index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_269_18039
Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5-7% of school-age children. ADHD is usually marked by an ongoing pattern of inattention or hyperactivity-impulsivity, leading to functioning or developmental problems. A common ADHD assessment tool is the Swanson, Nolan, and Pelham (SNAP) questionnaire. However, such scales provide only a subjective perspective, and most of them are used to evaluate therapeutic effects at least 3-12 months after medication initiation. Therefore, we employed an objective assessment method to provide more accurate evaluations of therapeutic effects in 25 children with ADHD (23 boys and 2 girls). To evaluate the participants' improvement and treatment's effectiveness, the pixel subtraction technique was used in video analysis. We compared the efficacy of 1-month Ritalin or Concerta treatment by evaluating the movement in each video within 3 h of medication administration. The movement value was defined as the result of a calculation when using the pixel subtraction technique. Based on behavior observation and SNAP scores, both parent- and teacher-reported scores decreased after 1 month of medication (reduction rates: 19.61% and 16.38%, respectively). Specifically, the parent-reported hyperactivity subscale and teacher-reported oppositional subscale decreased more significantly. By contrast, the reduction rate was 39.27%, as evaluated using the average movement value (AMV). Considering symptomatic improvement as a >25% reduction in scores, the result revealed that the AMV decreased in 18 patients (72%) compared with only 44% and 56% of patients based on parent- and teacher-reported hyperactivity subscale scores. In conclusion, the pixel subtraction method can serve as an objective and reliable evaluation of the therapeutic effects of ADHD medication in the early stage.
10.3390/ijerph19063163
pubmed_857_18931
Cartagena, Colombia, was one of the last cities in the Americas known to have endemic poliomyelitis. After 3 cases were identified in 1991, two approaches for detecting continued silent transmission of wild polioviruses within a high-risk community were used: stool surveys of healthy children and virologic analysis of community sewage. Wild type 1 polioviruses were isolated from 8% of the children studied and from 21% of sewage samples. The proportions of wild polioviruses, vaccine-related polioviruses, and nonpolio enteric viruses were similar for both approaches. Wild poliovirus sequences were also amplified directly from processed sewage samples by the polymerase chain reaction using primer pairs specific for the indigenous type 1 genotype. The last reported cases associated with wild polioviruses in the Americas occurred in Colombia (8 April 1991) and Peru (23 August 1991). Direct sampling for wild polioviruses in high-risk communities can provide further evidence that eradication of the indigenous wild polioviruses has been achieved in the Americas.
10.1093/infdis/168.6.1510
pubmed_881_21486
BACKGROUND In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms. The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate (FP) and budesonide (B) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients. METHODS Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second (FEV1) 89.0% predicted and mid forced expiratory flow (FEF25-75) 58.9% predicted, on 400 micrograms/day or less of inhaled corticosteroid, were studied in a double blind, placebo controlled, crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms, 500 micrograms, and 1000 micrograms twice daily. Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing. Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours, 10 hours after the eighth dose. RESULTS The plasma cortisol levels (nmol/ l) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels: F500 333.8, B500 415.2 (95% CI 28.9 to 134.0); F1000 308.3, B1000 380.3 (95% CI 10.5 to 133.5); F2000 207.3, B2000 318.5 (95% CI 5.8 to 216.7); placebo 399.9. Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio (nmol/mmol) at all three dose levels: F500 3.12, B500 5.55 (95% CI 0.16 to 3.79); F1000 2.54, B1000 6.12 (95% CI 1.25 to 5.91); F2000 2.07, B2000 6.09 (95% CI 0.88 to 7.18); placebo 5.23. CONCLUSIONS With repeated dosing across a dose range of 250-1000 micrograms twice daily, fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol. It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients. Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency, prolonged receptor residency time, greater tissue retention, and a longer elimination half life.
10.1136/thx.52.1.55
pubmed_763_15178
UNLABELLED Many insects exploit skylight polarization as a compass cue for orientation and navigation. In the fruit fly, Drosophila melanogaster, photoreceptors R7 and R8 in the dorsal rim area (DRA) of the compound eye are specialized to detect the electric vector (e-vector) of linearly polarized light. These photoreceptors are arranged in stacked pairs with identical fields of view and spectral sensitivities, but mutually orthogonal microvillar orientations. As in larger flies, we found that the microvillar orientation of the distal photoreceptor R7 changes in a fan-like fashion along the DRA. This anatomical arrangement suggests that the DRA constitutes a detector for skylight polarization, in which different e-vectors maximally excite different positions in the array. To test our hypothesis, we measured responses to polarized light of varying e-vector angles in the terminals of R7/8 cells using genetically encoded calcium indicators. Our data confirm a progression of preferred e-vector angles from anterior to posterior in the DRA, and a strict orthogonality between the e-vector preferences of paired R7/8 cells. We observed decreased activity in photoreceptors in response to flashes of light polarized orthogonally to their preferred e-vector angle, suggesting reciprocal inhibition between photoreceptors in the same medullar column, which may serve to increase polarization contrast. Together, our results indicate that the polarization-vision system relies on a spatial map of preferred e-vector angles at the earliest stage of sensory processing. SIGNIFICANCE STATEMENT The fly's visual system is an influential model system for studying neural computation, and much is known about its anatomy, physiology, and development. The circuits underlying motion processing have received the most attention, but researchers are increasingly investigating other functions, such as color perception and object recognition. In this work, we investigate the early neural processing of a somewhat exotic sense, called polarization vision. Because skylight is polarized in an orientation that is rigidly determined by the position of the sun, this cue provides compass information. Behavioral experiments have shown that many species use the polarization pattern in the sky to direct locomotion. Here we describe the input stage of the fly's polarization-vision system.
10.1523/JNEUROSCI.0310-16.2016
pubmed_824_3920
Kainate receptors (KARs) are glutamate-gated ion channels that play fundamental roles in regulating neuronal excitability and network function in the brain. After being cloned in the 1990s, important progress has been made in understanding the mechanisms controlling the molecular and cellular properties of KARs, and the nature and extent of their regulation of wider neuronal activity. However, there have been significant recent advances towards understanding KAR trafficking through the secretory pathway, their precise synaptic positioning, and their roles in synaptic plasticity and disease. Here we provide an overview highlighting these new findings about the mechanisms controlling KARs and how KARs, in turn, regulate other proteins and pathways to influence synaptic function.
10.1007/s11064-017-2450-2
pubmed_120_19696
The gap junction protein connexin-43 (Cx43) exists mainly in the phosphorylated state in the normal heart, while ischemia induces dephosphorylation. Phosphatase(s) involved in cardiac Cx43 dephosphorylation have not as yet been identified. We examined the acute effects of ischemia on the dephosphorylation of the gap junction protein connexin-43 in isolated adult cardiomyocytes and isolated perfused hearts. In addition we tested the effectiveness of protein phosphatase 1 and 2A (PP1/2A) inhibitors in preventing Cx43 dephosphorylation. In both models, significant accumulation of the 41 kDa non-phosphorylated Cx43, accompanied by decreased relative levels of the 43-46 kDa phosphorylated Cx43, was observed at 30 min of ischemia. Okadaic acid decreased ischemia-induced Cx43 dephosphorylation; it also decreased the accumulation of non-phosphorylated Cx43 at the intercalated discs of myocytes in the whole heart. Calyculin A, but not fostriecin, also decreased ischemia-induced Cx43 dephosphorylation in isolated cardiomyocytes. It is concluded that isolated adult myocytes respond to ischemia in a manner similar to whole hearts and that ischemia-induced dephosphorylation of Cx43 is mediated, at least in part, by PP1-like phosphatase(s).
pubmed_120_19696
pubmed_631_24928
OBJECTIVES Diagnostic patterns play a role in asthma prevalence estimates and could have implications for disease management. We sought to determine the extent to which questionnaire-derived estimates of childhood asthma reflect the disease's true occurrence. MATERIALS AND METHODS Children aged 6-12 years from Katowice, Poland, were recruited from a cross-sectional survey (N = 1822) via primary schools. Students were categorized into three mutually exclusive groups based on survey responses: "Asthma" (previously diagnosed asthma); "Respiratory symptoms" (no previous diagnosis of asthma and one or more respiratory symptoms during last year), "No respiratory symptoms" (no previous diagnosis of asthma or respiratory symptoms). A sample of children from each group (total N = 456) completed clinical testing to determine asthma presence according to GINA recommendations. RESULTS Based on the survey, 5.4% of children were classified with asthma, 27.9% with respiratory symptoms, and 66.7% with no respiratory symptoms or asthma. All previously known 41 cases of asthma were confirmed. New diagnoses of asthma were made in 21 (10.9%) and 8 (3.6%) of subjects from the "Respiratory symptoms" (N = 192) and "No respiratory symptoms" (N = 223) groups, respectively. The overall prevalence of childhood asthma, incorporating the results of clinical examination, was 10.8% (95% CI: 9.4-12.2), compared to the questionnaire-derived figure of 5.4% (95% CI: 4.4-6.5%) and affected females more than males. CONCLUSIONS Asthma prevalence was underestimated in this population possibly resulting from under-presentation or under-diagnosis. This could have potential implications for proper management and well-being of children. Questionnaire estimates of prevalence should be considered carefully in the context of regional diagnostic patterns.
10.2478/s13382-013-0162-7
pubmed_36_21896
Clostridium difficile is a bacterial enteric pathogen, which causes clinical disease among solid organ transplant (SOT) recipients. This large, single-center, retrospective study describes incidence, demographics, and impact of C. difficile infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in our population during the 40-month period of study was 4%. CDI incidence among cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and 3.2%, respectively (P=0.03 between organ-types). Median time from transplant to CDI for all was 51 (14-249) days, with liver recipients having the shortest time to infection, median 36 (15-101) days, and lung recipients having a longer time to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%, 58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant recipients, respectively. Most patients (83%) were hospitalized within the 3 months preceding CDI. Recipients were followed for a median time of 23 (16-31) months; at the time of last follow-up, 83% of allografts were functioning, and 86% of patients were alive. One death and 1 graft failure were causally related to CDI. CDI had an overall incidence of 4%; clinicians should have heightened awareness for CDI, especially among patients receiving antibiotics, with increased monitoring and aggressive management of CDI.
pubmed_36_21896
pubmed_1010_25382
BACKGROUND Heart failure (HF) is a chronic condition with a variety of diverse symptoms. Patients with HF are usually elderly with multimorbidity, which are both multifaceted and challenging. Being a next of kin to patients with HF is described as a complex task consisting of managing care and treatment, monitoring illness and being an emotional support, while also being able to navigate the healthcare system especially in long-term contact. However, few studies have investigated next of kin's perceptions of continuity of care in connection with HF. The present study aimed to describe continuity of care as perceived by the next of kin who care for patients with HF. METHODS This study used a qualitative descriptive design. Semi-structured interviews were conducted with the next of kin (n = 15) of patients with HF to obtain their perceptions of continuity of care. A phenomenographic analysis method was used to capture the participants' perceptions of the phenomenon. RESULTS The analysis reveals that the next of kin perceive that support from healthcare professionals was strongly associated with experiences of continuity of care. Four categories reveal the next of kin's perceptions of continuity of care: Want to be involved without being in charge; A desire to be in control without acting as the driving force in the care situation; A need for sustainability without being overlooked; and Focusing on making life meaningful while being preoccupied with caregiving activities. CONCLUSIONS Next of kin perceive continuity of care, when they have access to care and treatment and when caregivers collaborate, regardless of healthcare is given by primary care, municipalities or specialist clinics. A sense of "being in good hands" sums up the need for continuous support, shared decision-making and seamless transitions between caregivers. It seems important that healthcare organisations safeguard effective and collaborative models. Moreover, professionals need to plan and perform healthcare in collaboration with patients and next of kin.
10.1186/s12877-019-1390-x
pubmed_499_11274
Spontaneous point mutations are one of the main actors in evolution, and the tautomerization of organic bases in the DNA is hypothesized to be the underlying mechanism of this crucial process. Tautomerization can be induced by proton tunneling, and if it occurs in single-stranded DNA (ssDNA) during the replication process, tautomerized bases might give rise to a mismatch, which will eventually defect the genetic code. In the present work, we report on the tautomerization time in the guanine base of the ssDNA. The model we use includes an intra-base tunneling mechanism such that time tunneling (delay time) is estimated to be around a few pico-seconds. The time delay is found to be biologically relevant which indicates that it is long enough to induce point mutations. Our results close a gap in the literature and sheds light on the importance of point mutations originating from quantum effects in the ssDNA.
10.1016/j.pbiomolbio.2022.05.009
pubmed_551_20233
OBJECTIVES To evaluate safety and efficacy of add-on low-dose azathioprine or interferon (IFN)-beta in patients with active multiple sclerosis despite monotherapy. METHODS This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either IFN-beta or azathioprine, who received add-on azathioprine or IFN-beta, respectively. In a subgroup of 23 patients, 10-year data were analysed. Clinical (relapse frequency, disability) and laboratory effects were compared preceding and following the addition of second drug and between the two treatment regimens. Potential serious adverse events were evaluated. RESULTS The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts decreased, being below the physiological levels in 8-26% and 13-52% of patients at each time point, respectively. The drop in relapse rate was independent from the dosage of azathioprine or changes in lymphocyte count. Comparison between the two treatment regimens showed that, with the exception of lymphocyte count, these effects were triggered by the add-on of interferon but not azathioprine. The combination therapy was well tolerated; however, after 5 years on treatment a moderately increased incidence of cancer was observed. CONCLUSIONS IFN-beta as add-on to azathioprine decreases relapse activity in active multiple sclerosis. In contrast, azathioprine add-on in patients with suboptimal response to IFN-beta does not improve the control over the disease activity.
10.1179/1743132812Y.0000000090
pubmed_55_744
Pancreatic endocrine tumors are rare but are among the most common neuroendocrine neoplasms of the abdomen. At diagnosis many of them are already advanced and difficult to treat. We report on an initially inoperable malignant pancreatic endocrine tumor in a 33-year-old woman, who received neoadjuvant peptide receptor radionuclide therapy (PRRT) as first-line treatment. This resulted in a significant downstaging of the tumor and allowed its subsequent complete surgical removal. Follow-up for eighteen months revealed a complete remission. This is the first report on neoadjuvant PRRT in a neuroendocrine neoplasm with subsequent successful complete resection.
10.3748/wjg.15.5867
pubmed_533_13299
Emerging infectious diseases caused by fungal taxa are increasing and are placing a substantial burden on economies and ecosystems worldwide. Of the emerging fungal diseases, chytridomycosis caused by the fungus Batrachochytrium dendrobatidis (hereafter Bd) is linked to global amphibian declines. Amphibians have innate immunity, as well as additional resistance through cutaneous microbial communities. Despite the targeting of bacteria as potential probiotics, the role of fungi in the protection against Bd infection in unknown. We used a four-part approach, including high-throughput sequencing of bacterial and fungal communities, cultivation of fungi, Bd challenge assays, and experimental additions of probiotic to Midwife Toads (Altyes obstetricans), to examine the overlapping roles of bacterial and fungal microbiota in pathogen defense in captive bred poison arrow frogs (Dendrobates sp.). Our results revealed that cutaneous fungal taxa differed from environmental microbiota across three species and a subspecies of Dendrobates spp. frogs. Cultivation of host-associated and environmental fungi realved numerous taxa with the ability to inhibit or facilitate the growth of Bd. The abundance of cutaneous fungi contributed more to Bd defense (~45% of the fungal community), than did bacteria (~10%) and frog species harbored distinct inhibitory communities that were distinct from the environment. Further, we demonstrated that a fungal probiotic therapy did not induce an endocrine-immune reaction, in contrast to bacterial probiotics that stressed amphibian hosts and suppressed antimicrobial peptide responses, limiting their long-term colonization potential. Our results suggest that probiotic strategies against amphibian fungal pathogens should, in addition to bacterial probiotics, focus on host-associated and environmental fungi such as Penicillium and members of the families Chaetomiaceae and Lasiosphaeriaceae.
10.3389/fmicb.2017.02494
pubmed_467_1751
BACKGROUND Tuberculosis is a public health problem in developing countries. Tuberculosis of the chest wall is rare and often presents as cold abscess (to differentiate from pyogenic abscess) or pseudotumoral mass whose diagnosis is difficult and often requires a surgical biopsy. PATIENTS AND METHODS The medical series of 16 patients with cold chest wall abscess treated with surgery in association to anti-tubercular therapy were analysed retrospectively for the period of 7 years between January 2011 to December 2017 at Mohamed V Military Teaching Hospital - Rabat - Morocco. RESULTS The clinical examination provided a correct preoperative diagnosis of the abscess in all cases. Five patients had a past history of pulmonary tuberculosis and three patients had concomitant active infection. There were 6 cases on the left side, 9 cases on the right side and one case on the anterior chest wall. All patients underwent surgical drainage and debridement with specimens for bacteriology and histology. It was not necessary to resect ribs or sternum in all cases (sample costal or sternal curettage in one case each). Anti-tubercular treatment was routinely administered (6-9 months) with drug combinations of Isoniaside, Rifampicin, Pyrazinamide and Ethambutol. The evolution was favorable in all cases without complications or recurrences. CONCLUSION Drainage of chest wall abscess and complete debridement provide adequate treatment. Post-operative anti-bacillary therapy should be combined with surgical procedures to minimize local complications and recurrence of infection.
10.1016/j.amsu.2020.02.001
pubmed_919_3034
OBJECTIVE Microarray analysis was used to characterize the labor-selective transcriptome of the human myometrium during labor. One highly up-regulated transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized. METHODS Expression of MCP-1 was evaluated in the myometrium, the placenta, the gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR, Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content of primary myometrial cultures treated with inflammatory cytokines was quantified by ELISA. RESULTS Up-regulation of the myometrial MCP-1 transcript in term laboring patients was demonstrated by microarray and confirmed by real time (RT)-PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in GM during term labor. The IR content of myometrial MCP-1 was increased during term labor and in the AF from patients experiencing preterm delivery. Levels of IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta. CONCLUSION The expression of myometrial MCP-1 was significantly increased during term labor and was similarly increased in vitro in response to interleukin 1-beta, a pro-inflammatory substance known to play a role in preterm birth. The increased IR content of MCP-1 within the AF preceding preterm delivery may render this protein a useful predictor of preterm birth.
10.1016/j.placenta.2004.09.012
pubmed_257_6257
High doses of oestradiol (150 micrograms/kg) or an oestradiol/progesterone combination (150 micrograms/kg oestradiol plus 6.25 mg/kg progesterone) were administered subcutaneously on alternate days to immature ovariectomised and mature intact female Beagle dogs for 13 weeks. The effects of hormonal treatment on different parameters were studied. The results revealed severe anaemia (mainly at week 3) and the blood films showed morphological indication of blood loss and abnormal erythrogenesis. Neutrophil leucocytosis and non-progressive thrombocytopenia were also observed. Treatment with oestradiol alone induced changes in the endometrial stroma and myometrium, whereas treatment with the oestradiol/progesterone combination induced cystic endometrial hyperplasia. The pituitary glands of the dogs treated with oestradiol alone had a slight increase in the number of ACTH cells. These cells and STH cells showed cytological changes indicative of accelerated secretory activity; the PRL and gonadotropin-producing cells were not affected significantly. The oestradiol/progesterone combination increased the number of ACTH and PRL cells. These cells as well as STH cells exhibited several cytological criteria typical of a pituitary cell with accelerated activity; the gondadotropin-producing cells showed involutionary changes. The mammary glands of oestradiol-treated dogs showed stromal and ductal cell proliferation; whereas the oestradiol/progesterone combination induced secretory epithelial cell proliferation in addition to stromal and ductal cell proliferation.
pubmed_257_6257
pubmed_635_3995
Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.We report a case of a young Ataxia-Telangiectasia patient with a severe immunological and neurological involvement, who developed granulomatous skin lesions diagnosed by skin biopsy as acne rosacea. Considering the severe clinical picture and the lack of improvement to multiple topic and systemic therapies, treatment with Isotretinoin was started and the skin lesions disappeared after five months. However the therapy was stopped due to drug-hepatotoxicity.Systemic treatment with Isotretinoin should be carefully considered in patient with Ataxia-Telangiectasia for the treatment of multi-drug resistant acne rosacea, however its toxicity may limit long-term use and the risk/benefit ratio of the treatment should be evaluated.
10.1186/s13052-015-0125-7
pubmed_368_994
PURPOSE Ex-PRESS shunt is an alternative filtration procedure to trabeculectomy. This study aimed to compare the 1-year cost differences between the 2 operations. METHODS Subjects were enrolled in a randomized controlled trial comparing Ex-PRESS to trabeculectomy. Surgical cost difference and 1-year postoperative costs (follow-up visits, additional procedures, and medications) were determined and compared. The 95% confidence interval of incremental cost-effectiveness ratio was estimated using bootstrap method. RESULTS Forty-three subjects with 1-year follow-up were included. Success rate was not significantly different for Ex-PRESS (65%) versus trabeculectomy (55%, P=0.49). Ex-PRESS had a net surgical cost of $956 greater than trabeculectomy. There was no significant difference in the overall postoperative cost [median (interquartile range); $485 (337, 822) vs. $609 (387, 820), P=0.78], cost of follow-up visits [$303 (275, 358) vs. $317 (275, 385), P=0.75], additional procedures [$182 (0, 365) vs. $182 (0, 365), P=0.69], or glaucoma medication [$0 (0, 68) vs. $0 (0, 90), P=0.8] for Ex-PRESS versus trabeculectomy, respectively. The overall 1-year cost was significantly greater for Ex-PRESS and the incremental cost-effectiveness ratio was $9625 (95% confidence interval, $2435-548,084). CONCLUSIONS Ex-PRESS is associated with greater surgical cost compared with trabeculectomy. This needs to be considered in conjunction with efficacy and safety if Ex-PRESS is to supersede trabeculectomy.
10.1097/IJG.0b013e31827a06f4
pubmed_680_4342
BACKGROUND Diffuse midline glioma H3 K27M-mutant is a distinct subtype of glial tumors newly introduced in the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System. They are aggressive pediatric tumors with a poor prognosis but have also been reported in adults. OBSERVATIONS The authors present the case of a man in his 60s who presented with rotatory vertigo, taste disorder, and right facial paralysis. Magnetic resonance imaging showed a tumor expanding from the cerebellum to the pons, which was histologically identified as glioblastoma, grade IV, IDH wild type. After tumor resection, the patient received chemoradiotherapy but showed only a partial response. His condition gradually worsened, and he died of progressive disease 12 months postoperation, after which an autopsy was performed. Tumor cells with a high nuclear-to-cytoplasm ratio were immunohistochemically analyzed and found to test positive for H3 K27M and negative for H3 K27me3. Furthermore, mutational analysis revealed HIST1H3B K27M mutation, and the tumor was finally identified as a high-grade glioma H3 K27M-mutant. The tumor invaded widely along the cerebral ventricle and disseminated to the spinal cord. LESSONS When a glioblastoma shows localization or dissemination patterns different from those of typical glioblastoma, an H3 K27M-mutant glioma should be suspected.
10.3171/CASE20112
pubmed_703_19334
Diabetes mellitus has become a prevalent disease in the world. Diagnostic protocol for the onset of diabetes mellitus is the initial step in the treatments. The intravenous glucose tolerance test (IVGTT) has been considered as the most accurate method to determine the insulin sensitivity and glucose effectiveness. It is well known that there exists a time delay in insulin secretion stimulated by the elevated glucose concentration level. However, the range of the length of the delay in the existing IVGTT models are not fully discussed and thus in many cases the time delay may be assigned to a value out of its reasonable range. In addition, several attempts had been made to determine when the unique equilibrium point is globally asymptotically stable. However, all these conditions are delay-independent. In this paper, we discuss the range of the time delay and provide easy-to-check delay-dependent conditions for the global asymptotic stability of the equilibrium point for a recent IVGTT model through Liapunov function approach. Estimates of the upper bound of the delay for global stability are given in corollaries. In addition, the numerical simulation in this paper is fully incorporated with functional initial conditions, which is natural and more appropriate in delay differential equation systems.
10.1016/j.mbs.2011.11.005
pubmed_1020_1513
The application of anatomical models and surgical templates in maxillofacial surgery allows, among other benefits, the increase of precision and the shortening of the operation time. Insufficiently precise anastomosis of the broken parts of the mandible may adversely affect the functioning of this organ. Applying the modern mechanical engineering methods, including computer-aided design methods (CAD), reverse engineering (RE), and rapid prototyping (RP), a procedure used to shorten the data processing time and increase the accuracy of modelling anatomical structures and the surgical templates with the use of 3D printing techniques was developed. The basis for developing and testing this procedure was the medical imaging data DICOM of patients treated at the Maxillofacial Surgery Clinic of the Fryderyk Chopin Provincial Clinical Hospital in Rzeszów. The patients were operated on because of malignant tumours of the floor of the oral cavity and the necrosis of the mandibular corpus, requiring an extensive resection of the soft tissues and resection of the mandible. Familiarity with and the implementation of the developed procedure allowed doctors to plan the operation precisely and prepare the surgical templates and tools in terms of the expected accuracy of the procedures. The models obtained based on this procedure shortened the operation time and increased the accuracy of performance, which accelerated the patient's rehabilitation in the further course of events.
10.3390/jcm10235525
pubmed_804_23270
The analytical performance of the multi enzymes loaded single electrode sensor (SES) and dual electrode sensor (DES) was compared for the detection of adenosine and metabolites. The SES was fabricated by covalent binding of tri-enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XO) along with hydrazine (Hyd) onto a functionalized conducting polymer [2,2:5,2-terthiophene-3-(p-benzoic acid)] (pTTBA). The enzyme reaction electrode in DES was fabricated by covalent binding of ADA and PNP onto pTTBA coated on Au nanoparticles. The detection electrode in DES was constructed by covalent binding of XO and Hyd onto pTTBA coated on porous Au. Due to the higher amount (3.5 folds) of the immobilized enzymes and Hyd onto the DES than SES, and the lower Michaelis constant (Km) value for DES (28.7 µM) compared to SES (36.1 µM), the sensitivity was significantly enhanced for the DES (8.2 folds). The dynamic range obtained using DES was from 0.5 nM to 120.0 µM with a detection limit of 1.43 nM ± 0.02, 0.76 nM ± 0.02, and 0.48 nM ± 0.01, for adenosine (AD), inosine (IN), and hypoxanthine (Hypo) respectively. Further, the DES was coupled with an electrochemical potential modulated microchannel for the separation and simultaneous detection of AD, IN, and Hypo in an extracellular matrix of cancerous (A549) and non-cancerous (Vero) cells. The sensor probe confirms a higher basal level of extracellular AD and its metabolites in cancer cells compared to normal cells. In addition, the effect of dipyridamole on released adenosine in A549 cells was investigated.
10.1016/j.bios.2018.03.031
pubmed_559_16930
In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-kappaB (NF-kappaB) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-kappaB inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals.
10.2337/db05-1570
pubmed_270_5173
BACKGROUND Serial MRI scanning of autosomal dominant mutation carriers for Alzheimer's disease provides an opportunity to track changes that could predate symptoms or clinical diagnosis of the disease. We used hierarchical modelling to assess how hippocampal and whole-brain volumes change as familial Alzheimer's disease progresses from the presymptomatic stage through to diagnosis. METHODS Nine mutation carriers had serial clinical assessments and volumetric MRI scans (41 scans: range 3-8 per patient) at different clinical stages (presymptomatic, mild cognitive impairment, or clinical Alzheimer's disease). 25 healthy controls had serial scanning (54 scans: range 2-4 per patient) for comparison. We measured whole brain and total hippocampal volumes using semi-automated techniques, and adjusted for total intracranial volume. Hierarchical models were developed to estimate differences in volume and atrophy rate between mutation carriers and controls in relation to when the disease was clinically diagnosed. FINDINGS Mutation carriers had significantly increased hippocampal and whole-brain atrophy rates compared with controls and these differences increased with time. Differences in hippocampal and whole-brain atrophy rates between controls and mutation carriers were evident 5.5 and 3.5 years, respectively, before diagnosis of Alzheimer's disease. At a cross-sectional level, differences in mean hippocampal volume between mutation carriers and controls became significant 3 years before clinical diagnosis, whereas differences in mean brain volumes became significant only 1 year before diagnosis. INTERPRETATION Structural changes can be seen on MRI scans that predate the clinical onset of familial Alzheimer's disease. Longitudinal measures of atrophy rates can identify differences between mutation carriers and controls 2-3 years earlier than cross-sectional volumetric measures.
10.1016/S1474-4422(06)70550-6
pubmed_666_22154
The deuteriodifluoromethyl group (CF2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF2 H) gas in the continuous flow deuteriodifluoromethylation and gem-difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D2 O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product.
10.1002/anie.202004260
pubmed_436_24925
Adverse drug reactions represent a major source of morbidity in hospitalized- and outpatients. Adverse drug reactions may affect the function of any organ or system. Due to their clinical nonspecificity adverse drug reactions are often difficult to be recognized. The clinical manifestation, the type and severity of adverse drug reactions vary a great deal depending on patient- and drug-related factors. In recent years growing evidence has emerged implicating involvement of free radicals and reactive oxygen species in chronic degenerative diseases and in acute conditions, such as stroke and infection. The review focuses on the role of reactive oxygen species in the pathogenesis of drug-induced disease with special reference to hepatotoxicity, nephrotoxicity and allergic disease. The participation of reactive oxygen species in the development of adverse drug reactions induced by special drug classes (non-steroidal anti-inflammatory drugs, anti-infective agents, cytostatics) is described. Results from studies on animals and humans reveal the putative implication of oxidative stress in drug-induced disease states.
pubmed_436_24925
pubmed_548_7160
The purpose of this research is to determine the cause of nasal perforation symptoms and to predict post-operative function after nasal perforation repair surgery. A realistic three-dimensional (3D) model of the nose with a septal perforation was reconstructed using a computed tomography (CT) scan from a patient with nasal septal defect. The numerical simulation was carried out using ANSYS CFX V13.0. Pre- and post-operative models were compared by their velocity, pressure gradient (PG), wall shear (WS), shear strain rate (SSR) and turbulence kinetic energy in three plains. In the post-operative state, the crossflows had disappeared, and stream lines bound to the olfactory cleft area had appeared. After surgery, almost all of high-shear stress areas were disappeared comparing pre-operative model. In conclusion, the effects of surgery to correct nasal septal perforation were evaluated using a three-dimensional airflow evaluation. Following the surgery, crossflows disappeared, and WS, PG and SSR rate were decreased. A high WS.PG and SSR were suspected as causes of nasal perforation symptoms.
10.1007/s00405-014-3438-z
pubmed_402_5317
AIMS To describe the design and organisation of a voluntary regional external quality assessment (EQA) scheme in histopathology, and to record the results obtained over a three year period. METHODS A protocol is presented in which circulation of EQA slides alternated with teaching sessions. Procedures for the choice of suitable cases, evaluation of submitted diagnoses, and feedback of results to participants are described. The use of teaching sessions, complementary to the slide circulations, and dealing with current diagnostic problems is also outlined. RESULTS Participation rates in the nine slide circulations varied between 66% and 89%, mean 85%. Overall scores were predictably high but 4% of returns, from 10 pathologists, were unsatisfactory. These low scores were typically isolated or intermittent and none of the participants fulfilled agreed criteria for chronic poor performers. CONCLUSIONS This scheme has been well supported and overall performances have been satisfactory. The design was sufficiently discriminatory to reveal a few low scores which are analysed in detail. Prompt feedback of results to participants with identification of all "incomplete" and "wrong" diagnoses is essential. Involvement of local histopathologists in designing, running, and monitoring such schemes is important.
10.1136/jcp.51.12.910
pubmed_1021_2300
A case with percutaneous transluminal coronary angioplasty (PTCA) for the stenosis of saphenous vein bypass graft was reported. A 68-year-old woman developed repeated effort angina two months after emergency triple CABG. Coronary angiographic study revealed 90% stenotic lesion in a sequential vein graft which was located between proximal and distal OM. PTCA was successful to dilate the stenotic lesion from 90% to 25% narrowing. She has been free from angina after the CABG and PTCA.
pubmed_1021_2300
pubmed_401_17263
BACKGROUND The COVID-19 pandemic has increased barriers to accessing preventive healthcare. This study identifies populations disproportionately underrepresented in screening and surveillance colonoscopies during the COVID-19 pandemic. METHODS In this single-center cohort study, colonoscopy procedures were reviewed during 6-month intervals before the pandemic (July 1, 2019 - December 31, 2019) and during the pandemic (July 1, 2020 - December 31, 2020 and January 1, 2021 - June 30, 2021). 7095 patients were categorized based on procedure indication, demographics, Charlson Comorbidity Index and Social Vulnerability Index (SVI). Statistics performed using VassarStats. RESULTS 2387 (2019) colonoscopies pre-pandemic and 2585 (2020) and 2123 (2021) during the pandemic were identified. There was a decrease in colonoscopies performed during months when COVID-19 cases peaked. The total number of average CRC risk patients presenting for first colonoscopy declined during the pandemic: 232 (10 %) pre-pandemic to 190 (7 %) in 2020, 145 (7 %) in 2021 (p < 0.001). Fewer of these patients presented from highly vulnerable communities, SVI > 0.8, during the pandemic, 39 in 2019 vs 16 in 2020 and 22 in 2021. Of all screening and surveillance patients, fewer presented from communities with SVI > 0.8 during the pandemic, 106 in 2019 versus 67 in 2020 and 77 in 2021. CONCLUSION It is important to address the decline in CRC preventive care during this pandemic among average CRC risk first-time screeners and vulnerable community patients. An emphasis on addressing social determinants of health and establishing patients in gastroenterology clinics is imperative to promote future health in these populations.
10.1016/j.canep.2022.102212
pubmed_1084_18245
DNAzymes are single stranded DNA molecules that exhibit catalytic activity and are exploited in medicine, biology and material sciences. Development in this area is related to the many advantages of DNAzymes over conventional protein enzymes, such as thermal stability and simpler preparation. DNAzymes with peroxidase-like activity have recently attracted great interest. To assure such catalytic activity, oligonucleotides have to adopt a G-quadruplex structure, which can bind the hemin molecule. This system facilitates a redox reaction between the target molecule and hydrogen peroxide, which results in the appearance of an oxidized target molecule (product). DNAzymes with peroxidase-mimicking activity have great potential in bioanalytical chemistry. This review presents fundamentals concerning the design and engineering of DNAzymes with peroxidase-like activity, describes their properties and spectral characteristics and shows how DNAzymes can contribute to bioanalytical research. Examples of bioanalytical applications of DNAzymes with peroxidase-like activity include nucleic acid probes with DNAzyme labels for the detection of specific DNA sequences in colorimetric or chemiluminescent assays. Assays for telomerase or methyltransferase activity, which are potential targets in anticancer therapy, are also described in this review. Other applications include the determination of metal cations such as Ag(+), K(+), Hg(2+), Pb(2+) or Cu(2+) and amplified detection of small molecules such as adenosine, cocaine or AMP and proteins such as lysozyme or thrombin. In the last decade, DNAzymes have become part of numerous applications in many areas of science from chemistry to biology to medicine.
10.1016/j.aca.2011.08.050
pubmed_913_10492
A case of superfoetation following artifical insemination in a ewe is reported. Estimation of the age of the lambs was based on the maturity of the liver, lung, kidney, brown adipose tissue and skin, showing a difference in gestational age of approximately thirty-six days. The possibility of spontaneous superfoetation as well as that of a second fertilization after artificial insemination is discussed.
pubmed_913_10492
pubmed_615_14661
The Odd-skipped gene, first identified as a Drosophila pair-rule zinc-finger transcription factor, plays an important role in Drosophila development. The mammalian homolog, Odd-skipped related 2 (Osr2), regulates limb, tooth, and kidney development in mouse embryos. However, the detailed expression pattern of Osr2 during neonatal development remains unclear. In this study, we investigated Osr2 expression patterns in mouse neonatal and embryo tissues using qPCR and in situ hybridization methods. First, we examined the tissue distribution of Osr2 by qPCR, and found it to be highly expressed in the uterus and moderately in the testes, small intestine, and prostate. That expression was also found in eye, kidney, placenta, lung, thymus, lymph node, stomach, and skeletal muscle tissues, and in all embryonic stages. On the other hand, Osr2 was not expressed in brain, heart, liver, or spleen samples. Next, we examined the tissue localization of Osr2 using in situ hybridization. Osr2 was found in the craniofacial region on E13.5, with notable expression in dental germ mesenchyme as well as the renal corpuscle on E17.5. As for neonatal tissues, Osr2 was expressed in the dental papilla, dental follicle, Harderian gland, nasal bone, eyelid dermis, synovial joint, and tibial subcutis. Our findings suggest that Osr2 functions in reproductive system organs, such as the uterus, testes, prostate, placenta, and ovaries. Furthermore, based on its expression in kidney, Harderian gland, eyelid dermis, and tibial subcutis tissues, this transcription factor may be involved in hormone synthesis and function. Together, our results demonstrate the role of Osr2 in postnatal development and embryogenesis.
pubmed_615_14661
pubmed_171_20718
PURPOSE This study compared the expansion parameters of four different new-generation balloon-expandable stents in a curved stenotic phantom model. MATERIALS AND METHODS Five stents for each length and type, each with a 3.5-mm diameter (AVE, 12 mm and 18 mm; Penta, 13 mm and 18 mm; BX-Sonic, 13 mm and 18 mm; and Jostent Flex Master, 12 mm and 16 mm), were implanted in curved silicon models 3.25 mm in diameter with 58% concentric elastic stenoses. The forces exerted on the inner curvature were continuously registered. Minimal luminal diameter (MLD) and reference luminal diameter (RLD) of the stents, inflated balloon diameter at both ends of the stents during inflation (BD(ref)), and balloon diameter at the stenotic site during inflation (BD(min)) were determined by magnification radiography. RESULTS The Penta and AVE stents presented greater RLD (Penta, 3.78 mm +/- 0.08; AVE, 3.75 mm +/- 0.13; BX-Sonic, 3.47 mm +/- 0.06; Jostent, 3.28 mm +/- 0.06) and MLD values (Penta, 2.94 mm +/- 0.18; AVE, 3.05 mm +/- 0.19; BX-Sonic, 2.68 mm +/- 0.06; Jostent, 2.53 mm +/- 0.09) than the BX-Sonic and Jostent stents. Displacement forces after stent placement were greater for AVE (0.034 N +/- 0.015) and Penta stents (0.023 N +/- 0.017) than for BX-Sonic (0.013 N +/- 0.007) and Jostent stents (0.009 N +/- 0.007; P <.05). BD(min) was correlated in a linear fashion with MLD (r = 0.84; P <.001), as was BD(ref) with RLD (r = 0.92; P <.001), for all stents. CONCLUSIONS Inflated balloon diameter was the main determinant of stent expansion. The AVE and Penta stents gained larger MLD values than the BX-Sonic and Jostent stents, but they excessively dilated the nonstenotic region of the model.
10.1097/01.rvi.0000133522.45958.52
pubmed_181_15192
INTRODUCTION Perforation of the Schneiderian membrane is the most common complication in sinus floor augmentation (SFA). When volume of grafting is qualified to prevent enlargement of the membrane perforation, lack of bone volume may occur in optimal site. CASE PRESENTATION SFA was performed in sites #24 to 26 in a 63-year-old male. However, a 10-mm size perforation of the Schneiderian membrane occurred in site #26. Although the sinus cavity was grafted with deproteinized bovine bone mineral (DBBM) after repair of membrane perforation, insufficient bone formation was observed on palatal and distal aspects of site #26 at 5 months after SFA. Although additional SFA was required for implant placement, it seemed to be difficult to elevate the membrane by a conventional lateral approach in the palatal aspect of the sinus floor (site #26). Considering the configuration of new bone formation, it was decided to perform the palatal antrostomy approach. The Schneiderian membrane was elevated without perforation, and the sinus cavity was grafted with DBBM mixed with venous blood. Two 12-mm long, 4.1-mm diameter implants were placed in sites #14 and 16. Four months after implant placement, abutment-connection surgery was successfully performed. The radiographic image indicated improved radiopacity, without obvious bone resorption in site #26. CONCLUSION The palatal window osteotomy technique could be considered as an alternative method for augmentation of maxillary sinus in cases where difficulty is encountered to elevate a membrane by a conventional approach (e.g., in cases in which buccal bone height is long).
10.1186/s40729-015-0018-y
pubmed_881_7068
A fast, simple method for the detection of the Escherichia coli polyphosphate kinase (ppk) gene by means of PCR amplification is described. The method uses filters to recover cells from the samples, which makes it suitable for environmental studies. The detection of the ppk gene was achieved from samples containing 10(2) E. coli cells, either in saline solution or in river water.
pubmed_881_7068
pubmed_424_23219
The present study evaluated, in vitro, the temperature alterations on the external root surface during instrumentation with four different rotary systems. A total of 20 extracted human maxillary lateral incisors were instrumented using either the ProFile, MicroMega, Quantec or K3 systems and the thermal alterations on the root surface were recorded by means of three thermocouples attached to the coronal, middle and apical portions of the root. Mean temperature increases no higher than 0.4 degrees C +/- 1.0 degrees C (ProFile system) were recorded, which indicates that these instruments are safe for the surrounding periodontal tissues.
10.1590/s0103-64402004000200006
pubmed_600_14488
OBJECTIVES The study aimed to analyze whether poor mental health in adolescence predicts heavy alcohol consumption over the long term. METHODS Alcohol consumption in the population cohort (n = 1010) was surveyed at the ages of 16, 18, 21, 30 and 42. Utilizing latent class growth analysis, six consumption trajectories ranging from 'Late Onset Low' to 'Early Onset High' were defined and analyzed with respect to internalization (depressiveness and anxiousness) and externalization (truancy and vandalism) at age 16. RESULTS Poor mental health predicted the Early Onset High trajectory (risk ratios in relation to the compliant trajectory 3.59 for anxiousness, 2.85 for depressiveness, 5.69 for truancy and 7.75 for externalized vandalism). Moreover, significant associations were found for the Early Onset Moderate and Early Onset Low trajectories. CONCLUSIONS This is the first study to show an association between internalized mental health problems in adolescence and lifelong heavy drinking. The study also confirmed a strong association between externalized behavior and heavy drinking, indicating a need of preventive measures in this group. Nevertheless, the analyses demonstrated that most teenagers with mental health problems continue along a reasonable drinking trajectory.
10.1007/s00038-015-0651-5
pubmed_836_3048
The extinction of the giant tortoises of the Seychelles Archipelago has long been suspected but is not beyond doubt. A recent morphological study of the giant tortoises of the western Indian Ocean concluded that specimens of two native Seychelles species survive in captivity today alongside giant tortoises of Aldabra, which are numerous in zoos as well as in the wild. This claim has been controversial because some of the morphological characters used to identify these species, several measures of carapace morphology, are reputed to be quite sensitive to captive conditions. Nonetheless, the potential survival of giant tortoise species previously thought extinct presents an exciting scenario for conservation. We used mitochondrial DNA sequences and nuclear microsatellites to examine the validity of the rediscovered species of Seychelles giant tortoises. Our results indicate that the morphotypes suspected to represent Seychelles species do not show levels of variation and genetic structuring consistent with long periods of reproductive isolation. We found no variation in the mitochondrial control region among 55 individuals examined and no genetic structuring in eight microsatellite loci, pointing to the survival of just a single lineage of Indian Ocean tortoises.
10.1046/j.1365-294x.2003.01834.x
pubmed_753_18606
People generally try to keep their eyes on a moving target that they intend to catch or hit. In the present study we first examined how important it is to do so. We did this by designing two interception tasks that promote different eye movements. In both tasks it was important to be accurate relative to both the moving target and the static environment. We found that performance was more variable in relation to the structure that was not fixated. This suggests that the resolution of visual information that is gathered during the movement is important for continuously improving predictions about critical aspects of the task, such as anticipating where the target will be at some time in the future. If so, variability in performance should increase if the target briefly disappears from view just before being hit, even if the target moves completely predictably. We demonstrate that it does, indicating that new visual information is used to improve precision throughout the movement.
10.1016/j.humov.2010.12.007
pubmed_516_14724
The efficacies of 2 new teat dip formulations were tested against experimental challenge by contagious mastitis pathogens Staphylococcus aureus and Streptococcus agalactiae over a 12-wk period. Formulations contained an iodine complex (0.5 or 1.0% iodine) and skin conditioning agents (propylene glycol, polyvinylpyrridone, glycerine, lanolin, allantoin, and aloe). Percentage reduction (dipped vs. control mammary quarters) in new contagious mastitis pathogen intramammary infections for the 0.5 and 1.0% iodine dips was 65.4 and 84.5, respectively. Both dips were significantly effective in reducing new contagious intramammary infections. Teat skin scores and teat end scores varied over time but were virtually identical for both treated and control teats, for both treatments. Thus, both dips were effective in reducing new contagious mastitis infections without untoward effects on teat skin condition.
10.3168/jds.S0022-0302(06)72329-3
pubmed_835_398
Helicobacter pylori (H. pylori) has been proposed as the foremost risk factor for the development of gastric cancer. We found that H. pylori express the enzyme glucose-6-phosphate dehydrogenase (HpG6PD), which participates in glucose metabolism via the pentose phosphate pathway. Thus, we hypothesized that if the biochemical and physicochemical characteristics of HpG6PD contrast with the host G6PD (human G6PD, HsG6PD), HpG6PD becomes a potential target for novel drugs against H. pylori. In this work, we characterized the biochemical properties of the HpG6PD from the H.pylori strain 29CaP and expressed the active recombinant protein, to analyze its steady-state kinetics, thermostability, and biophysical aspects. In addition, we analyzed the HpG6PD in silico structural properties to compare them with those of the HsG6PD. The optimal pH for enzyme activity was 7.5, with a T1/2 of 46.6 °C, at an optimum stability temperature of 37 °C. The apparent K values calculated for G6P and NADP+ were 75.0 and 12.8 µM, respectively. G6P does not protect HpG6PD from trypsin digestion, but NADP+ does protect the enzyme from trypsin and guanidine hydrochloride (Gdn-HCl). The biochemical characterization of HpG6PD contributes to knowledge regarding H. pylori metabolism and opens up the possibility of using this enzyme as a potential target for specific and efficient treatment against this pathogen; structural alignment indicates that the three-dimensional (3D) homodimer model of the G6PD protein from H. pylori is different from the 3D G6PD of Homo sapiens.
10.3390/microorganisms10071359
pubmed_336_21259
Natto is a popular soyfood in Japan, and the U.S. is the largest supplier of natto soybeans. However, information on natto seed chemical and sensory properties is very limited. The objectives of this study were to evaluate differences of seed chemical and sensory properties among natto types and determine heritability and correlation. A total of 15 small-seeded natto genotypes (three superior, nine moderate and three inferior) were evaluated for protein, oil, calcium, manganese, boron and sugar content and processed into a natto product to evaluate appearance, stickiness, flavor, texture and shelf-life. The superior natto group had a higher sugar content but lower protein plus oil, calcium, manganese and boron content than other two groups. Most seed quality traits exhibited high heritability. The natto sensory preference was positively correlated with sucrose and oil content, but negatively correlated with seed hardness, protein, protein plus oil, calcium, manganese, and boron contents. Selecting soybean lines with low protein, protein plus oil, calcium, manganese, and boron content while with high sucrose will be an effective approach for soybean breeding for natto production.
pubmed_336_21259
pubmed_216_12174
Evidence supporting the plastic capacity of the adult cortex is abundant. Changes have been associated with exposure to enriched environments, learning, peripheral lesions and central lesions. The initial loss of function caused by a lesion is generally followed by a certain amount of recovery that is believed to be due, at least in part, to adaptive plasticity. In particular, the reorganization of cortical representational maps has been associated with improvement of performance. Therefore, areas undergoing such reorganization following lesions are generally assumed to participate in the recovery. We review evidence demonstrating the remodeling of representational maps of the forelimb in adult cortex and the structural plasticity that has been coupled with it. A particular emphasis is paid to non-human primate studies and stroke.
10.1515/revneuro.2006.17.6.561
pubmed_820_9599
Laser-welded technology has become a viable alternative to the conventional lost wax-casting technique in the field of implant dentistry. Studies have demonstrated the predictable nature of laser-welded titanium frameworks for endosseous implants in the partial and totally edentulous patient. A standardized impression and fabrication procedure is required for an accurate and predictable superstructure. More long-term studies are needed for more widespread acceptance and usage by dental practitioners.
10.1563/779.1
pubmed_1131_15873
BACKGROUND Oral lichen planus (OLP) is a chronic inflammatory disease that causes bilateral white striations, papules, or plaques on the buccal mucosa, tongue, and gingivae. Erythema, erosions, and blisters may or may not be present. Several empirical therapies have been used in the treatment of (OLP). OBJECTIVE To evaluate the effect of low level laser therapy (LLLT) versus topical steroids for the treatment of erosive-atrophic lichen planus. SUBJECTS AND METHODS Twenty-four patients with erosive-atrophic (OLP) were categorized into two groups. In the first group patients were treated with 970 nm diode laser irradiation, while, in the second group patients used topical corticosteroids (0.1% triamcinolone acetonide orabase). The gender, medical history and pain score were recorded. The pain score was measured before and after treatment by visual analogue scale (VAS). RESULTS Steroid-treated group (0.1% triamcinolone acetonide orabase) show reduced pain score than laser group. CONCLUSION Topical steroids are more effective than LLLT. LLLT may be used as an alternative treatment for symptomatic OLP when steroids are contraindicated.
10.3889/oamjms.2015.072
pubmed_868_16331
BACKGROUND Although an orthotic device of the lower limb improves the functionality of neurological patients, anecdotally clinical experience suggests that the compliance is rather limited. OBJECTIVES The aim was to determine the satisfaction and acceptance of a lower limb orthotic device. STUDY DESIGN A qualitative observational pilot study with a mix-method design. METHODS Adult neurological patients who had a prescribed lower limb orthotic device were included. One published and clinically used questionnaire about satisfaction (D-Quest) and one ad hoc constructed questionnaire about acceptance of the orthotic device (MIRAD-ACCORT questionnaire) were used for data collection. RESULTS In total, 33 patients participated (28 ankle-foot orthotic device, 3 knee-ankle-foot orthotic device and 2 other types). In general, they were satisfied about their orthotic device and the services. Less than one-fourth of the patients had some negative comments about the 'visual aspects' and the 'ability to hide' of their orthotic device. These, however, had a lower priority when compared with functionality, which was reported as a main advantage and is a reason for continuing the use of their orthotic device. CONCLUSION Patients were satisfied in relation to their lower limb orthotic device. With regard to acceptance, it can be concluded that factors associated with functionality and comfort are more important than the aesthetic and psychological aspects of the orthotic device. Clinical relevance Patients were satisfied with their lower limb orthotic device. Some patients had some negative comments about the 'aesthetics aspects' and the 'ability to hide' their orthotic device. However, improvements in functionality were mostly reported as a main advantage and a reason for continuing the use of their orthotic device.
10.1177/0309364615592696
pubmed_560_22074
BACKGROUND Chyle fistulas may occur after left neck dissections that include level IV, due to injury of the thoracic duct or of 1 of its major branches. Despite being unusual, this complication carries substantial postoperative morbidity and even mortality. So far, no effective intraoperative maneuver has been reported to detect this fistula at the end of a neck dissection. In this cohort study, we sought to describe a simple new maneuver, intraoperative abdominal compression, which can effectively help to identify an open major lymphatic duct on level IV at the end of a neck dissection. PATIENTS AND METHODS From March 1989 to September 2010, 206 patients underwent neck dissections involving left level IV, and underwent intraoperative abdominal compression. There were 119 men and 87 women, with ages ranging from 18 to 81 years (median, 52 years). One hundred forty-four patients had squamous cell carcinomas, 54 had thyroid carcinomas, 5 had malignant melanomas, and 3 had salivary cancers. Distribution by type of left neck dissection was: selective including levels II, III, and IV (73 cases; 35.4%), selective including levels II, III, IV, and V (55 cases; 26.6%), selective including levels I, II, III, and IV (12 cases; 5.8%), modified radical (47 cases; 22.8%), and radical (19 cases; 9.2%). In all cases, at the end of the procedure, the endotracheal tube was temporarily disconnected from the ventilator. Keeping the dissected level IV area under clear visualization, an abdominal compression was performed. At this moment, any detected lymphatic leak was carefully clamped and tied with nonabsorbable sutures. After ventilating the patient, the intraoperative abdominal compression was repeated to reassure complete occlusion of the lymphatic vessel. RESULTS In 13 cases (6.3%), a chyle leak was detected after performing the intraoperative abdominal compression. All leaks except for 2 were successfully controlled after 1 attempt. In these 2 patients, a patch of muscle and fat tissue was applied with fibrin glue on the top. In 1 of these patients, another chyle leak in a different location was detected only at the second intraoperative abdominal compression, and was also effectively closed. Postoperatively, there were 2 (1%) chyle fistulas, both among these 13 cases, and all were successfully managed with clinical measures only. No fistulas occurred among the remaining 193 patients in whom intraoperative abdominal compression did not demonstrate lymphatic leak. CONCLUSION To our knowledge, this is the first description of a specific maneuver to actively detect a lymphatic fistula at the end of a left neck dissection involving level IV. In this study, intraoperative abdominal compression was able to detect an open lymphatic vessel in 6.3% of the cases, as well as to assure its effective sealing in the remaining 93.7% of the patients. Moreover, no life-threatening high-volume fistula was noted in this study.
10.1002/hed.21956
pubmed_54_24469
Gene expression is disrupted by sepsis. Genetic markers can only reveal a patient's genotype, and they are not affected by environmental biological processes. These processes are expressed by proteins. This study was aimed to advance the insight into the molecular foundations of sepsis. It employed proteomic techniques to identify and analyze differential serum protein expressions taken from a patient throughout the stages of sepsis (sepsis, severe sepsis and septic shock). Serum samples were collected at each stage of sepsis and submitted to one-dimensional electrophoresis, on gradient strips of immobilized pH, followed by two-dimensional 12.5% polyacrylamide gel electrophoresis. The gels obtained were stained, scanned and analyzed by the ImageMasterPlatinum program. Proteins that were differentially expressed in the gels were excised, digested with trypsin and identified through mass spectrometry. Fourteen differentially expressed proteins were identified throughout the stages of sepsis, as well as a protein that was not expressed in all stages, suggesting the potential existence of a biomarker. The differentially expressed proteins identified were: serum amyloid A, apolipoprotein A-1 (2 isoforms), zinc finger protein 222, human albumin, PRO 2619, immunoglobulin kappa light chain VLJ region, monoclonal immunoglobulin M cold agglutinin, 7 proteinase inhibitors - alpha-1 antitrypsin. The findings of this pilot study demonstrate the involvement of the complement and coagulation pathways, of the lipid metabolism and of genetic information in sepsis. The vast majority of proteins identified are involved in the immune system and the proteinase inhibitor proteins are predominant.
pubmed_54_24469
pubmed_1047_583
Monitoring was made to examine the lungs. With this mode of hyperbaric oxygenation (0.3 MPa for 5 hours), rats developed mild oxygen intoxication which alleviated on day 3 and ceased on day 7 after its exposure. At the same time there were profound changes in the surfactant levels of protein, phospholipids, and cholesterol, which became normal on day 7 of postexposure. Chemiluminescence analysis and measurements of lipid peroxidation (PLO) products indicated that PLO rates in the surfactant decreased during hyperbaric oxygenation and remained at low levels within 24 hours of postexposure, whose cause might be activated by the antioxidative systems, as considered by the authors. However, on day 3 PLO enhances and on day 7 a new level of free-radical processes established, which was characterized by higher concentrations of free radicals and enhanced the activity of the antiradical systems.
pubmed_1047_583
pubmed_979_6999
When the three major structural proteins, VP2, VP6, and VP7, of rotavirus are co-expressed in insect cells infected with recombinant baculoviruses, they self-assemble into triple-layered virus-like particles (VLPs) that are similar in morphology to native rotavirus. In order to establish the most favorable conditions for the synthesis of rotavirus VLPs, we have compared the kinetics of 2/6/7-VLP synthesis in two different insect cell lines: High Five cells propagated in Excell 405 medium and Spodoptera frugiperda 9 cells in Excell 400 medium. The majority of VLPs produced in both cell lines were released into the culture medium, and these released VLPs were predominantly triple-layered and were found to be stable for the period of six or seven days examined. The optimal synthesis of VLPs depended upon the cell line and the culture medium used as well as the time of harvesting infected cell cultures. The highest yield of VLPs was obtained from High Five cultures in the late phase of infection when the yield was at least 5-fold higher than that from S. frugiperda 9 cultures on a per cell basis. Our results demonstrate the usefulness of High Five cells for the production of VLPs as potential rotavirus subunit vaccines.
10.1002/(sici)1097-0290(19981105)60:3<369::aid-bit14>3.0.co;2-h
pubmed_55_2883
IMPORTANCE OF THE FIELD Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated. AREAS COVERED IN THIS REVIEW This is a review of seven studies on dronedarone. WHAT THE READER WILL GAIN DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL. TAKE HOME MESSAGE Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.
10.1517/14740330903514105
pubmed_273_21533
The interactive effects of salinity and potassium deficiency on the growth, mineral elements and photosynthetic performance were investigated in wild (Hordeum maritimum L.) and cultivated barley (Hordeum vulgare L. var. Manel). At 28 d of growth, plants were treated with 3 mM K and 0 mM NaCl (3-0); 3 mM K and 100 mM NaCl (3-100); 0 mM K and 0 mM NaCl (0-0), 0 mM K and 100 mM NaCl (0-100) for 14 d. In both species, biomass production decreased considerably when the two constraints were applied simultaneously. Salinity affected shoots more than roots, whereas for potassium deficiency, the reverse occurred. Generally, potassium uptake was more affected in wild than in cultivated barley and, independent of potassium availability, 100 mM NaCl increased Na+ content in both species, whereas K+ deprivation increased Na(+) content only in H. maritimum shoots (0-0). Potassium-use efficiency (KUE) increased in all treated plants. Potassium deficiency increased the negative effects induced by salt in the photosynthetic process of H. vulgare, and this species seemed to be unable to counteract the negative effects of salinity. H. maritimum showed limitation in CO2 photoassimilation, but this species displayed mechanisms that play a role in avoiding PSII photodamage aimed to dissipate the excess energy.
10.1016/j.jplph.2009.06.013
pubmed_324_8628
There is increasing concern about occurrences of perfluorinated compounds (PFCs) in the environment due to their persistent, bioaccumulation, and potentially toxic effects. We investigated contamination of 11 PFCs (C4-C12) in the Yodo River system, which is a major source of drinking water for more than 11 million people of Kansai region in Japan. PFCs were detected in higher concentration even exceeding more than 1000 ng/L in some cases. Composition profile of total PFCs concentration showed that PFOS, PFHxA, PFOA, and PFNA were occurring dominantly in the river system. PFOS and PFOA concentration were nearly proportional to a previous study in the same river system, indicating continuous sink of the compounds into the river system. Although discharge of PFCs from wastewater effluents at upstream could be one of the major point sources, concentration did not exceed 29.4 ng/L at the downstream of main Yodo River, possibly, due to dilution effects. Total mass load of PFCs in mainstream of Yodo River was estimated 451.7 g/d based on observed river discharge and PFCs concentration. Results showed that Yodo River system could have a unique upstream-downstream linkage of PFCs contamination and the river could be a continuous pathway of PFCs exposure to the people of Kansai region.
10.2166/wst.2011.020
pubmed_230_12117
INTRODUCTION Nutritional supplements used by athletes can be classified as sports food, dietary supplements and ergogenic aids. The aim of this study was to examine the use of such supplements among university athletes in Singapore. METHODS 82 athletes from 16 sport disciplines completed a questionnaire which sought information on demographical parameters, type of supplements, frequency of use, motivations, knowledge, expenditure and side effects. RESULTS The prevalence of supplement use was 76.8 percent and 20 different products were used. Each individual consumed a mean and standard deviation of 3.18 +/- 1.7 products over a 12-month period. The mean number of products consumed daily was 2.1 +/- 1.2. Popular products included sports drinks, vitamin C, multivitamins and traditional/herbal preparations such as essence of chicken, bird's nest and ginseng. Before using a product, 65.9 percent sought information, usually from the media, the Internet, coaches and fellow athletes. However, many did not know where to obtain reliable information and 86.4 percent were also unaware that supplementation can have adverse effects. CONCLUSION Although there is a high prevalence of supplement use in our study population, many do not have accurate information about these products. Hence, there is an urgent need to provide athletes with education and access to scientific and unbiased information.
pubmed_230_12117
pubmed_349_17534
BACKGROUND Early clinical results of anterolateral ligament (ALL) reconstruction are promising, but concerns exist due to high rates of complications after other types of lateral extra-articular tenodesis. The rate of surgery after combined anterior cruciate ligament (ACL) and ALL reconstruction is not known. PURPOSE To determine the rate of reoperation after combined ACL and ALL reconstruction. STUDY DESIGN Case series; Level of evidence, 4. METHODS A retrospective analysis of prospectively collected data from the Scientific ACL Network International (SANTI) Study Group database was performed to include all patients who had undergone combined ACL and ALL reconstruction between January 2012 and June 2014. At the end of the study period, all patients were contacted by telephone, and the operative notes of those who stated that they had undergone reoperation were reviewed to determine the type and rates of the subsequent procedures performed. Descriptive data were analyzed for the entire patient cohort. RESULTS The study population comprised 548 quadruple hamstring graft (4HT)+ALL reconstructions. The mean age (±SD) was 24.3 ± 7.9 years (range, 11.9-55.7 years), and 70.3% of subjects were male. The mean duration of follow-up was 35.5 ± 8.0 months (range, 24-54 months). Seventy-two patients (13.1%) underwent ipsilateral reoperation. This comprised a total of 77 procedures. Graft revision occurred in 14 knees (2.6%) at a mean of 18.3 months (±7.4 months) after the index procedure. There were 63 reoperations for ipsilateral, non-graft rupture-related indications (meniscus, n = 30; arthrofibrosis, n = 22; removal of hardware, n = 4; deep infection, n = 3; arthroscopic lavage without infection, n = 4). The only specific complications related to the ALL procedure (n = 3) were all related to femoral hardware that required removal. In both univariate and multivariate analyses, only the presence of a medial meniscal lesion at the index procedure was significantly associated with ipsilateral reoperation (odds ratio, 2.58; 95% CI, 1.43-4.76; P = .002). CONCLUSION The reoperation rate after combined ACL and ALL reconstruction in this series is broadly comparable to the reoperation rate after isolated ACL reconstruction as reported in previous studies. In addition, the high rates of knee stiffness and reoperation reported in historical series of nonanatomic, lateral extra-articular tenodesis were not observed in the current series.
10.1177/0363546517708982
pubmed_735_19805
Fresh fruit juice is an essential component of human diet and there is considerable evidence of health and nutritional benefits. However, nature of the fruits used in juicing and unhygienic processes in the value chain may cause poor quality of juice. This cross- sectional study was conducted to assess physicochemical characteristics and hygienic practices along the value chain of raw fruit juice vended in Dar es Salaam, Tanzania. A total of 90 juice vendors were interviewed. Ninety juice samples were collected and analysed for physicochemical quality. The pH of juices ranged between 2.7 and 6.4, acidity 0.01% and 1.3% and, total soluble solids ranged between -1.5 and 18.04 °Brix. Most juices (67.8%) had -Brix levels below Codex recommended values classified as weak and watery. Juices were made of mango, passion, tamarind, sugar cane and mixture of these fruits sourced from open markets in the city. Water for washing of fruits and dilution of juices was from deep wells (53.3%) and taps (46.7%). About one third (37.8%) of the juice vendors didn't wash the fruits before juicing and 44.4% didn't boil water for juice dilution. Juice extraction was done by kitchen blenders, boiling in water and squeezing by simple machines. Juice pasteurization was not done. The majority of vendors (78.9%) stored juices in plastic buckets and juice was sold in glass cups, reused plastic bottles and disposable cups. Vending sites were restaurants, bus stands and along roadsides. The majority of premises (78.9%) were in unhygienic condition that likely encouraged or introduced contaminants to the juices. It is concluded that, the overall handling, preparation practices and physicochemical quality of raw fruit juices vended in Dare es Salaam City are poor. The government should educate the vendors on food safety and hygiene as well as enforcing regular monitoring of the quality of street fruit juices.
10.4314/thrb.v16i4.3
pubmed_912_16255
INTRODUCTION Our purpose was to analyze the long-term evolution of wide neck cerebral aneurysms treated with stent assistance. METHODS Data of consecutive patients treated with the Neuroform stent over 9 years were retrospectively analyzed with emphasis on periprocedural complications, aneurysm occlusion grade evolution, and in-stent stenosis rates. RESULTS Altogether, 113 patients with 117 unruptured and ruptured aneurysms were subject of analysis. Mean aneurysm size was 9.4 mm, and mean neck size was 4.7 mm. Procedural thromboembolic and hemorrhagic complications affected eight (6.8%) and four cases (3.4%), respectively. Immediate complete occlusion and occlusion with residual neck was achieved in 85% of cases, which at the first follow-up of 6 months, changed to 77 and 76 % at 36 months. Aneurysms ≥10 mm showed a higher tendency of recurrence. During the overall follow-up time ranging from 1 to 9 years, an in-stent stenosis of ≥50 % was observed only in three cases, all of them being asymptomatic. CONCLUSIONS Stent-assisted coiling of wide neck aneurysms provided stable occlusion over the long-term follow-up, with very low and silent in-stent stenosis rates. Some incompletely occluded aneurysms showed a tendency of progressive occlusion; however, this was counterbalanced by the regrowth of others.
10.1007/s00234-013-1143-z
pubmed_118_741
BACKGROUND Shared decision-making (SDM) is a means of allowing people with dementia to take part in making choices, be autonomous and participate in social activities. Involving them in SDM is an important way of promoting social health. However, including families and dementia residents in decision-making can be challenging for care staff working in nursing homes. The objective of this study was to identify barriers and facilitators regarding the implementation of an SDM framework for care planning in two nursing homes, one in Italy and one in the Netherlands. METHODS Focus group interviews were conducted with healthcare professionals who, after being trained, applied the SDM framework. Content analysis was used to analyze the data. RESULTS Six months after the feasibility trial, focus group interviews with healthcare professionals (n = 10 in Italy; n = 9 in the Netherlands) were held. We found 6 themes and 15 categories. Within these themes, facilitators and barriers were identified. The categories of team collaboration, communication skills and nursing home policy were found to be facilitators to the implementation process, whereas regulations, lack of funding and of involvement of family caregivers were the main barriers. Family attitudes towards SDM could be both. The main difference between countries concerned the residents' cognitive status that influenced their degree of involvement. CONCLUSION Communication skills training for professionals, training of family caregivers, and involvement of the management in the implementation process seem to be crucial factors in successfully implementing SDM in nursing homes, and increasing the involvement of families and dementia residents in decision-making.
10.1080/13607863.2016.1255715
pubmed_568_9517
INTRODUCTION The efficacy of gabapentin for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of gabapentin versus placebo on the postoperative pain intensity of arthroscopy. METHODS We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of gabapentin versus placebo on pain control of arthroscopy. This meta-analysis is performed using the random-effect model. RESULTS Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group for arthroscopy, gabapentin remarkably decreases pain scores at 24 hour (standard mean difference [SMD]=-0.68; 95% confidence interval [CI]=-1.15 to -0.02; P = .21), analgesic consumption (SMD = -18.24; 95% CI=-24.61 to -11.88; P < .00001), nausea and vomiting (OR = 0.42; 95% CI = 0.21 to 0.84; P = .01), but has no obvious influence on pain scores at 6 h (SMD = -1.30; 95% CI = -2.92 to 0.31; P = .11) or dizziness (OR = 1.12; 95% CI = 0.56 to 2.24; P = .75). CONCLUSIONS Gabapentin is effective for pain control after arthroscopy.
10.1097/MD.0000000000025740
pubmed_854_7148
OBJECTIVES The purpose of this study was to characterize the effect of epinephrine on T-wave morphology in patients with congenital long QT syndrome (LQTS). BACKGROUND QT prolongation is a paradoxical, LQT1-specific response to low-dose epinephrine infusion. At rest, notched T waves are more common in LQT2. METHODS Thirty subjects with LQT1, 28 with LQT2, and 32 controls were studied using epinephrine provocation. Twelve-lead ECG was recorded continuously, and QT, QTc, and heart rate were obtained during each stage. Blinded to phenotype and genotype, T-wave morphology was classified as normal, biphasic, G1 (notch at or below the apex), or G2 (distinct protuberance above the apex). RESULTS At baseline, 97% LQT1, 71% LQT2, and 94% control had normal T-wave profiles. During epinephrine infusion, G1- and G2-T waves were more common in LQT2 than in LQT1 (75% vs 26%, P = .009). However, epinephrine-induced G1-T waves were present in 34% of control. Epinephrine-precipitated biphasic T waves were observed similarly in all groups: LQT1 (6/30), LQT2 (3/28), and control (4/32). During low-dose epinephrine infusion (< or =0.05 microg/kg/min), G1-T waves occurred more frequently in LQT2 (LQT1: 25% vs 3%; control 9%, P = .02). Low-dose epinephrine-induced G2-T waves were detected exclusively in LQT2 (18%). Low-dose epinephrine elicited G1/G2-T waves in 8 of 15 LQT2 patients with a nondiagnostic baseline QTc. CONCLUSIONS Biphasic and G1-T waves are nonspecific responses to high-dose epinephrine. Changes in T-wave morphology during low-dose epinephrine (<0.05 microg/kg/min) may yield diagnostic information. G2-notched T waves elicited during low-dose epinephrine may unmask some patients with concealed LQT2.
10.1016/j.hrthm.2004.11.008
pubmed_482_4811
Breaking the pH limitation of the enzyme-like activity of nanomaterials is of great importance for extending their applications in environmental and biomedical fields. Herein, to mimic the role of histidine residues in horseradish peroxidase (HRP), adenosine 5'-triphosphate (ATP) is reported to improve the peroxidase-like activity of hollow Prussian blue nanocubes (hPBNCs). Due to the inherited porous structures, hPBNCs can expose all the binding sites as far as possible to ATP to significantly amplify their catalytic activity and broaden their applicable pH range up to pH 12. Introduction of ATP provides the possibility of realizing efficient catalytic reactions under alkaline conditions. Upon binding with hPBNCs, ATP can enhance the stability of hPBNCs, increase the affinities of the catalysts towards substrates and improve the conductivity of hPBNCs as well as change the decomposed product from H2O2. Moreover, on the basis of the different catalytic activities of hPBNCs towards ATP, adenosine 5'-diphosphate and adenosine 5'-monophosphate, hPBNCs-ATP is utilized to construct a novel colorimetric sensor for the detection of alkaline phosphatase (ALP) activity in biological fluids, which is significantly important for the clinical diagnosis of ALP-related diseases.
10.1039/d0an00405g
pubmed_897_23344
OBJECTIVES To study possible effects of aerosol exposure on lung function, fractional exhaled nitric oxide (FeNO) and inflammatory markers in blood from Norwegian cement production workers across one work shift (0 to 8 h) and again 32 h after the non-exposed baseline registration. METHODS 95 workers from two cement plants in Norway were included. Assessment of lung function included spirometry and gas diffusion pre- and post-shift (0 and 8 h). FeNO concentrations were measured and blood samples collected at 0, 8 and 32 h. Blood analysis included cell counts of leucocytes and mediators of inflammation. RESULTS The median respirable aerosol level was 0.3 mg/m(3) (range 0.02-6.2 mg/m(3)). FEV(1), FEF(25-75%) and DL(CO) decreased by 37 ml (p=0.04), 170 ml/s (p<0.001) and 0.17 mmol/min/kPa (p=0.02), respectively, across the shift. A 2 ppm reduction in FeNO between 0 and 32 h was detected (p=0.01). The number of leucocytes increased by 0.6×10(9) cells/l (p<0.001) across the shift, while fibrinogen levels increased by 0.02 g/l (p<0.001) from 0 to 32 h. TNF-α level increased and IL-10 decreased across the shift. Baseline levels of fibrinogen were associated with the highest level of respirable dust, and increased by 0.39 g/l (95% CI 0.06 to 0.72). CONCLUSIONS We observed small cross-shift changes in lung function and inflammatory markers among cement production workers, indicating that inflammatory effects may occur at exposure levels well below 1 mg/m(3). However, because the associations between these acute changes and personal exposure measurements were weak and as the long-term consequences are unknown, these findings should be tested in a follow-up study.
10.1136/oem.2010.057729
pubmed_643_6110
Restoration works in the old Clunisian Saint-Vivant monastery in Burgundy revealed an unidentified wine bottle (SV1) dating between 1772 and 1860. Chemical evidence for SV1 origin and nature are presented here using non-targeted Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Nuclear Magnetic Resonance analyses. The SV1 chemical diversity was compared to red wines (Pinot Noir) from the Romanée Saint Vivant appellation and from six different vintages spanning from 1915 to 2009. The close metabolomic signature between SV1 and Romanée Saint Vivant wines spoke in favor of a filiation between these wines, in particular considering the Pinot noir grape variety. A further statistical comparison with up to 77 Pinot noir wines from Burgundy and vintages from nearly all the 20th century, confirmed that SV1 must have been made more than one hundred years ago. The increasing number of detected high masses and of nitrogen containing compounds with the ageing of the wine was in accordance with known ageing mechanisms. Besides, resveratrol was shown here to be preserved for more than one hundred years in wine. For the first time, the age of an old unknown wine along with its grape variety have been assessed through non-targeted metabolomic analyses.
10.1038/s41538-017-0001-5
pubmed_105_1207
Patients with breast cancer may be offered adjuvant radiation therapy (RT) after surgery. Up to 95% of these patients develop radiation dermatitis (RD) during or following RT. Randomized clinical trials and other literature provide evidence that RD can be prevented or reduced. The aim of this article is to propose a Clinician Guide and Evidence-based Skin Care Plan to prevent and/or reduce radiation dermatitis and promote the comfort of breast cancer patients receiving RT. As an integrative review, the databases searched were CINAHL and Medline, using the key terms: breast cancer, skin care, radiation, radiation therapy, radiotherapy, radiation dermatitis, and radiation skin reaction, prevention, and management. Search criteria included English language, full text, published between 2012 through 2020, and peer-reviewed. The search yielded 320 articles. Relevant articles were evaluated using the Quality Assessment Tool (QAT), and highly rated articles were selected to be included in the review of literature. The outcomes were the development of a Clinician Guide to offer holistic, patient-centered care and an Evidence-based Skin Care Plan. The research literature supports a standard skin care regimen, along with use of an emollient cream to the treatment area, use of deodorants depending on patient preferences, and application of a topical steroid cream daily throughout treatment and two weeks post RT. Clinician's weekly assessments of patients offers therapeutic support and ensures optimal skin care during and post-RT. The comfort of breast cancer patients receiving RT requires the best level of evidence regarding the efficacy of interventions, coupled with clinician's judgement, and patient's preferences and wishes. The clinician-patient relationship is essential in addressing the physical, emotional, social, spiritual, and functional challenges associated with a cancer diagnosis and adjunctive radiation therapy to improve long-term survival.
10.3390/healthcare10081496
pubmed_897_8308
OBJECTIVES The aim of the present study was the assessment of left ventricular (LV) remodeling during the surgical management of degenerative mitral valve regurgitation (DMR) with the application of 2 emerging imaging modalities: real-time 3-dimensional echocardiography (3DE) and speckle tracking. METHODS A total of 40 patients with DMR were prospectively recruited. Two-dimensional echocardiography, 3DE, and speckle tracking studies were performed before surgery and 6 months postoperatively. The LV volumes, stroke volume, and ejection fraction were calculated. The strain of all myocardial segments, as well as dyssynchrony, was assessed. Receiver operating characteristic curves and regression analysis were used to assess the independent predictors of mitral regurgitation recurrence and LV remodeling. RESULTS Of the 40 patients, 21 underwent mitral valve repair and 19 valve replacement. Their mean age was 59.5 ± 15.4 years. The postoperative LV 3DE analysis revealed a significant reduction in LV end-diastolic volume (103.9 cm(3) from 165.2 cm(3) preoperatively, P < .001). A synchronous decrease in the LV end-diastolic diameter (48 mm from 53.5 mm preoperatively, P < .001) and left atrial diameter (42.8 mm from 53.1 mm preoperatively, P = .005) were identified after DMR surgery. Regression analysis demonstrated incremental favor toward mitral valve repair in reverse ventricular remodeling. Independent factors were identified for regurgitation recurrence after surgery. The most significant were late diastolic (A') wave of the septal apical wall of < 3.2 cm/s (area under the curve [AUC], 0.82), late diastolic (A') wave of the mid-septal wall of ≤ 3.66 cm/s (AUC, 0.82), mid-lateral radial strain of ≤ -27 (AUC, 0.81), and apical lateral radial strain of ≤ -25 (AUC, 0.80). CONCLUSIONS 3DE and speckle tracking proved to be important imaging tools in assessing reverse LV remodeling after DMR surgery. Subtle regional preoperative changes in diastolic function of the septal and lateral wall could be identified preoperatively, aiding in optimizing the referral timing and recognizing potential culprits as indicators of disease recurrence after mitral repair.
10.1016/j.jtcvs.2010.11.030
pubmed_490_5698
A previous donor intervention trial found that therapeutic hypothermia reduced delayed graft function (DGF) after kidney transplantation. This retrospective cohort study nested in the randomized dopamine trial (ClinicalTrials.gov identifier: NCT000115115) investigates the effects of spontaneous donor hypothermia (core body temperature <36°C) on initial kidney graft function, and evaluates 5-year graft survival. Hypothermia assessed by a singular measurement in the intensive care unit 4-20 hours before procurement was associated with less DGF after kidney transplantation (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.34-0.91). The benefit was greater when need for more than a single posttransplant dialysis session was analyzed (OR 0.48, 95%CI 0.28-0.82). Donor dopamine ameliorated dialysis requirement independently from hypothermia in a temporal relationship with exposure (OR 0.93, 95%CI 0.87-0.98, per hour). A lower core body temperature in the donor was associated with lower serum creatinine levels before procurement, which may reflect lower systemic inflammation and attenuated renal injury from brain death. Despite a considerable effect on DGF, our study failed to demonstrate a graft survival advantage (hazard ratio [HR] 0.83, 95%CI 0.54-1.27), whereas dopamine treatment was associated with improved long-term outcome (HR 0.95, 95%CI 0.91-0.99 per hour).
10.1111/ajt.14541
pubmed_573_25255
BACKGROUND In order to benefit from the highly conformal irradiation of tumors in ion radiotherapy, sophisticated treatment planning and simulation are required. The purpose of this study was to investigate the potential of MRI for ion radiotherapy treatment plan simulation and adaptation using a classification-based approach. METHODS Firstly, a voxelwise tissue classification was applied to derive pseudo CT numbers from MR images using up to 8 contrasts. Appropriate MR sequences and parameters were evaluated in cross-validation studies of three phantoms. Secondly, ion radiotherapy treatment plans were optimized using both MRI-based pseudo CT and reference CT and recalculated on reference CT. Finally, a target shift was simulated and a treatment plan adapted to the shift was optimized on a pseudo CT and compared to reference CT optimizations without plan adaptation. RESULTS The derivation of pseudo CT values led to mean absolute errors in the range of 81 - 95 HU. Most significant deviations appeared at borders between air and different tissue classes and originated from partial volume effects. Simulations of ion radiotherapy treatment plans using pseudo CT for optimization revealed only small underdosages in distal regions of a target volume with deviations of the mean dose of PTV between 1.4 - 3.1% compared to reference CT optimizations. A plan adapted to the target volume shift and optimized on the pseudo CT exhibited a comparable target dose coverage as a non-adapted plan optimized on a reference CT. CONCLUSIONS We were able to show that a MRI-based derivation of pseudo CT values using a purely statistical classification approach is feasible although no physical relationship exists. Large errors appeared at compact bone classes and came from an imperfect distinction of bones and other tissue types in MRI. In simulations of treatment plans, it was demonstrated that these deviations are comparable to uncertainties of a target volume shift of 2 mm in two directions indicating that especially applications for adaptive ion radiotherapy are interesting.
10.1186/1748-717X-8-51
pubmed_1049_5193
The African mosquito species Anopheles gambiae sensu lato s.l. and Anopheles funestus rank among the world's most efficient vectors of human malaria. Their unique bionomics, particularly their anthropophilic, endophagic and endophilic characters, guarantee a strong mosquito-host interaction, favorable to malaria transmission. Olfactory cues govern the various behaviors of female mosquitoes and here we review the role of semiochemicals in the life history of African malaria vectors. Recent evidence points towards the existence of human-specific kairomones affecting host-seeking A. gambiae s.l., and efforts are under way to identify the volatiles mediating this behavior. Based on examples from other Culicidae spp., it is argued that there is good reason to assume that mating, sugar feeding, and oviposition behavior in Afrotropical malaria vectors may also be mediated by semiochemicals. It is foreseen that increased knowledge of odor-mediated behaviors will be applied in the development of novel sampling techniques and possibly alternative methods of intervention to control malaria.
10.1146/annurev.ento.44.1.131
pubmed_198_8072
We report here the ultrastructural localization of S-100b protein-like immunoreactivity in the centriole, cilia, and basal body. Duodenum and trachea of guinea pigs and rats were fixed and immunostained by the protein A-gold method. All centrioles, cilia, and basal bodies observed showed clear S-100b protein-like immunoreactivity. Specific colloidal gold particles were located over the microtubules in these cell organelles. However, other microtubules scattered throughout the cytoplasm were devoid of immunoreactivity. Although the functional significance of S-100b protein-like immunoreactivity in the centriole, cilia, and basal bodies remains to be elucidated, the present results introduce new perspectives into the investigation of localization and function of S-100 proteins.
10.1177/36.6.3367052
pubmed_132_5286
Every year over 885,000 dog bites require serious medical attention. Based on human injury and insurance claims, six dog breeds were designated as "vicious" (Akitas, Chows, Dobermans, Pit Bulls, Rottweilers, and Wolf-mixes). This study was conducted to expand on previous research examining antisocial tendencies and personality styles of people choosing to own vicious breeds. Seven hundred and fifty-four college students completed a questionnaire assessing type of dog owned, criminal thinking, callousness, personality, alcohol usage, and deviant lifestyle behaviors. Vicious dog owners reported significantly higher criminal thinking, entitlement, sentimentality, and superoptimism tendencies. Vicious dog owners were arrested, engaged in physical fights, and used marijuana significantly more than other dog owners. However, the homogeneous sample utilized could impact the generalizability of these findings. Choosing to own a vicious dog may be a "thin slice" indicator of more antisocial tendencies.
10.1111/j.1556-4029.2011.01961.x
pubmed_902_2919
Highly cross-linked polyethylene (HXLPE) was developed to reduce wear of articular bearing surface in total hip arthroplasty patients. Several studies have shown reduced wear of HXLPE compared with conventional polyethylene; however, these studies had used HXLPE in combination with a Co-Cr metal head. The purpose of this study was to compare the 5-year in vivo wear of HXLPE with that of conventional PE using a zirconia femoral head. Forty-five hips with a Trilogy HXLPE (Zimmer, Warsaw, Ind) were matched and compared with a control group of 20 conventional Trilogy PE hips. The 2-dimensional linear wear rate was significantly less in the HXLPE group between 1 and 5 years postoperation (P < .001). The results show that HXLPE reduces short-term polyethylene wear against not only a Co-Cr head but also a zirconia head.
10.1016/j.arth.2009.11.005
pubmed_415_22289
Direct-acting antiviral agents in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) significantly improve sustained virologic response rate and reduce duration of therapy among both treatment-naïve and treatment-experienced patients with genotype 1 chronic hepatitis C. One of the most important considerations with both boceprevir and telaprevir is the potential development of resistant variants with therapy. Patients with poor intrinsic responsiveness to interferon, and those with incomplete virological suppression on protease inhibitor therapy, appear to be at higher risk for resistance. In this article we will define antiviral resistance and review the data on both in vitro and in vivo resistance to protease inhibitors, concentrating on data on boceprevir and telaprevir. We will also explore the significance of resistant variants present at the baseline, as well as the fate of the resistant variants and the ways to minimize the development of resistance to protease inhibitors.
10.1007/s11894-011-0237-1
pubmed_20_2029
Physicians are legally and ethically compelled to present their patients with available evidence on the potentially beneficial and harmful effects of a proposed medical or surgical treatment. This, however, is only half the story. It does not offer the patient a clear view of the pros and cons of one treatment option versus another, or even versus no treatment at all. Explicitly stating the number of patients who will not benefit from the proposed treatment, in combination with the risk of a complication, may better inform patients and help them determine and express their treatment preference. This may also help standardize the informed consent procedure.
10.1097/SLA.0000000000001522
pubmed_909_16683
BACKGROUND Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder, in which platelet glycoprotein (GP)IIb-IIIa and GPIb-IX are the two most frequently targeted autoantigens. Our previous studies in animal models of ITP demonstrated that intravenous immunoglobulin G (IVIG) could protect against anti-GPIIb-IIIa autoantibody-mediated thrombocytopenia but failed to ameliorate ITP induced by most anti-GPIb-IX autoantibodies. OBJECTIVES The objective of this human study was to evaluate the association between the specificity of antiplatelet autoantibodies and response to IVIG treatment. PATIENTS/METHODS In this retrospective study, a cohort of 156 previously untreated adults with severe ITP who underwent IVIG therapy (0.4 g kg(-1)  day(-1) for 5 days) was analyzed. The primary outcome was response defined as platelet counts of ≥ 30 × 10(9)  L(-1) and a doubling of baseline counts within 7 days of dosing, and an absence of bleeding. RESULTS AND CONCLUSIONS Among the 66 patients with anti-GPIb-IX autoantibodies, only 24 (36.4%) achieved a response, as compared with 72 of 90 patients (80.0%) who were negative for anti-GPIb-IX autoantibodies (relative risk 2.2; 95% confidence interval 1.6-3.1). This study found no difference in response between patients with anti-GPIIb-IIIa autoantibodies (61.7%) and those without anti-GPIIb-IIIa autoantibodies (61.3%). Logistic regressions, including main effects and the interaction between these two autoantibodies, showed no influence of anti-GPIIb-IIIa autoantibodies on the effects of anti-GPIb-IX autoantibodies with regard to their association with IVIG response. Thus, in adults with ITP, the presence of anti-GPIb-IX autoantibodies is a predictive factor for poor response to IVIG treatment. TRIAL REGISTRATION ClinicalTrials.gov NCT01666795.
10.1111/jth.12524
pubmed_1134_2704
Carbon starvation is a significant stress encountered by the opportunistic fungal pathogen Candida albicans, and mutations in several pathways required to assimilate non-fermentable carbon sources attenuate virulence. These pathways -- beta-oxidation, the glyoxylate cycle and gluconeogenesis -- are compartmentalized in the fungal cell between the peroxisome, mitochondria and cytosol; thus, the cell must transport key intermediates between these organelles. Transport of acetyl-CoA, a particularly important intermediate of carbon metabolism, is catalysed by membrane-associated carnitine acetyltransferases (CATs). We report here the characterization of the three predicted CAT genes in C. albicans, CTN1, CTN2 and CTN3. Strains lacking CTN1 or CTN2 were unable to grow on ethanol or acetate as sole carbon source; additionally, citrate was utilized poorly (Deltactn2) or not at all (Deltactn1) and the Deltactn2 mutant failed to grow on fatty acids as well. In contrast, deletion of CTN3 had no observable phenotype. All three genes were upregulated in the presence of non-fermentable carbon sources and after macrophage phagocytosis. CTN1 and CTN3 were able to complement the corresponding Saccharomyces cerevisiae Deltayat1 and Deltayat2 mutants. However, these mutants had no obvious attenuation in virulence in a mouse model of disseminated candidiasis, in contrast to other carbon metabolism mutants. These findings extend our understanding of nutrient stress in vivo and in vitro and the contribution of metabolic pathways to virulence in C. albicans.
10.1099/mic.0.2007/014555-0
pubmed_201_5628
BACKGROUND Although several hypotheses have been proposed, the true origin and pathogenesis of aortic intramural hematoma (IMH) remain unclear. Evolution of patients with aortic IMH is highly variable. Progression to classic aortic dissection, aneurysm or to complete resolution have been described. Our purpose was to assess in-hospital and mid-term evolution of patients with aortic IMH. METHODS From 2000 to 2015, 40 patients with aortic IMH were prospectively and consecutively recruited in a tertiary care referral center. Aortic IMH was defined as the presence of a circular or crescent-shaped thickening of the aortic wall (≥5mm) in the absence of detectable blood flow inside, within the context of acute aortic syndrome. RESULTS Twenty three patients (57.5%) had type A, and 17 (42.5%) type B IMH. Up to 34.7% of patients with type A and 47.1% with type B IMH showed intimal tears in the imaging test at admission. In-hospital mortality was higher in the type A IMH group. All-cause mortality after discharge was 20%, without significant differences among groups. Out of hospital death was related to the aortic pathology in just one patient. At follow-up, radiological persistence of IMH was observed in 35.7% of patients with type A and 60% of those with type B IMH. CONCLUSIONS IMH related mortality takes place primarily during the acute phase of the disease. Clinical evolution after discharge is favorable, either in cases of reabsorption or persistence of the IMH. Imaging test findings rekindle the debate on the true training mechanism of the aortic IMH.
10.1016/j.ijcard.2017.09.170
pubmed_92_8594
Diverse pathogens have evolved to survive and replicate in the endosomes or phagosomes of the host cells and establish persistent infection. Ehrlichiae are Gram-negative, intracellular bacteria that are transmitted by ticks. Ehrlichiae reside in the endosomes of the host phagocytic or endothelial cells and establish persistent infection in their vertebrate reservoir hosts. CD4(+) T cells play a critical role in protection against phagosomal infections. In the present study, we investigated the expansion, maintenance, and functional status of antigen-specific CD4(+) T cells during persistent Ehrlichia muris infection in wild-type and interleukin-10 (IL-10)-deficient mice. Our study indicated that early induction of IL-10 led to reduced inflammatory responses and impaired bacterial clearance during persistent Ehrlichia infection. Notably, we demonstrated that the functional production of gamma interferon (IFN-γ) by antigen-specific CD4(+) T cells maintained during a persistent phagosomal infection progressively deteriorates. The functional loss of IFN-γ production by antigen-specific CD4(+) T cells was reversed in the absence of IL-10. Furthermore, we demonstrated that transient blockade of IL-10 receptor during the T cell priming phase early in infection was sufficient to enhance the magnitude and the functional capacity of antigen-specific effector and memory CD4(+) T cells, which translated into an enhanced recall response. Our findings provide new insights into the functional status of antigen-specific CD4(+) T cells maintained during persistent phagosomal infection. The study supports the concept that a better understanding of the factors that influence the priming and differentiation of CD4(+) T cells may provide a basis to induce a protective immune response against persistent infections.
10.1128/IAI.02101-14
pubmed_72_17367
We study the feasibility and capability of the kernel temporal difference (KTD)(λ) algorithm for neural decoding. KTD(λ) is an online, kernel-based learning algorithm, which has been introduced to estimate value functions in reinforcement learning. This algorithm combines kernel-based representations with the temporal difference approach to learning. One of our key observations is that by using strictly positive definite kernels, algorithm's convergence can be guaranteed for policy evaluation. The algorithm's nonlinear functional approximation capabilities are shown in both simulations of policy evaluation and neural decoding problems (policy improvement). KTD can handle high-dimensional neural states containing spatial-temporal information at a reasonable computational complexity allowing real-time applications. When the algorithm seeks a proper mapping between a monkey's neural states and desired positions of a computer cursor or a robot arm, in both open-loop and closed-loop experiments, it can effectively learn the neural state to action mapping. Finally, a visualization of the coadaptation process between the decoder and the subject shows the algorithm's capabilities in reinforcement learning brain machine interfaces.
10.1155/2015/481375
pubmed_567_22281
We assessed the bladder neck (BN) by perineal ultrasonography of 39 patients before and 1 year after hysterectomy, and we compared them with 30 control cases in terms of stress urinary incontinence. We evaluated the BN position and mobility in the downwards and backwards directions. The bladder neck was found to be significantly lower at rest, in the downwards direction, in the postoperative period. The stress position of the BN was not significantly different. Its downwards mobility decreased, but not significantly. There was no significant difference in the location of the BN with respect to the pubis, at rest and during stress, in the backwards direction, between the preoperative and postoperative periods. Backwards mobility of the BN decreased significantly following hysterectomy. Stress incontinence was not significantly different between the study group and the control group after one year. We concluded that hysterectomy did not weaken urethral support and did not increase the rate of stress incontinence.
10.1111/j.1479-828x.1999.tb03381.x
pubmed_245_6779
The aim of the study was to compare ex vivo the toxic effects of six root canal sealers immediately after mixing or setting on human periodontal ligament fibroblasts (HPdLF). Freshly mixed (I group) or set (allowed to dry for 24 h) (II group) specimens of AH Plus Jet (AH), Apexit Plus (AP), MTA Fillapex (FL), GuttaFlow (GF), MetaSEAL Soft (META), and Tubli-Seal (TS) were prepared. HPdLF were exposed for 24 h to the specimens. 3-(4,5-dimethylthiazolo-2-yl)-2,5-diphenyltetrazolium bromide assay was used to examine the effect of the root canal sealers on mitochondrial metabolic activity. Fluorescein isothiocyanate (FITC)-annexin V (AnV) and propidium iodide staining followed by flow cytometry was used to identify the effects of the materials on cell apoptosis/necrosis. Statistical analyses were performed by one-way ANOVA followed by post hoc tests, and significance was determined at P < 0.05. Most materials from the two groups reduced the viability of the cultured cells compared with the control group (P < 0.05). Statistical analysis showed significant differences in HPdLF viability between the individual materials in each group (P < 0.001). AH and AP induced a significant increase in the percentage of apoptotic cells, while TS, FL, and META elevated the proportion of necrotic cells compared with other materials and the controls (p < 0.05). The cytotoxic effects of the tested root canal sealers (both fresh and set) on HPdLF varied. Both forms of sealers were able to cause toxic effects by inducing apoptosis and necrosis in HPdLF. The cytotoxicity of FL, META, TS was mainly associated with necrosis, while AH and AP with apoptosis.
10.1007/s10266-017-0329-y
pubmed_550_12075
The creation of tissue-engineered constructs with autologous cells is a central goal in regenerative medicine. With respect to ligament replacement, we have evaluated the influences of matrix and growth factors on hMSCs (human mesenchymal stromal cells). hMSCs were seeded in two different 3D (three-dimensional) systems consisting of either a collagen type I gel or a synthetic PLA [poly-(L-lactic acid)] scaffold. After cultivation for 14 days with rhTGFbeta1 (recombinant human transforming growth factor beta1), rhPDGF-BB (recombinant human platelet-derived growth factor homodimer of B-chain) or rhBMP13 (recombinant human bone morphogenetic protein 13), we assessed the proliferation potential, mRNA expression and protein expression of various matrix-interacting and matrix-degrading molecules by quantitative real-time RT (reverse transcriptase)-PCR, immunohistochemistry and gelatin zymography in comparison with unstimulated cells. Cellular reactions to the type of scaffold or soluble factors could be found in the expression of tenascin-C as well as integrin subunits alpha1, alpha3 and beta1. Collagen type X expression was induced by 3D culture and stimulated by rhTGFbeta1 on PLA. The expression of MMP-1 (matrix metalloproteinase 1) tended to increase, and MMP-13 was induced in the collagen culture system. The activation of MMP-2 was stimulated by the cultivation of MSCs within the collagenous matrix. These results demonstrated that various interactive effects of growth factors and scaffolds influence the cell-biological behaviour of MSCs. It is important to take these complex interactions, which partly differ from differentiated cells, into account in further tissue-engineering approaches.
10.1042/BA20070071
pubmed_540_11930
The immune memory to common cold coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016-2019 in young adults and assessed CCC-specific CD4+ T cell and antibody responses. Notably, CCC responses were commonly detected with comparable frequencies as with other common antigens and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ signals, and their magnitude did not correlate with yearly CCC infection prevalence. Similarly, CCC-specific and spike RBD-specific IgG responses were stable in time. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results provide a valuable reference for understanding the immune response to endemic coronaviruses and suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells due to repeated earlier exposures and possibly occasional reinfections.
10.1016/j.chom.2022.07.012
pubmed_569_21738
Several observational studies, randomized controlled trials, and meta-analyses suggested that pretreatment with clopidogrel in addition to aspirin could reduce the rate of ischemic events, especially in the setting of acute coronary syndromes. Newer P2Y12 inhibitors like prasugrel and ticagrelor, which provide faster and stronger platelet inhibition compared with clopidogrel, would enhance the benefits of pretreatment. However, 2 recent randomized trials, A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction and the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery studies, aimed at assessing the effects of the timing of administration of novel P2Y12 inhibitors in acute coronary syndromes, failed to meet their primary end points. In this report, we review clinical data on pretreatment with dual oral antiplatelet therapy and comment on some criticisms raised from recent trials.
pubmed_569_21738
pubmed_440_5421
Physical properties of carbon nanotubes (CNTs) are closely related to the atomic structure, i.e. the chirality. It is highly desirable to develop a technique to modify their chirality and control the resultant transport properties. Herein, we present an in situ transmission electron microscopy (TEM) probing method to monitor the chirality transition and transport properties of individual few-walled CNTs. The changes of tube structure including the chirality are stimulated by programmed bias pulses and associated Joule heating. The chirality change of each shell is analyzed by nanobeam electron diffraction. Supported by molecular dynamics simulations, a preferred chirality transition path is identified, consistent with the Stone-Wales defect formation and dislocation sliding mechanism. The electronic transport properties are measured along with the structural changes, via fabricating transistors using the individual nanotubes as the suspended channels. Metal-to-semiconductor transitions are observed along with the chirality changes as confirmed by both the electron diffraction and electrical measurements. Apart from providing an alternative route to control the chirality of CNTs, the present work demonstrates the rare possibility of obtaining the dynamic structure-properties relationships at the atomic and molecular levels.
10.1016/j.ultramic.2018.07.012
pubmed_638_16372
BACKGROUND Many reports indicate that skin diseases are affected by lifestyle factors. OBJECTIVE To examine the relationship between reported skin diagnoses, smoking and alcohol consumption in an urban population. METHODS Cross-sectional questionnaire-based health study among 18,747 adults in Oslo. RESULTS For current smokers, odds ratio for reporting psoriasis was 1.49 (95% CI 1.11-2.00) for males, and 1.48 (95% CI 1.15-1.91) for females, as compared to never smokers. There was no association between reported atopic dermatitis or hand eczema and smoking. High consumption of cigarettes was associated with an increased reporting of psoriasis in men, but not women. Reporting drinking alcohol 4-7 times per week was crudely associated with reporting psoriasis in men, but not in the adjusted model. CONCLUSION Cigarette smoking was associated with reported psoriasis, but not with atopic dermatitis or hand eczema.
10.1159/000109357
pubmed_718_13130
Steady-state pattern visual evoked potentials were recorded from the surface of the cat primary visual cortex before and after the intravenous administration of physostigmine, an agent that blocks the enzyme responsible for the breakdown of synaptically released acetylcholine. Under pentobarbital anesthesia, physostigmine increased the amplitude and changed the phase of the second response harmonic of the visual evoked potential, whereas the amplitude and phase of the fourth harmonic were not affected. These effects persisted for 15 to 45 minutes and were blocked by prior treatment with scopolamine or atropine. In addition, scopolamine or atropine administered 5 to 10 minutes after physostigmine returned the visual evoked potential to the baseline state. In comparison, when nitrous oxide was used, physostigmine caused a marked reduction in visual evoked potential amplitude, an effect that was reversed by subsequent atropine. These results indicate that the cholinergic system influences the visual evoked potential via a muscarinic pathway and that this influence is strongly affected by the anesthetic regimen used.
10.1007/BF01203658
pubmed_339_15229
Early gastric cancer can be macroscopically classified into elevated and depressed types. To clarify the relationship between macroscopic appearance of early gastric cancer and apoptosis or cell proliferation, formalin-fixed paraffin-embedded tissue specimens of 44 intestinal-type early gastric cancers were investigated by the TUNEL method and immunohistochemical techniques. Diffuse type was excluded in this study. When tissue sections of gastric cancer were vertically classified into the 3 compartments of luminar, intermediate and basal, the apoptosis index (%) was significantly higher in the basal compartment of depressed type (1.76 +/- 2.04, mean +/- SD) than in the basal compartment of elevated type (0.63 +/- 0.81, P = 0.01). In depressed type, the apoptosis index (%) was significantly higher in the basal compartment than in the luminar compartment (0.76 +/- 0.85, P = 0.03). Apoptosis-inducing protein, Bax, was expressed more in each of the compartments of depressed type than in those of elevated type, while there were no significant differences in expression of anti-apoptotic protein, Bcl-2, between the two types. Moreover, the apoptosis index (%) of Bax-positive gastric cancer was significantly higher in the basal compartment (P = 0.03), compared to that of Bax-negative gastric cancer, while there were no significant differences in apoptosis index (%) in any compartment between Bcl-2-positive and Bcl-2-negative gastric cancers. There were no significant differences in Ki-67 expression, either between the two types, or among the compartments of depressed type. These results indicate that increased apoptosis with excessive expression of Bax in the basal compartment is involved in the morphogenesis of the depressed type in intestinal-type early gastric cancer.
10.1111/j.1349-7006.2001.tb02142.x
pubmed_166_18652
Heptosyltransferase I (HepI) catalyzes the addition of l-glycero-β-d-manno-heptose to Kdo2-Lipid A, as part of the biosynthesis of the core region of lipopolysaccharide (LPS). Gram-negative bacteria with gene knockouts of HepI have reduced virulence and enhanced susceptibility to hydrophobic antibiotics, making the design of inhibitors of HepI of interest. Because HepI protein dynamics are partially rate-limiting, disruption of protein dynamics might provide a new strategy for inhibiting HepI. Discerning the global mechanism of HepI is anticipated to aid development of inhibitors of LPS biosynthesis. Herein, dynamic protein rearrangements involved in the HepI catalytic cycle were probed by combining mutagenesis with intrinsic tryptophan fluorescence and circular dichroism analyses. Using wild-type and mutant forms of HepI, multiple dynamic regions were identified via changes in Trp fluorescence. Interestingly, Trp residues (Trp199 and Trp217) in the C-terminal domain (which binds ADP-heptose) are in a more hydrophobic environment upon binding of ODLA to the N-terminal domain. These residues are adjacent to the ADP-heptose binding site (with Trp217 in van der Waals contact with the adenine ring of ADP-heptose), suggesting that the two binding sites interact to report on the occupancy state of the enzyme. ODLA binding was also accompanied by a significant stabilization of HepI (heating to 95 °C fails to denature the protein when it is in the presence of ODLA). These results suggest that conformational rearrangements, from an induced fit model of substrate binding to HepI, are important for catalysis, and the disruption of these conformational dynamics may serve as a novel mechanism for inhibiting this and other glycosyltransferase enzymes.
10.1021/acs.biochem.6b00850
pubmed_160_3415
The Schiff base molecule of the title compound, C(14)H(12)N(4)O(6)·C(5)H(5)N, was obtained from the condensation reaction of 2-hy-droxy-3-meth-oxy-benzaldehyde and 2,4-dinitro-phenyl-hydrazine. The C=N bond of the Schiff base has a trans arrangement and the dihedral angle between the two benzene rings is 3.49 (10)°. An intra-molecular N-H⋯O hydrogen bond generates an S(6) ring. In the crystal, O-H⋯O hydrogen bonds link the Schiff base mol-ecules.
10.1107/S1600536810029971
pubmed_152_15526
BACKGROUND Studies examining the effects of oral contraceptives (OCs) on mood, affect, and affect variability are reviewed. METHODS MEDLINE and PsycLIT data bases were examined to identify studies that compared OC users with nonusers using daily ratings of mood, affect, or affect variability. RESULTS Compared to non-users, OC users experience less variability in affect across the entire menstrual cycle, and less negative affect during menstruation (i.e. withdrawal bleeding). In women with OC-related negative mood and affect change, potential mediators of the relation between OCs and mood or affect were identified: a history of depression, psychiatric symptoms, dysmenorrhea, and premenstrual mood symptoms prior to OC use; a history of pregnancy-related mood symptoms; a family history of OC-related mood complaints; being in the postpartum period; and age. Furthermore, a lower ratio of progesterone to estrogen is associated with more negative mood change in women with a history of premenstrual emotional symptoms, higher progesterone to estrogen ratios are associated with increased negative mood effects in women without such a history, and monophasic OCs have a greater stabilizing effect on mood than triphasic OCs. LIMITATIONS The 'survivor effect', psychological factors, and indirect pharmacological effects (e.g. weight gain) have not yet been systematically investigated. Furthermore, most studies have examined only negative mood or affect, as opposed to both positive and negative affect and affect variability; and few affect studies have assessed potential mediators of OC-related affect change. CONCLUSIONS While the only consistent OC-related mood effects experienced by most women are beneficial, a subgroup of women do experience negative mood change. Future research must focus on expounding the individual difference and OC-related risk factors for negative mood change.
10.1016/s0165-0327(01)00356-1
pubmed_415_465
Many fungi growing on plant biomass produce proteins currently classified as glycoside hydrolase family 61 (GH61), some of which are known to act synergistically with cellulases. In this study we show that PcGH61D, the gene product of an open reading frame in the genome of Phanerochaete chrysosporium, is an enzyme that cleaves cellulose using a metal-dependent oxidative mechanism that leads to generation of aldonic acids. The activity of this enzyme and its beneficial effect on the efficiency of classical cellulases are stimulated by the presence of electron donors. Experiments with reduced cellulose confirmed the oxidative nature of the reaction catalyzed by PcGH61D and indicated that the enzyme may be capable of penetrating into the substrate. Considering the abundance of GH61-encoding genes in fungi and genes encoding their functional bacterial homologues currently classified as carbohydrate binding modules family 33 (CBM33), this enzyme activity is likely to turn out as a major determinant of microbial biomass-degrading efficiency.
10.1371/journal.pone.0027807
pubmed_465_1048
Recessive mutations in two negative control elements, CRE1 and CRE2, have been obtained that allow the glucose-repressible alcohol dehydrogenase (ADHII) of yeast to escape repression by glucose. Both the cre1 and cre2 alleles affected ADHII synthesis irrespective of the allele of the positive effector, ADR1. However, for complete derepression of ADHII synthesis, a wild-type ADR1 gene was required. Neither the cre1 nor cre2 alleles affected the expression of several other glucose-repressible enzymes. A third locus, CCR4, was identified by recessive mutations that suppressed the cre1 and cre2 phenotypes. The ccr4 allele blocked the derepression of ADHII and several other glucose-repressible enzymes, indicating that the CCR4 gene is a positive control element. The ccr4 allele had no effect on the repression of ADHII when it was combined with the ADR1-5c allele, whereas the phenotypically similar ccr1 allele, which partially suppresses ADR1-5c, did not suppress the cre1 or cre2 phenotype. Complementation studies also indicated that ccr1 and snf1 are allelic. A model of ADHII regulation is proposed in which both ADR1 and CCR4 are required for ADHII expression. CRE1 and CRE2 negatively control CCR4, whereas CCR1 is required for ADR1 function.
10.1093/genetics/108.4.833
pubmed_592_13491
We used magnetic resonance imaging (MRI) velocity mapping to assess the velocity profile of early diastolic mitral inflow in 11 normal subjects. Velocity maps of left ventricular inflow were obtained in the horizontal long axis of the left ventricle at the time of peak early diastolic filling. Velocity profile curves across the mitral inflow were obtained at 1-cm intervals from the mitral ring to 4 cm into the cavity. The jet width was 3.06 +/- 0.64 cm at the mitral ring level, increasing to 3.6 +/- 0.61 cm at 4 cm. The peak/mean velocity was 1.2 +/- 0.07 at the mitral ring and increased to around 1.4 at 3-4 cm from the mitral ring. The point at which the peak velocity was recorded at each level was skewed towards the septal side by 10%-13% of jet width from the center at the mitral ring and 2-4 cm from the ring. However, at a depth of 1 cm, corresponding to the mitral tip level, the peak velocity was at the center of the jet. The ratio of vertical and horizontal dimensions of the jet cross section was 1.11 +/- 0.05. Thus, the mitral inflow velocity profile is relatively flat at the mitral ring and tip level; the inflow jet cross section is effectively circular.
10.1007/BF01744902
pubmed_681_8091
The purpose of this study was to compare the histologic appearance of the normal larynx and the larynx presumably affected by reflux. A secondary objective was to determine the safety of performing laryngeal biopsies. Biopsy specimens from the interarytenoid area of 15 patients with reflux laryngitis were compared with specimens from 9 control subjects. Control subjects were asymptomatic, had normal 24-hour pH studies, and had a normal videostroboscopic laryngeal examination. Patients with reflux laryngitis had abnormal pH studies and videostroboscopic examinations. There were no consistent changes in mucosal detail or cellular infiltration that distinguished the biopsies from normal patients and those with reflux laryngitis. In this small sample of subjects it was not possible to define any characteristic histologic features of reflux laryngitis.
10.1016/s0002-9343(03)00206-7
pubmed_445_1693
Generation of cytotoxic T lymphocytes (CTL) in mixed leukocyte cultures was suppressed by a factor elaborated by alloantigen-activated T cells. This suppressor factor, CTL-TsF, in contrast to a factor that suppresses proliferative responses in mixed leukocyte reactions (MLR-TsF), was effective only when added during the first 24 hr of a 6-day-culture period. Moreover, removal of CTL-TsF 24 hr after culture initiation failed to restore CTL responses. CTL activity could be rescued from suppressed cultures, however, by addition of 2-mercaptoethanol on days 3 or 4. Similarly, transfer of nonadherent cells at 3 or 4 days from cultures treated with CTL-TsF to cultures of adherent cells initiated in control factor restored CTL responses. Mixing experiments with cells pulsed with CTL-TsF for 4 hr at culture initiation identified a target of CTL-TsF as a Thy-1 negative cell that was adherent to plastic and to Sephadex G-10. Suppression was not due to interference with physiologic accessory cell function, but more likely was accomplished via a negative signal from CTL-TsF-pulsed cells. The results thus suggest that CTL-TsF acts early, but reversibly, in the CTL differentiative process via a second suppressor effector cell, possibly a macrophage.
pubmed_445_1693
pubmed_186_11656
The prevention of femoral head collapse and the maintenance of hip function would represent a substantial achievement in the treatment of osteonecrosis of the femoral head; however it is difficult to identify appropriate treatment protocols to manage patients with pre-collapse avascular necrosis in order to obtain a successful outcome in joint preserving procedures. Conservative treatments, including pharmacological management and biophysical modalities, are not supported by any evidence and require further investigation. The appropriate therapeutic approach has not been identified. The choice of surgical procedures is based on patient clinical conditions and anatomopathological features; preservation of the femoral head by core decompression may be attempted in younger patients without head collapse. Biological factors, such as bone morphogenetic proteins and bone marrow stem cells, would improve the outcome of core decompression. Another surgical procedure proposed for the treatment of avascular necrosis consists of large vascularized cortical bone grafts, but its use is not yet common due to surgical technical issues. Use of other surgical technique, such as osteotomies, is controversial, since arthroplasty is considered as the first option in case of severe femoral head collapse without previous intervention.
10.11138/ccmbm/2015.12.3s.043
pubmed_695_3772
Gaining detailed insights into the role of host immune responses in viral clearance is critical for understanding COVID-19 pathogenesis and future treatment strategies. Although studies analyzing humoral immune responses against SARS-CoV-2 were available rather early during the pandemic, cellular immunity came into focus of investigations just recently. For the present work, we have adapted a protocol designed for the detection of rare neoantigen-specific memory T cells in cancer patients for studying cellular immune responses against SARS-CoV-2. Both CD4+ and CD8+ T cells were detected after 6 d of in vitro expansion using overlapping peptide libraries representing the whole viral protein. The assay readout was an intracellular cytokine staining and flow cytometric analysis detecting four functional markers simultaneously (CD154, TNF, IL-2, and IFN-γ). We were able to detect SARS-CoV-2-specific T cells in 10 of 10 COVID-19 patients with mild symptoms. All patients had reactive T cells against at least 1 of 12 analyzed viral Ags, and all patients had Spike-specific T cells. Although some Ags were detected by CD4+ and CD8+ T cells, VME1 was mainly recognized by CD4+ T cells. Strikingly, we were not able to detect SARS-CoV-2-specific T cells in 18 unexposed healthy individuals. When we stimulated the same samples overnight, we measured significant numbers of cytokine-producing cells even in unexposed individuals. Our comparison showed that the stimulation conditions can profoundly impact the activation readout in unexposed individuals. We are presenting a highly specific diagnostic tool for the detection of SARS-CoV-2-reactive T cells.
10.4049/jimmunol.2000811
pubmed_35_16420
INTRODUCTION Vasculitis are characterised by the inflammatory infiltrate, chiefly of mononuclear cells, in the walls of the blood vessels, which can lead to occlusion with necrosis and the subsequent infarction of the affected tissue. AIMS The Objective of this study was to determine the clinical, anatomicopathological and neurophysiological aspects of vasculitic neuropathies in infancy. PATIENTS AND METHODS Each patient was submitted to the following tests: a complete hemogram, systemic lupus erythematosus cells (LE cells), lupus anticoagulant, antinuclear antibodies, neutrophil anticytoplasmic antibodies, venereal disease research laboratory test (VDRL), erythrocyte sedimentation rate, liver transaminases, serological testing for hepatitis C, B and A, cytochemical study of the cerebrospinal fluid, study of motor and sensory conduction, electromyography and nuclear magnetic resonance, when required; a biopsy of the sural nerve was performed, which was replaced by a necropsy if the patient died. RESULTS 15 patients from a total of 25 who were studied had vasculitic neuropathies; the most usual presentation was multiple mononeuropathy; aetiologies found included microscopic polyangiitis, systemic lupus erythematosus, JRA, overlap syndrome and several undetermined vasculitis. Of the patients who were submitted to a biopsy, 75% showed signs of vasculitis, which affected the small and medium sized vessels in 62.5% of patients. CONCLUSIONS The presence of neuropathy in association with symptoms and signs of systemic involvement suggested the possibility of a neuropathy in the course of a vasculitis. The examination of biopsy specimens of the sural nerve is useful for the diagnosis and classification of the aetiology of vasculitis. Response to treatment with immunosuppressant drugs was good, both in the case of the neuropathy and of the underlying disease.
pubmed_35_16420
pubmed_1090_8258
A review of 21 women irradiated because of stage IV-A carcinoma of the cervix was undertaken to determine whether applied external beam pelvic irradiation (EBPI) and intracavitary brachytherapy (ICB) for the disease would result in improved survival but at the price of irradiation-induced fistula formation in the tumor-involved bladder or rectum. Based on the 14 evaluable patients who received megavoltage EBPI, the five-year survival rate was better when EBPI was applied with ICB than with EBPI alone, 33% versus 0%, respectively (p = 0.06). All seven cases of vesicovaginal or rectovaginal fistulas were observed in the presence of malignant tumor. Fistula formation did not occur in any of the six patients who received EBPI with ICB.
pubmed_1090_8258