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pubmed_240_24248
This study utilized audiometry, and cervical vestibular-evoked myogenic potential (cVEMP), ocular VEMP (oVEMP) and caloric tests to investigate the sequence of vestibular deficits in patients with noise-induced hearing loss (NIHL). Thirty patients with NIHL underwent an inner ear test battery. Another 30 normal controls with age- and sex-matched were included for comparison. The abnormal percentages of the audiometry, and cVEMP, oVEMP and caloric tests were 100, 70, 57 and 33 % in NIHL patients, which showed significant differences from 13, 13, 7 and 3 % in normal controls, respectively. A significantly decreasing trend among the four tests, with the sequence of damage from the cochlea, followed by the saccule, utricle, and semicircular canals was noted in NIHL patients, but not in normal controls. In conclusion, the decreasing order of abnormal percentages in the function of the cochlea, saccule, utricle and semicircular canals after chronic noise exposure further supports that the pars inferior (cochlea and saccule) is more vulnerable to noise exposure than the pars superior (utricle and semicircular canals).
10.1007/s00405-012-2270-6
pubmed_93_2133
A simple technique for transverse mode selection in a large-mode-area (multimode) fiber laser is described. The technique exploits the different spectral responses of feedback elements based on a fiber Bragg grating and a volume Bragg grating to achieve wavelength-dependent mode filtering. This approach has been applied to a cladding-pumped thulium-doped fiber laser with a multimode core to achieve a single-spatial-mode output beam with a beam propagation factor (M2) of 1.05 at 1923 nm. Without mode selection the free-running fiber laser has a multimode output beam with an M2 parameter of 3.3. Selective excitation of higher order modes is also possible via the technique and preliminary results for laser oscillation on the LP11 mode are also discussed along with the prospects for scaling to higher power levels.
10.1364/OE.19.012434
pubmed_137_9081
BACKGROUND Elderly metastatic renal cell carcinoma (mRCC) patients are under-represented in clinical trials, whose results are therefore difficult to translate into routine management of older patients. We aimed at exploring treatment outcomes and prognostic factors in our real-life elderly mRCC cohort receiving first-line tyrosine kinase inhibitor (TKI) monotherapy. PATIENTS AND METHODS We retrospectively analyzed demographic and clinicopathological characteristics, and treatment data of elderly (≥ 70 years old at first-line start) mRCC patients starting either pazopanib or sunitinib as first-line treatment in our institution between March 2012 and April 2018. Baseline characteristics included age-adjusted Charlson comorbidity index (CCI). RESULTS In total, the records of 35 elderly mRCC patients were identified and retrospectively analyzed. Overall response rate, median progression-free survival, and median overall survival were 20%, 9.7 months, and 21.6 months, respectively. Karnofsky performance status ≤ 70%, sarcomatoid features, absolute neutrophil count greater than upper limit of normal, and treatment-related Grade 3 arterial hypertension were independently associated with survival after multivariate analysis. Age-adjusted CCI was significantly associated with survival in univariate analysis only. The overall incidence of Grade 3 to 5 toxicities was 74%. Seven patients (20%) received early crossover to either sunitinib or pazopanib because of toxicity. Dose reduction was applied in 24 (73%) of the 33 patients who completed at least 1 cycle. CONCLUSION First-line TKI monotherapy provided clinical benefit in our elderly mRCC cohort. Relatively frequent dose reductions helped to maintain an acceptable tolerability profile. Further research is warranted to explore the significance of prognostic factors in elderly mRCC patients.
10.1016/j.clgc.2019.03.012
pubmed_958_3858
In the evaluation of pharmacologic therapies, the controlled clinical trial is the preferred design. When clinical trial results are not available, the alternative designs are observational epidemiologic studies. A traditional concern about the validity of findings from epidemiologic studies is the possibility of bias from uncontrolled confounding. In studies of pharmacologic therapies, confounding by indication may arise when a drug treatment serves as a marker for a clinical characteristic or medical condition that triggers the use of the treatment and that, at the same time, increases the risk of the outcome under study. Confounding by indication is not conceptually different from confounding by other factors, and the approaches to detect and control for confounding--matching, stratification, restriction, and multivariate adjustment--are the same. Even after adjustment for known risk factors, residual confounding may occur because of measurement error or unmeasured or unknown risk factors. Although residual confounding is difficult to exclude in observational studies, there are limits to what this "unknown" confounding can explain. The degree of confounding depends on the prevalence of the putative confounding factor, the level of its association with the disease, and the level of its association with the exposure. For example, a confounding factor with a prevalence of 20% would have to increase the relative odds of both outcome and exposure by factors of 4 to 5 before the relative risk of 1.57 would be reduced to 1.00. Observational studies have provided important scientific evidence about the risks associated with several risk factors, including drug therapies, and they are often the only option for assessing safety. Understanding the methods to detect and control for confounding makes it possible to assess the plausibility of claims that confounding is an alternative explanation for the findings of particular studies.
10.1111/j.1532-5415.1999.tb01603.x
pubmed_57_19374
The electronic medical record (EMR) has significantly improved efficiency in many areas of radiology workflow. Following implementation of an electronic protocol selection process for cross-sectional imaging at the University of Colorado Hospital, the interventional radiology (IR) division desired to have a similar tool. Evaluation of the IR workflow demonstrated the need for a multilayered solution, which accounted for consultation, physician review, authorization and scheduling, pre-procedural nursing evaluation, physician rounding, and resource allocation and prioritization. This paper outlines the rationale for and components of this process.
10.1007/s10278-013-9666-8
pubmed_275_13288
AIMS/HYPOTHESIS We investigated the associations of type 2 diabetes and a history of myocardial infarction (MI) with coronary heart disease, stroke, cardiovascular and total mortality, and whether these effects are different in men and women. METHODS Study cohorts included 51,735 Finnish men and women aged 25-74 years. Smoking status and the history of MI and type 2 diabetes were recorded, and height, weight, blood pressure and serum cholesterol levels were measured at baseline. Additional data on the occurrence of diabetes and MI prior to baseline survey were obtained from national hospital discharge and drug registers through computerised register linkage. Mortality data were obtained from the national mortality register. RESULTS During a mean follow-up period of 17.2 years, 9,201 deaths were recorded. Hazard ratios (HRs) for coronary mortality were 2.1, 4.0 and 6.4 among men with diabetes alone, men with MI alone, and men with diabetes and MI, respectively, compared with men with neither diabetes nor a history of MI. The corresponding HRs among women were 4.9, 2.5 and 9.4, respectively. The equivalent HRs for cardiovascular and total mortality were 2.2, 3.3 and 6.0, and 1.8, 2.3 and 3.7 in men, and 4.4, 2.4 and 6.5, and 3.2, 1.7 and 4.4 in women, respectively. Diabetic men and women had similar total mortality rates, whereas total mortality rates were markedly higher among men in the other three diabetes-MI categories. CONCLUSIONS/INTERPRETATION Diabetes and MI markedly increase cardiovascular and all-cause mortality. In women, the association between diabetes and mortality was stronger than that between MI and mortality, whereas the converse was true among men.
10.1007/s00125-005-1730-6
pubmed_228_7446
This study asks parents who have children with Down syndrome (DS) how they feel about their lives so that such information could be shared with expectant couples during prenatal counseling sessions. A valid and reliable survey instrument was mailed to 4,924 households on the mailing lists of six non-profit DS organizations. Of the 2,044 respondents, 99% reported that they love their son or daughter; 97% were proud of them; 79% felt their outlook on life was more positive because of them; 5% felt embarrassed by them; and 4% regretted having them. The parents report that 95% of their sons or daughters without DS have good relationships with their siblings with DS. The overwhelming majority of parents surveyed report that they are happy with their decision to have their child with DS and indicate that their sons and daughters are great sources of love and pride.
10.1002/ajmg.a.34293
pubmed_570_23141
People with traumatic brain injury (TBI) experience memory and learning difficulties. Difficulty in the initial acquisition of information is a primary reason people with TBI experience difficulties in learning and memory. Treatment focusing on improving the acquisition of information will likely improve both recall and recognition performance. In the "generation effect," items self-generated are remembered better than items read or otherwise provided. The purpose of this study was to examine the application of the generation effect in improving memory for functional activities. The study used a within-subjects design and included 10 participants with TBI and 15 healthy control participants. Results demonstrated that material learned under the generated learning conditions was recalled better than when generated under provided learning conditions. This finding was true in both the TBI and the control groups. These results provide initial evidence supporting the use of self-generation to improve new learning of functional tasks for people with TBI.
10.5014/ajot.2010.09020
pubmed_58_18201
BACKGROUND/AIMS The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. METHODS High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. RESULTS HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. CONCLUSION These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.
10.3904/kjim.2017.207
pubmed_5_13743
During interphase in the budding yeast, Saccharomyces cerevisiae, centromeres are clustered near one pole of the nucleus as a rosette with the spindle pole body at its hub. Opposite to the centromeric pole is the nucleolus. Chromosome arms extend outwards from the centromeric pole and are preferentially directed towards the opposite pole. Centromere clustering is reduced by the ndc10 mutation, which affects a kinetochore protein, and by the microtubule poison nocodazole. This suggests that clustering is actively maintained or enforced by the association of centromeres with microtubules throughout interphase. Unlike the Rabl-orientation known from many higher eukaryotes, centromere clustering in yeast is not only a relic of anaphase chromosome polarization, because it can be reconstituted without the passage of cells through anaphase. Within the rosette, homologous centromeres are not arranged in a particular order that would suggest somatic pairing or genome separation.
10.1242/jcs.113.11.1903
pubmed_442_2500
BACKGROUND To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. METHODS Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. RESULTS The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. CONCLUSIONS Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy.
10.1159/000448787
pubmed_298_11783
OBJECTIVE To compare the rate of parastomal hernia in patients undergoing anterior fascial fixation of the ileal conduit with that in patients without fascial fixation. Limited data exist on whether anterior fascial fixation of the ileal conduit impacts the rate of parastomal hernia. METHODS A total of 496 consecutive patients undergoing radical cystectomy and ileal conduit reconstruction from 1995 to 2012 were retrospectively evaluated for parastomal hernia. All patients had a 2-fingerbreadth aperture and the ileal conduit brought through the rectus muscle and sheath. Patients were divided into 1 of 3 groups based on stoma fixation and/or reinforcement: anterior fascial fixation, posterior reinforcement, or no fascial fixation. A parastomal hernia was defined as a palpable bulge at the stoma site. Multivariate logistic regression was conducted for the primary end point of parastomal hernia, controlling for other patient- and treatment-related factors that might affect the rate of parastomal hernia. RESULTS Median follow-up was 16 months (range, 1-189 months). The parastomal hernia rate was significantly greater in the anterior fascial suture group (43 of 281; 15.3%) than the no fascial suture group (12 of 164; 7.3%; P=.02). Multivariate logistic regression analysis modeled for the occurrence of a parastomal hernia demonstrated that anterior fascial fixation was an independent predictor of the development of parastomal hernia (odds ratio, 2.3; 95% confidence interval, 1.03-5.14; P=.04). CONCLUSION Anterior fascial fixation of the ileal conduit does not reduce the risk of parastomal hernia formation compared with the patients treated without fascial fixation. Surgeons should consider avoiding anterior suture fixation during ileal conduit creation.
pubmed_298_11783
pubmed_372_7100
Silicon (Si) can alleviate aluminum (Al) toxicity in rice (Oryza sativa L.), but the mechanisms underlying this beneficial effect have not been elucidated, especially under long-term Al stress. Here, the effects of Al and Si on the suberization and development of rice roots were investigated. The results show that, as the Al exposure time increased, the roots accumulated more Al, and Al enhanced the deposition of suberin in roots, both of which ultimately inhibited root growth and nutrient absorption. However, Si restricted the apoplastic and symplastic pathways of Al in roots by inhibiting the uptake and transport of Al, thereby reducing the accumulation of Al in roots. Meanwhile, the Si-induced drop in Al concentration reduced the suberization of roots caused by Al through down-regulating the expression of genes related to suberin synthesis and then promoted the development of roots (such as longer and more adventitious roots and lateral roots). Moreover, Si also increased nutrient uptake by Al-stressed roots and thence promoted the growth of rice. Overall, these results indicate that Si reduced Al-induced suberization of roots by inhibiting the uptake and transport of Al in roots, thereby amending root growth and ultimately alleviating Al stress in rice. Our study further clarified the toxicity mechanism of Al in rice and the role of Si in reducing Al content and restoring root development under Al stress.
10.1093/pcp/pcac001
pubmed_125_15798
In this article, we report the autopsy findings of a 48-year-old man who sustained blunt trauma to the thorax. A medical record review revealed no history of cardiac disease. He presented to the hospital with a computed tomography-verified fracture of the left fourth and fifth ribs, and pulmonary and cardiac contusion. He was released from the hospital in stable condition at his own request 7 days later. Because of sudden deterioration, he was readmitted to the hospital the next day. Electrocardiogram detected cardiac arrhythmia on the 15th day after chest trauma. Electrocardiography detected pericardial effusion and severe mitral insufficiency resulting in left ventricular failure. Death was attributed to diffuse alveolar damage-complicating pneumonia due to cardiac contusion with mitral insufficiency occurring 25 days after hospital admission. Internal examination revealed diffuse fibrinous pericarditis, left atrial tear right above the anterior mitral valve leaflet with intrapericardial granulation tissue, and no sign of myocardial damage. Immunohistochemistry showed significantly more CD68-positive macrophages within tissue taken from the heart, a finding indicative of previous atrial and ventricular myocardial contusion. This case report demonstrates that routine hematoxylin and eosin staining may not always reveal significant myocardial damage.
10.1097/PAF.0000000000000590
pubmed_327_10011
This study investigated the effects of microinfusion of scopolamine into the medial septum (MS Scp) on hippocampal neurophysiology and learning of the rabbit's classically conditioned jaw movement response. The percentage of hippocampal theta slow waves (2-8 Hz) decreased after drug infusion in the MS Scp group but did not change in control groups that received infusion of saline into the MS or scopolamine into the cortex. Unit recordings from the MS Scp group showed significantly smaller conditioning-related hippocampal neural responses than seen in controls, and during conditioning, rabbits in the MS Scp group took significantly longer to reach learning criterion than either control group. Thus, the neural and behavioral impairments previously reported for systemic muscarinic blockade were reproduced by microinfusions restricted to the medial septal nucleus.
10.1037//0735-7044.114.6.1068
pubmed_415_21431
The complex-induced aggregation of perylene bisimides by p-sulfonatocalix[n]arenes was studied, where the aggregation stability, aggregation distance, as well as the degree of order of aggregation were all improved.
10.1039/c2ob06973c
pubmed_428_11917
BACKGROUND The profile and management of self-inflicted abdominal stab wounds (SI-ASW) patients is still obscure. METHODS The National Trauma Data Bank (2012) was queried for adults with abdominal stab wounds (n = 9544). Patients with SI-ASW (n = 1724) and non-SI-ASW (n = 7820) were compared. Predictors for non-therapeutic laparotomy/laparoscopy (non-TL) in SI-ASW patients were identified. RESULTS SI-ASW patients were older, had more females and behavioral disorders, similar physiology, but a lower Injury Severity Score. They had more laparotomies overall (54 versus 48%, p < 0.0001) and more non-TL (42 versus 32%, p < 0.0001), but less injuries (43 versus 53%, p < 0.0001), although peritoneal violation rate was similar. Complications and mortality were similar. In the SI-ASW cohort, non-TL patients were more likely to be female and younger, and to have Glasgow Coma Scale (GCS) ≥13 and a higher systolic blood pressure. History of psychiatric, drug and alcohol disorders was associated with SI-ASW, but did not independently predict the need for treatment in adjusted models. CONCLUSION Patients with SI-ASW underwent more non-TL than patients with non-SI-ASW. Female gender, younger age, and a higher GCS and systolic blood pressure predicted non-TL in this group.
10.1007/s00268-017-4083-7
pubmed_1038_12383
A South American opossum (Monodelphis domestica) is a model animal for studies on the health effects of exposure to ultraviolet radiation (UVR). As part of a broad evaluation of immune function in this animal, we have tested in vitro mitogenic responses using whole blood cultures. Lymphocytes proliferated in the presence of phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM), but were unresponsive to bacterial lipopolysaccharide (LPS).
10.1016/0165-2427(92)90083-3
pubmed_71_20285
The identification of the molecular composition of the mitochondrial calcium uniporter has allowed for the genetic manipulation of its components and the creation of various in vivo genetic models. Here, we review the initial attempts to modulate the expression of components of the calcium uniporter in a range of organisms from plants to mammals. This analysis has confirmed the strict requirement for the uniporter for in vivo mitochondrial calcium uptake and for maintaining mitochondrial calcium homeostasis. We further discuss the physiological effects following genetic manipulation of the uniporter on tissue bioenergetics and the threshold for cell death. Finally, we analyze the limited information regarding the role of various uniporter components in human disease.
10.1007/978-3-319-55330-6_3
pubmed_617_2917
Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation pharyngoplasty, using different implants, have all been used to address this trouble. We hereby present our results following rhinopharyngeal autologous fat injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between 2004 and 2007. The degree of hypernasal speech was evaluated pre- and postoperatively by a speech therapist and an ENT specialist and quantified by an acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with preoperative speech therapy (average, 8 years). The mean value of the nasalance score was 37% preoperatively and 23% postoperatively (p = 0.015). The hypernasality was reduced postoperatively in all patients (1-3 degrees of the Borel-Maisonny score). There were no major complications, two minor complications (one hematoma, one cervical pain). The autologous fat injection is a simple, safe, minimally invasive procedure. It proves to be efficient in cases of mild velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.
10.1007/s00405-009-1157-7
pubmed_235_21179
BACKGROUND Detection of childhood traumas is important both in clinical practice and in research. There is a pressing need for methods that are relatively simple but comprehensive, non-intrusive, and possess adequate psyc - ho metric properties. In this study we translated one of the most widely used and well-studied measure of childhood abuse and neglect and explored the psychometrical properties of this questionnaire. METHODS The study was based on data from a clinical (N=171) and a normative (N=358) sample. In total 529 adults participated in the testing process. Beside the trauma questionnaire Parental Bonding Inventory, Impact of Events Scale and Dissociative Experiences Scale were administered. RESULTS We examined the internal consistency of the translated trauma questionnaire. The Cronbach's a coefficients for the five subscales ranged from 0,639 to 0,934. Participants in the clinical sample reached higher scores on all trauma subscales except sexual abuse, than normative adults [PA: t (398)=-2,771; p=0,006; PN: t (398)=-5,990; p=0,000; EA: t (398)=-3,679; p=0,000; EN: t (398)=-4,759; p=0,000; total score: t (398)=-4,669; p=0,000]. Correlations among the trauma questionnaire total score and the scales of Parental Bonding Inventory indicating some medium effects (with maternal care: r=-0,661; p=0,000; with paternal care: r=-0,483; p=0,000). CONCLUSION Our preliminary findings suggest that this trauma questionnaire is practical and facilitates the systema - tic evaluation of adverse early life events and maximizes the possibility of detecting childhood abuse and neglect.
pubmed_235_21179
pubmed_494_24557
BACKGROUND Worldwide, familial Mediterranean fever (FMF) is the most common autoinflammatory disease. It has been suggested that environmental factors affect the phenotype as some patients do not develop the complication of secondary amyloidosis. OBJECTIVE To analyse whether disease severity in Turkish children with FMF, living in Turkey and Germany is different. PATIENTS AND METHODS A total of 55 Turkish children living in Turkey were compared with 45 Turkish children born and raised in Germany. Mean age among the group from Turkey and Germany was 42.2 and 44.29 months, respectively. M694V was the leading mutation in both groups. The severity scores were compared with two scoring systems, modified according to published paediatric data for dosage. RESULTS There was no significant difference between the mean C-reactive protein and erythrocyte sedimentation rate levels of the two groups. According to the modified Sheba Center score, 78.2% of patients from the group living in Turkey had a severe course compared with 34.1% from the group living in Germany. The modified score of Pras et al also showed more severe disease in the patients from Turkey. The difference between the two groups for both scoring systems were significant (both p<0.05). CONCLUSIONS We believe the modified scores that we introduce can be widely used for children. Our results suggest that the environment affects the phenotype of a monogenic disease of the innate inflammatory pathway.
10.1136/ard.2008.092031
pubmed_78_15520
The study compared performance of children with high levels of attention deficit hyperactivity disorder (ADHD; n=22), children with ADHD and oppositional defiant disorder (ODD; n=19), and a control group (n=20) on a Go-No-go test in a self-paced and computer-paced condition. Each condition, in turn, was run in a reward and a nonreward condition. The children were recruited through screening of a school population without ADHD or ODD (N=450). Findings indicated that children having high levels of ADHD plus ODD showed poor impulse control in all 4 conditions. No poor impulse control was found in the group with high levels of ADHD. This group demonstrated slower RTs across the computer-paced conditions. Findings were discussed in terms of the response-inhibition hypothesis, as formulated by Barkley (1997), the delay-aversion theory (Sonuga-Barke, 1995), and the state-regulation theory (Van der Meere, 2002).
10.1207/s15326942dn2801_1
pubmed_58_16457
Understanding the processes underlying speciation has long been a challenge to evolutionary biologists. This spurs from difficulties teasing apart the various mechanisms that contribute to the evolution of barriers to reproduction. The study by Rafati et al. () in this issue of Molecular Ecology combines spatially explicit whole-genome resequencing with evaluation of differential gene expression across individuals with mixed ancestry to associate the genomic architecture of reproductive barriers with expression of reproductive incompatibilities. In a natural hybrid zone between rabbit subspecies, Oryctolagus cuniculus cuniculus and O. c. algirus (Figure ), Rafati et al. () use landscape-level patterns of allele frequency variation to identify potential candidate regions of the genome associated with reproductive isolation. These candidate regions are used to test predictions associated with the genomic architecture of reproductive barriers, including the role of structural rearrangements, enrichment of functional categories associated with incompatibilities, and the contribution of protein-coding versus regulatory changes. A lack of structural rearrangements and limited protein-coding changes in candidate regions point towards the importance of regulatory variation as major contributors to genetic incompatibilities, while functional enrichments indicate overrepresentation of genes associated with male infertility. To quantify phenotypic expression of proposed incompatibilities, the authors assess gene expression of experimental crosses. Extensive misregulation of gene expression within the testes of backcross hybrids relative to F1 and parental individuals provides an important link between genotype and phenotype, validating hypotheses developed from assessment of genomic architectures. Together, this work shows how pairing natural hybrid zones with experimental crosses can be used to link observations in nature to mechanistic underpinnings that may be tested experimentally.
10.1111/mec.14516
pubmed_978_12371
Visual acuities obtained with a high contrast Bailey-Lovie chart (HCBL) and a low contrast Bailey-Lovie chart (LCBL) were compared with clinical contrast sensitivity function (CSF) measurements in a group of normal subjects with a wide range of refractive errors. We found high and significant correlations for the measurements obtained with the visual acuity tests, and between measurements obtained with the acuity tests and the CSF chart. These results indicate that the CSF test provides little additional information as a screening test in routine practice, and could probably be restricted in its use to patients in whom ocular disease is suspected.
10.1097/00006324-198907000-00010
pubmed_88_10152
The amenability of the stable population model to certain situations where net maternity function need not be invariant over time is exemplified by relating the changes in fertility at 2 time points by the equation m(a,t) = m(a) h(a,t)/h(t) where the form of h(t) is general and can be determined based on observed birth trajectories. Using the extended form of Easterlin's hypothesis, h(t) is taken as the reciprocal of NRR at t. The model is then applied to project NRR.
pubmed_88_10152
pubmed_176_12482
A 17-year-old boy with adenomatous polyposis and a history of an adenomatous polyposis coli (APC) gene mutation (IVS13(-2) A>G) presented for evaluation of vertical, binocular diplopia. Examination was suggestive of a fourth (trochlear) nerve palsy. A history of headaches was elicited and led to further investigation with neuroimaging, which identified a germinoma in the tectal plate and secondary hydrocephalus. We report the clinical, radiological, and histopathological findings of this patient, who to our knowledge is the first reported case of a germinoma occurring in association with adenomatous polyposis.
10.1016/j.jaapos.2010.11.004
pubmed_1015_1269
Perirenal hematoma is an uncommon, but significant complication of renal biopsy. Ultrasound provides a quick, non-invasive means of diagnosis.
10.1007/BF02926690
pubmed_177_18690
The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor-α inhibitors; infliximab and adalimumab, one anti-interleukin (IL)-12/23p40 antibody; ustekinumab, and IL-17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti-IL-17A antibodies. Brodalumab is an anti-IL17RA antibody. In this review, we pick up topics which have drawn attention regarding the safety of biologics and discuss them with recent published work.
10.1111/1346-8138.14096
pubmed_873_10548
OBJECTIVE(S) The aim of this study was to investigate exosomal markers and inflammatory cargo of extracellular vesicles (EVs) obtained from cerebrospinal fluid (CSF) and plasma in the aging process. We also studied the inflammatory cargo by quantifying IL-1β levels. METHODS Male Wistar rats, aged 3 and 21 months, were used (n = 12 in each group). The CSF and plasma of animals were collected, and isolation of EVs was performed using a commercial kit. Total protein concentration, acetylcholinesterase (AChE) activity, and CD63 and IL-1β levels were evaluated. RESULTS AChE activity in EVs increased in both samples, specifically in the circulating EVs and those in the CSF of the older group. An age-related increase was observed in CD63 levels in EVs from the CSF but a decrease was observed in plasma EVs of the older group. Student's t test showed that the young adult rats had significantly higher circulating IL-1β levels in the EVs compared to the aged ones, without any effect on central content. CONCLUSION Our data suggest that the normal aging process causes different changes in the profiles of central and circulating EVs. Altered IL-1β levels in circulating EVs can be linked, at least partly, to age-related inflammatory conditions, and a disruption of the CFS exosomes in aged rats, evaluated by CD63 levels, can be related to susceptibility to neurodegenerative disorders.
10.1159/000488943
pubmed_582_10264
BACKGROUND To report on Areca chewing (AC) in Xiangtan, Hunan province, China, and to test the knowledge of chewers related to side effects of the habit. METHODS Interviews with 276 individuals were performed. A questionnaire including general data, chewing habits, educational level and knowledge about side effects were used. Data were analysed using SPSS. Chi-square test was used at a significance level of P < 0.05. RESULTS Around 257 individuals were chewers (male: 54.1%; female: 45.9%) and 19 were former chewers (male: 31.6%; female: 68.4%). Mean age of chewers was 36.1 years. Around 42.4% of chewers smoked; 58.0% had a drinking habit. Average period of chewing was 11.2 years. Around 88.3% of chewers did not include the nut (seed). Around 79.0% considered AC habits negative for general health and 85.2% for oral health. CONCLUSIONS Most respondents did not know that AC may induce oral submucous fibrosis and oral cancer. The 'betel quid' chewed in Xiangtan usually does not contain Areca 'nut' (seed, endosperm), but consists of the husk. As no studies on the chemical composition of the Areca husk have been published such investigations are urgently needed.
10.1111/j.1600-0714.2008.00640.x
pubmed_12_4969
Superoxide dismutase (SOD) plays a major part in the destruction of oxygen-free radicals in the body. SOD activity is impaired by several trace elements including aluminium and silicon which are found in increased levels in plasma and tissues of uremic man. SOD activity was investigated in the erythrocytes of normal controls and of dialysis patients to determine if lack of SOD-protective activity could be a contributory cause to the increased hemolysis of uremia. It was found that SOD levels in red cell hemolysate were significantly lower in dialysis patients (41.4 +/- 9.1 units/100 ml) compared to control (49.3 +/- 7.2 units/100 ml) (U = 7.3; p less than 0.005). When expressed per 100 ml of whole blood SOD levels were 3.25 +/- 0.93 units/100 ml in dialysis patients and 6.46 +/- 0.99 units/100 ml in controls (U = 96; p less than 0.001). It is concluded that inhibition of SOD activity in the erythrocytes of dialysis patients may contribute to their anemia.
10.1159/000185970
pubmed_263_21154
BACKGROUND Rotator cuff surgery in wheelchair-bound patients is challenging, and clinical data on this condition are limited. We hypothesized that rotator cuff repair in these patients might improve functional outcomes. METHODS In a retrospective study, data on 13 paraplegic patients (8 men and 5 women; 16 shoulders) who underwent rotator cuff repair were analyzed. The average age at the time of surgery was 48.7 years. The causes of paraplegia were poliomyelitis in 9 patients, spinal fracture in 4, and cerebral infarction in 2. Open rotator cuff repair was performed in 11 patients and arthroscopic repair in 2 patients. No wheelchair propulsion was allowed until 6 months postoperatively to protect the repaired cuffs. American Shoulder and Elbow Surgeons (ASES) score and Constant score were used for functional evaluation. To assess tendon integrity, magnetic resonance imaging or ultrasonography was used at an average of 31.2 months postoperatively. RESULTS ASES scores improved from 53 to 85, and Constant scores improved from 48 to 75. Radiographic evaluation revealed healing in 88% of the cases and retear in 12%. In the retear group, functional scores improved. CONCLUSION Rotator cuff repair surgery for paraplegic wheelchair-bound patients provides satisfactory functional outcomes. Careful postoperative management can help in obtaining positive functional outcomes.
pubmed_263_21154
pubmed_617_17470
Chloroform is a potent central nervous system and respiratory depressant. The toxicities associated with chloroform frequently occur after inhalation. Hepatotoxicity is secondary to production of a toxic metabolite, with a peak elevation of liver enzymes 72 hours after exposure. Acute liver failure after chloroform inhalation is rarely described, this syndrome being produced mainly by viral hepatitis, idiosyncratic drug-induced liver injury, and acetaminophen ingestion. This report describes the case of a 46-year-old woman who presented to emergency department with coma, signs of respiratory failure, and solvent odor of her breath after chloroform inhalation and binge drinking. In evolution appeared lethal acute liver failure and rhabdomyolysis, despite maximum supportive care. Necroptic examination revealed microvesicular steatosis and tubular renal necrosis, specific for chloroform toxicity. This case illustrates the dramatic impact on liver of two well-recognized hepatotoxins. Mechanisms of chloroform and alcohol-induced liver toxicity are reviewed.
10.1177/0960327109357142
pubmed_397_21498
Despite recent advances using more conservative approaches, standard classical radical neck dissection is still one of the most frequently performed procedures in head and neck cancer patients who have advanced metastatic neck disease. The trapezius muscle paralysis following division of the spinal accessory nerve results in severe pain and cosmetic disturbance related to malalignment of the shoulder joint. The objective of this study is to report our results with a newly developed orthosis to prevent and correct shoulder dysfunction following standard radical neck dissection. Thirty-four patients who underwent standard radical neck dissection as a part of their surgical treatment from 1997-2002 were rehabilitated by the shoulder orthosis. Beginning 2 weeks after surgery, the patients were allowed to use their orthosis. By using a standard questionnaire, the pain and activity scores were recorded at the 1st, 3rd, 6th and 12th months postoperatively. Six patients were excluded from the study, of whom two succumbed to their disease and four discontinued the use of the orthosis. Of 28 patients included in the study, 20 (72%) were completely pain free within 3 months following the surgery. Four patients (14%) noted their pain level as tolerable, and four patients (14%) reported no considerable gain in the pain threshold and/or physical activity levels. Despite the fact that the active abduction range increased only 5 to 20 degrees , the relief of pain and improved malalignment of the scapula and consequently clavicle and humerus led to functional gains, which increased the patients' endurance. At the end of the study, 23 patients (82%) were able to return to their previous jobs or activity levels. Current preliminary reports suggest that this orthosis can be recommended to prevent significant disability in patients with trapezius palsy due to ablative cancer surgery or other reasons.
10.1007/s00405-005-1017-z
pubmed_273_8712
PURPOSE The purpose of this study was to determine the differences in polysomnographic variables between obese adolescents with polycystic ovarian syndrome (PCOS) and healthy, normal-weight and obese controls, as the prevalence of obstructive sleep apnea syndrome (OSAS) is increased in adults with PCOS. METHODS Twenty-two obese adolescents with PCOS (mean age 15.2 +/- 1.3 years, mean BMI 31.7 +/- 6.2 kg/m(2)), 18 healthy, normal-weight adolescents (mean age 15.0 +/- 0.9 years, mean BMI 20.6 +/- 2.3 kg/m(2)), and 11 healthy, obese adolescents (mean age 15.0 +/- 1.0 years, mean BMI 34.8 +/- 8.7 kg/m(2)) underwent polysomnography to compare mean transcutaneous arterial oxygen saturation (Sat O(2)), apnea index (AI), hypopnea index (HI), apnea-hypopnea index (AHI), the absolute number of obstructive apneas (NOA), percentage sleep stages 3 and 4 of non-REM sleep (stages 3 and 4), percentage of REM sleep (%REM), sleep-onset latency, and sleep efficiency. RESULTS We found no differences between the three groups concerning Sat O(2), AI, HI, AHI, NOA, and stages 3 and 4. The girls with PCOS differed from normal-weight and obese controls regarding sleep-onset latency and sleep efficiency and from the normal-weight controls regarding %REM. CONCLUSIONS OSAS does not seem to be more prevalent in adolescents with PCOS. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.
10.1007/s11325-009-0276-0
pubmed_1050_15601
Advancement of technology and device miniaturization have made near infrared spectroscopy (NIRS) techniques cost-effective, small-sized, simple, and ready to use. We applied NIRS to analyze healthy human muscles in vivo, and we found that this technique produces reliable and reproducible spectral "fingerprints" of individual muscles, that can be successfully discriminated by chemometric predictive models. The dataset presented in this descriptor contains the reflectance spectra acquired in vivo from the ventral and dorsal aspects of the arm using an ASD FieldSpec® 4 Standard-Res field portable spectroradiometer (350-2500 nm), the values of the anthropometric variables measured in each subject, and the codes to assist access to the spectral data. The dataset can be used as a reference set of spectral signatures of "biceps" and "triceps" and for the development of automated methods of muscle detection.
10.1016/j.dib.2020.106480
pubmed_462_19214
Three cases of symptomatic bradycardia due to topical ocular timolol administration are reported. Two patients had syncope related to atrioventricular block, and the other one complained of dizziness due to sinus bradycardia. Heart disease was not present in any case, although a right bundle branch block was observed in one patients. A normal sinus rhythm resumed in all patients after discontinuation of timolol.
pubmed_462_19214
pubmed_456_24606
In this study, the Delphi method was used to develop evidence-based indicators of intensive care unit (ICU) nursing quality of care in China. Nursing quality indicators reflect elements of patient care that are directly affected by nursing practice. A comprehensive literature search identified 2,857 potentially relevant articles. From the 50 articles that were included in this study, researchers identified 38 commonly used nursing quality indicators. A panel of experts reduced these to 20, which were then subjected to two rounds of Delphi discussion by a different panel, and a final consensus was achieved. The 20 indicators were grouped into three dimensions: structure, process, and outcome (including adverse consequences). The agreement among the experts for the 20 indicators was high. These evidence-based nursing quality indicators provide for ease in data collection and a basis for clinical application and improvement in the quality of ICU nursing throughout China.
10.1002/nur.21925
pubmed_464_4492
To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.
10.1089/jwh.2021.0152
pubmed_170_8319
This article reviews antisocial personality disorder, psychopathy, and violence and develops a three factor model of personality traits. Then a discussion of related personality disorders precedes the development of a categorical two factor model of impulsive versus remorseless violence. A paradigm of proactive, medical, and school based early intervention and prevention is advocated as a useful addition to the reactive detention of criminal justice. Integration of psychological tests, neuroimaging, and genomic data in early childhood and school based intervention strategies to prevent the development of conduct disorder and attenuate criminal propensity inform this approach.
10.1002/bsl.932
pubmed_647_22504
BACKGROUND Although physical fitness has been suggested to improve physical and psychosocial health for a variety of population profiles, there is a lack of information about the safety and effectiveness of aerobic exercise for adults with Down syndrome. OBJECTIVES To evaluate the effectiveness and safety of aerobic exercise training programmes for physiological and psychosocial outcomes in adults with Down syndrome. SEARCH STRATEGY Search terms and synonyms for "aerobic exercise" and "Down syndrome" were used within the following databases:CENTRAL (2005, Issue 2); MEDLINE (1966 to March 2005); EMBASE (2005 to April 2005); CINAHL (1982 to March 2005); LILACS (1982 to March 2005); PsycINFO (1887 to March 2005); ERIC (1966 to March 2005); CCT (March 2005); Academic Search Elite (to March 2005), C2- SPECTR (to March 2005 ), NRR (2005 Issue 1), ClinicalTrials.gov (accessed March 2005)and within supplements of Medicine and Science in Sports and Exercise. SELECTION CRITERIA Randomised or quasi-randomised controlled trials using supervised aerobic exercise training programmes with behavioral components accepted as co-interventions. DATA COLLECTION AND ANALYSIS Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, data was pooled using meta-analysis with a random effects model MAIN RESULTS The two studies included in this trial used different kinds of aerobic activity: walking/jogging and rowing training. One included study was conducted in the USA, the other in Portugal. In the meta-analyses, only maximal treadmill grade, a work performance variable, was improved in the intervention group after aerobic exercise training programmes (-4.26 [95% CI -6.45, -2.06]) grade. The other outcomes in the meta-analysis showed no significant differences between intervention and control groups, as expressed by weighted mean difference: VO(2) peak -0.30 (95% CI -377, 3.17) mL.Kg.min(-1); peak heart rate, -2.84 (95% CI -10.73, 5.05) bpm; respiratory exchange ratio, 0.01 (95% CI -0.04, 0.06); pulmonary ventilation, -5.86 (95% CI -16.06, 4.34) L.min(-1). 30 other measures including work performance, oxidative stress and body composition variables could not be combined in the meta-analysis. Trials reported no significant improvements in these measures. AUTHORS' CONCLUSIONS There is insufficient evidence to support improvement in physical or psychosocial outcomes of aerobic exercise in adults with Down syndrome. Although evidence exists which supports improvements in physiological and psychological aspects from strategies using mixed physical activity programmes, well-conducted research which examines long-term physical outcomes, adverse effects, psychosocial outcomes and costs are required before informed practice decisions can be made.
10.1002/14651858.CD005176.pub2
pubmed_294_21263
Membrane-bound Na, K-ATPase was digested with trypsin in the presence of Rb+ to form the stable 19-kDa and smaller fragments of the alpha-chain known to preserve occlusion of Rb+ (K+) or Na+. The trypsinized membranes obtained from pig kidney and shark rectal gland were analyzed by electron microscopy. Tryptic digestion preserved general membrane structure but removed both the surface particles observed by negative staining and the protruding cytoplasmic portion of the alpha-subunit identified in thin sections. However, intramembrane particles defined by freeze-fracture were preserved after trypsinization suggesting that the remaining membrane spanning protein fragments retain the native structure within the lipid bilayer after proteolysis.
10.1016/0014-5793(93)80910-m
pubmed_509_2960
AIM To demonstrate that human platelet-derived growth factor-B (PDGF-B) cDNA could be expressed in primary cultured cat corneal endothelia cells by using gene transfer techniques; to explore a useful tool for the further studies of the molecular mechanisms of corneal endothelium failure and provide a potential effective genetic therapy for the blind patients. METHODS Human PDGF-B cDNA was isolated from human placent by RT-PCR and inserted into pcDNA(4) vector to construct recombinant eukaryotic expression plasmid pcDNA(4)-PDGF-B. The full length was confirmed by the DNA sequencing analysis. By tearing endothelium technique we obtained pure single layer of cat corneal endothelial cells. The pcDNA(4)-PDGF-B eukaryotic expression vector was transferred into cat corneal endothelial cells by Effectene™ lipofectine. The transfection efficiency of Effectene™ lipofectine in pcDNA(4)-B was detected with pcDNA(4)-GFP. 5 days later, RT-PCR was used to check the PDGF-B expression. Cell viability was tested by modified tertrozalium salt (MTT) method. Cell morphology was observed under inverted phase contrast microscope. RESULTS The human PDGF-B cDNA was isolated successfully from healthy parturien placent tissue and the sequence was confirmed by computer automatic sequence and PCR analysis. Pure single layer cat corneal endothelial cells were successfully cultured by tearing endothelium technique. Effectene™ lipofectine transfection technique could be effectively used to transfer pcDNA(4)-PDGF-B into cat corneal endothelial cells in vitro, the transfection efficiency was 30%. RT-PCR result showed that human PDGF-B gene was highly expressed in transfected cat corneal endothelial cells. The expressed PDGF-BB protein promoted the viability of cat corneal endothelial cells. CONCLUSION Human platelet-derived growth factor-B (PDGF-B) cDNA could be highly expressed in cultured cat corneal endothelial cells by gene transfection techniques. Expressed PDGF-BB protein significantly promoted the viability of cat corneal endothelial cells, thus provided a potential effective method for corneal endothelium blindness genetic therapy.
10.3980/j.issn.2222-3959.2012.01.04
pubmed_680_20164
INTRODUCTION No studies have reported data on 2-year prevalence and recovery rates of self-reported COVID-19-related quantitative and qualitative olfactory and gustatory dysfunction. The aim of the present study was to estimate the 2-year prevalence and recovery rate of self-reported COVID-19-related olfactory and gustatory dysfunction in a cohort of patients with antecedent mild-to-moderate disease. METHODS This is a prospective observational study, measuring the prevalence of altered sense of smell or taste at follow-up and their variation from baseline, on adult patients consecutively assessed at Trieste University Hospital, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction during March 2020. RESULTS Overall, 174 (68.8%), 53 (20.9%), and 36 (14.2%) of 253 responders reported an altered sense of smell or taste (SNOT-22 >0) at baseline, 12 months, and 24 months, respectively. Among the 174 patients who have complained a COVID-19-associated olfactory or gustatory dysfunction at baseline, 138 (79.3%) reported complete resolution of smell or taste impairment with 17 subjects (9.8%) recovering after more than 1 year after the initial infection, 33 (19.0%) reported a decrease in the severity, and only 3 (1.7%) reported that the symptom was unchanged at the 24-month interview. Twenty subjects (7.9%) complained of at least one qualitative long-term symptom. CONCLUSION Two years after the infection, most patients experience a favourable evolution of COVID-19-related olfactory or gustatory dysfunction. A late recovery was observed in 10% of subjects.
10.1159/000525861
pubmed_967_429
In some 99mTc-iminodiacetic acid studies, separation of the gallbladder from the duodenum can be difficult, despite multiple views. When faced with this problem, we have had the patient ingest 250 cc of tap water. This ingestion clears the duodenum of activity and has allowed us to see the residual activity in the gallbladder. This "water-ida" view may be a useful addition in difficult to interpret hepatobiliary studies.
10.1007/BF00276464
pubmed_1122_9670
Ferric-nitrilotriacetate (Fe-NTA) is a known renal carcinogen. In the present study, we report the effect of a potent lignin-derived herbal antioxidant, nordihydroguairetic acid (NDGA), against Fe-NTA-mediated tissue toxicity. Fe-NTA (alone) treatment of mice enhances ornithine decarboxylase activity to 259% in liver and 341% in kidney and increases [3H]thymidine incorporation in DNA to 250% in liver and 324% in kidney compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 138 and 123%, respectively, in liver at a higher dose of 2 mg NDGA/day/animal whereas in kidney the reduction was to 118 and 102%, respectively, compared with the corresponding saline-treated controls. In the Fe-NTA (alone)-treated group, a 12% renal tumour incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA-promoted animals, the percentage tumour incidence was increased to 68% as compared with untreated controls. No tumour incidence was recorded in the DEN-initiated, non-promoted group. The administration of NDGA, afforded >80% protection against DEN- and Fe-NTA-mediated renal tissue injury in vivo. Fe-NTA treatment also enhanced hepatic and renal microsomal lipid peroxidation to 170 and 205% of saline-treated controls, respectively, and hydrogen peroxide generation by >2.5-fold in both tissues accompanied by a 51 and 21% decrease in the level of glutathione and 35-48 and 35-50% decrease in the activities of glutathione-metabolizing and antioxidant enzymes in liver and kidney, respectively. These changes were reversed significantly in animals receiving a pre-treatment of NDGA. Our data show that NDGA can abrogate the toxic and tumour-promoting effects of Fe-NTA in liver and kidney of mice and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and tumorigenesis.
10.1093/carcin/20.4.599
pubmed_547_18631
Quantitative structure-activity relationships (QSARs) within substrates, inducers and inhibitors of cytochromes P450 involved in xenobiotic metabolism are reported, together with QSARs associated with induction, inhibition and metabolic rate. The importance of frontier orbitals and shape descriptors, such as planarity (estimated by the area/depth(2) parameter) and rectangularity (estimated by the length/width parameter) is discussed, particularly in the context of the COMPACT system which discriminates between several P450 families associated with the activation and detoxication of xenobiotics. The use of parameters, particularly those derived from homology modelling of mammalian (especially human) P450s that are involved in exogenous metabolism, in generating QSARs for P450 substrates is discussed in the context of explaining differences in the binding affinities of human P450 substrates which are pharmacologically active.
10.1163/156856003321547112
pubmed_622_6358
High concentrations of thrombin (Thr) have been linked to neuronal damage in cerebral ischemia and traumatic brain injury. In the present study we found that Thr markedly enhanced swelling-activated efflux of (3)H-glutamate from cultured astrocytes exposed to hyposmotic medium. Thr (0.5-5 U/mL) elicited small (3)H-glutamate efflux under isosmotic conditions and increased the hyposmotic glutamate efflux by 5- to 10-fold, the maximum effect being observed at 15% osmolarity reduction. These Thr effects involve its protease activity and are fully mimicked by SFFLRN, the synthetic peptide activating protease-activated receptor-1. Thr potentiation of (3)H-glutamate efflux was largely dependent on a Thr-elicited increases in cytosolic Ca(2+) (Ca(2+) (i)) concentration ([Ca(2+)](i)). Preventing Ca(2+) (i) rise by treatment with EGTA-AM or with the phospholipase C blocker U73122 reduced the Thr-increased glutamate efflux by 68%. The protein kinase C blockers Go6976 or chelerythrine reduced the Thr effect by 19%-22%, while Ca/calmodulin blocker W7 caused a 63% inhibition. In addition to this Ca(2+)-sensitive pathway, Thr effect on glutamate efflux also involved activation of phosphoinositide-3 kinase (PI3K), since it was reduced by the PI3K inhibitor wortmannin (51% inhibition). Treating cells with EGTA-AM plus wortmannin essentially abolished Thr-dependent glutamate efflux. Thr-activated glutamate release was potently inhibited by the blockers of the volume-sensitive anion permeability pathway, NPPB (IC(50) 15.8 microM), DCPIB (IC(50) 4.2 microM), and tamoxifen (IC(50) 6.6 microM. These results suggest that Thr may contribute to the excitotoxic neuronal injury by elevating extracellular glutamate release from glial cells. Therefore, this work may aid in search of neuroprotective strategies for treating cerebral ischemia and brain trauma.
10.1002/glia.20513
pubmed_1023_13679
Results are presented of studying structural and functional changes in rat liver mitochondria during freezing-thawing in sucrose and saline medium. It is found that maximal disturbances in the structural and functional state of mitochondria are observed in the saline medium.
pubmed_1023_13679
pubmed_778_7626
PURPOSE Three cases of oral cavity mucosal verruciform xanthoma were studied to investigate the pathogenesis of verruciform xanthoma. METHODS Immunohistochemical staining with S-P and in situ hybridization using the probe to detect HPV mRNA and MMP-2, MMP-9 RNA. RESULTS The foam cells were strongly positive for CD68 (KP1) and Vimentin. The cytokeratin, PCNA and S-100 showed negative in foam cells. ISH testing failed to detect HPV (types 6, 11, 16, 18) in any of the three cases of verruciform xanthoma. MMP-2, MMP-9 showed positive staining in epithelial cells and foam cells. CONCLUSIONS Verruciform xanthoma is most likely not a human papillomavirus associated lesion and the foam cells like that, are most likely derived from monocyte-macrophage lineage.
pubmed_778_7626
pubmed_362_10779
The pyridazinone core has emerged as a leading structure for fighting inflammation, with low ulcerogenic effects. Moreover, easy functionalization of various ring positions of the pyridazinone core structure makes it an attractive synthetic and therapeutic target for the design and synthesis of anti-inflammatory agents. The present review surveys the recent advances of pyridazinone derivatives as potential anti-inflammatory agents to provide insights into the rational design of more effective anti-inflammatory pyridazinones.
10.1002/ardp.202200067
pubmed_216_169
PURPOSE to confirm or infirm structural modification of oral mycosis at the summit after fifteen days of wearing removable resin partial dentures. METHODS our study took place at the health center of Rufisque in Senegal from January to July 1998, involved fourteen patients divided into two groups according to sex: seven males and seven females who came for removable resin partial dentures. The macroscopic examination was conducted through to inspection and touching of mycosis at the level of toothless summit before the wearing of the denture. A biopsy was conducted on each patient before and after the wearing of the resin dentures. Tissue reaction was appreciated qualitatively through morphological analysis. RESULTS Before the wearing of the removable resin partial dentures 92.9% of patients had epithelial hyperplasia; 7.1% epithelial hypoplasia and 85.7% keratosis at the level of the chorion the number of collagen fibbers (28.6% discrete, 50% moderate, 21.4% important), fibroblasts (35.7% discrete; 42.9% moderate ; 21.4% important), inflammatory cells (71.4% discrete; 28.6% moderate; 0% important) and for blood vessels (64% discrete; 35.70% moderate; 0% important) after fifteen days of wearing partial denture. After fifteen days of the wearing removable resin partial dentures: 85.7% of patients had epithelial hyperplasia; 14.3% normal epithelial and 100% de keratosis at the level of the chorion the number of collagen fibbers (14.3% discrete; 21.4% moderate; 64.3% important), fibroblasts (42.9% discrete; 42.90% moderate; 14.3% important), inflammatory cells (50% discrete, 35.7% moderate: 14.3% important), blood vessels (43% discrete; 28.6% moderate; 28.6% important). CONCLUSION Biopsies of the summit are reliable contribution; they provide precise information on the quality of tissue supporting resin partial dentures. This tissues may seem healthy appearance (inspection and touching) but show sign of suffering at this anatomy-pathological examination.
pubmed_216_169
pubmed_1132_13175
PURPOSE It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls. METHODS We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype. RESULTS Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers. CONCLUSION A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.
10.1371/journal.pone.0059051
pubmed_768_4288
BACKGROUND To compare the safety and efficacy of saxagliptin 2.5 mg twice daily (BID) versus placebo add-on therapy to metformin immediate release (IR) in patients with type 2 diabetes and inadequate glycemic control with metformin alone. METHODS This multicenter, 12-week, double-blind, parallel-group trial enrolled adult outpatients with type 2 diabetes (glycated hemoglobin [HbA1c] 7.0%-10.0%) on stable metformin IR monotherapy (≥1500 mg, BID for ≥8 weeks). Patients were randomized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week, single-blind, placebo add-on therapy lead-in period. The primary end point was the change from baseline to week 12 in HbA1c. Key secondary end points included change from baseline to week 12 in fasting plasma glucose (FPG) and the proportion of patients achieving HbA1c <7.0% or HbA1c ≤ 6.5% at week 12. Efficacy was analyzed in all patients who received randomized study drug with ≥1 postbaseline assessment. Safety was assessed in all treated patients. RESULTS In total, 74 patients were randomized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy. At week 12, least-squares mean changes (95% CI) from baseline HbA1c (adjusted for baseline HbA1c) were significantly greater (P = 0.006) in the saxagliptin + metformin group -0.56% (-0.74% to -0.38%) versus the placebo + metformin group -0.22% (-0.39% to -0.06%). Adjusted mean changes from baseline in FPG were numerically greater with saxagliptin versus placebo; the difference (95% CI) -9.5 mg/dL (-21.7 to 2.7) was not statistically significant (P = 0.12). A numerically greater proportion of patients in the saxagliptin group than the placebo group achieved HbA1c < 7.0% (37.5% vs 24.2%) or HbA1c ≤6.5% (24.6% vs 10.7%). There were no unexpected safety findings. Hypoglycemia occurred in 4 patients (5.4%) in the saxagliptin group and 1 patient (1.2%) in the placebo group; confirmed hypoglycemia (symptoms plus fingerstick glucose ≤50 mg/dL) occurred in 1 patient in the placebo group. CONCLUSIONS Addition of saxagliptin 2.5 mg BID to metformin therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy reduced HbA1c compared with placebo added to metformin, with an adverse events profile similar to placebo and no unexpected safety findings. TRIAL REGISTRATION ClinicalTrials.gov NCT00885378.
10.1186/1472-6823-14-17
pubmed_19_8076
Existing approaches to non-drug regulation and induction of human sleep are analyzed with an attempt of their classification. The main attention is paid to the methods that utilize modern computer technologies of registration and analysis of various characteristics of human organism functioning, basically to the electroencephalogram (EEG). Normal human sleep EEG correlates and their changes during different sleep stages are reviewed. Modern opportunities to regulate and induce human sleep via utilization of different EEG characteristics are analyzed.
pubmed_19_8076
pubmed_374_21281
BACKGROUND Fractional exhaled nitric oxide (FENO) is a noninvasive strategy for diagnosing and managing asthma, but limited evidence is available for the effects of FENO-guided asthma management in children. This meta-analysis aimed to evaluate the effectiveness of FENO for asthma management in children. METHODS In total, six databases were searched, and 23 randomized controlled trials that compared the effects of FENO-guided asthma management with those not using FENO in pediatric asthma were included. Methodological quality was assessed using the Cochrane risk-of-bias tool. Data for relevant endpoints were extracted and analyzed. RESULTS Our meta-analysis of the effectiveness of FENO for asthma management in children showed that FENO-guided asthma management helped reduce the numbers of children with asthma exacerbations (risk ratio: 0.73; 95% confidence interval [CI:] 0.63-0.84; P < .0001) and the exacerbation frequency (standardized mean difference: -1.57; 95% CI: -2.25 to -0.88; P < .00001). Furthermore, it improved the predicted forced expiratory volume in 1 minute (weighted mean difference [WMD]: 3.67; 95% CI: 0.91-6.43; P = .009) and was also found to be associated with an increase of daily inhaled corticosteroid (ICS) dose (WMD: 64.17 μg; 95% CI: 53.59-74.75; P < .00001). CONCLUSIONS This meta-analysis indicated that the FENO-guided asthma management strategy could partially improve the outcomes of pediatric asthma at the expense of increased ICS use.
10.1002/ppul.24898
pubmed_117_8221
Squamous penile cancer displays a rare human papillomavirus (HPV)-associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.
10.1158/1535-7163.MCT-20-0173
pubmed_1129_2308
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocyte disorder most commonly characterized by multifocal osteosclerotic lesions of the long bones demonstrating sheets of foamy histiocyte infiltrates on biopsy with or without histiocytic infiltration of extraskeletal tissues. ECD can be difficult to diagnose since it is a very rare disease that can affect many organ systems. Diagnosis is based on the pathologic evaluation of involved tissue interpreted within the clinical context. Patients who have the BRAF V600E mutation are treated first line with vemurafenib. For those without the mutation with symptomatic ECD, conventional or PEGylated interferon alpha is recommended. For patients who are either intolerant or nonresponsive to interferon alpha, systemic chemotherapy with or without corticosteroids can be used. We present a rare case of Erdheim-Chester disease with concurrent Langerhans cell histiocytosis which occurs in only one fifth of the cases and often presents as a diagnostic and therapeutic challenge.
10.1155/2018/7865325
pubmed_949_19381
Vitamin K-dependent protein S, a cofactor of the anticoagulant enzyme-activated protein C, has four epidermal growth factor (EGF)-like modules, all of which have one partially hydroxylated Asp (EGF 1; beta-hydroxyaspartic acid) or Asn (EGF 2, 3, and 4; beta-hydroxyasparagine) residue. The three C-terminal modules have a typical Ca2+ binding sequence motif that is usually present in EGF modules with hydroxylated Asp/Asn residues. Using the chromophoric Ca2+ chelators Quin 2 and 5,5'-Br2BAPTA, we have now determined the Ca2+ affinity of recombinant fragments containing EGF modules 1-3, 1-4, 2-3, and 2-4. EGF modules 1-4 and 2-4 each contains two very high affinity Ca2+-binding sites, i.e. with dissociation constants ranging from 10(-10) to 10(-8) M in the absence of salt and from 10(-8) to 10(-6) M in the presence of 0.15 M NaCl. In contrast, in EGF 1-3 and EGF 2-3, the Ca2+ affinity is 2-4 orders of magnitude lower. EGF 4 thus appears to have the highest Ca2+ affinity, and furthermore it seems to influence the Ca2+ affinity of its immediate N-terminal neighbor EGF 3 by a factor of approximately 230. In addition, EGF 4 seems to influence the Ca2+ affinity of EGF 2 by a factor of approximately 25. The Ca2+ affinity of the binding sites in EGF modules 3 and 4 in fragments EGF 1-4 and EGF 2-4 is 10(3)-10(5)-fold higher than in the corresponding isolated modules, implying important contributions to the Ca2+ affinity of each module from interactions with neighboring modules. This difference is much higher than the approximately 10-fold difference previously found in similar comparisons of EGF modules from fibrillin. However, the modules studied in protein S and fibrillin appear to have the similar Ca2+ ligands. The structural basis for the difference in Ca2+ affinity is not yet understood.
10.1074/jbc.272.37.23255
pubmed_1054_4261
We have reported previously that during optic nerve regeneration in Rana pipiens, axons are misrouted into the opposite nerve and retina. In the present investigation we have examined the time course of formation of these "misrouted" axons and their cells of origin. The right eye of 31 frogs was injected with 3H-proline at various times after right optic nerve crush. In every frog examined 2 weeks and later after nerve crush, the distribution of autoradiographic label indicated that axons from the right eye had grown into the left optic nerve at the chiasm. The amount of label increased from 2 weeks to reach a maximum at 6 weeks where the entire left nerve was filled with silver grains. At 5 to 6 weeks after crush, labeled axons were found within the ganglion cell fiber layer (GCFL) of the retina of the opposite eye for a maximum distance of 2.3 mm from the optic disc. In frogs examined at intervals later than 6 weeks after crush, the amount of label within the left eye and nerve progressively decreased, indicating a gradual disappearance of the misrouted axons. Studies using anterograde transport of horseradish peroxidase (HRP) after nerve injection confirmed these autoradiographic findings. The position of ganglion cells in the right eye whose axons were misrouted to the left eye was determined by retrograde transport of HRP. Five or 6 weeks after crushing the right optic nerve, the left eye was injected with HRP and labeled ganglion cells were found throughout the right eye retina. The largest percentage of labeled cells was found within the ventral half of the retina, particularly within the temporal quadrant, and nearly all of the labeled cells were found in more peripheral portions of the retina. Since few retino-retinal axons are found during normal development, the present results show that the factors guiding regenerating axons in the adult frog differ substantially from those present during development.
10.1002/cne.901960407
pubmed_530_16018
This article presents an international perspective of the proposed changes to the DSM-5 for learning disabilities (LD) and attention-deficit/hyperactivity disorders (ADHD) across ten countries: Australia, Germany, Greece, India, Israel, Italy, Spain, Taiwan, the United Kingdom, and the United States. We provide perspectives of the present situation for youth with LD and youth with ADHD and describe the legislation, prevalence rates, and educational systems that serve students with disabilities in the respective countries. We also present a discussion of the expected impact of the proposed changes for the diagnosis of LD and ADHD in each country.
10.1177/0022219412464353
pubmed_942_6252
The granule-bound starch-synthases from normal and waxy maize kernels have been solubilized, partially purified, and characterized. Two broad categories of starch synthases were revealed with representatives in the soluble phase and also on granules from both normal and waxy maize though the activity associated with granules from waxy was small. Data for native molecular weights, kinetic parameters, and immunological relatedness are used to demonstrate that the granule-bound isozymes from normal maize are different from the soluble enzymes. These distinct granule-bound enzymes are missing in waxy maize granules and a further novel form of starch synthase is revealed. These findings are discussed in relation to the type of starch produced in tissue affected by the waxy mutation.
10.1104/pp.78.4.849
pubmed_646_11880
Myositis ossificans circumscripta (MOC) is an uncommon disease that has been reported to develop after trauma, burns, and infections, as well as in cases in which the pathogenesis is unknown. Although most cases of MOC develop below the clavicles, it has been reported in the head and neck area, where it primarily involves the muscles of mastication. To our knowledge, there have been only 4 previous reports of MOC affecting the paraspinal muscles. We report the fifth such case, which developed in a human immunodeficiency virus-positive patient, and describe the longitudinal imaging changes of MOC.
10.1001/archotol.126.6.785
pubmed_585_22456
Anoxia modulates the expression of molecules associated with endothelial dysfunction and vascular diseases. Polyphenols have potent antioxidant properties due to their ability to modulate genes involved in oxidative tissue damage. In this study, we investigated the effect of polyphenol extract from olive pomace (PEOP) and its main constituents, Tyrosol and Oleuropein, on endothelial cells subjected to anoxia by evaluating the expression of molecules critical for endothelial function, proliferation and migration, and the signaling pathway involved. EAhy926 human endothelial cells were exposed to anoxic stress in the presence or absence of PEOP. Anoxia increased the nitric oxide (NO) level and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNFα). These effects were prevented by PEOP treatment in a dose-dependent manner. Moreover, PEOP prevented the proliferation and migration associated with anoxia in EAhy926 cells, down-regulated the levels of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type-1 MMP (MT1-MMP) and increased tissue MMP inhibitor-1 (TIMP-1) expression. Purified Oleuropein or Tyrosol restored to a basal level the anoxia-induced expression of MMP-9 and partially of MMP-2. The expression of TNFα was reduced by both polyphenols in a dose-dependent manner, but more efficiently by Tyrosol. Conversely, Oleuropein and Tyrosol had no significant effects on iNOS, COX-2 and TIMP-1 expression when used at the concentration found in PEOP. PEOP induced a time-dependent phosphorylation of p38 MAPK and ERK1/2 and inhibited anoxia-induced NF-κB activation. PEOP treatment restores the endothelial functions that are impaired by anoxia by regulating the expression of genes involved in proteolysis, angiogenesis and inflammation more efficiently than the single purified components. Therefore, the combined use of polyphenols, as in PEOP, could represent a powerful tool for the treatment and chemoprevention of endothelial dysfunction-associated vascular diseases.
10.1016/j.mvr.2012.02.010
pubmed_1109_19387
The use of embryonic stem cells (ESCs) to regenerate distal lung epithelia damaged by injuries or diseases requires development of safe and efficient methodologies that direct ESC differentiation into transplantable distal lung epithelial progenitors. Time-consuming culture procedure and low differentiation efficiency are major problems that are associated with conventional differentiation approaches via embryoid body formation. The use of a growth factor cocktail or a lung-specific cell-conditioned medium to enrich definitive endoderm for efficient differentiation of mouse ESCs (mESC) into alveolar epithelial progenitor type II cells (ATIICs) has been reported, but not yet successful for generating a homogenous population of ATIICs for tissue regeneration purpose, and it remains unclear whether or not those mESC-derived ATIICs possess normal biological functions. Here, we report a novel method using a genetically modified mESC line harboring an ATIIC-specific neomycin(R) transgene in Rosa 26 locus. We showed that ATIICs can be efficiently differentiated from mESCs as early as day 7 by culturing them directly on Matrigel-coated plates in DMEM containing 15% knockout serum replacement. With this culture condition, the genetically modified mESCs can be selectively differentiated into a homogenous population (>99%) of ATIICs. Importantly, the mESC-derived ATIICs (mESC-ATIICs) exhibited typical lamellar bodies and expressed surfactant protein A, B, and C as normal control ATIICs. When cultured with an air-liquid-interface culture system in Small Airway Epithelial Cell Growth Medium, the mESC-ATIICs can be induced to secrete surfactant proteins after being treated with dibutyryl cAMP+dexamethasone. These mESC-ATIICs can synthesize and secrete surfactant lipid in response to secretagogue, demonstrating active surfactant metabolism in mESC-ATIICs as that seen in normal control ATIICs. In addition, we demonstrated that the selected mESC-ATIICs can be maintained on Matrigel-coated plates for at least 4 days with robust proliferative capacity. When cultured in DMEM medium containing 10% FBS, mESC-ATIICs spontaneously differentiated into alveolar epithelial type I cells. Collectively, these data demonstrate that the genetically modified mESCs can be selectively differentiated into a homogenous population of functional ATIICs, providing a reliable cell source to explore their therapeutic potential in lung tissue regeneration.
10.1089/ten.TEC.2013.0415
pubmed_842_21247
PURPOSE The National Health Service (NHS) Local Improvement Finance Trust (LIFT) programme was launched in 2001 as an innovative public-private partnership to address the historical under-investment in local primary care facilities in England. The organisations from the public and private sector that comprise a local LIFT partnership each have their own distinctive norms of behaviour and acceptable working practices - ultimately different organisational cultures. The purpose of this article is to assess the role of organisational culture in facilitating (or impeding) LIFT partnerships and to contribute to an understanding of how cultural diversity in public-private partnerships is managed at the local level. DESIGN/METHODOLOGY/APPROACH The approach taken was qualitative case studies, with data gathering comprising interviews and a review of background documentation in three LIFT companies purposefully sampled to represent a range of background factors. Elite interviews were also conducted with senior policy makers responsible for implementing LIFT policy at the national level. FINDINGS Interpreting the data against a conceptual framework designed to assess approaches to managing strategic alliances, the authors identified a number of key differences in the values, working practices and cultures in public and private organisations that influenced the quality of joint working. On the whole, however, partners in the three LIFT companies appeared to be working well together, with neither side dominating the development of strategy. Differences in culture were being managed and accommodated as partnerships matured. RESEARCH LIMITATIONS/IMPLICATIONS As LIFT develops and becomes the primary source of investment for managing, developing and channelling funding into regenerating the primary care infrastructure, further longitudinal work might examine how ongoing partnerships are working, and how changes in the cultures of public and private partners impact upon wider relationships within local health economies and shape the delivery of patient care. ORIGINALITY/VALUE To the authors' knowledge this is the first study of the role of culture in mediating LIFT partnerships and the findings add to the evidence on public-private partnerships in the NHS.
10.1108/14777261111178538
pubmed_937_12302
DNA sequencing of the antigen receptor genes remains the gold standard for the establishment of clonal relationships between samples. However, a variety of strategies may be employed as surrogates for the determination of the actual sequence of the clonally rearranged antigen receptor genes. The methods described in this chapter provide a framework for the rapid determination of clonal relationships between (microdissected) lymphoid populations. All of the methods described are PCR-based because of its versatility and ability to utilize very small amounts of DNA. For illustration purposes, the descriptions have been confined to B-cell populations. Although not described here, Ig kappa or Ig lambda PCR may also be utilized for determination of B-cell clonality and clonal relationships in the same manner. Similarly, the principles utilized may be extended to T-cell populations and T-cell receptor chain genes. Regardless of the methodology or targets involved, it is strongly recommended that all assays on microdissected material be run on parallel replicates of each sample to ensure reproducibility of results. The information about clonal relationships obtained by LCM has more than an academic significance and has utility in routine diagnostics for the establishment of minimal residual disease and the determination of microscopic disease recurrence vs the development of a secondary malignancy.
10.1016/s0076-6879(02)56936-6
pubmed_528_22549
Cadherin-mediated cell-cell interactions are dynamic processes, and cadherin function is tightly regulated in response to cellular context and signaling. Ultimately, cadherin regulation is likely to reflect the interplay between a range of fundamental cellular processes, including surface organization of receptors, cytoskeletal organization and cell trafficking, that are coordinated by signaling events. In this review we focus on recent advances in understanding how interplay with membrane trafficking and other cell-cell junctions can control cadherin function. The endocytosis of cadherins, and their post-internalization fate, influences surface expression and metabolic stability of these adhesion receptors. Similarly, at the surface, components of tight junctions provide a mode of cross-talk that regulates assembly of adherens junctions.
10.1016/j.ceb.2007.09.008
pubmed_271_15557
Among the many complications of celiac disease, mesenteric lymph node syndrome cavitated is considered one of the rarest, there is few case series published in the literature. The etiology and pathophysiology are unknown but because of its high mortality rate, estimated to be around 50%, it should recognize at an early stage in order to institute appropriate therapy as soon as possible.
10.4321/s1130-01082011001200009
pubmed_675_20985
A simple dual-colour fluorescent nanoprobe has been designed composed of blue and yellow emission carbon quantum dots (CQDs). This system is inexpensive and easy to operate and was successfully employed for on-site measurements based on a smartphone app. The designed nanoprobe exhibited increased selectivity for Cr(VI), leading to a double stable response of the two CQDs. The dual-emission nanoprobe showed blue-violet fluorescence upon UV irradiation, and the fluorescent emission peaks were located at 418 nm and 552 nm. The blue light emission of CQDs was quenched with increasing Cr(VI) concentration due to the inner filter effect, whereas the yellow light emission was enhanced due to the aggregation-induced emission effect. The different responses of the dual emissions to Cr(VI) resulted in a fluorescent colour variation, thus enabling facile macroscopic visualization. With a smartphone, the change in the fluorescence colour could be observed more apparently than that of a single fluorescence nanoprobe, and the response increased linearly so that the nanoprobe could be applied to instantaneous measurements. Furthermore, the dual-emission nanoprobe was successfully employed for analysing food and water samples. Accurate concentrations were obtained by constructing a calibration plot using a fluorescence spectrometer and a smartphone app; the recoveries were 81.6% to 107.7%, and the relative standard deviation was below 3.6%. Therefore, this smartphone-integrated dual-emission detection system is promising as a new portable method for the on-site measurement of Cr(VI) ions. * Y-CQDs: yellow emission carbon quantum dots. B-CQDs: blue emission carbon quantum dots. B/Y-CQDs: a mixture of B-CQDs and Y-CQDs.
10.1007/s00604-021-04747-8
pubmed_595_16940
The ionophore lasalocid A forms 1:1 complexes with phenethylamines (1-amino-1-phenylethane and 1-amino-2-phenylethane) and catecholamines (dopamine and norepinephrine) in nonpolar solution. We have undertaken high-resolution proton nuclear magnetic resonance studies to deduce structural and kinetic information on the ionophore-biogenic amine complexes in chloroform solution. The coupling constant, chemical shift, and relaxation time data demonstrate that the lasalocid backbone conformation and the primary amine binding sites in the complexes are similar to those determined earlier for the alkali and alkaline earth complexes of this ionophore in solution. The exchange of lasalocid between the free acid (HX) and the primary amine complexes (RNH(3)X) in chloroform solution have been evaluated from the temperature-dependent line shapes at superconducting fields. The kinetic parameters associated with the unimolecular dissociation [Formula: see text] and the bimolecular exchange [Formula: see text] reactions have been deduced from an analysis of the lifetime of the complex as a function of the reactant concentrations. The relative stability of the complex decreases in the order phenyl > n-pentyl for substituents on the carbon alpha to the amino group (1-amino-1-phenylethane and 2-aminoheptane) and phenyl > 3,4-dihydroxyphenyl for substituents on the carbon beta to the amino group (1-amino-2-phenylethane and dopamine). These results suggest that nonpolar interactions between the biogenic amine side chain and the lasalocid molecule contribute to the stability of the complex in solution.
10.1073/pnas.74.11.4734
pubmed_1037_15324
Crenobalneotherapy is a treatment commonly used in Europe and Middle East. It uses mineral water sometimes combined with different hydrotherapy techniques. Most patients treated in spa centers suffer from low back pain. The purpose of this work is to identify clinical trials on crenobalneotherapy for low back pain. Publication research was performed on Medline, Cochrane, and PEDRO databases. Clinical trials were analyzed for internal validity, external validity, quality of statistical analysis, and quality of collection of adverse events. We present the best level of evidence. Bibliographic research identified 21 clinical trials and the coauthors added 5 references. The 26 trials represent 2695 patients. Some have good methodological quality and allow considering crenobalneotherapy as a potential treatment for low back pain, even if the role of mineral water remains uncertain. The methodological quality of therapeutic trials should be improved. These trials should be analyzed in the future guidelines on low back pain.
10.1007/s00484-021-02188-9
pubmed_638_13406
Knocking out primary cilia of adult mouse tissues or a specific subset of cilia from POMC-expressing neurons in the brain initiates uncontrolled eating. This behavior leads to obesity and kidney disease.
10.1016/j.cub.2007.09.006
pubmed_388_933
A gene 32 amber (am) mutant, amNG364, fails to grow on Escherichia coli Su3+ high temperatures, suggesting that the tyrosine residue inserted at the am codon by Su3+ leads to a temperature-sensitive gene 32 protein (P32). By plating amNG364 on E. coli Su3+ 45 degrees C, several pseudorevertants were found that proved to contain a suppressor (su) mutant in addition to the original am mutation. Crosses of two of these amNG364su strains to am+ phage indicated that the suppressors themselves are in or close to gene 32. Phage strains carrying either of the two su mutations, without amNG364, grew normally. When cells were infected by these su mutants and the proteins produced were examined by sodium dodecyl sulfate-gel electrophroesis, specific overproduction of P32 was found. Maximum overproduction compared to am+ phage was 6.6-fold for one su mutant and 2.4-fold for the other. Other proteins were produced in normal amounts and in normal time sequence. When amNG364su phage were allowed to infect E. coli S/6/5(Su-), the gene 32 am fragments produced were present at the same derepressed levels as in an infection by amNG364 without a suppressor. The suppressor mutations are interpreted as causing derepression of P32 by altering sites in this autogenously regulated protein involved in template recognition. Previously, specific derepression of gene 32 had only been shown using gene 32 conditional lethal mutants grown under restrictive conditions. We have shown that P32 can also be derepressed under permissive conditions, indicating that loss of P32 function is not necessary for specific derepression.
10.1128/JVI.21.2.619-625.1977
pubmed_1132_1880
A polysaccharide from Ganoderma atrum (PSG-1) was purified and characterized, and its hypoglycemic and hypolipidemic effects were investigated in high fat diet- and streptozotocin-induced type 2 diabetic rats. Oral administration of PSG-1 at 200 or 400 mg/kg body weight significantly reduced fasting blood glucose and serum insulin levels. PSG-1 significantly decreased the levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, free fatty acid and insulin resistance, and increased high-density lipoprotein cholesterol level and insulin sensitivity. In addition, PSG-1 inhibited the expression of pro-apoptotic protein, Bax and increased the expression of anti-apoptotic protein, Bcl-2 in pancreatic cells, suggesting that PSG-1 exerted a protective role in the pancreas of diabetic rats. These results indicated that PSG-1 may have a potential for the treatment of hyperglycemia, hyperlipidemia, hyperinsulinemia and insulin resistance in type 2 diabetes.
pubmed_1132_1880
pubmed_839_15089
The effect of medium supplementation on heterologous production of human serum transferrin (hTF) in the fission yeast Schizosaccharomyces pombe has been investigated. The productivity of recombinant hTF was low in wild-type S. pombe cells. To overcome this impediment, culture media supplements were screened for their ability to improve secretion of hTF. Casamino acids (CAA), which have been reported to increase heterologous protein productivity in Pichia pastoris, improved the secretion hTF by more than fourfold. An anion surfactant deoxycholate or polyethylene glycol also improved the secretion hTF. Interestingly, dextran sodium sulfate (DSS), a poly-anion surfactant, was found to enhance production of secreted hTF better than any other supplement tested. Addition of DSS in the presence of 2% CAA exhibited a synergistic effect on increasing hTF secretion, resulting in an increase of about sevenfold relative to conventional conditions. Cell growth was not found to be affected by the addition of DSS or CAA. DSS may act as a surfactant and may also facilitate the anchoring of liposomes, and these properties may contribute to efficient secretion or exocytosis through the plasma membrane.
10.1007/s00253-009-2130-5
pubmed_878_15930
BACKGROUND The presence of diabetes and plasma glucose concentration on admission are associated with adverse outcomes after an acute myocardial infarction (AMI), as high glucose can induce vascular endothelial cell apoptosis. This study explored the relative associations among admission plasma glucose level, soluble Fas (sFas) concentration, and long-term survival in patients with acute ST-elevation myocardial infarction (STEMI). METHODS This prospective cohort study include 83 patients with acute STEMI. Based on their admission plasma glucose levels (7.8 and 11.1 mmol/L as the limits for low and high levels, respectively), patients were allocated into one of three groups: normal glucose (n = 33), median glucose (n = 24), and high glucose (n = 26). The admission plasma level of sFas was measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Patients were followed up for an average of 89 ± 20 months for all causes of death and cardiovascular death. RESULTS sFas levels were significantly higher in the high glucose group compared to the normal glucose group (5.87 ± 1.70 mmol/L vs. 3.07 ± 0.93 mmol/L, respectively, P < 0.05). The sFas level was positively associated with the admission plasma glucose level. The correlation coefficient (R) was 0.747, and R2 was 0.559. Mortality was significantly higher in the high glucose group compared to the normal glucose group (19.2% vs. 3.0%, respectively, P < 0.05). CONCLUSIONS In patients with acute STEMI, plasma glucose level was high on admission, and sFas apoptosis levels were increased. Long-term follow-up revealed that a high admission plasma glucose level was associated with higher mortality compared to a normal admission glucose level.
10.1186/1475-2840-12-171
pubmed_1128_9187
The in vivo conditions needed for the induction of nitrogen oxide synthesis by hepatocytes were determined. Hepatocytes obtained from rats injected with killed Corynebacterium parvum spontaneously produced NO2(-)+NO3- in culture and were found to contain cytosolic enzyme activity for nitrogen oxide synthesis. The enzyme activity required both L-arginine and NADPH, and was not found in hepatocytes obtained from normal rats or rats injected with lipopolysaccharide (LPS) alone. In contrast, nonparenchymal cells were stimulated to synthesize NO2(-)+NO3- by LPS. These results show the presence of inducible cytosolic enzyme activity for nitrogen oxide synthesis in hepatocytes, which is distinct from nonparenchymal cell NO. synthesis.
10.1016/0006-291x(90)91133-d
pubmed_1010_16759
This study explored parenting styles and values internalization. Perceived parenting styles were measured in Grade 7 (n = 749) and Grade 12 (n = 468), and values were measured in Grade 12 (n = 271) and one year postschool (n = 291). We measured three aspects of valuing: priority (extrinsic, intrinsic importance); regulation (controlled, autonomous); and successful enactment of values (success). Mothers' authoritative parenting in Grade 7 predicted increased importance and autonomous regulation of values one year postschool. Fathers' authoritative parenting in Grade 7 predicted decreased importance of extrinsic values. Fathers' permissive parenting in Grade 7 predicted decreased importance of intrinsic values. Authoritarian parenting in Grade 12 predicted more controlled values regulation postschool, particularly for extrinsic values. Parenting in early and late adolescence predicts values internalization in emerging adulthood.
10.1111/jora.12542
pubmed_265_14229
Low birth weight is still important health problem in many countries. Children's low birth weight increases mortality, injures central nervous system, somatic, interferes with intellectual and emotional development. Low birth weight is frequently occurring in Poland--between 7-9% of live births. There are many risk factors, among them behavioural and environmental. In Poland an attention was put on chemical and physical environmental factors. Behavioural factors (stress) are disregarded. In the present paper it was decided to check the relationship between stress during pregnancy (estimated by pregnant), child birth weight and frequency of low birth weight. The research was carried out by use of a questionnaire using the "case-control study". In the research were involved 450 mothers of new-born children (the group of cases: untimely, premature delivery or child birth weight below 2500 g) and 450 mothers of new-born children (control group-physiologically delivered). Mothers were asked about their relations to the pregnancy; professional and personal stress during pregnancy was estimated. The results were analysed by counting risk ratio coefficient (RR) and correlation coefficient. The research showed, that there is no relation between acceptation of pregnancy, stress and frequency of low birth weight or the average child birth weight. The researches didn't prove unfavourable influence of stress reaction caused by professional and personal stressors on intrauterine foetus development.
pubmed_265_14229
pubmed_407_18623
Mixed zinc-lanthanide (Zn-Ln) metal-organic frameworks (MOFs) based on the 3,5-pyrazoledicarboxylate ligand exhibit an unusual three-dimensional (3D) inorganic subnetwork and display highly efficient photoluminescence.
10.1039/c2cc33223j
pubmed_310_10858
Ran, which functions in nucleocytoplasmic transport and mitosis, binds to and is regulated in part by RanBP1. We have identified a zebrafish RanBP1 cDNA and report that it encodes for a polypeptide of 233 amino acids with considerable similarity to human and Xenopus RanBP1, despite the fact that it is 10% longer due to an extension at its carboxy terminus. RanBP1 mRNA is present as a maternal transcript and is expressed ubiquitously throughout the developing embryo. At the protein level, RanBP1 is present at all embryonic stages. Surprisingly, the ectopic overexpression of the protein had no obvious effect on embryogenesis. Attempts were also made to down-regulate RanBP1 activity by RNA interference. Injecting double-stranded RNA augmented both the mortality rate and the frequency of induced defects. Specific defects accompanied by changes in RanBP1 expression were not seen, leading us to propose that RNAi is not a reliable method for deregulating the activity of constitutively expressed genes, like RanBP1, in zebrafish. Mol. Reprod. Dev. 59:235-248, 2001.
10.1002/mrd.1028
pubmed_335_20610
Forest fire risk depends on the hazard factors, affected body, and hazard prevention and reduction ability. The integrated risk assessment is the foundation for developing scientific fire mana-gement policies and carrying out the forest fire prevention measures. A forest fire risk assessment model and index system were established based on the classic natural disaster risk model and available data, and the model was used to assess the forest fire risks in past and future. The future climate scenario data included outputs from five global climate models (GFDL-ESM2M, HadGEM2-ES, IPSL-CM5A-LR, MIROC-ESM-CHEM and NorESM1-M) for RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5, respectively. Each component index of Fire Weather Index (FWI) system was calculated daily for each grid in 1987-2050 for the historical observations and future climate scenarios according to the maximum temperature, minimum relative humidity, wind speed and daily precipitation. The results showed that areas with high and very high fire danger ratings in 1987-2010 accounted for 21.2% and 6.2%, respectively, which were distributed in Greater Xing'an Mountains and the Changbai Mountain area, most parts of Yunnan, and many fragment areas in southern China. The areas with high and very high burn possibilities were mainly distributed in the northeast and southwest region, accounting for 13.1% and 4.0%, respectively. Compared with the observation period, the areas with high and very high fire danger ratings in 2021-2050 would increase by 0.6%, 5.5%, 2.3%, and 3.5% under RCP 2.6, RCP 4.5, RCP 6.0, and RCP 8.5 respectively, and North China would show significant increase. The regions with high-risk forest fires would also increase due to climate change, with the most significant increase under RCP 8.5 scenario (+1.6%).
10.13287/j.1001-9332.201603.034
pubmed_462_18380
This in vitro study investigated the effect of dental surface treatments on the seal of porcelain and resin laminate veneers to tooth structure. Nine groups of 20 teeth were prepared for labial veneers--six groups with the apical margin of the veneer in dentin, two groups with the veneer wholly bordered by enamel, and one group with the apical margin coincident with the apical margin of a previously placed glass ionomer restoration. The teeth were treated with a variety of dentin-bonding agents prior to restoration of eight groups with porcelain veneers and one group with Visio-Gem microfilled resin veneers. After placement, the veneers were stored in water for 4 days, then subjected to thermocycling before silver staining and sectioning. Results showed no leakage around the margins of the veneers wholly bordered by enamel. Complete leakage was found around the glass ionomer restorations, and nearly total leakage was found along the resin-dentin interface of the resin veneers. The porcelain veneers that extended onto dentin showed variable but limited leakage for four of five of the dentin-bonding treatments.
10.1016/0022-3913(92)90038-c
pubmed_781_23816
This study investigated the ion mobility (IM) and the collision cross section (CCS) of fatty acids (FAs) using electrospray IM MS. The IM analysis of 18 FA ions showed intriguing differences among the saturated FAs, monounsaturated FAs, multi-unsaturated FAs, and cis-isomer/trans-isomer with respect to the aliphatic tail chains. The length of aliphatic tail chain present in the ion structures had a strong influence on the differentiation of drift, while the number of double bond showed a weaker influence. The tiny drift differences between cis-isomer and trans-isomer were also observed. In the CCS measurements, two internal standards were involved in the mobility calibration and accuracy estimation. It insured our empirical CCS values were of high experimental precision (±0.35% or better) and accuracy (±0.25% or better). Moreover, the mass-to-charge ratio (m/z) - mobility plots obtained by ion mobility spectrometry with mass spectrometry analysis of FAs - was used to investigate the structural relationship between the molecules. Each series of FAs sharing a similar structure was aligned in the linear plot. Finally, the developed procedure was applied to the determination of FAs in rat adipose tissues, and it allowed the presence of 13 FAs to be confirmed with their exact masses and CCS values. These studies reveal the direct relationship between the behaviors in IM and the molecular structures and thus may provide further validations to the FA identification process.
10.1002/jms.3600
pubmed_405_23433
OBJECTIVES Phyllocaulis boraceiensis mucus has been studied as a potential source of new natural compounds that are capable of inducing proliferation and remodeling tissue. The aim of this study was to evaluate the clinical aspects of healing in the wounded mouse skin, which was treated with an ointment that was composed of mucus, which was released by P boraceiensis. MATERIALS & METHODS Mice were submitted to a 1-cm dorsal excision. The control group (T1) was treated with papain; the T2 group was treated with papain that was associated with 0.18 μg/μL of mucus; and the T3 group was treated with papain that was associated with 0.012 μg/μL of mucus. RESULTS Accelerated proliferation was observed after 3 days in the T3 group, presenting a high deposition of fibroblasts at the wound margin, whereas accelerated proliferation in the T1 group began 5 days after surgery. The T2 group presented inflammation during all periods of observation, and even when healing had already begun, the new tissue showed capillary fragility. Remodeling began after 4 days in the T3 group, whereas remodeling began after 6 days in the other groups. T3 showed edema, hyperemia, and bleeding only until the fifth day, and granulation and scar tissues intensely appeared from the 11th day forward. T1 and T2 groups exhibited edema, hyperemia, and bleeding until the 11th day, and granulation and scar tissues appeared after the 13th day. CONCLUSION The healing process and wound closure were efficient after the daily application of 0.012 μg/μL P boraceiensis mucus.
10.1097/01.ASW.0000456683.55591.af
pubmed_793_2614
This paper presents two unique aspects of aerospace psychiatry: the influence of the specialized stressors and occupational requirements of an aviation career and the ambiguous role of the aerospace psychiatrist. Aerospace psychiatrists have multiple, sometimes conflicting, responsibilities to the organization and society (the social control task) and to the individual aviator (the humanistic and medical tasks). In the two case reports below the authors describe airmen who had vasovagal syncope and how the psychiatrist intervened and resolved these conflicting tasks.
10.1176/ajp.137.8.956
pubmed_565_10060
Lichen sclerosus et atrophicus is a chronic inflammatory disease that mainly affects women in the 5th decade. Although lichen sclerosus most often affects the anogenital region, it may occur in other cutaneous or mucosal sites. Increased fibroblast activity causes cutaneous sclerosis. Recent studies have identified lichen sclerosus as an autoantibody-mediated chronic inflammatory dermatosis. Autoantibodies against the extracellular matrix protein-1 are present in up to 80% of affected patients. In addition to the well-accepted therapy with potent corticosteroids, promising results have been obtained using calcineurin antagonists in the treatment of lichen sclerosus. Interdisciplinary management with regular monitoring can improve the clinical manifestations and quality of life.
10.1007/s00105-005-0955-0
pubmed_614_6326
Endosymbiotic bacteria of the genus Wolbachia often manipulate the reproductive system of their hosts to propagate themselves in host populations. Ostrinia scapulalis moths infected with Wolbachia (wSca) produce female-only progeny (sex chromosomes: ZW), whereas females cured of the infection by antibiotic treatment produce male-only progeny (ZZ). The occurrence of female- and male-only progeny has been attributed to the specific death of the opposite sex during embryonic and larval development. In this bidirectional sex-specific lethality, embryos destined to die express a phenotypic sex opposite to their genotypic sex. On the basis of these findings, we suggested that wSca carries a genetic factor that feminizes the male host, the W chromosome of the host has lost its feminizing function, and discordance between the genotypic and phenotypic sexes underlies this sex-specific death. In the present study, we examined whether the failure of dosage compensation was responsible for this sex-specific mortality. Quantitative PCRs showed that Z-linked gene expression levels in embryos destined to die were not properly dosage compensated; they were approximately two-fold higher in the male progeny of wSca-infected females and approximately two-fold lower in the female progeny of infected-and-cured females. These results support our hypothesis that misdirection of dosage compensation underlies the sex-specific death.
pubmed_614_6326
pubmed_191_9961
UNLABELLED Topical retinoic acid has demonstrated its efficacy in acne. Glycolic acid has also keratolytic action and could be interesting to treat acne. OBJECTIVE To evaluate the efficacy and safety of topical glycolic acid (Glyco A 12%) and retinoin acid (Kefrane 0.05%) on facial acne lesions. METHOD It was a randomised double blind study of 40 patients, divided in 2 groups, 20 receiving GlycoA cream (Group A) and 20 receiving Kefrane cream (group B). Medical exam was realised by the same physician at day 0, 21 and 45. The improvement of acne as well as side effects were assessed by both the physician and the patients themselves. RESULTS 2 patients developed severe eczema of the face and were excluded (one from group A and one from group B). 22 patients followed totally the study. 90% of group A and 83.3% of group B patients improved significantly their lesions. A comparative tolerability was observed for both groups. CONCLUSION Glyco A cream could be a good treatment for acne even in dark skin patients.
pubmed_191_9961
pubmed_868_16589
Both in the performative arts and in emotion research, professional actors are assumed to be capable of delivering emotions comparable to spontaneous emotional expressions. This study examines the effects of acting training on vocal emotion depiction and recognition. We predicted that professional actors express emotions in a more realistic fashion than non-professional actors. However, professional acting training may lead to a particular speech pattern; this might account for vocal expressions by actors that are less comparable to authentic samples than the ones by non-professional actors. We compared 80 emotional speech tokens from radio interviews with 80 re-enactments by professional and inexperienced actors, respectively. We analyzed recognition accuracies for emotion and authenticity ratings and compared the acoustic structure of the speech tokens. Both play-acted conditions yielded similar recognition accuracies and possessed more variable pitch contours than the spontaneous recordings. However, professional actors exhibited signs of different articulation patterns compared to non-trained speakers. Our results indicate that for emotion research, emotional expressions by professional actors are not better suited than those from non-actors.
10.1007/s10919-015-0209-5
pubmed_569_6149
We demonstrate the application of Atomic Force Microscopy (AFM) for mapping optical near-fields with nanometer resolution, limited only by the AFM probe geometry. By detecting the optical force between a gold coated AFM probe and its image dipole on a glass substrate, we profile the electric field distributions of tightly focused laser beams with different polarizations. The experimentally recorded focal force maps agree well with theoretical predictions based on a dipole-dipole interaction model. We experimentally estimate the aspect ratio of the apex of gold coated AFM probe using only optical forces. We also show that the optical force between a sharp gold coated AFM probe and a spherical gold nanoparticle of radius 15 nm, is indicative of the electric field distribution between the two interacting particles. Photo Induced Force Microscopy (PIFM) allows for background free, thermal noise limited mechanical imaging of optical phenomenon over wide range of wavelengths from Visible to RF with detection sensitivity limited only by AFM performance.
10.1038/srep10610
pubmed_175_15945
Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB/c mice develop an acute infection with B. pseudomallei, whereas the C57BL/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD50 of the B. pseudomallei K96243 strain in both female and male BALB/c and C57BL/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis.
10.3390/pathogens9020113
pubmed_374_18817
Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred, with peaks in 1999, 2004, and 2008. We conducted whole-genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik, Iceland, from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types, emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a 2-fold increased penicillin G and ampicillin MIC among the isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A) and Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern.
10.1128/JCM.00638-20
pubmed_147_20809
Although some theorists conceptualize the relationship between emotion dysregulation and suicidal behavior as direct, recent research suggests that this relationship may be indirect and mediated by repeated experiences with certain behaviors (e.g., non-suicidal self-injury; NSSI) common among individuals with heightened emotion dysregulation. To date, however, this research has been limited in both scope (e.g., examining few components of emotion dysregulation) and generalizability (e.g., over-emphasis on undergraduate samples). This study sought to extend the research in this area by examining the mediating role of NSSI in the association between one relevant aspect of emotion dysregulation (i.e., low distress tolerance [DT]) and suicidal behavior with a clear intent to die among an at-risk sample of substance use disorder (SUD) patients in residential treatment. SUD patients (N=93) completed a structured interview assessing past suicidal behavior and questionnaires assessing DT and NSSI. Consistent with hypotheses, results revealed a significant indirect association between low DT and lifetime suicide attempts through NSSI frequency. These results suggest that exposure to painful and provocative events through experience with NSSI may be one pathway through which certain facets of emotion dysregulation increase the risk for suicidal behaviors (consistent with theories that individuals low in DT may be unable and/or unwilling to engage in suicidal behavior unless they have experienced sufficient levels of painful and/or provocative events capable of changing their relationship with and experience of pain and fear of death).
pubmed_147_20809
pubmed_630_7790
We present preliminary clinical experience with combined consideration of the commonly used BMI (body mass index) and the newly developed ABSI (a body shape index) using a point of care anthropometric calculator for comparisons of index values and associated relative risks to population normals. In a series of 282 patients, BMI and ABSI were close to being independently distributed, supporting the value of considering both indices. Three selected cases illustrate scenarios where assessment of ABSI together with BMI could inform patient care and counseling. These data suggest that combined assessment of BMI and ABSI may prove useful in clinical practice.
10.1155/2016/1526175
pubmed_411_3310
Claudins are a family of integrated membrane-bound proteins involving in paracellular tightness, barrier forming, ion permeability, and substrate selection at tight junctions of chordate epithelial and endothelial cells. Here, 39 putative claudin genes were identified in the Pungitius sinensis based on the high throughput RNA-seq. Conservative motif distribution in each group suggested functional relevance. Divergence of duplicated genes implied the species' adaptation to the environment. In addition, selective pressure analyses identified one site, which may accelerate functional divergence in this protein family. Pesticides cause environmental pollution and have a serious impact on aquatic organisms when entering the water. The expression pattern of most claudin genes was affected by organophosphorus pesticide, indicating that they may be involved in the immune regulation of organisms and the detoxification of xenobiotics. Protein-protein network analyses also exhibited 439 interactions, which implied the functional diversity. It will provide some references for the functional study on claudin genes.
10.1007/s00360-020-01301-5
pubmed_373_18264
Because intracranial germinomas are readily curable with radiation and chemotherapy or radiation therapy alone, the role of radical surgery has become debatable. This study assesses the optimum degree of surgical resection for intracranial germinomas. Twenty-nine patients who underwent surgery for germinoma were retrospectively analyzed (male/female ratio 27:2, median age 18 years). Among these 29 patients there were 10 solitary pineal, seven solitary neurohypophyseal/hypothalamic, and 12 multifocal or disseminated tumors. Biopsy samples were obtained in 16 patients (stereotactically in eight, transsphenoidally in four, and via frontotemporal craniotomy in four). Partial resection was attained in five patients (via a frontotemporal approach in three and occipitotranstentorially in two). Gross-total resection was achieved via an occipitotranstentorial route in eight patients with pineal masses. After surgery, 10 patients were treated with radiotherapy alone, and 19 received radiation and chemotherapy; complete remission was achieved in all 29 patients. The overall tumor-free survival rate was 100% at a median follow-up period of 42 months. There was no significant difference in outcome related to the extent of surgical resection. Postoperative neurological improvement was seen in only two patients, whereas transient postoperative complications, mainly upgaze palsy, were observed in six. One patient experienced a slight hemiparesis, bringing the surgical morbidity rate to 3% (one of 29). It is concluded that radical resection of intracranial germinomas offers no benefit over biopsy. The primary goal of surgery should be to obtain a sufficient volume of tumor tissue for histological examination. If there is strong evidence of germinoma on radiological studies, biopsy samples should be obtained. When a perioperative histological diagnosis of pure germinoma is made during craniotomy, no risk should be taken in continuing the resection.
10.3171/jns.1997.87.2.0262
pubmed_880_10392
This study investigated the active microbial community in a full-scale granular activated carbon-anaerobic fluidized bed (GAC-AFB) reactor treating wastewater from the manufacturing of phenolic resin, using 16S rRNA-based molecular analyses. The results of cDNA from 16S rRNA revealed that Methanosaeta-related (83.9% of archaeal clones) and Syntrophorhabdaceae (formerly named Deltaproteobacteria group TA)-related (68.9% of bacterial clones) microorganisms were as the most predominant populations in the phenol-degrading GAC-AFB reactor. The high abundance of Syntrophorhabdaceae was supported by a terminal restriction fragment length polymorphism (T-RFLP) analysis, which showed that a Syntrophorhabdaceae-like fragment of 119 bp (~80% of total fragments) was the most predominant phylotype. Furthermore, fluorescence in situ hybridization (FISH) analyses suggested that Syntrophus- and Chloroflexi-like cells were also in high abundance in the GAC biofilm. A non-layered structure of microorganisms was found in the GAC biofilm, where Methanosaeta (thick filamentous), Syntrophorhabdaceae (oval-shaped), Syntrophus (small rods) and Chloroflexi (thin-filamentous) were randomly distributed with high abundance. These findings greatly improve our understanding of the diversity and distribution of microbial populations in a full-scale mesophilic bioreactor treating an actual phenol-containing waste stream.
10.1264/jsme2.me09109