T-cell determinants. | 10.1002/jmr.300040104 |
pubmed_1012_8453 | Double-labelling immunofluorescence combined with retrograde tracing revealed three subpopulations of galanin-immunoreactive nerve fibres innervating the porcine ovary. The first group originated in ipsilateral dorsal root ganglia Th11-L5 and exhibited colocalization with substance P-, but not with tyrosine-hydroxylase- or dopamine-beta-hydroxylase-immunoreactivity. These fibres supplied primordial follicles and large arteries of the ovarian hilus. The second group, arising from the sympathetic inferior mesenteric ganglion, was galanin-immunoreactive, but non-reactive to substance P-, dopamine-beta-hydroxylase- or tyrosine-hydroxylase-antisera. Fibres of this type were sparsely distributed in the ovarian cortex. They were observed in connection with small cortical arterioles or in the ovarian cortical stroma. The third group of galanin-containing nerve terminals originated from postganglionic neurons located in sympathetic chain ganglia Th15-L3 and S1. Most of them contained tyrosine-hydroxylase- and dopamine-beta-hydroxylase-immunoreactivity. This subset of galanin-positive nerve fibres was the least frequent and was almost exclusively associated with cortical arterioles. The findings are indicative of an involvement of galanin in autonomic and sensory neuronal functions in the ovaries, possibly control of follicle maturation and blood flow. | pubmed_1012_8453 |
pubmed_847_20243 | HLA-C*06:325 differs from HLA-C*06:02:01:01 by a non-synonymous nucleotide substitution in codon 145, changing Arginine to Histidine. | 10.1111/tan.14618 |
pubmed_55_1035 | OBJECTIVE
To evaluate the efficacy of anterior cervical decompression, fusion and titanium plate fixation in sub axial cervical spine injuries in respect of neurological outcome, postoperative stability and early rehabilitation. The Descriptive case series study was conducted at Department of Neurosurgery, Liaquat University Hospital, Jamshoro, Sindh Pakistan during year 2005 to 2007.
METHODS
Patients with cervical spine injuries were admitted during study period were included in this study. All cases were evaluated for their clinical features. During initial phase, level and degree of neurological injury was assessed using ASIA impairment scale. Cervical traction was applied to all patients. Operative and post operative record with x-rays and MRI were maintained. Patients with Injury to C3-6 underwent decompression, fusion and local titanium plate implant fixation by anterior approach. The follow-up ranged from 6 to 12 months with clinical and radiological assessment.
RESULTS
37 cases of sub axial cervical spine injuries included in this study during year 2005 to 2007. Out of these, 28 (75.67%) were males and 9 (24.32%) females. Age range was 8-60 years mean (32-40%). Common mode of injury was fall. Post operative follow up showed good clinical and radiological outcome, bony fusion and favour early rehabilitation. No immediate complication found except temporary dysphagia.
CONCLUSION
Anterior decompression, fusion and titanium plate fixation is an effective method with good neurological and radiological outcome. | pubmed_55_1035 |
pubmed_550_1059 | Muscle dysfunction is a characteristic feature of chronic obstructive pulmonary disease (COPD). Recent studies suggest that cytokines may operate as local regulators of both muscle function and regeneration. The aim of the present study was to characterise the expression of different cytokines in the external intercostal muscle of COPD. Muscle biopsies were obtained from 25 stable COPD patients and eight healthy controls. Local tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, -6 and -10 expressions (real-time PCR and ELISA), sarcolemmal damage (immunohistochemistry), and the transcript levels of CD18 were assessed. Muscle TNF-alpha and IL-6 transcripts were significantly higher in COPD patients compared with controls, and IL-1beta and sarcolemmal damage showed a strong tendency in the same direction. Similar results were observed at protein level. The CD18 panleukocyte marker was similar in COPD and controls. Respiratory muscle function was impaired in COPD patients and it correlated to both the severity of lung function impairment and TNF-alpha muscle expression. Chronic obstructive pulmonary disease is associated with the upregulation of pro-inflammatory cytokines in the intercostal muscles. This phenomenon might be involved in respiratory muscle dysfunction. | 10.1183/09031936.00152005 |
pubmed_99_15654 | Isovolumic relaxation abnormalities have been noted in the ischemic left ventricle, but altered end-diastolic distensibility, as well as the role of right ventricular distention, is debated. Accordingly, left ventricular end-diastolic pressure and myocardial segment length were studied in the open-chest dogs with critical (90% diameter reduction) stenoses on both left anterior descending and circumflex coronary arteries. Regional segment length was measured with ultrasonic crystals placed subendocardially, and ischemia was induced by pacing tachycardia for 3 minutes. Transient vena caval occlusion was done to unload the right ventricle and to produce a series of left ventricular end-diastolic pressure and left ventricular end-diastolic segment length points before and after pacing tachycardia. After pacing tachycardia, left ventricular end-diastolic pressure (9.3 +/- 0.9 to 16.9 +/- 1.5 mm Hg, P less than 0.001) and time constant T of left ventricular isovolumic pressure decline (46 +/- 3 to 60 +/- 5 msec, P less than 0.01) increased, with an increase in left ventricular end-systolic segment length (9.8 +/- 0.3 to 10.5 +/- 0.3 mm, P less than 0.001), and a decrease in fractional shortening (17.6 +/- 1.7 to 14.5 +/- 1.3%, P less than 0.01) in the ischemic region, although right ventricular end-diastolic pressure was unchanged. With vena caval occlusion, right ventricular diastolic pressure fell promptly to near zero, followed by decrease in left ventricular pressure and segment length. In each dog, the left ventricular end-diastolic pressure-end-diastolic segment length relation shifted upward after pacing tachycardia. Pacing tachycardia was performed again in six dogs without stenoses. In this group, fractional shortening was preserved after pacing tachycardia (15.7 +/- 2.3 to 15.3 +/- 2.3%, NS), and left ventricular end-diastolic pressure (9.4 +/- 1.8 to 9.8 +/- 1.8 mm Hg, NS) was unchanged. The left ventricular end-diastolic pressure-segment length relation did not shift upward after pacing tachycardia. These data indicate that extrinsic compression of left ventricle by right ventricle is unlikely to be responsible for the upward shift in this model, and the upward shift in end-diastolic left ventricular pressure-segment length relations, as well as dynamic left ventricular diastolic pressure-segment length, supports the concept that persistent myosin-actin interaction throughout diastole plays an important role in the diastolic abnormalities in this angina physiology model. | 10.1161/01.res.55.2.203 |
pubmed_509_24212 | BACKGROUND
The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, multi-institutional, collaborative network of 27 epilepsy centers throughout the U.S., Australia, and Argentina, with the objective of collecting detailed phenotypic and genetic data on a large number of epilepsy participants. The goals of EPGP are (1) to perform detailed phenotyping on 3750 participants with specific forms of non-acquired epilepsy and 1500 parents without epilepsy, (2) to obtain DNA samples on these individuals, and (3) to ultimately genotype the samples in order to discover novel genes that cause epilepsy. To carry out the project, a reliable and robust informatics platform was needed for standardized electronic data collection and storage, data quality review, and phenotypic analysis involving cases from multiple sites.
METHODS
EPGP developed its own suite of web-based informatics applications for participant tracking, electronic data collection (using electronic case report forms/surveys), data management, phenotypic data review and validation, specimen tracking, electroencephalograph and neuroimaging storage, and issue tracking. We implemented procedures to train and support end-users at each clinical site.
RESULTS
Thus far, 3780 study participants have been enrolled and 20,957 web-based study activities have been completed using this informatics platform. Over 95% of respondents to an end-user satisfaction survey felt that the informatics platform was successful almost always or most of the time.
CONCLUSIONS
The EPGP informatics platform has successfully and effectively allowed study management and efficient and reliable collection of phenotypic data. Our novel informatics platform met the requirements of a large, multicenter research project. The platform has had a high level of end-user acceptance by principal investigators and study coordinators, and can serve as a model for new tools to support future large scale, collaborative research projects collecting extensive phenotypic data. | pubmed_509_24212 |
pubmed_190_15878 | OBJECTIVE
The objective was to examine the psychometric properties of two brief screening questionnaires for common mental disorders in general practices in areas speaking the three main Nigerian languages.
METHOD
Consecutives attendees of selected general practices in Ibadan, Enugu and Kaduna were screened with the General Health Questionnaire 12-item version (GHQ12) and K6. We selected all cases and 50% of noncases for second-stage interview with the Composite International Diagnostic Interview. The receiver operating characteristic curves were generated for both questionnaires, and optimal cutoffs were determined. Exploratory factor analysis was done for both questionnaires.
RESULTS
The K6 had an area under the curve (AUC) of 0.62 for depression and 0.58 for anxiety disorder. The GHQ12 had an AUC of 0.74 for depression, while that for generalized anxiety disorder was 0.6. The GHQ12 was able to correctly classify 75% of the subjects with or without depression, while the K6 was able to correctly classify 56% of the subjects with or without depression. The optimal cutoff for both questionnaires was 4, selecting the point of best balance of sensitivity and specificity.
CONCLUSION
The findings suggest that the GHQ12 will be a useful tool in screening for common mental disorders in general practice in Nigeria. | pubmed_190_15878 |
pubmed_22_25475 | OBJECTIVE
Type 1 diabetes mellitus (T1DM) is a lifelong, metabolic disorder, typically arising in childhood and adolescence. Despite recent advances in diabetes management techniques, glycemic control remains substandard for many individuals This study examined the role of parental and child self-regulation in predicting effective glycemic control in children and adolescents with Type 1 diabetes mellitus (T1DM).
METHOD
Sixty-three families (with children aged 3-18 years) with T1DM participated. Child, maternal, and paternal measures of temperament, including surgency (behavioral self-regulation), negative affect (emotional selfregulation), and effortful control (cognitive self-regulation) were collected, along with demographic information and haemoglobin A1c (glycemic control).
RESULTS
Higher parental and child effortful control was associated with better glycemic control. Higher child negative emotionality was associated with poorer glycemic control. No significant interactions between child and parent measures were identified.
CONCLUSIONS
Both parental and child self-regulation play an independent role in glycemic control, and serve as targets for intervention in improving diabetes management in children and adolescents. (PsycINFO Database Record | 10.1037/hea0000554 |
pubmed_913_8115 | Although the cellular ribonucleates in normally growing cells are virtually saturated with respect to their customary complement of methyl substituents, it has often been reported that 'marginal' levels of (homologous) methylation can be detected when ribonucleates and enzymes from the same source material are incubated, together with S-adenosylmethionine, in vitro. Experiments were designed to acquire new insights that might be useful for circumscribing the number of possible interpretations that could be advanced to account for the introduction of 'supernumerary' methyl groups during (homologous) methylation of wheat RNA by wheat enzymes, in vitro. For a large fraction of the supernumerary methyl groups that can be introduced into wheat RNA, in vitro, it was not possible to adduce convincing evidence in support of the view that any appreciable quantity of methyl groups is ever introduced at these same sites, in vivo. The possibility that these supernumerary methyl groups might have transient existence, in vivo, and the potential physiological significance of any such occurrence are dealt with as part of a more general discussion of the experimental findings. | 10.1139/o77-155 |
pubmed_762_13366 | Predicting who will develop cancer and how the cancer will behave and respond to therapy after diagnosis are some of the potential benefits of the ongoing genetic revolution that can be envisioned within the next decade. Translational applications of genomic-based research efforts may actually precede the development of effective therapeutic agents that can exploit the vast amounts of data derived from these efforts. In the future, understanding the wealth of information generated by high-throughput molecular efforts and how it can be applied to clinical problems will likely be critical to the surgeon who guides the multidisciplinary care of the cancer patient. This review will discuss the advances in our understanding of the human genome (DNA), its derived transcriptome (RNA), and its translated proteome (proteins) and will focus on the translation of this information into routine clinical practice. In particular, we will focus on the potential for clinical application of microarray-based gene-expression profiling to the diagnosis, prognosis, and therapy of malignancies. | 10.1245/aso.2003.05.031 |
pubmed_765_15386 | AIM
We investigated the impact of varying definitions on the prevalence of neurodevelopmental impairment (NDI) in children born very preterm at 6.5 years of age.
METHODS
Cognitive development and neurosensory impairments were assessed in 91 children (40/51 girls/boys) born <32 gestational weeks, in 2004-2007 in Uppsala county, Sweden. The results were compared with data from a reference group of 67 children born full term. The prevalence of NDI in the present cohort was reported according to definitions used by seven contemporary studies of children born very or extremely preterm.
RESULTS
The prevalence of severe NDI varied from 2% to 23% depending on the definition used. The prevalence of cognitive impairment varied from 2% (-3 SD according to test norms) to 16% (-2 SD according to control group), the prevalence of cerebral palsy from 0% (severe) to 9% (any) and the prevalence of severe visual impairment from 0% (blindness) to 1% (visual acuity < 0.3). There were no children with severe hearing impairment.
CONCLUSION
A high variability in definitions affects the reporting of the prevalence of NDI in long-term follow-up studies of very or extremely preterm born children. There is a need for a better consensus to enable comparisons across studies. | 10.1111/apa.15464 |
pubmed_72_25116 | Studies pertaining to sexually transmitted infections (STIs) among rural young adults in Ethiopia are limited. This study provides information on knowledge about common STIs, and the perceptions, preferences and use of health services for STIs, among youths and healthcare providers in predominately rural Butajira, a town in south-central Ethiopia. We performed mixed-method research, using a cross-sectional survey among 3 743 randomly selected youths aged 15-24 years, in 2004, and in-depth interviews with ten healthcare providers, in 2006. Less than 38% of the youths knew the common STIs. Among the sexually active youths (n = 802), 3.9% reported having at least one STI symptom in the past 12 months, and one-half of those who had had an STI symptom did not seek care from any source. The healthcare providers reported that the stigma associated with premarital sexual activity, the shamefulness of having an STI, and a perceived lack of confidentiality and uneasiness with the public health services were impediments to treatment-seeking in the study area. The youths in this study preferred to consult with healthcare providers of the same gender who were young, friendly and had a reputation for being empathetic. Embarrassment about having an STI and fear of being noticed by a familiar individual were perceived barriers to healthcare-seeking among the youths. The results suggest that young people are vulnerable to HIV exposure due to lack of knowledge about STIs and especially as a result of having an untreated STI. Health services that are uncoordinated and unable to handle youths' sexual and reproductive health problems, as well as judgemental health professionals and prevailing sexual taboos, were also reported as impediments to youths seeking healthcare. Reorientation of the public health services and healthcare providers could improve youths' healthcare-seeking for STIs. | 10.2989/AJAR.2009.8.2.2.854 |
pubmed_649_7396 | An alloalbumin characterized by thermolability at 56 degrees C of its slow migration band is described in this paper. The comparison between this new variant and correspondent standard of the "Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio" (CISMEL) allow some remarks upon classification of variants based on the electrophoretic mobility. | pubmed_649_7396 |
pubmed_64_9692 | INTRODUCTION
Both animal studies and clinical trials have shown that daily parathyroid hormone administration promotes bone fracture healing. We previously found that weekly injections of the recombinant human parathyroid hormone teriparatide at a dosage of 20 μg/kg promoted tibial fracture healing to the same extent as daily injections of teriparatide at a dosage of 10 μg/kg in a rodent model. However, the effect of weekly teriparatide administration on human fracture healing is unreported. This protocol describes a randomised controlled clinical trial designed to evaluate whether weekly administration of teriparatide accelerates fracture repair in humans.
METHODS AND ANALYSIS
This single-centre, double-blind, randomised controlled trial will be conducted in Peking University Third Hospital. Eligible patients with Colles' fracture incurred within 48 hours will be randomly divided into two groups (n=40 per group) that will receive 14 weekly subcutaneous injections of either saline or teriparatide (40 μg/week). The primary outcome will be the time taken to achieve radiographic healing, as assessed using the modified radiographic union scale for tibial fractures. The secondary outcomes will be functional assessments, including the self-administered Patient-Rated Wrist Evaluation questionnaire, grip strength and rate of fracture non-union.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Peking University Third Hospital Medical Science Research Ethics Committee (M2020207). The findings will be disseminated in peer-reviewed publications.
TRIAL REGISTRATION NUMBER
NCT04473989: protocol version: 1. | 10.1136/bmjopen-2020-043137 |
pubmed_1020_11999 | AIMS
Recently, Apolipoprotein CIII (Apo-CIII) has gained remarkable attention since its overexpression has been strongly correlated to cardiovascular disease (CVD) occurrence. The aim of this review was to summarize the latest findings of Apo-CIII as a CVDs and diabetes risk factor, as well as the plausible mechanisms involved in the development of these pathologies, with particular emphasis on current clinical and dietetic therapies.
DATA SYNTHESIS
Apo-CIII is a small protein (∼8.8 kDa) that, among other functions, inhibits lipoprotein lipase, a key enzyme in lipid metabolism. Apo-CIII plays a fundamental role in the physiopathology of atherosclerosis, type-1, and type-2 diabetes. Apo-CIII has become a potential clinical target to tackle these multifactorial diseases. Dietetic (omega-3 fatty acids, stanols, polyphenols, lycopene) and non-dietetic (fibrates, statins, and antisense oligonucleotides) therapies have shown promising results to regulate Apo-CIII and triglyceride levels. However, more information from clinical trials is required to validate it as a new target for atherosclerosis and diabetes types 1 and 2.
CONCLUSIONS
There are still several pathways involving Apo-CIII regulation that might be affected by bioactive compounds that need further research. The mechanisms that trigger metabolic responses following bioactive compounds consumption are mainly related to higher LPL expression and PPARα activation, although the complete pathways are yet to be elucidated. | 10.1016/j.numecd.2021.09.035 |
pubmed_471_14360 | As a hole transport layer, PEDOT:PSS usually limits the stability and efficiency of perovskite solar cells (PSCs) due to its hygroscopic nature and inability to block electrons. Here, a graphene-oxide (GO)-modified PEDOT:PSS hole transport layer was fabricated by spin-coating a GO solution onto the PEDOT:PSS surface. PSCs fabricated on a GO-modified PEDOT:PSS layer exhibited a power conversion efficiency (PCE) of 15.34%, which is higher than 11.90% of PSCs with the PEDOT:PSS layer. Furthermore, the stability of the PSCs was significantly improved, with the PCE remaining at 83.5% of the initial PCE values after aging for 39 days in air. The hygroscopic PSS material at the PEDOT:PSS surface was partly removed during spin-coating with the GO solution, which improves the moisture resistance and decreases the contact barrier between the hole transport layer and perovskite layer. The scattered distribution of the GO at the PEDOT:PSS surface exhibits superior wettability, which helps to form a high-quality perovskite layer with better crystallinity and fewer pin holes. Furthermore, the hole extraction selectivity of the GO further inhibits the carrier recombination at the interface between the perovskite and PEDOT:PSS layers. Therefore, the cooperative interactions of these factors greatly improve the light absorption of the perovskite layer, the carrier transport and collection abilities of the PSCs, and especially the stability of the cells. | 10.1007/s40820-017-0140-x |
pubmed_257_21501 | The authors described the clinical signs and consequences of suffocations during sleep apnea. They presented the results of the surgical intervention of nasal obstruction in patients with sleep apnea. The during-all-night examinations of these patients proved the possibility of positive effects of surgical intervention of nasal obstruction in patients with sleep apnea. | pubmed_257_21501 |
pubmed_164_8632 | An analysis of the compartmentation and fluxes of inorganic phosphate in isolated cladophyll cells from Asparagus officinalis was made in parallel with an ultrastructural study. The elution pattern of labelled inorganic phosphate (which indicates that the asparagus cells are behaving as a system of three compartments in series) was used to quantify the fluxes between the vacuole, cytoplasm and free space. A relaxation time of 198 min was calculated for inorganic phosphate exchange between the vacuole and cytoplasm. It is, therefore, suggested that the vacuole serves to buffer the cytoplasmic inorganic phosphate concentration in the long term. However, in the short term, exchange with the vacuole will not appreciably affect the cytoplasmic inorganic phosphate concentration and thus the partitioning of photosynthetically fixed carbon. | 10.1007/BF00407084 |
pubmed_227_2576 | BACKGROUND AND AIMS
Statins are considered contraindicated in patients with chronic liver disease. Our objective was to determine the risk of developing hepatotoxicity from statin therapy in hyperlipidemic patients with hepatitis C.
METHODS
Changes in liver biochemistry values within 12 months compared with baseline were determined in 3 cohorts matched for age, sex, and body mass index: (I) 166 anti-hepatitis C virus (HCV)-positive hyperlipidemic veterans who were initiated on statin therapy; (II) 332 anti-HCV-positive veterans who had not received statin therapy; and (III) 332 anti-HCV-negative hyperlipidemic veterans who were initiated on statin therapy. An increase in liver biochemistry values was defined as mild-moderate or severe as proposed in a previous study on statin hepatotoxicity in a non-hepatitis C population.
RESULTS
In patients with hepatitis C, statin therapy (cohort I) was associated with a higher incidence of mild-moderate liver biochemistry value increases compared with those not on statin therapy (cohort II) (22.9% vs 13.3%, respectively, P = .009), but a lower incidence of severe increases (1.2% vs 6.6%, respectively, P = .015). Among patients started on statin therapy (cohorts I and III), the incidence of mild-moderate liver biochemistry value increases (22.9% vs 16.3%, respectively, P = .094), severe increases (1.2% vs 1%, respectively, P = .874), or discontinuation of statin therapy as a result of hepatotoxicity (21.6% vs 9.2%, respectively, P = .147) were similar in hepatitis C-positive and hepatitis C-negative patients.
CONCLUSIONS
Statin therapy was not associated with a higher risk of severe hepatotoxicity in patients with chronic hepatitis C and appeared safe. | 10.1016/j.cgh.2006.03.014 |
pubmed_686_10598 | Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin. | 10.1063/1.2121668 |
pubmed_150_7309 | Traumatic splenic vein aneurysm (SVA) is an extremely rare entity. Traditionally, treatment varied from noninvasive followup to aneurysm excision with splenectomy. However, there has been no prior report of traumatic SVA treated with endovascular stent graft for SVA via percutaneous transsplenic access. Therefore, we report the case of a 56-year-old man successfully treated with endovascular stent graft for traumatic SVA via percutaneous transsplenic access. | 10.4174/astr.2016.91.1.56 |
pubmed_781_20583 | The objective of this study was to evaluate the performance of 119 full sib progenies of the fifth cycle of reciprocal recurrent selection (RRS) derived from of Universidade Federal de Lavras maize breeding program. The experiment was carried out in an 11 x 11 triple lattice design at two locations (Lavras, Lambari). The plots consisted of two rows of 3 m, with four plants per 1 m and 0.60 meters of spacing between lines. The grain yield was obtained as kg/plot through weighing of husked ears. The contrast between progenies and controls was not significant, indicating there were no significant differences among the average grain yields of the progenies and controls. When considering the joint analysis, heritability was 64.2%; however, this estimate did not differ from the values estimated for each location separately. Estimates of genetic and phenotypic variance among progenies ranged from 0.21 to 0.28 and 0.30 to 0.47, respectively. Estimates of selection gain, for 10% selection intensity, indicated gains of 16% in the joint analysis of the two locations. The progenies of the fifth cycle of RRS had high average grain yield, associated with high variability. In comparison to the average grain yields exhibited by the controls, it was concluded that the progenies have the potential to be commercially exploited. | 10.4238/2015.July.27.11 |
pubmed_50_13240 | BACKGROUND
Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.
METHODS
In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.
RESULTS
Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).
CONCLUSIONS
Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .). | 10.1056/NEJMoa1800149 |
pubmed_111_10228 | During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects "compensated" distortion and not absence of it. | 10.1152/jappl.1985.59.2.295 |
pubmed_242_15122 | AIMS
Atrial fibrillation (AF) cycle length (CL) has been demonstrated to be one of the predictors for termination during ablation for AF. We evaluated the AF CL gradient between right atrium (RA) and left atrium (LA) and their mean AF CL in predicting the extent of substrate ablation.
METHODS AND RESULTS
One-hundred and thirty-six patients undergoing first ablation for persistent AF were studied. Stepwise ablation, sequentially in the following order: pulmonary veins (PV), LA, and RA, was performed to achieve AF termination. Stepwise ablation terminated AF in 110 patients (81%). In the AF termination group, AF was terminated by PV isolation (PVI) (Group P), PVI plus LA ablation (Group L), and PVI plus LA plus RA ablation (Group R) in 14 patients (13%), 49 patients (44%), and 47 patients (43%), respectively. Group R had much shorter mean AF CL than Group L (156 ± 18 vs. 174 ± 24 ms, P < 0.001) and mean AF CL in Group L was much shorter than Group P (174 ± 24 vs. 209 ± 36 ms, P = 0.004). The RA to LA AF CL gradient was not significantly different between left-side ablation (Group P + Group L) and additional RA ablation (Group R) (P = 0.177). Mean AF CL >180.50 ms predicted AF termination by PVI (Group P) with 79% sensitivity and 84% specificity while mean AF CL >165.25 ms predicted AF termination by left-side ablation (Group P + Group L) with 67% sensitivity and 75% specificity. After a mean follow-up of 15 ± 7 months, freedom from arrhythmia recurrence was significantly higher in left-side ablation (Group P + Group L) than additional RA ablation (Group R) (P = 0.024).
CONCLUSION
Baseline mean AF CL may identify the subset of patients in whom persistent AF can be terminated by different extent of substrate ablation, which may in turn predict the chance of recurrence. However, baseline RA to LA AF CL gradient cannot predict the need for additional RA ablation. | 10.1093/europace/euu330 |
pubmed_170_13060 | INTRODUCTION
leptospirosis is a zoonosis of worldwide importance. The disease is endemic in Brazil. This study was conducted to describe the clinical and laboratory presentation of leptospirosis in a metropolitan city of Brazil.
METHODS
this is a retrospective study including 201 consecutive patients with leptospirosis admitted to tertiary hospitals in Fortaleza, Brazil, between 1985 and 2006. All patients had clinical and epidemiological data suggestive of leptospirosis, and positive laboratorial test for leptospirosis (microscopic agglutination test, MAT, higher than 1:800).
RESULTS
a total of 201 patients were included, with mean age of 38.9 + or - 15.7 years; 79.1% were male. The mean length from onset of symptoms to admission was 7 + or - 3 days. The main clinical signs and symptoms at admission were fever (96.5%), jaundice (94.5%), myalgia (92.5%), headache (74.6%), vomiting (71.6%) and dehydration (63.5%). Hemorrhagic manifestations were present in 35.8%. Acute kidney injury was found in 87% of the patients. Platelet count was less than 100,000/mm(3) in 74.3%. Hematuria was found in 42.9%. Death occurred in 31 cases (15.4%).
CONCLUSIONS
leptospirosis is a globally relevant disease with potential fatal outcome. Signs and symptoms suggestive of leptospirosis must be known by any physician in order to institute early adequate treatment to improve outcome. Early indication and daily hemodialysis seems to be beneficial in this group of patients. | pubmed_170_13060 |
pubmed_536_24276 | Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative diseases that have a tremendous impact on the lives of affected individuals. There is a great probability of developing concurrent parkinsonism in AD and vice versa than would be predicted by independent prevalence of each disease. Both diseases have genetic familial forms with a prevalence of less than 5-10%, but the majority of the cases are sporadic. Several hypotheses exist regarding the etiology of these diseases, such as oxidative stress, inflammatory processes, ubiquitin-proteasome system dysfunction, energy deficits, cell cycle deficiencies and glutamate exitotoxicities. Since diagnosis occurs in late-stage disease after neuronal loss, it decreases the opportunity for neuroprotective/neurorestorative therapies. Therefore, early and specific diagnosis is required as well as new therapy approaches for the growing burden of AD and PD. | 10.1586/14737175.8.12.1865 |
pubmed_585_8383 | The first attempted bone marrow transplant (BMT) dates back to 1896. In the following centuries, the medical community pioneered an ongoing progression of breakthroughs. In 1954 the first successful solid organ transplant, the kidney, was performed. In the 1960s advances led to the first successful lung, pancreas, liver and heart transplant and in 1973 the first successful BMT was achieved. BMT has traditionally been used to treat malignant diseases. However, scientific and technological progress has expanded its scope and today, BMT is used to treat a spectrum of diseases. While BMT is a complex procedure, the medical community expects that it will one day play a role in the treatment of other diseases. As the science evolves, it is essential that nurses educate themselves about these emerging transplant populations, one of which is children with osteogenesis impefecta. This manuscript will provide nurses with a critical background on the disease, a description of the transplant theory, and the implications for the nursing care of these children. | 10.1177/1043454211426576 |
pubmed_1104_2276 | The effects of palm (P) and mixtures of palm and soybean (PS), palmolein and soybean (POS), palmstearin and soybean (PSS) oils on serum lipids and fecal fat and fatty acid excretions of humans were studied. Each oil was the dominant fat in diets consumed by ten normolipidemic live-in individuals. Test diets were assigned by randomization. All four diets had a similar influence on total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglycerides (TG) and phospholipids (PL). Fecal fat excretion was higher (1.81, 1.80 g/d) with PS and PSS and lower (1.78, 1.42 g/d) with P and POS diets. Excretions of palmitic (C16: 0), oleic (C18: 1), and linoleic (C 18: 2) acids were similar for all diets. Excretions of stearic acid (C 18: 0) were higher when feeding POS and PSS, and lower with feeding P and PS; the changes were statistically significant at p <0.05. More linolenic acid (C18: 3) was excreted when P was fed compared to the feeding of PS, POS, and PSS. Changes in linolenic acid excretion between P and POS were statistically significant at p <0.05. It was concluded that there were no significant differences in serum lipid concentrations due to feeding palm or any of the refined palm and soybean oil mixtures. However, a significant difference was found in C18: 0 excretions with feeding POS and PSS compared to when P and PS were fed. Similarly, significant C18: 3 excretion was found with feeding P compared to when POS was fed. | 10.1023/a:1011136724577 |
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