index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_598_14080
Hypophosphatasia (HPP) when diagnosed at a young age may induce premature fusion of one or several cranial sutures, resulting in a craniocerebral disproportion. The main forms of craniosynostosis associated with HPP are loss of the sagittal suture (scaphocephaly), alone or associated with loss of the coronal sutures (oxycephaly) or associated with loss of the coronal and lambdoid sutures (pansynostosis). Craniosynostosis is accompanied by putatively functional consequences. Diagnosis must thus be early and lead to management by a specialized team.
10.1016/S0929-693X(18)30022-8
pubmed_113_17577
Synapses are critical actors of neuronal transmission as they form the basis of chemical communication between neurons. Accurate computational models of synaptic dynamics may prove important in elucidating emergent properties across hierarchical scales. Yet, in large-scale neuronal network simulations, synapses are often modeled as highly simplified linear exponential functions due to their small computational footprint. However, these models cannot capture the complex non-linear dynamics that biological synapses exhibit and thus, are insufficient in representing synaptic behavior accurately. Existing detailed mechanistic synapse models can replicate these non-linear dynamics by modeling the underlying kinetics of biological synapses, but their high complexity prevents them from being a suitable option in large-scale models due to long simulation times. This motivates the development of more parsimonious models that can capture the complex non-linear dynamics of synapses accurately while maintaining a minimal computational cost. We propose a look-up table approach that stores precomputed values thereby circumventing most computations at runtime and enabling extremely fast simulations for glutamatergic receptors AMPAr and NMDAr. Our results demonstrate that this methodology is capable of replicating the dynamics of biological synapses as accurately as the mechanistic synapse models while offering up to a 56-fold increase in speed. This powerful approach allows for multi-scale neuronal networks to be simulated at large scales, enabling the investigation of how low-level synaptic activity may lead to changes in high-level phenomena, such as memory and learning.
10.3389/fncom.2021.733155
pubmed_265_18909
This paper presents the results of the evaluation testing of six 12-lead electrocardiographs, three purpose-built instruments and three of the recently introduced personal computer-based type (PC-based). As for PC-based electrocardiographs, three examples of the MRT systems, two examples of the 300 Hz CardioScope model and one prototype of the 1200 Hz CardioScope were examined but only results for one representative example of each are given here. It was of particular interest to compare the performance advantages and limitations of the PC-based electrocardiographs with that of instruments currently in use. A test procedure was developed that can be used by a medical technical department to evaluate an electrocardiograph before making a purchase decision. The procedure includes tests of frequency response, sampling rate, 50 Hz filter attenuation, gain and common mode rejection ratio (CMRR) plus tests based upon simulated electrocardiograms (ECGs). The procedure takes account of the AHA and ECRI recommendations for electrocardiograph checks and can be completed in less than two hours. The only equipment required being an ECG simulator and a signal generator. The results of this work show that purpose-built electrocardiographs meet all normal performance requirements, whereas the PC-based types, whilst having the potential to at least equal these requirements, currently exhibit software and hardware related problems.
10.3109/03091909809010002
pubmed_150_22020
In brief: Women were admitted to the US Naval Academy in Annapolis, Maryland, a little more than a decade ago. To compensate for differences between men and women, some modifications were made in the physical training program, which originally had been designed for men. For example, the personal defense requirement includes judo, boxing, and wrestling for men and judo, hand-to-hand defense, and fencing for women; all these activities are believed to develop poise, fortitude, and combat strategy. The authors point out that athletic women have more success than nonathletes at the academy, probably because athletes tend to possess the stamina, strength, and self-discipline required to survive the academy's tough, uncompromising physical environment.
10.1080/00913847.1989.11709708
pubmed_448_13119
Aims: In the central nerve system, neurotensin (NT), and neurotensin receptor 1 (NTR1) modulate the dopamine system. Gene variations in the dopamine system have been demonstrated to influence certain defense mechanisms, but no studies have investigated possible effect of NTR1 gene polymorphisms in the biological determination of these defenses. The present study therefore examined this link. Methods: In 412 healthy Han Chinese, single nucleotide polymorphisms rs6090453C/G, rs6011914C/G, and rs2427422A/G of the NTR1 gene were genotyped, and the defense mechanisms were measured by the self-reporting Defense Style Questionnaire 88. Results: Significant male-specific differences in the projective identification among the rs6090453 genotypes (p = 0.003); in the intermediate defense, reaction formation, and projective identification among the rs6011914 genotypes (p = 0.011, 0.010, and 0.011, respectively); and in the projective identification among the rs2427422 genotypes (p = 0.005) were found when the level of significance was adjusted by the Bonferroni correction. There was no significant difference in any of the defense scores among genotypes of any single nucleotide polymorphism in the total cohort or female subjects (all p > 0.017). The distributions of genotypes between the low and high score subgroups showed significant differences in the rs2427422 genotype distributions for help-rejecting complaining, regression, and projective identification (p = 0.010, 0.022, and 0.044, respectively). Significant differences were found between males and females in 10 defense mechanisms (all P < 0.05). Conclusions: The gene variations in the NTR1 polymorphisms were involved in the biological mechanisms of intermediate defense mechanisms, and this effect was influenced by sex.
10.3389/fpsyt.2021.762276
pubmed_143_16984
Numerous studies have demonstrated that microRNAs (miRNAs) are dysregulated in esophageal squamous cell carcinoma (ESCC). Changes in miRNA expression may be associated with ESCC formation and progression. Therefore, the identification of ESCC-associated miRNAs may facilitate the development of effective therapeutic approaches for patients with ESCC. Recently, miRNA-652 (miR-652) was recognized as a cancer-associated miRNA in a number of different types of cancer. However, the expression status and roles of miR-652 in ESCC as well as the molecular mechanisms modulated or altered by it remain largely unknown. In the present study, it was demonstrated that miR-652 was downregulated in ESCC tissues and cell lines. Functional assays showed that upregulation of miR-652 expression decreased proliferation and invasion of ESCC cells. Mechanistically, fibroblast growth factor receptor 1 (FGFR1) was determined to be a direct target of miR-652 in ESCC cells. Additionally, FGFR1 was upregulated in ESCC tissues, and the expression of FGFR1 was inversely correlated with miR-652 expression. Furthermore, restoring FGFR1 expression abolished the suppressive effects of miR-652 overexpression on the proliferation and invasion of ESCC cells. These findings demonstrated that miR-652 inhibits the proliferation and invasion of ESCC cells by directly targeting FGFR1.
10.3892/etm.2019.8072
pubmed_762_18254
BACKGROUND The aim was to assess quality of life in a group of patients who had a curative resection for gastric cancer. METHODS The European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire with a gastric cancer-specific module was used in patients who had undergone R0 gastrectomy between 1992 and 1999, and who had no disease at the last check-up. A response was obtained from 54 patients, 36 men and 18 women, of mean age 67 years. Of these, 24 patients had total gastrectomy and 26 D2 lymphadenectomy. RESULTS Significant differences were found only in the social domain of quality of life in patients aged over 70 years (P = 0.036); there was no impact of operation type on overall quality of life. CONCLUSION The quality of life of patients undergoing curative surgery for gastric cancer, regardless of age, was not significantly influenced by the type of gastrectomy, or whether lymphadenectomy was performed.
10.1002/bjs.4011
pubmed_3_496
The aim of this empirical investigation is to analyse the social movements brought about by autism-related issues. It is suggested that both the autism-category changes in the late 1980s, and the development of educational and behavioural methods in the United States, have given rise to a large-scale mobilisation around the changes in the definition of autism and interventions in many countries. The present paper highlights the historical dynamics of the mobilisation of French parents' associations and the engagement of autistic persons' organisations. The role of the French parents' associations has been studied over the last 40 years to show how they have contributed to shaping public policy in France and how they have favoured the American model of autism despite the French professionals' resistance. At the international level, the newly-born associations of autistic individuals have introduced new actors who sometimes reproach the parents' associations for speaking on their behalf. These new associations, such as self-help groups, have a political identity problem. Their members no longer want to be considered as patients but as individuals with a different cognitive mode of functioning. Their actions can be analysed in the broader context of the disability movement. If the disability movement is considered as the latest generation of social movements, the action of autistic persons can be viewed as the latest generation of the disability movements.
10.1111/j.1467-9566.2007.01053.x
pubmed_667_13468
PURPOSE The purpose of our study was to evaluate the MR findings in the wrists of pediatric patients who have sustained acute wrist injuries and to determine if this imaging method yields more information than combined serial radiographs and physical examinations. METHOD Eighteen skeletally immature patients (11 boys and 7 girls, age range 8-15 years) who had presented to the emergency room within 2 days following acute wrist trauma underwent serial clinical, radiographic, and MR examinations if there was a suspicion of a scaphoid fracture. RESULTS Ten patients had a scaphoid abnormality on MR images. Six had fractures and four had regional bone marrow edema. Initially, all but two fractures were radiographically occult, although the other fractures eventually became evident on later studies. Those with marrow edema did not progress to fractures. Obliteration of the scaphoid fat stripe occurred in five patients with a scaphoid fracture and in six patients who did not have a fracture. Dorsal soft tissue swelling occurred in eight patients, five of whom had scaphoid fractures. Seven patients had evidence of extensor tenosynovitis on MRI. CONCLUSION A normal initial MR image had a negative predictive value of 100%. Persistent snuffbox pain may represent injury to the scaphoid, extensor tendons, or dorsal soft tissues. An outcome study evaluating the benefits of early application of MR in the pediatric population is warranted.
10.1097/00004728-199707000-00001
pubmed_874_8912
Proteins with membrane-attack complex/perforin (MACPF) domains are found in almost all kingdoms of life, and they have a variety of biological roles, including defence and attack, organism development, and cell adhesion and signalling. The distribution of these proteins in fungi appears to be restricted to some Pezizomycotina and Basidiomycota species only, in correlation with another group of proteins with unknown biological function, known as aegerolysins. These two protein groups coincide in only a few species, and they might operate in concert as cytolytic bi-component pore-forming agents. Representative proteins here include pleurotolysin B, which has a MACPF domain, and the aegerolysin-like protein pleurotolysin A, and the very similar ostreolysin A, which have been purified from oyster mushroom (Pleurotus ostreatus). These have been shown to act in concert to perforate natural and artificial lipid membranes with high cholesterol and sphingomyelin content. The aegerolysin-like proteins provide the membrane cholesterol/sphingomyelin selectivity and recruit oligomerised pleurotolysin B molecules, to create a membrane-inserted pore complex. The resulting protein structure has been imaged with electron microscopy, and it has a 13-meric rosette-like structure, with a central lumen that is ~4-5 nm in diameter. The opened transmembrane pore is non-selectively permeable for ions and smaller neutral solutes, and is a cause of cytolysis of a colloid-osmotic type. The biological significance of these proteins for the fungal life-style is discussed.
10.1007/978-94-017-8881-6_14
pubmed_1098_829
Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.
10.1016/j.cmet.2022.09.008
pubmed_1095_2495
Matrix metalloproteinases (MMPs) are of central importance in the proteolytic remodeling of matrix and the generation of biologically active molecules. MMPs are distinguished by a conserved catalytic domain containing a zinc ion, as well as a prodomain that regulates enzyme activation by modulation of a cysteine residue within that domain. Because nitric oxide (NO) and derived reactive nitrogen species target zinc ions and cysteine thiols, we assessed the ability of NO to regulate MMPs. A dose-dependent, biphasic regulatory effect of NO on the activity of MMPs (MMP-9, -1, and -13) secreted from murine macrophages was observed. Low exogenous NO perturbed MMP/tissue inhibitor of metalloproteinase (TIMP)-1 levels by enhancing MMP activity and suppressing the endogenous inhibitor TIMP-1. This was cGMP-dependent, as confirmed by the cGMP analog 8-bromo-cGMP, as well as by the NO-soluble guanylyl cyclase-cGMP signaling inhibitor thrombospondin-1. Exposure of purified latent MMP-9 to exogenous NO demonstrated a concentration-dependent activation and inactivation of the enzyme, which occurred at higher NO flux. These chemical reactions occurred at concentrations similar to that of activated macrophages. Importantly, these results suggest that NO regulation of MMP-9 secreted from macrophages may occur chemically by reactive nitrogen species-mediated protein modification, biologically through soluble guanylyl-cyclase-dependent modulation of the MMP-9/TIMP-1 balance, or proteolytically through regulation of MMP-1 and -13, which can cleave the prodomain of MMP-9. Furthermore, when applied in a wound model, conditioned media exhibiting peak MMP activity increased vascular cell migration that was MMP-9-dependent, suggesting that MMP-9 is a key physiologic mediator of the effects of NO in this model.
10.1073/pnas.0702761104
pubmed_1086_7714
This paper examined the influence of religion on the adoption of female sterilization, using data from the 1992/93 Indian National Family Health Survey. The influence of religion at both individual and district levels was examined, and a multi-level modelling methodology was used for assessing community variations in the influence of religion on the adoption of sterilization. Individual religion was a strong predictor of the decision to adopt sterilization, and residence in a district in which more than 20% of the people were Muslims significantly lowered the odds of adoption of sterilization. There was more variation in the adoption of sterilization between districts for Muslim women and women from minority religious groups. The results demonstrate the influence of community conservatism on the choice of contraceptive methods and point to the mediating effects that community characteristics can have on access to sterilization services for women from religious minority sub-groups.
pubmed_1086_7714
pubmed_470_18273
The Escherichia coli trehalose-6-phosphate synthase gene(otsA) was engineered under the control of cauliflower mosaic virus regulatory sequences (CaMV35S) for expression in plants. OtsA gene was incorporated into the chromosome DNA by Agrobacterium-mediated transfer and expressed in Nicotiana tabacum. The otsA gene transgenic plant exhibited multiple phenotypic alteration: improved stunted growth and drought tolerance. The detached leaves from the transgenic plant, their water loss slower than that of the controls. Trehalose accumulated in transgenic plant was determined by HPLC suggest that synthesis of the sugar improving plant to stress tolerance.
pubmed_470_18273
pubmed_328_5567
BACKGROUND There are a limited number of studies that have examined the real-world effectiveness of smoking cessation aids and relapse longitudinally in population-representative samples. This study examines the association between use of nicotine gum, patch, bupropion, and varenicline and time to relapse as well as any changes in the association with increased length of abstinence. METHODS Data of 1821 current adult smokers (18+) making their first serious quit attempt were compiled from 4504 individuals enrolled in the Ontario Tobacco Survey, a representative telephone survey of Ontario adults, which followed smokers every 6 months for up to 3 years. Use of cessation aids at the time of initial report of a quit attempt was analyzed. A flexible parametric survival model was developed to model length of abstinence, controlling for potential confounders. RESULTS The best fit model found knots at 3, 13, 43, and 212 days abstinent, suggesting different rates of relapse in the periods marked by those days. Use of the patch and varenicline was associated with lower rates of relapse, but no positive effect was found for bupropion or nicotine gum. The effectiveness of the patch reversed in effect after the first month of abstinence. CONCLUSIONS This study is one of few reports of long-term quitting in a population-representative sample and demonstrates that the effectiveness of some pharmacological cessation aids (the patch and varenicline can be seen in a population sample). Previous failures in real-world studies of the effectiveness of smoking cessation aids may reflect differences in the products individuals use and differences in the timing of self-reported cessation. IMPLICATIONS While a large number of randomized controlled trials have shown the efficacy of many pharmaceutical smoking cessation aids, evidence of their effectiveness in observational studies in the real world is ambiguous. This study uses a longitudinal cohort of a representative sample of smokers to show that the effectiveness of pharmaceutical cessation aids can be demonstrated in real-world use situations, but effectiveness varies by product type and has time-varying effects.
10.1093/ntr/nty194
pubmed_238_6640
Since the hippocampus plays an important role in memory and spatial cognition, the study of spatial computation models inspired by the hippocampus has attracted much attention. This study relies mainly on reward signals for learning environments and planning paths. As reward signals in a complex or large-scale environment attenuate sharply, the spatial cognition and path planning performance of such models will decrease clearly as a result. Aiming to solve this problem, we present a brain-inspired mechanism, a Memory-Replay Mechanism, that is inspired by the reactivation function of place cells in the hippocampus. We classify the path memory according to the reward information and find the overlapping place cells in different categories of path memory to segment and reconstruct the memory to form a "virtual path", replaying the memory by associating the reward information. We conducted a series of navigation experiments in a simple environment called a Morris water maze (MWM) and in a complex environment, and we compared our model with a reinforcement learning model and other brain-inspired models. The experimental results show that under the same conditions, our model has a higher rate of environmental exploration and more stable signal transmission, and the average reward obtained under stable conditions was 14.12% higher than RL with random-experience replay. Our model also shows good performance in complex maze environments where signals are easily attenuated. Moreover, the performance of our model at bifurcations is consistent with neurophysiological studies.
10.3390/brainsci12091176
pubmed_1046_17727
Introduction: Treatment of multiple myeloma (MM) in the relapsed setting remains challenging, despite recent impressive advances in the management of these patients. Venetoclax (ABT-199) is a BCL-2 inhibitor recently approved by the US food and drug administration for treatment of chronic lymphocytic leukemia but the drug has shown activity in a number of hematological malignancies. Venetoclax has broadened the treatment options for patients with relapsed or refractory MM. Approximately, 20% of myeloma patients will exhibit t (11;14) associated with high BCL-2 expression making venetoclax an attractive therapeutic option. The efficacy of venetoclax is not uniquely restricted to this population. Areas covered: This review will summarize the mechanism of action, toxicity profile, and published data on venetoclax use in MM, moving the field toward personalized medicine in the treatment of myeloma. Expert commentary: Numerous phase 1/2 clinical trials are evaluating the efficacy and safety of venetoclax monotherapy and in combinations in the relapse setting. These trials show better outcomes in the subgroup of patients harboring t(11;14).
10.1080/17474086.2018.1548931
pubmed_877_17328
Abdominal pain is a common symptom that patients refer to a hospital. Organic causes should be differentiated in patients with abdominal pain and treatment should be administered in accordance with the causes. A meticulous history taking and physical examination are highly useful in making a diagnosis, and blood tests, imaging modalities, and endoscopy are useful for confirming diagnosis. However, in many cases, patients have functional disorders with no obvious abnormal findings obtained even if many diagnostic tests are performed. Patients with functional disorders usually complain the vague abdominal pain located in the center and other portions of the abdominal area. Although the most representative disease is irritable bowel syndrome, functional abdominal pain syndrome is currently researched as a new disease entity of functional abdominal pain. As various receptors related to functional abdominal pain have been discovered, drugs associated with those receptors are used to treat the disorders, and additional new drugs are vigorously developed. In addition, medical therapy with pharmacological or non-pharmacological psychiatric treatment is effective for treating functional abdominal pain.
10.4166/kjg.2018.71.2.89
pubmed_301_11647
OBJECTIVES The four study objectives were to determine (1) the prevalence of use of four herbal product types promoted to reduce menopause symptoms (phytoestrogens, St. John's wort, Ginkgo biloba, and ginseng) among primary care patients approaching or in menopause, (2) the extent to which women who use these types of herbal products report menopause-related symptoms compared with herbal product nonusers, (3) the frequency of reported symptom reduction after use, and (4) if use was disclosed to their physicians. METHODS A cross-section of ethnically diverse women 40-55 years of age (35.5% African American, 60.2% Caucasian) who were recruited from eight primary care centers in Michigan to complete a self-report survey. The questionnaire included demographic items, health history, recent use of four herbal product types purported to relieve menopause symptoms and perception of symptom improvement, and interest in additional herbal product information. RESULTS Of 397 women, 24.9% reported taking, in the previous 6 months, at least one of the four study herbs. Herbal product use did not vary by patient demographics or health characteristics. Herbal product users reported more menopause symptoms than nonusers, and 68% of the users said that the herbs improved their symptoms; 56.4% said that their physician was aware of their herbal product use. CONCLUSIONS Primary care patients experiencing common menopausal symptoms are likely to use herbal products that are purported to provide menopause symptom relief, and many believe that these products improve their menopausal symptoms. Healthcare providers should be aware of patient's positive attitude, use patterns, and lack of disclosure of use of herbal medicines. Inquiry of herbal product use is another way for physicians to learn about patient self-medication of bothersome symptoms.
10.1089/154099903322404285
pubmed_663_12176
The degree to which lipid and myoglobin (Mb) oxidation processes interact in meat can be species-specific. We investigated the effects of beef and pork sarcoplasmic extracts containing different Mb concentrations on lipid oxidation in a liposome system. Sarcoplasm was extracted from beef and pork longissimus dorsi and psoas major muscles. Beef sarcoplasm was diluted with 0.1 M phosphate buffer to obtain a Mb concentration equivalent to that in pork sarcoplasm. Conversely, equine heart Mb was added to pork sarcoplasm to match the myoglobin concentration of beef sarcoplasm. This resulted in beef and pork sarcoplasms, each with 2 different Mb concentrations for the longissimus (0.02 mM and 0.07 mM) and psoas (0.05 and 0.12 mM). Sarcoplasm (or phosphate buffer control) was incorporated within a phosphatidylcholine liposome preparation and incubated at 25 degrees C. Thiobarbituric acid reactive substances (TBARS) were measured at 0, 30, 60, 90, and 120 min of incubation. Regardless of species, greater Mb concentration within the sarcoplasm increased lipid oxidation (P < 0.05). Across muscles, pork sarcoplasm had lower TBARS values than beef sarcoplasm (P < 0.05). Our results suggest that pork sarcoplasm has a lesser effect on lipid oxidation than beef sarcoplasm for a common Mb concentration. However, increased myoglobin concentration within sarcoplasm promotes lipid oxidation regardless of species.
10.1111/j.1750-3841.2008.01021.x
pubmed_1096_4722
The advantages and limitations of techniques for measuring the presence and amount of cavitation, and for quantifying the removal of contaminants, are provided. After reviewing chemical, physical, and biological studies, a universal cause for the cleaning effects of bubbles cannot yet be concluded. An "ideal sensor" with high spatial and temporal resolution is proposed. Such sensor could be used to investigate bubble jetting, shockwaves, streaming, and even chemical effects, by correlating cleaning processes with cavitation effects, generated by hydrodynamics, lasers or ultrasound.
pubmed_1096_4722
pubmed_528_24883
BACKGROUND High blood pressure, left ventricular hypertrophy and diastolic dysfunction may cause hemodynamic and morphological changes in the left atrium, consequently instability and heterogeneity in atrial conduction. This is seen as an increase in maximum P wave duration (P(max)) and P wave dispersion (PD) on the electrocardiogram (ECG). P wave dispersion on ECG has been encountered as a risk factor for atrial fibrillation (AF). The aim of this study is to examine whether PD and P(max) can be used as a non-invasive marker of target organ damage (LVH and diastolic dysfunction) in a hypertensive population. MATERIAL AND METHODS The study registered a total of 120 cases (mean age 46.9 +/- 10.6 years; 58 [48.3%] males and 62 [51.7%] females), of whom 60 were patients diagnosed as essential hypertension (group 1), and 60 were healthy individuals, who constituted the control group (group 2). Systolic and diastolic functions of all cases were evaluated by echocardiography, and maximum P wave duration (P(max)), and PD was calculated. RESULTS Maximum P wave duration was 91.6 +/- 10.2 ms in group 1, and 64 +/- 10.2 ms in group 2 (p < 0.01), while PD was 56.1 +/- 5.8 ms in group 1, and 30.3 +/- 6.6 ms in group 2 (p < 0.01). Blood pressure, left atrium diameter, DT, IVRT, and E/A ratio, as well as left ventricular mass index increased markedly in group 1. CONCLUSION High blood pressure, LVH, diastolic dysfunction and increased left atrium diameter and volume shows parallelism in hypertensive cases. These physiopathological changes may cause different and heterogeneous atrial electrical conduction. This led to a marked increase in P(max) and PD in our cases. Thus, the results support the hypothesis that PD can be used as a non-invasive marker of target organ damage (LVH and LV diastolic dysfunction) in the hypertension population.
10.1007/s00392-007-0587-8
pubmed_872_12211
Rett syndrome is a dominant neurological disorder caused by loss-of-function mutations of methyl-CpG-binding protein 2 (MeCP2). MeCP2 is an abundant chromatin-associated protein that contains two well characterized domains. Through an N-terminal domain it recognizes methyl-CpGs and binds to nonmethylated DNA. A domain in the middle of the protein can act as a transcriptional repressor in transient transfection studies. The C-terminal region of the protein is equally essential for the function of MeCP2, as documented by recurrently found frameshift mutations. However, little is known about its functional role. Here we mapped a domain within MeCP2 capable of binding specifically to Group II WW domains of splicing factors formin-binding protein (FBP) 11 and HYPC. Binding was assessed by glutathione S-transferase pull-down assays and coimmunoprecipitation assays. The Group II WW domain binding region was localized from residue 325 to the C-terminus, with the interacting proline-rich sequence at its center. We then used comparison with genotype-phenotype studies in Rett syndrome patients to evaluate the relevance of Group II WW domain interactions of MeCP2 for pathogenesis. Truncation of the WW domain binding region by 48 C-terminal amino acids (to residue 438), causing Rett syndrome, resulted in reduced or loss of WW domain binding activity. Truncation to residue 400, representing a large group of frameshift mutations accounting for approx. 10% of Rett syndrome cases, abolished WW domain binding activity completely. On the other hand, two benign missense mutations did not affect binding. Furthermore, a short C-terminal truncation and an internal deletion, both causing mild to moderate mental retardation in males, were associated with weak or loss of WW domain binding activity.
10.1007/s00109-003-0497-9
pubmed_820_5317
Angiotensin converting enzyme (ACE) influences vessels tone and the coagulation/fibrinolysis system. The ACE gene I/D polymorphism has been linked with PAI-1 and fibrinogen levels and with Factors VII and X activities. Therefore, we aimed to test whether I/D polymorphism could be related to thrombolysis safety and efficacy. We studied strokes involving the middle cerebral artery (MCA) territory of patients who received t-PA <3 h of stroke onset. Blood samples were obtained before t-PA administration to measure fibrinogen, PAI-1, Factors VII and X. I/D polymorphism was determined by polymerase chain reaction and agarose electrophoresis. Recanalization rates were serially evaluated by Transcranial Doppler. Among 96 included patients the genotype frequency was: DD=33.3%, ID=57.3% and II=9.4%. A strong association was found between DD homozygous and successful recanalization rates (DD=69.2%, ID+II=31.6%, p=0.002 at 1 h; DD=91.3%, ID+II=51%, p=0.001 at 6 h; DD=100%, ID+II=72.3%, p=0.003 at 24 h post-t-PA administration). In fact, DD genotype was an independent predictor of recanalization (OR=4.3 95% CI 1.35-13.49, p=0.013). No relation was found between I/D polymorphism and symptomatic hemorrhagic complications (p=0.237). No association between ACE genotypes and Factor VII or Factor X activities, neither with fibrinogen or PAI-1 levels was observed. DD homozygous is strongly associated with MCA recanalization following t-PA treatment. Mechanisms of benefit remain unknown since I/D polymorphism had similar FVII and X activities and PAI-1 and fibrinogen levels in our stroke population.
10.1016/j.neulet.2005.12.079
pubmed_246_9560
Possible use of ethidium bromide immobilized on polyacrylamide gel for DNA extraction from biological media, e.g., cell lysates and blood serum, is discussed. The ability of the affinity gel to cause fractionation of single- and double-stranded DNA is demonstrated.
pubmed_246_9560
pubmed_430_13946
Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC. The oral contraceptive had the opposite effect on acebutolol AUC and Cmax but this was not significant. The oral contraceptive had no detectable effects on the tmax and t 1/2 values of any of the beta-adrenoceptor blockers.
10.1111/j.1365-2125.1984.tb02435.x
pubmed_553_3976
Three questions have been analysed in the study on patients in a state of psychosocial crisis : Who is coming? Who is intervening? Where are they sent? Three epidemiological studies have been taken into account : one study on 16 medical surgical centers in Brussels, the second study on two public emergency services linked to psychiatric services and the third one on a psychiatric district of a popular suburb in Brussels. The study stresses the importance of alcoholism and analyses the differences in population, intervention and response brought by the hospital or the district.
pubmed_553_3976
pubmed_298_19255
Newly fabricated few-layer black phosphorus and its monolayer structure, phosphorene, are expected to be promising for electronic and optical applications because of their finite direct band gaps and sizable but anisotropic electronic mobility. By first-principles simulations, we show that this unique anisotropic free-carrier mobility can be controlled by using simple strain conditions. With the appropriate biaxial or uniaxial strain (4-6%), we can rotate the preferred conducting direction by 90°. This will be useful for exploring unusual quantum Hall effects and exotic electronic and mechanical applications based on phosphorene.
10.1021/nl500935z
pubmed_318_2471
A refined bronchoscopic method of sampling bronchial secretions is presented. The results show that this gives higher yields of aerobic pathogens than examination of expectorated sputum and the method also avoids pharyngeal contamination in suspected cases of anaerobic lung infection. Our results indicate that anaerobic organisms do not play a major role in causing sputum purulence in patients with chronic bronchitis, bronchogenic carcinoma or with less florid degrees of bronchiectasis. Anaerobic infections did not appear to occur as often as suggested by some reports from the United States.
10.1016/0007-0971(77)90126-7
pubmed_1001_17296
OBJECTIVE The efficacy of isoniazid (INAH) prophylaxis against tuberculosis (TB) in patients taking corticosteroid remains controversial. Hong Kong is an endemic area for TB, with an annual risk of 0.11/100 in the general population. Patients with systemic lupus erythematosus (SLE) have an increased susceptibility to TB because of their intrinsic immunocompromised state and the use of corticosteroid therapy. We examined the usefulness of INAH in the prevention of recurrences of TB in patients with SLE receiving high dose corticosteroid therapy. METHODS Medical records of a cohort of patients with SLE were reviewed. Patients with a history of TB who had previously been adequately treated were retrospectively examined for subsequent recurrence of TB. A comparison was performed based on the use of INAH at the discretion of the attending physician in some patients (INAH group) but not others (non-INAH group) during lupus exacerbation that required the use of prednisolone >/= 15 mg/day or equivalent. RESULTS A total of 91 episodes of TB from 76 individuals in a cohort of 652 SLE patients with a duration of followup of 13.9 +/- 7.5 years were identified (prevalence of 1.06/100 patient-years). 43 episodes were given INAH while 48 were not. There were 18 recurrences of TB (recurrence rate of 1.66/100 patient-years). Recurrence rates in the INAH and non-INAH groups were 1.59 and 1.74 per 100 patient-years (p = 0.72). However, patients in the INAH group had more lupus exacerbations. Further, extrapulmonary TB was also found to have a higher recurrence rate than pulmonary TB. A case-controlled analysis was thus performed (n = 46) matching patients for the number of lupus exacerbations, cumulative doses of prednisolone, and initial site of TB. There was no difference in the recurrence rates of TB between the matched INAH (0.55/100 patient-years) and non-INAH (1.100 patient-years) groups (p = 0.66). CONCLUSION Patients with SLE have a higher prevalence of TB infection than the general population. They are at risk of TB recurrence when given immunosuppressive doses of corticosteroid.
pubmed_1001_17296
pubmed_617_3200
PURPOSE Most software systems for oral implantology are based on a two-dimensional multi-view approach, often accompanied with a surface rendered model. Usually they are affected by common errors like anisotropy of the volume and distortion on measurements. A more integrated and realistic 3D approach for implant surgery is desirable in order to gain a deeper and surer knowledge of patient's anatomy before inserting the implants, thus reducing the risk of damaging surrounding structures. METHODS We present a 3D software system for oral implant planning where computer graphic techniques have been used to create a smooth and user-friendly fully integrated 3D environment to work in. Both volume isotropy and correctness in measurements are obtained through slices interpolation to achieve, respectively, an isotropic voxel and the freedom of choosing arbitrarily, during the planning, the best cross-sectional plane. Correct orientation of the planned implants is also easily computed, by exploiting a radiological mask with radio-opaque markers, worn by the patient during the CT scan. RESULTS Precision in measures was validated by considering several different scans and comparing the measures achieved with the ones got through the common methodology. It has been also calculated error percentages, algorithms efficiencies, and performances. Precision achieved outperforms usual DentaScan multi-view approach one, and it is comparable with or better than that obtained by the DentalVox tool (from 0.16 to 0.71% error in measures). CONCLUSIONS The proposed software system provides a user-friendly, correct and precise work context for oral implant planning, avoiding similar software common errors. The 3D environment can be also exploited in the final surgical phase, in order to provide a flapless surgical guide, through the use of an anthropomorphic robot.
10.1007/s11548-009-0394-y
pubmed_908_2028
The rendering of proper care for the patient with intestinal failure requires the provider to have a functional understanding of digestion and absorption, nutrient requirements, and intestinal adaptation. Inherent in those concepts is that not only is nutritional absorption compromised, but medication absorption is as well. The principles of the management of home parenteral nutrition must be mastered and then proper and controlled weaning of parenteral nutrition may be commenced by use of dietary and pharmacologic means with appropriate clinical outcome measures followed. This complicated management requires a team experienced in both medical and surgical management of intestinal failure.
10.1016/j.gtc.2018.01.006
pubmed_456_6891
STUDY DESIGN Electronic survey administered to Scoliosis Research Society members. OBJECTIVE To determine the prevalence of minimally invasive surgery (MIS) techniques for the treatment of adult spinal deformity. SUMMARY OF BACKGROUND DATA There is a paucity of data available on the practice pattern, prevalence of minimally invasive spine surgery, and the preferred minimally invasive techniques in the treatment of adult spine deformity. METHODS An electronic nine-question survey regarding individual usage pattern of minimally invasive spine surgery techniques was administered in 2016 to the members of the Scoliosis Research Society. Determinants included complexity in condition of patient population, prevalence of use of minimally invasive techniques in the surgeon's practice, prevalence of use of a particular MIS technique, strategy elected during surgery, adoption of staging of procedures and timing between staging of procedures. RESULTS A total of 357 surgeons responded (61.3% response rate), and 154 (43.1%) of the respondents said that they use MIS as a part of their surgical treatment of adult spinal deformity. However, of these 154 respondents, 67 (43.5%) said that their MIS usage in deformity practice was between 1% and 20%. Only 11 (7.2%) said that they used MIS 81% to 100% of the time. The top MIS approaches that surgeons chose were MIS lateral lumbar interbody fusion 109 (70.59%) and MIS percutaneous screws 91 (58.8%). CONCLUSIONS The low rate of adoption of these techniques among the SRS members may be due to the false perception that there is not enough data to support that MIS techniques are better. This and the fact that a practitioner needs to be facile at different MIS techniques may be the true impediment to the adoption of MIS techniques in the treatment of ASD. LEVEL OF EVIDENCE Level IV.
10.1016/j.jspd.2018.08.014
pubmed_749_12907
Vitreoscilla filiformis is a Gram-negative bacterium isolated from spa waters and described for its beneficial effects on the skin. We characterized the detailed structure of its lipopolysaccharide (LPS) lipid A moiety, an active component of the bacterium that contributes to the observed skin activation properties. Two different batches differing in postculture cell recovery were tested. Chemical analyses and mass spectra, obtained before and after mild-alkali treatments, revealed that these lipids A share the common bisphosphorylated β-(1→6)-linked d-glucosamine disaccharide with hydroxydecanoic acid in an amide linkage. Short-chain FAs, hydroxydecanoic and dodecanoic acid, were found in a 2:1 ratio. The two lipid A structures differed by the relative amount of the hexa-acyl molecular species and phosphoethanolamine substitution of the phosphate groups. The two V. filiformis LPS batches induced variable interleukin-6 and TNF-α secretion by stimulated myelomonocytic THP-1 cells, without any difference in reactive oxygen species production or activation of caspase 3/7. Other different well-known highly purified LPS samples were characterized structurally and used as standards. The structural data obtained in this work explain the low inflammatory response observed for V. filiformis LPS and the previously demonstrated beneficial effects on the skin.
10.1194/jlr.M072900
pubmed_323_1118
Participation from the business community is critical to effectively addressing the problem of obesity. This commentary builds on the recent Institute of Medicine report - Accelerating Progress in Obesity Prevention - which calls for participation from the business community, particularly food outlets, to effectively address the problem of obesity. This commentary specifically discusses the importance of collecting information on fiscal-related outcomes (e.g., revenue) in order to better engage local food outlets in obesity prevention activities in the community. The routine collection of fiscal indicators in obesity prevention studies is critical so that the argument for more involvement from local food outlets, particularly for those interventions which are revenue positive or revenue neutral, can be more persuasively made.
pubmed_323_1118
pubmed_1020_23978
Purpose: The maternal mortality ratio for the United States (US) has consistently risen over recent decades. This mortality is especially pronounced within minority populations who experience a maternal mortality and morbidity rate that are much higher than their non-Hispanic white counterparts. Qualitative data are critical in gaining true insight from minority pregnant and postpartum persons. Such data should serve as the basis for building interventions and programs that seek to eradicate perinatal inequities. This review examines the qualitative literature on racial and ethnic minority pregnant patients with low income and their experiences during perinatal care (PNC) to identify recurrent themes that can be addressed through targeted interventions. Methods: PubMed, CINAHL, and Web of Science databases were searched for qualitative studies on racial and ethnic minority pregnant patients with low income and their experiences during PNC. Twenty-two articles were included for analysis. Thematic synthesis was performed to identify categories and recurring themes in each article. Results: Five major categories were identified as consistent experiences of pregnant patients with PNC clinicians: support, education, connection, communication, and trust. Of these, clinician support was the most consistently coded category. Eighteen of the 23 articles discussed tangible support patients had received from their clinicians, such as care coordination and referrals to support services. The second most coded category was education, which was represented in 16 articles. Education was mostly represented negatively as lack of adequate perinatal care education given during the perinatal period. Finally, the categories of connection, communication, and trust were represented by 18, 17, and 17 articles, respectively. Conclusions: These qualitative studies provided specific examples of what racial and ethnic minority pregnant patients with low income deemed positive and negative during the perinatal period and outline ways that these experiences can be improved. Future studies can take the experiences reported in this review to help inform interventions to improve patient experiences and health outcomes that minority persons face in the perinatal period.
10.1089/heq.2021.0017
pubmed_507_10590
Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.
10.2353/ajpath.2010.081152
pubmed_829_2220
Leptospirosis is a re-emerging infectious disease affecting both animals and humans worldwide. This infection is associated with occupational contact with animals, recreational exposure and contact with leptospires as a consequence of flooding. Multiple organ involvement may be encountered in acute severe leptospirosis and early renal involvement is commonly characterized by tubulo-interstitial nephritis and tubular dysfunction. Leptospirosis has been increasingly recognized as an important infectious disease in Taiwan since 1997 and Leptospira santarosai serovar Shermani is the main serovar encountered. The most common presentations are fever, jaundice and acute renal failure. This triad presentation in patients with acute multiple organ dysfunction should alert physicians to the possibility of leptospirosis. Penicillin treatment is effec- Dr. Chih-Wei Yang tive and may dramatically save patients from multiple organ failure provided it is given early. The rapid IgM assay may aid screening of Leptospirosis, thus allowing effective treatment to be initiated early. Leptospirosis appears to be underestimated in Taiwan and affects at least 10% of patients with multiple organ dysfunction. Therefore, a high level of clinical suspicion may help in identifying underestimated leptospirosis in Taiwan.
pubmed_829_2220
pubmed_1020_6956
Next-generation sequencing has provided rapid collection and quantification of 'big' biological data. In particular, multi-omics and integration of different molecular data such as miRNA and mRNA can provide important insights to disease classification and processes. There is a need for computational methods that can correctly model and interpret these relationships, and handle the difficulties of large-scale data. In this study, we develop a novel method of representing miRNA-mRNA interactions to classify cancer. Specifically, graphs are designed to account for the interactions and biological communication between miRNAs and mRNAs, using message-passing and attention mechanisms. Patient-matched miRNA and mRNA expression data is obtained from The Cancer Genome Atlas for 12 cancers, and targeting information is incorporated from TargetScan. A Graph Transformer Network (GTN) is selected to provide high interpretability of classification through self-attention mechanisms. The GTN is able to classify the 12 different cancers with an accuracy of 93.56% and is compared to a Graph Convolutional Network, Random Forest, Support Vector Machine, and Multilayer Perceptron. While the GTN does not outperform all of the other classifiers in terms of accuracy, it allows high interpretation of results. Multi-omics models are compared and generally outperform their respective single-omics performance. Extensive analysis of attention identifies important targeting pathways and molecular biomarkers based on integrated miRNA and mRNA expression.
pubmed_1020_6956
pubmed_89_21295
Halitosis is formed mainly by the volatile compounds produced by periodontal bacteria. Three volatile sulfur compounds (VSCs), hydrogen sulfide, methanethiol, and dimethyl sulfide, have attracted attention as major components of halitosis. However, these compounds cannot account for all odors. In this study, we profiled volatile compounds from the culture supernatants of periodontal bacteria using gas chromatography/mass spectrometry/olfactometry analysis with a monolithic silica gel adsorption device to investigate the potential odorous compounds. Periodontal bacteria have been found to produce volatile compounds belonging to various classes, such as alcohols, ketones, fatty acids, and aromatic compounds, in addition to VSCs. In addition, VSCs different from hydrogen sulfide and methanethiol, which are considered important causative compounds, may also influence to halitosis.
10.1016/j.jbiosc.2022.04.002
pubmed_406_13264
The tolerance of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) has been investigated over 18 months after oral administration in rats and over 1i months after intragastric application in dogs. Further the influence of the compound on pregnant animals and their fetuses after intragastric application has been investigated in rats and rabbits. The investigation of the influence on fertility and breeding capacity as well as on the peri- and postnatal development was carried out in rats after peroral administration. In the course of the chronic experiments a dose related increase of the excretion of fluid and electrolytes was observed. Side-effects, which mainly occurred during the last weeks of the experiment in the highest dosage group, were most probably due to the exhaustion of the fluid and especially of the electrolyte reserves of the animals. The experiments in rats and rabbits did not yield any findings indicating teratogenic properties. Fertility and breeding capacity were likewise not influenced by etozolin. An influence on the peri- and postnatal development could be demonstrated only in the toxic dose range.
pubmed_406_13264
pubmed_603_18832
Restricted solid-on-solid (RSOS) growth models are studied on two different decagonal quasicrystal lattices, namely the Penrose tiling lattice and the random tiling lattice. There exist two types of growth blocks-fat and skinny tiles-which may have different sticking probabilities. We found that the RSOS growths on both lattices belong to the Kardar-Parisi-Zhang universality class when they have the same sticking probabilities in spite of the lack of periodicity in the substrates. However, when they have tile-type dependent sticking probabilities, the RSOS models on two lattices may produce different scaling behaviors. Growth on Penrose tiling shows that the roughness exponent is around 0.4 while that on random tiling is around 0.49. Our observation may provide an effective way to investigate the bulk structures of decagonal quasicrystals.
10.1103/PhysRevE.85.061118
pubmed_181_4033
BACKGROUND Working adolescents, with less experience and less training than adults, may take more risks and get exposed to a wide variety of toxic substances in the workplace. They may get injured when working in inadequately ventilated areas or entering areas of exposure with improper or no protective equipment. OBJECTIVE The purpose of this study was to describe adolescent occupational exposures reported to poison centers. SUBJECTS Occupational exposures reported to Texas poison centers during 2000-2015 where patients were 13-19 years in age. METHODS The distribution of the cases was determined for various factors. RESULTS There were 2430 adolescent occupational exposures. The most frequently reported major substance categories were chemicals (18%), household cleaning substances (18%), hydrocarbons (10%), and industrial cleaners (9%). Forty-five percent occurred during May-August. Males accounted for 66% of the patients; 27% were 18 years and 37% were 19 years. The most common exposure routes were inhalation (28%), dermal (27%), ingestion (26%), and ocular (24%). The patients were managed on site in 51% of the exposures. Twenty-three percent of the exposures had serious outcomes. CONCLUSION Adolescents involved in occupational exposures tended to be male and older. Adolescent occupational exposures were likely to involve chemicals and household cleaning substances, occur by ingestion and ocular route, and likely to be managed on site. Most were not likely to have serious outcomes.
pubmed_181_4033
pubmed_943_4740
Mrf-2 is a member of a new class of DNA-binding proteins known as the AT-rich interaction domain family or ARID. Chemical shift indices and characteristic NOE values indicate that the three-dimensional structure of the Mrf-2 ARID in complex with DNA is nearly identical to that of the free protein. The backbone dynamics of the Mrf-2 domain free and in complex with DNA have been characterized by (15)N NMR relaxation measurements and model-free analysis. Chemical shift perturbations and dynamic studies suggest that two flexible interhelical loops, the flexible C-terminal tail, and one alpha-helix are involved in DNA recognition, indicating the importance of protein dynamics in DNA binding. Some well-structured regions, in particular the putative DNA-contacting helix, in Mrf-2 show a decrease in the order parameters (S(2)) upon complex formation. The less well-structured loops and the unstructured C-terminus show reduced flexibility upon DNA binding. In addition, the model-free analysis indicates motions on the picosecond to nanosecond and micro- to millisecond time scales at the DNA-binding surface of the bound Mrf-2 ARID, suggesting a model where interactions between the protein and DNA are highly dynamic.
10.1021/bi010476a
pubmed_795_13232
Functional magnetic resonance imaging (fMRI) was used to investigate how focal cortical inhibition affects the blood oxygen level-dependent (BOLD) signal. Phasic low force pinch grip reduces excitability of the ipsilateral primary motor cortex. This task was used to study BOLD signal changes during inhibition. Six right-handed normal volunteers participated in the study. They were asked to perform a right-handed pinch grip repetitively at 1 Hz and 5% of their individual maximal voluntary contraction (MVC). Data were acquired with a 1.5 Tesla Magnetom and continuous multislice T2*-weighted images. The contralateral primary motor cortex (M1) revealed an activation in the knob-shaped hand representation of the central sulcus area. More importantly, a decreased (often referred to as "negative") BOLD signal in the ipsilateral M1 was observed. We suggest phasic low force pinch grip as a reproducible, easy model of focal inhibition. Decreased cortical excitability presents as decreased BOLD signal using fMRI.
10.1006/nimg.2002.1077
pubmed_329_1877
UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer. Abnormally glycosylated forms of mucin 1 (a substrate of the enzyme), are used clinically as a biomarker for breast cancer. There is potential for other products of the pp-GalNAc- T6 catalyzed reaction to be used. It is also possible that pp-GalNAc-T6 itself could be used as a biomarker, since levels of this protein tend to be low in non-malignant tissues. pp- GalNAc-T6 has been implicated in malignant transformation and metastasis of cancer cells. As such, it has considerable potential as a target for chemotherapy. To date, no selective inhibitors of the enzyme have been identified. However, general inhibitors of the enzyme family result in reduced cell surface O-linked glycosylation and induce apoptosis in cultured cells. Thus, a selective inhibitor of pp-GalNAc-T6 is likely to target cancer cells and could be developed into a novel anticancer therapy.
10.2174/1568009616666160922102641
pubmed_715_2113
Transplantation of cells and tissues to the mammalian brain and CNS has revived the interest in the immunological status of brain and its response to grafted tissue. The previously held view that the brain was an absolute "immunologically privileged site" allowing indefinite survival without rejection of grafts of cells has proven to be wrong. Thus, the brain should be regarded as a site where immune responses can occur, albeit in a modified form, and under certain circumstances these are as vigorous as those seen in other peripheral sites. Clinical cell transplant trials have now been performed in Parkinson's disease, Huntington's disease, demyelinating diseases, retinal disorders, stroke, epilepsy, and even deafness, and normally are designed as cell replacement strategies, although implantation of genetically modified cells for supplementation of growth factors has also been tried. In addition, some disorders of the CNS for which cell therapies are being considered have an immunological basis, such as multiple sclerosis, which further complicates the situation. Embryonic neural tissue allografted into the CNS of animals and patients with neurodegenerative conditions survives, makes and receives synapses, and ameliorates behavioral deficits. The use of aborted human tissue is logistically and ethically complicated, which has lead to the search for alternative sources of cells, including xenogeneic tissue, genetically modified cells, and stem cells, all of which can and will induce some level of immune reaction. We review some of the immunological factors involved in transplantation of cells to CNS.
10.1602/neurorx.1.4.472
pubmed_921_9383
Drospirenone is a new synthetic progestogen with both progestational, antimineralocorticoid and antiandrogenic properties. In combination with ethinylestradiol, it is being developed as an oral contraceptive which will contain 30 micrograms ethinylestradiol and 3 mg drospirenone (Yasmin, Schering AG, Germany). The effects of drospirenone alone, and in combination with ethinylestradiol, upon the renin-angiotensin-aldosterone system (RAAS) have been evaluated in healthy female volunteers. RAAS activity was assessed by measurement of plasma renin substrate (PRS) concentration (otherwise known as angiotensinogen), plasma renin activity (PRA), and plasma aldosterone (P-Aldo) concentration. An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5-3.0 mg/day for one cycle. The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA. When ethinylestradiol (30 micrograms) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles, an increase in PRS was observed with both preparations, which was indicative of estrogenic stimulation, and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone. Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3. The effect of the preparation containing 30 micrograms ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 micrograms ethinylestradiol but combined with 150 micrograms desogestrel (Marvelon). Over a period of 13 cycles, increases in PRS were seen with both treatments, the effect being slightly more pronounced with 30 micrograms ethinylestradiol/150 micrograms desogestrel. A markedly greater increase in PRA was seen following treatment with 30 micrograms ethinylestradiol/3 mg drospirenone, and, in cycle 3, this difference was statistically significant. In contrast, P-Aldo was increased markedly with 30 micrograms ethinylestradiol/3 mg drospirenone in all measured cycles, whereas, in the 30 micrograms ethinylestradiol/150 micrograms desogestrel group, changes were minimal. The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone. PRS increases under all combinations are an expression of estrogenic stimulation. Measurement of body weight and blood pressure in the studies with combined ethinylestradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight, while blood pressure remained largely unchanged. Overall, the results indicate that 30 micrograms ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect.
10.3109/09513590009167683
pubmed_608_23468
OBJECTIVE The aim of our study was to compare yttrium -90 (90Y) dosimetry obtained from pre-therapy 99mTc-macroaggregated albumin (MAA) SPECT/CT versus post-therapy PET/MRI imaging among patients with primary or metastatic hepatic tumors. MATERIALS AND METHODS Prior to 90Y radioembolization (RE), 32 patients underwent a scan using MAA mimicking 90Y distribution. After RE with 90Y microspheres, the patients were imaged on a PET/MRI system. Reconstructed images were transferred to a common platform and used to calculate 90Y dosimetry. The Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between dosimetry values. RESULTS For MAA and PET/MRI modalities, the mean liver doses for all 32 subjects were 43.0 ± 20.9 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 3.4 ± 6.2 Gy. The repeatibility coefficient was 12.1 (27.0% of the mean). The Spearman rank correlation coefficient was high (ρ = 0.92). Although, there was a substantial difference in the maximum doses to the liver between the modalities, the mean liver doses were relatively close, with a difference of 24.0% or less. CONCLUSIONS The two main contributors to the difference between dosimetry calculations using MAA versus 90Y PET/MRI can be attributed to the changes in catheter positioning as well as the liver ROIs used for the calculations. In spite of these differences, our results demonstrate that the dosimetry values obtained from pre-therapy MAA SPECT/CT scans and PET/MRI post-therapy 90Y studies were not significantly different.
10.1016/j.ejrad.2018.10.015
pubmed_180_24196
The physical compatibility of bivalirudin (Angiomax) with 96 selected other drugs during simulated Y-site injection was evaluated by visual observation, turbidity measurement, and electronic particle content assessment (when appropriate). Five-milliliter samples of bivalirudin 5mg/mL in 5% dextrose injection were combined with 5mL of 96 other drugs (anti-infectives, analgesics, anihistamines, diuretics, steroids, or other supportive-care drugs that were either undiluted or diluted with either 5% dextrose injection or 0.9% sodium chloride injection [the diluent for drugs incompatible with 5% dextrose injection ]). Visual examinations were performed with the unaided eye in normal, diffuse fluorescent light with a Tydall beam (a high-intensity monodirectional light beam) to enhance the visualization of small particles and low-level turbidity. The turbidity of each sample was measured as well. The particle content of samples that did not exhibit a visible incompatibility was measured. Evaluation of the samples was performed initially and at 1 and 4 hours after preparation. Eighty-seven of the 96 test drugs were compatible with the bivalirudin dilution during the 4-hour observation period. However, the combination of bivalirudin solution with each of nine drugs resulted in haze formation, microparticulate formation, or gross preciptiation. Bivalirudin should not be administered simultaneously with those incompatible drugs.
pubmed_180_24196
pubmed_411_19424
INTRODUCTION This report aims to describe the epidemiology, clinical presentation, diagnostic workup, treatment, and rehabilitation, natural course, and possible risk factors of the rare entity spontaneous iliopsoas tendon rupture. METHODS One case of spontaneous iliopsoas tendon rupture was encountered. The patient was followed during the hospital stay, her journal was later reviewed, and one telephone follow-up after 90 days was performed. Structured reviews of the literature in the PudMed and Micromedex databases were performed. RESULTS The patient recovered fully within 6 weeks of conservative treatment with small doses of acetaminophen and opioid. The literature reviews yielded 14 previously reported spontaneous iliopsoas tendon ruptures but no strong evidence regarding possible risk factors. CONCLUSION Spontaneous iliopsoas tendon rupture is a rare event, typically occurring in the elderly female. MRI is generally diagnostic, but signs are also often present on CT scans and sometimes even on plain X-ray. Conservative treatment has an excellent prognosis of full recovery within 6 weeks. The evidence on possible risk factors is scarce and conflicting.
10.1007/s00402-020-03523-2
pubmed_1094_15798
During prostate cancer treatment with HDR brachytherapy, catheters are inserted into the prostate. Between planning and treatment, catheters may move inferiorly due to edema. If undetected, treatment proceeds without correcting the catheter displacement, and an incorrect treatment is delivered. The purpose of this study was to investigate the consequences of catheter displacement on prostate coverage and critical structure avoidance. Ten patient plans were selected in which movement of the catheters had been observed. The original treatment plan, generated using Nucletron PLATO (ver. 14.3.2), was adjusted introducing inferior catheter offsets of 5, 10, 20, and 30 mm. The original treatment dwell times were re-entered into the offset plans to determine the consequences of the displacement. DVH data was calculated for the prostate, rectum, urethra, and bladder. Prostate V100 decreased from 99% to 36% over the ten patients studied. For the urethra, the D10 increased (114.1% to 128.2%), as did the V125 (2.7% to 12.8%). In the rectum the V75 initially increased as the catheters shifted inferiorly, but dropped as the shift increased beyond 10 mm. In the penile bulb the V75 increased as a function of shift (from 2.1% to 44.8%). Every effort should be made to ensure that the catheters do not move during prostate treatment. A small shift, 5 mm, would result in a small deviation of the dose distribution. In this case a re-optimization of the plan is unnecessary. Larger shifts will have a serious impact on the dose delivered to the prostate and to sensitive normal structures.
10.1118/1.2966001
pubmed_40_18515
Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78-1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79-21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.
10.1371/journal.pone.0068041
pubmed_1077_13187
Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, β-hexachlorocyclohexane, and p,p'-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003-2005, we enrolled 499 boys aged 8-9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10-13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)(2))) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p'-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p'-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12-13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin.
10.1093/aje/kwu212
pubmed_308_25443
Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on γ-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABAA receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE-exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by δ-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE-exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by δ-GABAA receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ-GABAA subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ-GABAA tonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood.
10.1111/adb.12353
pubmed_222_16777
OBJECTIVE To evaluate the efficacy and tolerability of treatment with a levonorgestrel-releasing intrauterine device (IUD) in women affected by adenomyosis-associated menorrhagia. SETTING Tertiary care center. DESIGN Prospective, open, noncomparative study. PATIENT(S) Twenty-five women aged 38 to 45 years with recurrent menorrhagia associated with adenomyosis diagnosed at transvaginal ultrasonography participated in this study. INTERVENTION(S) An IUD releasing levonorgestel 20 mcg/day was inserted in each patient within 7 days of the start of menstrual flow. All of the patients were requested to compile a pictorial blood loss assessment chart each month. They underwent clinical and transvaginal ultrasound examinations 3, 6, and 12 months after IUD insertion. MAIN OUTCOME MEASURE(S) Menstrual pattern; serum hemoglobin, ferritin, and iron level changes. RESULT(S) One patient experienced IUD expulsion 2 months after device insertion and another requested removal of the IUD 4 months after insertion because of persistent irregular blood loss. Six months after IUD insertion, amenorrhea was observed in 2 patients and oligomenorrhea in another, spotting occurred occasionally in 7, and 13 had scanty but regular flow. One year of follow-up has been completed by the remaining 23 women: 2 with amenorrhea, 3 with oligomenorrhea, 2 with spotting, and 16 with regular flows. Significant increases in hemoglobin, hematocrit, and serum ferritin have been observed, but the lipid metabolism and clotting variables have remained unchanged. CONCLUSION(S) Our findings indicate that marked and safe relief from adenomyosis-associated menorrhagia can be obtained with the use of a levonorgestrel-releasing IUD.
10.1016/s0015-0282(97)00245-8
pubmed_1030_11063
Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia, cartilage destruction and bone erosion. Visnagin (VIS) is a proven anti-inflammatory agent and in this study, we aimed to evaluate the anti-arthritic activity of VIS when administered via intra-articular (I.A.) route of administration. Materials and methods RAW 264.7 ​cells were stimulated with lipopolysaccharide (LPS) (1 ​μg/mL) and treated with VIS at concentrations of 12.5 and 25 ​μM. Arthritis was induced in Sprague Dawley rats by administering Complete Freund's Adjuvant (CFA) (1 ​mg/mL) through (I.A.) route and treated with VIS via (I.A.) route at doses of 3 and 10 ​mg/kg twice a week for 3 weeks. Protective effects were assessed by arthritic score, behavioral studies for pain evaluation, radiological assessment, histopathological examination and molecular studies. Results Our results indicated that VIS significantly reduced LPS induced inflammation in RAW 264.7 ​cells. While in arthritic rats, VIS reduced the disease scorings with improvement towards pain. Pathological examination demonstrated that VIS reduced knee joint inflammation and cartilage destruction. Radiographic analysis and molecular studies also supported the protective effects of VIS. Conclusion The results of the study imply that VIS exerted potential anti-inflammatory and anti-arthritic activity in in vitro and in vivo models of RA.
10.1016/j.crphar.2022.100114
pubmed_1076_11038
We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance, plasma adiponectin, postprandial plasma glucose, insulin, and intact proinsulin levels in a nondiabetic population at cardiovascular risk. One hundred twenty-five nondiabetic patients at cardiovascular risk were randomized to pioglitazone (PIO), pioglitazone and simvastatin (PIO/SIM), or simvastatin (SIM) treatments. Blood samples were taken for the measurement of adiponectin and lipid levels. In addition, an oral glucose load with the measurements of glucose, insulin, and intact proinsulin levels was performed. Adiponectin levels increased from 14.0+/-8.2 to 27.6+/-14.5 microg/mL (P<.0001) during PIO treatment and from 11.7+/-10.0 to 26.7+/-15.7 microg/mL (P<.0001) during PIO/SIM treatment. A decrease in adiponectin levels from 15.5+/-12.7 to 11.6+/-7.0 microg/mL (P<.05) was observed during SIM treatment. Although fasting intact proinsulin levels remained unchanged, the increase in postprandial intact proinsulin levels could be reduced from 29.5+/-21.4 to 22.1+/-17.5 pmol/L (P<.01) during PIO treatment and from 24.3+/-27.4 to 21.1+/-16.5 mmol/L (P<.05) during PIO/SIM treatment. Lipid parameters improved during SIM treatment but not during PIO treatment. Combined treatment with PIO/SIM was superior in improving overall cardiovascular risk profile than every single drug.
10.1016/j.metabol.2006.11.007
pubmed_933_25089
1. Injection of vesicular stomatitis virus into the leg muscles of young mice gives rise to flaccid paralysis of the inoculated extremity as the first clinical sign of a disease which is invariably fatal; old mice similarly injected with the largest doses of virus survive without exhibiting any signs of illness. 2. In young mice the virus was shown to multiply at the site of inoculation and to invade the sciatic nerve and spinal cord; there was no evidence of multiplication of virus in the blood or viscera. 3. In old mice, after intramuscular injection of as much as 10 million M.C.L.D., there was no evidence of either local or systemic multiplication; in spite of the persistence of thousands of M.C.L.D. of virus at the site of inoculation for at least 4 days, there was no detectable invasion of the sciatic nerve or the central nervous system. 4. Injection of the virus directly into the sciatic nerve of old mice led to the typical paralytic disease in half the number of animals. 5. For 3 days after intrasciatic injection the virus could be demonstrated in the nerve but not in the spinal cord or brain. At the onset of paralysis (6th day) virus was detectable in the spinal cord but no longer in the inoculated nerve. 6. The capacity of the virus to invade the central nervous system from the nerve but not from the muscle suggested the existence of a barrier in the muscle or myoneural junction. 7. Injection of the virus into the vitreous humor of the eye is followed by a fatal encephalitis in 15 day old mice, but 1 year old mice, with few exceptions, survive without showing signs of disease. 8. The spread of virus in the brains of intraocularly injected, 15 day old mice was too rapid to indicate the pathways which were pursued, but in 21 day old mice there was evidence that the primary pathway was probably along the axons of the optic nerve with decussation to the contralateral diencephalon and mesencephalon, and subsequent early spread to the corresponding occipital cortex. In resistant, old mice, however, no virus was found in any part of the brain.
10.1084/jem.66.1.35
pubmed_210_12416
Thiourea can effectively inhibit the formation of highly toxic chlorinated aromatics in postcombustion zone. However, the inhibition mechanism was still not adequately understood. In this study, naphthalene was adopted as a model aromatic compound to investigate the inhibition effect and mechanism of thiourea on the formation of chlorinated aromatics via electrophilic chlorination over Cu and Fe chlorides. Thiourea addition resulted in the reductions of 77.6-99.8% and 36.4-98.1% in the yield of polychlorinated naphthalenes from naphthalene chlorination mediated by CuCl2 and FeCl3 at 150-300 °C, respectively. The inhibition efficiency of chlorination presented a decreasing tendency with increasing reaction temperature and O2 content in flue gas. X-ray diffraction analysis revealed that the thiourea-induced reduction of highly active Cu (II) and Fe (III) chlorides to less active Cu (I) and Fe (II) chlorides was a primary mechanism for inhibiting aromatic chlorination. [thiourea-Cu]+ complex generated during the reduction process could be transformed into CuS and Cu2S, and isomeric reaction product NH4SCN could react with Cu2+ to produce Cu(SCN)2 and then also form Cu sulfides, suggesting sulfidization of Cu chloride was another important inhibition mechanism. Chlorination inhibition induced by the volatile decomposition products of thiourea might only play a minor role.
10.1021/acs.est.0c05605
pubmed_796_22840
Within the past several years a number of substances have been identified in the mammalian brain that are capable of (1) preventing the death of injured neurons and (2) promoting the regeneration of severed neuronal processes. The goal of this review article is to update the clinical neurologist in this area by presenting a brief, general overview of this subject, including a glimpse at potential clinical implications. Recent advances in neuronal transplantation and molecular techniques underlying nerve growth are discussed. Possible therapeutic approaches are presented for many neurologic disorders, ranging from stroke to Alzheimer's disease to acquired immunodeficiency syndrome, based on regrowing or saving injured neurons. The clinical neurologist will become important in practical applications and research into prolonging neuronal survival and fostering axonal regeneration. Over the coming years, with further research, it is anticipated that patients will be treated with these or similar modulatory agents.
10.1001/archneur.1989.00520470113038
pubmed_957_12493
ETHNOPHARMACOLOGICAL RELEVANCE As a traditional edible fungus in China and many other Asian countries, Hericium caput-medusae (Bull. Fr.) Pers. is widely used to improve the health of the gastrointestinal tract. For example, the drug "Weilexin Granules" is mainly composed of H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate. However, the mechanism of action remains to be elucidated. AIMS OF THE STUDY The purpose of this study was to assess whether polysaccharides from H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate (HFP) exerts a gut protective effect and a regulatory effect on the intestinal microbiota through the chloride channels and mucus secretion. MATERIALS AND METHODS HFP was extracted, characterized and different concentrations of HFP (100, 200, 400 mg/kg) were administered to mice for 14 days. The changes in gut microbiota were observed via 16S high throughput sequencing. Short-chain fatty acids (SCFAs) was detected by GC-MS. AB-PAS staining was used to observe the secretion of mucus. The chloride channel activity and protein expression were verified by short-circuit current measurement and Western blot. RESULTS HFP regulated the abundance of gut microbiota in mice, with increased levels of Ruminococcaceae and Lachnospiraceae and reduced proportions of Staphylococcus and Enterobacter. HFP enhanced mucus volume as well as increased intestinal fluid secretion by activating the chloride channels. In addition, short-circuit current experiments also proved that HFP activates Cl⁻ currents targeting cystic fibrosis transmembrane conductance regulator (CFTR) and Anoamin1 (ANO1). CONCLUSION In conclusion, HFP might increase intestinal fluid secretion by promoting Cl⁻ secretion, which in turn advanced mucus hydration as well as regulated gut microbiota to improve intestinal health. Therefore, H. caput-medusae (Bull. Fr.) Pers. could be potentially used in the regulation of intestinal secretion and microbes.
10.1016/j.jep.2022.115721
pubmed_468_13112
New health roles and models are needed to address future workforce shortages in Australian health care. A pilot trial of introducing two United States-trained physician assistants (PAs) at Queen Elizabeth Hospital, from October 2008 to October 2009, demonstrated difficulties in introducing PAs into the South Australian health system. Unforeseen delays in planning and implementing the trial occurred. This led to a loss of personnel and a second round of recruitment. The PAs' scope of practice was limited, and they could not demonstrate their work as they do in the US. Full use of their prescribing licence was not allowed until 3 months into the trial, and their authority to order radiology tests was limited. The issues faced at Queen Elizabeth Hospital could be avoided in future trials, ensuring a smoother trial period.
10.5694/j.1326-5377.2011.tb02959.x
pubmed_291_7513
We report risk factors associated with intraocular penetration of caterpillar hair seen at our institute from January 2005 to December 2007. Records of all patients with caterpillar hair induced ophthalmitis (CHIO) were retrospectively reviewed for clinical characteristics, anatomic location of lodgment of the caterpillar hair, treatment methods, and outcomes. Out of a total of 544 cases of CHIO, 19 eyes (seven in the anterior chamber and 12 in the posterior segment) experienced intraocular penetration (3.5%). The presence of deep intracorneal hair (80 cases, 14.7%) was found to be the only risk factor for intraocular penetration ( P < 0.001). The removal of intracorneal hair was possible in only 29 out of 80 eyes (36%) and this was associated with a significantly reduced risk of intraocular penetration ( P = 0.022). Patients with retained intracorneal hairs should be counseled regarding risk of intraocular penetration and closely followed up for at least six months.
10.4103/0301-4738.71711
pubmed_849_24620
The purpose of the Olympic Games should be to contribute to the social development by leaving behind economic, cultural and environmental legacies to the hosting region. While tangible examples such as venues are often recognized as representative legacies of the Olympics, intangible aspects such as the environment, culture, policy and human resources have been gaining in importance. The Olympic Games, at its most fundamental level, is a sporting event. Sports not only is closely related to the physical health, but is also instrumental to fostering mental health through inspiration. One of the most important sports legacies was the general change in the population's perception on sports and physical activities; due to such change, people were able to enjoy sports as part of healthy and active everyday life and benefit physically. However, compared to tangible legacies such as the facilities, social legacies such as the general health and their planning, execution and achievements are hard to monitor. Therefore, for the Olympics to leave behind socio-cultural legacies that contribute to the development of the hosting region, there must be a thorough business plan that takes into account region-specific purpose, and is divided into stages such as before, during and after the Games. Should the 2018 Winter Olympic Games hope to create continuing contribution to its hosting region, it must leave behind 'Health Legacies' that will enhance the happiness of the hosting region's population. To this end, establishment of region-specific purpose and systematic promotion of business via detailed analysis of precedents are a must. This article aim to review the health legacy endeavors of past host cities and suggest the appropriate forms of health legacy of 2018 Pyeongchang Winter Olympic and Paralympic Games.
pubmed_849_24620
pubmed_293_3717
Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure and increased cancer risk. FA is caused by mutation of any 1 of 22 genes, and the FA proteins function cooperatively to repair DNA interstrand cross-links (ICLs). A central step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which occurs within chromatin. How FANCD2 and FANCI are anchored to chromatin remains unknown. In this study, we identify and characterize a FANCD2 histone-binding domain (HBD) and embedded methyl-lysine-binding domain (MBD) and demonstrate binding specificity for H4K20me2. Disruption of the HBD/MBD compromises FANCD2 chromatin binding and nuclear focus formation and its ability to promote error-free DNA interstrand cross-link repair, leading to increased error-prone repair and genome instability. Our study functionally describes the first FA protein chromatin reader domain and establishes an important link between this human genetic disease and chromatin plasticity.
10.1128/MCB.00194-19
pubmed_265_10770
BACKGROUND Acute hydrocephalus as a consequence of subarachnoid hemorrhage is a relatively frequent problem. It is associated with more neurologic impairment and mortality than subarachnoid hemorrhage without hydrocephalus. A review of the literature was done to determine its frequency of presentation, the associated causes of morbidity and mortality, its clinical presentation, and treatment options. METHODS A search was done through the Med-Line system to obtain pertinent literature of the last 10 years. Articles before this date were obtained from references from the original search. RESULTS Acute hydrocephalus is present in 20% of patients with subarachnoid hemorrhage. One third of them may be asymptomatic on admission; 50% of those who have clinical hydrocephalus recover spontaneously within the first 24 h. The presence of acute hydrocephalus after subarachnoid hemorrhage is associated with additional morbidity and higher mortality secondary to rebleeding, to cerebral infarction or to shunt infection. Once hydrocephalus develops, ventricular size is not related to the clinical status of the patient, nor to the associated complications. CONCLUSIONS If a patient presents with subarachnoid hemorrhage accompanied by acute hydrocephalus and preserved level of consciousness, he/she should be carefully observed for the first 24 h. If deterioration of consciousness ensues and is not attributable to rebleeding or metabolic causes, ventriculostomy should be performed. If a patient presents with subarachnoid hemorrhage accompanied by acute hydrocephalus and depressed level of consciousness ventriculostomy should be immediately placed. After ventriculostomy, intracranial pressure should be maintained above 15 mm Hg to prevent rebleeding. Prophylactic antibiotics and long subcutaneous catheters should be used to avoid shunt infections.
10.1016/s0090-3019(97)00342-x
pubmed_454_9440
PURPOSE To analyze longitudinal changes in each subscale of a quality of life (QOL) measure and to explore their relationships to effective QOL predictors in breast cancer surgery patients. PATIENTS AND METHODS This prospective study analyzed 172 patients at two tertiary academic hospitals. All patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at baseline and at 1 and 2 years postoperatively. The 95% confidence intervals for differences in responsiveness estimates were derived by bootstrap estimation. Scores derived by these instruments were interpreted by generalized estimating equation (GEE) before and after surgery. RESULTS A 2-year follow-up survey of the examined population revealed significant (P < 0.05) improvement in each QOL subscale. In both postoperative surveys, effect size was largest in the QLQ subscales for patients who had received mastectomy with reconstruction and lowest in those who had received modified radical mastectomy. After adjusting for time effects and baseline predictors, GEE approaches revealed the following explanatory variables for QOL: time, type of surgical procedure, age, chemotherapy, radiotherapy, hormone therapy, and preoperative functional status. CONCLUSIONS When evaluating QOL after breast cancer surgery, several factors other than the surgery itself should be considered. Patients should also be advised that their postoperative QOL might depend not only on the success of their operations, but also on their preoperative functional status.
10.1016/j.ejso.2011.05.008
pubmed_703_7529
Synthesis of sulfated and unsulfated (glyco)peptide fragments of Hirudin P6 (a potent anticoagulant from the leech Hirudinaria manillensis) is described. The effect of O-glycosylation and tyrosine sulfation on thrombin binding and peptidolytic activity was investigated, together with the inhibition of fibrinogen cleavage.
10.1039/c1cc14773k
pubmed_507_9354
AIM To study neutrophil bacterial and absorptive functions and the specific features of their impairments in gout. SUBJECTS AND METHODS The study included 48 male patients with a valid diagnosis of gout (mean age, 59.7 +/- 10.3 years; duration of the disease, 9.2 +/- 2.1 years; blood uric acid (UA), 520 +/- 80 micromol) (Group 1); 25 apparently healthy volunteers (mean age 55.1 +/- 6.2 years; blood UA, 350 micromol/l) (Group 2). Neutrophil functional activity was estimated from the phagocytic-nitroblue tetrazolium reduction (NBT test) and myeloperoxidase (MPO) activity, the determination of non-enzyme cationic proteins (CP) and their spontaneous and induced indices. Neutrophil phagocytic function was also studied. RESULTS In Group 1, the content of active oxygen forms (AOF) was increased, on average, to 113.3 +/- 8.65 conventional units (CI) versus 88.22 +/- 5.23 CI in Group 2; p < 0.05). In 34 (70.8%) of the 48 male patients with gout, spontaneous MPO activity was significantly reduced as compared with that in Group 2: 348.4 +/- 13.6 and 509.2 +/- 12.2 CI, respectively (p < 0.01). In Group 1, the level of CP was noticeably decreased to 60.1 +/- 2.06 CI whereas in Group 2, it was 84.91 +/- 5.36 CI (p < 0.05). In gouty patients, the CP stimulation index averaged 0.70 +/- 0.13; in Group 2, it was significantly higher--1.2 +/- 0.05 (p < 0.05). CONCLUSION In the majority of gouty patients, neutrophil functional activity suffers due to its lower phagocytic function, which suppresses the body's antioxidant defense and contributes to the chronic pattern of an inflammatory process.
pubmed_507_9354
pubmed_310_3342
OBJECTIVE This article reports on the selection of screening items to detect Mexican or Mexican-American patients in the emergency department (ED) who have alcohol problems and could benefit from an intervention or a referral for treatment. Items are tested against the Rapid Alcohol Problems Screen (RAPS), which has been optimized from standard screening instruments and has outperformed these instruments. METHOD The performance of individual items from standard screening instruments (CAGE, TWEAK, AUDIT, TRAUMA and BMAST) against International Classification of Diseases, Tenth Revision and Diagnostic and Statistical Manual, Fourth Revision criteria for alcohol abuse and dependence was evaluated in a merged probability sample (N = 869; 72% men) of 537 ED patients from three hospitals in Pachuca, Mexico, and 332 Mexican-American ED patients in Santa Clara County, CA. Logistic regression and tree-classification models were used for item selection. RESULTS We found a prevalence of 15% for alcohol dependence and a prevalence of 28% for alcohol abuse or dependence in the merged sample. The RAPS items did not perform as well in terms of sensitivity (93%) as the optimal five items identified in these analyses (sensitivity = 98%) for alcohol dependence, but did demonstrate better specificity (79%) than the optimal five items (65%), which is an important consideration in a time of cost containment. Both sets of items showed better sensitivity and positive predictive value but similar Receiver Operating Characteristic values for respondents in the high acculturation group compared to those at other levels of acculturation. Differences in positive predictive value across all subgroups tended to increase at increased cutpoints, especially for the RAPS. CONCLUSIONS These analyses suggest that the RAPS performs favorably compared to those items optimized, in this sample of Hispanic ED patients. Based on comparative item performance in these analyses, the RAPS may hold promise as a useful tool for screening for alcohol dependence, but requires further evaluation as a stand-alone instrument in comparison with other standard screening instruments.
10.15288/jsa.2001.62.277
pubmed_595_209
A single-tube duplex nested polymerase chain reaction (sdn-PCR) was developed for the detection of and discrimination between ovine herpesvirus-2 (OvHV-2) and alcelaphine herpesvirus-1 (AIHV-1). These viruses respectively cause sheep- and wildebeest-associated malignant catarrhal fever (SA-MCF and WA-MCF). In the first step of the sdn-PCR, two primers with high annealing temperatures based on conserved regions of the tegument genes were used for DNA amplification. In the second step, two primer sets based on variable regions of the respective OvHV-2 and AIHV-1 genes and with annealing temperatures > 11 degrees C below the primers used in the first step, were used. Internal regions of different sizes from amplicons produced in the first step were amplified. This single-tube test obviates the need for two separate assays to detect both viral types, thereby reducing time, labour and cost.
10.4102/ojvr.v72i4.184
pubmed_269_18912
The present study investigated the effect of biochar (BC) addition on mechanical, thermal, and water resistance properties of PLA and hemp-PLA-based composites. BC was combined with variable concentration to PLA (5 wt%, 10 wt%, and 20 wt%) and hemp (30 wt%)-PLA (5 wt% and 10 wt%); then, composites were blended and injection molded. Samples were characterized by color measurements, tensile tests, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and water contact angle analysis. Experimental results showed that adding 5 wt% of BC enhanced the composite's tensile modulus of elasticity and strength. Hence, the use of optimized loading of BC improved the mechanical strength of the composites. However, after BC addition, thermal stability slightly decreased compared with that of neat PLA due to the catalytic effect of BC particles. Moreover, the water-repelling ability decreased as BC content increased due to the specific hydrophilic characteristics of the BC used and its great porosity.
10.3390/ma15062271
pubmed_290_17754
Seven new species from India are described in the Mesovelia horvathi species complex and assigned to two putatively monophyletic species groups. Mesovelia brevia sp. nov. and M. dilatata sp. nov., both occurring in Tamil Nadu and Meghalaya, and M. occulta sp. nov., known from only Tamil Nadu, are described and placed in the Mesovelia horvathi species group. Mesovelia andamana sp. nov. from the Andaman Islands, M. bispinosa sp. nov. and M. isiasi sp. nov. from Meghalaya, and M. tenuia sp. nov. from Tamil Nadu, are described and placed in the M. andamana species group. Photographs of morphological characters, distribution maps, and a key to males are provided for all of the species treated.
10.11646/zootaxa.4651.3.4
pubmed_3_11911
INTRODUCTION Advanced stage/metastatic soft tissue sarcoma (STS) has a poor prognosis especially after failure of the established first-line treatment. In patients with relapsed leiomyosarcoma, however, the combination of gemcitabine (G) and docetaxel (D) recently has emerged as a valuable salvage therapy. PATIENTS AND METHODS A retrospective analysis of G (900 mg/m2, days 1+8) and D (100 mg/m2, day 8) was performed in 34 patients with STS, and response rate (RR), overall survival (OS), time to progression (TTP), and toxicities were evaluated. RESULTS Analysis of these 34 patients revealed a RR of 15% with no complete remission (CR) and 5 partial remissions (PR). Of note, 4/5 PR were achieved in patients with leiomyosarcoma. In 13 patients (38%) disease stabilization (SD) could be achieved resulting in a clinical benefit rate (CBR), defined as CR+PR+SD, of 53%. Median OS was 12.5 and TTP was 2.4 months for the whole group and 2.8 months for patients with leiomyosarcoma. A progression- free rate at 3 months of 38% and 45%, respectively, was observed in these 2 groups. Major side effects were 47% hematological and 26% grade 3/4 nonhematological toxicity. CONCLUSION With regard to the observed CBR further use of GD seems to be warranted even in pretreated patients with STS.
10.1159/0000111756
pubmed_1045_18214
This is in continuation of the previous article published in this Bulletin of the Indian Institute of the History of Medicine, Volume XXVII, No. 2, July 1997. P. Nos 163 to 171, under the title of "Definition of Nidana Panchaka (First Chapter of Madhava Nidana"). It deals with Nadana, Purvarupa, Rupa, Upashaya and Samprapti as described in the first Chapter of Madhavanidana.
pubmed_1045_18214
pubmed_886_15845
In this study, the effect of water soluble homopolymer of vinylsulfonic acid on spontaneous crystallization of calcium oxalate (CaOx) was investigated. CaOx crystals exhibiting different shapes and phase structures were produced in the presence of polymer. While the crystal growth of calcium oxalate was inhibited by homopolymer, the morphology of calcium oxalate transformed from monohydrate to dihydrate. Inhibition of calcium oxalate crystallization was provided by adsorption of homopolymer onto the active growth sites of crystals on account of the charge and hydrophilic effects. Polyelectrolyte effects were interpreted in terms of the adsorption of inhibitors onto the active growth sites on the crystal surface.
10.1016/j.colsurfb.2010.03.030
pubmed_921_16905
This article reports on the efficacy and safety of the selective serotonin reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data were derived from naturalistic drug utilization observation (DUO) studies with fluoxetine (n = 18,759 patients). Data collection--at the start and the end of the observation period (< or =6 weeks)--included patient characteristics, diagnoses, medication, co-medication, efficacy, and adverse events (AEs). Nonparametric statistics and descriptive p values (two-tailed) were used. Analyses revealed various differences between PN (n = 56) and GPI (n = 157) samples as to patient and treatment characteristics (p < 0.001-0.08). Based on both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements in their symptomatology over time, including suicidality (all p < 0.001; there were no group differences). Overall AE rates were higher in PN patients (p < 0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were typical for fluoxetine and the total DUO samples. In fact, AE rates were lower compared to controlled trials. Findings suggest that PN patients were more severely ill at observation start and suffered a more complicated treatment course. However, clinical efficacy showed highly significant improvements in both subgroups; AE rates were low in both--although higher in PN patients. Thus, results support a positive benefit/risk ratio of fluoxetine use for this young patient population.
10.1089/cap.2000.10.91
pubmed_705_15349
BACKGROUND Transanal rectal advancement flap repair is an operation to treat trans-sphincteric fistula which leaves the external sphincter muscle essentially untouched. Anal sphincter function was evaluated prospectively before and after this procedure. METHODS Anorectal manometry was performed in 24 patients before operation and 3 months after surgery. A detailed standardized questionnaire on faecal continence was answered before surgery, then at 3 and 48 months after surgery. RESULTS No significant differences were seen between mean(s.e.m.) preoperative and postoperative values for maximum squeeze pressure (100.0(9.7) versus 118.0(12.7) mmHg), maximum resting pressure (56.6(4.3) versus 52.8(4.1) mmHg), rectal compliance (4.4(0.6) versus 3.5(0.5) ml/mmHg) or any other parameter of anorectal manometry. The questionnaire revealed the occurrence of minor incontinence in two patients following surgery, which remained unchanged for 4 years. Three other patients had continence disturbances 4 years after surgery which were probably unrelated to the procedure. CONCLUSION In addition to high success rates, transanal rectal advancement flap repair also yields excellent functional results. This procedure should be performed for trans-sphincteric fistula in place of alternative treatments whenever feasible.
10.1046/j.1365-2168.1998.00557.x
pubmed_28_9718
Universities increasingly play an important role in entrepreneurship, which has contributed to gender equality in the business world. The aim of this study is to establish a causal model of entrepreneurial intentions and explore it by gender, based on the dimensions of the Theory of Planned Behavior, and how these are mediated by the individuals' resilience and psychological well-being. The previous work experience was considered as one of the control variables, in order to analyze whether this influence the entrepreneurial intention. With a convenience sample of 644 Portuguese students, Structural Equation Modeling (SEM) was used. For a better understanding, multivariate analyses were performed and each one was individually reported, and for appropriate comparisons by gender, the t-student test was used. The comparison of means, between genders, showed that there are differences only between perceived behavioral control, subjective norm, and entrepreneurial intention, with women scoring the highest values, and psychological well-being, with men scoring the higher. A serial mediation path was performed, and psychological resilience was found to mediate a significant effect between perceived behavioral control and intention in females, but not in males. It also mediates a significant effect between attitude and intention in females, but not in males. These results show that attitude is a determining factor for females to become entrepreneurs. Finally, after discussing the results, theoretical and practical contributions are analyzed, with regard to the field of entrepreneurship in Portugal, and alternatives are pointed out for a more entrepreneurial future, reinforcing the role of higher education institutions.
10.3389/fpsyg.2020.615910
pubmed_418_6
AIMS Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including the isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and ejection time (ET). The myocardial performance index (MPI) was defined as [(IVCT + IVRT)/ET]. Our aim was to investigate if cardiac time intervals can be used to predict atrial fibrillation (AF) in the general population. METHODS AND RESULTS A total of 1915 participants from the general population underwent a health examination including TDI echocardiography. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or heart failure (HF) after the diagnosis of AF. Participants with known AF were excluded (n = 54). During a median follow-up of 11 years, 166 participants (9%) were diagnosed with AF and of these 44 participants (27%) developed HF or stroke. Assessing the association between IVCT and incident AF, the risk increased with 27% per 10 ms increase in IVCT [per 10 ms increase: hazard ratio (HR) 1.27, 95% confidence interval (CI) (1.17-1.38); P < 0.001]. The association remained significant after multivariable adjustment [per 10 ms increase: HR 1.22, 95% CI (1.09-1.35); P < 0.001]. No associations between the IVRT, ET, MPI, and AF remained significant after multivariable adjustment. The IVCT also predicted complicated AF and the association remained significant even after multivariable adjustment [per 10 ms increase: HR 1.39, 95% CI (1.06-1.81); P = 0.015]. CONCLUSION In the general population, the IVCT provides novel and independent prognostic information on the long-term risk of AF. Additionally, the IVCT can identify persons in risk of complicated AF.
10.1093/ehjci/jez059
pubmed_1014_4706
Understanding new particles formation in the free troposphere is key for air quality and climate change, but requires accurate observation tools. Here, we discuss on the optical requirements ensuring a backscattering device, such as a lidar, to remotely observe nucleation events promoted by nonspherical desert dust or volcanic ash particles. By applying the Mie theory and the T-matrix code, we numerically simulated the backscattering coefficient of spherical freshly nucleated particles and nonspherical particles. We hence showed that, to remotely observe such nucleation events with an elastic lidar device, it should operate in the UV spectral range and be polarization-resolved. Two atmospheric case studies are proposed, on nucleation events promoted by desert dust, or volcanic ash particles. This optical pathway might be useful for climate, geophysical and fundamental purposes, by providing a range-resolved remote observation of nucleation events.
10.1364/OE.22.0A1009
pubmed_897_5238
Stromules are stroma-filled tubules extending from plastids whose rapid extension toward or retraction from other plastids has suggested a role in interplastidic communication and exchange of metabolites. Several studies point to sporadic dilations, kinks, and branches occurring along stromule length but have not elucidated the underlying basis for these occurrences. Similarly, although specific details on interacting partners have been missing, a consensus viewpoint suggests that stromules increase the interactive surface of a plastid with its cytoplasmic surroundings. Here, using live imaging, we show that the behavior of dynamic, pleomorphic stromules strongly coincides with that of cortical endoplasmic reticulum (ER) tubules. Covisualization of fluorescent protein-highlighted stromules and the ER in diverse cell types clearly suggests correlative dynamics of the two membrane-bound compartments. The extension and retraction, as well as directional changes in stromule branches occur in tandem with the behavior of neighboring ER tubules. Three-dimensional and four-dimensional volume rendering reveals that stromules that extend into cortical regions occupy channels between ER tubules possibly through multiple membrane contact sites. Our observations clearly depict coincidental stromule-ER behavior and suggest that either the neighboring ER tubules shape stromules directly or the behavior of both ER and stromules is simultaneously dictated by a shared cytoskeleton-based mechanism. These new observations strongly implicate the ER membrane in interactions with stromules and suggest that their interacting surfaces might serve as major conduits for bidirectional exchange of ions, lipids, and metabolites between the two organelles.
10.1104/pp.110.170480
pubmed_292_16360
Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are endogenous neuromodulators that regulate presynaptic neurotransmitter release in neurons throughout the central and peripheral nervous systems. While substantial information is known about the eCBs, less is known about a number of endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N-oleoylethanolamine, OEA). We report the comparative effects of parathion and chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis cannulae into the right striatum, followed by microdialysis two or four days later. Additional rats were similarly treated and sacrificed for evaluation of tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%), while MAGL activity was significantly but lesser affected (37-62% inhibition) by parathion and chlorpyrifos. Signs of toxicity were noted only in parathion-treated rats. In general, chlorpyrifos increased eCB levels while parathion had no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were significantly different between parathion and chlorpyrifos exposures. Differential changes in extracellular and/or tissue levels of eCBs and eCBLs could potentially influence a number of signaling pathways and contribute to selective neurological changes following acute OP intoxications.
pubmed_292_16360
pubmed_41_5064
OBJECTIVE Women experience a variety of changes at midlife that may affect sexual function. Qualitative research approaches can allow a deeper understanding of women's experiences. We conducted 20 individual interviews and three focus groups among sexually active women aged 45 to 60 years (total n = 39) to explore how sexual function changes during midlife. METHODS Interviews and focus groups were conducted by a trained facilitator using a semistructured guide. All data were audio-recorded and transcribed. Two investigators used a subsample of data to iteratively develop a codebook. The primary investigator coded all data. A second investigator coded a randomly selected 25% of interviews. Codes regarding changes in sexual function were examined and key themes emerged. RESULTS The mean age was 52, and most women were peri- or postmenopausal. Fifty-four per cent of women were white, 36% black, and 10% of another race. Participants discussed positive and negative changes in sexual function. The most common negative changes were decreased frequency of sex, low libido, vaginal dryness, and anorgasmia. Participants attributed negative changes to menopause, partner issues, and stress. Most participants responded to negative changes with adaptation, including changing sexual behavior and prioritizing different aspects of sex. Participants also reported positive changes, attributed to higher self-confidence, increased self-knowledge, and better communication skills with aging. CONCLUSIONS In this qualitative study, women described experiencing both positive and negative changes in sexual function during midlife. When negative changes occurred, women often adapted behaviorally and psychologically. Providers should recognize that each woman's experience is unique and nuanced, and they should provide tailored care regarding sexual function at midlife.
10.1097/GME.0000000000000988
pubmed_933_11255
Inversion (rotation around 180 degrees ) impairs body recognition and affects early electrophysiological responses (especially the N170). However, the relationship between electrophysiological responses and behavior is as yet unclear. Furthermore, the presence of the head seems to have an impact on body recognition performances as well as on related electrophysiological responses. The present study aimed to investigate the course of behavioral and electrophysiological body inversion effects depending upon the degree of deviation from the upright position (0 degrees , 360 degrees ) to the inverted position (180 degrees ). Body stimuli were presented either with heads (masked face) or without heads in a delayed matching task. For human bodies presented with and without heads, there was a quadratic relationship between the angle of rotation and the behavioral performance as well as the N170 amplitude, with maximum performance disruption at 180 degrees deviation from the upright stimulus. The data indicate that configural body processing occurs during the structural encoding of body stimuli.
10.1016/j.neuroimage.2009.10.046
pubmed_317_20404
Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single-center study was conducted between 1995 and 2008 and is based on 247 tacrolimus-treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93-15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57-2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.
10.1111/ajt.13018
pubmed_211_2874
Several clinical studies document a greater discrimination between asthmatic and healthy subjects in bronchial responsiveness to a range of stimuli such as cold air, distilled water and sodium metabisulphite, than to conventional bronchoconstrictor agonists including histamine and methacholine. One of the mechanisms thought to account for the bronchoconstriction induced by these agents is via reflex activation of the cholinergic pathway. An increase in sensory nerve (afferent) activity in asthma might account for the increased responsiveness to these agents. If so, a number of strategies are available to inhibit the function of afferent nerves which could lead to a suppression of bronchial hyperresponsiveness, including (1) inhibition of afferent activity, (2) inhibition of neuropeptide release and (3) antagonism of tachykinin receptors. As there are numerous reviews dealing with the latter, in this review Domenico Spina, Saloni Shah and Selena Harrison focus on the first two strategies.
10.1016/s0165-6147(98)01261-9
pubmed_232_23235
Reticulocyte counting by flow cytometry (Bayer H*3, ADVIA 120) in blood of prematures, infants and children > 1 year of age was compared with microscopic counting under research conditions (9000 counted red blood cells per slide). While in children >1 year a good concordance of both methods was observed, 2.3-2.4-fold higher values were obtained in neonates by microscopy (Brilliant Cresyl Blue stain, 0.5%). However, another laboratory found good agreement between H*3-counting and microscopy in samples also obtained from neonates using the same methods. Despite very similar results for all age groups in comparative flow cytometry measurements in both laboratories, counting of smears from neonates differed, showing an approximately 2.3-fold larger amount of reticulocytes in our laboratory. The reason for these observations was a greater enlargement (1250-fold) used routinely in our laboratory compared with 800-fold in the other one. Thus very mature reticulocytes frequently found in neonates could only be detected using a 1250-fold enlargement. Similarly, the low concentration of the colouring matter used in the H*3 (0.0005% oxazin or 0.001% ADVIA 120) is obviously not sufficient for detection of mature reticulocytes. Therefore, it is important to consider this phenomenon and to standardise microscopic enlargement, especially for comparisons in multicentre studies.
10.1515/CCLM.2004.234
pubmed_436_19705
This article comments on the role of the most important biochemical markers that are already applied in clinical practice or are still under research, in Acute Coronary Syndromes (ACS). Cardiac troponin (cTn) is established as the 'gold standard' in the diagnosis of ACS. C-reactive protein (CRP) and especially high-sensitivity CRP (hs-CRP) are considered to be the most useful inflammatory markers for clinical practice in the setting of acute coronary syndrome. Brain-type natriuretic peptide (BNP) and the amino terminal fragment of the prohormone BNP (NT-proBNP) appear to provide prognostic information in individuals admitted for acute coronary syndromes. Microalbuminuria in nondiabetics appears to be a signal from the kidney that the vasculature, particularly the endothelium, is not functioning properly. Increased plasma levels of cystatin C, neopterin, myeloperoxidase, and pregnancy associated protein are associated with adverse cardiovascular outcomes, cardiovascular and noncardiovascular death, and possibly cerebrovascular disease. Furthermore, recent evidence suggests that serum levels of CD40-CD40L pathway exert important roles in progression, and outcome of acute coronary syndrome. In the future further, studies are necessary to elucidate the exact role of the new biochemical markers in ACS.
10.2174/092986708784534965
pubmed_914_18136
Proximal humerus fracture devascularizing the humeral head may require management by prosthesis. Hemiarthroplasty is a logical attitude in such cases, but analysis of functional results and complications has identified a certain number of risk factors limiting indications. Strict analysis of patient characteristics and of fracture type is an essential prerequisite to deciding against treatment by immobilization or osteosynthesis. Results in hemiarthroplasty are primarily dependent on respecting the rules of the art, which aim at stable anatomic osteosynthesis of the surrounding structures so as to restore normal shoulder function. The critical steps are the adjustment of implant height and retroversion, reduction and fixation of tuberosities and good management of the postoperative course. The recent development of fracture-dedicated shoulder implants should improve results. In elderly patients, when local conditions are unsuitable to hemiarthroplasty, a reverse prosthesis may be used, with an adapted surgical technique. Whatever the type of prosthesis, implantation for proximal humerus fracture is a demanding operation with definitive impact on the functional evolution of the shoulder.
10.1016/j.otsr.2010.07.001
pubmed_713_20171
Cyanobacterial cell factories trace a vibrant pathway to climate change neutrality and sustainable development owing to their ability to turn carbon dioxide-rich waste into a broad portfolio of renewable compounds, which are deemed valuable in green chemistry cross-sectorial applications. Cell factory design requires to define the optimal operational and cultivation conditions. The paramount parameter in biomass cultivation in photobioreactors is the light intensity since it impacts cellular physiology and productivity. Our modeling framework provides a basis for the predictive control of light-limited, light-saturated, and light-inhibited growth of the Synechocystis sp. PCC 6803 model organism in a flat-panel photobioreactor. The model here presented couples computational fluid dynamics, light transmission, kinetic modeling, and the reconstruction of single cell trajectories in differently irradiated areas of the photobioreactor to relate key physiological parameters to the multi-faceted processes occurring in the cultivation environment. Furthermore, our analysis highlights the need for properly constraining the model with decisive qualitative and quantitative data related to light calibration and light measurements both at the inlet and outlet of the photobioreactor in order to boost the accuracy and extrapolation capabilities of the model.
10.3389/fmicb.2021.639482
pubmed_134_16100
The substantial complexity and vast dynamic range of protein abundance in biological fluids, notably serum and plasma, present a formidable challenge for comprehensive protein analysis. Integration of multiple technologies is required to achieve high-resolution and high-sensitivity proteomics analysis of biological fluids. We have implemented an orthogonal three-dimensional intact-protein analysis system (IPAS), coupled with protein tagging and immunodepletion of abundant proteins, to quantitatively profile the human plasma proteome. Following immunodepletion, plasma proteins in each of paired samples are concentrated and labeled with a different Cy dye, before mixing. Proteins are subsequently separated in three dimensions according to their charge, hydrophobicity, and molecular mass. Differences in the abundance of resolved proteins are determined based on Cy dye ratios. We have applied this strategy to profile the plasma proteome for changes that occur with acute graft-versus-host disease (GVHD), following allogeneic bone marrow transplantation (BMT). Using capillary HPLC ESI Q-TOF MS, we identified 75 proteins in the micromolar to femtomolar range that exhibited quantitative differences between the pre- and post-GVHD samples. These proteins included serum amyloid A, apolipoproteins A-I/A-IV, and complement C3 that are well-known acute-phase reactants likely reflecting the post-BMT inflammatory state. In addition, we identified some potentially interesting immunologically relevant molecules including vitamin D-binding protein, fetuin, vitronectin, proline-rich protein 3 and 4, integrin-alpha, and leukocyte antigen CD97. IPAS provides a combination of comprehensive profiling and quantitative analysis, with a substantial dynamic range, for disease-related applications.
10.1074/mcp.M400126-MCP200
pubmed_241_16044
With spontaneous ventilation, sufficient exhaust resistance at the adjustable pressure-limiting (APL) valve when fully opened ensures that the reservoir bag fills and adequately supplies gas to patients. A lack of exhaust resistance with the APL valve fully open caused inadequate gas supply to patients with four types of anesthesia machines: SA2 (Dräger), Excel-210 SE (GE), Fabius (Dräger), and Cato (Dräger). Mechanically, the SA2 and Excel-210 SE APL valve systems, which are of the spring-loaded disc type positioned horizontally, cannot maintain sufficient exhaust resistance with the APL valve fully open. As for the Fabius and Cato, an exhaust valve independent of the APL valve should maintain sufficient exhaust resistance continuously. However, accumulated viscous substances on the thin diaphragm of the exhaust valve contributed to hindrance of diaphragm closure.
10.1007/s00540-010-0958-6
pubmed_1052_8243
We report on highly uniform resistive switching properties of amorphous InGaZnO (a-IGZO) thin films. The thin films were fabricated by a low temperature photochemical solution deposition method, a simple process combining chemical solution deposition and ultraviolet (UV) irradiation treatment. The a-IGZO based resistive switching devices exhibit long retention, good endurance, uniform switching voltages, and stable distribution of low and high resistance states. Electrical conduction mechanisms were also discussed on the basis of the current-voltage characteristics and their temperature dependence. The excellent resistive switching properties can be attributed to the reduction of organic- and hydrogen-based elements and the formation of enhanced metal-oxide bonding and metal-hydroxide bonding networks by hydrogen bonding due to UV irradiation, based on Fourier-transform-infrared spectroscopy, X-ray photoelectron spectroscopy, and Field emission scanning electron microscopy analysis of the thin films. This study suggests that a-IGZO thin films have potential applications in resistive random access memory and the low temperature photochemical solution deposition method can find the opportunity for further achieving system on panel applications if the a-IGZO resistive switching cells were integrated with a-IGZO thin film transistors.
10.1021/am500048y
pubmed_637_3816
Objective to analyze the power relations that permeate the work of the family health team, and to discuss perspectives of emancipation of these subjects, focusing on nursing and community health agents. Method a qualitative study with a family health team from a municipality in the countryside of the state of São Paulo. Data were collected through systematic observation and interview with workers. A thematic content analysis was performed. Results three categories were identified: the work of the family health team and power relations; power relations between the nurse and the healthcare team; and the relations among the nursing team and between community agents and the nurse. The team produces relations of power moved by hierarchical knowledge that move in the search for the reordering of powers. Final considerations it is necessary to review the contradictions present in the performance scenario of the family health teams, with a view toward making power relations more flexible.
10.1590/0034-7167-2015-0171
pubmed_910_5855
This case report describes a 35-year-old female with acute cholecystitis 36 weeks into her pregnancy. Laparoscopic cholecystectomy was assessed not to be possible. An ultrasonic guided percutaneous transhepatic gall bladder drainage was performed resulting in immediate pain relief. The patient was discharged two days later, and the drain sat in place until a caesarian section was per--formed. A post-surgery cholangiography demonstrated stones in the gall bladder but no stones in the common bile duct. An uneventful laparoscopic cholecystectomy was carried out three months after surgery. The case report demonstrates that percutaneous transhepatic gall bladder drainage is a safe procedure to be considered in women with cholecystitis in which cholecystectomy is not possible or assumed to be associated with an unacceptable high risk.
pubmed_910_5855
pubmed_844_3090
We report a rapid and sensitive colorimetric approach to quantitate the amount of glucose transporters exposed at the surface of intact cells, using L6 muscle cells expressing GLUT4 containing an exofacial myc epitope. Unstimulated cells exposed to the surface 5 fmol GLUT4myc per mg protein. This value increased to 10 fmol/mg protein in response to insulin as 2-deoxyglucose (10 microM) uptake doubled. The results are substantiated by immunofluorescent detection of GLUT4myc in unpermeabilized cells and by subcellular fractionation. We further show that wortmannin and the cytoskeleton disruptors cytochalasin D and latrunculin B completely blocked these insulin effects. The rapid quantitative assay described here could be of high value to study insulin signals and to screen for potential anti-diabetic drugs.
10.1016/s0014-5793(98)00423-2
pubmed_873_17404
Zinc oxide (ZnO) nanophotocatalyst is a promising candidate for degrading organic pollutants but has an extremely low photocatalytic activity under nature sunlight. In this work, flower-like MoS2 quantum dots/ZnO (MQ/ZnO) nanospheres with the size of approximately 1.26 μm are prepared at low temperature. The resultant flower-like MQ/ZnO nanospheres displayed higher photocatalytic activity than pure ZnO nanospheres under natural sunlight and without stirring, with the decomposition rate of the MQ/ZnO composites approximately 3.3 times higher than that of the pure ZnO nanospheres. Furthermore, the introduction of MoS2 QDs endowed ZnO nanospheres with optical memory ability. The enhanced sunlight-driven photocatalytic activity is dependent on the unique electrical properties of MoS2 QDs and the synergistic effect between ZnO and MoS2 QDs.
10.1016/j.jcis.2018.07.015
pubmed_323_16884
Substance abuse is a global menace with immeasurable consequences to the health of users, the quality of life and the economy of countries affected. Although the prominently known routes of initiation into drug use are; by contact between potential users and individuals already using the drugs and self initiation, the role played by a special class of individuals referred to as drug lords can not be ignored. We consider a simple but useful compartmental model of drug use that accounts for the contribution of contagion and drug lords to initiation into drug use and drug epidemics. We show that the model has a drug free equilibrium when the threshold parameter R0 is less that unity and a drug persistent equilibrium when R0 is greater than one. In our effort to ascertain the effect of policing in the control of drug epidemics, we include a term accounting for law enforcement. Our results indicate that increased law enforcement greatly reduces the prevalence of substance abuse. In addition, initiation resulting from presence of drugs in circulation can be as high as seven times higher that initiation due to contagion alone.
10.3934/mbe.2013.10.843