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pubmed_30_5079
Eighty-five menopausal women (mean age 56 years) with endometrial hyperplasia without (65 patients, group 1) and with cytologic atypia (20 patients, group 2) were followed up prospectively from 2 to 12 years (mean 7 years) to shed insight into their respective response to oral medroxyprogesterone acetate therapy. In group 1 9 of 65 patients (14%) had persistence, 4 (6%) had recurrence, and none developed carcinoma. In group 2 10 of 20 patients (50%) had persistence and 5 had recurrence with cytologically atypical disease. Five of 20 patients (25%) developed adenocarcinoma at 2 to 7 years (mean 5.5 years) after starting medroxyprogesterone acetate therapy. The data suggest that most women with hyperplasia respond to progestogenic therapy and are not at increased risk of developing cancer. The patients with an unfavorable response to medroxyprogesterone acetate and a significant elevation in cancer risk can be identified on the basis of cytologic atypia.
10.1016/0002-9378(89)90103-8
pubmed_73_4219
OBJECTIVE Psychiatric residents spend much time as teachers and mentors to medical students. Recently, the Canadian Medical Education Directions for Specialists (CanMEDS) roles identified the importance of this role as a scholar. Residents are now expected to develop skills to fulfill this role, one of which involves the ability to teach. However, lack of tools to facilitate the development of resident teaching skills poses a significant problem. METHODS This article describes the development and evaluation of a resident teaching manual, written by psychiatric residents for use by fellow residents, in their teaching endeavors with medical students at the University of Alberta. RESULTS Residents appreciated using this manual to enhance their skills in teaching medical students. CONCLUSION The development of, and the preliminary survey of this psychiatric resident teaching manual, is encouraging in furthering the development of future psychiatrist teachers.
10.1176/appi.ap.34.4.305
pubmed_598_4166
Amphetamine-induced augmentation of striatal dopamine and its blunted release in prefrontal cortex (PFC) is a hallmark of schizophrenia pathophysiology. Although N-methyl-D-aspartate receptor (NMDAR) hypofunction is also implicated in schizophrenia, it remains unclear whether NMDAR hypofunction leads to dopamine release abnormalities. We previously demonstrated schizophrenia-like phenotypes in GABAergic neuron-specific NMDAR hypofunctional mutant mice, in which Ppp1r2-Cre dependent deletion of indispensable NMDAR channel subunit Grin1 is induced in corticolimbic GABAergic neurons including parvalbumin (PV)-positive neurons, in postnatal development, but not in adulthood. Here, we report enhanced dopaminomimetic-induced locomotor activity in these mutants, along with bidirectional, site-specific changes in in vivo amphetamine-induced dopamine release: nucleus accumbens (NAc) dopamine release was enhanced by amphetamine in postnatal Ppp1r2-Cre/Grin1 knockout (KO) mice, whereas dopamine release was dramatically reduced in the medial PFC (mPFC) compared to controls. Basal tissue dopamine levels in both the NAc and mPFC were unaffected. Interestingly, the magnitude and distribution of amphetamine-induced c-Fos expression in dopamine neurons was comparable between genotypes across dopaminergic input subregions in the ventral tegmental area (VTA). These effects appear to be both developmentally and cell-type specifically modulated, since PV-specific Grin1 KO mice could induce the same effects as seen in postnatal-onset Ppp1r2-Cre/Grin1 KO mice, but no such abnormalities were observed in somatostatin-Cre/Grin1 KO mice or adult-onset Ppp1r2-Cre/Grin1 KO mice. These results suggest that PV GABAergic neuron-NMDAR hypofunction in postnatal development confers bidirectional NAc hyper- and mPFC hypo-sensitivity to amphetamine-induced dopamine release, similar to that classically observed in schizophrenia pathophysiology.
10.1093/schbul/sby003
pubmed_886_14238
BACKGROUND Previous studies have reported seasonal variation in peptic ulcer disease (PUD), but few large-scale, population-based studies have been conducted. METHODS To verify whether a seasonal variation in cases of PUD (either complicated or not complicated) requiring acute hospitalization exists, we assessed the database of hospital admissions of the region Emilia Romagna (RER), Italy, obtained from the Center for Health Statistics, between January 1998 and December 2005. Admissions were categorized by sex, age (<65, 65-74, > or = 75 yrs), site of PUD lesion (stomach or duodenum), main complication (hemorrhage or perforation), and final outcome (intended as fatal outcome: in-hospital death; nonfatal outcome: patient discharged alive). Temporal patterns in PUD admissions were assessed in two ways, considering a) total counts per single month and season, and b) prevalence proportion, such as the monthly prevalence of PUD admissions divided by the monthly prevalence of total hospital admissions, to assess if the temporal patterns in the raw data might be the consequence of seasonal and annual variations in hospital admissions per se in the region. For statistical analysis, the chi2 test for goodness of fit and inferential chronobiologic method (Cosinor and partial Fourier series) were used. RESULTS Of the total sample of PUD patients (26,848 [16,795 males, age 65 +/- 16 yrs; 10,053 females, age 72 +/- 15 yrs, p < 0.001)], 7,151 were < 65 yrs of age, 8,849 between 65 and 74 yrs of age, and 10,848 > or = 75 yrs of age. There were more cases of duodenal (DU). (89.8%) than gastric ulcer (GU) (3.6%), and there were 1,290 (4.8%) fatal events. Data by season showed a statistically difference with the lowest proportion of PUD hospital admissions in summer (23.3%) (p < 0.001), for total cases and rather all subgroups. Chronobiological analysis identified three major peaks of PUD hospitalizations (September-October, January-February, and April-May) for the whole sample (p = 0.035), and several subgroups, with nadir in July. Finally, analysis of the monthly prevalence proportions yielded a significant (p = 0.025) biphasic pattern with a main peak in August-September-October, and a secondary one in January-February. CONCLUSIONS A seasonal variation in PUD hospitalization, characterized by three peaks of higher incidence (Autumn, Winter, and Spring) is observed. When data corrected by monthly admission proportions are analyzed, late summer-autumn and winter are confirmed as higher risk periods. The underlying pathophysiologic mechanisms are unknown, and need further studies. In subjects at higher risk, certain periods of the year could deserve an appropriate pharmacological protection to reduce the risk of PUD hospitalization.
10.1186/1471-230X-10-37
pubmed_817_17243
Capacitive plasma pickup is a well-known and difficult problem for plasma-facing edge diagnostics. This problem must be addressed to ensure an accurate and robust interpretation of the real signal measurements vs noise. The Faraday cup fast ion loss detector array of the Joint European Torus (JET) is particularly prone to this issue and can be used as a testbed to prototype solutions. The issue of separation and distinction between warranted fast ion signal and electromagnetic plasma noise has traditionally been solved with hardware modifications, but a more versatile post-processing approach is of great interest. This work presents post-processing techniques to characterize the signal noise. While hardware changes and advancements may be limited, the combination with post-processing procedures allows for more rapid and robust analysis of measurements. The characterization of plasma pickup noise is examined for alpha losses in a discharge from JET's tritium campaign. In addition to highlighting the post-processing methodology, the spatial sensitivity of the detector array is also examined, which presents significant advantages for the physical interpretation of fast ion losses.
10.1063/5.0099314
pubmed_167_6852
OBJECTIVE The integrity of the scalp overlying a cochlear implant receiver stimulator (RS) is critical for the long-term survival of the implant. Exposure or extrusion of the device will likely result in the need for its removal. There is a global trend of acceleration of population aging, thus raising the prevalence of cochlear implantation (CI) in the elderly. The aim of this study was to define age-dependent changes in scalp thickness and discuss the implication of that anatomical characteristic for CI in the geriatric population. METHODS Scalp thickness over the location of the RS in the temporo-parietal area was measured directly with a needle in patients of various ages. RESULTS Two-hundred thirty-six temporo-parietal scalps were measured in patients aged 18 to 85 years. A strong inverse correlation was found between age and scalp thickness (rs = -0.723, P < .001). Scalp thickness decreased with age from a mean of 8 mm in the third decade of life to 5 mm in the ninth decade of life. CONCLUSION The human scalp thins with age and most likely undergoes a reduction in its strength. As a consequence, implantable hearing devices that are shielded by the scalp can be at increased risk of exposure and extrusion in the aging recipient. This needs to be taken into account when considering an implantation procedure, the surgical approach and patient instructions on need for and venues for continuing care over time. LEVEL OF EVIDENCE 2B.
10.1002/lio2.218
pubmed_918_15152
Cancer immunotherapy has been one of the highlights in the advancement of cancer care. Certain immune checkpoint inhibitors bind to PD-1 on T cells and mediate an antitumour immune response. Given that immune checkpoint inhibitors are becoming part of standard care, a new class of adverse events-immune-related adverse events-has emerged. Among them is endocrine toxicity, most commonly targeting the thyroid, pituitary, or adrenal glands. New-onset diabetes mellitus has been reported in fewer than 1% of patients. We present a patient with type 1 diabetes mellitus secondary to immunotherapy, together with an overview of the associated literature. Patients who develop type 1 diabetes mellitus experience a rapid course, and diabetic ketoacidosis is commonly the presenting symptom. Insulin is currently the treatment of choice; oral antidiabetics or corticosteroids do not assist in management. Several predictive factors are under investigation, but physician awareness and prompt management are key to a positive outcome.
10.3747/co.26.4151
pubmed_710_20141
Slowly melting snowfields in mountain and polar regions are habitats of snow algae. Orange blooms were sampled in three European mountain ranges. The cysts within the blooms morphologically resembled those of Chloromonas nivalis (Chlorophyceae). Molecular and morphological traits of field and cultured material showed that they represent a new species, Chloromonas hindakii sp. nov. The performance of photosystem II was evaluated by fluorometry. For the first time for a snow alga, cyst stages collected in a wide altitudinal gradient and the laboratory strain were compared. The results showed that cysts were well adapted to medium and high irradiance. Cysts from high light conditions became photoinhibited at three times higher irradiances (600 µmol photons m-2 s-1) than those from low light conditions, or likewise compared to cultured flagellates. Therefore, the physiologic light preferences reflected the conditions in the original habitat. A high content of polyunsaturated fatty acids (about 60% of total lipids) and the accumulation of the carotenoid astaxanthin was observed. They are regarded as adaptations to cope with extreme environmental conditions of snow that include low temperatures, freeze-thaw cycles, and variable light intensity. The intraspecific ability of adaptation of the photosynthetic apparatus to different irradiance regimes seems to be advantageous for thriving in different snow habitats.
10.3390/microorganisms7100434
pubmed_54_13294
Despite well-documented benefits for patients after myocardial infarction, cardiac rehabilitation is underutilized in most countries. In France, a recent study showed a participation rate of 22.7 %, with huge regional disparities for unknown reasons. In this paper, we analyze some demographic particularities for explaining these curious results. Then, we review in the literature the complex factors influencing patient's referral in cardiac rehabilitation (patient's believes, role of the physician, health system's organization…), and the best ways of improving cardiac rehabilitation rate or finding adequate alternatives.
pubmed_54_13294
pubmed_633_18462
BACKGROUND Cavernous hemangioma is a frequent and the most common, primary, benign tumor of the orbit in adults. It is typically single and unilateral, considered not to recur after having been completely excised. Multiple orbital cavernous hemangiomas without signs of hemangiomatosis are rare. Multiple cavernous hemangiomas may recur after a complete excision and may exist with concurrent systemic tumors. Tumor recurrence is supposed to develop from vasculature that is present already in response to a proliferate stimulus. CASE REPORT A 39-year-old female with painless proptosis of the right orbit was found to have four orbital tumors. The first orbitotomy was performed in 1984 by excising four cavernous hemangiomas. Six years later, another, the fifth one cavernous hemangioma was totally excised from the same orbit. Nine years after the first operation, reorbitotomy was performed because of positive radiological and clinical signs of de novo tumor in the orbit. The operation did not confirm the tumorous tissue. The fourth orbitotomy was performed 24 years after the first operation and two cavernous hemangiomas were totally excised. CONCLUSION This case show the possibility of cavernous hemangioma recurrence after a previously totally excised tumor, separated more than two decades. A very long follow-up of the patients operated for these benign tumor lesions is recommended.
10.2298/vsp1006507n
pubmed_174_842
Clinical trials of intravenous amrinone were performed in 462 patients severely ill with congestive heart failure. All were monitored invasively. Adverse reactions were complicated by underlying disease severity and concomitant drug therapy. No consistent pattern of arrhythmias emerged in relation to intravenous amrinone administration. Thrombocytopenia was noted in 2.4% of patients, but it was asymptomatic with no demonstrable bone marrow depression or antiplatelet antibodies. Gastrointestinal adverse effects, hypotension and fever were rare, each occurring in fewer than 2% of patients. Liver enzyme alterations were seen in 1 patient, but it could not be determined whether these changes were related to intravenous use of the drug. Chest pain and irritation at the site of injection were noted in 1 patient each. Spontaneous anecdotal postapproval reports cited tachycardia, liver enzyme elevation, thrombocytopenia, intravenous site irritation, failure to respond and anaphylactoid response as adverse effects or possible adverse effects; each was mentioned in 3 or fewer reports. Drugs contraindicated for concomitant use with intravenous amrinone are listed, and chemical interactions with glucose solutions and intravenous furosemide are discussed.
10.1016/0002-9149(85)91195-6
pubmed_1072_24874
OBJECTIVE In the elderly and patients with dysphagia, masticatory problems often cause aspiration or choking. Although simple methods to predict aspiration and silent aspiration exist, methods for evaluating the masticatory function of patients with dysphagia are lacking. Accordingly, we developed a simple test to assess the chewing and swallowing ability of patients with dysphagia. METHODS One hundred and five patients with dysphagia were included. We used the Saku-Saku Test (SST), in which patients were asked to eat a rice cracker, and evaluated the quality of mandibular rotation during mastication. We studied the participants' ability to grind, aggregate, and swallow using videoendoscopic evaluation (VE) and investigated its association with mandibular rotation. RESULTS The SST showed good reliability between two examiners, with a kappa coefficient of 0.80. 92.4% of the patients ate the rice cracker without aspiration. The SST showed a high sensitivity of 73.3% and specificity of 93.3% for the degree of grinding. The degree of food bolus aggregation had a sensitivity of 45.0% and specificity of 90.6%, and aspiration had a sensitivity of 25.0% and specificity of 84.5%, both of which showed high specificity. CONCLUSIONS The results of this study suggested that the SST might be simple and useful for identifying patients with dysphagia who are able to masticate, even if they do not eat foods that need chewing and could be used before starting these patients on foods that need chewing.
10.1016/j.archger.2017.10.010
pubmed_43_3705
BACKGROUND The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). METHODS A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher's exact test and continuous demographic and imaging variables using the Mann-Whitney U test. RESULTS IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9 cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), <50% excised with biopsy (p = 0.02), and atypia involving IDP (p = 0.045). Age, clinical presentation, and concurrent contralateral cancer were not significantly associated with upgrade. Lowest upgrade risk (0%) was in pure IDP ≤1 cm with >50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. CONCLUSIONS After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.
10.1245/s10434-021-10520-1
pubmed_499_18984
PURPOSE Although pain phenotype affects clinical score in patients with knee osteoarthritis (OA), little information has been available on the relationship between pain phenotype and gait analysis. The purpose was to investigate the relationship between pain phenotype and gait parameters.  METHODS: A total of 34 patients (24 females and 10 males) with end-stage medial compartmental knee OA participated. All the patients were evaluated based on pain detect questionnaire (PD-Q) and pain catastrophizing scale (PCS). They were divided into two categories: Group Low (PD-Q score ≤ 12) and Group High (PD-Q score > 12), PCS + (PCS ≥ 23) and PCS- (PCS < 23). Gait analysis was performed using three-dimensional motion analysis system. Statistical analysis was done to compare gait parameters between groups for each allocation of PD-Q or PCS, separately.  RESULTS: Peak vertical ground reaction forces in Group Low and High were 0.99 ± 0.054 and 0.82 ± 0.17, respectively (P = 0.015). Peak knee adduction moments in Group Low and High were 0.70 ± 0.19 and 0.39 ± 0.14, respectively (P = 0.0022). For PCS allocation, knee extension limitation during mid-stance during gait were significantly larger in PCS- (P = 0.038). CONCLUSIONS Patients with high PD-Q score had atypical gait pattern with smaller peak vertical ground reaction force and knee adduction moment, compared to patients with low PD-Q score. Moreover, patient with low PCS had different gait pattern in extension limitation, compared to those with high PCS. PD-Q and PCS would affect gait pattern in patients with knee OA. LEVEL OF EVIDENCE III.
10.1186/s40634-022-00492-w
pubmed_507_14385
OBJECTIVE The need for revision stapes surgery has many causes, and among these, we describe a particular displacement of the piston: the "lateralized piston syndrome". The goal of this study is to define criteria and surgical management of this syndrome. STUDY DESIGN Retrospective study over 13 years. SETTING Tertiary reference center. PATIENTS A review of 1,289 consecutive stapes operations revealed 119 revisions (9%) from which 22 cases (18.5%) could be classified under the lateralized piston syndrome. INTERVENTION Revision stapedotomy. MAIN OUTCOME MEASURES Medical files, preoperative and postoperative audiograms, computed tomographic scans, and operative reports. RESULTS The 22 cases presented as a delayed conductive hearing loss in 95.5% of cases. Preoperative computed tomographic scans showed a lateralized piston out of the stapedotomy in 81% of cases and touching the tympanic membrane in 54.5% of cases. Revisions revealed a lateral displacement of the piston out of the entire oval window in 86% of cases, with closure of the stapedotomy in all cases and incus necrosis in 77% of cases. Conventional pistons were fitted in 12 cases. In case of a significantly eroded incus, total prostheses (TORPs) in 6 cases and offset pistons in 4 cases were placed. Air-bone gap (ABG) was closed to within 20 dB in 82% of cases. Air-conduction puretone audiometry improvement was 17.2 dB (standard deviation [SD], 19.2), with a mean postoperative ABG of 16.2 dB (SD, 12.7). Only 1 ear, operated with TORP, had a sensorineural deterioration of 20 dB. With offset pistons, ABG was closed to within 20 dB in 100% of cases with a mean postoperative ABG of 8.8 dB (SD, 7.2). CONCLUSION The lateralized piston syndrome was found in 18.5% of stapes surgery revisions. Surgical management was effective in correcting the conductive hearing loss. In the event of significant eroded incus, we observed better results with offset pistons than with TORPs.
10.1097/mao.0b013e3181c0e80f
pubmed_1021_16770
A 203-base-pair sequence 5' of the latency-associated transcripts (LATs) of herpes simplex virus type 1 contains a 7-base consensus sequence TGCGTCA that is identical to the cAMP-response element of the proenkephalin gene. This consensus sequence is at -38 relative to the putative 5' end of the LATs with a TATA box at the -24 position. In transient chloramphenicol acetyltransferase assays in rat pheochromocytoma (PC12) cells, this enhancer region stimulated gene expression up to 3-fold in the presence of dibutyryl cAMP, forskolin, nerve growth factor, or phorbol 12-myristate 13-acetate. Mutation of the cAMP-response element to TGCG-CAA resulted in a 4-fold reduction of basal activity and a complete loss of inducible stimulation. In DNA gel retardation assays, purified cAMP-response element-binding protein and a nuclear protein from PC12 cells were shown to bind specifically to this element. Furthermore, it was demonstrated that the reactivation of wild-type herpes simplex virus type 1 from dissociated latently infected murine trigeminal ganglia was significantly accelerated (P less than 0.005) by the addition of cAMP analogs or adenylate cyclase activators. However, these reagents did not accelerate reactivation of a deletion mutant that lacks the putative cAMP-response element-containing promoter region, transcriptional start site, and 1015 base pairs of the LATs. These studies demonstrate that the promoter region of the LATs contains a functional cAMP-response element and that expression of the LATs is likely controlled by second messenger signal transduction and imply a role for cAMP in triggering viral reactivation.
10.1073/pnas.88.1.48
pubmed_988_6533
Cytochrome P-450cam cationic surface charges at Lys 344, Arg 72, and Lys 392 have been altered by site-directed mutagenesis techniques. The residues at Lys 344 and Arg 72 were previously suggested as salt bridge contacts in the cytochrome b5-cytochrome P-450cam association complex and implicated in the physiological putidaredoxin-cytochrome P-450cam complex [Stayton, P. S., Poulos, T. L., & Sligar, S. G. (1989) Biochemistry 28, 8201-8205]. Mutations to neutralize the basic charge at Arg 72 (R72Q) and to both neutralize and reverse the charge at Lys 344 (K344Q, K344E) resulted in alteration of NADH oxidation rates in the reconstituted physiological electron-transfer system, which is rate limited by putidaredoxin-cytochrome P-450cam electron transfer. The steady-state Vmax values were apparently unperturbed, suggesting that the observed rate differences were largely attributable to Km effects. The Km values observed for the K344Q (24 microM) and K344E (32 microM) mutants are in the direction expected for neutralization and reversal of a salt bridge charge interaction. A control mutation at a basic surface charge located away from the proposed site of interaction, Lys 392 (K392Q), resulted in overall activities quantitated by NADH oxidation rates that are similar to that of wild-type cytochrome P-450cam. Calculation of the cytochrome P-450cam electrostatic field revealed a patch of positive potential at the modeled cytochrome b5 interaction site lying directly above the nearest proximal approach to the buried heme prosthetic group. These results provide experimental and theoretical evidence for the modeled cytochrome P-450cam binding site implicated in both cytochrome b5 and putidaredoxin association.(ABSTRACT TRUNCATED AT 250 WORDS)
10.1021/bi00484a005
pubmed_1094_21780
Triple-negative breast cancer (TNBC) indicates a subset of breast carcinomas that does not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). According to the literature, TNBCs are aggressive tumors, characterized by a high incidence of recurrence and a high risk of disease progression. Lactoferrin (LF) is a single-chain, iron-binding glycoprotein of ~700 amino acids, which is involved in a wide range of biological activities, including iron-trafficking and carcinogenesis. The present study aimed to assess LF expression in human TNBC samples and the possible correlation with clinico-pathological parameters associated with biological aggressiveness. LF immunohistochemical expression was investigated in formalin-fixed, paraffin-embedded samples of human TNBC. Cases were analyzed according to an intensity distribution (ID) score, and only those showing an ID score of >2 were considered as positive for LF. LF immunostaining was encountered in 26.15% cases. A significant correlation was found between LF expression and a low Ki-67 labeling index (P=0.040), the absence of recurrence (P=0.010) and alive status (P=0.020). LF may assist in identifying a subset of TNBC with less aggressive biological behavior. The meaning of LF expression in TNBC remains unclear and is controversial. The present findings indicated that LF expression is correlated with a low growth fraction in these tumors. Thus, it is possible that the inhibition of the LF axis may be a valid therapeutic target for TNBC, and this should be confirmed by future studies.
10.3892/ol.2017.5859
pubmed_887_6254
Appropriate treatment of an intracranial lesion is based upon establishing a definitive diagnosis. CT-stereotactic biopsy procedures are highly accurate, are associated with few complications, and are usually performed only with local anesthesia. Stereotactic biopsy is the preferred method for histologically confirming the nature of an intracranial lesion in the immunocompromised patient. The mortality and morbidity approach 1 per cent, respectively. In the large reported series of stereotactic surgery for biopsy, diagnostic accuracy is over 95 per cent. Stereotactic techniques can also be used to aspirate abscesses or localize abscesses or neoplastic lesions excised by craniotomy.
pubmed_887_6254
pubmed_387_5146
Corpora lutea were removed from regularly cycling dairy cows, dissociated with collagenase and cultured for 8 or 10 days in Ham's F-12 medium. In Exp. 1 treatment with insulin, or an insulin-transferrin-selenium combination (ITS), increased progesterone production from basal levels on Day 4 of culture to 234% (P less than 0.01) above controls on Day 10. LH alone increased progesterone production 45% above controls on Day 10 (P greater than 0.05). When LH was combined with insulin or ITS, progesterone production was stimulated to an average of 1802% (P less than 0.01) above controls on Day 10 of culture. Transferrin or selenium without insulin did not allow LH to stimulate progesterone synthesis. In Exp. II, LH alone or LH plus gentamicin or penicillin-streptomycin increased progesterone production from basal levels on Day 2 steadily to an average of 468% (P less than 0.01) above controls (no antibiotics) by Day 8 of culture. The addition of amphotericin-B, alone or in combination with the other antibiotics, inhibited all LH-stimulated progesterone synthesis, but did not affect basal progesterone levels. We conclude that insulin is essential for maximal steroidogenesis in a bovine luteal cell culture system, and that LH-stimulated progesterone production is inhibited in the presence of amphotericin-B, but is not inhibited by gentamicin or penicillin-streptomycin. The elimination of amphotericin-B, coupled with the addition of insulin to the cell culture system increased the responsiveness of the cells to LH. These culture conditions represent the first report in which LH increased total progesterone production for 10 days, maintaining luteal function in a chemically-defined culture system.
10.1530/jrf.0.0820135
pubmed_680_16650
People with long-term mental health problems that affect their daily activities are a growing proportion of the UK working population and they have a particularly low employment rate. We analyse gaps in labour market outcomes between mental health disabled and non-disabled people during the COVID-19 pandemic in the UK. We also decompose the outcome gaps in order to explore the relative importance of different factors in explaining these gaps. Our results suggest that the employment effects of the pandemic for mental health disabled people may have been temporary. However, they were more likely to be away from work and/or working reduced hours than people without a disability. Workers with mental health disability were over-represented in part-time work and in caring, leisure and other service occupations, which were disproportionately affected by COVID-19 and the economic response. This is important new evidence on the contribution of segmentation and segregation in explaining the labour market position of people with mental health disability. The longer term effects of the pandemic were still not apparent at the end of our analysis period (2021:Q3), but the concentration of disabled workers in cyclically sensitive sectors and part-time work means that they will always be particularly vulnerable to economic downturns.
10.1016/j.labeco.2022.102253
pubmed_418_24397
Scarce data exist on the use of complementary and alternative medicine (CAM) by asylum seekers in Switzerland and their perception of discrimination. A cross-sectional study assessed the prevalence and type of CAM used by asylum seekers in one region of Switzerland and evaluated their self-perceived discrimination. Among the 61 asylum seekers who participated, lifetime prevalence of CAM use was 46%, with 28% reporting its use during the last year. Herbal medicine was the most frequently used CAM. Self-perceived discrimination was reported by 36% of asylum seekers, mainly related to their national origins. CAM users had a tendency to report more discrimination than non-users (44% vs. 30%). CAM use is prevalent among asylum seekers. Considering the importance of herbal medicine use and that only half of the respondents disclosed CAM use to their physician, clinicians should ask about it, notably because of potential risks of herb-drug interaction.
10.1007/s10903-019-00895-5
pubmed_122_5597
The left supramarginal gyrus (SMG) is a critical structure in tool use actions, including such simple acts as selection of appropriate grasps and, if necessary, their on-line corrections. Yet, its temporal contribution to initial planning of functional grasps of tools is largely unknown. We used MRI-guided, event-related transcranial magnetic stimulation (TMS) to determine the time point when SMG involvement in processing of tools for functional grasp decision was affected most. In Exp. 1, with 15 participants, triple-pulse (10 Hz) TMS was applied to either the left anterior-to-mid SMG (amSMG; subdivisions PFt/PF) or vertex at three different time points: starting from 17 ms (i.e., delivered at 17/117/217 ms), 117 ms (117/217/317 ms) or 217 ms (217/317/417 ms) after stimulus onset. In Exp. 2, with 12 participants, we applied single-pulse TMS to either left amSMG or the left rostral middle frontal gurus (rMFG; area 46) at these same time points relative to stimulus onset. Subject- and item-based analyses of response times (RTs) were performed. Whereas the amSMG and vertex stimulation with triple pulse has revealed differential effects on RTs in general, as well as on tool orientation processing, it gave only vague pointers as to their temporal contributions to the task. Yet, amSMG and rMFG stimulation with single pulse demonstrated that, while the processing in both of these areas can be enhanced at 17 ms and no doubt at 117 ms (as compared to 217 ms), the earliest stimulation facilitated amSMG (vs. rMFG) contribution, and the latest stimulation had the opposite effect, facilitating rMFG (vs. amSMG) contribution to planning functional grasps. These outcomes demonstrate that the critical role of SMG in tool-related actions can be invoked substantially earlier than previously thought.
10.1016/j.cortex.2018.10.010
pubmed_422_17982
Saccharomyces cerevisiae HTR1 mutants are severely impaired in the uptake of glucose. We have cloned dominant HTR1 mutant alleles and show that they encode mutant forms of the Mth1 protein. Mth1 is shown to be involved in carbon source-dependent regulation of its own, invertase and hexose transporter gene expression. The mutant forms block the transduction of the Snf3- and Rgt2-mediated glucose signals upstream of the Rgt1 transcriptional regulator.
10.1128/JB.182.2.540-542.2000
pubmed_533_24478
Wind-induced upwelling of hypoxic waters containing hydrogen sulfide (H2S) sometimes causes mass mortalities of aquatic organisms inhabiting coastal areas, including the hypoxia-tolerant Manila clam Ruditapes philippinarum. We examined the tolerance of Manila clam to H2S under controlled laboratory conditions. Larvae and juveniles obtained by artificial fertilization or from a wild population were exposed to normoxic or to hypoxic water with or without un-ionized H2S (concentrations, 0.2-52.2 mg/L). Twenty-four-hour exposure experiments revealed ontogenetic changes in the clam's tolerance to H2S exposure: tolerance was enhanced from the larval stages to juveniles just after settlement but was attenuated as juveniles grew. Tolerance of larvae and juveniles to H2S exposure weakened as the water temperature rose from 20 to 28 °C. Prolonged 48-h exposure to H2S attenuated the tolerance of juveniles to H2S. Temporary suspension of H2S exposure by 24-h reoxygenation improved the ability of juveniles to withstand repeated H2S exposure.
10.1016/j.marenvres.2017.12.019
pubmed_683_21512
Arterial oxygen saturation of the fetus during labour (SPO2) measured with a fetal pulse oximeter was compared to the neonatal condition measured by umbilical vein pH and Apgar score. Changes in oxygen saturation (index of desaturation) during the second stage of labour were also compared to neonatal outcome. Fifty-five patients with abnormal fetal heart rate pattern during labour had a continuous monitoring of fetal oxygen saturation using the Nellcor N-400 pulse oximeter. SPO2 measurement during the last 10 min of labour was significantly correlated to umbilical vein pH and to 1-min Apgar score (P = 0.022 and P = 0.025, respectively). A much higher correlation was found between the index of desaturation and umbilical vein pH at birth and with 1-min Apgar score (P = 0.002 and P < 0.001, respectively). When considering the lower value of umbilical vein pH at birth to be 7.20, and the normal value of SPO2 during labour to be > or = 40% (negative test), we observed a 100% negative predictive value of oximetry. If these results are confirmed in a larger series of patients, analysis of the changes in fetal arterial oxygen saturation during labour (index of desaturation) could be a good indicator of the condition of the newborn. A normal SPO2 value during labour could be reassuring in case of abnormal fetal heart rate.
10.1016/0028-2243(94)90046-9
pubmed_121_21300
BACKGROUND Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation. OBJECTIVE To develop a prediction model for urinary tract cancer in patients referred with haematuria. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism. RESULTS AND LIMITATIONS The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy. CONCLUSIONS This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation. PATIENT SUMMARY We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation.
10.1016/j.euf.2022.06.001
pubmed_886_5388
INTRODUCTION Postanaesthetic shivering is a common condition after surgery which needs proper management with pharmacologic agents so as to make postoperative period comfortable to the patient and prevent from the untoward complications that can arise from it. This study was done to compare the effectiveness of Pethidine and Doxapram in the treatment of postanaesthetic shivering. METHODS Patients were randomly divided into three groups, ten in each. All received volume of 3 ml as Group I (Doxapram 1.5 mg/kg), Group II (Pethidine 0.35 mg/kg) and Group III (Normal Saline). All patients were observed for 30 minutes after reversal of muscle relaxant and occurrence of shivering within this period was observed, scored and treated. All treated patients were observed for 10 minutes after the test drug was given for control of shivering and any untoward effects. RESULTS Pethidine was found more effective than Doxapram in treating postanaesthetic shivering as it was effective in 80% followed by Doxapram in 60% and Normal saline in 20%. Statistically the results between Normal saline and Pethidine was significant as P < 0.05. As statistical significance between Doxapram and Normal Saline was p = 0.16; and between Pethidine and Doxapram was p = 0.62, the difference is statistically not significant. CONCLUSIONS Pethidine was found to be more effective compared to Doxapram in treating patients with postoperative shivering.
pubmed_886_5388
pubmed_301_5345
INTRODUCTION Extracapsular hip infected nonunion after stabilization with a sliding hip screw (SCS) is uncommon and a convincing treatment method has not yet been reported in the literature. PATIENTS AND METHODS Thirteen consecutive patients who sustained such a disability were treated with removal of SCS, local radical debridement, vancomycin powder with or without gentamicin solution application, re-insertion of a new SCS, and autogenous cancellous bone grafting. Postoperatively, ambulation with regulated weight bearing was encouraged as early as possible. Infectious microorganisms in 76% (10/13) of the lesion sites were oxacillin-resistant staphylococcus aureus (ORSA). RESULTS Twelve patients were followed-up for at least 2 years (range, 2~6 years; median, 4 years) and all nonunions healed. The union rate was 100% (12/12) with a median union period of 4 months (range, 3~6 months). No wound infection recurred at the last follow-up. The satisfactory rate of hip function was 92% (11/12, P<0.001). CONCLUSIONS We, therefore, recommend this surgical procedure to treat all patients with a similar disability because of its high success rate and low complication rate.
10.1007/s00402-003-0563-3
pubmed_520_3560
BACKGROUND There is growing interest in identifying factors associated with healthy aging. This cross-sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). METHODS Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m2 ) with T2DM enrolled in Look AHEAD (a multi-site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10-year intervention was discontinued. The following items were assessed approximately 14.4 years post-randomization in a cross-sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self-report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF-36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ-9) and mental QOL (SF-36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. RESULTS Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self-reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self-reported disability and grip strength. CONCLUSIONS Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross-sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond "loss and decline" to highlight opportunities to facilitate healthy aging.
10.1111/jgs.17986
pubmed_1057_13566
Emerging scientific evidence indicates that frequent digital technology use has a significant impact-both negative and positive-on brain function and behavior. Potential harmful effects of extensive screen time and technology use include heightened attention-deficit symptoms, impaired emotional and social intelligence, technology addiction, social isolation, impaired brain development, and disrupted sleep. However, various apps, videogames, and other online tools may benefit brain health. Functional imaging scans show that internet-naive older adults who learn to search online show significant increases in brain neural activity during simulated internet searches. Certain computer programs and videogames may improve memory, multitasking skills, fluid intelligence, and other cognitive abilities. Some apps and digital tools offer mental health interventions providing self-management, monitoring, skills training, and other interventions that may improve mood and behavior. Additional research on the positive and negative brain health effects of technology is needed to elucidate mechanisms and underlying causal relationships.
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10.31887/DCNS.2020.22.2/gsmall
pubmed_524_12284
BACKGROUND Pragmatic and comparative effectiveness randomized controlled trials (RCTs) aim to be highly generalizable studies, with broad applicability and flexibility in methods. These trials also address recruitment issues by minimizing exclusions. The trials may also appeal to potential subjects because of lower risk and lower burdens of participation. We sought to examine rates of refusal and uses of waivers of informed consent in pragmatic and comparative effectiveness RCTs. METHODS A systematic review of pragmatic and comparative effectiveness RCTs performed wholely or in part in the United States and first published in 2014 and 2017. RESULTS 103 studies involving 105 discrete populations were included for review. Refusal data was collected for 71 RCTs. Overall, studies reported an average rate of 31.9% of potential subjects refused participation; on an individual basis, 38.4% of people asked to take part refused at some point during recruitment. 23 trials (22%) were performed, at least in part, with a waiver of informed consent, 7 (30%) of which provided any form of notice to subjects. CONCLUSIONS Overall refusal rates for pragmatic and comparative effectiveness RCTs appear roughly the same as other types of research, with studies reporting about a third of people solicited for participation refuse. Moreover, informed consent was waived in 22% (95% Binomial exact Confidence Interval 13.9-30.5%) of the trials, and further study is needed to understand when waivers are justified and when notice should be provided.
10.1016/j.cct.2021.106361
pubmed_227_17857
The epidemiology of suicide in Serbia and Montenegro from 1989 to 2003, a period of civil war, is presented. Following the break-up of former Yugoslavia, Serbia and Montenegro underwent a period of war from 1991-1994 and another in 1999. During the war years, the number of suicides increased, reaching its peak in 1993. Male suicides outnumbered female suicides by a ratio of 2:1. Male suicides decreased slightly after the war of 1991-1994 only to rise in 1997 and continue at this higher level throughout the nineties. In Serbia alone, male suicide reached its peak in 2002 (nearly 29/100,000). The methods of suicide changed significantly, with the use of firearms doubling during and after the war years. Speculations are offered about the findings, many consistent with Durkheim's classical hypothesis concerning suicide and unpopular wars.
10.1080/13811110600582406
pubmed_614_3750
Here, we report the draft genome sequence of an anthracimycin producer, Streptomyces sp. TP-A0875. The genome contains at least two type I polyketide synthase (PKS) gene clusters, two type II PKS gene clusters, and three nonribosomal peptide synthetase gene clusters. The gene cluster for anthracimycin biosynthesis was identified based on the PKS domain organization.
pubmed_614_3750
pubmed_476_20868
This study aimed to investigate the effects of chitooligosaccharide (COS) on intestinal barrier, antioxidant capacity, and immunity of lipopolysaccharide (LPS)-challenged laying hens. A total of 360 Hy-line Brown laying hens (80-wk-old) were randomly divided into 5 groups with 6 replicates of 12 birds. Hens were fed a corn-soybean meal basal diet supplemented with different COS levels (0; 5; 10; 15; 20 mg/kg) for 8 wk. The results showed that 15 mg/kg COS administration elevated albumen height and Haugh unit (P < 0.05), and numerically optimized productive performance (P > 0.05), therefore, the dosage of 15 mg/kg was chosen for the subsequent experiment. Thereafter, 12 birds from non-supplemented group were randomly selected and assigned into 2 groups, and birds in each group were administered (1.5 mg/kg BW, i.p.) with saline (control group) or LPS (challenge group). Another 6 hens from 15 mg/kg COS-supplemented group were selected and injected with LPS in the same way. Compared with the control group, LPS-challenged birds exhibited elevated circulating diamine oxidase activity, and reduced jejunal villus height and ratio of villus height to crypt depth, and these indices were reversed to control levels by COS (P < 0.05). Also, LPS increased malondialdehyde accumulation and reduced several antioxidant enzyme activities in the intestinal mucosa (P < 0.05). Additionally, LPS increased jejunal secretory IgA and interferon-γ (IFN-γ), and ileal secretory IgA, IgM, and interleukin-1β (IL-1β) concentrations, whereas COS reduced jejunal IFN-γ and IL-1β, and ileal IgM levels (P < 0.05). Moreover, LPS down-regulated mRNA abundance of jejunal occludin and claudin 2, and upregulated expression of jejunal nuclear factor erythroid-2 related factor 2, superoxide dismutase 1, and IFN-γ as well as ileal IL-1β (P < 0.05). Besides, COS increased jejunal occludin and ileal claudin 2, nuclear factor erythroid-2 related factor 2, and heme oxygenase-1 expression, and decreased jejunal IFN-γ and IL-1β abundance (P < 0.05). These results suggested that COS could alleviate LPS-induced intestinal barrier impairment, and oxidative and immunological stress in laying hens.
10.1016/j.psj.2022.101701
pubmed_963_749
5-Fluorouracil (5-FU), a drug with numerous mechanisms of action which has a long-term suppressive effect on human cancer cell proliferation, mediates both partial dephosphorylation and inactivation of poly(A) polymerase (PAP) [EC. 2.7.7.19] as detected by immunoblotting analysis and non-specific enzyme assay, respectively, in human carcinoma HeLa and diploid WISH cells at a concentration of 100 microM. When the same experiment is done in the presence of phosphatase inhibitors, 5-FU-induced partial PAP dephosphorylation is abolished. Moreover, a cell type-modulated, differential response of HeLa cells (5-FU chemosensitive cells) versus WISH cells (drug-resistant diploid cells) is observed. These results suggest that 5-FU induces early direct or indirect changes in the structure and function of PAP and may regulate pre-mRNA cleavage-polyadenylation.
10.1177/172460080001500403
pubmed_42_19951
We recently demonstrated that oncostatin M (OSM) in the presence of glucocorticoid promotes development of fetal hepatic cells in a primary culture system. Our results also suggested that OSM transduces differentiation signals through gp130, a common subunit of the interleukin (IL)-6 family cytokine receptors. However, an essential downstream pathway required for hepatic development remains unknown. To address this issue, we expressed signal molecules by a retroviral expression vector in primary fetal hepatic cells and investigated a signaling pathway essential for OSM-mediated hepatic development. Expression of a dominant-negative form of STAT3 (DeltaSTAT3), but not DeltaSTAT5, suppressed differentiated phenotypes of hepatocytes induced by OSM. On the other hand, dominant-negative forms of Ras (RasN17) and SHP-2(C463A) rather augmented the expression of hepatic differentiation markers, suggesting that the Ras pathway negatively regulates hepatic development. Consistently, expression of a constitutively activated form of Ras (RasV12) inhibited cellular responses to OSM. Our results indicate that STAT3 is an essential signaling component for OSM-induced hepatic development, while activation of Ras appears to negatively regulate this process. Thus, retrovirus-mediated gene transfer is an effective means to analyze function of a gene in primary fetal hepatic culture.
10.1053/jhep.2000.19815
pubmed_663_17685
The heart diseases that account for a large amount of morbidity and mortality in the developed world (coronary artery disease, myocardial infarction and heart failure) are phenotypically heterogeneous disorders. It has been suspected for many years that genetics may have an important role in these diseases and their poor outcome. However, their complex and likely polygenic pathophysiology has confounded clear understanding of the genetic contribution to their etiology. Despite technological progress and great promise associated with genome-wide association studies, to date the results of their application to coronary artery disease, myocardial infarction and heart failure have yielded limited insights into these common diseases. This review discusses the current status of genome-wide association studies as they have been applied to these cohorts. The potential limitations of these studies, as well as potential future directions for identifying important genes are also discussed.
10.2217/14622416.10.2.213
pubmed_49_8096
Effectiveness of a pentavalent leptospiral vaccine to protect cattle from infection and reproductive problems caused by Leptospira interrogans serovar hardjo type hardjo-bovis was evaluated. Seven cows were vaccinated once and 8 cows were vaccinated twice with a USDA-licensed pentavalent leptospiral vaccine. Five cows were maintained as nonvaccinated controls. Cows were bred 1 to 2 months after the last vaccination. During the 4th to 6th month of gestation, all cows were challenge exposed on 4 occasions by conjunctival instillation of 10(8) serovar hardjo type hardjo-bovis organisms and on 3 occasions by conjunctival instillation of urine from a cow shedding hardjo-bovis. All control cows and 13 of 15 vaccinated cows became infected and shed leptospires in the urine. Leptospires were detected in fewer urine samples collected from vaccinated cows, compared with those collected from control cows. Four stillborn calves and 3 weak calves were born to control and vaccinated cows. Leptospires were detected in the kidneys of 11 apparently healthy calves born to vaccinated and control cows. Agglutinating antibodies were not detected in the precolostral serum of these calves.
pubmed_49_8096
pubmed_1059_688
Many investigators in Europe and the USA have usually found high rates of serum conversion after vaccination with the rubella vaccines Cendehill and RA 27/3, but the resistance of vaccinated individuals against superinfection without disease induced by wild virus strains under experimental or natural conditions seems to be very low; e.g. up to 80% of the vaccinees reacted with increasing titers of hemagglutination inhibiting antibodies after super-infection with a wild virus in a special epidemiological situation. In our two studies performed under natural conditions of infection including an observation period of three years resp. five years after vaccination a more favourable picture evolved, perhaps reflecting a different epidemiological situation, a different susceptibility or a less virulence of wild virus in our region: Three years after vaccination of 14 years old girls with Cendehill and RA 27/3 in a double blind trial a significant increase in the titers of hemagglutination inhibiting antibodies was observed after vaccination with Cendehill by the subcutaneous route in only 1,16% (1/86) and in 1,18% (1/85) after vaccination with RA 27/3 by the same route. In the same observation period the infection rate in a control group not protected by natural immunity or by vaccination was 54,72% (87/159) and in a second control group, protected by natural immunity 1,82% (3/165)...
pubmed_1059_688
pubmed_674_9128
It remains an ongoing challenge to develop cheap, highly active, and stable electrocatalysts to promote the sluggish electrocatalytic oxygen evolution, oxygen reduction, and hydrogen evolution reactions for rechargeable metal-air batteries and water-splitting systems. In this work, we report the morphology-controllable synthesis of zinc cobalt mixed sulfide (Zn-Co-S) nanoarchitectures, including nanosheets, nanoplates, and nanoneedles, grown on conductive carbon fiber paper (CFP) and the micronanostructure dependent electrochemical efficacy for catalyzing hydrogen and oxygen in zinc-air batteries and water electrolysis. The formation of different Zn-Co-S morphologies was attributed to the synergistic effect of decomposed urea products and the corrosion of NH4F. Among synthesized Zn-Co-S nanostructures, the nanoneedle arrays supported on CFP exhibit superior trifunctional activity for oxygen reduction, oxygen evolution, and hydrogen evolution reactions than its nanosheet and nanoplate counterparts through half reaction testing. It also exhibited better catalytic durability than Pt/C and RuO2. Furthermore, the Zn-Co-S nanoneedle/CFP electrode enables rechargeable Zn-air batteries with low overpotential (0.85 V), high efficiency (58.1%), and long cycling lifetimes (200 cycles) at 10 mA cm-2 as well as considerable performance for water splitting. The superior performance is contributed to the integrated nanoneedle/CFP nanostructure, which not only provides enhanced electrochemical active area, but also facilitates ion and gas transfer between the catalyst surface and electrolyte, thus maintaining an effective solid-liquid-gas interface necessary for electrocatalysis. These results indicate that the Zn-Co-S nanoneedle/CFP system is a low cost, highly active, and durable electrode for highly efficient rechargeable zinc-air batteries and water electrolysis in alkaline solution.
10.1021/acsami.6b16602
pubmed_740_11971
We calculate the transverse momentum dependent gluon-to-gluon splitting function within [Formula: see text]-factorization, generalizing the framework employed in the calculation of the quark splitting functions in Hautmann et al. (Nucl Phys B 865:54-66, arXiv:1205.1759, 2012), Gituliar et al. (JHEP 01:181, arXiv:1511.08439, 2016), Hentschinski et al. (Phys Rev D 94(11):114013, arXiv:1607.01507, 2016) and demonstrate at the same time the consistency of the extended formalism with previous results. While existing versions of [Formula: see text] factorized evolution equations contain already a gluon-to-gluon splitting function i.e. the leading order Balitsky-Fadin-Kuraev-Lipatov (BFKL) kernel or the Ciafaloni-Catani-Fiorani-Marchesini (CCFM) kernel, the obtained splitting function has the important property that it reduces both to the leading order BFKL kernel in the high energy limit, to the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi (DGLAP) gluon-to-gluon splitting function in the collinear limit as well as to the CCFM kernel in the soft limit. At the same time we demonstrate that this splitting kernel can be obtained from a direct calculation of the QCD Feynman diagrams, based on a combined implementation of the Curci-Furmanski-Petronzio formalism for the calculation of the collinear splitting functions and the framework of high energy factorization.
10.1140/epjc/s10052-018-5634-2
pubmed_770_10205
Bovine mammary epithelial cells were cultured in nutrient medium containing D-valine substituted for L-valine in an attempt to control fibroblast overgrowth. Contamination of epithelial cell cultures with fibroblasts was prevented in cultures maintained in D-valine but not in control cultures containing L-valine. Microscopic examination of cells cultured in the D-valine medium demonstrated similar morphology as controls after 27 days in culture. Concentration of alpha-lactalbumin in the D-valine medium was similar to levels found in control medium. Results suggest D-valine modified medium controls fibroblast overgrowth of cell cultures, but doesn't impair epithelial cell morphology or function.
10.1016/0309-1651(88)90060-4
pubmed_269_8263
INTRODUCTION Large scale investigation of the clinical effectiveness of neuraminidase inhibitors for circulating influenza viruses are important along with the surveillance of virus susceptibility in vitro. METHODS The duration of fever and other influenza symptoms as markers of the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) were investigated in the Japanese 2017/18 and 2018/19 influenza seasons and compared with the results of the previous six seasons. RESULTS Influenza A(H1N1)pdm09, A(H3N2), and B were found in 14, 45, and 52 patients in the 2017/18 season and in 22, 62, and 0 in the 2018/19 season, respectively. The median duration of fever for B was significantly longer than for A(H1N1)pdm09 and A(H3N2) in the 2017/18 season (p = 0.0461) and for A(H3N2) than for A(H1N1)pdm09 in the 2018/19 season (p = 0.0290). However, the differences were subtle in both seasons for other symptoms, with no significant differences in their median duration in comparison of the circulating types/subtypes. Over the eight seasons with the previous six seasons added, the median durations of fever were consistently longer for B than for A, but the relation between the A subtypes was inconsistent. The median durations of fever were comparable over the eight seasons for the virus types/subtypes, as were the median durations of other symptoms. The percentage of febrile patients decreased in a similar pattern over the eight seasons for each type/subtype. CONCLUSIONS The results confirmed that laninamivir has continued to be clinically effective against all types/subtypes of influenza viruses, with no safety issues.
10.1016/j.jiac.2022.03.008
pubmed_1086_10188
BACKGROUND Public access defibrillation has been introduced to improve the outcome of patients experiencing out-of-hospital cardiac arrest (OHCA). The aim of this study was to examine the best location for automated external defibrillators (AED). METHODS AND RESULTS All patients who were resuscitated after OHCA by emergency medical technicians in Takatsuki City over 6 years were enrolled. The annual incidence of OHCA and the number of 1-year survivors with good neurological outcome in each of 21 sub-location categories were investigated, as well as the ratio of ventricular fibrillation (VF) as the initial rhythm to the total OHCA in each of 5 location categories. In total, there were 1,112 patients with OHCA, 62 (5.6%) with VF and 14 (1.3%) with good neurological outcome. The annual incidence of cardiac arrest (CA) per site was the highest in railway stations (0.3000), followed by hospitals (0.1802), homes for the aged (0.1115), playgrounds (0.0769) and golf courses (0.0667). However, none of the patients experiencing CA at railway stations, homes for the aged and golf courses had a good neurological outcome. The ratio of VF to total CA was the highest in the workplace (35.3%). CONCLUSIONS The 6 locations, including workplace, are recommended as appropriate locations for AED.
10.1253/circj.70.827
pubmed_1125_12293
An immunohistochemical study of cytokeratins (CK) in a case of trichilemmal carcinoma (TLC). CK expression showed the presence of CK 1, 10, 14 and 17, suggesting that TLC differentiates toward follicular infundibulum. In a comparison of CK expression between TLC and trichilemmoma, the absence of CK 15 and 16 in TLC may be related to transformation from trichilemmoma to TLC. Trichilemmal carcinoma (TLC) is a rare cutaneous tumor, and is considered as a malignant counterpart of trichilemmoma. The histogenesis of TLC remains unclear. The features of TLC resemble the outer root sheath. Monoclonal antibodies against cytokeratin (CK) are crucial markers for evaluating the origin of epithelial tumors and the stage of differentiation. To elucidate the origin and the stage of differentiation of TLC, an immunohistochemical study of CK was performed using nine different anti-keratin antibodies against CK1, 7, 8, 10,14,16,17, 18 and 19.
pubmed_1125_12293
pubmed_290_9300
OBJECTIVE To describe cases and estimate subacute sclerosing panencephalitis (SSPE) risk following large-sale measles outbreaks in Georgia. A rare, fatal late complication of measles, SSPE is often overlooked in assessments focused on the acute illness. Georgia had 8377 and 11,495 reported measles cases during the 2004-2005 and 2013-2015 outbreaks, respectively, but SSPE burden has not been assessed. METHODS SSPE cases diagnosed during 2008-2017 were identified from hospitalization registries in major neurological departments likely to admit SSPE patients. Information on reported measles cases and deaths was obtained from the national measles surveillance system and published reports. The risk of SSPE (number of measles cases per one SSPE case) was calculated for cases associated with the 2004-2005 outbreak. Crude estimates were adjusted to account for potential under-reporting of measles, using 50%, 25% and 10% estimates of completeness of reporting. RESULTS Sixteen SSPE cases diagnosed during 2008-2017 were identified. Eleven (92%) of 12 SSPE cases with a known history of measles had infection at ≤2 years and one (8%) at 3 years of age. Crude estimate of SSPE risk for the 2004-2005 outbreak was 1:1396. Adjusted estimates were 1:2792, 1:1:5584 and 1:13 960, assuming 50%, 25% and 10% completeness of reporting measles cases, respectively. CONCLUSIONS The review demonstrated substantial risk of SSPE in Georgia, supporting recent data suggesting that risk of SSPE following measles infection is higher than previously thought. To prevent SSPE in Georgia, very high timely immunization coverage for measles should be achieved among children, and immunity gap among adults should be closed.
10.1016/j.cmi.2019.10.035
pubmed_363_22411
The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples. Vaccinations were well-tolerated. The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.
10.1016/s0264-410x(02)00357-2
pubmed_537_3577
Thrombin binds to fibrin at two classes of non-substrate sites, one of high affinity and the other of low affinity. We investigated the location of these thrombin binding sites by assessing the binding of thrombin to fibrin lacking or containing gamma' chains, which are fibrinogen gamma chain variants that contain a highly anionic carboxyl-terminal sequence. We found the high affinity thrombin binding site to be located exclusively in D domains on gamma' chains (Ka, 4.9 x 10(6) M-1; n, 1.05 per gamma' chain), whereas the low affinity thrombin binding site was in the fibrin E domain (Ka, 0.29 x 10(6) M-1; n, 1.69 per molecule). The amino-terminal beta15-42 fibrin sequence is an important constituent of low affinity binding, since thrombin binding at this site is greatly diminished in fibrin molecules lacking this sequence. The tyrosine-sulfated, thrombin exosite-binding hirudin peptide, S-Hir53-64 (hirugen), inhibited both low and high affinity thrombin binding to fibrin (IC50 1.4 and 3.0 microM respectively). The presence of the high affinity gamma' chain site on fibrinogen molecules did not inhibit fibrinogen conversion to fibrin as assessed by thrombin time measurements, and thrombin exosite binding to fibrin at either site did not inhibit its catalytic activity toward a small thrombin substrate, S-2238. We infer from these findings that there are two low affinity non-substrate thrombin binding sites, one in each half of the dimeric fibrin E domain, and that they may represent a residual aspect of thrombin binding and cleavage of its substrate fibrinogen. The high affinity thrombin binding site on gamma' chains is a constitutive feature of fibrin as well as fibrinogen.
10.1074/jbc.271.38.23121
pubmed_39_18112
PURPOSE To determine diagnostic precision with magnetic resonance (MR) imaging of the brain, the most predictive MR imaging features, and the added value of comparison with previous data for the diagnosis of asymptomatic progressive multifocal leukoencephalopathy (PML) associated with natalizumab (NTZ). MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and written informed consent was obtained. Eleven consecutive patients with multiple sclerosis (MS) who had received a definitive diagnosis of asymptomatic NTZ-associated PML (NTZ PML, 18 brain lesions) underwent 3-T MR imaging. The control group included 40 patients with MS but without PML who were treated with NTZ. Three readers independently performed blinded analysis of MR images. First, the readers were asked to detect NTZ PML lesions without comparing current images with previously obtained MR imaging data by evaluating MR images for the following features: U fiber and/or cortex involvement, lesion signal intensity and borders, and occurrence of punctate lesions. Second, they reassessed NTZ PML lesions with all the previous MR imaging data available. Diagnostic precision with MR imaging was assessed with and without comparison with previously obtained data. Logistic regression analyses were performed to identify the association of MR imaging features with NTZ PML. RESULTS Overall interobserver agreement was good (κ = 0.76; 95% confidence interval [CI]: 0.71, 0.81). Hyperintensity on diffusion-weighted images and involvement of U fibers were the most predictive features (odds ratio, 33.7; 95% CI: 4.9, 229.7 [P < .0001] and odds ratio, 8.7; 95% CI: 1.2, 61.4 [P = .03], respectively), while punctate lesions were exclusively observed in patients with NTZ PML. Comparison with previous MR imaging data improved specificity of MR imaging for the detection of NTZ PML lesions (from 88% to 100%, P = .05). CONCLUSION Recognition of the most predictive imaging features and comparison with previous MR imaging data may facilitate the detection of asymptomatic NTZ PML.
10.1148/radiol.2015150673
pubmed_216_25224
There is a wide variety of resistance mechanisms that hosts may evolve in response to their parasites. These can be functionally classified as avoidance (lower probability of becoming infected), recovery (faster rate of clearance), tolerance (reduced death rate when infected), or acquired immunity. It is commonly thought that longer lived organisms should invest more in costly resistance. We show that due to epidemiological feedbacks the situation is often more complex. Using evolutionary theory we examine how the optimal investment in costly resistance varies with life span in a broad range of scenarios. In the absence of acquired immunity, longer lived populations do generally invest more in resistance. If hosts have acquired immunity, the optimal resistance may either increase or decrease with increasing life span. In addition, there may be evolutionary bistability with high and low investments in avoidance or tolerance. The optimal investment in the duration of acquired immunity always increases with life span, and due to bistability, shorter lived hosts may commonly not evolve any immunity. In contrast, the optimal investment in the probability of acquiring immunity initially increases and then decreases with life span. Our results have important implications for the evolution of invertebrate and vertebrate immunity, and for the evolution of acquired immunity itself.
10.1111/j.1558-5646.2007.00001.x
pubmed_444_14409
Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H2 S and slightly acidic microenvironment. Here, a core-shell Cu2 O@CaCO3 nanostructure for CRC "turn-on" therapy is reported. With CaCO3 responsive to pH decomposition and Cu2 O responsive to H2 S sulfuration, Cu2 O@CaCO3 can be triggered "on" into the therapeutic mode by the colorectal TME. When the CaCO3 shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO3 shell exposes the Cu2 O core to be sulfuretted by H2 S to form metabolizable Cu31 S16 nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu2 O@CaCO3 can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu2 O@CaCO3 nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.
10.1002/adma.202004647
pubmed_481_12309
The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.
10.1093/sleep/20.9.739
pubmed_234_16186
The efficiency of axial gas dispersion during ventilation with high-frequency oscillation (HFO) is improved by manipulating the oscillatory flow waveform such that intermittent oscillatory flow occurs. We therefore measured the velocity profiles and effective axial gas diffusivity during intermittent oscillatory flow in a straight tube to verify the intermittency augmentation effect on axial gas transfer. The effective diffusivity was dependent on the flow patterns and significantly increased with an increase in the duration of the stationary phase. It was also found that the ratio of effective diffusivity to molecular diffusivity is two times greater than that in sinusoidal oscillatory flow. Moreover, turbulence during deceleration or at the beginning of the stationary phase further augments axial dispersion, with the effective diffusivity being over three times as large, thereby proving that the use of intermittent oscillatory flow effectively augments axial dispersion for ventilation with HFO.
10.1115/1.2798008
pubmed_718_17230
In an effort to find potent antifungal agents, optically active sulfur-containing triazole derivatives, sulfides (3) and sulfonamides (4), were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The sulfides (3) were prepared by the reaction of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl )-2-butanol (1) with various heteroarylmethyl chlorides in the presence of sodium methoxide. The sulfonamides (4) were synthesized starting from the disulfide (15) in three steps including oxidation of the corresponding sulfenamides (17). Some of the sulfur-containing triazole derivatives (3, 4) showed strong protective effects against candidosis in mice.
10.1248/cpb.42.85
pubmed_365_2127
We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast cancer samples by simultaneous RT-PCR and have investigated correlations between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT-PCR and ICA and with Ki67 immunostaining. A direct association was found between c-erbB3 and c-erbB4 mRNA and ER marker status measured by either RT-PCR (c-erbB3 P = 0.0003; c-erbB4 P = 0.02) or ICA (c-erbB-3 P = 0.002; c-erbB4 P = 0.01). Inverse associations were seen between c-erbB3 and c-erbB4 mRNA marker status and EGFR membrane protein (c-erbB3: P = 0.003; cerbB4: P = 0.003) and mRNA (c-erbB4: P = 0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A significant relationship was seen between Ki67 and c-erbB4 mRNA status and level. Measurements of c-erbB3 protein levels in tumour samples removed from a further 89 patients of known response to endocrine therapy: (i) confirmed the relationship between c-erbB3 and ER and (ii) identified that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to benefit from endocrine measures. A non-significant trend was recorded between c-erbB3 levels and Ki67 immunostaining. These results clearly demonstrate that increased c-erbB3 and c-erbB4 expression appears to be associated with the prognostically-favourable ER phenotype.
10.1038/sj.onc.1202107
pubmed_67_4855
The meningioma brain tumor detection and segmentation method is a complex process due to its low intensity pixel profile. In this article, the meningioma brain tumor images were detected and tumor regions were segmented using a convolutional neural network (CNN) classification approach. The source brain MRI images were decomposed using the discrete wavelet transform and these decomposed sub bands were fused using an arithmetic fusion technique. The fused image was data augmented in order to increase the sample size. The data augmented images were classified into either healthy or malignant using a CNN classifier. Then, the tumor region in the classified meningioma brain image was segmented using an connection component analysis algorithm. The tumor region segmented meningioma brain image was compressed using a lossless compression technique. The proposed method stated in this article was experimentally tested with the sets of meningioma brain images from an open access dataset. The experimental results were compared with existing methods in terms of sensitivity, specificity and tumor segmentation accuracy.
10.15430/JCP.2022.27.3.192
pubmed_126_21402
It was shown in this paper rarely appearing fetus defect namely,acranial fetus with placenta growing into the osteocranium. The aneurysm of the left carotid artery in the mother was the second complication in this pregnancy what was the indication to finish the pregnancy by cesarean section. The symptoms of osteocranium destruction caused by the trophoblast were not identified. The appearance of so heavy a CNS defect could be associated with deficiency of vitamin compounds particularly folic acid in the periconception period.
pubmed_126_21402
pubmed_769_3922
CTNNB1 encodes for the β-catenin protein, a component of the cadherin adhesion complex, which regulates cell-cell adhesion and gene expression in the canonical Wnt signaling pathway. Mutations in CTNNB1 have been reported to be associated with cancer and mental disorders. Recently, loss-of-function mutations in CTNNB1 have been observed in patients with intellectual disability and some other clinical manifestations including motor and language delays, microcephaly, and mild visual defects. We report an 8-year-old Iranian girl with intellectual disability, hypotonia, impaired vision such as vitreomacular adhesion, motor delay, and speech delay. A novel, de novo nonsense mutation (c.1014G > A; p.Trp338Ter) in exon 7 of the CTNNB1 (NM_001904) gene was detected and confirmed by whole-exome sequencing and Sanger sequencing, respectively. This study helps to expand the growing list of loss-of-function mutations known in the CTNNB1 gene.
10.1007/s10072-022-05904-4
pubmed_489_3327
Induction of embryogenesis from isolated microspore cultures is a complex experimental system where microspores undergo dramatic changes in developmental fate. After ~40 years of application of electron microscopy to the study of the ultrastructural changes undergone by the induced microspore, there is still room for new discoveries. In this work, high pressure freezing and freeze substitution (HPF/FS), the best procedures known to date for ultrastructural preservation, were used to process Brassica napus microspore cultures covering all the stages of microspore embryogenesis. Analysis of these cultures by electron microscopy revealed massive processes of autophagy exclusively in embryogenic microspores, but not in other microspore-derived structures also present in cultures. However, a significant part of the autophagosomal cargo was not recycled. Instead, it was transported out of the cell, producing numerous deposits of extracytoplasmic fibrillar and membranous material. It was shown that commitment of microspores to embryogenesis is associated with both massive autophagy and excretion of the removed material. It is hypothesized that autophagy would be related to the need for a profound cytoplasmic cleaning, and excretion would be a mechanism to avoid excessive growth of the vacuolar system. Together, the results also demonstrate that the application of HPF/FS to the study of the androgenic switch is the best option currently available to identify the complex and dramatic ultrastructural changes undergone by the induced microspore. In addition, they provide significant insights to understand the cellular basis of induction of microspore embryogenesis, and open a new door for the investigation of this intriguing developmental pathway.
10.1093/jxb/ert151
pubmed_15_21604
Acetylcysteine has been used to treat acetaminophen overdose for nearly 50 years. While no placebo controlled trials have been conducted, the efficacy of acetylcysteine is accepted for the prevention of hepatic injury when administered early after acetaminophen overdose. Acetylcysteine can be administered as an infusion or oral solution. The duration of treatment varies from 21 to 72 hours, depending on the protocol. Acetylcysteine also prevents death when administered to patients with hepatic failure from acetaminophen.
10.2174/138920112802273146
pubmed_219_9490
Today, old age does not represent a formal contraindication to kidney transplantation. Rather, there is evidence that in elderly patients renal transplantation offers longer life expectancy and better quality of life in comparison with dialysis. Yet, the results of renal transplantation in recipients older than 65years are inferior to those observed in younger adults, death with functioning graft representing a major cause of failure. Therefore, the selection of aged patients is of paramount importance. Apart from the routine clinical and biological investigations, three aspects have been relatively neglected by the transplant community and may require a careful analysis in elderly candidates to transplantation: the presence and degree of frailty, the presence of comorbidities and the adherence to prescriptions. Although there are rapid and simple tests for assessing the degree of frailty in the elderly, there is no clear cut-off value to decide whether a patient should be accepted or not. With advanced age the prevalence and severity of cardiovascular events and other diseases tend to increase. The use of combined age-comorbidity indices may be helpful to identify patients at high risk of mortality. Another critical point is the poor unintentional adherence to treatment, often caused by forgetfulness and mild cognitive impairment. These drawbacks may be further enhanced by a high number of pills to take and by changes in the dosage or type of prescriptions. A careful screening of the presence and degree of frailty, comorbidity and poor compliance to treatment is highly recommended before admitting older candidates to the waiting list for transplantation.
pubmed_219_9490
pubmed_750_429
Calcium-activated phospholipid scramblase mediates the energy-independent bidirectional translocation of lipids across the bilayer, leading to transient or, in the case of apoptotic scrambling, sustained collapse of membrane asymmetry. Cells lacking TMEM16F-dependent lipid scrambling activity are deficient in generation of extracellular vesicles (EVs) that shed from the plasma membrane in a Ca2+-dependent manner, namely microvesicles. We have adapted chemical induction of giant plasma membrane vesicles (GPMVs), which require both TMEM16F-dependent phospholipid scrambling and calcium influx, as a kinetic assay to investigate the mechanism of TMEM16F activity. Using the GPMV assay, we identify and characterize both inactivating and activating mutants that elucidate the mechanism for TMEM16F activation and facilitate further investigation of TMEM16F-mediated lipid translocation and its role in extracellular vesiculation.
10.1073/pnas.1817498116
pubmed_260_4291
We report the use of a micropipet-supported ITIES (interface between two immiscible electrolyte solutions, also called a liquid/liquid (L/L) or water/oil (W/O) interface) as a scanning electrochemical microscopy (SECM) tip to detect silver ion and explore Ag+ toxicity in living cells. A 1,2-dichloroethane solution containing a commercially available calixarene-based Ag+ ionophore (IV) was injected into a micrometer-size glass pipet to construct an Ag+-selective SECM tip. The local Ag+ concentration, down to the micromolar level, in the vicinity of living fibroblast cells, was monitored by SECM approach curves and through imaging of the uptake and efflux of Ag+ by living fibroblast cells in real time. The results show that several stages of interaction between Ag+ and fibroblast cells exist. Since a number of biological processes of cells are involved with non-redox-active ions, the work presented here provides a new way to explore cell metabolism, drug delivery, and toxicity assessment by SECM.
10.1021/ac070318a
pubmed_1075_3155
A novel parasitoid ciliate, Pseudocollinia brintoni gen. nov., sp. nov. was discovered infecting the subtropical sac-spawning euphausiid Nyctiphanes simplex off both coasts of the Baja California peninsula, Mexico. We used microscopic, and genetic information to describe this species throughout most of its life cycle. Pseudocollinia is distinguished from other Colliniidae genera because it exclusively infects euphausiids, has a polymorphic life cycle, and has a small cone-shaped oral cavity whose left wall has a field of ciliated kinetosomes and whose opening is surrounded on the left and right by 2 'oral' kineties (or ciliary rows) that terminate at its anterior border. Two related species that infect different euphausiid species from higher latitudes in the northeastern Pacific Ocean, Collinia beringensis Capriulo and Small, 1986, briefly redescribed herein, and Collinia oregonensis Gómez-Gutiérrez, Peterson, and Morado, 2006, are transferred to the genus Pseudocollinia. P. brintoni has between 12 and 18 somatic kineties, and its oral cavity has only 2 oral kineties, while P. beringensis comb. nov. has more somatic kineties, including 3 oral kineties. P. oregonensis comb. nov. has an intermediate number of somatic kineties. P. beringensis comb. nov. also infects Thysanoessa raschi (a new host species). SSU rRNA and cox1 gene sequences demonstrated that Pseudocollinia ciliates are apostome ciliates and that P. brintoni is different from P. beringensis comb. nov. High densities of rod-shaped bacteria (1.7 µm length, 0.2 to 0.5 µm diameter) were associated with P. brintoni. After euphausiid rupture, high concentrations of P. brintoni and bacteria cluster to form 3 to 6 cm long filaments where tomites encyst and transform to the phoront stage; this is a novel place for encystation. P. brintoni may complete its life cycle when the euphausiids feed on these filaments.
10.3354/dao02450
pubmed_299_16368
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of these new therapy classes and if they have renoprotective effects in patients with CKD.
10.2147/CPAA.S82008
pubmed_1053_3372
Research on quality of life may herald a welcome psychosomatic change in biomedical research and clinical practice. The many promising horizons available, however, do not prevent miscommunication, random effort and faulty reasoning. An illusion of simplicity has caused many investigators to believe that the measurement of quality of life is simple and feasible, whereas only the psychosocial variables affecting quality of life can be assessed by current, reliable psychometric methods. The areas concerned with biomedical research on quality of life are reviewed and some methodological issues are discussed.
10.1159/000288381
pubmed_392_12299
BACKGROUND Social support network offers a large potential in augmenting suicide prevention efforts tailored for the young generation (YG), but has so far been largely overlooked in population health studies. Key issues that remain scarcely understood include the composition of the YG's activated support network when they faced psychological distress, along with the prevalence and suicide risk profile associated with these patterns. METHODS Using data from three consecutive population-representative surveys (2018-2020) on help-seeking behaviors of the YG living in Hong Kong, we first conducted latent class analysis to derive the YG's help-seeking patterns. Next, we conducted multinomial logistic regression to identify unique factors associated with each pattern and multiple logistic regressions for suicide risk indicators to examine risk levels associated with each pattern. RESULTS Analyses revealed 4 underlying patterns of help-seeking behaviors among the study population. Each pattern was consistently associated with a distinct suicide risk profile based on constituents' level of distress and history of suicide risk behaviors. Severity of suicide risk increased as individuals increased the activation radius of their social convoy, and this increase was more pronounced when individuals extended the radius beyond their inner circle. Individuals whose activated inner circle consisted of family members in addition to just friends & partner had lower suicide risks. CONCLUSIONS Social support networks hold much potential in augmenting suicide prevention efforts tailored for the general young population. Such efforts may be directed at empowering the inner circle of their convoy, given its predominance for the YG to seek help from.
10.1016/j.jad.2021.10.106
pubmed_74_7621
BACKGROUND Although air pollutants have been associated with cardiopulmonary mortality, their effects on the occurrence of atrial fibrillation (Afib) remain unclear. This study examined the association between ambient air pollutants and Afib occurrence. METHODS Using a representative sample from the National Health Insurance Database of Taiwan, we applied a case-crossover study design to explore the associations between air pollutants and patients hospitalized with Afib from 2006 to 2011. The event day was when a patient was hospitalized with Afib, and the control days were the same days of the following weeks of the same month. The association between Afib occurrence and levels of ambient air pollutants (including particulate matter [PM] 2.5 PM10, NO2, SO2, and O3) was examined after adjusting for temperature and relative humidity. A two-pollutant model was used to examine the effect of the second pollutant when the first pollutant was determined to be significantly related to Afib. RESULTS During 2006-2011, 670 patients hospitalized with the first onset of Afib were identified. The occurrence of Afib was associated with PM2.5, in which a 22% (95% confidence interval = 3-44%) increase was related to an interquartile range increase (26.2 μg/m3) on the same day and a 19% (95% confidence interval = 0-40%) increase on the second day. A two-pollutant model was applied, and the results indicated that the effect of PM2.5 was significantly associated with the occurrence of Afib. Patients aged over 65 years with DM and with hyperlipidemia were more susceptible to the effect of PM2.5. CONCLUSIONS In conclusion, the occurrence of Afib was associated with short-term exposure to fine particulate air pollutants in the general population.
10.1186/s12940-019-0554-7
pubmed_656_10136
Measles is characterized by fever and a maculopapular skin rash, which is accompanied by immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear cells in the epidermis, around hair follicles and near sebaceous glands. Here, we address the pathogenesis of measles skin rash by combining data from experimentally infected NHPs, ex vivo infection of human skin sheets and in vitro infection of primary human keratinocytes. Analysis of NHP skin samples collected at different time points following MV inoculation demonstrated that infection in the skin precedes onset of rash by several days. MV infection was detected in lymphoid and myeloid cells in the dermis before dissemination to the epidermal leukocytes and keratinocytes. These data were in good concordance with ex vivo MV infections of human skin sheets, in which dermal cells were more targeted than the epidermal cells. To address viral dissemination to the epidermis and to determine whether the dissemination is receptor-dependent, we performed experimental infections of primary keratinocytes collected from healthy donors. These experiments demonstrated that MV infection of keratinocytes is mainly nectin-4-dependent, and differentiated keratinocytes, which express higher levels of nectin-4, are more susceptible to MV infection than proliferating keratinocytes. Based on these data, we propose a model to explain measles skin rash: migrating MV-infected lymphocytes initiate the infection of dermal skin-resident CD150+ immune cells. The infection is subsequently disseminated from the dermal papillae to nectin-4+ keratinocytes in the basal epidermis. Lateral spread of MV infection is observed in the superficial epidermis, most likely due to the higher level of nectin-4 expression on differentiated keratinocytes. Finally, MV-infected cells are cleared by infiltrating immune cells, causing hyperemia and edema, which give the appearance of morbilliform skin rash.
10.1371/journal.ppat.1008253
pubmed_52_8336
This review will discuss developments in the field of pulmonary vaccine delivery. The possibilities of adopting aerosol-generation technology and specific pharmaceutical formulations for the purpose of pulmonary immunization are described. Aerosol-generation systems might offer advantages with respect to vaccine stability and antigenicity. Adjuvants and their inclusion in vaccine-delivery systems are described. Other formulation components, such as surfactants, particulate systems and dispersion of the aerosols are detailed in this paper. The noninvasive, relatively safe and low-cost nature of pulmonary delivery may provide great benefits to the public health vaccination campaign.
10.1586/14760584.6.2.213
pubmed_1088_23948
INTRODUCTION The aim of this study was to review the management and outcome of patients with Boerhaave's syndrome in a specialist centre between 2000-2007. PATIENTS AND METHODS Patients were grouped according to time from symptoms to referral (early, < 24 h; late, > 24 h). The effects of referral time and management on outcomes (oesophageal leak, reoperation and mortality) were evaluated. RESULTS Of 21 patients (early 10; late 11), three were unfit for surgery. Of the remaining 18, immediate surgery was performed in 8/8 referred early and 6/10 referred late. Four patients referred late were treated conservatively. Oesophageal leak (78% versus 12.5%; P < 0.05) and mortality (40% versus 0%; P < 0.05) rates were higher in patients referred late. For patients referred late, mortality was higher in patients managed conservatively (75% versus 17%; not significant). CONCLUSIONS The best outcomes in Boerhaave's syndrome are associated with early referral and surgical management in a specialist centre. Surgery appears to be superior to conservative treatment for patients referred late.
10.1308/003588409X428298
pubmed_299_14848
This study was conducted to assess the anti-inflammatory effect of a novel synthesized phenanthridine alkaloid (PHE-4i) and to examine the possible involvement of hydrogen sulfide (H2S) in anti-inflammatory mechanism. The synthesized phenanthridine derivative PHE-4i (2, 5, and 10 mg/kg) was administered intraperitoneally to rats. One hour following treatment, inflammation was induced by intraplantar injection of carrageenan (1 %), in the hind paw. Paw volume as the index of inflammation was measured before and after carrageenan injection. Neutrophil sequestration into the hind paw was quantified by measuring tissue myeloperoxidase (MPO) activity and was compared for the inhibition of H2S production. Pretreatment with PHE-4i significantly reduced carrageenan-induced hind paw weight, MPO activity, leukocyte infiltration, and H2S production in a dose-dependent manner (p < 0.001). These results indicate that the anti-inflammatory effect of PHE-4i on carrageenan-induced rat paw oedema could be via the inhibition of the gaseous mediator H2S.
10.1007/s10787-016-0273-4
pubmed_714_249
This study has examined in detail the effect of temperature (7-37 degrees C) and water availability (water activity, a(w), 0.89-0.97) on fumonisin B1 (FB1) production by an isolate of Fusarium moniliforme and F. proliferatum on irradiated maize grain after incubation for 28 days. The optimum conditions for F. moniliforme and F. proliferatum were 30 degrees C at 0.97 a(w) and 15 degrees C at 0.97 a(w), respectively. The maximum concentrations were 2861 mg kg(-1) and 17,628 mg kg(-1) dry wt. maize grain, respectively. At marginal a(w)/temperature conditions for growth (e.g. 0.89-0.91 a(w)) no FB1 was detected (<0.1 mg kg(-1)). A high variability was found between replicates for F. moniliforme, but not for F. proliferatum. These data were used to construct two-dimensional diagrams of all the a(w) x temperature conditions favourable for FB1 production for the first time. The data were also subjected to a polynomical regression, which demonstrated that there was a very good fit for the 15-30 degrees C range of temperature and at 0.97 a(w). However, at marginal environmental conditions this was not possible. This suggests that it may be possible to predict within a limited environmental range the potential for significant FB1 production.
10.1016/s0168-1605(99)00115-4
pubmed_751_10711
Urinary incontinence may be a formidable hardship in many girls with myelodysplasia. In those patients who fail treatment with intermittent self-catheterization and pharmacotherapy surgical augmentation of outlet resistance may successfully alleviate incontinence. In patients with less severe degrees of urethral sphincteric incompetence suprapubic endoscopic vesical neck suspension in conjunction with intermittent self-catheterization can be successful. Patients must be selected carefully, with particular attention directed at detecting decreased detrusor compliance. Poor detrusor compliance must be controllable or corrected before augmentation of urethral resistance to prevent postoperative upper urinary tract deterioration.
10.1016/s0022-5347(17)45529-7
pubmed_789_6970
BACKGROUND Radical rectal resection with total mesorectal excision is the current standard of care for the operative treatment of rectal cancer. Local excision is an acceptable alternative in selected patients with early disease (T(is)0-T(1)) and low-risk features, in whom radical resection may be associated with unacceptably high morbidity. With recent data demonstrating favorable results in well-selected patients, the role of local excision for rectal cancer is expanding.1 (,) 2 Transanal endoscopic microsurgery (TEM), which requires the use of an operating anoscope, has been used for the local excision of mid-upper rectal tumors. We describe an alternative approach to TEM for rectal cancer. METHODS We present a stepwise technique for TEM using a single-incision laparoscopic (SILS) port. The patient is a 64 year-old male with a right anterolateral rectal polyp 7 cm from the anal verge, which on snare polypectomy demonstrated in-situ carcinoma with positive margins. Endoscopic ultrasound demonstrated uT(1) disease with no lymphadenopathy. He opted for local excision and underwent TEM. Our stepwise approach includes: (1) delineation of excision margins, (2) full thickness incision of the rectal wall, (3) circumferential dissection, and full thickness excision, and (4) suture repair. RESULTS The procedure was performed without intraoperative or postoperative complications. Final pathology revealed in-situ carcinoma with widely negative margins. At 1- and 3-week follow-up visits, the patient was pain free with normal bowel activity and no rectal bleeding or genitourinary dysfunction. DISCUSSION TEM using a SILS port is an effective technique for the local excision of mid-upper rectal cancer in well-selected patients.
10.1245/s10434-012-2359-6
pubmed_891_8782
The marine drug histochrome is a special natural antioxidant. The active substance of the drug is echinochrome A (Ech A, 7-ethyl-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), the most abundant quinonoid pigment in sea urchins. The medicine is clinically used in cardiology and ophthalmology based on the unique properties of Ech A, which simultaneously block various links of free radical reactions. In the last decade, numerous studies have demonstrated the effectiveness of histochrome in various disease models without adverse effects. Here, we review the data on the various clinical effects and modes of action of Ech A in ophthalmic, cardiovascular, cerebrovascular, inflammatory, metabolic, and malignant diseases.
10.3390/md19080412
pubmed_229_18857
The efficacy and toxicity of a combination of fludarabine and cyclophosphamide (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL). Between April 1997 and July 1998, 36 patients with CLL (median age 59 years) received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1-3. Cycles were repeated every 28 d. Twenty-one patients had received between one and three different treatment regimens prior to the study, while 15 patients had received no prior therapy. The median Eastern Cooperative Oncology Group performance score was 1. One patient was at Binet stage A, 18 were stage B and 17 patients were stage C. Objective responses, assessed according to the revised guidelines of the National Cancer Institute-sponsored Working Group, were recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial remissions and five complete remissions were observed. Two patients showed no change and one patient showed disease progression. At February 2000, three of the responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No treatment-related deaths and no grade 3 or 4 infections occurred. We conclude that the combination of fludarabine and cyclophosphamide showed significant activity in patients with CLL. Myelosuppression was the major side-effect. These results warrant further study on the FC combination in randomized trials.
10.1046/j.1365-2141.2001.02959.x
pubmed_984_4753
A ridge waveguide technology exhibiting high polarization dependency is developed for new efficient multi-section passive polarization rotator applications. In the presented configuration, the calculated mode coupling between the waveguide sections is very efficient and allows a polarization rotation with a high extinction ratio at lambda=1,55 mum. Experimental results show efficient polarization rotation with low cross-talk levels (-16dB) and no significant excess losses between sections. However, the overall transmission efficiency is limited by propagation losses and coupling losses to standard optical fibers.
10.1364/oe.15.012436
pubmed_400_3100
Three types of sea alga distributed along the Syrian coast have been collected and analyzed for radioactivity and trace elements. Results have shown that (137)Cs concentrations in all the analyzed sample were relatively low (less than 1.2 Bq kg(-1) dry weight) while the levels of naturally occurring radionuclides, such as (210)Po and (210)Pb, were found to be high in most samples; the highest observed value (27.43 Bq kg(-1) dry weight) for (210)Po being in the red Jania longifurca alga. In addition, most brown alga species were also found to accumulate (210)Po, which indicates their selectivity to this isotope. On the other hand, brown alga (Cystoseira and Sargassum Vulgare) have shown a clear selectivity for some trace metals such as Cr, As, Cu and Co, this selectivity may encourage their use as biomonitor for pollution by trace metals. Moreover, the red alga species were found to contain the highest levels of Mg while the brown alga species were found to concentrate Fe, Mn, Na and K and nonmetals such as Cl, I and Br.
10.1016/S0265-931X(02)00177-7
pubmed_649_12820
A 20 cm length of the main mesenteric lymph duct in the sheep was cannulated at both ends and measurements were made in both conscious and anaesthetized animals of the ability of the duct to pump saline from an inflow reservoir to an outflow at the same height. Fluid was propelled only when the lymphatic contracted and this was unaffected by movements of the animal round the cage or by fluctuations in abdominal pressure or by respiratory movements. It was confirmed that the mesenteric duct was 'isolated' from the rest of the lymphatic system by closing the inflow tap whereupon fluid propulsion ceased. Raising transmural pressure by varying inflow and outflow by the same amount had the effect of increasing fluid output; this was achieved by an increase in both the frequency and force of lymphatic contractions. Lymphatic frequency of contraction and fluid output increased when the animals were frightened. Intravenous infusions of noradrenaline increased the frequency of lymphatic contraction and increased fluid propulsion, while isoprenaline infusions depressed flow. This preparation demonstrates that it is possible to study the control of lymphatic pumping in conscious sheep without the complication of changing rates of lymph formation.
10.1113/jphysiol.1986.sp016210
pubmed_392_25652
OBJECTIVE The aim of this study was to compare the characteristics and distribution of trauma surgeries performed in the first phase of the COVID-19 pandemic, the second phase of the pandemic, and the normal period before the pandemic. METHODS Three different time periods were determined.Group 1 represented the first wave of the pandemic, in which lockdowns andrestrictions were strictly applied and only emergency and trauma surgeries wereperformed, between 1 April and 31 May 2020. Group 2 represented the second waveof the pandemic, during which restrictions were not applied and only emergencyand trauma surgeries were performed, from 1 September to 31 October 2020. Group3 represented the normal period before the pandemic, including surgeriesperformed between 1 September and 31 October 2019. In addition, patients ineach group were divided into two groups as younger than 16 or older than 16 inorder to understand the difference between paediatric and adult orthopaedictraumas. The distribution of patients and their fractures were evaluated. RESULTS In Group 1, the rates of intra-articular fractures, distal extremity fractures, and proximal humerus fractures decreased, while the rate of proximal femur fractures increased (P < 0.05 for all). The frequency of hand fractures treated in Groups 1 and 2 compared to Group 3 was reduced (P < 0.05 for both). There was no statistically significant difference between Groups 2 and 3 for fractures in different parts of the body except for hand fractures (P = 0.001 for hand fractures, P > 0.05 for the other fractures). CONCLUSION We observed that the frequency of fractures decreased, and the distribution changed due to severe restrictions and lockdowns in the first wave of the pandemic. When the restrictions and lockdowns were removed in the second wave, the frequency of fractures decreased, but the distribution of fractures was similar to the normal period in 2019. LEVEL OF EVIDENCE Level III, Diagnostic Study.
10.5152/j.aott.2021.21117
pubmed_263_12856
BACKGROUND Gram-negative bacillary (GNB) meningitis is a rare cause of meningitis in adults and can occur as a spontaneous infection or as a complication of a neurosurgical procedure or trauma. We aimed to describe the characteristics and outcomes of adults with spontaneous GNB meningitis. METHODS A retrospective cohort analysis was performed of 26 patients with GNB meningitis seen at a single hospital in Soweto, South Africa. RESULTS A predisposing condition was found in 24 (92%) patients. The 19 (73%) HIV-infected patients had a median CD4 count of 24/mm(3). Chronic renal disease, diabetes mellitus, myeloma, and alcoholism were other underlying conditions. The HIV-infected had a median cerebrospinal fluid (CSF) neutrophil count of 2/mm(3) compared to the HIV-non-infected of 560/mm(3). Common organisms were Escherichia coli, Klebsiella pneumoniae, and non-typhoidal Salmonella in HIV-positive patients and K. pneumoniae in the HIV-negative group. Ten (38%) isolates were resistant to third-generation cephalosporins. Mortality was 65%. CONCLUSIONS A disproportionate burden of GNB meningitis fell on the HIV-infected, among whom absent or low CSF white cells was common. Management was complicated by high rates of resistance to third-generation cephalosporins.
pubmed_263_12856
pubmed_609_12161
The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.
10.1093/infdis/173.3.758
pubmed_868_12328
OBJECTIVE To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. METHODS A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. RESULTS At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. CONCLUSION Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.
10.1097/AOG.0000000000000926
pubmed_612_4633
Diheme cytochromes, the simplest members in the multiheme family, play substantial biochemical roles in enzymatic catalysis as well as in electron transfer. A series of diiron(III) porphyrin dimers have been synthesized as active site analogues of diheme cytochromes. The complexes contain six-coordinated iron(III) having thiophenol and imidazole at the fifth and sixth coordination sites, respectively. The iron centers in the complexes have been found to be in a low-spin state, as confirmed through solid-state Mössbauer and electron paramagnetic resonance (EPR) spectroscopic investigations. Mössbauer quadrupole splitting of complexes having mixed ligands is substantially larger than that observed when both axial ligands are the same. Rhombic types of EPR spectra with narrow separation between g, g, and g clearly distinguish heme thiolate coordination compared to bis(imidazole)-ligated low-spin heme centers. The redox potential in diheme cytochromes has been found to be tuned by interheme interactions along with the nature of axial ligands. The effect of mixed-axial ligation within the diiron(III) porphyrin dimers is demonstrated by a positive shift in the Fe(III)/Fe(II) redox couple upon thiophenolate coordination compared to their bis(imidazole) analogues. The pKa of the imidazole also decides the extent of the shift for the Fe(III)/Fe(II) couple, while the potential of the mixed-ligated diiron(III) porphyrin dimer is more positive compared to their monomeric analogue. A variation of around 1.1 V for the Fe(III)/Fe(II) redox potential in the diiron(III) porphyrin dimer can be achieved with the combined effect of axial ligation and a metal spin state, while such a large variation in the redox potential, compared to their monomeric analogues, is attributed to the heme-heme interactions observed in dihemes. Moreover, theoretical calculations also support the experimental shifts in the redox potential values.
10.1021/acs.inorgchem.1c01215
pubmed_107_11716
Fluorescent carbocyanine dye (diI), applied to the glossopharyngeal (IX) nerve of the axolotl, transneuronally labeled solitary cells in the non-taste lingual epithelium. With diaminobenzidine (DAB), the diI was photoconverted to a dark, electron-dense product. The labeled cell had a large nucleus with invaginations, dense-cored vesicles in the cytoplasm, and finger-like processes. These are reminiscent of morphological features of cutaneous Merkel cells, suggesting that solitary cells innervated by the IX nerve are associated with mechanosensory function of the IX nerve system.
10.1016/0304-3940(94)90275-5
pubmed_1057_9136
BACKGROUND Fasciotomy incision closure is often performed with skin grafts that can lead to cosmetic and functional complications after surgical intervention. Because fasciotomy incisions do not result in skin loss, the authors hypothesized that better closure can be achieved by reducing tissue edema with negative-pressure wound therapy (NPWT) and reducing stress on the skin with the shoelace surgical technique. METHODS This 1-year prospective study included eight patients with acute compartment syndrome after extremity fractures and/or blunt injuries. Patients were treated with fasciotomies closed with the shoelace technique and NPWT for wound margin approximation. The NPWT device was changed every second day; the shoelace traction tension was tightened at the same time. MAIN RESULTS The mean time from fasciotomy to wound closure was 11.8 days (range, 5-30 days). There was no need for a skin graft or flap in any patient. CONCLUSIONS The shoelace technique plus NPWT may be successful in closing skin fasciotomies after acute compartment syndrome without causing additional morbidity.
10.1097/01.ASW.0000672492.38463.58
pubmed_229_13636
BACKGROUND AND OBJECTIVES The differential diagnosis between multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) may be uncertain in some cases; this problem is reflected by discrepancies between different classification systems with an accordance in only 2/3 of cases. We studied whether flow-cytometric characteristics of plasma cells (PC) can be used for the differentiation between MGUS and MM. DESIGN AND METHODS Patients were divided into 3 groups: Group A included 13 myeloma patients with a plasma cell infiltration of the bone marrow of 10-30%, serum M-protein < or = 3.5 g/dL (IgG) or < or = 2 g/dl (IgA) and without bone lesions in conventional radiography. Group B consisted of 53 patients who fulfilled the Durie and Salmon diagnostic criteria including at least one major criterion, and group C individuals with MGUS (n=17). The ratio of immunophenotypically normal (i.e. CD19(+)/CD56(-)) to all bone marrow plasma cells (BMPC), the number of peripheral blood PC (PBPC), the percentage of BMPC in S-phase and the DNA content of BMPC were analyzed. RESULTS All individuals with MGUS and no patient with MM in group A or group B had a ratio of phenotypically normal to all BMPC > or = 20%. The median of monoclonal PBPC was 0/microL (range 0-2/ microL) in MGUS, 1/microL (range 0-30/microL) in MM group A and 2.4/microL (range 0-211/microL) in MM group B. The median percentage of BMPC in S-phase was 1.6% both in MGUS and in group A and 3% in group B. Aneuploidy was found in 12%, 11% and 41% in MGUS, group A and group B, respectively. INTERPRETATION AND CONCLUSIONS The ratio of immunophenotypically normal to all BMPC was the only flow-cytometric parameter for the differentiation of MGUS and MM group A (p<0.0005). The other parameters were significantly different between MGUS and MM group B, but not group A.
pubmed_229_13636
pubmed_745_13164
Streptozotocin-induced diabetes increased sorbitol levels in the rat renal medulla. The activities of renal medullary aldose reductase and sorbitol dehydrogenase, responsible for the formation and metabolism of sorbitol, favor sorbitol formation and did not change in diabetes. The elevated sorbitol concentration appears to be due to an increase in medullary glucose concentration.
10.1159/000469124
pubmed_667_9856
Novel lignin is formed in a mutant loblolly pine (Pinus taeda L.) severely depleted in cinnamyl alcohol dehydrogenase (E.C. 1.1.1.195), which converts coniferaldehyde to coniferyl alcohol, the primary lignin precursor in pines. Dihydroconiferyl alcohol, a monomer not normally associated with the lignin biosynthetic pathway, is the major component of the mutant's lignin, accounting for approximately 30 percent (versus approximately 3 percent in normal pine) of the units. The level of aldehydes, including new 2-methoxybenzaldehydes, is also increased. The mutant pines grew normally indicating that, even within a species, extensive variations in lignin composition need not disrupt the essential functions of lignin.
10.1126/science.277.5323.235
pubmed_800_14977
BACKGROUND The high rate of recurrences of cholesteatomas after surgery is mostly caused by insufficient removal of matrix. Another factor may be intraoperative scattering of matrix cells e. g. with the running burr, which later may become the origin of new cholesteatoma growth. In this paper we tried to visualize these cells for gaining further informations. PATIENTS AND METHODS In 10 patients intraoperative contact endoscopy of the cholesteatoma was carried out during mastoidectomy. After intravital staining with methylene blue the very superficial tissue layers can directly be considered via a contacting endoscope. In addition, sucked-off rinsing fluid was cytologically examined for epithelial cells. RESULTS Both investigations show only very rare vital squamous cells - besides other cells like or ciliated cells and foreign body giant cells. DISCUSSION AND CONCLUSIONS Inspite of their small number, these squamous cells in principle could cause dispersed growth of cholesteatoma. However, this seems to be much less significant than the assumption of matrix left behind intraoperatively. The danger of dispersed cell growth can further be diminished by adequate operating techniques with sufficient rinsing, smoothing the bony cavity walls and avoiding blind corners.
10.1055/s-2001-17092
pubmed_740_6042
BACKGROUND Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. METHODS We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications. RESULTS We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, P<0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population. CONCLUSION We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.
10.2147/BTT.S150958
pubmed_361_10184
The effect of heredity on blood pressure is established. However, not all genetically predisposed individuals develop an elevated blood pressure. Thus, an environmental factor may also be required for expression of this genetic predisposition. To elucidate this effect further, as well as to examine the relationship between inherited factors and the influence of salt intake, we conducted acute and chronic investigations in normal subjects. We present evidence that renal function, the renin-angiotensin-aldosterone system, and sympathetic nervous system are all influenced by genetic variance. We found that the blood pressure response to both acute changes in volume and changes in salt intake is normally distributed, supporting the notion of salt sensitivity and resistance of blood pressure. We identified phenotypes of haptoglobin as possibly useful indicators of salt sensitivity and resistance. We documented a parent-offspring resemblance in blood pressure and also a maternal-offspring resemblance in the change in blood pressure with salt reduction. We present evidence that suggests that salt-sensitive persons exhibit differences in renin-aldosterone relationships and natriuretic responses consistent with volume expansion compared to salt-resistant individuals. Finally, we identified a potential role for altered adrenoreceptors in the development of salt sensitivity. Our observations speak to the inherited nature of salt sensitivity and resistance of blood pressure. They may have mechanistic implications as well.
pubmed_361_10184
pubmed_456_4400
AIM To elucidate uptake mechanisms and immunomodulatory potential of differently sized gold nanoparticles (GNPs) in lung adenocarcinoma cells (A549) to enable their use as an adjunct therapy for treating inflammation-linked lung cancer. METHODS Internalization of the synthesized (5, 15 and 30 nm) GNPs by various endocytosis pathways was determined. Immunomodulatory mechanisms induced by differently sized GNPs in A549 cells in the presence of TLR4 and TLR9 ligands were evaluated. RESULTS GNPs were size-dependently internalized efficiently by A549 cells. Various sized GNPs downregulated the expression of proinflammatory signaling molecules (5 nm most potent). Mechanistically, 5-nm GNPs attenuated TLR4 signaling by downregulating TLR4 expression in A549 cells. CONCLUSION Our study suggests the use of immunomodulatory GNPs as an adjunct therapy against inflammation-linked lung cancer.
10.2217/nnm-2018-0266
pubmed_292_21154
Degradation of 2,4,6-trinitrotoluene (TNT), a nitroaromatic explosive found in the soil and ground water, was investigated using Pseudomonas aeruginosa in in vitro experiments . Biodegradable abilitiy of this bacteria was performed with 50 and 75 mg L (-1) TNT concentrations in a defined liquid medium for 96 h time period. Treatment of TNT in supernatant samples taken at 0, 6, 12, 24, 48, 72 and 96 h from agitated vessels was followed by reverse-phase high-performance liquid chromatography (HPLC). In cultures supplemented with 50 and 75 mgL (-1) TNT, after 96 h of incubation 46% and 59% reduction were detected respectively. Two metabolites as degradation intermediates with nitrite release into the medium, 2,4-dinitrotoluene (2,4-DNT) and 4-aminodinitrotoluene (4-ADNT), were elucidated by thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS). These findings clearly indicate that Pseudomonas aeruginosa can be used in bioremediation of TNT contaminated sites.
10.1590/S1517-838246120140026
pubmed_921_19846
OBJECTIVE To estimate morbidity due to Bordetella pertussis infection in a representative population of Australian adults. DESIGN Telephone survey using structured questionnaire. PARTICIPANTS Adults (aged 20 years and over) notified with pertussis to a public health unit in western Sydney between 1 December 1997 and 31 May 1998. MAIN OUTCOME MEASURES Duration of cough; time to improvement; symptoms and complications; time to diagnosis; health resource use; lost work days. RESULTS Of 90 eligible patients, 73 (81%) completed questionnaires. Cough lasted a median of 60 days, but persisted over 90 days in 20 people (27%). Presentation was within a median of seven days of symptom onset, but diagnosis of pertussis took a median of 21 days. Participants reported a mean of 3.7 general practitioner visits and 1.2 prescription drugs. Of those employed, 17 (35%) missed more than five work days (range, 0-93 days). CONCLUSIONS B. pertussis infection in adults can result in prolonged, significant disruption to social and working life. Results suggest that, in 1998, there were more than 8000 general practitioner visits and 15,000 lost work days caused by pertussis in Australian adults.
10.5694/j.1326-5377.2000.tb139246.x
pubmed_122_7293
Magnetic beads (AO-γ-Fe2O3) of alginate (A) impregnated with citrate coated maghemite nanoparticles (γ-Fe2O3) and oxidized multiwalled carbon nanotubes (OMWCNTs) were synthesized and used as adsorbent for the removal of methylene blue from water. The XRD analysis revealed that the diameter of γ-Fe2O3 is 10.24 nm. The mass saturation magnetization of AO-γ-Fe2O3 and γ-Fe2O3 were found to be 27.16 and 42.63 emu·g-1, respectively. The adsorption studies revealed that the data of MB isotherm were well fitted to the Freundlich model. The Langmuir isotherm model exhibited a maximum adsorption capacity of 905.5 mg·g-1. The adsorption was very dependent on initial concentration, adsorbent dose, and temperature. The beads exhibited high adsorption stability in large domain of pH (4-10). The thermodynamic parameters determined at 283, 293, 303, and 313 K revealed that the adsorption occurring was spontaneous and endothermic in nature. Adsorption kinetic data followed the intraparticle diffusion model. The AO-γ-Fe2O3 beads were used for six cycles without significant adsorptive performance loss. Therefore, the eco-friendly prepared AO-γ-Fe2O3 beads were considered as highly recyclable and efficient adsorbent for methylene blue as they can be easily separated from water after treatment.
10.1016/j.ijbiomac.2018.11.102
pubmed_275_7982
OBJECTIVE The aim of this study was to investigate the relationship of serum FSH and LH levels at the commencement of stimulation to ovarian follicular development in women undergoing pituitary down-regulation and controlled ovarian hyperstimulation with gonadotropins in IVF or intracytoplasmic sperm injection (ICSI) cycles. DESIGN Retrospective analysis. SETTING An IVF program in a tertiary medical center. PATIENT(S) A total of 245 women proven to be pituitary down-regulated by their serum E(2) levels. INTERVENTION(S) Patients treated with a GnRH agonist and FSH and hMG underwent assisted reproductive technique (ART). MAIN OUTCOME MEASURE(S) Mature oocyte yield, pregnancy rate (PR), and live birth rate. RESULT(S) The serum FSH levels and the FSH-to-LH ratio at the commencement of gonadotropin stimulation were inversely correlated to the number of mature oocytes (r = -0.193 and r = -0.224, respectively). When assessed with receiver-operating characteristic (ROC) analysis, there was statistically significant ability for the FSH/LH ratio to differentiate between the "poor response" cycles (with mature oocyte yield < or =4) and the normal response cycles. Using the cutoff value derived from ROC analysis, cycles with the FSH-to-LH ratio > or =3 produced less mature oocytes (8.25 vs. 11.74), lower peak E(2) levels (1,975.3 pg/mL vs. 3,324.8 pg/mL), and higher percentage of poor ovarian response cycles (32.5% vs. 14.3%). CONCLUSION(S) The serum FSH-to-LH ratio at the start of gonadotropin stimulation after pituitary down-regulation provided a practical method for early prediction of mature oocyte yield.
10.1016/j.fertnstert.2004.10.040
pubmed_969_9127
The results of comparative RFLP analysis in some DNA loci of chromosome 7 in the populations of different Ukrainian regions are presented. Significant differences in RFLP-genotype distributions among regional populations are found. The role of different genetical processes which take place in the populations of different regions of the Ukraine is under discussion.
pubmed_969_9127