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pubmed_80_19869
Purpose: To examine the burden and cost of diabetes among fee-for-service Medicare beneficiaries. Methods: Medicare 5% File data for type 1 diabetes (T1D) and type 2 diabetes (T2D) consisting of 1,397,933 enrollees in fee-for-service without Medicare Advantage during the period 2012-2013 were analyzed by race and ethnicity. Results: Although non-Hispanic whites (nHWs) comprised most of this population (86%), prevalence of T1D and T2D was higher for Hispanics than nHWs (3.4% vs. 1.8%, p=0.0006, for T1D and 33.4% vs. 21.9%, p<0.0001, for T2D). Hispanics also had more acute hospital admissions (p=0.0235 for T1D and p=0.0009 for T2D) and longer lengths of stay (7.5 vs. 6.9 days for T1D, p=0.0105, and 6.7 vs. 6.2 days for T2D, p<0.0001) compared with nHWs. Allowed and paid costs per member per month adjusted for confounding were higher for Hispanics than nHWs for T2D (both p<0.0001) and lower for those with T1D (both p<0.0001). Mean number of chronic diseases in patients with diabetes was higher in Hispanics than nHWs (both T1D and T2D, p<0.0000). For T2D, Hispanics were more likely to have glycated hemoglobin (HbA1c) and lipid testing as well as nephropathy screening (all p<0.0001). Hispanics with T1D were also more likely to have HbA1c and lipid tests (p=0.0014 and p=0.0011, respectively); retinopathy and nephropathy screening rates did not differ significantly from rates among nHWs. Conclusion: Diabetes disproportionately impacts US seniors, with Hispanics almost twice as likely as nHWs to be diagnosed. Racial and ethnic disparities exist in the burden and cost of diabetes care for Medicare recipients.
10.1089/heq.2019.0004
pubmed_207_13532
Drainage in thyroid surgery has been a routine but empirical practice with no scientific evidence to support its benefit. The largest series to date of non-drainage in thyroid surgery is presented, comprising 260 patients over a 15-year period. No case selection for non-drainage was employed. Two hundred and fifty-nine cases were not drained and included toxic goitres, and bilateral and redo procedures. There was one thyroid storm and two cases of subcutaneous fluid collection, treated by needle aspiration. No cases of recurrent laryngeal nerve injury, airway obstruction or death were recorded. This study strongly demonstrates the safety of non-drainage in routine thyroid surgery.
pubmed_207_13532
pubmed_762_14283
This study was designed to elucidate the mechanism of YMB Injection on anti-CAD therapy. Fufang Danshen Injection was used as positive control and saline was taken as negative control to study the effects of traditional medicine YMB Injection on hemorheological parameters in normal rats and hypostasis rats. The results showed YMB Injection had no effect on hemorheological parameters of normal rats, but it could effectively decrease whole blood viscosity and whole blood reduction viscosity of hypostasis rats. The data implied that YMB Injection could decrease blood viscosity and hence improve blood supply of the graft in anti-CAD therapy.
pubmed_762_14283
pubmed_64_10982
Xylosma longifolia is a tree species within Salicaceae and is distributed in Guizhou, Yunnan, Fujian, Guangxi, Guangdong, and Hainan provinces of China as well as in Vietnam, Laos, and India. There are no studies utilizing the complete plastome of Xylosma longifolia in the current literature. Therefore, this report provides a reference for the plastid gene sequence of Xylosma longifolia, and it contributes to the phylogenetic placement and species identification. In this report, we described the complete plastome sequence of Xylosma longifolia. The complete plastome length of Xylosma longifolia is 156,938 bp and has the typical quadripartite structure and gene content of angiosperms, including two inverted repeat (IR) regions of 27,514 bp, a large single-copy (LSC) region of 85,221 bp and a small single-copy (SSC) region of 16,689 bp. The plastome contains 130 genes, including 86 protein coding genes, 36 tRNA genes, eight rRNA genes (5S rRNA, 4.5S rRNA, 16S rRNA, and 23S rRNA). The GC content of the plastome is 36.8%. The complete plastome sequence will be a valuable resource for studies involving the phylogenetic inference of Salicaceae.
10.1080/23802359.2021.1899870
pubmed_1021_19394
Among 115 subjects suffering from peripheral neuropathies of various origins, in 71 (61.7%) no fasciculations were noticed in the lower limbs, while they were present in 27 (23.4%); 17 (14.7%) reported the presence of fasciculations that, however, were not observed during the neurological examination or on EMG. The only difference between the subjects without and with fasciculations seems to be the greater number of polyphasic potentials registered at the EMG in the latter.
pubmed_1021_19394
pubmed_162_23156
BACKGROUND Ketamine is a general anesthetic thought to act by antagonizing N-methyl-D-aspartate receptors. However, ketamine acts on multiple channels, many of which are potential targets-including hyperpolarization-activated cyclic nucleotide-gated and potassium channels. In this study we tested the hypothesis that potassium leak channels contribute to the anesthetic action of ketamine. METHODS Adult mouse cortical slices (400 µm) were exposed to no-magnesium artificial cerebrospinal fluid to generate seizure-like event activity. The reduction in seizure-like event frequency after exposure to ketamine (n = 14) was quantified as a signature of anesthetic effect. Pharmacologic manipulation of hyperpolarization-activated cyclic nucleotide-gated and potassium channels using ZD7288 (n = 11), cesium chloride (n = 10), barium chloride (n = 10), low-potassium (1.5 mM) artificial cerebrospinal fluid (n = 10), and urethane (n = 7) were investigated. RESULTS Ketamine reduced the frequency of seizure-like events (mean [SD], -62 [22]%, P < 0.0001). Selective hyperpolarization-activated cyclic nucleotide-gated channel block with ZD7288 did not significantly alter the potency of ketamine to inhibit seizure-like event activity. The inhibition of seizure-like event frequency by ketamine was fully antagonized by the potassium channel blockers cesium chloride and barium chloride (8 [26]% and 39 [58%] increase, respectively, P < 0.0001, compared to ketamine control) and was facilitated by the potassium leak channel opener urethane (-93 [8]%, P = 0.002 compared to ketamine control) and low potassium artificial cerebrospinal fluid (-86 [11]%, P = 0.004 compared to ketamine control). CONCLUSIONS The results of this study show that mechanisms additional to hyperpolarization-activated cyclic nucleotide-gated channel block are likely to explain the anesthetic action of ketamine and suggest facilitatory action at two-pore potassium leak channels.
10.1097/ALN.0000000000002147
pubmed_378_8255
The purpose of this research was to determine whether motor cortex excitability assessed using transcranial magnetic stimulation (TMS) is less variable when subjects maintain a visually controlled low-level contraction of the muscle of interest. We also examined the dependence of single motor evoked potential (MEP) amplitude on stimulation intensity and pre-stimulus muscle activation level using linear and non-linear multiple regression analysis. Eight healthy adult subjects received single pulse TMS over the left motor cortex at a point where minimal stimulation intensity was required to produce MEPs in extensor digitorum communis (EDC). Voluntary activation of the muscle was controlled by visual display of a target force (indicated by a stable line on an oscilloscope) and the isometric force produced as the subject attempted to extend the fingers (indicated by a line on the oscilloscope representing the finger extension force) while subjects were instructed to: exert zero extension force (0%) and produce forces equal to 5 and 10% of maximum voluntary finger extension under separate conditions. Relative variability (coefficient of variation) of single MEPs at a constant stimulus intensity and of pre-stimulus muscle EMG was lower during maintained 5 and 10% contractions than at 0% contraction levels. Therefore, maintaining a stable low intensity contraction helps stabilize cortical and spinal excitability. Multiple regression analyses showed that a linear dependence of single MEPs on stimulation intensity and pre-stimulus muscle activation level produced similar fits to those for a non-linear dependence on stimulus intensity and a linear dependence on pre-stimulus EMG. Thus, a simple linear method can be used to assess dependence of single MEP amplitudes on both stimulus intensity (to characterize slope of the recruitment curve) and low intensity background muscle activation level.
10.1007/s00221-006-0468-9
pubmed_697_18450
INTRODUCTION Scoliosis is a complex spinal deformity whose etiology is still unknown, and its treatment presents many challenges. Finite element modeling (FEM) is one of the analytical techniques that has been used to elucidate the mechanism of scoliosis and the effects of various treatments. METHODS A literature review on the application of FEM in scoliosis evaluation and treatment has been undertaken. A literature search was performed in each of three major electronic databases (Google Scholar, Web of Science, and Ovid) using the key words "scoliosis" and "finite element methods/model". Articles using FEM and having a potential impact on clinical practice were included. RESULTS A total of 132 abstracts were retrieved. The query returned 105 articles in which the abstracts appeared to correspond to this review's focus, and 85 papers were retained. The current state of the art of FEM related to the biomechanical analysis of scoliosis is discussed in 4 sections: the etiology of adolescent idiopathic scoliosis, brace treatment, instrumentation treatment, and sensitivity studies of FEM. The limitations of FEM and suggested future work are also discussed.
10.1016/j.jspd.2013.09.007
pubmed_121_5670
BACKGROUND Optical coherence tomography (OCT) is a modern, non-invasive technique for examining the posterior segment of the eye in vivo. The quality of images is crucial for the diagnostic process. Despite good image quality and high signal strength, we still obtain images with less relevant diagnostic data, especially in relation to RNFL and GCL thickness in myopic and hyperopic eyes. AIM To evaluate the change of RNFL, GCL thickness and rim and disk areas in myopic eyes that underwent OCT examination before and after refractive correction with contact lenses or glasses. METHOD A prospective cross-sectional pilot study included 43 eyes in 22 patients with myopia and hyperopia, with or without astigmatism. Patients were examined using OCT with and without contact lenses or glasses. RESULTS RNFL thickness, GCL thickness, rim area and disk area average and minimum values were significantly changed after correction with glasses or contact lenses. CONCLUSION Myopic patients with greater than -2.50 D have to be examined using OCT with their contact lens or glasses corrections in the case of borderline data. Uncorrected myopic eyes show a thinner RNFL and GCL and smaller disk areas, which may mislead ophthalmologists.
10.3390/jcm11123430
pubmed_926_8401
Theoretical spectroscopic parameters are derived for all isotopologues of HCO+ and HOC+ involving H, D, 16O, 17O, 18O, 12C, and 13C by means of a two-step procedure. Full-dimensional rovibrational calculations are first carried out to obtain numerically exact rovibrational energies for J = 0-15 in both parities. Effective spectroscopic constants for the vibrational ground state, ν1, ν2, and ν3 are determined by fitting the calculated rovibrational energies to appropriate spectroscopic Hamiltonians. Combining our vibration-rotation corrections with the available experimental ground-state rotational constants, we also derive the new estimate for the equilibrium structure of HCO+, re(CH) = 1.091 98 Å and re(CO) = 1.105 62 Å, and for the equilibrium structure of HOC+, re(HO) = 0.990 48 Å and re(CO) = 1.154 47 Å. Regarding the spectroscopic parameters, our estimates are in excellent agreement with available experimental results for the isotopic variants of both HCO+ and HOC+: the agreement for the rotational constants Bv is within 3 MHz, for the quartic centrifugal distortion constants Dv within 1 kHz, and for the effective ℓ-doubling constants qv within 2 MHz. We thus expect that our results can provide useful assistance in analyzing expected observations of the rare isotopologues of HCO+ and HOC+ that are not yet experimentally known.
10.1063/1.4998467
pubmed_439_11275
Nanoscale assemblies of amphiphiles have been vividly explored in pharmaceutical formulations as drug nanocarriers. Aqueous interfaces of liquid crystals (LCs) are known to direct the self-assembly of a range of amphiphiles. These amphiphile-decorated interfaces of LCs have evoked interest for applications as diverse as the detection of disease markers, screening of toxins, mimicking complex biomolecular interactions, and cell-based sensing. Aiming to explore these interfaces for encapsulation and enzyme-triggered release, we report a simple and rational design of enzyme-responsive LC interfaces programmed with a cleavable non-ionic surfactant. We encapsulated a hydrophobic dye within the surfactant micelles and investigated the enzyme-triggered dye release. Interestingly, we found that LC droplets, when decorated with the dye-loaded micelles, offer significant advantages over the conventional micellar nanocarriers. The LC droplets showed controlled release features which weren't affected at high dilutions. Our work, although exploratory in nature, provides fresh approaches for tailoring LC interfaces as vehicles for drug delivery.
10.1039/d2tb00098a
pubmed_543_4524
Lactulose is a poorly absorbed synthetic disaccharide frequently used in the treatment of portasystemic encephalopathy. Because lactulose syrup contains small amounts of absorbable sugars, it may cause hyperglycemia in diabetic individuals, but is usually well tolerated. We report the case of a patient with diet-controlled diabetes and cirrhosis who experienced a marked deterioration in glycemic control, requiring insulin use, when he began using a different brand of lactulose syrup. The hyperglycemia resolved and insulin was discontinued after use of the original brand of lactulose syrup was resumed.
10.1097/00007611-199504000-00025
pubmed_828_14223
OBJECTIVE This study aimed at identifying the gaps, barriers and successes/solutions associated with mental health services in Mi'kmaq communities in Nova Scotia. METHODS Community-based participatory research, which is consistent with Ownership, Control, Access and Possession principles of research with Aboriginal communities, was employed for this work. Health directors of the 13 Mi'kmaq communities in Nova Scotia were involved with the research question, design and write-up of the study. This qualitative descriptive study consisted of open-ended structured interviews with consumers, family members and health care providers. Systematic data collection and analysis of interviews present an understanding of issues of mental health services in the communities. RESULTS The findings identified barriers and successes/solutions in mental health services in First Nations communities, where services and resources are different from those in more urban communities. Core programs, covering aspects of education, collaboration and culturally relevant community-based services, were identified as solutions to problems identified by participants. Service providers specified core funding for services as essential for continuity and sustainability. DISCUSSION While efforts have been made in the past to address mental illness in Mi'kmaq communities, many of these efforts have been proposal driven or crisis oriented. The need for community-based, culturally appropriate, coordinated and sustainable services is evident on the basis of the study's findings. The final report has been disseminated to local community members, participants, Atlantic First Nations and Inuit Health Branch, the Provincial Department of Health and the Atlantic Policy Congress to provide evidence that can inform policy and practice related to mental health in Mi'kmaq communities in Nova Scotia.
pubmed_828_14223
pubmed_1128_20779
Ninety patients with glottic and eighteen patients with supraglottic laryngeal cancer (anyN, M0) were treated by conventional fractionation radiotherapy between July, 1963 and August, 1988. Tumor control and cause specific survival were evaluated according to tumor location (glottic or supraglottic) and tumor size (T1, T2, T3, or T4). As a result, the steepness of dose-response curve for the tumor control in T1-2 glottic and T2 supraglottic tumors was more slanting upwards than that in other laryngeal tumors, and the patients whose tumors were irradiated at larger doses had a tendency to survive longer. These results suggested that T1-2 glottic and T2 supraglottic laryngeal tumors can have a good application for hyperfractionation radiotherapy which is a radiation therapy with multiple fractions per day with a small fraction size and with which tumors can receive larger radiation doses than with conventional fractionation radiotherapy. Five patients with glottic or supraglottic tumors treated by hyperfractionation radiotherapy obtained CR, and now show no recurrence. We are going to investigate the usefulness of hyperfractionation radiotherapy after treating more patients with Twice-A-Day fractionation radiotherapy.
pubmed_1128_20779
others_224_9275
The growth of microorganisms in foods is different from that in axenic liquid culture in laboratory media. In natural environments, including food, microorganisms generally grow in mixed culture and in close proximity to each other, as a result of which antagonistic or synergistic interactions can occur. In addition, most foods are solids, with the consequence that organisms are spatially fixed and will only grow at sites that provide the correct growth conditions. At different sites within foods there are differences in pH, oxygen concentration, nutrient level, water activity and also, in some foods, preservatives. This results in the establishment of a series of micro-environments, only some of which will provide appropriate conditions for growth. Antibody-linked probes can be used for the immuno- location of microorganisms or their products in natural food systems to demonstrate the sites at which growth has occurred, and thereby suggest methods of reducing microbially produced spoilage. In this study, the use of antibodies raised against species of Pseudomonas, Brochothrix thermosphacta, and nisin produced by Lactococcus lactis are discuss
10.1080/09540109609354923
pubmed_1103_18139
Stimulated by the widespread use of tilt table testing, disorders of autonomic function with orthostatic hypotension have recently gained attention by clinical cardiologists. At the same time, improved characterization of the underlying circulatory responses have led to a reclassification of these syndromes. In particular, three subgroups of chronic primary dysautonomia have been defined such as Pure Autonomic Dysfunction, Multiple System Atrophy, and the Postural Orthostatic Tachycardia Syndrome. On the other hand, acute dysautonomias represent a rare yet clinically sometimes dramatic form of autonomic disorders. Several diseases as well as enzymatic disorders, and pharmacological drugs may cause secondary dysautonomia. The clinical correlate of all these forms of dysautonomia is orthostatic hypotension and syncope. Thus, a careful history forms the basis of a successful diagnostic workup of the underlying cause of syncope. This review summarizes the current knowledge of autonomic disorders, their classification and diagnostic and therapy strategies.
10.1007/s003920050323
pubmed_345_18296
X-ray focus optimization and characterization based on coherent scattering and quantitative speckle size measurements was demonstrated at the Linac Coherent Light Source. Its performance as a single-pulse free-electron laser beam diagnostic was tested for two typical focusing configurations. The results derived from the speckle size/shape analysis show the effectiveness of this technique in finding the focus' location, size and shape. In addition, its single-pulse compatibility enables users to capture pulse-to-pulse fluctuations in focus properties compared with other techniques that require scanning and averaging.
10.1107/S1600577515004361
pubmed_83_13666
Mucinous lesions of appendix are a rare clinical entity and may be neoplastic or non-neoplastic. The diagnosis is usual incidental during computed tomography scan or colonoscopy performed for general abdominal symptoms or occasional finding during operation for acute appendicitis. For this reason, initial treatment should be tailored to the situation, aiming at complete resection of the appendix with disease-free margins: this can be achieved by simple appendectomy or more extensive resection. The pathological examination of the specimen is the key to offer the patient a correct and complete treatment, and, if a neoplastic pathology is found, the case should be discussed in multidisciplinary group. We describe three cases with different clinical presentation leading to different surgical treatment: one elective case, in which the diagnosis was suspected preoperatively; and two urgent cases, one mimicking an intussusception and another one presenting as an acute appendicitis.
10.1093/jscr/rjaa344
others_73_5251
Nine patients with active systemic lupus erythematosus entered a double-blind randomized trial to study the therapeutic effect of vigorous versus sham reinfusion plasmapheresis. Four of them received real plasmapheresis while five received sham reinfusion plasmaphersis. In the present communication we report the effects of these procedures on T lymphocytes in peripheral mononuclear cells, proliferative responses to mitogens, allogeneic mixed lymphocyte reaction and cell-mediated lympholysis, as well as the effect of plasmapheresis on the spontaneous and pokeweed mitogen induced immunoglobulin secreting cells in peripheral blood. Several mononuclear cell functions were abnormal at the beginning of the study but no significant changes related to plasmapheresis occurred in any of the parameters stud
others_73_5251
pubmed_491_10448
Some investigators have emphasized restoring the relationship between the sesamoid complex and the first metatarsal head to reduce the risk of hallux valgus recurring after surgical reconstruction. In a prospective study, we analyzed whether the first metatarsophalangeal joint could be realigned after scarf-Akin bunionectomy without lateral soft tissue release. A total of 25 feet, in 22 patients, were prospectively enrolled and analyzed using anteroposterior radiographs and coronal computed tomography scans obtained before and 3 months after surgery. The Yildirim sesamoid position decreased from a preoperative of 2 (range 1 to 3) to a postoperative position of 0 (range 0 to 1; p < .001), the mean first intermetatarsal angle decreased from 12.6° ± 2.4° to 5.8° ± 2.1° (p < .001), and the mean distance between the second metatarsal and the tibial sesamoid changed from 25.7 ± 4.6 to 25.9 ± 4.6 (p = .59). Our findings suggest that dislocation of the sesamoid complex is actually caused by displacement of the first metatarsal. In conclusion, the scarf-Akin bunionectomy adequately restores the alignment of the first metatarsophalangeal joint, including restoration of the sesamoid apparatus, without direct plantar-lateral soft tissue release.
pubmed_491_10448
pubmed_516_16796
There is currently controversy on whether the insufficient response to penile venous surgery done in an attempt to restore erectile function is due to recurrent or residual veins. In order to elucidate this issue, we report a study on those patients who failed to respond to the first venous surgery and subsequently underwent or declined a second operation. From July 1996 to July 2003, a total of 83 patients, aged 25 to 83, who were dissatisfied with their first venous surgery and were later diagnosed with a persistent veno-occlusive dysfunction via our dual cavernosography, were recruited into our study. Subsequently, 45 men underwent penile venous stripping surgery for a second time and were assigned to the surgery group, whereas the remaining 38 men were subject to follow-up and routine management and were assigned to the control group. All were evaluated with the abridged 5-item version of the international index of erectile function (IIEF-5) every 6 months for 1 to 5 years and cavernosogram, if necessary. In the surgery group their preoperative IIEF-5 score was 10.1 +/- 3.7, which increased to 17.1 +/- 3.2 (P < .001) after the first surgery and further increased to 20.7 +/- 3.1 (P < .001) after a second venous stripping of the cavernosal vein that was consistently demonstrated on the cavernosogram. Overall, 41 men (91.1%) reported a positive response to further venous surgery, with more satisfactory coitus, after the residual veins were stripped thoroughly, although eventually 4, 3, and 3 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. The follow-up period ranged from 12 months to 72 months, with an average of 37.0 +/- 11.5 months. In the control group, however, their corresponding IIEF-5 score changed from 17.4 +/- 2.9 to 16.9 +/- 3.2 (P > .05). Finally, 11, 7, and 8 men required additional oral sildenafil, penile implant, and intracavernosal injection, respectively. Although there was no statistical significance between the 2 groups in the first postoperative IIEF-5 scores, there was a significant difference in their IIEF-5 after further venous surgery. In this study, we propose that the clinical relapse of erectile dysfunction is a result of "residual" veins rather than "recurrent" ones.
10.2164/jandrol.106.000737
others_290_12162
Proso millet (Panicum miliaceum L.) has many favored nutritional and agronomic traits, which makes it appropriate for cultivation and consumption all around the world. Genomic resources for proso millet are still very limited but the set of genomic data is improving. In this study, we genotyped six Slovenian landraces of proso millet (P. miliaceum L.) along with one Slovene autochthonous cultivar, Sonček. The chosen set of 11 SSR markers showed that there is low overall heterozygosity (0.561) among Slovenian landraces of proso millet. However, we were able to determine distinct groups on the dendrogram for different landraces and the cultivar by using UPGMA clustering. The PCoA scatter plot showed dispersion of unique individuals. The SSR markers used proved to be efficient for assessing the genetic diversity of Slovenian landraces of proso millet. Furthermore, we performed a 3-year field experiment and determined grain yield (ranging from 1032 to 1667 kg ha − 1 ) and yield stability using Kang’s yield stability index (YSi). The morphology of panicles and grain was described as well. © TÜBİTAK
10.3906/bot-1807-83
pubmed_761_18257
This article aims to analyse a possible manner of approaching the birth of intersexual children. We start out by summing up what intersexuality is and how it is faced in the dominant clinical practice (the "treatment paradigm"). We then argue against this paradigm, in favour of a postponement of genital surgery. In the second part of this paper, we take into consideration the general question of whether only two existing sexes are to be recognized, arguing in favour of an expansion of sex categories. In the third part, we illustrate the reasons supporting provisional sex attribution: the child's best interest and respect for their developing moral autonomy. This position aims to increase the child's well-being and self-determination, limiting parents' freedom to take decisions on behalf of others, in particular, those decisions concerning basic aspects of their children's personal identity.
10.1007/s11673-018-9880-7
pubmed_26_1249
Pigment cells of lower vertebrates provide an excellent model to study organelle transport as they specialize in the translocation of pigment granules in response to defined chemical cues. This review will focus on the well-studied melanophore/melanocyte systems in fish, amphibians, and mammals. We will describe the roles of melanin, melanophores, and melanocytes in animals, current views on how the three motor proteins dynein, kinesin, and myosin-V are involved in melanosome transport along microtubules and actin filaments, and how signal transduction pathways regulate the activities of the motors to achieve aggregation and dispersion of melanosomes. We will also describe how melanosomes are transferred to surrounding skin cells in amphibians and mammals. Comparative studies have revealed that the ability of physiological color change is lost during evolution while the importance of morphological color change, mainly via transfer of pigment to surrounding skin cells, increases. In humans, pigment mainly has a role in protection against ultraviolet radiation, but also perhaps in the immune system.
10.1016/S1937-6448(08)01606-7
pubmed_530_11061
INTRODUCTION Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid/rhabdoid tumor (ATRT) is a rare, high-grade embryonal brain tumor that occurs most commonly in young children and carries a very poor prognosis. ATRTs are characterized by absence of the chromatin remodeling protein SMARCB1. Given the role of EZH2 in regulating epigenetic changes, we investigated the role of EZH2 in ATRT. METHODS Microarray analysis was used to evaluate expression of EZH2 in ATRT tumor samples. We used shRNA and a chemical inhibitor of EZH2 to examine the impact of EZH2 inhibition on cell growth, proliferation, and tumor cell self-renewal. RESULTS Here, we show that targeted disruption of EZH2 by RNAi or pharmacologic inhibition strongly impairs ATRT cell growth, suppresses tumor cell self-renewal, induces apoptosis, and potently sensitizes these cells to radiation. Using functional analysis of transcription factor activity, we found the cyclin D1-E2F axis to be repressed after EZH2 depletion in ATRT cells. CONCLUSIONS Our observations provide evidence that EZH2 disruption alters cell cycle progression and may be an important new therapeutic target, particularly in combination with radiation, in ATRT.
10.1093/neuonc/nos285
pubmed_114_7842
The more rapid rate of rise of alveolar anesthetic partial pressure in children compared with adults may be explained in part by an increasing solubility of volatile anesthetics in blood with age. To investigate this possibility, the authors measured the blood-gas partition coefficients of isoflurane, enflurane, halothane, and methoxyflurane in four groups of fasting subjects: 10 full-term newborns (at delivery), 11 children (3-7 years old), 11 adults (20-40 years old), and 10 elderly adults (75-85 years old). The blood-gas partition coefficients were greatest in adults: isoflurane 1.46, enflurane 2.07, halothane 2.65, and methoxyflurane 16.0; and least in newborns: 1.19, 1.78, 2.14, 13.3, respectively. The blood-gas partition coefficients in children (1.28, 1.78, 2.39, 15.0, respectively), which were intermediate between those in newborns (P less than 0.005) and those in adults (P less than 0.005), were not significantly different from those in elderly adults (1.29, 1.79, 2.41, 15.0, respectively). The blood-gas partition coefficients of both isoflurane and enflurane correlated directly with the serum albumin and triglyceride concentrations; that of halothane correlated directly with the serum cholesterol, albumin, triglyceride, and globulin concentrations; and that of methoxyflurane correlated directly with the serum cholesterol, albumin, and globulin concentrations. The authors conclude that age significantly affects blood-gas partition coefficients, and the lower blood-gas partition coefficients in children explain in part the more rapid rise of alveolar anesthetic partial pressure in this age group.
10.1097/00000542-198408000-00005
pubmed_505_2641
OBJECTIVE To estimate the proportion of patient referral and to identify the factors associated with unsuccessful referral in Karachi, Pakistan. METHODS In a cross-sectional survey, a total of 347 patients referred to different health care facilities by the LHWs were interviewed. Data was collected using a structured questionnaire, on demographic characteristics of patients (age, sex, income etc) and potential factors (seriousness of medical condition, distance of health facility, attitude of health center staff etc) that can affect patient referral outcome. RESULTS An overall referral rate of 55% was found in this study. Out of a total of 347 patients interviewed, 265 (76.4%) were successful while 82 (23.6%) were unsuccessful referrals. Multivariate logistic regression analysis showed that objection to referral (Adjusted OR, 2.96; CI: 1.44-5.52), never referred before (Adjusted OR, 1.25; CI: 1.34-6.90), not visited the referral site before (Adjusted OR, 4.04; CI: 2.50-6.08) and no knowledge of who to meet at the referral site (Adjusted OR, 1.30; CI: 1.01-2.96) were the factors associated with unsuccessful referral. Other factors found significant were duration of the illness of the patient, anyone not known at the referral site and failure of LHW to follow up. CONCLUSION Our study found that a significant proportion of patients seen by the LHWs are referred to different health facilities. Improved management skills of LHWs for simple medical problems would probably reduce the number of referrals. Efforts should also be directed to enhance the communication and counseling skills of LHWs, which may reduce a significant proportion of unsuccessful referrals.
pubmed_505_2641
pubmed_286_15295
Cytotoxicity and inflammation-associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo, respectively. However, the mechanism involved in LPS-induced cardiac malformation in prenatal fetus is still unknown. In this study, we demonstrated that LPS was induced in gut microbiota imbalance mice, and next, LPS exposure during gastrulation in the chick embryo increased the incidence of cardia bifida. Gene transfection and tissue transplantation trajectory indicated that LPS exposure restricted the cell migration of cardiac progenitors to primary heart field in gastrula chick embryos. In vitro explant allograft of GFP-labeled anterior primitive streak demonstrated that LPS treatments could inhibit cell migration. A similar observation was also obtained from the cell migration assay of scratch wounds using primary culture of cardiomyocytes or H9c2 cells. In the embryos exposed to LPS, expressions of Nkx2.5 and GATA5 were disturbed. These genes are associated with cardiomyocyte differentiation when heart tube fusion occurs. Furthermore, pHIS3, C-caspase3 immunohistological staining indicated that cell proliferation decreased, cell apoptosis increased in the heart tube of chick embryo. Meanwhile, in vivo, pHIS3 immunohistological staining and Hochest/PI staining also draw the similar conclusions. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos. At last, we showed that LPS-induced cardia bifida could be partially rescued through the addition of antioxidants. Together, these results reveal that excess ROS generation is involved in the LPS-induced defects in heart tube during chick embryo development.
10.1002/jcp.26175
pubmed_11_3561
The Pacific Basin Consortium session on Nanotechnology and toxicology brought together experts from biology and the physical sciences and engineering to discuss the environmental and health impacts of nanotechnology and nanomaterials in particular. The discussion included new findings in the area of inhalation toxicology as well as aquatic toxicology. Opportunities for engineering new forms of particles for toxicology studies were also presented.
pubmed_11_3561
pubmed_1048_3438
A total of 154 adult patients with sleep complaints underwent a polysomnography and a craniofacial cone beam computed tomography (CBCT). OSA was defined as an apnea and hypopnea index (AHI) or an oxygen desaturation index (ODI) ≥ 10. Soft tissues and craniofacial bones volumes were prospectively measured by CBCT and collected blindly from sleep polysomnography. Among the study patients, 127 (83%) suffered from OSA and 27 (17%) did not. OSA patients demonstrated a narrower maxillo-palatine core volume (11.7±3.2 vs 14.6±4.9cm3) even when adjusting for age, gender, height, neck circumference and body mass index. These upper airway measures provide a comprehensive analysis of bony structures and soft tissues, which can be involved in OSA.
10.1016/j.ortho.2016.10.003
pubmed_795_17073
Listerial brain abscess is extremely rare; only two cases have been reported in Japan. We encountered a female patient with immunoblastic lymphadenopathy, who developed listerial brain abscess after 8 years of treatment with antineoplastic agents and corticosteroids. Brain MRI revealed multiple space occupying lesions, suggesting abscesses which were possibly caused by hematogenous spread of the bacteria. Immediate blood culture enabled early diagnosis, and she entered into complete remission with high-dose ampicillin. Blood culture and brain imaging seem to play a crucial role in making an early diagnosis, and the administration of high dose of antibiotics is recommended for improvement of this disease.
10.2169/internalmedicine.41.1073
pubmed_716_16480
Increased error-related negativity (ERN), a measure of error monitoring, has been suggested as a biomarker of obsessive-compulsive disorder (OCD). Additional insight into error monitoring is possible using time-frequency decomposition of electroencephalographic (EEG) data, as it allows disentangling the brain's parallel processing of information. Greater error-related theta is thought to reflect an error detection signal, while delta activity may reflect more elaborative post-detection processes (i.e., strategic adjustments). Recent investigations show that decreased error-related alpha may index attentional engagement following errors; additionally, increases and decreases in error-related beta could reflect motor inhibition and motor preparation, respectively. However, time-frequency dynamics of error monitoring in OCD are largely unknown. The present study examined time-frequency theta, delta, alpha and beta power in early adolescents with OCD using a data-driven, cluster-based approach. The aim was to explore electrocortical measures of error monitoring in early adolescents with (n = 27, 15 females) and without OCD (n = 27, 14 females) during an arrowhead version of the flanker task while EEG activity was recorded. Results indicated that the OCD group was characterized by increased ERN and error-related theta, as well as reduced error-related beta power decrease (i.e., greater power) compared to participants without OCD. Greater error-related beta explained variance in OCD over and above the ERN and error-related theta. By examining separate time-frequency measures, the present study provides novel insights into the dynamics of error monitoring, suggesting that pediatric OCD may be characterized by enhanced error monitoring (i.e., greater theta power) and post-error inhibition (i.e., reduced beta power decrease).
10.1111/psyp.14216
others_58_12341
Although melittin, a water-soluble 26-amino acid peptide derived from bee venom of Apis mellifera, is known to exert anti-proliferative effects on various tumor cell lines, very little is known about its potential molecular mechanism(s) of action. In the present study, we investigated the effects of melittin on the AKT/mTOR/S6K1/4E-BP1 activation, associated gene products, cellular proliferation, and apoptosis in several tumor cells. We found that melittin inhibited both constitutive phosphorylation of AKT and mTOR and exerted a significant time-dependent anti-proliferative effect on MM1.S cells as compared to other types of tumor cells. Indeed, melittin clearly suppressed the constitutive activation of AKT/mTOR/S6K1/4E-BP1 signaling cascades, which correlated with the induction of apoptosis. Melittin can cause broad-spectrum inhibition of AKT/mTOR/S6K1/4E-BP1 axes in multiple myeloma cells when compared with various pharmacological AKT/mTOR inhibitors. Aberrant AKT activation by pcDNA3-myr-HA-AKT1 plasmid could not prevent the observed suppressive effect of melittin on constitutive mTOR, S6K1, and 4E-BP1 activation and overexpression of Bcl-2 also attenuated melittin-mediated apoptosis in the cells. Our results clearly indicate that melittin can interfere with multiple signaling cascades involved in carcinogenesis and thereby used as a potential drug candidate for both the prevention and treatment of cancer. © 2014, Institute of Korean Medicine, Kyung Hee University and Springer Science+Business Media Dordrech
10.1007/s13596-014-0172-4
pubmed_313_19853
BACKGROUND The proportion of saturated fatty acids/unsaturated fatty acids in the diet seems to act as a physiological regulation on obesity, cardiovascular diseases, and diabetes. Differently composed fatty acid diets may induce satiety of the hypothalamus in different ways. However, the direct effect of the different fatty acid diets on satiety in the hypothalamus is not clear. METHODS Three experiments in mice were conducted to determine whether: different compositions of fatty acids affects gene mRNA expression of the hypothalamus over time; different types of fatty acids administered into the stomach directly affect gene mRNA expression of the hypothalamus; and fat composition changes in the diet affects gene mRNA expression of the hypothalamus. RESULTS The type of fat in cases of purified fatty acid administration directly into the stomach may cause changes of gene expressions in the hypothalamus. Gene expression by dietary fat may be regulated by calorie amount ingested rather than weight amount or type of fat. CONCLUSION Therefore, the calorie density factor of the diet in regulating hypothalamic gene in food intake may be detrimental, although the possibility of type of fat cannot be ruled out.
10.4093/dmj.2017.41.2.121
pubmed_92_22631
BACKGROUND Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. METHODS We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8-14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. RESULTS Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. INTERPRETATION Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children.
pubmed_92_22631
pubmed_970_18678
Pyrazine-based compounds are of great importance in medicinal chemistry. Due to their heteroaromatic nature, they uniquely combine properties of heteroatoms (polar interactions) with the properties of aromatic moieties (nonpolar interactions). This review summarizes results of a systematic analysis of RCSB PDB database focused on important binding interactions of pyrazine-based ligands cocrystallized in protein targets. The most frequent interaction of pyrazine was hydrogen bond to pyrazine nitrogen atom as an acceptor, followed by weak hydrogen bond with pyrazine hydrogen as donor. We also identified intramolecular hydrogen bonds within pyrazine ligands, π-interactions, coordination to metal ions, and few halogen bonds in chloropyrazines. In many cases the binding mode of the pyrazine fragment was complex, involving a combination of several interactions. We conclude that pyrazine as a molecular fragment should not be perceived as a simple aromatic isostere but rather as a readily interacting moiety of drug-like molecules with high potential for interactions to proteins.
10.1021/acs.jmedchem.9b02021
pubmed_543_13
The problems with repeated failure of cartilage grafting in reconstructive surgery are not yet resolved. Humoral immunoreactivity against chondrocytes as well as typical cartilage collagens type II, IX and XI was investigated in patients who showed resorptions and/or rejections of transplanted cartilage grafts. The presence of antibodies against isolated human chondrocytes was determined using an indirect immunofluorescence method, an enzyme-linked immunosorbent assay (ELISA) for chondrocytes and immunoblotting with chondrocyte cell membranes. Furthermore, an ELISA for collagens type II, IX and XI as well as immunoblotting with purified collagens type II and XI were used. The control groups consisted of patients with successful cartilage transplantation, patients suffering from rheumatoid arthritis and healthy persons. Patients with unsuccessful cartilage transplantation showed significantly elevated titres of antibodies against chondrocytes (p < 0.001) and collagens type IX and XI (p < 0.001) compared to the control groups. In one patient with unsuccessful cartilage graft, we could also find a humoral reactivity against collagen type XI by immunoblotting. In contrast, no humoral immune reactivity was demonstrable against chondrocyte cell membranes by immunoblotting. In all examined patients fifty percent of patients with repeated resorptions or rejections of transplanted grafts showed antinuclear antibodies (ANA), demonstrating a possible but not yet declared autoimmune disease. These data confirm a humoral immunoreactivity against chondrocytes as well as against collagen which could be responsible for resorptions and/or rejections observed after cartilage graft.
10.1055/s-2007-997692
others_373_6603
Clubroot (Plasmodiophora brassicae) is an important disease of canola (Brassica napus) and other brassica crops. Accurate estimation of inoculum load in soil is important for evaluating producer risk in planting a susceptible crop, but also for evaluation of management practices such as crop rotation. This study compared five molecular techniques for estimating P. brassicae resting spores in soil: quantitative polymerase chain reaction (qPCR), competitive positive internal control PCR (CPIC-PCR), propidium monoazide PCR (PMA-PCR), droplet digital PCR (ddPCR) and loop-mediated isothermal DNA amplification (LAMP). For ddPCR and LAMP, calibrations were developed using spiked soil samples. The comparison was carried out using soil samples collected from a long-term rotation study at Normandin, Québec, with replicated plots representing 0-, 1-, 2-, 3-, 5- and 6-year breaks following susceptible canola infested with clubroot. CPIC-PCR and ddPCR provided repeatable estimates of resting spore numbers in soil compared with estimates from qPCR or LAMP alone. CPIC-PCR provided the most robust measurement of spore concentration, especially in the 2 years following a crop of susceptible canola, because it corrected for effects of PCR inhibitors. PMA-PCR demonstrated that a large proportion of the DNA of P. brassicae detected in soil after the susceptible canola crop was derived from spores that were immature or otherwise not viable. Each assay provided a similar pattern of spore concentration in soil, which supported the conclusion of a previous study at this site that resting spore numbers declined rapidly in the first 2 years after a susceptible crop, but much more slowly subsequently. © 2019 Her Majesty the Queen in Right of Canada Plant Pathology
10.1111/ppa.13007
others_237_4098
Since the conception of the pentavalent technetium polynuclear complex of dimercaptosuccinic acid, Tc(V)-DMS, a great number of papers published on its clinical applicability forced us to question 'how tumor tissue appropriates the Tc(V)-DMS.' Preliminary in vitro studies with Ehrlich ascites tumor cells (EATC) indicated the pH-sensitive character of this tumor agent. From this finding and the well-established notion that malignant tumors are more acidic than normal tissue, the in vivo correlation of Tc(V)- DMS accumulation in tumor tissue with its tissue acidification was considered of interest. The systemic lowering of tumor tissue pH by the stimulation of aerobic glycolysis has been well reported. In the present paper, the response of Tc(V)-DMS tumor accumulation to acidification induced by the glucose administration was explored in EATC-bearing mice. Measurement of tumor tissue pH was carried out by direct microelectrode technique and by histochemical umbelliferone technique in tumor tissue excised from EATC bearing mice. The regional acidity distribution is correlated with the regional radioactivity distribution registered by autoradiography. Evidence related to the pH sensitiveness of Tc(V)-DMS in response to glycolytic acidification was gathered; the pH measurement and the in vivo biodistribution of the double- tracer macroautoradiography with C-14 deoxyglucose (C-14-DG) demonstrated that the regional tissue distribution of Tc(V)-DMS was superimposed to that of C-14-DG. The glucose interventional modality offers the premier foundation for the interpretation of Tc(V)-DMS accumulation in diagnostic studies of malignant tumors
10.1016/S0969-8051(98)00012-2
pubmed_725_8380
Submaximal treadmill exercise electrocardiography and 48 hour ambulatory electrocardiographic monitoring were performed in 30 patients with hypertrophic cardiomyopathy both with and without beta adrenergic blocking therapy. During ambulatory electrocardiographic monitoring 1 patient (3 percent) had no arrhythmia, 14 patients (46 percent) had supraventricular tachycardia or paroxysmal atrial fibrillation, 13 (43 percent) had multiform or paired ventricular extrasystoles and 8 (26 percent) had ventricular tachycardia. The frequency of these ventricular arrhythmias was almost identical with and without beta adrenergic blocking drugs (mean dose in "propranolol equivalents" 280 mg daily). With beta blocking therapy fewer patients had supraventricular tachycardia; however, the difference was not significant. During exercise testing 18 patients (60 percent) had ventricular extrasystoles and 3 patients (10 percent) had paired ventricular extrasystoles and the frequency was almost identical with and without beta adrenergic blocking therapy. No routine echocardiographic or hemodynamic measurement predicted the serious ventricular arrhythmias. It is concluded that asymptomatic ventricular arrhythmia is a common occurrence in patients with hypertrophic cardiomyopathy and its frequency is not reduced with beta adrenergic blocking therapy. Because occult arrhythmia may be the cause of sudden death it is important to detect it in these patients so that an effort can be made to improve prognosis with specific antiarrhythmic treatment.
10.1016/0002-9149(80)90212-x
pubmed_721_16346
We characterized a number of important features of the structure of the cohesive overlap region of the DNA genome of duck hepatitis B virus. The 5'-terminal nucleotide of minus-strand DNA was localized to nucleotide 2537, a G residue within the 12-base repeat sequence DR1. This G residue was shown to be the site of a covalent linkage to a protein, consistent with speculation that this protein is the primer of minus-strand synthesis, which occurs by reverse transcription. The 3' terminus of the minus strand was heterogeneous, being mapped to nucleotides 2530 and 2531, indicating that the minus strand is terminally redundant by seven or eight bases and ends at the putative 5' end of the transcribed RNA template (pregenome) for reverse transcription. We previously demonstrated that the presumptive RNA primer of plus-strand synthesis remains attached to plus-strand DNA during virus maturation; moreover, the sequence of this primer suggested an origin from the 5' end of the pregenome (J.-M. Lien, C. E. Aldrich, and W. S. Mason, J. Virol. 57:229-236, 1986). We show here that over 75% of plus-strand primers are capped, further supporting the idea that these primers are uniquely derived from the 5' end of the pregenome. Finally, we found that seemingly mature duck hepatitis B virus genomes are incomplete by at least 12 bases, in that the 12-base repeat sequence DR2 is not copied into plus-strand DNA during virus maturation. Since DR2 in virion DNA is duplexed with the RNA primer of plus-strand synthesis, it is possible that the failure to make complete plus strands is due to an inability of the viral DNA polymerase to carry out a displacement of the bound RNA primer.
10.1128/JVI.61.12.3832-3840.1987
others_73_12029
Immunization of goats and mules with human thrombin resulted in an antiserum that reacted only weakly with the parent molecule, prothrombin. Some of the antibodies in this antiserum showed a greater affinity for thrombin complexed to its naturally occurring inhibtor, antithrombin-III, than for active thrombin. An antiserum against the human thrombin inhibitor, antithrombin-III, produced 2 precipitin lines against human serum but only 1 against plasma. The 2nd line in serum was shown to represent precipitation of a complex of thrombin with antithrombin-III. The neoantigens appearing in antithrombin-III after complex formation were also present in complexes prepared with purified clotting factor Xa and antithrombin-III. Since purified host (mule) thrombin was also capable of causing formation of the neoantigenic sites when complexed to human antithrombin-III, it seems likely that these determinants result from interaction in the host between the immunogens (either human thrombin or antithrombin) and the appropriate interacting host protein (mule antithrombin-III or thrombin, respectively). Studies by radioimmunoassay showed that the antibodies formed are not completely specific for the neoantigens since they also react to a lesser extent with the free proteins
others_73_12029
pubmed_407_13977
Treating bed bug bites is straightforward; helping patients control and even prevent future infestations is another matter. Here's how you can help.
pubmed_407_13977
pubmed_1041_16807
Conjunctival melanocytic tumors represent a spectrum of pigmented tumors that include benign, premalignant and malignant tumors. Conjunctival nevi are the most common pigmented tumors and are typically found in the interpalpebral bulbar conjunctiva. These lesions usually contain fine clear cysts on slit lamp biomicroscopy. Primary acquired melanosis includes lesions from increased melanin pigmentation without proliferation of melanocytes to melanoma in situ. In the new classification system, the idea is to use the term 'primary acquired melanosis' only as a clinical description, highlighting the fact that the biologic behavior of acquired melanotic lesions cannot be predicted solely based upon clinical grounds without histopathologic examination. Conjunctival melanoma represents only 5% of all melanomas arising in the ocular region and is associated with a high mortality rate. The management of primary acquired melanosis, nevi and conjunctival melanomas involves various modalities used either alone or concomitantly depending on the size and extent of the lesion.
10.2217/fon.11.12
pubmed_1061_24829
No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4+ and CD8+ T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4+ T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4+ T cell response and augmented CD8+ T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor's escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.
10.1038/s41598-019-51106-y
pubmed_339_15662
Podophyllin, a crude plant extract with low efficacy, high toxicity, and a serious mutagenicity profile does not comply with the WHO guidelines for plant derived treatments and should be removed from clinical treatment protocols. Home treatment with pharmaceutical products based on podophyllotoxin-the purified, standardised active antiwart ingredient of podophyllin-represents safe and effective first line therapy for patients with anogenital warts.
10.1136/sti.77.6.409
pubmed_483_15010
Long noncoding RNAs (lncRNAs) are important regulators of biological processes, and regulate genomic imprinting in cis and/or trans to induce monoallelic expression with parent-origin-specific pattern. DLK1-DIO3 domain is one of the largest imprinted clusters in mammals, and maternally expressed noncoding RNAs of this region is related to the pluripotency of the embryonic stem cells. Previously, we sequenced the cDNA of two maternally expressed noncoding RNAs, MEG8 and MEG9, and mapped a lncRNA (LINC24061) between the two genes in the cattle DLK1-DIO3 domain on chromosome 21. In this study, we identified LINC24065, a novel long intergenic noncoding RNA (lincRNA), which was also located between MEG8 and MEG9. We identified four variants of LINC24065 (LINC24065-v1, LINC24065-v2, LINC24065-v3 and LINC24065-v4) that were a result of alternative splicing from 18 exons. LINC24065-v1 and LINC24065-v2 showed tissue-specific expression patterns in adultbovine tissues, and LINC24065-v3 and LINC24065-v4 were detected in all eight analysed tissues (heart, liver, spleen, lung, kidney, skeletal muscle, adipose and brain). Using single-nucleotide polymorphism (SNP)-based method, LINC24065 was identified to have monoallelic expression in adult tissues, suggesting that it is imprinted in cows. These results provide a foundation for further investigation about whether LINC24065 plays a role in regulating imprinting of the DLK1-DIO3 domain.
pubmed_483_15010
pubmed_929_7518
BCR/TCR-based adaptive immune systems arise in the jawed vertebrates, and B cell receptors (BCRs) play an important role in the clonal selection of B cells and their differentiation into antibody-secreting plasma cells. The existence of BCR-like molecule and the activation mechanism of the downstream response are still not clear in invertebrates. In this study, an ancient BCR-like molecule (designated as CgIgR) with an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic tail was identified from the Pacific oyster Crassostrea gigas to investigate its involvement in immune response. CgIgR could bind different bacteria through five extracellular Ig domains and formed dimers. The activated CgIgR recruited CgSyk to promote CgERK phosphorylation. The CgIgR-mediated signaling promoted the production of immunoglobulin domain-containing proteins (CgICP-2 and CgLRRIG-1) through inducing CgH3K4me2. The produced CgICPs eventually facilitated hemocytes to phagocytize and eliminate V. splendidus. This study proposed that there was an ancient BCR-like molecule and BCR-like signaling in molluscs.
10.1016/j.isci.2020.100834
pubmed_435_16280
Extracellular ATP is an emerging target for cancer treatment because it is a key messenger for shaping the tumor microenvironment (TME) and regulating tumor progression. However, it remains a great challenge to design biochemical probes for targeted imaging of extracellular ATP in the TME. A TME-driven DNA nanomachine (Apt-LIP) that permits spatially controlled imaging of ATP in the extracellular milieu of tumors with ultrahigh signal-to-background ratio is reported. It operates in response to the mild acidity in the TME with the pH (low) insertion peptide (pHLIP) module, thus allowing the specific anchoring of the structure-switching signaling aptamer unit to the membrane of tumor cells for "off-on" fluorescence imaging of the extracellular ATP. Apt-LIP allows for acidity driven visualization of different extracellular concentrations of exogenous ATP, as well as the monitoring of endogenous ATP release from cells. Furthermore, it is demonstrated that Apt-LIP represents a promising platform for the specific imaging of the extracellular ATP in both primary and metastatic tumors. Ultimately, since diverse aptamers are obtained through in vitro selection, this design strategy can be further applied for precise detection of various extracellular targets in the TME.
10.1002/adma.201901885
pubmed_897_6167
Oxidative stress causes damage at the cellular level and activates a number of signaling pathways. Earlier, we have demonstrated that pollutant-related oxidative stress upregulates heat-shock protein 90 alpha (HSP90α) against stress insult in hepatocytes of Mugil cephalus living in a polluted estuary. However, the impact of pollution-induced HSP90α upregulation on stress tolerance is not clear. Here we propose that the effect of stress resistance depends on the ability of HSP90α to modulate the signaling pathways involving proteins such as apoptosis signal-regulating kinase 1, c-Jun NH(2)-terminal protein kinase 1/2, signal transducers and activators of transcription, extracellular signal-regulated kinase 1/2, protein kinase B, nuclear factor-kappa binding, Ets-like protein 1, and B cell lymphoma-2. In order to investigate this, the activation of HSP90α-associated signaling molecules was examined by Western blotting and immunohistochemistry. The relationship between the protein expression patterns was identified by Spearman's rank correlation analysis. The signaling proteins exhibited differential modulation as revealed from their expression patterns in pollutant-exposed fish hepatocytes, in comparison with the control fish hepatocytes. The results suggested that in spite of the prevalence of oxidative stress in pollutant-exposed fish hepatocytes, the stress-mediated induction of HSP90α enabled the hepatocytes to become stress tolerant and to survive by modulating the actions of key proteins and kinases in the signal transduction pathways.
10.1007/s12192-011-0255-9
pubmed_757_8893
Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections.
10.1007/s00284-021-02631-5
pubmed_1021_21724
Herpes simplex virus (HSV) latency in sensory ganglion neurons is well documented, but the existence of extraneuronal corneal latency is less well defined. To investigate the possibility of extraneuronal latency during ocular HSV infection, corneal specimens from 18 patients with quiescent herpes simplex keratitis (HSK) were obtained at the time of keratoplasty. Polymerase chain reaction (PCR) amplification followed by southern blot hybridization with a radiolabeled oligonucleotide probe was done to detect the presence of HSV-1 genome in these human corneal samples. Two pairs of oligonucleotides from the region of the HSV thymidine kinase (TK) gene and the latency-associated transcript (LAT) gene were used as primers in the PCR amplification. The DNA sequences from either the TK or the LAT gene were identified in 15 of 18 HSK corneas (83%). These results demonstrate that the HSV genome was retained, at least in part, in human corneas during quiescent HSV infection, giving further support to the concept of corneal extraneuronal latency.
pubmed_1021_21724
pubmed_292_9995
The authors present a case of 3-year-old female with Stage 4 neuroblastoma originating from the left adrenal gland. Biopsy of the left adrenal tumor showed neuroblastoma. After three courses of chemotherapy, the left adrenal gland including the left adrenal tumor was surgically removed. Pathological findings of the resected tumor revealed that most of the neuroblastoma tissues changed to pheochromocytoma-like cells. The tumor cells were arranged in well-defined nests surrounded by a delicate fibrovascular stroma and had granular eosinophilic cytoplasm, and round to oval nuclei. Immunohistological analysis of the biopsy samples showed strongly positive Ganglioside GD2-staining cells, whereas almost all of the tumor cells in the resected specimen were Ganglioside GD2-negative; cells were very weakly stained. The authors suggest that a part of the neuroblastoma in the left adrenal gland exhibited unusual differentiation toward pheochromocytic lineage Ganglioside GD2-negative neuroblastoma in a patient who had been treated with intensive chemotherapy.
10.3109/15513815.2015.1068413
pubmed_1114_20685
OBJECTIVE We examined the efficacy of a crisis-based intervention in improving mother-child interaction and children's play functioning for families who had experienced domestic violence. METHOD Using a pretest-posttest two-group control study design, we assigned the intervention group (n=20 mother-child dyads) to the Family Intervention for Improving Occupational Performance (FI-OP) program and the control group (n=17 dyads) to a playroom program. Both programs consisted of eight 30-min sessions. We videotaped dyads during free play and used standardized tools to assess interactions, play skills, and playfulness. RESULTS After the intervention, mother-child interaction was significantly better in the FI-OP group than in the playroom group. The children in the FI-OP group also demonstrated significantly greater improvement in play skills, but not in playfulness. CONCLUSION FI-OP is a promising program for improving aspects of mother-child interaction and children's play functioning among survivors of domestic violence.
10.5014/ajot.2015.013375
pubmed_267_3707
The percentage of journal articles covered by dsh Abstracts and the time it took these articles to appear as abstracts in this secondary publication were analyzed. Articles were obtained from nineteen communicative disorders journals every other year for the years from 1968 to 1976. Then the author index of dsh Abstracts was searched each year for up to five years following journal publication to determine whether each article was included in this abstracting service's coverage of the world literature. Of the 5548 articles included in the study, 3270 (59%) were covered by this abstracting service within a mean time of 9 months; however, time lag and coverage varied considerably for individual journals on a year by year basis. It was concluded that for historical searches and current awareness needs this secondary publication may not be meeting the information needs of communicative disorders specialists.
pubmed_267_3707
pubmed_857_20964
Irradiation (350 nm) of air-saturated solutions of reagents containing an anthraquinone group linked to quaternary alkyl ammonium groups converts supercoiled DNA to circular and to linear DNA. Generation of linear DNA does not occur by accumulation of numerous single-strand cuts but by coincident-site double-strand cleavage of DNA. Irradiation forms the triplet state of the anthraquinone, which reacts either by hydrogen atom abstraction from a sugar of DNA or by electron transfer from a base of the DNA. Subsequent reactions result in chain scission. The quinone is apparently reformed after this sequence and reirradiation leads to double-strand cleavage.
10.1111/j.1751-1097.1993.tb04931.x
others_14_12742
After reevaluation of the taxonomic position of 27 yeast collection strains of different origin by UP-PCR followed by dot-hybridization, only 22 strains were assigned to the biological species Zygowilliopsis califomica (Lodder) Kudriavzev. Four strains were identified as Williopsis suaveolens (Klöcker) Naumov et al. Universal primers L45 and N21 are recommended for identification of the Z. californica yeasts. © 2001 MAIK "Nauka/Interperiodica"
10.1023/A:1012316407385
pubmed_778_2932
An integration of SENSitivity Encoding (SENSE) with continuously moving table (CMT) MRI for extended field-of-view (FOV) acquisitions is described. In this work, the approach in which receiver coils are attached to the object and move in synchrony with the scanner table is considered. Technical issues dealing with the implementation of SENSE-CMT are addressed, including coil calibration, correction for non-uniform magnetic gradients, and specific reconstruction steps. An explanation of combining SENSE with gradient non-linearity correction is given, as the latter becomes necessary in CMT acquisitions where a large sampling FOV is used. It is hypothesized that SENSE can provide at least a 2-fold improvement in lateral spatial resolution compared to non-accelerated CMT acquisitions. The hypothesis is tested in phantoms, where the effectiveness of both SENSE and gradient non-linearity correction to improve spatial resolution is shown. The SENSE-CMT technique is further demonstrated in vivo with contrast-enhanced MR angiography of the peripheral vasculature.
10.1002/mrm.20639
pubmed_28_1178
Chinese northeast suancai represents a typical and valuable food product that has been handed down by traditional household procedures over centuries. Nitrite is formed and accumulated during the suancai fermentation process and commonly causes food safety problems. The biogeochemical cycle of nitrite may provide a reference and guidance for the enzymatic degradation of nitrite in fermented food. The potential nitrogen metabolic pathways in the microbially driven suancai fermentation were reasonably inferred through monitoring nitrogen conversions and detecting the genes of different functional enzymes. Complex microbial metabolism is responsible for the unique nitrogen conversions during suancai fermentation. The metagenomic results showed that Pseudomonas with nitrate reductase genes (narG, narH, narI) and nitrite reductase genes (nirB, nirD) contributed the most to both nitrite reduction and nitrate reduction. The majority of the sequences of nitrate reductase and nitrite reductase were derived from the families of Pseudomonadaceae, Erwiniaceae and Yersiniaceae. According to the physicochemical analysis, the nitrite concentration of the fermentation broth reached the peak value (0.48 mM) and gradually decreased to the minimum (0.02 mM). The downward trend of the pH and nitrite concentration were closely associated with the nitrite enzymatic degradation period before the acid degradation period. Our results indicated that nitrite removal in suancai fermentation involved the reduction of nitrite to ammonia and denitrification, which were mainly contributed by the reduction of nitrite to ammonia mediated by the nirB/nirD enzyme (Indentified ECs: 1.7.1.15). This research offers new insights into the metagenome-based bioinformatic roles of the previously unstudied microorganisms in spontaneous suancai fermentation for the enzymatic degradation of nitrite. It provides helpful basis for the detection and even elimination of nitrite in suancai and for improving the safety level of suancai.
10.1016/j.foodres.2020.109924
pubmed_592_5387
This phase II study combined paclitaxel (Taxol; Bristol Myers Squibb Company, Princeton, NJ) 135 mg/m2 by 3-hour infusion on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 (in the first 14 patients) or on days 1 and 3 (in the subsequent 20 patients). The courses were repeated every 3 weeks. The second vinorelbine dose (on days 3 or 8) was reduced or omitted according to the toxicities encountered. Thirty-four patients have been treated to date; 21 had received one prior regimen of chemotherapy, 11 had two prior regimens, and two had three prior regimens. Only two patients (6%) had not been exposed to anthracyclines. One hundred twenty-six courses have been administered: 52 with vinorelbine given on days 1 and 8, and 74 with vinorelbine administered on days 1 and 3. The most frequent toxicity was grade 4 neutropenia, which occurred in 64% of the courses; 13 episodes of febrile neutropenia have been reported in eight patients. Filgrastim was administered in 43% of the courses because of febrile neutropenia or delayed recovery (> 72 hours) from grade 4 neutropenia. Mucositis was observed in 18% of the courses (12% grade 1, 3% grade 2, and 3% grade 3). The dose of vinorelbine was reduced or omitted in 86% of courses with the days 1 and 8 schedule, and in 48% of courses with the days 1 and 3 schedule. Among 28 evaluable patients, two complete and 10 partial responses have been observed (response rate, 43%, 95% confidence interval, 19% to 51%). Median duration of response is 5+ months (range, 1 to 15 months). In conclusion, this combination is active and has acceptable toxicities in anthracycline-pretreated breast cancer patients. The delivered dose intensity of vinorelbine is higher with the schedule adopted later in the study, with vinorelbine given on days 1 and 3.
pubmed_592_5387
pubmed_130_14861
Transmissible gastroenteritis virus (TGEV) can cause diarrhea, dehydration, and high mortality in piglets, which is closely related to intestinal epithelial cell apoptosis caused by TGEV infection. All-trans retinoic acid (ATRA) is the active metabolite of vitamin A, which has antioxidant and anti-apoptotic properties. However, it is unknown whether ATRA can attenuate TGEV-induced IPEC-J2 cells apoptosis. Therefore, we investigated the protective effects of ATRA on TGEV-induced apoptosis of IPEC-J2 cells and explored the potential molecular mechanism. Our results indicated that TGEV infection caused IPEC-J2 cells damage and apoptosis. However, ATRA treatment attenuated TGEV-induced IPEC-J2 cells damage by upregulating the mRNA expressions of ZO-1, Occludin, and Mucin-1. ATRA treatment also attenuated TGEV-induced apoptosis in IPEC-J2 cells by downregulating the expression of Caspase-3, which is related to the inhibition of death receptor (Fas and Caspase-8) and mitochondrial (Bax, Bcl-2, and Caspase-9) pathways. Moreover, ATRA treatment prevented TGEV-induced ROS and MDA production and the upregulation of P38MAPK phosphorylation level, which is related to the increase in the activities of antioxidant enzymes (SOD, CAT, and T-AOC) and the mRNA abundance of antioxidant-related genes (GPX1, GPX2, SOD1, CAT, GCLC, and GCLM). In addition, treatment of TGEV-infected IPEC-J2 cells with the ROS inhibitors (NAC) significantly reduced the protein levels of p-P38MAPK, Fas, Bax, and Cleaved-caspase-3 and the percentage of apoptotic cells. Our results indicated that ATRA attenuated TGEV-induced apoptosis in IPEC-J2 cells via improving the antioxidant capacity, thereby inhibiting the cell damage. the mechanism of which is associated with the inhibition of ROS-mediated P38MAPK signaling pathway.
10.3390/antiox11020345
pubmed_279_17243
The inner stripe of the outer medullary collecting duct (OMCDis) is a major site of HCO3- reabsorption and urinary acidification. Whether this nephron segment consists of a single or multiple cell types remains unclear. Apical incubation of rabbit OMCDis via luminal perfusion with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester resulted in heterogeneous fluorescence, suggesting two cell types. This heterogeneity was not prevented by inhibition of either carbonic anhydrase or organic anion transport. Subsequent studies were directed at characterizing the major intracellular pH (pHi) regulatory transporters in these two cell populations. Both cell populations demonstrated similar rates of Na+/H+ exchange, as assessed by peritubular Na(+)-dependent, amiloride-sensitive pHi recovery from an intracellular acid load. In contrast, Na(+)-independent, HCO3(-)-independent pHi recovery from an acid load was present in both cell populations but had two to three times greater activity in a minority cell population. In vivo deoxycorticosterone acetate administration increases this rate in both populations but to a greater extent in the minority cell population. In CO2/HCO3(-)-containing solutions, Cl- removal from the peritubular solution caused 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive alkalinization of all cells. Again, the magnitude and rate of alkalinization were significantly greater in the minority cell population. These studies demonstrate that the OMCDis consists of qualitatively similar cells in different states of functional activity. Although they are similar in most characteristics, a minority of cells more actively secrete H+ (independent of Na+) and reabsorb HCO3-.
10.1152/ajprenal.1993.265.3.F406
pubmed_954_21322
Lipid vesicles are widely used as models to investigate the interactions of proteins, peptides, and small molecules with lipid bilayers. We present a sonication procedure for the preparation of well-defined and ready-to-use small unilamellar vesicles composed of phospholipids with the aid of a beaker resonator. This indirect but efficient sonication method does not require subsequent centrifugation or other purification steps, which distinguishes it from established sonication procedures. Vesicles produced by this method reveal a unimodal size distribution and are unilamellar, as demonstrated by dynamic light scattering and (31)P nuclear magnetic resonance spectroscopy, respectively.
pubmed_954_21322
pubmed_516_17001
The International Commission on Radiological Protection (ICRP) 2005 Recommendations, which were released at the International Radiation Protection Association's congress held in Madrid (May 2004), have been available for public comment via the ICRP's Web site. The comment period has now closed and the Recommendations are presumably being re-worked. There are several inconsistencies in the Recommendations and they are exemplified by looking at the exclusion levels in more detail. The relevant text of the Recommendations is included in this paper as an . It is suggested that the International Atomic Energy Agency's approach is more balanced where each nuclide receives its own exclusion level instead of the incomplete and arbitrary categories proposed by the ICRP.
10.1097/01.HP.0000196110.12298.c9
pubmed_559_12666
OBJECTIVE Bilateral living-donor lobar lung transplantation has become an accepted approach in response to the cadaveric lung donor shortage. Because only one lobe is implanted in each chest cavity, this procedure is usually confined to patients of small size. The purpose of this study was to develop a technique of bilateral native lung-sparing lobar transplantation that can be applied to large adult patients. METHODS Bilateral native lung-sparing lobar transplantation was performed in 12 pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the natural anatomic position with sparing native right upper, left upper, and middle lobes. In an acute study (n = 6), transplanted graft function was assessed for 3 hours after ligation of the pulmonary artery branches to the native spared lobes. In a chronic study (n = 6) the immunosuppressed recipients were observed for 3 weeks to assess the quality of bronchial healing and long-term pulmonary function. RESULTS Morphologic adaptation of the 2 grafts was found to be excellent. All 6 animals in the acute study showed excellent pulmonary function. Five of 6 animals in the chronic study survived for 3 weeks, with excellent pulmonary function and satisfactory bronchial healing. CONCLUSION Bilateral native lung-sparing lobar transplantation was technically possible and associated with excellent pulmonary function and good bronchial healing in a canine experimental model.
10.1016/j.jtcvs.2006.07.012
pubmed_328_13682
BACKGROUND AND AIMS Familial hypercholesterolemia (FH) is amongst the most common genetic disorders encountered in primary care. Yet, only a minority of affected patients is diagnosed and treated. This interim analysis of the CaRe High Registry aims at examining the state of treatment and attainment of lipid goals in German FH patients. METHODS The CaRe High registry includes FH patients from lipid clinics and private practices. Data have been collected using questionnaires filled in by the recruiting physicians and by interviewing the participating patients. RESULTS We examined 512 F H patients diagnosed according to clinical criteria. Median age at the time of the first FH diagnosis was 39 (25th and 75th percentile: 27-50) years, median treatment naïve LDL cholesterol (LDL-C) was 239.4 mg/dl (6.19 mmol/l), 25th to 75th percentile 191.8-342.5 mg/dl (4.96-8.86 mmol/l). 27% of the participants did not receive lipid-lowering drugs. Among the patients treated with lipid-lowering drugs, 19% received a PCSK9 inhibitor (PCSK9i) in combination with a statin, 9% were treated with a PCSK9i alone and 3% were treated with a combination of PCSK9i and a non-statin drug. Patients with pre-existing CVD were more likely to be treated with lipid-lowering drugs and more likely to receive a PCSK9i, but LDL-C targets were only achieved by a minority of patients (<20%). Gap to target LDL-C was lowest and the median achieved LDL-C reduction was 1.4 times higher with PCSK9i treatment than with (oral) lipid-lowering therapy without PCSK9i. CONCLUSIONS The Care High registry has included patients with the typical clinical features of familial hypercholesterolemia. PCSK9i treatment in addition to standard therapy allows attainment of target values in many patients with initially very high LDL-C.
10.1016/j.atherosclerosis.2018.08.050
pubmed_22_24401
Various nanomechanical movements of bacteria provide a signature of bacterial viability. Most notably, bacterial movements have been observed to subside rapidly and dramatically when the bacteria are exposed to effective antibiotics. Thus, monitoring bacterial movements, if performed with high fidelity, could offer a path to various clinical microbiological applications, including antibiotic susceptibility tests. Here, we introduce a robust and ultrasensitive electrical transduction technique for detecting the nanomechanical movements of bacteria. The technique is based on measuring the electrical fluctuations in a microfluidic channel, which the bacteria populate. The swimming of planktonic bacteria and the random oscillations of surface-immobilized bacteria both cause small but detectable electrical fluctuations. We show that this technique provides enough sensitivity to detect even the slightest movements of a single cell; we also demonstrate an antibiotic susceptibility test in a biological matrix. Given that it lends itself to smooth integration with other microfluidic methods and devices, the technique can be developed into a functional antibiotic susceptibility test, in particular, for urinary tract infections.
10.1039/c7lc01019b
pubmed_36_13420
In resource-scarce settings governments have increasingly looked at ways of engaging the private sector in achieving national health system goals. This study is a comparative analysis of institutional contracting for hospital services in three southeast and east Asian countries, namely Thailand, the Philippines and South Korea. In addition, the case of Singapore, where public hospitals are corporatized, is reviewed. Primary data were collected through in-depth-interviews and analysed under a triangulation approach. Institutional contracting is only used in three out of four countries. In these three countries, institutional contracting inter alia aims at increasing access to hospital services, although the scale of private hospital participation depends on contextual factors. Neither strategic provider selection mechanisms nor a preferred provider system is part of the institutional contracting models reviewed. In Thailand and the Philippines, performance-based rewards or sanctions have played a limited role so far and there is relatively little dialogue between contract parties, indicating that the contracting tool has not been used to the fullest extent possible and suggesting that capacity development especially regarding contract and relationship management is needed. Although there is virtually no information available about the cost of contracting, the findings of this study suggest that the potential of institutional contracting arrangements should be explored further to improve health system outcomes and thereby support countries in their quest for universal health coverage.
pubmed_36_13420
pubmed_164_12757
This study deals with the use of the dynamics of dissolved oxygen concentration for water quality assessment in polder ditches. The dynamics of the dissolved oxygen concentration, i.e. the temporal and spatial variations in a few polder ditches under a range of natural, pollution and management conditions is presented.Five requisites formulated for the water quality indicator are discussed: (1) its relation with water quality goals, (2) nature and amount of information it provides, (3) if it could be standardized, (4) if it could be manipulated and (5) its measurability.
10.1007/BF00396227
pubmed_726_3590
In sickle cell disease, the factors involved in vasoocclusive crisis (VOC) include the sickling of red blood cells (RBC), abnormal blood rheology, inflammation, vascular adhesion, oxidative stress, coagulation, and vascular tone modulation. The aim of this study was to further characterize the molecular response of some factors involved in VOC by inducing a hypoxia/reoxygenation stress in sickle SAD mice. Results show that a hypoxia/reoxygenation stress in SAD mice can induce: (i) a decrease in reticulocytes count, and mean corpuscular volume along with an increase in lactate dehydrogenase (p = 0.07) and sickled cell proportion; (ii) a significant increase in lung VCAM-1, ICAM-1, IL-1β, ET-1, eNOS, and TF mRNA associated with an increase in VCAM-1 expression on lung endothelium; (iii) a rise in cardiac oxidative stress with increased lipid oxidation and decreased anti-oxidant enzyme activities, and (iv) an increase in plasma TNF-α and IL-6 and a decrease in plasma ET-1. In SAD mice, hypoxia/reoxygenation stress induces hemolysis that, together with oxidative stress, inflammation, vascular adhesion, and coagulation, may induce vascular occlusion and consequently RBC sickling. The present results give the kinetics of VOC molecular markers in SAD mice which may aid in testing the efficiency of new therapeutic processes against VOC.
10.3233/CH-131735
pubmed_448_2922
PROBLEM/CONDITION Autism spectrum disorder (ASD). PERIOD COVERED 2018. DESCRIPTION OF SYSTEM The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.
10.15585/mmwr.ss7011a1
pubmed_450_19457
Accelerated progression of residual non-small cell lung cancer (NSCLC) after incomplete radiofrequency ablation (RFA) has frequently been reported. In this study, NSCLC cells A549, CCL-185, and H358 were treated using a water bath at 47°C for 5, 10, 15, 20, and 25 min gradually to establish the sublines A549-H, CCL-185-H, and H358-H, respectively. A549-H, CCL-185-H, and H358-H cells showed a significant increase in proliferation rate when compared with their corresponding parental cellsin vitro The expression of hypoxia-inducible factor-1α (HIF-1α) was obviously upregulated in both A549-H and CCL-185-H cells. Silencing of HIF-1α abolished the insufficient RFA-induced proliferation in A549-H and CCL-185-H cells. Furthermore, insufficient RFA treatment markedly elevated the phosphorylation of ERK1/2 and Akt, but not of p38 MAPK or JNK, in A549-H and CCL-185-H cells. The inhibitor of Akt, LY294002, but not the inhibitor of ERK1/2, PD98059, suppressed the upregulation of HIF-1α and the proliferation of A549-H and CCL-185-H cellsin vitro Thein vivoresults confirmed that insufficient RFA could trigger the tumor growth, upregulate the HIF-1α expression, and activate Akt in A549 xenograft tumors. Our data suggest that insufficient RFA can promote thein vitroandin vivogrowth of NSCLC via upregulating HIF-1α through the PI3K/Akt signals.
10.1093/abbs/gmw005
pubmed_216_5413
Congruity of the ulnohumeral joint, especially its anterior portion, is an important stabilizer of the elbow joint. We report on 3 patients in whom the insufficiency of the coronoid process, such as nonunion or a flattened trochlear notch, was associated with posterolateral rotatory instability of the elbow. In our opinion, addressing the anterior bony integrity of the ulnohumeral joint, in addition to the ligamentous stabilizer and mechanical axis, is essential to achieve stability in these circumstances. This issue is discussed with a review of the literature.
10.1016/j.jhsa.2006.11.001
pubmed_576_22708
It has been hypothesized that voltage-sensitive conductances present on the dendrites of neurons can influence summation of excitatory postsynaptic potentials (EPSPs) and hence affect how neurons compile information. Greater than linear summation of EPSPs has been postulated to facilitate coincidence detection by cortical neurons. This study examined whether the summation of subthreshold AMPA-mediated EPSPs generated on layer V neocortical pyramidal neurons in vitro was linear and if any nonlinearities could be attributed to dendritic conductances. Evoked EPSPs (1-12 mV) were recorded somatically by means of intracellular sharp electrodes in the presence of 100 microM amino-5-phosphonopentanoic acid (AP-5) and 3 microM bicuculline. Two independent EPSPs were evoked by a stimulating electrode in layer I and another in layers III-V. The areas of stimulation were isolated from each other by a horizontal cut below layer I. By subtracting the algebraic sum of the individual EPSPs from the evoked response when both EPSPs were evoked simultaneously, we determined that they summed linearly to supralinearly. Supralinear summation was more likely when the soma was hyperpolarized by DC current injection. Summation was predominantly linear when postsynaptic conductances (i.e., Na(+) and Ca(2+)) were blocked with intracellular QX-314. The supralinear summation of EPSPs (without QX-314) decreased as the time between inputs was increased from 0 to 30 ms. To determine the role of dendrites in nonlinear summation, we substituted a current pulse (simulated EPSP) delivered at the soma for either or both of the evoked EPSPs. Simulated EPSPs combined with either an evoked EPSP or another simulated EPSP showed significantly less supralinear summation than two evoked EPSPs, indicating that the dendritic conductances were largely responsible for the observed supralinear summation.
10.1152/jn.2000.83.6.3310
pubmed_77_10280
Most studies concerning the nutritional status of alcoholics have focused on the indigent alcoholic but programs now increasingly consider the working patient. The role of socioeconomic status in determining nutritional status of the alcoholic is further clarified in this study. One hundred patients from an alcoholic population were studied, 50 with low socioeconomic status and 50 with middle or higher socioeconomic status. The nutritional status of these two different socioeconomic groups was examined and compared. The middle-income alcoholic had significantly higher values in weight to height index (P less than .02), the triceps skinfold (P less than .01), the midarm muscle circumference (P less than .05), hematocrit (P less than .01), and epilation force (P less than .001) than the lower-income alcoholic group. Hair-pulling tension was compared in both groups as an index of protein malnutrition. There was a highly significant difference in the two groups.
10.1080/07315724.1983.10719925
pubmed_722_14545
Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (p<0.01). Treatment with rosiglitazone decreased blood glucose levels to 80% at 1h after pretreatment of rosiglitazone (p<0.05). In addition, pretreatment with rosiglitazone significantly reduced the cerebral infarct volume compared with that of the control group. These findings suggest that this method may be useful for simultaneous and continuous determination of rosiglitazone and glucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect.
10.1016/j.jpba.2010.10.008
pubmed_162_20450
Physical inactivity and sedentary behavior relate to poor health outcomes independently. Healthy inactive adults are a key target population for prevention. This systematic review and meta-analysis aimed to evaluate the effectiveness of physical activity and/or sedentary behavior interventions, measured postintervention (behavior change) and at follow-up (behavior change maintenance), to identify behavior change techniques (BCT) within, and report on fidelity. Included studies were randomized controlled trials, targeting healthy inactive adults, aiming to change physical activity and/or sedentary behavior, with a minimum postintervention follow-up of 6 months, using 16 databases from 1990. Two reviewers independently coded risk of bias, the "Template for Intervention Description and Replication" (TIDieR) checklist, and BCTs. Twenty-six studies were included; 16 pooled for meta-analysis. Physical activity interventions were effective at changing behavior (d = 0.32, 95% confidence intervals = 0.16-0.48, n = 2,346) and maintaining behavior change after 6 months or more (d = 0.21, 95% confidence intervals = 0.12-0.30, n = 2,190). Sedentary behavior interventions (n = 2) were not effective. At postintervention, physical activity intervention effectiveness was associated with the BCTs "Biofeedback," "Demonstration of the behavior," "Behavior practice/rehearsal," and "Graded tasks." At follow-up, effectiveness was associated with using "Action planning," "Instruction on how to perform the behavior," "Prompts/cues," "Behavior practice/rehearsal," "Graded tasks," and "Self-reward." Fidelity was only documented in one study. Good evidence was found for behavior change maintenance effects in healthy inactive adults, and underlying BCTs. This review provides translational evidence to improve research, intervention design, and service delivery in physical activity interventions, while highlighting the lack of fidelity measurement.
10.1093/tbm/iby010
pubmed_970_23661
The antidiabetic properties of Tiliacora triandra ethanol extract in diabetic rats induced with high-fat diet (HFD)/streptozotocin (STZ) was investigated. Rats were fed with HFD for 4 weeks to induced insulin resistance, and thereafter administered with 35 mg/kg of STZ to induce diabetes. Diabetic rats received 100 and 400 mg/kg of T. triandra daily for 30 days. The body weight, blood glucose level, food and fluid intake were monitored. Furthermore, biochemical and histological assessment was performed to evaluate the hypoglycemic effect of the extract in the treated rats. T. triandra significantly decreased the blood glucose level, increased the body weight and insulin secretion. Furthermore, T. triandra attenuated hyperlipidemia, improved liver and kidney functions of treated diabetic rats. Thus, T. triandra could effectively attenuate diabetes and it complications. PRACTICAL APPLICATIONS: Tiliacora triandra is a common vegetable consumed in Thailand and Laos. It is traditionally employed in the treatment of fever, cancer, malaria, and diabetes. The extract from the aerial part was investigated for its antidiabetic properties. The results obtained provides important pharmacological information that supports the use of T. triandra in management of diabetes.
10.1111/jfbc.13239
pubmed_834_5315
A method described previously for determining the concentration of influenza virus antihemagglutinin antibody molecules, the number of epitopes per virus particle and the equilibrium constant of virus antibody interaction was adapted to the use with escape variants (EVs), produced by multiplication of influenza virus A/Brazil (H1N1) in presence of monoclonal antibody directed to each of the four hemagglutinin sites (Sa, Sb, Ca and Cb). The EVs were found to possess an altered antigenic site, which was both antigenic and immunogenic. By use of selected EVs and antibody preparations, the number of epitopes per antigenic site was determined and it was found that each of the four sites was represented by about 390 epitopes per virus particle, suggesting that each of the about 400 hemagglutinin spikes per virion possessed one epitope of the specificity Sa, Sb, Ca and Cb. Alteration of site Sa but not of site Ca increased the avidity of antibody to react with the unchanged sites.
10.1016/0166-0934(93)90178-t
pubmed_1088_7262
Sacral insufficiency fractures can cause severe, debilitating pain to patients concerned. The incidence of this fracture type correlates with the appearance of osteoporosis in the elderly population. A polymethylmethacrylate (PMMA) cement injection procedure called sacroplasty has been recently described as an optional method for the treatment of this fracture type. However, the correct cement placement in the complex anatomical structure of the sacrum is a surgical challenge. The aim of the study is to compare the precision, safety, and radiation exposure of standard multiplanar fluoroscopy and computed tomography (CT) guidance for PMMA application to the sacrum using both balloon-assisted sacroplasty and conventional sacroplasty. A controlled experimental investigation in a human cadaver trial has been performed. Two imaging and two application modalities to monitor percutaneous PMMA injection to the sacrum were examined. The application forms were randomized from side to side of the pelvis. We found less cement extravasation in the CT-guided groups, but also a significant higher radiation exposure (P < 0.05) by using CT guidance. The conventional fluoroscopy-guided sacroplasty revealed the shortest procedure time (incision to closure time) of all treatment groups (P < 0.01). These findings show no difference regarding cement extravasation between ballon-assisted and conventional sacroplasty. Further, in comparison to fluoroscopy-assisted technique, the CT-guided cement injection seems to decrease the risk of cement extravasation, irrespective of the use of an additional balloon assistance. However, we have to consider a greater radiation exposure using CT guidance. Further investigations will proof the suitability in the normal course of clinical life.
10.1007/s00586-009-1001-1
pubmed_736_1033
Crude culture filtrates of strains of Bacillus cereus, B. thuringiensis, and B. mycoides caused an increase in vascular permeability when injected intradermally into rabbits. The time course of the change in permeability was determined, and could easily be distinguished from a more transient effect induced by purified (from B. cereus) phospholipase C. The properties of the responsible factor were found to be similar to those reported for the guinea pig dermal factor and the ileal loop fluid inducing factor, namely: synthesis by vigorously aerated, logarithmically growing cells; inactivation by heating at 56 C; non-dialyzability; precipitation with ammonium sulfate; and antigenic characteristics. Permeability factor was not related to either the phospholipase C or the hemolysin produced by B. cereus. Activity of this B. cereus toxin, as measured in the vascular permeability and ileal loop assays, can easily be quantitated, but the greater simplicity, reliability, and economy of the vascular permeability test make it the method of choice for screening cultures or following toxin purification.
10.1128/iai.10.2.299-303.1974
pubmed_518_13934
The accessory gene regulator (agr) system of staphylococci regulates the expression of virulence factors in response to cell density. The extracellular signaling molecule encoded by this system is a thiolactone-containing pheromone peptide whose primary sequence varies among staphylococcal strains. A post-translational modification of the peptide is believed to be carried out by an enzyme with a novel function, AgrB. Staphylococcal pheromones show cross-inhibiting properties: Pheromones of self and pheromones of non-self induce and suppress the agr response, respectively, and have therefore been proposed as novel anti-staphylococcal drugs. As inhibition of agr leads to diminished expression of toxins, but to increased expression of colonization factors and biofilm formation, their therapeutic potential remains yet to be evaluated in depth.
10.1016/s0196-9781(01)00495-8
pubmed_867_4645
The circadian rhythms in the numbers of circulating formed elements in the peripheral blood were studied in 712 CD2F1, 188 BDF1, and 250 Swiss Webster mice kept under a lighting regimen of LD 12:12 (L 0600 to 1800 hr), a room temperature of 21 +/- 1 degree C, and food and water available ad libitum. The circadian rhythms were evaluated by the single cosinor procedure. The rhythm parameters--mesor, amplitude, and acrophase--the percentage of total variability attributable to the circadian rhythm, and the extent of the circadian rhythm are presented as guidelines for experimental design and evaluation. Under the conditions of this study, the mice of all three strains and both sexes show circadian variations, which are similar in their timing, in their red and white cell parameters. The percent of the total variance attributable to the circadian rhythms of each function varies between the strains studied in our laboratory being lowest in the Swiss Webster female mice. The extent of the circadian variation as expressed by the double amplitude as percent of mesor is similar in the three strains and between males and females. In relation to rest and activity spans, the hematologic circadian time structure in the nocturnally active mouse is different from that in diurnally active human subjects. The red-cell parameters show an acrophase in the middle of the rest span instead of the middle of the activity span as in human subjects. The lymphocytes and eosinophils in the mouse show an acrophase during the rest span that is similar to human subjects. In contrast to human subjects, however, neutrophils and monocytes show their acrophase in the first half of the rest span rather than during the second half of the daily activity span. The circulating formed elements in the peripheral blood thus follow a different circadian timing in the mouse than in human subjects; this has to be kept in mind when the time structure of the two species is compared, e.g., in models for experimental chemotherapy.
pubmed_867_4645
pubmed_98_7992
Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are proteins and protein segments that usually do not acquire well-defined folded structures even under physiological conditions. They are abundantly present and challenge the "one sequence-one structure-one function" theory due to a lack of stable secondary and/or tertiary structure. Due to conformational flexibility, IDPs/IDPRs can bind with multiple interacting partners with high-specificity and low-affinity and perform essential biological functions associated with signalling, recognition and regulation. Mis-functioning and mis-regulation of IDPs and IDPRs causes disorder in disordered proteins and disordered protein segments which results in numerous human diseases, such as cancer, Parkinson's disease (PD), Alzheimer's disease (AD), diabetes, metabolic disorders, systemic disorders and so on. Due to the strong connection of IDPs/IDPRs with human diseases they are considered potentential targets for drug therapy. Since they disobey the "one sequence-one structure-one function" concept, IDPs/IDPRs are complex systems for drug targeting. This review summarises various protein disorder diseases and different methods for therapeutic targeting of disordered proteins/segments. Targeting IDPs/IDPRs for diseases will open up a new era of rational drug design and drug discovery.
10.1016/j.bpc.2021.106742
pubmed_1071_14375
AIM To evaluate the effect of the anxiolytic adaptol on blood pressure (BP) level in its concurrent use with a fixed dose angiotensin-converting enzyme (ACE) inhibitor/diuretic combination on quality of life and on the correction of psychoautonomic disorders. SUBJECTS AND METHODS The trial included women aged 40-60 years with the verified diagnosis of Stage 2B arterial hypertension (AH), risk 2, and a disease history of at least 5 years. A study group received a fixed dose ACE inhibitor/diuretic combination once daily and adaptol 500 mg twice daily for 2 months. A comparison group had only the fixed dose ACE inhibitor/diuretic combination once daily without adaptol. RESULTS By the end of one-month therapy, a more pronounced statistically significant BP reduction was achieved in the study group receiving the ACE inhibitor/diuretic combination and adaptol than in the comparison group. The quality of life was improved in 6 of the 8 items in the study group and in 3 items in the comparison group. The total scores of psychoautonomic disorders decreased from 48.7 to 25.8 in the study group and from 47.8 to 38 in the comparison one. CONCLUSION It is expedient to combine antihypertensive therapy and anxiolytics in female hypertensive patients with autonomic dystonic disorders.
pubmed_1071_14375
pubmed_900_1579
BACKGROUND Microsurgical procedures, although equipment- and labor-intensive, allow efficient treatment of selected soft-tissue, bone, and peripheral nerve defects. The precise surgical skills required and the high equipment and institutional costs have been deterrents to initiating programs in developing countries. The authors report their 15-year international effort in facilitating the development of microsurgical techniques in Vietnam. METHODS The authors reviewed their educational, logistical, and operative experience from 11 Operation Smile International missions to Vietnam and the microsurgical procedures performed independently by Vietnamese surgeons at the Central Military Hospital 108 in Hanoi. RESULTS Over 15 years, Operation Smile International missions to Vietnam performed 108 free tissue transfer operations with 15 peripheral nerve transfer procedures and 143 nonmicrosurgical reconstructive operations. Visiting surgeons with specialized expertise taught facial reanimation, flap prefabrication, and perforator flaps. During this same period, Vietnamese surgeons became facile with microsurgical techniques and independently performed a wide array of these procedures in the institutions visited. Vietnamese surgeons have organized microsurgery divisions within some hospital departments and now teach microsurgical techniques. Repeated missions allowed for patient follow-up, staged procedures, educational exchange, and quality control. Several Vietnamese surgeons have traveled abroad to obtain additional training and have set up training programs in other areas of Vietnam. CONCLUSIONS Charitable organizations can help surgeons in developing countries master complex microsurgical techniques through short-term medical missions, donation of equipment and supplies, and the encouragement of institutional support. A continuing education program, including local conferences, microsurgical laboratory training facilities, and study abroad, can aid this introduction.
10.1097/01.prs.0000254544.65054.95
pubmed_381_14034
Accurately recognizing health-related conditions from wearable data is crucial for improved healthcare outcomes. To improve the recognition accuracy, various approaches have focused on how to effectively fuse information from multiple sensors. Fusing multiple sensors is a common choice in many applications, but may not always be feasible in real-world scenarios. For example, although combining biosignals from multiple sensors (i.e., a chest pad sensor and a wrist wearable sensor) has been proved effective for improved performance, wearing multiple devices might be impractical in the free-living context. To solve the challenges, we propose an effective more to less (M2L) learning framework to improve testing performance with reduced sensors through leveraging the complementary information of multiple modalities during training. More specifically, different sensors may carry different but complementary information, and our model is designed to enforce collaborations among different modalities, where positive knowledge transfer is encouraged and negative knowledge transfer is suppressed, so that better representation is learned for individual modalities. Our experimental results show that our framework achieves comparable performance when compared with the full modalities. Our code and results will be available at https://github.com/comp-well-org/More2Less.git.
10.1109/EMBC48229.2022.9871472
pubmed_1011_782
Employers often ignore the different levels of skill among social workers and regard the non-MSW as merely a less expensive, second choice after the MSW for the same job. The author discusses a more productive allocation of work among MSWs and BSWs and describes its application in a medical setting.
10.1093/hsw/1.2.113
pubmed_765_24035
OBJECTIVES The study aimed to determine the role of inward rectifier potassium channel 2.1 protein and connexin 40 expressions in regulating the duration of repolarization and conduction velocity of right atrial myocardium in rats following hypothermic ischemia-reperfusion. METHODS The Langendorff isolated rat cardiac perfusion models were divided into control (C) and hypothermic ischemia-reperfusion groups, with 8 models in group C and 16 models in group ischemia-reperfusion. Depending on the incidence of atrial arrhythmia after reperfusion, the models in group ischemia-reperfusion were further divided into reperfusion non-atrial arrhythmia or reperfusion atrial arrhythmia subgroup. Right atrial monophasic action potential duration at 50% and 90% of repolarization after 30 minutes of continuous perfusion in group C and group ischemia-reperfusion (T0), 105 minutes of continuous perfusion in group C or after 15 minutes of reperfusion in group ischemia-reperfusion (T1) and 120 minutes of continuous perfusion in group C or 30 minutes of reperfusion in group ischemia-reperfusion (T2) were recorded. Right atrial conduction velocity and effective refractory period were recorded at T2. Then, the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 in the right atrial myocardium were detected. RESULTS Monophasic action potential duration at 50% and 90% were higher at T1 and T2 than those at T0 in subgroup reperfusion atrial arrhythmia (p < 0.05); monophasic action potential duration at 50% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T1 and T2 (p < 0.05); monophasic action potential duration at 90% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T1 and T2 (p < 0.05); effective refractory period in subgroup reperfusion atrial arrhythmia was greater than that in group C and subgroup reperfusion non-atrial arrhythmia, and the conduction velocity and the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 were significantly lower than group C and subgroup reperfusion non-atrial arrhythmia (p < 0.05). CONCLUSIONS The prolonged duration of repolarization and a decrease in conduction velocity of the atrial myocardium occur in rats after hypothermic ischemia-reperfusion. These observed effects may be related to the downregulated expressions of connexin 40 and inward rectifier potassium channel 2.1.
10.1177/0267659120934612
pubmed_861_7331
Objective: To compare the risk of hospitalization and costs associated with major bleeding (MB) or stroke/systemic embolism (SE) among elderly patients with nonvalvular atrial fibrillation (NVAF) who initiated apixaban then switched to another oral anticoagulant (OAC) vs. those who continued with apixaban treatment. Methods: NVAF patients (≥65 years) initiating apixaban were identified from the Humana database (1 January 2013-30 September 2017) and grouped into switcher and continuer cohorts. For switchers, the earliest switch from apixaban to another OAC was defined as the index event/date. A random date during apixaban treatment was selected as the index date for continuers. Patients were followed from index date to health plan disenrollment or 31 December 2017, whichever was earlier. Multivariable regression analyses were used to examine the association of switchers vs. continuers with risk of MB-related or stroke/SE-related hospitalization and healthcare costs during follow-up. Results: Of 7858 elderly NVAF patients included in the study, 14% (N = 1110; mean age: 78 years) were switchers; 86% (N = 6748; mean age: 79 years) were continuers. Apixaban switchers vs. continuers had significantly greater risk of MB-related hospitalization (hazard ratio [HR]: 2.00; 95% CI: 1.52-2.64; p < .001) during follow-up; risk of stroke/SE hospitalization did not differ significantly (HR: 1.36, 95% CI: 0.89-2.06, p = .154). MB- and stroke/SE-related medical costs were higher for switchers vs. continuers, although total all-cause healthcare costs were similar. Conclusion: Elderly patients with NVAF in the US who continued with apixaban treatment had a lower risk of MB-related hospitalization and lower MB- and stroke/SE-related medical costs compared to patients who switched to another OAC.
10.1080/03007995.2019.1623187
pubmed_254_7321
BACKGROUND Some previous reports have shown a reduced number of admission in stroke cases during the coronavirus disease 2019 (COVID-19) pandemic period. The present study aimed to investigate this changing pattern and the potential causes behind it at an academic neurology and neurosurgery center in Iran. METHODS Patients admitted to our center with the diagnosis of ischemic and hemorrhagic stroke, between March 1, 2019, Jun 1, 2019, and the similar 3-month period in 2020 (COVID-19 pandemic period), were compared in terms of clinical characteristics and outcome. Poisson regression was also conducted to assess the correlation between daily admissions and the COVID-19 pandemic period. RESULTS A total of 210 patients with stroke (ischemic and hemorrhagic) in 2019 were compared with 106 patients in 2020. COVID-19 pandemic period was significantly associated with the decline in the number of daily admissions in ischemic stroke (IRR, 0.51 [95% CI, 0.4-0.64]). A significant reduction (P = 0.003) in time from onset to arrival at hospital from median 12 h [IQR, 5-32] in 2019 to median 6 h [IQR, 4-16] in 2020 was found in ischemic stroke cases. National Institute of Health Stroke Scale (NIHSS) was significantly increased (P < 0.001) from median 4 [IQR, 2-7] in 2019 to median 9 [IQR, 4-14] in 2020. Glasgow coma scale (GCS) was significantly decreased from 13.9 (SD, 2) in 2019 to 12.8 (SD, 2.9) in 2020 (P < 0.001). CONCLUSIONS The present study provided new pieces of evidence regarding the changed pattern of hospital admission in stroke especially the possible reasons for its decline.
10.1007/s10072-020-05030-z
pubmed_591_5840
Mandibular distraction is a surgical process that progressively lengthens bone. To improve the distraction procedure and devices, the load of distraction and the mechanical strain of soft tissues during the process must be determined. We tested the assumption that it could be the periosteum primarily opposing distraction. Therefore we assessed the mechanical properties of the human mandibular periosteum and compared the stress-strain data with the torque measured on the activator during a cadaveric mandibular distraction. A 20 mm horizontal mandibular distraction was performed in 7 cadavers using standard distractors. Torque was measured with a torquemeter placed on the activation rods of the devices, providing a load (Lt) for each millimeter of distraction. In parallel, 18 periosteum samples were harvested from 9 cadaver mandibles. Uniaxial tensile tests were performed on the specimens and an estimated load (Lc) was calculated using periosteal stress-strain data and mandibular dimensions. During the distraction process, we observed an increase of the load Lt from 11.6 to 50.6 N. The periosteum exhibited a nonlinear viscoelastic stress-strain relationship, typical of biological tissues composed of collagen and elastin. The median Lc and Lt were not significantly different for the first millimeter of distraction. We demonstrated the periosteum is primarily responsible for opposing the distraction load.
10.1371/journal.pone.0199116
pubmed_857_8465
It is widely accepted in the American literature that the cricothyroid muscle is responsible for the paramedian position of the vocal fold in recurrent laryngeal nerve paralysis. However, support in the literature for this theory is not conclusive, and the cadaveric vocal fold position expected after lesions of the vagus nerve has also been reported in patients with an intact superior laryngeal nerve. This study compares the configuration of the glottis in patients with unilateral paralysis due to known lesions of either the recurrent laryngeal or vagus nerve. Normal subjects were studied as controls. Results indicate that the alteration of glottic configuration in laryngeal paralysis cannot be adequately characterized by standard terms of vocal fold position. The paralyzed vocal fold is shortened, with anterior rotation of the arytenoid. Patients with vagus nerve lesions had a statistically insignificant tendency for a more lateral vocal fold position, but a discrete difference in position between the two groups was not identified. This study also confirms prior observations that paralyzed vocal folds are frequently not denervated. These findings have significant implications for management of laryngeal paralysis.
10.1288/00005537-199311000-00004
pubmed_869_4786
We report a study of acid-terminated self-assembled monolayers of alkanethiols of different length, 11-mercaptoundecanoic acid (11-MUA) and 16-mercaptohexadecanoic acid (16-MHDA), on Au(111). Scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and contact angle techniques were used for characterization, and the results were compared with those obtained from n-alkanethiols of similar chain length, providing a detailed description of the two-dimensional crystalline structure. Molecular resolution STM images show that 11-MUA forms a dense-packed monolayer arranged in a (square root 3 x square root 3)R30 degrees structure with a c(2 x 4) superlattice, where the simple hexagonal phase, the c(2 x 4) superlattice, and nonordered areas coexist. 16-MHDA assembles in a uniform monolayer with similar morphology to that of 11-MUA, but molecular resolution could not be reached in STM due to both the hydrophilicity of the acid groups and the poor conductivity of the thick monolayer. Nevertheless, the monolayer thicknesses estimated by XPS and electrochemistry and the highly blocking character of the film observed by electrochemistry as well as the low water contact angle are consistent with 16-MHDA molecules forming a compact monolayer on the Au(111) substrate with fully extended alkyl chains and acid groups pointing away from the surface. The results obtained for 16-MHDA were reproducible under different preparation conditions such as the addition or omission of acetic acid to the ethanolic solution. Contrary to other reports, we demonstrate that ordered acid-terminated self-assembled monolayers are obtained with the same preparation conditions as those of the methyl-terminated ones, without any additional treatment.
10.1021/la0605539
pubmed_618_8580
The Notch signaling pathway plays versatile roles during heart development. However, there is contradictory evidence that Notch pathway either facilitates or impairs cardiomyogenesis in vitro. In this study, we developed iPSCs by reprogramming of murine fibroblasts with GFP expression governed by Oct4 promoter, and identified an effective strategy to enhance cardiac differentiation through timely modulation of Notch signaling. The Notch inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) alone drove the iPSCs to a neuronal fate. After mesoderm induction of embryoid bodies initiated by ascorbic acid (AA), the subsequent treatment of DAPT accelerated the generation of spontaneously beating cardiomyocytes. The timed synergy of AA and DAPT yielded an optimal efficiency of cardiac differentiation. Mechanistic studies showed that Notch pathway plays a biphasic role in cardiomyogenesis. It favors the early-stage cardiac differentiation, but exerts negative effects on the late-stage differentiation. Therefore, DAPT administration at the late stage enforced the inhibition of endogenous Notch activity, thereby enhancing cardiomyogenesis. In parallel, DAPT dramatically augmented the expression of Wnt3a, Wnt11, BMP2, and BMP4. In conclusion, our results highlight a practicable approach to generate cardiomyocytes from iPSCs based on the stage-specific biphasic roles of Notch signaling in cardiomyogenesis.
10.1371/journal.pone.0109588
pubmed_167_25774
Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current I (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (-20 pA/pF at -140 mV, n = 14) with properties typical of I in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.
10.3390/molecules24010181
pubmed_765_14456
INTRODUCTION In 2014, Brazil introduced a universal immunization program against the hepatitis A virus (HAV) for children in the second year of life, using a single dose of inactivated virus vaccine. The objective of this study was to evaluate the vaccination coverage (VC) against HAV in Brazil, against the incidence of cases reported five years after the implementation of the program. METHODOLOGY Secondary data were obtained by searching free access electronic sites of the Ministry of Health, Department of Informatics of the Unified Health System (Departamento de Informática do Sistema Único de Saúde - DATASUS), for incidence analysis and VC from 2014 to 2018. RESULTS VC ranged from 60.13 to 97.07%. The homogeneity of VC against hepatitis A did not reach the established goal throughout all states but for a few exceptions. After 2015, CV decreased in all regions of the country. Despite insufficient coverage, a concomitant reduction in the incidence of Hepatitis A took place throughout the country. The incidence rate fell from 3.29 to 0.80/100,000 between 2014 and 2018. However, there was an interruption in the pace of incidence fall between 2017 and 2018, which may be a consequence of insufficient VC. This phenomenon seems to be part of a widespread downward trend in vaccination effort across the country, also verified for other vaccines, such as poliomyelitis and measles, mumps and rubella vaccine. CONCLUSION These figures suggest the need for implementing efforts to improve hepatitis A VC rates in the country.
10.1590/1980-549720200073
pubmed_32_11460
Selective decontamination of the digestive tract (SDD) has been evaluated as a method to prevent colonization and infection in ventilated patients in 40 trials. On the basis of an assumption that cross-infection would be reduced as a consequence of SDD and that this would distort the results of SDD studies that used concurrent controls, 14 studies used historic controls. To test this assumption, three observations from the two types of studies were compared. (i) The differences between observed and expected event rates for each study were used to perform a meta-analysis. This revealed that the summary odds ratios for bacteremia and respiratory infection were marked by significant heterogeneity (P > 0.95) and inconsistencies between those derived from studies with concurrent versus studies with historic controls. (ii) Where the data were available, the rates of acquisition of colonization in control groups were higher in studies with concurrent controls than in studies with historic controls. (iii) At least four studies with concurrent controls have shown a pattern of pathogenic isolates consistent with cross-infection between groups. These results are contrary to the initial assumption and suggest the possibility that SDD represents a major cross-infection hazard.
10.1128/AAC.39.4.941
pubmed_621_1957
Data are accumulating to support a role for adipose-derived mesenchymal stem cells (MSCs) in breast cancer progression; however, to date most studies have relied on adipose MSCs from non-breast sources. There is a particular need to investigate the role of adipose MSCs in the pathogenesis of basal-like breast cancer, which develops at a disproportionate rate in pre-menopausal African-American women with a gain in adiposity. The aim of this study was to better understand how breast adipose MSCs (bMSCs) contribute to the progression of basal-like breast cancers by relying on isogenic HMT-3255 S3 (pre-invasive) and T4-2 (invasive) human cells that upon transplantation into nude mice resemble this tumor subtype. In vitro results suggested that bMSCs may contribute to breast cancer progression in multiple ways. bMSCs readily penetrate extracellular matrix components in part through their expression of matrix metalloproteinases 1 and 3, promote the invasion of T4-2 cells and efficiently chemoattract endothelial cells via a bFGF-independent, VEGF-A-dependent manner. As mixed xenografts, bMSCs stimulated the growth, invasion and desmoplasia of T4-2 tumors, yet these resident stem cells showed no observable effect on the progression of pre-invasive S3 cells. While bMSCs form vessel-like structures within Matrigel both in vitro and in vivo and chemoattract endothelial cells, there appeared to be no difference between T4-2/bMSC mixed xenografts and T4-2 xenografts with regard to intra- or peri-tumoral vascularity. Collectively, our data suggest that bMSCs may contribute to the progression of basal-like breast cancers by stimulating growth and invasion but not vasculogenesis or angiogenesis.
10.4161/cbt.20561
pubmed_150_21636
This work deals with the systematics and taxonomy of orthobunyaviruses, little-studied dangerous and new iruses Akabane, Aino, Schmallenberg, Cache Valley diseases, Oropouche fever. The significance of the reassortment mechanism of their origin and diversification is discussed.
pubmed_150_21636